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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 271 records · Page 15Linked to original sources
PubMed1983

Abnormalities of cells and extracellular matrix of T/T embryos.

The dominant mutation T, (Brachyury), of the T/t-complex in the mouse causes severe disorganization in neural tube, notochord, and somites in homozygotes. The use of scanning electron microscopy to investigate the relationships of cells to one another and to the extracellular matrix in the three axial organs and in the head mesenchyme reveals that cells in all areas examined are abnormal in size, shape, and arrangement in T/T embryos. Cells of T/T head mesenchyme and somites are arrayed in flat sheets of broadened cells with fewer cytoplasmic processes than those of normal littermates. The notochord is discontinuous and its surface is exposed rather than covered by a dense matrix as in the normal. Likewise the sheath of the T/T neural tube is less dense than normal. Cell size and shape are very irregular whereas normal neural tube cells are all about the same size. Extracellular matrix in T/T embryos is greatly decreased in all areas.

Animals↗
PubMed1983

Characterization of an antigen present on testicular cells and preimplantation embryos whose expression is modified by the t12 haplotype.

In attempts to identify cell surface molecules specified by lethal genes in the T/t-complex, we prepared a rabbit antiserum that has cytotoxic activity against testicular cells from males heterozygous for t12, but not against wild type cells. However, anti-t12 serum immunoprecipitates the same major component, a glycoprotein of mol. wt. 87,000 daltons, from galactose-labelled C3H. +/t12 testicular cell lysate and from congenic C3H. +/+ lysate, although the gp87 molecule precipitated from +/t12 cells appears to be more highly galactosylated than the +/+ form. The antigen is heavily glycosylated in both genotypes, since when testicular cells are treated with tunicamycin before immunoprecipitation, a protein of 40,000-42,000 daltons is obtained. Gp87 is also present on pre-implantation embryos, and on teratocarcinoma cells, but is barely detectable on any adult somatic cells examined. Its expression is developmentally regulated during pre-implantation stages, but the temporal pattern of its expression appears to be different between wild type and t12 embryos. Thus, we believe we have identified a molecule that may play a role in the differentiation of testicular cells and pre-implantation embryos, and that is either specified by genes in the t12 haplotype, or responsive in some way to the effects of t12.

Animals↗
PubMed1983

Reduction in infarct size, arrhythmias and chest pain by early intravenous beta blockade in suspected acute myocardial infarction.

Four hundred seventy-seven patients suspected of having had acute myocardial infarction within less than 12 hours were randomized to receive i.v. atenolol followed by oral treatment for 10 days or to a control group. In patients with ECG changes indicative of infarction at entry, i.v. atenolol significantly reduced enzyme release by one-third and enhanced R-wave preservation. In patients without such ECG changes, treatment significantly prevented the development of infarction in a proportion of patients. There was also a significant reduction in R-on-T ectopics, repetitive ventricular arrhythmias and supraventricular arrhythmias. Treated patients had significantly greater pain relief and required fewer opiate analgesics. Significantly fewer atenolol-treated patients died by 10 days (the treatment period), had nonfatal cardiac arrests, developed heart failure, or suffered reinfarction.

Administration, Oral↗
PubMed1982

Hip luxation in small animals: an evaluation of some methods of treatment.

The results of closed manipulative reduction and De Vita pinning in the treatment of small animal hip luxations have been analysed. Closed reduction is worth attempting as an initial form of treatment even in chronic luxations, but successful relocation may require more than one manipulative reduction. Inadequate placement of De Vita pins or their early migration predisposes to reluxation. Hip luxations are prone to reluxation during the eight weeks following reduction.

Animals↗
PubMed1982

Gene mapping within the T/t complex of the mouse. I. t-Lethal genes are nonallelic.

The t haplotypes of mouse chromosome 17 are natural polymorphisms in wild populations that contain mutations that affect or control such diverse functions as tail length, embryonic lethality and maturation and function of male germ cells. The major impediment to dissecting the genetics of this complex region has been its unusual property of recombination suppression in heterozygotes with wild-type chromosomes. Recently it was shown that recombination suppression does not occur in heterozygotes containing two different t haplotypes, which suggested that t chromosomes may be mismatched with respect to wild-type but share sequences that permit crossing-over between them. Thus for the first time questions of allelism and map positions of the t-lethal mutations can be addressed. We report here the results of three experiments that analyzed the tw12 haplotype trans to either tw5, tw32 or tw18. In all cases these lethal mutations were nonallelic to tw12. These results, together with evidence for functional relatedness, suggest the t-lethals may be a gene family spread out over more than 15 centiMorgans of chromosome 17.

Alleles↗
PubMed1982

Gene mapping within the T/t complex of the mouse. II. Anomalous position of the H-2 complex in t haplotypes.

Naturally occurring t haplotypes are chromosome 17 polymorphisms that suppress genetic recombination in t/+ heterozygotes over a long distance that includes the H-2 complex. There is strong linkage disequilibrium between t haplotypes and H-2 haplotypes; over 20 independently isolated t chromosomes representing eight different complementation groups share only four H-2 haplotypes. Thus t haplotypes and their associated H-2 loci are inherited en bloc as a "supergene" complex, whose frequency is driven in wild mouse populations by their high transmission from male t heterozygotes. This phenomenon must therefore serve as an important regulator of H-2 polymorphisms. Genes within the region of recombination suppression in t haplotypes have been mapped by crossing-over that occurs readily between two different t haplotypes situated in trans, and by this means we show here that the H-2 complex occupies an anomalous position in t haplotypes, mapping proximal to the locus of tf closely flanked by t-lethal mutations.

Animals↗
PubMed1982

Genetic structure and origin of t haplotypes of mice, analyzed with H-2 cDNA probes.

We investigated the genetic organization and evolutionary origin of t chromosomes of mice by examining the restriction fragment patterns of DNA from t haplotypes and normal chromosomes with cDNA probes to H-2 class I genes. On genomic DNA blots, the restriction fragments containing H-2-related sequences were highly variable among different inbred strains of mice, whereas they were very similar among different t haplotypes even when the t haplotypes carried serologically different H-2 haplotypes. These observations suggest that all t haplotypes have a common origin and are not products of independent mutational events. We also mapped the position of several restriction fragments characteristic of t DNA by using a battery of recombinant t haplotypes, defined with respect to their t-lethal factors and H-2 haplotypes. We thus show that restriction fragments containing H-2-related sequences map to the left of the H-2 class I genes in t chromosomes, a region in which the tw32 b-lethal factor also maps. The cloning of these fragments can be expected to provide an entry for the structural analysis of t DNA.

Animals↗