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Biomedical subjects

X Ma

Publications and source records attributed to X Ma.

391 records · Page 22Linked to original sources
PubMed1985

Analysis of mouse major urinary protein genes: variation between the exonic sequences of group 1 genes and a comparison with an active gene out with group 1 both suggest that gene conversion has occurred between MUP genes.

Here we compare the exonic sequences of four Group 1 mouse major urinary protein (MUP) genes and four Group 1 cDNA sequences. These define seven different nucleotide sequences which differ from each other by 0.35% of bases on average, and which would code for seven different MUP proteins that could probably be resolved physically into at least five classes. The sequences differ at 13 nucleotide positions and at six codons, and although they are closely related their descent cannot be described by a simple series of duplications. We also describe the sequence of another liver cDNA (pMUP15) which has diverged from the Group 1 consensus sequence in 14.6% of bases. The divergence is much greater over exons 1-3 than over exons 4-6, suggesting that an ancestral gene conversion event has occurred. pMUP15 also differs from the Group 1 genes in having a longer signal peptide sequence and a different splice configuration between exons 6 and 7. Unlike the Group 1 sequences, pMUP15 contains a potential N-linked glycosylation site. Other published work has shown that a shorter cDNA clone which is identical over their common sequence to pMUP15 codes for MUP proteins that are unusually large in size and acidic in pI. We show here that mouse urine does indeed contain a glycosylated MUP protein with those properties, presumably the product of the gene that corresponds to pMUP15.

Animals↗
PubMed1984

Synthesis of simian virus 40 chromosomes in nuclear extracts from dihydroxyanthraquinone-treated cells.

The effect of dihydroxyanthraquinone (DHAQ), a new antitumor drug, on mammalian chromosome replication was investigated using simian virus 40 (SV40) as a model system. The maximum effect of inhibition on viral DNA synthesis was observed within 30-40 min after the addition of the drug. The extent of inhibition of viral DNA synthesis appeared to be directly related to the number of viral replicons which interact with DHAQ molecules in vivo. No apparent strand breakage of SV40 DNA was observed in infected cells treated with DHAQ ranging from 0.3 to 10 microM. However, strand breakage was induced upon cell lysis presumably by released nuclease. Repair of the damaged SV40 chromosomes in vitro resulted in the synthesis of completed supercoiled SV40 DNA. This repair synthesis was mostly confined to the region containing the replication origin of SV40 DNA as judged by the digestion of DNA with restriction endonucleases HindII and HindIII. Since SV40 DNA sequences close to the origin of replication are not complexed with histones to form a nucleosome structure, the results suggested that DHAQ may disturb chromosome structure by interacting preferentially to the nucleosome-free regions and causing the aberrant gene duplication and expression.

Anthraquinones↗
PubMedDate not supplied

Novel mechanisms in the treatment of heart failure: inhibition of oxygen radicals and apoptosis by carvedilol.

Carvedilol is a novel cardiovascular drug of proven efficacy in the treatment of hypertension, angina, and heart failure. Several mechanisms may account for the beneficial effects of carvedilol in patients with heart failure. As with other beta-blockers, blockade of cardiac beta-adrenergic receptors (both beta1 and beta2), and hence reduction of cardiac work load and oxygen consumption, plays an important role in the actions of this agent. Additional benefit is provided by vasodilation (alphal-adrenergic blockage) at peripheral resistance vessels, which decreases preload and after-load, thereby further reducing cardiac work and wall tensions. In addition, potential advantages of carvedilol resulting from alpha1-adrenergic blockade are likely because alpha1-adrenergic receptors mediate cardiac remodeling by inducing hypertrophy. Finally, carvedilol is a potent antioxidant and is unique among beta-blockers in this respect. In recent years, evidence has accumulated in support of the role played by reactive oxygen radicals in chronic pathological states of the myocardium. In this article, the role of oxygen radicals in heart failure is discussed with special reference to apoptosis, a phenomenon believed to be involved in progressive cardiac myocyte loss in ischemic or myopathic heart diseases. The potential role of the antioxidant actions of carvedilol, especially in prevention of apoptotic cell death, is highlighted as a novel mechanism of action in heart failure.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Purification of developmentally regulated avian 400-kDa intermediate filament associated protein. Molecular interactions with intermediate filament proteins and other cytoskeleton components.

IFAPa-400, a 400-kDa developmentally regulated protein thought to be associated with intermediate filaments, has been purified from chick embryo hearts to investigate its interaction with vimentin and other IF proteins and to identify other cellular components to which this cytoskeletal protein associates. Previous studies suggested that this protein was associated with the vimentin-containing intermediate filament lattice of myoblasts and neuroblasts before their terminal differentiation, providing these cells with a particular intermediate filament cytoskeleton that could satisfy specific mechanical requirements during their intense morphogenetic activities. Although IFAPa-400 partially reassociated with vimentin and desmin in disassembly-reassembly experiments using crude IF preparations from chick embryo hearts, in vitro recombination of purified IFAPa-400 with vimentin and desmin failed to demonstrate any direct association. When purified IFAPa-400 was used as a probe in blot overlay assays, however, specific binding to vimentin and desmin was observed, providing the first evidence of a physical association between IFAPa-400 and intermediate filament proteins. The blot overlay experiments also demonstrated that IFAPa-400 binds to two unidentified polypeptides of 19 and 32 kDa. These results are thus consistent with the hypothesis that a structural lattice requiring a vimentin-IFAPa-400 combination constitutes the intermediate filament system of myogenic and neurogenic cells.

Animals↗
PubMedDate not supplied

Characterization of major phosphoproteins in the cGMP-mediated protein phosphorylation system of vascular smooth muscle membranes.

G(0) (215-250 kD) and G(1) (120-140 kD), the unidentified major phosphoproteins in the cGMP-mediated protein phosphorylation system of vascular smooth muscle membranes, were compared for biochemical and immunological properties with the type 1 inositol 1,4, 5-trisphosphate receptor (InsP(3)R, 240 kD) and the myosin-binding subunit (MBS, 138 kD) of myosin phosphatase, both of them substrates for cGMP-dependent protein kinase. Two microsomal proteins that were immunoreactive with antibodies to InsP(3)R and MBS were detected, and comigrated with G(0) and G(1), respectively, on SDS-PAGE. When thiophosphorylated G(0) and G(1) were subjected to immunoprecipitation, MBS antibody induced the precipitation of a 138-kD phosphoprotein, but did not significantly affect the amount of G(1) remaining in the supernatant, while InsP(3)R antibody precipitated G(0) almost completely. Unexpectedly, InsP(3)R antibody coprecipitated a large portion of G(1), which did not cross-react with either antibody to MBS or InsP(3)R. Just like InsP(3)R, G(0) bound to the calmodulin column in a Ca(2+)-dependent manner, and, again, a large portion of G(1) was copurified with G(0). These results suggest that G(0) is identical to InsP(3)R, while G(1) consists of several phosphoproteins, including the 138-kD protein associated with InsP(3)R as a major component. MBS is not G(1) or may represent only a minor component of it.

Animals↗
PubMedDate not supplied

Comparison of acute hepatocellular proliferating cell nuclear antigen labeling indices and growth fractions, p34cdc2 kinases, and serum enzymes in carbon tetrachloride-treated rats.

We evaluated various biomarkers associated with cell proliferation immediately following insult with the classic hepatotoxicant carbon tetrachloride (CCl4). Rats were administered a single necrogenic dose of CCl4 and euthanized at either t = 4, 8, 12, 16, or 24 hr postdose. Parameters evaluated included the following: immunohistochemical detection of hepatocellular proliferating cell nuclear antigen labeling indices (PCNA-LIs; percentage of cells in S phase) and growth fractions (PCNA-GFs; percentage of cells in the cell cycle); PCNA and the cyclin-dependent kinase p34cdc2 (CDK) protein in S-9 fractions by Western blot and enzyme-linked immunosorbent assay (ELISA); and liver-related serum enzymes. An increase in PCNA-GF was observed at t = 4 hr, concomitant with elevations in CDK and PCNA protein (Western blot). PCNA-LIs were increased by t = 24 hr, as were CDK and PCNA by ELISA. Sorbitol dehydrogenase was the most sensitive enzyme, with increases observed at t = 4 hr. Our results indicate that PCNA-GF, CDK, and PCNA levels reflect hepatocellular regeneration as early as 4 hr following CCl4 insult. We conclude that these assays are early and sensitive indicators of acute hepatotoxicity that may be advantageous to evaluate in the early stages of exploratory studies.

Alanine Transaminase↗
PubMedDate not supplied

Active MR tracking on a 0.2 Tesla MR imager.

An active MR tracking system was implemented on a 0.2 Tesla open MRI system. Interventional devices with receive-only microcoils at their tips were developed and investigated on the scanner. Microcoils having a diameter of about 1 mm and 20 turns were found to provide sufficient signal-to-noise ratios for stable tracking. Positional accuracy and precision were found to be acceptable under practical conditions. Simulation of MR-guided biopsy using biplane images with tracking was performed in a gelatin phantom and dog livers. Successful tracking of catheters with integrated microcoils was also demonstrated in the aorta and IVC of live dogs.

Animals↗
PubMedDate not supplied

In vitro and in vivo evaluation of microencapsulated porcine islets.

To provide a plentiful supply of pancreatic islets for future clinical transplants into diabetic patients, the authors have developed a simple and consistent method of isolation of porcine islets. Both in vitro and in vivo studies demonstrated that the islets were viable and functional. Xenotransplants of 1.5 x 10(3) - 2.5 x 10(3) of microencapsulated porcine islets into diabetic mice resulted in restoration of normoglycemia in 13 of 18 experimental animals for up to 10 months. A xenograft of 50 x 10(3) microencapsulated porcine islets into a spontaneously diabetic monkey normalized hyperglycemia for more than 150 days. This experiment indicated that the transplantation of encapsulated porcine islets has great potential as a clinical treatment in diabetes mellitus.

Animals↗