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E Simpson

Publications and source records attributed to E Simpson.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1981

Generation of effector cells from T cell subsets. III. Synergy between Lyt-1 and Lyt-123/23 lymphocytes in the generation of H-2-restricted and alloreactive cytotoxic T cell.

Lyt-123/23 and Lyt-1 T cell subsets, positively selected by separation on the fluorescence-activated cell sorter, were tested in vitro for their role in the generation of H-2-restricted and alloreactive cytotoxic T cells. It is shown that in the proliferation assay, both T cell subsets responded equally well to H-2 and non-H-2 antigens (H-Y), respectively. In contrast, none of the selected Lyt subsets, but only the mixed population containing Lyt-1 and Lyt-123/23 lymphocytes gave rise to both H-2-restricted (anti H-Y, anti-trinitrophenyl) and alloreactive (anti-H-2) cytotoxic lymphocytes. The data imply an essential role of Lyt-1 cells as inducers or helpers in the generation of all cytotoxic lymphocytes from their precursors in the Lyt-123/23 pool.

Animals↗
PubMed1981

Functional and binding activity of monoclonal anti-Thy-1 antibodies: evidence for different expression of the two alleles.

Monoclonal anti-Thy-1.1 and anti-Thy-1.2 antisera selected for complement-dependent cytotoxicity have high cytotoxic and binding titers on thymocytes and peripheral T cells of mouse strains bearing the appropriate Thy-1 allele. The effect of both anti-Thy=1.1 and anti-Thy-1.2 monoclonal antisera plus complement on cytoxic T cell effectors is to abrogate their activity. On the functional activity of precursor cytotoxic T cells, monoclonal antisera against the two alleles have different effects: anti-Thy1.2 plus complement removes precursor activity of Thy-1.2-bearing strains, including (Thy-1.1 X Thy-1.2) F heterozygotes, In contrast, six different anti-Thy-1.1 monoclonals, including four of the IgM class and two of the IgG class, failed to remove cytotoxic precursor activity from the splenic T cells of AKR, A. Thy-1.1 or (CBA X AKR) F1 mice. Analysis by florescence-activated cell sorting of in vitro cultured AKR spleen cells shows that Thy-1.1 antigen appears on the cel surface during the five-day culture period.

Alleles↗
PubMed1981

Analysis of haplotype preference in the cytotoxic T-cell response to H-Y.

The mechanisms determining which parental haplotype is selected in (CBA X B10) (k X b)F1 female mice for major histocompatibility complex (H-2) restricted, male-specific (H-Y), immune, cytotoxic T-cell (Tc-cell) responses, was investigated. The data show that haplotype preference is variable, and may be directed towards one, both, or neither of the parental haplotypes. This preference is reflected in the precursor or frequency of memory Tc cells as measured by limiting dilution assays. It was further shown that maternal influence, antigen dose, route of immunization, and a feedback mechanism on the stimulator cells in vivo could not influence haplotype preference or its observed variability. Evidence for cross-reactive killing by H-2k and H-2b H-Y immune Tc cells on H-2b and H-2k allogeneic targets, respectively,, (i.e., the independent haplotype of the other parent of the F1 mice), provide evidence for natural tolerance as a possible mechanism to explain haplotype preference.

Animals↗
PubMed1981

Measurement of Protein Degradation in Leaves of Zea mays Using [H]Acetic Anhydride and Tritiated Water.

The rate of protein degradation in Zea mays leaves has been estimated by using tritiated water and [(3)H]acetic anhydride as the labeling agents. Both methods circumvent many of the problems usually associated with measuring protein degradation in plants. The half-life of ribulose-1,5-bisphosphate carboxylase protein in second leaves of 13-day-old seedlings under continuous light was found to be 7.8 +/- 0.9 days by the tritiated water technique and 6.5 +/- 0.8 days by the [(3)H]acetic anhydride method. The half-lives determined under a 14-hour-light, 10-hour-dark photoperiod are 6.2 +/- 0.8 days with tritiated water and 5.4 +/- 0.4 days with [(3)H]acetic anhydride. Whereas the values obtained by the two methods do not differ significantly, the use of either method for the determination of protein half-life can be recommended.

Journal Article↗
PubMed1981

T-cell hybridomas producing hapten-specific suppressor factors.

We have made several T-T hybridomas which secrete soluble factors capable of suppressing an in vitro antibody response to nitrophenol (NP), but not other unrelated antigens. These factors bind specifically to NP, and express determinants coded for in the I-J region of the mouse major histocompatibility complex. No determinants that cross-react with the constant regions of mouse immunoglobulins are present on the factors. Three sub-clones originating from the same initial culture well of hybridoma cells secrete factors which carry I-J determinants of different haplotypes. One clone expresses I-J determinants derived from the suppressor cell parent, another expresses I-J determinants derived from the tumour cell parent, and a third expresses both. This correlates exactly with I-J determinants expressed on the cell membrane, and suggests the participation of at least two genes in the determination of suppressor-factor structure.

Animals↗
PubMed1980

Delayed-type hypersensitivity responses to H-Y: characterization and mapping of Ir genes.

This paper examines the delayed-type hypersensitivity (DTH) response to male (H-Y) antigen(s). Female mice of the H-2b haplotype developed delayed footpad reaction to syngeneic or allogenic male thymus and spleen cells after priming with syngeneic male thymus and spleen cells. The reaction peaks at 24 h, has classical DTH histology and is specific to H-Y antigen as it is not elicited with female cells. Cell transfer studies show that donor/recipient matching at the I-Bb subregion is necessary for successful transfer of DTH and that the effective primed population is Thy-1+, Lyt-1+, 2-. DTH response to H-Y antigen appears to be confined to mice of the H-2b haplotype. There appears to be a lack of associative recognition between H-Y antigen and MHC-coded determinants in the effector phase of DTH, and macrophage processing of H-Y seems likely, since nonresponder haplotypes can elicit the DTH response. Studies with H-2b recombinant mouse strains indicate that the dominant Ir gene is located in the I-B region. Female F1 hybrid mice derived from matings of strains not involving H-2b haplotype failed to develop DTH to H-Y. In summary, these data imply that a complete correlation exists between DTH to H-Y and the ability to reject male skin graft, suggesting that the effector mechanisms of skin-graft rejection may closely involve DTH cells.

Animals↗
PubMed1980

Allogeneic tolerance in embryo aggregation mouse chimeras studied by mixed lymphocyte culture and cell-mediated lympholysis.

Tolerance in embryo aggregation (EA) mouse chimeras was investigated using mixed lymphocyte culture (MLC) reaction and cell-mediated lympholysis (CML). In most cases, spleen or lymph node cells from EA chimeras were specifically unresponsive toward their parental cells in both MLC and CML. There was no evidence to support the involvement of "serum-blocking factors" or suppressor cells under these experimental conditions. There was, however, an exceptional chimera in which cytotoxic T cell percursors reactive against one parental cell may have been present. We argue for classical clonal elimination being the primary mechanism for tolerance in EA chimeras and discuss a role of suppressor mechanisms for self-tolerance.

Animals↗
PubMed1980

Calcium metabolism in a fatal case of sodium fluoride poisoning.

A patient was admitted to a district general hospital within an hour of ingesting a fatal dose of sodium fluoride. The results of laboratory investigations, together with some in vitro findings, support the hypothesis that the hypocalcaemia of fluoride poisoning is the result of fluorapatite formation and not calcium fluoride precipitation, and that its persistence reflects the severity of the calcium deficit and not an inhibitoin of normal homeostatic mechanisms. It is suggested that the role of renal clearance of fluoride may be more important than had been realised hitherto.

Apatites↗