Search PubMed⌕ Search

Biomedical subjects

W Chung

Publications and source records attributed to W Chung.

At least 37 records · Page 2Linked to original sources

Origin of extracellular matrix synthesis during coronary repair.

BACKGROUND: Coronary injury triggers differentiation of activated adventitial fibroblasts to myofibroblasts, which may contribute to neointimal formation and vascular remodeling. Accordingly, the purpose of this study was to examine the cellular origin of the enhanced synthesis of extracellular matrix proteins during coronary repair. METHODS AND RESULTS: The time course and localization of collagen and elastin expression were examined by in situ hybridization and immunohistochemistry in porcine coronary arteries after balloon-induced injury. Procollagen-alpha 1(I) transcripts and intracellular type I procollagen protein increased in the adventitia within 2 days after injury. This was followed by a sustained synthesis of type I procollagen in neointima beginning at 7 days and the extracellular accumulation of type I collagen in both layers. The origin of synthetic cells was further examined by colocalization of type I procollagen and bromodeoxyuridine labeling to activated adventitial cells, which translocated to neointima. Neointimal cells exhibited sustained synthetic activity manifested by the presence of type I procollagen and elastin at 3 months after injury. In contrast, the media showed only minor changes in the synthesis of collagen or elastin throughout coronary repair. CONCLUSIONS: Activated adventitial fibroblasts are endowed with synthetic capabilities after coronary injury. They express type I procollagen, with some of them translocating to the intima, where they continue to synthesize procollagen. The accumulation of type I collagen is evident in the adventitia and neointima, whereas elastin accumulates mainly in neointima. These findings support the involvement of adventitial fibroblasts in coronary repair and remodeling after endoluminal injury.

Angioplasty, Balloon↗

Molecular genetic analysis of a human neuropeptide Y receptor. The human homolog of the murine "Y5" receptor may be a pseudogene.

Neuropeptide Y is a 36-amino-acid peptide amide with numerous biological activities. These functions are mediated through several pharmacologically distinct receptors. To date five receptor subtypes have been cloned. Here we report the isolation, by low stringency homology cloning from a hypothalamic library, of a cDNA encoding the human homolog of the murine neuropeptide Y receptor subsequently reported (). Translation of the human Y1-like receptor clone suggested that it encoded a receptor which is truncated in the third extracellular loop. Comparison of the human Y1-like sequence to that of the human Y1 receptor suggested that the truncated receptor could have resulted from a frameshift due to a single nucleotide deletion in the sixth transmembrane domain. Southern blot analysis suggested that the gene is single copy in the human genome. The gene is located on chromosome 5q. To test the hypothesis that allelic variation of nucleic acid length within the sixth transmembrane domain of the Y1-like receptor may exist to produce a functional receptor, genomic DNA from 192 individuals of various ages, ethnic backgrounds, and degrees of obesity were analyzed electrophoretically and by direct sequencing. No variation was detected in any of the subjects, indicating that this receptor subtype may be a transcribed pseudogene in humans.

Amino Acid Sequence↗

Developmental specificity of immunoglobulin heavy chain switch region recombination activities.

To understand the regulation of enzymes that carry out immunoglobulin heavy chain class switch recombination, we have assayed recombination of extrachromosomal substrates carrying switch region sequences in cell lines representing different stages of lymphoid cell development. Both pre-B and mature B cell lines supported switch substrate recombination, but B cell lines derived from later stages of cell development did not. Recombination did not occur in an erythroid or a macrophage line. Most recombination junctions in the substrates recovered from transfection of pre-B and B cells mapped to heterogeneous sites within the S mu and Sgamma regions, as do chromosomal switch junctions. Some recombination did occur in T cell lines, but most recombination junctions involved an upstream promoter and did not map preferentially to S regions. Culture of the pre-B cell lines PD31 and 70Z/3 with LPS increased recombination two-fold, to levels approaching those observed in LPS-cultured primary B cells. These results show that the full complement of factors necessary for switch recombination is present only in cells representing a limited spectrum of B cell development and that LPS, which can activate resting splenic B cells to carry out chromosomal recombination, can also stimulate recombination activity in immortalized pre-B cell lines.

Animals↗

TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor.

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for several members of the TNF receptor superfamily. We have identified a novel member of the TRAF family by degenerate oligonucleotide polymerase chain reaction amplification that contains a zinc RING finger and zinc finger motifs, a coiled-coil region, and a C-terminal "TRAF" homology domain. In vitro translated TRAF5 binds to the cytoplasmic region of the lymphotoxin-beta receptor (LT-betaR) but not to several other related receptors including CD40, both TNF receptors, Fas, and nerve growth factor receptor. TRAF5 and LT-betaR coimmunoprecipitate when overexpressed in COS7 cells. TRAF5 mRNA expression is found in all visceral organs and overlaps with LT-betaR. These features distinguish TRAF5 from the other members of the TRAF family. The transcription factor NF-kappaB is activated in HEK293 cells by overexpression of full-length TRAF5 but not a truncated form lacking the zinc binding region. Furthermore, overexpression of LT-betaR in HEK293 cells also results in activation of NF-kappaB, which is partially inhibited by the truncated TRAF5 mutant. These results show TRAF5 is functionally similar to TRAF2 in that both mediate activation NF-kappaB and implicate TRAF5 as a signal transducer for LT-betaR.

Amino Acid Sequence↗

Behavioral relaxation training for tremor disorders in older adults.

Two adult men, aged 86 and 63, with essential tremor and Parkinson's-disease-related tremor, respectively, were provided Behavioral Relaxation Training in reclined and upright seated positions. Multiple measures were recorded, including the Behavioral Relaxation Scale (BRS), clinical and self-rated tremor severity, informant ratings, ratings of disability in activities of daily living (ADL), and forearm EMG. Results showed increased relaxation skills on the BRS, with reductions in EMG, tremor ratings, and some ADL disabilities. Upright BRS scores did not change during reclined training, but improved rapidly during upright training. The second man was found to suffer from dyskinesia when he relaxed during baseline, which declined markedly during training. A two-week follow-up indicated that most improvements were maintained by both men. Statistical analyses of data for each man showed significant changes. These results suggest that relaxation may be useful in the treatment of idiopathic and pathologic tremor disorders in older adults.

Aged↗

The impact of a summer asthma camp experience on asthma education and morbidity in children.

BACKGROUND: This study examines whether an educational program emphasizing self-management skills can be successfully implemented in an asthma camp setting, and the degree to which this camp experience would affect asthma-associated morbidity among children attending such a program. METHODS: Ninety asthmatic children between the ages of 6 and 12 years who were attending a summer asthma camp were enrolled in the study. A precamp questionnaire was sent to the parents of these children to assess asthma morbidity during the preceding 12 months and to determine the prevalence of the use of peak flow meters and spacer devices by their children. At camp, children received educational sessions on asthma self-management, including training in the proper use of spacer devices and peak flow meters. Follow-up questionnaires were sent to the parents at 1 and 6 months after camp to assess the use of these devices and to measure subsequent asthma morbidity. RESULTS: Precamp use of spacer devices among all participants was 51.9%; the 1-month and 6-month post-camp use of spacer devices significantly increased to 92.4% (P < .001) and 85.9% (P < .001), respectively. The precamp use of peak flow meters was 50.0%; the 1-month and 6-month postcamp use was increased to 95.0% (P < .001) and 87.7% (P < .001), respectively. Six-month follow-up revealed a significant decrease in urgent outpatient visits for asthma exacerbations and a significant decrease in school day absences due to asthma. CONCLUSIONS: An asthma camp is an effective environment for a patient education program emphasizing self-management skills. Children with moderate to severe asthma who attend such a camp may experience a decrease in subsequent asthma-associated morbidity.

Ambulatory Care↗

Intracranial aneurysms: depiction on MR angiograms with a multifeature-extraction, ray-tracing postprocessing algorithm.

PURPOSE: To compare a new method for postprocessing data, soft thresholding and depth cueing of unrestricted techniques (STANDOUT), with maximum intensity projection (MIP) for magnetic resonance (MR) angiograms of intracranial aneurysms. MATERIALS AND METHODS: Eighteen patients with 19 intracranial aneurysms were studied. Images generated with STANDOUT were compared with those of MIP for both three-dimensional (3D) time-of-flight (TOF) and 3D phase-contrast (PC) techniques. Images were assessed for detection of aneurysms, scored for delineation of aneurysmal features and overall MR angiographic characteristics, and compared with catheter angiograms. RESULTS: Both postprocessing techniques demonstrated aneurysms on most TOF and PC MR angiograms. Statistically significant improvement of aneurysmal features, aneurysmal neck definition, and delineation of adjacent arterial anatomy was seen on both TOF and PC MR angiograms with STANDOUT. Feature definition was most improved for smaller aneurysms. TOF and PC MR angiograms with STANDOUT showed improved elimination of artifactual intraluminal signal loss in normal large vessels, reduced artifactual narrowing of vessel caliber, and better small vessel delineation. CONCLUSION: STANDOUT has great benefits for postprocessing of intracranial MR angiograms, regardless of the technique of data acquisition.

Cerebral Arteries↗

An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms.

Five DNA polymorphisms were detected in the promoter of the apolipoprotein CIII gene of a type III hyperlipidemic subject with severe hypertriglyceridemia (HTG). The polymorphic sites were C-641-->A, G-630--> A, T-625-->deletion, C-482-->T, and T-455-->C, with the previously reported base at each site designated allele 1 and the variant base designated allele 2. The sites were in strong linkage disequilibrium with each other and with a polymorphic Sst I site in the apolipoprotein CIII 3' untranslated region whose presence (S2 allele) has previously been shown to be associated with HTG. The distribution of haplotypes of the form -625 -482 Sst I among 78 normolipidemic adults and 79 adults with severe HTG was estimated by maximum likelihood analysis. The 211 haplotype was estimated to be 3.8-fold more common in normal subjects than in HTG subjects (estimated proportions, 0.186 and 0.049, respectively). This haplotype was associated with reduced HTG risk (relative risk, 0.28; P = 0.005) when compared with other haplotypes lacking the Sst I site (S1 allele). The 222 haplotype was estimated to be present on 48 of the 54 S2-containing chromosomes observed and was associated with increased risk for HTG (relative risk, 3.14; P < 0.0025). These results support the existence of apolipoprotein CIII promoter/Sst I haplotypes conferring either protection against or susceptibility to severe HTG.

Alleles↗

Flavin-containing monooxygenase: a major detoxifying enzyme for the pyrrolizidine alkaloid senecionine in guinea pig tissues.

Evidence based on optimal pH, thermal stability, and enzyme inhibition data suggests that the NADPH-dependent microsomal N-oxidation of the pyrrolizidine alkaloid senecionine is carried out largely by flavin-containing monooxygenase in guinea pig liver, lung, and kidney. In contrast, the hepatic microsomal conversion of senecionine to the pyrrole metabolite (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) is catalyzed largely by cytochrome P450. However, the rate of senecionine N-oxide formation (detoxication) far exceeded the rate of DHP formation (activation) in guinea pig liver microsomes over a range of pHs (pH 6.8 to 9.8). In guinea pig lung and kidney microsomes, N-oxide was the major metabolite formed from senecionine with little or no production of DHP. The high rate of detoxication coupled with the low level of activation of senecionine in liver, lung, and kidney may help explain the apparent resistance of the guinea pig to intoxication by senecionine and other pyrrolizidine alkaloids.

Animals↗