Biomedical subjects

C S Uhm

Publications and source records attributed to C S Uhm.

7 recordsLinked to original sources

PubMed1999

Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting.

Using degenerate polymerase chain reaction, we isolated a cDNA encoding a novel 493-amino acid protein from human and mouse adult heart cDNAs and have designated it angiopoietin-related protein-2 (ARP2). The NH(2)-terminal and COOH-terminal portions of ARP2 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in angiopoietins. ARP2 has two consensus glycosylation sites and a highly hydrophobic region at the NH(2) terminus that is typical of a secretory signal sequence. Recombinant ARP2 expressed in COS cells is secreted and glycosylated. In human adult tissues, ARP2 mRNA is most abundant in heart, small intestine, spleen, and stomach. In rat embryos, ARP2 mRNA is most abundant in the blood vessels and skeletal muscles. Endothelial and vascular smooth muscle cells also contain ARP2 mRNA. Recombinant ARP2 protein induces sprouting in vascular endothelial cells but does not bind to the Tie1 or Tie2 receptor. These results suggest that ARP2 may exert a function on endothelial cells through autocrine or paracrine action.

Amino Acid Sequence↗

PubMed1999

Magnetic resonance image-based cerebellar volumetry in healthy Korean adults.

The effects of age and gender on cerebellar size have not been established yet. To understand these effects, the area of cerebellar vermis and the volume of cerebellum were measured using serial magnetic resonance images of 124 Korean adults free of neurologic symptoms and signs. Cerebellar volume of male was significantly larger than that of female, although the size of vermis did not show significant gender difference. Correlation analysis revealed that cerebellar volume was not affected by aging. Regressional analysis demonstrated that female vermis had a tendency to shrink after age of 50, whereas male vermis and total cerebellar volume in both sexes were not altered with aging. The different response of vermis with aging and maintenance of cerebellum volume need to be more explored.

Adult↗

PubMed1999

Morphologic investigation of rolling mouse Nagoya (tg(rol)/tg(rol)) cerebellar Purkinje cells: an ataxic mutant, revisited.

Rolling mouse Nagoya (rolling: tg(rol)) is a neurologic mutant mouse exhibiting severe ataxia. Two alleles of the rolling mutation, tottering (tg) and leaner(tg(la)), have been identified as mutations in the voltage-dependent calcium channel alpha1A subunit. No specific light and electron microscopic findings have been reported for the rolling mouse cerebellum except a decreased number of granule cells, while altered Purkinje cell/parallel fiber synapses have been observed in tottering and leaner cerebella. Rolling mouse cerebella were analyzed using anti-calbindin-D immunohistochemistry and transmission electron microscopy to investigate Purkinje cell morphology and synaptic contacts between Purkinje cell dendritic spines and parallel fiber varicosities. Multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities were frequently observed in rolling cerebella. The correlation between the presence of altered Purkinje cell synapses and ataxia in rolling mice warrants further investigation.

Alleles↗

PubMed1998

MK-801, a non-competitive NMDA receptor antagonist, prevents postischemic decrease of inositol 1,4,5-trisphosphate receptor mRNA expression in mongolian gerbil brain.

Changes of inositol 1,4,5-trisphosphate receptor (IP3R) mRNA expression after transient brain ischemia and the effect of MK-801, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, on the IP3R mRNA expression was studied in mongolian gerbil brain by in situ hybridization. Transient ischemia was induced by ligating left common carotid artery for 10 min, and the animals were allowed recovery from 15 min to 24 h. MK-801 was introduced intraperitoneally 30 min before ischemia. IP3R mRNA expression was decreased in dentate gyrus and hippocampus from 90 min until 24 h after ischemia. MK-801 pretreatment prevented the change of IP3R mRNA expression after ischemia. These results suggest that IP3R mRNA expression in ischemia may be related with NMDA receptor.

Animals↗

PubMed1997

alpha1-antitrypsin gene mutation hot spot associated with the formation of a retained and degraded null variant [corrected; erratum to be published].

Null alpha1-antitrypsin (alpha1AT) alleles represent the end of a continuum of variants associated with profound alpha1AT deficiency and an increased risk of emphysema. This study characterizes the molecular basis of QOclayton, a new example of an alpha1AT null allele arising from a mutational hot spot in the alpha1AT gene. The QOclayton allele is identical to the normal M1(V213) alpha1AT allele except for an insertion of a cytosine. This insertion occurs in the alpha1AT sequence which normally has seven cytosines corresponding to amino acid residues 360 to 362. The QOclayton mutation is located in the same reiterated DNA sequence as the alpha1AT QObolton deletion mutation and the insertion mutation allele QOsaarbruecken. The QOclayton cytosine insertion causes a 3' frameshift and results in the formation of a termination codon at residue 376, the same consequence as the alpha1AT QOmattawa mutation (L353 T-insertion with a 3' frameshift). To determine the molecular mechanisms responsible for the absence of alpha1AT associated with the QOclayton gene, an in vitro model of QOclayton was established using Chinese hamster ovary cells (CHO) transfected with the QOclayton gene. These cells were evaluated for alpha1AT mRNA expression, protein synthesis and secretion. Although the QOclayton gene expresses a similar amount of alpha1AT mRNA as compared with the normal alpha1AT gene, no QOclayton protein is secreted. Protein trafficking and double-label immunofluorescence demonstrate that the QOclayton protein is retained in the rough endoplasmic reticulum or pre-Golgi compartment and is degraded (t1/2 = 6.5 h). Since QOmattawa, QObolton, and QOsaarbruecken have similar termination sites in the alpha1AT mRNA, they may share a similar intracellular fate.

Animals↗

PubMed1995

Acetylcholine receptor aggregation at nerve-muscle contacts in mammalian cultures: induction by ventral spinal cord neurons is specific to axons.

We used a novel mammalian coculture system to study ACh receptor (AChR) redistribution and synaptic structure at nerve-muscle contacts. Ventral spinal cord (VSC) neurons were plated on cultures containing extensive myotubes but few fibroblasts. Neurite-induced redistribution of AChRs occurred within 6 hr after plating neurons and was maximal between 36-48 hr. This AChR redistribution appeared in two patterns: (1) AChR density at sites directly apposed to the neurite where neurites crossed preexisting AChR patches was sharply reduced, (2) Newly aggregated AChRs formed swaths lateral to the neurite path. VSC neurons induced more AChR aggregation than hippocampal, superior cervical ganglion and dorsal root ganglion neurons. The 43 and 58 kDa postsynaptic proteins were colocalized with AChR-enriched domains in all VSC neurite-induced aggregates whereas the colocalization of laminin was variable. Electron microscopy of regions with neurite-induced AChR aggregation showed postsynaptic membrane specializations characteristic of developing synapses and, in older cultures, features of more mature synaptic structure. Thus, the coculture system is useful for studying early stages of neuromuscular junction (NMJ) formation. Neurites in these cocultures were identified as axons or dendrites by morphological criteria and by their immunoreactivity for synaptophysin and phosphorylated heavy neurofilament subunits or for microtubule associated protein 2 (MAP2), respectively. Axons showed a 10-fold higher induction of AChR aggregation than did dendrites. Thus, at least one essential signaling molecule necessary for the induction of AChR aggregation at sites of interaction with muscle appears to be expressed in a polarized fashion in developing VSC neurons.

Animals↗

PubMedDate not supplied

Altered expression of tropomodulin in cardiomyocytes disrupts the sarcomeric structure of myofibrils.

Tropomodulin is a tropomyosin-binding protein that terminates "pointed-end" actin filament polymerization. To test the hypothesis that regulation of tropomodulin:actin filament stoichiometry is critical for maintenance of actin filament length, tropomodulin levels were altered in cells by infection with recombinant adenoviral expression vectors, which produce either sense or antisense tropomodulin mRNA. Neonatal rat cardiomyocytes were infected, and sarcomeric actin filament organization was examined. Confocal microscopy indicated that overexpression of tropomodulin protein shortened actin filaments and caused myofibril degeneration. In contrast, decreased tropomodulin content resulted in the formation of abnormally long actin filament bundles. Despite changes in myofibril structure caused by altered tropomodulin expression, total protein turnover of the cardiomyocytes was unaffected. Biochemical analyses of infected cardiomyocytes indicated that changes in actin distribution, rather than altered actin content, accounted for myofibril reorganization. Ultrastructural analysis showed thin-filament disarray and revealed the presence of leptomeres after tropomodulin overexpression. Tropomodulin-mediated effects constitute a novel mechanism to control actin filaments, and our findings demonstrate that regulated tropomodulin expression is necessary to maintain stabilized actin filament structures in cardiac muscle cells.

Actins↗