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Biomedical subjects

E Simpson

Publications and source records attributed to E Simpson.

At least 181 records · Page 10Linked to original sources
PubMed1983

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the discussion of published results of XX males carrying the Sxr mutation and XO females, and the presentation of unpublished data from XY females carrying the YPOS or YORB chromosome, XY females carrying Thp on chromosome 17, and a series of mice carrying X-Y recombination products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↗
PubMed1983

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↗
PubMed1983

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.

Animals↗
PubMed1982

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.

Animals↗
PubMed1982

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.

Animals↗
PubMed1982

Genetic analysis of the non-H-2-linked Ir genes controlling the cytotoxic T-cell response to H-Y in H-2d mice.

The T-cell mediated immune responses to the male specific minor histocompatibility antigen H-Y in mice have been studied extensively as a model for immune responses to other weak antigens like tumor antigens or autoantigens. In a recent analysis of the strain distribution of the cytotoxic T-cell (Tc-cell) responsiveness to H-Y, it has been found that genes both within and outside the H-2 complex exert an interactive control. Whereas the H-2b strains all are high responders, independent of their non-H-2 background, other H-2 haplotypes (d, k, and s) only allow for a response if they are combined with certain non-H-2 genes. The H-2-linked immune response genes (Ir-genes) have been previously mapped to the I and K or D region of the H-2 complex, but the mapping of the non-H-2 genes has not yet been established. In this study evidence is presented, using recombinant inbred strains and immunoglobulin heavy chain (Igh) congenic strains of mice, to show that there is more than one non-H-2 Ir-gene involved, that the main controlling genes are not linked to the Igh complex, and that at least one non-H-2 Ir-gene is linked to the H-3 region on chromosome 2. This region includes genes for beta-2-microglobulin (beta 2m), the Ly-m11 alloantigen a polymorphic cell surface glycoprotein (Pgp-1), a B-cell specific antigen Ly-4, a transplantation antigen H-3, and genes (Ir-2) controlling the immune response to Ea-1 and H-13.

Animals↗
PubMed1982

H-2-associated differences in replicated strains of mice divergently selected for body weight.

A random-bred strain (Q) was established and divided into six replicates. Each replicate was divergently selected for 6-week weight (for over 30 generations) and each had an unselected control. We have investigated the H-2 haplotype of individual mice of the 18 selected Q strains to determine whether selection for size had also selected for H-2 or H-2-linked genes. From the results it appeared that only the H2b and H-2q haplotypes were present in the foundation stock. A large number of individuals of the six small sublines were of H-2b haplotype, while the majority of those of the six large sublines were of the H-2q haplotype. Individuals in the six control strains were H-2b, H-2q or both (i.e., H-2 heterozygotes and/or H-2 recombinants). These results suggest that control of body size is associated with H-2 or an H-2-linked gene(s).

Animals↗
PubMed1982

Dermatoglyphic analyses of 24 individuals with the Prader-Willi syndrome.

Dermatoglyphic parameters of 24 PWS individuals, 14 males, 10 females, were examined using standard techniques. Nomenclature followed that of Schaumann & Alter (1976). There were no differences found in the position of the axial triradius or the frequency of hypothenar patterns, but there was a decrease in fingertip ulnar loop patterns in both sexes with an increase in whorls in males (P less than 0.01) and whorls and arches in females (P less than 0.05). In males, the main line A terminated in the thenar area on the left palm more frequently than in the controls (P less than 0.01) and generally the main line A terminated low in both sexes. The total finger ridge counts were not different from controls indicating smaller than usual pattern size. Of 48 hallucal patterns, 26 were loops, 21 were whorls and there was one arch. This study confirms previous data that there are no pathognomonic dermatoglyphic distortions in PWS.

Adolescent↗
PubMed1981

Supposed lamarckian inheritance of immunological tolerance.

The notion that an adaptation acquired during an organism's lifetime can somehow be imprinted on the genome and so become heritable has been faulted by every critical test to which it has hitherto been exposed, but many naturalists have lost their faith in what seems to them to be the all-encompassing explanatory glibness of neo-darwinism. Although this criticism is unfair it is entirely proper that neo-darwinism should be under constant critical scrutiny. Interest was therefore aroused by the claim of Gorczynski and Steele that tolerance of A strain antigens induced in CBA mice by injecting into them (CBA x A/J)F1 spleen and bone marrow cells could be transmitted down the male line. Such a claim is of particular interest because spermatozoa, unlike oocytes, are produced throughout life and might thus conceivably have participated in the mechanism envisaged by Steele as that responsible for the supposed transfer of genetic information from soma to germ plasm. It was claimed that as many as 60% of the progeny of tolerant fathers mated with normal CBA females were unresponsive or hyporesponsive in an in vitro assay in which their spleen cells were tested for reactivity against A/J strain histocompatibility antigens in the cell-mediated lympholysis assay (CML). We describe here our failure to confirm these findings and our inability to extend them by testing the progeny for their reactivity against skin allografts from the tolerance-conferring strain.

Adaptation, Physiological↗
PubMed1981

Immune reactivity of progeny of tetraparental male mice.

Steele and Gorczynski have recently suggested that inbred male mice rendered tolerant at birth to the alloantigens of an H-2 plus non-H-2 incompatible inbred strain can transmit this tolerance or hyporeactivity, as measured in a primary anti-H-2 cytotoxic T-cell test in vitro, to their progeny, born of normally reactive females syngeneic with the males. As a corollary, it might be expected that the progeny of tetraparental males which are tolerant because from earliest fetal development they are chimaeric with respect to all tissues, including haematopoietic cells and germ cells, might in turn be tolerant to the other set of paternal alloantigens. We have now found, on the contrary, that inbred progeny of one component of a tetraparental male showed heightened responsiveness to the other paternal alloantigens.

Animals↗