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Biomedical subjects

X Bu

Publications and source records attributed to X Bu.

59 records · Page 4Linked to original sources
PubMed1992

Sensorineural deafness inherited as a tissue specific mitochondrial disorder.

We present here a large Israeli-Arab kindred with hereditary deafness. In this family 55 deaf subjects (29M, 26F), who are otherwise healthy, have been identified and traced back five generations to one common female ancestor. The deafness is progressive in nature, usually presenting in infancy and childhood. Audiometry on six deaf and seven unaffected subjects was consistent with severe to profound sensorineural hearing loss. Based on formal family segregation analysis, the inheritance of deafness in this family closely fits the expectation of a two locus model owing to the simultaneous mutation of a mitochondrial gene and an autosomal recessive gene. Thus, this disorder appears to have the unusual features of being an inherited tissue specific mitochondrial disease and apparently requiring the homozygous presence of a nuclear gene for clinical expression. Most importantly, this disorder presents a unique opportunity to investigate the molecular basis of hereditary non-syndromic deafness and normal hearing.

Adult↗
PubMed1992

The gene for familial Mediterranean fever in both Armenians and non-Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity.

Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, we studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the alpha-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3' HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lodmax] = 9.76 at maximum recombination fraction [theta] = .076). In the Armenians, the lodmax = 3.61 at theta = .10; and for the non-Ashkenazi Jews, lodmax = 6.28 at theta = .06. There was no evidence for genetic heterogeneity between the Armenians and the non-Ashkenazi Jews (chi 2 = 1.28; P = .26) or within either ethnic group (chi 2 = .00; P = .50). Thus, the gene for FMF is linked to the alpha-globin complex on chromosome 16p in both non-Ashkenazi Jews and Armenians.

Armenia↗
PubMed1991

Platelet-derived growth factor stimulates phosphorylation of the 25 kDa mRNA cap binding protein (eIF-4E) in human lung fibroblasts.

Platelet-derived growth factor exerts rapid effects on protein synthesis and polysome formation in cultured cells. We report that platelet-derived growth factor stimulates a rapid phosphorylation of eIF-4E in WI-38 human lung fibroblasts. The effect was dependent on both time and PDGF concentrations. Phosphoserine was the sole phosphoamino acid identified and tryptic phosphopeptide maps showed a single phosphopeptide under both control and PDGF conditions. Phosphorylation of eIF-4E may be of the events required for initiating entry into G1 and commitment into S phase of the cell cycle.

Amino Acids↗
PubMedDate not supplied

Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity.

PURPOSE: Aminoglycoside-induced deafness has been described in a number of Chinese pedigrees. In nearly all of these families, affected individuals were related through the maternal side. Because mitochondrial DNA is transmitted exclusively through mothers, it had been speculated that a mutation in the mitochondrial DNA might predispose these maternally related family members to aminoglycoside ototoxicity. Recently, we analyzed three such families with multiple cases of ototoxic deafness and identified a pathogenic mutation in the mitochondrial 12S ribosomal RNA gene at nucleotide position 1555. The purpose of the current study is to analyze individuals with no family history of deafness, who had severe hearing loss after aminoglycoside exposure, for presence or absence of this particular mitochondrial DNA mutation. MATERIALS AND METHODS: Blood was obtained from 36 Chinese individuals who became deaf after aminoglycoside exposure and had no family history of deafness. The DNA of these individuals was extracted, amplified by the polymerase chain reaction, and analyzed for the mitochondrial ribosomal RNA gene mutation by allele-specific oligonucleotide hybridization and Southern blot analysis. RESULTS: In one of these 36 sporadic cases, we identified the nucleotide 1555 A-->G mutation in the mitochondrial genome. CONCLUSION: This finding implies that a small proportion of individuals at risk for aminoglycoside ototoxicity harbor the specific mitochondrial DNA mutation identified in the familial cases. In these individuals, a genetic susceptibility to the ototoxic effects of aminoglycosides can be diagnosed, and deafness can be prevented in maternal relatives by avoiding the use of these antibiotics.

Adolescent↗