Biomedical subjects

V Maloney

Publications and source records attributed to V Maloney.

3 recordsLinked to original sources

PubMed2006

A highly complex rea(2;3;11) and aniridia by position effect.

A two-year-old boy presenting with bilateral aniridia and psychomotor retardation had a de novo (2;3;11) highly complex rearrangement which was characterized as far as possible by means of G-banding and FISH assays with multiple probes including cosmids for the Wilms, Aniridia, Genital anomalies and Retardation (WAGR) region, alphoid repeats for chromosomes 2, 3 and 11, subtelomere probes for 2p/2q, 3p/3q and 11q and BACs for 2q32 and 3q13. We identified approximately 15 breakpoints with at least three interchromosomal and three intrachromosome anomalies involving chromosome 11. Both parents had normal karyotypes and no cryptic 11p rearrangements revealed by the chromosome 11 cosmid panel. The lack of a deletion of PAX6 pointed to the direct insertion of an approximately 300-kb segment involving the cosmids FO2121 and AO4160, and more specifically the insertion's proximal breakpoint in the approximately 150-kb segment between FO2121 and FAT5 (PAX6), as the responsible factor for the patient's aniridia via a position effect resulting in functional haploinsufficiency of the PAX6 gene. This case illustrates the importance of recognizing that de novo complex chromosomal rearrangements found in patients with diverse clinical features may contribute to the phenotype, but that multiple mechanisms and higher levels of complexity may be unmasked by high resolution molecular cytogenetic studies.

Aniridia↗

PubMed1994

Purification and characterization of simian immunodeficiency virus (SIVmac) envelope glycoprotein gp130 from virus-infected cells.

A non-denaturing method has been developed for the purification of the envelope glycoprotein gp130 of the simian immunodeficiency virus (SIV) using infected cells as starting material. The procedure involves solubilization of cells infected with SIV (SIVmac251), enrichment of glycoproteins by lectin affinity chromatography, fractionation by reverse phase chromatography and purification by immunoaffinity chromatography. This procedure results in a greater than 95% purification of gp130 as assessed by polyacrylamide gel electrophoresis. There is no evidence for the presence of other virus-derived proteins after Western blot analysis using antibodies specific for virus proteins. Lectin-binding studies suggest that carbohydrate groups on the infected-cell-derived gp130 may differ from those on recombinant counterparts expressed in Chinese hamster ovary cells and Baculovirus-infected insect cells. The purified gp130 is highly immunogenic in rabbits and maintains the capacity to bind the CD4 receptor. A sufficient quantity of the infected-cell-derived gp130 has been prepared for immunization studies and subsequent live virus challenge studies in macaques.

Amino Acid Sequence↗

PubMed1992

Contractile arrest accelerates myosin heavy chain degradation in neonatal rat heart cells.

Mechanical forces influence the growth and metabolism of a variety of cells, including cultured neonatal rat ventricular myocytes. To determine whether mechanical activity affected the synthesis and turnover of myosin heavy chain (MHC) in these striated muscle cells, MHC fractional degradative rates were measured in spontaneously beating cells and in arrested myocytes in which contractile activity was prevented by L-channel blockade (with verapamil, nifedipine, nisoldipine, and diltiazem) or K+ depolarization. MHC degradative rates were measured as the difference between rates of MHC synthesis and accumulation and in pulse-chase biosynthetic labeling experiments. Both methods indicated that contractile arrest markedly increased MHC degradation. Contractile arrest produced by L-channel blockade accelerated MHC degradation to a greater extent than K+ depolarization. The signal transduction pathway linking contractile activity to alterations in MHC degradation did not involve protein kinase C (PKC), because MHC degradation was unaffected by activating PKC in arrested cells or inhibiting PKC in spontaneously beating cells. Chloroquine and E-64 did not suppress the accelerated MHC degradation, suggesting that the rate-limiting step in MHC turnover occurred before degradative processing by cellular proteinases. Using a computer simulation, we hypothesize that the rate-limiting step in MHC turnover preceded (or was coincident with) MHC release from thick filaments. Thus mechanical forces may influence MHC half-life by regulating the rate of myosin disassembly.

Animals↗