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E Simpson

Publications and source records attributed to E Simpson.

At least 181 records · Page 10Linked to original sources

Expression of H-Y antigen by female mice carrying Sxr.

The minor transplantation antigen H-Y can cause graft rejection and can stimulate the generation of H-2-restricted T cell responses. We have used both responses to type karyotypically abnormal mice for the presence of H-Y antigen, in order to investigate the role of H-Y in sex determination. The mice under scrutiny were Sxr5-carrying females derived by crossing females carrying the T(16;X)16H translocation with Sxr carrying males. These females were fully fertile and were H-Y positive. These results are consistent with the testis determining gene, Tdy, which may or may not be H-Y, having a threshold effect on testis differentiation during embryogenesis. They also show that the presence of H-Y in adult females does not impair reproduction.

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Dermatoglyphic analyses of 32 parents of Prader-Willi syndrome individuals.

Dermatoglyphic analyses were performed on 22 mothers and 10 fathers of 24 PWS individuals (32 normal relatives). The frequency of fingertip patterns in the parents was the same as in their PWS offspring with respect to a decrease in ulnar loops, and this decrease was significant when compared with controls (P greater than 0.01). It was more marked in the fathers than in the mothers. The fingertip arches and whorls were more evenly redistributed in the parents than in their PWS offspring. The TFRC of the parents showed a positive correlation with the TFRC of the PWS offspring (P less than 0.01). These data indicate heritability of the fingertip dermatoglyphics. No heritable traits were found in the palmar dermatoglyphic configurations. The fathers showed palmar anomalies greater than in control males (P less than 0.05).

Adult↗

Review lecture. Immunology of H-Y antigen and its role in sex determination.

H-Y was originally discovered as a transplantation antigen that caused female mice of certain inbred strains to reject skin from otherwise identical males. The ability to make the skin graft rejection response and, in vitro, cytotoxic T cell responses against H-Y is controlled by genes within the major histocompatibility complex, H-2, and by non-H-2 genes. H-Y belongs to a class of weak transplantation antigens characterized by an inability to elicit responses under many conditions. Although genetic factors are very important in determining responsiveness, their action can be modified by immunization procedures. H-Y has been proposed as the differentiation signal that causes the formation of the testes from the undifferentiated gonad in the developing embryo. This hypothesis has been explored by using a series of mice whose karyotype and phenotypic sex are paradoxical.

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H-Y typing of karyotypically abnormal mice.

It has been proposed that the male-specific transplantation antigen H-Y is the trigger for testis formation (Ohno's hypothesis). We have tested this hypothesis by examining the H-Y status of a number of mice with abnormal or aberrant karyotypes relative to their gonad development. This analysis includes the discussion of published results of XX males carrying the Sxr mutation and XO females, and the presentation of unpublished data from XY females carrying the YPOS or YORB chromosome, XY females carrying Thp on chromosome 17, and a series of mice carrying X-Y recombination products derived from the Y* chromosome. The XX Sxr males have testes and are H-Y transplantation antigen positive; XO females have ovaries and are H-Y negative; mice with X-Y reciprocal recombinant chromosomes resulting from an abnormal Y chromosome show concordance between the presence of testes and the presence of the H-Y antigen. All of these findings are in accord with Ohno's hypothesis. In contrast are our findings that three types of C57BL/6J XY females are H-Y positive, two inheriting a Y chromosome from the mouse species Mus domesticus, either YPOS or YORB, and the other a mutation associated with Thp. Genetic analysis of the inheritance of this paradoxical phenotype indicates that normal testis differentiation involves the interaction of two or three genes, and is not simply a function of a Y-linked gene product. We conclude that H-Y is not the sole Y-linked testis determining gene.

Animals↗

Genetic control and effector cells in host-versus-graft responses to H-Y antigen in mice.

T cell responses to the male-specific H-Y antigen in mice include skin graft rejection, delayed-type hypersensitivity and cytotoxic T cell responses; these are under complex H-2 and non-H-2 Ir gene control. The effector cells for these two in vivo responses are Ly 1+2-, and the cytotoxic T cell effectors generated in secondary mixed lymphocyte reactions in vitro are Ly1+2+, although their development requires the presence of Ly 1+2- T helper cells. We investigated the Ir gene control of another in vivo response to H-Y, the host-versus-graft response (HVGR), measured by popliteal lymph node enlargement. The strain distribution pattern (SDP) of primary and secondary HVG responses to H-Y indicates that there are both H-2 and non-H-2 Ir genes involved in controlling responsiveness. Cell transfer of the secondary response identifies an Ly 1+2- effector T cell for this response: this information together with the SDP of cytotoxic T cell responses suggests that the HVGR may represent activation of the T helper population involved in the generation of cytotoxic T cells.

Animals↗

Characterization and localization of calcitonin messenger ribonucleic acid in rat thyroid.

DNA/RNA hybridization assays have been used to examine calcitonin (CT) RNA production in normal rat thyroids. A cloned CT cDNA which codes for the entire rat CT precursor was radiolabeled to a high specific activity and used in hybridization assays to explore 1) the sizes and relative quantities of CT RNA extractable from thyroids obtained from rats of differing ages; 2) the effect of calcium on the in vitro production of CT RNA in rat thyroid tissue slices; and 3) the localization, by hybridization histochemistry, of C cells in rat thyroid that contain CT RNA. The relative concentrations of CT RNA, per microgram of total thyroid RNA, increased remarkably with age, with 14-month-old rats having approximately 14-fold elevated concentrations of thyroidal CT RNA compared to 19-day-old rat fetuses. Of interest was the finding that a second larger species of CT RNA is only evident in thyroids obtained from 14-month-old animals. The effect of calcium on the in vitro production of CT RNA in rat thyroid tissues was studied over 3- and 6-h periods. Although previous investigations have shown that calcium causes an immediate and linear increase in CT secretion from the thyroid gland, no net increase vs. controls in the amount of CT RNA extractable from calcium-stimulated thyroid slices was observed. Finally, hybridization histochemistry, a technique that identifies in fixed tissue sections those areas that contain a specific mRNA population, was used to localize C cells in the thyroid containing CT RNA. Specific areas of rat thyroid hybridized with the CT cDNA probe and autoradiography revealed these areas to be parafollicular cells located only in the central portion of the thyroid lobes, mRNA quantities detected by hybridization histochemistry showed little variation over the central area of the thyroid, indicating the C cells in this region of the thyroid are accumulating CT RNA at approximately the same rate.

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Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes.

Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.

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Non-H-2 and H-2-linked immune response genes control the cytotoxic T-cell response to H-Y.

The immunoregulation of cytotoxic T-cell responses to the male-specific antigen H-Y in mice has been found to be genetically controlled by genes of the major histocompatibility complex (H-2). Responsiveness was mainly confined to H-2b strains, but it has also been found in recombinant strains, F1 hybrids, and chimeras that carry at least part of the H-2b haplotype. By using a different immunization procedure it has been shown recently that an H-2k mouse strain (CBA) is also able to mount an equivalent H-Y-specific response. We investigate here, by applying this immunization technique, the responsiveness of other H-2k strains and of strains of other independent H-2 haplotypes. Both responders and nonresponders are found in three haplotypes: k, s, and d. The strain distribution pattern of responsiveness shows a combined influence of non-H-2 and H-2 genes. In certain strains there is a high variability in responsiveness between genetically identical individual animals. We discuss a model of immune response (Ir) gene function which could account for these observations.

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