Assay for cell tumorigenicity in subhuman primates treated with antilymphocyte globulin.
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Biomedical subjects
Publications and source records attributed to R L Kirschstein.
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Fifty percent of New Zealand white rabbits became profoundly weak, had generalized seizures and died between 22 and 47 hours after an intravenous injection of 1000 IU/kg of L-asparaginase. The biochemical correlate of this syndrome is severe hypocalcemia associated with marked, single cell, oxyphilic necrosis in the parathyroid glands. Although survivors remained clinically well, they also developed hypocalcemia and parathyroid necrosis but to a lesser degree. Rabbits given an equivolumetric amount of saline did not develop alterations in any of these parameters. L-Asparaginase, therefore, exerts a direct toxic effect on the parathyroid glands of rabbits. The implications of this finding for man are briefly discussed.
Measles virus isolated from the brain of a patient with subacute sclerosing panencephalitis was injected intracerebrally (ic) into 34 rhesus monkeys. Groups of these animals were injected with measles antigen in Freund's complete adjuvant or treated by schedules used for suppression of the general or cell-mediated immune responsiveness. In another group of animals, experimental allergic encephalitis was induced parallel with measles infection. Measles virus was isolated from the brains of monkeys up to 13 days after ic inoculation. No virus was detected in the central nervous system after 3 to 4 weeks, the longest postinoculation period examined. It was concluded that the subacute sclerosing panencephalitis-derived virus either lost its neurotropic properties at the passage level at which it was used or that it submerged into a silent stage and escaped detection. Neither immunosuppression nor concomitant autoimmune encephalitis had an effect on the survival of measles virus in the central nervous system. The histology of the nervous tissue was basically normal except for characteristic lesions of experimental allergic encephalitis in animals receiving the respective treatment.
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Avian leukosis virus (ALV)-free candidate primary and secondary seed lots were indistinguishable from corresponding ALV-contaminated lots with respect to (i) potency as measured by titration in newborn and weanling mice and in the MA-104 plaque system, (ii) degree of viscerotropism as measured by viremia in monkeys, (iii) neurotropism as determined by the monkey neurovirulence test, and (iv) potency as determined by antibody response in monkeys inoculated by the intracerebral route.
Analysis of large and small plaque mutants of simian virus 40 using antisera prepared against each has revealed quantitative and possibly qualitative antigenic differences for each plaque type. A sensitive micro radioisotope precipitation test permitted evaluation of immunochemical similarities and differences of capsid antigens by inhibition of precipitation.
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Takemoto, K. K. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), R. L. Kirschstein, and K. Habel. Mutants of simian virus 40 differing in plaque size, oncogenicity, and heat sensitivity. J. Bacteriol. 92:990-994. 1966.-Three mutants of simian virus 40 were isolated on the basis of the type of plaques produced in primary cultures of African green monkey kidney cells and designated as L (large), S (small), and M (minute) strains. Significant differences in oncogenicity for hamsters were observed, with the 50% oncogenic dose being 10(4.5) for the L, 10(5.2) for the S, and 10(5.8) for the M strains. All three strains were capable of transforming human diploid cells (W138 strain). At temperatures up to 41 C, the S and M mutants were capable of multiplying to titers almost equivalent to those obtained at 37 C. In contrast, infectious virus was not produced when cells were infected with the L mutant and were incubated at temperatures above 39 C, although complement-fixing viral and tumor antigens were formed. The temperature-sensitive phase of replication of the L strain was shown to be a late stage in viral maturation or assembly.