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2018-04-03T01:41:22.368Z
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1973-03-01T00:00:00.000Z
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30502711
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s2ag/train
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Epidemiology of acute myelomonocytic leukemia in children
Acute myelomonocytic leukemia was diagnosed in 73 children at the Children's Cancer Research Foundation and the Children's Hospital Medical Center in Boston, 1949–1971. Although the disorder may occur within the first year of life, no association was found with inherited disorders or with prenatal exposure to potential carcinogens. Three patients had a well‐documented history of antecedent aplastic anemia, suggesting that prolonged myelodepression is an etiologic factor or precursor state in myelomonocytic leukemia. In addition, eight others appeared to have antecedent anemia, thrombocytopenia, or pancytopenia for months to years, a finding previously described in adults with myelomonocytic leukemia.
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v2
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2018-04-03T03:17:55.570Z
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1973-03-01T00:00:00.000Z
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1564496
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s2ag/train
|
Serum Creatine Phosphokinase Activity in Acute Psychosis
During the last 7 years, there have been a number of investigations of the incidence of various types of neuromuscular dysfunction in patients with schizophrenic and affective illnesses and their first-degree relatives in comparison with appropriate controls, including nonpsychotic psychiatric patients. Before reviewing these studies, it may be of value to discuss why neuromuscular dysfunction might be expected in virtually any disease of the nervous system—a category in which, thanks to recent genetic studies, we may now confidently include schizophrenia and the primary affective illnesses. The evidence for central nervous system involvement in a variety of diseases with apparently primary skeletal muscle involvement will also be presented. There are numerous instances of known disease of the brain in which pathologic changes in lower motor neurons, with consequent effects on skeletal muscle fiber morphology and function, are found. "Central atrophy" is the name given to the atrophy of skeletal muscle fibers, which frequently develops after various chronic brain diseases, particularly tumors of the parietal lobe (Fenichel, Daroff, and Glaser 1964, Koinov and Markov 1971, and Van Crevel 1969). Depth electrode studies in chronic schizophrenics have demonstrated abnormal electrical discharges in various parts of the cerebral cortex, including the parietal lobe (see Mirsky 1969). The mechanism of central atrophy is believed to be loss of the trophic (nutrient) influence of the upper
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v2
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2018-04-03T03:21:27.231Z
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1973-03-01T00:00:00.000Z
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2723671
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s2ag/train
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Alteration of circadian temperature rhythm with third ventricular obstruction.
✓ Body temperature and endocrine function were studied in three hydrocephalic patients with tumors in the region of the hypothalamus. A circadian temperature rhythm was present under normal intraventricular pressure but was upset during elevated pressure. The results suggest that the absence of a circadian temperature rhythm in patients with third ventricular neoplasms indicates ventricular obstruction with consequent intracranial pressure and/or hydrocephalus. Conversely, the presence of a circadian temperature rhythm indicates that ventricular obstruction has not occurred or that a shunt system placed to bypass such an obstruction is functioning.
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v2
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2018-04-03T03:55:53.307Z
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1973-03-01T00:00:00.000Z
|
37076872
|
s2ag/train
|
Prominent inferior labial artery.
Prominence of the inferior labial artery may suggest tumor to the examining medical or dental physician. Seven examples of this apparently unreported tumefaction have recently been observed. Attempted excision or removal of a specimen for biopsy without preparation for managing arterial bleeding could be embarrassing to the physician and a stressful experience for the patient. Diagnosis or recognition of the lesion is of practical importance but removal is usually not necessary.
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v2
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2018-04-03T04:18:46.676Z
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1973-03-01T00:00:00.000Z
|
38551715
|
s2ag/train
|
THE LEVEL AND CIRCADIAN RHYTHM OF PLASMA FREE 11‐HYDROXYCORTICOIDS IN PATIENTS WITH LOCALIZED INTRACRANIAL PROCESSES, ESPECIALLY OF THE SELLAR REGION
The circadian plasma cortisol pattern was studied in 35 cases with pituitary tumours, in 49 cases where a pituitary tumour, had been removed, in 20 cases with optic atrophy not caused by tumour and in 65 cases with other localized intracranial processes. Nineteen persons served as controls. In the control group the mean plasma cortisol level was 14.9 (SD = 3.4) μg/100 ml plasma and the difference between the highest measured morning value and the lowest measured evening value was 16.6 (SD = 5.1) μg/100 ml plasma. The diurnal rhythm was normal in patients with intrasellar tumours and in those with optic atrophy. In patients with a suprasellar extension of the pituitary tumour and in patients from whom a pituitary tumour had been removed the plasma cortisol rhythm and/or level was pathological in 23 out of 58 cases. In these cases the mean values of the plasma cortisol levels were significantly lower than in the control group. A high frequency of abnormalities of the plasma cortisol pattern was also found in patients with suprasellar meningiomas and diencephalic tumours. In cases with tumours of the sellar region a correlation was found between the occurrence of pathologically low plasma cortisol levels and rhythms and pathological results of the metyrapone test. In processes outside the sellar and diencephalic region there was no correlation between the localization of the lesion and a pathological plasma cortisol rhythm or level. It was found that increased intracranial pressure may give an abnormally high plasma cortisol level.
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v2
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2018-04-03T05:16:46.314Z
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1973-03-01T00:00:00.000Z
|
42093729
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s2ag/train
|
Pulmonary surface activity alterations associated with pulmonary edema following preoptic hypothalamic lesions in rats.
Clinical central nervous system lesions including intracranial tumors and cerebral trauma are 'commonly accompanied by pulmonary edema (1-5). In the experimental animal cerebral trauma produced in a variety of ways or the intracranial injection of certain substances results in pulmonary edema (6-12). In the rat pulmonary edema has been readily produced by electrolytic lesions in the preoptic area of the hypothalamus ( 13). The mechanisms whereby these clinical and experimental lesions cause pulmonary edema are not understood. There is much evidence that deficiency or destruction of the normal pulmonary surface active material causes alveolar collapse and atelectasis (14, 15). A decrease in alveolar surface activity may also result in pulmonary edema (16). Furthermore, experimental neurologic lesions (vagotomy) cause a diminished surface activity of extracts of the lung of the animal (17). On the other hand, a loss in surface activity can apparently be a result of the pulmonary edema itself ( 18). The purpose of this study was to determine if alterations in surface activity of rat lung extracts occurs in experimental neurogenic pulmonary edema, and if this does occur, to determine whether surfactant loss may be the cause of pulmonary edema in these animals. Materials and Methods. Forty-five male Sprague-Dawley rats weighing 181 to 215
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v2
|
2018-04-03T05:23:43.587Z
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1973-03-01T00:00:00.000Z
|
42653775
|
s2ag/train
|
Effect of cobalt-60 irradiation upon cell-mediated immunity.
In a study of 45 humans, the effects of cancericidal cobalt-60 radiation upon cell-mediated immunity was estimated in vivo by determination of delayed hypersensitivity response (DHR) to a nonspecific challenge system—dinitrochlorbenzene. Therapeutic doses of cobalt 60 did not adversely affect the immune responses in 85% of the patients studied, as measured by this method. The method is considered superior to the previously described in vitro procedures that lead to ambiguous conclusions. Further deterioration of DHR in the remaining 15% of patients is attributed to natural biological tumor burden rather than to radiation effect.
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v2
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2018-04-03T05:35:47.291Z
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1973-03-01T00:00:00.000Z
|
43562774
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s2ag/train
|
Immune complex disease in the kidneys of lymphoma-leukemia patients: the presence of an oncornavirus-related antigen.
Subclinical glomerular immune complex disease was found in 9 of 94 kidneys obtained post mortem from patients with lymphoma and leukemia. The incidence was highest in patients with acute myelocytic leukemia (16%) and lowest in patients with solid Iymphoreticular malignancies (3%). Evidence was obtained that an antigen related to the interspecies (gs-3) antigen of mammalian oncornaviruses was present in the kidneys of 2 patients with acute myelocytic leukemia. The high incidence of immune complex disease in kidneys from patients with acute leukemia, as well as the presence of the gs-3 antigen in 2 of these patients, parallels experience demonstrating the presence of this disease in AKR mice and suggests homology in the etiology of human and murine leukemia.-J Natl Cancer Inst 50: 633-644,1973.
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v2
|
2019-03-15T13:12:33.781Z
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1973-03-01T00:00:00.000Z
|
80272994
|
s2ag/train
|
Preliminary Study of the Bacterial Flora and Indications for Antibiotic Therapy in Cancer Patients
A retrospective evaluation of infections that occurred at the National Cancer Institute of Milan during 1971 showed that the majority of them were still produced by gram-positive bacilli, even in myelosuppressed patients with leukemia and lymphoma. Only in patients with urinary tract infection and in febrile patients with bronchogenic carcinoma was the incidence of gram-negative higher than that of gram-positive infections. The persistence of the predominance of gram-positive versus gram-negative bacilli could be partly due to the fact some new antibiotics have been introduced into clinical practice later in Italy then in other countries. The incidence of fungi positive cultures was comparable to that reported in other centers. The importance of knowing the bacterial ecology in a given center or ward in order to choose the appropriate initial antibiotic therapy is discussed.
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v2
|
2018-04-03T02:31:29.442Z
|
1973-03-17T00:00:00.000Z
|
33765419
|
s2ag/train
|
Trephine lung biopsy.
Forty-five percutaneous trephine lung biopsies using the Steel apparatus were performed on 38 patients. Tissue was obtained on 42 occasions (94%) leading to histological or culture diagnosis in 33 patients (87%). Pneumothoraces (12 patients), bleeding into the airways or pleural space (4 patients), and tumour seeding along the needle track (1 patient) occurred in 38% of biopsy attempts (45% of patients). In contrast to the Vim-Silverman technique, the Steel trephine appears to produce a higher tissue yield and superior specimens for histological study. Trephine lung biopsy is comparable to open lung biopsy in providing positive diagnoses. With anticipation and expeditious management of complications, trephine lung biopsy is both safe and useful in the diagnosis of pulmonary disease.
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v2
|
2018-04-03T02:28:50.691Z
|
1973-03-26T00:00:00.000Z
|
33773940
|
s2ag/train
|
[Anticonception with the progestational hormone Depo-Provera].
Conization was performed on a woman who had cervical cancer; later checkups showed that the patient was cancer-free. The patient underwent a normal pregnancy despite oral contraceptive use and wished to use Depo-Provera an injectable preparation consisting of 150 mg medroxyprogesterone acetate. There are no studies that prove that use of oral contraceptives can cause cancer; if there are no signs of cancer then pregnancy or oral contraception would be safe. Depo-Provera is slightly less effective than oral contraceptives. It has been reported that 30-40% of the women using it develop bleeding irregularities e.g. amenorrhea. Only 84% of the women who used Depo-Provera had normal menstruation 18 months after discontinuing its use. Therefore Depo-Provera is contraindicated for young women women who will later have children and older women (because of increased incidence of bleeding irregularities).
|
v2
|
2014-10-01T00:00:00.000Z
|
1973-03-31T00:00:00.000Z
|
18449197
|
s2orc/train
|
The production of vesicular stomatitis virus by antigen- or mitogen-stimulated lymphocytes and continuous lymphoblastoid lines.
A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lytic, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines. In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6% in the VPA and 1.9% by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a) cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained by VPA and morphologic examination was usually quite good. Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM)–5.7% (VPA) were associated with VSV. These were characteristic transformed lymphocytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum. Two cultured murine lymphomas containing lymphocytes with the θ surface marker (L5178Y and EL-4) showed a 15–100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57Bl/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (<2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
infected with a virus, and plated in agar above an indicator monolayer for the virus, it has been possible to estimate the number of antigen-sensitive cells in cell populations from delayed hypersensitive individuals. In exquisitely sensitive donors, the maximal number of virus plaque-forming cells is of the order of 0.5-2% (16).
The purpose of this study is to explore at the ultrastructural level the nature of the cells engaged in the production of vesicular stomatitis virus (VSV) in different lymphoid cell populations, particularly after stimulation with several different agents. Specifically, we have examined (a) lymph node cells from guinea pigs with delayed hypersensitivity activated by specific antigen, (b) murine spleen cells activated by selective B cell and T cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines.
Materials and Methods
Preparation of Sensitized Guinea Pig Lymph Node Cdls.--Lymph node cells in suspension were prepared from guinea pigs sensitized with complete Freund's adjuvant 2-4 wk previously as described elsewhere (13). The cells were cultured for 3 or 4 days at 20 X l0 s viable cells/1.5 ml in Leighton tubes in Eagle's minimal essential medium (MEM) supplemented with penicillin (100 U/ml), streptomycin (100/ag/ml), glutamine (2 mM), and 5% normal guinea pig serum. For specific activation 25 #g/ml tuberculin purified protein derivative (PPD) (Ministry of Fisheries, Food & Agriculture, Weybridge, Surrey, England) was added at zero time for a period of 4 days.
Preparation of Mouse Spleen Cdls.--Spleens were removed aseptically from C57B1/10 mice, rinsed in cold Hanks' balanced salt solution, and sliced into three pieces in MEM supplemented with 6% fetal calf serum, penicillin, streptomycin, and 2 mM glutamine in concentrations as listed above. The cells were gently dispersed from the tissue fragments with a loosely fitting Potter homogenizer, the capsule was allowed to settle, and the cell suspension was washed twice. Approximately" 2 X l0 s cells were obtained from a single spleen. The cells were cultured in Leighton tubes at a density of 15 X 106 cells in 1.5 ml of medium RPMI 1640 supplemented with 10% fetal calf serum, penicillin, streptomycin, glutamine, and 30 #g/ml of Mycostatin. The cultures were stimulated either with 2.5 #g/ml of concanavalin A (Con A) (Calbiochem, San Diego, Calif.), purified on Sephadex (17), or 20 #g/ml of Escherichia coli lipopolysaecharide (LPS-B) (Dlfco Laboratories, Detroit, Mich.). Control cultures were prepared without mitogens.
Maintenance of Continuous Cell Lines.--Human lymphoblastoid cell lines (Wil-2, 8866, and Rail) were maintained in stationary cultures in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum (DME). Twice a week cells were counted and diluted with fresh medium to 0.4 X 106 cells/ml. Cell densities ranged from 0.4 X 106 to 2 X 106/ml. Mouse leukemic cell lines (L1210, L5178Y, and C57B1/6 leukemia) at 0.5 f 106 cells/ml were grown in Fisher's medium containing 2.5% horse serum and 0.2% trypticase soy broth. The EL-4 mouse leukemic cell line grew best at 0.5 X 106-1 X 106 cells/ml in DME. Guinea pig leukemia L2C was passed in strain II guinea pigs and maintained in short-term culture in medium RPMI 1640 with 20% fetal calf serum. All media contained 100 U/ml penicillin, 100 /zg/ml streptomycin, and 2 mM glutamine.
VS V and Infection of Cells.--The stock of VSV used throughout these experiments was prepared in secondary chick embryo fibroblasts (18) and its titer on mouse L cells was 109 plaqueforming units (PFU)/ml. Guinea pig anti-VSV serum was prepared as previously described (18). Cells (2 X 106) were routinely infected at a multiplicity of infection (MOI) of 10 for 2 or 24 h at 37°C. At the end of this period cells were washed once with MEM and treated for 1 h at 4°C with 0.02 ml of anti-VSV serum per sample, an amount of antiserum sufficient to neutralize completely all the input virus. Infected cells were then washed three times with MEM and used either for the VPA or electron microscopy (EM).
VPA.~irus-producing cells were assayed as previously described (18). Briefly, 0.2 ml samples of infected cells at 10-fold dilutions (102-10 .5 cells) were plated in duplicate on monolayers of L cells in 60 mm Falcon tissue culture dishes (Falcon Plastics, Oxnard, Calif.) and overlaid with warm 1% agar in MEM (Ionagar no. 2, Oxnid, Colab Laboratories, Inc., Chicago Heights, Ill.). The plates were incubated for 2 days at 37°C in 5% CO2 in air, and plaques were counted after staining with neutlal red (0.1 mg/ml in phosphate-buffered saline pH 7.2). The number of cells was determined at the time of plating by counting in a Coulter particle counter (Coulter Electronics, Inc., Hialeah, Fla.) a sample of infected cells diluted 1:10. Results were expressed as follows: % Infected cells = No. plaques/plate ;< 5 )< dilution factor )< 100.
No. cells/ml EM.--Cells infected with VSV for 24 h were washed, chilled to 0°C, and the pellet was resuspended and fixed for l h at 0°C in a solution of 0.5% formaldehyde-2% glutaraldehyde (Ladd Corp., Wilmette, Ill.) in Millonig's buffer, pH 7.3, made freshly each time. After fixing cells were washed three times in Millonig's buffer, immersed for 1 h in cold 2% osmic acid (J. A. Samuel & Co., Inc., New York), washed twice in distilled water, and stained with 0.2% uranyl acetate (Fisher Scientific Co., Pittsburgh, Pa.) in water at room temperature overnight. The samples were then washed twice in distilled water and resuspended in 3-ml conical tubes in a 2% solution of agar in water, prewarmed to 50°C, and centrifuged to form a pellet. This procedure prevented any further loss of cells from samples. The tips of cooled, solidified agar cones containing the infected cells were loosened by injection of water between the agar and tube wall through a no. 18 needle, cut off, dehydrated, and embedded in Dureupan ACM-Fluka (ICN Corp., Chemical & Radioisotopes Div., Irvine, Calif.).
The number and percent of infected cells were calculated from an enumeration of intact cells with virus, of all intact cells, and of damaged cells. An intact cell was considered to be infected with virus if one or more identifiable VSV particles was budding from the surface membrane or was located not more than 650 A (diameter of VSV) from the surface. At least three sections of each block were counted and the mean of infected cells, intact cells, and damaged cells was determined. Cell types with virus are noted in Results.
Replication of VSV in Lymphoid Cells from Hypersensitiz~e Guinea Pigs.-
Lymph node cells obtained from tuberculin-sensitive guinea pigs were cultured for 4 days in medium either with or without specific antigen, PPD. After infection they were plated for assay of infectious centers or fixed for EM. The results of 10 experiments of the VPA are presented in Table I A. There is a background of virus plaque-forming cells of approximately 1/1,000 cells (range 0.03-0.3 %) in unstinmlated cultures. In cultures stimulated by antigen the number of cells able to produce VSV by VPA rose to approximately 1.6 % (range 0.8-6.0%). In these experiments ultrastructural examination of control unstimulated cultures revealed five virus-producing cells among 395 intact and damaged cells, an incidence of 1.3 % of those seen, but none of these were lymphocytes. In PPD-stimulated cultures the incidence of lymphocytes with VSV was 1.9% of total cells. (See below for further comment on these results.) :~ Four of these five cells were macrophages; one cell, without visible nucleus, was either a macrophage or a blast cell. § 4 of these 28 cells were macrophages. I1 Cells were cultured for 48 h with Con A or LPS. VSV was added at an MOI of 10 for an additional 20-24 h. ¶ ND, not determined. ** Two of these cells were macrophages.
Cells associated with virus were usually large lymphocytes which displayed some of the morphological features of transformed lymphocytes but were not typical mature blast cells (Figs. 1 and 2). Their cytoplasm, moderately abundant, contained numerous ribosomes and some polysomes, a few profiles of rough endoplasmic reticulum, inclusions, and several mitochondria, but no lysosomes. Nuclei were large and showed a relative decrease of heterochromatin and an increase of euchromatin. Virions associated with infected cells were few in number and localized to a short segment of cell membrane; occasionally only one was seen budding from the surface. Of the 28 cells seen to be producing virus in the PPD-stimulated culture, 4 appeared to be macrophages ( Fig. 3). Of the five cells with virus in control populations, four were macrophages and one could not be classified since the section did not include the nucleus. This cell was large and was either a macrophage or a blast cell.
Replication of VS V in Mouse Spleen Cells Cultured with Con A or LPS.--In mouse spleen both T and B lymphocytes are present and may be selectively stimulated to undergo blast transformation by Con A (19) and by LPS (20). When mouse spleen cells were incubated with Con A for 48 h and then exposed to VSV for an additional 24 h in two experiments, approximately 4.5 % of the total lymphocytes were seen in the electron microscope to be associated with VSV. In the VPA the percentage of VSV-producing lymphocytes found in 18 experiments averaged 5.7 % (range 3-10 %). When LPS was used to stimulate the spleen cultures in 10 experiments, the incidence of infected cells in the FIO. 1. Lymphocyte from sensitized guinea pig lymph node incubated for 3 days with PPD, and an additional day with VSV. Particles of VSV are clustered close to and budding from a narrow segment of the surfaces (inset). The nucleus is large and has peripheral heterochromatia and some euchromatin. The cytoplasm contains a small number of profiles of rough endoplasmic reticulum and numerous ribosomes. Arrows indicate areas shown in insets. X 20,000. Insets: Typical structure of VSV and budding are seen. X 47,000.
VPA was 0.32% (range 0.03-1.0%), while in two experiments the figure was 4% by EM. Mouse spleen cells cultured in medium without mitogens yielded an average of 0.09% virus plaques in 14 experiments and were consequently not scanned in the electron microscope.
The cells associated with VSV were atypical lymphocytes (Figs. 4 and 5) that displayed the morphology of transformed lymphocytes; i.e. they were large, with a b u n d a n t cytoplasm and large irregularly shaped nuclei, and contained FIG. 2. Lymphocyte from sensitized guinea pig lymph node incubated for 3 days with PPD, and for an additional day with VSV. Particles of VSV are found adjacent to a segment of the surface and single particles (arrows) are seen on the opposite side. The cell is a large lymphocyte with an indented nucleus, abundant cytoplasm, numerous ribosomes, a few simple profiles of rough endoplasmic reticulum, two swirls of smooth membranes, and several mitochondria. X 14,000. Fro. 4. Lymphocyte from mouse spleen stimulated with Con A for 48 h. A number of virus particles are scattered at periphery of cell (arrows). Cell shows features of a transformed lymphocyte: a large euchromatic nucleus, profiles of rough endoplasmic reticulum, many mitochondria, numerous ribosomes. )< 12,500. C57B1/6, which do not carry the 0 surface marker for T lymphocytes nor the complement receptor characteristic of B lymphocytes (10), were found by VPA to produce low levels of VSV, both at 2 and 24 h. Similarly, the L2C guinea pig leukemia, a known B cell leukemia (10), yielded a low percent of virus plaque-forming cells. A murine plasmacytoma, MOPC-104, that secretes large amounts of IgM immunoglobulin was active in producing VSV. In these cells typical cylindrical virions of VSV were seen budding from the surface and A-type particles were present in the cytoplasm (Fig. 6).
In contrast to the results observed with L1210 and C57B1/6, two murine FIG. 5. Lymphocyte from mouse spleen stimulated by LPS for 48 h and exposed to VSV for an additional 24 h. No virus is seen in this micrograph. The cell displays an extensive and dilated rough endoplasmic reticulum, greater and more complex than that usually visible in mouse splenic lymphocytes. Many lymphocytes with such characteristics were seen after exposure to LPS, a few of which had virus on their surfaces. X 18,000. lymphomas containing lymphocytes with 0 surface antigens (L5178Y and EL-4) showed a 15-100-fold higher incidence of virus-producing cells when infected for 2 h. At 24 h the percent of virus-producing cells decreased to 1-3 % of the 2 h level in the LS178Y line and to 4 10% of the 2 h level in the EL-4 line. From examination of these lines in the electron microscope at 24 h after infection, the number of intact cells was low and the percent of cells with virus was higher than that determined by VPA. Three human lymphoblastoid lines supported replication of VSV but at different levels of efficiency (Table II). Wil-2 showed a high percent of infected cells, particularly at 24 h, reaching 80 % by VPA and almost 70 % by electron microscopic examination (Fig. 7). In the Raji and 8866 lines (the latter secretes IgG), virus plaque-forming cells at 24 h ranged from 5 to 20% by VPA and from 11 to 24% by morphologic examination (Fig. 8). In these lines, the percent of virus-producing cells was markedly lower at 2 h than at 24 h, a result that differed from that observed in some of the mouse lines. Virus particles on Raji and 8866 cells were less numerous than the numbers found associated with Wil-2, and often appeared over a few segments of the cell surface in clusters (Fig. 8). In all of the cell lines studied, both human and mouse, the number of virus particles per producer cell was greater than that seen in lymphoid cells from donor animals that were exposed to specific antigen, Con A or LPS.
DISCUSSION
The intent of this work was to examine morphologically the kinds of lymphoid cells, both in primary and in long-term cultured populations, that are capable of replicating VSV. VSV was chosen since it had been shown that human lymphocytes, stimulated by phytohemagglutinin (PHA) and infected simultaneously, produced maximum yields of VSV in 24 h (14) ; i.e., the ability to produce VSV reflects a relatively early step in the activation of lymphocytes. Secondly, the virus has a distinctive morphological appearance (21). Thirdly, it was the virus best studied in the VPA. (mRNA) for viral protein synthesis, and then replicated. Finally the virus must be assembled before mature particles start budding at the host cell surface considerably. The host cell is ultimately lysed, but VSV buds at the membrane before lysis occurs. I t is known that there is a rapid inhibition of host cell macromolecular synthesis after infection of cells that are highly susceptible to VSV (23)(24)(25). There is no information concerning the interaction of VSV with cells that do not replicate this virus efficiently. Activation of cells to produce VSV cannot at present be explained by what is known of the intra-cellular events that occur in antigen or mitogen-stimulated cells. Nor is it feasible at this time to relate activation to one or more events associated with the different stages of the mitotic cycle. Nonetheless, replication of VSV seems to be an excellent means of enumerating a small number of sensitized lymphocytes that respond to antigen.
Among guinea pig lymph node cells from sensitized donors, 1.5-2.0% were capable of replicating VSV in vitro in the presence of antigen. Lymph node cells from the same pools cultured in the absence of antigen yielded a low background of infectious centers and a somewhat higher background level by morphologic examination. In the electron microscope four of five cells with VSV were macrophages and the fifth was not a lymphocyte. Among antigenstimulated cells, 4 of 28 cells with VSV were macrophages and the remainder were large lymphocytes. Neither small lymphocytes nor blast cells were found to replicate the virus. These observations indicate that (a) the cells responsive to antigen, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes were capable of replicating VSV even without antigenic stimulation; and (c)the correlation of results obtained by VPA and morphologic examination was very close.
When mouse spleen cells were stimulated by mitogens that act selectively on the T lymphocytes (Con A) or B lymphocytes (LPS), an increase in virusproducing cells was found. In the case of Con A this was of the order of 5.7 % and in the case of LPS, 0.3 % of the cells. The agreement between the VPA and EM counts was very good with Con A and less so with LPS. The cells producing VSV in the Con A-stimulated cultures, presumably T lymphocytes, showed the features of transformed lymphocytes, reminiscent of PHA-stimulated human lymphocytes (5). Cells with VSV in LPS-stimulated cultures, presumably B lymphocytes, showed an extensive rough endoplasmic reticulum resembling lymphocytes transformed by pokeweed mitogen (26,27), and these were readily distinguished from lymphocytes transformed by Con A.
In an attempt to determine if there was a predilection of T or B lymphocytes for virus replication, several murine tumor lines were studied. Two murine lymphomas bearing the 8 marker of T lymphocytes were capable of VSV replication. So was the MOPC-104, a plasma cell tumor line presumed to be derived from B lymphocytes. This finding raises the questions of whether VSV is produced equally well by activated B and T lymphocytes or whether tumor cells have an intrinsic quality, associated with neoplasia, that facilitates VSV replication. For example, granulocytes and mast cells are unable to produce virus (28), yet the mast cell tumor P 815 replicates VSV at approximately 80 % efficiency3 Determination of the percent of virus-producing cells in murine cell lines by VPA and EM examination yielded somewhat differing results. At 24 h after VSV infection, the percent of cells with virus was higher by EM enumeration than the percent calculated by VPA. This may be explained on the basis that the lyric cycle in these cells was considerably shorter than 24 h. When infected cells were plated on monolayers 24 h after infection, many may have already been killed and could no longer form infectious centers during the ensuing 48 h. In addition, the numbers of intact and damaged cells of the murine lines remaining at 24 h after infection with VSV were small and did not provide a suitable basis for accurate calculation.
By contrast, the human lymphoblastoid lines showed at 24 h an increase of virus-containing cells over the 2 h levels. This ma~ have been due to infection of new cells by VSV released from a small number, and to an enduring viability, at least for some hours, despite VSV infection. The ability to produce VSV among the human lymphoblastoid lines varied considerably. The basis for these differences is not clear. For example, in Raji, a nonsecretor of immunoglobulin (29) and in 8866, a secretor of immunoglobulin, virus production was poor, while in Wil-2, which only produces surface IgG, efficiency of VSV production was ahnost as great as in HeLa cells. Interestingly, at the beginning of this study the 8866 line produced VSV at an efficiency of only 3 %, and 9 mo later its ability to replicate the virus had risen spontaneously to 30%. The possibility that Raji and 8866 cell lines produce interferon was examined by preincubating secondary human skin fibroblasts in supernatants from growing lymphoblastoid cells and challenging the monolayer with VSV. No protecting activity was found in the supernatants at dilutions of 1:8 or greater.
Technical Considerations: Comparison between EM and VPA.--For quantitative measurement by either assay, it must be possible to distinguish virusproducing cells from the remaining number of cells. It is difficult to obtain an accurate count of total cells after several days in culture, since the viability of the cultured cells varies drastically with cell source, type of stimulation, and duration of culture. Fewer cells survive 3-5 days in nonstimulated cultures of primary lymphoid cells than in cultures stimulated by antigen or mitogen. With VPA, one selects essentially for viable cells because during the procedures of infection, neutralization, eight centrifugations, etc., nonviable cells largely disintegrate. On the other hand, an unknown number of viable cells may be damaged in the handling. With respect to processing for EM study, there are losses of cells during fixation and dehydration, which are partially overcome by the agar-embedding technique. In the electron microscope the percentage of damaged cells that could be visualized ranged from 25 to 90%. The great advantage of the VPA is the ability to sample 104-106 cells on a single plate for virus plaque-forming cells. However, it is clear that cells other than lymphocytes can replicate VSV, and the great virtue of the electron microscope is that it enables one to distinguish cell types, and often stages of development within the lymphoid cell series. The major drawback is that of screening enough sections and cells to detect low percentages of cells replicating viruses. In those instances in which sufficient numbers of cells were observed, the correlation between the EM analysis and VPA was excellent. SUMMARY A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lyric, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines.
In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6 % in the VPA and 1.9 % by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a)cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained b3 VPA and morphologic examination was usually quite good.
Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM) 5.7% (VPA) were associated with VSV. These were characteristic transformed lymphoeytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum.
Two cultured routine lymphomas containing lymphocytes with the 0 surface marker (L5178Y and EL-4) showed a 15-100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57B1/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (<2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
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v2
|
2017-04-14T15:58:28.402Z
|
1973-04-01T00:00:00.000Z
|
18529385
|
s2ag/train
|
Microfluorometric comparisons of chromatin thermal stability in situ between normal and neoplastic cells.
Summary Microfluorometric comparisons of chromatin thermal stability in situ were made among nuclei isolated from various types of normal and neoplastic cells of the mouse. Normal tissue cell nuclei were isolated from liver, kidney, and spleen. Neoplastic cell nuclei were derived from transplanted murine lymphoma, sarcoma, mammary adenocarcinoma, and Ehrlich ascites tumor. The isolated nuclei were seeded on glass slides in equal densities, fixed, and heated to various temperatures in 0.15 m NaCl-0.015 m sodium citrate containing formaldehyde in order to induce denaturation of the chromatin. The nuclei were subsequently stained with acridine orange. Chromatin thermal stability was compared by measuring the fluorescence emission ratios of the chromatin-ligand complex at 530 and 590 nm for each temperature. The fluorescence emission profiles obtained were characteristic of each tissue type. However, the curves from all normal tissue cells showed a gradual shift in the emission ratio with temperature while those of the neoplastic cells, in general, showed a rapid shift in the fluorescence emission ratio and achieved a consistently higher maximum ratio. The data indicate that the chromatin of these neoplastic cells is more thermolabile than that of normal tissue cells and suggest the possible application of the method to cytodiagnosis.
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v2
|
2017-05-10T23:34:30.617Z
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1973-04-01T00:00:00.000Z
|
33765558
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s2ag/train
|
Factors in human serum affecting the proliferation of normal and leukemic cells.
Serum factor(s) regulate the rate of proliferation of normal and leukemic bone marrow cells. Nine patients with solid tumors and normal marrow function were treated with cyclophosphamide (60.0 mg/kg) on each of 2 successive days. Following aplasia, the granulocytic proliferative fraction of the patients' marrow increased twofold (tritiated thymidine autoradiography). With maturation of the marrow elements, the tritiated thymidine indices fell below pretreatment values. Serial serum samples obtained from these patients affected the incorporation of tritiated thymidine into DNA in primary cultures of normal bone marrows. In relation to pretreatment sera, samples obtained during the proliferative phase caused a twofold increase in tritiated thymidine incorporation by target cells, and sera obtained during the marrow maturation phase caused a twofold decrease. Identical results were obtained when these sera were incubated with marrows from patients with acute lymphoblastic and acute myelocytic leukemia (> 95% tumor) and when they were assayed with the long-term cultured cell lines.
Thus, factor(s) are present in these sera that can affect tritiated thymidine uptake in both normal and leukemic hematopoietic cells.
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v2
|
2017-07-21T16:03:47.900Z
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1973-04-01T00:00:00.000Z
|
20218601
|
s2ag/train
|
Bleomycin as a possible synchronizing agent for human tumor cells in vivo.
At low doses bleomycin (BLM) reversibly inhibits cell progression at the S-G2 boundary. Cells located in other stages of the cell cycle are essentially unaffected; therefore, when present for a complete cell cycle, BLM becomes a prospective in vivo cell-synchronizing agent. In the five trials reported here, BLM was used to synchronize human malignant melanoma cells in vivo . Tumor biopsies were pulse-labeled with tritiated thymidine and assayed by liquid scintillation and autoradiographic techniques. Following the synchrony block, cells at the S-G2 boundary progressed to S phase in a partially synchronized wave. The labeling indices indicated about 1.5 to 4 times the normal number of cells in S phase at the peak times following the first BLM treatment. Therefore, BLM partially synchronizes cells in vivo , and this technique provides a rapid and accurate means of locating the synchronized cells and for scheduling of a second drug for a maximum effect on tumor cell killing.
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v2
|
2018-04-03T01:44:37.300Z
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1973-04-01T00:00:00.000Z
|
30886861
|
s2ag/train
|
Versatility of adrenal photoscanning. Diagnosis of unilateral adrenal failure.
Selective adrenal phlebography is useful in detecting small adrenal tumors. 1-4 However, there are several disadvantages inherent in this technique. First, about 5% of patients are sensitive to contrast media—a factor precluding the use of this method. Second, even in the most experienced hands, it is frequently impossible to direct the catheter into one of the adrenal veins, particularly the right one. Third, the technique requires the availability of a radiologist with great expertise in the manipulation of a catheter. The fourth and major disadvantage is the occasional occurrence of rupture of intra-adrenal capillaries in the course of the procedure, with extravasation of contrast material and hemorrhage into the gland. 5 This complication may result in destruction of all glandular tissue within the capsule. 4,6,7 There have been recent 8-11 reports on the advantages of a new technique, adrenal photoscanning, for the diagnosis of adrenal abnormalities. In the course of
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v2
|
2018-04-03T03:17:55.570Z
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1973-04-01T00:00:00.000Z
|
2269239
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s2ag/train
|
Question: do herpesviruses cause cancer? Answer: of course they do.
It is time to give attention to those viruses known to infect both humans and animals and to be multipotential. Of particular interest would be those viruses with the ability to persist in the body for extended periods coupled with the potential to cause a variety of clinical illnesses 1 of which may be the neoplastic process. The hyperviruses are a major group of viruses that have such qualities under natural conditions both in animals and in humans. Attention in this discussion is on the involvement of herpesvirsuses in animal neoplasias multipotential of human herpesviruses the case for Epstein-Barr virus and the case for herpes simplex virus. The more virulent the virus the less likely that virus-specific products will be easily detected in the transformed cells. Continued accumulation of circumstantial evidence is required in order to link these viruses to the etiology of the various neoplasms with which they have already been associated. At this time it is known that the herpesviruses are frequently at the right place at the right time and they seem to have the properties that qualify them as candidates for the role of human cancer viruses.
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v2
|
2018-04-03T05:54:11.248Z
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1973-04-01T00:00:00.000Z
|
44817250
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s2ag/train
|
Suppression of pituitary tumor growth and function by ergot alkaloids.
Summary The in vivo and in vitro effects of ergot derivatives on prolactin and growth hormone biosynthesis in the rat have been studied. Injection with 0.05 or 0.2 mg ergotamine tartrate had no effect on in vitro prolactin synthesis by the pituitary gland. Ergocornine and ergocryptine, however, inhibited both synthesis and release of prolactin. Incubation of glands with 4 or 40 µm ergotamine greatly decreased prolactin synthesis and release but had no effect on growth hormone. Ergocornine, 10 µm, and ergocryptine, 10 µm, almost completely blocked prolactin release and decreased synthesis and release of growth hormone as well. Daily administration of 0.05 mg ergotamine for 13 days to rats bearing the prolactin- and adrenocorticotropic hormonesecreting pituitary Tumor 7315a dramatically inhibited tumor growth and reversed the adrenal hypertrophy caused by the tumor adrenocorticotropic hormone. Ergotamine, ergocryptine, and ergocornine were all effective in suppressing the growth of pituitary tumors and reversed the splenohepatomegalia caused by growth hormone-secreting tumors. In addition, the ergots decreased the high circulating prolactin levels found in tumor-bearing animals. Ergotamine alone was able to overcome the atrophy of the pituitary glands of tumor-bearing animals and allow gland function to return toward normal. Ergocryptine and ergocornine tended further to suppress gland function. These data demonstrate that hormone synthesis and release by the pituitary gland and pituitary tumors can be inhibited by derivatives of the ergot alkaloids.
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v2
|
2018-04-03T01:33:33.549Z
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1973-04-07T00:00:00.000Z
|
30004024
|
s2ag/train
|
Treatment of Status Asthmaticus
SIR,-I note with interest the recent correspondence on the value of hysterectomy in the treatment of hydatidiform mole from Sir John Stallworthy (20 January, p. 170) and Dr. K. D. Bagshawe (17 February, p. 414). Dr. Bagshawe states that "it [routine hysterectomy] has nothing to offer in terms of saving life and it does not eliminate the risk of choriocarcinoma." This crrtainly is not our experience in Singapore. The report from Singapore' quoted by Dr. Bagshawe in support of his view was taken out of context from a paper published to demonstrate the futility of methotrexate for prophylaxis of choriocarcinoma. An earlier paper from Singapore2 had reported on the value of prophylactic hysterectomy in the primary treatment of hydatidiform mole and would throw light on the problem under consideration. In a prospective study of 400 consecutive cases of hydatidiform mole treated from 1959 to 1964 primary hysterectomy had reduced fatalities from malignant sequelae by 70%. Our experience with the first 200 cases had shown that women aged 40 or more and those under 40 with parity of three or more had malignancy rates of 36-6% and 14-3% respectively. The performance of primary hysterectomy for these two "risk groups" in the second 200 cases reduced the deaths from choriocarcinoma from 10 to 3. All these 13 deaths were of patients who, for various reasons, had initially been treated by uterine conservation. On the other hand primary hysterectomy was associated with no mortality. (Although in the later publication' two deaths were encountered in the hysterectomy group, the overall result is still decisively in favour of primary hysterectomy in women of high risk.) While we recognize that in some cases metastatic choriocarcinoma is associated with a healthy uterus, and the patient would therefore derive no benefit from hysterectomy, nevertheless the majority of cases commence with a primary tumour in the uterine site. Timely hysterectomy in such cases would offer the best possible chances of cure and eliminate the risks of metastatic disease, which must increase with the passage of time. We concede that Dr. Bagshawe's unit is superbly equipped for the early detection of chorionic malignancy. We would also agree with him that close and regular follow-up is absolutely essential in cutting down mortality. But we fail to see the logic of his statement that "by excluding the presentation of choriocarcinoma with uterine haemorrhage, hysterectomy favours presentation with intracranial haemorrhage or other metastatic catastrophe." The presence of a uterine growth would most certainly favour the development of cerebral and other metastatic catastrophes. Finally, I fully concur with Sir John Stallworthy's remarks. After our initial disastrous experience with hysterotomy in 1959-60 we have abandoned it as a useless and unprofitable exercise; certainly vastly inferior to evacuation by the vaginal route.-I am, etc.,
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v2
|
2017-04-14T08:06:05.897Z
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1973-05-01T00:00:00.000Z
|
5823956
|
s2ag/train
|
Depression of antilymphoma allograft reactivity by tumor-associated factors.
Relatively small numbers of viable or killed tumor cells (102 to 105) of five transplantable mouse leukemias and one carcinoma were inoculated into syngeneic or allogeneic adult mice. The inoculations depressed the allograft reactivity of the recipients as judged from reduced resistance to the growth of a second transplant of 106 to 107 H-2 -incompatible strain-specific lymphoma cells. A single injection of the most effective conditioning cells caused long-lasting depression of antilymphoma reactions (up to 3 months) regardless of whether the H-2 antigens of challenging and conditioning tumors were different or alike. The active factor was extractable from cells in suspension and separable by filtration through Millipore membranes. Of 338 mice pretreated with tumor material under a variety of conditions and schedules, 326 were rendered susceptible to allogeneic lymphoma grafts, whereas only 19 of 219 untreated control mice failed to reject the tumors. Depression of antilymphoma reactions was not caused by cells of normal spleen and of two other leukemias and one carcinoma. However, lactic dehydrogenase-elevating virus, a contaminant of all tumors used, and Moloney sarcoma virus did cause nonspecific depression, thus imitating the tumors. Depressive factors capable of breaking the major histocompatibility barrier of the species (possibly viruses, viral products, or tumor cell products) were associated with as few as 100 neoplastic cells. If this association would also occur during oncogenesis, it could favor the escape of antigenic tumors from host surveillance.
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v2
|
2018-04-03T00:21:10.265Z
|
1973-05-01T00:00:00.000Z
|
10926894
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s2ag/train
|
Natural infection of germfree rats with Mycoplasma pulmonis.
found to be a reliable and sensitive method for detection of the infection in the live rat. The isolations of M. pulmonis were correlated with typical lesions in the respiratory tract and middle ears. Uterine infection was found in 27% of the infected, germfree female rats. M. pulmonis was also cultured from each of 39 conventionally raised rats but from none of 47 cesarean-derived, barrier-maintained rats, all of the same stock as the germfree rats. The data suggest that the infection was introduced into the germfree isolators via the infected uterus and that neither vertical nor horizontal transmission, in the absence of other microorganisms, is a likely event. Hysterectomy of the pregnant rat at term and rearing of the young in a controlled environment are key features of the mass production of pathogenfree rats. Rats so derived and maintained in isolators according to established procedures [1] are commonly referred to as "germfree"' (GF), provided the environment in the isolator (food, water, bedding, feces, etc.) remains free of bacteria and fungi [2]. Detailed cultural study of the GF status of the rat per se appears to be limited. In at least one major laboratory where an extensive search was made, no microbial agent was detected in GF rats [3]. The viruses of lymphocytic choriomeningitis, murine mammary tumor, and murine leukemia have been found, however, in GF mice [4], and all GF mice are believed to be infected with murine leukemia
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v2
|
2018-04-03T01:12:30.526Z
|
1973-05-01T00:00:00.000Z
|
28641000
|
s2ag/train
|
Human Serum Dopamine‐β‐Hydroxylase: Relationship to Hypertension and Sympathetic Activity
Serum dopamine-β-hydroxylase activity varied from 3 to 581 units/ml in a group of 168 untreated adults (90 normals, 78 with borderline or overt hypertension). Levels did not correlate with blood pressure or age, but mean values were significantly lower in blacks than they were in whites. Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine. Pronounced blood pressure reduction by antihypertensive drugs did not change serum dopamine-β-hydroxylase activity, and intensive bicycle exercise produced only small and variable increases. Two subjects with severe sympathetic dysfunction, i.e., orthostatic hypotension, showed normal levels of dopamine-β-hydroxylase activity (89–123 units/ml). Serum dopamine-β-hydroxylase activity varied from 450 to 950 units/ml in five subjects with pheochromocytomas and decreased to one-tenth the preoperative level in one subject who underwent curative surgery. Therefore, serum dopamine-β-hydroxylase activity is not a satisfactory index of sympathetic function; moreover, activity levels do not correlate with prevailing blood pressure. Subjects with pheochromocytomas, however, may show increased serum levels of the enzyme, which demonstrates that such tumors can release dopamine-β-hydroxylase.
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v2
|
2018-04-03T05:13:47.557Z
|
1973-05-01T00:00:00.000Z
|
42132685
|
s2ag/train
|
Bacteremia in the burned patient.
(52 cases); (d) benign prostatic hypertrophy-clinical diagnosis only (60 cases); (e) other cancers (57 cases); (f) other urological illness (22 cases); (g) miscellaneous disease (116 cases); (h) undiagnosed (15 cases). The mean activity (SD) of the miscellaneous group was 1 97 (1-07) IU/litre at 37°C, giving an upper normal limit (mean + 2 SD) of 4 1 IU/litre. The AcPase values in this group did not correlate with age (r = 0 040). Eight patients with untreated carcinoma of prostate (22%) had values < 4 1 IU/litre. Six of these had no prostatic enlargement and no metastases; the remaining two had enlarged prostates but no evidence of metastases. All 28 patients in this series with soft tissue (7) or bony (21) metastases had AcPase > 4-1 IU/litre. Values > 4 1 IU/litre were found in seven cases (6%) of benign hypertrophy, three cases (5%) of non-prostatic cancer, two cases (2%) of miscellaneous illness, and one case (6%) of uncertain diagnosis. No values > 4 1 IU/litre were found in the patients with other urological illness. Sixty per cent of patients (26 cases) with untreated prostatic carcinoma had elevated serum alkaline phosphatase activity (APase), ie, > 15 KAU/100 ml as determined by an AutoAnalyzer adaptation of the method of Kind and King (1954). Correlation between the two phosphatases was not significant (I = 0'294; p > 0-05). APase was elevated in the presence of normal AcPase in only three cases of prostatic cancer, but all three were without metastases. Two further cases with minimal elevation of AcPase had APase > 50 KAU/100 ml. While APase is less frequently elevated than AcPase in prostatic cancer patients, it provides valuable confirmation of the diagnosis when the latter is normal or equivocal.
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v2
|
2018-04-03T06:24:14.349Z
|
1973-05-01T00:00:00.000Z
|
46519957
|
s2ag/train
|
Carcinoma and diffuse interstitial fibrosis of lung
A review of 16 cases of diffuse interstitial fibrosis of the lung revealed three cases of coexistent carcinoma of the lung. All three tumors occurred in regions of severe fibrosis. There was one instance each of squamous cell carcinoma, small cell undifferentiated carcinoma, and adenocarcinoma. The three patients were men with a mean age of 66 years. Review of the tissue sections of the diffuse interstitial fibrosis suggests an apparent transition from atypical or dysplastic bronchiolar‐alveolar epithelium to carcinoma. The greater rarity of pulmonary carcinomas in diffuse interstitial fibrosis, as contrasted with localized or focal interstitial fibrosis, may be related to the shortening of life by the diffuse lesion.
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v2
|
2018-04-03T05:57:49.753Z
|
1973-05-15T00:00:00.000Z
|
19470481
|
s2ag/train
|
Amino acid absorption by mouse ascites-tumour cells depleted of both endogenous amino acids and adenosine triphosphate.
1. Despite the depletion of both their content of exchangeable endogenous amino acids and reserves of ATP, starved hypo-osmotically shocked preparations of the tumour cells accumulated relatively large amounts of (14)C-labelled 2-aminoisobutyrate, l-alanine, glycine, l-leucine, l-methionine, l-phenylalanine and l-serine, against their respective concentration gradients, by a process apparently driven by the spontaneous flow of Na(+) ions into the cellular phase. Dependent on (a) which compound was used, (b) its concentration and (c) the direction of the Na(+) ion gradient, the peak value of the ratio of the cellular to extracellular amino acid concentration varied from about 0.4 to 7. 2. The extent to which ATP increased the ratio was defined for l-methionine. 3. Chemical analysis of the cellular amino acid content showed that this increased in parallel with the absorption of (14)C. 4. The accumulation of l-methionine and of glycine, against their own concentration gradients, continued in the presence of either 0.3mm-ouabain or 10mug of oligomycin/ml. Thus the sodium pump was probably not involved in the process when ATP was lacking. 5. l-Leucine caused 0.72+/-0.12 (s.e.m.; 6) extra equivalents of Na(+) to enter the shocked starved tumour cells in parallel with the uptake of leucine itself. Only a small loss of K(+) was induced. 6. The influx and efflux of l-methionine in preparations depleted of ATP were both markedly accelerated by the presence of Na(+) ions. 7. The observations provide further examples of the application of the ion-gradient hypothesis, according to which Na(+) ions act as co-substrates of the amino acid pump. The quantitative importance of parallel Na(+)-independent systems was studied with a new mathematical model.
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v2
|
2018-04-03T06:01:30.127Z
|
1973-05-15T00:00:00.000Z
|
45134640
|
s2ag/train
|
Immunoradioautography test for alpha‐fetoprotein in the differential diagnosis of germinogenic tumors of the testis and in the evaluation of effectiveness of their treatment
The diagnostic value of detecting AFP with the indirect immunoradioautography (IR) method has been investigated for teratoblastomas of the testis in adult patients. It is shown that the IR method permits an approximately two‐fold increase in the number of serologically diagnosed teratoblastomas, as compared with the standard gelprecipitation method. The results for patients with primary testicular teratoblastomas were 19 AFP‐positives in a group of 21 (90.5%). The diagnostic specificity of the test has been lowered insignificantly with the high‐sensitivity method: only 8 AFP‐positive cases were found in a control group of 215 patients, and all the seropositives suffered from tumors of the gastro‐intestinal tract with metastases to the liver. Application of the IR method has greatly increased the possibility of following the course of disease and effectiveness of treatment by the AFP test; in a number of cases it has also permitted a more accurate diagnosis of primary tumor, when metastases are present.
|
v2
|
2018-04-03T01:59:59.924Z
|
1973-05-21T00:00:00.000Z
|
31884937
|
s2ag/train
|
A great leap backward in the treatment of carcinoma of the breast.
In 1863 Sir James Paget, one of the foremost surgeons of his time and an authority on the treatment of breast cancer, wrote, "I am not aware of a single clear instance of the recovery, that is, as that the patient should live more than ten years free of disease...." Paget, like other surgeons of his time, treated breast cancer by the local removal of the primary breast tumor, together with a limited margin of the surrounding breast tissue. But the generation of surgeons following Paget—Charles H. Moore in London, Richard von Volkmann in Halle, and Samuel W. Gross in Philadelphia—had the vision and the courage to attack the disease more vigorously, removing the entire breast, the pectoral fascia, and the axillary lymph nodes. Occasional long-term survival was achieved, but local recurrence developed in 65%. Then in 1882, Halsted began performing the first true radical mastectomy, which included sacrifice of
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v2
|
2017-05-03T17:44:50.559Z
|
1973-06-01T00:00:00.000Z
|
34869213
|
s2ag/train
|
Effects of diethylstilbestrol on hybridizability of mouse testicular RNA.
Cytoplasmic RNA's (cyt RNA's) were prepared from cryptorchid testes of BALB/c mice after treatment with diethylstilbestrol (DES) for 3 days and 10, 22, 26, and 28 weeks. Testes of this strain show a “spurt” in DNA synthesis within 3 days after beginning DES treatment and develop a high proportion of malignant interstitial cell tumors when treated with the estrogen for periods of 7 months or longer. Comparable preparations were made from untreated animals of similar ages. The cyt RNA's were then tested for their ability to complete against RNA-3H synthesized on mouse DNA in vitro , using both “presaturation” and simultaneous hybridization techniques. The preparations from the DES-treated animals always competed better than the equivalent controls. The difference was greater after long periods of treatment.
Cyt RNA's from cryptorchid testes of DES-treated C3HB1 × AB1 F1 mice treated for 3 days with DES did not show any increase in competitive ability over untreated controls. This strain develops relatively few Leydig cell tumors after a much longer period of estrogen treatment and does not exhibit an early “spurt” in DNA synthesis in the interstitium. Preparations of cyt RNA from the livers of BALB/c mice treated with DES also did not compete better than similar preparations from livers of untreated controls. There appears to be a correlation between the DNA “spurt” in the interstitial cells, the tendency to develop Leydig cell tumors, and the increased ability of components of testicular cyt RNA's to compete for sites on mouse DNA.
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v2
|
2018-04-03T01:06:51.132Z
|
1973-06-01T00:00:00.000Z
|
28087292
|
s2ag/train
|
The transcription and state of herpes simplex virus DNA in productive infection and in human cervical cancer tissue.
Summary We are reporting on the transcriptional program of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) in productive infection in human epidermoid (HEp-2) cells and on the transcription and the stat eof HSV-2 DNA in a human cervical tumor. Our results may be summarized as follows. In productive infection, a total of 48% of HSV-1 DNA is transcribed. Analysis of the transcripts shows two kinds of controls. “Off-on” control of transcription is evident from the fact that early, before the onset of viral DNA synthesis, the transcripts arise from 44% of the DNA whereas late in infection the transcripts present in the infected cell arise from 48% of the DNA. The extent of transcription of the HSV-1 DNA early in infection is not affected by cycloheximide, an inhibitor of protein synthesis. Control of RNA abundance is evident from the observation that the transcripts present both early and late in infection form two classes differing in molar ratios. The abundant RNA is complementary to 14 and 19% of viral DNA early and late in infection, respectively, whereas the scarce RNA is complementary to 30 and 28%, respectively, of the DNA at the same time intervals. Several lines of evidence suggest that the abundant RNA specifies structural proteins of the virus. The transcriptional program of HSV-2 DNA differs from that of HSV-1 DNA in two respects. First, the amount of DNA transcribed early and late in infection corresponds to 21 and 50%, respectively. Second, while the viral RNA present late in infection also forms two classes differing in abundance, that present early in infection forms only one abundance class. Cycloheximide does affect transcription of HSV-2 DNA in that in the presence of the drug 45% of viral DNA is transcribed by 2 hr postinfection indicating that at least one “off-on” control of transcription is mediated by protein synthesis. HSV-1 and HSV-2 DNA9s share in common approximately 50% of their sequences with good matching of base pairs. Analysis of the transcription of the DNA sequences shared in common indicates that they are about evenly distributed among the templates for abundant and scarce RNA. However, the common sequences form 71% of the total sequences specifying abundant RNA and only 39% of the sequences specifying scarce RNA. A cervical tumor free of virus or viral antigen was analyzed by DNA-RNA hybridization techniques for the presence of viral RNA transcripts. The cervical tumor contained viral RNA transcripts complementary to 5% of HSV-2 DNA, and preliminary studies show that they correspond to both early and late transcripts. Analysis of the cervical DNA for the presence of HSV-2 DNA sequences led to three conclusions, i.e. , first, only a fragment representing 40% of HSV-2 DNA was present; second, the fragment was present at concentrations of 1 mole/mole of cell DNA and, third, at least parts of this fragment are covalently linked to host DNA.
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v2
|
2018-04-03T03:26:41.052Z
|
1973-06-01T00:00:00.000Z
|
5641959
|
s2ag/train
|
Ultrastructure of a virilizing ovarian Sertoli‐Leydig cell
A case of virilizing ovarian Sertoli‐Leydig cell tumor in a young female was studied by light and electron microscopy. The ultrastructural findings were similar to those reported in the literature and suggest the presence of two types of cells which have a common origin. The patient's aunt and grandmother had had similar tumors; the one in the aunt proved malignant. The English literature review revealed the familial occurrence of virilizing ovarian tumor in only two previous cases. Virus‐like particles were seen in our case and the significance of this observation was discussed.
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v2
|
2018-04-03T03:51:14.834Z
|
1973-06-01T00:00:00.000Z
|
36675748
|
s2ag/train
|
Adjuvant therapy for adenocarcinoma of the kidney: present position and prospects.
Although the only hope of cure for patients with adenocarcinoma of the kidney rests with nephrectomy, this operation fails to prevent death from this disease within 5 years in at least 50% of surgical cases. Attention is now being directed to ancillary methods of treatment which may augment or assist the main surgical attack on the primary tumour, and thereby prevent or delay the development of local recurrence and distant metastases. The present communication is concerned with these methods which may be considered. The methods include radiotherapy, cytotoxic drugs, hormones, and immunotherapy. (auth)
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v2
|
2018-04-03T05:10:57.882Z
|
1973-06-01T00:00:00.000Z
|
41903921
|
s2ag/train
|
Effect of herpesvirus type 2 and hormonal imbalance on the uterine cervix of the mouse.
BALB/c mice were treated with different combinations of hormones (estrogens, progesterone, and Enovid) and herpesvirus type 2 (HSV-2). Characteristic cytological changes of herpesvirus infection were observed in 40% of 140 mice treated with the virus; these mice had previously been immunized with HSV-2 inactivated with ultraviolet light. No significant differences were observed in the frequency of precancerous and cancerous lesions of the cervix and/or vagina between the group treated with estrogens plus HSV-2 (47.2%) and that treated with estrogens alone (41.2%), or between the group treated with Enovid plus HSV-2 (22.6%) and that treated with Enovid alone (31.2%). No carcinomas were observed in either the group treated with progesterone alone or the two control groups, but one carcinoma was found in the group treated with progesterone and HSV-2, and two carcinomas were found in the group treated with HSV-2 alone. These three carcinomas are of special interest since spontaneous cervical carcinoma in mice has not been described, and progesterone has been found to exert a protective effect against chemical carcinogens in the mouse cervix. These results suggest that, at least in these three animals, HSV-2 may have a role in tumor induction.
|
v2
|
2018-04-03T06:16:05.627Z
|
1973-06-01T00:00:00.000Z
|
46179683
|
s2ag/train
|
Psychiatric Liaison on a Neoplastic Inpatient Service
Psychiatric liaison on an inpatient neoplastic service provides unique opportunities for medical and nursing staff to gain psychological understanding of patients in general and to improve communication for the welfare of the patient. The natural anxiety generated by facing dying patients can work as a catalyst in bridging the conceptual gap between medicine and psychiatry. The psychiatrist can point out in a group setting that such anxiety is shared by everyone, including the psychiatrist. The anxiety-provoking dilemma to tell or not to tell the “truth” to cancer patients should depend on an accurate understanding of the patients' communications. “Telling the truth” does not always relieve the physician's anxiety; many doctors feel more uncomfortable and more avoidant of the patient afterwards because they are unprepared to deal frankly with the topic of death once it has been exposed.
|
v2
|
2018-04-03T03:39:28.360Z
|
1973-06-09T00:00:00.000Z
|
7747521
|
s2ag/train
|
Aids to diagnosis in closed abdominal trauma.
oestrogens in low doses, or orchidectomy, appears still to be the best treatment.7 According to a recent report by a research group the average patient with prostatic cancer derives no benefit from immediate treatment with sitilboestrol or by orchidectomy unless the cancer is causing serious symptoms.7 The excess mortality associated with oestrogen therapy, even when the dose is restricted to 5 mg daily by mouth, shows that this treatment should be given only to patients whose growth is causing serious clinical symptoms. There appears to be no point in combining oestogen therapy with orchidectomy. Adrenalectomy offers no clinical improvement, and hypophysectomy, though practised in some centres, is not generally recommended by this reserch group. Perhaps one of the most heartening reports was that from the radiotherapists, who were able to show that in certain hands radiotherapy can produce survival rates at 5 and 10 years comparable with other methods of treatment.8 In very advanced cases some benefit may be derived from chemotherapy, particularly with aniline mustard. It was suggested that those tumours respond best which produce fglucuronidase, and this may form the basis of a predictive test. This agent is known to circulate in the body as a glucuronide, and it is assumed its activation will occur preferentially in tissue with a high 8-glucuronidase activity.
|
v2
|
2018-04-03T02:03:17.419Z
|
1973-06-16T00:00:00.000Z
|
32130424
|
s2ag/train
|
Purpura associated with vomiting.
SIR-I read with interest the latest instalment from Messrs. A. E. Mackinnon and J. Banceweicz in the long story of intramuscular iron therapy and human cancer (5 May, p. 227). As the authors themselves suggest, the occurrence of the malignant tumours at the site of earlier injections of iron dextran may be entirely fortuitous. I entirely agree with this view and it is a pity that no data were given that might lend support to it. For example, one would like to have some idea of the number of people who have been treated with repeated intramuscular iron dextran and have not developed tumours. Those treated, say, 15 years ago would provide valuable data in this respect. One would also like to know the incidence of sarcona (or lack of it) at the site of intramuscular injection of other types of pharmaceutical preparations (such as insulin and penicillin). Admittedly, this information is not readily available, but one would anticipate that hospital records would provide valuable information of this sort. Turning to the animal data, I feel that the authors did not emphasize sufficiently the importance of "iron overload" in the production of local sarcoma by iron dextran injections in rats and mice. The exhaustive studies of Golberg and his colleaguesl-3 leave little room for doubt that tumours developed only in those animals treated repeatedly with high doses (of the order of 0-5 ml in the rat and 0 2 ml in the mouse). Lower doses, which were insufficient to produce an "iron overload," did not produce tumours. This is an important consideration since the doses to the human are unlikely to cause an "iron overload."4 In addition, it is felt that insufficient attention has been given to the "iron-laden" macrophages that have been reported`7 by a number of workers in the sarcomas produced by iron dextran in rats and mice. In my view, their albsence from the human tumours studied by Messrs. MacKinnon and Bancewicz merited some comnnent. With regard to the "distant" as opposed to local tumours reported by Langvad,8 I would point out that these were reported only in mice. In an earlier publication from this institute9 the reasons for interpreting with caution the results of carcinogenicity tests in mice have been discussed at length, so that in my view there is no valid evidence that iron dextran induced tumours at sites other than the injection site in rodents. I do feel that in any report of cases of sarcomas arising at the sites of injection of iron dextran-or other pharmaceutical preparations-it would be more helpful if sufficient background data could be provided to enable readers to place such reports in their proper perspective.-I am, etc.,
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v2
|
2018-04-03T04:44:21.547Z
|
1973-06-16T00:00:00.000Z
|
40111647
|
s2ag/train
|
Hematology and biochemistry of ankylosing spondylitis.
but personally, looking through the bronchoscope or at bronchotomy, I have never seen anything whiter than a light pink. The majority have been red, some very red, emphasizing their vascularity. I would like to comment on one or two other points. The statement that the mass that projects into the bronchial lumen is only a snall part of a more extensive tumour needs modification. It may be and usually is, and is manifestly so in large tumours, but in some cases the tumour does not extend through the whole thickness of the -bronchial wall. I have on three occasions resected a tumour via a bronchotomy without excising the whole thickess of the bronchial wall. Two of the patients are free from recurrence 14 and 16 years later and the third was lost sight of after four years when he emigrated. Finally, I am in no way qualified to express an opinion on the histology, but I have the impression that the boundary between bronchial adenoma and adenocarcinoma may be hazy and that pathologists do not always speak with the same voice. A tumoox which some would classify as an adenoma may be classified as an adenocarcinoma by others. The histological report in the three cases mentioned above was '"benign bronchial adenoma," and I see no reason to suspect that the reports were incorrecL It sems to me that there is still need for further study before we can apph the treatment of bronhial tumour with complete confidence. If we regard all of them as malignant or potentially so we shall avoid the surgical error of treating a malignan lesion as though it were a benign one, but will we avoid the surgical mniiortune of treating a benign lesion as though it were a malignant one?-I am, etc.,
|
v2
|
2019-03-09T14:02:32.132Z
|
1973-06-16T00:00:00.000Z
|
72129959
|
s2ag/train
|
Supporting Service for the Mentally Handicapped
but personally, looking through the bronchoscope or at bronchotomy, I have never seen anything whiter than a light pink. The majority have been red, some very red, emphasizing their vascularity. I would like to comment on one or two other points. The statement that the mass that projects into the bronchial lumen is only a snall part of a more extensive tumour needs modification. It may be and usually is, and is manifestly so in large tumours, but in some cases the tumour does not extend through the whole thickness of the -bronchial wall. I have on three occasions resected a tumour via a bronchotomy without excising the whole thickess of the bronchial wall. Two of the patients are free from recurrence 14 and 16 years later and the third was lost sight of after four years when he emigrated. Finally, I am in no way qualified to express an opinion on the histology, but I have the impression that the boundary between bronchial adenoma and adenocarcinoma may be hazy and that pathologists do not always speak with the same voice. A tumoox which some would classify as an adenoma may be classified as an adenocarcinoma by others. The histological report in the three cases mentioned above was '"benign bronchial adenoma," and I see no reason to suspect that the reports were incorrecL It sems to me that there is still need for further study before we can apph the treatment of bronhial tumour with complete confidence. If we regard all of them as malignant or potentially so we shall avoid the surgical error of treating a malignan lesion as though it were a benign one, but will we avoid the surgical mniiortune of treating a benign lesion as though it were a malignant one?-I am, etc.,
|
v2
|
2019-02-14T14:06:55.218Z
|
1973-06-30T00:00:00.000Z
|
62575383
|
s2ag/train
|
Approach to Urology
Readers of this paperback will be grateful to its authors for presenting such an excellent outline of the anatomy, physiology, and pathology of the urinary system. Its brevity inevitably means omissions and oversimplification, but such deficiencies are not serious detractions. The important diseases of the urinary system are considered and though therapy is not stressed the text indudes enough principles, based on physiological concepts whenever possible, to provide sound guide-lines for rational treatment of patients with urological disease. Emphasis throughout is on function and abnormalities of function. The account of the basic physics of solvent and solute movement across cell membranes with particular reference to osnotic activity and filtration, the rationale of use of serum creatinine values, the explanation of clearances, the mechanisms of active and passive tubule transport of endogenous and exogenous substances, the handling of H+ ions and bicarbonate in relation to renal control of systemic acid4base balance, and the account of the juxtaglomerular apparatus and renin release mechanisms are all easy to understand and are invaluable. Reproductions of the relevant histology and electron microscopy are first rate. The section devoted to fluid and electrolyte imbalance draws attention to errors of interpretation of serum sodium concentrations and isolated central venous pressure observations while emphasizing the value of a good clinical history of blood, electrolyte, and fluid loss, and weight changes. The danger of overenthusiastic correction of acid-base disorders is presented and the use and place of the Astrup in the clinical management of such patients with complicated metabolic and respiratory abnormalities are discussed. Water sodium potassium, acid-base, and blood requirements are well explained, and there is good advice about stabilizing abnormal situations in preference to mathematical correction. Hormones -produced by and acting on the kidney, the renal excretion of drugs, including diuretics, and nephrotoxic drugs are all adequately discussed. The photomicrographs and account of the varieties of glomerular disease based on aberrations of normal glonerular structure and function are outstandingly good and acute and chronic tubule disorders receive ample consideration. There are sections on arterial and arteriolar disease in relation to hypertension, aldosterone tumours, malignant hypertension, pyelonephritis, analgesic nephropathy, urinary tract obstruction and infection, calculi, and tumours. All contain valuable information quite obviously based on experience and familiarity with the relevant literature. The final chapter, which is on the clinical approach to disease of the urinary system, accurately summarizes the suwbjective and objective data available for diagnosing and assessing the severity of urological disease, and it concludes with a brief but rational acomunt of the treatment of patients with severe renal failure. I thoroughly enjoyed reading this book and feel that many others, not only medical students as the authors imply in their preface, will do so as well.
|
v2
|
2016-05-12T22:15:10.714Z
|
1973-07-01T00:00:00.000Z
|
10544242
|
s2orc/train
|
Enzyme activated alkylating agents.
S OF MEMBERS PROFFERED PAPERS 81 IN VITRO SENSITIVITY SCREENING SYSTEM FOR HUMAN CANCERS TO DRUGS AND HYPERTHERMIA (420C). J. A. DICKsoN and M. SUZANGAR. Cancer Research Unit, Department of Clinical Biochemistry, University of Newcastle upon
Approximately 75 % of a series of over 200 human solid neoplasms were sensitive to either hyperthermia (42°C) or cytotoxic drug(s), or a combination of these, as defined by a 30% or greater inhibition of respiration and/or anaerobic glycolysis brought about by the agent in fresh and/or cultured tumour.
The inhibition was paralleled by decreased radioactive precursor incorporation into DNA, RNA and protein by the tumour slices. In a solid Yoshida rat tumour there was close correlation between the biochemical response in vitro to heat and drugs and the in vivo response of the tumour. Sensitivity in this system is taken to indicate a drug and/or heat responsive cell population within the tumour. The extent to which such a result predicts patient response will depend upon the existence or emergence of resistant cells in the tumour in vivo, and on the sensitivity of metastatic cells. In order to define the biochemical change responsible for the induction of resistance towards a potent antitumour agent methylene dimethane sulphonate, tumours in vivo have been transferred to in vitro conditions in which they grow continuously as single cell suspension cultures. Both resistant and sensitive cells are maintained in vitro anc cross-resistant studies indicate that the two, cell lines show a similar wide difference in" sensitivity to ultraviolet radiation and sulphur mustard, but no difference to x-rays and methyl methane sulphonate. This pattern of sensitivity implies a deficiency on the part of the sensitive cells of a step in the repair of damage produced in the DNA by u.v. or MDMS but not by x-rays and MMS. This has been shown to be the case and the Yoshida sensitive line thus resembles the human repair deficiency disease of xeroderma pigmentosum.
Two ethyl derivatives of an intermediate of cyclophosphamide metabolism, 4-hydroxycyclophosphamide, have now been isolated and identified, by T.L.C. and mass spectrometry, in extracts of microsomal incubations with [32P]-cyclophosphamide. By the use of a cell culture bioassay technique, these derivatives have been shown to be highly toxic to Walker ascites cells. The toxicities of various previously identified metabolites were assessed in an in vitro bioassay system. The results were consistent with the view that the formation of 4-hydroxycyclophosphamide is the important step in the activation of cyclophosphamide, as this metabolite can break down spontaneously to the active alkylating agent, phosphoramide mustard [N,N-bis(2-chloroethyl) phosphorodiamidic acid], and acrolein. 4-hydroxycyclophosphamide has been tentatively inferred as the hydrolysis product of both ethyl derivatives isolated, but attempts to extract more than minute quantities of the free metabolite from in vitro microsomal incubations have been unsuccessful. ENZYME ACTIVATED ALKYLATING AGENTS. C. R. BALL, J. A. DOUBLE and J. GOODBAN. Department of Cancer Research, University of Leeds.
Recently Ross and co-workers (Bukhari, Everett and Ross, Biochem. Pharmac., 1971, 21, 963) published the syntheses of 3 conjugates of p-hydroxyaniline mustard which they suggested might be selective for tumours with high levels of ,B-glucuronidase, phosphatase and sulphatase. The 0-glucuronide, 0-phosphate and 0-sulphate respectively were expected to be deconjugated in vivo by the appropriate enzymes. High enzyme activity in a particular tumour could lead to selectivity of action due to the greater release of the rapidly reacting p-hydroxyaniline mustard in the tumour than elsewhere.
We have determined the ability of the appropriate enzymes to utilize these drugs (kindly supplied by Professor Ross) as sub-strates. The 0-phosphate was readily deconjugated by all acid and alkaline phosphatases tested but no evidence was obtained for cleavage of the 0-sulphate by limpet or rat liver microsomal or lysosomal sulphatases. The 0-glucuronide was a good substrate for mammalian liver lysosomal glucuronidases. These results appear to eliminate the 0sulphate as a suitable drug for enzyme activation but substantiate the possible usefulness of the 0-phosphate and 0glucuronide. The effects of ICRF 159 were studied on transformed hamster cells in culture. 5 cm dishes were each plated with 104 cells and cultured at 37°C for up to 72 hours in Eagle's medium containing a range of concentrations of ICRF 159. The cells were either harvested at the completion of the culture period or were transferred to drug-free medium.
Cell numbers increased to 2*5 x 104 during the first 24 hours in various concentrations of ICRF 159 up to 20 ,tg/ml, but the rate of increase diminished with increasing drug concentrations during the next 48 hours. The rate of increase returned towards control values when cells were transferred to drugfree medium, provided the change occurred before 72 hours and only in drug concentrations of less than 10 tug/ml. Specific morphological changes occurred in cells exposed to the drug which may enable the site of action of the drug to be determined.
MOORE. Cancer and Radiobiology Research
Laboratories, General Hospital, Northampton.
As the survival of an experimental tumour graft depends largely on the formation by the host of a new tumour stroma to replace that of the graft which is absorbed within 48-72 hours of implant, the study of substances with " anticoagulant " and fibrinolytic properties is of importance (O'Meara, Irish J. med. Sci., 1958, 474;Jolles, Lancet, 1963, iii, 1234. In previous work, the effects of interference with some fundamental events in connective tissue by heparin (Jolles and Greening, Acta Un. int. Cancer., 1960, 16, 682) and of laminarin, a mucopolysaccharide derived from the seaweed Laminaria cloustoni (Jolles, Remington and Andrews, Br. J. Canicer, 1963, 17, 109) have been shown to reduce the rate of growth of Sarcoma S.180 in mice.
In the present series, in which the design of the experiments was along the same lines as those followed in the heparin and laminarin studies, a degraded Carrageenan derived from red seaweeds injected subcutaneously (0 05 ml in a 1-0, 1-5 or 2% Although prolactin is of supreme importance in the aetiology and genesis of rodent mammary tumours (Muhlbock and Boot, Cancer Res., 1959, 19, 402;Pearson et al., Trans. Ass. Am. Physns, 1969, 82, 225), it is not known whether it is implicated in mammary carcinogenesis in other species. In view of the many similarities that exist between human and canine breast cancer (Misdorp, 1964, Thesis, Utrecht;Schneider, Cancer, N. Y., 1970, 26, 419), an investigation was carried out of the prolactin concentration in the adenohypophysis of dogs afflicted with breast tumours.
Baseline values were established for normal dogs in which pituitary prolactin concentration was found to vary according to reproductive state (e.g. low in dioestrus, high in lactation). In bitches with mammary carcinoma, prolactin levels were significantly higher than in normal subjects of comparable endocrine state. This finding indicates that prolactin imbalance may be involved in canine mammary neoplasia.
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v2
|
2017-04-06T17:37:15.940Z
|
1973-07-01T00:00:00.000Z
|
11718369
|
s2ag/train
|
Phenotypes of the Regan isoenzyme and identity between the placental D-variant and the Nagao isoenzyme.
Summary We observed an unexpectedly high incidence of the D-variant placental phenotype in Regan isoenzyme-positive sera of cancer patients: Such D-variant-positive sera exhibit a high degree of inhibition by l-leucine, a phenomenon earlier associated with the Nagao isoenzyme. Unlike normal placentae, a diffuse phenotype of heat-stable alkaline phosphatase is usually noted in cancer sera containing Nagao isoenzyme.
|
v2
|
2017-04-15T04:59:51.122Z
|
1973-07-01T00:00:00.000Z
|
46092543
|
s2ag/train
|
Effect of corticosteroid on protein and nucleic acid synthesis in human glial tumor cells.
Summary The biochemical effects of 6-α-methylprednisolone-21-succinate, a synthetic corticosteroid hormone, were further investigated on a long-term culture of human glioma cells. Following treatment with this corticosteroid, cellular mitosis was suppressed within 24 hr in proportion to the dose and duration of exposure. Incorporation of tritiated thymidine into glial tumor cells was inhibited over 60% after a 2-hr exposure to the drug; however, less effect on uridine (25% inhibition) and leucine (5% inhibition) incorporation was observed. The primary site of action of this corticosteroid might involve the inhibition of DNA synthesis.
|
v2
|
2017-06-26T03:58:54.243Z
|
1973-07-01T00:00:00.000Z
|
20227563
|
s2ag/train
|
Phytohaemagglutinin-induced lymphocyte transformation in patients before and after resection of large intestinal cancer
Lymphocyte responses to stimulation with phytohaemagglutinin (PHA) have been compared in 20 patients with large intestinal cancer, 10 patients whose large intestinal cancers have been removed, and in 30 age- and sex-matched control individuals. Responses were markedly reduced in the tumour-bearing patients and were unaffected by substituting normal for autologous plasma during incubation. Responses, however, were normal after tumour resection suggesting that the defect in lymphocyte responsiveness is a reversible one and related to the presence of tumour tissue.
|
v2
|
2018-04-03T00:10:46.566Z
|
1973-07-01T00:00:00.000Z
|
10247097
|
s2ag/train
|
Paravesical granuloma presenting as a late complication of herniorrhaphy.
This paper deals with our experience in the management of four patients who have come to our notice during the past 15 years, each presenting with a clinical picture strongly suggestive of bladder malignancy. Each of them had, however, some months or years prior to the development of urinary symptoms, undergone an inguinal herniorrhaphy in which silk had been used for the repair. The pseudo-neoplasm of the bladder was believed in each instance to be due to a paravesical granuloma following the use of non-absorbable sutures. Awareness of this complication helped to prevent unnecessary major surgery in two of the four patients.
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v2
|
2018-04-03T00:28:14.683Z
|
1973-07-01T00:00:00.000Z
|
11973386
|
s2ag/train
|
Surgery for Acoustic Neurinoma
This presentation is concerned with the one-stage translabyrinthine operation of small acoustic neurinomas and a combined translabyrinthine suboccipital staged operation for removal of large acoustic neurinomas. The technique for the translabyrinthine approach to the cerebellopontine angle is described in detail and demonstrated by photographs of the dissection as it progresses. The technique includes both a one-staged translabyrinthine operation for removal of small acoustic neurinomas and preparation of the involved field when the second stage suboccipital operation is necessary. The first 75 consecutive cases are reviewed. Total removal of tumor was accomplished in 43 of these patients by the translabyrinthine route with incidence of 12% permanent facial nerve paralysis. Twenty-seven patients required a second stage suboccipital operation. Total removal was accomplished in 16 of these patients. Only three of the 11 patients with subtotal removal of tumor have required additional surgery. There was an incidence of permanent facial nerve paralysis in eight of these patients. Five of 75 patients underwent a translabyrinthine operation with subtotal removal of tumor. A second stage suboccipital operation was not performed in these patients because of advanced age or refusal. One of these five patients has a permanent facial paralysis and none have required further surgery to date. There was an incidence of 18% permanent facial paralysis among the entire 75 cases. The author prefers the hypoglossal facial nerve anastomosis procedure for rehabilitation for those patients with facial nerve paralysis. There has been no operative mortality in this entire series and 94% of the patients have been able to resume their previous level of work and activity. There was only one transient episode of cerebrospinal fluid otorhinorrhea among the 75 patients.
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v2
|
2018-04-03T01:08:23.318Z
|
1973-07-01T00:00:00.000Z
|
28389102
|
s2ag/train
|
Effects of the antifertility drug enovid in five strains of mice, with particular regard to carcinogenesis.
The antifertility drug, Enovid, was tested for possible carcinogenicity in female mice of 5 specially selected strains: BALB/c, C3H, C3HfB, A, and C57BI. Enovid was chosen for testing since it is one of the most widely used oral contraceptives. The 5 strains of mice provided maximum genetic variation in the test animals. The drug was fed at 3 dose levels: 5 mcg/gm, 10 mcg/gm and 20 mcg/gm of food. The lowest dose did not prevent reproduction. The 10 mcg dose prevented some females from reproducing. The 20 mcg dose prevented all females from reproducing. The strains of mice differed in their response to Enovid. Weight gain was reduced in all strains. Effect on life-span varied, partly because of the tumors. Cervical and vaginal lesions showed invasion of the epithelium into the stroma but was limited, with few exceptions to the BALB/c females. In the BALB/c strain these lesions occurred in controls as well, but showed more progression and a higher incidence with the highest dose of Enovid. None of these lesions appeared grossly as tumors and none had extended beyond the vaginal wall or metastasized. They were observed only on histologic sections. Neither ovarian nor mammary gland tumors were increased in any strain. In the C3H strain such tumors seemed to be inhibited. In the C3HfB strain there was some inhibition of hepatomas and in the BALB/c strain some inhibition of adrenocortical adenoma. Chromophobe adenomas of the hypophysis were significantly increased in old C57BI females treated with the highest dose of Enovid. Offspring of Enovid-treated females showed no abnormalities. Enovid increased the occurrence and may have advanced the progression of epithelial lesions of the cervix and vagina of old BALB/c females. A study of the lesions in untreated females of this strain might help the understanding of carcinoma in situ in women and possibly the appearance of adeno-carcinoma of the vagina of young women whose mothers had been treated with stilbestrol during the first trimester to maintain pregnancy. Other neoplasms in this strain were not increased by the Enovid therapy. In the C3H strain mammary tumors were reduced by the Enovid and those that did occur were found later than in controls. Results from experimental animals should be applied to humans with care. Such results are of greatest value in directing attention to certain areas for investigation.
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v2
|
2018-04-03T01:17:52.061Z
|
1973-07-01T00:00:00.000Z
|
28679516
|
s2ag/train
|
A tumor associated antigen in human nephroblastomas.
Abstract
Antisera prepared against extracts of human nephroblastomas (Wilms' tumors) allowed the characterization in these extracts, and in a few extracts of tumors of other organs, of a tumor-associated antigen. This antigen is different from all previously described antigens, and was named W antigen (W for Wilms). It does not seem to be a carcinoembryonic antigen, and hence it could be of viral origin.
|
v2
|
2018-04-03T01:52:25.092Z
|
1973-07-01T00:00:00.000Z
|
31293513
|
s2ag/train
|
Pitfalls in the diagnosis of acoustic and other cerebellopontine angle tumors
The early detection of acoustic and other cerebellopontine angle tumors depends upon a high index of suspicion on the part of the otolaryngologist. He must be willing to perform a routine neuro‐otologic evaluation on every patient with unilateral tinnitus, unilateral sensori‐neural hearing loss or any symptoms of an inner ear disorder. The audiometric and vestibular examinations should be reliable and X‐rays of the temporal bone must be of excellent quality.
|
v2
|
2018-04-03T02:10:58.325Z
|
1973-07-01T00:00:00.000Z
|
19557083
|
s2ag/train
|
Molecular probes in studies of the relationship of viruses to human neoplasia.
Extensive studies in a number of laboratories have established the role of ribonucleic acid (RNA) viruses in the origin of animal neoplasms of diverse types. Recent studies have characterized the viruses biochemically and have developed biochemical tools for study of human tumors. These technics have been applied to an analysis of the role of viruses in human solid tumors and leukemia. In a series of studies based on the animal leukemia–sarcoma virus model system, cultures derived from human fibrosarcoma desmoides and from giant cell tumor of bone were inoculated with fresh bone marrow aspirates from patients with acute, lymphocytic leukemia. Foci of morphologically altered cells appeared in these cultures several tissue culture passages after inoculation. Cell lines were derived from the altered cells and were characterized biologically and biochemically. The cells exhibited growth properties and tumorigenicity characteristic of malignant cells in immunosuppressed mice. The cells were also found to release particles (buoyant density 1.15 to 1.17 Gm. per ml.) containing reverse transcriptase and high molecular weight RNA. The data obtained suggest that genetic information similar to that of animal RNA tumor viruses was present in the cells and was activated during transformation. The results add further evidence implicating RNA tumor viruses in the etiology of some types of human neoplasia, such as leukemia, giant cell tumor, and fibrosarcoma desmoides.
|
v2
|
2018-04-03T02:15:44.713Z
|
1973-07-01T00:00:00.000Z
|
32805478
|
s2ag/train
|
False positive roentgenologic diagnosis of small intracanalicular acoustic neurinomas.
1. Two false positive contrast studies are presented. The first was due to either inflamed vestibular nerves or incomplete filling to the internal canal. The second was due to arachnoiditis and adhesions between the dura and seventh and eighth cranial nerves.2. The technique of using a small amount of pantopaque (1 cc.) combined with polytomography is described and discussed briefly.3. The procedure of inner ear fluid tap (diagnostic labyrinthotomy) is a reliable procedure for detection of a small intracanalicular tumor. Therefore, it should be performed when the contrast study is equivocal or unsatisfactory, or there is a question of whether or not the filling defect represents an intracanalicular tumor. It is important especially in those patients who present with a progressive unilateral sensorineural loss with normal tomographic findings of the internal auditory canals, and those who are allergic to contrast media.
|
v2
|
2018-04-03T03:30:41.700Z
|
1973-07-01T00:00:00.000Z
|
6393138
|
s2ag/train
|
Age- and sex-associated diethylnitrosamine dealkylation activity of the mouse liver and hepatocarcinogenesis.
Summary In order to evaluate the possible implication of the enzymatic competence of liver in the carcinogenesis by diethylnitrosamine, we assayed liver homogenates from 1-, 7-, 15-, 28-, 42-, and 70-day-old C57BL × C3H F1 mice of both sexes for dealkylating activity. These studies were complemented by a series of carcinogenesis bioassays in which 15- and 42-day-old mice of the same strain were administered diethylnitrosamine i.p. (10 µg/g body weight, once). Groups of mice were killed at 56 and 66 weeks of age, and the incidence of liver tumors was assessed. The results indicated that enzymatic competence was already present in newborn animals and that, henceforth it increased and reached peak activity in both sexes at between the 7th and 15th day of age; at those ages, no difference between the sexes was observed. Thereafter, enzymatic activity decreased with age in both sexes but decreased more rapidly in females. This resulted in a statistically significant sex difference beginning with the 28th day of life. Carcinogenesis bioassay series showed a significantly higher incidence of liver tumors in mice treated at Day 15 than in those treated when 6 weeks of age. The sex difference in the incidence of liver tumors which was observed at week 56 disappeared by the 66th week of life in animals treated with diethylnitrosamine as infants, indicating the same degree of inception of carcinogenesis for both sexes and a slower rate of neoplastic expression for females. The positive correlation between degree of diethylnitrosamine dealkylation and hepatocarcinogenesis suggested their causal relationship without excluding the role of other age-associated factors.
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v2
|
2018-04-03T03:49:46.580Z
|
1973-07-01T00:00:00.000Z
|
19825582
|
s2ag/train
|
Effect of inhibitors of adenosine triphosphate: L-methionine S-adenosyltransferase on levels of S-adenosyl-L-methionine and L-methionine in normal and malignant mammalian tissues.
Low levels of ATP:L-methionine S -adenosyltranferase (adenosyltransferase, EC [2.5.1.6][1]) have been detected by a sensitive radioactive assay procedure in transplantable neoplasms, including the Walker 256 tumor of the rat, and the Lewis lung tumor and B-16 melanoma of C57 black mice. These enzymatic activities and those of a number of normal rodent tissues are all significantly inhibited by 1-aminocyclopentanecarboxylic acid (cycloleucine) and by L-2-amino-4-hexynoic acid, which are structural and conformational analogues of L-methionine.
Following single intraperitoneal injections to rats, the plasma cycloleucine levels remain almost constant for at least 96 hr, whereas the L-2-amino-4-hexynoic acid plasma levels fall with a half-life of about 60 hr. Both cycloleucine and L-2-amino-4-hexynoic acid are highly concentrated in the Walker 256 tumor, while the acetylenic amino acid is concentrated in the Lewis lung tumor.
Administration of pharmacological doses of cycloleucine (5.19 mmoles/kg) or L-2-amino-4-hexynoic acid (2.64 mmoles/kg) elevates plasma and tissue levels of these amino acids in a dose- and time-depenent manner to concentrations which are probably sufficiently high to achieve significant inhibition of the tissue adenosyltransferases. Mice and rats treated with these adenosyltransferase inhibitors display dramatic elevations of free L-methionine levels in all tissues examined (liver, spleen, kidney, brain, plasma, Walker 256 tumor, and Lewis lung tumor). These effects are dose-dependent. The levels of five other amino acids (isoleucine, leucine, tyrosine, phenylalanine, and valine) in liver or spleen show only minor changes in response to this treatment, except for a doubling of the phenylalanine level in the spleen. Treatment of animals with high doses of other amino acid analogues that do not inhibit the adenosyltransferases (L-norvaline, L-valine, DL-homoserine) had no effect on the L-methionine levels.
Treatment with pharmacological doses of cycloleucine and L-2-amino-4-hexynoic acid depresses the levels of (-)- S -adenosyl-L-methionine (Ado-Met) by 20-40% in most normal and malignant tissues (including spleen, kidney, pancreas, brain, adrenal, Walker 256 tumor of rats, and Lewis lung and L1210 tumors of mice). These effects are time- and dose-dependent. Amino acids (L-norvaline, L-serine, and L-valine) that are not adenosyltransferase inhibitors are without effect on tissue Ado-Met concentrations. In contrast to the findings in other tissues, the Ado-Met levels of liver are invariably increased following administration of adenosyltranferase inhibitors.
ACKNOWLEDGMENTS The authors are grateful to Mary Karen Burch for expert technical assistance. Susan Roland Webb kindly performed some of the tissue analyses for S -adenosyl-L-methionine. Dr. A. W. Coulter and Patricia Margulies supplied generous quantities of L-2-amino-4-hexynoic acid. Dr. Ann Marie Benson provided advice on amino acid determinations. The chemotherapeutic studies on L1210 leukemia were kindly carried out by the Cancer Chemotherapy National Service Center (Drs. Saul Schepartz, J. M. Venditti, and H. B. Wood, Jr.). Mr. Isidore Wodinsky of Arthur D. Little supplied tumor-bearing animals upon request of the National Cancer Institute.
[1]: pending:yes
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v2
|
2018-04-03T05:06:29.608Z
|
1973-07-01T00:00:00.000Z
|
41714392
|
s2ag/train
|
Primordial cell pool size and lineage relationships of five human cell types*
Several aspects of normal and neoplastic development can be studied in individuals who have two or more genetically distinct types of cells. Females heterozygous at the X-linked glucose-6phosphate dehydrogenase (G-6-PD) locus are cellular mosaics by virtue of fixed inactivation of one X chromosome in each somatic cell early in embryogenesis (Lyon, 1968). Thus, a given somatic cell in a GdBIGdA heterozygote has either GdB or GdA active (Beutler, Yeh & Fairbanks, 1962; Davidson, Nitowsky & Childs, 1963; DeMars & Nance, 1964). Clones derived from cells with an active GdA allele can be distinguished from those in which GdB is active by subjecting the respective enzymes to starch-gel electrophoresis the A type migrates more rapidly than the B enzyme. Therefore G-6-PD heterozygotes have two cell populations each of which is marked or tagged by the type of enzyme it produces. Since the first report by Linder & Gartler (1965) this system has been used extensively to trace the origin and development of human neoplasms (reviewed in Fialkow, 1972). A tumour with a clonal origin in a GdB/GdA heterozygote should contain only type B or type A enzyme (depending upon whether GdB or GdA was active in the single progenitor cell) ; a tumour with multicellular origin may contain both A and B enzymes. Similarly, the G-6-PD method can also be used to trace normal development. One application is to compare the ratio of A to B enzyme in the same organ from many subjects. Since the enzyme composition reflects the mosaic cell composition, with certain assumptions estimates can then be made of how many cells gave rise to that organ during embryogenesis. If it were derived from a single cell after X inactivation has occurred, only one type of enzyme, A or B, should be found. If there were two progenitor cells, the organs from 114 of heterozygotes should type as A, 112 a,s AB, and 114 as B, and so on. If the number of primordial cells is large, the organ from almost a.11 GdB/GdA females should contain approximately equal amounts of A and B enzyme. Another application study of many different tissues from a single subject provides information about cell lineage relationships. If two tissues are derived from a common progenitor pool they should show correlations in the ratio of the two isoenzymes. For example, Gandini & Gartler (1969) found excellent correlations among the ratios of A to B enzymes in red cells, granulocytes and blood lymphocytes and concluded that these cell lines are derived from a common stem cell pool. In previous reports the mosaic compositions of blood cells have been compared with that of skin in only two patients (Gandini et al. 1968). We have studied five human cell types red cells, granulocytes, blood lymphocytes, lymph nodes, skin a.nd muscle from 42 GdB/GdA heterozygotes.
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v2
|
2019-03-10T13:03:43.726Z
|
1973-07-01T00:00:00.000Z
|
72485056
|
s2ag/train
|
(8) Dermatomyositis and carcinoma of the rectum (resected)
Total thyroidectomy specimen (290/69). The so called 'papillary' tumour was in fact a medullary thyroid carcinoma, consisting of sheet-like masses of rounded cells (Fig. 3) separated into islands of variable size by the irregular trabecular stroma containing identifiable amyloid (Fig. 4). Progress. Patient clinically free from tumour recurrence 3 years after thyroidectomy. However, now complains of 'nerves in stomach' and excessive sweating. Comment, (i) J.S.'s prognosis worsened by changing the diagnosis from papillary to medullary carcinoma. The para-folheular ' C cells of this tumour secrete calcitonin; hence the raised random serum calcitonin is evidence for presence of previously unsuspected residual tumour. (2) J.S. more likely to be a patient with a genetically determined (autosomal dominant) rather than a sporadic thyroid carcinoma. Genetic counselling will have to be considered. (3) Other endocrine tumours, e.g. phaeochromocytomas, can occur in this syndrome. J.S.'s new symptoms of sweating and 'nerves in stomach', together with raised urinary catecholamines, are suggestive of occult phaeochromocytomas. (4) As in this case, the oral mucosal neuromas, arranged in a pathognomonic distribution, appear in the first few years of life. They antedate the potentially fatal thyroid malignancy by up to 10 years, hence the importance of awareness of the syndrome when confronted by multiple oral mucosal neuromas. A full report of this case, with a review of the literature, appeared in the British Journal of Dermatology {19-/3,) 88, 599.
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v2
|
2019-03-16T13:11:16.333Z
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1973-07-01T00:00:00.000Z
|
78538286
|
s2ag/train
|
Stress and Hypertension
Renin secreting tumours; primary reninism In a recently studied case, the circulating levels of renin, angiotensin and aldosterone remained elevated despite control of blood pressure thus raising the possibility of a relatively autonomous renin secretion from a tumour'. The patient, now aged 8 years, presented 2 years ago at another hospital with severe headaches, vomiting, bed wetting and failure to grow. The blood pressure was 170/130 mm.Hg; serum sodium 137, potassium 2.6, bicarbonate 32 mEq. per 1. and urea 15 mg. per cent. Intravenous urography was normal. Peripheral plasma levels of renin, angiotensin I and II and of aldosterone were raised and the concentrations of both renin and angiotensin II in the left renal vein were consistently higher than those on the right. When reviewed in the light of these findings the left renal arteriograms revealed a translucent area consistent with a tumour. This suspicion was confirmed very recently when the left kidney containing an 8 mm. tumour was excised. Histologically the appearances were those of a benign tumour of the juxataglomerular apparatus. In the week since the operation the blood pressure has been lower and the plasma electrolyte abnormalities have disappeared. This case therefore appears to be the 7th reported case of primary reninism and the first to be diagnosed pre-operatively in Britain.
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v2
|
2019-03-16T13:11:20.314Z
|
1973-07-01T00:00:00.000Z
|
78301915
|
s2ag/train
|
The Case for Treating Severe Hypertension; Two Reversible Complications of Malignant Phase Hypertension; Renin-Secreting Tumours Another Reversible Cause of Secondary Aldosteronism in Hypertension
Hypotensive therapy is indicated in cases of severe hypertension particularly when complicated by cardiac failure, encephalopathy or entry to the malignant phase. Return of the blood pressure to more normal levels is accompanied by a reduction in morbidity and mortality, the latter change being particularly evident in patients studied before and during the era of powerful hypotensive drugs", Two complications of malignant phase hypertension have attracted attention recently.
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v2
|
2019-03-17T13:05:31.753Z
|
1973-07-01T00:00:00.000Z
|
80190368
|
s2ag/train
|
Persistence of Focal Arhythmic Delta Activity in Non-Progressive Cerebral Lesions
Focal arhythmic delta activity (FAD) recorded on e!ectroencephalograms has been emphasized as representing severe neurological disease, Joynt et al. ( l ) , Walter ( Z ) , and Fischer-Williams et al. ( 3 ) . Berger (4) was first to correlate slow electrical activity in the EEG with an indication of disease of the brain. Walter ( 5 ) was the first to record focal slow activity over a hrain tumor, and coined the term “delta” for very slow activity, defined as any waves with a frequency below four cycles per second. Previous studies have pointed to the importance of FAD in destructive and/or acute cserelxal disturbances. It may be seen in patients suffering from brain tumor, Williams and Gilhs ( 6 ) , cerebiovascular disease, Liberson and Sequin (7) , and Meyer et al. ( 8 ) , hain alxcess, Walter (9) , head injury, Williams ( l o ) , and Rogers ( l l ) , and infection, Gibbs and Gibbs (12), and Turrell and Roseman (13) . Dennis Williams (14) refers to persistence of the slow activity up to five years after head injury in one patient. The present study was carried out to assess the incidence of persistent chronic FAD (for five or more years in follow-up EEGs) among patients who were not suffering from progressively destructive or expanding (neoplastic) brain lesions.
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v2
|
2018-04-03T00:11:54.123Z
|
1973-08-01T00:00:00.000Z
|
9557739
|
s2ag/train
|
The protective effect of antisera against leukaemia in vivo--a reappraisal.
The ability of antibody to co-operate with certain non-immune lymphoid cells in the rejection of tumours has been studied both in vitro and in vivo. Anti-serum raised in rabbits against a PVGc rat leukosis can be rendered “tumour specific” by in vivo absorption in normal PVGc rats and this antiserum can be shown to have lymphocyte dependent antibody (LDA) activity against the tumour cell in vitro. Complement lytic activity of the antiserum is weak or absent against the tumour. Passive administration of the antiserum to rats protects the animals against the development of leukaemia. Maximum protection occurs if the anti-serum is given before the tumour inoculum and is less effective given after the tumour inoculum. No protective effect can be demonstrated with “tumour specific” allo-antisera or syngeneic antisera against the tumour and no in vitro LDA activity can be detected against the tumour in vitro. Good correlation exists between LDA activity in the sera of the recipients and the in vivo protective effect.
The results are discussed in terms of the kinetics of cell killing after models described for killing by chemotherapeutic agents in animals.
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v2
|
2018-04-03T00:33:45.580Z
|
1973-08-01T00:00:00.000Z
|
12887291
|
s2ag/train
|
Hydroxyurea and macrocytosis
Nine patients who were treated for psoriasis with hydroxyurea displayed peripheral macrocytosis. Mild megaloblastic changes were also seen in the bone marrow of three patients. One patient receiving hydroxyurea developed mild anaemia, another leukopenia. Macrocytosis did not appear to be secondary to an alteration in serum B12 or folate levels. The haematological side‐effects of hydroxyurea therapy, at the relatively low doses used to treat psoriasis, are similar to those seen with the higher doses used for the treatment of malignant tumours or leukaemia.
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v2
|
2018-04-03T00:34:51.618Z
|
1973-08-01T00:00:00.000Z
|
13020951
|
s2ag/train
|
Xenotransplantation of established human endometrial cells into newborn hamsters.
Summary A human cell line derived from a nonmalignant endometrium can produce tumors when inoculated into newborn hamsters i.p. In addition to the epithelial cells that were originally transplanted, the tumors also contained bone marrow; their origins were investigated using isozyme patterns by glucose 6-phosphate dehydrogenase. This observation indicates that xenotransplantation of human cells accompanied by ossification in nonimmunosuppressed hamsters is not a unique phenomenon seen only in the prostatic cells as Richman reported.
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v2
|
2018-04-03T02:26:27.973Z
|
1973-08-01T00:00:00.000Z
|
33530925
|
s2ag/train
|
Cellular immunity to breast carcinoma and malignant melanoma.
Abstract
We have examined the effect of extracts of benign and malignant tumours on the migration of leucocytes from the peripheral blood of 55 melanoma patients, 73 breast carcinoma patients and 162 control donors in the leucocyte migration test. The leucocytes from a majority of tumour bearing patients were inhibited on contact with extracts of histogenetically similar tumours but only occasionally by extracts of dissimilar tumours and preparations from non-neoplastic breast tissue. Control donor's leucocytes were rarely inhibited by any of the tissue extracts. In both patients with malignant melanoma and those with breast carcinoma there was a striking decline in the frequency of tumour extract mediated leucocyte migration inhibition in patients with metastases.
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v2
|
2017-04-14T19:34:20.683Z
|
1973-09-01T00:00:00.000Z
|
7334326
|
s2ag/train
|
A comparative study of the interaction between concanavalin A and mitochondria from normal and malignant cells.
The concanavalin A (con A)-binding capacity of mitochondria isolated by sucrose density gradient methods from host livers, from Morris hepatomas 7800 and 7777, and from mouse myeloma MOPC-46 were compared. con A binding to the various mitochondrial preparations was quantitated using an isotopic assay procedure in which con A-acetyl-3H is used and by a spectrophotometric agglutination method using native con A. Readily accessible con A-binding sites were determined using washed, intact mitochondria, and total binding sites were evaluated by carrying out incubations in the presence of Triton X-100 (1%). Detergent treatment caused extensive disruption of mitochondrial membranes and increased 2.5- to 3.0-fold the amount of con A-acetyl-3H bound by control liver mitochondria. Tumor-derived mitochondria bound significantly less con A than did the corresponding host liver preparations, indicating an alteration in the glycoproteins of tumor mitochondria. Triton X-100-treated hepatoma 7800 and 7777 mitochondria were capable of binding only 50 and 70% as much con A-acetyl-3H, respectively, when compared with mitochondria isolated from the host liver controls.
The data suggest either that there is a decrease in the concentration of glycoproteins in tumor mitochondria or that there are qualitative changes in the structure of their oligosaccharide side chains. The altered reactivity of tumor mitochondria to con A cannot be accounted for on the basis of differential growth rates of tumor and host liver tissue since mitochondria isolated from regenerating rat liver do not differ from normal rat liver mitochondria in their con A-binding properties.
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v2
|
2018-04-03T00:00:34.947Z
|
1973-09-01T00:00:00.000Z
|
8285722
|
s2ag/train
|
Natural course of inoperable lung cancer.
Of more than 7,500 men with nonresectable lung cancer with extensive disease treated on various regimens assigned at random, 1,068 received the best possible supportive treatment without any specific chemotherapeutic agent. This group of patients was reviewed for information pertinent to the natural history of bronchogenic carcinoma. The prognosis for lung cancer patients is usually poor. Median survival time was related mainly to patient's status at entry into the study: performance status using the Karnofsky scale, cell type and extent of disease.
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v2
|
2018-04-03T03:10:41.393Z
|
1973-09-01T00:00:00.000Z
|
1185721
|
s2ag/train
|
260 laryngeal carcinomas. Staging and end results.
This was a retrospective study of carcinoma of the larynx presenting statistics on age, sex, race, smoking, and duration and type of symptoms. Pathological staging and clinical staging were compared. Special attention was paid to recurrence of tumor after radiation and subsequent salvage by surgery. The complication rate was 39% if patients treated by radiation alone were excluded. The cure rate with primary treatment and over all cure rate, which included secondary treatment were compared: (1) stage 1, 73.2% and 88%; (2) stage 2, 56.5% and 68.5%; (3) stage 3, 22% and 33%; (4) stage 4, 16% and 22%. Of 114 cures, 22 were salvages. Of the 22 salvages, 20 were by surgery and two were by radiation.
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v2
|
2017-04-15T18:58:04.985Z
|
1973-10-01T00:00:00.000Z
|
14058980
|
s2ag/train
|
The stimulatory effect of tumor bearing upon the T- and B-cell subpopulations of the mouse spleen.
Summary The numbers and certain functions of T- and B-cell subpopulations of the spleen have been assessed in C57BL/6 and CBA mice over the course of bearing transplanted, syngeneic methylcholanthrene fibrosarcomas. The level of proliferative activity in this population increases progressively over the 5- to 8-week course of tumor bearing. The size of the θ-antigen-bearing subpopulation and the T-cell functions of graft- versus -host reactivity, in vitro responses to phytohemagglutinin, and primary stimulation by alloantigen in one-way mixed leukocyte cultures were found to increase significantly, provided that the data are expressed on the basis of total numbers of cells or degree of total function in the spleen. Numbers of plaque- or rosette-forming cells per spleen also increased over control values, both after direct immunization with sheep erythrocytes and when the primary response of spleen cells to sheep red blood cells was assayed adoptively in an irradiated host. The subpopulation responding to the mitogenic effect of lipopolysaccharide in vitro was greatly increased during tumor bearing. The data suggest that both T- and B-cell subpopulations and their functions are not diminished but are augmented significantly by tumor bearing.
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v2
|
2017-06-07T15:51:38.808Z
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1973-10-01T00:00:00.000Z
|
628103
|
s2ag/train
|
Expression of tumor-specific antigens in mouse somatic cell hybrids.
Inbred 129/Sv mice were resistant to inoculation of teratocarcinoma cells when preimmunized with (129-teratocarcinoma × C3H L-cell) somatic cell hybrids obtained by fusion with UV-inactivated Sendai virus. Resistance of DBA/2 mice to the highly malignant L1210 leukemia was also obtained by the use of (L1210 × C3H L-cell) hybrids. That this resistance was specific was suggested by regular takes of L1210 cell challenge in all DBA/2 mice immunized against different tumor cells unrelated to L1210. These experiments indicate the existence of teratocarcinoma- and L1210 leukemia-specific antigens in their respective hybrids, even when hybrids do not produce tumors in compatible F1 mice.
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v2
|
2017-06-10T00:11:51.180Z
|
1973-10-01T00:00:00.000Z
|
35486964
|
s2ag/train
|
The terminal care of patients with lung cancer
Lung cancer is the commonest form of malignant disease seen at St Christopher's Hospice. More than 35% of the male and about 8% of the female cancer patients are admitted with this diagnosis. This means that each year approximately 100 patients with lung cancer are amitted and cared for at the hospice. The more common symptoms experienced by 185 consecutive terminal lung cancer patients admitted to St Christopher's Hospice are listed in Table 1.
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v2
|
2017-09-25T11:41:53.619Z
|
1973-10-01T00:00:00.000Z
|
24322639
|
s2ag/train
|
Surface antigens common to mouse cleavage embryos and primitive teratocarcinoma cells in culture.
Syngeneic antisera have been produced in mouse strain 129/Sv-CP males against the primitive cells of teratocarcinoma. These sera react specifically with the primitive cells and are negative on various types of differentiated teratoma cells derived from the same original tumor. They are negative on all other mouse cells tested, with the exception of male germ cells and cleavage-stage embryos. Thus, teratoma cells possess cell-surface antigens in common with normal cleavage-stage embryos.
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v2
|
2018-04-03T02:21:30.837Z
|
1973-10-01T00:00:00.000Z
|
33375084
|
s2ag/train
|
Responses of serum luteinizing hormone and follicle-stimulating hormone levels to synthetic luteinizing hormone-releasing hormone (LH-RH) in various forms of testicular disorders.
ABSTRACT Synthetic luteinizing hormonereleasing hormone (LH-RH) was administered to normal men and to patients with oligospermia, azoospermia and hypergonadotropic and hypogonadotropic eunuchoidism. Intramuscular injection of 100 μg of LH-RH provoked significant increases in both serum LH and FSH levels in 30 min. The magnitude of responses in serum LH and FSH levels was largely dependent on basal levels, i.e., larger increments were observed in cases with higher basal levels. Responses of serum LH levels in cases with hypogonadotropic eunuchoidism were below the normal range, while those of serum FSH levels showed a considerable overlap into the normal range of responses. There were no responses of LH or FSH levels to LH-RH in cases of hypogonadotropic eunuchoidism under the treatment with testosterone or in cases of prostatic cancer under estrogen treatment.
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v2
|
2018-04-03T04:16:02.670Z
|
1973-10-01T00:00:00.000Z
|
38311812
|
s2ag/train
|
Roentgenologic demonstration of spontaneous reversal of portal blood flow in cirrhosis and primary carcinoma of the liver.
Angiographic studies were carried out on 49 cases of liver cirrhosis and 47 cases of primary liver cell carcinoma.An unequivocal retrograde portal blood flow was demonstrated in 1 cirrhotic patient. The portal vein was visualized during celiac arteriography in 5 patients with hepatoma, In 1, the portal flow was to- and-from, the direction depending upon the force of the contrast medium injection. In 4 hepatoma patients in whom retrograde portal flow was seen, there were tumor thrombi in the portal vein, and in 1 patient, in the collateral veins.Thus, retrograde portal flow does occur in cirrhosis of the liver, but very rarely, and it occurs more often in primary liver cell carcinoma, probably due to arterial neovascularization and arteriovenous communications.
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v2
|
2018-04-03T06:22:38.890Z
|
1973-10-01T00:00:00.000Z
|
46423628
|
s2ag/train
|
Effects of cations and colchicine on the release of prolactin and growth hormone by functional pituitary tumor cells in culture.
Monolayer cultures of the GH3 clone of functional rat pituitary cells have been used to study the short-term effects of cations and colchicine on the release of prolactin (PRL) and growth hormone (GH). Intracellular and extracellular concentrations of the hormones were measured by immunological methods. Increased extracellular concentrations of potassium (50 HIM) enhanced the release of both PRL and GH while the same concentration of sodium had no effect. Reduced or elevated levels of extracellular calcium had no acute (3 hr) effect on hormone release. Similarly, increased extracellular magnesium (10 HIM) did not affect hormone release. High potassium, but not high sodium, calcium or magnesium, had a hormone-releasing effect on cells in which the synthesis of PRL and GH had been stimulated by thyrotropin-releasing hormone or hydrocortisone, respectively. The hormone- releasing effect of high potassium treatment did not occur if the culture medium was low in calcium. Colchicine (5 X 10-6 M ) inhibited acut...
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v2
|
2018-04-03T01:54:46.366Z
|
1973-10-15T00:00:00.000Z
|
31371243
|
s2ag/train
|
Malignant pleural disease. A radiotherapeutic approach to the problem.
The effectiveness of external beam irradiation was evaluated in the control of nonlymphomatous malignant pleural disease, especially recurrent pleural effusion. Seventeen patients were treated by the 4-cm moving-strip technique. Fourteen had proven lung cancer and three had metastatic breast cancer. The data from 14 patients were analyzed. Ten patients demonstrated no reaccumulation or significant decrease in reaccumulation of pleural effusion. One patient had dramatic pain relief and disappearance of pleural lesions. These 11 patients were considered treatment successes. Three patients required more extensive treatment following radiotherapy and were considered treatment failures. These preliminary results show a control rate of approximately 80% and suggest that this technique offers a simple, safe, and effective means for controlling malignant pleural disease.
|
v2
|
2019-02-13T14:08:40.799Z
|
1973-10-27T00:00:00.000Z
|
60546717
|
s2ag/train
|
Cancer and the Patient
SIR,-I wholeheartedly agree with all that Mr. Charles Wright said in his Personal View (6 October, p. 45). I have always felt that if a patient asks for the diagnosis, whatever it may be, we have no right to withhold this information, with a full discussion of its implications. What right have we to lie to and deceive our patients? Most doctors are quite willing to explain to a natient the significance of an illness which may be of a much more serious nature than many carcinomas; and yet, when cancer is the diagnosis, they immediately start hedging and even deceiving. One result of this is that a distrust and strain develops between the patient and the doctor and between the family and the ipatient. The other consequence is to perpetuate the fear of cancer in the general public and to set it apart as a dreadful and frightening illness which should not e-ven be sooken about, even though the outlook for many patients may be excellent. But even for those less fortunate, a frank and honest explanation will do a lot to help the oatient to come to terms with his illness. I often feel that many doctors are evading their duty and responsibility to the patient by maintaining their silence and taking the "easy way out," and all their reasons given for their policy of silence are merely poor rationalizations. A full exolanation to the patient involves time and effort and a continuing support, which many doctors are not willing to undertake. I am fully aware that there are occasions when information may be harmful to the patient and should be withheld, but I am convinced that these are the exception rather than the rule.-I am, etc.,
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v2
|
2014-10-01T00:00:00.000Z
|
1973-11-01T00:00:00.000Z
|
14448023
|
s2orc/train
|
Retroperitoneal Fibrosis Associated with Malignant Disease
The clinical features of 19 patients with malignant infiltration of the retroperitoneal tissues are described. These patients usually presented with unexplained uraemia and nonspecific symptoms; only a few had other evidence of malignancy. The diagnosis was resolved only by histological examination of multiple biopsy specimens. Since the prognosis is usually very poor it is essential to distinguish this condition from non-malignant causes of retroperitoneal fibrosis. ImagesFig. 2Fig. 3Fig. 1
Summary.-The clinical features of 19 patients with malignant infiltration of the retroperitoneal tissues are described. These patients usually presented with unexplained uraemia and nonspecific symptoms; only a few had other evidence of malignancy. The diagnosis was resolved only by histological examination of multiple biopsy specimens. Since the prognosis is usually very poor it is essential to distinguish this condition from non-malignant causes of retroperitoneal fibrosis.
RETROPERITONEAL fibrosis, or periureteric fibrosis, was first fully described by Ormond (1948) and Raper (1956) although an earlier case report by Albarran (1905) has since been discovered. Despite various hypotheses the aetiology of this condition still remains obscure (Kay, 1963) and only an association with methysergide has been claimed (Graham et al., 1966). The term " idiopathic " helps to distinguish this now well recognized clinical entity from those cases in which a cause has been established. Thus, retroperitoneal fibrosis may be considered in three groups-idiopathic, non-malignant and malignant. The nonmalignant condition is a benign retroperitoneal fibrosis secondary to some known cause such as aortic or colonic surgery, radiotherapy or retroperitoneal infection (Cerny and Scott, 1971). Malignant retroperitoneal fibrosis may be secondary to a variety of primary tumours including breast, stomach, prostate and cervix (Ormond, 1960), reticulum cell sarcoma (Treves, 1958) and Hodgkin's disease (Nitz et al., 1970). In this paper we have examined 19 cases of histologically proven malignant retroperitoneal fibrosis in order to characterize the clinical features of a condition in which the diagnosis is often delayed and the prognosis, though poor, is often uncertain.
Patients
In the 12 year period 1960-72, 35 cases of retroperitoneal fibrosis were treated in this unit; of these 10 were idiopathic, 6 non-malignant and 19 malig- lymph nodes. However, clinical examination of these patients did not often prove helpful in establishing the main diagnosis. The blood urea concentration on admission was markedly raised in 18 cases and ranged from 200 mg/100 ml to 470 mg/100 ml, with a mean of 316 mg/O00 ml; in one case it was 23 mg/100 ml. The erythrocyte sedimentation rate (ESR) was raised in the 8 cases in which it was recorded. Two cases had an ESR in excess of 100 mm in one hour (Westergren method). Only 2 patients were not anaemic, all the others having a haemoglobin level of less than 10-0 g/l00 ml. No patients showed a leucoerythroblastic blood film. Abnormal liver function, manifest as a raised alkaline phosphatase and 5' nucleotidase value, was found in only one case. All the patients underwent x-ray examination of the chest and abdomen. Chest x-ray revealed a malignant pleural effusion in one case. Plain x-ray of the abdomen was not helpful in the diagnosis of retroperitoneal fibrosis, although in one patient fluid levels of subacute small bowel obstruction (due to reticulum cell sarcomatous masses) were seen.
Twelve of the 19 patients underwent cystoscopy and ureteric catheterization. At all these examinations the ureteric catheter passed easily up one and often both ureters; when there was an obstruction to the catheter a bulb ureteropyelogram was carried out. Of the 7 who did not have this investigation, 4 had been previously diagnosed at laparotomy, one had a uretero-colic anastomosis, one had an ileal conduit and one was too ill for further investigation. The non-uraemic patient developed bilateral ankle oedema and was the only patient to undergo inferior vena cavography. This showed occlusion of the inferior vena cava with multiple lumbar collateral vessels. Lymphangiography was not performed in any of the patients in this series.
Treatment
Dialysis.-7 patients required dialysis: 3 had peritoneal dialysis, 2 had haemodialysis and 2 were treated by both forms of dialysis.
Operation. 4 patients underwent diagnostic laparotomy. Two had no further procedure because of the extent of the disease; 1 had a uretero-ureterostomy at the time and had had a ureterostomy performed 2 weeks before the laparotomy. Biopsies were taken at each operation from the fibrous tissue surrounding the ureters and any other suspicious tissue or enlarged lymph nodes. An operative procedure to relieve urinary obstruction was undertaken in 9 patients (Table III).
Other methods.-The non-uraemic patient had a reticulum cell sarcoma and was given 3 courses of cyclophosphamide and vincristine, to which he made a dramatic response. He was the only patient successfully treated with chemo- therapy and has continued on combination therapy (cyclophosphamide, vincristine, procarbazine, prednisone) under the care of Dr L. Szur. Another patient, with giant follicular lymphoma, was given melphalan but died within 10 days from bronchopneumonia. None of the patients received radiotherapy.
Pathology
The primary tumours are listed in Table 1. The macroscopic appearance of the retroperitoneal fibrosis tissue at operation was never obviously malignant and in several cases the appearances closely resembled idiopathic retroperitoneal fibrosis. The diagnosis in these doubtful cases was made from the histology of the biopsy specimen. The microscopic appearances showed dense collagen tissue infiltrated with chronic inflammatory cells and nests of malignant cells (Fig. 1, 2, 3). Aggregates or sheets of malignant cells were seen in some cases and usually showed sufficient differentiation to diagnose or confirm the diagnosis of the primary lesion. In some cases further confirmation of the malignant process was made from the involved lymph nodes, which showed either secondary carcinoma or lymphomatous change.
There were 4 patients with reticuloses. with lymphosarcoma, as well as in the patient with a reticulum cell sarcoma, was confined to the peritoneum. The patient with giant follicular lymphoma had tumour involvement of peripheral lymph nodes and vertebral bodies as well as diffuse retroperitoneal infiltration.
DISCUSSION
The mean age of the patients in this series was 54 years, compared with a mean age of 44 years in the series with non-malignant retroperitoneal fibrosis reported by Webb and Dawson-Edwards (1967b). Malignant retroperitoneal fibrosis appears to occur with about equal frequency in men and women. In reviewing a series of 95 patients with idiopathic retroperitoneal fibrosis, Ormond (1960) observed that men were affected twice as often as women.
The distinction between the three groups of retroperitoneal fibrosis may be difficult. The history, clinical examination, radiological findings and even the macroscopic appearances at laparotomy may not distinguish the benign from the malignant type. Histology from an operative specimen is always needed to confirm the diagnosis and this applies as much to those where the fibrosis is thought to be benign as to those likely to be malignant.
A previous history of malignancy is helpful and half of the patients in this series were known to have been treated for malignancy when they first presented. Abnormal liver function was found in only one case; this patient had a squamous cell carcinoma of the renal pelvis. Liver function may be disturbed if there are hepatic secondaries or if the patient has received cytotoxic therapy, while a primary renal carcinoma may also affect liver function (Chisholm and Roy, 1971). It is evident from this, and other reported series of retroperitoneal fibrosis associated with malignant disease, that no one type of tumour has a particular predisposition to the development of retroperitoneal spread. In this series obstruction to the lower ureter due to local spread, as from carcinoma of bladder, has been excluded and none of the patients had received radiotherapy.
Retrograde uretero-pyelography remains an essential step in the investigation of obstructive uropathy. In patients who have had a previous urinary diversion, a high dose intravenous pyelogram or an antegrade pyelogram can be useful (Sherwood and Stevenson, 1972). Idiopathic retroperitoneal fibrosis produces characteristic radiological features and can usually be recognized (Dineen, Asch and Pearce, 1960). However, the distinction between the benign and malignant causes of fibrosis was not often possible from pyelographic appearances in this series. Lymphangiography and inferior vena cavography have been used in the investigation of such cases (Clouse, Fraley and Litwin 1964), but only occasionally has lymphangiography been useful in separating benign from malignant retroperitoneal fibrosis (Webb and Dawson-Edwards 1967a).
Dialysis is mandatory in the undiagnosed uraemic patient so that the primary cause may be sought and a fill assessment made.
Laparotomy may be undertaken as a diagnostic measure and may proceed to a palliative operation to relieve the urinary obstruction. At operation metastatic spread in the retroperitoneum may be obvious; however, since it is usually difficult to distinguish the gross appearance of benign retroperitoneal fibrosis from the malignant variety, it is essential to take multiple and deep biopsies. Discrete nodal masses or secondary deposits should be biopsied. It is possible in a plaque of malignant retroperitoneal fibrosis to miss an area of malignant cells, thus emphasizing the need for multiple biopsies. Because of the importance of a tissue diagnosis in the management of retroperitoneal fibrosis, we would recommend that all cases should have a biopsy of the retroperitoneal tissues, especially before embarking on treatment of the idiopathic variety with steroids (Charlton, 1968).
Whether urinary obstruction with uraemia should be relieved in a patient with malignant disease is still a question for clinical judgment in the individual case. Indications for palliative interference are probably few as the results are so poor. A surgical procedure was considered justified in 9 of the 19 patients and of these, 2 had an acceptable result in terms of length and quality of survival. All those not considered suitable for relief of obstruction died within 4 weeks. In a study of malignant obstruction with uraemia, the six-month survival for carcinoma of the bladder was 30%0, carcinoma of the cervix 20%, and carcinoma of the prostate 50%0 (Chisholm and Shackman, 1968). The comparable figure in the present series with malignant retroperitoneal fibrosis was 10%.
We wish to thank Dr J. G. Azzopardi and Dr I. D. Ansell for their advice on the histological sections, the Department of Medical Illustration for the figures and Dr L. Szur for his comments on those patients with reticuloses.
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v2
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2017-04-08T18:24:21.872Z
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1973-11-01T00:00:00.000Z
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11990438
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s2ag/train
|
Specific glucocorticoid binding in human hemopoietic cell lines and neoplastic tissue.
Summary Triamcinolone acetonide-3H (TA-3H) binding to subcellular macromolecular fractions was studied in three human lymphoid cell lines (HRIK, RPMI 8226, and MOLT-4), in four lymphosarcomatous tumors, and in leukemic leukocytes obtained from the peripheral blood of three patients with acute lymphocytic leukemia, six with acute myelocytic leukemia, eight with chronic lymphocytic leukemia, and two with chronic myelocytic leukemia. Specific binding, which was manifested by a high binding affinity of TA-3H to the macromolecular fractions and by a greater inhibition of this binding by cortisol, compared with that of inactive steroid epicortisol, was found in the lymphoid cell lines, lymphosarcomatous tissue, acute lymphocytic leukemia cells, and two of the six acute myelocytic leukemia cells. Sedimentation coefficients “S” of the TA-3H macromolecular complex were studied in one of the lymphosarcomatous tumors. When the cells were incubated at 0°, extraction with low-salt buffer produced a 6.5 S TA-3H macromolecular complex, while extraction with high-salt buffer produced a 4 S complex. After incubation at 37°, extraction with high-salt buffer produced a 4 S complex, while extraction with low-salt buffer yielded only a small amount of the complex sedimenting at 6.5 S. However, a 4 S complex was extracted with high-salt buffer from the 27,000 × g pellet of the low-salt extract, suggesting that incubation at 37° resulted in movement of the TA-3H macromolecular complex into the nucleus. Incubation of HRIK cells in the presence of 10-5 and 10-4m cortisol resulted in 22.5 and 50% inhibition of uridine-3H uptake by the cells, while incorporation of the uridine-3H into cellular RNA was inhibited only after incubation with 10-4m cortisol. The relative insensitivity of these cells to cortisol, despite their high specific-binding capacity, indicate that factors other than steroid binding by the subcellular fractions play an important role in determining the sensitivity of cells to glucocorticoid action.
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v2
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2018-04-03T00:11:22.828Z
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1973-11-01T00:00:00.000Z
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10501547
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s2ag/train
|
Simian Virus 40-Host Cell Interactions. I. Temperature-Sensitive Regulation of SV40 T Antigen in 3T3 Mouse Cells Transformed by the ts*101 Temperature-Sensitive Early Mutant of SV40
BALB/3T3 and Swiss/3T3 mouse cells transformed at permissive temperature (33 C) by the early temperature-sensitive mutant of simian virus 40 (SV40), ts*101, exhibited a temperature-dependent modulation of SV40 tumor (T) antigen as assayed by immunofluorescence. The percentage of T antigen-positive nuclei in ts*101 transformed cells was reduced at restrictive temperature (39 C) when compared to 33 C and to wild-type SV40 transformed cells at either 33 C or 39 C. The percentage of T antigen-positive nuclei in ts*101 transformed cells returned to the 33 C control level when the cells were shifted from 39 to 33 C. The ts*101 transformed cells could be superinfected with wild-type, but not ts*101, virions at 39 C as assayed by an increase in T antigen-positive nuclei.
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v2
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2018-04-03T00:40:11.222Z
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1973-11-01T00:00:00.000Z
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26180907
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s2ag/train
|
Alternate complement pathway: elevation of cobra venom-induced hemolytic activity in sera of tumor-bearing mice.
We have recently reported that sera of cancer patients possess greater lytic capacity for unsensitized erythrocytes after interaction with a cobra venom protein, CVF, (1). This antibody independent lytic process results from utilization of the terminal complement components (C3 to C9) through an alternate pathway that can be initiated by an enzymatically active complex formed by CVF, C3 proactivator (properdin factor B) and other serum constituents (2–4). A hemolytic assay for this reaction sequence has been described in (5).
For minimizing the number of variables inherent in studies of this type with sera of hospitalized patients, an experiment was designed to evaluate levels of CVF-mediated lytic activity in the sera of tumor-bearing mice. Toward this end, mice of both sexes (25 ± 2g), were inoculated subcutaneously with 0.5 mg of 3-methylcholanthrene (3MC) dissolved in sterile corn oil. The largest experimental group contained mice of the Swiss-Webster strain maintained as an outbred colony in this Institute.
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v2
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2018-04-03T00:45:08.649Z
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1973-11-01T00:00:00.000Z
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26496373
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s2ag/train
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N-demethylation of the antineoplastic agent hexamethylmelamine by rats and man.
Summary The metabolism and physiological distribution of hexamethylmelamine (HMM), an effective human anticancer chemotherapeutic agent, was studied in cancer patients and in rats. Administration of HMM-methyl- 14 C to two patientst p.o. was followed by the prompt appearance of respiratory 14 CO 2 within 1 hr, accumulating to 9% of administered dose in 6 hr. After 72 hr, 29% of the radioactivity was recovered in the urine, and 0.5% was recovered in the feces. In rats, p.o. and i.p. administration of HMM- 14 C led to the recovery of 13 and 30%, respectively, of the dose as 14 CO 2 in 24 hr. After 72 hr, 58% of the p.o. dose of radioactivity was recovered, 16% as 14 CO 2 , 38% in the urine, and 4% in the feces; while in the same interval, 80% of the i.p. dose was recovered, 33% as 14 CO 2 , 42% in the urine, and 5% in the feces. No unmetabolized HMM was detected in urine; instead four distinct compounds could be chromatographically separated. The major urinary metabolites in patients and rats exhibited identical chromatographic and spectroscopic properties. Use of gas chromatography and mass spectrometry led to the identification of the major urinary metabolites as N 2 , N 4 , N 6 -trimethylmelamine, N 2 , N 4 -dimethylmelamine, monomethylmelamine, and melamine. Thus, N -demethylation appears to be of major significance in the metabolism of HMM in man and in rats. HMM and its metabolites did not demonstrate significant alkylating activity, as evidenced by their failure to react with 4-( p -nitrobenzyl)pyridine.
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v2
|
2018-04-03T02:40:47.403Z
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1973-11-01T00:00:00.000Z
|
34616690
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s2ag/train
|
Distribution of radioactivity and metabolism of formic acid 2-(4-(5-nitro-2-furyl)-2-14C-2-thiazolyl)hydrazide following oral administration to rats and mice.
Summary Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]hydrazide (FNT) has demonstrated carcinogenic activity in rats and mice, inducing high incidences of kidney and breast tumors in rats and forestomach tumors and lymphocytic leukemia in mice. Tumors of other organs were also induced in lower incidences. The excretion patterns in rats and mice were essentially similar when FNT was administered intragastrically, with a majority of the radioactivity excreted within 24 hr in the urine and less in the feces after 24 hr. Very little was expired as 14 CO 2 and less than 2.5% of the radioactivity was left in the animal after 96 hr. The tissue distribution of the radioactivity in rats demonstrated the highest concentrations in the kidney and forestomach of the rat and mouse, respectively. Concentrations in the rat breast and mouse thymus and spleen were comparable to the levels in the carcass, while levels in other tissues were similar to or somewhat higher than those in the carcass. When the urine from these animals was chromatographed on Whatman No. 1 paper and developed with methanol:butanol:benzene:water:glacial acetic acid (40:20:20:20:1), the radioactivity with an R F corresponding to the original chemical was less than 10% (usually 2 to 5%) of the total activity in the urine. This suggested that the chemical was metabolized before being excreted in the urine. After administration of FNT intragastrically at 0, 4, and 8 hr to weanling female rats, the rats were killed at 12 hr and the kidneys and liver were fractionated by ultracentrifugation. Distribution of radioactivity in the nuclear, mitochondrial, microsomal, and cytosol fractions was 28.4, 14.6, 5.7, and 51.2% and 20.2, 8.0, 3.4, and 68.4% in liver and kidney, respectively. When the cytosol fraction was chromatographed on Sephadex G-25 columns, 51.4% of the radioactivity appeared in the macromolecular peak from kidney and 19.8% appeared from liver. Comparable amounts of cytosol radioactivity were precipitated by cold trichloroacetic acid. When the labeled chemical was added to “cold” homogenate, greater than 90% of the radioactivity appeared in the cytosol fraction of kidney and liver and none appeared in the macromolecular peak when chromatographed on Sephadex G-25 columns. These data suggest that FNT interacts with kidney and liver macromolecules and that it must be metabolized before the interaction can occur. They synthesis of FNT is described.
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v2
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2018-04-03T02:42:16.770Z
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1973-11-01T00:00:00.000Z
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34689391
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s2ag/train
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Antibody Cytotoxicity Studies in Ovarian and Cervical Malignancies
This study evaluates the cytotoxic affect of serum from patients with progressive squamous cell carcinoma of the cervix and adenocarcinoma of the ovary prior to treatment. The cytotoxic ability of six specific rabbit antisera prepared by immunizing rabbits with fresh tissue homogenates of adenocarcinoma of the ovary were also studied and all six demonstrated a definite injurious affect. Twelve of the 20 patients with advanced squamous cell carcinoma of the cervix and 5 of the 8 patients with advanced adenocarcinoma of the ovary also illustrated a definite cytocidal serum activity. Explanations for the concomitant presence of cytotoxic antibodies and progressive disease are suggested.
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v2
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2018-04-03T03:34:09.691Z
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1973-11-01T00:00:00.000Z
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6756635
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s2ag/train
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Electron microscopic studies of human pituitary tumors. I. Chromophobic adenomas.
Ten cases of chromophobic adenoma have been studied by electron microscopy; seven were associated with hypopituitarism and three with acromegaly. Comparison of the tumors revealed that morphological variations in parenchymal cell types were slight, and, based on characteristics of the secretory granules, a single cell type was predominant and common to both varieties of the tumor. The predominant cell type contained varying amounts of secretory granules that measured 80–200 mμ or more in diameter, and had an electronopaque core and perigranular halo. Though the features of these secretory granules were most like those in “normal” adult basophils this classification is considered doubtful. The core material of the secretory granules was homogeneously electron-opaque in some granules and particulate in others. In addition to electron-opaque core material many secretory granules contained aggregates of clear vesicles. Some granules did not contain clear vesicles but were closely associated with numerous cytoplasmic vesicles. Lysosomes were abundant and a consistent feature of the tumor cells. The present observations indicate that cell features are significantly altered in the cells of both varieties of chromophobic adenoma so that ultrastructural criteria used to identify cell types in “normal” pituitary glands are not applicable to the tumor cells.
Chromophobic adenomas associated with acromegaly varied more with respect to the features of the predominant cell type than did chromophobic adenomas associated with hypopituitarism. Cell features varied between cells with electronlucent cytoplasmic matrix and scant development of organelles to others with more electron-opaque cytoplasmic matrix and more complex development of organelles. Common to both varieties of tumor were marked variations in the number and structure of mitochondria from cell to cell; occasionally mitochondria filled the cytoplasm.
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v2
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2019-03-08T14:21:20.398Z
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1973-11-01T00:00:00.000Z
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71285822
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s2ag/train
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The Management of Musculo-Skeletal Problems in the Haemophilias
For example, no doctor faced with the management of a patient with acute leukaemia would end up knowing what to do if he consulted this book. Details of treatment are sketchy, and there are virtually no references to recent important work which he could consult. Similarly in the section on Hodgkin's disease, much is made of single agent treatment which is now virtually a thing of the past, but the MOPP protocol is only mentioned in passing and no reference to it is given. The section on solid tumours is rather better than that on leukaemia and lymphoma, but again any clinician referring to it would be hard put to end up knowing what to do about some of the tumours which are described. In contrast, Greenwald's book on 'Cancer chemotherapy' is an excellent short description of the state of the art at present. It is really quite remarkable for the amount of information which it contains and the bibliography is extensive and up to date. The physician consulting this book should have no difficulty in obtaining enough information adequately to manage most malignancies with chemotherapy. It is probably the best short book on the subject for the occasional chemotherapist, and is highly recommended.
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v2
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2019-03-16T13:11:19.381Z
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1973-11-01T00:00:00.000Z
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79294014
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s2ag/train
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On the Etiology of Cancer of the Uterus
CANCER OF the cervix has been associated with certain exogenous factors such as low socioeconomic status, early and frequent intercourse, childbearing, and the state of circumcision of the partner. Cancer of the corpus has been related to endogenous factors, particularly to obesity, hypertension, diabetes, and delayed menopause. Among the exogenous mutagens, smegma and various microorganisms —especially the herpes genitalis ' virus —have been implicated. But Coppleson and Reid are of the opinion that the main mutagens are spermatozoa. Carcinogenesis depends on the nature of the mutagen and on the susceptibility of the substrate to it, i.e. on the capacity of the mutagen to enter the nucleus and to combine with the host's genome. The susceptibility of any one tissue to carcinogens is not a constant feature. It is subject to such variables as the degree of cellular maturation, the microenvironment, and the hormone levels. Thus it has been shown that the application of dimethylbenzanthracene onto rat cervix during the diestrus phase induced local and distant tumors whereas delivery of the same amount of carcinogen during the estrus phase did not have this effect. Similarly, it has been demonstrated that
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v2
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2018-04-03T00:58:38.535Z
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1973-11-15T00:00:00.000Z
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27644097
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s2ag/train
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Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Control of polymerization by J chain.
Cell suspensions of mouse plasma-cell tumours secreting IgA (immunoglobulin A) and IgM (immunoglobulin M) were incubated with radioactive leucine for various periods of time. The secreted immunoglobulins were precipitated from the culture medium with specific rabbit antisera to determine the relative distribution of radioactivity among the different molecular species, and to estimate the fraction of total radioactivity in the J chain. For IgM-secreting cells there is a balanced synthesis of 7S subunits and J chains, and the secreted product is uniformly assembled to the pentamer. In cells secreting IgA, however, the results demonstrate that the pool of intracellular J chain is less than the intracellular IgA pool. The concentration of J chain is therefore limiting and is less than the requirement for complete polymerization. The major factor that determines whether an intracellular monomer is secreted as such or is polymerized with the addition of J chain is therefore the amount of intracellular J chain. When this is limiting, as it is in cells secreting IgA, then monomer will be secreted.
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v2
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2018-04-03T06:10:26.248Z
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1973-11-15T00:00:00.000Z
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45758332
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s2ag/train
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Intracerebral transplantation of human rhabdomyosarcoma cells into fetal and newborn kittens
A human rhabdomyosarcoma cell line (RD) was transplanted intracerebrally in fetal kittens in an attempt to repeat the recovery of an RD‐114‐like virus. No virus was recovered from six such transplant tumors. Similar transplant tumors formed by RD cells productively infected prior to transplantation with feline leukemia virus or murine sarcoma virus released viruses that were not detectably altered from the parent viruses.
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v2
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2018-04-03T00:33:45.580Z
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1973-11-19T00:00:00.000Z
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12946210
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s2ag/train
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Occult carcinoma of second breast following mastectomy.
In 18 years six women were seen with metastatic carcinoma in contralateral axillary nodes some time after a radical mastectomy. With no other evidence of tumor, a second radical mastectomy was performed in six of the breasts, and new primary tumor was found in four. Two patients died of carcinoma, one is alive with metastatic disease six years after surgery, and three are alive and well 8,10, and 14 years after the second mastectomy.
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v2
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2018-04-03T00:28:22.588Z
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1973-12-01T00:00:00.000Z
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11628151
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s2ag/train
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Differential diagnosis of brain lesions by gallium scanning.
The effectiveness of gallium and technetium scanning was compared in the detection of brain tumors and to evaluate whether the combined use of both radionuclides might help in the differential diagnosis of tumors versus infarcts. Seventy-seven patients were studied, 28 with brain tumors and 43 with infarcts. Twenty-eight infarction cases had positive technetium brain scans while the gallium scan was negative. An additional nine cases showed a marked disparity between the technetium and gallium accumulation with the gallium study read as equivocal. In six cases no differential was possible since the gallium uptake approached that of technetium. Of the 28 intracranial neoplasms studied, nine showed gallium uptake to be greater than technetium uptake, using visual comparison of the density ratio in lesion to calvarium as criterion. In four of these cases the lesions were detected with gallium and not with technetium. Two cases showed gallium uptake slightly less than with technetium. It is concluded that /sup 67/Ga scanning is a useful adjunct to brain scanning with /sup 99m/Tc, particularly in the early detection of certain tumors as well as the differentiation of tumor from infarct. (auth)
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v2
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2018-04-03T01:23:54.463Z
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1973-12-01T00:00:00.000Z
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23872435
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s2ag/train
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Effects of Polyadenylic Acids on Functions of Murine RNA Tumor Viruses
Single-stranded polyribonucleotides, which competitively inhibit murine RNA tumor virus reverse transcriptase in vitro, were tested as inhibitors of various virus functions in cell culture. The compounds had two concentration-dependent effects. At high concentrations (100 μg/ml), both poly(adenylic acid) [poly(A)] and poly(2′-O-methyladenylic acid) [poly(Am)] inhibited the uptake of radioactively labeled leukemia virus by Swiss mouse embryo cells, but neither had a similar effect on Sindbis virus adsorption. At low concentrations (10 μg/ml), poly(Am) did not inhibit the uptake of leukemia virus but did inhibit virus replication by 85%; in contrast, the replication of Sendai virus and Sindbis virus was not inhibited significantly at this concentration. Both compounds were effective only when added prior to or early during virus infection. Poly(Am) was a much more effective inhibitor than poly(A), probably due to the nuclease resistance of the former compound. Poly(Am) at 5 μg/ml also inhibited transformation of 3T3 cells by Moloney sarcoma virus. However, neither poly(A) nor poly(Am) at high concentrations inhibited the activation of endogenous leukemia virus by iododeoxyuridine in AKR mouse embryo cells. These results suggest that virus reverse transcriptase plays an essential role in both the replication of exogenous murine leukemia viruses and the transformation of cells by murine sarcoma viruses but probably has no role in the activation of endogenous leukemia virus.
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v2
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2018-04-03T01:54:55.019Z
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1973-12-01T00:00:00.000Z
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11886
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s2ag/train
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Tumor Metastases to the Small Bowel from Extra‐Abdominal Sites
Rarely is the small bowel involved by metastatic lesions emanating from primary tumors in extra-abdominal sites. We have seen 12 such patients at our institution over the past 20 years. None had involvement of the small bowel by direct extension. The primary sites were skin (malignant melanoma), embryonal rhabdomyosarcoma arising in the neck, reticulum cell sarcoma arising on the back, and branchogenic carcinoma. Presenting symptoms were intestinal bleeding, intestinal obstruction, or intestinal perforation. Intestinal resection was performed successfully in nine patients; of these, two are still alive. The longest survivor had bronchogenic carcinoma and is now disease-free eight years after resection of the small bowel metastases. Gastrointestinal bleeding and obstruction may be caused, in rare instances, by metastatic tumors to the small bowel. Surgical resection of these lesions may afford worthwhile palliation and occasional long-term survival.
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v2
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2018-04-03T03:58:52.570Z
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1973-12-01T00:00:00.000Z
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7658374
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s2ag/train
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High- and low-tumorigenic culture lines of rat uterine adenocarcinoma and their isozyme patterns of lactate dehydrogenase and hexokinase.
Summary The isozymes of lactate dehydrogenase (LDH) and hexokinase were studied in high- and low-tumorigenic cloned cells of rat uterine adenocarcinoma originatly induced by 7,12-dimethylbenz[a]anthracene in vivo . Only LDH-5 (muscle type) and LDH-4 were detected in hightumorigenic cells. However, in addition to LDH-5 and LDH-4, LDH-3 was present in low-tumorigenic cells, whereas normal rat endometrial tissue contained all 5 isozymes of LDH. The specific activity of the enzyme was higher in high- than in low-tumorigenic cells, which had still higher activity than normal endometrium. Both uterine adenocarcinoma cells were characterized by a marked type II hexokinase, as well as a weak type I hexokinase, and by a loss of type III hexokinase, which was detected in normal endometrium, as were types I and II. Specific hexokinase activity was also highest in high-tumorigenic cells. When these culture cells were reinoculated into isologous hosts, LDH-3, -2, and -1 and type III hexokinase appeared in the tumor tissues. No significant difference in these isozyme patterns was detected between the tumors that developed by inoculation of high- and low-tumorigenic cells.
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v2
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2018-04-03T04:42:38.074Z
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1973-12-01T00:00:00.000Z
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40157661
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s2ag/train
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Thymus‐dependent cytotoxic lymphocytes in the rat
The nature of effector cells mediating cytotoxicity in vitro in a rat tumor allograft model using 51Cr release assays has been investigated. On the basis of a series of in vitro cell depletion techniques including glass absorption, removal of Fc receptor‐bearing cells and lysis of thymus‐dependent lymphocytes with a cytotoxic rabbit anti‐thymus cell sera, the predominant effector cell in this situation appears to be a thymus‐dependent lymphocyte. The main difference from previous published studies in mice appears to be the more rapid evolution of cytotoxic activity in the rat and the difficulty in detecting marked cytotoxic activity in the thoracic duct cells. Determination of the antigenic specificity of these cytotoxic cells by an inhibition assay suggests that their specificity is directed solely to transplantation antigens on the tumor cell.
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v2
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2018-04-03T05:01:32.960Z
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1973-12-01T00:00:00.000Z
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20816703
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s2ag/train
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Correspondence: radiosensitivity of surviving cells in tumours pretreated with continuous irradiation.
In his comment on our paper entitled “Effects of continuous irradiation at low dose-rates on a rat rhabdomyosarcoma” (Kal and Barendsen, 1972), Dr. Liversage implies that the greater response of surviving cells in tumours pretreated at low dose rates as compared with cells in untreated tumours to an acute dose of 800 rads, may be entirely due to accumulation of sublethal damage during the protracted pretreatment (Liversage, 1973). From our experimental data it can be deduced, however, that at least three factors can play a part in the response of these cells, namely a rapid reoxygenation, changes in cell age distribution, and repair of sublethal damage.
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v2
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2017-04-15T02:54:53.297Z
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1974-01-01T00:00:00.000Z
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86029053
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s2ag/train
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I. ENHANCEMENT OF SARCOMA I INDUCED BY IgM, IgGl, AND IgG2*
The mechanism whereby passively-transferred antibodies lead to enhancement of tumor allografts in mice is still unclear. Different hypotheses have been derived from conflicting results on similarly constructed experiments, and cont roversy extends to the immunoglobulin class of the responsible antibodies (1-8). However, the absolute quan t i ty of an t ibody used has not been determined, which prevents resolution of these discrepancies. We have determined immunochemical ly the amounts of specific a l loant ibody in three purified mouse immunoglobulin preparat ions and have shown tha t IgM, IgG1, and IgG2 antibodies are all capable of inducing tumor enhancement when used in adequate concentrations.
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v2
|
2017-06-21T03:12:22.225Z
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1974-01-01T00:00:00.000Z
|
19164163
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s2ag/train
|
Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours
Nakratzas, G., Wagenaar, J. P. M., Reintjes, M., Scheffer, E., and Swierenga, J. (1974).Thorax, 29, 125-131. Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours. Two cases of tracheal tumour are described, one a carcinoid and the other an adenoid cystic carcinoma (cylindroma). Both patients were treated by repeated partial bronchoscopic resections. The patients are in good health nine and three years respectively after treatment.
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v2
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2017-06-22T18:38:57.721Z
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1974-01-01T00:00:00.000Z
|
8480164
|
s2ag/train
|
Effects of tumour viruses on cell growth
Cells in higher organisms, from hydra to human beings, are subject to marvellously precise control of growth, and the loss of this control may lead to cancer. Cultured cells in vitro are also subject to control of growth in a rather crude form, which may nevertheless bear some relation to thesystems operating in vivo in whole organisms. Since tumour viruses modify these growth controls in cultured cells, model systems are available which could teach us something about real cancer. Up to the present nearly all studies have been made on fibroblasts, the name loosely applied to the spindle-shaped cells which predominate in culture. Primary cultures, which are heterogeneous but mostly fibroblastic, and homogeneous populations of fibroblasts, obtained by cloning of cell lines such as BHK 21 hamster cells or 3T3 mouse cells, are used, and although there are some important differences, all show similar general features.
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v2
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2017-09-06T10:52:19.400Z
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1974-01-01T00:00:00.000Z
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19329089
|
s2ag/train
|
Reverse transcriptase of an oncornavirus-like particle derived from human HeLa cells.
Oncornavirus-like particles have been observed and isolated from HeLa cells that contain a DNA polymerase actikity with properties similar to RNA tumor vims reverse transcriptase. The virions have a density of 1.16-1.17 g/cm3 and contain nucleic acid species that sediment as RNA (1.68 g/ml) in a Cs2SOI equilibrium density gradient. Antigenically the HeLa virus DNA polymerase is related to the Mason-Pfizer monkey virus DNA polymerase. The presence of virus-like particles, rnorphologically similar to those of the known RNA tumor viruses, has been recently observed in HeLa cells (1). Further electron microscopical analysis revealed maturation of an intracellular A-type particle at the cell membrane releasing a particle with properties oi'both Band C-type virus particles (2). Comparative studies suggested these vims particles to be morphologically sirnilar to the Mason-Pfizer monkey vims (MP-MV). Frori these results, it was of considerable interest to examine the biochemical and serological properties of these particles which is currently under investigation. It is the purpose of this communication to report some physicd and biochemical properties of the HeLa virus and a particle-associated DNA polymerase activity. Materials and me thods Unlabelled deoxyribonucleoside triphosphates, bovine pancreatic ribonuclease and oligodeoxythymidylate (10) ~ol~riboadenylate [oligo (dT) poly (rA)] were products of Boehringer-Mannheim. Tritiated thymidine 5' triphosphate (48 Ci/mmole) was purchased from New England Nuclear. Cesium sulfate was obtained from Merck and Nonidet-P40 was kindly supplied by Deutsche Shell Chemie Gesellschaft mbH. Viruses. HeLa vims was produced in culnire from a line of HeLa cells originally obtained from Dr. W. A. K. Schmidt, Düsseldorf. Ceils had been cultivated for three years in Homburg/Saar and one year in Berlin in Eagle's medium supplemented with 4-10 % heat-inactivated calf Serum. Cultures were continudly exarnined for contamination by Mycopiasma sdivarium and were treated with antiPPLO (Tylocine, Grand Island Biologicd Company). Culture supernatants were collected every 24 hr and subjected to lour speed centrifugations of 3000 X g for 15 min and 16,000 X g for 20 min before the material was pelleted by high speed centrifugation (90,000 x g, 60 rnin, 4 OC). The pellets were then resuspended in TNE, pH 7.4 (0.01 M Tris, 0.1 M NaCl and 0.003 M EDTA), centrifuged 5 rnin at 2,000 rpm and the virus-containing supernatant was layered over a linear 20-70 % (w/v) sucrose density gradient for equilibrium density centrifugation (15 hr, 4 "C, 23,000 rpm in a Spinco SW 25.1 rotor). Mason-Pfizer monkey virus (W-MV) was a gift of H. Daams, Amsterdam and avian myeloblastosis virus (AMV) was obtained by methods previously described (3) from the blood of chicks in the terminal stage of myeloblastic leukemia. 32P04-labelled vinis was prepared by first washing HeLa cell cultures with Eagle-Dulbecco medium (Flow Laboratories) lacking phosphates (1 0 mlldish). The cultures were then incubated for 20 hr at 37 OC in phosphate-free medium containing 100 pCi/ml of 32P-orthophosphate (earrier free, Radiochemical Centre, Amersham, England) and 10 % dialyzed calf serum. PO4-labelled nucleic acid was extracted by the method of Kacian et al. (4) from virus banding in the region of density 1.15-1.18 g/cm3 of a sucrose equilibrium density gradient. For DNA polymerase studies, a pool of the region of density 1.15-1.18 g/cm3 was made, diluted to 30 ml with TNE buffer (0.01 M Tris-HCL, pH 7.4, 0.1 M NaC1, 0.003 M EDTA) and centrifuged 60 rnin at 4' and 23,000 rpm in a Spinco SW 25.1 rotor. The concentrated pellet was resuspended in 0.5 ml of TNE buffer and stored in ice. Unless otherwise indicated this was the source of virus DNA polyme rase. Before use, the material was disrupted 15 min at 4 OC with Nanidet -P40 detergent (0.05 % for endogenous and 0.2 % for exogenous-templated reactions) and then standard reaction mixtures (100 pl) for DIVA polymerase were prepared essentially as described previously. The specific activity of 3H-TTP was 200-400 cpmlpmole for the synthetic RNA-DNA hybrid and DNA-templated reactions and 3,500 cpm/pmole for the endogenous DNA polymerase reactions. Assays for neutrdization of HeLA DNA polymerase activity by anti-MP-MV DNA polyrnerase IgG were carried out as described previously (5). Purified IgG fractions from normal rabbit serum (obtained prior to immunization) and rabbit anti-Mason-Pfizer monkey virus DNA polyrnerase serum were kindly supplied by Dr. A. YANIV, Institute of Cancer Research, Columbia University, New York, N. Y.
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v2
|
2017-10-17T05:48:21.778Z
|
1974-01-01T00:00:00.000Z
|
28264202
|
s2ag/train
|
Elongation factor 1 from Krebs II mouse ascites cells. Purification, structure and enzymatic properties.
The three major forms of elongation factor 1 (EF-1) occurring in Krebs II mouse ascites tumor cells were investigated with respect to their affinities for guanosine nucleotides and aminoacyl-tRNA. The binding of GTP, GDP and 5′-guanylyl-methylene-diphosphonate (Guo-5′-P2-CH2-P) to a pure preparation of the tetramer form of EF-1 and to partially purified dimer and hexamer preparations of the same factor was studied by equilibrium dialysis techniques. Another series of experiments was designed to describe the interaction of the tetramer and dimer form of EF-1 with aminoacyl-tRNAs. The following results were obtained.
1
When measured at 2 °C, the association constants for the complexes between pure EF-I and GTP or GDP were both 92 mM−1.
2
There is one guanosine nucleotide binding site per molecule of the EF-1 tetramer which can be occupied by GTP, GDP or Guo-5′-P2-CH2-P.
3
The affinities of the dimer and hexamer forms of EF-I for GTP and GDP were of the same order of magnitude as the corresponding values relating to the tetramer.
4
Large (tetramer) and small (dimer) aggregates of EF-1 provide equal protection of aminoacyl-tRNA against hydrolytic deacylation. This protective effect depends on the previous interaction of the factor with GTP. Although GDP and Guo-5′-P2-CH2-P bind to EF-1, they cannot replace GTP in this reaction.
5
The protective effect of EF-1 on aminoacyl-tRNAs is limited to tRNA species which can function in polypeptide chain elongation. Met-tRNAtMet and the chemically formylated Met-tRNAMet are only poorly protected by EF-1 indicating that these tRNAs are not well recognized by the factor.
The significance of these results with respect to our understanding of the function of elongation factor 1 in mammalian cells is discussed.
|
v2
|
2017-11-02T18:39:10.218Z
|
1974-01-01T00:00:00.000Z
|
3173363
|
s2ag/train
|
Oncogenicity of an Endogenous C-Type Virus Chemically Activated from Mouse Cells in Culture
RNA C-type viruses are known to exist in an unexpressed form in all mouse cells. These endogenous viruses can be activated from cells in tissue culture under certain experimental conditions. The biologic activity in vivo of one class of chemically-activated C-type virus has been studied. This virus is shown to induce a specific tumor, lymphatic leukemia, in mice of a low leukemic incidence strain.
|
v2
|
2018-04-03T00:06:11.398Z
|
1974-01-01T00:00:00.000Z
|
8467910
|
s2ag/train
|
Carcinoembryonic‐like antigen in the urine of patients with carcinoma of the bladder and normal controls
The urine and plasma of 16 patients with carcinoma of the bladder, and 27 normal individudls were studied for the presence of carcinoembryonic antigen (CEA). An attempt was made to determine whether urine CEA‐like antigens are filtered by the kidney or shed directly by the bladder tumor itself. There were elevated levels of CEA in the plasma of patients with bladder tumors. The urine of patients with bladder carcinoma had significantly higher levels of CEA‐like antigen than the urine of normal individuals. These same bladder tumor patients did not have a positive correlation between their plasma CEA and the urine CEA‐like antigen levels. It appears from these findings that urinary carcinoembryonic‐like antigen is shed directly into the urine and not filtered by the kidneys.
|
v2
|
2018-04-03T00:27:24.563Z
|
1974-01-01T00:00:00.000Z
|
11792341
|
s2ag/train
|
Two cases of Cushing's syndrome. Tumour and bilateral hyperplasia.
Two patients, one with Cushing's syndrome and one with Cushing's disease, are presented. In the first case the syndrome was caused by a tumour of the right suprarenal gland which was treated by unilateral adrenalectomy, and the second case was diagnosed as hyperplasia of the left suprarenal gland, eventually leading to removal of all cortical tissue. Subsequently the typical features of Nelson's syndrome developed.
|
v2
|
2018-04-03T00:50:01.502Z
|
1974-01-01T00:00:00.000Z
|
26804398
|
s2ag/train
|
Proteoglycans of microsomal fraction of mouse mastocytoma.
Abstract Proteoglycans have been isolated from a microsomal fraction of a mouse mastocytoma by procedures which should minimize alteration of the original protein-polysr, ccharide molecule. The methods used include in vivo labeling of sulfate-containing proteoglycans with35S-sulfate, centrifugation of the tumor homogenate at 105, 000 g, solubilization of the microsomal pellet using sodium dodecyl sulfate, cetylpyridinium fractionation, DEAE-cellulose column chromatography and Geon resin electrophoresis. Two major sulfated proteoglycan fractions were obtained. The analytical data obtained were interpreted to indicate that one of these fractions contained keratan sulfate-like material (KSP), the other a heparin-like polymer (HP). KSP was found to contain sialic acid. The protein content of KSP was considerably higher than that of HP. Results of amino acid analysis indicate that glutamic acid and leucine were predominant in KSP, but serine and glycine in HP. Both KSP and HP were found to be homogeneous when ...
|
v2
|
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