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Biomedical subjects

W Zhu

Publications and source records attributed to W Zhu.

At least 163 records · Page 9Linked to original sources
PubMed2000

[A cross-sectional study on injuries in the residents of Shijiazhuang city].

OBJECTIVE: To comprehend current status of injury in the residents of Shijiazhuang city and to lay a foundation for prevention from injury. METHODS: A retrospective study on injury in the 21,544 residents of two and six rural villages was conducted by multi-stage stratified sampling. RESULTS: Standardized incidence rate of injury was 4.21% in Shijiazhuang city, higher in the rural than in the urban areas and higher in men than in women. The top three causes of injuries were traffic accidents, falls and poisoning. Traffic accidents and poisoning ranked the first place in the urban areas and in the rural areas, respectively. Falls occurred mostly in those aged less than 14 years and more than 60 years. Gas poisoning and traffic accidents occurred more often in those aged 15 - 34 years and traffic accidents ranked the first in the age group of 35 - 59 years old. Standardized mortality rate of injury was 48.78 per 100,000, higher in the rural than in the urban areas. Standardized mortality rate of suicide was the highest with 23.21 per 100,000 in the countryside and that of traffic accidents ranked the next. In average, 22 years of potential life lost, 17 work years of potential life lost and nine valued years of potential life lost for each death were caused by injury. Disability rate caused by injury was 1.1 percent. Direct economic loss for each case with injury cost 679.98 RMB yuan. Incidence rate for traffic accidents ranked the highest and the most severe in all injuries. CONCLUSION: Injury has become an important public health problem harmful to the people's health.

Accidental Falls↗
PubMed2000

[Taxol-induced apoptosis in Jurkat T cell lymphoma cell line and its molecular mechanisms].

OBJECTIVE: To observe whether antimicrotubular drug taxol can induce apoptosis in Jurkat T cell lymphoma cell line and the role of bcl-2 gene family in this process. METHODS: Different concentrations of taxol were used to treat Jurkat cells. Cell morphology was observed under light and electron microscope. Flow cytometry and electrophoresis were used to analyze DNA contents and DNA fragments. bcl-2 gene family proteins and mRNAs were studied by immunohistochemistry and semi-quantitative RT-PCR technique. RESULTS: Taxol could inhibit Jurkat cell growth. Within a certain range of treating time and dose, cells were induced apoptosis with a time and dose related manner. The expressions of bax protein and mRNA were increased and bcl-x(s) mRNA became detectable after taxol treatment. CONCLUSION: Taxol can specifically induce Jurkat cell apoptosis. It might provide a theoretical basis for clinical treatment and a good model for studying apoptotic gene modulation. Bax and bcl-x(s) participate in the taxol induced apoptosis of Jurkat cells.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.

Androgens via their receptor (AR) may play a role in prostate cancer etiology. This study focuses on the inhibitory effects of resveratrol on androgen action in the LNCaP prostate cancer cell line. We found that resveratrol represses different classes of androgen up-regulated genes at the protein or mRNA level including prostate-specific antigen, human glandular kallikrein-2, AR-specific coactivator ARA70, and the cyclin-dependent kinase inhibitor p21. This inhibition is likely attributable to a reduction in AR contents at the transcription level, inhibiting androgen-stimulated cell growth and gene expression. This study suggests that resveratrol may be a useful chemopreventive/chemotherapeutic agent for prostate cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells.

Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques.

Apoptosis↗
PubMed1999

MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes.

BACKGROUND: Although anthracyclines, such as daunomycin (DM) and adriamycin, are potent chemotherapeutic agents, they have serious adverse effects, including cardiac toxicity. In the present study, we investigated the molecular mechanisms of DM-induced cardiomyocyte impairment. METHODS AND RESULTS: When cultured cardiac myocytes of neonatal rats were exposed to 1 micromol/L DM for 24 hours, many cells became positive for TUNEL staining, with morphological changes characteristic of apoptosis. Fragmentation of DNA into oligonucleosome-size fragments was recognized by agarose gel electrophoresis in DM-treated myocytes. DM activated 3 members of the mitogen-activated protein kinase (MAPK) family dose-dependently, such as extracellular signal-regulated protein kinases (ERKs), c-Jun NH(2)-terminal kinases, and p38 MAPK in cardiac myocytes. Oxyradical scavengers or Ca(2+) chelators inhibited DM-induced activation of ERKs and p38 MAPK. DM-induced activation of ERKs was also inhibited by overexpression of dominant negative mutants of Ras (D.N.Ras), and the p38 MAPK activation was attenuated by D.N.Rho. The number of DM-induced apoptotic cells was markedly increased when the ERK signaling pathway was selectively blocked by a specific MAPK/ERK kinase inhibitor, PD98059, whereas pretreatment with a specific inhibitor of p38 MAPK, SB203580, significantly reduced the amount of apoptosis. CONCLUSIONS: These results suggest that DM activates MAPKs through reactive oxygen species and Ca(2+) and that the MAPK family plays important roles in DM-induced apoptosis in cardiac myocytes. ERKs protect cardiomyocytes from apoptosis, whereas p38 MAPK is involved in the induction of cardiomyocyte apoptosis.

Animals↗
PubMed1999

Experience of the treatment of severe electric burns on special parts of the body.

The treatment in these eight cases with severe electric burns on special parts of the body was successful. Our experience can be summarized as follows: (1) The role of the immediate measures including resuscitation at the scene of the accident cannot be understated. If the patient presents with a complex injury such as open pneumothorax, first aid should be provided immediately and then the patient should be transferred to a specialized treatment center. (2) General conditions such as the presence of shock, water-electrolyte balance, renal function, and others should be continuously monitored. (3) Antibiotics should be suitably administered and combined with antianaerobic drugs. (4) For different wound sites, different plans of treatment, including various immediate and delayed procedures, could be appropriate. In life-threatening cases such as exposed carotid artery, perforative injury of the chest wall, spinal cord damage, and others, first-stage repair using skin flap or myocutaneous flap must be performed after early debridement. For other wound sites, such as oral area and tongue, eye socket, and penis, second-stage reconstruction may be more suitable for better cosmetic appearance and function. (5) Adequate nutritional supply and early treatment of anemia may expedite wound healing.

Accidents, Occupational↗
PubMed1999

Expression of mouse mammary tumor virus envelope protein does not prevent superinfection in vivo or in vitro.

Inbred mice expressing endogenous mouse mammary tumor virus envelope proteins can be infected with exogenous virus, and the mammary tumors that develop in these mice usually have many proviruses integrated in their genomes, indicating that this virus is not subject to receptor interference. We show here that transgenic mice expressing an exogenous mouse mammary tumor virus (C3H) envelope protein can still be infected with this virus. Moreover, cultured mammary gland cells expressing the mouse mammary tumor virus (C3H) envelope protein can be superinfected with pseudotyped viruses bearing that same protein. Thus cellular expression of the mouse mammary tumor virus envelope protein does not block superinfection in vivo or in vitro.

Animals↗
PubMed1999

Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation.

An orphan nuclear receptor, termed the pregnane X receptor (PXR), has recently been cloned from mouse and human and defines a novel steroid signaling pathway (Cell 92, 73-82, 1998; Proc. Natl. Acad. Sci. USA 95, 12208-122313, 1998). Transient cotransfection experiments demonstrate that the PXR responds to structurally dissimilar compounds and confers the induction of cytochrome P4503A (CYP3A), a subfamily of enzymes that involve the metabolism of two-thirds of drugs and other xenobiotics. In this report, we describe the molecular cloning, tissue distribution, and xenobiotic regulation of a rat PXR designated rPXR-1. rPXR-1 exhibits a 95% sequence identity with the mouse PXR, but only 79% identity with the human PXR, providing the molecular basis that rats and mice have a similar CYP3A induction profile but differ from humans. rPXR-1 gene was expressed abundantly in liver, intestine, and, to a lesser extent, kidney, lung, and stomach. The tissue distribution and the relative abundance of rPXR-1 mRNA among these tissues resemble those of CYP3A, suggesting that PXR is important not only for induction but also for constitutive expression of these enzymes. Xenobiotics known to induce liver microsomal enzymes showed differential effects on the rPXR-1 expression as determined by Northern blot analysis. Dexamethasone, for example, increased the accumulation of rPXR-1 mRNA, whereas troleandomycin slightly suppressed it. Compounds that increase PXR expression (inducers) and compounds that interact with PXR (ligands) likely have synergistic effects on CYP3A induction, which provides a novel molecular explanation for drug-drug interactions.

Amino Acid Sequence↗
PubMed1999

Analysis of linked human epsilon and gamma transgenes: effect of locus control region hypersensitive sites 2 and 3 or a distal YY1 mutation on stage-specific expression patterns.

Stage-specific expression of the human beta-like globin genes is controlled by interactions between regulatory elements near the individual genes and additional elements located upstream in the Locus Control Region (LCR). Elucidation of the mechanisms that govern these interactions could suggest strategies to reactivate fetal (gamma) or embryonic (epsilon) genes in individuals with severe hemoglobinopathies. This study extends an earlier analysis of a transgenic construct, HS3epsilon gamma, testing: (A) the effect of substitution of HS2 for HS3 on stage-specific expression of the epsilon and gamma genes and, (B) the role of an evolutionarily conserved YY1 binding site in transcriptional regulation of the gamma gene. The data show that both HS3epsilon gamma and HS2epsilon gamma can individually support embryonic expression of epsilon and fetal expression of Agamma. Thus, the cis regulators of distinct expression patterns for epsilon and gamma are likely to reside near the genes, rather than in specific hypersensitive sites of the LCR. Alterations in Agamma expression patterns observed in transgenic lines carrying a construct with a mutation in a conserved YY1 binding site at -1086 indicate that this site might function to facilitate active transcription of the gamma gene in fetal life.

Animals↗
PubMed1999

Rho family small G proteins play critical roles in mechanical stress-induced hypertrophic responses in cardiac myocytes.

-Mechanical stress induces a variety of hypertrophic responses, such as activation of protein kinases, reprogramming of gene expression, and an increase in protein synthesis. In the present study, to elucidate how mechanical stress induces such events, we examined the role of Rho family small GTP-binding proteins (G proteins) in mechanical stress-induced cardiac hypertrophy. Treatment of neonatal rat cardiomyocytes with the C3 exoenzyme, which abrogates Rho functions, suppressed stretch-induced activation of extracellular signal-regulated protein kinases (ERKs). Overexpression of the Rho GDP dissociation inhibitor (Rho-GDI), dominant-negative mutants of RhoA (DNRhoA), or DNRac1 significantly inhibited stretch-induced activation of transfected ERK2. Overexpression of constitutively active mutants of RhoA slightly activated ERK2 in cardiac myocytes. Overexpression of C-terminal Src kinase, which inhibits functions of the Src family of tyrosine kinases, or overexpression of DNRas had no effect on stretch-induced activation of transfected ERK2. The promoter activity of skeletal alpha-actin and c-fos genes was increased by stretch, and these increases were completely inhibited by either cotransfection of Rho-GDI or pretreatment with C3 exoenzyme. Mechanical stretch increased phenylalanine incorporation into cardiac myocytes by approximately 1.5-fold compared with control, and this increase was also significantly suppressed by pretreatment with C3 exoenzyme. Overexpression of Rho-GDI or DNRhoA did not affect angiotensin II-induced activation of ERK. ERKs were activated by culture media conditioned by stretch of cardiomyocytes without any treatment, but not of cardiomyocytes with pretreatment by C3 exoenzyme. These results suggest that the Rho family of small G proteins plays critical roles in mechanical stress-induced hypertrophic responses.

Angiotensin II↗
PubMed1999

Transcatheter closure of a large residual shunt after deployment of the Das-Angel Wings device using the Amplatzer septal occluder.

A 35-year-old female patient with a large residual shunt following transcatheter closure of a large secundum atrial septal defect using the Das-Angel Wings device underwent successful complete closure of the residual shunt using a 15-mm Amplatzer Septal Occluder. Transesophageal (two- and three-dimensional) echocardiography was of great help during the closure procedure. Cathet. Cardiovasc. Intervent. 48:184-187, 1999.

Adult↗
PubMed1999

Connexins in tumour suppression and cancer therapy.

Malignant cells usually show altered gap junctional intercellular communication and are often associated with aberrant expression or localization of connexins. Transfection of connexin genes into tumorigenic cells restores normal cell growth, suggesting that connexins form a family of tumour suppressor genes. Some studies have also shown that specific connexins may be necessary to control growth of specific cell types. Although we have found that genes encoding connexin32 (Cx32; beta 1), Cx37 (alpha 4) and Cx43 (alpha 1) are rarely mutated in tumours, our recent studies suggest that methylation of the connexin gene promoter may be a mechanism by which connexin gene expression is down-regulated in certain tumors. We have produced various dominant negative mutants of the genes encoding Cx26 (beta 2), Cx32 and Cx43, some of which prevent the growth control exerted by the corresponding wild-type genes. A decade ago, we proposed a method to enhance killing of cancer cells by diffusion of therapeutic agents through gap junctions. Recently, we and others have shown that gap junctional intercellular communication is responsible for the bystander effect seen in herpes simplex virus thymidine kinase/ganciclovir gene therapy. Thus, connexin genes can exert dual effects in tumour control: tumour suppression and a bystander effect for cancer therapy.

Animals↗
PubMed1999

Expression of human prohormone convertase PC2 in a baculovirus-insect cell system.

PC2 is a member of the eukaryotic family of subtilisin-related proprotein convertases which are thought to be involved in the intracellular proteolytic processing of prohormones and proneuropeptides. The presence of only small amounts of PC2 in the secretory granules of certain mammalian neuroendocrine cell types has made the characterization and further study of this enzyme difficult. We report here the expression of proteolytically active human PC2 protein in the insect cell-baculovirus system. Human PC2 expressed in insect cells is a calcium-dependent intracellular protein active at neutral pH. In insect cells, human PC2 was found intracellularly as 75-kDa and 71-kDa proteins. Both 73-kDa and 68-kDa forms were found in the conditioned medium, but no PC2 proteolytic activity was detected. We demonstrated the presence of a soluble inhibitor in infected-cell medium which may block PC2 activity.

Animals↗
PubMed1999

The C terminus of AvrXa10 can be replaced by the transcriptional activation domain of VP16 from the herpes simplex virus.

The avirulence gene avrXa10 of Xanthomonas oryzae pv oryzae directs the elicitation of resistance in a gene-for-gene manner in rice lines carrying the resistance gene Xa10. We have localized a transcriptional activator domain in the C terminus of AvrXa10 by using amino acid replacement mutagenesis. One mutant, with replacements at three hydrophobic amino acid residues in the C-terminal domain, was defective for transcriptional activation in yeast and avirulence activity in rice. The activation domain from the herpes virus protein VP16 restored the ability of the bacteria expressing the hybrid protein to elicit a resistance reaction. Elicitation was specific for Xa10, and the reaction had the hallmarks of the response to AvrXa10. The results indicate that a domain with the properties of a transcriptional activator plays a critical role in AvrXa10 function. The results also indicate that the protein has the potential to interact with the plant transcriptional program, although a role for the domain in the stability or conformation of the protein in the plant cannot be excluded. In a broader sense, the transcriptional activation domain of avrXa10 may represent a prokaryotic version of the acidic transcriptional activation domain, which heretofore has been found exclusively in eukaryotes.

Amino Acid Sequence↗
PubMed1999

Defining a novel 75-kDa phosphoprotein associated with SS-A/Ro and identification of distinct human autoantibodies.

Mothers of children with neonatal lupus erythematosus (NLE) and heart block, as well as patients with Sjögren's syndrome (SS) and systemic lupus erythematosus, have serum autoantibodies that recognize SS-A/Ro autoantigens including the 60-kDa ribonucleoprotein. By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) that interacts with the carboxyl 70% of 60-kDa SS-A/Ro. The specificity of interaction was confirmed using mammalian 2-hybrid and chemical crosslinking studies. Immunoprecipitation with radiolabeled HeLa cell extracts showed that pp75 was phosphorylated and associated with 2 other phosphoproteins of 64 kDa. In Northern blot analysis, pp75 was expressed in all tissues analyzed; the highest expression was in the human heart. Based on immunofluorescence of transfected HeLa cells, pp75 is localized predominantly in the cytoplasm, an observation confirmed by immunohistochemistry in untransfected cells. Based on Western blot and ELISA assays, sera from 14 of 84 mothers of children with NLE recognized pp75, including 1 mother in whom anti-SS-A/Ro antibodies were not detected. In addition, sera from 5 of 80 patients with SS were positive for anti-pp75 antibody. Identification of molecular partners is a first step toward elucidating the functions and possible involvement in pathogenesis of long-recognized autoantigens such as 60-kDa SS-A/Ro, which are at present poorly understood.

Adaptor Proteins, Signal Transducing↗
PubMed1999

A nonsteroidal anti-inflammatory drug, flufenamic acid, inhibits the expression of the androgen receptor in LNCaP cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in chemoprevention of colon cancer and others by inhibiting prostaglandin synthesis. In this report, we used LNCaP cells, an androgen-responsive human prostate carcinoma cell line, to study the effects of two NSAIDs, flufenamic acid (FA) and piroxicam (PXM), on the cancer cell growth stimulated by androgens. We found that FA had much higher potency to inhibit LNCaP cell growth than PXM. FA dramatically reduced the expression of androgen inducible genes, such as prostate-specific antigen (PSA) and the homeo-domain transcription factor Nkx3.1, but PXM did not. In vitro transfection experiments showed that FA down regulated the PSA expression at the transcription level. Western and northern blot analyses demonstrated that FA inhibited the androgen receptor (AR) expression at mRNA and protein levels. Suppressed AR expression may be the cause of FA-mediated inhibition of the androgen inducible gene expression. Our data also showed that FA significantly reduced the AR promoter-mediated transcription activities. This study indicated that AR might be a target for FA to inhibit LNCaP cell growth. FA and other similar NSAIDs may be potential candidates for chemoprevention of human prostate cancer by modulating the expression of AR.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression.

T3 plays an important role in the regulation of cell growth and differentiation. In this study, we show the interactive effects of T3 and androgens on the growth response and expression of the prostate-specific genes, PSA (prostate-specific antigen) and hK2 (human glandular kallikrein), in the human prostate cancer cell line, LNCaP. T3 alone showed pronounced growth enhancement in a dose-dependent fashion. However, in the presence of androgens, higher concentrations of T3 were required to produce additional proliferative effects. T3, androgens, or a combination of the two up-regulated PSA protein production in a dose-dependent fashion, but T3 had little stimulatory effect on hK2 protein expression, regardless of the presence or absence of androgens. Using gene transfer assays, T3 alone showed no effect on transcriptional activation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T3 potentiated the androgen-mediated transcription of the PSA gene but not that of the hK2 gene. A previous study suggested that the T3 effect on PSA protein expression was caused by an up-regulation of the androgen receptor (AR) protein by T3. Our results contradict these. Although AR expression was increased by T3 alone, Western blot analysis showed that the total cellular AR level was not further increased by T3 in the presence of androgens, in comparison with cells stimulated by androgens alone. Both Western blot analysis and a gel DNA band shift assay revealed that nuclear AR was not increased by T3. This study suggests that transcription factor(s) other than the AR may mediate T3 enhancement of androgenic induction of PSA expression.

Androgens↗