Gestational changes in hamster adrenocortical function.
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Biomedical subjects
Publications and source records attributed to L Kilham.
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Adult thymectomy prevents the development of suppressor T cells without impairing the induction of immunologic tolerance to the same antigenic determinant. This finding demonstrates that the cellular mechanisms underlying immune suppression and immune tolerance are different.
Virus particles were detected within the nuclei and cytoplasm of odontogenic cells in the developing teeth of young hamsters infected with a small DNA virus (MVM). Disturbances of normal cytodifferentiation and organogenesis occurred as a result of viral multiplication. Virions were also observed in dense lysosome-like bodies of activated monocytes within the periodontal ligament and adjacent connective tissues. Fibrolytic and osteolytic lesions in the periodontal ligament and adjacent alveolar bone were associated with the inflammatory cell infiltrate.
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Ribavirin, a synthetic nucleoside with marked antiviral activity, induced developmental malformations when administered to pregnant hamsters by oral, intraperitoneal or intravenous routes. Abnormalities of the limbs, eyes and brain were the most common defects found in the hamster. Higher doses (about 10 x) were required to induce anomalies in rat embryos and the malformations were generally restricted to the head region. In both rats and hamsters oral administration of the drug seemed to be more teratogenic than administration by other routes suggesting that metabolism of ribavirin in the maternal gastro-intestinal tract and/or liver may change it into its active form.
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Ribavirin, when given to pregnant hamsters in relatively small single doses, induces congenital anomalies of limbs, ribs, eyes, and central nervous system, as well as fetal deaths. On the basis of these findings, caution should be used in giving ribavrin to women of child-bearing age.
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Exposure of pregnant hamsters on gestation day 8 to 40 or 41 degrees C for one hour caused an increased rate of resorption and a high frequency of exencephaly and encephalocele. Longer exposures often killed pregnant females. Hamsters that had fetuses with abnormalities usually experienced body temperature elevations of 3-4 degrees C above normal (37 degrees C).
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This study focused on the unique nature of K-virus pneumonitis in suckling mice. This process, rather than being a conventional pneumonitis, is characterized by viral replication and cytopathic effects restricted exclusively to pulmonary endothelium. The selective viral attack on this air-blood interface suggests that K-virus is an endotheliotrope that requires a richly oxygenated intracellular milieu for replication. This possibility has been explored by studies of the course of K-virus infection in suckling mice under conditions of normal (21 per cent), increased (40 per cent), and decreased (10 per cent) 02 content of inspired air. The absence of critical modulating influences of these varied environmental conditions rules out a significant role of tissue 02 concentrations as determinants of the selective tropism of K-virus.
During studies of transplacental virus infections in random bred hamsters purchased with timed pregnancies from three commercial dealers, spontaneous hemorrhagic necrosis of the central nervous system was seen in fetuses harvested near term. Ninety-seven pregnant hamsters from three colonies were examined during a 6-month period; this condition was seen in 25 of 41, 19 of 36, and five of 20 litters. Hamsters from another commercial colony were received, housed, and fed under the same conditions, but remained free of the disease. The pathological process was characterized by multiple spreading zones of edema, malacia, and hemorrhage. Lesions were restricted to neural tissues, including the retina and internal ear. Neuroepithelial proliferation with rosette formation, accompanying the destructive process, constituted a striking reparative response. No inflammatory reaction or cytopathic effects suggestive of virus-induced disease were seen. Studies on the cause of this condition were negative at the time when the disease disappeared spontaneously.
Groups of BALB/c mice were treated with various conjugates of 2,4 dinitrophenyl (DNP) and BALB/c myeloma proteins belonging to the four subclasses of IgG (IgG1, IgG2, IgG2b, IgG3). Immediately therafter, they were challenged with DNP-keyhole limpet hemocyanin in complete Freund's adjuvant and antibody to the hapten was measured by direct and indirect hemolytic plaque assay. The results show that all subclasses of IgG are effective as tolerance-inducing carriers. However, the ability of induce tolerance is dependent upon the concentration of hapten bound to each myeloma protein. Tolerogenic conjugates suppress both direct and indirect plaque-forming cells in all types of antibodies measured (IgG1, IgG2a, IgG2b, IgGa), whereas, non-tolerogenic conjugate failed to suppress them. The intact molecule of IgG but not its fragments (Fab, F(ab)2', Fc) appear necessary as tolerance-inducing carriers. It is suggested that the ability to induce tolerance is related to the capacity of the tolerogenic conjugates to cause receptor blockade.
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The abilities of a low-passage strain and of a live, attenuated vaccine strain of mumps virus to induce congenital hydrocephalus in hamsters were tested by intraamniotic inoculation on the 10th day of pregnancy. Examination of term fetuses and neonates, with cytoplasmic inclusions, cytopathic effects, and specific immunofluorescence used as indicators, demonstrated an oronasal portal of entry for both strains. The vaccine strain appeared to be more pathogenic; it spread primarily into the respiratory tract and hence to the central nervous system. Inclusions were observed as long as 21 days after inoculation. Hydrocephalus and ependymal involvement, potentially capable of producing aqueductal stenosis, were observed in 19 of 81 animals studied 11-29 days after inoculation.