Biomedical subjects

S Wayne

Publications and source records attributed to S Wayne.

6 recordsLinked to original sources

PubMed2000

Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.

Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive deafness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D10S1737, approximately 0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA.

Alleles↗

PubMed1992

Appendicular skeletal muscle areas assessed by magnetic resonance imaging in older persons.

Measurements of cross-sectional muscle areas of the upper-arm and mid-thigh from MRI images were compared to corresponding estimates from anthropometric measurements of limb circumferences and skinfold thicknesses in 25 normal, healthy, elderly persons. The anthropometric method significantly overestimated actual muscle areas, and the amount of error increased systematically with level of adiposity. These results agree with those from other, similar studies using CT in younger adults, but indicate that the degree of error is 2 to 3 times greater for elderly persons. At present, there does not appear to be any simple way to "correct" the anthropometric method. Prediction methods may be developed, but these will still produce large errors for some individuals. Alternative approaches are discussed.

Adipose Tissue↗

PubMed1992

The importance of N-linked glycoproteins and dolichyl phosphate synthesis for fusion of L6 myoblasts.

Myoblasts fuse to form multinucleated myotubes, one of the early steps in the formation of multinucleated muscle fiber. The fusion reaction is accompanied by biochemical differentiation resulting in the expression of a variety of enzyme activities and macromolecules, particularly creatine phosphokinase. The fusing myoblast is thus an excellent system for use in studies on the molecular basis of cellular recognition. This report focuses on the role played by glycoproteins in this process. It was found that alteration of cell-surface glycoproteins, using oligosaccharide-processing inhibitors that interfered with the synthesis of the high-mannose type of N-linked oligosaccharide, resulted in the inhibition of both the fusion reaction and biochemical differentiation as determined by measurement of creatine phosphokinase. Ketoconazole, compactin, and lovastatin, which affect dolichol and cholesterol biosynthesis, were also potent fusion inhibitors. These observations, coupled with earlier studies on the characterization of fusion-defective myoblast cell lines defective in glycoprotein biosynthesis, point to the importance of surface glycoproteins in cellular recognition in L6 myoblasts.

1-Deoxynojirimycin↗

PubMed1992

Fat distribution and blood lipids in a sample of healthy elderly people.

The cross-sectional sample consisted of data for 41 white men and 63 white women, 67-92 years of age who were healthy volunteer participants in the Aging Process Study at the University of New Mexico School of Medicine in Albuquerque, New Mexico. The variables consisted of anthropometric measures of body fatness, blood lipids and blood pressures. Correlations were computed between principal component scores, ratios of body circumferences, W/S2, blood lipid values and blood pressures for each sex. In the men, the significant correlations were of the abdomen/hip and abdomen/thigh ratios with W/S2, and the principal component scores with HDL cholesterol, triglyceride and systolic blood pressure. In the women, the abdomen/hip ratio had a low negative correlation with HDL cholesterol but a low positive correlation with triglyceride levels. The principal component scores also had low correlations with blood pressure and triglycerides. Multiple regressions were used to determine further associations between risk factors and fat distribution indices. In the men, the relationships of age and levels of body fatness with HDL cholesterol were much stronger and more complex than those with triglyceride or systolic blood pressure. In the women, only HDL cholesterol and triglyceride were associated with abdomen/hip ratio after removing the effects of overall fatness. The present findings indicate that a large abdominal circumference, implying a correspondingly large internal adipose tissue deposit, produces negative health alterations in blood lipid levels in this sample of elderly individuals. In younger adults, these changes are considered to increase the risk for cardiovascular disease.

Adipose Tissue↗

PubMed1990

Studies on the effect of ketoconazole on the fusion of L6 myoblasts.

The effect of ketoconazole on the fusion of L6 myoblasts was studied. Ketoconazole was a potent inhibitor of myoblast fusion at concentrations as low as 0.1 microM, but fusion was restored when the inhibitor was removed. The inhibitor resulted in decreased binding of conA and WGA to cell surface oligosaccharides showing that it was inhibiting N-linked cell surface glycoproteins. Inhibition of fusion by ketoconazole was accompanied by reduced creatine phosphokinase activities showing that it is affecting biochemical differentiation. Incorporation of labelled mannose from GDP-mannose into lipid-sugar and lipid-oligosaccharide complexes involved in the synthesis of N-linked oligosaccharides was also inhibited by ketoconazole, but the inhibition was reversed by addition of exogenous dolichol phosphate to the incorporation mixture. The main conclusion from these studies was that ketoconazole inhibited fusion of L6 myoblasts by affecting the synthesis of dolichol-phosphate required for the synthesis of lipid-oligosaccharides needed for the synthesis of fusogenic cell surface N-linked glycoproteins.

Animals↗

PubMed1989

Studies on glycosyltransferases in fusion-defective conA-resistant L6 rat myoblast cell lines.

1. Sialyl- and galactosyl-transferase activities were determined in wild type and conA-resistant L6 rat myoblasts with substrates derived from fetuin, alpha 1-acid glycoprotein and bovine submaxillary mucin; fetuin was the best acceptor for both enzyme activities, whereas the mucin did not act as an acceptor. 2. The optimum pH for sialyltransferase was 6.6 in both cell lines. 3. The optimum pH for galactosyltransferase in the wild type cell line was 6.2 which was slightly higher than the value of 5.8 found for the conA-resistant cells. 4. Values for Km for both enzyme activities increased five to ten-fold in the variant cell line with both acceptors. 5. The main sialyltransferase activity was the Gal beta 1----4GlcNAc alpha 2----3sialyltransferase for N-linked chains. The galactosyltransferase was most likely the enzyme that is responsible for the synthesis of the Gal beta 1----4GlcNAc structure.

Animals↗