# embeddings_queue

created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1025
encoding: FLOAT32
metadata:
{"title": "Exclusion of autosomal dominant polycystic kidney disease (ADPKD2) from 160 of chromosome", "chroma:document": "linkage with chromosome 16 markers in someADPKD\nfamilies.'7'0 The type of ADPKD localised to the\nshort arm of chromosome 16 is known as ADPKD1,\nwhile the type unlinked to chromosome 16 is known\nas ADPKD2. In the latter case, there is a possibility\nthat families with 'ADPKD2' may also be genetically\nheterogeneous in which case further subdivision may\nbe warranted. The proportion of families unlinked to\nchromosome 16 (ADPKD2) has been estimated to be\n7%.11\nThe discovery of the linked markers has provided a\nmethod for diagnosis of ADPKD before the develop-\nment of detectable renal cysts. This method also\npermits prenatal detection of gene carriers. However,\nthe accuracy of prediction by linkage is dependent\nupon the relative frequency of the unlinked type of\nADPKD. The greater the proportion of ADPKD2,\nthe greater the likelihood of diagnostic error. This is\nespecially true in small families since large families\ncan provide enough information to verify the presence\nof linkage with known chromosome 16 markers. This\ndifficulty in small families could be largely avoided if\nthe linkage relationship of the ADPKD2 gene were\nknown. Hence, we have continued our studies on\nlocalising the ADPKD2 gene. The present paper\nconcerns the results of analysis of several markers,\nspanning chromosome 1, used for linkage studies with\nthe ADPKD2 gene.\nMaterials and methods\nThe family studied in the present investigation is a\nlarge kindred with over 250 members. The original\nancestors emigrated to America from Sicily and the\nfamily has been followed by the Renal Division at the\nUniversity of Colorado Health Sciences Center for the\npast 20 years. The pedigree has already been published\nelsewhere.7 The diagnosis ofADPKD was confirmed\nby ultrasonography. Any persons having at least one\ncyst in each kidney and at least two cysts in one\nkidney was considered affected. 12\nGenomic DNA was isolated from either lympho-\ncytes or transformed lymphoblasts. The digestion of 5\nto 10 ,tg of DNA from each family member was"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1026
encoding: FLOAT32
metadata:
{"title": "Exclusion of autosomal dominant polycystic kidney disease (ADPKD2) from 160 of chromosome", "chroma:document": "performed under standard conditions.'3 The appro-\n697"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1027
encoding: FLOAT32
metadata:
{"title": "Medical genetics around the world Medical genetics in South Africa", "chroma:document": "7\nMed Genet 1990; 27: 760-779\nMedical genetics around the world\nMedical genetics in South Africa\nTrefor Jenkins\nMedical practice in South Africa is firmly grounded in\nthe British tradition. The country's\nfirst medical\nfaculty was established at the South African College\n(soon to become the University of Cape Town) in\n1917 and, although the second followed in Johannes-\nburg three years later, another 23 years. were to elapse\nbefore another came into being. Today there are\nseven medical schools (eight\nif one includes the\nsmall, recently established one at Umtata in Transkei,\none of the 'independent' homeland states), which,\nbetween them, produce some 900 doctors each year.\nBefore 1918 South Africans went to British medical\nschools to train, although preclinical courses were\noffered at the South African College from 1911. Many\nof the country's medical academics have pursued\nspecialist training in the United Kingdom, with\nsmaller numbers'proceeding to the USA or Holland\nfor postgraduate studies. There are approximately\n20 000 registered doctors in South Africa (95% are\nwhite and 85% are male) and the doctor:population\nratio was 1:1344 in 1985 (up from 1:2157 in 1960),\nwhich compares with 1:650 in the UK, 1:520 in the\nUSA, and 1:10 500 in Kenya. (For these and the\nfollowing statistics relating to medical practice in\nSouth Africa I am indebted to Kirsch and Benatar.')\nIn the major urban areas of South Africa the ratio is\n1:875 but in the 'homelands' (rural areas inhabited\nalmost exclusively by black people) it is much less\nfavourable. In Transkei it is 1:19 000 and in Qwa\nQwa, another of South Africa's national states, it is\n1: 1 16 000. In the 1940s the ratio ofgeneral practitioners\nto specialists was 7:1, but the figure has gradually\nfallen until it is now 3:1. In western Europe the ratio\nis 1:1. Successful completion of a six year course and a\none year internship makes the candidate eligible for\nMRC Human Ecogenetics Research Unit, Department of\nHuman Genetics, School of Pathology, South African"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1028
encoding: FLOAT32
metadata:
{"title": "Medical genetics around the world Medical genetics in South Africa", "chroma:document": "Institute for Medical Research, Hospital Street, PO Box\n1038, Johannesburg 2000, and University of the Wit-\nwatersrand, Johannesburg, South Africa.\nT Jenkins\nregistration as a general practitioner. Specialisation\nrequires four to five years of recognised training and\npassing an examination.\nMedical genetics is not a recognised speciality and\nthe handful of South African medical geneticists are\nspecialists\nin\ninternal\nmedicine,\npaediatrics,\nor\npathology, who have subsequently undergone further\ntraining as geneticists either in South Africa or in the\nUSA. There may be a need for medical genetics to\nbecome a recognised speciality in South Africa, but\nuntil more academic departments are brought into\nbeing this is unlikely to occur. Medical scientists with\nPhD degrees in biological subjects can register with\nthe South African Medical and Dental Council (the\nequivalent of the General Medical Council in the\nUnited Kingdom) as Medical Natural Scientists. One\nis head of a university medical genetics department\nand others are in administrative positions with the\nDepartment\nof National\nHealth and\nPopulation\nDevelopment (DNHPD) Genetic Services Division.\nTertiary health care is of a high standard; the\nacademic hospitalshavethe full rangeofsub-specialities\nand 'high-tech' medicine is as much in evidence in\nthese hospitals as it is in the teaching hospitals of\nEurope and North America. There is considerable\ndebate within the profession about the appropriateness\nof much of this training because, in the first place,\nlarge numbers of the medical graduates leave the\ncountry within afew years ofqualifyingand, secondly, a\nlarge proportion of the population (more than 50%)\nlives in rural areas, and there is a reluctance on the\npart of doctors to work in these relatively remote\nareas.\nThe infant mortality rates (IMRs) (death occurring\nwithin the first year of life per 1000 births) in South\nAfrica averaged over 1981 to 1985 are 12-3 for white,\n17-9\nfor Indian,\n51-9\nfor\n'Coloured'\n(or mixed"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1029
encoding: FLOAT32
metadata:
{"title": "Medical genetics around the world Medical genetics in South Africa", "chroma:document": "(or mixed\npeoples), and 94 to 124 for African populations.2 The\nfigure for Africans can be broken down to show a\nvalue of 25-6 for those resident in Soweto and 130 for\nthose in the Transkei; the IMR for 'Coloureds' shows\na 2-6 times higher rate in rural compared with urban\nareas. The commonest causes of death in the 1 to 12\n760"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1030
encoding: FLOAT32
metadata:
{"title": "Glaucoma-induced changes in ciliary ganglion", "chroma:document": "Brit. J. Ophthal. (I975) 59, 573\nGlaucoma-induced changes in the ciliary ganglion\nSHASHI KAPOOR AND M. SOOD\nFrom the Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research,\nPondicherry-6, India\nThe ciliary ganglion\nis a parasympathetic relay\nstation, related to the innervation of the uvea. It is\ncomposed\nmainly\nof\nparasympathetic\nganglion\ncells (Kurus, 1956). It has been shown to undergo\ndegenerative\nchanges\nafter corneal\ncauterization\n(Bach,\nI899; Bernheimer,\nI897;\nMarina,\nI899),\niridectomy (Warwick, I954), exenteration (Warwick,\nI954),\nand\nevisceration\n(Tobari,\nI97I)\nbut\nits\nrelationship\nwith\nglaucoma\nis\nstill\nuncertain.\nChanges in intraocular pressure have been found\non stimulation of the ciliary ganglion (Lele and\nGrimes, I960; Schmerl and Steinberg, 1949). The\naim of the present study was to find out what\nhappens to the ciliary ganglion in experimental\nglaucoma.\nMaterial and methods\nGlaucoma was induced experimentally in one of the\neyes of seven rhesus monkeys by inserting a hypodermic\nneedle (26 gauge) into the anterior chamber through\nthe temporal limbus under paraldehyde anaesthesia.\nThe needle was connected to a saline reservoir which\nwas elevated so as to maintain the intraocular pressure\nAddress for reprints: Dr Shashi Kapoor, Department of Ophthal-\nmology, Jawaharlal Institute of Postgraduate Medical Education\nand Research, Pondicherry-6, India\nat 75 mm for iz hours, after which the animals were\nkilled. The globe, optic nerves, and ciliary ganglia were\nthen examined histopathologically. Sections of io ,tum\nthickness were stained with haematoxylin and eosin\nand methyl green pyronin.\nResults\nThe\nciliary ganglion\ncomprises many ganglion\ncells. In a normal ciliary ganglion, each cell has a\ncentral nucleus, uniformly distributed Nissl gran-\nules in the cytoplasm, and a complete ring of glial\ncells around it (Figs i and 2).\nThe\nhistopathological\nchanges\nseen\nin\nthe\nciliary ganglia after 12 hours of acute glaucoma were"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1031
encoding: FLOAT32
metadata:
{"title": "Glaucoma-induced changes in ciliary ganglion", "chroma:document": "eccentric displacement or extrusion of the nucleus,\nand\nchromatolysis\nin\nthe\nform\nof\nperipheral\nclumping or disappearance of the Nissl granules.\nNo change was observed in the interstitial cells\n(Figs 3-5). The changes are summarized in the\nTable.\nDiscussion\nThe relationship of the ciliary ganglion\nto the\ninnervation of the uvea has been demonstrated by\nthe experiments of Tobari (I97i) and Warwick\nTable\nGanglion cell changes in experimental acute glaucoma\nAnimal\nNucleus\nNissl granules\nAbnormal\nNormal\n1328\n1369\n1274\nI288\n1509\n1350\nI I85\nNo.\n337\n358\n324\n347\n365\n338\n288\n9303\n2357\n(0)\n20-24\n20-73\n20-27\n2I*22\nI9-48\n20-04\n19.55\n20-2\n(average)\nCells\nexamined\n478\n452\n413\n449\n489\n465\n376\nAbnormal\nNormal\nNo.\n(%)\n56\n422\n88-28\n43\n409\n90-48\n44\n369\n89.33\n53\n396\n88-20\n72\n417\n85-27\n62\n403\n86-66\n41\n335\n89-o8\n3122\n371\n2751\n88-2\n(average)\n2\n3\n4\n5\n6\n7\nTotal\nCells\nexamined\nI665\n1727\n1598\nI635\nI874\ni688\n'473\nii66o"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1032
encoding: FLOAT32
metadata:
{"title": "TB granuloma: CD30 co-stimulation for CD4 T cell co-operation", "chroma:document": "INSIGHTS\nTB granuloma: CD30 co-stimulation for CD4+ T cell\nco-operation\nAbigail R. Gress1 and Tyler D. Bold1\ue840\nTuberculosis granuloma T cells express an array of mediators including the CD30 co-stimulatory receptor and its ligand,\nCD153. CD4 T effector cells require signals through CD30, potentially provided co-operatively by other T cells, to completely\ndifferentiate and protect against disease (Foreman et al., 2023. J. Exp. Med. https://doi.org/10.1084/jem.20222090).\nA new study by Foreman et al. (2023) re-\nveals a novel mechanism by which T cells\nco-operate through co-stimulation in the\ngranuloma to develop protection against\ntuberculosis (TB). Adaptive immunity\nagainst the intracellular pathogen Myco-\nbacterium tuberculosis (Mtb) epitomizes the\ncanonical paradigm of the CD4 T helper\n1 (Th1) cell, with IFN-\u03b3 help for macro-\nphages at the forefront of its functional\narmamentarium. But there is still more to\nunderstand\nabout\nprecisely\nhow\nthese\nlymphocytes protect hosts against TB dis-\nease, particularly at the site of primary lung\ninfection, in the organized immunologic en-\nvironment of the granuloma. Foreman et al.\n(2023) have found that signaling in CD4\nT cells through the CD30 co-stimulatory\nreceptor\nvia\nits\nligand\nCD153,\nboth\nhighly expressed by T cells in the gran-\nuloma, is essential for the development\nof protective T cells in TB (Foreman\net al., 2023).\nTo identify T cell protective mecha-\nnisms that function at the site of TB in-\nfection, Foreman et al. (2023) explored the\ntranscriptome\nof\nbulk\nCD4\nand\nCD8\nT cells isolated from lung granulomas of\nMtb-infected rhesus macaques, compar-\ning these cells to T cells in either the blood\nor bronchoalveolar lavage \ufb02uid from the\nsame infected hosts. Granuloma T cells\ndifferentially expressed an array of hom-\ning receptors, cytokines, chemokines, and\ntranscription factors when compared to\nT cells from these other two anatomic\nsites. This included 887 genes in CD4\nT cells and 849 in CD8 T cells that were\nspeci\ufb01cally expressed in the granuloma, a"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1033
encoding: FLOAT32
metadata:
{"title": "TB granuloma: CD30 co-stimulation for CD4 T cell co-operation", "chroma:document": "\ufb01nding that offers strong justi\ufb01cation for\nthe targeted study of T cells recruited to\nMtb-infected tissues across hosts.\nCompared to naive T cells in the blood,\ngranuloma CD4 and CD8 effector T cells\ndifferentially expressed a large array of co-\nstimulatory molecules including TNFRSF8\n(CD30), TNFRSF4 (OX40), and TNFRSF9 (4-\n1BB). Interestingly, the ligands for several\nof these receptors, TNFSF8 (CD30L/CD153)\nand TNFSF9 (4-1BB-L), were also differen-\ntially expressed only in granuloma CD4\nT cells. Further data analysis correlating the\nexpression of genes relative to the bacterial\nburden\nof\nindividual\nlung\ngranulomas\ncon\ufb01rmed that TNFRSF8 (CD30) was one of\nthe most highly expressed genes in both\ngranuloma CD4 and CD8 T cells indepen-\ndent of the potential confounding variable\nof bacterial load, suggesting that it may play\nan important role in protection.\nA previous publication from the same\ngroup found that CD153, the ligand for\nCD30, is highly expressed by a protective\nCD4 T cell population in the lung paren-\nchyma of Mtb-infected mice and is re-\nquired for CD4 T cell\u2013mediated protection\nin the mouse model of TB (Sallin et al.,\n2018). The authors further investigated\nthe mechanistic role of CD30 in T cell\u2013\nmediated\nprotection\nusing\nthe\nmouse\nmodel. Similar to CD153\u2212/\u2212 mice, CD30\u2212/\u2212\nmice succumbed earlier to Mtb infection\nthan wild-type mice. However, both mu-\ntant strains maintained similar frequen-\ncies of Mtb-speci\ufb01c T cells in the lungs,\nindicating that neither protein is neces-\nsary for the generation or initial differ-\nentiation of antigen-speci\ufb01c effector cells.\nDespite this, the authors found that donor\nCD4 T cells isolated from either CD30\u2212/\u2212 or\nCD153\u2212/\u2212 mice failed to protect T cell\u2013\nde\ufb01cient recipient mice, suggesting that\nboth elements of this co-stimulatory sig-\nnaling axis must be expressed by T cells\nfor protection (Foreman et al., 2023).\nIn their previous study focused on\nCD153, the authors hypothesized that\nCD153 expressed on CD4 T cells could\nmediate protection against Mtb by stim-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1034
encoding: FLOAT32
metadata:
{"title": "TB granuloma: CD30 co-stimulation for CD4 T cell co-operation", "chroma:document": "ulating CD30 on infected macrophages\n(Sallin et al., 2018). To test this in the\npresent study, the authors used mixed\nInsights from Abigail R. Gress and Tyler D. Bold.\n.............................................................................................................................................................................\n1Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN, USA.\nCorrespondence to Tyler D. Bold: tbold@umn.edu.\n\u00a9 2023 Gress and Bold. This article is distributed under the terms of an Attribution\u2013Noncommercial\u2013Share Alike\u2013No Mirror Sites license for the \ufb01rst six months after the\npublication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution\u2013Noncommercial\u2013Share Alike 4.0\nInternational license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).\nRockefeller University Press\nhttps://doi.org/10.1084/jem.20230547\n1 of 3\nJ. Exp. Med. 2023 Vol. 220 No. 8\ne20230547"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1035
encoding: FLOAT32
metadata:
{"title": "Concordant cerebral oligodendroglioma in identical twins", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:706-708\nShort report\nConcordant cerebral oligodendroglioma in identical\ntwins\nNCA ROELVINK,* W KAMPHORST,t D LINDHOUT,T HPONSSEN*\nFrom the Departments ofNeurosurgery,* Pathologyt and the Institute ofHuman Genetics,: Free University,\nAmsterdam, The Netherlands\nSUMMARY A case of concordant oligodendroglioma in monozygotic twins is reported. The twins\nwere also concordant for uterine leiomyoma and one twin partner had fibroadenoma and lipoma of\nthe breast and myelofibrosis. As very few cases of concordant glioma in monozygotic twins have\nbeen published and no such cases in dizygotic twins, a genetic influence in the aetiology of glioma\ncan only be suggested.\nFour histologically proven cases of concordant gli-\noma in monozygotic twins have been published so far,\namongst\nwhich\nthere\nwas\nno\ncase\nof\noligo-\ndendroglioma.' 4 Study of concordant and discor-\ndant brain tumours may shed light on the con-\ntribution of genetic and non-genetic factors to the\npathogenesis of these tumours. Therefore, we report\non a twin pair concordant for oligodendroglioma and\nuterine leiomyoma.\nCase histories\nThe female twins were born in 1928. The parents were\nhealthy and non-consanguinous. At time of delivery pater-\nnal age was 36 years and maternal age 38 years. Data about\nplacenta(s) and the composition of fetal membranes were\nnot available. The twins were of identical resemblance from\ntheir early childhood till in their fifties. Both had blood-\ngroup A Rhesus factor positive and they were right handed.\nThey were reared and lived together till 1952. The younger\nsister\nis hypermetropic and has concomitant convergent\nsquint of the left eye. The family history was negative for\nhereditary diseases.\nTwin A\nThis twin has had hypermetropia, convergent squint and\namblyopia of the left eye from early childhood. She acquired\npulmonary tuberculosis during the second world war, com-\nAddress for reprint requests: NCA Roelvink, Free University Hospi-\ntal, Department of Neurosurgery, de Boelelaan"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1036
encoding: FLOAT32
metadata:
{"title": "Concordant cerebral oligodendroglioma in identical twins", "chroma:document": "1117,\n1007 MB\nAmsterdam, The Netherlands.\nReceived 26 March 1985 and in revised form 24 August 1985.\nAccepted I September 1985\nplicated by abdominal tuberculosis at the age of 26. She\nremained without offspring. At the age of 38 a uterine lei-\nomyoma was removed. The first symptoms suggesting brain\npathology consisted of paresthesiae in the right arm and leg\nat the age of 56 years. No other neurological abnormalities\nwere evident. There were no signs of phacomatoses. Cyto-\ngenetic analysis of peripheral lymphocytes showed a normal\nkaryogram (46, XX). On computed tomography of the brain\nan irregular hypodense area was seen in the left parietal lobe.\nAt craniotomy a slight bulging of the left parietal bone was\napparent. Only partial removal of the tumour was possible.\nHistological\nexamination\nshowed\nit\nto\nbe\nan\noligo-\ndendroglioma, grade B' (figs a). Radiotherapy was given\nwith a megavolt apparatus at a dose of 6120 cGy in 34 ses-\nsions in 49 days. Twelve months after surgery there are still\nno clinical or CT scan signs of tumour recurrence.\nTwin B\nShe\nhad\nhad\nhypermetropia,\nconvergent\nsquint\nand\namblyopia of the right eye from early childhood. She had 4\nchildren one of whom had an ovarian cyst. At the age of 30\nand 47 years she suffered from psychiatric disturbances\nwhich were explained by environmental circumstances. At\nthe age of 38 a uterine leiomyoma was removed. The first\nunequivocal symptom pointing to brain pathology was an\nattack of vertigo after a sudden head movement at the age of\n56 years. No neurological abnormalities or signs of pha-\ncomatoses were found. Computed tomography of the brain\nshowed a hypodense mass with hyperdense spots in the right\nfrontal lobe. At craniotomy frontal lobectomy was carried\nout for radical removal of the tumour. Histological exam-\nination revealed an oligodendroglioma, grade D' (fig, b).\nRadiotherapy was given with a telecobalt apparatus at a\ndose of 5000cGy in 20 sessions in 21 days.\nSix months after surgery severe anaemia was discovered.\n706"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1037
encoding: FLOAT32
metadata:
{"title": "Limb apraxia in patients with damage confined the left basal ganglia and thalamus", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1030-1038\nLimb apraxia in patients with damage confined to the\nleft basal ganglia and thalamus\nE DE RENZI,\nP FAGLIONI, M SCARPA, G CRISI\nFrom the Departments ofNeurology and Radiology, University ofModena, Italy\nSUMMARY Limb apraxia was investigated with standardised tests in 14 patients whose CT scan\nprovided evidence of a vascular lesion confined to the left basal ganglia, or the thalamus, or both,\nand not involving the cortex or adjacent white matter. Five patients were severely impaired in\nimitating movements and pantomiming object use. Four of them also performed poorly when tested\nwith real objects. In two patients the lesion was primarily thalamic and in three the lesion was\nprimarily in the lenticular nucleus and the posterior limb of the internal capsule. Patients without\napraxia generally had smaller injuries, but there were exceptions. Apraxia is currently conceived of\nas due to damage of cortical areas and their cortico-cortical connections, but the present data\nsuggest that the model should be enlarged to include the deep nuclei and the pathways running\nthrough them.\nThe introduction of CT examination in neurological\npractice has opened new avenues\nto\nthe under-\nstanding of the anatomical basis of higher nervous\nfunction disorders. On the basis of CT results, it has\nbeen discovered that deep hemispheric structures,\nplay a hitherto unsuspected role in the genesis of\nsymptoms that were thought to be the province of the\nneocortex\nand\nthe\nunderlying\nwhite\nmatter.\nDepending on the side of lesion, Aphasia`6 and uni-\nlateral neglect' 2 7-10 have been reported to result\nfrom damage restricted to the striatum, or the thal-\namus, or both, suggesting that the circuits subserving\nlanguage and lateral attention must be enlarged to\ninclude these structures. No comparable evidence has\nhitherto been reported for apraxia, a condition tradi-\ntionally attributed to the involvement of parietal and\nfrontal cortical areas of the hemisphere dominant for"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1038
encoding: FLOAT32
metadata:
{"title": "Limb apraxia in patients with damage confined the left basal ganglia and thalamus", "chroma:document": "speech and/or to the fibre bundles connecting them\nwithin the same hemisphere and through the corpus\ncallosum with the premotor cortex of the contra-\nlateral hemisphere.\" -\nl\nOur interest in the relationship between left deep\nnuclei damage and movement organisation disorders\nwas first aroused by a patient who had severe limb\napraxia following a haematoma slhown by CT scan to\nReceived 25 June 1985 and in revised form 28 October 1985.\nAccepted 2 November 1985\nAddress for reprint requests: Dr E De Renzi, Clinica Neurologica,\nVia Del Pozzo 71, Modena 41 100, Italy.\ninvolve the left thalamus, the posterior limb of the\ninternal capsule and the posterior part of the lenticu-\nlar nucleus. Alerted by this case, we searched the files\nof left brain-damaged patients examined with apraxia\ntests in the course of previous studies and for whom\nthere was CT scan documentation that the lesion was\nconfined to the deep nuclei, sparing the cortex and the\nunderlying white matter. Fourteen such cases (inclu-\nsive of the one originally examiined) were recovered;\nin five of them there was unequivocable evidence of\nlimb apraxia. We report in detail the five positive\ncases and contrast them with those not showing\napraxia.\nMethods\nThe 14 patients of the present study were, with one excep-\ntion, admitted to the wards in the early days of their disease\nand were tested for apraxia within 10 to 50 days of the onset\nof their illness. They were all alert and cooperative at the\ntime of testing. Four patients had a haematoma and 10 had\na softening of the left hemisphere in an area between the wall\nof the third ventricle medially and the external capsule\nlaterally.\nLesion sites were assessed with CT scan sections at 00 to\nthe canthomeatal line. In describing the lesion we will make\nreference to the three sections where the basal ganglia are\nrepresented (Sections 10, 9 and 8 of Matsui and Hirano's\nAtlas'5) and will designate them as the inferior, middle and\nsuperior section, respectively.\nPraxis evaluation was based on the performance on a"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1039
encoding: FLOAT32
metadata:
{"title": "Limb apraxia in patients with damage confined the left basal ganglia and thalamus", "chroma:document": "movement imitation test and an object use pantomime test\n1030"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1040
encoding: FLOAT32
metadata:
{"title": "Local cerebral glucose utilisation in chronic alcoholics: positron tomographic study", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1165-1170\nLocal cerebral glucose utilisation in chronic alcoholics:\na positron tomographic study\nYVES SAMSON,* JEAN-CLAUDE BARON,*t ANDRE FELINE,:\nJACQUES BORIES,\u00a7 CHRISTIAN CROUZEL*\nFrom Service Hospitalier Frederic Joliot CEA, Departement de Biologie (Orsay),* Clinique des Maladies du\nSysteme Nerveux, La Salp&triere,t Service de Psychiatrie, H6pital Kremlin Bicetre,t Service de\nNeuroradiologie, La Salpetriere,\u00a7 Paris, France\nSUMMARY\nUsing positron tomography,\na study of regional cerebral glucose utilisation\nwas\nperformed prospectively in a highly selected group of six neurologically unaffected primary chronic\nalcoholics. In this group, neuropsychological, behavioural and CT scan anomalies were comparable\nwith those previously reported in more extensive studies. With respect to age-matched control\nvalues, cerebral metabolic rate was not significantly modified in the selected cortical, subcortical and\ncerebellar regions of interest. However, the metabolic regional distribution index, which reflects the\ndistribution pattern of glucose utilisation, was selectively and significantly decreased in the medio-\nfrontal area, pointing to a limbic metabolic dysfunction apparently linked to chronic alcoholism.\nEven in apparently neurologically unaffected sub-\njects, chronic alcohol abuse may be associated with\nsome\ndegree\nof\ncerebral\ndysfunction.\nNeuro-\npsychological studies have demonstrated impairment\nof several motor, spatio-visual and memory func-\ntions,\ndespite\napproximately\npreserved\nIQ.' -\nChanges\nin cerebral blood flow have been\nalso\nreported.68 Although pathological studies reported\nonly equivocal cortical alterations in chronic alcohol-\nics,5 9 10 the occurrence of widened cortical\nsulci\n(cerebral atrophy) has been demonstrated in vivo by\nnumerous CT\nscan\nstudies. \" - 16\nHowever,\nthe\nprecise mechanism of the reported morphological\nand neuropsychological\nchanges,\nand\nthe\ninter-\nrelationships\namong\nthe\ntwo,\nremain\nlargely"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1041
encoding: FLOAT32
metadata:
{"title": "Local cerebral glucose utilisation in chronic alcoholics: positron tomographic study", "chroma:document": "largely\nunknown.2 Experimentally, alterations of neuronal\nmembranes,17 alteration of dopaminergic and gab-\naergic systems,'8-2' as well as selective vulnerability\nof hippocampal neurons,22 23 have been reported,\nstrengthening the hypothesis that alcohol alters neu-\nron function and even perhaps structure. The present\nstudy was an attempt to determine by means of posi-\ntron tomography (PET) if abnormal cerebral glucose\nutilisation (CMRGIu) could be found in a clinically\nhomogeneous\nsample\nof\nhighly\nselected\nneu-\nrologically unaffected chronic alcoholics.\nAddress for reprint requests: Yves Samson, Service Hospitalier\nFrederic Joliot Hopital d'Orsay, 91406 Orsay, France.\nReceived 13 August 1985 and in revised form 9 December 1985.\nAccepted 15 December 1985\nMethods\nSix subjects admitted to the psychiatric department of a gen-\neral hospital were prospectively selected on the following\ncriteria: 30-60 years of age, chronic dependence on alcohol\n(DSM III), present hospital admission directly related to\nalcoholism, right handedness, provision of informed con-\nsent. Criteria of exclusion were: preexistent psychiatric, neu-\nrological\nor severe physical\ndisease (including alcohol-\nrelated\nencephalopathy),\nhead\ntrauma\nwith\nloss\nof\nconsciousness, seizures, clinically obvious hepatic cirrhosis\nor insufficiency and drug abuse.\nNeurological and psychiatric clinical examination, includ-\ning a standardised questionnaire about drinking history and\nsociobehavioural alterations was performed for each sub-\nject, as well as EEG, CT and routine biological laboratory\ntests.\nNeuropsychological\ntesting\nwas\nalso\nperformed,\nincluding performance and verbal IQ determination, cog-\nnitive tasks (Wisconsin Cards Sorting test), Rey's figure\ncopy and delayed reproduction, Weschler memory test or\nbattery 144,24 Luria series.\nUsing\nthe\n'8F-fluoro-2-deoxy-D-Glucose\n('8FDG)\nmethod26 PET studies were carried out on an ECAT II,\nbetween the end of the first week and the end of the first\nmonth of the hospital admission with apparent abstinence."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1042
encoding: FLOAT32
metadata:
{"title": "Local cerebral glucose utilisation in chronic alcoholics: positron tomographic study", "chroma:document": "Three adjacent brain\nlevels were scanned consecutively\n(respectively 15, 35, 55 mm above and parallel to the orbito-\nmeatal line) on subjects at rest, eyes closed, ears unplugged\nand free from any medication for at least 24 hours, accord-\ning to our usual protocol.25 Briefly, all images were cor-\nrected for attenuation using Ge68-Ga68 transmission scans;\n18FDG radioactivity blood curve was obtained from cross-\ncalibrated plasma counting of serial arterial blood samples,\n1165"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1043
encoding: FLOAT32
metadata:
{"title": "Convolution in human rods: ageing", "chroma:document": "British Journal of Ophthalmology, 1979, 63, 181-187\nConvolution in human rods: an ageing process\nJOHN MARSHALL,' JOHN GRINDLE,2 PAUL\nL. ANSELL,1 AND\nBESSIE BORWEIN3\nFrom the 'Department of Visual Science, Institute of Ophthalmology, London, England; the 2Department of\nClinical Ophthalmology, Institute of Ophthalmology and Moorfields Eye Hospital, London, England; and\nthe 3Department of Physics, University of Western Ontario, London, Canada\nSUMMARY\nIn a morphological survey of 73 human retinae spanning 9 decades, and including 20\nretinae which were obtained from eyes enucleated for malignant melanomas, nodular excrescences\nwere noted in the outer segments of rods with an incidence which increased with age. These\nstructures were sectioned in both their vertical and horizontal axes and on electron microscopical\nexamination were seen to result from the localised convolution of affected outer segments. The\ntopographic morphology of such convolutions is described and their modes of formation are\ndiscussed.\nThe process of ageing and its manifestations in the\ncells of the human retina has for some time been a\nmajor research interest in our laboratory. These\nstudies include the electron microscopical examina-\ntion of 73 human\nretinae obtained from both\nenucleations and cadaver eyes. This series contains\nspecimens from each of 9 decades, the youngest eye\nbeing 19 years and the oldest 90 years. The detailed\nmorphology of the photoreceptor cells, the pigment\nepithelium,\nand\nBriich's\nmembrane\nhave\nbeen\ninvestigated in order to establish control reference\nmaterial\nfor\na\nfuture\nstudy\nof\nsenile macular\ndegenerations and inherited retinal dystrophies. We\nwere interested therefore by a recent report pur-\nporting to show the fusion of the outer segments of\njuxtapositioned rod photoreceptor cells in the retina\nof a 47-year-old woman whose eye was enucleated\nbecause of the presence of a choroidal melanoma\n(Borwein et al., 1977). In the present paper morpho-\nlogical evidence shows that this suggested fusion of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1044
encoding: FLOAT32
metadata:
{"title": "Convolution in human rods: ageing", "chroma:document": "appositioned cells is an age-related process occurring\nwithin the outer segments of individual rods.\nMethods\nOne of the commonest conditions that leads to\nenucleation of human eyes is malignant melanoma\nof the uveal tract. The retinae of 20 such eyes have\nbeen studied in the present survey, with an age\nAddress for reprints: Dr John Marshall, Department of\nVisual Science, Institute of Ophthalmology, Judd Street,\nLondon WC1H 9QS\nrange spanning 7 decades. The immediate post-\noperative procedures\nvaried with\nthe individual\ndemands of participating centres. In most centres\ncorneal discs were trephined for subsequent use in\ngraft procedures. One centre required the dissection\nof the globe and the hemisection of the unfixed\ntumour so that samples could be processed for tissue\nculture as well as histopathology. In some cases\nintact\nglobes were\npresented\nimmediately\nafter\nenucleation, and here transcorneal incisions were\nmade in the sagittal plain before immersion in\nfixative.\nAll eyes were fixed within minutes of enucleation\nby immersion in 100 ml of 0 3 M glutaraldehyde\nbuffered\nin 0-1 M sodium cacodylate containing\n10 mg/ml of calcium chloride with a final pH 7-4.\nIntact globes were progressively dissected in this\nsolution, the cornea being removed at the sulcus\nsclerae after 5 minutes, the iris after a further 5\nminutes, and the lens, ciliary body, and vitreous 20\nminutes after the initial immersion.\nAfter a total of 1 hour in fixative all posterior eye\ncups were washed\nin\n0-1 M sodium cacodylate\ncontaining\n7-5 %\nsucrose,\nand\nin\nthis\nsolution\nexperimental samples were isolated under a dis-\nsecting microscope. In all cases the tumour was\nisolated\nfirst\nand\nsubsequently\nprocessed\nfor\nconventional histopathology. Where the topography\nof the tumour allowed,\n5\nsets of samples were\nisolated for electron microscopical study. These\nwere the macula and 4 bands of tissue radiating\nfrom the macula to the ora serrata in the cardinal\naxes.\nAll samples were\ndissected so\nthat\ntheir\n181"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1045
encoding: FLOAT32
metadata:
{"title": "A systematic analysis of the human immune response to Plasmodium vivax", "chroma:document": "The Journal of Clinical Investigation   \nC L I N I C A L  M E D I C I N E\n1\nIntroduction\nPlasmodium vivax causes more than half of all malaria cases in the \nAmericas and Southeast Asia (1) and its distinct biology (cf P. fal-\nciparum) presents unique challenges for control and elimination. \nDormant liver-stage parasites can trigger multiple relapses over \nmany months or years (2); asexual blood-stage parasites prefer-\nentially accumulate in the spleen to promote chronic infection \n(3); and gametocytes develop rapidly within the bone marrow to \nmaximize transmission (4). Total pathogen load is nevertheless \nreduced compared with P. falciparum and severe disease is a much \nless common outcome of infection (5). This may be explained in \npart by P. vivax invading CD71+ reticulocytes (as opposed to mature \nred cells) and sequestering far less effectively than P. falciparum \n(6, 7). But parasite virulence may also be influenced by the host \nresponse to infection (8). It is well established that the pyrogenic \nthreshold is far lower for P. vivax (indicating differential regulation \nof the acute-phase response) and that clinical immunity (leading \nto asymptomatic infection) is acquired much more quickly (9\u201313). \nParasite species may therefore regulate the immune response to \nshape the discrete patterns of disease observed in human malaria.\nThere are large gaps in our understanding of the immune \nresponse to P. vivax compared with the better-studied P. falciparum \n(14). We know the P. vivax genome is enriched in CpG motifs that \ncan bind TLR9 to trigger type I interferon (IFN) production (15, \n16) and that monocytes and neutrophils are highly phagocytic \n(and generate reactive oxygen species) during acute infection (17, \nBACKGROUND. The biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the \nimmune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1046
encoding: FLOAT32
metadata:
{"title": "A systematic analysis of the human immune response to Plasmodium vivax", "chroma:document": "isolate of P. vivax and tracked their response through infection and convalescence.\nMETHODS. Participants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real \ntime by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and \ncytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. \nComparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled \nhuman malaria infection studies.\nRESULTS. P. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. \nThis acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at \nRNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation \nwere significantly increased in volunteers infected with P. falciparum. Heterogeneous CD4+ T cells were found to dominate \nthis adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and \nautoinflammatory disease.\nCONCLUSION. P. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced \npyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why \nfalciparum malaria more frequently causes severe disease.\nTRIAL REGISTRATION. ClinicalTrials.gov NCT03797989.\nFUNDING. The European Union\u2019s Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society.\nA systematic analysis of the human immune response \nto Plasmodium vivax\nFlorian A. Bach,1 Diana Mu\u00f1oz Sandoval,1,2 Michalina Mazurczyk,3 Yrene Themistocleous,4 Thomas A. Rawlinson,4  \nAdam C. Harding,1 Alison Kemp,5 Sarah E. Silk,4,6 Jordan R. Barrett,4,6 Nick J. Edwards,4 Alasdair Ivens,1 Julian C. Rayner,5"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1047
encoding: FLOAT32
metadata:
{"title": "A systematic analysis of the human immune response to Plasmodium vivax", "chroma:document": "Angela M. Minassian,4,6 Giorgio Napolitani,3 Simon J. Draper,4,6 and Philip J. Spence1\n1Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom. 2Insitute of Microbiology, Universidad San Francisco de Quito, Quito, Ecuador. 3MRC Human \nImmunology Unit, Weatherall Institute of Molecular Medicine, and 4The Jenner Institute, University of Oxford, Oxford, United Kingdom. 5Cambridge Institute for Medical Research, University of Cambridge, \nCambridge, United Kingdom. 6Department of Biochemistry, University of Oxford, Oxford, United Kingdom.\nConflict of interest: YT is a contributor to intellectual property (ChAdOx1 nCOV-19 Clini-\ncal Data) licensed by Oxford University Innovation to AstraZeneca (no. 18003 DD002).\nCopyright: \u00a9 2023, Bach et al. This is an open access article published under the \nterms of the Creative Commons Attribution 4.0 International License.\nSubmitted: June 17, 2021; Accepted: August 22, 2023; Published: October 16, 2023.\nReference information: J Clin Invest. 2023;133(20):e152463.  \nhttps://doi.org/10.1172/JCI152463."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1048
encoding: FLOAT32
metadata:
{"title": "The differential involvement of subcortical nuclei in senile dementia of Alzheimer's", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1988;51:842-849\nThe differential involvement of subcortical nuclei in\nsenile dementia of Alzheimer's type\nG K WILCOCK,* M M ESIRI,t D M BOWEN,4\nA 0 HUGHES\u00a7\nFrom the Department ofCare of the Elderly, Frenchay Hospital,* Bristol, Department ofNeuropathology,\nRadcliffe Infirmary, Oxford,t Department ofNeurochemistry, Institute ofNeurology, London,J and Department\nofEpidemiology & Community Medicine, University ofBristol,\u00a7 Bristol, UK\nSUMMARY\nCell counts have been performed on cholinergic subcortical nuclei, dorsal raphe nucleus,\nand locus caeruleus from up to 18 cases of Alzheimer's disease and 10 age-matched control subjects.\nIn general, the extent of the cell loss in these structures was similar. In the basal nucleus the\nanteromedial subdivision was the least, and the posterior subdivision the most affected. A subgroup\nof demented subjects with Alzheimer's disease had a relatively preserved basal nucleus, and frontal\nlobe (CAT) choline acetyltransferase activities similar to those in control subjects, but significantly\nmore neuronal loss in the locus caeruleus.\nNeuropathological changes in the neocortex of sub-\njects with Alzheimer's disease are known to be accom-\npanied by a reduction in certain neurotransmitter\nsubstances or their marker enzymes, and this has\nstimulated examination of the subcortical sites associ-\nated with their synthesis. The nucleus basalis of Mey-\nnert (NBM) in the substantia innominata (together\nwith the medial septal nucleus (MSN) and the nucleus\nof the diagonal band of Broca (DBB)) is the predom-\ninant cholinergic source, and has been shown to be\naffected by neuronal loss and other histological fea-\ntures of Alzheimer's disease since the early studies of\nPilleri.' 2 Others have also described the presence of\nneurofibrillary tangles in the NBM.3-' The neuronal\nloss in the basal forebrain in particular has been\nconfirmed by many studies using either cresyl violet\nstained material5 6 8-10 or more specific stains for"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1049
encoding: FLOAT32
metadata:
{"title": "The differential involvement of subcortical nuclei in senile dementia of Alzheimer's", "chroma:document": "cholinergic marker enzymes such as choline acetyl-\ntransferase (CAT),7 11 12 and the loss of larger neu-\nrons has been reported to be as great as 90% in some\ncases. Pearson et al,'3 however, using a monoclonal\nantibody staining technique for CAT failed to dem-\nonstrate a significant loss of cholinergic cells from the\nNBM, but rather a shrinkage of neuronal perikarya.\nIn a detailed study dividing the NBM into six sub-\npopulations adapting Mesulam's nomenclature from\nthe monkey to man,14 Arendt and his colleagues re-\nported an average overall loss of neurons of 57%,\nwith the most extensive loss occurring in the posterior\nAddress for reprint requests: Professor G K Wilcock, Department of\nCare of the Elderly, Frenchay Hospital, Bristol, BS16 ILE, UK.\nReceived\n14 July\n1987 and in revised form\n12 January\n1988.\nAccepted 21 January 1988\npart of the nucleus in three of their five cases. How-\never, all subjects showed an individual pattern of\nNBM degeneration.15 They also found that there was\na significant correlation between the degree of cell loss\nand the number of neocortical senile plaques.\nThe locus caeruleus (LC) is the main subcortical\nsite for the synthesis of noradrenaline and its precur-\nsor enzymes. Reduction in the number of pigmented\nneurons in this structure in Alzheimer's disease has\nbeen demonstrated in several studies since 1978,16-19\nand the extent of the cell loss been shown to correlate\nwith the severity of the dementia and neurofibrillary\ntangle and senile plaque formation,'7 25 although this\nhas not been found in all studies.20 The central por-\ntion of the locus caeruleus, which is considered to\nproject predominantly to the temporal cortex and\nhippocampus, that is, areas of cortex which are usu-\nally severely affected by neurofibrillary tangle and\nsenile plaque formation, has been reported to show\nthe most extensive loss of cells.2'\nThe serotoninergic dorsal raphe nuclei (DRN)\nhave\nbeen\nless\nextensively\nexamined,\nalthough\nneurofibrillary tangle formation and neuronal loss"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1050
encoding: FLOAT32
metadata:
{"title": "The differential involvement of subcortical nuclei in senile dementia of Alzheimer's", "chroma:document": "have also been described in these structures.4 18 22-24\nFew studies have compared the changes in different\nsubcortical structures in each of an age-matched\nseries of brains from subjects with Alzheimer's disease\nand undemented control subjects. Mann and col-\nleagues examined the NBM, the LC and the DRN\nand the substantia nigra, and reported that the great-\nest cell loss occurred in the locus caeruleus with a\nstrong correlation between cortical plaque and tangle\ncounts, and nerve cell atrophy and loss in all four\nareas.25 However, in this study they used material\n842"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1051
encoding: FLOAT32
metadata:
{"title": "Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia*", "chroma:document": "British Journal of Ophthalmology, 1980, 64, 818-825\nExperimental occlusion of the central artery of the\nretina. IV: Retinal tolerance time to acute ischaemia*\nSOHAN SINGH HAYREH AND THOMAS A. WEINGEIST\nFrom the Department of Ophthalmology, University of Iowa, Iowa City, USA\nSUMMARY\nOphthalmoscopic, fluorescein angiographic, electrophysiological, and morphological\nstudies on 63 eyes of rhesus monkeys with acute transient experimental occlusion of the central\nartery of the retina (OCAR) showed that the retina suffered irreparable damage after ischaemia of\n105 minutes but recovered well after ischaemia of 97-98 minutes. The tolerance time of the brain\nto acute transient ischaemia is many times shorter than that of the retina. The metabolism of\nischaemic neurones (in the retina and brain) is discussed with a view to explaining this difference,\nand also the various factors possibly responsible for the retina's longer tolerance of ischaemia, as\ncompared to the brain.\nOcclusion of the central artery of the retina (OCAR)\nis a true ophthalmic emergency, when every minute\nthat elapses increases the chances of death of the\nretina. It is therefore absolutely essential to know\nhow long it takes for acute retinal ischaemia to\nproduce irreversible damage. Much of the confusion\nabout this length of time is due to the many con-\nflicting claims reported in anecdotal clinical case\nstudies and in animal experiments, so that it is not\nat all surprising that in spite of the considerable\ninterest which this subject has attracted no definite\nconclusion has been reached so far.\nPrevious studies\nCLINICAL CASE REPORTS\nTable 1 comprises most of the available reports in\nthe English literature plus a few from other lan-\nguages. Recovery of retinal function is said to take\nplace\nafter an ischaemia of anything from\n10\nminutes to as much as 36 hours. In addition there\nare 2 more reports in which slow recovery of vision\nafter OCAR has been described. Story9 in 1899\ndescribed 2 such cases. A 35-year-old man suddenly"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1052
encoding: FLOAT32
metadata:
{"title": "Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia*", "chroma:document": "lost vision in the left eye to light perception (LP)\nwhich improved to counting of fingers (CF) and to\n*A brief summary of a part of this paper formed a part of\nthe paper presented at the American Academy of Ophthal-\nmology meeting on 7 November 1979 in San Francisco.\nCorrespondence to Dr S. S. Hayreh, Department of Ophthal-\nmology, University of Iowa Hospitals and Clinics, Iowa\nCity, Iowa 52242, USA.\n6/24 after 16 and 24 days respectively, and to 6/9\nand 6/6 after 43 and 112 days respectively, with an\nophthalmoscopically normal fundus. And a 39-year-\nold woman, who suddenly lost vision in the left\neye, recovered to CF in 7 days and to 6/9 in 32\ndays. Werner'0 described a 27-year-old syphilitic\nwoman who, when seen 14 days after a sudden loss\nof vision in the left eye, was considered to have\nclassical ophthalmoscopic findings of OCAR and\ndoubtful LP. One week later the vision was LP in\nthe superior nasal quadrant. One week after that\nshe suddenly lost vision in the right eye with OCAR\nand was found to have doubtful LP in the right eye\nand CF in the left eye. The visual acuity in the left\neye improved to 6/9 42 days after the occlusion and\nin the right eye to 6/12 and 6/9 14 and 20 days after\nthe occlusion.\nEXPERIMENTAL STUDIES\nThese are summarised in Table 2. There is a good\ndeal of inconsistency in the results obtained, one\nreport alleging irreversible retinal damage within\n3 minutes, while in others much longer was needed.\nThe relevance of those findings to clinical OCAR in\nman is open to criticism because of the following\nlimitations in most of these studies.\nSome of the animals used in these studies are not\nsuitable for such an investigation; for example,\nrabbits have virtually no retinal circulation and the\nretina depends almost entirely for its nutrition on\nthe choroidal\ncirculation;\ncats have no\ncentral\nartery of the retina. The retinal ischaemia in these\nexperiments was mostly produced by raising the\n818"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1053
encoding: FLOAT32
metadata:
{"title": "Experimental posterior penetrating injury in the rabbit. Method of production and natural history", "chroma:document": "British Journal of Ophthalmology, 1979, 63, 306-311\nExperimental posterior penetrating eye injury in the\nrabbit.\nI. Method of production and natural history\nPHILIP\nE. CLEARY\nAND STEPHEN\nJ. RYAN\nFrom the Department of Ophthalmology, University of Southern California, and Estelle Doheny Eye\nFoundation, Los Angeles, California, USA\nSUMMARY A technique has been developed which produces an experimental posterior penetrating\neye injury that reproducibly results in traction retinal detachment in rabbit eyes. The standard\ninjury is an incision through the pars plana with vitreous prolapse and incarceration; the wound\nis then carefully closed with microsurgical techniques. It appears that blood in the vitreous is an\nessential factor in the development of vitreous traction and of traction retinal detachment. The\nmodel, which has been successfully transferred to Rhesus monkey eyes, is considered useful for\nfurther histological, electromicroscopical, electrophysiological, and ultrasound studies of posterior\npenetrating injuries of the eye. Our immediate goal is to assess in a controlled experiment whether\npars plana vitrectomy can interrupt the sequence of events leading to traction retinal detachment\nafter a posterior penetrating injury.\nAlthough the prognosis for penetrating eye injuries\nhas greatly improved, this\nis largely reflected in\ninjuries which involve only the anterior segment\n(Moncrieff and Scherible, 1945; Snell, 1945; Roper-\nHall, 1959; Remky et al., 1967; Watz and Reim,\n1973; Eagling, 1975). Unfortunately there has been\nlittle change in the prognosis for injuries to the\nposterior segment in the past 15 years (Johnson,\n1971; Eagling, 1975), and severe injuries involving\nboth the anterior and the posterior segments still\nresult in a blind or excised eye\nin most cases\n(Johnson,\n1971;\nCinotti\nand\nMaltzman,\n1975;\nEagling, 1975). Many of these eyes suffer an expul-\nsive choroidal haemorrhage, with disruption of the\nintraocular contents and prolapse of the retina, so"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1054
encoding: FLOAT32
metadata:
{"title": "Experimental posterior penetrating injury in the rabbit. Method of production and natural history", "chroma:document": "that there is no potential for visual recovery (Eagling,\n1975). However, not all eyes losing useful vision are\ndamaged\nbeyond\npotential\nrepair;\nfor\ninjuries\nconfined to the posterior segment traction retinal\ndetachment is the main reason for loss of vision\n(Johnson, 1971 ; Eagling, 1975; Faulborn et al., 1977).\nThe development of vitreous traction and traction\nretinal detachment after a penetrating eye injury\nhas been linked\nclinically with the presence of\nvitreous haemorrhage and vitreous incarceration in\nthe\nwound\n(Roper-Hall,\n1959;\nPercival,\n1972;\nJohnson,\n1971;\nEagling,\n1975; Faulborn\net\nal.,\nAddress for reprints: Mr Philip E. Cleary, FRCS, Ardkeen\nHospital, Waterford, Ireland\n1977). Clinical and histopathological observations\nsuggest that fibrovascular ingrowth from the scleral\nwound, vitreous haemorrhage, injury to the lens,\nand injury to the ciliary body may all contribute to\na fibroblastic response within the vitreous, which\noften\nprogresses\nto\nthe formation of a\ncyclitic\nmembrane, in which detached retina may be incor-\nporated (Hogan and Zimmerman, 1964; Coles and\nHaik, 1972; Eagling, 1975).\nIt has been postulated that the importance of the\nvitreous is that it provides a framework or scaffold\nfor fibrosis from other sources. Removal of this\nscaffold is a rationale for vitrectomy in the treat-\nment of complicated\npenetrating\ninjuries which\ninvolve the posterior segment (Coles and Haik,\n1972). Furthermore, after a posterior penetrating\ninjury the blood is typically loculated within the\nvitreous (Winthrop et al., 1978), and removal of\nthis blood by vitrectomy may reduce the stimulus to\ninflammation and organisation.\nThe introduction of pars plana vitrectomy has\noffered a new approach to the treatment of compli-\ncated posterior penetrating injuries (Machemer and\nNorton, 1972; Michels and Ryan, 1975; Peyman\net al., 1975; Benson and Machemer, 1976; Hutton\net al., 1976; Faulborn et al., 1977; Conway and\nMichels, 1978). Yet despite the encouraging pre-\nliminary results the indications and optimum timing"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1055
encoding: FLOAT32
metadata:
{"title": "Experimental posterior penetrating injury in the rabbit. Method of production and natural history", "chroma:document": "for vitrectomy remain a matter of controversy.\nAttempts to address the issues by establishing a\n306"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1056
encoding: FLOAT32
metadata:
{"title": "Dichotic listening and manual performance in relation magnetic imaging after closed head", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1989;52:1162-1169\nDichotic listening and manual performance in relation\nto magnetic resonance imaging after closed head\ninjury\nHARVEY S LEVIN,* WALTER M HIGH, JR,* DAVID H WILLIAMS,*\nHOWARD M EISENBERG,* EUGENIO G AMPARO,t FAUSTINO C GUINTO, JR,t\nJEFF EWERTt\nFrom the Division ofNeurosurgery* and the Department ofRadiology,t The University of Texas Medical\nBranch, Galveston and Department ofPsychology,: University ofHouston, Texas, USA\nSUMMARY\nIn order to investigate post-traumatic hemispheric disconnection effects, dichotic\nlistening and intermanual tasks were administered to 69 patients who had sustained a closed head\ninjury of varying severity. The manual tasks consisted of naming objects palpated in either hand,\ntransfer ofpostures from one hand to the other and writing. Consistent with predictions, the degree of\near asymmetry in dichotic listening performance was directly related to the severity ofthe head injury\nas reflected by the degree of impaired consciousness. Depth and localisation of parenchymal lesion\ncharacterised by magnetic resonance imaging were also related to the degree of ear asymmetry.\nParenchymal lesions situated in sites which could potentially interfere with callosal auditory or\ngeniculocortical pathways produced a greater disparity in response to left versus right ear inputs as\ncompared with parenchymal lesions in areas such as the frontal lobes which are purportedly unrelated\nto asymmetries in dichotic listening performance. The results provide further evidence for the effects\nof multifocal brain lesions involving the white matter on tasks which require intra and/or\ninterhemispheric integration.\nStrich' first published microscopic findings of diffuse\naxonal injury (DAI) which she attributed to mechan-\nical disruption (that is, shearing, tearing) of nerve\nfibres at the moment of impact in severe closed head\ninjury (CHI). Focal haemorrhages involving the cor-\npus callosum, the dorsolateral quadrant(s) of the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1057
encoding: FLOAT32
metadata:
{"title": "Dichotic listening and manual performance in relation magnetic imaging after closed head", "chroma:document": "rostral brainstem and the white matter of the superior\ncerebellar peduncle are frequent pathological findings\nin DA`.'-5 Degeneration of the cerebral white matter,\nwhich presumably occurs over periods ofup to several\nmonths, has been implicated in lateral ventricular\nenlargement' 256 and long tract signs such as ataxia.7\nConsistent with disruption of intra and interhemis-\npheric white matter connections in DAI, clinical\nreports have documented neurobehavioural distur-\nbances such as ideomotor apraxia using the left hand,\nalexia without agraphia and tactile anomia for objects\nCorrespondence to: Harvey S Levin, PhD, Division of Neurosurgery\nD-73, The University of Texas Medical Branch, Galveston, Texas\n77550, USA.\nReceived 11 October 1988 and in revised form 10 March 1989.\nAccepted 21 March 1989\npalpated by the left hand.\"'0 Utilising the dichotic\nlistening technique, Alexander and Warren\" recently\nreported a survivor of severe CHI who exhibited an\nexaggerated right ear advantage (that is, left ear\nsuppression),\na\nfinding\nwhich\nthe\ninvestigators\nattributed to a haemorrhagic lesion in the callosal\nauditory pathways. Although neuropathologic find-\nings by Oppenheimer'2 indicated the presence of DAI\nand corpus callosum lesions in two patients who\nsustained relatively mild head injuries and died from\nother causes, more recent neuropathological and\nantemortem\nmagnetic\nresonance\nimaging (MRI)\nstudies'3 4 have shown that deep white matter lesions\nare generally restricted to CHI which produces coma.\nThis positive relationship between impairment of\nconsciousness and depth of lesion is also compatible\nwith\nprevious\nexperimental work\nin nonhuman\nprimates by Ommaya and Gennarelli.'5 In view of\nprevious studies'S\nimplicating nontraumatic brain\nlesions in the auditory interhemispheric connections,\ngeniculocortical pathways and temporal cortex in\nabnormal dichotic listening, it is plausible that the\nlocalisation of brain lesion is related to ear asymmetry\n1162"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1058
encoding: FLOAT32
metadata:
{"title": "Sex differences in adipose tissue It is not only a question of quantity and distribution", "chroma:document": "review\nAdipocyte 2:3, 128\u2013134; July/August/September 2013; \u00a9 2013 Landes Bioscience\n128 \nAdipocyte \nvolume 2 issue 3\nIntroduction\nThe obesity epidemic is a primary health concern in most indus-\ntrialized countries, as being obese increases the risk of mortality \ndue to associated comorbidities. Although both males and females \nare affected, there is a difference among sexes with regards to the \npropensity to develop obesity and the related metabolic compli-\ncations.1-4 Substantial differences in the metabolic responses to \ndietary challenges, weight gain, weight loss, and pharmacological \ninterventions have been reported between males and females;2,5,6 \nhowever, the mechanisms underlying this dimorphism remain \nlargely unknown.\nDifferences in circulating gonadal steroid levels play an impor-\ntant role in many sexually dimorphic features, but they cannot \naccount for all of the metabolic dissimilarities observed between \nmales and females. Indeed, there are clear differences even before \nthe onset of puberty.7,8 Identifying the mechanisms underlying the \ndifferent metabolic responses in males and females will not only \nadvance our general understanding of metabolic control, but it is \nfundamental for the development of effective treatments of obe-\nsity and its complications in both sexes. Here, we briefly review \nsome of the advances in our understanding of sex differences in \n*Correspondence to: Julie A Chowen;  \nEmail: julieann.chowen@salud.madrid.org\nSubmitted: 01/31/13; Revised: 02/21/13; Accepted: 02/21/13\nhttp://dx.doi.org/10.4161/adip.24075\nObesity and its associated secondary complications are active \nareas of investigation in search of effective treatments. As \na result of this intensified research numerous differences \nbetween males and females at all levels of metabolic control \nhave come to the forefront. These differences include not \nonly the amount and distribution of adipose tissue, but also \ndifferences in its metabolic capacity and functions between"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1059
encoding: FLOAT32
metadata:
{"title": "Sex differences in adipose tissue It is not only a question of quantity and distribution", "chroma:document": "the sexes. Here, we review some of the recent advances in \nour understanding of these dimorphisms and emphasize the \nfact that these differences between males and females must \nbe taken into consideration in hopes of obtaining successful \ntreatments for both sexes.\nSex differences in adipose tissue\nIt is not only a question of quantity and distribution\nesther Fuente-Mart\u00edn,1,2,\u2020 Pilar Argente-Ariz\u00f3n,1,2,3 Purificaci\u00f3n ros,3,4 Jes\u00fas Argente,1,2,3 and Julie A Chowen1,2,*\n1Department of Pediatric endocrinology; Hospital infantil Universitario Ni\u00f1o Jes\u00fas; instituto de investigaci\u00f3n La Princesa; Madrid, Spain; 2Centro de investigaci\u00f3n Biom\u00e9dica \nen red de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CiBerobn); instituto de Salud Carlos iii; Madrid, Spain; 3Department of Pediatrics; Universidad Aut\u00f3noma de Madrid; \nMadrid, Spain; 4Department of Pediatrics & Division of Pediatric endocrinology; Hospital Universitario Puerta de Hierro-Majadahonda; Madrid, Spain\n\u2020Current affiliation: institute for Diabetes and Obesity; Helmholtz Center Munich; Neuherberg, Germany\nKeywords: sexual dimorphism, leptin, steroids, metabolism, morphology\nwhite adipose tissue (WAT) and how this may affect the differen-\ntial responses of males and females to some metabolic challenges.\nAdipose Distribution\nSex differences in fat distribution can be observed even before \npuberty, although they become much more pronounced after \npubertal onset.7,8 Females experience a continuous increase in \nboth absolute and percent body fat throughout development and \nalthough males as well display a persistent increase in absolute \nbody fat, they have the highest percentage of body fat during \npuberty.9 Thus, the gradual changes in adipose accrual through-\nout early development can result in differences between post-\npubertal males and females in the percentage of body fat, with \na divergent distribution of adipose tissue also becoming clearly \napparent.9-12 While females predominantly accumulate subcuta-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1060
encoding: FLOAT32
metadata:
{"title": "Sex differences in adipose tissue It is not only a question of quantity and distribution", "chroma:document": "neous fat, males amass significantly more visceral fat.10-13 This \nsex difference in visceral adipose diminishes at older ages as \npostmenopausal women have increased visceral fat accrual,14,15 \nemphasizing the role of gonadal steroids in this phenomenon. \nFat distribution is not only influenced by sex, but also by ethnic \nbackground, as the reported sexually dimorphic adipose distri-\nbution is less apparent in some ethnic groups.13,16 Although sex \nsteroids are involved in determining adipose distribution, other \nfactors are certainly important. Indeed, Chen et al. recently \nreported that the number of X chromosomes affects adipose tis-\nsue function in mice.17 This study suggests that genes expressed \non the X chromosome are specifically implicated in the control of \nadiposity and that dosage or parental imprinting of these genes \nmay be involved in the metabolic differences between males and \nfemales.\nThe differential location of fat has functional implications as \nadipokine production, development of insulin sensitivity, inflam-\nmatory responses, mitochondrial function, lipolysis, and free fatty \nacid (FFA) release differs between adipose depots.1,12,18-20 One \nclear example of the importance of adipose distribution vs. total \nbody fat is circulating leptin levels. Leptin is a hormone that is pri-\nmarily produced by adipose tissue,21 with circulating levels being \npositively correlated with total body fat in both human adults \nand children,22,23 as well as in rodents.24 Serum leptin levels are \nsexually dimorphic in post-pubertal humans22,25 and rodents;26,27"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1061
encoding: FLOAT32
metadata:
{"title": "Welding maculopathy and fluphenazine", "chroma:document": "BritishJournal ofOphthalmology, 1991,75,433-435\nWelding arc maculopathy and fluphenazine\nWilliam J Power, Stephen P Travers, David J Mooney\nAbstract\nA 45-year-old male patient presented with a\nbilateral maculopathy following unprotected\nexposure of less than two minutes' duration to\na manual metal arc welding unit. He had been\nreceiving the drug fluphenazine for the pre-\nvious 10 years for treatment ofdepression. We\nbelieve that the drug fluphenazine, which had\naccumulated in his retinal pigment epithelium,\nmay have rendered him particularly suscept-\nible to retinal photic damage.\nResearch Foundation,\nRoyal Victoria Eye and\nEar Hospital, Adelaide\nRoad, Dublin 2, Ireland\nW J Power\nS P Travers\nD J Mooney\nCorrespondence to:\nWilliam J Power, FRCS.\nAccepted for publication\n13 December 1990\nThe retina is susceptible to at least three different\nforms of light damage - thermal, mechanical,\nand photochemical. \" Thermal damage is pro-\nduced when the retina is exposed to a tempera-\nture rise of 100 to 200C. Photochemical damage\nmost likely results from longer exposure to bright\nsources that produce a considerable amount of\nblue or near ultraviolet\nlight.3 Light levels\nrequired\nto\ncause\nacute\nphotoretinitis\nare\nencountered by exposure only to very bright light\nsources, such as the sun, welding arcs, arc lamps,\nand tungsten halogen lamp filaments. The type\nofretinal damage depends on wavelength, energy\nlevel, duration of exposure, and degree of\npigmentation.4\nThe radiation emitted from welding units\ncovers a wide spectrum, from infrared to ultra-\nviolet and beyond. Excessive exposure to ultra-\nviolet radiation can result in photophthalmia\n('welder's flash') and may, under chronic ex-\nposure, result in UV cataract.56 Retinal injuries\nresulting from exposure to welding arc radiation\nhave been reported but are not commonly\nseen.7\"10 We report here a case of welding arc\nmaculopathy in a patient who had been taking\nthe phenothiazine drug fluphenazine.\nCase report\nA 45-year-old man noticed bilaterally decreased"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1062
encoding: FLOAT32
metadata:
{"title": "Welding maculopathy and fluphenazine", "chroma:document": "visual acuities soon after welding. There was no\naccurate record ofthe exact duration ofexposure.\nHowever, the patient's instructor, who was\nobserving him from a distance, estimated it to be\ncertainly no longer than two minutes. The\npatient had just begun a training course and had\nno previous welding experience. He had raised\nthe protective visor which he was wearing in\norder to see more clearly. This was not noticed by\nthe instructor as the patient was crouched and\nhad his back towards him. He had been using a\nmanual metal arc welding unit with a flux coated\nrod.\nWhen seen the next day the patient com-\nplained\nof\nbilateral\nscotomata\nand\nmeta-\nmorphopsia. At no time did he complain of\nocular pain. His best corrected visual acuity was\n6/18 in the right eye and 6/12 in the left. The\nanterior segments were normal. There was no\nevidence of a punctate keratopathy when the\ncorneas were stained with fluorescein. There was\na circular yellow oedematous lesion approxi-\nmately 250 Am in diameter present at each fovea\n(Figs lA, B). Fluorescein angiography carried\nout five days later was normal. In an effort to\ndemonstrate the capillary-free zone better an\nenhanced fluorescein angiogram was prepared.\nThe angiogram negative was printed in contact\nregister with an unsharp mask to produce the\nfinished\nresult.\nThis\nenhanced\nangiogram\ndemonstrated mild diffuse fluorescence in the\nfoveal avascular zone (Fig 2). The patient was\nfollowed up on a regular basis for the next six\nmonths. During this period his visual acuities\nreturned to 6/5 in each eye. The results ofAmsler\ngrid testing and pattern electroretinograms were\nalso normal in both eyes. Examination of his\nFigure JA\nRight eye.\nFigure IB\nLeft eye.\nFigure lA, B\nFundus photographs showingyellow oedematous lesions at bothfoveas.\n433"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1063
encoding: FLOAT32
metadata:
{"title": "Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases", "chroma:document": "NEURAL REGENERATION RESEARCH\uff5cVol 19\uff5cNo. 1\uff5cJanuary 2024\uff5c55\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nReview\nAbstract  \nExtracellular vesicles are released by all cell types and contain proteins, microRNAs, mRNAs, and other \nbioactive molecules. Extracellular vesicles play an important role in intercellular communication and in \nthe modulation of the immune system and neuroinflammation. The cargo of extracellular vesicles (e.g., \nproteins and microRNAs) is altered in pathological situations. Extracellular vesicles contribute to the \npathogenesis of many pathologies associated with sustained inflammation and neuroinflammation, \nincluding cancer, diabetes, hyperammonemia and hepatic encephalopathy, and other neurological \nand neurodegenerative diseases. Extracellular vesicles may cross the blood-brain barrier and transfer \npathological signals from the periphery to the brain. This contributes to inducing neuroinflammation \nand cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in \nneurodegenerative diseases. The mechanisms involved are beginning to be understood. For example, \nincreased tumor necrosis factor \u03b1 in extracellular vesicles from plasma of hyperammonemic rats \ninduces neuroinflammation and motor impairment when injected into normal rats. Identifying the \nmechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will \nhelp to develop new treatments and diagnostic tools for their easy and early detection. In contrast, \nextracellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above \npathologies, by reducing inflammation and neuroinflammation and improving cognitive and motor \nfunction. These extracellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and \nhave advantages as therapeutic tools: they are less immunogenic, may not differentiate to malignant \ncells, cross the blood-brain barrier, and may reach more easily target organs. Extracellular vesicles"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1064
encoding: FLOAT32
metadata:
{"title": "Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases", "chroma:document": "from mesenchymal stem cells have beneficial effects in models of ischemic brain injury, Alzheimer\u2019s \nand Parkinson\u2019s diseases, hyperammonemia, and hepatic encephalopathy. Extracellular vesicles from \nmesenchymal stem cells modulate the immune system, promoting the shift from a pro-inflammatory \nto an anti-inflammatory state. For example, extracellular vesicles from mesenchymal stem cells \nmodulate the Th17/Treg balance, promoting the anti-inflammatory Treg. Extracellular vesicles from \nmesenchymal stem cells may also act directly in the brain to modulate microglia activation, promoting \na shift from a pro-inflammatory to an anti-inflammatory state. This reduces neuroinflammation \nand improves cognitive and motor function. Two main components of extracellular vesicles from \nmesenchymal stem cells which contribute to these beneficial effects are transforming growth factor-\u03b2 \nand miR-124. Identifying the mechanisms by which extracellular vesicles from mesenchymal stem \ncells induce the beneficial effects and the main molecules (e.g., proteins and mRNAs) involved may \nhelp to improve their therapeutic utility. The aims of this review are to summarize the knowledge of \nthe pathological effects of extracellular vesicles in different pathologies, the therapeutic potential of \nextracellular vesicles from mesenchymal stem cells to recover cognitive and motor function and the \nmolecular mechanisms for these beneficial effects on neurological function.\nKey Words: extracellular vesicles; inflammation; cognitive function; mesenchymal stem cells; \nneurodegenerative diseases; neuroinflammation; therapy; transforming growth factor-\u03b2\nIntroduction \nExtracellular vesicles (EVs) play a key role in intercellular communication \n(Y\u00e1\u00f1ez-M\u00f3 et al., 2015). There is increasing evidence of their contribution to \nthe development of different pathologies including cancer and neurological \nand neurodegenerative diseases (Y\u00e1\u00f1ez-M\u00f3 et al., 2015; Th\u00e9ry et al., 2018)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1065
encoding: FLOAT32
metadata:
{"title": "Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases", "chroma:document": "The analysis of the content of extracellular vesicles may become a very useful \ndiagnostic tool in different pathologies. Although extracellular vesicles play \na pathological role in many pathologies, some types of extracellular vesicles, \ni.e. those released by mesenchymal stem cells (MSCs), have therapeutic \neffects which may be beneficial in pathologies associated with sustained \nperipheral inflammation and neuroinflammation including neurological and \nneurodegenerative diseases (B\u00f6rger et al., 2017; Harrell et al., 2019). We \nwill summarize here the role of EVs in some pathologies, the therapeutic \npotential of EVs from MSCs, and some underlying mechanisms, focusing on \nnew findings in the field that highlight the therapeutic potential of EVs from \nMSCs to reduce peripheral inflammation and neuroinflammation, restoring \ncognitive function in neurological diseases.\nLiterature Search Strategy\nA computer-based online search of the PubMed database was performed \nto retrieve articles published until January 31, 2023. A combination of the \nfollowing text words (MeSH terms) was used to maximize search specificity \nand sensitivity: \u201cextracellular vesicles\u201d, \u201cmesenchymal stem cells\u201d, \u201ccognitive \nfunction\u201d, \u201ctherapy\u201d, \u201cneurodegenerative diseases\u201d, \u201cinflammation\u201d, \n\u201cneuroinflammation\u201d. The results were further screened by title and abstract, \nand studies focused on the role of EVs in pathology or EVs from MSCs as a \ntherapy were reviewed. Studies without full text available were excluded. No \nlanguage or study type restrictions were applied. Clinical trials were searched \nusing the database hosted at https://clinicaltrials.gov (date: March 31, 2023). \nSearch queries were \u201cextracellular vesicles\u201d and \u201cmesenchymal stem cells\u201d. \nTrials were then filtered by recruitment status, selecting those \u201ccompleted\u201d or \n\u201crecruiting\u201d.\nRole of Extracellular Vesicles in Different \nPathologies\nThe International Society of Extracellular Vesicles defines EVs as \u201cparticles"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1066
encoding: FLOAT32
metadata:
{"title": "Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases", "chroma:document": "naturally released from the cell that are delimited by a lipid bilayer and \ncannot replicate, i.e. do not contain a functional nucleus\u201d (Th\u00e9ry et al., 2018).\nEVs are released by all the cells in the organism and are present in different \nbody fluids, such as blood, urine, or cerebrospinal fluid (Y\u00e1\u00f1ez-M\u00f3 et al., \n1Laboratory of Neurobiology, Centro Investigaci\u00f3n Pr\u00edncipe Felipe, Valencia, Spain; 2Neuronal and Tissue Regeneration Laboratory, Centro Investigaci\u00f3n Pr\u00edncipe Felipe, Valencia, Spain\n*Correspondence to: Vicente Felipo, PhD, vfelipo@cipf.es.\nhttps://orcid.org/0000-0003-3145-9538 (Vicente Felipo)\nFunding: This work was supported in part by the Ministerio de Ciencia e Innovaci\u00f3n Spain (PID2020-113388RB-I00 to VF and PID2021-124359OB-I00 to VMM), Conseller\u00eda Educaci\u00f3n \nGeneralitat Valenciana (CIPROM/2021/082 to VF), and co-funded with European Regional Development Funds (ERDF) to VF and VMM. \nHow to cite this article: Izquierdo-Altarejos P, Moreno-Manzano V, Felipo V (2024) Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative \ndiseases. Neural Regen Res 19(1):55-61. \nFrom the Contents\nIntroduction\n55\nLiterature Search Strategy\n55\nRole of Extracellular Vesicles in Different Pathologies \n55\nTherapeutic Potential of Mesenchymal Stem Cells\n56\nAdvantages of Mesenchymal Stem Cell-Derived \nExtracellular Vesicles versus Mesenchymal Stem Cells in \nTherapy \n56\nBeneficial Effects of Extracellular Vesicles from \nMesenchymal Stem Cells on Neuroinflammation and \nNeurological and Neurodegenerative Diseases \n57\nMechanisms Underlying the Beneficial Effects of \nExtracellular Vesicles from Mesenchymal Stem Cells: \nRegenerative Properties\n57\nMechanisms Underlying the Beneficial Effects of \nExtracellular Vesicles from Mesenchymal Stem Cells: \nAnti-Inflammatory Properties and Effects on the \nPeripheral Immune System \n57\nMechanisms Underlying the Beneficial Effects of \nExtracellular Vesicles from Mesenchymal Stem Cells: \nDirect Effects in the Brain (Modulation of Microglia"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1067
encoding: FLOAT32
metadata:
{"title": "Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases", "chroma:document": "Polarization)\n58\nMechanisms Underlying the Beneficial Effects of \nExtracellular Vesicles from Mesenchymal Stem Cells: Role \nof miR-124 and Transforming Growth Factor-\u03b2\n58\nTherapy with Extracellular Vesicles from Mesenchymal \nStem Cells: Challenges and Future Perspectives\n59\nConclusions\n59\nPathological and therapeutic effects of extracellular \nvesicles in neurological and neurodegenerative diseases\nhttps://doi.org/10.4103/1673-5374.375301\nDate of submission: February 23, 2023 \nDate of decision: April 8, 2023 \nDate of acceptance: April 20, 2023\nDate of web publication: May 31, 2023 \nPaula Izquierdo-Altarejos1, Victoria Moreno-Manzano2, Vicente Felipo1, *"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1068
encoding: FLOAT32
metadata:
{"title": "Circulating Spike Protein Detected in Post\u2013 COVID-19 mRNA Vaccine Myocarditis W", "chroma:document": "Circulation\nCirculation. 2023;147:867\u2013876. DOI: 10.1161/CIRCULATIONAHA.122.061025 \nMarch 14, 2023\nCirculation is available at www.ahajournals.org/journal/circ\n867\n \nCorrespondence to: Lael M. Yonker, MD, Massachusetts General Hospital, 55 Fruit St, Jackson 14, Boston, MA 02114. Email Lyonker@mgh.harvard.edu; or David R. Walt, \nPhD, Brigham and Women\u2019s Hospital, 60 Fenwood Rd, Boston, MA 02115. Email dwalt@bwh.harvard.edu\n*L.M. Yonker, Z. Swank, and Y.C. Bartsch contributed equally.\n\u2020A. Fasano and D.R. Walt contributed equally.\nSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.122.061025.\nFor Sources of Funding and Disclosures, see page 875.\n\u00a9 2023 American Heart Association, Inc.\nORIGINAL RESEARCH ARTICLE\nCirculating Spike Protein Detected in Post\u2013\nCOVID-19 mRNA Vaccine Myocarditis\nLael M. Yonker\n, MD*; Zoe Swank, PhD*; Yannic C. Bartsch, PhD*; Madeleine D. Burns\n, MS; Abigail Kane\n, MD;  \nBrittany P. Boribong, PhD; Jameson P. Davis, BS; Maggie Loiselle, BS; Tanya Novak\n, PhD; Yasmeen Senussi\n, MBBS;  \nChi-An Cheng\n, PhD; Eleanor Burgess, MS; Andrea G. Edlow, MD; Janet Chou, MD; Audrey Dionne\n, MD; \nDuraisamy Balaguru\n, MD; Manuella Lahoud-Rahme\n, MD; Moshe Arditi\n, MD; Boris Julg, MD, PhD;  \nAdrienne G. Randolph\n, MD; Galit Alter, PhD; Alessio Fasano\n, MD\u2020 ; David R. Walt\n, PhD\u2020 \nBACKGROUND: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory \nsyndrome coronavirus 2 (SARS-CoV-2)\u2013targeted mRNA vaccines have been reported globally, but the underlying \nimmunoprofiles of these individuals have not been described in detail.\nMETHODS: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were \nhospitalized at Massachusetts General for Children or Boston Children\u2019s Hospital for myocarditis, presenting with chest pain \nwith elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1069
encoding: FLOAT32
metadata:
{"title": "Circulating Spike Protein Detected in Post\u2013 COVID-19 mRNA Vaccine Myocarditis W", "chroma:document": "for SARS-CoV-2\u2013specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant \nvirome, SARS-CoV-2\u2013specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with \nthose from 45 healthy, asymptomatic, age-matched vaccinated control subjects.\nRESULTS: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were \nessentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A \nnotable finding was that markedly elevated levels of full-length spike protein (33.9\u00b122.4 pg/mL), unbound by antibodies, \nwere detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic \nvaccinated control subjects (unpaired t test; P<0.0001).\nCONCLUSIONS: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine\u2013induced \nimmune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free \nspike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, \nadvancing insight into its potential underlying cause.\nKey Words: COVID-19 \u25fc mRNA \u25fc myocarditis \u25fc SARS-CoV-2 \u25fc vaccine\nEditorial, see p 877\nW\nithin 9 months of coronavirus disease 2019 \n(COVID-19) reaching pandemic proportions, \nnovel, lifesaving severe acute respiratory syn-\ndrome coronavirus 2 (SARS-CoV-2)\u2013targeted mRNA \nvaccine technologies received emergency regulatory \napprovals and were distributed to many developed \ncountries. Following a tiered approach that prioritized \nhigh-risk individuals, infants \u22656 months of age are now \neligible for vaccination with SARS-CoV-2 mRNA vac-\ncines in select countries. SARS-CoV-2 mRNA vaccines"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1070
encoding: FLOAT32
metadata:
{"title": "Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice", "chroma:document": "636  \uff5cNEURAL REGENERATION RESEARCH\uff5cVol 19\uff5cNo. 3\uff5cMarch 2024\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nResearch Article\nVisualizing Wallerian degeneration in the corticospinal \ntract after sensorimotor cortex ischemia in mice\nAbstract  \nStroke can cause Wallerian degeneration in regions outside of the brain, particularly in the corticospinal tract. To investigate the fate of major glial cells and \naxons within affected areas of the corticospinal tract following stroke, we induced photochemical infarction of the sensorimotor cortex leading to Wallerian \ndegeneration along the full extent of the corticospinal tract. We first used a routine, sensitive marker of axonal injury, amyloid precursor protein, to examine \nWallerian degeneration of the corticospinal tract. An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the \nischemic cortex, with no positive signal in distal parts of the corticospinal tract, at all time points. To improve visualization of Wallerian degeneration, we \nnext utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent \nprotein-expressing axons. Using this approach, we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke. \nIn addition, microglia mobilized and activated early, from day 7 after stroke, but did not maintain a phagocytic state over time. Meanwhile, astrocytes showed \nrelatively delayed mobilization and a moderate response to Wallerian degeneration. Moreover, no anterograde degeneration of spinal anterior horn cells was \nobserved in response to Wallerian degeneration of the corticospinal tract. In conclusion, our data provide evidence for dynamic, pathogenic spatiotemporal \nchanges in major cellular components of the corticospinal tract during Wallerian degeneration."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1071
encoding: FLOAT32
metadata:
{"title": "Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice", "chroma:document": "Key Words: corticospinal tract; green fluorescent protein; microglia; spinal anterior horn cells; stroke; virus trace; Wallerian degeneration\nhttps://doi.org/10.4103/1673-5374.380903\nDate of submission: December 6, 2022 \nDate of decision: March 11, 2023 \nDate of acceptance: June 6, 2023 \nDate of web publication: July 20, 2023 \nIntroduction \nStroke remains a leading cause of acquired adult disability and incurs high \nsocio-economic costs worldwide (Rochmah et al., 2021; Saini et al., 2021; \nWestendorp et al., 2022). Ischemia in supratentorial motor systems usually \ncauses hemiparesis, so recovery of motor function is crucial for stroke \npatients to regain independence (Stinear, 2017). Currently, advanced research \nis aimed at discovering promising strategies to limit neuronal damage in the \npenumbra (Grade and G\u00f6tz, 2017; Zhou et al., 2018). Unfortunately, almost \nall neuroprotective agents that focus exclusively on cerebral gray matter in \nprimary injury locations have failed in clinical trials (Fisher et al., 2009; Luo \net al., 2020). Indeed, the death of cortical motor neurons causes Wallerian \ndegeneration (WD) of neurons along the full length of their projections at sites \ndistal from the original injury. The corticospinal tract (CST), which acts as the \nmajor descending pathway for voluntary motor control, is the most frequently \naffected tract in stroke patients (Yu et al., 2009; Sun et al., 2022; Zhang et al., \n2023). Early WD of the CST correlates with long-term neurological deficits and \npoor motor outcomes after stroke (DeVetten et al., 2010; Puig et al., 2010; \nSheng et al., 2022). \nWD is defined as progressive anterograde disintegration of axons and \naccompanying demyelination after an injury to the proximal axon or cell \nbody (Chen et al., 2017; Cai et al., 2022; Forbrig and Danek, 2022). After \nthe initial ischemic injury, distal axons retain morphological stability and \naxonal fast transport for several days, which potentially allows for effective"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1072
encoding: FLOAT32
metadata:
{"title": "Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice", "chroma:document": "pharmacological intervention (Vargas and Barres, 2007). Although significant \ninsight has been gained into WD pathogenesis, a full understanding has \nbeen limited by both technical and animal modeling issues. Previous studies \nhave used various antibodies to identify axonal damage during WD (Stone \net al., 2004; Czeiter et al., 2008). However, whether or not these antibodies, \nparticularly those to amyloid precursor protein (APP), can be used to detect \naxonal pathology within distal segments remains unclear (Wakita et al., \n2002; Zuo et al., 2019). In addition, different areas of the cortex exhibit \ndifferent CST projection patterns into the spinal cord (Steward et al., 2021). \nThe middle cerebral artery occlusion (MCAO) model used in previous studies \ngenerally results in widespread, severe cortical infarction, which complicates \ninterpretation of the pathophysiologic mechanisms governing stroke-induced \nWD of the CST. Thus, these technical and animal model issues have precluded \nexperimental analysis of dynamic WD from initial ischemic injury to ultimate \ndisintegration of axons within the CST projecting specific cortical regions. \nTo address these issues, we used photochemical infarction of the right \nforelimb representation of the sensorimotor cortex to induce WD along \nthe full extent of the CST in an animal model. This model caused selective \ndegeneration of fiber tracts that terminate in the cervicothoracic spinal cord, \nwithout extending to the thoracic levels and below. In addition, we utilized \nan orthograde virus that expresses green fluorescent protein (GFP) to follow \nthe fate of the CST. Unlike labeling with antibodies, this approach enables \nvisualization of WD through analysis of GFP-expressing axons. The goal of this \nstudy was to quantitatively definite the time frame during which WD-induced \naxonal degeneration and gliosis occur within the affected area of the CST."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1073
encoding: FLOAT32
metadata:
{"title": "Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice", "chroma:document": "1Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; 2Department of \nNeurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China\n*Correspondence to: Xiaoguang Li, PhD, lxgchina@sina.com or zzgc811@163.com; Zhaoyang Yang, PhD, wack_lily@163.com. \nhttps://orcid.org/0000-0001-8313-6998 (Zhaoyang Yang); https://orcid.org/0000-0003-4480-3676 (Xiaoguang Li)\nFunding: This study was supported by the National Natural Science Foundation of China, Nos. 31730030 (to XL), 81941011 (to XL), 31771053 (to HD), 82271403 (to XL), 82272171 (to \nZY), 31971279 (to ZY), and 82201542 (to FH); the Natural Science Foundation of Beijing, No. 7222004 (to HD); the Science and Technology Program of Beijing, No. Z181100001818007 \n(to ZY).\nHow to cite this article: Mu J, Hao L, Wang Z, Fu X, Li Y, Hao F, Duan H, Yang Z, Li X (2024) Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex \nischemia in mice. Neural Regen Res 19(3):636-641. \nWallerian \ndegeneration of \nthe corticospinal \ntract after \nstroke causes \ndelayed axonal \ndegeneration \nand subsequent \ngliosis but does \nnot alter spinal \nanterior horn \ncells in mice\nFrom the Contents\nIntroduction\n636\nMethods  \n637\nResults\n638\nDiscussion\n640\nJiao Mu1, Liufang Hao2, Zijue Wang2, Xuyang Fu2, Yusen Li2, Fei Hao1, Hongmei Duan2, Zhaoyang Yang2, *, Xiaoguang Li1, 2, *\nGraphical Abstract"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1074
encoding: FLOAT32
metadata:
{"title": "Correspondence", "chroma:document": "Annals of the Rheumatic Diseases, 1980, 39, 529-530\nCorrespondence\nAcute gout during hypouricaemic\ntherapy: prophylaxis with colchicine\nSir, The efficacy of the uricosuric diuretic agent tienilic\nacid in the treatment of both gout and hypertension is\nconfirmed in 2 papers.1\n2 During our inpatient study 3\nof the 4 patients suffered attacks of gout, as is often the\ncase when starting other kinds of hypouricaemic therapy.\nIt is commonly held that the concomitant use of col-\nchicine prevents such attacks, and accordingly we looked\ninto this in a long-term outpatient study. Twenty patients\nwere given tienilic acid alone and 10 patients were given\ntienilic acid together with colchicine\n1 mg b.d. on a non-\nselective basis. The patients were followed for between\n2 and 12 months, with encouraging results in lowering\nboth the blood pressure and serum uric acid, but owing\nto reports from elsewhere of hepatotoxicity the study\nhad to be abandoned. Of the patients who received\ntienilic acid alone 15 suffered 27 attacks of gout within\n2 months of starting therapy, whereas none of the 10\npatients who received colchicine in addition suffered\nan attack of gout over the same period.\nThis gives support to the unsubstantiated belief that\ncolchicine prevents the attacks of gout which are seen\nafter starting hypouricaemic therapy.\nP. HOLLINGWORTH, J. A. REARDON AND J. T. Scorr\nKennedy Institute of Rheumatology, London W6.\nCharing Cross Hospital, London W6."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1075
encoding: FLOAT32
metadata:
{"title": "Adult Still's disease and viral infections", "chroma:document": "Annals of the Rheumatic Diseases, 1988; 47, 764-767\nAdult onset Still's disease and viral infections\nJACQUES M G W WOUTERS,' JOHAN VAN DER VEEN,2\nLEVINUS B A VAN DE PUTTE,' AND DIRK-JAN R A M DE ROOIJ3\nFrom the Departments of 'Rheumatology and 2Microbiology, University Hospital Nijmegen, Nijmegen, The\nNetherlands; and 3St Maartens Clinic, Nijmegen, The Netherlands\nSUMMARY\nSeveral micro-organisms, especially viruses, have been associated with juvenile and\nadult onset Still's disease. In the present study a search for probable triggering viral infections in\nfive consecutive patients with early, active adult onset Still's disease has been made. In one\npatient echovirus 7 was identified as a probable triggering agent. Evidence of infection with this\nvirus was acquired by virus cultures and serological tests. In two patients the illness was probably\ninitiated by a rubella reinfection. Both had initially high stable monospecific IgG antibody titres\nbut no IgM antibodies to this virus. In the remaining two cases no particular triggering viral\ninfection could be designated. Evidence of a viral infection was thus found in three of these five\npatients. Adult onset Still's disease may represent a reaction pattern to certain infections.\nKey words: echovirus, rubella, cultures, serology.\nJuvenile and adult onset Still's disease are related\nclinical entities characterised by high spiking fever,\nan evanescent maculopapular rash, and arthritis.1 2\nOther features frequently found in both conditions\ninclude lymphadenopathy, splenomegaly, pericardi-\ntis, pleuritis, neutrophil leucocytosis, and hepatic\nabnormalities. Although the cause of these diseases\nis unknown, several recent reports have associated\ntheir\ndevelopment\nwith\na\nvariety\nof\nmicro-\norganisms, especially viruses.?12\nThe present study reports on virological studies\nperformed in five patients with adult onset Still's\ndisease in an early phase of the disease.\nPatients and methods\nPATIENTS\nDuring 1983 five patients with early, active adult"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1076
encoding: FLOAT32
metadata:
{"title": "Adult Still's disease and viral infections", "chroma:document": "onset Still's disease were seen at two hospitals in the\ncity\nof Nijmegen,\nThe\nNetherlands\n(Canisius-\nWilhelmina Hospital, University Hospital St Rad-\nboud). All presented with fever of unknown origin\nand fulfilled the criteria of Medsger and Christy.\"3\nMETHODS\nAs soon as it was suspected that a patient was\nAccepted for publication 26 November 1987.\nCorrespondence to Professor Levinus B A van de Putte, Depart-\nment of Rheumatology, University Hospital Nijmegen, Geert\nGrooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.\nsuffering from adult onset Still's disease virological\nstudies were started.\nSerology\nIgG antibody titres to adenovirus, respiratory syn-\ncytial\nvirus,\nmumps,\ncytomegalovirus,\nmeasles,\nherpes simplex, varicella, Coxsackie virus Bi, 2, 3,\n4,\n5,\nand\n6,\nCoxiella\nburneti,\npsittacosis, and\nMycoplasma\npneumoniae\nwere\nmeasured\nby\ncomplement fixation tests, IgG antibody titres to\nrubella and parainfluenza virus\n1, 2, and 3 by\nhaemagglutination inhibition tests, IgG antibody\ntitres to Epstein-Barr virus by immunofluorescence\ntests, and hepatitis B surface antigen (HBsAg) and\nIgG antibodies to HBsAg by means of an enzyme\nlinked immunosorbent assay (ELISA). IgG anti-\nbody titres to corona virus and influenza virus A, B,\nand C were measured by complement fixation and\nhaemagglutination inhibition tests. IgM antibodies\nto mumps, rubella, and parainfluenza virus 1, 2, and\n3 were assayed by haemadsorption immunosorbent\ntests and IgM antibodies to Epstein-Baff virus by\nimmunofluorescence tests.\nVirus cultures\nAll throat swabs and stool specimens were inocu-\nlated in Flow 2002 (human lung fibroblasts), HEp2\n(human larynx carcinoma), and primary rhesus\nmonkey kidney cells. Attempts to isolate rubella\nvirus were made only if the IgG antibody titres to\n764"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1077
encoding: FLOAT32
metadata:
{"title": "Lymphocytes bearing Fcy in rheumatoid arthritis. Phenotypic characterisation of mononuclear cells forming Facb in RA", "chroma:document": "Annals of the Rheumatic Diseases, 1985, 44, 2-7\nLymphocytes bearing Fcy receptors in rheumatoid\narthritis. II. Phenotypic characterisation of\nmononuclear cells forming Facb rosettes in RA\nVIVIENNE R WINROW,* LESLEY-JANE EALES,t N D HALL,\nN J GOULDING, AND\nI M HUNNEYBALLt\nFrom the ARC Research Group, Royal National Hospital for Rheumatic Diseases, Bath, the Pharmacology\nGroup,\nUniversity of Bath, and\n#the Boots Company PLC, Nottingham\nSUMMARY\nWe have previously reported an increased proportion of Facb-rosette forming cells in\nthe peripheral blood of patients with rheumatoid arthritis in comparison with healthy controls.\nThe present study investigates the surface phenotype of these cells by means of monoclonal\nantibodies and a variety of rosetting and lymphocyte fractionation techniques. Facb-R+ cells\nwere found to lack surface markers characteristic of T and B lymphocytes.\nStudies with\nmonoclonal reagents showed a positive reaction with OKIal, OKM1, and another monocyte-\nspecific antibody. Facb-R+ cells were recognised by anti-HLA-DR reagents but did not bind the\nmonoclonal antibody 17.15 that recognises a determinant on HLA-DR antigens expressed by\nlymphocytes but not monocytes. These results show that Facb-R' cells share certain surface\ncharacteristics with\nmonocytes, though they\nare\nnot phagocytic.\nThese observations\nare\nconsistent with an accessory role for Facb-R+ cells in the immune response.\nKey words: Fc receptor, surface marker, monoclonal antibody.\nReceptors which bind the Fc portion of IgG (FcyR)\nhave been demonstrated on the surface of many\nperipheral\nblood\nleucocytes\nincluding\nT\nlymphocytes,' B cells,2 null cells,?6 monocytes,7\nand neutrophils.8 These receptors play significant\nroles in chronic inflammation, since they are associ-\nated with phagocytosis\nof IgG aggregates8 and\nantibody-dependent cellular cytotoxicity9 and have\nalso been implicated in the regulation of humoral\nimmunity mediated by specific antibody.102 These\nobservations have led to the investigation of FcyR"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1078
encoding: FLOAT32
metadata:
{"title": "Lymphocytes bearing Fcy in rheumatoid arthritis. Phenotypic characterisation of mononuclear cells forming Facb in RA", "chroma:document": "expression on mononuclear cells from patients with\na variety of autoimmune diseases.\nSeveral authors have reported an increased pro-\nportion\nof\nperipheral\nblood\nmononuclear\ncells\nAccepted for publication 16 July 1984.\nCurrent\naddresses:\n*Bone and Joint Research\nUnit, London\nHospital Medical College, London El. tDepartment of Immu-\nnology, Wright-Fleming Institute,\nSt. Mary's Hospital Medical\nSchool, London, W2.\nCorrespondence to Dr N D Hall, Bath Arthritis Research Centre,\nTrim Bridge, Bath BAl 1HD.\n(PBMNC) exhibiting FcyR in patients with rheuma-\ntoid\narthritis\n(RA)\ncompared\nwith\nhealthy\ncontrols.'136 These authors did not identify the\nsubpopulation bearing the FcyR, although Sharpin\nand coworkers'7 have recently suggested that this\nincreased expression is due to an increase in Ty\ncells. Other authors have failed to demonstrate any\nincrease in FcyR expression on rheumatoid mono-\nnuclear cells18 or rheumatoid 3rd population (L)\nlymphocytes.19 20 In our laboratory mononuclear\ncells bearing a receptor capable of binding the Cy2\nregion of IgG have been detected in peripheral\nblood by a novel rosette assay employing calf red\nblood cells (CRBC) sensitised with the Facb frag-\nment of rabbit IgG anti-CRBC.2' It has been shown\nthat Facb-R' cells form an increased proportion of\nPBMNC from patients with RA compared with\nhealthy control subjects and patients with osteoar-\nthritis (OA) or ankylosing spondylitis (AS). In this\nreport a number of techniques have been utilised to\ninvestigate the surface characteristics of the Facb\nrosette forming cells in rheumatoid patients.\n2"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1079
encoding: FLOAT32
metadata:
{"title": "Relationships between C3b (CR1) activity of erythrocytes and positive Coombs'", "chroma:document": "Annals of the Rheumatic Diseases, 1986; 45, 367-372\nRelationships between C3b receptor (CR1) activity of\nerythrocytes and positive Coombs' tests\nYORITARO\nINADA,'\nMIKIO\nKAMIYAMA,'\nTSUNEYOSHI\nKANEMITSU,I\nWILLIAM S CLARK,' AND YOSHIYUKI ASAI2\nFrom the 'Medical Service, Division of Rheumatology, St Luke's-Roosevelt Hospital Center, The College of\nPhysicians and Surgeons of Columbia University, New York; and the 2Department of Immunology, Eisai\nCo., Ltd, Japan\nSUMMARY\nAlthough positive direct Coombs' tests occur in most patients with active systemic\nlupus erythematosus (SLE), haemolytic anaemia associated with antibody to erythrocytes (E)\noccurs in less than 10%. Our studies show an association between positive direct Coombs' tests\nand both the presence of circulating immune complexes and diminished activity of the C3b\nreceptor (CR1) of E. Data presented in this report suggest that in vivo binding of immune\ncomplexes and complement by the CR1 of E results in positive direct Coombs' tests in the absence\nof antibody to E. These observations explain the low frequency of haemolytic anaemia compared\nwith the high frequency of direct positive Coombs' tests in patients with SLE.\nKey words: circulating immune complexes.\nAnaemia is common in systemic lupus erythemato-\nsus (SLE).\nIts features and multiple causes have\nbeen reviewed.' Although positive direct Coombs'\ntests\nhave\nbeen\nreported\nin\n18-65%\nof these\npatients, haemolytic anaemia occurs in less than\n10%.2 A reasonable explanation for this discrepancy\nappeared during our studies of the complement\nreceptor (CR1) function of erythrocytes (E).\nHuman E possess, on their surfaces, receptors to\nthe\nthird complement component.\nIn\n1981\nwe\nreported a new method for measuring circulating\nimmune complexes (CIC) derived from the immune\nadherence\nhaemagglutination\n(IAHA)\nphenom-\nenon.3 Subsequently we reported\na method\nof\nmeasuring CR1 binding activity of E, which in-\nvolved the inhibition of IAHA.\nIn the application\nof these methods to clinical situations we observed"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1080
encoding: FLOAT32
metadata:
{"title": "Relationships between C3b (CR1) activity of erythrocytes and positive Coombs'", "chroma:document": "that both the presence of CIC and blunting of CR1\nactivity were\nconsistently\nassociated\nwith\ndirect\npositive Coombs' tests. With one exception in our\nstudies there was no association of positive Coombs'\ntests with haemolytic anaemia.\nIn this paper we report our observations on the\nAccepted for publication 30 September 1985.\nCorrespondence to Dr Yoritaro Inada, Medical Service, Division\nofRheumatology, St Luke's-Roosevelt Hospital Center, Amsterdam\nAvenue at 114th Street, New York, NY 10025, USA.\nrelation between types of positive direct Coombs'\ntests and the presence of CIC and diminished CR1\nactivity\nin\npatients with SLE and\nrelated CIC\nmediated syndromes.\nMaterials and methods\nCLINICAL MATERIALS\nThree hundred and eleven venous blood samples\nwere obtained from 205 patients. Heparinised blood\nfor E isolation and untreated blood for serum were\ncollected. Patient populations were as follows: 164\nblood samples from 103 patients with SLE, 46 from\n26 patients with rheumatoid arthritis, 33 from 18\npatients with vasculitis, nine from six patients with\nnephrotic syndromes, eight from six patients with\nchronic active hepatitis, six from four patients with\nidiopathic pulmonary fibrosis, four each from two\npatients with dermatitis herpetiformis and three\nwith mixed connective tissue disease, two each from\npatients with Sjogren's syndrome, sarcoidosis, and\nthrombotic thrombocytopenic\npurpura,\nand one\neach from patients with Behqet's syndrome, breast\ncancer,\nacquired\nimmune\ndeficiency\nsyndrome,\nhyperglobulinaemic purpura, meningitis, and mac-\nrogammaglobulinaemia. Also there were 25 samples\nfrom patients with unknown diseases who had CIC\nor defective CR1 activity of E, or both. Only one\n367"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1081
encoding: FLOAT32
metadata:
{"title": "Reaction of rheumatoid factors with IgG3 monoclonal anti-Rh(D) antibodies: more frequent reactivity to a monoclonal antibody of the Gm allotype G3m(5) in rheumatoid patients negative for G3m(5)", "chroma:document": "Annals of the Rheumatic Diseases, 1988; 47, 898-905\nReaction of rheumatoid factors with IgG3 monoclonal\nanti-Rh(D) antibodies: more frequent reactivity\nto a monoclonal antibody of the Gm allotype G3m(5)\nin rheumatoid patients negative for G3m(5)\nALISON H PUTTICK,' ELIZABETH A WILLIAMSON,' A H MERRY 2\nBELINDA M KUMPEL,3 K M THOMPSON,4 AND VALERIE E JONES'\nFrom the 'Postgraduate Medical School, University of Exeter, Barrack Road, Exeter, Devon; the 2Blood\nGroup Reference Laboratory, Radcliffe Infirmary, Woodstock Road, Oxford; the 3UK Transplant Service,\nSouthmead Road, Bristol; and the 4Department of Immunology, Institute ofAnimal Physiology, Babraham,\nCambridge\nSUMMARY\nHuman monoclonal anti-Rh(D) antibodies of known IgG isotype and Gm allotype\nwere bound to erythrocytes and then used as the target IgG antigens for rheumatoid factors\n(RFs) in a direct haemagglutination test. When serum samples from patients with rheumatoid\narthritis (RA) were tested for RF specificity towards these IgG monoclonal anti-D antibodies the\nincidence and titre of reactivity towards an IgG3 monoclonal anti-D antibody was considerably\ngreater than for a polyclonal anti-D antibody of the same Gm allotype, G3m(5). This difference\nwas not explained by the amount of each anti-D antibody which bound to erythrocytes.\nFurthermore, when patients with RA were divided into groups according to their Gm phenotype,\nsera from a greater proportion of patients negative for the phenotype G3m(5) reacted to the\nG3m(5) monoclonal anti-D antibodies than sera from those patients positive for this allotype.\nAnalysis of RF reactivities towards two IgG3 and three IgGl monoclonal anti-D antibodies, each\nwith different Gm allotypic epitopes, indicated, however, that individual serum samples\ncontained RFs with a spectrum of specificities; some sera appeared to react to a single set of Gm\nalleles, whereas others also reacted to isotypic or iso-allotypic epitopes, or both. Our data suggest"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1082
encoding: FLOAT32
metadata:
{"title": "Reaction of rheumatoid factors with IgG3 monoclonal anti-Rh(D) antibodies: more frequent reactivity to a monoclonal antibody of the Gm allotype G3m(5) in rheumatoid patients negative for G3m(5)", "chroma:document": "that RFs with specificity for Gm allotypes do not arise in patients who carry that particular\nallotype owing to tolerance induced in fetal-neonatal life. Conversely, RFs with apparent\nspecificity for a Gm allotype formed in patients negative for that allotype may be reacting to a\nclosely related but different epitope. Final proof requires precise specificities for each RF\nformed, and IgG3 monoclonal anti-D antibodies would be useful reagents for this purpose.\nKey words: rheumatoid arthritis, autoantibodies, immunoglobulin allotypes.\nRheumatoid factors (RFs) are the characteristic\nregion of autologous IgG, which includes isotypic\nautoantibodies in rheumatoid arthritis (RA). They\nand Gm allotypic epitopes, has been under invest-\ncan be detected early in the disease,' 2 they are\nigation for several decades. For example, in 1960\nimplicated in the chronic pathogenesis of rheumatoid\nHarboe showed that RFs to polyclonal IgG3 anti-D\nsynovitis,3 and their specificity may be related to\nantibodies are rare both in patients with RA and in\nputative triggers of the disease process.4\nnormal individuals.5 In 1970 Grubb summarised the\nThe specificity of RFs for epitopes on the Fc\npublished work on RF specificity for Gm allotypes,\nwhich also related this RF specificity to the Gm\nAccepted\nfor\npublication\n13 April 1988.\nstatus of the donor.6 From the few individuals\nAccepted for publication 13 April 1988.\nCorrespondence to Dr Valerie E Jones, Postgraduate Medical\nstudied, both Grubb and Harboe noted that anti-\nSchool, Barrack Road, Exeter, Devon EX2 5DW, UK.\nGm allotype donors, whether they were rheumatoid\n898"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1083
encoding: FLOAT32
metadata:
{"title": "The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study", "chroma:document": "1542  \uff5cNEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nResearch Article\nThe default mode network is affected in the early \nstage of simian immunodeficiency virus infection: \na longitudinal study\nAbstract  \nAcquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network. Most recent studies \nhave been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection \nand antiretroviral therapy. Specifically, when brain imaging data at only one time point are analyzed, determining the duration at which the default mode \nnetwork is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome. However, because infection times \nand other factors are often uncertain, longitudinal studies cannot be conducted directly in the clinic. Therefore, in this study, we performed a longitudinal \nstudy on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection. We found \nmarked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation. Significant \ninteractions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal \neye field (FEF). L, area 8/FEF.L and caudal temporal parietal occipital area (TPOC).R, and area 31/V6.R and TPOC.L. ART administered 4 weeks after infection not \nonly interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent. These findings suggest that the \ndefault mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1084
encoding: FLOAT32
metadata:
{"title": "The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study", "chroma:document": "in brain function and an objective indicator for making early clinical intervention decisions.\nKey Words: acquired immune deficiency syndrome; analysis of variance; antiretroviral therapy; default mode network; functional magnetic resonance imaging; \nhuman immunodeficiency virus; longitudinal study; rhesus monkeys; simian immunodeficiency virus; SIV-mac239\nhttps://doi.org/10.4103/1673-5374.360244\nDate of submission: March 31, 2022 \nDate of decision: July 13, 2022 \nDate of acceptance: August 29, 2022 \nDate of web publication: November 9, 2022\nIntroduction \nHuman immunodeficiency virus (HIV) infection can lead to brain impairments \nthat worsen with the duration of the disease, which greatly affects the quality \nof life of HIV patients, even in the current era of highly active antiretroviral \ntherapy (ART) (Nightingale et al., 2014; Watkins and Treisman, 2015; Tang et \nal., 2017a, b). The prolongation of HIV infection leads to the dysfunction of \nmultiple brain networks, especially the default mode network (DMN), which \nis the most active network at rest and is closely related to cognitive function \n(Mak et al., 2017; Smith et al., 2018). Several previous cross-sectional studies \nhave reported that the dysfunction of the DMN caused by HIV infection is \nassociated with cognitive deficits (Ortega et al., 2015; Cohen et al., 2018). \nIn earlier studies, HIV infection was shown to result in decreased functional \nconnectivity in the DMN in HIV-infected (Thomas et al., 2013) and perinatally-\nacquired HIV patients (Herting et al., 2015). Furthermore, it has been shown \nthat decreased functional connectivity of the DMN is correlated with poorer \nneurocognitive performance (du Plessis et al., 2017). In addition, another \nstudy found that abnormal activation of the posterior cingulate cortex in the \nDMN of HIV patients is related to deficits in Hopkins Verbal Learning Test-2 \nlearning performance (Cohen et al., 2018). Neurocognitive performance and \nfunctional connectivity of the DMN can be improved by providing patients"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1085
encoding: FLOAT32
metadata:
{"title": "The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study", "chroma:document": "with ART (Zhuang et al., 2017), and more recently, studies have demonstrated \nthat changes in the DMN are also closely related to various factors, such as \naging (Egbert et al., 2019) and HIV self-management interventions (Webel et \nal., 2019).\nHowever, most previous studies used a cross-sectional experimental design, \nand magnetic resonance imaging (MRI) data were acquired at one time point \nonly (Cohen et al., 2018; Egbert et al., 2019; Webel et al., 2019). Although \ncross-sectional studies are effective in investigating DMN changes, they are \nunable to reveal dynamic changes in the DMN following acquired immune \ndeficiency syndrome (AIDS) infection or ART over the disease or treatment \n1Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China; 2Key Laboratory of Big Data-Based \nPrecision Medicine (Beihang University), Ministry of Industry and Information Technology of the People\u2019s Republic of China, Beijing, China; 3Key Laboratory of Molecular Imaging, \nInstitute of Automation, Chinese Academy of Sciences, Beijing, China; 4Beijing Youan Hospital, Capital Medical University, Beijing, China; 5Renji Hospital, Shanghai Jiao Tong University \nSchool of Medicine, Shanghai, China; 6Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China \n*Correspondence to: Hong-Jun Li, MD, lihongjun00113@ccmu.edu.cn; Jie Tian, PhD, tianj@buaa.edu.cn; Hui Zhang, PhD, hui.zhang@buaa.edu.cn.\nhttps://orcid.org/0000-0003-2883-4931 (Hui Zhang); https://orcid.org/0000-0003-0498-0432 (Jie Tian); https://orcid.org/0000-0001-5887-5684 (Hong-Jun Li)\n#These authors contributed equally to this work.\nFunding: This study was supported by the National Natural Science Foundation of China, Nos. 82271963 (to HJL), 81771806 (to HJL), 61936013 (to HJL), 82001914 (to ZCT), 81871511 (to \nHZ); National Key R&D Program of China, No. 2021YFA1301603 (to ZCT); and the Natural Science Foundation of Beijing, No. 7212051 (to HJL)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1086
encoding: FLOAT32
metadata:
{"title": "The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study", "chroma:document": "How to cite this article: Tang ZC, Liu JJ, Ding XT, Liu D, Qiao HW, Huang XJ, Zhang H, Tian J, Li HJ (2023) The default mode network is affected in the early stage of simian \nimmunodeficiency virus infection: a longitudinal study. Neural Regen Res 18(7):1542-1547. \nGraphical Abstract\nLongitudinal default mode network (DMN) changes due to simian immunodeficiency virus infection\nFrom the Contents\nIntroduction\n1542\nMethods\n1543\nResults\n1544\nDiscussion\n1545\nZhen-Chao Tang1, 2, 3, #, Jiao-Jiao Liu4, #, Xue-Tong Ding1, 2, 3, #, Dan Liu5, Hong-Wei Qiao6, Xiao-Jie Huang4, Hui Zhang1, 2, 3, *, \nJie Tian1, 2, 3, *, Hong-Jun Li4, *"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1087
encoding: FLOAT32
metadata:
{"title": "Neuro-Oncology", "chroma:document": "Neuro-Oncology\n25(4), 617\u2013627, 2023 | https://doi.org/10.1093/neuonc/noac236 | Advance Access date 11 October 2022\n617\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.\nCellular immunotherapy for medulloblastoma\n  \nMichael\u00a0Y.\u00a0Schakelaar\u2020, Matthijs\u00a0Monnikhof\u2020, Sandra\u00a0Crnko, Emma\u00a0W.\u00a0Pijnappel, Jan\u00a0Meeldijk, \nToine\u00a0ten\u00a0Broeke, and Niels\u00a0Bovenschen\nDepartment of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands (M.Y.S., M.M., S.C., \nE.W.P., J.M., T.B., N.B.); Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, \nThe Netherlands (J.M., N.B.); Bachelor Research Hub, Education Center, University Medical Centre Utrecht, 3584 CX \nUtrecht, The Netherlands (S.C., E.W.P., J.M., T.B., N.B.)\nCorresponding Author: Niels Bovenschen, PhD, Department of pathology, University Medical Center Utrecht, Utrecht, The Netherlands \n(n.bovenschen@umcutrecht.nl).\n\u2020These authors contributed equally to this work.\nAbstract\nMedulloblastoma (MB) is the most common malignant brain tumor in children, making up ~20% of all primary \npediatric brain tumors. Current therapies consist of maximal surgical resection and aggressive radio- and chemo-\ntherapy. A\u00a0third of the treated patients cannot be cured and survivors are often left with devastating long-term side \neffects. Novel efficient and targeted treatment is desperately needed for this patient population. Cellular immu-\nnotherapy aims to enhance and utilize immune cells to target tumors, and has been proven successful in various \ncancers. However, for MB, the knowledge and possibilities of cellular immunotherapy are limited. In this review, \nwe provide a comprehensive overview of the current status of cellular immunotherapy for MB, from fundamental \nin vitro research to in vivo models and (ongoing) clinical trials. In addition, we compare our findings to cellular im-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1088
encoding: FLOAT32
metadata:
{"title": "Neuro-Oncology", "chroma:document": "munotherapy in glioma, an MB-like intracranial tumor. Finally, future possibilities for MB are discussed to improve \nefficacy and safety.\nKeywords \ncellular immunotherapy | cytotoxic lymphocytes | medulloblastoma\nThe incidence of central nervous system (CNS) tumors \nis most frequent in pediatric patients (0\u201321\u00a0 years of age). \nMedulloblastoma (MB), a World Health Organization (WHO) \ngrade IV classified malignancy, is the most prevalent1 and re-\nsponsible for over 60% of all intracranial embryonal tumors \nin the USA diagnosed between 2011 and 2015.2 The peak in-\ncidence is between 6 and 8\u00a0years of age.1 In childhood, ap-\nproximately 1 in 200\u00a0000 individuals is diagnosed with MB,2 \nwhereas the incidence in adulthood is much lower (1 in \n2\u00a0000\u00a0000).3 MB originates from the progenitor cell popula-\ntions in the cerebellum during early life and has been linked to \nspecific genetic aberrations. Based on these aberrations, four \nMB subgroups have been described; Wingless (WNT), Sonic \nHedgehog (SHH), Group\u00a03 (G3), and Group\u00a04 (G4).4,5 Although \nmorphologically all classified as MB, these subgroups are dif-\nferent in cell-of-origin, driver aberration, and prognosis thus \nshould be treated as biologically distinct entities (Figure 1).\nIn most WNT-MB patients, an activating mutation in the \ngene encoding \u03b2-catenin results in a constitutively active WNT \nsignaling that contributes to enhanced cell growth and pro-\nliferation.6 Patients often have a favorable prognosis mainly \nattributed to an altered vasculature in the brain and higher \npermeability of blood brain barrier (BBB), making it more \nsusceptible to systemic chemotherapies.1 SHH-MB is genet-\nically best characterized with most mutations found within \nthe SHH pathway. This subgroup is more heterogenetic com-\npared to WNT-MB and is divided in four additional subgroups \n(SSH\u03b1, SSH\u03b2, SSH\u03b3, and SSH\u03b4).7 Depending on the subtype of \nSSH-MB, adult patients can be treated by inhibiting proteins \nupstream of SSH. However, children cannot use these inhibi-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1089
encoding: FLOAT32
metadata:
{"title": "Neuro-Oncology", "chroma:document": "tors because of potential skeletal abnormalities resulting in a \nfar worse prognosis.1 Additionally, TP53-mutant tumors dras-\ntically decrease survival in both children and adults.8 For sub-\ngroups 3 and 4, less than a third of cases can be dedicated \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License \n(https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any \nmedium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1090
encoding: FLOAT32
metadata:
{"title": "Skeletal evidence of osteoarthritis: palaeopathological perspective", "chroma:document": "Annals ofthe Rheumatic Diseases 1995; 54: 443-450\nREVIEW\nSkeletal evidence of osteoarthritis:\na palaeopathological perspective\nRobert D Jurmain, Lynn Kilgore\nOsteoarthritis\n(OA),\nor\ndegenerative\njoint\ndisease, is the most common form of joint\npathology, and\nit has an extensive history.\nIndeed, it has been observed in a variety of\nfossil animals, and has been reported in the\nfossil remains of dinosaurs.'\nAmong\npreindustrial human\ngroups,\nas\ndocumented by skeletal remains, osteoarthritic\nchanges are quite frequently the most common\npathological lesion seen. Such degenerative\nchanges have been described for archaeological\nsamples varying widely in time and location.2\"\nIn many cases,\"'5 frequencies of involvement\nhave also been calculated and presented.\nSkeletal evidence from archaeological sites\nthus has potential to expand considerably the\nrange of epidemiological data concerning OA.\nHuman populations long since extinct can be\nsampled.\nCurrent epidemiological\ndata\nare\nlimited\nalmost\nentirely\nto\nclinical\nsamples\ndrawn from urban contexts, mostly from North\nAmerica\nand\nEurope.\nEarlier\npopulations,\nranging from arctic hunters, to early Romano-\nBritish agriculturists, to Mediaeval Nubians\n(and, obviously, many others) may have led\nlifestyles very different from those character-\nistic of contemporary groups. Accordingly,\nskeletal analysis provides a 'window' into a\nvastly broader sample of human groups than\nafforded solely by clinical samples. If varying\nlevels of mechanical loading are important in\nthe aetiology of OA, as suggested by the 'stress\nhypothesis','6\nearlier\npopulations\ncould be\nexpected to exhibit definitive patterns of joint\ninvolvement. Such patterns should be reflected\nin differential involvement both within and\namong joints; moreover, patterns of bilateral\nasymmetries, sex based variation, and perhaps,\nmost crucially, clearly demarcated frequencies\nof involvement among prehistoric populations\nshould be manifest.\nAvailable materials\nIn recognition of the fact the osteoarthritic"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1091
encoding: FLOAT32
metadata:
{"title": "Skeletal evidence of osteoarthritis: palaeopathological perspective", "chroma:document": "process begins in articular cartilage, analysis of\nthe 'hard' tissues can provide another window\nnot commonly available to the clinician. With\njoint surfaces free of overlying tissue, subtle\ndegenerative changes involving bone are easily\nseen. Presumably slight arthritic involvement\nincludes small marginal lipping (osteophytes)\nor small erosive changes to the joint surface\nitself. In modern contexts, such minor bone\ninvolvement is not usually recognised as it does\nnot\npresent\nradiographically;\noccasionally,\nfollowing surgical replacement, a few macer-\nated specimens have become\navailable,'7 18\nthereby giving researchers a rare glimpse of\nunderlying bony tissue.\nIn addition, materials derived at postmortem\nare a most useful supplement and help bridge\nthe gulf between clinical data and fully macer-\nated remains. Several detailed studies have, in\nfact,\ninvestigated the frequency of OA\nin\npostmortem collections.'9-21 Moreover, in a few\ncases large numbers of macerated specimens\nhave carefully been obtained from dissecting\nroom\nsamples\nand have been\ncurated\nas\npermanent collections (most notably, the Todd\nCollection\nat\nthe\nCleveland\nMuseum\nof\nNatural History and the Terry Collection at the\nUS National Museum of Natural History).\nThese collections have proven a rich source of\ninformation,\nas\nthe\nskeletons\nare\nvirtually\nintact,\nsex\nand\nage\n(approximated)\nwere\nrecorded at the time of dissection, and for\nmany individuals cause of death (and some\nclinical history) is also noted. Building upon\nthis rich data source, skeletal biologists2 9 20\nhave used dissecting room skeletal collections\nto refine their descriptions of osseous degener-\native lesions, and to make epidemiological\ncomparisons with other groups.\nFor\narchaeologically\nderived\nspecimens\nthere are tens of thousands of examples of\nremodelled\njoint\nsurfaces.\nMoreover, when\nskeletal materials are well preserved, numerous\nregions can be systematically observed,\nin-\ncluding the large peripheral joints, the vertebral\ncolumn\n(body\nsurfaces\nin\naddition\nto"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1092
encoding: FLOAT32
metadata:
{"title": "Skeletal evidence of osteoarthritis: palaeopathological perspective", "chroma:document": "to\napophyseal articulations), and the numerous\nsmall articulations of the hands and feet. In\nthis way,\na pattern\nof involvement within\nindividuals and, more generally, within popu-\nlations can be established.\nFinally, in addition to a palaeoepidemiology\nof degenerative arthritis in human groups, such\ncomparative perspectives can be expanded to\ninclude non-human animals. Recent work with\nnon-human primates,22 23 especially the study\nof joint involvement in great apes,2426 has\nopened the potential\nfor an even broader\nperspective concerning the aetiology of osteo-\narthritis. By studying animals with differing\npostural/locomotory\nadaptations and\ncorre-\nlating these factors with the pattern of degener-\native lesions, we should be able to gain a fuller\nunderstanding of some\nof the mechanical\nfactors influencing the aetiology of OA.\nDepartment of\nAnthropology,\nSan Jose State\nUniversity,\nSan Jose,\nCA 95192, USA\nR D Jurmain\nDepartment of\nAnthropology,\nColorado State\nUniversity,\nFort Collins,\nCO, USA\nL Kilgore\nCorrespondence to:\nR D Jurmain.\nAccepted for publication\n13 October 1994\n443"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1093
encoding: FLOAT32
metadata:
{"title": "Third International Symposium the Immunotherapy ofthe Rheumatic Diseases Introduction and overview", "chroma:document": "Annals of the Rheumatic Diseases 1995; 54: 757-778\nThird International Symposium on\nthe Immunotherapy ofthe Rheumatic Diseases\n10-14 May 1995, Cyprus\nIntroduction and overview\nWhen the First International Symposium on the Immuno-\ntherapy of the Rheumatic Diseases was held in London in\nFebruary 1991, immunotherapy was an exciting but largely\ntheoretical concept. That meeting, focusing exclusively on\nimmune cells and mediators as therapeutic targets, was\nalmost entirely restricted to in vitro and animal studies, as\nonly a few small open studies had been performed in\nhumans in vivo. Just four years later, the situation has\nevolved beyond all recognition. Whilst in vitro and animal\nexperiments are still vital, an increasing variety of treat-\nments have been tested in vivo in humans in double blind\nplacebo controlled trials. In addition, the purview of the\nSymposium is now much broader as the mesenchyme,\nincluding synoviocytes, proteolytic enzymes, and angio-\ngenesis, is now an active target for antirheumatic drug\ndevelopment.\nInevitably,\nthere have\nalso been some\nfailures over the past four years. Some initially promising\ntreatments,\nsuch\nas major histocompatibility complex\n(MHC) blocking peptides and lymphocyte depleting anti-\nbodies, appear to have fallen by the wayside and, even\nmore disappointingly perhaps, we are no further forward\nin\nidentifying\nthe\nputative\nautoantigens\ninvolved\nin\ntriggering or perpetuating the disease. However, as can be\nseen from the ensuing review and abstracts, gains have far\noutweighed losses, setting the scene for a fascinating\nconference.\nSomewhat paradoxically for a meeting on the Immuno-\ntherapy of the Rheumatic Diseases, the conference started\nwith a Keynote Address by Dr L Adorini (Milan) on\nthe non-obese diabetic (NOD) mouse as a model for\ndeveloping and testing immunotherapy in human diabetes.\nThere was method in the apparent madness. Diabetes in\nthe NOD mouse represents one of the best spontaneously\ndeveloping animal models available, as it has a similar"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1094
encoding: FLOAT32
metadata:
{"title": "Third International Symposium the Immunotherapy ofthe Rheumatic Diseases Introduction and overview", "chroma:document": "pathology, analogous genetic susceptibility and identical\nputative\nautoantigens\nas\nobtain\nin human\ndiabetes.\nExamination of how data from this model can be applied\nto the human disease may help us to interpret information\nfrom the rather less satisfactory animal models available for\nthe rheumatic diseases.\nThe Symposium proper began with an overview of the\npathogenesis ofrheumatoid arthritis (RA) (Dr G H Kingsley),\nfollowed by five presentations on various topical aspects.\nDr Panayi put forward the hypothesis that RA is an organ\nspecific\nautoimmune\ndisease\nin\nwhich\nthe\nimmune\nresponse\nis directed to the chondrocyte. As immune\nresponses to two putative cartilage autoantigens, collagen\ntype II and cartilage proteoglycan, have proved difficult to\nfind, the group has developed a chondrocyte expression\nlibrary and is screening it with RA serum to identify\nchondrocyte specific proteins which may have a role in RA.\nThe identification of such candidate antigens would allow\ntherapeutic approaches using antigen specific tolerance\nsimilar to those for diabetes discussed in the Keynote\nAddress.\nDr\nNatvig's\ngroup\nhas\ndemonstrated\nthat\nrheumatoid factor in healthy individuals is subject to a\ncontrolling mechanism which limits affinity maturation.\nHe suggested that the apparent loss of such control in\nRA may be of pathogenetic significance; the question of\nwhat role rheumatoid factor has in synovitis remains\nunanswered. Turning to T cells, Dr Amento has found, in\nseveral autoimmune animal models, that administration of\nTCR peptides from disease perpetuating T\ncells can\nsuppress disease by upregulating counter regulatory T\ncells; however, as the question ofwhether there is restricted\nT cell receptor (TCR) usage in RA remains unresolved,\nthe potential of this type of treatment in humans is as yet\nunknown. The collagen induced arthritis developed by\nDr Bontrop and colleagues in rhesus monkeys is probably\nthe\nbest\ncharacterised\nprimate\ninflammatory\narthritis\nmodel, and should allow the testing of pathogenetic and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1095
encoding: FLOAT32
metadata:
{"title": "Third International Symposium the Immunotherapy ofthe Rheumatic Diseases Introduction and overview", "chroma:document": "therapeutic hypotheses in much the same way as the NOD\nmouse model does in diabetes. In the last presentation on\nimmunopathogenesis, Dr David reviewed the\nrole of\nhuman MHC class II genes in mediating susceptibility to\narthritis, using a new model system. In this model, human\nMHC class II genes from RA susceptible or resistant\nhaplotypes were introduced into mice from which the\nendogenous class II genes had been 'deleted', so that their\nonly functional class II molecules were those coded by the\nhuman\ngenes. The\neffect of these manipulations on\narthritis\nsusceptibility\ncould then be examined\nin\na\ncontrolled fashion which may help to explain the role of\nMHC class II in determining disease susceptibility in\nhumans.\nThe\nnext\nmajor\ntheme\nof the\nmeeting\nwas\nthe\nimmunologist's holy grail, the induction of tolerance.\nImmunosuppressive approaches to the treatment of auto-\nimmune disease have two major drawbacks-the need for\nlong term treatment to prevent return of disease, and the\nrisk of infection or tumour as a result of a generalised\nloss of immune function. In contrast, the reinduction of\ntolerance to the putative rheumatoid autoantigen(s) has\nthe potential to provide a permanent and highly selective\ntreatment. Three different approaches to induction of\ntolerance were discussed at the meeting. In session II,\nDrs Hafler, Wraith and Sieper reviewed tolerance induced\nby\nnasal\nor\noral\nantigen\nadministration.\nWhilst\nthis\ntechnique has progressed the furthest in clinical terms\n(indeed, the results of two double blind placebo controlled\nclinical trials of oral collagen in RA were presented, one\npositive and one negative), the mechanisms underlying\noral and nasal tolerance remain far from clear. Dr Cohen\nand Dr Sette discussed ways of interfering with the specific\nT cell receptors (TCR) involved in the 'autoimmune'\nMHC-antigen-TCR complex. Though potentially very\n757"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1096
encoding: FLOAT32
metadata:
{"title": "Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus in ethnic of Singapore", "chroma:document": "Journal of Medical Genetics, 1979, 16, 431-434\nAssociation of glucose-6-phosphate dehydrogenase\ndeficiency with diabetes mellitus in ethnic groups of\nSingapore\nN. SAHA\nFrom the Department ofPhysiology, Faculty of Medicine, University of Singapore, Singapore\nSUMMARY\nSix hundred and nine male patients suffering from maturity onset diabetes mellitus,\ncomprising 422 Chinese, 66 Malays, and 121 Indians, were investigated to determine the incidence\nof G6PD deficiency, ABO blood groups, and haemoglobin types, and these were compared with\nnormal healthy controls. A positive association with a higher incidence of G6PD deficiency in\ndiabetics was observed in Chinese and Indian patients. There was no significant difference in the\nfrequencies of ABO blood groups and haemoglobin types between the patients and the controls in\nany of the ethnic groups studied.\nThe genetic association of diabetes mellitus has been\nstudied in the past mainly by the relative incidence of\nblood groups and serum proteins (Craig and Wang,\n1955;\nMcConnell\net\nal.,\n1956;\nAndersen\nand\nLauritzen, 1960; Macafee, 1964; Berg et al., 1967;\nKlebe and Nielsen, 1972; Lamba et al., 1974), but\nthe results, far from being in agreement, are rather\nconflicting. From an epidemiological study into the\nincidence\nof cancer\nand\ndiabetes\nmellitus\nand\nglucose-6-phosphate dehydrogenase (G6PD)\ndefi-\nciency in different populations of the world, Kessler\n(1970) suggested a negative association of G6PD\ndeficiency in cancer and a positive relationship in\ndiabetes\nmellitus.\nNaik\nand\nAnderson\n(1971)\nobserved a negative association of G6PD deficiency\nin cancer in American Negro patients, but only in\nthe case of females. In an earlier study on a pooled\nsample of smaller size we failed to observe any\nassociation of G6PD deficiency and ABO blood\ngroups in diabetes mellitus (Saha, 1971). The three\nethnic groups in Singapore (Chinese, Malays, and\nIndians), who have different incidences of the disease,\nwith a higher incidence among Indians compared\nwith the other two (Cheah et\nal.,\n1972,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1097
encoding: FLOAT32
metadata:
{"title": "Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus in ethnic of Singapore", "chroma:document": "1972,\n1975),\nprovided an excellent opportunity to study the\npossible association ofG6PD deficiency, ABO blood\ngroups, and haemoglobin types in diabetes mellitus.\nWe present in this report the incidence of G6PD\ndeficiency, ABO blood groups, and haemoglobin\ntypes in maturity onset diabetes mellitus compared\nwith healthy controls in the three ethnic groups of\nSingapore.\nReceived for publicaiion 16 February 1979\nMaterials and methods\nPATIENTS\nSix hundred and nine male patients, comprising 422\nChinese, 66 Malays, and 121 Indians, attending the\nDiabetic Clinic at the Tan Tock Seng Hospital,\nSingapore, were investigated for the distribution of\nG6PD deficiency, ABO blood groups, and haemo-\nglobin\ntypes.\nThese\nwere\nconsecutive\ncases\nof\nmaturity onset diabetes mellitus as confirmed by\nstandard glucose tolerance tests after oral glucose.\nFive diabetic patients with G6PD deficiency at the\nfirst test were followed up and tested for blood\nglucose levels and G6PD deficiency on three or four\nsubsequent visits while undergoing treatment.\nCONTROLS\nFor comparison,\ncontrols\nwere taken from\n(a)\npatients proved to be normal and (b) series in\npublished reports.\n(a) Seven hundred and forty seven male subjects\ncomprising 523 Chinese, 87 Malays, and 137\nIndians attending the same diabetic clinic\nformed the control series. These were con-\nsecutive cases confirmed as non-diabetic by\nstandard glucose tolerance tests. They were\ninvestigated for the distribution of G6PD\ndeficiency, ABO blood groups, and haemo-\nglobin types.\n(b) Published\ndata. ABO\nblood\ngroups\nwere\ncompared with the series of Chan (1962), cases\nofG6PD deficiency with the series of Saha and\nBanerjee (1971a, b), and for comparison with\n431"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1098
encoding: FLOAT32
metadata:
{"title": "Medical genetics in China", "chroma:document": "Journal of Medical Genetics, 1979, 16, 330-337\nMedical genetics in China\nW. F. BODMER1 AND C. A. CLARKE2\nFrom the Genetics Laboratory, Department of Biochemistry, University of Oxford,\nOxford OX] 3QU2; and the Royal College ofPhysicians Medical Services Study Group, King's Fund\nCentre, London NWJ 7NF2\nIn July 1978 a Royal Society delegation visited the\nPeople's Republic of China for about three weeks to\ndiscuss medicobiological matters with the Chinese\nAcademy of Sciences, in particular the reason for the\nhigh incidence of cancer of the oesophagus in one\ncounty in the north and ofnasopharyngeal carcinoma\nin the south. Dr Michael Stoker was the leader (the\nChinese are insistent on this protocol) and the other\nscientific members were Professor Walter Bodmer,\nSir Cyril Clarke, Sir Richard Doll, and Professor\nAvrion Mitchison. We were accompanied by Miss\nElizabeth Wright, Director of the Great Britain-\nChina Centre. She spoke excellent Chinese and\nreported on the translation of our lectures and other\ndiscussions.\nThis\nvaried\ngreatly\nbut was\nnever\nmanipulated.\nThe authors of this paper thought that readers of\nthe Journal might be interested to hear about our\nimpressions of genetics in the Republic, genetics\nbeing interpreted in the liberal Lederberg sense of\n'anything interesting.'\nMedical statistics\nWe did not come across any organisation such as our\nown OPCS (Office of Population Censuses and\nSurveys) and\nit seems probable\nthat\nthe most\nreliable data are those relating to cancer, particu-\nlarly in the high incidence areas; these are collected\nby the Oncology Institutes.\nIn each commune (essentially a group of villages\nwith,\non\naverage,\nbetween\n50 000 and\n100 000\npeople)\nindividual\nregistration\nis\nrequired\nfor\nrationing\npurposes.\nIt\nis\ntherefore\npossible\nto\nobtain basic information about the\nsize of the\npopulation. This is then looked at in more detail for\none of the 10 to 20 communes which make up each\ncounty, and by summing the total populations from\neach commune, a rough estimate of the population"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1099
encoding: FLOAT32
metadata:
{"title": "Medical genetics in China", "chroma:document": "structure of the whole county can be made by\nextrapolation. The provinces, which are large regions,\nReceived for publication 7 February 1979\nare divided for administrative purposes into counties\ncorresponding roughly to those in the UK.\nAs regards malignancy, data obtained from the\nPeking Institute of Oncology showed that cancer\nmortality had been determined by means of a retro-\nspective\nstudy\nof death\ncertificates\nin\nselected\nprovinces over the 3-year period 1972, 1973, and\n1974, and is now being determined for the whole\ncountry by a similar study in 1975. Information\nobtained in discussion suggested that a positive\ndiagnosis\nof cancer on\na death\ncertificate was\nreasonably reliable. In Kiangsu Province (containing\nShanghai and Nanking, and not ahighincidencearea)\nwe were shown a detailed map of the cancer mortality\nin each commune and how the diagnosis had been\narrived at. This was by microscopy in 16 % of cases,\nby hospital investigation including x-ray in 65%,\nby clinical examination in 15%, and by history or\nbarefoot doctor alone in 4%. Similar information is\navailable from the high cancer incidence areas.\nData on congenital malformations seemed to be\nbased only on personal experience and individual\nhospital records. For example, in discussing anence-\nphaly, spina bifida, and hydrocephalus in Peking,\nwe were told that there was an extraordinarily high\nincidence: up to 1 % of births in Peking itself, and\nup to 3 % further north, but much lower in Shanghai.\nThis seems highly improbable and it may be that\nthere was some confusion and that the Chinese\nwere talking about total malformations. In Taiwan,\nthe\nincidence\nof anencephaly\nis\n'intermediate',\naround 1 17/1000 births (Emanuel et al., 1972).\nVisits to Genetics Institutes\nACADEMY INSTITUTE OF GENETICS, PEKING\nThe Institute was started in 1951, at first doing mainly\nplant genetics, but in 1959 animal work was started\nas well. There are now 250 research workers (the\ndistribution\nbetween\nscientists,\ntechnicians,\nand"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1100
encoding: FLOAT32
metadata:
{"title": "Medical genetics in China", "chroma:document": "and\nothers is not clear) in five departments. One of these\ndealt with human and animal genetics, and we paid it\ntwo visits. The first time, we heard a great deal about\n330"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1101
encoding: FLOAT32
metadata:
{"title": "Genetic polymorphisms in diabetics and non-diabetics", "chroma:document": "Journal of Medical Genetics, 1979, 16, 351-357\nGenetic polymorphisms in diabetics and non-diabetics\nD. R. R. WILLIAMS AND R. A. CARTWRIGHT\nFrom the MRC Dunn Clinical Nutrition Centre, Addenbrookes Hospital, Trumpington Street,\nCambridge CB2 1 QE; and the Yorkshire Regional Cancer Organisation, Cookridge Hospital,\nLeeds LS16 6QB\nSUMMARY\nPhenotype distributions of some genetic polymorphisms are reported in a sample of\n721 diabetics and 515 non-diabetic, non-blood donor controls. Reference is also made, in the case\nof the ABO and Rhesus systems, to previously published results for blood donors resident in the\nDurham area. Non-insulin-taking diabetics show an increased frequency of blood group A1 (and\nA1 + A2) when compared with controls. This difference is particularly marked in male diabetics.\nWhen diabetics are compared with age matched controls, the difference is confined to the older cases.\nIt is proposed that this effect is predominantly the result of a deficiency of group A1 in controls\nrather than the result of increased susceptibility to the disease among A1 people. No association with\nany of the Rhesus phenotypes is shown. In non-diabetics, the results suggest an enhanced survival\nvalue for the rr genotype.\nNo significant associations are seen when the MNSs, Kell, Lewis, Duffy, haptoglobin, red cell\nacid phosphatase, phosphoglucomutase, adenylate kinase, and adenosine deaminase distributions\nin these groups of subjects are compared.\nThe ABO blood groups of diabetics have been\nextensively studied since McConnell's suggestion, in\n1955, of an increased frequency of blood group A in\nthese patients. Despite considerable effort, however,\nthis approach has contributed little to knowledge of\nthe hereditary factors involved in the predisposition\nto diabetes, and there has been some measure of\ndisagreement among the authors concerned. Other\nred cell polymorphisms and serum protein systems\nhave been less well studied in diabetics and few clear\nconclusions have been drawn."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1102
encoding: FLOAT32
metadata:
{"title": "Genetic polymorphisms in diabetics and non-diabetics", "chroma:document": "The present study was undertaken to investigate\nthe distribution of some of these polymorphisms in\ndiabetics and in non-diabetic controls. The results\nfor the esterase-D polymorphism in these subjects\nhave\nbeen\npublished\nelsewhere\n(Williams\nand\nCartwright,\n1978),\nas have those for the histo-\ncompatibility antigens (Williams, 1977).\nTwo features distinguish this particular study.\nFirstly, the sample of diabetics consists of a large\nproportion\nof\nthe\nout-patients\nattending\none\nparticular hospital, and the phenotype frequencies in\nthese patients are analysed\nin terms of current\ntreatment,\ncurrent\nage,\nand\nsex.\nSecondly,\nthe\ncontrols are drawn from the same geographical area\nas the diabetics, are age matched with them for\nReceived for publication 29 December 1978\nanalysis, and are not a sample of blood donors,\nthough previously published data from donors are\nincluded for comparison.\nMaterials and methods\nDIABETIC SUBJECTS\nPatients were chosen from those attending out-\npatient\nclinics\nat\nDryburn\nHospital,\nDurham.\nVenous blood samples were taken from 721 of the\ndiabetics attending between November 1974 and\nJune 1976. This represents about 75% of the total\nattendance during\nthis time. Sampling was not\nrandom since patients attending more frequently had\na greater chance of selection. The series collected was\nslightly younger in mean age and consisted of a\nhigher proportion of insulin-taking patients and a\nlower proportion of diet-treated patients than the\ncomplete\nout-patient\npopulation,\nthough\nthese\ndifferences were not significant (Williams, 1977).\nCONTROL SUBJECTS\nThese were selected from three sources: (a) age and\nsex matched neighbours of some of the diabetics\n(72 subjects); (b) patients attending the orthopaedic\ndepartment of Dryburn hospital for treatment of\ntraumatic conditions, mainly fractures and head\n351"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1103
encoding: FLOAT32
metadata:
{"title": "Non-progressive cerebellar ataxia, aplasia of pupillary of iris, and mental subnormality (Gillespie's syndrome) affecting 3 members of non-consanguineous family in 2 generations", "chroma:document": "Journal of Medical Genetics, 1979, 16, 373-378\nNon-progressive cerebellar ataxia, aplasia of\npupillary zone of iris, and mental subnormality\n(Gillespie's syndrome) affecting 3 members of a\nnon-consanguineous family in 2 generations\nM. d'A. CRAWFURD,1 R. B. HARCOURT, AND P. A. SHAW2\nFrom the Department of Genetics, University ofLeeds'; and the Ophthalmic Department, Leeds\nGeneral Infirmary,2 Leeds\nSUMMARY\nA family is reported in which a brother and sister both showed non-progressive cere-\nbellar ataxia, aplasia of the pupillary zone of the iris, and mild mental subnormality. These clinical\nfindings were similar to those in two previous case reports. Despite the birth of an affected son to the\naffected sister, this family is considered to confirm autosomal recessive inheritance of this syndrome.\nThe paternity of the mother's husband is supported by blood groups and biochemical markers and\nit is presumed that the husband is a heterozygote, even though no consanguinity could be detected.\nThe hereditary ataxias are an ill-defined group of\ndisorders of which the best known is Friedreich's\nataxia. Many other syndromes have been described,\nsome of which are clearly defined entities, but others\nare of uncertain clinical, pathological, and genetic\nstatus. The clear delineation\nof further\nspecific\ndisorders is helpful in the classification of this group\nand is of practical use in genetic counselling.\nGillespie (1965) first reported the combination of\npartial aniridia, cerebellar ataxia, and mental sub-\nnormality affecting a brother and sister. Sarsfield\n(1971) described a sporadic case of a boy similarly\n'Present address: Division of Inherited Metabolic Diseases,\nMRC Clinical Research Centre, Watford Road, Harrow,\nMiddlesex HAI 3UJ.\n2Present\naddress:\nConsultant Ophthalmic Surgeon,\nCity\nGeneral Hospital, Stoke-on-Trent, Staffs.\nReceived for publication 29 December 1978.\nT\n1r1\n2r'\n3r7\naffected. We report here a further family of a young\nman, his elder sister, and her son, all with the same"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1104
encoding: FLOAT32
metadata:
{"title": "Non-progressive cerebellar ataxia, aplasia of pupillary of iris, and mental subnormality (Gillespie's syndrome) affecting 3 members of non-consanguineous family in 2 generations", "chroma:document": "association of abnormalities (Fig. 1).\nCase reports\nCASE\n1 (III.8)\nThis Caucasian female, the first of three sibs, was\nborn at term in 1955. She was delivered at home after\na prolonged labour of about 36 hours and weighed\n3300 g. In the first few months of life she suffered\nunexplained episodes of vomiting and had difficulty\nwith feeding. The parents also noticed a tremor of\nthe hands and feet from early infancy and she was\nlate in passing most of her milestones. She first sat\nat 15 months, stood at 20 months, and first spoke at\n2 years; there was also some delay in walking and\nshe was backward in her social behaviour. At the\n1976\nFig. 1\nPedigree offamily.\nGenetic family L1013\n373"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1105
encoding: FLOAT32
metadata:
{"title": "X;15 translocation in retarded girl: X inactivation pattern and localise the hexosaminidase A and other loci", "chroma:document": "Journal of Medical Genetics, 1979, 16, 254-262\nX;15 translocation in a retarded girl: X inactivation\npattern and attempt to localise the hexosaminidase A\nand other loci\nRENEE BERNSTEIN, BRONWEN DAWSON, RUDI KOHL, AND\nTREFOR JENKINS\nFrom the Department ofHuman Genetics, School ofPathology, The South African Institute for Medical\nResearch and University ofthe Witwatersrand, Johannesburg; and the Department ofPaediatrics,\nState Hospital, Windhoek, SWA/Namibia\nSUMMARY\nCytogenetic studies on a retarded girl showed a complex X; 15 translocation, karyotype\n45,X,- 1 5,+t(X;1 5). The translocation X chromosome was non-randomly partially inactivated, the\ninactivation being mainly confined to the X segment and in some cells only to the X long arm. Gene\nmarker studies failed to show anomalous segregation of the hexosaminidase A gene or any other gene\nmarkers tested.\nNearly 50 patients with an X autosome translocation\nhave been reported and attempts made to correlate\nthe phenotypic expression with the type and site of\ntranslocation, as well as with the X inactivation\npattern (Cohen et al., 1972; Summitt et al., 1974;\nTherman and Patau, 1974; Gilgenkrantz et al., 1975;\nBartsch-Sandhoff et al., 1976; Hagemeijer et al.,\n1977). A further 18 X;autosome translocations are\nlisted by Borgaonkar and Dolling (1977). Every\nautosome except chromosomes 10 and 20 has been\nimplicated and in at least 5 cases the autosome has\nbeen identified as chromosome 15 (Engel et al., 1971;\nLucas and Smithies, 1973; Sujansky et al., 1973;\nLaurent, 1971, quoted by Gilgenkrantz et al., 1975;\nBartsch-Sandhoffet al.,1976).\nThe X inactivation pattern of sufficient numbers of\nsuch cases has now been studied to establish that\nbalanced X;autosome translocations usually show\nnon-random inactivation of the normal X chromo-\nsome,\nwhile\nin\nunbalanced\ntranslocations,\nthe\nderivative abnormal X\nis usually completely or\npartially\ninactivated,\nwith\nresultant\ndiversity\nof\nphenotypic expression. For a valid correlation to be\nmade between the phenotype and the karyotype in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1106
encoding: FLOAT32
metadata:
{"title": "X;15 translocation in retarded girl: X inactivation pattern and localise the hexosaminidase A and other loci", "chroma:document": "these patients, it is important to determine whether\nX inactivation has spread from the X segment to the\nattached autosome. Such an exercise was often\ndifficult\nwith\nautoradiographic\ntechniques,\nbut\nincorporation of 5-BrdU during DNA synthesis\n(Dutrillaux et al., 1973) has provided a simple and\nReceived for publication 11 October 1978\naccurate means ofstudying the replication patterns of\nchromosomal DNA,\nincluding\nthe\ninactivation\npatterns ofthe X chromosome.\nWe report the investigation of a markedly retarded\ngirl, who was found to have a complex translocation\nof chromosomes X and\n15\n(45,X,-X,-15,+t\n(X;15)) in the majority of her peripheral blood\nmetaphases, and a minor mosaic 45,X (Turner)\ncell-line. The translocation X chromosome\nwas\nfound to be non-randomly partially inactivated.\nSerogenetic studies were performed on the child and\nher parents in an attempt to localise genes on\nchromosomes X and 15.\nCase report\nA\n4-year-old\ngirl\nwas\nbrought\nto\nhospital\nin\nWindhoek, Namibia/South West Africa from a\nremote country area for investigation of marked\nmental and physical retardation. She was the fourth\nborn of 5 children, and was delivered normally after\nan uneventful pregnancy. Both parents and the 3\nolder sibs, all boys, are phenotypically normal, as was\nthe youngest sib, a girl, who died recently of 'con-\ngested\nlungs'.\nThere\nis\nno\nknown\nhistory\nof\nabnormality in either parent's family. The mother is\nof (black) Tswana origin, while the father has mixed\nTswana/Caucasoid ancestry.\nThe birthweight is not known, but the child was\nsaid to be weak and had difficulty in sucking. The\nmother thought the child was normal until 3 months\nof age, but development was then noted to be slow\n254"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1107
encoding: FLOAT32
metadata:
{"title": "Congenital haemolytic anaemia resulting from glucose phosphate isomerase deficiency: genetics, clinical picture, and prenatal diagnosis", "chroma:document": "Journal of Medical Genetics, 1979, 16, 189-196\nCongenital haemolytic anaemia resulting from glucose\nphosphate isomerase deficiency: genetics, clinical\npicture, and prenatal diagnosis\nA. G. L. WHITELAW,\nP. A. ROGERS, D. A. HOPKINSON, H. GORDON,\nP. M. EMERSON,\nJ. H. DARLEY, C. REID, AND M. d'A. CRAWFURD\nFrom the Departments ofPaediatrics, Obstetrics, and Haematology, Northwick Park Hospital; the\nDivision of Inherited Metabolic Disease, Clinical Research Centre, Northwick Park Hospital;\nthe MRC Human Biochemical Genetics Unit, The Galton Laboratory, University College London; and\nthe Department ofHaematology, Radcliffe Infirmary, Oxford.\nSUMMARY\nGlucose phosphate isomerase (GPI) deficiency with severe haemolysis and hydrops\nfetalis was found in the first child of unrelated, healthy Caucasian parents. The child died at 3 hours.\nBoth parents were found to have 50 % of normal red cell GPI activity and qualitative tests on their\nred cells and white cells showed that each was heterozygous for a different GPI variant allele associa-\nted with enzyme deficiency. Tests on the placenta showed that the propositus was a 'compound'\nheterozygote.\nExamination of amniotic cells obtained by amniocentesis on the mother at 28 weeks in her second\npregnancy led to the prenatal diagnosis of GPI deficiency. This second child, a 'compound' hetero-\nzygote at the GPI locus indistinguishable from the first, was successfully treated by immediate\nexchange transfusion and subsequent blood transfusions.\nGlucose phosphate isomerase (EC: 5.3.1.9) (GPI) is\na dimeric enzyme which catalyses the interconversion\nof fructose-6-phosphate and glucose-6-phosphate. It\nis determined by an autosomal locus which has been\nassigned to chromosome 19 (McMorris et al., 1973).\nSeveral electrophoretic variants have been identified\nin population studies on normal healthy subjects\nin addition to the common phenotype GPI 1 (Detter\net al., 1968; Shinoda, 1970; Tariverdian et al., 1970;\nWelch, 1971; Omoto and Blake, 1972). The variant"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1108
encoding: FLOAT32
metadata:
{"title": "Congenital haemolytic anaemia resulting from glucose phosphate isomerase deficiency: genetics, clinical picture, and prenatal diagnosis", "chroma:document": "alleles are mostly rare with the exception of GPI3\nwhich\nreaches\npolymorphic\nfrequency\nin\nsome\nIndian populations (Blake et al., 1971).\nSome electrophoretic variants are associated with\ndeficient activity of GPI and may manifest with non-\nspherocytic\nhaemolytic\nanaemia.\nThe\naffected\nsubjects may be homozygous for the variant allele\ncausing GPI deficiency, for example, GPI Espeln,\nalso known as phenotype GPI 9 (Arnold et al., 1973).\nIn other cases, patients have been shown to be\nheterozygous for two different variant alleles both\nassociated with GPI deficiency, for example, GPI\nSeattle, also known as phenotype GPI 9-10 (Baughan\net al., 1968; Detter et al., 1968). In some other cases,\nReceived for publication 30 August 1978\nthe product of the variant allele is indistinguishable\nelectrophoretically from normal, and indeed some-\ntimes the alleles appear to be 'silent'.\nThe various reports of GPI deficiency associated\nwith haemolytic anaemia were reviewed by Paglia\nand Valentine (1974). Several new cases have been\nidentified since then; for example, GPI Utrecht\n(van Biervleit, 1975), GPI Nordhorn (Schroter et al.,\n1974), and GPI Barcelona (Kahn et al., 1977), and\nthe genetic and molecular\nbasis\nfor haemolysis\nbecause\nof GPI\ndeficiency\nhas\nbeen\nreviewed\nrecently (Kahn et\nal.,\n1976,\n1977; Schrbter and\nTillmann, 1977). Most of the cases are relatively\nmild, but there is a report of a family from Kentucky\nin which 3 of 4 affected children in a family of 8\ndied, one at the age of 11 days (Hutton and Chilcote,\n1974).\nA family is described here in which 2 sibs have\nhad severe congenital non-spherocytic haemolytic\nanaemia because of deficient activity of GPI. The\nfirst child died at 3 hours with hydrops fetalis. The\nsecond child was diagnosed antenatally by amnio-\ncentesis at 28 weeks' gestation, and was successfully\ntreated by exchange transfusion following delivery at\n35 weeks and subsequent blood transfusions. Each\n189"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1109
encoding: FLOAT32
metadata:
{"title": "Review Article Sex Chromatin*", "chroma:document": "Review Article\nJ. med. Genet. (i964), I, 50.\nSex Chromatin*\nURSULA MITTWOCH\nFrom Galton Laboratory, University College, London\nThe term 'sex chromatin', in present-day usage,\ndenotes a body in the nuclei of cells, which indicates\nthe sex of the organism from which the cell origi-\nnated.\nThe sex chromatin body is present in the\nnucleus\nonly\nduring interphase and\ndisappears\nduring mitosis.\nThe term 'sex-chromatin' had\npreviously been used in a different sense by Wilson\n(1925) to describe the (hypothetical) part of the\nsex chromosomes that acted as a sex differentiator\nin development.\nAlthough the subject of sex chromatin has be-\ncome a part of human genetics only within the last\ndecade or so,\nit has attracted very considerable\ninterest and today provides one of the most active\ngrowing points. One reason for this is practical.\nIt\nhas been estimated that about 2 or 3 persons per\ni,ooo suffer from an abnormality of their sexual\ndevelopment (Overzier, i963), and it appears that\nthe incidence may be even higher at birth (see p.\n70). The sex chromatin test provides a simple and\noften indispensable aid in the diagnosis of such\npatients.\nMoreover, the technique has made it\npossible to screen large populations and thus obtain\nestimates regarding the incidence of these abnor-\nmalities. On a more theoretical level, the origin of\nthe sex chromatin and its relation to the sex chromo-\nsomes has given rise to speculations, which are\nfurther stimulating experimental work, as to the\nway in which the X chromosome functions, both in\nsex determination and in general.\nSome Landmarks in the Development of the\nSex Chromatin Concept\nThe discovery of sex chromatin\nis generally\nplaced in I949, when Barr and Bertram, in London,\nOntario,\ndescribed\na\nmorphological\ndistinction\nbetween neurones of male and female cats.\nThe\nsex difference consisted of a small body which was\npresent in the nuclei of nerve cells from female cats\nbut was absent in those of males (Fig.\ni).\nThe\n*Received February 13, I964"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1110
encoding: FLOAT32
metadata:
{"title": "Review Article Sex Chromatin*", "chroma:document": "body, which stained with nuclear dyes, was inti-\nmately associated with the nucleolus and was at\nfirst called a 'nucleolar satellite'. This term became\ninappropriate when\nBarr (I95I) found\nthat in\nneuroglial cells of the cat the sex differentiating body\nlies against the inner side of the nuclear membrane.\nHenceforth, the term 'sex chromatin' was employed.\nThe finding of the sex chromatin in the cat was an\nunexpected result of experimental neurocytology.\nBarr and Bertram (1949) wrote: 'It appears not to\nbe generally known that the sex of a somatic cell as\nhighly differentiated as a neurone may be detected\nwith no more elaborate equipment than a compound\nmicroscope following staining of the tissue with the\nroutine Nissl method'.\nSections of brain, spinal\ncord, or sympathetic ganglia could now be readily\nattributed to the correct sex of the animal from\nwhich they originated.\nA few years before the appearance of the paper by\nBarr and Bertram, S. G. Smith (I944, I945a, b), in\nOttawa, Ontario, found that in cells of the larvae\nof the spruce budworm, Choristoneura (Archips)\nfumiferana (Clem.), a darkly staining body was\npresent in the nuclei of the female and was absent\nfrom the male (Fig. 2). This body could be used for\nsexing larvae prior\nto the development of the\ngonads, and it was suggested that this method might\nbe applied to other organisms, including mammals.\nThese findings are of importance not only because\nthey provide the first indication that a nuclear body\npresent in interphase can be used as an indicator of\nsex, but also because the spruce budworm is a\nmember of the Lepidoptera, and in this order the\nfemale is the heterogametic sex. A female spruce\nbudworm has only one X chromosome, and Smith\npostulated that the single X remained condensed\n(heteropycnotic) in interphase nuclei, in contrast\nto the two X chromosomes of the male, which be-\ncame invisible. Thus, the situation appears to be\nprecisely the opposite from that found in mammals.\nSex chromatin in heterogametic females will be"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1111
encoding: FLOAT32
metadata:
{"title": "Review Article Sex Chromatin*", "chroma:document": "further discussed later (p. 68).\n50"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1112
encoding: FLOAT32
metadata:
{"title": "Discordance in Monozygotic Twins: One Diabetic, the Other Idiot with Neurological Abnormalities*", "chroma:document": "J. med. Genet. (I964).\ni, 88.\nDiscordance in Monozygotic Twins: One Diabetic, the\nOther an Idiot with Neurological Abnormalities*\nNEVILLE PARKERt\nFrom the Medical Research Council Psychiatric Genetics Unit, Maudsley Hospital, Londont\nWhile our knowledge of aetiology remains in-\ncomplete, the reporting of examples of discordant\nmonozygotic twins continues to be of value.\nCases\nwhere the difference has been present from birth\nalso serve to remind us of a fact, commonly over-\nlooked, that in exceptional circumstances the intra-\nuterine environment may be significantly different\nfor monozygotic twins.\nThe few case reports available are of consider-\nable interest but often of limited value.\nIn the\nearlier papers zygosity could not be established to\nthe satisfaction of workers today, and in almost\nevery study the particular prenatal factor could\nnot be determined.\nThe pair to be described, though looking iden-\ntical for the first few months of life, were distinctly\ndifferent in health, and with time this difference\nbecame more exaggerated.\nNow, at I9 years, one\nis a bed-ridden idiot with small head and spastic\ndiplegia, subject to frequent grand mal seizures,\nwhile his twin, a farm labourer of dull normal in-\ntelligence,\nsuffers from diabetes.\nNeither twin\nshows any features of the other's condition.\nCase Report\nThe proband (Twin A) was included in an unselected\nseries of twins attending the Maudsley Hospital Child-\nren's Department.\nHe was referred in 1957 for an\nopinion as to whether he was epileptic. The twins were\nconceived 5 years after the mother's only other preg-\nnancy, which resulted in a healthy female child, and\nwere born in the summer of I944; the mother was then\naged 30 and the father 3I.\nThe only incident during\nthe nine-month pregnancy was a fall at 8 weeks which\nresulted in a broken finger, but no per vaginam loss.\nThe mother can recall no minor illnesses while she\nwas carrying the twins; there were no signs of toxaemia\nnor any suggestion of threatened abortion.\nThe only"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1113
encoding: FLOAT32
metadata:
{"title": "Discordance in Monozygotic Twins: One Diabetic, the Other Idiot with Neurological Abnormalities*", "chroma:document": "The only\nradiological examination was two weeks before the\nconfinement to confirm the multiple pregnancy, and\nshe was taking no drugs.\nAfter a labour lasting 8 to io hours Twin A presented\nas a vertex and was born without difficulty, weighing\n6 lb. 9 oz. (2976 g.).\nTen minutes later Twin B pre-\nsented as a breech and was also delivered without any\ntrouble; he weighed 4 lb. 6 oz. (I984 g.).\nThe first-\nbom was a healthy baby, but the second was 'slightly\nshocked' and jaundiced, and was placed in an oxygen\ncot; the mother did not see him until IO days later.\nThe only information available about the afterbirth is\nfrom the midwife's record, which refers to, 'binovular\nplacenta and membranes complete'.\nThe twins were both on bottles when they were taken\nhome from hospital at 3 weeks of age, and their sub-\nsequent progress was recorded by the health visitor.\nTwin B was a lazy placid baby, and great difficulty was\nexperienced in getting him to suck; it was realized from\nthe outset that something was wrong, and after getting\nopinions from several doctors the parents took him to\nthe Hospital for Sick Children, Great Ormond Street,\nwhen he was 14 months old.\nThe consultant there\nconsidered he was microcephalic, obviously retarded,\nand possibly with impaired vision, and recommended\nre-examination after a lapse of twelve months.\nBefore\nthis time, however, his management had become such\na problem that he was admitted to hospital; he was\nthen 21 months old. He was diagnosed as a 'microce-\nphalic idiot with spastic paralysis of the lower limbs'\nand transferred to a colony for mental defectives four\nyears later; and there he has remained. On admission\nto the colony he was a 'helpless incontinent bedridden\nmicrocephalic idiot' who had no awareness of what\nwas going on around him, and his mental age was\nassessed at about 3 months.\nThe only change in his condition has been in the\ncharacter of his frequent epileptic seizures; at first these\nwere petit mal, but since the age of I5 years tonic and\ngrand mal seizures have predominated"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1114
encoding: FLOAT32
metadata:
{"title": "Discordance in Monozygotic Twins: One Diabetic, the Other Idiot with Neurological Abnormalities*", "chroma:document": "Due to his\ncomplete inability to co-operate, he is still fed on a\nliquid diet, and is taking phenobarbitone and primi-\ndone mysoline.\nHis only illnesses have been mild\nattacks of measles at 9 months, chicken-pox at 21 months,\nand otitis media at the age of 8 years. At no time have\nreducing substances been found in his urine, and a\nglucose tolerance test is within normal limits. Examina-\n88\n* Received August 27, 1963.\nt This work was done during the author's tenure of a Nuffield\nDominion Travelling Fellowship.\n$ Present address: Depts. of Genetics and Psychiatry, University\nof Queensland, Brisbane, Queensland, Australia."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1115
encoding: FLOAT32
metadata:
{"title": "Blood Groups in the Philippines*t", "chroma:document": "7. med. Genet. (I964).\nI, 107.\nBlood Groups in the Philippines*t\nG. R. FRASER,+ E. R. GIBLETT, E. STRANSKY, and A. G. MOTULSKY\nFrom the Department of Medicine and Genetics, University of Washington, Seattle; King Country Central Blood Bank,\nSeattle, and the Department of Pediatrics, Philippine General Hospital, Manila, Philippines\nDuring I960 blood samples were obtained from\n413 adult Philippinos living in Manila but origi-\nnating from\nall parts of the island (Motulsky,\nStransky, and Fraser,\nI964).\nThe main object\nof this study was to determine the incidence of\nabnormal haemoglobins and G6PD deficiency but\nthe opportunity was\nalso taken to\ncharacterize\nthe blood and serum group frequencies of this\npopulation.\nBlood Groups\nABO System.\nBlood groups following ABO\nsystem are set out in Table I.\nTABLE I\nABO\nNumbers\nFrequency\nSystem\n0\n183\no0454\nA\nI04\n0-258\nB\n92\n0-228\nAB\n24\no-o6o\n403\nThe gene frequencies were determined by the\nmethod of Race and Sanger (I962): A = OI7;\nB = OI5; 0 = o 58.\nThe value of x' for one degree of freedom, based\non the differences between the observed and ex-\npected numbers of AB, is 0-39, showing an ex-\ntremely good fit.\nThese gene frequencies are in good agreement\nwith the very large sample of Atienza\n(1955):\nA = o i68; B = o i6o; 0 = o-672.\n* Received February 6, I964.\nt This study was supported by U.S. Public Health Service Grants\nH 309I and H 5780.\nt Present address: Department of Ophthalmology.\nRoyal College\nof Surgeons, Lincoln's Inn Fields, London, W.C.2.\nMNSs System.\n(Table II).\nand anti-s sera were used.\nAnti-M, anti-N,\nTABLE II\nGenotypes\nNumber\nNumber\nObserved\nExpected\nMMSS\n3\n4-3\nMMSs, MMss\nII9\n129-4\nMNSS\n7\n5.2\nMNss, MNSs\n213\n1917\nNNSS\nI\n'-5\nNNSs, NNss\n60\n70-9\nThe chromosome frequencies were\ncalculated\naccording to the methods of Mourant (I954) as:\nMS = O0103; Ms = 0473; NS =o-o62; Ns =\n0362.\nThe fit is not very good, reflecting the hetero-\ngeneous origin of the sample.\nThe X2 value for\none degree of freedom for the MN frequencies\nalone is 5-5 and for the above table, including Ss,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1116
encoding: FLOAT32
metadata:
{"title": "Blood Groups in the Philippines*t", "chroma:document": "is 6i for two degrees of freedom (o 05 > p > 0 OI\nin both cases).\nThese frequencies are somewhat\nsimilar to those for Chinese (Miller, Rosenfield,\nand Vogel, I95I).\nRhesus System.\nAnti-D, anti-C, anti-E, and\nanti-c sera were used and tests were done with\nanti-Du on all those persons negative with anti-D\n(Table III).\nGene frequencies were estimated by a suitable\nmodification of the methods of Mourant (1954):\nR1 + Rul (CDe + CDue) = o08Io; R, (cDE)=\n0-092; R2 (CDE) = o-o65; r (cde) = o0033.\nThese figures agree reasonably well with those\nof Simmons and Graydon (1945).\nThese authors,\nhowever, did not use anti-c and were therefore\nunable to identify the R, chromosome.\nThe frequency of Ru1 or CDue may be estimated\nas i/i8 of the frequency of R, + Ru1 (= 0o045),\nsince one case with the genotype CDue/cde and 17\nwith CDe/cde were found.\nThis would give a\nfrequency of R, of o0765.\nI07"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1117
encoding: FLOAT32
metadata:
{"title": "Review Article Profound Childhood Deafness*", "chroma:document": "Review Article\nJ. med. Genet. (I964).\nI, II8.\nProfound Childhood Deafness*\nG. R. FRASER\nFrom the Godfrey Robinson Memorial Unit, Department of Ophthalmology, Royal College of Surgeons, London W.C.2\n'It will be a great step forward whn the physician takes part in the work for defec-\ntives who have hitherto been entrusted wholly to teachers in schools.... The prob-\nlems of deafness are deeper and more complex, if not more important, than those of\nblindness. Deafness is a much worse misfortune.\nFor it means loss of the most vital\nstimulus-the sound of the voice-that brings language, sets thought astir and keeps\nus in the intellectual company of man.'\nFrom The Deaf Child,\nby J. Kerr Love, Simpkin and Co., London, I9Ii.\nDefinition and Introduction\nThe term profound childhood deafness is used\nin preference to the old-established one of deaf-\nmutism, since it is now clear that, contrary to the\naccepted dogma current from antiquity to recent\ntimes, mutism is not due to a pathological lesion\nof the speech apparatus associated with failure to\nhear, but to a lack of suitable training which can\noften be remedied.\nProfound childhood deafness\nis a socio-educational entity and may be defined as\ndeafness with an early enough onset and of suffi-\ncient degree to necessitate the use of special or\nsupplementary methods for the learning of speech.\nThis definition excludes the very common deaf-\nness of adult life often inherited in a dominant\nmanner, whether conductive (otosclerosis) or per-\nceptive.\nMany rare genetical syndromes are also\nexcluded of which deafness of a less severe nature\nand/or of late onset is a component part.\nThese\ninclude such recessive syndromes as perceptive\ndeafness,\natypical\nretinitis\npigmentosa,\nchronic\npolyneuritis and ataxia (Refsum, Salomonsen, and\nSkatvedt,\n1949),\nand\nperceptive\ndeafness\nwith\noptic atrophy and diabetes (Shaw and Duncan,\nI958), with diabetes mellitus, retinal degeneration,\nand\nobesity\n(Alstrom,\nHallgren,\nNilsson,\nand\nAsander,\nI959) with congenital\nfacial paralysis\n(Thomas,\n1898;"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1118
encoding: FLOAT32
metadata:
{"title": "Review Article Profound Childhood Deafness*", "chroma:document": "1898;\nCadwalader,\nI922), and many\nothers; in addition, the dominant syndromes of\nperceptive deafness with nephritis (Alport, 1927),\nwith auditory neurofibromata (Gardner and Frazier,\nI930), and with ectodermal dysplasia (Helweg-\n* Received July 20, x964.\nLarsen and Ludvigsen, I946; Robinson, Miller,\nand Bensimon, I962) and others, and of conductive\ndeafness with osteogenesis imperfecta (van der\nHoeve and de Kleijn, I9I7).\nOccasionally pro-\nfound childhood deafness will occur in association\nwith one of these conditions; conversely, persons\nwill occasionally suffer from only mild losses of\nhearing in association with syndromes more usually\nassociated with profound childhood deafness. No\nbiological classification can be expected to follow\nvery closely lines of demarcation defined on the\nbasis of socio-educational criteria.\nThere is even\nno absolute correlation between educational seg-\nregation and degree of hearing loss.\nThus severe\nhearing loss in infancy is sometimes compatible\nwith normal education, and special schooling may\noccasionally be necessary with a relatively mild\ndeafness.\nOther,\nas yet ill-understood, factors\nmay condition the extent of the child's adaptation\nto the hearing loss.\nMany other difficulties stand in the way of an\nunambiguous biological classification of profound\nchildhood deafness.\nThus an unequivocal dif-\nferentiation between congenital and postnatal onset\nis often impossible, since the diagnosis of deafness\nmay only be made when speech fails to develop\nnormally in the first two years of life or even later.\nFurthermore,\ncongenital and postnatal\ndeafness\ncannot be equated simply with genetical and ac-\nquired forms.\nCongenital deafness may be due to\nmaternal rubella, and, owing to diagnostic diffi-\nculties in infancy, evidence is lacking as to whether\ngenetical\nchildhood\ndeafness\nis\nin\nfact usually\ncongenital\nor\nrapidly progressive\nin\nearly\nlife.\nII8"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1119
encoding: FLOAT32
metadata:
{"title": "Blood and Serum Groups in Taiwan*", "chroma:document": "J. med. Genet. (I965).\n2, 2I.\nBlood and Serum Groups in Taiwan*\nG. R. FRASERt, E. R. GIBLETT, TING-CHIEN LEE, and A. G. MOTULSKY\nFrom the Departments of Medicine and Genetics, University of Washington, the King County Central Blood Bank,\nSeattle, Washington, and the Department of Pediatrics, National Taiwan College of Medicine, Taipeh, Taiwan\nDuring I960 blood samples were collected in\nTaiwan from 300 male adolescents and adults in\nthe capital town of Taipeh and in the small com-\nmunities of Chi-Chi (centre of Island) and Chung-\nLi (N.W.)\n(Motulsky, Lee, and\nFraser,\nI964).\nThe donors from Taipeh originated in all parts\nof Taiwan.\nThe main object of the study was to\ninvestigate the distribution of abnormal haemo-\nglobins and G6PD deficiency but the opportunity\nwas also taken of characterizing blood and serum\ngroups of this population.\nAn attempt was made\nto restrict this study to the main group of Formosan\nChinese who had imnigrated from Fukien pro-\nvince on the mainland in the I7th century.\nBlood Groups\nThe blood groups are set out in Table I.\nTABLE I\nABO\nTaipeh\nChi-Chi\nChung-Li\nTotal\n0\n46\n6i\n44\n15I\nA\n28\n20\n31\n79\nB\nI9\nI5\ni6\n50\nAB\n5\n4\nII\n20\n98\n100\n102\n300\nThe gene frequencies (Table II) were calculated\nby the method described by Race and\nSanger\n(I962) and a X2 value for one degree of freedom\nwas derived, based on the difference between the\nobserved and expected numbers of AB individuals.\nTABLE II\nGENE FREQUENCIES\nTaipeh\no-I8\nO-I3\no-69\n0-03\nChi-Chi\n0091\nO079\nI-*Is\nChung-Li\n0-21\nO-II\no-68\n4.45\nA G test was performed to test heterogeneity\nbetween the samples by the method of Woolf\n(I957). A value of 8-42 was obtained which is not\nsignificant at the 5 % level if we assume that this\nvalue follows the distribution of X2 on four degrees\nof freedom.\nIt is legitimate, therefore, to pool the sample and\ncalculate gene frequencies for the whole group.\nThe same method was employed and gave the\nfollowing gene frequencies: A = o1I7; B = o-II;\n0 = 072 (x2 = 5.37).\nThese figures do not agree very well with pub-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1120
encoding: FLOAT32
metadata:
{"title": "Blood and Serum Groups in Taiwan*", "chroma:document": "lished data for Formosa (Mourant, Koped, and\nDomaniewska-Sobczak\nI958)\nin\nthat\nthe\nfre-\nquency of B in most previous samples has been\nhigher.\nMNSs Groups.\nAnti-M, anti-N, and anti-s\nsera were used, but there were no negative re-\nactors with the last.\nOnly the frequencies of the\nalleles M and N can, therefore, be considered\n(Table III).\nTABLE III\nTaipeh\nChi-Chi\nChung-Li\nTotal\nMM\n25\n32\n32\n89\nMN\n5I\n52\n52\n155\nNN\n22\nI5\nI8\n55\nThe gene frequencies are given in Table IV.\nTABLE IV\nGENE FREQUENCIES\nM\n04585\n3o-587\n0-569\n04557\nN\n0-48:5\n0 413\n0-431\nO 443\nXi\n0-17\no-67\nO-I6\n1I84\nThe G test for heterogeneity was again per-\nformed and gave a value of X% of 2 I6. The values\nwere, therefore, combined for a pooled estimate\nof M and N frequencies.\n21\nReceived February 6, I964.\nv This study was supported by U.S. Public Health Service Grants\nH 309I and H 5780.\nt Present address: Department of Ophthalnology, Royal College of\nSurgeons, Lincoln's Inn Fields, London W.C.2."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1121
encoding: FLOAT32
metadata:
{"title": "Congenital Hereditary Lymphoedema*", "chroma:document": "J. med. Genet. (I965).\n2, 93.\nCongenital Hereditary Lymphoedema*\nJOHN R. ESTERLY\nFrom Division of Medical Genetics, Department of Medicine and Department of Pathology, Johns Hopkins University\nSchool of Medicine, Baltimore, Maryland, U.S.A.\nOccasionally\nprimary\nlymphoedema\nis\nboth\ncongenital and familial. The first reports by Nonne\n(I89I) and Milroy (I892) were of families in which\nthe oedema was present at birth and was described\nas non-tender chronic swelling of the lower ex-\ntremities, not influencing the general health of the\nsubjects or their longevity.\nThis is distinguished\nfrom the familial form of lymphoedema praecox\n(Letessier, I865; Meige, I898, I899) characterized\nby an abrupt onset, most often at puberty, and\nfrequently associated with signs and symptoms of\nacute inflammation. The congenital form of familial\nlymphoedema is usually called Milroy's disease and\nthe form with later onset, Meige's disease.\nThe oedema of the affected individuals in the\nfamily described in this report is typical of the\ncondition described by Milroy and is of genetic\ninterest for several reasons, including the presence\nof an apparent\n'skipped'\ngeneration.\nLinkage\nstudies were practical in view of the size of the\nkindred and the number of affected persons.\nReceived January 4, I965.\n* This study was supported in part by U.S.P.H. Research Grant\nNo. H-3313\nFamily History\nThere were i5 affected individuals in three generations\nof this family including, by history, a stillbirth.\nIn\naddition, the family tree for three preceding generations\nwas known with a total of 245 members (Fig. i). There\nwas no history of consanguinity nor any suspicion of\naffected persons outside the progeny of I.2 (Fig. 2).\nThere was no evidence of concomitant lymphoedema\npraecox.\nThe proposita (II.5) was a 35-year-old white woman\nof excellent general health and strength, with bilateral\nswelling of the legs and feet, which had been present\nsince birth.\nThere was no history of any pain or in-\nflammation\nassociated\nwith\nthe oedema, though\nit"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1122
encoding: FLOAT32
metadata:
{"title": "Congenital Hereditary Lymphoedema*", "chroma:document": "it\nprogressed in severity during the first decade of life.\nOn several occasions significant but incomplete reduc-\ntion in the swelling had accompanied prolonged bed-\nrest.\nThe physical examination was within normal\nlimits save for the gross enlargement of her lower\nextremities.\nThe massive oedema extended above the\nknees and pitted with ease (Fig. 3). The overlying skin\nhad no trophic changes and was impressively warm to\ntouch.\nThere was a constant tachycardia (90-iOO a\nminute).\nRadiographs and laboratory tests were not\nremarkable;\nin particular, serum proteins and renal\nfunction were normal.\nThe mother of the proposita, the probable mutant\n*\nAFFECTED\nO\nNORMAL\no\nSTILLBIRTHS\not PROPOSITA\nFIG. I. Pedigree chart.\n93\n-MG1"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1123
encoding: FLOAT32
metadata:
{"title": "Smallpox Vaccination: ABO and Rhesus Blood Groups", "chroma:document": "J. med. Genet. (I965).\n2, I22.\nSmallpox Vaccination: ABO and Rhesus Blood Groups\nGEOFFREY J. BOURKE, NOEL CLARKE,* and EDWARD H. THORNTONt\nFrom the Departments of Social Medicine, Pathology, and Statistics, Trinity College, Dublin, Eire\nThe hypothesis has been advanced (Pettenkofer\nand Bickerich, I96o) that vaccinia virus and, by\nimplication, variola virus contain antigenic proper-\nties similar to human blood group A substance.\nVogel, Pettenkofer, and Helmbold (I960) assert\nthat possession by\nvariola\nvirus of a material\nserologically resembling human blood group A\nsubstance may have been responsible, in\npart,\nfor determining the present-day global distribution\nof the human ABO blood groups.\nPettenkofer,\nStoss, Helmbold, and Vogel (I962) claim that,\nin smallpox infection, persons with blood groups\nB or 0, in whom anti-A normally occurs, have an\nimmunological advantage over persons of blood\ngroups A and, presumably, AB who lack this\nantibody.\nIn support of their work these authors\nreport that of I03 Germans with severe post-\nvaccination reactions (more than go % encephalitis)\na\nsignificantly\nhigher\nproportion\nbelonged\nto\nblood groups A and AB; moreover, in India and\nPakistan, among 358 subjects with severe smallpox\nscars a similar excess of blood groups A and AB\nwas demonstrated.\nIf the above hypothesis is correct, and recent\nexperimental work (Harris, Harrison, and Rondle,\nI963) suggests that it is not, one would expect,\namong a group of individuals vaccinated against\nsmallpox that: (i) persons of blood groups B or 0,\nwho\npossess anti-A substance, would be more\nlikely to\nresist the procedure, and present an\nunsuccessful vaccination, than groups A or AB;\n(ii) persons of blood groups A or AB, who do not\npossess anti-A in their serum, would have a more\nsevere clinical response, and might be expected to\nproduce a larger lesion following successful vac-\ncination, and to have a greater\nscar area from\nprevious vaccination than persons of blood groups\nB or 0.\nThe present study is concerned with the distri-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1124
encoding: FLOAT32
metadata:
{"title": "Smallpox Vaccination: ABO and Rhesus Blood Groups", "chroma:document": "bution of the ABO and Rhesus blood groups\namong a number of university students vaccinated\nagainst smallpox.\nThe materials and methods,\nreading of results, and observations on clinical\nreaction have already been outlined (Bourke and\nClarke, I963, 1964).\nResults\nThe results relate tO 78I persons of the 994\nincluded in the original study, on whom ABO\nand\nRhesus\nblood\ngroup\ndeterminations\nwere\nmade by a tube technique.\nThese 78I subjects\nhave been found to be fully representative of the\noriginal group, for all pertinent data.\nOf these\n78I\nsubjects,\n6I2\nhad\nsuccessful\nvaccinations\n(Tables I and III), and of these 6I2, 565 completed\nquestionnaires\nrelating to\ntheir symptomatology\nand to the severity of clinical reaction (Tables IV\nand V).\nIt will be seen from Table I that there is no\nsignificant\ndifference between any of the ABO\nand Rhesus blood groups in the proportion falling\ninto the successful and unsuccessful categories.\nMoreover, when groups A and AB are combined\nand compared with groups B and 0 taken together,\nthe\nx2\nvalue\nis\nreduced\n(X2 = o038o,\nn = I)\no7o > p > o.50).\nSince the outcome of vaccina-\ntion may be affected by country of origin and the\ntime since the previous vaccination, it was necessary\nto standardize for these factors; such corrections\nwere found not to alter the original, negative,\nconclusion.\nTable II shows that the scar area varies little\nbetween the ABO groups, and that there are no\nsignificant\ndifferences\nbetween\nthe\nmean\nscar\narea of the Rhesus positive and negative groups.\nSimilarly, in Table III the mean lesion size shows\nlittle change from one blood group to another.\nCorrections for period since last vaccination for\nboth scar area and lesion size do not alter the\nfindings.\nTable IV demonstrates that in three instances\nstatistically significant associations between blood\nI22\nReceived July 30, 1964.\n* Present address: Department of Pathology, University College,\nDublin.\nt Present address: Middle East Technical University, Ankara."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1125
encoding: FLOAT32
metadata:
{"title": "Family Studies and Aetiology of Club Foot", "chroma:document": "J. med. Genet. (I965).\n2, 227.\nFamily Studies and Aetiology of Club Foot\nRUTH WYNNE-DAVIES\nFrom the Medical Research Council, Research Group on Genetic Problems in Orthopaedic Disease, Department of\nOrthopaedic Surgery, University of Edinburgh\nCongenital club foot and talipes are used to\ndescribe various abnormalities of the foot in the\nnewborn child.\nThe most serious of these\nis\ntalipes\nequinovarus\nin\nwhich\nthere\nis\nplantar\nflexion of the ankle and inversion of the foot.\nThis deformity is difficult to treat, having a marked\ntendency to recur, and causes a real disability.\nAbout\nhalf\nthe\ncases\nare\nbilaterally\naffected.\nPatients frequently attend hospital for the\nfirst\nIo-i5 years of life. A long-term follow up of the\nresults of treatment of patients with talipes equino-\nvarus\nhas\nbeen\nreported\nelsewhere\n(Wynne-\nDavies, I964a).\nThe family findings in a series of\npatients with talipes equinovarus, mild (postural)\ntalipes equinovarus, talipes\ncalcaneo-valgus, and\nmetatarsus varus have been reported in summary\nform (Wynne-Davies, I964b).\nIn this paper the\nfamily data, especially that on talipes equinovarus,\nare presented and discussed in more detail.\nCases\nsecondary\nto\nspina\nbifida,\ncerebral\npalsy,\nand\narthrogryposis are not included.\nSubjects and Method\nThe present study is based on patients attending\nthe Princess Elizabeth Orthopaedic Hospital, Exeter,\nwho were born in I940-6I.\nThis Orthopaedic Hospital serves the greater part\nof the largely rural county of Devon (excluding the\nPlymouth area), and there is available a stable popula-\ntion, making the tracing of families\nrelatively easy.\nThe orthopaedic service is based on the hospital at\nExeter, and out-patient\nclinics are held at intervals\nof one, two, or four weeks throughout the county-at\nExeter, Torquay, Newton Abbot, Okehampton, Barn-\nstaple,\nBideford,\nHoniton, and\nTiverton.\nPatients\nattending currently for treatment during I96I were\nseen at one of their routine visits to a clinic.\nFormer\npatients were first approached by letter and were then"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1126
encoding: FLOAT32
metadata:
{"title": "Family Studies and Aetiology of Club Foot", "chroma:document": "seen at the outlying clinic which they had previously\nattended. A family history was taken from the individual,\nor where more appropriate, a parent, and nearly all\naffected relatives were personally examined.\n(Details\nof families with an affected first-degree\nrelative are\nReceived February 22, I965.\ngiven in Appendix A.) In the only two instances where\nan affected first-degree relative was not seen personally,\nthere was reliable medical evidence of the deformity\n(Index patients 30 and io8).\nRelatives stated to be\nnormal were not specially examined, though in fact\nmany were seen, as they attended with the patient.\nIn the case of talipes equinovarus, with the standard\nof school and other medical services easily available\nin this country, it is most unlikely that such a severe\ndeformity would pass unnoticed or ignored, and the\nascertainment of affected relatives will be nearly com-\nplete. In the case of postural talipes equinovarus, talipes\ncalcaneo-valgus, and metatarsus varus, relatives were\nnot examined since these deformities almost invariably\ndisappear and retrospective diagnosis is not possible.\nOnly those cases confirmed by medical evidence have\nbeen classed as affected, but obviously many\ncases\nnever reach hospital, and the ascertainment of affected\nrelatives will be incomplete.\nFor talipes equinovarus, I63 case sheets were available\nfor patients born from I940 to I96I.\nOf these, I44\nwere traced of whom I33 were seen personally and\nii replied to questionnaires.\nOf the remaining\nI9,\n13 were not traced, 2 were foster children, and 4 refused\nto co-operate.\nIndex patients with the three other\ncommon forms of talipes were those born between\nI948 and I96I; 31 patients were traced with postural\nequinovarus, 74 with talipes calcaneo-valgus, and 72\nwith metatarsus varus.\nResults\nIncidence.\nSince\nthe\nPrincess\nElizabeth\nOrthopaedic\nHospital\nis\nthe\nonly\northopaedic\nhospital in the area and both private and National\nHealth\nService\npatients\nhave\nbeen\nincluded,\nascertainment of cases needing hospital treatment"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1127
encoding: FLOAT32
metadata:
{"title": "Family Studies and Aetiology of Club Foot", "chroma:document": "will be nearly complete.\nComparing the numbers\nof patients with the Registrar General's figures\nfor all live births in the area over the same period,\nthe incidences of the different forms of the mal-\nformation\nwere:\ntalipes\nequinovarus-i -24\nper\niooo live births (males\ni 62 per IooO, females\no-8o);\npostural\ntalipes\nequinovarus-o 5o\nper\nIooO live births (males 0-24 per Ioo, females\no-78); talipes calcaneo-valgus\n-o9 per IooO live\nbirths (males o-o7 per IooO, females o-33); meta-\n227"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1128
encoding: FLOAT32
metadata:
{"title": "Epidermolysis Bullosa", "chroma:document": "J. med. Genet. (I965).\n2, 233.\nEpidermolysis Bullosa\nB. C. CLARE DAVISON\nFrom Medical Research Council, Population Genetics Research Unit, Old Road, Headington, Oxford\nThe term epidermolysis bullosa is applied to\na group of conditions where vesicles occur most\ncommonly on the skin but sometimes on mucous\nmembranes.\nThe\ncontent of these vesicles\nis\nserous but may become turbid or haemorrhagic,\nand secondary infection sometimes occurs.\nApart\nfrom a type that may follow administration of\nsulphonamides (Bloom, I953),\nall forms appear\nto be genetically determined at single gene loci.\nFurther,\nall cases appear to be determined by\nautosomal mutations, with the exception of the\npatients in one family where epidermolysis bullosa\nappears as part of a widespread syndrome deter-\nmined by a sex-linked gene.\nThis family first\ndescribed by Mendes da Costa and Van der Valk\n(I908) has subsequently been reported by various\nauthors over a number of years under varying\ntitles: perhaps the most generally used\nat the\npresent\ntime\nbeing\ndystrophia\nbullosa,\ntypus\nmaculatus (Woerdeman, I958).\nDetermination\nby\nautosomal\ndominant\nand\nrecessive genes has long been known and, as is\nusual in other traits where this phenomenon is\nfound, the recessive forms are on the whole more\nsevere in their effects.\nHowever, in epidermolysis\nbullosa there appears to be considerable overlapping\nin severity of forms determined in the two ways.\nThe most distinctive clinical finding is whether\nor not\nscarring follows\nthe\nhealing of lesions\n(Pearson,\nI962;\nSchnyder, Jung, and\nSalamon,\nI964).\nThis division corresponds to 'dystrophic'\nand 'simplex' (non-dystrophic) forms.\nIt has been\ndemonstrated by Johnson and Test (1946) that in\nthe simplex type the blisters form in the epidermis\nor are subcorneal, while Touraine (I942) showed\nthat in the dystrophic form the blister formation\nwas subepidermal.\nParent Investigation\nAscertainment of Cases in the Oxford Area.\nIn I962 all general practitioners in the Oxford\nReceived February IO, I965.\n-MG2\nRegional\nHospital\nBoard"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1129
encoding: FLOAT32
metadata:
{"title": "Epidermolysis Bullosa", "chroma:document": "Board\narea\nwere\nasked\nto\nnotify cases of epidermolysis bullosa.\nFirst noti-\nfication of I2 cases was from this source.\nIn\naddition the six consultant dermatologists in the\narea notified all cases seen by them and subse-\nquently they reported new cases as seen. Twenty-\ntwo index patients first became known through\ndermatologists.\nFour individuals could not be traced and in\ntwo notified patients the diagnosis was not con-\nfirmed, so that in all 28 families were ascertained\nthrough index cases.\nIt was realized that ascertain-\nment was incomplete and it was decided not to\nmake more determined\nefforts\nas\nit was\nsoon\nobvious that all severely affected cases were known\nto dermatologists while many subjects with milder\ntypes\nsimply regarded\nthemselves\nas prone\nto\nblistering and never attended a doctor.\nIn the\nfollowing\ndiscussions\nof\nclinical\naspects,\nan\nadditional\nfamily\nseen\nin Northern\nIreland\nis\nconsidered, so that in all 29 families were seen.\nIn all these families at least one member had\nbeen seen by a dermatologist.\nIn i0, only one\nmember was affected. In the I9 families with more\nthan one affected the pedigree suggested dominant\ngene inheritance in 17 and recessive gene inheritance\nin two.\nClinico-genetic\nGrouping of Cases.\nThe\nmost clear-cut division of cases where more than\none case occurred is on the basis of mode of inherit-\nance.\nAs\nalready\nnoted,\nthe\nprimary\nclinical\nseparation is on the basis of severity-scarring or\ndystrophic and non-scarring or simplex.\nIt seems\nlikely that the recessive form is always dystrophic,\nnever simplex, and that the dominant form is more\ncommonly\nmilder\nor\nsimpJex.\nThe\ndominant\nsimplex form appears to have two variants, one\nwhere only the feet are affected (Cockayne, 1938),\nand one where the blisters are widespread though\nmost commonly occurring on the extremities. The\nfamily cases therefore\nfall into three (or four)\ngroups-dominant simplex (dominant Cockayne),\ndominant\ndystrophic,\nand\nrecessive\ndystrophic.\n-33"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1130
encoding: FLOAT32
metadata:
{"title": "ABO and Rhesus Blood Group Distribution Patients Attending Venereal Diseases Clinics", "chroma:document": "J. med. Genet. (I966).\n3, IO.\nABO and Rhesus Blood Group Distribution among\nPatients Attending Venereal Diseases Clinics\nC. B. S. SCHOFIELD\nFrom the Department of Venereology, clo Ruchill Hospital, Glasgow\nIn one of the earliest papers on blood groups in\n-disease\nAlexander\n(192I),\nwhile\ninvestigating\nmalignancy in Dundee, used as controls 50 cases of\n'active syphilis', together with a like number of\nnormal subjects and of patients with tuberculosis.\nHe did not find any significant differences, and\nthe frequencies of the 'active syphilis' group and\nthe normals were almost\nidentical.\nApart from\nPoehlmann (I934), who investigated 300 patients\nwith positive Wassermann reactions and found them\nto have the same ABO blood group distribution as\namong the general Munich population, there would\nnot appear to be any published investigations into\nthe\ndistribution\nof\nblood\ngroups\nin\nvenereal\ndiseases, and this investigation was planned to find\nout if there were any differences in the commoner\nconditions for which patients attend a venereal\ndiseases clinic.\nPresent Investigation\nInformation as to the ABO and Rhesus blood groups\nof patients\nattending\nthe\nclinics\nat Newcastle and\nTynemouth between July I956\nand\nOctober\n1958,\ntogether\nwith\nclinical manifestations and\nsex, were\nrecorded on punch-cards for later analysis.\nControls for the ABO blood groups for the Newcastle\nupon Tyne Hospital Region already\nexist.\nRoberts\n(I953), using material supplied by the Regional Blood\nTransfusion Service, analysed a total of 54,579 record\n,cards of blood donors for ABO groups. The frequencies\nhe found are as follows: 0, 49-484%; A, 38-627%; B,\n9-I26%; AB, 2-763%, and these figures have been used\nin\nthis\ninvestigation,\nbut unfortunately there\nis no\nsimilar control for the Rhesus (D) distribution in this\narea.\nResults\n2,575 sera were tested, I,63I (63%) from men\nReceived September 29, I965.\nand 944 (37%) from women. Approximately 55%\nof the patients were suffering from syphilis, I4-5%\nfrom\ngonorrhoea,\nI3-5%\nfrom\nnon-gonococcal"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1131
encoding: FLOAT32
metadata:
{"title": "ABO and Rhesus Blood Group Distribution Patients Attending Venereal Diseases Clinics", "chroma:document": "urethritis, while the remainder (about I7%) were\nwithout evidence of venereal disease (NVD). The\nfrequency distributions of the blood groups and\ntheir incidence relative to one another for these\nmain classifications are set out in Table I.\nAlthough there are some differences in blood\ngroup distribution, these differences are without\nstatistical significance.\nThe vast majority of all\nfemale patients and those men with syphilis were\nnative to Tyneside, while a number of men with\ngonorrhoea\nand\nnon-gonococcal\nurethritis\nwere\nperipatetic.\nIn view of the possibility that the syphilis group\nwas not homogeneous, it was broken down into the\nanatomical diagnoses.\nThere was no significant difference in the ABO\ndistribution among patients with contagious syphi-\nlis, neuro-syphilis, or benign tertiary syphilis, or of\nany of the clinical entities within these groups, but\nwhen patients with cardiovascular\nsyphilis were\ndivided arbitrarily into those with aortic valvular\ndamage (aortic incompetence) and those without\n(aortitis and aneurysms of the aorta), as shown in\nTable II, it was found that the excess of male\npatients with blood group A and suffering from\naortitis and/or aneurysms of the aorta had significant\nstatistical difference when compared with (a) the\ncontrols, (b) with women having the same com-\nplaint, and (c) with men and women suffering from\naortic incompetence.\nWhile there was a wide range in the incidence of\nRhesus positives, the differences were not significant\nin any entity.\nDiscussion\nThe ABO frequencies of men and women, though\nnot parallel, do not differ significantly from the\nIOI"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1132
encoding: FLOAT32
metadata:
{"title": "The Use of the Surname Genetic Marker in Wales", "chroma:document": "J. med. Genet. (I966).\n3, 203.\nThe Use of the Surname as a Genetic Marker in Wales\nDAVID J. B. ASHLEY and H. DUNCAN DAVIES\nFrom Morriston Hospital, Swansea\nTo some extent the population of the Principality\nof Wales, especially the industrial areas of South\nEast\nWales,\nis\nheterogeneous,\ncomprising\nthe\nWelsh, descended from the long-standing inhabi-\ntants of this part of the world and the immigrants\nwho have arrived mostly within the past hundred\nor so years. The two populations live in the same\nphysical environment and, in the industrial social\nmilieu, tend to work side by side in the factories and\nmills, though it is possible that the traditional craft\nof coal-mining claims a higher proportion of Welsh-\nmen than do some of the newer industries.\nIt would be interesting and useful if these two\npopulations could be identified by some easy marker\nso that the proportions of Welsh and non-Welsh\ncould be assessed in relation to their illnesses,\nimmunities, and other possibly genetically deter-\nmined traits.\nThe typical Welshman tends to be\nshort in stature, long-headed, black-haired, and\npale-faced, and many of us can readily call to mind\nsuch an individual. Unfortunately, however, many\nmen\nof English\ndescent\nhave\nsimilar\nphysical\ncharacteristics and many Welshmen are burly of\nfigure and ruddy of complexion.\nPhysical assess-\nment is a notoriously unreliable method of assigning\nindividual people into broad categories if a large\nblock of 'middlemen' is not to be avoided, and it is\nextremely difficult, vide the problems of the colour\nbar,\nto define exact parameters which may be\napplied in such a context.\nThe second character\nof the Welshman,\nnot commonly\nacquired by\nimmigrants, is the use of the Welsh language.\nIt\nmay fairly be suggested that one who speaks Welsh\nis a Welshman, the occasional exception serving\nonly to underline the general truth of the assertion.\nIn the present series only 9 of 231 people born\noutside Wales were Welsh speaking. Command of\nthe Welsh language is, however, rarely recorded as\na"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1133
encoding: FLOAT32
metadata:
{"title": "The Use of the Surname Genetic Marker in Wales", "chroma:document": "a\ndescriptive item in hospital\ncase notes, with\nwhich\nwe\nare\nprincipally\nconcerned,\nand\nthe\ncharacter becomes useless for retrospective investi-\ngation and hardly more\nuseful\nfor\nprospective\nReceived September 14, I965.\ninvestigations involving more than a small number\nof people.\nIn very large-scale inquiries involving\nthe whole of the country, the proportion of Welsh-\nspeaking people in different areas may prove useful\nwhere whole counties can be taken as the units of\ninvestigation.\nFor\nexample,\nin\nthe\nCounty\nof\nCarmarthen more than 70% of the men over the\nage of 45 claim to be Welsh-speaking, whereas in\nthe County of Brecknock 36% do so and in Mon-\nmouth only 5.5% speak this tongue.\nThe final, easily determined, character, and the\none on which this investigation is based, is the\nsurname. The surname can, in males, be regarded\nas a character inherited in the holandric manner.\nA man hands on his surname to his sons, as he does\nhis Y chromosome, and they in turn pass it on to\ntheir sons. The number of surnames in use among\nWelshmen is small, and each is characteristically\nderived from a Christian name: Davies, Evans,\nThomas, Williams, Owens, Roberts, and Phillips,\nby the simple use of the genitive case, and others,\nPrice, Pritchard, Pugh, and Parry, for example, by\nelision of the Welsh prefix Ap 'the son of'.\nIn\ncontrast English surnames most often derive from\nplace names, as does Ashley; from occupations,\nSmith, Weaver, Miller; or from nicknames, Arm-\nstrong, White, Black, and Small. The characteristic\nWelsh surnames have been used (Legon, i963) in\nan observation on the frequency of gastric carcinoma\nin the Welsh and non-Welsh inhabitants of North\nWales. The present investigation is an attempt to\nvalidate the use of this parameter as a marker by\nwhich the two components of a heterogeneous\npopulation may to some extent be separated.\nMethods and Procedures\nA questionnaire was circulated among a miscellaneous\ngroup of the male inhabitants of Swansea and the\nsurrounding districts. Each man was asked to give his"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1134
encoding: FLOAT32
metadata:
{"title": "The Use of the Surname Genetic Marker in Wales", "chroma:document": "name, address, and age, his mother's maiden name, the\nplace of birth of himself and his two parents, and\nwhether or not he and his parents were Welsh-speaking.\nIn all 558 completed forms were analysed.\nIn most\ncases all the information requested was available; in a\n203"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1135
encoding: FLOAT32
metadata:
{"title": "A Pair ofTwins, One ofwhom has Chronic Granulocytic Leukaemia", "chroma:document": "J. med. Genet. (I966).\n3, 2I7.\nA Pair ofTwins, One ofwhom has Chronic Granulocytic\nLeukaemia\nLESLEY DOUGAN*, IAN D. SCOTT, and H. J. WOODLIFF\nFrom the Cancer Council of Western Australia, the Department of Genetics, University of Western Australia, and the\nDepartment of Haematology, Royal Perth Hospital, Western Australia\nThe finding that one of our patients with chronic\ngranulocytic leukaemia had an apparently identical\ntwin brother led us to undertake genetic studies to\nestablish\nzygosity, and\nto study\ncarefully\ntheir\nhistory\nfor any\npossible leukaemogenic\nfactors.\nBone-marrow cells of the affected twin contained\nthe Ph' chromosome whereas those of his brother\ndid not (Woodliff and Dougan, I965).\nMaterial and Methods\nBlood was collected from the twins, one sib, and their\nparents by venepuncture (Fig.).\nBlood groups were determined by standard methods at\nthe Human\nGenetics\nUnit,\nUniversity\nof Wesstern\nAustralia.\nThe\nantisera used were\nanti-A, en l-A,\nanti-B, anti-AB, anti-C, anti-c, anti-D, ar,.;-E. anti-e,\nanti-Cw, aniti-Ew, anti-ET, anti-V, anti-M,anti-N., anti-S,\nanti-s,\nanti-Mia, anti-Vw, anti-Mg, anti-PL, anti-K,\nanti-k, anti-Kpb, anti-Kpa, anti-Lea, anti-Leb, anti_Fyb,\nanti-Lub, anti-Xga, anti-Vel, anti-Wra., anti-Dia, anti-jsa,\nanti-Jka, anti-Jkb, and anti-Fya. The Gm and Inv types\nwere done by courtesy of Dr. Arthur G. Steinberg.\nTransferrin and haptoglobin types were determined by\nvertical starch gel electrophoresis by the method of\nSmithies (I959). Serum alkaline phosphatase types were\nexamined by a modification of the method of Arfors,\nBeckman, and Lundin (I963), as previously described\n(I. D.\nScott and M. K.\nScott,\nI966, unpublished\nobservations).\nThe parents, the twins, and the younger sister were\ncarefully interviewed concerning their family history,\nand a standard questionnaire was completed for the\ntwins.\nResults\nGenetic Study.\nThe detailed findings of the\nblood group-Ing investigation and the examination\nof the serum genetic markers are given in Table I."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1136
encoding: FLOAT32
metadata:
{"title": "A Pair ofTwins, One ofwhom has Chronic Granulocytic Leukaemia", "chroma:document": "In addition, all subjects were found to be Cw(-),\nEW(_), V(-)., Mg(-)I VW(-)3 Vel(-)., Di(a-),\nWr(a-), and Js(a-).\nResults of the Gm typing\nshowed that I.2 was homozygous for the factors\nReceived April I8, I966.\nGm3'\nD13\n1, and that the subjects I.I, II.3, II.4, and\nII.5 were heterozygous Gm'/Gm 3 5,13,14\nAll sub-\njects were of the Inv phenotype Inv(i -).\nThe\nnomenclature is that proposed by a committee of\nW.H.O. (I965).\nFrom the results of the Gm typing and the\nfindings set out in Table I, the probability that this\npair of twins was monozygotic was calculated as\nsuggested by Dr.\nC. W. Cotterman (Race and\nSanger, I962), and is as shown in Table II.\nIt was calculated that the probability that the\ntwins were monozygotic was 0o995.\nPersonal and Family Histories\nThe twins E.F. and F.F. were bom at King Edward\nMemorial\nHospital\nfor Women,\nSubiaco,\nWestern\nAustralia, on March 30, 1928; the parents were Roman\nCatholics who had recently migrated to Australia from\nItaly.\nThis was the mother's third pregnancy and it\ncontinued to term.\nShe had no recollection of any\nantenatal X-ray examinations.\nF. was bom first as a\nvertex presentation and E. within the next few minutes\nby the breech.\nTheir early development was quite\nnormal and the first IO years were spent in an inner\nsuburb of metropolitan Perth. In I938, when the twins\nI\nb.lU\n1\n2\nb. 1921\nb.l1922\nd. 1922\n2\n1901\nb. 1901\n3\n4\nb.1928\nb.1928\n5\nb.1931\n0\nmale studied\n/$ifemcle studied\nmale with Ph+ chronic\nfemale not studied\nG\ngranulocytic leukoemia\ne\nFiG. Pedigree chart.\n217"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1137
encoding: FLOAT32
metadata:
{"title": "Review Article Fetal and Embryonic Haemoglobins", "chroma:document": "Review Article\nJournal of Medical Genetics (1973).\n10, 50.\nFetal and Embryonic Haemoglobins\nP. A. LORKIN\nMRC Abnormal Haemoglobin Unit, University Department of Biochemistry, Cambridge\nHaemoglobin has been the subject of intensive\nresearch for many years and is one of the most\nthoroughly understood of all protein molecules.\nThe amino-acid sequences of haemoglobins from\nmany species of animals have been determined\n(tabulated by Dayhoff, 1969) and the molecular\nstructures of horse and human haemoglobins have\nbeen determined in great detail by x-ray crystallo-\ngraphy (Perutz et al, 1968a and b; Perutz 1969).\nA\nmechanism of action of haemoglobin has been pro-\nposed\n(Perutz,\n1970a and\nb and\n1972).\nThe\nhaemoglobins of higher organisms share a common\ntetrameric structure built up of two pairs of unlike\nchains; the a chains containing\n141 amino-acid\nresidues and the non-a chains containing generally\n145 or 146 amino acids.\nIn man, five types of\nnon-a chains have been recognized, /3, y, 8, E. and 4,\ncorresponding to different stages of ontogenesis.\nThe globin chains of haemoglobin and ofmyoglobin\nhave a similar overall tertiary structure composed of\nsegments of a helix interspersed with non-helical\nregions forming a compact structure of great com-\nplexity.\nAmino-acid residues whose side chains\nare of a polar nature, ie, those which bear an electric\ncharge or a strong dipole movement are located at\nthe outer surface of the molecule in contact with the\naqueous\nsurroundings,\nwhereas\nthe\nnon-polar\nhydrocarbon side chains are, in general, located\nwithin the interior of the molecule.\nThe haem\ngroups are accommodated within deep cavities or\npockets lined with non-polar side chains and are\nanchored in position by links between the haem iron\nand the imidazole side chains of histidines.\nThe\nnon-aqueous environment of the haem promotes\nreversible binding of oxygen and protects the iron\nfrom oxidation to the ferric form characteristic of\nmethaemoglobin which is incapable of reversible\noxygen binding."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1138
encoding: FLOAT32
metadata:
{"title": "Review Article Fetal and Embryonic Haemoglobins", "chroma:document": "The four chains of the tetramer fit together to\nReceived 27 November 1972.\nform a nearly spherical molecule with extensive\nareas of contact between unlike chains; the two\nmain types of contact are denoted alp, and alg2\nThe\ntetramer\nexhibits\ncooperative\nbehaviour\nor\nhaem-haem interaction.\nAs each haem combines\nwith oxygen the affinity of successive haems in-\ncreases.\nThe oxygen affinity curve of the tetramer\nis sigmoidal and may be represented approximately\nby the Hill equation:*\n=\nkpo2n\ny +kpo2n\nOxygen affinity data are usually presented\nin\nterms of P102, the partial pressure of oxygen re-\nquired to attain half saturation with oxygen, and of\nn, the exponent of the Hill equation.\nThese para-\nmeters respectively give measures of the oxygen\naffinity and of the degree of haem-haem interaction.\nFor normal haemoglobin n\nis approximately\n3.\nMyoglobin, isolated chains, and tetramers composed\nof one type of chain such as Hb H (4) show no\nhaem-haem interaction, their oxygen dissociation\ncurves are hyperbolic and the n value is 1.\nThe haemoglobin tetramer has a lower oxygen\naffinity, more appropriate of its physiological func-\ntion, than single chains.\nThe cooperative behaviour\nof the tetramer renders it more efficient in releasing\noxygen in response to relatively small changes in\noxygen\ntension.\nThe\ntetramer\nexhibits\nother\nphysiologically advantageous properties; the oxygen\naffinity varies withpH (Bohr effect) in such a manner\nas to facilitate the release of oxygen in the tissues.\nHaemoglobin binds CO2 at the N terminus of the\n/\nchains (Kilmartin and Rossi-Bernardi, 1969) and\nassists its transport from the tissues to the lungs.\nFurthermore\nits\noxygen\naffinity\nis\nreduced\nin\nthe presence of organic phosphates\nparticularly\n2,3\ndiphosphoglycerate\n(2,3 DPG) and\ninositol\n* Hill equation: y =fraction of haemoglobin in oxy form, P02\npartial pressure of oxygen, k and n are constants.\n50"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1139
encoding: FLOAT32
metadata:
{"title": "CD30 co-stimulation drives differentiation of Mycobacterium tuberculosis protective T cells during infection", "chroma:document": "ARTICLE\nCD30 co-stimulation drives differentiation of\nprotective T cells during Mycobacterium tuberculosis\ninfection\nTaylor W. Foreman1\ue840, Christine E. Nelson1\ue840, Michelle A. Sallin1\ue840, Keith D. Kauffman1\ue840, Shunsuke Sakai1\ue840, Francisco Otaizo-Carrasquero2\ue840,\nTimothy G. Myers2\ue840, and Daniel L. Barber1\ue840\nControl of Mycobacterium tuberculosis (Mtb) infection requires generation of T cells that migrate to granulomas, complex\nimmune structures surrounding sites of bacterial replication. Here we compared the gene expression profiles of T cells in\npulmonary granulomas, bronchoalveolar lavage, and blood of Mtb-infected rhesus macaques to identify granuloma-enriched\nT cell genes. TNFRSF8/CD30 was among the top genes upregulated in both CD4 and CD8 T cells from granulomas. In mice,\nCD30 expression on CD4 T cells is required for survival of Mtb infection, and there is no major role for CD30 in protection by\nother cell types. Transcriptomic comparison of WT and CD30\u2212/\u2212 CD4 T cells from the lungs of Mtb-infected mixed bone\nmarrow chimeric mice showed that CD30 directly promotes CD4 T cell differentiation and the expression of multiple effector\nmolecules. These results demonstrate that the CD30 co-stimulatory axis is highly upregulated on granuloma T cells and is\ncritical for protective T cell responses against Mtb infection.\nIntroduction\nMycobacterium tuberculosis (Mtb) is a leading cause of global\nmortality due to infectious disease. The current vaccine for\nMtb infection, Bacillus Calmette-Gu\u00b4erin (BCG), is adminis-\ntered neonatally and provides protection against severe\nforms of tuberculosis (TB) in children, but it does not pro-\nvide sufficient protection in adolescents and adults to dras-\ntically reduce the global burden TB. Over the past few years,\nclinical vaccine trials using BCG re-vaccination or an ad-\njuvanted fusion protein have demonstrated \u223c40\u201350% pro-\ntection (Nemes et al., 2018; Van Der Meeren et al., 2018), and\nseveral vaccine studies in non-human primates (NHPs) have"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1140
encoding: FLOAT32
metadata:
{"title": "CD30 co-stimulation drives differentiation of Mycobacterium tuberculosis protective T cells during infection", "chroma:document": "afforded extraordinary levels of protection, showing that a\nhighly effective vaccination for TB is achievable (Darrah\net al., 2020; Dijkman et al., 2019; Hansen et al., 2018;\nKaushal et al., 2015; Sharpe et al., 2016; White et al., 2015). A\nbetter understanding of the mechanisms of host protection\nagainst Mtb infection would improve our ability to develop\nnovel vaccination as well as host-directed therapeutic\nstrategies for TB.\nControl of Mtb infection requires the generation of T cells\nthat can traffic to pulmonary granulomas, but little is known\nabout the basic biology of granuloma T cells (i.e., the mecha-\nnisms regulating the generation, differentiation, homing, and\neffector functions of protective granuloma T cells). CD4 T cell\nresponses to mycobacterial infections in humans, NHPs, and\nmice are primarily comprised of IFN\u03b3-producing effector cells.\nHowever, there are differences in the quality of CD4 T cell dif-\nferentiation observed in response to mycobacterial infection in\nC57Bl/6 mice compared to macaques and humans. In mice, Mtb-\nspecific CD4 T cells develop into highly polarized Th1 cells, with\nsome cells even differentiating into terminally differentiated\nTh1 effector cells. In contrast, these terminally differentiated\ncells are not observed in NHPs or humans (Kauffman et al.,\n2018b). Instead, in primate hosts, Mtb-specific T cells mostly\ndifferentiate into atypical IFN\u03b3-producing cells referred to as\nTh1* cells that are characterized by a mixture of Th1 and Th17-\nlike features (Acosta-Rodriguez et al., 2007; Burel et al., 2018;\nLindestam Arlehamn et al., 2013; Singhania et al., 2021). Another\n.............................................................................................................................................................................\n1T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1141
encoding: FLOAT32
metadata:
{"title": "CD30 co-stimulation drives differentiation of Mycobacterium tuberculosis protective T cells during infection", "chroma:document": "2Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.\nCorrespondence to Daniel L. Barber: barberd@niaid.nih.gov\nT.W. Foreman\u2019s current affiliation is Discovery, Early Oncology R&D, AstraZeneca, Gaithersburg, MD, USA. M.A. Sallin\u2019s current affiliation is Maryland Department of\nHealth, Linthicum Heights, MD, USA.\nThis is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. This article is distributed under the\nterms of an Attribution\u2013Noncommercial\u2013Share Alike\u2013No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After\nsix months it is available under a Creative Commons License (Attribution\u2013Noncommercial\u2013Share Alike 4.0 International license, as described at https://\ncreativecommons.org/licenses/by-nc-sa/4.0/).\nRockefeller University Press\nhttps://doi.org/10.1084/jem.20222090\n1 of 14\nJ. Exp. Med. 2023 Vol. 220 No. 8\ne20222090"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1142
encoding: FLOAT32
metadata:
{"title": "Review Article Immunoglobulins", "chroma:document": "Review Article\nJournal of Medical Genetics (1974).\n11, 80.\nImmunoglobulins\nJOHN BRADLEY\nSub-Department of Immunology, University of Liverpool Medical School\nAn immunoglobulin is a protein which is com-\nposed of a characteristic unit of four polypeptide\nchains: a pair of identical 'light' chains with a mole-\ncular weight of 22,000, consisting of - 214 amino-\nacid residues which do not contribute at all to class\nspecificity but are common to all the immuno-\nglobulins, and a pair of identical 'heavy' chains,\nmolecular weight 50,000-70,000.\nThe heavy poly-\npeptide chains of the immunoglobulin classes and\nsubclasses vary in amino-acid composition and se-\nquence and it is these variations that give each class\nor subclass its specificity.\nThese chains are linked\nby disulphide bridges.\nAmong the classes and\nsubclasses of immunoglobulins, members with anti-\nbody activity have been identified.\nThe approxi-\nmate molecular weights of immunoglobulins range\nfrom 160,000 for IgG to 900,000 for the IgM mole-\ncule which consists of five monomeric IgM units\nlinked by disulphide bonds to form the IgM mole-\ncule.\nHowever, monomeric IgM (7S IgM) does\nexist in the serum of normal individuals as well as in\na number of disease states.\nIn man, five distinct\nclasses have so far been identified according to their\ngeneral properties and the class of their heavy\nchains; these are IgG, IgA, IgM, IgD, and IgE.\nImmunoglobulin Classes\nImmunoglobulin G is the major immunoglobu-\nlin component of serum and of the body extravascu-\nlar\nspaces.\nMembers\nof\nthis\nimmunoglobulin\ngroup\nneutralize\nbacterial\ntoxins,\nenhance\nthe\nphagocytosis of micro-organisms, and may pro-\nduce cell lysis by activation of the complement se-\nquence.\nAnalysis of IgG myeloma proteins have\nrevealed the presence of four subclasses, IgG1,\nIgG2, IgG3, and IgG4.\nThese subclasses (Table I)\nvary in amino-acid composition and the number of\ndisulphide bridges present.\nThey also vary in their\nReceived 30 July 1973.\n80\nTABLE I\nIgG SUBCLASSES\nDisulphide Complement\nCross\nMacrophages\nTotal"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1143
encoding: FLOAT32
metadata:
{"title": "Review Article Immunoglobulins", "chroma:document": "Total\nBridges\nFixation\nPlacenta\nBinding\nIgG\nIgG,\n2\n+ + +\n+ +\n+ + +\n65-70\u00b0,,\nIgG2\n4\n+\n-\n+\n20-23%,\nIgG3\n5\n+ + + +\n+ +\n+ + +\n8%,'\nIgG4\n2\n++\n\u00b1\n4%\nability to activate complement, to fix to macro-\nphages, and to cross the placenta.\nImmunoglobulin A appears selectively in sero-\nmucous secretion tears, nasal secretions, saliva, and\ngastrointestinal secretions.\nIn these secretions it is\npresent as a dimer with an additional secretory com-\nponent synthesized by the local secretory epithelium.\nIgA is also present in the serum but mainly as the\nbasic 7S monomer.\nThe s!cretory IgA present in\ncolostrum, although not absorbed from the gastro-\nintestinal tract of the newborn, probably helps to\ncontrol the intestinal flora.\nSerious neonatal in-\nfections are less frequent in babies whose milk intake\nis from the breast in the first few days of life (Win-\nberg and Wessner, 1971).\nAlthough IgA does not\nappear to\nactivate the\nclassical complement se-\nquence, there is evidence that aggregated IgA can\ndo so via the 'alternate pathway' by acting on C3\nproactivator to generate C3a.\nThe two subclasses\nof IgA are differentiated immunochemically and\ncalled IgAj and IgA2.\nStructurally these sub-\nclasses are quite different; IgA2 lacks the interchain\ndisulphide bonds linking the heavy and light chains\nwhich\nare\ncharacteristic\nof\nall\nother immuno-\nglobulins.\nBecause of this, the subclasses can be\ndifferentiated by electrophoresis in starch or acryla-\nmide gel by suitable conditions (8M urea, pH3)\nwhich dissociates the heavy and light chains of IgA2.\nNormally human serum consists of approximately"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1144
encoding: FLOAT32
metadata:
{"title": "Evidence for mutation being the of the abnormal for plasma cholinesterase", "chroma:document": "Journal of Medical Genetics (1974).\n11, 117.\nEvidence for mutation being the source of the\nabnormal gene for plasma cholinesterase\nR. T. EVANS and P. J. MAGILL\nBiochemistry Department, Southmead Hospital, Bristol\nSummary.\nResults of cholinesterase, dibucaine and fluoride numbers, and\nscoline hydrolysis rates are presented in a family found to have normal, silent and\nabnormal genes for plasma cholinesterase.\nFive sibs, confirmed by red cell group-\ning and tissue typing, have been shown to possess a cholinesterase pattern which\ncannot be explained on the basis of accepted theories of inheritance.\nIn view of\nthis it is suggested that, in this family, a mutation has occurred from a normal or\nsilent gene to an abnormal gene.\nSoon after the introduction of succinyl dicholine\n(Scoline, Suxamethonium) as a short acting muscle\nrelaxant in 1949 it was recognized that the brief\nperiod of action was due to its rapid breakdown by\nplasma cholinesterase (acetyl choline acyl hydrolase\nE.C. 3.1.1.8) (Bovet-Nitti, 1949).\nSubsequently it\nwas discovered that some patients are peculiarly\nsensitive to the drug, muscle relaxation lasting for\nseveral hours rather than the normal 2-3 minutes\n(Evans et al, 1952).\nLehmann and Ryan (1956)\nshowed that this sensitivity could often be attribu-\nted to the inheritance of two co-dominant genes for\nan abnormal enzyme, which was later demonstrated\nto be unable to hydrolyse scoline at pharmacological\nconcentrations (Davies, Marton, and Kalow, 1960).\nThe observations of Kalow and Genest (1957)\nthat this protein could be differentiated from the\nnormal on the basis of a simple biochemical test\nrepresented a considerable advance in the labora-\ntory\ndetection\nof\nsensitive\nindividuals.\nThese\nworkers showed that the abnormal enzyme was\nresistant to inhibition by the local anaesthetic agent\ndibucaine and devised the concept of the dibucaine\nnumber (DN), which was defined as the percentage\ninhibition ofthe enzyme by 10- 5M dibucaine.\nThe\nDN is 80 \u00b1 4 for normal enzyme, but only 20 \u00b1 4 for"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1145
encoding: FLOAT32
metadata:
{"title": "Evidence for mutation being the of the abnormal for plasma cholinesterase", "chroma:document": "enzyme from persons homozygous for the abnormal\ngene.\nAn intermediate group of subjects were ob-\nserved to have dibucaine numbers of 60\u00b15 and\nthese were shown to be heterozygotes.\nThese ob-\nservations have since been confirmed (Johnson and\nReceived 19 November 1973.\nWhitehead, 1965; Fishtal, Evans, and Chapman,\n1972).\nOther selective inhibitors are now well recog-\nnized, the most important of which is fluoride, and a\ngene has been described which is responsible for the\nproduction of enzyme specifically resistant to fluo-\nride inhibition (Harris and Whittaker, 1961).\nIn 1962, profound Scoline sensitivity was re-\nported in a patient having no detectable plasma\ncholinesterase\nactivity\n(Liddell,\nLehmann,\nand\nSilk, 1962).\nSeveral other cases have since ap-\npeared in the literature (Doenicke\net al,\n1963;\nSzeinberg et al, 1966; Heyworth and Firth, 1967).\nThese patients are believed to be homozygous for\nthe so-called 'silent gene' but evidence is at present\nequivocal as to whether there is a complete failure of\nenzyme synthesis, or whether enzyme is present, but\nin an inactive form (Goedde, Gehring, and Hof-\nmann, 1965; Hodgkin et al, 1965).\nThe incidence\nof this condition is low, approximately 1 in 300,000\nin Caucasians, but it has been observed to be very\nhigh in some isolated Eskimo communities where it\nis present in an estimated 1-5% of the population\n(Gutsche, Scott, and Wright, 1967).\nFour allelic genes determining plasma cholines-\nterase are now recognized:\nEu-the normal or usual gene.\nEa-the abnormal, dibucaine-resistant gene.\nEf-the fluoride resistant gene.\nEs-the silent gene.\nAll the expected\ngenotypes corresponding to\n117"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1146
encoding: FLOAT32
metadata:
{"title": "Observations human amniotic fluid cell strains in serial culture", "chroma:document": "Journal of Medical Genetics (1974).\n11, 190.\nObservations on human amniotic fluid cell strains\nin serial culture\nGRANT R. SUTHERLAND, RHONA BAULD, and A. DOUGLAS BAIN\nDepartment of Pathology, Royal Hospital for Sick Children and University of Edinburgh, Edinburgh EH9 ILF\nSummary.\nObservations made on 31 amniotic fluid cell strains serially cul-\ntured until senescent are recorded.\nThe cell strains had an average life in culture of\n13-9 passages (range 3-29).\nThe source of the amniotic fluid from which the cul-\ntures were initiated did not influence the behaviour of the cell strains.\nThe be-\nhaviour ofthe cell strains was unrelated to the growth characteristics ofthe primary\ncultures from which they were derived.\nCell strains derived from serial samples of\namniotic fluid from three women were compared and their characteristics were no\nmore related to each other than to the group as a whole.\nThe cell types found in\namniotic fluid cultures are described.\nThe karyology of 12 of the cell strains was\nmonitored and no significant changes from normal diploidy were seen.\nPossible\nreasons for the highly variable and unpredictable behaviour of amniotic fluid cell\nstrains are discussed.\nCultured amniotic fluid cells are now in wide-\nspread use for the antenatal diagnosis of chromo-\nsome disorders and inborn errors of metabolism\n(Emery,\n1970; Sutherland,\n1972; Emery, 1973;\nMilunsky, 1973).\nAn accurate knowledge of the\nbehaviour of normal cultured amniotic fluid cell\nstrains is therefore essential for their use in genetic\nstudies.\nHowever,\nlittle\nappears\nto be known\nabout the characteristics of these cells in tissue cul-\nture.\nIt has been stated (Melancon, Lee, and\nNadler, 1971) that there are at least two morpho-\nlogically distinguishable cell types in amniotic fluid\ncell cultures-an epithelial type which cannot be\nsubcultured more than two to five times and a\nfibroblast-like cell which can be cultured for more\nthan 30 passages.\nOn the other hand, Littlefield\n(1971) has said that '. . . 6 to 8 weeks of rapid cul-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1147
encoding: FLOAT32
metadata:
{"title": "Observations human amniotic fluid cell strains in serial culture", "chroma:document": "ture can approach the limit of the growth potential\nof amniotic fluid cells.. .'.\nThis report records\nobservations made during the long-term culture of\n31 amniotic fluid cell strains.\nMaterials and Methods\nAmniotic\nfluids\nwere obtained from hysterotomy\nspecimens\n(HS), by\namniocentesis\non Rhesus\niso-\nimmunized women (RhS) and by artificial rupture of\nReceived 5 November 1973.\nmembranes (ARM) for the induction of labour.\nThe\nprimary cultures were set up as previously described\n(Sutherland and Bain, 1972) and subcultured according\nto the method of Butterworth et al (1973).\nThe cell\nstrains were maintained in 250-ml glass vessels with a\ngrowth surface area of 40 cm2 and regularly subcul-\ntured on reaching confluency, using a 1:2 subculture\nratio.\nThroughout this study, all cell strains were cul-\ntured in Ham's F10 tissue culture medium supple-\nmented with 30% fetal calf serum and with the anti-\nbiotics kanamycin, or penicillin and streptomycin in\ncombination.\nThe methods used for cytogenetic studies\non primary cultures have been described (Sutherland,\nGrace, and Bain, 1973b).\nOnce cell strains became\nestablished, chromosome preparations were made using\nstandard methods.\nCell strains were stored in 10%\ndimethyl sulphoxide in culture medium in the vapour\nphase of a liquid nitrogen unit.\nResults\nThe 31 cell strains were derived from amniotic\nfluid samples taken from 25 women, ie, one woman\ncontributed four samples, another three, and another\ntwo at different stages of pregnancy.\nThe gesta-\ntional ages, means of collection, and chromosomal\nsexes of the amniotic fluids are shown in Table I.\nAll had normal karyotypes with the exception of two\nsamples from one pregnancy which had a karyotype\n46,XY,t(1 ;12)(p21 ;q21).\n190"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1148
encoding: FLOAT32
metadata:
{"title": "Translocation, t(4q 3q+), in three generations resulting in partial trisomy of the long of chromosome 4 in the fourth generation", "chroma:document": "Journal of Medical Genetics (1974).\n11, 201.\nTranslocation, t(4q -;13q+), in three generations\nresulting in partial trisomy of the long arm\nof chromosome 4 in the fourth generation\nHELMUT G. SCHROTT,* SUMIKO SAKAGUCHI,t UTA FRANCKE,t\nLUIGI LUZZATTI,t and PHILIP J. FIALKOW**\nSummary.\nThe karyotype of a child with severe mental retardation, micro-\ncephaly,\nminor\nfacial\nanomalies, and urinary\ntract\noutflow obstruction\nwas\nfound to be 46,XY,13q+mat.\nTrypsin-Giemsa banding studies showed an in-\nherited translocation, t(4q-;13q+), in several asymptomatic members of the\nfamily including the propositus' mother. This indicates that the propositus had\npartial trisomy for the distal one-third of the long arm of chromosome 4.\nReview\nofthe literature suggests that urinary tract and genital anomalies may be a consistent\nfeature of this partial trisomy.\nChromosomal translocations are found in approxi-\nmately 0-140/% (1/700) of all newborn babies (Sergo-\nvich et al, 1969, Walzer, Breau, and Gerald, 1969;\nLubs and Ruddle,\n1970;\nRatcliffe\net\nal,\n1970;\nTurner and Wald, 1970). Of these, one-third are\nreciprocal translocations resulting from the mutual\nexchange of chromosome segments between two\nnon-homologous chromosomes.\nIndividuals bear-\ning both products of the exchange ('balanced translo-\ncation carriers') are generally normal phenotypically\nbecause they have lost little or no genetic material.\nHowever,\nsuch\ntranslocation\nheterozygotes may\ntransmit to their offspring only one of the two\ntranslocation chromosomes, and this results in a\nchild with chromosomal deficiency or duplication.\nIt is the consequent congenital anomalies that bring\nthe family to the attention of a physician.\nWe\nreport here a family in which a balanced transloca-\nReceived 20 August 1973.\n* Department of Internal Medicine, University of Iowa, University\nHospitals, Iowa City, Iowa 52240, USA.\nt Department of Pediatrics, Stanford University School of Medi-\ncine, Stanford, California 94305, USA.\nt Department of Pediatrics, School of Medicine, University of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1149
encoding: FLOAT32
metadata:
{"title": "Translocation, t(4q 3q+), in three generations resulting in partial trisomy of the long of chromosome 4 in the fourth generation", "chroma:document": "California at San Diego, La Jolla, California 92037, USA.\n** Departments of Medicine (Division of Medical Genetics) and\nGenetics, University of Washington, Seattle, Washington 98195,\nUSA.\ntion, presumably reciprocal, was transmitted through\nthree generations and was then unmasked in the\nfourth generation by the birth of a child with\nmultiple congenital defects.\nThe child had partial\ntrisomy of the distal long arm of chromosome 4.\nCase Report\nThe propositus was admitted to Stanford University\nHospital at 3 months of age because of multiple con-\ngenital defects and failure to thrive.\nHe was the second\nchild of unrelated parents, a 25-year-old mother and 26-\nyear-old father.\nA 4-year-old brother was normal and\nthere was no history of previous spontaneous abortions.\nDelivery allegedly occurred 1 month early; birth weight\nwas 1986 g.\nShortly after birth, the patient was noted to\nurinate\nonly\nby\ndribbling.\nIntravenous\npyelogram\nshowed absence of renal function on the left and moder-\nate hydronephrosis and hydroureter on the right side.\nVoiding cystourethrogram showed a small, thickened\nbladder with bilateral ureteral reflux.\nThe obstruction\nwas relieved by a suprapubic cystostomy.\nFollow-up\npyelogram showed a normally functioning right kidney\nand a hydronephrotic left kidney.\nAt 2 months of age,\nthe patient had aspiration pneumonia.\nWeight was\n2560 g, length was 48-7 cm, and head circumference was\n32-6 cm.\nHe had a good cry, although muscle tone was\npoor.\nThe head was normal in shape and the anterior\nfontanelle was closed.\nThe nose was prominent and the\n201"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1150
encoding: FLOAT32
metadata:
{"title": "Congenital limb anomalies: frequency and aetiological factors", "chroma:document": "hUVi41y74\nJournal of Medical Genetics (1974).\n11, 221.\nCongenital limb anomalies: frequency and\naetiological factors\nData from the Edinburgh Register of the Newborn (196448)\nE. J. ROGALA, R. WYNNE-DAVIES, A. LITTLEJOHN, and J. GORMLEY\nDepartment of Orthopaedic Surgery, University of Edinburgh\nSummary.\nThis paper reports a detailed follow up of 156 patients with struc-\ntural upper and lower limb anomalies, obtained from the Edinburgh Register ofthe\nNewborn (a registration of 52,029 consecutive births between 1964 and 1968).\nAt\nthe time ofthis survey the patients were between 4 and 9 years of age.\nThe Register had noted probably 96% of all children born with limb defects in\nEdinburgh between 1964 and 1968.\nIt was found that the diagnosis was completely\naccurate in only 26% of cases, and partially so in a further 42%.\nThe frequency of each anomaly has been noted, subdivided into isolated ano-\nmalies; those that occurred with other limb anomalies, and those that formed part\nof a syndrome.\nSyndactyly of toes, post-axial polydactyly of the fingers, polysyn-\ndactyly, and brachydactyly were found to have a genetic basis.\nAll 'absence' de-\nfects, pre-axial polydactyly, and multiple limb deformities appeared to be sporadic.\nAmongst the sporadic group, the main aetiological factors noted were an excess of\nmaternal toxaemia of pregnancy and of illegitimate children, when compared with\nthe Register Control Data.\nLittle is known about the frequency of the indi-\nvidual structural deformities of the limbs.\nSome\nsurveys mention 'skeletal anomalies' without fur-\nther definition, and in others delineation of the indi-\nvidual anomalies is difficult because of variation in\nterminology and the general, purely descriptive\nterms so often used (Carter, 1963; Stevenson et al,\n1966;\nButler and Alberman,\n1969).\nA\nfurther\nsource of error is that most surveys have included\nonly hospital (not domiciliary) births and thus many\nof the less severe anomalies will have been omitted.\nMcIntosh\net\nal\n(1954),\nMarden,\nSmith,\nand"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1151
encoding: FLOAT32
metadata:
{"title": "Congenital limb anomalies: frequency and aetiological factors", "chroma:document": "and\nMcDonald (1964), and Stewart, Keay, and Smith\n(1968/69) all used more detail in recording limb ano-\nmalies but their population samples (4412, 5964,\nand 2500, respectively) were too small to give a re-\nliable population frequency.\nBirch-Jensen (1949), by searching through all the\nDanish hospital records, found 625 patients with\n'absence' deformities of the upper extremities who\nReceived 7 December 1973.\nwere living in Denmark and had been born before\n1 January 1947.\nHe defined 'absence' deformities\nas 'those due to absence or atrophy of larger or\nsmaller portions of the skeleton of the extremity'.\nAfter classification, he related them to the popula-\ntion of Denmark published in the Danish Year\nBook of Statistics (1946) thus establishing the fre-\nquency of the separate deformities.\nHowever, this\ncannot have given the true incidence at birth since it\nexcluded both\nperinatal and\nlater\ndeaths.\nHis\nstudy did not include any other congenital de-\nformities of the limbs.\nNone of these surveys had\nfollow-up studies to establish whether other de-\nfects became evident with growth.\nGenetic factors have been described for several of\nthe\nstructural limb anomalies,\nparticularly\nsyn-\ndactyly, polydactyly, and brachydactyly (Temtamy\nand McKusick,\n1969; Woolf and Woolf,\n1970;\nDavid, 1972), and there have been innumerable re-\nports of individual families with limb anomalies.\nHowever, most congenital limb\ndefects\nseen in\nclinical practice are sporadic, whether occurring in\n221\nli."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1152
encoding: FLOAT32
metadata:
{"title": "Giemsa banding of chromosome qh+ and linkage analysis", "chroma:document": "Journal of Medical Genetics (1975).\n12, 44.\nGiemsa banding of chromosome qh+ and linkage\nanalysis\nPATRICIA N. HOWARD,* GAYLE R. STODDARD,* MICHAEL W. GODDARD,\nand J. RODMAN SEELY\nFrom the Department of Pediatrics and Clinical Research Center, Oklahoma Children's Memorial Hospital, University\nof Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma 73190, USA\nSummary.\nA four-generation transmission of a lqh+ chromosome was ascer-\ntained by routine chromosome analysis of a mildly dysmorphic and retarded 6j-\nyear-old female.\nConcordance between synophrys and the lqh+ marker was the\nonly consistent phenotypic relationship.\nThe variant chromosome did not appear\nuncoiled, and Giemsa centromeric staining (C-bands) revealed an increased width\nof the heterochromatin commensurate with the increased length of the long arm.\nGiemsa banding ofthe entire chromosome (G-bands) revealed two heterochromatin\nbands, identical in appearance, in the centromeric region with the remainder of the\nchromosome showing normal banding.\nThe distribution of Duffy blood groups\nin the pedigree was consistent with the locus being on chromosome No. 1.\nVariant No. 1 chromosomes with an increase in\nthe length of the long arm are reported fairly fre-\nquently.\nData from the New Haven newborn sur-\nvey (Lubs and Ruddle, 1971) show this variant to\noccur in about one of every 400 Caucasian births.\nThis type ofvariant has been reported in both abnor-\nmal and normal individuals (Cooper and Hernits,\n1963; Yunis and Gorlin, 1963; Donahue et al, 1968;\nYing and Ives, 1968).\nFurther characterization of these chromosomes is\nnow possible by means ofthe fluorescent and Giemsa\nbanding techniques (reviewed by Pearson, 1972).\nLobitz, McCaw, and Hecht (1972) have reported a\nthree-generation pedigree segregating for a\n1q +\nvariant showing an increased number of bands in\nthe centromeric region of the long arm.\nHolzer,\nRosenkranz, and Glatzl (1972) have described a\nfamily with a segregating lqh + chromosome and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1153
encoding: FLOAT32
metadata:
{"title": "Giemsa banding of chromosome qh+ and linkage analysis", "chroma:document": "noted that four individuals have the variant in a\nhomozygous state.\nOsztovics et al (1973) and Kim\n(1973) also reported lqh + chromosomes.\nWe have investigated a four-generation pedigree\nsegregating for a similar variant chromosome No. 1.\nWe have shown this chromosome to have an in-\nReceived 4 June 1974.\n* Present address: Institute of Genetics, University of Southern\nMississippi, Hattiesburg, Mississippi, USA.\n44\ncreased length due to an increase in the hetero-\nchromatic region and have studied the linkage ofthis\nmarker with three traits.\nMethods and materials\nSlides were made from cultures of human lympho-\ncytes and centromeric banding (C-bands) and individual\nbanding pattems (G-bands) were produced as previ-\nously described (Howard, Stoddard, and Seely, 1973).\nDetermination of the Duffy and Rhesus blood group\nphenotypes was done by standard techniques.\nCase report\nThe proposita, a part American Indian female, was\nreferred at 6+ years of age because of poor school per-\nformance and dysmorphic features. Phenotype included\na prominent synophrys, mild hypertelorism, epicanthal\nfolds, uptumed nose with a wide philtrum, a high nar-\nrow palate, and a small, downtumed mouth.\nOther\nfeatures included generalized hypertrichosis, brachy-\ndactyly with broad great toes, clinodactyly of the little\nfingers, and abnormal dermatoglyphics.\nRadiographic\nevaluation revealed anomalies of the lumbar spine and\nmalrotation of the right kidney.\nPsychometrics showed\na dull normal intellectual function.\nThe phenotype of the proposita's father was normal;\nher mother had significant dysmorphic features which"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1154
encoding: FLOAT32
metadata:
{"title": "Haemoglobin Lepore Boston and elliptocytosis in family of Indonesian-German", "chroma:document": "Journal of Medical Genetics (1975).\n12, 83.\nHaemoglobin Lepore Boston and elliptocytosis in a\nfamily of Indonesian-German ancestry\nL. N. WENT, W. W. de JONG,* and S. E. BOS\nDepartmenzt of Human Genetics, Faculty of Medicine and Elisabeth Hospital, Leiden, The Netherlands\nSummary.\nA family is presented in which Hb Lepore Boston was found in six\nindividuals over three generations.\nThe gene must have had its origin either in Java\n(Indonesia) or in what is now the Federal Republic ofGermany.\nThe haemoglobin\nwas characterized by amino-acid analysis of the six tryptic peptides that have a dif-\nferent composition in the\n/- and the 3-chain.\nThe ratio of glycine to alanine in\nposition 136 ofthe fetal haemoglobin, which was somewhat raised in the Hb Lepore\ncarriers, averaged 31:69.\nIn addition an elliptocytosis gene was found, which was inherited independently\nfrom Hb Lepore; the simultaneous presence of elliptocytosis in three family mem-\nbers did not seem to aggravate the mild anaemia caused by Hb Lepore.\nThe Lepore haemoglobins are interesting from a\nmolecular-, clinical-, and population-genetical point\nof view.\nStructurally they are characterized by the\npresence of globin chains which are fusion products\nof 8- and ,8-chains.\nThese 83/-chains seem to be the\nresult of unequal crossing-over between the closely\nlinked\n3- and /3-genes\n(Baglioni,\n1962).\nThree\ndifferent types of Hb Lepore are known, which\ndiffer in the position of the crossing-over.\nThe\nregions of 3/3 fusion in Hb Lepore Hollandia, Hb\nLepore\nBaltimore, and Hb Lepore Boston\nare\nlocated between residues 22 and 50, 50 and 86, and\n87 and 116, respectively.\nHb Lepore Hollandia is\nrather common among the Papuans of New Guinea\n(Barnabas and Muller, 1962).\nHb Lepore Balti-\nmore has\nbeen\ncharacterized\nonce\nin\na North\nAmerican negro (Ostertag and Smith, 1969).\nHb\nLepore Boston is rather wide spread in middle- and\neastern-Mediterranean populations (Fessas, Stama-\ntoyannoupoulos,\nand\nKaraklis,\n1962;\nQuattrin,\n1967; Duma et al, 1968) and is also present in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1155
encoding: FLOAT32
metadata:
{"title": "Haemoglobin Lepore Boston and elliptocytosis in family of Indonesian-German", "chroma:document": "Jamaican negroes (Ahern et al, 1972). Definite bio-\nchemical characterization of the 3/-chain of Hb\nLepore Boston has only been performed in some\nindividuals of Italian ancestry (Baglioni, 1965; Labie,\nSchroeder,\nand\nHuisman,\n1966;\nBaglioni\nand\nVentruto, 1968), in three Jamaican negro families\n(de\nJong,\n1969;\nAhern\net\nal,\n1972),\nin two\nMacedonians (L. F. Bernini, personal communi-\ncation), and in a case from Greece (Baglioni and\nVentruto, 1968).\nWe now report the finding and\ncharacterization of Hb Lepore Boston in a Dutch\nfamily of Indonesian and German ancestry.\nThis\nfamily possessed in addition a gene for hereditary\nelliptocytosis, which provided the opportunity to\nstudy\nthe\ninteraction between Hb Lepore and\nelliptocytosis.\nMethods\nHaematological data were obtained using standard\nmethods.\nStarch gel electrophoresis of haemolysates\nwas carried out in Tris-EDTA-borate buffer, pH 8-9\n(Smithies,\n1965).\nFetal haemoglobin was\nestimated\nusing the alkali-denaturation procedure of Singer, Cher-\nnoff, and Singer (1951).\nQuantitation of Hb Lepore and\nHb A2 was done on DEAE-cellulose columns according\nto the method of Bernini (1969).\nThe methods for the\nstructural characterization of Hb Lepore were the same\nas described previously (de Jong, Bemini, and Khan,\n1971) and comprised the isolation of pure Hb Lepore,\nconversion to globin, separation of a- and Spl-chains,\naminoethylation and tryptic digestion, peptide mapping,\nand amino-acid analyses of tryptic peptides.\nThe proportions of the two types of y-chains, Ay and\nGy were determined in the fetal haemoglobin present in\n83\nReceived 9 April 1974.\n* Present\naddress:\nDepartment\nof Biochemistry,\nFaculty\nof\nScience, Nijmegen, The Netherlands."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1156
encoding: FLOAT32
metadata:
{"title": "Neuropathological findings in patients dying after open-heart", "chroma:document": "Thorax (1963), 18, 29!\nNeuropathological findings in patients\ndying after open-heart surgery\nJ.\nB. BRIERLEY\nFrom\nthe Departmetnt of Neuropathology, Institute of Psychiatry, London\nAlthough cerebral damage has been regarded as\nthe cause of death in some patients dying after\nopen operations on the heart, this conclusion rests\nalmost entirely on clinical evidence such as an\nimpaired level of consciousness after the opera-\ntion, abnormalities of muscle tone and reflexes,\nvisual and extrapyramidal disorders or epilepsy.\nAccounts of cerebral pathology in fatal cases\nare limited to that of Bjork and Hultquist (1960)\nand a group of papers describing the cerebral\nemboli due to the anti-foam agent employed in the\noxygenator\n(Yates,\nCassie,\nDark,\nJack,\nand\nRiddell,\n1959;\nSmith,\n1960;\nLindberg,\nLucas,\nSheagren, and Malm, 1961 ; Thomassen, Howbert,\nWinn, and Thompson, 1961).\nIn the 11 patients reported by Bjork and Hult-\nquist, death was attributed to cerebral damage in\neight, all children. As yet there appears to have\nbeen no detailed pathological study of the brains\nof adults dying from presumed cerebral damage.\nHere we present the neuropathological findings\nin the first 11 of a series of patients who died from\nsix and a half hours to 11 days after open cardiac\nsurgery. The brains, received from six cardiac sur-\ngery units, were from patients 10 to 51 years of\nage, and all but one were subjected to some degree\nof hypothermia.\nThe cases are divided into two groups: Group I,\ntwo cases in which cardio-pulmonary bypass was\nnot employed and in which there was deliberate\ncirculatory arrest under mild hypothermia; and\nGroup II, nine cases in which cardio-pulmonary\nbypass was effected by a pump oxygenator. Mild\nto moderate hypothermia was employed in eight,\nbeing produced by a heat exchanger in seven and\nby surface cooling in one. There was no deliberate\narrest of the circulation by interruption\nof the\nperfusion.\nMATERIAL AND METHODS\nUnless previously dissected, the brains were cut into"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1157
encoding: FLOAT32
metadata:
{"title": "Neuropathological findings in patients dying after open-heart", "chroma:document": "coronal slices after removal of the brain stem and\ncerebellum.\nBlocks were taken from\nthe temporal\nlobes (to include basal ganglia), frontal and occipital\nlobes, midbrain, pons, medulla, and cerebellum and\nembedded in nitrocellulose. Sections were stained with\nhaematoxylin\nand\neosin,\nhaematoxvlin\nand\nVan\nGieson's\ncounterstain,\nthe method\nof\nNissl\n(using\ncresyl\nviolet),\nwith\nMallory's phosphotungstic\nacid\nhaematoxylin,\nwith Heidenhain's haematoxylin. and\nby the periodic acid Schiff technique.\nFrozen sections were stained with Oil Red 0.\nSUMMARIES OF CASES IN GROUP\nI\nTHE principal cerebral structures referred to in the\ntext are indicated in Diagrams\n1 and 2.\nCASE\n1 (MaudsleY No. 1339)\nA boy aged 16 years\nhad\ncongenital\npulmonary\nstenosis\nwithout\nseptal\ndefect.\nOperation\nCooling\nwas\nobtained\nby\nthe\nveno-\nvenous technique of Ross (1954) from 36\u00b0 to 31'C. in\n27 minutes. The heart was arrested for 4 min. 20 sec.\nand the valve was incised. Rewarming to 33.2\u00b0C. took\n12 minutes. The heart re-started\nsatisfactorily and\nthe blood pressure was normal.\nPost-operative course\nThere were signs of extreme\ncerebral irritation on leaving the theatre, and so intra-\nvenous\nurea and\nsucrose were\ngiven,\nbut without\neffect. Athetoid movements were noted and five left-\nsided fits occurred within an hour. Tracheostomy and\nassisted\nrespiration\nbecame\nnecessary\nand\nsurface\ncooling to 32\u00b0C. was carried out. On the first post-\noperative day the patient was unconscious. A right\nfrontal burr hole excluded a subdural haematoma.\nOn the third post-operative day an anuric regime was\nbegun\nand\nwas\nsuccessful.\nOn\nthe\nseventh\npost-\noperative day athetoid movements of the right arm\nand leg were noted and there was gradual deteriora-\ntion to death on the tenth post-operative day.\nNecropsy\nSome antemortem thrombus was\nseen\nin the inferior vena cava and portal vein; there was\nalso altered blood in the small and large intestines.\nMacroscopic\nexamination\nof\nthe\nbrain\nshowed\nslight convolutional flattening and considerable con-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1158
encoding: FLOAT32
metadata:
{"title": "Neuropathological findings in patients dying after open-heart", "chroma:document": "gestion both most marked over the occipital lobes. A\nthin\nfilm of subarachnoid blood covered the right\noccipital lobe. There were no internal herniae and the\nbasal vessels were normal.\nThe right hemisphere was slightly expanded and its\nventricles small. A recent haemorrhage (1-0 cm. dia-\nmeter) was noted\nin the white\nmatter of the\nleft\n291"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1159
encoding: FLOAT32
metadata:
{"title": "Familial interstitial pulmonary fibrosis", "chroma:document": "Thorax (1964), 19, 515.\nFamilial interstitial pulmonary fibrosis\nE.\nW. HUGHES\nFrom Tehidy Hospital, Camborne, Cornwall\nIn\n1944 Hamman\nand\nRich\nfirst\ndescribed\na\ndisease that caused an acute diffuse\ninterstitial\nfibrosis of the lungs, and which resulted in the\ndeath of four patients within six months of the\nonset of symptoms. Since then countless further\ncases have been reported in the literature, and our\nknowledge of the subject has advanced.\nIt is recognized that the interstitial fibrotic pro-\ncess may be localized as well as diffuse; that more\noften than not the disease follows a more pro-\ntracted course than it did in the cases first de-\nscribed; that natural remissions may sometimes\noccur; and that corticosteroid therapy is some-\ntimes effective in 'suppressing' the disease process\nand delaying its progress.\nLittle,\nhowever,\nhas\nbeen\nlearned\nabout\nits\ncausation. It is known that interstitial pulmonary\nfibrosis, may be the consequence of a variety of\npulmonary diseases, such as sarcoidosis or chronic\npulmonary tuberculosis, or that it may occur as\na manifestation of various systemic diseases such\nas scleroderma. But in the vast majority the aetio-\nlogy remains obscure, and we are\nleft with a\nheterogeneous group of cases which many authors\nare wont to class together under the general head-\ning of Hamman-Rich syndrome.\nThis may be\ninadvisable when\nit is\nstill not known whether\nthe acute, subacute, and chronic types represent\nvarying\nreactions\nto\none,\nor more\nthan\none,\naetiological agent, and on this account Scadding\n(1960)\nrecommends the use of descriptive terms.\nOne of the most remarkable features at the pre-\nsent time is the absence in the English literature\nof any examples of the familial type of the disease\nwhich has been recorded by several authors in\nAmerica and on the Continent. Here\nI record\nthree such cases of diffuse interstitial pulmonary\nfibrosis from one family who have been under\nmy care for the past three years and who also\nmanifest the acute, subacute, and chronic forms\nof the disease."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1160
encoding: FLOAT32
metadata:
{"title": "Familial interstitial pulmonary fibrosis", "chroma:document": "CASE REPORTS\nCASE 1\nJ. S., a woman aged 30.\nSingle. Occupation:\nhousekeeper.\nThis young lady had a normal chest radiograph in\nJanuary 1959 and was in good health until January\n1961, when breathlessness on exertion was first experi-\nenced. It became progressively more severe, and when\nadmitted\nto another hospital\nat\nthe end\nof May\nshe was acutely ill and had a slight productive cough.\nOn\nexamination\nthere\nwas\ncentral\ncyanosis,\nand\ncrepitations were audible at the bases of both lungs.\nClubbing\nwas\nnot\npresent.\nThe\ntemperature\nwas\nraised, reaching on occasions 105\u00b0 F., and there was a\nsinus tachycardia of 140/minute. Hb 68%\nW.B.C.\n9,000\nper\nc.mm.;\npolymorphs\n460\n;\nlymphocytes\n38%; monocytes 16%; E.S.R. 131 mm. in one hour.\nThe\nchest\nradiograph\nshowed\ngeneralized\nfine\nmottling throughout both lungs and dilatation of the\npulmonary\nartery. The\nfever was\nuninfluenced\nby\nbroad-spectrum\nchemotherapy, but\nsettled by\nlysis\nwhen the antibiotics were withdrawn during the third\nweek. In the meantime the breathlessness had become\nso severe that speech was barely possible, and, in\nthe middle of June, she was transferred to Tehidy\nHospital for further investigation.\nThe chest signs were as before except for an in-\ncrease in the rate of respiration from 20 to 40 excur-\nsions per minute.\nThe heart sounds were normal\nand there was no evidence of heart failure. The blood\npressure was\n120/70 mm. Hg; Hb 54% ;\nR.B.C.\n2,550,000 per c.mm.; W.B.C. 5,200 per c.mm.; poly-\nmorphs 62%; lymphocytes\n31 %;\nmonocytes\n1 %;\nmyelocytes 2%; metamylocytes 4%; E.S.R. 77 mm.\nin one hour; blood group A Rhesus negative-, serum\nalbumin 4 g./100 ml.; serum globulin 2-8 g./100 ml.;\nalpha\n1\nglobulin 0 3 g./100 ml.; alpha 2 globulin\n0 5\ng./100 ml.; beta globulin 0 3 g./100 ml.; gamma\nglobulin\n1-3 g./100 ml.; R.A. (latex) test negative;\nL.E. (latex) test negative; Mantoux 1/100 O.T. nega-\ntive.\nThe\nchest\nradiograph\nshowed\nextension\nof\nmottling with areas of confluence in the left middle\nand right lower zones (Fig.\n1). All other measures\nhaving\nfailed,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1161
encoding: FLOAT32
metadata:
{"title": "Familial interstitial pulmonary fibrosis", "chroma:document": "failed,\nadrenocorticotrophic\nhormone\n(A.C.T.H.) was given on an empirical basis, and from\nthat time her condition slowly but steadily improved.\nWithin four days the pulse rate fell from 120 to 90\nper minute, the dyspnoea became noticeably less, and\nthe chest radiograph showed considerable clearing of\nthe scattered mottling. A week later dyspnoea was\nonly mild, the weight had increased by 6 lb., crepita-\ntions were no longer audible, and radiologically the\npicture was one of continuing resolution. One month\nafter admission\nshe\nwas\nwell enough\nfor\na lung\n515"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1162
encoding: FLOAT32
metadata:
{"title": "Tracheal atresia associated with biloculare", "chroma:document": "Thorax (1964), 19, 530\nTracheal atresia associated with\ncor biloculare\nA. W. McCRACKEN, NEIL FLANAGAN, AND\nPAUL FLANAGAN\nFrom the Royal Air Force Institute of Pathology and Tropical Medicine, Halton, Bucks\nAtresia of the trachea is an extreme rarity (Willis,\n1962), and cor biloculare\nis a very uncommon\ncardiac anomaly. These two abnormalities were\nfound together in the case described, a combina-\ntion which, we believe, has not been previously\nreported.\nCASE REPORT\nThe infant was the second child of healthy parents.\nThere was no history of congenital abnormalities in\nthe family. The mother's pregnancy had been normal\nup to the thirty-second week, when uterine enlarge-\nment was found to be equivalent to that of a 36-week\npregnancy. Radiographic examination showed a single\nfoetus. A\ndiagnosis\nof moderate\nhydramnios\nwas\nmade. The mother's blood group was B Rhesus posi-\ntive. She did not contract any infectious disease or\ntake any drugs during her pregnancy.\nLabour began spontaneously at 39 weeks. There\nwas a precipitate vertex delivery of a female infant\nweighing 6 lb. 9 oz. On delivery the infant gave a\nfew gasps and showed obvious respiratory difficulty.\nTracheal intubation was unsuccessful. Tracheostomy\nwas attempted but was abandoned when no trachea\nwas found. Thirty minutes after delivery no heart\nbeat could be detected.\nNECROPSY\nThere was marked cyanosis and complete\ntracheal atresia from immediately below the cricoid\ncartilage. A thin fibrous tissue condensation imme-\ndiately\nanterior\nto\nthe\noesophagus\nsuggested\nthe\nusual\ncourse of the\ntrachea. The two main\nstem\nbronchi were normal and joined each other smoothly\nin the mid-line, 3 cm. below the larynx (Fig.\n1). A\ndirect fistula, 1 mm. in diameter, from the oesophagus\nentered the bronchi at this point. The oesophagus was\notherwise normal.\nThe route of the circulation\nis shown in Fig.\n2.\nThe heart was\nsited normally in the mediastinum.\nBlood entered the atrium from four sources-the pul-\nmonary veins, the superior and inferior venae cavae,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1163
encoding: FLOAT32
metadata:
{"title": "Tracheal atresia associated with biloculare", "chroma:document": "and the coronary sinus, which also drained a patent\nvein of Marshall. Blood passed through a single atrio-\nventricular valve\ninto\nan enlarged\nsingle\nventricle\nwith a wall 2 mm. thick. There was a normal pul-\nmonary valve and proximal pulmonary artery. Dis-\ntally,\nthe\npulmonary\nartery\ndivided\ninto\nthree\nbranches; the right and left pulmonary arteries, and\nFIG. 1.\nDiagram of the tracheal atresia. L, larynx; Tr,\ntracheal remnant;\nF,\ntracheo-oesophageal fistula;\nBr,\nbronchi; 0, oesophagus; S, stomach.\ncm.\nFIG. 2.\nDiagram of the heart showing the abnormal route\nof the circulation. SVC, IVC, superior and inferior venae\ncavae; VM, vein of Marshall; PV, pulmonary veins; At,\nsingle atrium; V, single ventricle; PA, pulmonary artery;\nR, rudimentary chamber; DA, ductus arteriosus; Ao,\naorta; LPA, left pulmonary artery; DAo, &scending aorta.\n530"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1164
encoding: FLOAT32
metadata:
{"title": "Oesophageal obstruction following hyperemesis gravidarum", "chroma:document": "Thorax (1965), 20, 528.\nOesophageal obstruction following\nhyperemesis gravidarum\nR. ABBEY SMITH AND C.\nS. NELSON\nFrom the Thoracic Surgical Unit, King Edward VII Chest Hospital, Hertford Hill, near Warwick\nAlthough\nsince\n1921\n(Vinson,\n1921)\nsevere\nobstruction of the oesophagus has been known\nto follow vomiting in pregnancy, little is known\nabout the subject, and the significance of a history\nof vomiting\nin pregnancy\nis not always\nrecog-\nnized. We record five patients with severe oeso-\nphageal\nobstruction\nthought\nto\nbe\ncaused\nby\nhyperemesis gravidarum. The poor outlook for\nspontaneous and complete cure of the oesophageal\nobstruction is apparent.\nIt\nis\ngenerally\nbelieved\nthat\npost-pregnancy\noesophageal obstruction is associated with a hiatus\nhernia and is due to oesophagitis from vomiting\nor reflux of gastric\njuice, producing\na fibrous\nstricture\nin the oesophagus\n(Allison, Johnstone,\nand Royce, 1943\n; Rennie, Land, and Park, 1949;\nand Cranmer, 1955). In one of our patients a hiatus\nhernia could\nnot be demonstrated\non repeated\nexamination. A number of points regarding the\ncause of the obstruction will be discussed.\nDutton and Bland (1953) observed nine patients\nin a maternity unit between 1950 and 1952. Each\nof these nine patients had a sliding hiatus hernia.\nOne patient suffered transient dysphagia; another\ndeveloped\nsevere dysphagia within three months\nof delivery. This patient vomited excessively from\nthe twentieth week of pregnancy. The oesophageal\nstricture, which was the cause of the obstruction,\nwas subsequently resected. These authors suggest\nthe need for a large-scale investigation to ascertain\nthe\nrole of\nhiatus\nhernia\nin\nthe\nvomiting\nof\npregnancy; they state that a patient with a hiatus\nhernia may be symptom-free.\nMarchand (1955) examined 250 women within\none week\nof\ndelivery;\n180 (70%)\nexperienced\nheartburn during pregnancy, sufficiently severe in\n93\nto require a regular antidote. Of these, only\nthree had\nsymptoms\nbefore\npregnancy.\nOf\n14\npatients examined radiologically, none was found\nto\nhave\na\nhiatus"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1165
encoding: FLOAT32
metadata:
{"title": "Oesophageal obstruction following hyperemesis gravidarum", "chroma:document": "a\nhiatus\nhernia\nand\nno\npatient\nwith\ndysphagia\nwas\nrecorded.\nThese\nfigures\nsuggest\nthat reflux occurs in pregnancy where no hiatus\nhernia\nexists. The\napparent\nanomalies\nbetween\nMarchand's\nfindings\nand\nthose\nof Dutton\nand\nBland are presumably explained by the higher inci-\ndence of abnormal pregnancy in the latter's patients.\nIt seems certain that dysphagia is more likely to\noccur after pregnancy complicated by hyperemesis\ngravidarum, and is more commonly encountered\ntherefore in a maternity unit treating complicated\npregnancy. The\npresence\nof\na\ngastro-duodenal\n(Ryle) tube in the oesophagus and stomach may\nbe\nimportant\nin\nthe\ngenesis\nof\noesophageal\nstricture.\nThe\nsubject\nhas\nbeen\ndiscussed\nby\nDouglas (1956). He regarded the Ryle tube as a\nfactor of secondary importance to the excessive\nvomiting; he stated that 'the combination of these\nthree factors,\nregurgitation,\nthe gastro-duodenal\ntube, and debilitation, may result in a stricture\nbeing formed'.\nHussain\n(1964) described\na 22-\nyear-old primigravida suffering from hyperemesis\ngravidarum who complained\nof dysphagia one\nweek after the removal of a Ryle tube which had\nbeen\npassed\nto\ntreat\nexcessive\nvomiting.\nA\nstricture of the oesophagus developed and was\nresected eight months later; a hiatus hernia was\npresent.\nIntubation of the oesophagus cannot seriously\nbe considered as a cause in our patients, nor is\nthere evidence that relaxation of the controlling\nmechanism at the cardia, due to anaesthesia or\nthe\ningestion\nof\nirritant\nanaesthetic\nagents\n(suggested by Hara (1949) as a possible cause),\nwas a factor of any importance in the production\nof the oesophageal obstruction.\nTo avoid repetition in the case histories of our\npatients a number of features common to each\nmust be mentioned. It was ascertained from the\nparents of each of these patients that none of the\npatients\never\nsuffered from\nfeeding\ndifficulties,\nexcessive\nvomiting,\nor\ndifficulty\nin\nswallowing\nduring infancy. The importance of this will be\ndiscussed later. Each suffered from hyperemesis"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1166
encoding: FLOAT32
metadata:
{"title": "Oesophageal obstruction following hyperemesis gravidarum", "chroma:document": "with excessive vomiting during her pregnancy and\nwas\ntold, when the dysphagia\nbegan,\nthat the\ncondition was of functional origin. Indeed, in two\npatients\npsychiatric\ntreatment\nwas\ngiven.\nNo\npatient complained of dysphagia whilst carrying\nthe\nbaby. Fear of exacerbating symptoms was\ngiven\nas\nthe\nreason\nfor\nfour\nof\nthe\npatients\n528"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1167
encoding: FLOAT32
metadata:
{"title": "Pedunculated haemangiopericytoma attached the thoracic aorta", "chroma:document": "Thorax (1966), 21, 193.\nPedunculated haemangiopericytoma attached to the\nthoracic aorta\nW. K. BLENKINSOPP AND\nJ. T. HOBBS\nFrom\nthe Department of Pathology and the Surgical Unit, St. Mary's Hospital, London W.2\nIn\n1942 Murray and Stout reported on\ntissue\nculture of the\n'epithelioid'\ncells of the glomus\ntumour and suggested that they were the pericytes\nof Zimmermann. In the same year these authors\n(Stout and Murray, 1942) published the first d>-\nscription\nof another tumour of the same\ncells\nwhich they named 'haemangiopericytoma'. Since\nthen more than 300 examples of this tumour have\nbeen reported, at least 90% of them in America.\nThis paper describes an unusual presentation of\nhaemangiopericytoma and remarks on the rarity\nof reported cases in this country.\nCASE REPORT\nIn\n1959\na\nwoman\nof\n63\nnoticed\na\n'scratching'\nsensation in her chest, but a chest radiograph at the\nHampstead\nChest\nClinic\nshowed\nno\nabnormality.\nFive years later she had acute bronchitis; this quickly\ncleared up with a course of tetracycline, but a chest\nradiograph at this time showed a mass in the para-\naortic region. Subsequent radiographic examinations\nshowed that the mass was increasing in size, and in\nJanuary 1965 the patient was referred to the thoracic\nsurgical unit at St. Mary's Hospital with a tentative\ndiagnosis of aortic aneurysm.\nThe patient gave a history of winter cough with\nsputum for six years; she had noticed that left chest\ndiscomfort was brought on by coughing and deep\ninspiration, and sometimes it was relieved by choline\ntheophyllinate. Her weight was increasing. Examina-\ntion showed a fit, slightly overweight, elderly woman\nwith no cardiovascular abnormalities except a blood\npressure of 150/100 mm. Hg; the pulse was regular\nat 73/minute. The chest was emphysematous, and\nthere were scattered rhonchi in both lung fields. The\nabdomen was obese, but no viscus or abnormal mass\nwas palpable.\nINVESTIGATIONS Haemoglobin 99%, packedcellvolume\n45%, white\ncell count 7,000/c.mm.;\nsedimentation"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1168
encoding: FLOAT32
metadata:
{"title": "Pedunculated haemangiopericytoma attached the thoracic aorta", "chroma:document": "rate 16 mm./hr.; plasma electrolytes normal, plasma\nurea 30 mg./100 ml., serum calcium 10 mg./100 ml.;\nWassermann reaction and Harris test both negative;\nblood\ngroup 0\nrhesus-positive;\nelectrocardiogram\nnormal. The forced vital capacity was 1,130 ml., and\nthe ratio of forced expiratory volume in one second\nto the forced vital capacity was 63-5%. Chest radio-\ngraphs (Fig. 1) revealed a large rounded mass in the\nleft\nparavertebral\ngutter,\nand\nchest\ntomography\nshowed normal thoracic vertebrae with the main mass\nposterior\nto the aortic plane but extending\nto the\naortic arch; an arch aortogram via the left axillary\nartery showed a normal lumen and no filling of the\nmass.\nA diagnosis of aortic aneurysm was thus not con-\nfirmed by angiography, and a provisional diagnosis\nof neurofibroma was doubted because there was no\nextension towards the intervertebral foramina and no\nwidening of the rib spaces locally; the possibility of\nan\nenteric\ncyst was\nconsidered.\nBecause\nthe mass\nhad been rapidly increasing in size a surgical explora-\ntion was decided upon, and on 9 March 1965 the left\nchest was\nopened\nthrough\nthe\nseventh\nintercostal\nspace. There was no pleural effusion and the pleura\nand left lung appeared normal, but when the lung\nwas\ndisplaced\nforwards\na\ntense,\nfleshy,\nmobile\ntumour, about 8 cm. long, was seen in the para-\nvertebral gutter, attached by a pedicle to the antero-\nlateral aspect of the descending aorta at the level of\nT8; there was no local infiltration. The mass was\neasily removed when a cleavage plane was formed in\nthe outermost layers of the adventitia of the aorta,\nand\nthe\nleft\nthoracotomy\nwas\nthen\nclosed.\nThe\npatient's recovery was uneventful,' and three months\nlater she was symptom-free.\nHISTOLOGY\nThe specimen was a firm, encapsulated\nmass, measuring 8-5 by 5-0 by 4-5 cm., including at\none end a pedicle\n1-5 cm. long and 3 cm. in dia-\nmeter. The cut surface\nof the tumour was\nfleshy,\nand the base of the pedicle was composed of loose\nconnective tissue. Histologically the tumour consisted\nof\nvery\nnumerous"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1169
encoding: FLOAT32
metadata:
{"title": "Pedunculated haemangiopericytoma attached the thoracic aorta", "chroma:document": "numerous\ncapillaries\nseparated\nby\nfairly\nregular rounded cells (Figs 2 and 3). Reticulin staining\nshowed the\ncells\nto be lying outside the capillary\nsheaths, and most of the cells were surrounded by\nreticulin\nfibres;\nthe\nreticulin was not arranged\nin\nalveoli. Scattered among the tumour cells there were\n193"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1170
encoding: FLOAT32
metadata:
{"title": "Dopaminergic medication normalizes aberrant cognitive control circuit signalling in Parkinson\u2019s disease", "chroma:document": "Dopaminergic medication normalizes \naberrant cognitive control circuit signalling in \nParkinson\u2019s disease\nWeidong Cai,1,2 Christina B. Young,3 Rui Yuan,1 Byeongwook Lee,1 Sephira Ryman,3 \nJeehyun Kim,3 Laurice Yang,3 Victor W. Henderson,2,3,4 Kathleen L. Poston2,3,5 \nand Vinod Menon1,2,3\nDopaminergic medication is widely used to alleviate motor symptoms of Parkinson\u2019s disease, but these medications \nalso impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication \nimpacts cognition and working memory in Parkinson\u2019s disease by modulating frontoparietal-basal ganglia cognitive \ncontrol circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual \ndifferences in response to dopaminergic medication. Here we use a novel state-space computational model with ul-\ntra-fast (490 ms resolution) functional MRI to investigate dynamic causal signalling in frontoparietal-basal ganglia \ncircuits associated with working memory in 44 Parkinson\u2019s disease patients ON and OFF dopaminergic medication, \nas well as matched 36 healthy controls.\nOur analysis revealed aberrant causal signalling in frontoparietal-basal ganglia circuits in Parkinson\u2019s disease pa-\ntients OFF medication. Importantly, aberrant signalling was normalized by dopaminergic medication and a novel \nquantitative distance measure predicted individual differences in cognitive change associated with medication in \nParkinson\u2019s disease patients. These findings were specific to causal signalling measures, as no such effects were de-\ntected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal cau-\nsal signalling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in Parkinson\u2019s \ndisease. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1171
encoding: FLOAT32
metadata:
{"title": "Dopaminergic medication normalizes aberrant cognitive control circuit signalling in Parkinson\u2019s disease", "chroma:document": "memory load and the strength of load-dependent causal weights was not related to individual differences in working \nmemory task performance in Parkinson\u2019s disease patients OFF medication. However, dopaminergic medication in \nParkinson\u2019s disease patients reinstated the relation with working memory performance.\nOur findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify \nmechanisms by which dopaminergic medication normalizes cognitive control circuits.\n1\nDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA\n2\nWu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305, USA\n3\nDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA\n4\nDepartment of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA\n5\nDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA\nCorrespondence to: Weidong Cai, PhD  \n1070 Arastradero Rd., Palo Alto, CA 94304, USA  \nE-mail: wdcai@stanford.edu\nCorrespondence may also be addressed to: Vinod Menon, PhD  \nE-mail: menon@stanford.edu\nReceived July 30, 2021. Revised December 03, 2021. Accepted December 10, 2021. Advance access publication August 19, 2022\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: \njournals.permissions@oup.com\nhttps://doi.org/10.1093/brain/awac007\nBRAIN 2022: 145; 4042\u20134055 | 4042"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1172
encoding: FLOAT32
metadata:
{"title": "Recurrent chest infections, ciliary abnormalities and partial complement deficiency in Jordanian family", "chroma:document": "Thorax 1981; 36: 502-7\nRecurrent chest infections, ciliary abnormalities and\npartial complement deficiency in a Jordanian family\nID STARKE, B CORRIN, PJ SELBY, ADB WEBSTER, M TURNER-WARWICK\nFrom the Cardiothoracic Institute andBrompton Hospital and St Thomas's Hospital Medical School,\nLondon, and the Clinical Research Centre, Harrow, Middlesex\nABSTRACT\nFour girls born to second cousin parents developed chronic chest infection and bronchi-\nectasis in infancy. Three were studied in detail: they all had the same HLA haplotype, all showed\nrandom orientation of cilia or compound cilia in the respiratory tract, and all had low levels of the\nCl and C2 components of the complement system. Although the cause of the respiratory disease in\nthis family remains unclear, it is suggested that the low Cl levels may have contributed to the\ndisease in two of the children while the low C2 levels were artefacts and the ciliary abnormalities\nwere secondary to chronic chest infection.\nWe have recently encountered a Jordanian family in\nwhich four children born to second cousin parents\nsuffered from recurrent chest infections and bronchi-\nectasis. An inherited abnormality was suspected and,\nbecause primary defects in host defence often have a\ngenetic\nbasis, 1-3\nwe\nhave\ninvestigated\ndefence\nmechanisms against infection as fully as possible in\nthis family.\nCase histories\nCASE\n1\nThis girl (As J, aged 10 years) had had a productive\ncough and catarrh since infancy. At 8 years she had\nbeen admitted to a sanatorium with suspected, but\nunconfirmed, pulmonary tuberculosis. At 9 years she\nhad undergone a left pneumonectomy. On examina-\ntion she was a small,\nthin child with scattered\ncrackles and wheezes over the right hemithorax. Her\nchest radiograph showed absence of the left lung,\nright\nmiddle\nlobe\ncollapse\nand\nbronchial\nwall\nthickening at the right base. The maxillary sinuses\nwere opaque and the frontal sinuses were absent.\nCASE 2\nThis girl (Kh J, aged 9 years) had been short of\nAddress for reprint requests: Dr ID Starke, MRC Leukaemia"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1173
encoding: FLOAT32
metadata:
{"title": "Recurrent chest infections, ciliary abnormalities and partial complement deficiency in Jordanian family", "chroma:document": "Unit, Royal Postgraduate Medical School, Hammersmith\nHospital, Ducane Road, London W12 OHS.\nbreath and had had a productive cough\nsince\ninfancy. On examination she had finger clubbing and\ncentral cyanosis. There was dullness to percussion\nand widespread crackles were heard over the left\nhemithorax. The chest radiograph showed a con-\ni\n'.\nII'\nFig 1\nChest radiograph ofpatient 2. There is contraction\nofthe left lung with widespread cavityformation, together\nwith some consolidation in the right lower zone.\n502\nja\n4"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1174
encoding: FLOAT32
metadata:
{"title": "The third in the lung: physiology clinical perspectives", "chroma:document": "Thorax 1984;39:561-567\nEditorial\nThe third nervous system in the lung:\nphysiology and clinical perspectives\nThe\nautonomic\nnervous\nsystem\ncontrols many\naspects of pulmonary function' and, until recently, it\nwas thought that this was achieved entirely by means\nof classical cholinergic and adrenergic mechanisms.\nThis view has recently been challenged by the\ndemonstration of a third nervous system in the air-\nways (fig). Although the identities of the neuro-\ntransmitters in this newly recognised nervous system\nare not certain, there is increasing evidence that they\nare peptides. This third nervous system is of particu-\nlar interest as it is the predominant inhibitory nerv-\nous pathway to human airway smooth muscle and\nthis raises the possibility that a functional defect in\nthis nervous system might underlie bronchial hyper-\nreactivity in asthma. The recognition that a third\ncomponent of the autonomic nervous system regu-\nlates airway smooth muscle tone and other aspects\nof lung physiology has stimulated great interest,\nsince it may provide new insights into diseases such\nas asthma and chronic obstructive lung disease, and\nmay also lead to novel therapeutic approaches.\nA third component of the autonomic nervous system\nThe existence of a nervous system in the gastrointes-\ntinal\ntract\nwhich\nis\nneither\nadrenergic\nnor\ncholinergic has been established for many years.\nNon-adrenergic, non-cholinergic (NANC) nerves\ncontrol gut motility and secretions and have been\ndemonstrated in vertebrates from fish to man.23\nIndeed, the presence of NANC nerves in primitive\nvertebrates\nindicates\nthat\nthis\nnervous\nsystem\ndeveloped early in evolution. The third nervous sys-\ntem has also been demonstrated in the urogenital\ntract,\nthe\neye, and\nthe\ncardiovascular\nsystem.3\nBecause the airways develop embroyologically from\nthe foregut it is not surprising to find that NANC\nnerves are also present in the lung.\nNANC nerves in the airways\nInhibitory nerves which relax toad lungs and which\nAddress for reprint requests: Dr Peter J Barnes, Department of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1175
encoding: FLOAT32
metadata:
{"title": "The third in the lung: physiology clinical perspectives", "chroma:document": "Medicine (Respiratory\nDivision), Royal Postgraduate Medical\nSchool, Hammersmith Hospital, London W12 OHS.\nare\nneither\nadrenergic\nnor\ncholinergic\nwere\ndescribed by Campbell in 1971.4 Since then NANC\nnerves which relax airway smooth muscle have been\nfound in several species, including man.55 In these\nstudies airway strips are mounted in an organ bath\nand stimulated by an electrical current that selec-\ntively activates nerves. In guinea pig tracheal strips\nelectrical field stimulation produces an initial con-\ntraction that is blocked by the anticholinergic drug\natropine and therefore due to acetylcholine release\nfrom cholinergic nerves. The initial contraction is\nfollowed by a relaxation, which\nis only partially\ninhibited by ,3 adrenergic blockers.56 Thus, although\na\ncomponent\nof\nthe\ninhibitory\nresponse\nis\nadrenergic,\nthere\nis\na component\nthat\nis non-\nadrenergic. The nerve toxin tetrodotoxin abolishes\nthese responses to field stimulation and proves that\nthey are mediated by nerves (which must be post-\nganglionic), and not due to a direct effect on smooth\nmuscle. Thus guinea pig trachea appears to have\nexcitatory cholinergic nerves and inhibitory nerves\nwhich are both adrenergic and non-adrenergic. In\nsimilar studies on human airway smooth muscle a\ncholinergic contractile component is also demon-\nstrable, but the inhibitory response is unaffected by\nadrenergic blockade.78 This indicates, rather surpris-\ningly, that there is no functional sympathetic inner-\nvation of human airway smooth muscle and that\ninhibitory nerves are non-adrenergic. The absence\nof sympathetic nerves in human airway smooth\nmuscle is supported by histological studies showing\nan absence of adrenergic nerve terminals within\nsmooth muscle,79 by studies showing a lack of effect\nof cocaine (a neuronal uptake inhibitor) on norad-\nrenaline dose-response curves,'0 and by the lack of\neffect of tyramine (which directly releases norad-\nrenaline from nerve terminals) on airway function in\nman.\" There are, of course, adrenergic receptors in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1176
encoding: FLOAT32
metadata:
{"title": "The third in the lung: physiology clinical perspectives", "chroma:document": "airway smooth muscle,'2 and these are presumably\nregulated by circulating adrenaline.'3 NANC nerves\nappear to be the only neural inhibitory pathway in\nhuman airway smooth muscle from the trachea to\nthe smallest bronchi,7 and for this reason there is\nparticular interest in their physiological role and\nregulation.\nNANC nerves have also been demonstrated in\n561"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1177
encoding: FLOAT32
metadata:
{"title": "Cerebral blood flow during cardiopulmonary bypass in effect of arterial filtration", "chroma:document": "Thorax 1986;41:386-395\nCerebral blood flow during cardiopulmonary bypass\nin man: effect of arterial filtration\nLEIFHENRIKSEN, ERIKHJELMS\nFrom the Departments ofNeurology and Thoracic Surgery, State University Hospital, Copenhagen, Denmark\nABSTRACT Cerebral blood flow was recorded in 39 patients undergoing cardiac surgery by intra-\narterial injection of xenon 133. There were three subgroups of patients: 10 patients had a 20 micron\narterial filter (Johnson) and 11 a 40 micron filter (Pall), and 18 had no arterial filtration. All patients\nhad a 40 micron (Pall) filter in the coronary suction line. Significant changes in cerebral blood flow\noccurred during extracorporeal circulation (p < 0.0001). For all patients cerebral blood flow in-\ncreased from a resting prebypass level of 30 to 46 and 57 ml/100 g a minute during initial and stable\nhypothermic extracorporeal circulation respectively. Both measurements were obtained at 26\u00b0C and\nthe recordings were made on average 12 and 55 minutes after the extracorporeal circulation was\nstarted. During rewarming cerebral blood flow increased to 64, 53, 41, and 36 ml/g a minute at 310,\n330, 350, and 37\u00b0C respectively, and when measured four and 16 minutes on average after bypass it\nwas 44 and 41 ml/100 g a minute. This general brain hyperperfusion was noticed in all patients with\na high enough mean blood pressure to produce hyperaemia. Interposing 20 and 40 micron arterial\nfilters reduced cerebral blood flow but did not prevent this hyperaemia. The cerebral autoregulation,\nwhich maintains a constant cerebral blood flow within wide limits of perfusion pressures, was not\naffected by arterial filtration. The lower limit of blood pressure at which a further reduction in blood\npressure was followed by a reduction in cerebral blood flow was around 60mmHg in all three\ngroups.\nCurrently postoperative mortality is of little use as a\nmeasure of the quality of cardiac surgery, as mortality\nrates are generally low, despite strikingly different"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1178
encoding: FLOAT32
metadata:
{"title": "Cerebral blood flow during cardiopulmonary bypass in effect of arterial filtration", "chroma:document": "perfusion techniques. A new index of the quality of\nsurgery is emerging, based on psychometric analysis\nof the extent to which complex mental functioning is\npreserved in the early postoperative period, combined\nwith more quantitative methods, such as analysis of\nspinal\nfluid\nintracellular\nmarkers1- 3\nand\nmea-\nsurements of cerebral blood flow during and after car-\ndiac surgery.4-8\nIn our earlier studies of cerebral blood flow during\ncardiac surgery we found a consistent hyperperfusion\nof the brain during cardiopulmonary bypass6 -8 and a\ndiffusely reduced regional cerebral blood flow after\nsurgery,5 the most reasonable explanation being a\nAddress for reprint requests: Dr Leif Henriksen, Department of\nNeurology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen,\nDenmark.\nAccepted 13 November 1985\ndiffuse\nmicrovascular\nblockage\nof microembolic\norigin.\nFiltration of the blood returned from the coronary\nsuction line has become widely accepted, but the\nbeneficial effect of arterial line filters is still ques-\ntioned. The introduction of refined techniques for de-\ntecting microemboli present in the arterial line and in\nthe carotid arteries have suggested that the incidence\nof potentially hazardous microemboli during con-\nventional cardiopulmonary bypass is much greater\nthan previously realised. Since the size of micro-\nemboli that would be safe cannot be defined, it seems\nreasonable to reduce the quantity as much as possible.\nThe present study was designed\nto determine\nwhether arterial filtration could prevent the abnormal\nbrain hyperperfusion usually noted in our patients\nduring bypass.\nMethods\nThe results and their interpretation are based on a\nstudy of 39 unselected adult patients undergoing open\n386"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1179
encoding: FLOAT32
metadata:
{"title": "Endothelin, vasopressin, immunoreactivity in epithelium from rabbit", "chroma:document": "Thorax 1992;47:1044-1049\nEndothelin, vasopressin, and substance P like\nimmunoreactivity in cultured and intact\nepithelium from rabbit trachea\nR E Rennick, A Loesch, G Burnstock\nAbstract\nBackground\nThe\ncontrol\nof airways\nreactivity is essential to our understand-\ning of disease processes such as asthma.\nMany studies have examined the neural\ncontrol of the airways, but more recently\nthere has been evidence to show that the\nepithelium\nlining\nthe\nairways\nmay\ninfluence airways reactivity.\nMethods\nRabbit tracheal epithelial cells\nwere dispersed with enzymes, grown in\nprimary culture and fixed. Tissue from\nintact tracheas was also sampled and\nfixed. Localisation of the vasoactive sub-\nstances endothelin-1, arginine-vasopres-\nsin, and substance P was investigated by\nimmunolabelling techniques.\nResults\nScattered immunolabelling to\nendothelin-1, arginine-vasopressin, and\nsubstance P was found throughout the\ncultures (with\n< 20% of cells staining\npositively\nto\neach\nantibody).\nAt\nthe\nultrastructural\nlevel\nthis\nimmuno-\nreactivity was found in the cytoplasmic\nmatrix. In addition, immunoreactivity of\nintact tissue to endothelin-1, arginine-\nvasopressin,\nand\nsubstance\nP\nwas\nexamined and positively staining cells\nwere found to be scattered through the\nepithelium.\nConclusions\nThe\npresence\nof\nthese\nvasoactive substances within the epithe-\nlium lining the airways supports the view\nthat\nepithelial\ncells may\nprovide\nan\nadditional mechanism in the control of\nairways reactivity.\n(Thorax 1992;47:1044-1049)\nDepartment of\nAnatomy and\nDevelopmental\nBiology and Centre\nfor Neuroscience,\nUniversity College\nLondon, London\nWC1E 6BT\nR E Rennick\nA Loesch\nG Burnstock\nReprint requests to:\nProfessor Burnstock\nReceived 4 December 1991\nReturned to authors\n22 January 1992\nRevised version received\n8 June 1992\nAccepted 18 June 1992\nHyperreactivity of the airways is a characteris-\ntic feature of asthma. In such patients damage\nor loss of the airways epithelium is a common\nfinding.' The epithelium lining the airways was\noriginally\nconsidered\nmerely\nas\na"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1180
encoding: FLOAT32
metadata:
{"title": "Endothelin, vasopressin, immunoreactivity in epithelium from rabbit", "chroma:document": "as\na\nbarrier\npreventing passage of dust, microorganisms,\nand other airborne particles into the underlying\ntissue. More recently, however,\nit has been\nshown that removal of the airways epithelium\nleads\nto increased responses of the smooth\nmuscle of the airways to various contractile\nstimuli.2 This phenomenon occurs in the air-\nways of a number of different species, including\ndog, guinea pig, rabbit, and man.8 Studies by\nFlavahan and Vanhoutte9 showed that there\nwas increased sensitivity of the airways\nto\nhistamine, acetylcholine, and 5-hydroxytryp-\ntamine (5-HT) after removal of the epithelium.\nThey suggested that this might indicate that an\nepithelium derived relaxing factor, analogous\nto the endothelium derived relaxing factor\nreleased from vascular endothelial cells,'\" is\nactive in the airways. Orehek et al examined the\ninfluence on airways reactivity ofdrugs inhibit-\ning prostaglandin synthesis and their results\nsuggested\nthat\nrelease\nof products\nof the\ncyclooxygenase pathway may be responsible\nfor airways relaxation.\"\nSince the early 1970s it has been known that\nthere are amine precursor uptake and decar-\nboxylation (APUD) cells present in the airways\nepithelium.\"2 These cells are found throughout\nthe airways in innervated groups, known as\nneuroepithelial bodies, but in the trachea they\noccur only as\nsingle\ncells.'3\nStudies using\nmicrospectrofluorometry have shown that these\ncells contain amines such as 5-HT.'4'5 It is\npossible that other vasoactive substances that\nmay influence airways reactivity are present\nwithin the airways epithelium. In this study,\ntracheal epithelial cells were isolated and cul-\ntured and the presence, in both isolated cells\nand\nintact\ntissue,\nof endothelin- 1\n(ET- 1),\narginine-vasopressin (AVP), and substance P\n(SP) examined at the light and electron micro-\nscopic levels.\nMethods\nCELL CULTURE\nMale New Zealand White rabbits aged 4-6\nmonths were injected with a lethal dose of\nSagatal (RMB Animal Health, Dagenham,\nUK) and exsanguinated. Tracheal epithelial"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1181
encoding: FLOAT32
metadata:
{"title": "Endothelin, vasopressin, immunoreactivity in epithelium from rabbit", "chroma:document": "cells were isolated by enzymatic treatment.'6\nBriefly, the trachea was removed under sterile\nconditions and placed in Hanks' Balanced Salt\nSolution (HBSS; Gibco/Life Technologies,\nPaisley, UK) supplemented with penicillin\n(2 x 10' units/l; Glaxo Laboratories, Green-\nford), cleaned of adherent muscle and connec-\ntive tissue, then clamped at one end and filled\nwith a solution of 0- 1% protease (Sigma, Poole,\nUK) in HBSS. The other end was clamped so\nthat the tissue formed a sealed tube, and the\ntissue was then incubated overnight at 4\u00b0C.\nThe following morning the tissue was un-\nclamped, the lumen washed thoroughly with\nHBSS, and the resulting suspension centri-\nfuged at 100 g for 5 minutes. The resulting\npellet was resuspended in HBSS and spun as\nabove. The cells were resuspended in Ham's\nF12 media (Gibco) supplemented with 5%\n1044"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1182
encoding: FLOAT32
metadata:
{"title": "Gene therapy for respiratory diseases: potential applications and difficulties", "chroma:document": "Thorax 1995;50:484-486\nGene therapy for respiratory diseases: potential applications\nand difficulties\nThe use of genetic materials for treatment is a relatively\nsimple concept which, if successful, could revolutionise\nthe management of both inherited and acquired disease.\nThe aim is to modify production of a specific protein either\nthrough upregulation by introducing the DNA of interest,\nor downregulation through the use of antisense oligo-\nnucleotides. Such modification could be for long term\ncorrection of an inherited genetic defect such as cystic\nfibrosis or ot,-antitrypsin deficiency, on the one hand, or\nan acquired defect such\nas\ncancer on the other. Al-\nternatively, short term modification of protein production\ncould be used to alter inflammation in conditions such as\nasthma and oxidant-mediated lung injury. Although the\nconcepts are simple, the technology is complex and poorly\nunderstood, and it will be some time before gene therapy\nis routinely available in clinical practice. This editorial\noutlines the technology of gene transfer and reviews pro-\ngress towards therapy for the three lung conditions with\napproved gene therapy protocols, namely cystic fibrosis,\nocl-antitrypsin deficiency, and lung cancer.\nGene transfer techniques\nGene transfer requires two principal components\n- the\ncDNA of interest linked to an appropriate promoter, and\na gene transfer agent to facilitate entry into the cell. Most\ncurrent studies use \"ubiquitous\" promoters such as SV40,\nCMV and RSV which are derived from eukaryotic viruses\nand, in theory,\nare active in any nucleated cell. Lung\nspecific promoters such as SP-C (surfactant protein C) and\nCC 10 (Clara cell) are also being investigated.' There has,\nto date, been relatively little work done to define the relative\nadvantages of the different promoters. It is likely, however,\nthat cell specificity will prove to be valuable as it will limit\ngene expression to a desired cell population and may also\nbe easier to control.\nThe two main approaches being investigated with regard"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1183
encoding: FLOAT32
metadata:
{"title": "Gene therapy for respiratory diseases: potential applications and difficulties", "chroma:document": "to gene transfer agents are the use ofviruses and liposomes.\nEach has certain advantages and problems and future\nsystems may combine the best features of both.\nRetroviruses\ncan produce efficient gene transfer, in-\ncluding the integration of the DNA into the host genome.\nThese viruses are well suited to ex vivo transfection of cells\nwhich are removed from the body and then replaced in\na modified form\nas, for example, for hepatocytes and\nproduction of ac-antitrypsin considered below. They are,\nhowever, unsuitable for topical lung delivery since they only\ntransfect dividing cells and not the terminally differentiated\nairway epithelium. Furthermore, in vivo use may carry the\nrisks of germ line transfection and the induction of other\nunwanted changes by virtue of their random integration\ninto the host genome.\nAdenoviruses have the advantage of being trophic for\nthe respiratory epithelium and should, in theory, produce\nrelatively efficient gene transfer to the airways. However,\ntwo principal concerns about their use centre around safety\nand efficacy on repeated administration. Portions of the\nvirus's own genome are deleted, partly to provide space\nfor the gene of interest to be inserted and partly to produce\na replication incompetent virus. The principal problem\nrelates to the viral coat proteins which are immunogenic\nand which result in the production ofinflammation through\ncytotoxic T lymphocytes\nor neutralising antibodies\nre-\nducing\nthe\nefficiency\nand\nduration\nof repeated\nap-\nplications.2 A second theoretical risk is recombination with\na wild type virus which might restore the ability to replicate\nand cause infection. Increasingly extensive deletions of the\nviral genome are therefore being investigated to reduce\nimmunogenicity and replication potential.3\nLiposomes are lipid vesicles which form spontaneously\nwhen certain lipid preparations are mixed in polar so-\nlutions. Cationic liposomes form complexes with DNA\n(which has a net negative charge) and have been used"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1184
encoding: FLOAT32
metadata:
{"title": "Gene therapy for respiratory diseases: potential applications and difficulties", "chroma:document": "for some years for in vitro gene transfer. Liposomes are\nrelatively inefficient at gene transfer compared with viral\nvectors but have some major advantages. They have low\ntoxicity and are unlikely to provoke inflammation or to\ninitiate an immune reaction on repeated administration.\nLiposomes\nhave\ncomplex\nphysicochemical\nproperties\nwhich are only poorly understood and which probably\nunderlie their variable performance in gene transfer ex-\nperiments.4\nAdministration of gene transfer systems\nNebulisation is likely to be the most acceptable delivery\nsystem for routine repeated application to the lower airways\nin man. It has the advantages of widespread deposition\nwhich can, to a limited extent, be controlled by varying\ndroplet size. Contact time may also be enhanced by pro-\nlonged nebulisation, important in the light of mucociliary\nclearance within the airways. A theoretical disadvantage is\nthe considerable mechanical stress applied to the liquid\nduring the process of nebulisation. This might damage the\ngene transfer agent and, in particular, might alter the\nstructure of a liposome-DNA complex. The presence of\nmucus and airway surface liquid further complicates pre-\ndictions of whether efficient delivery can be achieved,\nparticularly since purulent secretions contain DNases. The\nmucus layer may impair access to the cell surface, whilst\nthe aqueous layer may dilute and alter the composition of\nany topically applied liquid. A recent report of pulmonary\nepithelial gene transfer following intravenous injection of\na liposome-reporter gene complex is tantalising5 and, if\nrepeatable, suggests the possibility of other gene transfer\nstrategies. One potential disadvantage is widespread gene\ntransfer to other organs, but organ or cell specific promoters\nor targeted gene transfer may help to overcome this dif-\nficulty.\nGene therapy for cystic fibrosis\nGene therapy for cystic fibrosis has become a possibility\nsince the isolation of the gene in 1989.6 The protein coded\nfor by this gene, cystic fibrosis transmembrane conductance"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1185
encoding: FLOAT32
metadata:
{"title": "Gene therapy for respiratory diseases: potential applications and difficulties", "chroma:document": "regulator (CFTR), functions as a cAMP-regulated chloride\nchannel on the mucosal surface of the airway epithelium.7\nInitial studies demonstrated that CFTR gene transfer into\ncystic fibrosis cells in vitro could correct this chloride\ndefect.89 Using both adenovirus'0 and liposome\" mediated\ngene transfer it was subsequently demonstrated that the\nCFTR gene could be expressed in the airways of normal\nmice in vivo. Instillation of the CFTR gene into the lungs\nwas followed by appearance of mRNA at day\n1, with\nexpression sustained for up to four weeks. Transgenic\ncystic\nfibrosis\nmice\nhave\nalso\nbeen\nused\nto\nassess\nCFTR gene transfer in vivo. Thus, both instillation'2 and\n4.84"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1186
encoding: FLOAT32
metadata:
{"title": "Sleep-related breathing disorders 1Series Obstructive sleep apnoea: definitions, epidemiology, and natural history", "chroma:document": "Sleep-related breathing disorders 1Series editor: PM A Calverley\nObstructive sleep apnoea: definitions,\nepidemiology, and natural history\nJ R Stradling\nDefinitions, epidemiology, and the natural his-\ntory of obstructive sleep apnoea (OSA) are\nusefully considered together. This is because\nOSA is not a condition that one either has or\ndoes not have, but it exists in a continuum\nbetween complete normality through to gross,\nall night, obstructive sleep apnoea. Thus, the\nprevalence of the condition depends critically\nupon definitions and where one draws the ar-\nbitrary line between normality and abnormality.\nA further complication is that, particularly in\nthe mid range of severity, there is considerable\nnight to night variation.' As with systemic hy-\npertension, it is probably not very useful to try\nto define a threshold for normality, but rather\nto accept that a continuum exists and quote\nprevalences for various levels of \"sleep apnoea\nactivity\". This should allow correlations with\nsymptoms and secondary consequences to be\ndrawn, and an attempt made to calculate risk!\nbenefit ratios for various treatments at these\ndifferent \"sleep apnoea activity\" levels - again,\nsimilar to the approach in systemic hyper-\ntension. This, or course, supposes that we\nknow exactly how to measure \"sleep apnoea\nactivity\" (as well as its main consequences,\nsleep fragmentation) but, as we discuss later,\nwe do not.\nbelieved to be the primary (and only) path-\nological event.3 An early definition of the\nsleep apnoea syndrome required the counting\nof these apnoeas, and >5/hour of >10 second\napnoeas was an early popular example.3 The\nchoice of >5/hour and of >10 second duration\nwas almost entirely arbitrary, but some defin-\nitions were needed in the early days to facilitate\nresearch in this area. The recognition of hypo-\npnoeas as arousing events4 required the ad-\ndition of some definition of these events too.\nDefinitions of hypopnoeas are less universal\nthan those for apnoea. Sometimes a 50% re-\nduction in ribcage and abdominal excursion"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1187
encoding: FLOAT32
metadata:
{"title": "Sleep-related breathing disorders 1Series Obstructive sleep apnoea: definitions, epidemiology, and natural history", "chroma:document": "for 10 seconds is required, the 10 second re-\nquirement may or may not be abandoned if a\ndip of >3% or >4% in Sao2 accompanies it,\nand the calculation of the preceding baseline\nvaries between laboratories as well. These rigid\ndefinitions have now largely outlived their clin-\nical usefulness5 because of the recognition of\nsleep disturbance from upper airways nar-\nrowing,\neven\nwithout hypopnoea\nor hyp-\noxaemia - a point to which we will return.\nThis might imply that the real requirement is\nto measure short arousals from the EEG but,\ndespite\nattempts\nto\ndefine\narbitrarily such\narousals,6 there is no useful recognised stand-\nAetiology\nAt sleep onset all skeletal muscle loses tone.\nThis is probably necessary to sleep comfortably.\nThe pharyngeal muscles that dilate and main-\ntain patency in the upper airway share in this\ngeneral loss of muscle tone so that even in\ntotally normal, non-snoring, individuals there\nis narrowing of the upper airway2 with an in-\ncrease in airways resistance (fig 1). This nar-\nrowing\nat\nsleep\nonset\nvaries\nconsiderably\nbetween individuals and, when occurring be-\nyond a certain degree, thepharyngeal walls come\nclose enough together (with or without the\nuvula within the lumen) to generate snoring.\nFurther narrowing allows complete collapse,\nhence the term \"sleep apnoea\". Although the\ndegree of narrowing is a continuous variable,\nthe onset of snoring and of complete collapse\nare clearly two \"steps\" in the process which\nhave been seized on as easily defined and meas-\nured consequences. So dramatic is the point\nof onset of apnoeas that initially these were\nN\nI\nE\n0Q\n'U\nCO\nU,1\nU)a.a.\n20 F-\n16 e\n12 H\n8\n4\nAwake\nNon-REM\nsleep\nFigure 1\nChanges in upper airways resistance with the\nonset of non-REM sleep in six normal, non-snoring,\nsubjects. Note the considerable interindividual variability.\nRedrawn from Wwgand et al.'\n24 r\nOsler Chest Unit,\nThe Churchill\nHospital,\nHeadington, Oxford\nOX3 7LJ, UK\nJ R Stradling\nn\nn%\nThorax 1995;50:683-689\n683\nv"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1188
encoding: FLOAT32
metadata:
{"title": "Preparing for the next viral threat with broad-spectrum antivirals", "chroma:document": "The Journal of Clinical Investigation   \nR E V I E W\n1\nIntroduction\nOver 200 viruses are known to cause disease in humans, yet cur-\nrently approved antiviral drugs are available to treat only about \n10 of these viral infections. The past decade has underscored the \nglobal threat posed by emerging viruses. Spillovers from animals \nto humans have resulted in several Ebola virus disease (EVD) out-\nbreaks, the Middle East respiratory syndrome (MERS) outbreak, \nand possibly the current coronavirus disease 2019 (COVID-19) \npandemic. Global warming, increased urbanization, and air trav-\nel have contributed to the spread of vector-borne viruses endem-\nic to various parts of the world, including dengue virus (DENV), \nestimated to infect 400 million people in over 128 countries, and \nZika virus (ZIKV), the causative agent of a 2015 outbreak. More-\nover, political instability in various parts of the world continues to \npose risks to our military forces and civilians from potential spread \nof biothreat agents, such as poxviruses \u2014 whose natural spread \ncaused the ongoing monkeypox virus (MPXV) outbreak \u2014 and \nVenezuelan equine encephalitis virus (VEEV) (1, 2). There is thus \na huge unmet need for the development of effective therapeutics \nfor the treatment of existing and newly emerging viral infections.\nMost approved antivirals target viral enzymes, particularly \nproteases and polymerases (Figure 1). Such direct-acting antivi-\nrals (DAAs) have shown tremendous utility for the treatment of \nhepatitis C virus (HCV) and human immunodeficiency virus type \n1 (HIV-1) infections, and more recently COVID-19. However, \nthis approach to drug development has several major limitations. \nFirst, the spectrum of coverage provided is typically narrow, rang-\ning from a single viral genotype to a few related viruses at best. \nMoreover, this approach is not scalable to address the large unmet \nneed. It takes, on average, an 8- to 12-year timeline (3) and an aver-\nage cost of over $2 billion to develop a new drug. Thus, targeting"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1189
encoding: FLOAT32
metadata:
{"title": "Preparing for the next viral threat with broad-spectrum antivirals", "chroma:document": "viruses individually is expensive and slow. While timely, effective \nefforts were noted during the COVID-19 outbreak, the rapid rollout \nof nirmatrelvir, for example, was enabled by accelerated derivat-\nization of an existing series of SARS-CoV-1 main protease (Mpro) \ninhibitors. No such DAAs are, however, currently available for the \nmajority of viral families. The inability to predict the next emerg-\ning viral infection is another limitation, hampering adequate global \nhealth protection and national security preparedness. Lastly, when \nused individually, treatment with conventional DAAs often results \nin rapid emergence of drug resistance, complicating monotherapy \nregimens for HIV, HCV, and influenza A virus (IAV). In the case of \nSARS-CoV-2, escape mutations conferring high-level resistance \nto remdesivir and nirmatrelvir have already been selected in vitro \nand identified in circulating strains (4, 5). While combining drugs \nthat target distinct viral functions can overcome viral resistance, as \nexemplified by HIV and HCV treatment, developing such \u201ccock-\ntail\u201d regimens for multiple acute infections is not feasible.\nAn alternative solution is the development of broad-spectrum \nantiviral drugs. One advantage of this approach is reduced time \nand cost associated with the early stages of drug development per \napproved indication. It can also diminish the clinical risks in more \nadvanced stages of development. The off-label use of approved \nantivirals against new viral indications can provide further eco-\nnomic incentives, as these drugs were already rigorously tested for \ntoxicity, pharmacokinetics, pharmacodynamics, dosing, etc. These \nadvantages have been recently demonstrated by the repurposing of \nremdesivir and molnupiravir \u2014 originally developed to treat EVD \nand VEEV, respectively \u2014 for the treatment of COVID-19 (6, 7). \nImportantly, this approach can facilitate readiness for future out-\nbreaks of newly emerging pathogens. Broad-spectrum antivirals"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1190
encoding: FLOAT32
metadata:
{"title": "Preparing for the next viral threat with broad-spectrum antivirals", "chroma:document": "could also be used to treat rare viral infections for which no drug is \navailable. Lastly, a broad-spectrum antiviral could be administered \nThere is a large global unmet need for the development of countermeasures to combat hundreds of viruses known to cause \nhuman disease and for the establishment of a therapeutic portfolio for future pandemic preparedness. Most approved \nantiviral therapeutics target proteins encoded by a single virus, providing a narrow spectrum of coverage. This, combined \nwith the slow pace and high cost of drug development, limits the scalability of this direct-acting antiviral (DAA) approach. \nHere, we summarize progress and challenges in the development of broad-spectrum antivirals that target either viral \nelements (proteins, genome structures, and lipid envelopes) or cellular proviral factors co-opted by multiple viruses \nvia newly discovered compounds or repurposing of approved drugs. These strategies offer new means for developing \ntherapeutics against both existing and emerging viral threats that complement DAAs.\nPreparing for the next viral threat with broad-spectrum \nantivirals\nMarwah Karim,1 Chieh-Wen Lo,1 and Shirit Einav1,2,3\n1Division of Infectious Diseases and Geographic Medicine, Department of Medicine, and 2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA. \n3Chan Zuckerberg Biohub San Francisco, San Francisco, California, USA.\nAuthorship note: MK and CWL contributed equally to this work.\nConflict of interest: The authors have declared that no conflict of interest exists.\nCopyright: \u00a9 2023, Karim et al. This is an open access article published under the \nterms of the Creative Commons Attribution 4.0 International License.\nReference information: J Clin Invest. 2023;133(11):e170236.  \nhttps://doi.org/10.1172/JCI170236."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1191
encoding: FLOAT32
metadata:
{"title": "Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2 mouse model", "chroma:document": "The Journal of Clinical Investigation   \nR E S E A R C H  A R T I C L E\n1\nIntroduction\nThe neuronal ceroid lipofuscinoses (NCLs) are a group of neuro-\ndegenerative lysosomal storage disorders affecting children and \nyoung adults (1). Classic late infantile NCL, or CLN2 disease, is \none of the most common forms of NCL and caused by a deficiency \nof tripeptidyl peptidase 1 (TPP1) (2\u20134). Patients with CLN2 disease \ndevelop signs typically between 2 and 4 years of age including sei-\nzures and ataxia, often accompanied by speech delay (5, 6). These \nare followed by progressive psychomotor deterioration, and, if \nuntreated, these children die during their teenage years (7). A dis-\nease-modifying enzyme replacement therapy (ERT) for CLN2 dis-\nease is now available and appears to slow disease progression (8, \n9). However, ERT requires invasive biweekly infusions and is not \ncurative. Therefore, a need remains to develop less invasive and \nmore effective therapies for CLN2 disease.\nProgress toward this goal has been hampered by a fundamen-\ntal lack of knowledge of how TPP1 deficiency affects the central \nnervous system (CNS). Therapy-resistant epilepsy is a major clin-\nical feature in children with CLN2 disease and causes significant \nmorbidity (5\u20137). Cln2 mice often die suddenly, and the timing \nappears to be coincident with seizure-like behavior. However, \ntheir epileptic seizure phenotype and how this relates to survival \nhave yet to be explored. The histopathological outcome measures \nused in NCL preclinical studies typically include storage material \naccumulation, glial activation, and neuron loss (10, 11). The onset \nand progression of these phenotypes have been characterized in \ndetail in mouse models of multiple other forms of NCL. These \nstudies have revealed temporal and regional differences between \nthe NCLs, information that is important for the targeting of ther-\napies (12\u201319). Similar neuropathological phenotypes are evident in \nCln2-knockout mice at the end stage and have been used to judge"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1192
encoding: FLOAT32
metadata:
{"title": "Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2 mouse model", "chroma:document": "efficacy at disease end stage in preclinical studies (20\u201322). Howev-\ner, the onset, the regional and cellular specificity of these pheno-\ntypes, and how they progress over time have yet to be determined.\nWe have addressed both of these knowledge gaps in a poten-\ntially new knockin mouse (Cln2R207X) that models the most com-\nmon human disease-causing mutation in the CLN2 gene (23). We \nreport a robust and potentially novel spontaneous seizure pheno-\ntype that is associated with a loss of cortical neurons, including \ninterneurons, and significantly contributes to morbidity. Our data \nalso reveal a range of pronounced differences in the staging of \nCLN2 disease neuropathology compared with other forms of NCL. \nHaving described these clinically relevant readouts, we then used \nAlthough a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor \nunderstanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, \nwe investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, \nwhich carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-\nterm electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, \nproviding a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple \ncortical neuron populations, including those stained for interneuron markers. Further histological analysis revealed early \nlocalized microglial activation months before neuron loss started in the thalamocortical system and spinal cord, which was \naccompanied by astrogliosis. This pathology was more pronounced and occurred in the cortex before the thalamus or spinal \ncord and differed markedly from the staging seen in mouse models of other forms of neuronal ceroid lipofuscinosis. Neonatal"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1193
encoding: FLOAT32
metadata:
{"title": "Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2 mouse model", "chroma:document": "administration of adeno-associated virus serotype 9\u2013mediated gene therapy ameliorated the seizure and gait phenotypes \nand prolonged the life span of Cln2R207X mice, attenuating most pathological changes. Our findings highlight the importance of \nclinically relevant outcome measures for judging preclinical efficacy of therapeutic interventions for CLN2 disease.\nGene therapy ameliorates spontaneous seizures \nassociated with cortical neuron loss in a Cln2R207X \nmouse model\nKeigo Takahashi,1 Elizabeth M. Eultgen,1 Sophie H. Wang,1 Nicholas R. Rensing,2 Hemanth R. Nelvagal,1 Joshua T. Dearborn,3 \nOlivier Danos,4 Nicholas Buss,4 Mark S. Sands,3,5 Michael Wong,2 and Jonathan D. Cooper1,2,5\n1Department of Pediatrics, 2Department of Neurology, and 3Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. 4REGENXBIO Inc., Rockville, Maryland, USA. \n5Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.\nConflict of interest: JDC has received research support from BioMarin Pharmaceutical \nInc., Abeona Therapeutics Inc., REGENXBIO Inc., and Neurogene and is a consultant \nfor JCR Pharmaceuticals. OD and NB were paid employees of REGENXBIO Inc. at the \ntime of the study.\nCopyright: \u00a9 2023, Takahashi et al. This is an open access article published under the \nterms of the Creative Commons Attribution 4.0 International License.\nSubmitted: October 5, 2022; Accepted: April 25, 2023; Published: June 15, 2023.\nReference information: J Clin Invest. 2023;133(12):e165908. \nhttps://doi.org/10.1172/JCI165908."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1194
encoding: FLOAT32
metadata:
{"title": "Cerebral infarction due carotid occlusion and carbon monoxide Pathophysiological and neuropathological investigations", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:756-767\nCerebral infarction due to carotid occlusion and\ncarbon monoxide exposure: I. Pathophysiological and\nneuropathological investigations\nRUDOLF LAAS, JORG IGLOFFSTEIN, SOLVEIGH MEYERHOFF\nFrom the Department ofNeuropathology, EppendorfHospitals, University ofHamburg, Hamburg, Federal\nRepublic of Germany\nSUMMARY\nLigation of one common carotid artery and exposure to carbon monoxide has proved\nto be a reliable method of producing unilateral cerebral infarcts in the rat, allowing controlled\nexperiments in any given sample size. Pathophysiological measurements in awake and narcotised\nrats has shown that, in contrast to hypoxic hypoxia, the carbon monoxide-induced functional\nanaemia (3000 ppm in room air) did not stimulate chemoreceptors, thus causing a severe sys-\ntemic hypotension owing to peripheral vascular dilatation. This hypotension is likely to represent\nthe main pathogenetic factor in this model. An inhibition of ferro-enzymes by carbon monoxide\ndid not seem to be involved. The only cause of death was shown to be diffuse ipsilateral brain\noedema with or without extra-vasation of serum proteins. The EEG, the systemic arterial pres-\nsure, rotational behaviour, and carotidal stump pressure proved to be reliable predictors of\noutcome.\nSmall animal models are valuable in the investiga-\ntion of brain infarction by providing a sample size\nsufficient for statistical analysis. Those models pro-\nducing unilateral infarcts are further advantageous\nin that the contralateral hemisphere is available for\ncomparison in morphological and biochemical inves-\ntigations. Moreover, unilateral infarcts allow the\nstudy\nof\nbrain\ndamage\nby way\nof\nlateralised\nneurological signs.\nThe mongolian gerbil is useful for the develop-\nment of unilateral brain infarcts after ligation of one\ncommon carotid artery owing to functional insuffi-\nciency of the circle of Willis.' However, this animal\nis not large enough for easy invasive monitoring of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1195
encoding: FLOAT32
metadata:
{"title": "Cerebral infarction due carotid occlusion and carbon monoxide Pathophysiological and neuropathological investigations", "chroma:document": "its effects. This objection does not hold for the\nLevine model in which unilateral brain infarcts are\nproduced in the rat by ligation of one common\ncarotid artery and subsequent exposure to hypoxic\nhypoxia.2\nHowever,\nthe\nhypoxia\ninduces\na\nsympatho-adrenal\nstimulation\nso that substantial\noxygen deficiency is required for cerebral infarcts to\nresult, and this demands close monitoring of the\nAddress for reprint requests: Rudolf Laas, MD, Department of\nNeuropathology, Eppendorf Hospitals, University of Hamburg,\nMartinistrasse 52, 2000 Hamburg 20, Fed Rep Germany.\nReceived 6 August 1982 and in revised form 18 January 1983.\nAccepted 4 March 1983\nindividual animal.34 This difficulty can only be over-\ncome by controlling hypoxaemia and arterial blood\npressure by means of continuous anaesthesia and\nartificial respiration.5 We therefore attempted to\navoid stimulation of the chemoreceptors by using a\nfunctional anaemia induced by carbon monoxide.\nThis procedure proved to be reliable and amenable\nto controlled experiments.\nMaterial and methods\nMale albino rats (Chbb:THOM strain) had free access to\nstandard rat chow and tap water.\nSeries I\nAfter anaesthesia with diethyl-ether one common carotid\nartery was ligated and transsected. Twenty-four hours later\nthe animals were exposed to carbon monoxide (3000 ppm\nin room air) for 90 minutes while held in a plastic box with\na volume of 3001, allowing the exposure of eight animals at\na time. The gas mixture was stirred by a fan. The concent-\nration of carbon monoxide was continuously monitored\ninside the plastic container and in its immediate vicinity by\nan infrared spectrometer (URAS I, Hartmann & Braun,\nFRG) to assure a continuous exposure of the animals and\nto protect laboratory personnel against accidental leaks. At\nthe 48th hour after exposure the rats were anaesthetised\nwith diethyl-ether and perfused via the ascending aorta\nwith formalin after briefly washing out the vasculature with\nsaline.\n756"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1196
encoding: FLOAT32
metadata:
{"title": "Cerebral infarction due carotid occlusion and carbon monoxide Influence of neck vein occlusion", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:774-779\nCerebral infarction due to carotid occlusion and\ncarbon monoxide exposure\nIII. Influence of neck vein occlusion\nRUDOLF LAAS, JORG IGLOFFSTEIN\nFrom the Department ofNeuropathology, Eppendorf Hospitals, University ofHamburg, Hamburg,\nFederal Republic of Germany\nSUMMARY\nUnilateral cerebral infarcts were produced in the rat by ligation of one common\ncarotid artery and a subsequent exposure to carbon monoxide. In animals which had undergone\nan additional ligation of the external jugular veins leading to a moderate increase of the cephalic\nvenous pressure the outcome of the procedure was ameliorated significantly. Venous pressure\nelevation was thought to reduce the venous vascular resistance effectively by preventing the\nleptomeningeal veins from collapsing. Collapse of the leptomeningeal veins probably occurred\nduring the severe carbon monoxide-induced hypotension causing a steep increase of cerebral\nvascular resistance.\nThere is evidence that the threshold value of cere-\nbral\nperfusion\npressure\nbelow\nwhich\ncerebral\ninfarcts occur is conspicuously clear-cut.' 2 We pre-\nsume that this in part can be attributed to the col-\nlapse of leptomeningeal veins, which is known to\nincrease flow resistance. Since a collapsed vessel can\nbe distended by adding a flow resistance to its outlet\nwe\ntested the hypothesis that the incidence of\nhypotension-induced brain lesions could be reduced\nby elevating the cephalic venous flow resistance. We\nused a modified Levine procedure which has been\ndescribed in detail.3\nMaterial and methods\nThe experiments were perfonned with unstarved male\nalbino rats of the Chbb:THOM strain.\nSeries I\nIn 88 of 175 animals (body weight: 300-400 g) both\nexternal jugular veins were ligated at the time of unilateral\ncommon carotid artery ligation. Twenty-four hours later\nthe carbon monoxide exposure (3000 ppm in room air, 90\nminutes duration) was performed.\nAddress for reprint requests: Rudolf Laas, MD, Department of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1197
encoding: FLOAT32
metadata:
{"title": "Cerebral infarction due carotid occlusion and carbon monoxide Influence of neck vein occlusion", "chroma:document": "Neuropathology, Eppendorf Hospitals, University of Hamburg,\nMartinistrasse 52, 2000 Hamburg 20, Fed Rep Germany.\nReceived 6 August 1982 and in revised form 18 January 1983\nAccepted 4 March 1983\nSeries II\nPathophysiological investigations.\nFifteen animals (body\nweight: 300-400 g) were anaesthetised with ketamine (125\nmg/kg body weight). The arterial blood pressure was\nmeasured distally and proximally to the common carotid\nartery ligation via PVC-catheters. The cephalic venous\npressure was measured by means of silastic catheters which\nwere inserted into one of the greater branches of one\nexternal jugular vein. Thereafter, both external jugular\nveins were occluded for two minutes by means of gentle\ncompression. This manoeuvre was repeated seven times\nwith intervals of 4 minutes. In the individual animal the\nmean arterial and venous pressures were computed from\nabout 50 values each for the occlusion and nonocclusion\nepisodes. In nine of the animals seven additional episodes\nof bilateral venous occlusion were performed during an\nexposure to carbon monoxide. For technical reasons the\ncarbon monoxide exposure was by an intraperitoneal injec-\ntion of technical carbon monoxide per 100 g body weight\naccording to Fodor et al.4 The carboxyhaemoglobin (CO-\nHb) concentration was determined discontinuously (for\ndetails see ref 3). In order to achieve steady state condi-\ntions occlusion of the jugular veins was not started before\n20 minutes after carbon monoxide injection. The exposure\nwas terminated by removing the gas from the abdominal\ncavity through a small incision made into the abdominal\nwall.\nResults\nSeries I\nLethality. Thirteen of 87 control animals and three\nof 88 experimental animals died within 48 hours\n774"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1198
encoding: FLOAT32
metadata:
{"title": "Behaviour disturbances during herpes simplex encephalitis", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983 ;46:809-8 17\nBehaviour disturbances during recovery from herpes\nsimplex encephalitis\nRICHARD GREENWOOD,* ASHOK BHALLA,* ALAN GORDON,t JEREMY ROBERTS*\nFrom The National Hospitals for Nervous Diseases, London, * and the Department ofNeurophysiology,\nSouthend Hospital, t Southend, UK\nSUMMARY\nBizarre behaviour disturbances in four patients occurring during incomplete recovery\nfrom herpes simplex encephalitis are described. Some aspects of their behaviour were similar to\nthat originally described by Kluver and Bucy in monkeys following bilateral temporal lobectomy.\nPrevious reports of behavioural disturbances in man after herpes simplex encephalitis are\nreviewed and attention drawn to the aggressive and disruptive behaviour that is often seen. With\nthe reduced mortality in herpes simplex encephalitis in recent years it is possible that behaviour\ndisturbances such as those described here will be seen more frequently.\nHerpes simplex virus, type 1, is probably the com-\nmonest\ncause\nof\nacute\nsporadic\nnecrotising\nencephalitis in temperate climates. Its clinical and\npathological features are now well recognised' as is\nthe tendency for the necrotic lesions to localise in\nthe inferior and medial parts of the temporal lobes\nand the orbito-frontal cortex. Recently this has been\ndemonstrated during\nlife by CT scanning.2 This\nlocalisation may be related to the route of entry of\nthe virus into the brain, either via the olfactory\ntracts3 or via fibres from the trigeminal ganglion\nsupplying the basal meninges of the middle and\nanterior fossae,4 and results in the characteristic\nfocal neurological features seen at presentation.\nOlfactory, gustatory and auditory hallucinations,\nspeech\nand\nmemory\ndisturbances,\nand\nbizarre\nbehaviour abnormalities leading to psychiatric con-\nsultation are all well documented.\nDocumented\nneurological\ndeficits\nin\nsurvivors\nalso accord with known limbic and temporal lobe\nmechanisms. A residual amnesic syndrome, origi-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1199
encoding: FLOAT32
metadata:
{"title": "Behaviour disturbances during herpes simplex encephalitis", "chroma:document": "nally described by Rose and Symonds,5 and subse-\nquently reported by others, 16-8 is now well recog-\nnised. Behavioural disorders following herpes sim-\nplex encephalitis are less well documented. Oxbury\nand Maccallum9 give some details of ten survivors,\ntwo\nof whom\nexhibited behaviour disturbances\nreminiscent of the Kluver-Bucy syndrome. A much\nmore detailed account of the cognitive, behavioural\nAddress for reprint requests: Dr R Greenwood, Hurstwood Park\nNeurological Centre, Haywards Heath, W. Sussex, RHI117 7SJ, UK.\nReceived 17 March 1983\nAccepted 16 April 1983\nand emotional deficits in ten survivors of a necrotis-\ning limbic encephalitis, probably due to herpes sim-\nplex, is given by Hierons, Janota and Corsellis.'0\nKluver-Bucy features were seen in some patients\nand this, they point out, emphasises the focal nature\nof the encephalitis,\nas does the amnesic deficit.\nOther authors have described single cases in the\nsame light\" 12 or as examples of the Kluver-Bucy\nsyndrome in man.'3-'8\nAlthough mortality in herpes simplex encephalitis\nhas probably been reduced in recent years,'9 the\nincidence of deficit in survivors is still high; such\ndeficits will thus be seen more frequently in the\nfuture. This aspect of the illness has received little\nattention in the past, apart from the literature cited\nabove.\nIn\ntheir monograph\non herpes simplex\nencephalitis Illis and Gostling,' for instance, devote\nonly two paragraphs to the neurological sequelae.\nBehaviour disturbances following herpes simplex\nencephalitis are probably more common than\nis\ngenerally recognised. We have recently observed\nbizarre behaviour disturbances in four patients dur-\ning\nincomplete\nrecovery\nfrom\nherpes\nsimplex\nencephalitis and report them here.\nCase reports\nCase I\nOn 18 January 1980 JBR, a 23-year-old interna-\ntional sportsman and electronics undergraduate, com-\nplained of a \"funny smell\". The following day he became\npyrexial and developed a sore throat and headache. On 22\nJanuary 1980, following a grand mal seizure, he was admit-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1200
encoding: FLOAT32
metadata:
{"title": "Behaviour disturbances during herpes simplex encephalitis", "chroma:document": "ted to the local hospital. He was alert and febrile and his\nneck was stiff. CSF examination revealed a protein of 0-56\n809"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1201
encoding: FLOAT32
metadata:
{"title": "Sex hormones, sexual activity anticonvulsant levels in male epileptics", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:824-826\nSex hormones, sexual activity and plasma\nanticonvulsant levels in male epileptics\nBK TOONE, M WHEELER, M NANJEE, P FENWICK, R GRANT\nFrom the David Lewis Centre for Epilepsy, Alderley Edge, and the Department of Chemical Pathology, St\nThomas's Hospital, London UK\nSUMMARY\nTestosterone, LH, FSH, PRL, and sex hormone binding globulin (SHBG) were meas-\nured in 72 male epileptic patients on chronic anticonvulsant drug regimes. Sexual activity was\nestimated and plasma anticonvulsants measured. Total testosterone (TT), LH, FSH, PRL, and\nSHBG\nwere\nincreased;\nfree\ntestosterone\n(FT)\nwas\ndecreased.\nSexual\nactivity appeared\ndiminished particularly in relation to reduced FT.\nDisturbances\nin male\nsex hormones have been\nrecently reported in male epileptic patients on anti-\nconvulsant drugs. Christiansen et all were the first to\nobserve diminished excretion of androsterone and\ndehydroepiandosterone compared with normal con-\ntrols. The same group2 studied endocrine change\nafter three months of treatment with either pheny-\ntoin or carbamazepine. They confirmed the reduced\nexcretion of androgens, but noted an increase in the\nserum concentration of testosterone in patients on\nphenytoin. An\nincrease\nin\nTT\nhas\nnow\nbeen\nreported by two further groups in association with\nraised SHBG34. LH and FSH were also increased\nFinally Dana-Haeri et a15 have observed reduced\nlevels of FT.\nThere have been numerous reports of disturbed\nsexual activity and orientation in epilepsy. Libido\nmay be increased or decreased; sexual orientation\nmay be disturbed, particularly in association with\ntemporal lobe epilepsy.6 However, there has been\nlittle attempt to explore the relationship between\nsexual activity and sex hormone function. In order\nto do this we have investigated the residential popu-\nlation at the David Lewis Centre for Epilepsy. This\npaper reports changes in sex hormone patterns,\nrelates these to sexual activity and dosage of anti-\nconvulsant drugs.\nPatients"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1202
encoding: FLOAT32
metadata:
{"title": "Sex hormones, sexual activity anticonvulsant levels in male epileptics", "chroma:document": "Patients\nAll male patients at the David Lewis Centre who were\nbetween the ages of 17 and 60 years and who were on\nanticonvulsant medication were considered. Twelve who\nAddress for reprint requests: Dr BK Toone, Maudsley Hospital,\nDenmark Hill, London SE5 8A2, UK.\nReceived 9 October 1982 and in revised form 24 February 1983.\nAccepted 7 May 1983\nwere receiving medication known to interfere with endoc-\nrine function were omitted, as were two patients with evi-\ndence of primary endocrine disorders. Seventy-two patients\n(mean age 34-5 years) finally entered the study. Only six\npatients were on a single anticonvulsant drug regime.\nForty-eight patients were prescribed phenytoin (mean\nplasma level 9-1 mg/I), 19 phenobarbitone (1 1-2 mg/I),\n41\ncarbamazepine\n(4.4\nmg/l),\n32\nsodium\nvalproate\n(25-3\nmg/l),\n24\nprimidone\n(2-4\nmg/l)\nand\nsix\nethosuximide. Each patient received an average of 2-3\nanticonvulsant\ndrugs.\nFifteen\npatients\nalso\nreceived\nsome\nform\nof\nbenzodiazepine,\nprincipally\nas\nnight\nsedation. A diagnosis of primary generalised epilepsy\nwas\nmade\nin\neight\ncases,\nsecondary\ngeneralised\nepilepsy in 19, temporal lobe epilepsy in 32, and some\nother form\nof focal epilepsy\nin\n12. Ten experienced\npartial seizures with simple symptomatology, 37 partial\nseizures with complex symptomatology, 44 secondary\ngeneralised\nseizures,\n19\ngeneralised\ntonic-clonic\nseizures, and five akinetic seizures. The average age of\nonset was 5-2 years and the duration of epilepsy 29*0\nyears.\nControls\nHormonal data was compared with a control group com-\nprising 82 male volunteers from the staff of St Thomas's\nHospital (mean age 38-8 years).\nMethod\nThe interview\nThe interview was conducted by a consultant psychiatrist\n(BKT or PF) and lasted approximately 30 minutes. The\nfirst part of the interview was unstructured: the subject was\nencouraged to describe his sexual interests, attitudes and\nexperiences. The meanings of certain technical terms were\nexplained. Complete confidentiality was assured. The sub-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1203
encoding: FLOAT32
metadata:
{"title": "Sex hormones, sexual activity anticonvulsant levels in male epileptics", "chroma:document": "ject was then questioned systemnatically about certain\naspects of bodily function, sexual interest, and activity.\nThese were selected to reflect the influence of androgens\non sexual behaviour. The level of sexual interest was partly\n824"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1204
encoding: FLOAT32
metadata:
{"title": "The orbicularis oculi after hemispheral damage", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:837-843\nThe orbicularis oculi response after hemispheral\ndamage\nA BERARDELLI, N ACCORNERO, G CRUCCU, F FABIANO, V GUERRISI,\nM MANFREDI\nFrom the Laboratorio di Neurofisiologia, V Clinica Neurologica and Servizio di Neuroradiologia,\nDipartimento di Scienze Neurologiche, Universit& di Roma \"La Sapienza\", Italy\nSUMMARY The corneal and blink reflexes were evaluated in 20 normal subjects and in 30 patients\nwith motor deficits secondary to unilateral hemispheral lesions of vascular origin. In the normal\npopulation there were no differences between subjects below and subjects above 50 years of age.\nIn the patients the reflex evoked by electrical stimulation of the cornea of the clinically affected\nside was depressed in 24 out of 30 cases. The depression mainly affected the afferent branch of\nthe circuit, which triggers both homolateral and contralateral orbicularis oculi discharge (afferent\nabnormality). In three cases the depression was exerted concomitantly on the efferent branch\n(afferent and efferent abnormality) and only in one case was it limited to the efferent branch\n(efferent abnormality). The late R2 component of the blink reflex was depressed in 15 out of 30\npatients. The early Rl component was slightly facilitated on the affected side. The changes of the\ncomeal reflex and of the R2 component of blink reflex were similar, but the blink reflex had a\ngreater safety factor.\nThe patients with an abnormal corneal reflex had more extensive damage than had the patients\nwith normal corneal response, as shown by computer tomography, but the site of the lesion was\ncomparable in the two groups. Conduction through the brain stem circuits mediating the\norbicularis oculi\nresponse\nis normally under pyramidal facilitatory influences while facial\nmotoneurons are subjected to pyramidal inhibition. After pyramidal damage the transmission of\nimpulses in the brain stem was slowed down, ultimately to a degree that abolished the reflex."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1205
encoding: FLOAT32
metadata:
{"title": "The orbicularis oculi after hemispheral damage", "chroma:document": "Removal of pyramidal inhibition on facial motoneurons is probably the basis of the slight facilita-\ntion of the Rl component of the blink reflex.\nSeveral authors'-4 have observed a depression of\nthe corneal reflex evoked from the eye contralateral\nto an hemispheral lesion, but Magladery and Teas-\ndalL,' using electromyographic recordings, reported\nthat the latency of the reflex was only slightly\nincreased\nafter\na\nunilateral\nhemispheral\nlesion.\nMore recently Ongerboer de Visser6 observed that\nthe electromyographic response was reduced\nin\nmost of the patients with unilateral cerebral lesions.\nThe blink reflex evoked by electrical stimulation\nof the supraorbital nerve also has been investigated.\nAddress for reprint requests: Prof. Mario Manfredi, V Clinica\nNeurologica, Universiti di Roma, Viale dell'UniversitA, 30 00185\n- Roma.\nReceived 12 November 1982 and in revised form 12 March 1983\nAccepted 16 April 1983\n837\nBoth direct and consensual R2 components elicited\nfrom the paretic side are depressed according to\nMessina and Quattrone,7 Kimura\" and Fisher et al,9\nwhile Dehen et all' found that R2 was depressed on\nthe affected side and facilitated on the normal one,\nwhether evoked from the normal or the paretic side.\nThe homolateral'R1 component was augmented on\nthe paretic side according to Messina and Quat-\ntrone7 while was unaffected\nin\nthe population\nstudied by Kimura.8 Fisher et al9 reported that the\nRl was delayed during the early phase after a\nstroke.\nIn the present study we compared the behaviour\nof the orbicularis oculi response (comeal reflex and\nblink reflex to supraorbital nerve stimulation) in a\ngroup of patients with unilateral hemispheral lesions\nand in normal controls. The comeal reflex has been\nelicited by mechanical stimuli and by electrical"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1206
encoding: FLOAT32
metadata:
{"title": "CT correlates of gesture recognition", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1983;46: 943-952\nCT scan correlates of gesture recognition\nJOSE M FERRO, ISABEL P MARTINS, GABRIELA MARIANO, A CASTRO CALDAS\nFrom the Neurobehavioral Unit, Centro de Estudos Egas Moniz, Department ofNeurology, Hospital de Santa\nMaria, Lisboa, Portugal\nSUMMARY The ability to recognise gestures was studied in 65 left-hemispheric stroke patients\nwhose lesions were located by CT scan. In the acute stage (first month) frontal lobe and basal\nganglia were frequently involved in patients showing inability to recognise gestures. In the later\n(third\nto fourth month) and chronic stages\n( >6 months) parietal lobe involvement was\nimportant; lesions causing gesture recognition impairment were larger, had more extensive and\nfrequent parietal involvement and produced less temporal lobe damage than those causing aural\ncomprehension defects. These findings are discussed in the light of recent models of cerebral\nlocalisation of complex functions.\nSeveral studies have demonstrated that some apha-\nsics do not recognise gestures.1-5 This disturbance\ncorrelates\nwith\ncomprehension\nimpairment,'24\nalexia34 and constructional apraxia.4 Gesture recog-\nnition impairment in aphasics has been attributed to\nasymbolia,l to an impairment of \"semantic under-\nstanding\",2 to damage to a \"symbolic unit\" that rela-\ntes gestures to the corresponding objects4 following\n\"plausability\"\nrules,5\nor due\nto\nloss\nof visuo-\nkinesthetic motor engrams of gestures.4\nNone of these previous studies addressed the\nquestion of the anatomical localisation of the lesions\nthat cause impairment of gesture identification. In a\nprevious work, we found that this disturbance of\ngesture recognition was more common and severe in\nglobal, transcortical and Wemicke's aphasics, inde-\npendent of the severity of auditory comprehension\nimpairment.4 This could reflect the major role of\nposterior\nleft\nhemispheric\nareas\nfor\ngesture\nidentification. The strong correlation found with.\nconstructional apraxia could indicate a more exten-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1207
encoding: FLOAT32
metadata:
{"title": "CT correlates of gesture recognition", "chroma:document": "sive involvement of the parietal lobe in aphasic\npatients displaying defective gesture recognition.\nThese suggestions were investigated in the present\nstudy.\nMethod\nThe study was of 65 adult right-handed patients, 41 males\nAddress for reprint requests: Jose M Ferro MD, Neurobehavioral\nUnit, Centro de Estudos Egas Moniz, Hospital de Santa Maria,\n1600 Lisboa, Portugal.\nReceived 3 December 1982 and in revised form 3 May 1983.\nAccepted 14 May 1983\nand 24 females (mean age 56-4 \u00b1 11.6 years) who had\nsuffered a single ischaemic cerebrovascular accident of the\nleft hemisphere. Patients with intracerebral haematomas,\ncerebral infarct associated with subarachnoid haemorrhage\nand those in whom CT scan showed multiple or bilateral\nlesions, or diffuse white matter hypodensity suggestive of\narteriosclerotic\nsubcortical\nencephalopathy6\nwere\nnot\nincluded in this series. Thirty-two patients were tested\nduring the 1st month after stroke (acute patients), 37\nduring the 3rd-4th months after stroke (recent patients)\nand 44 in the six or more months after stroke (chronic\npatients). Thirty-three patients were observed in more\nthan one period (acute, recent and chronic stages, 18\npatients; acute and recent, eight patients; recent and\nchronic, six patients; acute and chronic, one patient).\nAll patients had a comprehensive neuropsychological\nevaluation including testing for aphasia, alexia, agraphia,\napraxia and constructional ability. Diagnosis of aphasia\nwas carried out by means of a standardised battery.'7 Two\ntests of auditory comprehension deserve a brief description\nas their scores were compared with Gesture Recognition\nTest score. On the test of object identification by name,\npatients were requested to point to objects (two sets of\neight) named by the examiner, while on the test of oral\nunderstanding they had to follow four one-step and four\ntwo-steps oral.commands. Each correct response is scored\none point in both tests. Normal controls made no errors on\nthese tasks. Classification by aphasia types was based on"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1208
encoding: FLOAT32
metadata:
{"title": "CT correlates of gesture recognition", "chroma:document": "taxonomic criteria according to the scores obtained in the\ntests of speech fluency, naming, understanding of oral\ncommands and repetition of words.4\nThe ability to recognise gestures was assessed by means\nof the Gesture Recognition Test (GRT).4 This\nis a\nmultiple-choice test that requires the patient to point to 12\nobjects or drawings corresponding to gestures played by\nthe examiner. This test is divided in two parts, preceded by\ntwo training items. The training items (spoon, comb) are\nplaced in front of the patient. The examiner pantomimes\n943"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1209
encoding: FLOAT32
metadata:
{"title": "Old photographs: postencephalitic Parkinsonism in two small boys", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46: 953-955\nShort report\nOld photographs: postencephalitic Parkinsonism in\ntwo small boys\nJ PURDON MARTIN\nFrom the National Hospital for Nervous Diseases, Queen Square, London, UK\nSUMMARY My interest in posture and its central nervous control dates from my early days in\nneurology. That was also the time of the epidemic of encephalitis lethargica. A few years ago I\ncame upon some old photographs dating from this period and among them were several of two\nsmall boys suffering from the after-effects of encephalitis with severe disorders of postural\ncontrol. Each of these boys, if placed on an ordinary chair would let his body fall forward and\nwould \"roll\" off the chair and lie motionless on the floor. In more recent years it has been shown\nexperimentally that similar symptoms in monkeys are associated with bilateral lesions of the\nglobus pallidus; in post-encephalitic patients of long standing degenerative changes are present in\nthe pallida, but it now seems likely that deficiency of the neuro-transmitter, dopamine, may bear\nas much responsibility for their symptoms as anatomical lesions. Neurology was slow to appreci-\nate the contribution of the basal ganglia to postural activity.\nIn my early days in neurology the subject of posture\nand its central nervous control was very much in the\nair. Holmes,' in his Croonian lectures of 1922, gave\nthe classic description of \"The clinical symptoms of\ncerebellar\ndiseases\nand\ntheir\ninterpretation.\";\nWalshe,23 on his appointment to the honorary staff\nof the National Hospital, had been given six months\nleave of absence to go and study with Sherrington\nand after his return was applying Sherringtonian\nphysiology\nto\nthe\nhemiplegics and paraplegics;\nMagnus and de Kleijn had described various post-\nural reflexes (in the cat) from 1912 onwards, and\nMagnus's great \"Korperstellung\", in which they\nwere all brought together, appeared in 1924 and was\naccorded an eight page review by Walshe4 in Brain."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1210
encoding: FLOAT32
metadata:
{"title": "Old photographs: postencephalitic Parkinsonism in two small boys", "chroma:document": "In such an atmosphere one could hardly fail to\ndevelop a lasting interest in the subject.\nA few years ago among some old papers I came\nupon some photographs dating from this period.\nThey were all concerned with posture, and among\nthem were\nseveral showing the\nafter-effects of\nencephalitic lethargica and, in particular, these pic-\ntures (fig 1) of two small boys who had been in the\nhospital\nat the same time suffering from post-\nencephalitic Parkinsonism with severe postural dis-\nturbances. They had been taken by the late Dr WG\nWylie, who was at that time RMO at the National\nHospital, and afterwards physician to the Hospital\nAccepted 25 February 1983\nfor Sick Children and to Maida Vale Hospital.\nEncephalitis lethargica was still prevalent and its\nnumerous and very varied after-effects were becom-\ning known. In the children the usual sequelae were\nbehaviour\ndisorders\nand\ndisturbances\nof\nsleep\nrhythm, and the Parkinsonian state was not com-\nmon, and to have two very similar cases in the hospi-\ntal at the same time was a matter of considerable\ninterest. Unfortunately, the notes of these boys have\nbeen lost; what I remember best about them is that\neach of them, when placed on an ordinary chair,\nwould let his body gradually sink forward and would\n\"roll\" off the chair. The first reaction of the nursing\nstaff was to keep the boys in bed when a medical\nvisit was expected, and so the physician, and even\nthe house-physician on\nhis round, might easily\nremain in ignorance of this peculiar phenomenon.\nAt that time we had no armchairs for the patients to\nlie back in, let alone the modern harness to hold the\nincapable ones in position.\nIt is evident from the photographs that the smaller\nboy (fig 1) was much more rigid than the other one,\nand in spite of his rigidity his body sinks down as he\nstands. I do not know the intervals between the\nphotographs-the clinical cinematograph was still\nabout twenty-five years away-and so it is not poss-\nible to say exactly how quickly this occurred, but"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1211
encoding: FLOAT32
metadata:
{"title": "Old photographs: postencephalitic Parkinsonism in two small boys", "chroma:document": "from the evidence of other cases, it seems likely that\nit would be no more than a few minutes. The sharp-\nness of the pictures shows that there was no tremor.\n953"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1212
encoding: FLOAT32
metadata:
{"title": "The olfactory bulbs in Alzheimer's disease", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1984;47: 56-60\nThe olfactory bulbs in Alzheimer's disease\nMARGARET M ESIRI, GORDON K WILCOCK\nFrom the Departments ofNeuropathology and Geriatric Medicine, The Radcliffe Infirmary, Oxford, UK\nSUMMARY The olfactory bulbs have been examined in patients with Alzheimer's disease and\ncompared with those in elderly undemented and younger undemented control patients. In\nAlzheimer's disease neurofibrillary tangles were found in the anterior olfactory nucleus but not\nelsewhere in the olfactory bulb. Cell loss in the anterior olfactory nucleus was also found in\nAlzheimer's disease. It is clear that the olfactory sensory pathway is pathologically affected in\nAlzheimer's disease and would merit further study.\nAlzheimer's disease is characterised pathologically\nby\nthe\ndevelopment\nof\nnumerous\nargyophilic\nplaques and neurofibrillary tangles within the brain.\nRegions of the brain that are particularly severely\naffected in this disease include important parts of\nthe olfactory system such as the uncus' and the\ncortico-medial part of the amygdaloid nucleus.2 We\ntherefore decided to examine more peripheral parts\nof the olfactory sensory pathway. The olfactory\nbulbs and anterior olfactory nuclei have not to our\nknowledge been studied previously in Alzheimer's\ndisease. Neurofibrillary tangles have been described\nin\nthe\nolfactory\nbulbs of several\ncases of the\nParkinsonism-dementia complex of Guam but not in\nAlzheimer's disease.3 We report here our observa-\ntions\non\nthese\nstructures\nin\npatients\nwith\nAlzheimer's disease and in undemented young and\nelderly control patients.\nMaterials and methods\nPairs of olfactory bulbs from six patients with Alzheimer's\ndisease,\nfive\nundemented\nelderly\n(>60\nyrs)\ncontrol\npatients, and five younger (<60 yrs) control patients (see\ntable), were removed from the necropsy brains after\nfixation in 10% neutral formalin, and embedded in paraffin\nwax. Patients included in the group with Alzheimer's dis-\nease had been prospectively assessed for dementia during"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1213
encoding: FLOAT32
metadata:
{"title": "The olfactory bulbs in Alzheimer's disease", "chroma:document": "life and had the diagnosis confirmed neuropathologically\nby demonstrating the presence of numerous neurofibrillary\ntangles and argyrophilic plaques in frontal and temporal\nlobe neocortex. The elderly control patients had also been\nassessed prospectively and the absence of intellectual\nimpairment confirmed. The methods employed are dis-\nAddress\nfor\nreprint\nrequests:\nDr M\nEsiri,\nDepartment\nof\nNeuropathology,\nThe\nRadcliffe\nInfirmary,\nWoodstock\nRoad,\nOxford, OX2 6HE, UK.\nReceived 25 May 1983. Accepted 5 July 1983\ncussed in detail elsewhere.4 Examination of their brains at\nnecropsy had shown that neurofibrillary\ntangles were\nabsent or were present in very small numbers in the\nhippocampus and parahippocampal gyrus only. The young\nundemented patients had died of acute subarachnoid and\nintracerebral haemorrhage associated with the presence of\na ruptured berry aneurysm on a major cerebral artery.\nSerial 10 ,u horizontal sections of the olfactory bulb were\ncut and the first and every following 30th section stained\nusing Cross' modification of the Palmgren stain5 to demon-\nstrate neurofibrillary tangles. A 20 IL section immediately\nadjacent to each of these was stained with cresyl fast violet.\nQuantitative studies were made at a magnification of 320\non the anterior olfactory nuclei using a semi-automatic\nimage analyser (Graphic Information Systems). Within the\nbulb the arrangement of the cells of the anterior olfactory\nnuclei precluded cell counting in random fields. In each\ncase, therefore, the three fields which were judged by vis-\nual inspection to have the greatest cell density within the\nanterior olfactory nuclei were graded (on a scale of 0-3)\naccording to the number of neurofibrillary tangles present\n(0 = absence of tangle formation; 1= minimal; 2 = mod-\nerate; 3 = severe). The two highest grades in each case\nwere recorded for analysis. Cresyl fast violet-stained sec-\ntions were used to perform neuron cell counts on the\nanterior olfactory nuclei\nat 320 magnification using a"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1214
encoding: FLOAT32
metadata:
{"title": "The olfactory bulbs in Alzheimer's disease", "chroma:document": "Weibel graticule and a point counting technique on five\nfields where cell density was judged by visual inspection to\nbe highest. The three highest counts for each case were\nthen used for the analysis. Cells were only counted if they\nwere large (>20 .) and the nucleus contained a prominent\nnucleolus.\nResults\nThe several layers of the olfactory bulb were readily\ndistinguishable in all three groups of patients studied\nthough some distortion or irregularity of the cell\nlayers was common in all groups. As described by\nCrosby et al,6 the neurons of the anterior olfactory\nnuclei were visible lying deep within the olfactory\n56"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1215
encoding: FLOAT32
metadata:
{"title": "Common carotid in the gerbil stroke model", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1984;47: 365-371\nCommon carotid artery stump pressure in the gerbil\nstroke model\nRUDOLF LAAS\nFrom the Department ofNeuropathology, Eppendorf Hospitals, University ofHamburg, Fed Rep Germany\nSUMMARY\nIn 106 slightly anaesthetised adult mongolian gerbils one common carotid artery\n(CCA) was ligated and the blood pressure in the distal and in the proximal stump was monitored\nfor 8 minutes. The mean distal CCA stump pressure of the 39 nonsurvivors was 15 (\u00b16) mm Hg,\nthat of the 25 survivors with retinocerebral infarcts was 25 (\u00b1+6) mm Hg, and that of the 42 intact\nsurvivors was 31 (\u00b1+7) mm Hg. The corresponding mean arterial blood pressures (MABP), as\nmeasured in the proximal CCA stump, were 81 (+12) mm Hg, 84 (+13) mm Hg, and 87 (+11)\nmm Hg, respectively. There were no differences between the samples concerning sex, body\nweight, rectal temperature, arterial blood gases, arterial pH, and haematocrit. Measurements in a\nsecond series of 10 awake gerbils showed that the mean values of MABP, heart rate, and\nrespiratory rate of the nonsurvivors were less than those of the survivors during 90 minutes after\nCCA ligation. It is inferred that in the mongolian gerbil the lower threshold of the arterial blood\npressure for the development of brain infarcts ranges within 22 and 25 mm Hg, that is, within the\nvalues found in monkeys and cats. The longlasting depression of respiration and circulation in the\nnonsurvivors is considered to be related to the phenomenon of diaschisis.\nAs revealed by measurements in cats' and monk-\neys23 the threshold value of the arterial blood pres-\nsure for the development of brain infarcts appears to\nbe consistent and clear-cut. From experiments on\nrats we gained some evidence that this in part may\nbe due to collapse of the leptomeningeal veins which\nis considered to induce a steep increase of cerebro-\nvascular resistance.4 In order further to substantiate\nthis hypothesis, we determined the arterial blood\npressure threshold value in rodents."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1216
encoding: FLOAT32
metadata:
{"title": "Common carotid in the gerbil stroke model", "chroma:document": "We chose the mongolian gerbil as the experimen-\ntal animal, since this small rodent is inexpensive and\noffers some experimental advantages. Depending on\nthe size of the posterior communicating artery and\nits contribution to the anterior circulation, the ger-\nbils exhibit a greater or lesser susceptibility to brain\ninfarction\nafter ligation of one common carotid\nartery.56 From this we inferred that in the mon-\nAddress for reprint requests: Rudolf Laas, MD, Department of\nNeuropathology, Eppendorf Hospitals, University of Hamburg,\nMartinistrasse 52, 2000 Hamburg 20, Fed Rep Germany.\nReceived 7 July 1983 and in revised forn\n6 October\n1983.\nAccepted 28 October 1983\ngolian gerbil the threshold value in question could\nbe determined simply by measuring the arterial\nblood pressure distal to the common carotid artery\n(CCA) ligation and by relating this value to vital\nand/or histological outcome. Thus, the known risk of\nartificial reduction of systemic arterial blood pres-\nsure was avoided.3\nIn order to minimise stress, which is likely to\nworsen outcome, the measuring period was limited\nto a few minutes. We then attempted to gain insight\ninto the course of systemic circulation and respira-\ntion in a second series.\nMaterial and methods\nSeries I\nOne hundred and six adult mongolian gerbils (53 males, 53\nfemales) had free access to standard chow and tap water.\nThe animals were anaesthetised with diethylether. The\nleft common carotid artery (CCA) was ligated after mid-\nline incision of the neck. Catheters were inserted into the\ndistal and proximal stump and connected\nto pressure\ntransducers (P50, Statham, USA). The average duration of\nthe procedure was 10 minutes. Modest anticoagulation was\neffected by the injection of heparin, so that no uncontroll-\n365"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1217
encoding: FLOAT32
metadata:
{"title": "Pure psychic akinesia with bilateral lesions of basal ganglia", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1984;47: 377-385\nPure psychic akinesia with bilateral lesions of basal\nganglia\nDOMINIQUE LAPLANE, MICHEL BAULAC, DANIEL WIDLOCHER, BRUNO DUBOIS\nH6pital de la Salpetriere, Paris, France\nSUMMARY Three\npatients\nshowed\ndramatic\npsychic\nakinesia\nafter\nrecovery\nfrom\ntoxic\nencephalopathy. They had no or only mild motor disorders. The spontaneous psychic akinesia\nwas reversible when the patient was stimulated, as if there was a loss of self psychic activation.\nIntellectual capacities were normal. Two patients had stereotyped behaviours resembling com-\npulsions. In all patients CT cans showed bilateral lesions in the basal ganglia, mainly within the\nglobus pallidus.\nMental disorders occur very frequently\nin basal\nganglia\ndiseases,\nsuch\nas\nWilson's,\nParkinson's,\nHallervorden-Spatz\ndiseases, Huntington\nchorea,\nand progressive supranuclear palsy ... The clinical\npicture\nof these\nmental\ndisorders however,\nare\nextremely varied; they consist of psychiatric disor-\nders, personality changes and often various degrees\nof intellectual deterioration, but this last feature can\nbe absent. In spite of this diversity a peculiar clinical\npicture characterisation by slowing down of thought\nprocesses, inertia and memory disorders has been\nidentified in several degenerative diseases, and has\nbeen\ndescribed\nunder\nthe\nterm\nof\n'subcortical\ndementia\".' 2 Degenerative lesions are generally not\nlimited to the basal ganglia, so eventual role in men-\ntal processes cannot be established. Contrarily, in\nthe motor control field, there is much anatomical,\nphysiological and clinical evidence (the two latter\nlargely from the study of Parkinson's disease), lead-\ning to the conclusion that basal ganglia should be\nregarded as organs of motor control, as recently\nemphazised by Marsden.3\nWe have recently drawn attention to a psychic\npicture,4 5 possibly the consequence of bilateral sub-\ncortical\nlesions\nin\nthe\nbasal\nganglia, which was\ncharacterised by pure psychic akinesia without per-\nmanent\ndementia,\nand\nby"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1218
encoding: FLOAT32
metadata:
{"title": "Pure psychic akinesia with bilateral lesions of basal ganglia", "chroma:document": "and\nby\npseudo-obsessional\nactivities. We now report three similiar cases, which,\nin combination with some clinical and anatomical\ndata in the literature, may furnish some support to\nAddress for reprint requests: Dr D Laplane, H6pital de la Salpet-\nriere, 47 Boulevard de\nl-Hopital, 75651 Paris Cedex 13, France\nReceived 23 June 1983 and in revised form 10 October 1983\nAccepted 14 October 1983\nthe hypothesis of a role played by the basal ganglia\nin mental processes.\nCase reports\nCase 1: In 1968, Mr V, a 41-year-old healthy man was\nstung on the left arm by a wasp. He immediately sustained\na convulsive coma for 24 hours, then adopted intensive\nchoreic\nmovements\n(which\nwere\nalleviated\nby\nthio-\nproperazine),\nand\nimpairment\nof\ngait.\nThese\nextra-\npyramidal symptoms diminished\nover\nseveral\nmonths.\nThen, and during the twelve following years he appeared\nto be a mild dement, He was evaluated by us in 1980, and\nwas at this time not receiving drugs. All his activities were\ndramatically reduced. He spent many days doing nothing,\nwithout initiative or motivation, but without getting bored.\nThe patient described this state as \"a blank in my mind\".\nHis affect was disturbed. When talking about family prob-\nlems, sad or pleasant, he had an appropriate behaviour and\ngave signs of normal interest, but this attitude did not last\nand he became rapidly indifferent again. His fantasy life\nwas poor, but dreaming was preserved. But when stimu-\nlated by external events, or more specially by another per-\nson he could perform quite correct complex tasks (for\nexample,\nplaying\nbridge).\nThis\nfact was\ndramatically\ndemonstrated by neuropsychological tests which showed\nintellectual capacities within the normal range (table).\nTwo years after the encephalopathy, he began to show\nstereotyped activities. The most frequent consisted in men-\ntal counting, for example, up to twelve or a multiple of\ntwelve, but sometimes it was a more complex calculation.\nSuch mental activities sometimes were accompanied by"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1219
encoding: FLOAT32
metadata:
{"title": "Pure psychic akinesia with bilateral lesions of basal ganglia", "chroma:document": "gestures, such as a finger pacing of the counts. To switch on\nand off a light for one hour or more was another of his\nmost\ncommon\ncompulsions.\nWhen\nasked\nabout\nthis\nbehaviour he answered that he had to count. .. that he\ncould not stop it ... as that it was stronger than him ....\nOnce he was found on his knees pushing a stone with the\nhands; he gave the explanation that he must push the\n377"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1220
encoding: FLOAT32
metadata:
{"title": "Cholinergic and constructional praxis: further study of physostigmine in Alzheimer' disease", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:485-491\nCholinergic system and constructional praxis: a\nfurther study of physostigmine in Alzheimer' s disease\nOSAMU MURAMOTO,* MORIHIRO SUGISHITA,t KAZUYA ANDOt\nFrom the Department ofNeurology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, *\nDepartment ofNeurology, Institute ofBrain Research, University of Tokyo, t and National Centre for\nNervous, Mental and Muscular Disorders, Tokyo, t Japan\nSUMMARY Subcutaneous or intravenous administration of physostigmine improved the copying\nof geometric figures in three out of six patients with presumed Alzheimer's disease who showed a\nremarkable constructional disturbance. This improvement reached its maximum 30 to 60 minutes\nafter the physostigmine administration. These results not only provide further evidence support-\ning the hypothesis that central cholinergic potentiation ameliorates some of the impairments of\nAlzheimer's disease, but implicate a possible important role of the cholinergic system in the\nintegration of constructional praxis.\nSince the first reports of beneficial effects of physos-\ntigmine on the cognitive functions of patients with\nAlzheimer's disease appeared in 1979,'-3 several\ntrials have confirmed that memory disturbance in\nsome patients could be ameliorated by the use of\ncentrally active anticholinesterases. Some of these\ntrials produced substantial improvement,45 which\nwas considered to be consistent with the hypothesis\nof selective loss of central cholinergic neurons in\nAlzheimer's disease.67\nThe effect of physostigmine on constructional dis-\nability in Alzheimer's disease, which we first noted\nin a single case in 1979,3 has not yet been confirmed.\nSince our first report, we have examined five addi-\ntional patients with Alzheimer's disease of mild to\nmoderate\nseverity who could undergo repeated\npsychometric tests for drug evaluation under rela-\ntively constant conditions. Of the total sample of six\npatients, three showed an improvement in construc-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1221
encoding: FLOAT32
metadata:
{"title": "Cholinergic and constructional praxis: further study of physostigmine in Alzheimer' disease", "chroma:document": "tional ability when given physostigmine, as assessed\nby copying of geometric figures. In this report we\ndescribe\nfurther\nobservations on\nthe\neffect\nof\nphysostigmine\non\nconstructional\ndisability\nin\nAlzheimer's disease.\nSupported by Grant No. 80-09 and 81-03 from National Centre for\nNervous, Mental and Muscular Disorders (NCNMMD) of the\nMinistry of Health and Welfare of Japan.\nAddress for reprint requests: Dr Osamu Muramoto, Department of\nNeurology, Institute of Clinical Medicine, University of Tsukuba,\nIbaraki 305, Japan.\nReceived 23 June 1983 and in revised form 28 October 1983.\nAccepted 2 December 1983\nPatients and methods\nA description of six patients who participated in this study\nand the overall results appear in table 1. The patients were\nselected from sixteen patients clinically diagnosed as hav-\ning presenile dementia of the Alzheimer type whom we\nhave followed for the past four years. The criteria for selec-\ntion were as follows: (1) remarkable constructional distur-\nbance, (2) mild to moderate dementia and (3) willingness\nto undergo repeated psychometric tests under relatively\nconstant conditions. Clinical diagnosis of Alzheimeres dis-\nease was based on published research criteria.8 Other\ntreatable and non-treatable causes of dementia were ruled\nout by extensive physical, neurological, neuroradiological\nand laboratory examinations. All patients scored four or\nless on the ischaemic score of Hachinski et al.9 Clinical\nfeatures of these six patients was quite similar. They had\nmild to moderate degree of amnesia and disorientation.\nMost of them had difficulty in writing but their ability to\nread was relatively well preserved. Patients 1, 3 and 4 also\nshowed dressing apraxia. Patient 3 had a moderate degree\nof amnestic aphasia. Although no patient showed obvious\npyramidal or extrapyramidal signs, patients\n1, 3 and 4\nshowed occasional jerky movements of the limbs and\ntrunk, probably myoclonus. All patients showed diffuse\nbrain atrophy of mild to moderate severity on the CT scan."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1222
encoding: FLOAT32
metadata:
{"title": "Cholinergic and constructional praxis: further study of physostigmine in Alzheimer' disease", "chroma:document": "The EEG was abnormal with theta-dominant slowing, but\nwithout paroxysmal discharges\nin\nall patients.\nIt was\ndifficult to estimate objectively the rapidity of the progress\nof dementia in these patients because most of them were in\nthe early stage of the disease. However, at least at the time\nof this study, it was our impression that the disease prog-\nressed relatively rapidly. This was especially true in the\ncase of patients 1, 2, 3 and 6, whose constructional distur-\nbance deteriorated so rapidly that within half a year they\ncould no longer do the same tasks as they did in the present\n485"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1223
encoding: FLOAT32
metadata:
{"title": "Looking with paralysed adaptive plasticity of the vestibulo-ocular reflex", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:799-804\nLooking with a paralysed eye: adaptive plasticity of\nthe vestibulo-ocular reflex\nBRUNO ESTANOL,* GUILLERMO LOPEZ-RIOSt\nFrom the Departments ofNeurology* and Neuro-otology, t Hospital General, Centro Medico Nacional,\nInstituto Mexicano Del Seguro Social, Mexico City, Mexico\nSUMMARY When a patient with a peripheral monocular paresis is forced to look with the paretic\neye, head movements induce the sensation of an unstable visual world. The patient behaves as if\nhe had acute bilateral labyrinthine lesions. These symptoms are due to the lack of compensatory\nocular movement and the patients complain that the visual objects move in the direction opposite\nto the head. The patients develop ataxia, nausea, vomiting and past pointing. The symptoms,\nhowever, are transient and consistently disappear after approximately 48 hours. The central\nadaptation to looking and seeing with the paralysed eye is associated with a plastic change of the\nVOR. This plastic adaptation is probably induced by the large retinal slip produced by the lack of\ncompensatory movement of the eye and can be studied in the normally mobile eye in the dark.\nThe psychophysical adaptation is probably generated by an efferent copy or corollary discharge\nof the vestibular system to the visual system that cancels the retinal error.\nWhen a patient with a monocular paresis is forced to\nuse his paretic eye by patching his normally mobile\neye, head movements induce the sensation of an\nunstable visual world. The subject develops ataxia,\nnausea and vomiting. He develops hypermetria in\nthe finger to nose test with consistent over-shooting.\nIf he lies still without moving the head, the sensation\nthat the visual surroundings are moving decreases.\nThe patient behaves as if he had acute bilateral\nlabyrinthine lesions. Nevertheless, the symptoms\nconsistently disappear after the sound eye is persis-\ntently covered for 24 to 48 hours. The patient is able\nto walk again without ataxia. The nausea and vomit-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1224
encoding: FLOAT32
metadata:
{"title": "Looking with paralysed adaptive plasticity of the vestibulo-ocular reflex", "chroma:document": "ing and the overshooting vanish. The patient states\nthat the oscillopsia is greatly diminished. Since the\neye is paralysed there has occurred a central com-\npensation in subjects with a normal central nervous\nsystem. How does this compensation come about?\nTwo\ntypes\nof\nadaptation\nmay\nexplain\nthese\nphenomenon. A plastic change in the motor output\nof the vestibular system or the neurons of the\noculomotor nuclei or a psycho-physical adaptation\nAddress for reprint requests: Dr Bruno Estahiol,\nDivision de\nMedicina, Hospital General, Centro Medico Nacional, Instituto\nMexicano Del Seguro Social, Cuauhtemoc 330, Mexico 7, D.F.,\nMexico City Code: 06720.\nReceived 20 September 1983 and in revised form 4 February 1984.\nAccepted 18 February 1984\nto the increased retinal slip.\nWe postulated that the plastic adaptation of the\nvestibulo-ocular reflex (VOR) in turn, may be an\nincrease in the gain of the reflex that attempts to\ncompensate the large retinal error or a decrease in\nthe gain in the reflex in order to diminish the mis-\nmatch in the brain between visual and vestibular\nimpulses. An adaptive plasticity in the vestibulo-\nocular responses to a change in the visual retinal\nerror has been well demonstrated in the monkey and\nnormal human subjects.36 Thus, an increase in reti-\nnal error by wearing 2 x magnifying lenses, has been\nshown to induce a high gain of the VOR. We\ndecided to investigate the behaviour of the gain of\nthe VOR in the normally mobile eye in darkness in\npatients with monocular paralysis in order to eluci-\ndate\nthe central mechanisms operating when\na\npatient with a paretic eye is forced to look with the\nabnormal eye, the sound eye being covered. This\nmodel is ideal to study changes in gain of the VOR\nin human subjects because the normally mobile eye\nreceives a normal efferent outflow of impulses from\nthe vestibular and the ocular-motor systems.\nPatients and methods\nPatient 1\nA\n28-year-old\nfemale,\nwith\na\nhistory\nof\nmigraine,\ndeveloped a week prior to her admission, severe pain in the\n799"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1225
encoding: FLOAT32
metadata:
{"title": "EMG in abnormal involuntary induced by neuroleptics", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:1002-1008\nEMG patterns in abnormal involuntary movements\ninduced by neuroleptics\nN BATHIEN, RM KOUTLIDIS, P RONDOT\nFrom the Service de Neurologie, Hopital Saint-Anne, Cochin-Port-Royal, and the Laboratoire de Physiologie,\nFaculte de Medicine, Saint-Antoine, Paris France\nSUMMARY Electromyographic (EMG) activity of abnormal involuntary movements and their\nmodifications after Piribedil, a dopaminergic agonist, were analysed in patients presenting with\ntremor or tardive dyskinesia induced by treatment with neuroleptics. Quantitative analysis of\nEMG bursts and of their phase relationships with bursts of antagonist muscles revealed differ-\nences between tremor and tardive dyskinesia; three separate EMG types of the latter were found.\nIn tremor, EMG activity was coordinated between agonists and antagonists. Length and fre-\nquency of bursts are characteristic. In tardive dyskinesia, phase histograms of antagonist muscle\nbursts showed an absence of reciprocal organisation of EMG activity. This activity was made up\nof either rhythmical bursts (type I and II according to the frequency) or irregular discharges (type\nIII). Piribedil decreased tremor but facilitated EMG activity in tardive dyskinesia. These results\ngive an objective measurement or classification of tremor and tardive dyskinesia induced by\nneuroleptics.\nNeuroleptics have been known to produce abnor-\nmalities of movement ever since their introduction\ninto\npsychiatric\ntherapy\nin\n1952. Tremor\nand\nchoreoathetotic movements induced by neuroleptics\nwere first described by Delay et al.' Dyskinesia sec-\nondary to long-term neuroleptic treatment was then\nreported by Sigwald et a12 and was subsequently\ncalled tardive dyskinesia.3 From a pharmacological\npoint of view the mechanisms of these two motor\ndisorders are different. Tremor is caused by block-\nade of dopaminergic receptors4 whereas the gener-\nally accepted explanation for tardive dyskinesia is\nthat\nof functional\noveractivity\nof dopaminergic\nreceptors\ndue"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 1226
encoding: FLOAT32
metadata:
{"title": "EMG in abnormal involuntary induced by neuroleptics", "chroma:document": "due\nto\nhyper-sensitivity\ninduced\nby\n\"chemical denervation\".58\nAs regards tardive dyskinesia several discrepan-\ncies exist between the animal model and clinical\nexperience in man. For example, in rats, behavioural\nsupersensitivity to apomorphine after discontinua-\ntion of one year of neuroleptic treatment was pres-\nAddress for reprint requests: Dr N Bathien, Lab. Physiologie, Fac.\nMed. Saint-Antoine, 27, rue Chaligny, 75571 Paris Cedex 12,\nFrance.\nReceived 2 August 1983 and in revised form 19 December 1983.\nAccepted 4 February 1984\nent after one month, but had returned to normal\nafter 3 months.9 \"\u00b0 In man, however, tardive dys-\nkinesia may persist long after discontinuation of\nneuroleptic\ntreatment.\"\nFurther,\ntypical\ntremor\nactivity in the upper limbs has been recorded in\npatients with tardive dyskinesia activity localised in\nthe face or the lower limbs.'2 13 In the light of these\ndata we thought it appropriate to test the applicabil-\nity of the supposed pharmacological mechanisms to\nthe actual human model. In this work, EMG pat-\nterns of neuroleptic-induced tremor and tardive\ndyskinesia\nwere\nfirst\nestablished.\nPiribedil,\na\ndopaminergic agonist, was then injected and subse-\nquent modifications of these patterns were used to\nmeasure the response of the dopaminergic system.\nPatients and methods\nTwenty-four patients were included in the study, 16 with\ntardive dyskinesia and eight with Parkinsonism induced by\nneuroleptic treatment. Details of the clinical features are\ngiven in table\n1. The neurophysiological examinations\nwere carried out when the condition of each patient was\nstable. Recordings were performed with the patient in sit-\nting position while at rest. The patient was seated in an\narm-chair, the upper limb semi-flexed, the forearm sup-\nported. The leg was extended with the knee slightly flexed.\nMuscle activity was recorded from a pair of antagonist\n1002"}


