Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 55 records · Page 3Linked to original sources

PubMed2001

Hepatitis C viral genotype influences the clinical outcome of patients with acute posttransfusion hepatitis C.

Most patients with an acute infection of hepatitis C virus (HCV) will develop chronic hepatitis, and only about 15-20% of the cases will resolve spontaneously. The mechanism for the different outcomes in patients with acute HCV infection remains unclear. HCV genotype has been recognized as an important factor affecting the clinical course and outcome of chronic hepatitis C patients. In order to evaluate the role of HCV genotype in the clinical course and outcome of acute posttransfusion hepatitis C, 67 patients with acute posttransfusion hepatitis C from a prospective study of posttransfusion non-A, non-B hepatitis were enrolled. Thirty-nine patients (58.2%) were HCV genotype 1b. Among the 67 patients with acute posttransfusion hepatitis C, 53 (79.1%) progressed to chronic hepatitis. Significantly more patients with genotype 1b than non-1b genotypes developed chronic hepatitis (89.7% vs. 64.3%; P = 0.019). There was no significant difference in gender, mean age, amount of transfused blood, hepatitis symptoms, jaundice, incubation period, peak serum alanine transaminase, or serum HCV RNA titer between patients with HCV genotype 1b and non-1b infections. Patients who developed chronic hepatitis had a significantly greater incidence of genotype 1b infection (66.0% vs. 28.6%; P = 0.013) and a longer incubation period (7.3 weeks vs. 5.4 weeks; P = 0.052) than patients whose infection was resolved. Patients with a genotype 1b infection that resolved itself spontaneously all had an incubation period of less than 6 weeks. Multivariate logistic regression analysis revealed that genotype 1b and an incubation period > or = 6 weeks were significant predictive factors for the development of chronic hepatitis. Therefore, the HCV genotype can influence the outcome of patients with acute HCV infection.

Acute Disease↗

PubMed2001

[The research on applications of diagnostic software in single photon emission computed tomography].

In this paper, the structure of software system, the principles of overlay programming and the running mechanism of the programs for the Single Photon Emission Computed Tomography(SPECT) made by French SOPHA MEDICAL Corp. are analyzed in detail. On this basis, a method of extending functions of the system is introduced too. All the results of the extension in software functions for organ volume determination and of the measurements for living animals have proved the correctness and reliability of the method.

Software↗

PubMed2000

Heavy membrane-associated caspase 3: identification, isolation, and characterization.

Heavy membrane preparations from 697 lymphoblastoid cells contain a tightly bound caspase zymogen. This heavy membrane-bound procaspase can be efficiently liberated from membrane preparations using detergents. Alternatively, the procaspase can be rapidly processed and activated from membrane preparations by caspase-1 without detergents. The activated caspase-3 was purified using affinity chromatography and characterized by amino acid sequencing and inhibitor specificity analysis. The sequence indicates that this heavy membrane bound caspase is caspase-3. The kinetic properties and inhibitor binding specificity also show that this purified caspase is enzymologically indistinguishable from cytoplasmic or recombinant caspase-3. However, the N-termini of activated heavy membrane-bound and cytoplasmic caspase-3 are slightly different; peptide sequencing data indicate that the heavy membrane caspase-3 begins at Lys 14, whereas the cytoplasmic enzyme begins at Ser 10. Implications of this structural difference are discussed.

Amino Acid Sequence↗

PubMed2000

NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP.

The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of cysteine proteases, which play an important role in the execution of programmed cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the minimal region of XIAP that is needed for potent caspase-9 inhibition. The three-dimensional structure of the Bir3 domain of XIAP, determined by NMR spectroscopy, resembles a classical zinc finger and consists of five alpha-helices, a three-stranded beta-sheet, and a zinc atom chelated to three cysteines and one histidine. The structure of the Bir3 domain is similar to that of the Bir2 domain of XIAP but differs from the previously determined structure of the Bir3 domain of MIHB. Based on site-directed mutagenesis, we have identified the regions of the Bir3 domain of XIAP that are important for inhibiting caspase-9. Despite the structural similarities of the Bir2 and Bir3 domain of XIAP, a different set of residues were found to be critical for inhibiting the individual caspases. These results suggest that XIAP inhibits caspase-3 and caspase-9 in a different manner.

Amino Acid Sequence↗

PubMed2000

Taxol reduces cytosolic E-cadherin and beta-catenin levels in nasopharyngeal carcinoma cell line TW-039: cross-talk between the microtubule- and actin-based cytoskeletons.

Taxol affects microtubule dynamics by promoting microtubule assembly. To obtain a better insight into possible cross-talk between the microtubule- and actin-based cytoskeletons, we studied the short-term effects of Taxol treatment on the expression of actin and the E-cadherin/catenin complex in the nasopharyngeal carcinoma cell line TW-039 using immunofluorescence, immunoprecipitation, and immunoblotting methods. Morphologic changes in actin filaments, including ventral actin clumps and perijunctional actin blebs, were seen at Taxol concentrations > or =1 microM. Levels of detergent-soluble E-cadherin fell to 53% or 58% compared to controls in cells treated, respectively, with 1 or 5 microM Taxol, while levels of detergent-soluble beta-catenin fell to 76% or 74%. Levels of the detergent-soluble pool of alpha- and gamma-catenin and the detergent-insoluble pool of the E-cadherin/catenin complex were unchanged by Taxol treatment and no significant difference was seen in the levels of adenomatous polyposis coli or glycogen synthase-3beta or tyrosine phosphorylation patterns. These results suggest that modulation of microtubule dynamics by Taxol may have effects on the expression of actin and the cytosolic E-cadherin and beta-catenin in nasopharyngeal carcinoma cells through pathways not involving the phosphorylation of beta-catenin.

Actins↗

PubMed2000

Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.

Caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target. Caspases are cysteine proteases that are specific for substrates with an aspartic acid residue at the P(1) position and have an optimal recognition motif that incorporates four amino acid residues N-terminal to the cleavage site. Caspase-8 has been classified as a group III caspase member because it shows a preference for a small hydrophobic residue at the P(4) substrate position. We report the X-ray crystallographic structure of caspase-8 in complex with benzyloxycarbonyl-Asp-Glu-Val-Asp-aldehyde (Z-DEVD), a specific group II caspase inhibitor. The structure shows that the inhibitor interacts favourably with the enzyme in subsite S(4). Kinetic data reveal that Z-DEVD (K(i) 2 nM) is an almost equally potent inhibitor of caspase-8 as the specific group III inhibitor Boc-IETD-aldehyde (K(i) 1 nM). In view of this finding, the original classification of caspases into three specificity groups needs to be modified, at least for caspase-8, which tolerates small hydrophobic residues as well as the acidic residue Asp in subsite S(4). We propose that the subsite S(3) must be considered as an important specificity-determining factor.

Binding Sites↗

PubMed2000

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND: After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. METHODS: We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. RESULTS: We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). CONCLUSIONS: After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.

Aged↗

PubMed2000

The genetic basis of cardiac function: dissection by zebrafish (Danio rerio) screens.

The vertebrate heart differs from chordate ancestors both structurally and functionally. Genetic units of form, termed 'modules', are identifiable by mutation, both in zebrafish and mouse, and correspond to features recently acquired in evolution, such as the ventricular chamber or endothelial lining of the vessels and heart. Zebrafish (Danio rerio) genetic screens have provided a reasonably inclusive set of such genes. Normal cardiac function may also be disrupted by single-gene mutations in zebrafish. Individual mutations may perturb contractility or rhythm generation. The zebrafish mutations which principally disturb cardiac contractility fall into two broad phenotypic categories, 'dilated' and 'hypertrophic'. Interestingly, these correspond to the two primary types of heart failure in humans. These disorders of early cardiac function provide candidate genes to be examined in complex human heart diseases, including arrhythmias and heart failure.

Animals↗

PubMed2000

Correlation of intellectual impairment in Parkinson's disease with FDG PET scan.

This study investigated the relationship between regional glucose metabolism with intellectual impairment in patients with Parkinson's disease using statistical parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used the intellectual impairment score from the UPDRS. PET scans were analyzed with SPM96. Patients showed significant positive correlations with left limbic structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal gyrus. Patients showed significant negative correlations with associative neocortical posterior structures such as bilateral parietal and occipital gyrus. There were significant relationships between regional glucose metabolism and intellectual impairment.

Aged↗

PubMed2000

Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells.

In this study, we examined the effects of shark cartilage extract on the attachment and spreading properties and the focal adhesion structure of cultured bovine pulmonary artery endothelial cells. Treatment with cartilage extract resulted in cell detachment from the substratum. Immunofluorescence staining of those treated cells that remained attached showed that, instead of being present in both central and peripheral focal adhesions as in control cells, both integrin alpha(v)beta(3) and vinculin were found only in peripheral focal adhesion and thinner actin filament bundles were seen. In addition to causing cell detachment, cartilage extract partially inhibited the initial adherence of the cells to the substratum in a dose-dependent manner. Integrin alpha(v)beta(3) and vinculin staining of these cells also showed a peripheral focal adhesion distribution pattern. Vitronectin induced cell spreading in the absence of serum, but was blocked by simultaneous incubation with cartilage extract, which was shown to inhibit both integrin alpha(v)beta(3) and vinculin recruitment to focal adhesion and the formation of stress fibers. Dot binding assays showed that these inhibitory effects on cell attachment and spreading were not due to direct binding of cartilage extract components to integrin alpha(v)beta(3) or vitronectin. Shark cartilage chondroitin sulfate had no inhibitory effect on either cell attachment or spreading of endothelial cells. These results show that the inhibitory effects of cartilage extract on cell attachment and spreading are mediated by modification of the organization of focal adhesion proteins.

Acid Phosphatase↗

PubMed2000

Prevalence and risk factor analysis of TTV infection in prostitutes.

TTV, a DNA virus, has been isolated from patients with non-A to non-E post-transfusion hepatitis. In the past it was assumed that TTV was transmitted parenterally. It is unclear whether sexual contact leads to transmission of this virus. In this study, two sets of TTV-specific polymerase chain reaction primers were used to detect serum TTV DNA in 140 prostitutes and 136 controls. The prevalence of TTV DNA in prostitutes was significantly higher than in the control group (46/140 [32.9%] vs. 29/136 [21.3%]; P = 0.043). There was no significant difference in the prevalence of positive antibody to hepatitis A virus (anti-HAV) in either group (87.8% for prostitutes, 85.3% for controls). No particular risk factor was significantly associated with positive TTV DNA in prostitutes. In summary, TTV is highly prevalent in prostitutes. Transmission of TTV via sexual contact is not as efficient as transmission of hepatitis C and D viruses and GB virus-C hepatitis G virus. The high prevalence of TTV in controls indicates that there are diverse routes of transmission of this virus.

Adult↗

PubMed2000

Role of desmin filaments in chicken cardiac myofibrillogenesis.

Desmin filaments are muscle-specific intermediate filaments located at the periphery of the Z-discs, and they have been postulated to play a critical role in the lateral registration of myofibrils. Previous studies suggest that intermediate filaments may be involved in titin assembly during the early stages of myofibrillogenesis. In order to investigate the putative function of desmin filaments in myofibrillogenesis, rabbit anti-desmin antibodies were introduced into cultured cardiomyocytes by electroporation to perturb the normal function of desmin filaments. Changes in the assembly of several sarcomeric proteins were examined by immunofluorescence. In cardiomyocytes incorporated with normal rabbit serum, staining for alpha-actinin and muscle actin displayed the typical Z-line and I-band patterns, respectively, while staining for titin with monoclonal anti-titin A12 antibody, which labels a titin epitope at the A-I junction, showed the periodic doublet staining pattern. Staining for C-protein gave an amorphous pattern in early cultures and identified A-band doublets in older cultures. In contrast, in cardiomyocytes incorporated with anti-desmin antibodies, alpha-actinin was found in disoriented Z-discs and the myofibrils became fragmented, forming mini-sarcomeres. In addition, titin was not organized into the typical A-band doublet, but appeared to be aggregated. Muscle actin staining was especially weak and appeared in tiny clusters. Moreover, in all ages of cardiomyocytes tested, C-protein remained in the disassembled form. The present data suggest the essential role of desmin in myofibril assembly.

Actinin↗

PubMed2000

Prospective case-controlled trial of adjuvant chemotherapy after resection of hepatocellular carcinoma.

Recurrence of hepatocellular carcinoma (HCC) after curative hepatic resection is frequent and is an important factor adversely influencing long-term survival. The role of postoperative chemotherapy in the reduction of tumor recurrence rate is still controversial. During the period of 1992-1995 a series of 49 patients who underwent curative resection of HCC and had at least one risk factor of tumor recurrence were followed in this prospective study. Patients were allocated to adjuvant chemotherapy and control groups. Twenty-four patients received a combination of low dose intravenous epirubicin (20 mg/m2) and mitomycin (5 mg) monthly for seven courses starting 5 to 6 weeks after surgery. Twenty-five patients had no adjuvant treatment. The disease-free and overall survivals were compared for the two groups. A total of 154 courses of chemotherapy were given to the 24 patients. The chemotherapy-related side effects were mild and tolerable with no mortality. At a median follow-up of 39 months (range 9-71 months), 9 patients in the adjuvant chemotherapy group and 16 patients in the control group developed tumor recurrence. The respective 1-, 2-, 3-, and 5-year disease-free survival rates were 75%, 67%, 63%, and 63% for patients in the adjuvant chemotherapy group and 68%, 42%, 37%, and 32% for patients in the control group (p = 0.0575). The 1-, 2-, 3-, and 5-year overall survival rates were 100%, 96%, 77%, and 72% in the adjuvant chemotherapy group and 92%, 67%, 63%, and 51% in the control group (p = 0.0746). In conclusion, postoperative adjuvant chemotherapy using the present regimen has a tendency to reduce tumor recurrence rate and may improve long-term survival for high risk patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Characterization of a strain-specific monoclonal antibody to hepatitis delta virus antigen.

Sequences of the hepatitis delta virus (HDV) vary to different degrees among isolates. A monoclonal antibody, designated as HP6A1, against the antigen of HDV (HDAg) has been characterized for its specificity. HP6A1 bound to HDAg of isolate 25 (genotype I) that was used for immunization, but not to others of both genotypes I and II. The epitope recognized by HP6A1 was then determined by a phage library displaying various heptapeptides. A consensus peptide deduced has the best match with that of residues 4-10 of HDAg (isolate 25). To confirm the phage mapping result, Escherichia coli recombinant proteins containing different lengths and various segments of HDAg (isolate 25) were constructed. The shortest HDAg segment contained in the fusion protein that reacted with HP6A1 was residues 1-10. When this peptide was added to the N-terminus of a heterologous protein engineered for eucaryotic expression, the fusion protein was detected by HP6A1. It is concluded that HP6A1 recognizes an epitope located at the N-terminus of HDAg (isolate 25). Since viruses of quasi-species exist in natural infections, a question of how different viral strains interact in vivo remains to be explored. The highly specific MAb opens a possibility to examine the fate of one strain in the presence of other related species in a cell transfection system.

Amino Acid Sequence↗

PubMed2000

Correlation of neurological manifestations and MR images in a patient with Wilson's disease after liver transplantation.

Orthotopic liver transplantation (OLT) has been applied to patients with Wilson's disease (WD) for correction of irreversible liver cirrhosis. However, the neurological outcome and the correlation between clinical manifestations and neuroimage findings after OLT remain uncertain. We present a WD patient who showed an improvement in both liver functions and neurological manifestations after OLT. Serum levels of ceruloplasmin and copper returned to normal rapidly after the operation. His ataxic gait was improved 5 months later and dysmetria and tremor disappeared 11 months later. The high signal intensities on T2-weighted brain magnetic resonance images regressed at bilateral thalami 5 months later and disappeared in bilateral thalami and red nuclei 16 months after OLT. We conclude that the neurological improvement could be expected in WD patients after OLT. The improvement was correlated with the MRI changes in red nuclei and bilateral thalami.

Adult↗

PubMed2000

Salvage therapies after failure of Helicobacter pylori eradication with ranitidine bismuth citrate-based therapies.

BACKGROUND: Salvage therapies after initial Helicobacter pylori eradication failure of ranitidine bismuth citrate (RBC)-based regimens remain undefined. AIM: To test the efficacy of 1-week omeprazole, amoxycillin and clarithromycin as a second-line treatment and 1-week quadruple therapy after repeated failures of RBC- and proton pump inhibitor-based regimens. METHOD: Patients were recruited from a recently published prospective randomized study if confirmed to have failed H. pylori eradication with RBC-based regimens. They were given omeprazole 20 mg, amoxycillin 1 g and clarithromycin 500 mg (OAC) b.d. for 1 week. 13C-urea breath test was performed 4 weeks after the conclusion of medication. Those who failed to respond to OAC were given 1-week quadruple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg and metronidazole 400 mg q.d.s. plus omeprazole 20 mg b.d.). RESULTS: Among 398 patients receiving RBC-based therapies, 40 (10%) had failed eradication (RAC=7, RC-2=12, RMC=7, and RMT=14). OAC was prescribed to 31 patients (RAC=4, RC-2=9, RMC=6, and RMT=12) and 68% had successful eradication. Nine out of 10 patients with failed second treatment received quadruple therapy; successful eradication occurred in 83% (5 out of 6) after repeated failures of clarithromycin-based regimens. CONCLUSION: One-week OAC is not an optimal second-line therapy when RBC-clarithromycin combinations fail. Quadruple therapy appears to be effective despite repeated failures of clarithromycin-based RBC or proton pump inhibitor therapies.

Amoxicillin↗

PubMed2000

Helicobacter pylori infection is associated with milder gastro-oesophageal reflux disease.

BACKGROUND: We have previously demonstrated a negative relationship between the prevalence of Helicobacter pylori and gastro-oesophageal reflux disease (GERD). AIM: To study the effects of H. pylori infection on the severity of GERD. METHODS: Ethnic Chinese patients with frequent heartburn and/or endoscopic oesophagitis were studied. Endoscopic examination was performed to assess the severity of oesophagitis (modified Savary-Miller grading) and the presence of hiatus hernia. Biopsies were taken for rapid urease testing and confirmation of Barrett's oesophagus. Risk factors which may affect the severity of oesophagitis (age, sex, smoking, drinking, diabetes mellitus, hiatus hernia, H. pylori status and body mass index) were evaluated by a multiple regression model. The cagA status of H. pylori infected GERD and age-and-sex matched controls were determined by Western blot. Age-and-sex matched non-reflux patients were recruited as controls for comparison. RESULTS: Two hundred and twenty-five patients with GERD were studied, of whom 77 (34%) were infected with H. pylori. Oesophagitis and Barrett's oesophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe oesophagitis compared to the uninfected group (P=0.022). All patients with Barrett's oesophagus were uninfected. Factors that predicted severe oesophagitis included age over 60 years (P < 0.001) and hiatus hernia (P < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe oesophagitis (P=0.011). The prevalence of the cagA positive strain in endoscopy-negative GERD, erosive oesophagitis and control subjects was 70, 76 and 78%, respectively (P=0.75). CONCLUSIONS: H. pylori infection is associated with milder GERD.

Adult↗

PubMed2000

Detection and viral nucleotide sequence analysis of transfusion-transmitted virus infection in acute fulminant and non-fulminant hepatitis.

The impact of transfusion-transmitted virus (TTV) infection on acute fulminant and non-fulminant hepatitis is unclear. In this study, serum samples from 164 patients with acute hepatitis of various aetiologies, from 34 asymptomatic hepatitis B virus carriers and from 202 healthy adults were tested for TTV DNA by the semiconserved nested polymerase chain reaction. TTV viraemia was prevalent in patients with acute hepatitis C, in patients with acute hepatitis D virus superinfection and in patients with non-A-E hepatitis (27-30%) but the incidence was not significantly different from that of healthy controls (31 of 202, 15.3%). There were no significant differences in gender, age, presence of hepatitis G virus, the occurrence of fulminant hepatitis, or in serum albumin, bilirubin or alanine aminotransferase levels (9/30 vs 35/134) between patients with or without TTV viraemia. Seven of the nine TTV-positive patients with fulminant hepatitis were co-infected with hepatitis C, D or E. TTV clones from 18 subjects, with or without fulminant hepatitis, were sequenced and analysed phylogenetically. Eleven (61. 1%) belonged to TTV group 1, six (33.3%) to TTV group 2 and one to TTV group 3. No particular strain of TTV was associated with fulminant hepatitis. In summary, in Taiwan, TTV is prevalent in the general population as well as in patients with liver diseases. TTV plays an insignificant role in acute fulminant and non-fulminant hepatitis. Its influence on outcome requires a longitudinal study.

Acute Disease↗