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2018-04-03T01:24:06.656Z
1974-01-01T00:00:00.000Z
29122490
s2ag/train
CARCINOID HEART DISEASE: CARDIAC SURGERY FOR INTRACTABLE HEART FAILURE. Congestive heart failure is the leading cause of death in patients with malignant carcinoid syndrome. The congestive manifestations, secondary to involvement of the tricuspid and pulmonary valves by the tumor, are occasionally unresponsive even to intensive medical treatment. Since the growth rate of carcinoid tumors is usually slow, surgical correction of the causes of heart failure in such patients may be justified as a palliative procedure, thus alleviating progressive disability.
v2
2018-04-03T01:35:08.878Z
1974-01-01T00:00:00.000Z
30025921
s2ag/train
Cutaneous sebaceous neoplasms Ninety‐five patients, each having a single cutaneous sebaceous neoplasm, were selected for study. Lesions of the eyelids were excluded. The tumors were classified as sebaceous adenomas (46), basal cell carcinomas with sebaceous differentiation (43), and sebaceous carcinomas (6). Morphological criteria for separation into these categories are discussed and illustrated. Lesions considered transitional between the classes were observed. Recurrence was unusual, occurring in only three sebaceous adenomas, three basal cell carcinomas with sebaceous differentiation, and one sebaceous carcinoma. Only one tumor, a sebaceous carcinoma, showed aggressive local growth. None metastasized. This behavior contrasts with the frequently observed metastases and death associated with sebaceous carcinoma arising in eyelids, caruncle, or orbit.
v2
2018-04-03T02:02:10.439Z
1974-01-01T00:00:00.000Z
20463742
s2ag/train
Neoplastic diseases of the haematopoietic and lymphoid tissues. Systemic lymphosarcomas are common in all species of domestic mammal. A binomial classification of these tumours, based on both the anatomical form (i.e., distribution of lesions) and the type of cytology, is proposed. Mast cell tumours also are common, especially in the dog. The categories of lymphoid neoplasms described are: lymphosarcoma, lymphoid leukaemia, nodular lymphoid hyperplasia, tumours of the immunoglobulin-forming cells, and thymoma. The myeloid neoplasms described are: myeloid leukaemia, erythroleukaemia, acute erythraemia, polycythaemia vera, megakaryocytoid leukaemia, panmyelosis, myelosclerosis, and monocytoid leukaemia. Mast cell tumours are divided into mastocytoma and malignant mastocytosis.
v2
2018-04-03T02:05:39.445Z
1974-01-01T00:00:00.000Z
46790525
s2ag/train
Cell kinetic studies in patients with lung cancer. Widespread application of intralesional tritiated thymidine injection to obtain cell kinetic data in lung cancer is described. Thymidine-labeling indices were obtained in 28 patients with lung cancer, and the data analyzed by histologic cell types. The mean and median labeling indices were highest in small-cell carcinoma of the lung. Mean values were significantly higher in the small-cell and in the large-cell undifferentiated carcinoma groups than in the adenocarcinoma and epidermoid carcinoma. On the other hand, a labeled mitosis curve in a patient with small-cell carcinoma yielded a duration of DNA synthesis of 18.8 h; not unlike those obtained for other solid tumors. According to our concepts of tumor growth, these findings suggest that the fraction of proliferating cells may be significantly higher in the small-cell and large-cell undifferentiated carcinomas than in the more differentiated cell types of bronchogenic cancer. Knowledge of the growth fraction of these cancers may have implications in directing therapeutic approaches and in interpreting features of the natural history of the disease.
v2
2018-04-03T02:28:06.761Z
1974-01-01T00:00:00.000Z
33791444
s2ag/train
Surgery for Peptic Ulcer INDICATIONS FOR SURGERY Persistent disabling symptoms failing to respond to medical treatment is the commonest indication for operation, but it is often difficult to make an objective assessment in the individual patient. Gastric ulcer is more dangerous to temporize with than duodenal ulcer, because of the difficulty in excluding malignancy. Duodenal ulcers almost invariably continue to recur when symptoms have been present for five or more years, and the decision to operate, in the absence of complications, rests on the surgeon's ability to determine the degree of disability which the patient suffers from. Recurrent severe symptoms interfering with work are the usual criteria for recommending surgery. If complications such as haemorrhage, or vomiting suggestive of pyloric stenosis occur, the need for surgery is more pressing. Perforation is an absolute indication for operation.
v2
2018-04-03T02:38:06.899Z
1974-01-01T00:00:00.000Z
20024979
s2ag/train
(32P)phosphoryl transfer by endogenous protein kinase at the Ehrlich cell surface into extrinsic acceptor proteins. The presence of protein kinase(s) at the outer surface of Ehrlich mouse ascites tumour cells has been established. Endogenous protein of the cell surface as well as extrinsic proteins such as phosvitin and histone can act as acceptors for the (γ32P)-phosphoryl group of ATP. Phosvitin is much more effective as acceptor protein than either the endogeneous protein or the histone protein. The transfer of phosphoryl groups into the phosvitin molecule by the membrane-associated protein kinase is not further stimulated by cyclic AMP. The preferential transfer into phosvitin, rather than into histone, is discussed.
v2
2018-04-03T03:45:03.789Z
1974-01-01T00:00:00.000Z
36387779
s2ag/train
Complete regression of metastatic tumors of the adult with antimitotic treatment We have presented 7 patients in whom metastatic carcinoma regressed by chemotherapy alone. They are well without evidence of disease for 5 to 10 years. The patients include 4 embryonal carcinoma of the testis, 1 uterine chorioepithelioma, 1 prostatic sarcoma, and 1 trabeculo‐follicular epithelioma of the thyroid. They received 1 or more courses of chemotherapy (trenimon or nitromin alone, or triple association actinomycin D, methotrexate, and cytoxan). We cannot explain why these are apparently cured and why others, treated with the same drugs, had no regression at all. No immunological studies were done.
v2
2018-04-03T03:54:58.225Z
1974-01-01T00:00:00.000Z
37021420
s2ag/train
Tumours and dysplasias of the mammary gland. As mammary tumours occur frequently in the dog and cat but rarely in other domestic animals, only the tumours of these two species are classified. The epithelial tumours are termed "complex" when they consist of cells resembling both secretory and myoepithelial cells: these tumours are biologically less malignant than tumours of the "simple" type in which only one of these kinds of cell is present. The carcinomas are subdivided into adenocarcinoma, solid carcinoma, spindle cell carcinoma, anaplastic carcinoma, squamous cell carcinoma, and mucinous carcinoma. The term "carcinosarcoma or malignant mixed tumour" was used only when there were cells morphologically resembling not only one or both of the epithelial components but also connective tissue cells with their products of differentiation. The benign tumours are classed as adenoma, papilloma, fibroadenoma, or benign soft tissue tumour. The dysplasias are described under the following headings: cyst, adenosis, regular typical epithelial proliferation in ducts and lobules (epitheliosis), duct ectasia, fibrosclerosis, and lobular hyperplasia.
v2
2018-04-03T04:18:50.151Z
1974-01-01T00:00:00.000Z
38516449
s2ag/train
Persistence and expression of the herpes simplex virus type 2 genome in cervical tumor cells. Summary Findings providing information on the persistence and expression of the herpesvirus type 2 (HSV-2) genome in cervical tumor cells are presented and the results are discussed in terms of the virus-host cell interaction. Ex foliated but not biopsied tumor cells from patients with cervical carcinoma contain HSV-2 antigens, and HSV-2-specific surface antigens are observed in a small propor tion of one cervical tumor culture. A herpesvirus isolated from degenerated but not viable cervical tumor cells grown in vitro is identified as a type 2, different from a standard variant used in our laboratory, and 90% of patients with cervical carcinoma have antibody to HSV-2-induced tumor-specific antigen. The data suggest that cervical tumor cells harbor the viral genome in a partially repressed state characterized by the expression of only some viral functions. Under conditions of stress, complete expression of the viral genome may occur, resulting in the formation of viral components and/or infectious virus. Alternative interpreta tions are discussed.
v2
2018-04-03T04:23:53.498Z
1974-01-01T00:00:00.000Z
38907199
s2ag/train
IgA as a blocking factor in human malignant melanoma. Immunoglobulin A (IgA), isolated from the serum of patients with malignant melanoma, was found capable of abrogating the cytotoxic effect of sensitized lymphocytes on human melanoma target cells in vitro. IgG and IgM from melanoma serum, as well as IgA, IgG, and IgM from normal serum, did not have this ability. Blocking activity could be removed from melanoma serum or IgA fractions by absorption with melanoma tumor cells or antihuman IgA antiserum.
v2
2018-04-03T04:52:36.405Z
1974-01-01T00:00:00.000Z
40757307
s2ag/train
The transitory nature of a transmissible entity controlling the growth of a spontaneous tumor in mice Two hundred and sixty‐three control mice of the C3 H/ST inbreds bearing spontaneous tumors of mammary gland origin have been studied in reference to the injection of a specially prepared liver extract into one or more of their ancestors. Of these, 24 mice were from the original inbred strain in which no liver extract had ever been injected. Two hundred and thirty‐nine mice were among the descendants of a mouse that had received an intraperitoneal injection of a liver emulsion. These 239 mice were spread over 15 generations of lineal descent. All mice (263) of this experiment were kept as “controls” when their spontaneous tumors arose. The evidence obtained with the analysis of the growth rate of these tumors indicated the activity of a “transmissible entity” which increased in potency in suppressing these cancerous growths. The new evidence, obtained after six generations of lineal descent separation from the original injection of the liver extract, demonstrated quite convincingly that the amount of tumor inhibition became erratic and finally disappeared. The value of growth rate of tumors in mice of the 15th generation returned to the original rate obtained in mice of the 0 class in which there had been no treatment with liver extract in their ancestry.
v2
2018-04-03T05:31:39.666Z
1974-01-01T00:00:00.000Z
43168581
s2ag/train
Adriamycin chemotherapy—efficacy, safety, and pharmacologic basis of an intermittent single high‐dosage schedule A study designed to correlate clinical and pharmacologic observations was undertaken in 96 patients treated with adriamycin. The basic dosage schedule was 60 mg/m2 I.V. q 3 weeks. Pharmacokinetic studies showed a prolonged plasma half‐life, low urinary excretion, and undetectable levels in CSF. Patients with significantly impaired liver function had marked elevation and prolongation of plasma drug levels associated with severe toxicity unless dosage was reduced by 50‐75%. Of the 82 evaluable patients, 10/25 with sarcomas, 9/31 with carcinomas, and 15/26 with hematologic malignancies have achieved complete or partial remission. An additional 22/48 have improved. Six patients with solid tumors had progressive CNS disease while responding systemically. Adriamycin can be used with relative safety and high efficacy in a dosage schedule that resulted from pharmacologic studies. Dosage reduction in patients with liver disease is essential to avoid life‐threatening toxicity.
v2
2018-04-03T05:51:57.558Z
1974-01-01T00:00:00.000Z
44850001
s2ag/train
The carcinogen standard of the new Occupational Safety and Health Act. OA N May 3, 1973, the Department of Labor published in the Federal Register an Emergency Temporary Standard on Certain Carcinogens. Many of us with practical experience in this field wondered who had written this document. Obviously, whoever had written it had not had much practical experience in industry or much knowledge of carcinogens. The standard defined a carcinogen as any one of I4 diverse chemical compounds; there was no further attempt to define a carcinogen. By fiat, carcinogens were those 14 compounds-nothing else, presumably, was a carcinogen! This, obviously, is unacceptable. Second, the standard excluded regulation of compositions containing less than I% by weight of the listed carcinogens. This also is wrong. Anyone experienced in carcinogenesis knows that in animal experiments conducted with most of these 14 compounds they were administered in concentrations much smaller than i%, yet tumors were produced easily. It is immediately apparent that the 14 chemicals represent a mishmash of unsound and unscientific thinking. Some of the products cause cancer of the bladder, others cause cancer of the liver, still others cause cancer of the lung, some cause cancer of multiple sites, and some probably do not cause cancer at all! One compound, beta-naphthylamine, is no longer produced anywhere in the United States. Beta-naphthylamine is a proved bladder carcinogen both for animals and man; therefore its manufacture and use should be controlled carefully. However, since it is no longer made in this country, its use could be controlled by controlling imports.
v2
2018-04-03T05:52:22.102Z
1974-01-01T00:00:00.000Z
5507860
s2ag/train
Male breast cancer. 42 cases of male breast cancer were studied. The disease is diagnosed in males at a later stage than in females. The prognosis of this disease in males is more favorable than in females: in stage I there is an 83% 5-year survival, while in stage II there is 62% 5-year survival. Male breast cancer shows a high hormone dependency: 80% of patients are improved following orchiectomy and 64% following stilbestrol therapy. Data is reported regarding age, family status, community origin, histology, treatment and survival.
v2
2018-04-03T06:04:16.659Z
1974-01-01T00:00:00.000Z
45495801
s2ag/train
Adenocarcinomas of stomach, pancreas, liver, and biliary tracts. Survival of 328 patients treated with fluoropyrimidine therapy A series of 328 patients with advanced cancers of the stomach, pancreas, liver, and biliary tract were treated with intensive fluoropyrimidine therapy, including 5‐FU, 5‐FUDR, intra‐arterial infusions of 5‐FU, and 5‐FU plus radiotherapy. Survival patterns were analyzed with particular emphasis on survival over 1 year after treatment was begun. Patients with stomach cancer had median survivals of 5–7 1/2 months; over‐all survival of more than a year was seen in 22%. Radiation therapy plus 5‐FU was associated with slightly longer survival, as was prior resection of the primary tumor. Patients with pancreatic cancer survived four months median, with 12.5% surviving longer than 1 year. Survial was most dependent on extent of disease at the onset of therapy. Hepatobiliary cancer continued to present a very bleak prognosis. However, excellent responses occurred in 3/31 patients with liver cell or bile duct carcinoma. Intra‐arterial infusions for liver involvement in these patients appeared to contribute little benefit to over‐all survival, although dramatic responses were observed in two patients with primary liver tumors. It would appear that fluoropyrimidine therapy may modestly increase over‐all survival in advanced stomach cancer. Survival in pancreatic cancer does not seem to be favorably influenced by this therapy.
v2
2018-04-03T06:11:49.381Z
1974-01-01T00:00:00.000Z
45926134
s2ag/train
The Definition of Erythrocyte Osmotic Fragility in Normal and Abnormal Blood Summary The osmotic fragility of blood can be numerically defined by measuring the change in osmolarity (Δ mOsm) required to hemolyze 50% of the erythrocyte population when hemolysis is proceeding at the highest rate. In normal blood Δ mOsm = 11.8 ± 1.1 mOsm. In all blood dyscrasias which were studied this osmotic fragility index was significantly different from normal. It was abnormal in the bearers of sickle cell or thalassemia trait. It was also abnormal in Hodgkin's disease and in cancer patients.
v2
2018-04-03T06:12:56.386Z
1974-01-01T00:00:00.000Z
45871590
s2ag/train
Cutaneous responses to irritants and microbial antigens in lepromatous leprosy. Human steroid 5α-reductases (SRD5As) are membrane-embedded NADPH-dependent steroid and lipid reductases with diverse physiological and pathological roles Among them, SRD5A2 is a critical enzyme in steroid metabolism that catalyzes testosterone to dihydrotestosterone Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer Finasteride and dutasteride as SRD5A2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia and androgenic alopecia, which have recently been indicated in the treatment of COVID-19 The molecular mechanisms underlying enzyme catalysis and inhibition had remained elusive for SRD5A2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information We recently solved a crystal structure of human SRD5A2 at 2 8 Å with finasteride using the lipid mesophase (or LCP) crystallization method The structure reveals a unique structural topology of 7-transmembrane helices and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride, which binds in a largely enclosed binding cavity inside the membrane To our knowledge, similar NADPH adducts have not been reported previously Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the semi-irreversible finasteride inhibition involving residues E57 and Y91 of SRD5A2 Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region of SRD5A2 including three cytosolic loops regulating the NADPH/NADP+ exchange and their entry into the transmembrane region of SRD5A2 Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects In summary, our results offer critical and unprecedented structural insights into the function of integral membrane steroid reductases and will facilitate drug development
v2
2018-04-03T02:43:07.491Z
1974-01-05T00:00:00.000Z
34699316
s2ag/train
Editorial: Babies' blood pressure raised by eye drops. It is now over a year since Sir Keith Joseph announced' that pilot oncology centres would be set up in the Manchester, South West Metropolitan, Leeds, and Wessex regions. These units were to spearhead a new approach to the problem of cancer-a concept that came originally from a D.H.S.S. committee headed by Sir David Smithers, which had strongly urged the advantages that would come from redeployment and reinforcement of effort in clinical cancer management. Further support came from Lord Zuckerman,2 whose report to the Prime Minister on cancer research stated that these new centres would act as focal points for the treatment of rarer cancers, they would foster interdisciplinary co-operative effort in cancer management and research at both specialized and district hospital level, ensure that "the best available care becomes generally more available," and promote better understanding ofthe nature of cancer. The Government's announcements clearly implied that training would be provided and a career structure developed for those engaged in cancer research. The centres were given a very wide range, including all aspects of patient care, statistics, clinical trials, public and professional education, and the build-up of appropriate research programmes. Indeed at first sight it looked as if any project with relevance to cancer could form part of the oncology programme, and the immense potential ofthe N.H.S. clinical services could, at least in theory, be recruited to help achieve the goal. In the past year detailed plans have been submitted to the D.H.S.S. and considerable enthusiasm for the scheme has been generated. Already in some regions projects have been launched as part of the new oncology enterprise. What is now bedevilling the whole venture is that there has been no indication of the scale of the operation. Those engaged in planning for the regions are aware that success must depend on the generous voluntary help of clinicians-any form of coercion or direction might stifle the enterprise at the outset. Consequently doctors concerned with getting this help have had to adopt politicians' tactics, holding out promises of a brighter future and neatly side-stepping the question of the amount of money likely to be available. Indeed the sums of revenue money received so far do not even match up to the funds provided by charity for cancer research in these four regions. As details of the various proposals begin to be worked out it has become apparent that realistic schemes require the interplay of service and research within the N.H.S. and universities as well as integration with the cancer research charities and the Medical Research Council. So far, however, the Department does not appear to have set up its own co-ordinating machinery-and those working in the regions are finding that D.H.S.S. officials seem to be thoroughly confused, approaching each item piecemeal with little flexibility. Perhaps the Secretary of State would be well advised to appoint a co-ordinator who can appreciate the whole concept and help the scheme through its administrative difficulties. Furthermore, the sooner the D.H.S.S. makes a clear-cut policy statement saying what it intends to support, the sooner planners can stop wasting their time on schemes that are doomed from the outset. It is absurd to suppose that Sir Keith Joseph gave the goahead without being well informed of the projected capital and revenue budgets likely to be required by the oncology centres. If the centres are to function as pace-setters for the country more beds and laboratories will be needed, as existing facilities already carry a heavy burden. The staff-patient ratios, particularly in the provinces, are low compared with those in centres doing high-quality work elsewhere in the world. Lord Zuckerman suggested that cancer research suffered more from a lack of talent than from lack ofmoney. Nevertheless, it would be unrealistic to imagine that talented doctors and scientists will be attracted to work in cancer management or in research units until the problems of finance and career prospects have been resolved.
v2
2017-04-16T08:15:35.240Z
1974-02-01T00:00:00.000Z
5271499
s2ag/train
The surface antigenicity of serially transplantable malignant human lymphoid cells derived from subjects with infectious mononucleosis, Hodgkin's disease, chronic lymphatic leukemia, or acute lymphoblastic leukemia. Human lymphoid cells can be maintained as serially transplantable malignant tumors in rabbit anti-hamster thymocyte serum-immunosuppressed neonatal Syrian hamsters, and these tumors can be assigned to either of two categories on the basis of their biological behavior in serial transplantation. Some (Category A) have exhibited the manifestations of acute leukemia but cannot be demonstrated to synthesize immunoglobulins; these have been isolated solely from children with active acute lymphoblastic leukemia secondary to lymphosarcoma. The remainder (Category B) have been isolated from a wide diversity of malignant and nonmalignant states and, in the hamster, these secrete immunoglobulin and provide no convincing evidence of their capacity to progress to acute leukemia. It can be demonstrated, by the techniques of quantitative absorption and indirect immunofluorescence, that the Category B cell surface is characterized by the presence of common antigen(s) which is probably not surface immunoglobulin and which is restricted at or absent from the cell surface of the Category A acute lymphoblastic leukemia cells and from that of normal peripheral blood leukocytes as well. Some of the implications of these findings for the study of cell populations in the lymphoproliferative disorders are discussed.
v2
2017-06-16T21:31:03.513Z
1974-02-01T00:00:00.000Z
7071372
s2ag/train
An assessment of serum acid and alkaline phosphatase determinations in prostatic cancer with a clinical validation of an acid phosphatase assay utilizing adenosine 3′ -monophosphate as substrate Serum acid phosphatase (AcPase) was measured by a colorimetric method utilizing adenosine 3′ -monophosphate as substrate in 389 patients. In about half the cases blood was taken shortly after a rectal examination. The upper reference limit (mean + 2SD) for 116 cases with miscellaneous illness after eliminating outliers was 4·1 International Units per litre (U/I) at 37°C, and no correlation existed between AcPase activity and age in these subjects (r = 0·040). Eight of 18 patients with untreated carcinoma confined within the prostate gland had AcPase activities below 4·1 U/l, and all of 27 cases with extension to pelvic soft tissues or to bone exceeded this value. AcPase activities above 4·1 U/l were found in 6% of cases with benign hypertrophy of the prostate, in 5% of cases with non-prostatic cancer, and in none of 22 cases with other urological illness. Raised serum alkaline phosphatase (APase) activity was found in 60% of patients with untreated prostatic cancer and in only 6% of patients free of prostatic cancer, in most of whom there was a clinical explanation for the elevation. The correlation between the two phosphatase activities was not significant (r = 0·294). While APase activity does not reflect the stage of the disease as closely as AcPase activity, and is not so frequently elevated, it provided useful confirmation of the diagnosis in five patients of the present series whose AcPase levels were normal or only minimally elevated.
v2
2018-04-03T00:50:21.606Z
1974-02-01T00:00:00.000Z
26914898
s2ag/train
Kaposi sarcoma in kidney transplant recipients. A growing experience with tumors of lymphoreticular origin in patients immunosuppressed to prolong homograft survival has been reported by Penn et al.1,2In their most recent report,3these authors have collected data on 17 such tumors reported from various centers, including their own. The predominant lymphoreticular malignant tumor was reticulum cell sarcoma, which accounted for 12 of the 17 cases, with a seeming predilection for an intracerebral situation. Three cases of Kaposi sarcoma are included in this group, of which two are from our practice. The third case was of the visceral variety, and the case records have been recounted in detail by Siegal et al.4This article describes in detail the natural history of our two Kaposi sarcoma patients following intensive immunosuppressive therapy after renal transplantation. Patient Summaries Patient 1. —A 36-year-old woman had been found to have proteinuria in 1955 during an investigation for
v2
2018-04-03T01:08:23.318Z
1974-02-01T00:00:00.000Z
28246467
s2ag/train
Further investigation of the increased transfer ribonucleic acid methylase activity in tumours of the mouse colon. 1. Extracts prepared from tumours of the mouse colon induced by 1,2-dimethylhydrazine were considerably more active in catalysing the methylation of tRNA than were extracts from normal colon. The enhanced activity was observed when both unfractionated ;methyl-deficient' tRNA and purified tRNA preparations from yeast and bacteria were used as substrates for methylation. 2. The methylated bases produced in these reactions were identified. There were no differences between the products of the reaction catalysed by extracts of tumour and normal colon. 3. The increased activity of tRNA methylases was not due to the presence in the extracts of stimulatory or inhibitory molecules of low molecular weight such as polyamines or S-adenosylhomocysteine. 4. Other enzymes concerned with tRNA metabolism (RNA polymerase, ATP-tRNA adenylyltransferase, aminoacyl-tRNA ligases) were also increased in activity in the tumour tissue. 5. The extent of methylation of a limiting amount of tRNA was greater when tumour extracts were compared with controls, but in no case was it possible to achieve a stoicheiometric methylation of the purified tRNA preparations used as substrates, and the tumour extracts were not able to methylate tRNA obtained from normal mouse colon. We conclude that the tumours contained greater activities of tRNA methylases but that there was no evidence for changes in the specificity of these enzymes during neoplastic growth.
v2
2018-04-03T02:31:29.442Z
1974-02-01T00:00:00.000Z
22718226
s2ag/train
Brain tumors induced in rats by human adenovirus type 12. Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33) in SpragueDawley and 56% (14/25) in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.
v2
2018-04-03T02:35:12.270Z
1974-02-01T00:00:00.000Z
34192250
s2ag/train
The selective effect of heat in cancer. Heat (42 degrees C) exerted an inhibitory effect on the oxygen uptake of the rabbit VX2 carcinoma in vitro and led to a decrease in viability and growth potential of the cells as measured by vital dye uptake and their ability to produce tumours on injection into a host. Normal host tissue cells were unaffected by elevated temperatures. After heating in vivo, tumours showed an 80-95% reduction in volume, with marked necrosis of the tumour cells. Later, macrophage invasion and replacement fibrosis were evident. There was a 50% survival rate in animals treated by local heating and a 30% survival rate in those treated by total body heating, while all the control rabbits died at 10 weeks. The selective inhibitory effect of heat on cancer cells and its application to human neoplasms are discussed.
v2
2018-04-03T02:36:04.197Z
1974-02-01T00:00:00.000Z
34166477
s2ag/train
A clinicopathologic study of atypical lesions of the breast Following the detection of non‐infiltrating cancer, there have been more extensive microscopic studies for various atypical lesions of the breast. At Memorial Hospital, 296 patients with these lesions were seen during the period 1960 to 1972. These lesions were found more often in middle aged women than is the case in average cancer patients, commonly seen in nulliparous women, in patients in whom breast cancer was found in the opposite breast, and in patients with a history of breast cancer in the family. The clinical and mammographic findings are quite similar to those in non‐infiltrating cancer. Occasionally, these lesions are quite difficult to distinguish from minimal breast cancer by histologic examination. In this study, the cumulative risk of breast cancer was approximately 4‐5% at 30 months and 9% at 48 months.
v2
2018-04-03T04:05:58.327Z
1974-02-01T00:00:00.000Z
394058
s2ag/train
Mycetoma formation in Trichophyton rubrum infection An adult male patient with a chronic Trichophyton rubrum infection of the feet, toe nails and groin, for 15 years, developed on the dorsum of the right foot a tumour with draining sinuses. Histological examination of tissue from the growth revealed granulomatous inflammation with abscesses containing granules characteristic of mycetoma. T. rubrum was cultured from skin scrapings and toe nails. The concurrent complete clearing of the superficial lesions and the mycetoma during treatment with griseofulvin, as well as the disappearance of complement fixing antibodies against T. rubrum antigen, indicate that this hitherto unreported complication of a dermatophyte infection may be related and may not be coincidental to the infection.
v2
2018-04-03T04:08:45.094Z
1974-02-01T00:00:00.000Z
37928891
s2ag/train
Structure of the Mouse Mammary Tumor Virus: Polypeptides and Glycoproteins The polypeptide and glycoprotein compositions of the mouse mammary tumor virus virion from primary monolayer cultures of BALB/cfC3H mouse mammary tumor cells were studied by polyacrylamide gel electrophoresis by using internal and external labeling and Coomassie blue and periodic acid Schiff (PAS) staining. Twelve polypeptides were reproducibly resolved by the combined methods. Five major polypeptides were demonstrable with estimated molecular weights of 52,000, 36,000, 28,000, 14,000, and 10,000. Seven minor polypeptides were also consistently detected and had estimated molecular weights of 70,000, 60,000, 46,000, 38,000, 30,000, 22,000, and 17,000. Carbohydrate was associated with five of these polypeptides as measured by PAS stain or [3H] glucosamine labeling, or both. These glycoproteins had estimated molecular weights of 70,000, 60,000, 52,000, 36,000 and 10,000. The majority of the PAS stain and glucosamine was found in the 52,000 and 36,000 dalton peaks.
v2
2018-04-03T04:51:36.382Z
1974-02-01T00:00:00.000Z
40643521
s2ag/train
Oral involvement in neuroblastoma. Inasmuch as oral metastases were found in a substantial number of patients with neuroblastoma, the dentist should consider this condition in the differential diagnosis of jaw lesions. Eighty-three patients with neuroblastoma were examined retrospectively to determine the frequency with which this malignancy affects the osseous structures of the oral cavity. These structures were involved in 21 (25%) of all patients and in 21 (49%) of the 43 with bone metastases as judged from clinical, radiologic, and pathologic findings. Evidence of oral involvement led to diagnosis in two instances and was discovered during the initial evaluation in ten of the 21 patients with facial manifestations. The most common clinical signs were facial or intraoral, swellings or both, loose or displaced teeth, and paresthesia. The most important radiologic findings were lytic lesions, expansion of the dental follicle, and poorly defined borders around the crypts of developing teeth. This study indicates that oral involvement in neuroblastoma is much more common than was previously thought, and that clinical and radiologic evidence of jaw metastasis may be of value in early diagnosis.
v2
2018-04-03T05:50:30.483Z
1974-02-01T00:00:00.000Z
44735139
s2ag/train
Massive osteolysis. Report of a case. 1. A case of massive osteolysis of the bones and soft tissues of the left foot is reported. 2. Arteriography revealed slowed circulation in the foot, hut the tumour vessels did not fill with contrast medium. 3. Two years after below-knee amputation of the left leg and four years after the onset of symptoms, the patient appeared to be free from disease.
v2
2019-08-16T22:28:44.044Z
1974-02-01T00:00:00.000Z
200098214
s2ag/train
Book Review: Thomson's Concise Medical Dictionary Cancer of the Uterine Cervix edited by Eric C Easson pp viii+ 158 illustrated £4 London &c.: WB Saunders 1973 In this book we follow the development in Manchester since 1932 of a team approach within that community which covers every aspect of the disease from prevention to terminal care. Throughout there is evident an attitude of optimism towards treatment of the disease based on the local results. A team approach is stressed. Manchester techniques are explained and the results evaluated by statistical analysis of controlled trials. The authors express the view that routine cytological screening should not start later than age 25 years and discuss the reasons for poor acceptance of the test among high-risk groups. Their views on the reliability of sampling and the excellence of their recall and follow-up systems must be admired. Their views on the modifications which should be made to treatment after cone biopsy, amputation and repair operations are clearly expressed, whilst their comments on the present applicability of afterloading techniques, and the future possibility of using fast neutrons will be read with interest. The volume is excellently produced and can usefully be read by all who have to deal with patients at risk, whether family physicians, hospital doctors or experts in community medicine.
v2
2018-04-03T05:44:36.633Z
1974-02-23T00:00:00.000Z
43917495
s2ag/train
Subungual Malignant Melanoma: Difficulty in Diagnosis Subungual malignant melanoma developed on both great toes of a 61-year-old woman. The lesions had been diagnosed elsewhere as ingrowing toenails and had been treated as such for two years. The difficulty in clinical diagnosis is illustrated by the description of three other patients with subungual malignant melanoma. The tumour should be considered as a possible cause of any persistent abnormality of the nail bed or the nail itself, especially if it is pigmented.
v2
2014-10-01T00:00:00.000Z
1974-03-01T00:00:00.000Z
10637884
s2orc/train
The incidence of malignant tumours in patients with respiratory sarcoidosis. During the period 1962-71 a total of 2544 patients with respiratory sarcoidosis were reported to the Danish Institute of Clinical Epidemiology. Among them 48 patients developed a malignant tumour, the follow-up period ending on 31 December 1971. Only 33·8 cases of cancer were expected if sarcoidosis patients had had the same rates as the general population; the difference between the expected and observed number is statistically significant (0·02 > P > 0·01). Malignant lymphomata occurred 11 times and lung cancer 3 times more frequently than expected. For all other forms of cancer taken together, there was no significant difference between the expected and the observed number of cases. The increased cancer incidence may result from immunological deficiencies in patients with sarcoidosis. difference between the expected and the observed number of cases. The increased cancer incidence may result from immunological deficiencies in patients with sarcoidosis. ACCORDING to the theories of immunological surveillance in the human body, an intact immune apparatus is one of the conditions necessary to prevent or limit the development of malignant tumours. Thus a certain number of congenital, idiopathic or iatrogenic disturbances of the immune apparatus are known to be associated with an increased incidence of cancer, particularly of malignant lymphomata (Keast, 1970;Doll and Kinlen, 1970). Since various immunological disturbances usually accompany sarcoidosis (Chase, 1966), it might be reasoned that this disease could be associated with an increased incidence of malignant tumours, but studies of the incidence of malignancies in large series of sarcoidosis patients have apparently not been published. Case histories which show an association between sarcoidosis and malignant lymphomata or lung cancer have been reviewed by Brincker (1972) and Sakula (1963). These studies did not allow estimation of the frequency of the association of sarcoidosis with a malignancy. However, in Brincker's study (1972) 5 cases of true sarcoidosis were found in about 1500 cases of malignant lymphoma. This rate is very high in view of the fact that sarcoidosis occurs with an incidence of 5 per 100,000 in the general population (Horwitz, 1967;Horwitz, Payne and Wilbek, 1967). It seems remarkable that sarcoidosis has been diagnosed before malignant disease in all recorded instances of this association. The above observations suggest the possibility of an increased incidence of malignancies in patients with sarcoidosis. The present study was undertaken in order to test this hypothesis. MATERIALS AND METHODS Background.-Since 1962 all new cases of respiratory sarcoidosis diagnosed in Danish chest clinics have been reported to a central registry in The Danish Institute of Clinical Epidemiology (DICE) (previously the Danish Tuberculosis Index). This material repre-sents most cases of sarcoidosis diagnosed in Denmark, but a certain reporting deficit exists as some patients are diagnosed and treated in hospital departments other than the chest clinics and hence are not reported to the central register. The true size of this deficit is unknown but spot checks indicate a figure between 17 and 31 per cent (Alsbirk, 1964;R0mer et al., 1973). The unreported cases probably represent more severe symptomatic forms of the disease. Clinical and epidemiological data of the sarcoidosis patients reported to DICE have been described in detail elsewhere . The sex ratio was 1: 1, the median age 32 years. Half of the patients had only involvement of the hilar lymph nodes; the other half had a pulmonary lesion with or without hilar involvement. Since 1943 all new cases of malignant tumours diagnosed in Denmark should have been reported to the Danish Cancer Registry. The percentage of deaths being recorded from death certificates only had dropped to 8 in 1959, but there is no reporting deficit for cancer deaths since all death certificates are matched against the files of the Cancer Registry. There is no reason to believe that the reporting deficit is greater than 8 per cent in non-fatal disease. Since the latter patients represent only 25-30 per cent of the total cases, the combined reporting deficit for all cancer cases presumably does not exceed 2-2-4 per cent. The activities of the Danish Cancer Registry have been described in detail elsewhere (Clemmesen, 1965). During the decade 1962-71, 2561 newly diagnosed cases of respiratory sarcoidosis were reported to the central register. In September 1972 all the notifications were matched against the files of the Cancer Registry in order to see which sarcoidosis patients had a record in the Cancer Registry. All cases of cancer which had occurred before 1 January 1972 were registered and from the search through the records it was found that 65 patients had been registered with a malignant disease. In 17 patients the tumour was demonstrated before the diagnosis of sarcoidosis and they were therefore excluded. In the remaining 48 patients the malignancy was diagnosed simultaneously with, or after, sarcoidosis and the present study consists of those patients. The basic population thus consists of 2544 patients (1292 males and 1252 females) with sarcoidosis, who had not had cancer previously. Table I shows the distribution of the 48 cancer cases by diagnosis; none of the patients had more than one malignant disease. The number of men and women was fairly equal (26 and 22 respectively). Apart from cancer of the female reproductive system, lung cancer represents a marked sex difference as 8 of the 9 cases occurred in men. The remainder were 13 cases of urogenital cancer, 8 cases of cancer of the digestive tract, 7 cases of skin cancer, 7 cases of malignancies of lymph nodes and thymus and 4 cases of breast cancer. In order to calculate the expected number of cancer cases, the sarcoidosis patients were broken down by year of report, i.e., those reported in 1962, 1963 etc.; within each of these groups, the patients were split by sex and age. The sex and age specific incidence of cancer in the Danish general population (average for 1963-67) was applied to each of these cells. Although the entire observation period 1962-71 is not covered by the 1963-67 cancer incidence rates, the latter were used for the calculations because they represent the latest available Danish figures (Clemmesen. 1973, personal communication). The expected number depends, of course, on the length of the period at risk. The onset of this period was reckoned from the year that the sarcoidosis was reported in the register, and runs up to 1 January 1972; the period was thus on an average 91 years for those reported in 1962, 81 years for those reported in 1963 and so on, until for those reported in 1971 it was half a year. When the calculations were made, regard was also paid to the factor that the patient's age increased during the period of observation. The expected number of all forms of cancer taken together was calculated but special estimates were made for lung cancer and malignant lymphoma, based on the respective rates for the two diseases. The following formula has been used to calculate the significance levels: No review was made of the case records in order to check the diagnosis of any of the 48 patients who had both sarcoidosis and cancer; a rejection of the diagnosis in one or more of these cases would merely result in a statistically unacceptable alteration in the basis for the calculations. Table II shows that 48 cases of cancer were observed, whereas only 33.8 cases were expected. This difference is statistically significant (0-02 >P > 0 01). The higher incidence is due primarily to an increased number of cases in males, particularly of lung cancer. Nine cases of lung cancer were found but only 2-8 cases were expected; this difference is highly significant (P < 0 001). Six cases of malignant lymphoma occurred whereas only 0 5 cases were expected; this difference is also highly significant (P < 0 001). With regard to all other forms of cancer, there is no significant difference between the expected and the observed number of cases (30.5 cases vs 33). Table III shows that the expected number of cancer cases goes down with lapse of time. This results from the fact that only the patients reported in 1962 had up to 10 years follow-up; those reported in 1962 + 1963 had 9 years follow-up; those reported in 1962 + 1963 + 1964 had 8 years follow-up etc. In other words, the number of patients at risk is high for short intervals and decreases the longer the interval becomes. The expected incidence goes up gradually because the patients' age increases during the observation period; hence the risk of cancer also increases. It is striking that the observed cancer incidence is very high during the first 4 follow-up years; thereafter it drops to the normal level or per- haps a little lower. In other words, an excess morbidity exists only in the first 4 years after sarcoidosis was diagnosed. During this period, 38 cases of cancer were observed whereas only 21-2 cases were expected; the difference is highly significant (P < 0-001). DISCUSSION The diagnosis of respiratory sarcoidosis is beset with some uncertainty. A positive Kveim reaction is confirmative but the test is used only to a limited extent in Denmark. A number of other diseases which present similar roentgenological findings may therefore be confused with sarcoidosis and be reported. As a consequence one might expect that some cases of lung cancer and malignant lymphomata would be reported to DICE under a diagnosis of sarcoidosis. When the true nature of the disease became evident, then the case would be reported to the Cancer Registry. Conversely, true cases of sarcoidosis may be reported to the Cancer Registry as, say, lung cancer or malignant lymphomata. However, this possibility is considerably less likely to occur because most cases of cancer are verified histologically, whereas only about half of the sarcoidosis cases are verified by this means. Thus, the problem is whether the 9 cases of lung cancer and the 6 cases of malignant lymphomata represent genuine associations of sarcoidosis and cancer, or whether these cases or some of them represent a mistaken diagnosis of one or both diseases. The likelihood of a genuine association is greater the longer the interval between the time of diagnosis of sarcoidosis and the time of diagnosis of cancer. In 4 of the 9 cases of lung cancer more than one year passed; in 4 of the 6 cases of malignant lymphomata more than 2 years passed between the two diagnoses. These 8 cases probably represent true associations. In 4 of the 5 patients where lung cancer was diagnosed during the first year after the diagnosis of sarcoidosis, biopsies are available showing both noncaseating epithelioid cell granulomata and tumour tissue. Similarly, in one of the 2 patients in whom malignant lymphoma was diagnosed within the first year after sarcoidosis, a biopsy also containing noncaseating epithelioid cell granulomata exists. On the basis of these data (the time intervals and the biopsy findings), at least 8 of the 9 cases of lung cancer and 5 of the 6 cases of malignant lymphomata appear to represent genuine associations of sarcoidosis and cancer. Still, it must be borne in mind that sarcoid reactions may be seen in lymph nodes from patients with lung cancer (Sakula, 1963) or malignant lymphomata (Brincker, 1972); this reaction should not be considered as sarcoidosis disease. If we assume that patients with respira-tory sarcoidosis really have an increased frequency of lung cancer and malignant lymphomata, it is natural to ask why this is so. As regards lung cancer, the chronic pulmonary changes caused by sarcoidosis may act as an additional carcinogenic stimulus; it may also be that these changes lead to a decreased resistance to other carcinogenic stimuli. The increased incidence of malignant lymphomata may result from the immunological defects often noted in sarcoidosis patients; this is in line with the increased incidence of malignant lymphomata in patients who have immunological defects (Keast, 1970;Doll and Kinlen, 1970). Some of the sarcoidosis patients were treated with corticosteroids but since details of the treatment are not known in the central register, it cannot be determined what influence the steroid therapy may have had on the cancer incidence. Since the present study is based on information from matching between two central registries, the question may be posed whether or not the incidence of malignant tumours in the sarcoidosis patients is too low because of a reporting deficit. As mentioned previously, the reporting deficit concerning the malignant disease is negligible and plays no role. As regards sarcoidosis, the moderate reporting deficit might at first sight seem of no importance since the basis of the study is those cases which were in fact reported. However, the most severe cases of sarcoidosis are probably not reported to DICE as they are treated only in the medical departments. The present series is therefore likely to be dominated by the findings in mild, non-symptomatic cases. Such patients may have higher immunity and therefore also a lower cancer risk, if the incidence of malignant tumours is proportional to the degree of the immunological defect, and hence also the severity of the sarcoidosis. As the mild cases constitute about half of the present series, this might explain why the increased incidence of cancer was confined to lung cancer and malignant lymphomata. This hypothesis is supported by the fact that patients with symptomatic sarcoidosis had an observed cancer incidence which was 1-5 times higher than expected; among the non-symptomatic cases the ratio was only 1*2 times higher (see Table II). Thus, this fact also supports the assumption and previously quoted data indicating that a genuine association exists between cancer and sarcoidosis. We are indebted to Johannes Clemmesen and his staff at the Danish Cancer Registry for tracing the 2561 patients with sarcoidosis in the files of the Cancer Registry. Johannes Clemmesen also kindly placed at our disposal unpublished Danish cancer incidence figures for the years 1963-67. This study has been supported by a grant from the Danish Anti-Cancer League.
v2
2017-04-14T10:24:35.153Z
1974-03-01T00:00:00.000Z
16629526
s2ag/train
Lack of syncytium formation by a type C virus-producing XC cell line in the mixed culture cytopathogenicity test. XC cells, derived from a Rous sarcoma virus-induced Wistar strain rat tumor, form syncytia when cultured in the presence of murine leukemia virus-producing mouse cells. However, one XC cell culture (designated as XC-v cells), found to produce type C virus particles, fails to form syncytia in the presence of murine leukemia virus-producing mouse cells. Coculture of XC-v cells and XC cells negative for type C virus particles leads to a moderate degree of syncytium formation. Infection of XC cells with either the Moloney (M) strain of mouse leukemia virus or type C virus particles released by XC-v cells results in the loss of ability of XC cells to form syncytia in the mixed culture cytopathogenicity test. The syncytium-forming ability of XC cells, therefore, is altered by the presence of a type C virus in these cells.
v2
2018-04-03T00:05:47.114Z
1974-03-01T00:00:00.000Z
8572475
s2ag/train
CANCER CACHEXIA AND GLUCONEOGENESIS Cachexia has long been recognized as a leading cause of death in cancer.’ Though this condition has been thought by some to be the result of a progressively inadequate dietary intake, it is obviously not so simple; many patients present initially with significant weight loss as their first and only symptom in the face of a completely adequate dietary intake. This suggests a specific mechanism apparently peculiar to the cancerous condition by which weight loss and body debilitation can proceed. Such a thermodynamic mechanism for the production of cancer cachexia has been described by this author.2 It was shown that in cancer patients significant and progressive energy loss from host (i.e., noncancerous) tissues could occur by virtue of the establishment of a systemic energy-losing cycle dependent on an interplay of tumor glycolysis and host gluconeogenesis.
v2
2018-04-03T01:23:03.491Z
1974-03-01T00:00:00.000Z
29258401
s2ag/train
In vitro immune stimulation-inhibition to spontaneous canine tumors of various histologic types. Utilizing dogs with progressively growing tumors we are reporting on the in vitro reactivity of their lymph node or peripheral blood lymphocytes to their own tumor cells. Tumors, lymph nodes, and blood were collected aseptically during surgical treatment or before necropsy. Primary cultures were set up and shortly thereafter only viable glass-adhering tumor cells were utilized. The cells were first incubated with either media or various sera and then varying numbers of sensitized lymphocytes were added. The mixtures were incubated for 90 min in rotating test tubes and then plated into culture dishes or plates. Two and/or 5 days later, the cultures were fixed, stained, and viable target cells were counted. In vitro tumor cell destruction by high numbers of lymphocytes from dogs bearing tumors and the blocking of such reactivity by autologous serum were demonstrated. Serum from dogs with the same histologic type of neoplasm inhibited allogenic lymphocyte cytotoxicity, whereas serum from dogs with a different tumor, normal dogs, and a dog who had been clinically free of osteosarcoma after limb amputation 17 months earlier, did not significantly block the cellular-mediated reactivity. Stimulation of tumor growth in vitro by low ratios of sensitized lymphocytes to tumor cells was demonstrable. Autologous serum from dogs with progressively growing neoplasms appeared to potentiate the stimulation of tumor growth above a simple blocking of lymphocytic-mediated cytotoxicity. These results confirm our earlier reports of immune stimulation to tumor growth in vitro and support the hypothesis and work by Prehn that the early immune response to neoplasia might directly stimulate rather than inhibit tumor growth.
v2
2018-04-03T01:59:28.952Z
1974-03-01T00:00:00.000Z
31733781
s2ag/train
RELATION OF CELL‐MEDIATED IMMUNITY IN WOMEN WITH GENITAL TRACT CANCER TO ORIGIN, HISTOLOGY, CLINICAL STAGE AND SUBSEQUENT BEHAVIOUR OF NEOPLASM A quantitative study of cell‐mediated immunological reactivity was made in patients with female genital tract cancer. Prinary reactivity was measured by contact sensitization to dinitrochlorobenzene (DNCB) and secondary reactivity by delayed cutaneous hypersensitivity to skin test antigens (STA). In general, there was an increased incidence of anergic and impaired reactivity in patients with cancer of the cervix, corpus uteri or ovary, compared with age‐matched controls; however, differences between patient‐groups, regarding organ or origin or histological type, were small and insignificant. There was a progressive increase in incidence of anergic and impaired reactivity with worsening of clinical staging of the tumour. Significant differences in reactivity were noted between patients who had remained free of disease and those who had progressive disease after 12 months of follow‐up. It is considered that impairment of cell‐mediated immunity is an unfavourable factor in host‐tumour interactions, and the possibility of augmenting immunological reactivity should be considered in management.
v2
2018-04-03T02:32:17.509Z
1974-03-01T00:00:00.000Z
34040685
s2ag/train
Mediastinal parathyroid carcinoma detected on routine chest films. Carcinoma of the parathyroid gland is rare. The incidence ranges from less than 1 percent to 4 percent in patients with primary hyperparathyroidism. 6 , 9 In the majority of cases, the tumor arises from one of the lower two parathyroid glands in the neck. Parathyroid carcinoma originating in the mediastinum is believed to be very rare. The patient reported had pathologically advanced, but clinically silent, hyperparathyroidism caused by an ectopic parathyroid carcinoma located in the superior mediastinum.
v2
2018-04-03T04:47:09.515Z
1974-03-01T00:00:00.000Z
40376082
s2ag/train
Lipid‐rich carcinoma of the breast. A clinicopathologic analysis of 13 examples A critical review of over 900 mammary carcinomas treated at St. Louis University Hospitals disclosed 13 that fulfilled the histologic picture of lipid‐rich carcinoma. All clinical and pathologic data were tabulated; 1 case was studied by electron microscopy. Five of the patients were dead within 2 years, and 2 others had evidence of metastatic tumor within 2 years. One patient died 6 years after treatment. On the basis of the following characteristics we believe lipid‐rich carcinomas should be regarded as a specific type of mammary carcinoma: 1. The presence of non‐degenerative lipid material within the cytoplasm of tumor cells; 2. The presence of intramitochondrial crystals; 3. The pattern of metastatic involvement of lymph nodes and the orbit; 4. The presence of intraductal and lobular carcinoma in situ associated with this type of tumor; and 5. The more aggressive clinical behavior.
v2
2018-04-03T05:32:52.747Z
1974-03-01T00:00:00.000Z
43206745
s2ag/train
Studies on egg excretion and tissue egg burden in urinary schistosomiasis. Abstract Three 24-hour urinary egg excretion determinations were done on 25 patients with urinary schistosomiasis who were to undergo elective cystectomy. Tissue egg burdens were determined on the cystectomy specimens. There was no relationship between mean daily egg excretion and tissue egg burden in all cases. However, when cases were classed as “active,” (histologic evidence of active oviposition) and inactive, the mean daily egg excretion (EE) was dependent upon tissue egg burden. This relationship may be expressed as: EE = a + k (the number of eggs/urinary bladder), where a (a constant) and k (the regression coefficient) vary with the activity of the disease. The effect of malignant tumors upon egg excretion appears to vary with the activity of the disease also. It is suggested that egg excretion as an estimator of tissue egg burden or intensity of infection should not be interpreted without consideration of the stage or activity of the disease. Moreover, further studies to more closely define the regressions of egg excretion upon egg burden in the various stages of urinary schistosomiasis may permit accurate estimation of egg burden (and consequently severity of disease) in individuals and communities.
v2
2018-04-03T06:16:17.191Z
1974-03-01T00:00:00.000Z
46091437
s2ag/train
Proceedings: Testosterone potentiated radiophosphorus therapy of osseous metastases in prostatic cancer. Testosterone potentiated radiophosphorus therapy remains a most effective form of treatment for patients with widespread, painful, osseous metastases from prostatic adenocarcinoma.Including our series in a total population of 174 patients, 86 per cent of the courses administered were effective in promptly relieving pain to a significant degree.This is not the treatment of choice when soft tissue metastases are the predominant feature, and extensive vertebral involvement with incipient cord compression should be approached cautiously if testosterone potentiation is to be employed.Depression of hematopoietic elements may occur, but is usually minimal, unless multiple courses are given; then, thrombocytopenia is the most serious sequela.This treatment combination deserves a prominent place in our therapeutic armamentarium for patients with diffuse prostatic carcinoma.
v2
2018-04-03T03:52:49.237Z
1974-03-09T00:00:00.000Z
36886647
s2ag/train
Editorial: Coping with nose-bleeds. from the one launched by the B.U.P.A. for both private and health service patients in 1972. They should also be distinguished from the long-established contributory schemes like that of the Hospital Saving Association which in addition to cash payments to a contributor, or a spouse, in hospital makes grants towards spectacles and false teeth, for a stay in a convalescent home, for mental illness, for maternity (whether delivery takes place at home or in hospital), and for some of the cost of being ill at home. Other than the promoters three sets of people are potentially affected by the cash-in-hospital schemes-the patientbeneficiaries, their doctors, and hospital staffs and administrators. The benefits for patients are largely illusory. At £3 or £5 a night they go nowhere near paying for the cost of private treatment in hospital; nor, since they cease on a patient's discharge, do they compensate him for loss of earnings during illness, the length of which is unlikely to coincide with the length of a hospital stay. For these reasons hospital cash insurance was given short shrift' in Money Which? last year. Now the schemes have been criticised on actuarial grounds by C. E. B. Frost and Audrey W. M. Ward of the Department of Community Medicine of the University of Sheffield.2 Using the hospital inpatient inquiry for 1970, the mental health inquiry, and the Registrar-General's review to determine the risk of being admitted to hospital in the population as a whole, these authors calculated that all six commercial schemes analysed showed a considerable surplus of premiums received over benefit liabilities on subscribers aged under 35 on entry. Most of them showed a surplus on older subscribers too. The surplus tended to fall with an increase in age, but the authors commented that this cross-subsidisation among agegroups was reduced by practices that discriminated against the elderly. For instance, two schemes excluded people admitted to geriatric wards, all disallowed pre-existing illnesses until at least a year had elapsed, and all but two set a limit, in cash or time, to the total benefit payable. The benefit liabilities ofthe schemes were further reduced by the exclusion of mental illness as a cause for admission to hospital (another discrimination against the elderly), along with alcoholism, addiction, acts of war, and usually pregnancy and childbirth. Elderly people admitted to hospital do not usually have the financial responsibilities of a man ofworking age, and any cash payments for which they do manage to become eligible will not be compensating them for loss of earnings but will be additions to their pensions. As Frost and Ward shrewdly point out, for pensioners the schemes "cannot be considered as providing insurance against a quantifiable loss but rather as a means of gambling for the elderly." The B.M.A. has taken a deliberate decision3 4not to sponsor or support hospital cash insurance schemes (one of which had offered special terms to the Association's members). The decision was taken in the knowledge that in the U.S.A. patients had put pressure on doctors to admit them to hospital, or to prolong their stay, so that they could derive maximum benefit from their policies. Frost and Ward point out a possible pitfall for the doctor in addition to this unwelcome pressure. If a scheme offers additional benefits to someone admitted to hospital because of cancer, as at least one does, is the doctor legally obliged to tell him of his condition so that he can claim his extra cash? It is sometimes argued that doctors are too reluctant to tell patients the truth about their illnesses; but it would be unfortunate if they were constrained to do so against their judgement in a particular case because of hospital cash insurance. Lastly, there are the implications ofthis insurance for health service administration. The aim is a quick turnover of patients, with a reduced length of stay and an increasing number of conditions treated by day surgery; indeed, the "best buy" hospitals at Bury St. Edmunds and Frimley were planned on the basis that they would provide intensive hospital treatment backed up by full community care. There is a clear conflict between this policy and insurance schemes that pay benefits only for nights in hospital. Such a conflict does not yet appear to have become overt, perhaps because most subscribers are in the age-groups unlikely to be admitted to hospital and perhaps because in any case the schemes are not proving very popular. The non-profit-making B.U.P.A. scheme claims just under 10,000 subscribers. The commercial schemes, being competitive, are not so frank, but it would be surprising if between them they could claim 100,000, despite their aggressive advertising. By comparison, contributors to the standard plan of the Hospital Saving Association number 800,000 and to its Crown plan 50,000.
v2
2018-04-03T03:50:34.134Z
1974-03-15T00:00:00.000Z
36719652
s2ag/train
The importance of dose and proliferation of sv40‐transformed cells with different oncogenic potentials to the level of tumor immunity The immunizing effects of syngeneic SV40‐transformed mouse embryo cells derived from a cloned line, ME1 C9, were studied. The number of initially inoculated cells was of decisive importance for immunization when both irradiated and non‐irradiated (proliferative) cells were used. The 50% immunizing dose (ImD50) of highly oncogenic ME1 C9‐V15 cells against a weak challenge 3 weeks after immunization was found to be 104.1 irradiated or 102.7 non‐irradiated cells. Doses just below the ImD50 suppressed immunity; 104 irradiated cells had a tumor‐enhancing effect 3 weeks after but not 10 weeks after inoculation and 102 non‐irradiated cells did not significantly immunize until 6 weeks after inoculation, in spite of growing tumors. An immune state was reached more rapidly after resection of tumors induced by 102 cells, even when resections were performed at a time when the animals were still non‐immune. The immune suppression induced by a low dose of non‐irradiated (proliferating) cells seemed to be perpetuated and 10 weeks after inoculation there was still an immune deficit in comparison with the state of immunity in animals which had had their tumors resected. A second inoculation of a regularly non‐immunizing dose of 101‐102 cells 3 weeks after inoculation of 102 ME1 C9‐V15 cells enhanced the tumor incidence of the first inoculated cells. After inoculation of 105 irradiated or non‐irradiated ME1 C9‐V15 cells a one thousand‐fold increase in tumor resistance was obtained within 3 weeks. Before reaching a size of 12 mm the tumor mass did not affect the level of immunity in animals inoculated with ME1 C9‐V15 cells. Tumor resections 3 weeks after inoculation of 105 cells preserved the otherwise declining immunity. The ImD50s of weakly oncogenic (TPD50 > 105) and highly oncogenic (TPD50 < 104) non‐irradiated cells in irradiated animals against a weak challenge 10 weeks after immunization were 102.6 and 101.5 cells, respectively, measured in tumor‐free animals. Immunization doses of 101‐102 weakly oncogenic cells, i.e. below the ImD50, enhanced challenge tumor takes. Non‐tumor‐bearing animals inoculated with weakly oncogenic cells were less immune than non‐tumor‐bearing animals inoculated with highly oncogenic cells, when animals inoculated with equal numbers of cells or animals inoculated with greater than immunizing doses were compared. Animals with tumors induced by weakly oncogenic cells were less immune than animals with tumors of comparable size induced by highly oncogenic cells. The critical tumor size at which immunity against 105 ME1 C9‐V15 cells was broken was 11–12 mm for highly oncogenic and less than 4 mm for weakly oncogenic cells.
v2
2017-04-13T17:37:51.590Z
1974-04-01T00:00:00.000Z
7372569
s2ag/train
Selective cell survival and changes of marker properties during cryopreservation for up to 16 years. Cell features that may favor resistance to cryoinjury were investigated. Subpopulations of all tissue bank deposits tested (5 human cell lines and 19 mouse tumors) survived up to 16 years of storage at -78°. The replicating capacity of trypan blue-excluding cells after prolonged cryopreservation was estimated by comparing the number of unstained cells needed to produce <100% lethal takes with control values determined prior to freezing. Frozen-thawed bank deposits were reestablished in serial transplantation or in vitro , without obvious change in virulence or growth rate. Methotrexate tolerance in a drug-selected tissue culture of mouse Sarcoma 180 persisted at its prefreeze resistance level. Host strain specificity, an index of H -antigen stability, was lessened after freezing in only one of five different ascites lymphomas examined. The 6C3HED lymphoma, formerly restricted to growth in the C3H mouse of origin, continued to regress in three foreign strains but produced a few long-delayed lethal takes in three other strains with relatively low allograft resistance. In one case, this was accompanied by polyploidization. While modal chromosome numbers generally remained quite stable, the frequencies of characteristic marker chromosomes were altered in two of three murine carcinoma clones and in two lymphomas. These immunological and cytological changes observed in some old bank deposits were not yet evident during the initial 4 years of storage at -78°. Two polyploid sublines derived by endoreduplication and immunoselection prior to freezing from the near-diploid ELD carcinoma and 6C3HED lymphoma, as well as four heteroploid clones isolated by transplantation of single cells from the near-tetraploid Ehrlich-KL and Krebs 2 carcinomas, all showed significantly better long-term cryotolerance than the corresponding source tumors. Most neoplasms may be safely stored at -78° for 4 to 5 years without differential cell mortality and consequent shifts in nuclear and physiological properties.
v2
2017-06-19T18:50:16.410Z
1974-04-01T00:00:00.000Z
469571
s2ag/train
Changes in composition of mucin in the mucosa adjacent to carcinoma of the colon as compared with the normal: A biochemical investigation Fifteen surgical specimens from patients with carcinoma of the colon and rectum were studied. Scrapings from normal mucosa distant from the tumour and from macroscopically normal mucosa adjacent to the tumour (`transitional') were used for chemical estimation of hexosamines, sialic acid, and proteins. The presence of hexosamines and sialic acid was confirmed in both normal and transitional mucosa. Transitional mucosa showed increased levels of total hexosamines and sialic acid as compared with the normal and this was accompanied by an increase in neuraminidase-sensitive sialic acids. The present data have been compared with previous histochemical and autoradiographic studies and it is suggested that the changes described in the transitional mucosa are transformations representing an early stage of carcinogenesis.
v2
2017-10-01T06:38:01.765Z
1974-04-01T00:00:00.000Z
8255723
s2ag/train
Rectal biopsy and precancer in ulcerative colitis Forty-seven patients with ulcerative colitis subjected to elective proctocolectomy were investigated with regard to the occurrence of precancerous changes in the rectal biopsy and the operation specimen. In the rectal biopsy from seven patients precancerous lesions were found and in the operation specimens from these patients precancer was also found in other parts of the colon. In five of these patients the precancer was associated with carcinoma and in four of the patients the tumour had not been detected before operation. It is concluded that rectal biopsy is of great value in patients with ulcerative colitis for detection of early cancer and patients at risk of developing a colitis carcinoma.
v2
2018-04-03T00:16:28.056Z
1974-04-01T00:00:00.000Z
10647084
s2ag/train
Clear-cell carcinoma of the liver. A clinicopathologic study of 13 patients. From a 25-year period (1947 through 1971), records of 150 patients with primary carcinoma of the liver, treated at the Memorial Sloan-Kettering Cancer Center, were reviewed. Histologic examination of the primary lesions from these patients yielded 13 cases (8.7%) in which the tumors were characterized by large numbers of vacuolated “clear” cells. Historically, these lesions have on occasion been confused with heterotopic or metastatic renal–adrenal neoplasms. More recendy, these clear-cell variants of hepatocellular carcinoma have been recognized, and a relatively favorable clinical behavior has been attributed to them. Our present findings suggest that the prognosis of clear-cell carcinoma of the liver is similar to that of hepatocellular carcinoma in general.
v2
2018-04-03T03:19:04.897Z
1974-04-01T00:00:00.000Z
2155273
s2ag/train
Scintiscanning of pulmonary diseases with 67Ga-citrate. Scintiscanning with /sup 67/Ga-citrate was performed in 162 patients with various pulmonary diseases. Of the 70 cases of primary pulmonary carcinoma, 62 had a strongly positive and 7 a slightly positive scan and all 18 cases of metastatic pulmonary carcinoma had a positive scan, including a carcinoma of 1 to 2 cm in diam. According to the histopathological findings, the positive rate for squamous cell carcinoma and undifferentiated carcinoma tended to be higher than that for adenocarcinoma. By indicating the presence of infiltration of lymphatic metastasis in the mediastinum for which the roentgenologic diagnosis is difficult or a tumor which overlaps the heart shadow or is hidden in a large hydrothorax, / sup 67/Ga-citrate scanning has contributed valuable information on which to base a decision for operating or choice of surgical method and the establishment of the range of radiotherapy. Otherwise inflammatory lesions (pneumonia, purulent pulmonary infection, pulmonary tuberculosts, etc.) and sarcoidosis had more clearly positive scans in the acute stage than did carcinoma. (auth)
v2
2018-04-03T04:10:51.138Z
1974-04-01T00:00:00.000Z
38047852
s2ag/train
False-negative 75Se-selenomethionine scans in primary liver cancer. Selenium-75-selenomethionine and /sup 99m/Tc-sulfur colloid scans were performed in 45 Southern African blacks with proven primary cancer of the liver and 28 patients with other space-occupying hepatic lesions. In six of the cancer patients, the defect or defects visible on the /sup 99m/Tc-sulfur colloid scan were not seen on the /sup 75/Se-selenomethionine scan, and in 17 patients they had partially disappeared. In the remaining 22 cancer patients and the 28 control patients the two scans were identical. The high incidence of failure of uptake of /sup 75/Se-selenomethionine by the tumor is attributed to the anaplastic nature of the neoplasm and the frequency with which tumor necrosis occurs in Southern African blacks with primary cancer of the liver. (auth)
v2
2018-04-03T04:30:08.045Z
1974-04-01T00:00:00.000Z
39272301
s2ag/train
Prolactin receptors in mammary carcinoma cells. Three types of experimental mammary carcinomas, the 7,12-dimethylbenzanthracene-induced and R3230AC carcinomas in the rat and the C3HBA carcinoma of the mouse, were assayed for prolactin receptor activity. The prolactin-125I-binding activities of particles derived from the 7,12-dimethylbenzanthracene-induced and R3230AC carcinomas exhibited the properties of high affinity ( Kd = 7.1 × 10-9 and 6.0 × 10-9 m, respectively), low capacity, saturability at levels for physiological saturation, and hormonal specificity. However, two other hormones, placental lactogen and growth hormone, exhibited significant competitive displacement of bound prolactin-125I in proportion to their known lactogenic activities. The specific prolactin-125I-binding activities of these carcinoma cells were found to reside in the plasma membrane and were inactivated by treatment with trypsin or by heating. These properties of the prolactin-125I-binding activities of these carcinomas are identical to those of the prolactin receptor of the mammary alveolar cells of rats and mice. Quantitative assays of receptor activities in these carcinomas revealed three individual patterns. The 7,12-dimethylbenzanthracene-induced carcinoma, which is known to be characteristically dependent upon prolactin for growth, exhibited a range of specific activities which varied between 30 and 80% of the lactational mammary gland. The R3230AC carcinoma, which has been shown to be prolactin responsive for milk protein synthesis but not for growth, had a tissue concentration of prolactin receptor activity that was approximately 15% of that of lactational mammary gland. The C3HBA carcinoma, a relatively autonomous tumor, had no detectable prolactin receptor activity. The results provide evidence for the existence of prolactin receptors in certain mammary carcinoma cells and suggest that the degree of prolactin dependence of such carcinomas may be characterized by the relative numbers of prolactin receptors present.
v2
2018-04-03T05:28:04.035Z
1974-04-01T00:00:00.000Z
42939095
s2ag/train
Tumor sterilization with preoperative radiation in laryngeal cancer. If there were a method of predicting which larynges have been cured by radiotherapy, unnecessary surgery and loss of function might be avoided. In a large series of patients with advanced cancer of the larynx treated by high-dose preoperative radiotherapy, the apparent sterilization of the primary tumor and metastatic lymph nodes was studied. The results are compared with results from other large series. The present study indicates that at least 40% of patients would avoid laryngectomy. Further, clinical response following radiotherapy gives an excellent indication of which patients would be cured by radiotherapy. The delay of surgery in those cases that developed recurrence did not result in a high complication rate. This policy—radiotherapy with surgery for salvage of recurrences—has achieved a control rate comparable to that achieved by high-dose preoperative radiotherapy and surgery.
v2
2018-04-03T03:36:32.664Z
1974-04-15T00:00:00.000Z
7486215
s2ag/train
Rat α1F. XI. Immunological control of cell proliferation: Increased growth rate and α1F production by morris hepatoma 5123tc in rats treated with anti‐thymocyte serum The administration of anti‐thymocyte serum (ATS) to rats bearing transplantable Morris hepatoma 5123tc resulted in an increase in the growth rate of the tumor and in the rate of alpha1fetoprotein (α1F) production by the tumor. ATS‐treated rats not only had faster growing tumors and correspondingly higher serum α1F concentrations than untreated 5123tc tumor‐bearing rats, but also the amount of α1F per gram of tumor tissue was significantly greater. In addition, the mitotic index of tumors in ATS‐treated animals was twice that of the tumors in control animals. The results indicate that the rate of α1Fa production by hepatomas that have the capacity to synthetize α1Fa is directly related to the number of proliferating cells present at any given time. In addition, this report clearly demonstrates that the rate of growth of a tumor is not a fixed property of the tumor but may be accelerated by immunosuppression of the tumor‐bearing animal.
v2
2017-06-05T21:21:13.140Z
1974-05-01T00:00:00.000Z
20418184
s2ag/train
Immunological reactions to tumor-associated antigens in Burkitts lymphoma and other lymphomas. Summary Evidence for immune response to Burkitt9s tumor and other lymphomas is reviewed. The common tumorassociated antigens detected in some assays and the natural reactivity to some of these antigens are analogous to the findings in virus-induced tumors in experimental animals. Delayed hypersensitivity reactions to autologous tumor extracts were observed in Burkitt9s lymphoma, in Hodgkin9s disease, and in other lymphomas. Patients with leukemia and lymphoma, but not carcinomas, also reacted with extracts of tumor-derived lymphoid cell lines. Studies of in vitro cell-mediated cytotoxicity against autologous tumor cells, using the 51Cr release assay, also gave evidence for reactivity against tumor-associated antigens. In humoral and cell-mediated cytotoxicity assays against lymphoid tissue culture cells, widespread natural reactivity was found. The nature of the antigens detected in these assays is discussed, particularly the possible relationship to Epstein-Barr virus. Delayed skin reactivity to the extracts of lymphoid cell lines was found to correlate with elevated Epstein-Barr virus antibody titers.
v2
2017-06-22T19:49:10.400Z
1974-05-01T00:00:00.000Z
34946134
s2ag/train
Essential fatty acid deficiency in patients with lesions of the gastrointestinal tract The relative amounts of unsaturated fatty acids in the serum lipids of 14 patients who have undergone small bowel resection have been investigated. These results are compared with those from control subjects and also from patients suffering from cancer of the oesophagus. Both groups of patients showed patterns of unsaturated fatty acids suggesting essential fatty acid deficiency. In the resection patients there was no correlation between the extent of intestinal removal and the extent of the change in the unsaturated fatty acid pattern.
v2
2018-04-03T00:22:49.293Z
1974-05-01T00:00:00.000Z
11300518
s2ag/train
A maximum-likelihood method for estimating the disease predisposition of heterozygotes. There are many ways to analyze genetic predisposition to common diseases such as cancer or diabetes. In most instances clinical disease results from the interaction of several factors, and it is difficult to isolate the effect of any single diseasepredisposing gene. There are exceptions: rather uncommon single-gene syndromes clearly associated with a striking prevalence of cancer or diabetes in individuals who have the syndrome [1; 2, pp. 151-194]. One approach to detecting the disease-predisposing effect of single genes which are important in the general population is based on the hypothesis that a gene which produces a small increment in specific disease risk in the heterozygote may be associated with a recognizable syndrome in homozygotes [3, 4, 5]. There are several hundred known human autosomal recessive syndromes [6], and for most of them little is known of the disease tendencies of heterozygous carriers. Estimates of gene frequency suggest that for each of these recessive syndromes the heterozygote frequency is likely to be between .001 and .04. For any gene with a heterozygote frequency in this range, it is important to know whether the carriers of that gene are predisposed to any specific serious common disease. If we are interested in diabetes, for example, it seems sensible to examine the heterozygous carriers of genes causing recessive syndromes associated with carbohydrate intolerance [2, pp. 151194]. It is unlikely that any single gene of this category produces an overwhelming tendency to diabetes in heterozygotes-that would have been noticed on casual inspection of pedigrees. A less obvious effect may still be important if diabetes is determined polygenically [2, pp. 151-194]: genes identified in homozygotes by the recessive syndromes they cause may comprise, in heterozygotes, a substantial proportion of the polygenic system.
v2
2018-04-03T00:44:50.498Z
1974-05-01T00:00:00.000Z
26579674
s2ag/train
Letter: "High-dose" metronidazole: a preliminary pharmacological study prior to its investigational use in clinical radiotherapy trials. Chemicals which selectively radiosensitize hypoxic mammalian cells have been considered as adjuvants in the radiotherapy of human tumours (Adams, 1973). The screening of various nitroheterocyclic drugs indicated numerous structures which are active as sensitizers in mammalian cells in vitro (Chapman, Reuvers and Borsa, 1973). The discovery that some drugs with current clinical usage were excellent radiosensitizers of hypoxic mammalian cells (Reuvers, Chapman and Borsa, 1972; Chapman et al., 1972), generated some optimism as regards an early clinical trial. A successful application of such drugs in the radiotherapy of human tumours would depend upon favourable pharmacological properties. In the selection of metronidazole for this study, radiosensitizing effectiveness at low drug concentration was sacrificed in favour of acceptable pharmacological properties.
v2
2018-04-03T01:02:39.781Z
1974-05-01T00:00:00.000Z
27845198
s2ag/train
Intra‐arterial chemotherapy: making it safer and more successful Few nursing procedures carry greater responsibility than intra-arterial chemotherapy. For one thing, it's apt to be the end of the treatment line for cancer patients —their last hope of survival. So it creates a group of psychological reactions for you to deal with. For another thing, it can have potentially lethal complications. You have to know, for example, how to prevent clotting … what side effects to look for and how to deal with them … how to guard against infection.? This photographic guide, demonstrating intra-arterial injections for tumors of the head and neck, will give you the skills you need to make chemotherapy safer. And a lot less frightening for your patients. Photographs by Norwin Synnestvedt
v2
2018-04-03T01:23:40.015Z
1974-05-01T00:00:00.000Z
29103165
s2ag/train
A co-operative international study of gastric cancer (under the auspices of the International Federation of Surgical Colleges). In a co-operative prospective study of gastric cancer information relating to the aetiology, presentation, symptomatology, diagnosis, and treatment of the disease was collected from a total of go9 patients admitted to 7 centres in. different parts of Europe during the 3year period I966-68. The findings in the various centres were similar in almost all respects. Analysis of the data provided a uniformly depressing picture of a high frequency of advanced disease at the time of presentation, with correspondingly low resectability rates, high postoperative mortality, and short survival after resection. The best hope for improvement in the results of treatment of gastric cancer would appear to lie in the achievement of earlier dzagnosis, particularly by the wider adoption of fibreoptic gastroscopy in the routine investigation of dyspeptic symptoms and in screening for asymptomatic disease.
v2
2018-04-03T02:10:25.932Z
1974-05-01T00:00:00.000Z
20002355
s2ag/train
COLLOIDAL IRON USED AT pH'S LOWER THAN 1 AS ELECTRON STAIN FOR SURFACE PROTEINS The effects of hydrochloric acid on stability, charge and selective affinity of the colloidal ferric hydroxide were studied. The charge was tested electrophoretically. The stability was controlled by measuring the turbidity. The affinity was determined by applying colloid to gelled agarose sections containing hyaluronic acid, polyvinyl sulfate or polylysine. Affinity was also determined by applying the colloid to free tumor cells previously submitted to various types of chemical and enzymatic treatments (esterification, acetylation, periodic acid-hydroxylamine method; neuraminidase, phospholipase C, hyaluronidase) and to isolated rat liver surface membranes pretreated by lipid extraction or incubated with phospholipase C. It was found that the chloride ions at pH's lower than 1 bring about the recharging of the conventional positively charged colloid to a negative form. This negative colloid can be used as a new cytochemical method at the electron microscopic level, to visualize with relative specificity positively ionized groups such as the basic amino groups of protein side chains in the outer and inner hydrophilic leaflets of the cell surface membrane.
v2
2018-04-03T02:13:49.651Z
1974-05-01T00:00:00.000Z
20959658
s2ag/train
Immunotherapy of malignant melanoma with vaccinia virus. Twenty patients with either stage II or III metastatic malignant melanoma were treated with vaccinia virus injections into the tumor nodules. Average survival was 32.2 months for stage II and 4.6 months for stage III. Delayed hypersensitivity skin tests and 2,4-dinitrochlorobenzene sensitization were positive. Indirect immunofluorescence demonstrated humoral antibodies. Cellular cytotoxicity, as demonstrated by the colony inhibition technique, was strongly positive in all patients who made a good response to immunotherapy. Blocking antibodies were not found in the treated group. Vaccinia virus immunotherapy may act by activation of specific immune mechanisms or may reflect a nonspecific, cytotoxic, inflammatory reaction. This study supports the concept that vaccinia virus may activate the production of cell-mediated, cytotoxic immunity against melanoma cells. This cytotoxic immunity has been isolated with transfer factor and given to other patients with metastatic melanoma.
v2
2018-04-03T03:27:24.205Z
1974-05-01T00:00:00.000Z
6296769
s2ag/train
Cell-mediated immunity and specific serum factors in human cancer: the leukocyte adherence inhibition test. Blood leukocytes from patients with cancer (malignant melanoma; adenocarcinoma of colon, rectum, and breast) reacted with aqueous extracts of tumors of the corresponding type, with the result that adherence of the leu kocytes to glass was diminished. Leukocytes from normal individuals did not react. The leukocyte adherence inhibition (LAI) test could be completed in a few hours. Sera from tumor-bearing patients blocked the LAI reaction of their own leukocytes or leukocytes from other patients with the same type of tumor. Serum blocking activity was lost soon after surgical removal of the tumor; the patient’s serum then became unblocking. The LAI technique gave consistent results in a series of patients, analogous to those reported with the lymphocyte cytotoxicity test, and was easier and quicker.
v2
2018-04-03T04:01:38.578Z
1974-05-01T00:00:00.000Z
37430912
s2ag/train
Effect of murine milk samples and human breast tissues on human leukocyte migration indices. Summary A leukocyte migration procedure was used as a measure of cellular hypersensitivity responses of human leukocytes against human breast tissues and mouse milk samples. Leukocytes from adult women with and without benign and malignant breast lesions were tested against cryostat sections of autologous and homologous benign and malignant ( in situ and invasive) breast lesions. Simultaneous tests were made against RIII mouse milk samples that contain murine mammary tumor virus and against virus-free mouse milk samples from RIIIf and C57BL mice. Observations were also made on the response to a common environmental antigen (Varidase). The migration of leukocytes from control women, with and without benign breast lesions, was commonly inhibited by Varidase but was rarely inhibited by any of the mouse milk samples or by any of the benign or malignant breast lesions. The migration of leukocytes from breast cancer patients was commonly inhibited by Varidase but was not inhibited by virus-free mouse milk samples or by benign breast tissues. However, migration inhibition (>25%) was found in 31% of breast cancer patients tested against RIII milk, in 33% of tests against homologous in situ breast cancer, in 29% of tests against autologous invasive breast cancer, and in 16% of tests against homologous invasive breast cancer tissues. Responsiveness to breast cancer tissues was correlated with a high degree of cross-reactivity against RIII mouse milk. Conversely, leukocytes that responded to RIII milk cross-reacted in most of the tests against homologous in situ breast cancer and in approximately one-third of the tests against invasive breast cancer but were nonresponsive to RIIIf milk, C57BL milk, and benign breast lesions. It appears that the antigenicity of human breast cancer tissue is largely a reflection of a component that is similar to that found in murine mammary tumor virus-infected lactating mammary parenchyma. Such antigenicity is more regularly found among in situ breast cancer tissues than among invasive breast cancer tissues.
v2
2018-04-03T04:17:28.718Z
1974-05-01T00:00:00.000Z
38507876
s2ag/train
Melanocytoma of the conjunctiva. A 15-year-old girl was born with a unilateral pigmented lesion of the conjunctiva. The patient has been observed for 11 years, showing very slow but steady progression of the pigmentation. The tumor mass was biopsied and studied with light and electron microscopy. The pigmented portion of the lesion was composed of densely packed normal-appearing subepithelial melanocytes and a nonpigmented nodule consisting of ectopic lacrimal gland tissue.
v2
2019-03-11T13:08:51.169Z
1974-05-01T00:00:00.000Z
73134807
s2ag/train
Practical Clinical Hematology. Interpretations and Techniques literature dealing with those manifestations of the spread of human tumours which are to be observed by clinician and pathologist. It is a curious mixture consisting of catalogues of secondary tumours in various sites, little clinical asides, interesting short scientific essays based on his wide experience and reading, anecdotes, and of course a hobbyhorse or two-mesothelioma, Ewing's sarcoma, and details of all-but-forgotten polemics. With his direct and deceptively effortless style he has produced a work which, though parts of it are recondite, is for the general medical reader and is as readily to be comprehended and enjoyed by medical student and staff nurse as by their seniors. It is interesting, informative, and thought-provoking, but marred by the author's deliberate avoidance of mention and discussion of contemporary interests in tumour behaviour, for example, the modification of tumour spread resulting from treatment, the nature and spread of Hodgkin's disease, Burkitt's lymphoma, the immunological factors in tumour behaviour, and, though the retrogression of several varieties of metastic tumours is listed, thematter is left there without comment. Where he does discuss topics that interest him, he is marvellously lucid and a fine protagonist for his beliefs. Far too much space is taken up with statements of the type 'multiple intestinal deposits but with the liver clear were recorded by Ogle (1856), Godlee (1847), Thompson (1899), Davidson (1909), Goldzicher (1913), di Biassi (1926) ....' or 'Sturt (1900) saw secondary growths in stomach, small intestine, colon, kidneys, adrenals, pancreas, gall bladder, bones, lung and brain but only two small subcapsular nodules in the liver.' What we could do with is drastic pruning of the cataloguing, and expansion of Willis's mature considerations of the wider aspects of tumour spread, in which field he is a savant. The illustrations are excellent and well related to the author's them>. R. L. CARTER
v2
2018-04-03T05:45:26.527Z
1974-05-15T00:00:00.000Z
44284200
s2ag/train
An analysis of variables affecting the measurement of tumor immunity In vitro with 125I‐iododeoxyuridine‐labelled target cells. Studies of immunity to primary moloney sarcomas Variables affecting the measurement of immunity to adherent tumor cells in vitro have been analyzed using the immune response to primary Moloney sarcomas in BALB/c mice as a model system. IUdR, a gamma‐emitting isotope which is incorporated into the DNA of dividing tumor cells, was used to quantitate the number of adherent tumor cells in 0.2 ml cultures. Lymphoid cell‐mediated killing of tumor cells was measured by labelling tumor cells before they were cultured with effector cells (cytotoxicity test), and lymphoid cell‐mediated inhibition of tumor‐cell growth was measured by labelling those tumor cells surviving interactions with effector cells (cytostasis test). Addition of lymphoid cells to adherent tumor cells initiates complex interactions which have non‐specific (i.e., unrelated to recognition of tumor antigens) and specific (i.e., related to recognition of tumor antigens) effects on the survival and growth of tumor cells. The magnitude of these effects, as measured in the cytotoxicity or cytostasis tests, depends upon the number, kind, and state of activation and/or sensitization of effector cells and upon the number and susceptibility of tumor cells. Effector cells from control mice have only non‐specific effects whereas those from MSV‐immunized mice have both non‐specific and specific effects. Lymph‐node cells (LNC) from normal control mice non‐specifically kill IUdR labelled tumor cells in the cytotoxicity test, whereas killing and growth‐promoting influences are both present in the cytostasis test. Non‐specific cytotoxic effects also were mediated by LNC from MSV‐immunized mice, and these effects were of greater magnitude than those mediated by LNC from normal control mice. Our present and previous experiments suggest that non‐specific cytotoxicity of LNC is largely due to macrophages. In contrast, non‐specific promotion of tumor‐cell growth in the cytostasis test is apparently mediated by lymphocytes. Specific cytotoxicity or cytostasis was obtained only when non‐adherent LNC (NALNC) containing 99.8% lymphocytes and less than 0.2% macrophages were employed as effector cells. Although both cytotoxicity and cytostasis tests seem to give similar results, we conclude, for a number of reasons, that the cytotoxicity test is preferable for measuring cell‐mediated immune responses to adherent tumor cells. Our findings and conclusions should be generally applicable to studies of animal and human tumors.
v2
2018-04-03T00:31:03.519Z
1974-05-18T00:00:00.000Z
12440145
s2ag/train
Development of heart valve lesions during methysergide therapy. and a high incidence of uncertain scan findings, to be used as the only method of search for secondary deposits. The greater accuracy of "9mTc polyphosphate makes it more suitable as the principle means of search though in one patient of the 61 investigated with this isotope we were unable to identify metastases which were clinically and radiologically evident. Care also needs to be used in the interpretation of positive results since an isotopic "hot spot" is a non-specific indicator of abnormal metabolic bone activity and can therefore be produced by any metabolically active lesion, such as are seen, for example, in Paget's disease. We do not envisage that polyphosphate scintigraphy will completely replace x-ray examination in the identification of bone metastases, but we do feel that it should be used as the principle "search weapon" both in the initial assessment of the patient with prostatic cancer and in the continuing management of the disease.
v2
2019-03-08T14:08:58.281Z
1974-05-25T00:00:00.000Z
71551530
s2ag/train
Essentials of Cannulation This author writes from the department of physiology, University College, London: this I would consider to be a guarantee of excellent experimental work and unbiased investigations. It is a pity, therefore, for anybody interested in the study of the electrical activity of the braih to find that relevant literature and sound experiments of the past have been disregarded just for the sake of saying that the alpha rhythm is the electrical concomitant of tremor in the extra-ocular muscles. The pioneer work of Hans Berger, Lord Adrian, Grey Walter, Lindsley, and many others is unfairly attacked. Throughout the book there is an extraordinary lack of respect for so many careful observations, made not only by other physiologists, but also by reliable workers who have established the clinicopathological correlations of electroencephalography. Dr. Lippold neglects the well established observations that localized brain lesions, such as an abscess, a haemorrhage, a vascular occlusion, or a tumour, may alter the electrical activity of the brain recordable through the scalp. Moreover, not only the alpha rhythm but also important and well documented normal cerebral phenomena. such as the contingent negative variation, are considered as due to eye movement artefact in spite of careful exclusion of such interpretation by reputable workers. On page 226, Dr. Lippold mentions "the mechanisms underlying the generation of epileptic spike and wave phenomena" and says "perhaps one or the other is due to a fit involving the eye muscles." In his enthusiasm, Lippold forgets that the term epileptic may be applied to a subject suffering from seizures and not to an electrical phenomenon recorded from the brain (let alone the eye muscles!). This sequence of ideas is fairly typical of the confusion between fact and fantasy in this book. The careful studies of Chapman and his co-workers in 1971 demonstrated that a normal alpha rhythm could be recorded from both cerebral hemispheres from a patient who had lost both eyes and from two subjects who had complete exenteration of one eye, including removal of the eyeball, extra-ocular muscle, and periosteum. Lippold explains that what was recorded in these cases was "a wave form resembling alpha rhythm" and that "this does not mean that the origin of the alpha waves is not in the orbit." Even the anatomy is stretched in an attemnpt to demonstrate that the apex of the orbit is "nearly at the centre of the skull," or that "the site of stimulation used by Moruzzi and Magoun (1949) to produce their classical alerting response and desynchronization would seem to be suspiciously near the ocular motor nuclei." Lippold considers that the real importance of his work is towards the "prevention of wasted scientific effort." In this well printed book the conscientious student has an expensive opportunity of verifying from the many references quoted how other people's work has been interpreted.
v2
2017-04-30T14:25:46.338Z
1974-06-01T00:00:00.000Z
33692671
s2ag/train
Mechanism of reaction, tissue distribution, and inhibition of arylhydroxamic acid acyltransferase. The enzyme of rat liver that can transform N -hydroxy- N -2-fluorenylacetamide into a reactive derivative capable of introducing fluorenylamine groups into nucleic acids has been shown to be a sulfhydryl-dependent enzyme with a molecular weight of approximately 28,000. A 30-fold purification of the enzyme from 105,000 × g supernatants of liver has been achieved by precipitation with ammonium sulfate and gel filtration on Sephadex G-100. Evidence that this mechanism of activation involves transfer of the N -acetyl group to the oxygen of the hydroxylamine came from experiments that showed that O -methylation of N -hydroxy- N -2-fluorenylacetamide prevented activation of the hydroxamic acid. Distribution studies demonstrated considerable acyltransferase activity in kidney, stomach, small intestine, and colon; lung and spleen were less active; and blood, brain, and muscle were essentially without activity. Tissue distribution studies and protein purification experiments utilizing ammonium sulfate precipitation and gel filtration techniques disclosed that the enzyme responsible for the activation of N -hydroxy- N -2-fluorenylacetamide was inseparable from the enzyme that transfers the acetyl group of N -hydroxy- N -2-fluorenylacetamide to 4-aminoazobenzene. Acyltransferase-catalyzed activation of N -hydroxy- N -2-fluorenylpropionamide demonstrated that the activation of hydroxamic acids was not restricted to acetylated derivatives. Hepatic acyltransferase-catalyzed formation of fluorenylamine-substituted nucleic acid was inhibited by both arylamines and arylacetamides. This inhibition, considered with previous reports of the inhibition of N -hydroxy- N -2-fluorenylacetamide hepatocarcinogenesis by acetanilide and p -hydroxyacetanilide, suggest that acyltransferase-catalyzed activation of arylhydroxamic acids may be involved in the formation of liver tumors.
v2
2017-07-20T06:24:15.275Z
1974-06-01T00:00:00.000Z
28920926
s2ag/train
The binding of tritium-labeled phorbol esters to the macromolecular constituents of mouse epidermis. Single, promoting dosages of phorbol-12,13-didecanoate-3H were applied to the backs of mice. At all time points studied, the bulk of radioactivity recovered in epidermal preparations was easily extracted by methanol:ether washes. Only low levels of radioactivity remained covalently bound to protein, and negligible amounts remained bound to the nucleic acids. There was no positive correlation between the level of covalent binding to protein and the biological activity of phorbol-12,13-didecanoate-3H, a potent tumor promoter, and phorbol-12,13-dibenzoate-3H, a weak tumor promoter. Noncovalent associations of the labeled promoter were also investigated. Upon fractionation of the mouse epidermal tissue, the largest portion of radioactivity was recovered in the mitochondrial fraction. Phorbol-12,13-didecanoate-3H remained reversibly bound to a high-molecular-weight cytosol protein fraction after gel filtration chromatography.
v2
2017-08-16T06:10:08.289Z
1974-06-01T00:00:00.000Z
2970575
s2ag/train
The effect of autologous serum on lymphocyte response to human leukemia cells. The normal lymphocytes of 11 of 18 patients with acute leukemia in remission showed a positive blastogenic response in vitro to autologous leukemia cells. The effect of autologous serum on this response was studied to determine if there were factors which might abrogate or "block" this response. Serum obtained at diagnosis (i.e., during a tumor-bearing period) was compared with remission serum with the expectation of demonstrating a "blocking" effect of the former and no effect or perhaps even facilitation with the latter. However, this was not the case, and no consistent differences in blastogenesis in the presence of the two sera were seen. In addition, during the period of observation, there was little correlation between the presence or absence of in vitro response to autologous tumor and prognosis.
v2
2018-04-03T00:26:36.084Z
1974-06-01T00:00:00.000Z
11787716
s2ag/train
Immunochemical Characterization of Two Major Polypeptides from Murine Mammary Tumor Virus A major murine mammary tumor viral (MMTV) antigen, sl, originally described by Nowinski et al. (1967, 1968, 1971), has been purified from RIII mouse milk MMTV by sequential ion-exchange and gel chromatography. The purified protein with sl antigenic reactivity contains carbohydrate, and has an apparent minimal molecular weight of 52,000. It can be designated as gp52 (sl). Another major MMTV viral protein with a molecular weight of 27,000 has also been isolated, and antisera have been prepared against it. Both MMTV gp52 (sl) and p27 viral polypeptides have been iodinated with 125I and used in immunoprecipitation and competition assays. The two MMTV proteins differ absolutely from each other and from major mouse type C viral polypeptides in molecular weight, immunological reactivity, and amino acid composition. Purified gp52 (sl) in radioimmunoprecipitation inhibition assays reacted in two distinct patterns. One pattern showed partial displacement of antibody which could be converted to the second, a complete displacement, by heating the antigen, presumably by exposing additional reactive determinants. Biologically, the patterns of major MMTV polypeptide expression in milk correlated with spontaneous mammary tumor incidence in different strains of mice, indicating that the sl antigen is group specific for MMTV or that several mouse strains contain the same virus type.
v2
2018-04-03T00:28:14.683Z
1974-06-01T00:00:00.000Z
12193956
s2ag/train
Uptake of tritiated methotrexate by mouse brain tumors after intravenous or intrathecal administration. ✓ Malignant gliomas were induced in strain ddN mice by intracerebral implantation of a 20-methylcholanthrene pellet. The uptake and distribution of tritiated methotrexate (MTX-3H) in the tumor were investigated by radioactive assay and radioautography after single intravenous or intrathecal injections. By either route, a large amount of MTX-3H was taken up by gliomas, and a significantly higher concentration was observed in tumor than in the brain tissue. At 24 hours after intrathecal administration, the uptake of MTX-3H by gliomas exceeded that achieved after intravenous injection, although the drug dosage in the latter was 10 times that in the former.
v2
2018-04-03T02:58:55.645Z
1974-06-01T00:00:00.000Z
35753136
s2ag/train
Combination chemotherapy of Hodgkin's disease Fifty‐two patients with advanced Hodgkin's disease seen at the Massachusetts General Hospital since 1967 were treated with the MOPP (nitrogen mustard, vincristine, prednisone, and Procarbazine) combination. Of these patients, 35 had had no prior treatment, while 17 had relapsed after radiotherapy or single drug chemotherapy. The primary treatment group had a complete response rate of 91%, 66% of whom remain disease‐free at a median remission duration exceeding 22 months. Complete responses occurred in 71% of the secondary treatment group, of whom 47% remain free of disease with a median in excess of 21 months. All Stage IIIA and IVA patients remain in complete remission, but 50% of those treated in Stage IIIB and IVB have relapsed. Relapses have occurred in 5 of 8 patients over the age of 50 years; bone marrow toxicity from MOPP was more severe in the older patients. Cancer 33:1499–1504, 1974.
v2
2018-04-03T03:16:17.869Z
1974-06-01T00:00:00.000Z
2190991
s2ag/train
Specific receptors of the steroid hormones in breast cancer. Interference with the endogenous production of estrogens has been shown to be an effective palliative therapy for mammary cancer in 20-45% of cases. Additive hormone therapy has also been used as an effective palliative measure. The characteristic of some estrogen target cells with the capacity to bind estradiol-17beta specifically and with high affinity to estrogen-binding protein or "estrogen-receptors" has been shown. This reaction is a sequential process. The steroid 1st enters the target cell and combines with a cytoplasmic form of receptor protein. The hormone-receptor complex undergoes a transformation and then translocates into the nucleur where it binds to acceptor sites presumably in the chromatin of the target cell. The nuclear form of the receptor requires the presence of estradiol. Sucrose gradient centrifugation showed 2 steroid binding proteins sedimenting at 8-9S and 4-5S. The significance of the distribution of the 8-9S and 4-5S receptor species in human breast tumors is not known. About 50% of all breast carcinomas contain specific estrogen receptors. The amount of receptor varies from tumor to tumor. Histologic features of the cancers do not explain the variation in levels of estrogen receptors. The cellular composition of a breast tumor may also include estrogen-independent cells. Remissions after hormone manipulations have occurred in a majority of patients with estrogen receptors (44 of 56 in the authors cases). A few (5 of 80) patients with tumors lacking estrogen receptors have experienced remissions following endocrine therapy. More rigid quantitation of estrogen receptors correlated with clinical response may improve the predictive usefulness of receptor information.
v2
2018-04-03T03:35:58.359Z
1974-06-01T00:00:00.000Z
6965471
s2ag/train
Ultrasound and scintigraphy in the differential diagnosis of obstructive jaundice Eight cases of obstructive jaundice are described to illustrate how diagnostic ultrasonography may be used to differentiate between intra‐ and extrahepatic jaundice, especially in patients with malignancy. Ultrasound can also provide accurate anatomical localization of the tumor site and can reveal the cause of the obstruction. The ultrasound results are compared with the isotopic findings. Cold areas in the scintigram caused by dilatation of the biliary tree may be misinterpreted. The ability of ultrasound to differentiate between solid and cystic tumors produces more diagnostic data than can be obtained by isotopic scanning. Because of the limitations of radiological procedures in the deeply jaundiced patient, ultrasound is the method of choice for initial investigation.
v2
2018-04-03T04:55:29.479Z
1974-06-01T00:00:00.000Z
40942668
s2ag/train
The effect of calcium concentration on ACTH stimulation of steroidogenesis in mouse adrenal tumor cells Calcium is required for ACTH stimulated steroidogenesis in adrenal tumor cells in tissue culture. In the absence of calcium, the dose of ACTH required to induce half maximum steroidogenesis was increased 30 fold. In contrast to intact adrenal glands or isolated adrenal cells, high doses of ACTH (50 mU/ml) maximally stimulated steroidogenesis in the absence of calcium. Growth for up to six days in medium with low calcium did not affect basal or ACTH induced steroidogenesis. The addition of calcium to cells incubated with ACTH produced a maximum steroidogenic response in 15 minutes. In contrast to intact adrenal glands, calcium is not required for adenosine‐3′,5′‐cyclic monophosphate (cyclic AMP) stimulated steroidogenesis in adrenal tumor cells. These experiments support the concept that calcium is important at the level of ACTH‐membrane receptor site interaction or activation of adenyl cyclase in adrenal tumor cells.
v2
2018-04-03T05:20:04.251Z
1974-06-01T00:00:00.000Z
42442963
s2ag/train
The Incidence of Cancer Among In-Patients with Affective Disorders Mortality rates in psychiatric patients have been reported as higher than those of the general population in Scandinavia (Odegaard, 1952), the United States (Gorwitz et al., 1966; Babigian and Odoroff, 1968), and Scotland (Innes and Millar, 1970). These findings may be related both to a greater prevalence of physical disease amongst psychiatric patients (Kay and Roth, 1955; Culpan et al., 1960; Shepherd et al., 1964; Kay and Bergman, 1966; Eastwood and Trevelyan, 1972) and to a greater frequency of suicide (Stenstedt, 1952; Stenstedt, 1959; Pokorny, 1964).
v2
2018-04-03T05:54:11.583Z
1974-06-01T00:00:00.000Z
44935368
s2ag/train
Deltopectoral flaps. Repair of face and neck defects caused by radical excision of malignant tumors. Five cases are reported where face and neck defects created by radical excisions of cancer were repaired using deltopectoral flaps. In one patient the flap replaced a resected cervical esophagus. In another it was used with cartilage to repair a tracheal defect. In a third it replaced the excised tonsil fossa and adjacent structures. And in two it closed external soft tissue defects. The flap may be laterally based and depend on the acromiothoracic vessels or medially based and depend on the intercostal perforative vessels. The method requires only one secondary operation, the detachment of the flap some three weeks later.
v2
2018-04-03T06:10:37.251Z
1974-06-01T00:00:00.000Z
45742715
s2ag/train
Malignant lymphoma invading the facial nerve. A patient with generalized poorly differentiated lymphoblastic lymphosarcoma of the ileum developed paralysis of the left side of the face. Histologically, the facial nerve was infiltrated and the nerve structure destroyed by the sarcoma from the stylomastoid foramen up to the brain stem, including the stapedial, chorda tympani, and major petrosal nerves. Infiltration of the acoustic and vestibular nerves was less intense and, in some areas, normal nerve bundles were seen. Infiltration was restricted to the major nerves inside their sheath, the sensory organs being involved only to a minor extent. The tumor also spread into the hypotympanum and to the mastoid air cells toward the skull base on the left, and to the air cells close to the major petrosal nerves on both sides.
v2
2014-10-01T00:00:00.000Z
1974-07-01T00:00:00.000Z
16207268
s2orc/train
Cell surface antigens of a mouse testicular teratoma. Identification of an antigen physically associated with H-2 antigens on tumor cells. Rabbit antisera to a mouse testicular teratoma, absorbed with normal mouse tissues, react by immunofluorescence with plasma membrane antigens of a variety of transplantable mouse tumor cells and transformed fibroblast cell lines including Clone 1D, SV-40-3T3, and 3T12. Trypsin treatment of cells of "normal" lines, 3T3 and FR-SV-3T3, uncovers reactivity on these as well. Early passage mouse embryo fibroblast cell cultures do not react even after trypsinization. By cross-absorbtion studies, the anti-teratoma serum appears to react with an antigen common to most tumor cells investigated thus far. When this antigen on Clone 1D cells is "capped," H-2 antigens collect with the teratoma antigens in the cap indicating a physical association between the molecules. Molecules specified by both the H-2D and H-2K regions are bound to the teratoma antigens in the Clone 1D plasma membrane. This antigen is also found in soluble tumor cell fractions where it is believed to be free of H-2. A second cell surface antigen defined by anti-teratoma serum is expressed only by hepatoma and teratoma itself. This second antigen is apparently a secretory product of teratoma cells. A third surface antigen defined by anti-teratoma serum appears to be specific for the teratoma. Testicular teratomas are thought to arise from the proliferation of primary germ cells (1). Though almost unknown in most mice, these tumors occur in 1% of newborn strain 129 males, apparently due to multiple genetic factors in this inbred strain (1). Strain 129 spontaneous teratomas usually contain a bizarre collection of differentiated tissues, and differentiated cells persist indefinitely in most transplantable teratomas ('2). These differentiated cells appear to derive from undifferentiated pluripotent stem cells or "embryonal carcinoma" (3). Teratoma lines adapted to culture appear to remain undifferentiated. However, even after extended periods in culture, clones of teratoma were found to differentiate when reimplanted in mice (4)(5)(6)(7). The range of teratoma differentiation in vivo is similar to that of normal embryos grafted to adults (8,9). In particular both may produce "embryoid bodies," structures which morphologically and histologically resemble early gestation embryos (10,11). Teratoma cells then would seem an excellent starting point for an investigation of antigens common to tumors and normal embryos. One of us reported previously that a rabbit antiserum to strain 129/J mouse teratoma 402AX reacts specifically with SV-40 transformed 3T3 cells and early mouse embryos (12). Only cells of the embryonic portion of the conceptus, those cells which would later express H-2 antigens, reacted with the antiserum, suggesting that perhaps the teratoma antigens are precursors to H-2 in normal development. Antigens common to early embryos and virus-transformed cells have been reported in hamsters (13,14) and mouse antimouse embryo sera also define antigens common to a range of murine tumor cells (15,16). This report concerns our efforts to determine the antitumor reactivities of * Supported by NIH grant AM 11202 to Dr. Edidin, an American Cancer Society institutional grant, and training grant GM-57 to the Department of Biology. This is contribution number 779 from the Department of Biology. ~7 Present address: Division of Immunology, Duke University Medical Center, Durham, N. C. 27710. THE JOURNAL OF EXPERIMENTAL MEDICINE • VOLUME 140, 1974 61 rabbit anti-teratoma serum, and the relationship of these antigens to 11-2 on 20 day mouse embryos (19) and maintained in culture with Eagle's minimal essential medium supplemented with 20% fetal calf serum. Transplantable tumors: Adenocarcinoma BW 10232 (C57BL/6J), melanoma B16 (C57BL/ 6J), and lymphatic leukemia BW 5147 (AKR/J) were obtained directly from Jackson Laboratories, Bar Harbor, Maine, and were not passaged by us. Hepatoma BW 7756 (C57L/J), also from Jackson Laboratories, was passaged in the laboratory of Dr. G. M. Williams and generously supplied to us by him. Mastocytoma P815, a DBA/2 ascites tumor, was obtained from Dr. Christopher Henney. Two methylcholanthrene-induced C57BI/6J flbrosarcomas were obtained from Dr. Leon Parks; they were at passage 6 and 7, respectively, at the time of assay. Antisera.--Anti-teratoma serum was produced by injection of 2 X l0 T teratoma C cells suspended in 1.8 )< l0 s BCG (Research Foundation, Chicago, Ill.) into multiple intradermal sites on the fanks of New Zealand white rabbits. Rabbits were boosted with 2.5 )< 107 live teratoma C intravenously and bled 7-9 days later. Anti-teratoma serum was absorbed with 129/J male mesenteric lymph node, spleen, thymus, and kidney cells obtained by gentle teasing and pressing tissues through a 200-mesh wire screen. 0.7 ml of twice washed, packed cells were mixed with 2 ml of antiserum. After 3-5 h on ice, the cells were removed by centrifugation. After three such absorptions the antiserum did not react by immunofluorescence with fresh samples of the cells used for absorption. Normal rabbit serum was obtained prior to immunization with teratoma. Anfimouse cell reactivity was removed by absorption with 129/J cells as above. Rabbit anti-teratoma serum was tested for reactivity against a variety of murine viruses by Microbiological Associates, Bethesda, Md. The serum did not react with reovirus type-3, sendal, ectromelia, mouse adenovirus, mouse hepatitis virus, Theiler's mouse encephalomyelitis (GD VII), minute virus of mice, newborn mouse pneumonitis (K virus), pneumonia virus of mice, or lymphocytic choriomeningitis virus. It did, however, significantly inhibit polyoma virus induced agglutination of guinea pig red blood cells, and our own tests confirm this finding (Table I). We have further observed that extensive absorption of the anti-teratoma C serum with teratoma A cells fails to remove all antibody reacting by immunofluorescence with live teratoma C (Table I), indicating the presence of an antigen expressed by the cultured subline but not in detectable amounts by the parent ascites tumor. Polyoma 3T3 cells also react with teratoma A absorbed serum ( Table I), suggesting that perhaps the serum is reacting with a polyoma-specific cell surface antigen. The two activities, antipolyoma virus and anticell surface, are distinct from one another since appropriate absorption of the antiserum removes one without affecting the other (Table I). It is uncertain why rabbits injected with live teratoma C produce antibody to polyoma virus. It is probable from the results in Table I that teratoma C is transformed by the virus, but the cells are not producing virus in detectable amounts. Attempts to rescue polyoma virus from teratoma C by sendal virus fusion with both mouse and rabbit embryonic fibroblasts have been unsuccessful. Perhaps most surprising is the finding that the cultured cells express this polyoma-associated cell surface antigen, while the ascites tumor cells from which they were derived do not. Two separate lines of teratoma 402AX have subsequently been adapted to culture and both express the polyoma antigen. None of the tumor and cultured ceils reported in this study react with teratoma A absorbed antiserum by immunofluorescence. Tumor cells, eliminated from consideration because they did react with teratoma A absorbed serum were solid Sarcoma I, ascites Sarcoma I, and melanoma HP, all from Jackson Laboratories. Anti-//-g k alloantiserum was prepared by intraperitoneal injection of C57BL/6 X DBA/2 F1 mice with B10.Br lymphocytes. Serum was made//-g-specific by three serial absorbtions with B10.D2 lymph node and spleen ceils performed as described above. Monospecific anti-//-g.ll and H-g.3g were obtained from the Transplantation and Immunology Branch, NIAID. Rabbit anti-T-cell antigen was kindly provided by Drs. Gerry Cole and Christopher Henney. This antiserum, prepared by injection of mouse brain and absorbed on mouse red cells, reacts specifically with thymus-derived lymphocytes (20). Indirect Immunofluorescent Staining of Cells.--Unless otherwise indicated, cultured cells were harvested with 2.5% heat-inactivated chicken serum, 0.2% trypsin, 0.002% purified collagenase (Worthington Biochemical Corp., Freehold, N. J.) in Moscona's solution (22). 5 X 105 cells, washed twice in 0.01 M Hepes buffered Hank's solution (pH 7.3) containing 5% fetal calf serum (HHS), were incubated with 0.05 ml of antiserum on ice for 15 min. Antiserum was diluted in HH5 containing 2.5 mM dinitrophenol (DNP-HH5) to inhibit pinocytosis. The cells were washed twice with DNP-HH5 to remove excess serum and stained with 0.05 ml of the fluorescent conjugate for 15 min on ice. Excess conjugate and DNP were removed by three washes with HH5. All samples were encoded before observation and read as unknowns. Fluorescence microscopy was performed as described previously (21). Counts were done on 100-200 cells to determine the percentage of stained ceils. Pictures were taken using a Leica camera and GAF-500 color film. Film was processed with a GAF developing kit to an ASA of i,000. Capping.--Cl 1D cells were stained as described above except that DNP was omitted. After final washes, the cells were incubated at 37°C for 90 min for maximal capping of the fluorescent label. At the optimal serum concentration 60-90% of cells were capped by anti-H-g k and approximately the same percentage with anti-teratoma. Reactivity of the Anti-Teratoma Serum with Normal Mouse Tissues--The rabbit anti-teratoma serum displayed high titres of reactivity with the immu-nizing cells (Fig. 1). Surprisingly little of this activity is directed against antigens common to normal mouse cells, since as shown in Fig. 1 the antiserum reacts poorly with 129/J lymph node cells. A single absorbtion with lymph node cells removes this activity while having no effect on the staining of teratoma itself. To ensure removal of this activity, antiserum absorbed on cells from a collection of normal 129/J tissues (see Materials and Methods) was used for all experiments described here. The reactivity of the absorbed anti-teratoma serum with cells from a variety of adult mouse tissues is shown in Table II. With the exception of ovary, none of the normal cells, either teased apart or dissociated with trypsin, reacted with O, Teratoma C with unabsorbed or lymph node cell-absorbed anti-teratoma. A, 129/J lymph node cells with normal rabbit serum. A, Teratoma C with normal rabbit serum. the antiserum. If any antigens which react with the anti-teratoma serum are present on these normal cells, they are expressed at levels too low to be detected by our assay system. The fluorescent stain on dissociated ovary cells could not be removed by further absorption of the anti-teratoma serum with normal cells other than ovary itself. Staining of frozen sections of ovary with the anti-teratoma serum revealed bright cytoplasmic fluorescence on cells of the theca interna and luteinized stromal cells. Fig. 2 a, the anti-teratoma serum reacts strongly with living SV-40 transformed 3T3 cells and with 3T12 cells. It reacted weakly with 3T3 cells and SV-40 transformants which have reverted to normal growth regulation. However, if these "normal" cells are treated briefly with crude trypsin before 129/J organs were removed and dissociated by gentle teasing. A portion of each was dissociated with 0.25% Difco trypsin in phosphate buffered saline at room temperature. Peritoneal exudate cells were washed from the peritoneal cavity with HH1 and a portion treated with trypsin. NRS controls were done on trypsinized cells. Teratoma Antigens Expressed by Cultured Mouse Fibroblast Cells.--As shown in * Sera at 1:10 dilution; results presented as percentage stained cells. staining ( Fig. 2 b), their reaction with antiteratoma serum is greatly increased. Trypsin treatment has a slight effect on staining of the transformed cells as well, but this may be due simply to rounding of the cells, thus increasing the apparent brightness of the fluorescent stain. Intact primary and early passage mouse embryonic fibroblasts do not react significantly with the anti-teratoma serum, even after treatment with trypsin (Table III). Co-capping of the Teratoma Antigens and H-2 on C1 1D.--A subline of the C3H L-cell, C1 1D, also expresses teratoma antigens, most of which are available for fluorescent staining only after the cells are treated with trypsin ( Fig. 3). Trypsinized CI 1D cells were stained for the teratoma antigens and then incubated at 37°C. Under these conditions, between 60 and 90% of the cells "cap," that is, the fluorescent antigen-antibody complexes migrate to one pole of the cell (Fig. 4 a). These cells were then incubated with a mouse alloantiserum which reacts with several H-2 ~ specificities and FL-GaM in ice so that no further capping could occur. The co-incidence of rhodamine and fluorescein stain on the capped cells (Fig. 4 a and b) indicates that both the H-2 antigens and the teratoma antigens had been capped by the antiteratoma serum. The same result is observed when the H-2 antigens are capped and the cells stained in the cold with anti-teratoma (not shown). H-gD and H-2K molecules cap independently of one another in lymphocyte membranes (23), and the same is true of H-2 antigens on Cl 1D (M. Edidin and A. Weiss, unpublished). Therefore, monospecific anti-H-2 sera were used to determine which of the alloantigens was responsible for co-capping with teratoma antigens. When H-2D molecules are capped and the cells then stained with anti-teratoma, again capping of the teratoma antigens is observed (Fig. 4 c and d). Capping of the H-2K molecules (with anti-H-2.32) also caps the teratoma antigens (not shown). In both cases capping of the teratoma antigen was incomplete. To be certain that the observed co-capping of H-3 and teratoma antigens was in no way inherent to the procedure employed, the same sera and fluorescent reagents were used to look at capping with another fibroblast cell marker. Fibroblasts express 0-antigen (24), and a heterologous rabbit anti-T-cell serum reacts with C1 ID cells. In Fig. 4 e and/, C1 1D cells were capped with the polyspecific anti-H-2 k and then stained with the rabbit anti-T cell. No co-capping was observed. The reciprocal experiment, capping of the T-cell antigens and then staining with anti-H-2 k also failed to produce co-capping (not shown). Controls, shown in Table IV, were performed to ensure that the co-capping of H-2 and the teratoma antigens on C1 1D was not due to unexpected interactions among the reagents employed. The fluorescent reagents react only with the specified antiserum and not with the cells themselves or with each other. The anti-teratoma does not react with H-3 k lymphocytes, nor does it bind anti-H-2 k antibody. The anti-H-2 k does not bind to teratoma cells and does not react with the anti-teratoma antibody. Teratoma Antigens Expressed by Transplantable Murine Tumor Cells.--The anti-teratoma serum reacts with living cells from a variety of transplantable mouse tumors (Table V). Staining of these cells is little affected by trypsin. One tumor tested, a lymphatic leukemia, reacted poorly with the antiserum, and because of the limitations of the assay system, expression of antigens on these cells is questionable. Two tumors, both early passage methylcholanthrene-induced fibrosarcomas, clearly did not react with the antiserum even after treatment of the cells with trypsin. It was of interest to determine whether the various cells which react with the antiserum are expressing the same antigens, particularly the antigens which co-cap with H-2 on C1 1D cells. This question was approached by the absorption studies shown in Table VI. Absorption of the antiserum with any reactive cell tested completely removes antibody binding to C1 1D, melanoma and SV-3T3. This indicates that of the cells tested, all those reacting with the antiserum 69 express a common antigen or antigens, and furthermore these antigens are cross-reactive with those expressed on CI 1D cells. Also, since absorption of the serum with Cl 1D removes all staining on melanoma and SV-3T3, these cells are expressing only teratoma-defined antigens found on C1 1D. ( ¶) 1:8o. Aside from this common antigenic activity, the absorption studies revealed other reactivities in the anti-teratoma serum. Absorption with C1 1D, adenocarcinoma or melanoma, which removes the common antigens, has little effect on the staining of hepatoma and teratoma itself. Absorption with hepatoma however removes most antibody reacting with the teratoma, indicating that a second activity is shared by teratoma and hepatoma but not by the other tumor cells tested. Because absorbtion of the antiserum which removes the common antigens does not affect staining of the teratoma, most of the very high titer against teratoma cells must be due to the antigens shared by teratoma and hepatoma. It is probable that the serum reacts with a third antigen, one specific for teratoma only, since in repeated experiments absorbtion with hepatoma did not remove all antibody which reacts with teratoma. The antigen or antigens responsible for the verk high titer of the antiteratoma serum with teratoma itself appear to be secreted or shed by teratoma cells into their ascites fluid. Absorbtion of the antiserum with teratoma ascites fluid removes all reactivity when teratoma cells are stained at a serum dilution of 1 : 80, but extensive absorbtion with ascites fluid has no effect on staining at a dilution of 1:20 (Table VII). This result would indicate that absorbtion with ascites fluid removes activity with one antigen expressed by teratoma, probably the high-titered antigen shared by teratoma and hepatoma, but does not remove a second, lower titered, activity. Absorbtion with ascitic fluid has no effect on staining of CI 1D cells. Teratoma Antigens of Mouse Ovarian Cells.--Absorbtion studies were also used to determine which of the antigens reacting with anti-teratoma serum was responsible for staining of ovarian cells (Table VIII). Absorbtion of the antiserum with ovary removes antibody reactive with both teratoma and C1 1D * Ascites fluid from 129/J teratoma carriers was spun at low speed to remove cells and then at 100,000 g for 60 rain to remove cell fragments and debris. Antiteratoma serum at 1 : 2 was absorbed with an equal or 10-fold volume of clarified ascites fluid at room temperature 1-2 h. Ascites fluid alone does not stain either teratoma A or C1 1D cells. :~ Results are expressed as percent stained cells. Absorbtions were performed as described in Table VI. Ovaries from C3H females were used as absorbing and test ceils. Ovary cells were obtained by gentle teasing in the presence of 0.25% Difco trypsin in phosphate-buffered saline. Results are expressed as percent cells stained Serum dilutions: (*) 1:80; (*) 1:20. suggesting that both common and teratoma/hepatoma antigens are expressed in the ovary. Cl 1D absorbtion, which removes reactivity with the common antigen only, has no effect on staining of ovarian cells while absorbtion with hepatoma, which removes both activities, removes essentially all antiovary reactivity. This indicates that, as was the case with the teratoma, most of the stain on ovarian cells is due to the teratoma/hepatoma antigens. Staining of ovarian sections with absorbed antisera (not shown) gave results identical to those obtained with membrane stain on live cells. Cellular Distribution of the Common Teratoma Antigens.--The common teratoma antigens are not confined to the plasma membrane. Fixed C1 1D cells stain in the cytoplasm, and this fluorescence is removed by absorbtion of the antiserum with live C1 1D (Fig. 5 a and b). Cytoplasmic staining is also observed in melanoma, SV-40-3T3, and 3T3 cells. In each case absorbtion of the antiserum with live C1 1D removes the stain. At least a portion of the cytoplasmic antigens are soluble, not membrane bound, since absorbtion of the antiserum with a 100,000 g, 120 rain, supernate of lysed Cl 1D cells abolish cytoplasmic staining (Table IX). This supernate also absorbs antibody which binds to live cells, indicating that the cytoplasmic and plasma membrane antigens are identical, by serological criteria at least. Fro. 5. Anti-teratoma serum staining of fixed CI 1D. Cells, plated onto cover slips 48 h before staining, were air dried then fixed in acetone at --70°C. Fixed cells were incubated at room temperature with undiluted normal goat serum, rabbit antiserum, and TMR-GaR for 10 min each with rinses in HH5 between each step. All sera were at 1:20 dilution. (a) C1 1D plus anti-teratoma serum. (b) C1 1D with anti-teratoma serum absorbed on live C1 1D (see Table VI). Live C1 1D 2 5 C1 1D supernate* 7 10 Fixed C1 1D cells were prepared and stained as described in Fig. 5. Anti-teratoma serum was absorbed with live CI 1D as described in Table VI. Sera were used at 1:20 dilution. * CI 1D cells were lysed by gentle homogenization in a loose-fitting glass homogenizer and particulate debris removed by centrifugation at I00,000 g for 120 min. 1 vol of anti-teratoma serum at 1:2 was absorbed with 4 vol of this supernate overnight at 4°C. DISCUSSION Absorbtion studies of a n t i -t e r a t o m a serum reveal at least three antigens. these cells is unclear. However, the results indicate that similar concentrations ofreactive antigens are present on both "normal" and transformed fibroblast lines though their availability to antibody varies. This situation strongly parallels that observed for binding of concanavalin A (Con A) to normal and transformed fibroblasts (25). At 0°C, the temperature at which our incubations are performed, polyoma-transformed 3T3 cells bind three times as much [3H]Con A as do 3T3 cells. Trypsin treatment of 3T3 cells results in an almost threefold increase in binding at 0°C. While both transformed and normal mouse fibroblast cell lines express the common antigen on their surface, significant levels of the antigen were not detected on live primary and early-passage fibroblast cell cultures from several strains of mice. If these cells express the common antigen, it is at a level below the limit of sensitivity of our assay. Thus, expression of the antigen, in a quantitative sense at least, is a property of fibroblast cell lines, and not of cultured fibroblasts per se. The common teratoma antigen was found to co-cap with both the H-2D and H-2K molecules on C1 1D cells. Although we will refer to this antigen in the singular, it is not known whether the same or two different antigens are involved in the co-capping. Capping behavior of membrane markers in other experiments has agreed well with biochemical association of molecules following their removal from the membrane. The two H-2 polypeptides, H-2D and H-2K, are readily separable by specific immunoprecipitation following either detergent (26) or papain (27) solubilization and do not co-cap on lymphocytes (23). On the other hand, ~-2 microglobulin co-purifies with the human histocompatibility antigens, HL-A (28,29), and co-caps with the HL-A antigens of lymphocytes (30). Recently Fujimoto and co-workers (31) reported that H-2 antigens and a tumor-associated antigen co-purify on immunoabsorbtion of serum from lymphoma bearing mice. This tumor antigen was also defined by a heterologous antiserum, but nothing further is known about the tumor specificity of the antigens involved. Of the cells tested thus far, all those which express the common teratoma antigen in the plasma membrane stain for the antigen in the cytoplasm as well. At least a portion of this cytoplasmic antigen in C1 1D is not associated with particulate fractions. A similar cellular distribution has been observed for a tumor-associated embryonic antigen. Baldwin and his co-workers found that an antigen defined by multiparous rat serum was localized both in the plasma membrane and cell sap of many chemically-induced rat tumors (32). ]~t is possible that the soluble, cytoplasmic antigen is not associated with H-2. While preliminary results indicate that most of the common antigen in C1 1D cells is soluble, H-2 in cells is always membrane-bound (33). Of the normal tissues tested, only ovary contained the common tumor antigen. The identity of the ovarian cells expressing the common antigen is un-known since the very bright staining due to the teratoma/hepatoma antigen on ovarian sections effectively masks the presence of the weaker common antigen. However, since the common antigen is expressed by unfertilized mouse ova, 1 it is possible that immature ova and germ cells in the ovary are also expressing the antigen. Of the three antigens thus far found to react with our rabbit anti-teratoma serum, the strongegt is the teratoma/hepatoma antigen. This antigen appears to be a secretory product of teratoma cells, and it is also expressed on the surface of parietal yolk sac cells. 1 The tissue distribution of this antigen suggests it might be a-fetoprotein, a fetal serum protein found associated with and presumably synthesized by parenchymal cells of fetal liver and by parietal yolk sac (34). It is also secreted by many teratoma and hepatoma cells including hepatoma BW 7756 and several 129 teratomas (35). Although the homologous antigen is not immunogenic, a-fetoproteins from several species proved strong heteroantigens (36). Thus, if 402AX secretes a-fetoprotein, a rabbit antiserum to the cells would certainly react with this antigen. In a recent paper, Artzt and her co-workers describe the reactivities of an anti-teratoma serum prepared by injection of irradiated cells into syngeneic mice (37). Their teratoma F9, a subline of OTT-6050 (9), is composed entirely of embryonal carcinoma cells which have lost the ability to differentiate in vivo. Anti-F9 serum reacts with other embryonal carcinoma lines, with early cleavage embryos, and with testicular cells. It did not react with any of a variety of mouse tumor cells, while our rabbit anti-teratoma defines an antigen common to most of our tumor test cells. Very similar though not identical cells were used in the two studies, i.e., Artzt's 3T3 and SV-3T3 cells were derived from Swiss embryonic fibroblasts while ours were from BALB/c embryonic fibroblasts. One possible explanation for this difference is that the common antigen is not immunogenic in mice. A second possibility is that F9 does not express the common antigen. Teratoma 402AX differs from teratoma F9 in at least one important regard; 402AX retains the ability to differentiate in vivo. Perhaps then the common antigen reflects a commitment before differentiation, but is not expressed on fully differentiated normal tissues. ~t is reexpressed by cultured cells concomitant with the requisite changes involved in establishment of a cell line and by tumor cells. SUMMARY Rabbit antisera to a mouse testicular teratoma, absorbed with normal mouse tissues, react by immunofluorescence with plasma membrane antigens of a variety of transplantable mouse tumor cells and transformed fibroblast cell lines including Clone 1D, SV-40-3T3, and 3T12. Trypsin treatment of cells of "normal" lines, 3T3 and FR-SV-3T3, uncovers reactivity on these as well. Early passage mouse embryo fibroblast cell cultures do not react even after trypsinization. By cross-absorbtion studies, the anti-teratoma serum appears to react with an antigen common to most tu~nor cells investigated thus far. When this antigen on Clone 1D cells is "capped," H-2 antigens collect with the teratoma antigens in the cap indicating a physical association between the molecules. Molecules specified by both the H-2D and H-2K regions are bound to the teratoma antigens in the Clone 1D plasma membrane. This antigen is also found in soluble tumor cell fractions where it is believed to be free of H-2. A second cell surface antigen defined by anti-teratoma serum is expressed only by hepatoma and teratoma itself. This second antigen is apparently a secretory product of teratoma cells. A third surface antigen defined by anti-teratoma serum appears to be specific for the teratoma.
v2
2017-06-16T01:51:03.856Z
1974-07-01T00:00:00.000Z
92491
s2ag/train
Orosomucoid content of pleural and peritoneal effusions. 22 nonneoplastic, noninflammatory effusions (cirrhosis and congestive heart failure), 12 non-neoplastic inflammatory effusions (tuberculosis, lupus erythematosus, rheumatoid arthritis, and idiopathic pleuropericarditis), and 58 neoplastic effusions (cancer of lung, breast, ovary, and pancreas, and lymphoma) were analyzed by radial immunodiffusion for orosomucoid concentration. The average concentration +/-SE was 35+/-4, 65+/-17, and 130+/-13 mg/100 ml in the three types of effusion, respectively. By gel filtration and ion exchange chromatography, orosomucoid was isolated from 12 nonmalignant and 14 malignant fluids. The orosomucoid preparations reacted as single components in acrylamide gel electrophoresis at pH 9.0, and in immunodiffusion and immunoelectrophoresis against antisera to human serum and to human plasma orosomucoid. In radial immunodiffusion, the slope of the line relating concentration to the square of the diameter of the precipitate area was identical for orosomucoid isolated from normal human plasma and from nonneoplastic effusions, but was subnormal for orosomucoid isolated from neoplastic fluids. All orosomucoid preparations had normal amino acid composition. Orosomucoid from the nonmalignant effusions had normal carbohydrate content. 11 of 14 samples of orosomucoid isolated from neoplastic fluids had abnormalities in carbohydrate composition, consisting of subnormal content of sialic acid (11 of 14), hexose (10 of 14), and hexosamine (3 of 14), and abnormally high content of hexosamine (4 of 14). Discriminant analysis showed that concentration of orosomucoid distinguished between neoplastic and nonneoplastic noninflammatory effusions more effectively than concentration of total protein, albumin, alpha(1), alpha(2), beta, or gamma-globulin.
v2
2017-08-31T22:17:53.097Z
1974-07-01T00:00:00.000Z
11919536
s2ag/train
Selective toxicity of diphtheria toxin for malignant cells. Purified diphtheria toxin is shown to inhibit protein synthesis in Ehrlich-Lettré ascites carcinoma cells in vitro. Protein synthesis in Ehrlich-Lettré cells is at least 10,000 times more sensitive to toxin than protein synthesis in normal mouse spleen or thymus cells. This sensitivity correlates with the observation that Ehrlich-Lettré tumors regress in mice injected with diphtheria toxin but not diphtheria toxoid. Using the criterion of inhibition of protein synthesis in vitro, we show that other mouse malignancies (lymphoma and myeloma) are also more sensitive to diphtheria toxin than normal spleen or thymus. Metastatic human breast carcinoma cells from two individuals, cells from two melanoma nodules removed at different times from a third patient, and cells from melanoma nodules from three additional individuals are shown to be more sensitive to diphtheria toxin than some normal human cells. The toxin sensitivity of protein synthesis in some of the malignant cells tested was so much greater than that of normal cells, that we have proposed that diphtheria toxin should be studied further since it might prove a useful anti-cancer agent in patients whose tumors are first shown to be highly sensitive to toxin in vitro.
v2
2018-04-03T00:05:37.930Z
1974-07-01T00:00:00.000Z
9308766
s2ag/train
Ultrastructure of a Vaginal Myxoma of a Rat Ultrastructural study of a vaginal myxoma of an adult Wistar rat showed that the stroma consisted mainly of finely granular material with some fibers. The tumor cells contained numerous mitochondria, Golgi complexes, and associated vesicles, and moderate to abundant endoplasmic reticulum. Intracytoplasmic filaments and virus-like particles of about 120 nm were seen.
v2
2018-04-03T00:21:13.914Z
1974-07-01T00:00:00.000Z
11475226
s2orc/train
Human cancer virus vaccines Dr.Hilleman: Although many factors such as radiation, environmental carcino gens, aging, hormones and genetics undoubtedly play a part in the etiology of cancer, available data supports the concept that the pri mary element in human cancer might be a virus and that all other agents might play only a secondary role. This view is reinforced by the fact that cancer cells often appear to have a new genetic input that allows them to make new and unique viral-specified antigens that are present in the cells and on their surfaces; secondary factors do not provide such genetic input. Dr. Hilleman: Learning the method by which canceragentsare transmitted, either horizontally as in infectious disease, vertically as in chromosomal inheritance or by infection acquired in utero, is essential to decid ing whether a vaccine could be developed to combat them. Cancer transmitted horizontally by viruses might be prevented by viral vaccines. Transmitted vertically, it would be unlikely, although vaccines could possibly limit or prevent its clinical expression. Fortunately, evidence points largely to horizontal transfer, despite the so-called virogene-oncogene theory. Dr. Hilleman: The virogene-oncogenehypothesisholdsthat many, if not all, cells carry genetic DNA sequences called oncogenes and virogenes that code for malignant transformation of cells and for infec tious oncornaviruses. Normally â€oe¿ switched off,―these cells may be activated by carcinogenic chemicals, radiation, aging, DNA viruses or perhaps by the effect of RNA-helper viruses. In effect, the concept holds that genes for RNA tumor viruses are part of the heritable genome of animal cells and that these genes play a role in normal embryogenesis. Editor: 14'/zat data lead to this hypothesis? Dr. Hilleman: The oncogeneconceptis formulated on the basisof studiesin ani mals, particularly in highly inbred, highly leukemic mice. In these animals, vertical transmission, probably genetic, seems to be a sig nificant factor in the development of leukemia. But, vertical trans mission of leukemia might not be important in the real world of mice outside the laboratory; horizontal virus transmission in nature has not been adequately studied. viruses, stand in better stead than the oncornaviruses in at least two respects. One is their undisputed horizontal transmission, and the other is their ability to be grown in the laboratory. Although it has long been known that cancer in animals is caused by oncorna viruses, more than six decades of research have failed to establish their role in human cancer. Dr. Hilleman: The Epstein-Barr (E-B) virus is the prime suspectof the herpes viruses for several reasons: its ubiquitous presence in Burkitt's lymphoma and nasopharyngeal carcinoma; its role in causing lym phoblasts to replicate indefinitely in vitro; the observed time-space clustering of cases in epidemic Burkitt's lymphoma belts; and the inordinately high E-B antiviral antibody levels in patients with Burkitt's lymphoma. For the present, however, E-B virus is im practical to study from the vaccine standpoint because of its very limited proliferation in vitro. Similarly, herpesvirus hominis types 1 (oral) and 2 (genital) might play a role in a variety of human cancers of the nasal -oral pharyngeal region, the genitourinary tract, and the lower intes tine. Strong supporting evidence is provided by: (1)the demon stration of non-virion herpesvirus antibody in persons with such diseases; (2) the occurrence of inordinately high levels of herpes virus type 2 neutralizing antibody in persons with cervical carci noma (suggesting periodic productive replication of the virus); (3) the finding of herpesvirus antigens in exfoliating squamous carci noma cells of the uterus; (4) the isolation of herpesvirus 2 from cer vical carcinoma on cultivation at high pH; (5) the reported finding of herpesvirus genetic material in cells from cervical carcinoma; and (6) the neoplastic transformation of hamster cells infected with herpesvirus and rendered genetically defective by treatment with ultraviolet light or white light with neutral red. Editor: Would you describe the form that a vaccine could take regardless of whether the cancer agent is RNA or DNA ? Dr. Hilleman: The vaccinecould be composedof live, attenuatedor killed viruses. The killed vaccines could be made up of either whole virus particles or antigenic subunits alone, and the vaccine could be aqueous in form or given in an adjuvant, such as the emulsified peanut oil adjuvant 65 recently licensed for general use in the United Kingdom. Editor: What are the relative merits ofeach? Dr. Hilleman: Attenuated, live virus vaccines, presently being used to prevent acute illnesses, generally afford a higher level and longer lasting immunity than do killed vaccines. In addition, they require only a small amount of virus for immunization, which is often a practical necessity. However, live, attenuated vaccines need markers of viral attenuation to establish safety with some degree of reliability, even before initiating clinical trials in man. The present lack of such markers will be a real deterrent to development of live cancer virus vaccines in man. It may be important to note, however, that in domestic animals, experience with live herpesvirus vaccines has been excellent in terms of safety and efficacy as, for example, swine pseudorabies vaccine, infectious bovine rhinotracheitis vac cine, and the vaccine for Marek's disease in chickens. Since killed virus vaccines do not require markers of viral attenuation, they might be preferred in some cases. Furthermore, the poorer immun ologic performance of killed virus vaccines may be overcome in large measure by use of an emulsified peanut oil adjuvant to induce a higher level and longer lasting immunity while requiring a smaller antigenic mass than the ordinary aqueous vaccines. Editor: Would either a killed virus vaccine or an attenuated, live virus vac cine lie able to provide total protection against cancer? Dr. Hilleman: No vaccine canafford total protection againstreinfection with the same virus, whether the disease is poliomyelitis, smallpox or ru bella. The important fact is that vaccination limits the degree of rep lication of the subsequent virus infections and inhibits the extent of viral spread in which the critical damage is expressed, whether it be by cell lysis or neoplastic proliferation. In the case of cancer, an attenuated, live virus vaccine would not be expected to prevent reinfection with cancer virus, but it could prevent the infection from being expressed as clinical cancer. A good example is the highly effective vaccine against Marek's disease in chickens. The attenuated, live virus vaccine does not prevent reinfection or persistence of the virulent virus, but it does prevent its clinical expression as cancer. Editor: ‘¿ ti/hat rt'seamcli apJ)roachit your la/'oi-atom-v /)Ilr.t1!il!t,' (it 1/lit timii@' Dr. HiDeman: Our program is fixed on both RNA and DNA viruses. However, we are concentrating primarily on two viral groups, DNA herpesvirus hominis types I and 2, which cause labial and genital herpes in man, and the RNA feline leukemia-sarcoma virus complex, for which no human leukemia virus counterpart has been isolated as yet. Editor: ‘¿ t'%―ould ton describe your work on herpes virus /101)11/115 types I a/Ill 2 vaccines? Dr. Hilleman: Yes. Herpesvirus hominis vaccineshave no reliable marker for on cogenicity that might apply to man and, therefore, a live virus vac cine is not receiving primary emphasis in development. Even a killed whole virus vaccine raises doubts as to safety, based on data that show neoplastic transformation in vitro by viruses inactivated by ultraviolet light or by photodynamic effect, and induction of lymphoma in owl monkeys by heat-inactivated herpesvirus saimiri virus. Therefore, there is current preference for subunit vaccines that contain the immunologic determinants of the herpesviruses but are free of all viral nucleic acid. Editor: Hots' then would a .timhiomiivaccine be pm-educed:@ Dr. Hilleman: Herpesvirus hominis strainsderived from cells of chick embryos from special leukemia-free flocks appear to produce sufficient amounts of glycoproteins (which are probably the predominant de terminants for immunity), to be economically practical for vac cines. Further, their immunogenicity can probably be enhanced by coupling with larger molecules such as polypetides or by formula tion in adjuvant 65. These, I emphasize, are approaches and not realized accomplishments. Editor: What work is being done in your laboratory on timefeline leukemia sarcoma coin ple.v? Dr. Hilleman: Cats, like humans, are highly outbredand are subjectto many,of the same environmental conditions as man. Considering the dif ference in life span, they develop leukemia and sarcoma at roughly the same rates as man. Furthermore, evidence points to the hori zontal transfer in nature of the particular viruses that cause leuke mia in cats. Since the feline leukemia vaccine development is being used as a model for an eventual human vaccine, work is being directed toward developing a technology for making a killed virus vaccine that would be safe and hopefully practical for man. Significantly, there is no indication to date of immunologic tolerance to any of the feline leukemia-sarcoma virion or virus-associated cell membrane antigens in cats. Studies in the mouse and avian leukemia-sarcoma systems have provided data that should help researchers to predict what may be discovered in the feline studies. Neutralizing antibody, induced by killed or live virus, limits infection and prevents disease. Editor: %Vliat pro blems ha ic \‘oii encountered or might expect to encounter in your uork on cancer virus' vaccines ? Dr. Hilleman: First, the causalagentmust be reliably propagatedin the laboratory in sufficient quantity in some cell or tissue that is considered ac ceptable for human use. Then, there must be sensitive and ade quate means for detecting and quantifying the virus, and adequate procedures must be at hand for assessing its safety and efficacy. Editor: The evaluation of safety and efficacy would he a major hurdle to overcome iii developing (i vaccine. How could they be assessed? Dr. Hilleman: Becauseof the long incubationperiod for cancerin man, it might be a long time before the efficacy of vaccines to prevent cancer could be measured. However, an estimate of likely efficacy might be obtained from studies on the prevention of the acute lytic forms of the disease, viz., herpesvirus labialis and genitalis. In this in stance, limitation of viral events causing acute illness might be ex pected to indicate a reduced probability for neoplasia also. Another estimate of probable efficacy might be obtained from studying mar mosets and other primates. They develop lymphomas and leuke mia after inoculation with herpesvirus saimiri derived from squir rel monkeys. Herpesvirus saimiri vaccines prepared by the same procedure as a herpesvirus hominis vaccine and tested in the mar moset system might be expected to yield significant data that rea sonably could be extrapolated to man. Long-term tests for safety would, of course, have to be carried out, but the use of killed vac cines, especially subunit vaccines, should provide, a priori, a large amount of confidence for safety.
v2
2018-04-03T02:20:53.251Z
1974-07-01T00:00:00.000Z
33214051
s2ag/train
Inhibition by apomorphine of prolactin secretion in patients with elevated serum prolactin. ABSTRACT Apomorphine caused significant depression in prolactin (hPRL) in each of 6 patients with elevated serum levels, including 4 with hPRL-secreting tumors. A parallel rise in growth hormone (hGH) occurred in 5 of the 6 subjects. These results suggest that: i) a dopaminergic mechanism regulates hPRL and hGH secretion; and ii) that abnormal hPRL secretory states remain responsive to dopaminergic control.
v2
2018-04-03T02:23:24.811Z
1974-07-01T00:00:00.000Z
33374339
s2ag/train
Malignancy, weight loss, and the small intestinal mucosa The mucosal architecture and mucosal dynamics of the small bowel have been studied in patients with malignant disease not of the gastrointestinal tract but associated with severe weight loss. Mucosal changes in malignant disease are demonstrated by stereomicroscopy, mucosal architectural measurement, and decreased lactose utilization. Measurement of the epithelial DNA loss rate indicates, in association with mucosal measurement, that the architectural changes are caused by a hypoplasia of the epithelium. Similar findings are demonstrated in patients with profound weight loss due to other non-malignant wasting diseases. Although mucosal changes undoubtedly occur in malignant disease, the changes are not specific for malignancy and the concept of `cancer enteropathy' is not tenable. It is suggested that mucosal changes are the effect of and not the cause of cachexia.
v2
2018-04-03T02:49:23.484Z
1974-07-01T00:00:00.000Z
35179990
s2ag/train
Adenocarcinoma of the lacrimal gland with simultaneous pulmonary metastases. The first known case of a primary resectable adenocarcinoma of the lacrimal gland with simultaneous pulmonary metastases is presented. In the cases previously recorded, distant metastases have been detected only following the development of postoperative local recurrence of primary tumors. The present case demonstrates that, contrary to previous reports, adenocarcinoma of the lacrimal gland can metastasize early in the clinical course; and, therefore, patients with this disease should have extensive preoperative evaluation for metastases. When surgery is indicated, it should be aggressive in order to encompass the tumor completely.
v2
2018-04-03T03:42:25.205Z
1974-07-01T00:00:00.000Z
207268187
s2ag/train
Studies on Salivary Phosphatases III. On the Possible Relation Between Salivary Alkaline Phosphatase Activity and Gingival Inflammation. T H E ACRYLIC RESIN TOOTH IMPLANT. III. A CONTINUING REPORT Ashman, A. J. Prosthet. Dent., 29:549, May, 1973 No attempt was made to produce a porous polymer or to effect connective tissue ingrowth into the polymer, but rather to evalu­ ate the biocompatibility of one polymer. Plastic implants were placed into each quadrant of a healthy adult male German Shep­ herd dog approximately 45 minutes after extraction of a tooth at one-month time intervals, and stabilized immediately with a cold curing acrylic resin splint. Clinically there was minimal mobility, pocketing of 2 to 3 mm. and heavy calculus formation. The dog was sacrificed after 6 months and block sections were prepared. Histologically the implants were surrounded by fibrous connective tissue in which the collagen fibers tended to align parallel to the long axis of the implant. In addition there was no evidence of downward epithelial invagination. Osteoblastic and osteoclastic activity was found with the latter predominating in certain areas. Radiographically there was no evidence of alveolar bone loss. 200 Central Park South, New York, New York 10019. HODGKINS DISEASE OF MAXILLA Tiwari, R. M . J. Laryngol. and Otol., 87:85, January, 1973 Hodgkins Disease was described in a case report of a rare malignancy in the maxilla of a 40-year-old male with a six month history of left-sided nasal obstruction and epistaxis along with complaints of palatal swelling and toothache over the maxillary left molars for the previous three months. His clinical symptoms were slight swelling and puffiness under the left eye, an ulceroproliferative mass involving the left maxiliary alveolus, and loosening of the left lateral incisor, cuspid, and molar teeth. The left nasal cavity was filled with a proliferative mass and the sep­ tum was deviated to the right. The rest of his ears, nose, and throat were healthy except for soft, mobile, and palpable upper left deep cervical nodes. The patient was treated with Cobalt 60 radiation therapy for six weeks and later the residual disease was removed by a left palatal fenestration procedure. Bones are affected in less than 15 per cent of cases of Hodgkins Disease, and the maxilla is least common of all. Academisch Ziekenhuis, Paramaribo, Suriname, South America.
v2
2018-04-03T04:07:31.059Z
1974-07-01T00:00:00.000Z
37763110
s2ag/train
Osteomyelitis appearing as neoplasms. A diagnostic problem. Twenty-three patients with subacute or chronic osteomyelitis in whom the differential diagnosis between osteomyelitis and bone tumor was difficult were selected for presentation from a group of patients seen at Mayo Clinic between 1953 and 1972. Two thirds of the patients were in the younger age groups, and two thirds of the lesions were in the long bones of the lower extremities. The most common tumor suspected was Ewing sarcoma, followed by osteogenic sarcoma. Other suspected neoplasms were reticulum cell sarcoma, leukemia, osteoid osteoma, benign cyst, and chondromyxoid fibroma. Seven illustrative cases are presented. The best clinical method for establishing the correct diagnosis was the taking and retaking of a careful history. Treatment should never be instituted without a biopsy examination that includes an adequate amount of periosteum, cortical bone, and medullary tissue. A needle biopsy examination may not provide these.
v2
2018-04-03T05:57:23.525Z
1974-07-01T00:00:00.000Z
20137968
s2ag/train
AUTOMATED ANALYSIS OF DEOXYRIBONUCLEIC ACID, PROTEIN AND NUCLEAR TO CYTOPLASMIC RELATIONSHIPS IN TUMOR CELLS AND GYNECOLOGIC SPECIMENS Quantitative two-color fluorescence staining techniques, coupled with flow system multiparameter cell analysis and sorting instrumentation, have been used for rapid, simultaneous determination of deoxyribonucleic acid, protein, nuclear (N) and cytoplasmic (C) diameters and N:C ratios in mammalian tumor cells and human gynecologic specimens. Cells stained in suspension for deoxyribonucleic acid and total protein content, respectively, with propidium iodide (red fluorescence) and fluorescein isothiocyanate (green fluorescence), enter a flow chamber and intersect an argon laser beam which excites cellular fluorescence. Optical sensors measure both red and green fluorescence plus the time duration of each fluorescence signal which is proportional to nuclear and cytoplasmic diameters, respectively. The resulting signals are processed and displayed as frequency distribution histograms using a multichannel pulse height analyzer. Cells are also sorted based on N:C ratios. Illustrative examples of preliminary two-color fluorescence analysis and sorting of mouse squamous tumor cells and human exfoliative vaginal cells are presented.
v2
2018-04-03T05:58:24.482Z
1974-07-01T00:00:00.000Z
45040032
s2ag/train
Competition for ADP between pyruvate kinase and mitochondrial oxidative phosphorylation as a control mechanism in glycolysis. To assess a possible role of pyruvate kinase as a site for respiratory and glycolytic interaction, competition for ADP between pyruvate kinase and respiratory phosphorylation was measured in a model system consisting of rat liver mitochondria respiring in the presence of pyruvate kinase, phosphoenolpyruvate, ATP, and an ADP-regenerating system consisting of glucose and purified yeast hexokinase. This system allowed determination of total ATP production, equivalent to ADP utilization, by measuring glucose 6-phosphate formation; ADP utilization by pyruvate kinase by pyruvate formation; and respiratory ADP utilization by Pi uptake. O2 uptake was measured by means of an oxygen electrode. In the presence of a respiratory substrate such as succinate or glutamate-malate, the addition of pyruvate kinase and phosphoenolpyruvate reduced O2 uptake as well as oxidative phosphorylation about 80%. Respiration was increasingly inhibited with increasing pyruvate kinase, and this inhibition was decreased with increased hexokinase or ATP. Mitochondrial respiratory inhibition by pyruvate kinase and phosphoenolpyruvate was accompanied by an increase in the ATP/ADP ratio from 0.3 to 32. These inhibitory effects of pyruvate kinase on respiration were abolished by addition of 2,4-dinitrophenol. These results are in acccord with a role of pyruvate kinase as a determinant of glycolytic activity by competing with oxidative phosphorylation for the available ADP; and provide additional support for our previous suggestion that high glycolysis of certain tumors may be attributable to their extraordinarily high pyruvate kinase activity.
v2
2019-08-20T02:01:59.877Z
1974-07-01T00:00:00.000Z
221486179
s2ag/train
The pathology of lymphangioma eireumscriptum The role of B and T lymphocytes in nineteen patients with classical Alibert's mycosis fungoides (MF) was studied. In general there was no evidence of immune depression, not even in those who had had the disease for many years. The distribution of B cells in the peripheral blood was normal. No immunoglobulin bearing lymphocytes were detected in freshly liberated cells from the skin lesions, or on direct immunofiuorescence of those lesions. The mean serum IgE level was elevated even though most of the patients were not atopies. Auto-antibodies were detected in a large proportion of patients. Two cases of malignant lymphoma and one of Sezary syndrome contrasted strikingly with the MF group. Our results favour MF being a reactive granuloma to some persistent, probably exogenous, antigen. Malignancy, if it arises, is a direct consequence of this continued antigenic stimulation.
v2
2019-08-20T04:25:13.464Z
1974-07-01T00:00:00.000Z
209149352
s2ag/train
Scintigraphy of Trunk and Superficial Tumours Eighty-six patients, who had either p r imary tumours or metastases in subcutis or in parenchymatous organs, were admitted to the isotope laboratory for selenite scanning. In all, 88 scans were performed, including 23 chest scans, 32 scans of the abdomen and pelvis, 21 of the head and neck, and 12 of the extremities. Only one patient had a non-tumorous lesion, a swelling in the neck which was at first suspected of being mal ignant but which proved to be an abscess. The series of malignant cases comprised 64 p r imary tumours and 23 second­ aries. In 63 cases, histologic, and in 10 cases, cytologic diagnosis was obtained. In 3 cases the roentgen examination revealed evident signs of metastases in the lung and there was histologic diagnosis of the p r imary tumour. One case of vena cava compression had only clinical and roentgen diagnosis of the mediastinal tumour. In 10 cases the diagnosis of the scanned lesion was based on clinical findings. They comprised 3 axillary and 2 inguinal metastases and 5 metastases in the head and neck. The pr imary tumours were diagnosed histologically.
v2
2018-04-03T03:17:58.081Z
1974-07-08T00:00:00.000Z
1674011
s2ag/train
Acute monarticular arthritis following patellar metastasis. A manifestation of carcinoma of the lung. METASTATIC neoplasm to the patella is unusual, and a monarticular arthritis related to such a lesion appearing as the initial sign of a previously unrecognized carcinoma must be rare indeed. In most cases of arthritis associated with malignant neoplasms, the underlying tumor is evident. We describe a patient with monarticular arthritis secondary to metastatic patellar spread of bronchogenic carcinoma as the earliest symptom of his primary tumor. Report of a Case A 63-year-old man was admitted to the hospital for evaluation of arthritis in the left knee. The patient had been initially hospitalized at a sanatorium in 1968 for suspected pulmonary tuberculosis; sputum cultures were negative. In spite of this, he received triple antituberculous drug therapy for one year. Three months before his final admission, he noted pain in the left knee, following a fall. The knee became increasingly swollen until he was unable to bear weight. Chest x-ray films
v2
2018-04-03T03:25:37.092Z
1974-07-15T00:00:00.000Z
5925854
s2ag/train
Studies on a gross‐virus‐induced lymphoma in the rat. I. The cell‐mediated immune response The Gross virus‐induced lymphoma (C58NT) D, which was originally induced in the thymus of W/Fu rats, has been shown to be a virus‐releasing tumour with no detectable θ antigen or surface Ig. It is rapidly malignant in immunosuppressed rats with an LD50 of approximately 100 cells, but is strongly immunogenic in intact adult rats, inducing both long‐lasting immunity in vivo and a vigorous cell‐mediated immune response in vitro. A tumour challenge was rejected in an immune fashion within a maximum of 142 days after primary immunization, with the most rapid rejection at 9 and 62 days after immunization. CMI measured in an in vitro Cr51 release assay showed a sequential appearance in draining lymph nodes, thoracic duct lymph and the spleen with peak activity in days 6, 7 and 10 after immunization, followed by a rapid decline in activity. Spleen cells taken on the day of peak CMI adoptively conferred protection against tumour growth in vivo. The CMI response in vitro was shown to be specific for MuLV‐induced tumours, both by studying Cr51 release from a variety of tumour cells in the presence of immune spleen cells, and by comparing the ability of various unlabelled tumour cells to inhibit the lysis of Gross‐virus induced lymphoma cells by immune spleen cells. In addition purified Gross virus itself, but not NDV, was found to inhibit CMI in vitro. The effector cell in CMI in vitro was not removed by procedures which selectively depleted immune spleen cells of adherent and phagocytic cells and B lymphocytes. However, the removal of T lymphocytes either prior to immunization by thymectomy, irradiation and marrow reconstitution, or from immune spleen cells by the use of a specific antiserum, abrogated the CMI response. These results indicated that the effector cell in the in vitro assay was a T lymphocyte.
v2
2017-08-17T03:11:33.408Z
1974-07-27T00:00:00.000Z
21950738
s2ag/train
Clinical Importance of Infections due to Bacteroides fragilis and Role of Antibiotic Therapy Out of 200 infections due to Bacteroides fragilis occurring over a period of three years 133 were related to the intestinal tract, 55 to the genitourinary tract, and the remainder were in bedsores and ulcers; 56% occurred in patients undergoing major intestinal surgery. B. fragilis was isolated in pure culture from 56% of the infections. In mixed culture it was most commonly associated with Klebsiella and Enterobacter species. Other anaerobic bacteria were isolated in 9% of the mixed cultures. Altogether 131 (65·5%) of the patients recovered without antibiotic therapy or further surgery, but 59 (29·5%) developed complications and 10 (5%) died. The commonest complication was abscess formation, and the incidence was highest with infections associated with malignancy (44%) and lowest with obstetric infections (5%). The mortality was 5% overall but in the presence of bacteraemia it rose to 33%. Only 43 patients received appropriate chemotherapy. Clindamycin was the most effective antibiotic, having a recovery rate of 78%, but this rate was little better than in untreated patients (65%). The role of prophylactic antibiotic therapy in preventing bacteroides infection remains to be studied. The incidence of the isolation of bacteroides from wound infections after major intestinal surgery rose from 13% in 1970 to 81% in 1973. This increase was due to both the accurate collection and care of specimens while in transit to the laboratory and the use of selective media for the isolation of bacteroides in laboratory culture. The importance of these precautions is emphasized.
v2
2017-04-08T00:27:41.646Z
1974-08-01T00:00:00.000Z
16150424
s2ag/train
Cross-reacting tumor-associated antigen(s) of adenovirus type 9-induced fibroadenomas and a chemically induced mammary carcinoma in rats. Cross-reactivities among tumor-associated antigens of rat mammary fibroadenomas and among these fribroadenomas and a rat mammary carcinoma were investigated by in vitro techniques. Lymphocytes from five female W/Fu rats bearing mammary fibroadenomas were found to share a common reactivity against fibroadenoma target cells, as demonstrated by lymphocyte cytotoxicity tests on iododeoxyuridine-125I-labeled target cells and by microcytotoxicity tests. These lymphocytes were also cytotoxic to target cells derived from a rat mammary carcinoma induced by 3,2′-dimethyl-4-aminobiphenyl. Inversely, lymphocytes from a female W/Fu rat bearing this 3,2′-dimethyl-4-aminobiphenyl-induced mammary carcinoma were cytotoxic to the carcinoma and the fibroadenoma target cells. Neither the immune lymphocytes from fibroadenoma-bearing rats nor those from the rats with the mammary carcinoma were cytotoxic to polyoma virus-induced sarcoma cells or to normal rat breast cells. Neither immune lymphocytes from rats with polyoma tumors nor those bearing chemically induced colon carcinomas demonstrated cellular immunity against either mammary fibroadenoma or mammary carcinoma target cells. Sera from each of the fibroadenoma-bearing rats inhibited the cytotoxic effect of lymphocytes from rats bearing fibroadenoma or carcinoma against both mammary fibroadenoma and carcinoma target cells. Sera from the rat with the 3,2′-dimethyl-4-aminobiphenyl-induced mammary carcinoma inhibited the activity of its own lymphocytes on either fibroadenoma or carcinoma target cells. They also blocked the cytotoxicity of fibroadenoma-immune lymphocytes to fibroadenoma or to carcinoma target cells. The blocking sera of mammary fibroadenomatous and carcinomatous rats did not inhibit the cytotoxic effect of lymphocytes from polyoma sarcoma-bearing rats against polyoma tumor cells. Additionally, sera from rats with either polyoma virus-induced tumors or colon carcinomas, which blocked in their respective systems, did not inhibit the in vitro activity of mammary fibroadenoma or carcinomaimmune lymphocytes on mammary fibroadenoma or cacinoma target cells. These results indicate a common tumor-associated antigenicity among the mammary fibroadenomas and a shared (tissue type-specific?) antigen between the mammary fibroadenomas and the chemically induced mammary carcinoma.
v2
2017-04-13T03:38:22.430Z
1974-08-01T00:00:00.000Z
14751646
s2ag/train
Cerebral reticulum cell sarcoma after multiple renal transplants1 A case is reported of a 34 year old white male with chronic renal failure secondary to glomerulonephritis who received four renal transplants over a period of five years. He died 25 months after the fourth transplant. Necropsy revealed a reticulum cell sarcoma-microglioma of the brain. The possibility that multiple transplants may have had a synergistic effect in the development of a malignant cerebral lymphoma in this patient is briefly discussed in the light of the current theories concerning the pathogenesis of the tumours in transplant recipients and in the context of the present therapeutic approach to graft rejection.
v2
2017-04-13T15:42:29.252Z
1974-08-01T00:00:00.000Z
15216795
s2ag/train
67Ga binding to human serum proteins and tumor components. 67Ga is known to concentrate in a variety of malignant tumors. Immunoelectrophoresis combined with autoradiography of human serum incubated with 67Ga showed that the radionuclide is associated with transferrin, apart from a weak binding to β-lipoprotein. The thermodynamic constant for gallium was estimated and indicated that gallium citrate in the presence of serum proteins occurred in a colloid form bound to transferrin. Ultracentrifugation of tumor homogenates obtained from patients who had received i.v. injections of 67Ga citrate for scintigraphy demonstrated that 67Ga is preferentially bound to proteins in the nuclei fraction. Acrylamide gel electrophoresis of extracts of cancer tissue indicated that intracellular 67Ga is associated mainly with a fast-migrating substance, perhaps a protein, with a molecular weight lower than that of ferritin.
v2
2017-04-19T22:50:44.368Z
1974-08-01T00:00:00.000Z
15681706
s2ag/train
Correlation of in vivo and in vitro assays of immunocompetence in cancer patients. Of 52 cancer patients studied for their in vitro response in lymphocyte blastogenesis assays, 50 were also studied for immunocompetence by in vivo assays. The in vivo assays used were the delayed cutaneous hypersensitivity reaction to the primary stimulus of 2,4-dinitrochlorobenzene (DNCB), and the recall reactions to four common microbial antigens. The in vitro assays were the blastogenic response to three mitogens (phytohemagglutinin, pokeweed mitogen, concanavalin A) and the mixed lymphocyte culture (MLC) reaction. The carcinoma patients demonstrated an apparent impairment of skin test reactions, but the least impairment of their lymphocyte blastogenesis reactions. The melanoma patients had notable defects in lymphocyte function tests but less impairment of the skin test reactions. Results for sarcoma patients were intermediate in both in vivo and in vitro assays. When the patients were grouped according to response to DNCB, no significant differences in responses to mitogens between the DNCB reactors and nonreactors were observed. However, the DNCB nonreactors had markedly reduced responses in MLC. Those patients with a poor response in recall antigen skin tests showed a diminished response in MLC and also a reduced response to the mitogens. It is postulated that antigen recognition defects can exist in cancer patients that can be detected by the DNCB or MLC tests. Additionally, there may be lymphocyte proliferation defects demonstrable in patients with certain histopathologies of cancer, especially melanoma, or in those in whom secondary immune responsiveness, as reflected by recall antigen skin tests, is impaired. These data suggest that the mitogen concanavalin A and the MLC are probably more useful screening assays of in vitro immunocompetence than is the more commonly used mitogen, phytohemagglutinin.
v2
2017-06-23T22:20:16.524Z
1974-08-01T00:00:00.000Z
1347053
s2ag/train
Secretion of parathyroid hormone in patients with medullary thyroid carcinoma. The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor.
v2