Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 163 records · Page 9Linked to original sources

PubMed1996

Comparison of clinico-pathological features in hepatitis B virus-associated hepatocellular carcinoma with or without hepatitis D virus superinfection.

BACKGROUND/AIMS: Hepatitis D virus superinfection in hepatitis B virus carriers produces additional damage in an already injured liver. Earlier reports noted that the development of hepatocellular carcinoma may be accelerated in hepatitis D virus-superinfected patients. This study aimed to investigate the impact of hepatitis D virus on the clinical course of hepatitis B virus-associated hepatocellular carcinoma. METHODS: A total of 42 consecutive hepatocellular carcinoma cases seropositive for antibody against hepatitis D virus antigen (anti-HDV) were found from 1986 to 1994; the clinical manifestations, treatment and outcomes were compared with 255 consecutive hepatocellular carcinoma cases seropositive for hepatitis B virus surface antigen but seronegative for anti-HDV. RESULTS: The mean age was 60 years in both groups of patients. Other features, including sex, duration of follow-up, presence of cirrhosis or ascites, serum biochemistry, status of HBV-e antigen, and gross and microscopic tumor appearance, were not significantly different between the two groups. Though more patients in the anti-HDV-positive group underwent active treatment (operation or transcatheter arterial chemoembolization) than those in the anti-HDV-negative group (54.8% in 42 versus 34.9% in 255 cases, p = 0.02), the cumulative 4-year survival rates (9.5% versus 9.8%) were similar. For the anti-HDV-positive hepatocellular carcinoma patients, tumor size < 5 cm and active treatment were favorable prognostic predictors associated with survival > 18 months. CONCLUSION: Hepatitis D virus superinfection does not accelerate the development of hepatocellular carcinoma. The clinical manifestations were similar, and the outcome in anti-HDV-positive patients was not worse than in the general HBV-associated hepatocellular carcinoma patients, as long as they were diagnosed at an early stage and actively treated.

Adult↗

PubMed1996

Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s).

Primary hepatocellular carcinoma (HCC) extending to the adjacent organ(s) is sometimes encountered in patients with large, peripherally located tumours. Over a 4-year period, a total of 151 patients received curative resection of HCC at the Surgical Department of Veterans General Hospital-Taipei, Taiwan. Of these patients, 21 underwent hepatic resection combined with en-bloc resection of the adjacent organ(s) because tumour extension was found during operation. Subsequent histological examination of the resected specimens found evidence of HCC invasion into the resected adjacent organ(s) in only nine patients (group I), and the remaining 12 patients showed no evidence of extrahepatic HCC invasion (group II). Twenty-seven HCC patients with clinico-pathologically matched tumours but without extrahepatic extension were selected as controls (group III). One patient in group I died of hepatic failure after the operation. The morbidity rate was 48% in group I and group II patients, and 30% in group III patients. The difference was not statistically significant. On evaluating the clinico-pathological factors, including DNA ploidy status of the tumours, there were no significant differences between tumours with and without extrahepatic invasion. Patients with locally invasive HCC (group I) had disease-free and overall survival rates comparable with those of the patients without local tumour invasion (group II and III). We conclude that HCC with invasion to the adjacent organ(s) does not seem to be directly related to the 'aggressiveness' of the tumour, and extrahepatic infiltration of the tumour does not preclude a chance of cure. Our results underscore the need for en-bloc resection as treatment of choice for these patients.

Carcinoma, Hepatocellular↗

PubMed1996

An annealing mutation operator in the genetic algorithms for RNA folding.

An annealing mutation operator in the genetic algorithms (GA) for RNA folding on a MasPar MP-2 has been designed. The mutation probability descends along a hyperbola with respect to the size of the secondary structure, hence the total number of mutations at each generation drops linearly. Especially for long sequences with thousands of nucleotides as opposed to hundreds of nucleotides, the new mutation operator can make the distribution of free energies over all processors on MasPar MP-2 converge only after hundreds of generations. Based upon this new mutation operator, a technique to terminate the GA is also developed. The new mutation operator runs very efficiently. Some variations of the annealing mutation operator are also discussed.

Algorithms↗

PubMed1996

Prevalence and type of precore hepatitis B virus mutants in hepatitis D virus superinfection and its clinical implications.

To study the prevalence and type of the hepatitis B e antigen (HBeAg)-negative mutant in hepatitis D virus (HDV) superinfection, the precore region of hepatitis B virus (HBV) was analyzed by cycle sequencing. Of the 58 samples sequenced, 24 were wild type and 34 carried mutants. The precore stop mutation (TAG) at the 28th codon was found in 32 cases, other mutations were found in 7, and double mutations were found in 5. The absence of HBeAg showed a substantial agreement with the presence of mutants (kappa value, 0.74). Of the acute hepatitis patients, HDV replication and clinical manifestations were not significantly different between those with mutant and wild type virus, except that those with mutant virus were older (mean age, 48 vs. 28 years; P < .002). The absence of HBeAg in these patients is mainly due to HDV superinfection in older HBV carriers who already had precore mutant.

Acute Disease↗

PubMed1996

A method for screening antisense oligodeoxyribonucleotides effective for mRNA translation-arrest.

A transcription and translation coupled reticulocyte lysate system was established for rapid screening of antisense oligodeoxyribonucleotides (ODNs) to determine which are most effective for mRNA translation-arrest. A plasmid containing the target cDNA under the control of the T7 (or SP6) promoter was added to the lysate system in the presence of the T7 (or SP6) RNA polymerase, RNase H, and the antisense ODN under test. Transcription and translation were accomplished in a one-tube reaction. Translation-arrest caused by antisense ODN was evaluated in terms of the amounts of de novo-synthesized, [35S]-methionine or [35S]cysteine labeled target protein measured by gel electrophoresis and autoradiography. The properties of this system and optimal reaction conditions for use in antisense ODN screening were determined. Our method is simpler and more rapid than other in vitro screening methods.

Base Sequence↗

PubMed1996

Gonadotropin-releasing hormone-stimulated calcium mobilization is altered in pituitary cultures from anestrous ewes.

GnRH transiently increases intracellular calcium ([Ca2+]i) in pituitary gonadotrophs in culture. This effect is observed within 10 sec of GnRH treatment, lasts 1-5 min, and is thought to be an important intracellular signal leading to the secretion of LH. Recent studies with ovine pituitary cultures uncovered seasonal differences in this transient calcium response to GnRH. This finding led to the hypothesis that anestrus alters the pituitary response to GnRH and prompted this study on seasonal effects on LH secretion and [Ca2+]i mobilization. Inhibin was used to enhance pituitary sensitivity to GnRH. Results showed that pituitary cultures from 16 cycling ewes secreted an average of 9% +/- 2% of stored LH after treatment with 10 nM GnRH (stored LH = 470 +/- 66 ng/million cells); 9% +/- 1% of pituitary cells increased the concentration of [Ca2+]i from 75-150 nM up to 400-1400 nM. When cultures were pretreated with inhibin, GnRH released an average of 15% +/- 3% of stored LH (stored LH = same as above), and 38% +/- 4% of cells transiently increased [Ca2+]i above 400 nM. Results also showed that pituitary cultures from 11 acycling ewes secreted similar percentages of LH although the cells contained less LH to begin with (stored LH = 190 +/- 24 ng/million cells), but absolutely none of these cells (500 counted) increased [Ca2+]i after GnRH treatment, with or without inhibin present. Levels of GnRH receptor mRNA were unchanged by season. These data show that LH secretion and the rapid, transient increase in [Ca2+]i caused by GnRH are uncoupled in the unique situation of anestrus. It is possible, in fact, that these two parameters are not necessarily coupled during estrous conditions and that the transient change in [Ca2+]i is connected with LH synthesis or some other gonadotroph function. The data also show that inhibin can increase GnRH-responding cells up to 38%, a fact suggesting that inhibin may be a differentiation factor capable of transforming multipotent pituitary cells into gonadotrophs in sheep.

Animals↗

PubMed1996

Prognostic factor analysis of fulminant and subfulminant hepatic failure in an area endemic for hepatitis B.

In order to determine the criteria in selecting candidates for orthotopic liver transplantation (OLT), we assessed the aetiology and prognostic indicators in 61 patients with fulminant or subfulminant hepatitis during the past 13 years. Several previously reported models of high risk predictors were not suitable for a large portion of our patients with different aetiological and ethnic backgrounds. In the present study, serological markers of various hepatitis viruses were tested and clinical parameters were compared between survivors and non-survivors. Multiple virus infection and multifactorial causes were important in the pathogenesis (48%) of acute liver failure. Among the 13 clinical parameters, six were considered significant on univariate analysis: prothrombin time prolongation (P < 0.001), total bilirubin, creatinine and alpha-fetoprotein (P < 0.01), age and cholesterol (P < 0.05). With stepwise logistic regression using most discriminatory cut-off values, an age of > 43 years (P = 0.0001), total bilirubin levels of > 23 mg/dL (P < 0.005) and prothrombin time prolongation > 19 s (P < 0.0001) were independent predictors of non-survival. When applied to determine the index of poor prognosis, the sensitivity, specificity, positive predictive value, negative predictive value and predictive accuracy were 100, 67, 95, 100 and 95%, respectively, in the presence of any one of these prognostic factors. We conclude that these indicators may be useful for selecting patients with acute liver failure indicated for OLT.

Adolescent↗

PubMed1996

Mechanism of hydrogen peroxide and hydroxyl free radical-induced intracellular acidification in cultured rat cardiac myoblasts.

After a transient ischemic attack of the cardiac vascular system, reactive oxygen-derived free radicals, including the superoxide (O2-.) and hydroxyl (.OH) radicals can be easily produced during reperfusion. These free radicals have been suggested to be responsible for reperfusion-induced cardiac stunning and reperfusion-induced arrhythmia. Hydrogen peroxide (H2O2) is often used as an experimental source of oxygen-derived free radicals. Using freshly dissociated single rat cardiac myocytes and the rat cardiac myoblast cell line, H9c2, we have shown, for the first time, that an intriguing pHiota acidification (approximately 0.24 pH unit) is induced by the addition of 100 micromol/L H2O2 and that this dose is without effect on the intracellular free Ca2+ levels or viability of the cells. Using H9c2 as a model cardiac cell, we have shown that it is the intracellular production of .OH, and not O2-. or H2O2, that results in this acidification. We have excluded any involvement of (1) the three known cardiac pHi regulators (the Na+-H+ exchanger, the Cl--HCO3 exchanger, and the Na+-HCO3 co-transporter), (2) a rise in intracellular Ca2+ levels, and (3) inhibition of oxidative phosphorylation. However, we have found that H2O2-induced acidosis is due to inhibition of the glycolytic pathway, with hydrolysis of intracellular ATP and the resultant intracellular acidification. In cardiac muscle and in skinned cardiac muscle fiber, it has been shown that a small intracellular acidification may severely inhibit contractility. Therefore, the sustained pHi decrease caused by hydroxyl radicals may contribute, in some part, to the well-documented impairment of cardiac mechanical function (ie, reperfusion cardiac stunning) seen during reperfusion ischemia.

Acidosis↗

PubMed1996

Inhibin and estradiol alter gonadotropes differentially in ovine pituitary cultures: changing gonadotrope numbers and calcium responses to gonadotropin-releasing hormone.

Both inhibin (IN) and estradiol (E) use separate and distinct mechanisms to decrease the production of FSH 60%-80% while increasing receptors for GnRH (GnRH-Rec) 400%-600% in ovine pituitary cultures. To investigate how these hormones act to create outcomes that appear similar, individual cells in ovine pituitary cultures were analyzed for changes in GnRH-stimulated calcium signaling, GnRH binding, and gonadotropin content under IN or E treatments. Calcium mobilization studies showed that 10 nM GnRH increased intracellular calcium ([Ca++]i) in 9.2% +/- 0.8% of cells in control ovine pituitary cultures. After treatment with 10 nM E for 48 h, there was a small increase in the number of cells responding to GnRH (12.9% +/- 1.4% responded) and a major 5-fold increase in [Ca++]i response to GnRH as compared with untreated cells. By contrast, IN did not alter cellular calcium responses to GnRH but markedly increased the number of cells responding to GnRH (a 3.7-fold increase to 33.8 +/- 2.6%). Cytochemical studies measuring GnRH:GnRH-Rec complexes, FSH, and LH showed that E had no effect on the number of pituitary cells containing FSH, LH, or GnRH-Rec. In contrast, similar studies using IN showed that the number of cells containing GnRH-Rec and LH significantly increased (> 50%), whereas the number of FSH cells decreased (36%), and a lower than normal percentage of the remaining FSH cells carried GnRH-Rec. Thus, the net effect of IN on gonadotropes was to dramatically decrease the ratio of FSH:LH cells that contained GnRH-Rec, from 1:1 (untreated) to 1:8 (IN-treated) and to decrease the percentage of LH/FSH colocalization. In summary, these data indicate that E primarily operates on a fixed, preset number of ovine gonadotropes to inhibit FSH production and increase responsiveness to GnRH. IN, however, seems to change the very nature of ovine gonadotropes by completely turning off FSH synthesis in some cells, lowering GnRH-Rec in other FSH cells, and, finally, inducing LH and GnRH-Rec in newly recruited gonadotropes.

Animals↗

PubMed1996

Severe hyperbilirubinemia due to acute hepatitis A superimposed on a chronic hepatitis B carrier with glucose-6-phosphate dehydrogenase deficiency.

Taiwan is an endemic area for hepatitis A and B virus infections; nearly 90% of adults have serological markers for either virus. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is also common, ranging from 2% to 10%. We report the case of a 36-yr-old chronic HBV male carrier with G6PD deficiency who developed acute viral hepatitis A with severe hyperbilirubinemia and intravascular hemolysis. The hemolysis was in all likelihood the result of recent exposure to sulfa drugs. Fulminant hepatitis was the initial impression, because the peak serum total bilirubin concentration was alarmingly high, at 85.4 mg/dl. Exchange plasmapheresis was fresh frozen plasma was performed, and various laboratory studies gradually returned to near normal laboratory studies gradually returned to near normal over the next 3 wk. The patient made an uneventful recovery 1 month after admission.

Acute Disease↗

PubMed1996

Ruptured hepatocellular carcinoma: treatment strategy and prognostic factor analysis.

BACKGROUND: The prognosis of ruptured hepatocellular carcinoma (HCC) is generally poor, but few studies have focused on the analysis of prognostic factors of this catastrophic event. METHODS: Eighty-four consecutive patients with ruptured HCC were included. Twenty-nine clinical and laboratory variables were correlated to prognosis by using uni- and multivariate analyses. RESULTS: Epigastralgia and/or right upper quadrant abdominal pain was the most common initial presentation (70%), followed by shock (42%), abdominal distension (27%) and others (17%). Of these 84 patients, 50 patients were treated by supportive measure, 21 by operation and 13 by transcatheter arterial embolization (TAE). The median survival was 13, 30 and 202 days in each group, respectively, and 24 days overall. TAE showed the lowest hemostatic failure rate (20%). Univariate analysis showed that active treatment (operation or TAE), group I tumor with a solitary nodule or single nodule with proliferation into surrounding area, serum creatinine (< or = 1.2 mg/ml), alkaline phosphatase (< or = 95 U/L), alanine aminotransferase (ALT, < or = 40 U/L), total bilirubin (< or = 1.6 mg/ml), initial systolic blood pressure (> or = 90 mmHg), and absence of main portal vein thrombosis were correlated with a survival longer than 90 days (p < 0.05) in univariate analysis. Active treatment, ALT level and initial systolic blood pressure were still significant in multivariate analysis (p < 0.05). CONCLUSIONS: TAE may help stop the tumor bleeding. Treatment regimen, ALT levels and initial blood pressure are correlated with the prognosis of ruptured HCC.

Adolescent↗

PubMed1996

Autoimmune hepatitis in an area endemic for hepatitis B virus infection: a report of three cases.

The role of autoimmune hepatitis (AIH) in the pathogenesis of chronic hepatitis is usually neglected, and its prevalence in Taiwan is uncertain. This report described three cases of AIH among consecutive patients with abnormal liver function tests encountered during the past six years. The minimal follow-up period was three years. Two of them were elderly males and one was associated with spontaneous clearance of hepatitis B surface antigen before being recognized as AIH. Though multiple relapses were encountered in two patients, good response to low-dose corticosteroid therapy was evidenced clinically and histologically. The possibility of AIH as the underlying etiology should be considered when other causes of chronic hepatitis are excluded. Prompt recognition and management prevent untoward outcome.

Aged↗

PubMed1996

Seasonal variation in the incidence of peptic ulcer and esophageal variceal bleeding in Taiwan.

BACKGROUND: Seasonal variation of peptic ulcer and peptic ulcer bleeding has been reported in many western countries. To investigate the seasonal variation of peptic ulcer (PU) and esophageal variceal (EV) bleeding in Taiwan, this retrospective study was conducted. METHODS: Seven hundred and forty-six cases of gastric ulcer (GU) bleeding, 777 cases of duodenal ulcer (DU) bleeding and 264 cases of EV bleeding were recruited from January 1, 1991 to December 31, 1992. Patients were sent to the Medical Emergency Room (MER) for hematemesis and/or melena. Upper gastrointestinal (UGI) endoscopic examinations were completed within 24 hours for all patients. RESULTS: Significant seasonal variation was found in the incidence of PU and EV bleeding. PU bleeding was most often seen in March and EV bleeding was most often seen in February. CONCLUSIONS: The possible mechanism for the cyclic change of PU and EV bleeding is unclear, but clearly more manpower is needed during the months of February and March for better management of the increasing number of cases of PU and EV bleeding.

Aged↗

PubMed1996

Risk factor analysis of patients with chronic hepatitis C in Taiwan.

BACKGROUND: Parenteral transmission is the major route for hepatitis C virus (HCV) infection. However, in western countries, 40% of patients with chronic hepatitis C have no apparent risk factor of HCV infection. This study was designed to investigate the possible risk factors of HCV transmission in chronic hepatitis C patients in Taiwan. METHODS: One hundred and sixty-one consecutive patients with chronic hepatitis C and 161 age- and sex-matched healthy subjects were enrolled. Risk factors, including blood transfusion, injection with nondisposable needles, education status, surgery, dental procedure, tattooing, ear-piercing, sexual behavior and alcoholism, were obtained in every patient through questionnairing and interviewing. RESULTS: Patients with chronic hepatitis C, compared with healthy controls, had significantly higher rates of previous history of blood transfusion, frequent nondisposable needle injections, and lower education status (43.5% vs. 10.6%, 19.9% vs. 6.2%, 42.2% vs. 23.0%, respectively, all p < 0.05). Univariate logistic regression analysis showed blood transfusion, frequent nondisposable needle injections and low education as significant risk factors of HCV infection (all p < 0.05). Multivariate analysis again revealed them all to be independent significant risk factors associated with HCV infection in chronic hepatitis C patients. CONCLUSIONS: Parenteral transmission of HCV via transfusion and frequent nondisposable needle injections were the main routes of contracting HCV infection in patients with chronic hepatitis C in Taiwan. Also, people with low education ran the higher risk of transmission by HCV. Meticulous screening of the transfused blood for HCV, usage of disposable needles, and mass public education are important in our efforts to decrease chronic HCV infection in Taiwan.

Adolescent↗

PubMed1996

Polymerase chain reaction analysis for viral nucleic acids in acute sporadic hepatitis patients negative for serum hepatitis B surface antigen and antibodies to hepatitis C virus.

BACKGROUND: Polymerase chain reaction (PCR) is both very sensitive and very valuable in the clarification of the pathogenesis of viral hepatitis from type A to E (HAV to HEV). METHODS: This study was aimed to detect viral nucleic acids with PCR in 33 consecutive, acute sporadic hepatitis patients who were seronegative for hepatitis B surface antigen and antibody to hepatitis C virus by conventional radioimmununoassay or enzyme-linked immunoassay. RESULTS: Of the totals, 10 (30.3%) had detectable viral genomes. HBV DNA and HCV RNA were each detected in 2 (7.4%) of 27 patients with a self-limiting course. By contrast, HBV DNA was detected in the two (33.3%, p = 0.14) and HCV RNA in the three (50%, p = 0.03) of the six patents who became chronic; another one who had subsequent multiple exacerbations of hepatitis was positive for both HBV DNA and HCV RNA. HDV RNA was not detectable in all subjects. Although four (12.1%) were positive for antibody against HEV, none had detectable HEV RNA. Spontaneous disease resolution predominantly occurred in patients without detectable hepatitis B and hepatitis C genomes (100% of 23 patients vs 40% of 10 patients, p < 0.01). CONCLUSIONS: These results demonstrate that a combination of serological and molecular tests is mandatory for the appraisal of acute sporadic non-B non-C hepatitis and its clinical prognosis, they also raise the possibility of a hepatotrophic agent other than HAV to HEV. Recent documentation of the new GBV-C (hepatitis G virus) suggests the necessity of studying the unidentified pathogenesis in patients with non-A to E hepatitis.

Acute Disease↗

PubMed1995

Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus.

The IMP dehydrogenase from Tritrichomonas foetus has been identified as a potential target for antitritrichomonial chemotherapy. The gene encoding this enzyme was expressed in transformed Escherichia coli, and the recombinant protein was purified to homogeneity with an average yield of 3 mg of protein per liter of bacterial culture. Kinetic characterizations verified that the recombinant enzyme is in the authentic native state. 6-Cl-IMP, an irreversible inhibitor of the enzyme, was found to protect cysteine residue 319 of the enzyme against carboxymethylation by iodoacetamide. Radiolabeled IMP was covalently bound to the enzyme during the enzyme-catalyzed reaction via the formation of a specific adduct with cysteine residue 319. It is thus postulated that the conversion of IMP to XMP catalyzed by the IMP dehydrogenase from T. foetus is mediated by a nucleophilic attack of cysteine-319 in the enzyme protein to IMP at, most likely, its 2-position to facilitate a hydride transfer to NAD, resulting in the formation of a covalent intermediate between substrate and enzyme.

Animals↗

PubMed1995

Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D.

The outcome of hepatitis D virus (HDV) superinfection varies among patients and in different geographical areas. To find out whether HDV genotype affects outcome, we used a simple genotyping method based on restriction-fragment length polymorphism with enzymes XhoI and SacII for cleavage of PCR products of the HDV genome. Of samples from 88 patients studied, the genotypes of 61 were confirmed by two methods--analysis with both enzymes or by combined restriction-enzyme and direct sequencing analyses--with consistent results. No genotype III HDV was detected among these patients. The majority of patients with acute HDV infection (35/41 [85%]) had genotype II HDV. Among the 41 patients with acute infection, four of six with genotype I had fulminant disease compared with two of 35 with genotype II. Among patients in chronic stage, cirrhosis or hepatocellular carcinoma were found in 12 of 18 with genotype I HDV and eight of 29 with genotype II. Thus genotype II was the predominant HDV genotype in this study in Taiwan. Genotype II HDV was less frequently associated with fulminant hepatitis at the acute stage or with an unfavourable long-term clinical outcome at the chronic stage than was genotype I.

Acute Disease↗

PubMed1995

Non-sialate inhibitor of influenza A/WSN/33 neuraminidase.

An N1 strain of influenza A virus neuraminidase (A/WSN/33 NA) was purified and used to screen for inhibitors. As a result, a well-known tuberculostatic, 4'-formylacetanilide thiosemicarbazone (or thiacetazone), was identified. Thiacetazone is a non-sialate compound and inhibits the enzyme in a noncompetitive manner with respect to the substrate sialic acid. Mechanistic studies indicate that the inhibition was due to the competition of thiacetazone with Ca2+, which maintains N1 neuraminidase in an active conformation. The Ki for the inhibition was estimated to be about 4 microM. Equilibrium exchange experiments revealed that when purified A/WSN/33 NA was incubated with 5 microM 45CaCl2, 2 mol of 45Ca2+ ion was exchanged into each mole of NA tetramer and subsequently displaced from the enzyme upon the introduction of the inhibitor. Inhibition of plaque formation by thiacetazone in an MDCK cell culture that had been infected with the influenza A/WSN/33 virus was demonstrated. Thiacetazone was highly specific for A/WSN/33 neuraminidase, since little effect was noted when it was tested against NAs from the other strains of influenza virus or from bacteria. This compound might represent a group of non-sialate inhibitors of influenza NA that bind to a noncatalytic or an allosteric site on the enzyme.

Animals↗