Structural studies of murine I-E and human DR antigens.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Silver.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A recently-introduced laminated material which accepts light only over a small angle on either side of the normal was compared to standard Polaroid sunglasses. A preliminary trial failed to show any superiority of the new material in reducing glare for patients with moderate cataract.
Because of intolerance to oral steroids, a patient with Chronic Active Hepatitis and an active gastric ulcer was treated with rectal steroids in addition to azathioprine and carbenoxolone sodium. The liver function tests showed a marked improvement with this therapy, and the gastric ulcer healed. The possible advantages of steroid administration by suppositories are discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have studied the tumor (T) antigens induced by wild-type polyoma virus and several nontransforming mutants using immunoprecipitation with antisera from animals bearing polyomya-induced tumors followed by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. In a variety of mouse cells, wild-type virus induces a major T antigen species with apparent molecular weight of 100,000 daltons, and four minor T antigen species with apparent molecular weights of 63,000, 56,000, 36,000 and 22,000 daltons. Hr-t mutants, which have an absolute defect in transformation, induce a normal 100,000 dalton T antigen but are altered in the minor T antigen species. Hr-t deletion mutants induce none of the minor T antigen species seen in wild-type virus. In their place, these mutants induce T antigen species with molecular weights in the range of 6,000--9,000 daltons. The size of the very small T antigen products does not correlate in any simple way with the size or location of the deletions in the viral DNA. Point hr-t mutants induce two of the four minor T antigen species; they make apparently normal amounts of the 56,000 dalton product and reduced amounts of the 22,000 dalton product, but none of the 63,000 or 36,000 dalton species. Ts-a mutants, which have a temperature-sensitive defect in the ability to induce stable transformation, and which complement hr-t mutants, induce T antigens with the same mobility as wild-type; however, the 100,000 dalton T antigen of ts-a mutants is thermolabile compared to wild-type. A double mutant virus carrying both a ts-a mutation and a deletion hr-t mutation induces a thermolabile 100,000 dalton product and none of the minor T antigen species. Cell fractionation studies with productively infected cells have been carried out to localize the T antigen species.
Murine Ia and human DR antigens were isolated and purified by immunoprecipitation and sodium dodecyl sulfate/polyacrylamide gel electrophoresis with allo- and xenoantisera, respectively. The I-A subregion antigen consists of two chains, designated Aalpha and Abeta, with molecular weights of 35,000 and 26,000, respectively. The I-C subregion antigen likewise consists of two chains, designated Calpha and Cbeta, with molecular weights of 32,000 and 29,000, respectively. Under nonreducing conditions, the Cbeta chain migrates appreciably more rapidly on sodium dodecyl sulfate/polyacrylamide gels than the reduced Cbeta chain, reflecting the presence of an intrachain disulfide bond. The human DR antigen is also a two-chain unit and contains DRalpha and DRbeta components with molecular weights of 34,000 and 28,000, respectively. The DRbeta chain migrates more rapidly before reduction than afterward, like the murine Cbeta chain. The DRbeta and Cbeta chains are also strikingly homologous if a single amino acid shift is imposed on one of those chains. Thus, human DR antigens strongly resemble the murine I-C subregion antigens.
Explore the source record for details and available documents.
The ocular retardation (or) mutation in mice has been studied morphologically in serial 1 mu sections. This recessively inherited, fully penetrant mutation is characterized by an early arrest of retinal development, aplasia of the optic nerve, cataractous degeneration of the lens, and microphthalmia. We describe early alterations of normally occurring morphogenetic cell death in the optic cup and aberrations of optic fissure formation which appear to precede the arrest of retinal and optic nerve development. The subsequent disappearance of central retinal vessels and cataract formation are interpreted as secondary phenomena.
In the anophthalmic mutant of the mouse the optic primordia are "genetically enucleated" well before the usual emergence of retinal ganglion cell axons (Silver and Hughes, '74). In eyeless animals, a portion of the mediobasal hypothalamus and one of its constituent nuclear pairs, nucleus suprachiasmaticus (SCN), were markedly abnormal in the embryo and adult. It has been reported that the ventral portion of the SCN receives a substantial, direct retinal innervation (Moore and Lenn, '72) and that these nuclei may mediate several light-induced hormonal and behavioral circadian rhythms (Stetson and Whitmyre, '76). During day 13 of mutant embryogenesis, just prior to the time of optic chiasm formation in normal animals, a large portion of ependyma and adjacent brain tissue herniated into the lumen of the would-be suprachiasmatic region of the third ventricle. In 70% of the animals examined histologically during the latter phase of development and as adults, regulation occurred and the brains were largely comparable with those of controls. However, in the remaining mutant mice, the overall size of either, or sometimse both, SCN was much reduced. The basal (but not the apical) dendrites of SCN neurons failed to develop fully. Some basal dendrites normally invade the optic chiasm below. In several mutant animals one or the other SCN had greatly increased numbers of cells, while the contralateral one had diminished numbers. These observations suggest that regular formation of the suprachiasmatic region of the hypothalamus and especially the suprachiasmatic nuclei, may depend during development upon the presence of the eye or the subjacent optic axons.
Digestion of brain nuclei with micrococcal nuclease produces 11.2-S chromatin subunits which comprise up to 80% of the total nuclear DNA. Hybridization studies with excess subunit DNA demonstrate that subunits are distributed throughout the repeated and nonrepeated sequences of the genome. No class of nonrepeated DNA appears to be excluded from subunits. Transcribed DNA is present in chromatin subunits since in vitro labelled poly(A+)-mRNA hybridizes to excess subunit DNA with kinetics identical to that for total DNA.
Explore the source record for details and available documents.
Alloantisera directed against the alloantigens determined by the I-E and I-C subregions of the murine major histocompatibility complex precipitate two components that have molecular weights of 35,000 and 29,000. These components, when analyzed by partial NH2-terminal sequencing, show no homology to two components of similar size determined by the I-A subregion. However, the large chain determined by the murine I-E and/or I-C subregion is homologous to the large chain of the human HLA-D region alloantigen, although the small chains isolated from these two species do not display any such homology.
Explore the source record for details and available documents.
Explore the source record for details and available documents.