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Biomedical subjects

J Silver

Publications and source records attributed to J Silver.

At least 343 records · Page 19Linked to original sources

The MT4 allodeterminant is borne on an HLA-DS molecule on DR5 cells.

Human HLA-DR molecules have been shown to be structurally homologous to the murine I-E subregion molecules by amino acid sequence analysis. Recent studies have demonstrated the isolation of an I-A subregion-homologous molecule (HLA-DS) from human B-cell lines with the rabbit antiserum RbO3, made against a marmoset I-A-like Ia molecule. Previous work from our laboratory has demonstrated that the DR5 homozygous lymphoblastoid cell line Swei expresses at least two different Ia alpha chains and four different Ia beta chains, which associate to form four distinct human Ia molecules, alpha 1 beta 2, alpha 1 beta 3, alpha 2 beta 1, and alpha 2 beta 4, and that the alpha 2 beta 1 molecule bears the allodeterminants MB3 and MT4. To determine whether the MT4-bearing alpha 2 beta 1 molecule was an HLA-DS molecule, the alpha 2 beta 1 molecule reactive with an anti-MT4 alloserum was compared with the Ia molecule reactive with the rabbit xenoantiserum RbO3 by two-dimensional gel electrophoresis and sequential immunoprecipitation. The alpha 2 chain and the RbO3-reactive alpha chain yielded essentially similar spot patterns. The beta 1-chain spot pattern was a subset of the RbO3-reactive beta-chain spot pattern. Sequential immunoprecipitation indicated that RbO3 removed all molecules reactive with MGH88B. These results indicate that on DR5 cells the allosera-reactive alpha 2 beta 1 molecule, which bears MT4, is an HLA-DS molecule.

Electrophoresis, Agar Gel↗

Role of mink cell focus-inducing virus in leukemias induced by Friend ecotropic virus.

Recombinant viruses have been implicated in the pathogenesis of murine leukemias induced by a variety of long-latency retroviruses. Neonatal mice of several strains were inoculated with Friend ecotropic virus (F-Eco) and analyzed for the presence of mink cell focus-inducing (MCF) virus or DNA restriction enzyme fragments which were specific for Friend MCF virus (F-MCF). MCF virus was detected within 2 weeks of inoculation in NFS /N mice and at about 2 months after inoculation in BALB/c mice. Both of these strains developed erythroblastosis after inoculation with F-Eco. In contrast, MCF virus was not detected in F-Eco-inoculated C57BL mice. These mice were resistant to erythroblastosis but developed lymphoma or myelogenous leukemia or both at about 5 months after inoculation. Thus, although MCF viruses were associated with F-Eco erythroblastosis in NFS /N and BALB/c mice, they were not necessary for F-Eco-induced lymphoid or myeloid leukemias in C57BL mice. To investigate the association between resistance to erythroblastosis and absence of MCF virus, C57BL mice were inoculated with pseudotypic mixtures of F-Eco plus F-MCF; MCF virus replicated well in these mice, but the mice remained resistant to erythroblastosis. Furthermore, in genetic crosses between C57BL and NFS /N or BALB/c, some mice inherited resistance to F-Eco erythroblastosis without inheriting the C57BL resistance to the generation of MCF viruses. These results indicate that C57BL mice carry a gene for resistance to F-Eco erythroblastosis which is distinct from the C57BL genes which interfere with the generation of MCF viruses.

Animals↗

Ethnic differences in kidney graft survival.

Results of 73 first cadaveric donor renal transplants in Jerusalem between 1975 and 1980 are presented. There was a better 12-month graft survival in Arabs than in Jews (70.8% vs. 40.8%, P less than 0.035); however, 12-month patient survival was similar (83.3% vs. 85.7%). Acute rejection as the primary cause of graft loss occurred in 12.5% of the Arabs and 38.8% of the Jews (P less than 0.05). HLA-A, -B and -DR antigen-sharing was similar in both groups. Early acute rejection episodes had a poorer prognosis in Jews. Possible explanations for these findings are discussed, but the reason for the higher success rate in Arabs remains obscure.

Adolescent↗

An HLA-DR5 homozygous cell line expresses two DS (I-A-like) molecules.

Previous studies have indicated that LLA-DR homozygous cell lines express two DR molecules but only a single DS (I-A-like) molecule. This report demonstrates that an HLA-DR5 homozygous cell line expresses at least two distinct DS molecules. These two DS molecules are formed by the association of a single DS alpha chain with either of two DS beta chains. Four distinct Ia molecules have now been identified from this DR5 homozygous cell line.

Antigen-Antibody Reactions↗

Sodium-dependent idiopathic hypercalciuria in renal-stone formers.

Four patients with renal stones had hypercalciuria which was dependent on a high sodium intake. Moderate sodium restriction corrected the hypercalciuria. Sodium excretion should be measured in all patients with idiopathic hypercalciuria so that the easily treated sodium-dependent hypercalciuria can be diagnosed.

Adult↗

Postnatally induced formation of the corpus callosum in acallosal mice on glia-coated cellulose bridges.

Developing axons of the corpus callosum of mice are guided across the cerebral midline by a slinglike glial structure that forms transiently between the hemispheres. If the "sling" is cut at precallosal stages, the would-be callosal fibers whirl into paired neuromas adjacent to the longitudinal cerebral fissure. In experiments on such surgically acallosal animals, the aberrant commissural axons maintained a potential to regrow across the hemispheres at prenatal and early postnatal stages if they were presented with a properly aligned, glia-covered scaffold spanning the hemispheres.

Animals↗

Studies on cell migration and axon guidance in the developing distal auditory system of the mouse.

The events that take place along the potential route of distal auditory axons (future vestibular component) prior to and during their outgrowth were examined morphologically using timed mouse embryos. During embryonic (E) day 9.5 a discrete zone of cell death appears in the rostrolateral wall of the otic cup. Necrosis is accompanied by outward migration of epitheloid cells from the same region of the otic wall. Temporally and spatially correlated with these two events is the widening of extracellular spaces between otic neuroepithelial cells and the breakdown of basement membrane. During E 10.5 migrating epitheloid cells condense to form a funnel-shaped configuration. This cellular "funnel" begins narrowly at the dorsorostrolateral wall of the otocyst and broadens as it reaches the auditory ganglion. During E 11.5 through E 12.5, "pioneer" distal auditory axons take a circuitous route and ascend from the auditory ganglion to enter the otocyst. Axons extend toward the otocyst moving along cells of the "funnel," maintaining an orientation similar to that of the cells that compose it. Axon growth cones enter the otocyst at sites devoid of basement membrane and invade the wall of the otocyst moving tangentially along radially arranged cells that bridge the otocyst and the "funnel." These observations demonstrate that a preformed, funnel-shaped tissue exists along the future route of the auditory fibers. We suggest that the "funnel" may influence the growth and directionality of distal auditory axons as they extend from the auditory ganglion to the wall of the otocyst. At the otic wall, the transition provided by "bridge" epitheloid cells, together with the absence of basement membrane at specific sites of the otic wall, provide the auditory axons with a route into the otocyst.

Animals↗

Thy-1 cDNA sequence suggests a novel regulatory mechanism.

Thy-1 was originally defined in mice as a cell-surface alloantigen of thymus and brain with two allelic forms, Thy-1.1 and Thy-1.2 (ref. 1). Subsequently, the Thy-1.1 alloantigenic determinant was identified in rats. In both species, Thy-1 is present in large amounts on thymus and brain cells and in smaller quantities on fibroblasts, epidermal cells, mammary glands and immature skeletal muscle. In many of these tissues the level of Thy-1 expression changes dramatically during cell differentiation. The molecules expressing the Thy-1 antigenic determinant have been isolated from rat and mouse brain cells and have been shown to have a molecular weight of 17,500 (ref. 8). One-third of the Thy-1 molecule is carbohydrate and the remainder is a polypeptide of 111 amino acids whose sequence has been fully determined. We report here the isolation and characterization of a cDNA clone encoding the rat thymus Thy-1 antigen but find that the DNA sequence ends prematurely at a position corresponding to amino acid 103. It appears to be a complete transcript, however, as the last codon is followed directly by a poly(A) tract.

Amino Acid Sequence↗

Crystallin synthesis in the lens rudiment of a strain of mice with congenital anophthalmia.

Immunofluorescence with anti-crystallin antisera was done on the eye rudiments of mouse embryos of a congenitally anophthalmic strain. In a few of the embryos a lens vesicle formed, which, although much smaller than in controls and delayed in development, appeared morphologically normal. alpha-Crystallin could be identified in the cells of the rudiments. In addition the cells looked cytologically similar to those of the normal lens vesicle; they were elongated and the nuclei displayed interkinetic nuclear migration. Therefore, the surface ectoderm of the anophthalmia mouse can differentiate into a lens vesicle that appears biochemically and cytologically normal. This indicates that the optic vesicle in this mutant is capable of inducing a lens, while the surface ectoderm can respond to the stimulus in a normal fashion.

Animals↗

HLA-DS molecules and their relation to supertypic specificities.

We have analyzed the structures of HLA-DS molecules from DR1, 2, 3, 4, 5, and 7 cell lines by two-dimensional gel electrophoresis and examined the relationship of HLA-DS molecules to those expressing the supertypic specificities MT1, MB3, and MT3. These studies have allowed us to conclude that the HLA-DS locus is as polymorphic as HLA-DR and that the MT1 and MB3 supertypic specificities reside on DS molecules. Furthermore, MT1 molecules from DR1, DR2, and DRw6 cell lines are structurally different as are MB3 molecules from DR4 and DR5 cell lines. In addition, studies using two MT3 specific reagents, a monoclonal antibody, 109d6, and an alloantiserum, Hon, suggest that MT3 is a cross-reactive determinant present on products of two different loci: a DS4 molecule and a DR7-like molecule.

Antibodies, Monoclonal↗

Further characterization of HLA-DS molecules: implications for studies assessing the role of human Ia molecules in cell interactions and disease susceptibility.

HLA-DS molecules, the human homologs of murine I-A molecules, were analyzed and compared to DR molecules by two-dimensional gel analysis. These analyses allowed us to define six forms of DS molecules, suggesting that DS molecules were as polymorphic as DR molecules. The supertypic specificities, MT1 and MB3 were localized to DS molecules, whereas MT3 appeared to represent a crossreactive determinant present on products of two different loci encoding Ia-like molecules in man, a DS4 molecule and a DR7-like molecule. These studies also revealed that MT1 molecules isolated from DR1 and DR2 cell lines were different, as were MB3 molecules isolated from DR4 and DR5 cell lines. Extensive crossreactions between DR and DS molecules were observed by using several monoclonal antibodies. This sharing of epitopes between products of different loci for human Ia molecules has important functional implications.

Amino Acid Sequence↗

Ontophyletics of the nervous system: development of the corpus callosum and evolution of axon tracts.

The evolution of nervous systems has included significant changes in the axon tracts of the central nervous system. These evolutionary changes required changes in axonal growth in embryos. During development, many axons reach their targets by following guidance cues that are organized as pathways in the embryonic substrate, and the overall pattern of the major axon tracts in the adult can be traced back to the fundamental pattern of such substrate pathways. Embryological and comparative anatomical studies suggest that most axon tracts, such as the anterior commissure, have evolved by the modified use of preexisting substrate pathways. On the other hand, recent developmental studies suggest that a few entirely new substrate pathways have arisen during evolution; these apparently provided opportunities for the formation of completely new axon tracts. The corpus callosum, which is found only in placental mammals, may be such a truly new axon tract. We propose that the evolution of the corpus callosum is founded on the emergence of a new preaxonal substrate pathway, the "glial sling," which bridges the two halves of the embryonic forebrain only in placental mammals.

Animals↗

Cloning the heavy chain of human HLA-DR antigen using synthetic oligodeoxyribonucleotides as hybridization probes.

The recent development of the amino acid microsequence technique allows us to obtain partial sequence information using an extremely small amount of protein. Two sets of mixed oligonucleotide probes were chemically synthesized using the amino acid sequence information for the heavy chain of human HLA-DR antigen obtained by the microsequence technique. These two hybridization probes were used to screen cDNA clones constructed from cytoplasmic poly(A)+ mRNA from a human B lymphoblastoid homozygous cell line (LG-2). Of the 10,000 clones screened, two clones hybridized with the probes. DNA sequence analysis showed that the longer one of the two cDNA clones was 1183 nucleotides long, including the entire coding region, the signal peptide region, and the complete 3'-noncoding region. The deduced amino acid sequence of the HLA-DR alpha chain is identical to that of other cell lines with a different HLA-DR typing. However, several nucleotide differences are found in the 3'-untranslated region compared with that of other DR haplotypes.

Amino Acid Sequence↗

Reduction of asthenopia in patients with convergence insufficiency after fusional vergence training.

Seven patients with convergence insufficiency and related asthenopia underwent automated fusional convergence training. A matched-subjects control group crossover design was used to reduce placebo effects. All patients showed significant increases in vergence ranges with concurrent marked reduction of symptoms after training. All patients showed a flattening of and an increase in the base-out portion of their fixation disparity curve. Our results demonstrated the effectiveness of fusional vergence training in reducing asthenopia in these patients. Subsequent accommodation and vergence training using traditional orthoptic procedures yielded further reduction of asthenopia, as well as an increase in the base-out fusional range.

Adolescent↗