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E Simpson

Publications and source records attributed to E Simpson.

At least 145 records · Page 8Linked to original sources
PubMed1987

Pre-treatment with beta blockers and the frequency of hypokalaemia in patients with acute chest pain.

Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on beta blockers before admission. The potassium concentrations of patients admitted early (within four hours of onset of symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with beta blockers. This was not seen in patients who had been on beta blockers before admission. Non-selective beta blockers were more effective than cardioselective agents in maintaining concentrations of plasma potassium. These findings suggest a mechanism for the beneficial effects of beta blockers on morbidity and mortality in acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1987

Mapping the H-Y gene.

This paper uses cytotoxic and proliferative T cell clones specific for H-Y and restricted by MHC molecules to type mice and humans inheriting incomplete portions of the Y chromosome. The data have allowed us to map the H-Y antigen gene Hya in mouse to a position closely linked with, but separable from, Tdy on the Sxr fragment and thus presumably to a position of the normal mouse Y chromosome near the centromere. The human H-Y gene maps between deletion intervals 4B and 7, separate from TDF which is on interval 1. We are currently testing cells from a number of additional patients who have inherited different portions of the Y chromosome to pinpoint the mapping more closely. It is of interest that in mouse a Y-linked gene controlling spermatogenesis (Spy) maps near Hya on the Sxr fragment: they could be the same or closely linked genes. In man, a gene controlling spermatogenesis maps to Yq and the data so far do not exclude that it could be coincident with the H-Y gene.

Animals↗
PubMed1986

T-cell and antibody typing of a mouse population segregating for Sxr and H-2 haplotype.

During investigation of the frequency of recombination of the testis determining gene, Tdy, and the minor histocompatibility antigen gene Hya on the Sxr segment in an outbred mouse stock, we identified two fertile males, one XY and the other XYSxr, which typed H-2k positive using the H-2b anti-H-2k monoclonal antibody HB50, but whose cells failed either to stimulate H-Y specific H-2k restricted T-cell clones, or to be killed by anti-H-2k or anti-H-2k restricted H-Y specific cytotoxic T cells. We investigated these two mice and their existing relatives, using H-2 and H-Y typing methods. The progeny of their test matings with H-2b homozygous C57BL/6 females were also investigated. The results indicate that the transmission of the Hya gene on the Y chromosomes from both mice, and the additional Hya gene on the Sxr segment of the carrier male, allowed for the expression of the H-Y antigen and its detection in the presence of an H-2 haplotype for which we had H-2 restricted H-Y specific typing cells (H-2b and H-2k). Furthermore, we identified the haplotype of the two original males as expressed in the H-2 homozygous and heterozygous F2 progeny as H-2q and discovered an unexpected cross reactivity of the monoclonal anti KkDk antibody HB13 with half the cells of H-2q homozygotes, but not qb heterozygotes.

Animals↗
PubMed1986

H-Y status of X/X Sxr' male mice: in vivo tests.

Sex reversed X/X male mice carrying Sxr or the variant Sxr' were typed for expression of the male specific histocompatibility antigen H-Y, by skin grafting and by in vitro cytotoxic and proliferative tests. The X/XSxr males, like X/Y males, were H-Y positive by in vitro testing, and failed to reject semi-syngeneic male skin grafts. In contrast X/XSxr' males, like X/X females, were H-Y negative and rejected semi-syngeneic, male skin. Spleen cells from X/Y males sensitized C57BL/10 female recipients to reject syngeneic male skin rapidly, whilst immunization with X/X female or X/XSxr' male cells failed to stimulate such second-set responses. These data suggest that the H-Y antigen detected by cytotoxic T cells is the same as that detected by graft rejection responses, that the Sxr' variant is not a tissue-specific regulatory mutation, and that X/XSxr' individuals do not express H-Y antigen but nevertheless develop as phenotypic males.

Animals↗
PubMed1985

Calcitonin is a substrate for oligosaccharyltransferase in vitro.

Tumor-derived, large molecular weight forms of calcitonin, have been postulated to result from glycosylation of the hormone. To address this question we have examined the glycosylation of calcitonin in vitro and in cultured thyroidal C-cells. We show that native, undenatured calcitonin is an active substrate for oligosaccharyltransferase and that glycosylation of calcitonin by the transferase is inhibited by tunicamycin. In addition, calcitonin is an effective competitive inhibitor of the glycosylation of a known peptide substrate for oligosaccharyltransferase. Pulse-labelling of cultured medullary thyroid carcinoma cells with [3H]-mannose indicate that detectable quantities of carbohydrate-containing forms of calcitonin are produced in these cells. These data indicate that glycosylation of calcitonin is one mechanism whereby tumor cells could produce higher molecular weight forms of the hormone.

Animals↗
PubMed1985

Some aspects of calcium metabolism in a fatal case of ethylene glycol poisoning.

Laboratory results are presented for a patient who died following ingestion of an antifreeze solution containing ethylene glycol. It was observed that the measurement of osmolality, which is of value in the early stages of ethylene glycol poisoning, may give normal results if there are many hours delay between ingestion and admission. The hypocalcaemia which frequently accompanies ethylene glycol poisoning is shown to develop over several hours.

Calcium↗
PubMed1985

Identification of a messenger ribonucleic acid fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor.

Prostatic cancer is frequently associated with new bone formation although the tumor-derived factors responsible for changes in bone cell function have not been identified. We have examined the synthesis of osteoblast-stimulating factors in a cultured human prostatic cancer cell line (PC-3) and show that conditioned medium from PC-3 cells stimulate mitogenesis and alkaline phosphatase in cells with the osteoblast phenotype (cultured rat osteosarcoma cells) and collagen synthesis in fetal rat calvaria. In order to characterize tumor-derived gene products which stimulate cells of the osteoblast phenotype messenger RNA (mRNA) was isolated from PC-3 cells and microinjected into Xenopus laevis oocytes. mRNA-directed translation products which were secreted into the oocyte medium were collected and assayed for a number of osteoblast stimulating properties. Translation products from PC-3 mRNA-injected oocytes stimulated division of cultured osteosarcoma cells by 8-fold and increased DNA synthesis as measured by incorporation of [3H]thymidine into these cells. In addition, tumor-derived translation products stimulated the production of alkaline phosphatase activity, a marker enzyme for bone formation, in cultured osteosarcoma cells. Oocytes injected either with water or with mRNA from a tumor not associated with bone formation were devoid of these activities. Total mRNA from the human prostatic cancer cells was then denatured and fractionated by size by agarose gel electrophoresis. When individual fractions of mRNA were eluted from the gel, translated in Xenopus oocytes, and the secreted translation products were tested for alkaline phosphatase-stimulating activity on osteoblast-like cells, the majority of the activity could be recovered in a mRNA fraction which was approximately 1800 bases in length. These results indicate that the PC-3 prostatic cancer cell line synthesizes a mRNA of approximately 1800 bases which codes for a heretofore unrecognized osteoblast-stimulating factor.

Alkaline Phosphatase↗
PubMed1984

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.

Animals↗