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Biomedical subjects

T H Wang

Publications and source records attributed to T H Wang.

At least 73 records · Page 4Linked to original sources
PubMed1998

Loss of pS2 protein expression is an early event of intestinal-type gastric cancer.

To investigate the prevalence of pS2 expression in gastric cancer with respect to tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori) infection, pathologic specimens of 91 patients with gastric cancer were immunostained for pS2. Such immunoreactivity was correlated with the status of H. pylori infection, tumor staging, histology, subtyping, and associated intestinal metaplasia. Positive pS2 staining was seen throughout all non-neoplastic epithelia, and in all 9 patients with the complete type of intestinal metaplasia. In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2 staining (P < 0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2 expression in the cancer tissues proper. There was no correlation of pS2 expression with age, gender, depth of invasion, duodenal involvement, lymph node metastasis, venous invasion or H. pylori infection. Negative pS2 staining was significantly higher in the intestinal (74.5%) and Borrmann type I, II, III (64.2%) tumors than the diffuse (43.2%, P < 0.005) and Borrmann type IV (20%, P < 0.05) tumors. Our results indicate that loss of pS2 expression may occur as an early event in the malignant transformation process of intestinal-type tumors.

Adult↗
PubMed1998

Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.

Aged↗
PubMed1998

Optimized conditions for growth and fermentation of Helicobacter pylori.

This study attempted to optimize the growth conditions of Helicobacter pylori by comparing the growth of H. pylori in an anaerobic jar and an incubator. It was found that the primary isolation rate of H. pylori from gastric biopsies was higher in an anaerobic incubator (28/30) than in an anaerobic jar (21/30). In addition, growth rate in the subsequent passage was also higher in an incubator. By comparing different supplements in the liquid media, it was found that most strains grew best in Brucella broth containing 5% fetal calf serum, and some strains grew well with the supplement of 0.2% of beta-cyclodextrin. A large scale culture using a bioreactor indicated that a defoaming agent, polypropylenglycol, profoundly inhibited the growth of H. pylori. However, fermentation could be successfully performed by continuously infusing mixed airs composed of 5% O2, 10% CO2 and 85% N2. Moreover, the production of secreted proteins of H. pylori strains grown in the bioreactor was the same as that in an anaerobic jar. Results presented herein can be used to further optimize conditions for enhancing the growth of H. pylori.

Fermentation↗
PubMed1998

[The role of G protein, protein kinase C and Na(+)-H+ exchanger in endothelin-1-induced cardiomyocyte hypertrophic responses].

Endothelin-1 (ET-1) has been shown to be a potent growth factor and to induce cardiac hypertrophy. In the present study, we examined the role of G protein, protein kinase C (PKC) and Na(+)-H+ exchanger in ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes. ET-1 (10(-10)-10(-7) mol/L) induced promotion of 3H-leucine incorporation, increase in cell protein content and cell surface area in a dose-dependent manner with EC50 value of 5.2 x 10(-10), 5.2 x 10(-10) and 7.3 x 10(-10) mol/L respectively. All of these ET-1-induced cardiomyocyte hypertrophic responses were completely blocked by pretreatment with staurosporine (2 nmol/L), a protein kinase C inhibitor, and stimulated by 4-phorbol, 12-myristate, 13-acetate (PMA) (10(-8)-10(-6) mol/L), a protein kinase C activator, in a dose-dependent manner. Pretreatment of amiloride (10(-4) mol/L), a Na(+)-H+ exchange inhibitor completely inhibited the ET-1-induced, but not PMA-induced cardiomyocyte hypertrophic responses. The ET-1-induced increase in cardiomyocyte protein synthesis and cell surface area was significantly inhibited by pretreatment with pertussis toxin (150 ng/ml). These results suggest that ET-1-induced cardiomyocyte hypertrophy was linked with pertussis toxin sensitive G protein, and PKC and Na(+)-H+ exchange may be an important intracellular signaling transduction pathway during ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes.

Animals↗
PubMed1997

Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Adenocarcinoma↗
PubMed1997

Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection.

BACKGROUND & AIMS: A different spectrum of genetic changes including p53, c-erbB-2, c-met, adenomatous polyposis coli (APC), and deleted in colorectal cancer (DCC) is involved in gastric cancer (GC). The aim of this study was to correlate these alterations with histological subtypes, tumor stages, and Helicobacter pylori infection. METHODS: Specimens of 163 patients with GC were immunostained for p53, c-erbB-2, and c-met, and polymerase chain reaction was performed in them to determine loss of heterozygosity (LOH) of APC and DCC. RESULTS: Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC. Overexpression of c-erbB-2 occurred more commonly in intestinal GC and advanced GC of both types. Overexpression of c-met was greater in diffuse GC, particularly at advanced stage. LOH of APC was more common in intestinal GC irrespective of the stage but rarely in diffuse GC. LOH of DCC occurred primarily in advanced intestinal GC and infrequently in early GC or advanced diffuse GC. Alterations of these five genes were not correlated with H. pylori infection. CONCLUSIONS: A distinct genetic pathway exists in gastric carcinogenesis of different histological subtypes and their tumor progression, in which H. pylori infection may play an equal role or no role.

Adenomatous Polyposis Coli↗
PubMed1997

Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast.

The expression of the angiogenic growth factors, vascular endothelial cell growth factor (VEGF) and placenta growth factor (PIGF) was demonstrated in isolated human term cytotrophoblast and in vitro differentiated syncytiotrophoblast. RNase protection assays demonstrated VEGF expression in both cytotrophoblast and syncytiotrophoblast while prominent PIGF expression was detected in both types of trophoblast by Northern blot analyses. VEGF expression increased approximately eightfold in trophoblast cultured under hypoxic conditions (1 per cent O2) yet PIGF expression decreased 73 +/- 5.5 per cent in the same trophoblast. These results suggest distinct regulatory mechanisms govern expression of VEGF and PIGF in trophoblast. Characterization of the VEGF/PIGF receptors, KDR and flt-1, revealed the presence of flt-1 mRNA in isolated cytotrophoblast and in vitro differentiated syncytiotrophoblast. KDR was not detected in the isolated trophoblast. Exogenous rhVEGF induced c-Jun N-terminal kinase (JNK) activity in the normal trophoblast indicating that the flt-1 receptors on trophoblast are functional. Trophoblast-derived VEGF/PIGF could act in a paracrine fashion to promote uterine angiogenesis and vascular permeability within the placental bed. In addition, presence of function flt-1 on normal trophoblast suggests that VEGF/PIGF functions in an autocrine manner to perform an as yet undefined role in trophoblast invasion, differentiation, and/or metabolic activity during placentation.

Blotting, Northern↗
PubMed1997

Biometry and primary angle-closure glaucoma among Chinese, white, and black populations.

PURPOSE: Primary angle-closure glaucoma (PACG) is more prevalent among Chinese than whites. The authors tested the hypothesis that Chinese have shallower anterior chambers than do whites, a factor that may be related to PACG prevalence. METHODS: The authors compared anterior chamber depth, axial length, radius of corneal curvature, and refractive error among 531 Chinese, 170 whites, and 188 blacks older than 40 years of age using the same model of instruments and identical technique. RESULTS: Mean anterior chamber depth and axial length did not differ significantly for the three groups. Whites had a significantly higher prevalence of hyperopia > 2 diopters than did Chinese. Radius of corneal curvature was significantly smaller among Chinese than whites or blacks. CONCLUSIONS: These results suggest that Chinese do not differ on a population basis from other ethnic groups in many of the biometric risk factors known to be of importance for PACG. It will be necessary to identify other ocular biometric parameters to explain the excess burden of PACG among Chinese, which may improve the effectiveness of screening for this disease in all populations.

Adult↗
PubMed1997

Enhancement of immunohistochemical detection of HIV-1 p24 antigen in brain by tyramide signal amplification.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain has been demonstrated in formalin fixed, paraffin embedded post-mortem brain tissue (PM) by chromogenic immunohistochemistry for the HIV p24 antigen. The sensitivity of antigen detection is increased significantly by tyramide signal amplification (TSA) compared to the conventional peroxidase labelled Avidin-Biotin complex (ABC) technique. The TSA method also permitted the use of a lower concentration of primary antibody than is conventionally used. Sensitivity was enhanced further by microwave irradiation of the paraffin embedded tissues in citrate buffer. HIV-1 p24 antigen was also detected in PM brain tissue by TSA enhanced immunofluorescence and demonstrated increased sensitivity compared to the conventional immunofluorescence technique with a greatly reduced autofluorescence background.

Brain↗
PubMed1997

The effect of 0.5% timolol maleate on the ocular perfusion of ocular hypertensive patients by scanning laser flowmetry.

To understand the effect of 0.5% timolol maleate on the ocular perfusion of the optic disc and macula in ocular hypertensive patients, we enrolled 10 males and 15 females without any systemic or ocular disease, except intraocular pressure higher than 20 mmHg. Their average age was 33 +/- 13 y/o (range 14-45). Under the randomized, double-masked design, one drop of 0.5% timolol maleate was given in one eye, and placebo in the fellow eye. Heart rate, blood pressure, intraocular pressure, and ocular perfusion were measured at baseline, and then 30 minutes and 2 hours after treatment. Ocular perfusion was measured by Heidelberg Retina Flowmeter (Heidelberg Engineering GmbH, Heidelberg, Germany). We used 10 degrees measurement field and 10 x 10 pixels measurement frame. Four areas were measured, i.e., temporal upper, temporal lower, and nasal parts of the optic disc, and macula. In comparison to the baseline, the treated eyes had a slight reduction of blood flow, volume, and velocity 30 minutes after treatment, but these parameters came back close to the baseline value at 2 hours after treatment. Similar changes were also noted in the control eyes. The results showed that a single drop of 0.5% timolol had minimal effects on the retinal and macular circulation within 2 hours after treatment.

Adolescent↗
PubMed1997

Increased prevalence of Helicobacter pylori infection among patients affected with intestinal-type gastric cancer at non-cardiac locations.

Previous data on the association of Helicobacter pylori infection with gastric cancer by demographic or histological features are inconsistent due to a univariate analysis of limited case numbers. The aim of the present study was to determine such an association by the use of a large series of patients and multiple variables analysis. The serum IgG antibodies against H. pylori were measured in 397 patients with histologically verified gastric cancer. A multiple logistic regression analysis was used to define the association between seropositivity and demographic or tumour characteristics of gastric cancer. The overall seropositivity of H. pylori was 63%. In univariate analysis, the prevalence was significantly lower among patients with cardia (50%) or diffuse-type (56.6%) cancers than those with non-cardia (64.8%) or intestinal-type (70.3%) cancer (P < 0.05 and P < 0.01, respectively). There was no statistical difference between H. pylori infection rate and gender, age or tumour stage. A multiple logistic regression analysis showed tumour location and histology remained significant factors associated with seropositivity of H. pylori with an odds ratio of approximately 2.0. Analysis of combined histology and location revealed that patients with intestinal-type cancer at non-cardia locations had the highest odds ratio of 3.93 (95% confidence interval (CI): 1.55-10.0) compared with the lowest odds ratio of 0.69 (95% CI: 0.30-1.62) in diffuse cardia cancer (P < 0.005). Our data indicate H. pylori infection in gastric cancer is independently affected by the histological subtype and by tumour location.

Adult↗
PubMed1997

Benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis is a rare disorder of unknown etiology and has not yet been reported in Taiwan. We report a case with a typical clinical course. A 17-year-old Taiwanese boy had three episodes of pruritus and jaundice from February 1993 to July 1995, each lasting 3 to 4 months. Jaundice spontaneously subsided and he was symptom-free during periods of remission. A fourth episode of pruritus began in July 1995, with jaundice developing later and lasting for 3 months. Laboratory tests revealed direct hyperbilirubinemia. Endoscopic retrograde cholangiopancreatography showed normal intra- and extrahepatic biliary trees. Light microscopy of a liver biopsy sample revealed hepatocellular and canalicular cholestasis with bile retention in the Kupffer cells. Benign recurrent intrahepatic cholestasis was diagnosed after exclusion of other possible causes of jaundice. The patient made an uneventful recovery.

Adolescent↗
PubMed1997

Positive and negative strand of hepatitis C virus RNA sequences in peripheral blood mononuclear cells in patients with chronic hepatitis C: no correlation with viral genotypes 1b, 2a, and 2b.

Hepatitis C virus (HCV) has many genotypes which are closely associated with the severity of chronic hepatitis and the response to antiviral therapy. Although HCV is essentially hepatotropic, several lines of evidence suggest that this virus can infect peripheral blood mononuclear cells (PBMC) in most patients with chronic HCV infection. However, the methods used previously to detect negative-strand HCV RNA have been questioned, and the PBMC tropism of different HCV genotypes remains unknown. A stringent method was used to investigate the prevalence of positive- and negative-strand HCV RNA in the PBMC of 106 patients with chronic hepatitis C and to analyze the influence of HCV genotype on the tropism of PBMC. HCV type 1b was the predominant strain in the patients. Positive-strand RNA in PBMC was detected in 83 (78%) and 40% had negative-strand RNA. The demographic and clinical features were comparable among different patients grouped by the replication status of HCV in the plasma and PBMC samples. In addition, there was no significant difference of PBMC tropism between type 1b and non-1b HCV. In summary, HCV does indeed infect actively the PBMC of chronic hepatitis C patients and such infection is not correlated to the pathogenesis of liver cell damage. Moreover, the genotype is not associated specifically with PBMC tropism of HCV.

Adult↗
PubMed1997

Automated perimetry in primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness worldwide. Patients are usually asymptomatic until severe anatomic and functional damage occurs. Visual field examination is important in managing glaucoma patients, especially in the treatment and follow-up of moderate to advanced cases. This study was designed to investigate the patterns of automated visual field defects in POAG. We studied 296 POAG patients from the Glaucoma Clinic of the National Taiwan University Hospital from January 1986 to June 1996. The perimetry was performed using the Octopus program 32 or 38, or Humphrey program 30-2, and the results were analyzed according to the Glaucoma Hemifield Test design. The depth and frequency of locations of visual field defects were computed, and stratified by age and intraocular pressure (IOP). The results suggested that the most frequently affected locations in POAG were paracentral areas, while the deepest scotoma appeared in the upper and lower nasal areas. Patients with IOP higher than 25 mmHg or older than 50 years had higher mean sensitivity losses in both superior and inferior hemifields. The results of this study revealed the patterns of automated visual field defects in POAG may be a useful guide for the management of POAG patients.

Adolescent↗
PubMed1997

Genetic analysis of the cytotoxin-associated gene and the vacuolating toxin gene in Helicobacter pylori strains isolated from Taiwanese patients.

OBJECTIVE: Two virulence factors encoded by the cytotoxin-associated (cagA) gene and the vacuolating toxin (vacA) gene of Helicobacter pylori are known to be associated with gastroduodenal pathologic conditions. In this report, nucleotide sequence of cagA and vacA and the serum antibody response to the CagA antigen in H. pylori isolates from Taiwanese patients were studied. METHOD: cagA and vacA were characterized in 173 H. pylori strains by polymerase chain reaction and DNA hybridization analyses. The presence of serum IgG antibodies against CagA was assessed by Helico-blot Western blot system. Sequence analysis of polymerase chain reaction-amplified vacA and cagA was performed for two strains. RESULTS: cagA was detected in all the isolates with peptic ulcers and gastric cancer. Of 54 strains with non-ulcer dyspepsia, 51 were found to be cagA+. Serum antibodies to CagA were detected for 99.2% of cagA+ strains compared with 0% of strains lacking cagA. vacA was detected in all isolates. Sequence analysis of vacA and cagA indicated that sequences of two Taiwanese strains were closely related to each other (95.9% and 97% nucleotide identity, respectively) but less homologous to the published strains (90.9% and 91.4% mean nucleotide sequence identity, respectively). CONCLUSIONS: The strong association (98%) of cagA+ strains with Taiwanese patients suggests that the cagA+ phenotype could not be used as a single marker of high-risk patients in Taiwan. Moreover, sequence analysis indicates that Taiwanese strains contain different genetic sequences from those in other geographic regions.

Adolescent↗
PubMed1997

Characterization of Ca(2+)- and voltage-dependent nonselective cation channels in human HepG2 cells.

Nonselective cation channels have been identified and linked to important cell functions in rat hepatocytes. In this study, we characterized inward rectifying nonselective cation channels in detail by the patch clamp technique in human HepG2 cells. Channel properties were studied with high resistance borosilicate pipettes in cell-attached and inside-out configurations. With Ringer's solution and KCl as pipette solutions, the conductances were 19.7 +/- 2.1 and 22.2 +/- 0.0 picosiemens (pS), and reversal potentials were 30.9 +/- 3.5 and 31.3 +/- 4.6 mV, respectively. The channel was permeable to Ba2+, and the sequence of permeability ratios was Na+ > K+ > Cs+ > Ba2+. In the cell-attached configuration, the channel had a higher opening probability at depolarizing potential than at hyperpolarizing. In the inside-out patches with symmetric Ringer's solution, the current voltage curve was linear with conductance of 19.8 +/- 0.9 pS. Reversal potential shifted from -0.2 +/- 1.0 mV to 23.2 +/- 1.0 mV when the bath solution was replaced by dilute Ringer's solution. In the inside-out configuration, the gating was Ca(2+)-dependent, and the opening probability increased with increasing intracellular calcium concentration ([Ca2+]i). An outward rectifying channel appeared when [Ca2+]i was less than 1 mumol/L. The nonselective channel was reversibly blocked by 10 mumol/L internal flufenamic acid. We conclude that Ca(2+)- and voltage-dependent nonselective cation channels are present in human HepG2 cells. The channels might be involved in the regulation of Ca2+ influx and are associated with activation of other ion channels.

Animals↗
PubMed1997

Acute pancreatitis complicated by infarction of the spleen and spinal cord.

Complications of acute pancreatitis may include local pancreatic necrosis with pseudocyst or abscess formation, and extrapancreatic manifestations such as pulmonary renal, hepatic, endocrine, and coagulation abnormalities. Coagulation abnormalities associated with acute pancreatitis usually present as thrombophlebitis or widespread microthrombi; most occur in the venous or capillary circulation. We report a rare case of acute pancreatitis complicated by pseudocyst formation, splenic vein thrombosis, splenic infarction, and spinal cord infarction, which resulted in paraplegia. An association between acute pancreatitis and spinal cord infarction has not been reported before.

Acute Disease↗