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Biomedical subjects

K Perk

Publications and source records attributed to K Perk.

At least 55 records · Page 3Linked to original sources

Male sterility in the domestic fowl (Gallus domesticus) after 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitroso-trans-urea (NSC-95441) treatment of chicks.

Of 11 male baby chicks treated twice with 3 mg of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitroso-trans-urea (once on the day of hatching and once on the day after), 9 showed absolute lack of spermatogenesis and 2 showed severe inhibition when examined at the age of 6 months. Plasma testosterone level was not altered, however, and histologic examination revealed well-organized testicular interstitial tissue with an abundance of Leydig's cells. In the lining of the seminiferous tubules only Sertoli's cells were present. The weight of the testes from treated animals was only about 10% of control weight. These findings emphasized the possibility that the nitrosoureas cause severe damage to the reproductive system in man.

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Characterization of the oncornavirus particles in the plasma of guinea pigs with L2C leukemia.

The inoculation of L2C guinea pig leukemia cells into strain 2 guinea pigs results in the death of the animals within 12 to 15 days. Death is preceded by the simultaneous appearance in the plasma of (i) elevated leukocyte levels, (ii) extracellular virus particles, and (iii) a particle-associated RNA-directed DNA polymerase. This enzyme activity has a cation preference identical to that of the type B bromodeoxyuridine-induced guinea pig virus, i.e., an Mg2+ optimum at 20 mM and no activity using Mn2+. Competitive molecular hybridization studies also revealed that the plasma of leukemic guinea pigs contained approximately 2 X 10(9) genome equivalents per ml of an RNA that is homologous to the RNA of the bromodeoxyuridine-induced guinea pig virus. Morphological observations indicate that most, but not all, of the extracellular particles observed in leukemia plasma are derived from the intracisternal particles seen in the L2C tumor cells. The possibilities that either two viral populations are present or that the in vivo morphogenesis of the type B bromodexoyuridine-inducible guinea pig virus is markedly different from its in vitro morphogenesis are discussed.

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Histological and combined chemoimmunostimulation therapy studies against a murine leukemia.

A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 times 10(6) tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2-week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug-treated animals. A significant number of long-term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol-extracted residue of BCG) to animals in a drug-induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MER alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long-term survivors. The implication of these results for cancer therapy is discussed.

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Some aspects of host response to levamisole after chemotherapy in a murine leukemia.

Levamisole (LMS), when used with an effective remission-inducing drug in leukemic mice, resulted in a high percentage of long-term survivors. Histologic examination of spleens from treated leukemic mice showed that LMS caused an earlier return of lymphoid cells in the splenic lymphoid follicles and lymphoid elements in the red pulp.

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Studies on a transplantable murine rhabdomyosarcoma.

Well-differentiated rhabdomyosarcomas developed in 8 of 10 BALB/c mice inoculated with cell-free extracts of two lesions arising in bats previously inoculated with the Moloney strain of murine sarcoma virus. The tumors could be transplanted in BALB/c mice and other strains of mice compatible at the H-2 locus. A tumorigenic clonal cell culture line (R2) was established from a transplanted tumor. Ultrastructural studies of the primary and transplanted tumors and R2 cells revealed thick and thin myofilaments characteristic of myoblasts. These cells contained numerous cisternal type-A virus-like particles, but no type-C particles were found. Attempts to recover, rescue, or chemically induce transforming or nontransforming viruses from transplantable tumors and the R2 cell line were unsuccessful. The tumor cells lacked the murine type-C virus gs antigen. Hybridization data confirmed the apparent lack of viral RNA in the tumor cells.

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Biochemical properties of the bromodeoxyuridine-induced guinea pig virus.

The biophysical and biochemical properties of the virus particles released by guinea pig embryo cells treated with 5-bromo-2'-deoxyuridine (BUdR) have been compared to those of the B-type mouse mammary tumor virus (MMTV) and the C-type Rauscher murine leukemia virus. The high-molecular-weight (60 to 70S) RNA of the BUdR-induced guinea pig virus (GPV) has a molecular weight of 8 X 106 when measred by mixed agarose polyacylamide gel electrophoresis. The virus particles isolated from the tissue culture medium of BUdR-induced guniea pig cells have the following properties in common with MMTV: (i) a buoyant density of 1.18 g/ml in sucrose and 1.21 g/ml in CsCl, and (ii) a DNA polymerase that prefers Mg2+ over Mn2+ in an assay using the synthetic template poly(rC):oligo(dG). No nucleic acid sequence homology between GPV RNA and the viral RNAs of the MMTV, murine leukemia virus, hamster sarcoma virus, or Mason-Pfizer monkey virus could be observed in a competition hybridization assay using the radioactive-labeled GPV 60 to 70S RNA. By this same competition by hybridization assay the frequency of GPV proviral sequences was estimated to be at least 83 per haploid cellular genome of guniea pig cells. No nucleic acid sequences related to be GPV RNA were detected in the DNA of normal tissues of mice, rats, cats, dogs, baboons, or humans by direct RNA-DNA hybridization using radioactive GPV60 to 70S RNA.

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Some pathogenic aspects of murine sarcoma virus (Moloney) in rats.

The oncogenic effect of the murine sarcoma virus (Moloney) was tested in rats. Host-age and virus-dose dependent variations in the pathogenic spectrum were found. Four tumour "stages" were described: progressively lethal; lethal after long stationary period; complete tumour regression; tumour reoccurrence after complete regression. Virus recovery was highest from the progressively growing tumours and in the reoccurred neoplasms, while no virus was found in stationary tumours or in those sites where regression had occurred. Tumour onset and death was more rapid and frequent when inoculation of the virus was in muscle-rich tissues. When inoculation was into different visceral organs or intravenously, tumour development still occurred primary in muscle tissue.

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Drug therapy against a transplantable guinea pig leukemia.

The effects of six clinically active drugs were tested against a ttansplantable leukemia in inbred strain 2 guinea pigs. Cytoxan and 6-mercaptopurine were found to elicit a therqeutic response against this leukemia based on complete tumor regression of the established tumor as well as a substantial increase in survival time. Animals dying in the untreated control and drug-treated groups revealed typical generalized lymphoblastic leukemia. However, only Cytoxan-treated animals that had relapsed exhibited central nervous system involvement originating from the arachnoid membrane. A tow-drug combination of Cytoxan and 1-(2-chloroethyl)-3(trans-4-methylcyclohexyl)-1-nitrosourea was found not only to prevent meningeal leukemia development but also to result in "curing" all animals from their leukemia. This observation was based on a complete clinical, hematological, and histopathological "remission" period up to 176 days. The administration of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea alone was observed not only to control the systemic leukemia but also to prevent central nervous system involvement. No relapses occurred after the first "remission" period was achieved in the groups of animals that received 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea.

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Murine intracisternal A type particles fail to separate from the membrane of the endoplasmic reticulum.

Analysis of serial sections of murine cells containing intracisternal A particles revealed that over 99% of all A particles remain in a budding configuration. This indicates that these particles fail to detach from the membrane of the endoplasmic reticulum. This observation explains how, despite their intracellular abundance in certain murine tumors, no extracellular A-type particles can be found.

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