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Biomedical subjects

A Koestner

Publications and source records attributed to A Koestner.

At least 73 records · Page 4Linked to original sources

Comparative aspects of nuclear proteins and nuclear composition of cultivated embryonic, neonatal and neoplastic rat brain cells of glial origin.

Differences in nuclear composition and variations in the types of acid soluble nuclear proteins were identified when cultivated neoplastic and nontransformed rat brain cells were compared. HeLa S-3 cells were used as a biological reference in these studies. The nuclei of anaplastic glioma cells were found to contain more total nuclear protein and greater amounts of nuclear RNA, than the nuclei of nontransformed embryonic and neonatal rat brain cells. Densitometer profiles of samples developed by polyacrylamide gel electrophoresis indicated that all three major histone classes were present in the nuclei of the four different cell types examined. Each type of cell was grown in the presence of 3H-lysine or 3H-lysine plus 14C-arginine to further characterize both the histones and the acid soluble nonhistone proteins. Neoplastic and nontransformed cells contained similar quantities of histones H4, H3, H2A and H2B. In contrast, transformed cells were found to contain two dominant subspecies of lysine rich H1 histone, while only one histone H1 subcomponent was extracted from the nuclei of the embryonic and neonatal rat brain cells. Nuclei isolated from HeLa cells and anaplastic glioma cells also contained increased varieties and larger quantities of acid soluble nonhistone nuclear proteins.

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Host factors affecting perinatal carcinogenesis by resorptive alkylnitrosoureas in rats.

Host factors are operative in transplacental carcinogenesis. There are species, strain, sex, and individual differences in susceptibility to carcinogens. Rat fetuses are over 50 times more susceptible than adults to the oncogenic effects of ENU, yet are less susceptible to tumor induction with DMN. Immune mechanisms do not seem to affect the latency period, incidence, location, and type of neurogenic neoplasms, although tumor-specific antigens are demonstrable in neoplastic neuroectodermal cells. Although placental barriers, DNA repair capacities, age at exposure, hormonal interaction, and immune responsiveness may be singled out as possible causes for species, strain, sex, and individual variations in susceptibility to the neuro-oncogenic potential of ENU, no definitive proof of the mechanism of action of any of these factors has yet been presented.

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Canine distemper virus-associated encephalitis: modification by passive antibody administration.

Gnotobiotic puppies were intraperitoneally infected with R252-canine distemper virus (CDV), and treated with normal serum (NS) or CDV-specific antibody. Resultant central nervous system (CNS) lesions were evaluated by light and immunofluorescence microscopy. Lesions in NS-treated dogs, if present, consisted of small foci of neuronal degeneration and accompanying microgliosis, restricted to grey matter of the frontal lobe. Dogs receiving anti-CDV antibody, in contrast, had extensive lesions in the brain. Laminar cortical necrosis, gliosis and astrocytic activation of the grey matter of the frontal lobe was the most consistent lesion observed. In addition, foci of cerebellar granule cell layer degeneration and necrosis was seen along with segmental poliomalacia of the spinal cord. In several dogs, eosinophilic intracytoplasmic and intranuclear viral inclusion bodies were observe in neurons. The lesions observed in these dogs are compared to previously reported lesions of CDV infection in dogs.

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Canine distemper virus and multiple sclerosis.

Serum samples from patients with multiple sclerosis (M.S.), patients with subacute sclerosing panencephalitis (S.S.P.E.), and controls were examined for virus-neutralising antibodies against measles virus (M.V.) and 2 strains of canine distemper virus (C.D.V.). M.S. and S.S.P.E. patients had higher M.V. antibody titres than controls. In contrast, no significant differences were observed in mean C.D.V.-neutralising antibody titres between M.S. patients and controls. The results, though obtained from a small number of patients, fail to implicate C.D.V. in the aetiology of M.S.

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Influence of transplacentally acquired antibody on neonatal susceptibility to canine distemper virus in gnotobiotic dogs.

In utero acquistion of protective levels of neutralizing antibody to canine distemper virus (CDV) was observed in four litters of colostrum-deprived gnotobiotic and specific-pathogen-free puppies. Pregnant bitches with high antibody titers passively transferred antibody to these pups transplacentally in average titers of 1:7 to 1:16 per litter. Maternally derived antibody protected neonatal pups from otherwise fatal infection with virulent CDV. Protection was associated with a transient lymphopenia and viremia and temporary suppression of lymphocyte responses to phytohemagglutinin-P.

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Syncytia inhibition by immune lymphocytes: in vitro test for immunity to canine distemper.

A simple and rapid (24-h) assay for peripheral blood lymphocyte-associated immunity to canine distemper virus (CDV) is described. The test is based upon leukocyte-associated inhibition of CDV-induced syncytia formation in Vero cells. The technique quantitates the response morphologically, thereby eliminating the requirement for release of radiolabeled compounds. Positive results were determined from specific-pathogen-free and gnotobiotic dogs exposed to CDV via hyperimmunization, vaccination with a modified live virus vaccine, and after virulent virus infection. Preinoculation lymphocytes and lymphocytes from non-immune dogs did not inhibit CDV-induced syncytia formation. Maximum responses were observed 7 to 21 days after initial exposure and declined thereafter. The method can be used to further investigate the role of immune lymphocytes in the recovery from CDV infection.

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Increased susceptibility to feline leukemia virus infection in cats exposed to methylnitrosourea.

Exposure of adult specific-pathogen-free cats to methylnitrosourea resulted in increased susceptibility to infection by feline leukemia virus. A greater proportion of cats exposed to methylnitrosourea and feline leukemia virus (69%) became persistently viremic than those exposed to feline leukemia virus alone (17%). Segmented neutrophils were reduced by 90 to 99% within 3 days following exposure to methylnitrosourea, (15 to 20 mg/kg) whereas the effects on lymphocytes and erythrocytes, although less obvious, were also detected.

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Chemical carcinogenesis and immunity: immunologic status of rats treated with methylnitrosourea.

During the treatment of outbred Sprague-Dawley rats with methylnitrosourea (MNU) or the noncarcinogenic analog diphenylnitrosamine, antibody levels to teichoic acid as well as several parameters of lymphocyte and macrophage function were assessed in animals not overtly stimulated with antigen. Treatment with MNU did not appear to alter most immunologic parameters studied. Some alterations occurred in natural antibody levels, in spleen weight, and in peripheral blood differentials of rats that had received the highest carcinogen dose (4.5 mg/kg). These alterations, however, appeared to coincide with the development of tumors and were not observed in animals with premalignant lesions. Levels of chemical carcinogens that were capable of inducing tumors did not necessarily suppress the immune response.

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Evaluation of B-lymphocyte levels and functions in gnotobiotic dogs.

Quantitative and qualitative aspects of B-lymphocyte functions in gnotobiotic dogs and conventional dogs were determined. Using 3 different methods to identify B-cells by surface markers and 3 different methods to measure immunoglobulins (eg, serum electorphoresis, immunoelectrophoresis, and radial immunodiffusion), it was determined that gnotobiotic dogs were B-cell deficient. Related studies, however, indicate that the capacity to develop humoral immune responses was unimpaired. It is presumed that lack of immunogenic stimulation within the gnotobiotic isolation units accounts for this observation.

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Procedure for processing of central nervous system tissue for immunofluorescence, light, and electron microscopic evaluation.

A rapid and simple procedure has been developed for the simultaneous localization of viral antigen in central nervous system tissues by immunofluorescnece and concomitant correlation with viral induced lesions in the contralateral brain hemisphere. In this study, one-half of the brain was excised from the dog under deep general anesthesia and samples were collected for immunofluorescence by snap freezing in liquid nitrogen. The other half of the brain was perfused under pressure with a buffered glutaraldehyde-paraformaldehyde mixture for subsequent light microscopic and ultrastructural evaluation. The technique was useful in studying central nervous system diseases in large outbred experimental subjects in which economic and other considerations developed for tissue processing in rodents was not feasible.

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Derivation and maintenance of gnotobiotic dogs.

Revised techniques for derivation and maintenance of gnotobiotic dogs for research purposes were outlined. Gravid uteri were removed from pregnant beagle bitches and passed through a germicidal trap into a flexible plastic isolation unit. Pups were raised on a milk replacement diet and weaned to solid food by 4 weeks of age.

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Morphology and pathogenesis of tumors of the thymus and stomach in Sprague-Dawley rats following intragastric administration of methyl nitrosourea (MNU).

Intragastric intubation of MNU (20 mg/kg twice weekly for 9 weeks) into young Srague-Dawley rats resulted in a 100% incidence of thymic lymphomas and gastric carcinomas in animals surviving more than 14 weeks. Progressive thymic atrophy followed the successive MNU administration culminating in marked lymphoid depletion by the 5th week of MNU treatment. At 6 weeks, repopulation of the thymus with lymphoblastic cells was observed, which progressed to thymic neoplasia. The first thymic lymphoma appeared at the 6th week. By the 15th week all rats were either moribund or had succumbed to anoxia caused by pleural effusions associated with thymic neoplasia. Twenty-six of 31 thymic tumors were classified as lymphocytic lymphomas, 2 as histiocytic, 1 as mixed lymphocytic-histiocytic, 1 as bimorphic and 1 as an epithelial thymoma. All but 2 lymphomas were restricted to the thymus. Of these 2 (both histiocytic lymphomas), 1 involved the spleen, liver and abdominal lymph nodes and the other infiltrated locally into cervical and thoracic regions. Significant thymic enlargement occurred only after MNU treatment was stopped (MNU acting as an anti-cancer drug). The gastric carcinomas were restricted to the non-glandular portion of the stomach and developed as a final step following ulceration, hyperplasia and neoplastic transformation. The short latency period and the high incidence of thymic neoplasms represent valuable criteria for future use of this model for pathomorphogenetic as well as immuno- and chemotherapeutic investigations.

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Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system.

Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas. This could not be attributed solely to zones of regression or necrosis but was a general characteristic of the neoplasms. The activities were predominantly particulate and most likely lysosomal in localization. In schwannomas a similar increase in hydrolases was found in comparison with normal neural tissues but aryl-sulfatase was not increased. Cytochrome oxidase activities were markedly reduced in all tumors studied. The proportionate reduction with respect to normal brain was comparable to that noted in man. No differences were found with respect to fairly well differentiated gliomas.

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Diagnosis of experimental encephalitozoonosis in rabbits by complement fixation.

A complement-fixation (CF) test has been developed for detection of experimental encephalitozoonosis in rabbits. The antigen consisted of disrupted homogenates of Encephalitozoon cuniculi spores grown in and released from rabbit choroid plexus tissue culture cells. The test was sensitive and capable of detecting experimental encephalitozoonosis in rabbits as early as 15 days after intracerebral infection. The test was specific for infected animals, and no cross-reactivity was demonstrated between E. cuniculi antigen and Nosema apis, Trypanosoma congolese, Trypanosoma cruzi, rabbit liver powder, rabbit brain powder, and rabbit choroid plexus cell culture. Sera from rabbits infected with Toxoplasma gondii, Eimeria stiedai, and Eimeria perforans did not exhibit antibodies to E. cuniculi. No CF-inhibition activity was detected.

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