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Biomedical subjects

E S Raveche

Publications and source records attributed to E S Raveche.

45 records · Page 3Linked to original sources

Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/lpr mice.

MRL/lpr and NZB X NZW F1 mice were neonatally thymectomized or treated with androgens from 2 weeks of age, and their natural histories were studied. Neonatal thymectomy of MRL/lpr mice led to marked reduction in the usual massive lymphadenopathy as well as significant reduction in antibodies to native DNA and prolonged survival. In contrast, neonatal thymectomy of NZB X NZW F1 mice led to accelerated disease. Androgen therapy of both mice led to reduced anti-DNA and prolonged survival. This occurred in the MRL/lpr mice without significant reduction in lymphadenopathy. Taken together, these studies suggest that different T cell abnormalities may underlie the development of autoimmunity in MRL/lpr and NZB X NZW F1 mice, but that disease may be expressed through a common androgen-sensitive pathway.

Androgens↗

Approach to the study of the role of sex hormones in autoimmunity.

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNa are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization-induced antibodies to single-stranded DNA in NZB X NZW, NZB X C3H, NZB X CBA, NZB X DBA mice. Treatment of female NZB/W mice with testosterone or 5 alpha dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.

Age Factors↗

Studies of the effects of sex hormones on autosomal and X-linked genetic control of induced and spontaneous antibody production.

In these studies we investigated the modifying effect of sex hormones on both the levels of induced antibodies after immunization with single-stranded DNA (ssDNA) and the levels of spontaneously produced anti-T cell antibodies (NTA). To learn whether the responses were genetically determined or under hormonal regulation, we analyzed hybrids produced by crossing the autoimmune NZB strain with the nonautoimmune DBA/2 strain. For both anti-ssDNA and NTA, males usually had a lower response than females; this difference could largely be removed by castration of the males. Females given testosterone implants also had decreased antibody levels. The higher responses in females and suppression by testosterone were true for all mice studied except NZB mice. NZB mice appear to have an insensitivity to the suppressive effects of testosterone.

Animals↗

Apoptosis induction in fludarabine resistant malignant B-1 cells by G2-M cell cycle arrest.

A malignant B-1 cell line from a mouse model of CLL was resistant to fludarabine, but could be induced to undergo apoptosis by mitotic spindle inhibitors, colcemid or nocodazole, which blocked these cells in the G2-M phases of cell cycle prior to apoptosis induction. Bax mRNA levels increased with relative constitutive expression of bcl-2 mRNA levels. The mRNA levels of B-cell-specific-activator-protein (BSAP) decreased with colcemid treatment. This study shows that mitotic spindle inhibitors can induce apoptosis in fludarabine-resistant malignant B-1 cells by altering levels of bax/ bcl-2 ratio and BSAP which play different roles in cell cycle regulation and apoptosis induction.

Animals↗