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H M Wang

Publications and source records attributed to H M Wang.

At least 19 recordsLinked to original sources
PubMed2001

Thermodynamic characterization of the human acidic fibroblast growth factor: evidence for cold denaturation.

The thermodynamic parameters characterizing the conformational stability of the human acidic fibroblast growth factor (hFGF-1) have been determined by isothermal urea denaturation and thermal denaturation at fixed concentrations of urea using fluorescence and far-UV CD circular dichroism (CD) spectroscopy. The equilibrium unfolding transitions at pH 7.0 are adequately described by a two-state (native <--> unfolded state) mechanism. The stability of the protein is pH-dependent, and the protein unfolds completely below pH 3.0 (at 25 degrees C). hFGF-1 is shown to undergo a two-state transition only in a narrow pH range (pH 7.0-8.0). Under acidic (pH <6.0) and basic (pH >8.0) conditions, hFGF-1 is found to unfold noncooperatively, involving the accumulation of intermediates. The average temperature of maximum stability is determined to be 295.2 K. The heat capacity change (DeltaC(p)()) for the unfolding of hFGF-1 is estimated to be 2.1 +/- 0.5 kcal.mol(-1).K(-1). Temperature denaturation experiments in the absence and presence of urea show that hFGF-1 has a tendency to undergo cold denaturation. Two-dimensional (1)H-(15)N HSQC spectra of hFGF-1 acquired at subzero temperatures clearly show that hFGF-1 unfolds under low-temperature conditions. The significance of the noncooperative unfolding under acidic conditions and the cold denaturation process observed in hFGF-1 are discussed in detail.

Circular Dichroism↗
PubMed2001

Dual functions of largest NURF subunit NURF301 in nucleosome sliding and transcription factor interactions.

NURF is an ISWI complex of four proteins that uses the energy of ATP hydrolysis to catalyze nucleosome sliding. Three NURF components have been identified previously. We have cloned cDNA encoding the largest NURF subunit, revealing a 301 kDa polypeptide (NURF301) that shares structural motifs with ACF1. We have reconstituted full and partial NURF complexes from recombinant proteins and show that NURF301 and the ISWI ATPase are necessary and sufficient for accurate and efficient nucleosome sliding. An HMGA/HMGI(Y)-like domain of NURF301 that facilitates nucleosome sliding indicates the importance of DNA conformational changes in the sliding mechanism. NURF301 also shows interactions with sequence-specific transcription factors, providing a basis for targeted recruitment of the NURF complex to specific genes.

Amino Acid Motifs↗
PubMed2001

Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese.

p53 mutations are etiologically associated with the development of oral squamous cell carcinomas (OSCCs) or are associated with exposure to specific carcinogens. In this study, we used PCR-single strand conformation polymorphism and DNA sequencing to analyze the conserved regions of the p53 gene (exons 5-9) in OSCC tumor specimens from 187 patients with varied histories of betel quid, tobacco and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations at exons 5-9. The incidence of p53 mutations was not associated with age, sex, TNM stage, status of cigarette smoking or betel quid chewing. However, alcohol drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53 mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the incidence of p53 mutations was still statistically significant (RR = 2.24; 95% CI, 1.21-4.15) after adjustment for cigarette smoking and betel quid (BQ) chewing. G:C to A:T transitions were the predominant mutations observed and associated with BQ and tobacco use. Alcohol drinking could enhance these transitions. After adjustment for cigarette smoking and BQ chewing, alcohol drinking still showed an independent effect on G:C to A:T transitions (RR = 2.41; 95% CI, 1.01-5.74). These findings strongly suggest an important contributive role of tobacco carcinogens to p53 mutation in this series of Taiwanese OSCCs and alcohol might enhance these mutagenic effects. As safrole-DNA adducts have been detected in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients with a BQ chewing history, we cannot rule out the possibility that safrole or other carcinogens present in the BQ may cause a similar pattern of mutagenesis. Determination of the role of safrole and other carcinogens present in BQ on the pattern of p53 gene mutation in OSCC will require further study.

Adult↗
PubMed2001

Intra-arterial plus i.v. chemotherapy for advanced bulky squamous cell carcinoma of the buccal mucosa.

From July 1994 to December 1996, 41 patients with previously untreated, advanced bulky squamous cell carcinoma arising from the buccal mucosa (BSCC) were enrolled. All patients were males with a median age of 47 years (range 29-72). The tumor extent was stage III/IV: three of 38, T4: 85%, N2-3: 20%. Patients were initially scheduled to receive intra-arterial (i.a.) chemotherapy, followed by i.v. chemotherapy and regional therapy. The i.a. chemotherapy catheter was properly placed by external carotid artery angiography via the femoral artery. The i.a. chemotherapy consisted of cisplatin (P) 100 mg/m(2) day 1 plus 5-fluorouracil (F) 1000 mg/m(2) day 1-4, and the i.v. chemotherapy consisted of PF (10 patients) or PF plus methotrexate 200 mg/m(2) day 15 and 22 (31 patients). All chemotherapy regimens were administered at 4-week intervals. The response rate of i.a. plus i.v. chemotherapy for the primary site was 85% (35 of 41) with 29% complete remission (CR) (12 of 41). The response and CR rates of neck nodes were 82% (14 of 17) and 41% (seven of 17), respectively. The combined overall response rate was 80% (33 of 41) with a 29% CR (12 of 41). Major toxicity from i.a. chemotherapy of WHO grade > or = 3 included: mucositis of infusion area (76%), hemialopecia (56%) and leukopenia (5%). Three neurologic complications of i.a. chemotherapy including one hemiparesis occurred. The median follow-up time was 47 months (range 36-66 months), and the overall survival and disease-free survival were both 34% (14 of 41). Four patients were cured with chemotherapy alone and eight patients (19.5%) were cured without surgical intervention. Using i.a. chemotherapy as a cytoreductive therapy followed by subsequent i.v. chemotherapy produces a high response rate and an encouraging degree of complete response rate in advanced bulky BSCC. However, toxicity management and catheter placement will need to be improved in order to better define the role of this therapy in advanced BSCC.

Adult↗
PubMed2001

Surgical treatment for rectal prolapse.

BACKGROUND: The problem of full-thickness rectal prolapse is formidable, with no clear predominant treatment of choice. Several operations have been proposed to correct rectal prolapse which can be divided into transabdominal and perineal procedures. METHODS: From September 1982 to October 1999, 32 patients with rectal prolapse were treated with surgical procedures. There were 16 males and 16 females with a mean age of 58.3 years (Range 17-89). Forteen patients received rectopexy procedure, 6 patients received sigmoidectomy, 6 patients received perineal rectosigmoidectomy, 1 patient received Delorme procedure, 1 patient received Thiersch procedure and 4 patients received laparoscopic-assisted sigmoidectomy. The median follow up times were 7.5 years. RESULTS: In the rectopexy group, complication occurred in one patient (7.1%) and one patient recurred (7.1%). In the sigmoidectomy group, there were no complication but one patient recurred (10%). In the perineal rectosigmoidectomy group, there were no complication, but one patient recurred (16.7%). The total complication rate were 3.1% and total recurrence rate were 9.3%. CONCLUSIONS: Although, the best operation for rectal prolapse remains a controversial subject, we believe that laparoscopic-assisted sigmoidectomy offers a promising new option for the treatment of rectal prolapse.

Adolescent↗
PubMed2000

Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma.

BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity of gemcitabine in patients with chemotherapy-naïve, advanced hepatocellular carcinoma (HCC). METHODS: Twenty-eight patients with unresectable and nonembolizable HCC who had received no prior systemic chemotherapy and with objectively measurable tumors, adequate liver and renal function, and adequate bone marrow reserve were enrolled on this study. The therapy consisted of gemcitabine 1250 mg/m(2) intravenously over 30 minutes weekly in an outpatient clinic. One course of treatment included three consecutive weekly infusions of gemcitabine and a 1-week rest. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. RESULTS: All 28 patients were evaluable for response and toxicity. A partial response (PR) was achieved in 5 patients, for an overall response rate of 17.8% (95% confidence interval, 2.7-32.9%). Seven patients had stable disease (25%), and 16 patients had disease progression (57.2%). The median survival for all 28 patients was 18. 7 weeks, and, for those patients who achieved a PR, it was 34.7 weeks. The median time to progression was 12 weeks. National Cancer Institute Common Toxicity Criteria Grade 3-4 toxicity consisted primarily of leucopenia (10.7%), anemia (14.3%), thrombocytopenia (10.7%), and hepatotoxicity (14.3%). The spectrum of both hematologic and nonhematologic toxicity was mild, with thrombocytopenia constituting the dose-limiting side effect. CONCLUSIONS: Gemcitabine shows marginal antitumor activity in patients with advanced HCC, although the response duration is short-lived. Gemcitabine seems to be particularly promising because of its low toxicity profile. Further studies in combination with other active agents are warranted.

Adolescent↗
PubMed2000

Current seroprevalence of hepatitis A virus infection among kindergarten children and teachers in Taiwan.

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before the late 1980s. The seroprevalence of HAV infection was higher than 90% with most HAV infection occurring during childhood. This study was to estimate the seroprevalence of HAV infection among preschool children in central Taiwan. A community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas and 2 aboriginal areas randomly selected through stratified sampling. Serum samples of 2,549 healthy preschool children and 104 teachers in study kindergartens were screened for the HAV antibodies (anti-HAV) by means of a commercially available microparticle enzyme immunoassay (AxSYM HAVAB). Among aboriginal kindergarten children, more than 96% of them were anti-HAV seropositive due to a mass HAV vaccination program. In urban and rural areas, kindergarten children had a very low prevalence of anti-HAV (0.4%) in contrast to a high seroprevalence in their teachers (78%). There was no gender difference in seroprevalence of anti-HAV, while the anti-HAV seroprevalence was significantly higher in urban areas than in rural areas. Crowdedness of living in urban areas might facilitate the person-to-person transmission of infectious agents.

Adult↗
PubMed1999

Regression diagnostics for the class A regressive model with quantitative phenotypes.

Regression diagnostic methods are developed and investigated under the Class A regressive model proposed by Bonney [(1984) Am J Med Genet 18:731-749]. We call a family whose phenotypic distribution does not conform to the same genetic model as the majority of the families an etiotic family. The exact case-deletion approach for identifying etiotic families, based on examining the changes in each model parameter estimate by excluding one family at a time, is very time-consuming. We proposed three alternative diagnostic methods: the empirical influence function (EIF), the one-step approximation, and the approximated one-step approach. These methods can be computed efficiently and were incorporated into the existing software package S.A.G.E. A thorough Monte-Carlo investigation of the performance of the diagnostic methods was conducted and generally supports the EIF approach as the recommended alternative. The phenotypic variance is the parameter whose associated regression diagnostic most frequently and correctly identified etiotic families in the models that were examined. An analysis of body mass index data from 402 individuals in 122 Muscatine, Iowa families is used to illustrate the methods. A Class A regressive model with a recessive major locus and equal mother-offspring and father-offspring correlations provided the best-fitting model. The proposed regression diagnostics identified up to 7.4% of the 122 families as etiotic. As a result of this investigation, case-deletion diagnostic assessment is now a practical component in the analysis of quantitative family data.

Adolescent↗
PubMed1999

Impact of oral submucous fibrosis on chemotherapy-induced mucositis for head and neck cancer in a geographic area in which betel quid chewing is prevalent.

In Southeast Asia and Taiwan, betel quid chewing is prevalent. Patients with head and neck cancer who chewed betel quid habitually seem to experience more severe chemotherapy-induced mucositis in our clinical practice. To validate this issue, patients with untreated head and neck cancer who received cisplatin (cDDP) plus a 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy were included in this analysis. Information on the consumption of betel quid, tobacco, and alcohol were recorded before chemotherapy. Oral submucous fibrosis (OSF) was diagnosed clinically according to the fibrotic appearance of the mucosa and trismus. Mucositis was scored according to the World Health Organization criteria, and the mucositis score of the first course of chemotherapy was used for analysis. From December 1993 to April 1996, 120 patients were enrolled in this trial. Neither the betel quid chewing nor the cancer of the oral cavity was to be a significant factor for mucositis. However, clinically diagnosed OSF was found to display a significant correlation with more severe mucositis (p = 0.02). We concluded that in betel quid chewing-prevalent areas, OSF was a risk factor of more severe mucositis in head and neck cancer patients treated by CDDP and 5-FU-based regimens.

Adult↗
PubMed1999

Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection.

From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU.

Adult↗
PubMed1999

Weekly 24-h infusion of high-dose 5-flurouracil and leucovorin in patients with advanced gastric cancer.

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.

Adult↗
PubMed1999

Seroepidemiology of Helicobacter pylori infection among preschool children in Taiwan.

Helicobacter pylori is associated with chronic antral gastritis that is related to duodenal ulcer, gastric ulcer, and probably gastric adenocarcinoma. Infection with H. pylori during childhood is considered an important risk factor for gastric carcinoma in adult life. To examine the epidemiologic characteristics of H. pylori infection among preschool children in central Taiwan, a community-based survey was carried out in 54 kindergartens in 10 urban townships, 10 metropolitan precincts, and 2 aboriginal townships randomly selected through stratified sampling. Serum specimens of 2,551 healthy preschool children (3-6 years old) randomly sampled from study kindergartens were screened for antibodies to H. pylori by latex agglutination and ELISA methods. Multivariate-adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated by multiple logistic regression analysis. A total of 207 subjects were antibody-positive, giving a prevalence of 8.1%. The overall seropositive rates were 4.5% in 3-year-old group, 4.4% in 4-year-old group, 9.4% in 5-year-old group, and 11.7% in 6-year-old group. The older the age, the higher the seroprevalence (OR = 3.2, 95% CI = 1.5-6.8 for 3-year-old children versus the 6-year-old children). Seroprevalence was not different between boys and girls. The aboriginal townships had a seroprevalence greater than the urban townships and metropolitan precincts (OR = 2.6, 95% CI = 1.9-3.7). The larger the number of siblings, the higher the seroprevalence (OR = 2.4, 95% CI = 1.0-5.8 for those with no sibling versus those with > or = 3 siblings). In the multiple logistic regression analysis, the seroprevalence of H. pylori remained significantly increased with age, aboriginal township, and large sibship size after multivariate adjustment. A poor water supply system, sewage disposal, and other environmental hygiene in the aboriginal townships might have played some role in infection with H. pylori. The early childhood transmission among siblings might also be an important determinant of H. pylori seropositivity in Taiwan.

Antibodies, Bacterial↗
PubMed1998

Immune status in preschool children born after mass hepatitis B vaccination program in Taiwan.

A mass hepatitis B vaccination program began in Taiwan in 1984. In order to determine the immune status of hepatitis B virus (HBV) infection among preschool children, a total of 25 kindergartens in 20 townships and metropolitan precincts in central Taiwan were randomly selected through stratified sampling. Serum specimens of 2130 healthy preschool children aged 2-6 years old were screened for the HBV markers and liver function in 1996. HBV surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against HBV core antigen (anti-HBc) were tested by reverse passive hemagglutination (RPHA), enzyme immunoassay (EIA) and radioimmunoassay (RIA) using commercial kits. HBV vaccination rate of the preschool children was 98%, and complete vaccination rate (three or four doses of HBV vaccine) was 94%. The HBsAg seropositive rate was 4.5% among incomplete vaccinees and 1.3% among complete vaccinees. The anti-HBs was detectable in 1637 of 2000 complete vaccinees (81.9%) and in 53 of 88 incomplete vaccinees (60.2%). The overall prevalence rate of anti-HBc was 2.4% (52 of 2130). The older the age, the lower the anti-HBs seropositive rate. The anti-HBs seropositive rats for complete vaccinees were 100% at 2 years old and 75% at 6 years old. There were no significant differences in HBsAg-seropositive rates and anti-HBs-seropositive rates among different residential areas or ethnic groups. There were three children who were seropositive on HBsAg, anti-HBs and anti-HBc, whether they were infected by the vaccine-induced escape mutant of HBV deserves scrutiny.

Age Factors↗
PubMed1998

Hypopharyngeal carcinoma with clinical peritoneal carcinomatosis: a report of two patients.

Most patients with hypopharyngeal carcinomas show advanced disease, either at the primary site or in the neck, at the time of diagnosis. Despite intensive therapy, a great number of recurrences and distant metastases can be observed. The most common metastatic sites are the lung and bone, and only in autopsy cases has peritoneum carcinomatosis been mentioned as a metastatic site. Since January 1992, two of 78 patients (2.3%) with advanced hypopharyngeal squamous cell carcinomas (SCCs) treated initially by chemotherapy in our department developed clinical peritoneal carcinomatosis during their natural courses. Both patients were man patients with advanced locoregional disease at stage T4N3. Their clinical peritoneal carcinomatosis appeared during chemotherapy, with good disease control above the clavicle. Both patients eventually died of sepsis within 1 month after diagnosis of the peritoneal carcinomatosis. The authors suggest that peritoneal carcinomatosis is not as rare as previously believed, and should be included in the differential diagnosis in patients with advanced hypopharyngeal SCC with abdominal symptoms. Peritoneal carcinomatosis appears to be refractory to chemotherapy, and carried a poor prognosis in patients in the present study.

Antineoplastic Agents↗
PubMed1998

Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract carcinomas.

From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology-proven locally advanced or metastatic biliary tract carcinomas (BTC) were enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2 week break. The treatment was terminated if disease progressed, the patient refused or unacceptable toxicity occurred. All patients required a Port-A catheter insertion and were treated at outpatient clinics by portable infusion pumps. There were 12 males and seven females with a median age of 62 years (range 45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC), three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179 chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen patients were evaluable for response. The response rates were: 33% (six of 18) partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18) progressive disease (PD). All of the patients were evaluable for toxicity. The most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of 19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without treatment-related death. The median time to progression was 4 months. The overall median survival time was 7.0 months. The median survival time of the PR was not reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5-FU with LV by 24 h infusion in an outpatient setting for patients with BTC is effective, only mildly toxic and deserves further study.

Aged↗
PubMed1997

Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones.

Recent studies have suggested that 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (beta-lapachone) inhibits DNA topoisomerase I by a mechanism distinct from that of camptothecin. To study the mechanism of action of beta-lapachone, a series of beta-lapachone and related naphthoquinones were synthesized, and their activity against drug-sensitive and -resistant cell lines and purified human DNA topoisomerases as evaluated. Consistent with the previous report, beta-lapachone does not induce topoisomerase I-mediated DNA breaks. However, beta-lapachone and related naphthoquinones, like menadione, induce protein-linked DNA breaks in the presence of purified human DNA topoisomerase IIalpha. Poisoning of topoisomerase IIalpha by beta-lapachone and related naphthoquinones is independent of ATP and involves the formation of reversible cleavable complexes. The structural similarity between menadione, a para-quinone, and beta-lapachone, an ortho-quinone, together with their similar activity in poisoning topoisomerase IIalpha, suggests a common mechanism of action involving chemical reactivity of these quinones. Indeed, both quinones form adducts with mercaptoethanol, and beta-lapachone is 10-fold more reactive. There is an apparent correlation between the rates of the adduct formation with thiols and of the topoisomerase II-poisoning activity of the aforementioned quinones. In preliminary studies, beta-lapachone and related naphthoquinones are found to be cytotoxic against a panel of drug-sensitive and drug-resistant tumor cell lines, including MDR1-overexpressing cell lines, camptothecin-resistant cell lines, and the atypical multidrug-resistant CEM/V-1 cell line.

Antineoplastic Agents, Alkylating↗
PubMed1997

The VIP regimen effective treatment to refractory choriocarcinoma: a case report.

This is a case report of a female patient who tried another regimen after EMA-CO regimen failed. A 30-year-old female, gravida 4, para 2, abortus 2, blood grouping O (grouping B of her husband), was a victim of choriocarcinoma of the uterus and was resistant to multiple combination regimens of chemotherapy (EMA-CO, EMA-PE, BEP). She was finally cured by the VIP regimen of chemotherapy. The VIP regimen may be considered as an effective protocol to cure refractory choriocarcinoma.

Adult↗