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Biomedical subjects

W Chung

Publications and source records attributed to W Chung.

At least 19 recordsLinked to original sources
PubMed2000

A performance adequate computational model for auditory localization.

A computational model of auditory localization resulting in performance similar to humans is reported. The model incorporates both the monaural and binaural cues available to a human for sound localization. Essential elements used in the simulation of the processes of auditory cue generation and encoding by the nervous system include measured head-related transfer functions (HRTFs), minimum audible field (MAF), and the Patterson-Holdsworth cochlear model. A two-layer feed-forward back-propagation artificial neural network (ANN) was trained to transform the localization cues to a two-dimensional map that gives the direction of the sound source. The model results were compared with (i) the localization performance of the human listener who provided the HRTFs for the model and (ii) the localization performance of a group of 19 other human listeners. The localization accuracy and front-back confusion error rates exhibited by the model were similar to both the single listener and the group results. This suggests that the simulation of the cue generation and extraction processes as well as the model parameters were reasonable approximations to the overall biological processes. The amplitude resolution of the monaural spectral cues was varied and the influence on the model's performance was determined. The model with 128 cochlear channels required an amplitude resolution of approximately 20 discrete levels for encoding the spectral cue to deliver similar localization performance to the group of human listeners.

Humans↗
PubMed1999

A single-stranded loop in the 5' untranslated region of cucumber mosaic virus RNA 4 contributes to competitive translational activity.

The 5' untranslated region (UTR) of cucumber mosaic virus (CMV) RNA 4 confers a highly competitive translational advantage on a heterologous luciferase open reading frame. Here we investigated whether secondary structure in the 5' UTR contributes to this translational advantage. Stabilization of the 5' UTR RNA secondary structure inhibited competitive translational activity. Alteration of a potential single-stranded loop to a stem by substitution mutations greatly inhibited the competitive translational activity. Tobacco plants infected with wild type virus showed a 2.5-fold higher accumulation of maximal coat protein than did plants infected with a loop-mutant virus. Amplification of viral RNA in these plants could not explain the difference in accumulation of coat protein. Phylogenetic comparison showed that potential single-stranded loops of 12-23 nucleotides in length exist widely in subgroups of CMV.

5' Untranslated Regions↗
PubMed1999

Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin.

Pharmacological control of interleukin-12 production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study we investigated the effects of curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1, 6-heptadiene-3,5-dione) on the production of interleukin-12 from mouse macrophages stimulated with lipopolysaccharide. Curcumin potently inhibited the production of interleukin-12 in a dose-dependent manner. The effect of curcumin on interleukin-12 p40 promoter activation was analyzed by transfecting RAW264.7 monocytic cells with p40 promoter/reporter constructs. The repressive effect mapped to a region in the p40 promoter containing a binding site for nuclear factor kappaB (p40-kappaB). Furthermore, activation of macrophages by lipopolysaccharide resulted in markedly enhanced binding activity to the kappaB site, which significantly decreased upon addition of curcumin. These results suggest that curcumin-induced inhibition of interleukin-12 production in macrophages may explain some of the biological effects of curcumin including its anti-inflammatory activity.

Animals↗
PubMed1999

Role of matrix metalloproteinases and their tissue inhibitors in the regulation of coronary cell migration.

The migration of vascular cells is regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Because the activation of adventitial fibroblasts has been implicated in coronary repair, we have examined regional differences in cell outgrowth and the synthesis of MMPs/TIMPs in different layers of porcine coronary arteries. Coronary medial explants demonstrated significantly slower cell outgrowth than coronary adventitia in culture (P<0.001). These observations were paralleled by the predominant expression of TIMP-1 and -2 in the media (14-fold and 37-fold higher than in adventitia, respectively, P<0.001), whereas higher gelatinolytic activities (MMP-2 and -9) were released from adventitial explants. Smooth muscle cell outgrowth from the media was regulated by endogenous TIMPs, since TIMP inhibition (recombinant MMP-2 or neutralizing anti-TIMP antibodies) facilitated cell outgrowth (P<0.001). In contrast, the addition of recombinant TIMP-1 or -2 decreased adventitial cell outgrowth. In the coculture experiments, the presence of coronary media retarded adventitial cell outgrowth, whereas medial damage abrogated these effects, allowing for fibroblast migration (P<0.001). In conclusion, this study demonstrated differential migratory properties and distinct MMP/TIMP synthesis by coronary fibroblasts and smooth muscle cells. Endogenous TIMPs in the media may play an important role in maintaining coronary arterial wall homeostasis, whereas high levels of matrix-degrading activities confer the "invasive" characteristics of adventitial fibroblasts.

Animals↗
PubMed1998

Meningioma surgery in the elderly: a case-control study assessing morbidity and mortality.

GOAL: To assess the morbidity and mortality of meningioma surgery in patients over age 65 and compare our results with matched controls and with the present literature on meningioma surgery in the elderly. METHODS: An evaluation of 114 patients undergoing meningioma resection divided into two groups: 57 patients aged 65-87, and a control group of 57 patients aged 25-64 matched by ASA status and tumor site. Operative complications, 30-day mortality, and pre- and postoperative neurologic status were assessed with follow up one to three months. RESULTS: Complication rates in the two groups were similar and were low. Four out of fifty-seven elderly patients (7.0%) had a surgical complication compared with five younger patients (8.8%) Excluding asymptomatic DVT detected by screening, three elderly patients had medical complications (5.2%) compared with two controls (3.5%). The vast majority of patients-93% of the elderly group and 89.4% in the controls--experienced either improvement or no change in neurologic status at followup one to three months after surgery. There was one death among elderly patients within thirty days for a mortality rate of 1.8% compared with no mortality in the case control group. The elderly patient who died was an 80-year old man who died of pneumonia in a rehabilitation hospital three weeks after surgery. Our study group of 57 patients was compared by tumor site and preoperative general health status to other series in the literature. In a review from the literature of 417 patients over age 65 who underwent meningioma surgery, the average 30-day mortality was 16%. The complication rate averaged 39%. DISCUSSION: Our lower morbidity and mortality rates after meningioma surgery in the elderly may be a result of patient selection, surgical technique, or excellent pre- and post-operative care by the resident staff, anesthesiologists, and nurses. It suggests, however, that elderly patients can have meningioma surgery safely.

Adult↗
PubMed1998

Saphenous vein graft protection: effects of c-myc antisense.

OBJECTIVE: Saphenous vein grafting is associated with extensive medial remodeling, characterized by cellular proliferation, loss of smooth muscle cells, and an inflammatory response. In this study, we examined whether unfavorable responses to vein grafting could be modified by the intraoperative application of c-myc antisense oligomers. METHODS: The intragraft cell proliferation, macrophage infiltration, and medial preservation were examined in a porcine model in the control and antisense-treated groups (n = 36). RESULTS: Saphenous veins showed transmural distribution of oligomers within 30 minutes of the ex vivo incubation. A concentration-dependent inhibition of cell proliferation in the media of saphenous grafts was noted 3 days later (0 to 200 mumol/L, p = 0.005). The growth inhibition was sequence-specific, because control oligomers produced only insignificant effects (20 mumol/L). Vascular effects of c-myc antisense were associated with a significant attenuation of macrophage infiltration in saphenous grafts. A concentration-dependent decrease in tissue edema (p = 0.0005) and the attenuated loss of smooth muscle cells (p = 0.002) were noted in the media of the arterialized venous conduits after c-myc antisense. CONCLUSIONS: Direct application of synthetic DNA to harvested saphenous veins resulted in a rapid transmural distribution. The inhibition of the intragraft cell proliferation in vivo after c-myc antisense was sequence dependent. Decrease in vein graft injury resulted in an attenuated inflammatory response and better medial preservation. These findings provide a rationale for assessment of the long-term effects of vein graft protection with c-myc antisense.

Animals↗
PubMed1998

Pilomotor seizures.

We report pilomotor seizures in two patients who had piloerection or gooseflesh spreading in a pattern like the 'Jacksonian march', confined ipsilaterally to the lesion side. The first patient presented this in conjunction with complex partial seizures. Left anterior temporal lobectomy abolished pilomotor and other seizures. Pathological study demonstrated hippocampal sclerosis. A meningioma near the left sphenoid region, incompletely removed, is the likely cause of pilomotor seizures in the second patient. Carbamazepine reduced these attacks. To our knowledge, hippocampal sclerosis and meningioma have never been linked to pilomotor seizures.

Adult↗
PubMed1997

Remodeling of autologous saphenous vein grafts. The role of perivascular myofibroblasts.

BACKGROUND: Aortocoronary saphenous vein grafts (SVGs) undergo structural changes that render them susceptible to atherosclerosis. Accordingly, the origin of neointimal hyperplasia-was examined in porcine arterialized SVGs to determine the mechanism of vein graft remodeling. METHODS AND RESULTS: At 2 to 4 days after surgery, the percentage of cells lacking differentiation markers characteristic for smooth muscle (SM) cells (ie, alpha-SM actin, desmin, and SM myosin) increased within the media of SVGs interposed in the carotid arteries (P < .001). At 7 to 14 days, these cells acquired a differentiated phenotype (ie, alpha-SM-actin positive/ variable desmin/SM-myosin negative) and accumulated in the neointima. At 3 months, the neointima was positive for alpha-SM actin but mostly negative for desmin, which contrasted with medial SMCs that were invariably positive for alpha-SM actin, desmin, and SM myosin. To determine the role of nonmuscle cells in the above process, perivascular wound fibroblasts were selectively labeled and found to translocate through the media of newly placed SVGs, contributing to neointimal formation. These migrating cells differentiated to myofibroblasts exhibiting sustained alpha-SM-actin expression. The intima of human SVGs, retrieved during repeat aortocoronary bypass surgery, exhibited the profile of cytoskeletal proteins that resembled myofibroblasts seen in porcine SVGs. CONCLUSIONS: Perivascular fibroblasts may infiltrate injured media of arterialized SVGs, differentiate to myofibroblasts (acquiring alpha-SM actin), and contribute to vein graft remodeling. The similarities between porcine and human SVGs regarding the repertoire of cytoskeletal proteins suggest the involvement of myofibroblasts in graft remodeling in the clinical setting.

Actins↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗