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C H Wu

Publications and source records attributed to C H Wu.

At least 37 records · Page 2Linked to original sources
PubMed2001

The preventive effects of G115 on balloon injury-induced neointima formation in rats.

After percutaneous transluminal coronary angioplasty (PTCA), 30-50% of the patients may present with restenosis within 6 months. The aim of this study was to search for a preventive remedy against the balloon injury-induced neointima formation. Ginseng, with its wide indications on immune and cardiovascular functions, has prompted us to explore its role in neointima formation. In the present study, we aimed to explore if a standardized Panax Ginseng extract G115 was able to inhibit neointimal formation. With BrdU luminencence assay, maximal proliferation of rat smooth muscle cells was reduced to 24% of control values by G115. Norepinephrine-induced vasocontraction was antagonized in 21% and 44% by 1.44mg/ml and 2.88mg/ml of G115, respectively. Neointima-to-lumen area ratio of balloon-injured rat carotid arteries was reduced 77.3% by G115 as compared to the sham control. These results demonstrate the preventive effects of ginsenosides on angioplasty-mediated neointima formation.

Angioplasty, Balloon, Coronary↗
PubMed2001

Association of globular beta-actin with intracellular lipid droplets in rat adrenocortical cells and adipocytes.

Proteins located on the surface of lipid droplets may mediate intracellular lipid metabolism. In the present study, immunofluorescent staining and polyacrylamide gel electrophoresis demonstrated that actin (43 kD) is associated with isolated intracellular lipid droplets of rat adrenocortical cells and adipocytes. Two-dimensional gel electrophoresis and immunoblot analysis further confirmed that the lipid droplet-associated actin is the beta isoform. In cultured adrenocortical cells, stress fibers and the surface of intracellular lipid droplets were labeled with anti-beta-actin monoclonal antibody, whereas FITC-phalloidin staining did not mark the rim of lipid droplets. The present results provide the first morphological evidence that globular beta-actin is associated with intracellular lipid droplets. This significant association of actin with the surface of lipid droplets suggests that beta-actin might be involved in the regulation of intracellular lipid metabolism, particularly providing insight into the important transport of lipid constituents.

Actins↗
PubMed2001

Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.

Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.

Anthraquinones↗
PubMed2001

beta(2)-microglobulin induces apoptosis in HL-60 human leukemia cell line and its multidrug resistant variants overexpressing MRP1 but lacking Bax or overexpressing P-glycoprotein.

In this study, we examined whether exogenous beta(2)-microglobulin (beta(2)m) can induce apoptosis in the drug sensitive HL-60 leukemia cell line and its drug resistant variants and investigated the molecular mechanism of beta(2)m-induced apoptosis. Our data revealed that beta(2)m is very significantly down-regulated in two multidrug resistant variants of the HL-60 cells: (a) the MRP1-bearing, Bax-deficient HL-60/ADR cell line, and (b) the P-glycoprotein (P-gp) overexpressing HL-60/VCR cell line. However, exogenous beta(2)m induced similar levels of apoptosis in HL-60 cells and these drug resistant variants. beta(2)m-induced apoptosis in HL-60 and HL-60/VCR cells was associated with decreased mitochondrial membrane potential (Deltapsim) but did not affect Deltapsim in HL-60/ADR cells. Surprisingly, cyclosporin A (CsA), a known inhibitor of the mitochondrial permeability transition (MPT) pore, inhibited beta(2)m-induced apoptosis in HL-60/ADR cells but not in HL-60 and HL-60/VCR cells, suggesting that the pro-apoptotic effect of beta(2)m in these cells is not through MPT pore formation. Furthermore, beta(2)m induced the release of cytochrome c and the apoptosis-inducing factor (AIF) from mitochondria in HL-60 and HL-60/VCR cells, but not in HL-60/ADR cells. Additionally, Z-VAD-fmk, a general inhibitor of caspases which inhibited cytochrome c release in HL-60 and HL-60/VCR cells, had no effect on AIF release in any of these cell lines, but inhibited beta(2)m-induced apoptosis in all three cell lines. However, Western blot analysis revealed that caspases-1, -3, -6, -8, and -9 are not activated during beta(2)m-induced apoptosis in these cells. Therefore, beta(2)m-induces apoptosis through an unknown caspase-dependent mitochondrial pathway in HL-60 and HL-60/VCR cells and by a Bax-independent, non-mitochondrial, caspase-dependent pathway in HL-60/ADR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Advanced glycosylation end products induce nitric oxide synthase expression in C6 glioma cells: involvement of a p38 MAP kinase-dependent mechanism.

The mitogen-activated protein kinase (MAPK) pathway is believed to function as an important mediator of inducible nitric oxide synthase (iNOS) expression. In the present study, we investigated the role of the p38 MAPK signaling pathway in advanced glycosylation end products (AGEs)-induced iNOS expression in C6 glioma cells. AGEs caused a dose-dependent increase of nitrite accumulation in C6 glioma cells. The AGEs-stimulated nitrite production from C6 glioma cells was inhibited by actinomycin D, cyclohexamide, and the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), suggesting that the increase of AGEs-induced nitrite release is due to iNOS up-regulation. Consistently, treatment of C6 glioma cells with AGEs induced iNOS protein expression. AGEs-stimulated nitrite production was inhibited by pretreatment of C6 glioma cells with anti-AGEs antibodies (1:100 or 1:50). The tyrosine kinase inhibitor (genistein and tyrphostin), the Ras-farnesyl transferase inhibitor (FPT inhibitor-II), or the p38 MAPK inhibitor (SB203580) suppressed AGEs-induced iNOS expression and nitrite release from C6 glioma cells. AGEs activated p38 MAPK in C6 glioma cells, and this effect was blocked by genistein (20 microM), tyrphostin (30 microM), FPT inhibitor-II (20 microM), and SB203580 (10 microM). Taken together, our data suggest that AGEs may activate the pathways of tyrosine kinase and Ras to induce p38 MAPK activation, which in turn induces iNOS expression and NO production in C6 glioma cells.

Enzyme Activation↗
PubMed2001

Long-lived immune response to early secretory antigenic target 6 in individuals who had recovered from tuberculosis.

We sought to understand the persistence and relevance of the long-lived immune response to early secretory antigenic target (ESAT-6) of Mycobacterium tuberculosis in humans. ESAT-6 is recognized by memory cells involved in protection of animals against tuberculosis (TB). Recent reports also showed that ESAT-6 response can be recovered in patients with TB and in those soon after anti-TB therapy. We chose 18 individuals who had recovered from pulmonary TB (some in remission for >5 years), and 14 bacille Calmette-Guérin-vaccinated healthy individuals for this study. The results showed that peripheral blood mononuclear cells of 10 (55.6%) of 18 patients with TB remission responded to ESAT-6 with stimulation indices >3.0, whereas none of the healthy controls responded. Functional analysis showed that 13 (72.2%) of 18 patients with TB remission produced significant amounts of IFN-gamma in response to ESAT-6, whereas only 1 (7.1%) of the 14 healthy control subjects did so. It appears that responses to ESAT-6 can persist in individuals who had recovered from pulmonary TB.

Adult↗
PubMed2001

Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53.

p53 tumor suppressor is a transcription factor that functions, in part, through many of its downstream target genes. We have identified a p53-inducible gene by performing mRNA differential display on IW32 murine erythroleukemia cells containing a temperature-sensitive p53 mutant allele, tsp53(Val-135). Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter 1 (THTR-1). Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5 degrees C; upon shifting back to 38.5 degrees C, mTHTR-1 transcript was rapidly degraded with a half-life of less than 2 h. Elevation of mTHTR-1 expression was found in DNA damage-induced normal mouse embryonic fibroblast cells, but not in p53(-/-) mouse embryonic fibroblast cells, suggesting that mTHTR-1 induction was p53-dependent. A region within the first intron of the mTHTR-1 gene bound to p53 and conferred the p53-mediated transactivation. Furthermore, increased thiamine transporter activities were found in cells overexpressing mTHTR-1 and under conditions of DNA damage or p53 activation. Our findings indicate that p53 may be involved in maintaining thiamine homeostasis through transactivation of THTR-1.

Amino Acid Sequence↗
PubMed2001

Origin of microglia.

This paper reviews the various proposed hypotheses on the origin of microglia. The seminal study of del Rio-Hortega first stated that the cells were derived from the mesodermal pial cells that invaded the brain during embryonic development. Along with this was the description of precursor cells in the yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sac that later appeared in the mesenchymal tissue associated with the neuroepithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In this connection, circulating monocytes enter the developing brain to assume the form as amoeboid microglia that subsequently evolve to become the ramified microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found that carbon-labelled monocytes were the main source of brain macrophages, some of which transformed into microglia during the healing process. In conclusion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility that some microglial cells may arise from the pial mesenchymal macrophages that appear to originate from the yolk sac precursors.

Animals↗
PubMed2001

Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent.

To investigate the pattern of age-related and sex-dependent bone mineral density (BMD) changes in the six skeletal regions in healthy Chinese, total-body and regional BMD were measured by dual-energy X-ray absorptiometry (DXA) in 310 women and 387 men aged 20-80 years. In women, a five-phase change was discernible in the axial bones: (1) gradual bone increase from 20-29 years old to maximal BMD at 35-39 years old; (2) maintenance of this level from 35-39 to 40-44; (3) a mild bone decrease from 40-44 to 45-49; (4) a rapid bone decrease from 45-49 to 55-59; and (5) a decelerated bone decrease after 55-59 years old. After validation of menopause status, the decrease of BMD in the late 40s became insignificant in premenopausal women. In appendicular bones, no obvious peak was observed, and significant bone decrease started at 50-54 years old. The overall bone decrease from 35-39 to 70-80 years old was 19.3% for the total body, 16.4% for the head, 29% for the spine, 23% for the pelvis, 18.2% for the ribs, 23.9% for the arms, and 20.4% for the legs. In men, the maximal bone mass was attained at 30-34 and 35-39 years old for axial and appendicular bones, respectively. The age-related bone decrease in the skeletal regions was small, except from 60-64 to 65-69 years old. The overall bone decrease in each region from maximal bone mass to 70-80 years old was 6.7% for the total body, 1.7% for the head, 7.6% for the spine, 11.3% for the pelvis, 9.5% for the ribs, 7.8% for the arms, and 10.4% for the legs. The overall magnitude of reduction in total-body BMD in women was about three times greater than that in men. The pattern of BMD changes differs in each region and is age-related as well as sex-dependent. There appeared to be no significant premenopausal bone decrease.

Absorptiometry, Photon↗
PubMed2001

Blockade of U50488H on potassium currents of acutely isolated mouse hippocampal CA3 pyramidal neurons.

The actions of the opioid agonist U50488H on IA and IK were examined in acutely isolated mouse hippocampal CA3 pyramidal neurons using the whole-cell patch clamp technique. U50488H caused a concentration dependent, rapidly developing and reversible inhibition of voltage-activated IA and IK. The inhibitory actions were still observed in the presence of 30 microM naloxone or 5 microM nor-binaltorphimine dihydrochloride. The IC50 values for the blockade of IA and IK were calculated as 20.1.9 and 3.7 microM, respectively. In the presence of 3.3 microM U50488H, repetitive stimulation induced use-dependent inhibition of IA and IK. A 10 microM concentration of U50488H positively shifted the half-activation membrane potential of IA by +11 mV, but negatively shifted IK by -14 mV. These results demonstrate that U50488H can directly inhibit neuronal IA and IK without involvement of the activation of kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Mechanisms involved in the inhibition of neointimal hyperplasia by abciximab in a rat model of balloon angioplasty.

Monoclonal antibodies raised against beta(3) integrin are able to inhibit the binding of ligands to certain beta(3) integrins such as alpha(IIb)beta(3) (glycoprotein IIb/IIIa complex) and alpha(v)beta(3) (vitronectin receptor) and as such are inhibitors of platelet aggregation and smooth muscle cell (SMC) migration, both of which are involved in neointimal hyperplasia. The present study was designed to explore the detailed mechanisms of abciximab (Reopro), a monoclonal antibody (mAb) raised against alpha(IIb)beta(3) integrin in neointimal hyperplasia. In this study, carotid arteries of Wistar rats were damaged, and neointimal hyperplasia and lumen occlusion was determined at different time points. Abciximab was administered intravenously by an implanted osmotic pump. Abciximab (0.25 mg/kg/day) time-dependently inhibited both neointimal hyperplasia and lumen occlusion after angioplasty in carotid arteries of rats. Furthermore, the electromicrographs highlighted that SMCs were phenotypically different from the typical contractile, spindle-shaped SMCs normally seen in uninjured vessel walls. Platelet-derived growth factor (PDGF)-BB was strongly produced in thrombus formation and neointimal SMCs after angioplasty, while abciximab significantly reduced PDGF-BB expression in vessel lumens and neointimal SMCs after angioplasty. Balloon angioplasty caused a significant increase of nitrate and cyclic GMP as compared with sham-operated rats. Infusion of abciximab (0.25 mg/kg/day) did not significantly change. Furthermore, the plasma level of thromboxane B(2) (TxB(2)) obviously increased after angioplasty, while abciximab markedly suppressed the elevation of plasma TxB(2) concentration. The results indicate that abciximab effectively prevents neointimal hyperplasia, possibly through the following 2 mechanisms: (1) Abciximab binds to alpha(IIb)beta(3) integrin on platelet membranes resulting in inhibition of platelet adhesion, secretion, and aggregation in injured arteries, followed by inhibition of thromboxane A(2) formation and PDGF-BB release from platelets. (2) Abciximab may also bind to alpha(v)beta(3) integrin on SMCs, thus, subsequently inhibiting cell migration and proliferation.

Abciximab↗
PubMed2001

iProClass: an integrated, comprehensive and annotated protein classification database.

The iProClass database is an integrated resource that provides comprehensive family relationships and structural and functional features of proteins, with rich links to various databases. It is extended from ProClass, a protein family database that integrates PIR superfamilies and PROSITE motifs. The iProClass currently consists of more than 200,000 non-redundant PIR and SWISS-PROT proteins organized with more than 28,000 superfamilies, 2600 domains, 1300 motifs, 280 post-translational modification sites and links to more than 30 databases of protein families, structures, functions, genes, genomes, literature and taxonomy. Protein and family summary reports provide rich annotations, including membership information with length, taxonomy and keyword statistics, full family relationships, comprehensive enzyme and PDB cross-references and graphical feature display. The database facilitates classification-driven annotation for protein sequence databases and complete genomes, and supports structural and functional genomic research. The iProClass is implemented in Oracle 8i object-relational system and available for sequence search and report retrieval at http://pir.georgetown.edu/iproclass/.

Databases, Factual↗
PubMed2001

Inhibition of neointimal formation in porcine coronary artery by a Ras mutant.

BACKGROUND: Therapeutic approaches to reduce the neointimal formation caused by balloon injury have been focused mainly on experimental models of restenosis in the rat carotid artery. However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger animals and humans. METHODS: In this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative mutant RasN17 on balloon injury-induced restenosis. The viral particles were delivered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection. Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analysis. RESULTS: Neointima formation was prominent in the group receiving balloon injury as compared with the uninjured controls. A remodeling process with migration of collagen was also found in the injured coronary arteries. The application of AdRasN17 led to a 56% decrease in neointima formation and a 75% increase in lumen size, as compared with the balloon-injured vessels treated with AdLacZ control. CONCLUSIONS: These results suggest that AdRasN17 is an effective therapeutic gene in preventing balloon injury-induced neointimal formation in pig coronary arteries.

Animals↗
PubMed2001

Temporally patterned sound pulse trains affect intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus.

This study examined the effect of temporally patterned pulse trains on intensity and frequency sensitivity of inferior collicular neurons of the big brown bat, Eptesicus fuscus. Intensity sensitivity of inferior collicular neurons was expressed by the dynamic range and slope of rate-intensity functions. Inferior collicular neurons with non-monotonic rate-intensity functions have smaller dynamic ranges and larger slopes than neurons with monotonic or saturated rate-intensity functions. Intensity sensitivity of all inferior collicular neurons improved by increasing the number of non-monotonic rate-intensity functions when the pulse repetition rate of pulse trains increased from 10 to 30 pulses per second. Intensity sensitivity of 43% inferior collicular neurons further improved when the pulse repetition rate of pulse trains increased still from 30 to 90 pulses per second. Frequency sensitivity of inferior collicular neurons was expressed by the Q10, Q20, and Q30 values of threshold frequency tuning curves and bandwidths of isointensity frequency tuning curves. Threshold frequency tuning curves of all inferior collicular neurons were V-shape and mirror-images of their counterpart isointensity frequency tuning curves. The Q10, Q20, and Q30 values of threshold frequency tuning curves of all inferior collicular neurons progressively increased and bandwidths of isointensity frequency tuning curves decreased with increasing pulse repetition rate in temporally patterned pulse trains. Biological relevance of these findings to bat echolocation is discussed.

Animals↗
PubMed2001

Occlusal wear of a resin-modified glass ionomer cement following three surface treatments.

Unacceptable occlusal wear has been reported for resin-modified glass ionomer cements (RMGICs) placed in permanent molar teeth. Three different surface treatments of a RMGIC were evaluated over periods of up to 2 years for their effects on restoration wear behaviour: (a) sealing with a thin layer of low viscosity unfilled resin (sealed restoration), (b) sealing with a thicker layer of a lightly-filled pit and fissure sealant (sealant restoration), and (c) co-curing the RMGIC with a posterior resin composite (co-cured restoration). After 2 years the cumulative median (quartiles) wear was for (a) 100 (50-150) microns, (b) 25 (0-50) microns, and (c) 25 (25-38) microns. Although method (b) effectively reduced the surface wear of the RMGIC, this treatment required frequent re-sealing, involving 52% of the restorations. Sealing the surface of a RMGIC placed in permanent molars was not a satisfactory method for reducing occlusal wear. However, co-curing the RMGIC with a posterior resin composite reduced occlusal wear significantly (P < 0.0001), without the need for frequent reapplications of a pit and fissure sealant to the RMGIC.

Adolescent↗
PubMed2001

Response of amoeboid and differentiating ramified microglia to glucocorticoids in postnatal rats: a lectin histochemical and ultrastructural study.

After glucocorticoid injection(s), the number of amoeboid microglial cells (AMC) in the corpus callosum labelled by lectin was markedly reduced when compared with the corresponding control rats. In rats killed at the age of 7 days, all the labeled cells differentiated to become ramified microglia. Ultrastructurally, the AMC in glucocorticoid-injected rats were extremely vacuolated and showed increased lipid droplets. Furthermore, the cells displayed varied lectin labelling patterns especially at both the trans saccules of the Golgi apparatus and lysosomes. In differentiating ramified microglia, massive cellular debris and lectin-stained vesicles or vacuoles were observed; some of the latter appeared to fuse with the plasma membrane. The most striking feature after glucocorticoid (GCC) treatment was the complete diminution of lectin labelling at the Golgi saccules in some differentiating ramified microglia. The present results have demonstrated different effects of glucocorticoids on AMC and differentiating ramified microglia. The differential response of AMC and differentiating ramified microglia to the immunosuppressive drugs may be attributed to the fact that these cells in the postnatal brains subserve different functions or that they are at different differentiation stages. In other words, the sensitivity of microglial cells to the immunosuppressive drugs is dependent upon the stage of cell maturation/differentiation.

Animals↗