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Y C Wang

Publications and source records attributed to Y C Wang.

At least 73 records · Page 4Linked to original sources
PubMed2000

Correlation of genetic instability with mismatch repair protein expression and p53 mutations in non-small cell lung cancer.

To examine the etiological association of genetic instability in lung tumorigenesis, we investigated the frequency of microsatellite instability (MI) of eight dinucleotide repeat markers in 68 patients with non-small cell lung cancer. Twenty-eight patients (41.2%) evidenced instability in multiple tested microsatellite markers ranging from 3-7 and were defined as MI-positive patients. MI occurred more frequently in patients suffering from squamous cell lung carcinoma (P = 0.004). We examined the association between MI and expression of hMLH1 mismatch repair protein by immunohistochemical analysis of hMLH1 protein in paraffin-embedded tumors from 64 patients. Twenty MI-positive patients (76.9%) had no expression of hMLH1 protein. The data showed that MI was associated with altered hMLH1 expression (P = 0.03). To examine the role of genetic instability in the previous identified small intragenic deletion of the p53 gene, we explored the association between MI and p53 gene mutations. All patients, except one, containing small intragenic deletion in p53 gene showed MI (P = 0.018). In addition, we found that MI was not associated with the prognosis. Our data suggest that MI plays a significant role in non-small cell lung cancer tumorigenesis in Taiwan and that MI is associated with the altered expression of hMLH1 mismatch repair protein. In addition, MI may be involved in frequent small intragenic deletions of p53 gene.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Endoscopic endonasal transsphenoidal surgery for pituitary tumors.

BACKGROUND: The traditional transsphenoidal approach for pituitary surgery can be performed via transnasal, transseptal, or sublabial routes through unilateral or bilateral nostrils. It requires wide mucosal and septal dissection and postoperative nasal packing. Endoscopic surgery has been widely used because it allows excellent visualization with minimal invasion. Recently, it has also been applied to pituitary surgery. METHODS: From January, 1997 to February, 1999, 40 patients with pituitary adenomas underwent the transsphenoidal approach using a rigid endoscope via one nostril. Among the 40 cases, 18 were prolactinomas, seven were growth hormone-secreting adenomas and 15 were nonfunctional adenomas. RESULTS: After surgery, complete resolution or improvement of symptoms and restoration of normal hormone levels were achieved in 16 patients with prolactinomas, five with growth hormone-secreting adenomas and 12 with nonfunctional macroadenomas. One patient with a recurrent microprolactinoma needed a second operation to remove the cavernous portion of the tumor. Another male patient with a macroprolactinoma who experienced galactorrhea and gynecomastia showed improvement of clinical symptoms after the operation. Two patients with residual growth hormone-secreting macroadenomas in the cavernous sinus needed Sandostatin treatment. Three patients with nonfunctional macroadenomas underwent nearly total resection leaving residual tumor in the cavernous sinus, which then required adjuvant radiotherapy. No complications related to this approach were encountered in the patients during the follow-up period. CONCLUSIONS: Endonasal transsphenoidal endoscopic surgery can be employed for treating pituitary tumors without septal or sublabial complications. Postoperative suffering was reduced and hospitalization was shortened by this mini-invasive procedure. This surgical procedure can be used for both microadenomas and macroadenomas.

Adenoma↗
PubMed2000

Molecular diagnosis of fragile X syndrome and distribution of CGG repeats in the FMR-1 gene in Taiwanese.

BACKGROUND AND PURPOSE: Fragile X syndrome, the most frequent form of inherited mental retardation, is caused by abnormal expansion of the CGG trinucleotide repeats in the 5' untranslated region of the FMR-1 gene. In this study, we describe the prenatal diagnosis of fragile X syndrome and the distribution of CGG repeat numbers in the FMR-1 gene, which has not been previously reported in Taiwanese. METHODS: Using polymerase chain reaction (PCR), we determined the range of the CGG repeats in the FMR-1 gene in 316 normal individuals (350 X chromosomes) and 349 mentally retarded patients (429 X chromosomes). For prenatal diagnosis of fragile X syndrome, DNA extracted from amniotic fluid cells was used for PCR determination of CGG repeats. RESULTS: Because there were no significant differences between the distribution of the (CGG)n alleles between the mentally retarded and normal subjects, the data were pooled. Among the 779 X chromosomes studied, 24 different alleles were identified with a low of 16 and a high of 45 CGG repeats. The 29 repeat allele was the most common, followed by the 30 and the 28 repeat alleles. We effectively amplified slightly expanded premutation alleles of up to about 90 CGG repeats. In the prenatally diagnosed fetus, a normal 29 repeat allele was found. CONCLUSIONS: Determination of the distribution of the CGG repeats in the FMR-1 gene in Taiwanese is useful in genetic counseling regarding fragile X syndrome. Prenatal molecular diagnosis of the syndrome can be successfully performed using amniotic fluid cells.

Female↗
PubMed2000

[Cardiovascular reactions to gravitational force in different directions].

OBJECTIVE: To observe the features of the cardiovascular reactions to gravitational forces along different axes of the body. METHOD: Dogs were exposed to gravitational forces along axes of body on an animal centrifuge. RESULT: It was found that when the direction of G force changed from +Gz to +Gx, the predominating effect on the cardiovascular system changed from the drop of eye level blood pressure to the increase of central venous pressure, and the reactions of the organism changed from a presson reflex of the arterial system to the inhibition of cardiac activities at higher G levels. The turning point was found to be at the back angle of 75 degrees with respect to the direction of the gravitational force. CONCLUSION: These findings provide an important reference for choosing the optimal seat back angle in a manned space vehicle.

Acceleration↗
PubMed1999

Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors.

Serotonergic dysfunction is implicated in mood disorders and suicidal behaviors. Genetic variants of tryptophan hydroxylase (TPH), a rate-limiting enzyme in the biosynthesis of serotonin, were associated with suicidal behaviors in three reports, but were not found in other studies. We investigated the TPH A218C polymorphism in 151 subjects with mood disorders and 200 control subjects. The results demonstrated a significant difference in genotypic distribution between controls and depressed patients, but not bipolar patients. A positive association between TPH polymorphism and suicidal behaviors was found in depressed patients and not in bipolar patients. We suggest that the association of TPH variants and suicide might depend on the diagnosis, and TPH mutation plays no major role in the pathogenesis of bipolar disorders.

Adult↗
PubMed1999

Association analysis of the 5-HT6 receptor polymorphism C267T in Alzheimer's disease.

Serotonergic dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). This association study explores whether the serotonin 6 receptor (5-HT6) polymorphism (C267T) is a susceptibility factor for AD. Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and the normal controls (P = 0.006; and P = 0.023, respectively). These findings indicate that the 267C allele of the 5-HT6 gene is a risk factor for AD.

Aged↗
PubMed1999

Association study of serotonin-6 receptor variant (C267T) with schizophrenia and aggressive behavior.

The relative abundance of serotonin type 6 receptors (5-HT6) in some limbic regions and the high affinity of some antipsychotics to 5-HT6 receptors suggest that they might be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, C267T, of the human 5-HT6 gene confers susceptibility to schizophrenic disorders and associated aggressive behavior. We genotyped 5-HT6 receptors in 186 patients with schizophrenic disorders and 163 controls. The results demonstrated no significant difference in genotype or allele frequencies between patients with or without aggressive behaviors. However, genotype distribution was significantly different between schizophrenic patients and control subjects. This suggests that the 5-HT6 gene may play a role in the pathogenesis of schizophrenic disorders.

Adult↗
PubMed1999

Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy.

Modification of tumor cells with one or more costimulatory adhesion molecules has been proposed as a means to develop therapeutic cancer vaccines for use in human immunotherapy. Expression of B7-1 (CD80) in tumors by gene transfer creates an immunogenic tumor cell that induces antitumor immunity and protects mice from further challenge with wild-type tumor cells. In this report, we demonstrate that protein transfer of glycosyl-phosphatidylinositol (GPI)-anchored costimulatory molecules into tumor cell membranes could be used as an alternative to gene transfer for tumor immunotherapy. Incubation of isolated tumor membranes with purified GPI-anchored B7-1 results in stable incorporation of B7-1 on tumor cell membranes within a few hours. Immunization of C57BL/6 mice with EG7 tumor membranes modified to express GPI-B7-1 by protein transfer induces tumor-specific T-cell proliferation and CTLs. In addition, immunization with these EG7 membranes protects mice from parental tumor challenge. The protein transfer approach used here does not require foreign vectors or live tumor cells and is completed within a matter of hours. Irradiated cells or membrane preparations from fresh or frozen tumor tissue can be used. Therefore, protein transfer of glycolipid-anchored molecules provides an efficient and novel approach to modify tumor membranes for human immunotherapy. This approach is not limited to costimulatory molecules because any cell surface protein can be converted to a GPI-anchored form by recombinant techniques.

Animals↗
PubMed1999

TWEAK induces angiogenesis and proliferation of endothelial cells.

TWEAK is a recently described member of the Tumor Necrosis Factor (TNF) ligand family whose transcripts are present in a wide variety of human tissues (Chicheportiche, Y., Bourdon, P. R., Xu, H., Hsu Y. M., Scott, H., Hession, C., Garcia, I., and Browning, J. L. (1997) J. Biol. Chem. 272, 32401-32410). TWEAK is a weak inducer of apoptosis in transformed cells when administered with interferon-gamma or cycloheximide (Chicheportiche, Y., Bourdon, P. R., Xu, H., Hsu Y. M., Scott, H., Hession, C., Garcia, I., and Browning, J. L. (1997) J. Biol. Chem. 272, 32401-32410; Masters, S. A., Sheridan, J. P., Pitti, R. M., Brush, A. G., and Ashkenazi, A. (1998) Curr. Biol. 8, 525-528) and also promotes IL-8 secretion in cultured cells. We report here that picomolar concentrations of recombinant soluble TWEAK induce proliferation in a variety of normal human endothelial cells and in aortic smooth muscle cells and reduce culture requirements for serum and growth factors. Blocking antibodies to Vascular Endothelial Growth Factor (VEGF) do not significantly inhibit TWEAK-induced proliferation, indicating that TWEAK does not function indirectly through up-regulation of VEGF. Pellets containing TWEAK induce a strong angiogenic response when implanted in rat corneas, suggesting a role for TWEAK in vasculature formation in vivo.

Animals↗
PubMed1999

Smubp-2 represses the Epstein-Barr virus lytic switch promoter.

Smubp-2 is a novel transcription factor that was first identified through its interaction with the immunoglobulin Smu region (Mizuta et al., 1993) and has been cloned by virtue of its binding to two 12-O-tetradecanoylphorbol-13-acetate-responsive elements in the Epstein-Barr virus immediate-early BZLF1 promoter (Gulley et al., 1997). In this report, we examined the effect of Smubp-2 overexpression on BZLF1 prom oter activity. Overexpression of Smubp-2 in the B lymphocyte cell line BJAB caused repression of the BZLF1 gene promoter. A 14-bp region that partially overlaps with a 12-O-tetradecanoylphorbol-13-acetate-responsive element was required for maximal repression by Smubp-2, but some repression was also seen with a minimal promoter containing only the BZLF1 promoter TATA box and an initiation site. A 30-bp fragment containing the 14-bp region could transfer Smubp-2-mediated repression to heterologous promoters. Smubp-2 was found to associate with the basal transcription factor TATA binding protein (TBP) and to disrupt the formation of a stable TBP-TFIIA-DNA complex on the BZLF1 promoter TATA box and the adenovirus E1B promoter TATA box. Repression of the BZLF1 promoter by overexpressed Smubp-2 was rescued by overexpression of the basal factor TFIIA. These results suggest that complete repression of the BZLF1 promoter by Smubp-2 involves disruption of a functional TBP-TFIIA-TATA box complex and requires the -93 bp-to--79 bp region of the promoter.

Cell Line↗
PubMed1999

Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection.

CONTEXT: One or both commercial tuberculin skin test reagents (Aplisol and Tubersol) may have a high rate of false-positive reactions. OBJECTIVE: To compare the reaction size and specificity of skin testing with Aplisol, Tubersol, and the standard purified protein derivative (PPD-S1). DESIGN: Double-blind trial, conducted between May 14, 1997, and October28, 1997, in which each individual received 4 tuberculin skin reagents at sites assigned at random. SETTING: Health departments and universities in 6 US cities. PARTICIPANTS: A total of 1555 persons at low risk of latent tuberculosis infection. INTERVENTION: Simultaneous skin tests with Aplisol, Tubersol, PPD-S1, and either a second PPD-S1 or PPD-S2 (a proposed new standard). MAIN OUTCOME MEASURE: Reaction size at each injection site measured by 2 investigators blinded to type of reagent. RESULTS: Aplisol produced slightly larger reactions than Tubersol, but this difference did not significantly change skin test interpretation. The mean +/- SD reaction sizes were 3.4+/-4.2 mm with Aplisol, 2.1+/-3.2 mm with Tubersol, and 2.5+/-3.6 mm with PPD-S1. Assuming that all participants were uninfected and using a 10-mm cutoff, the specificities of the tests were high: Aplisol, 98.2%; Tubersol, 99.2%; and PPD-S1, 98.9%. Significant variability was not detected in interobserver, host, and lot-to-lot reagent comparisons. CONCLUSION: Using a cutoff of at least 10 mm, testing with 3 different PPD reagents resulted in similar numbers of uninfected persons being correctly classified.

Adult↗
PubMed1999

Prognostic significance of p53 codon 72 polymorphism in lung carcinomas.

Lung cancer is the leading cause of cancer death in Taiwan. Potential molecular markers associated with cancer susceptibility and prognosis are the genes involved in tumorigenesis. Therefore, we investigated the association of p53 codon 72 polymorphism with prognosis in 114 lung cancer patients. The estimated median survival times for patients with proline (Pro)/Pro, arginine (Arg)/Arg, and Arg/Pro genotypes were 25, 26 and 36 months, respectively. We also found that patients with the Pro/Pro genotype had a worse prognosis compared with those with Arg/Pro genotypes, especially for patients with squamous cell lung cancer (P = 0.013), male patients (P = 0.028) and those aged 60-69 years (P = 0.052). In patients with early stage lung cancer, patients with Pro/Pro and Arg/Arg genotypes had a tendency for a worse prognosis than those with the Arg/Pro genotype (P = 0.057). Our data suggest that p53 codon 72 polymorphism may be a potential prognostic factor in certain sub groups of lung cancer patients in Taiwan.

Aged↗
PubMed1999

Effect of novel CAAX peptidomimetic farnesyltransferase inhibitor on angiogenesis in vitro and in vivo.

Ras oncogenes can contribute to tumour development by stimulating vascular endothelial growth factor (VEGF)-dependent angiogenesis. The effect of Ras on angiogenesis may be affected by farnesyltransferase inhibitors (FTI) since farnesylation of Ras is required for its biological activity. In this paper we evaluated the effect of A-170634, a novel and potent CAAX FTI on angiogenesis. Human umbilical vein endothelial cell (HUVEC) tube formation and VEGF secretion were used to assess the effect of A-170634 on angiogenesis in vitro. In vivo, nude mice were injected with the K-ras mutant colon carcinoma cell line HCT116 and treated subcutaneously with A-170634 using osmotic minipump infusion for 10 days. The effect of A-170634 on corneal angiogenesis in vivo was assessed using pellets containing hydron, VEGF, A-170634 or vehicle. In vitro, A-170634 selectively inhibited farnesyltransferase activity over the closely related geranylgeranyltransferase I, inhibited Ras processing, blocked anchorage-dependent and -independent growth of HCT116 K-ras mutated cells, decreased HUVEC capillary structure formation, decreased VEGF secretion from tumour cells and HUVEC growth stimulating activity in a dose-dependent manner. In vivo, tumour growth was decreased by 30% and vascularisation in and around the tumours was reduced by 41% following drug-treatment with no apparent toxicity to the animals. VEGF-induced corneal neovascularisation was reduced by 80% following A-170634 treatment for 7 days. The data presented here demonstrated that A-170634 was a potent and selective peptidomimetic CAAX FTI with anti-angiogenic properties. These results implied that A-170634 may affect tumour growth in vivo by one or more antitumour pathways.

Alkyl and Aryl Transferases↗
PubMed1999

Oral ciprofloxacin as antibacterial prophylaxis after allogeneic bone marrow transplantation: a reappraisal.

The efficacy of ciprofloxacin as antibacterial prophylaxis for allogeneic bone marrow transplantation has been well documented, and it virtually eliminated bacteremias caused by gram-negative pathogens in early reports. Ciprofloxacin was therefore incorporated into the prophylactic antibiotic regimen during allogeneic bone marrow or peripheral blood stem cell transplantation at Veterans General Hospital, Kaohsiung from February 1997. In 12 consecutive patients receiving allogeneic bone marrow or peripheral blood stem cell transplantation, ciprofloxacin-resistant Escherichia coli bacteremia developed in three (25%). In addition to our data, increasing evidence suggests that the widespread use of a fluoroquinolone is associated with the emergence of resistant isolates as well as documented infections caused by these resistant strains. The incidence of Escherichia coli bacteremia in our transplant patients was 25%, which was similar to that in patients not receiving preventive therapy or in those receiving trimethoprim-sulfamethoxazole prophylaxis. The prophylactic efficacy of ciprofloxacin in allogeneic bone marrow transplant or peripheral blood stem cell transplant recipients should therefore be reassessed.

Administration, Oral↗
PubMed1999

Nesidioblastosis, myelodysplastic syndrome and nodular diabetic glomerulosclerosis in an elderly nondiabetic woman: an autopsy report.

Nesidioblastosis as the cause of hyperinsulinaemic hypoglycaemia in an adult is rare. We report here an additional case of nesidioblastosis, which resulted in fatal hyperinsulinaemic hypoglycaemia in a 72-year-old woman with an underlying myelodysplastic syndrome. The diagnosis of nesidioblastosis was established only after post-mortem examination with a careful exclusion of minute insulinoma. To our surprise, the renal pathology disclosed typical diabetic nodular glomerulosclerosis in the same patient who had no previous history of diabetes mellitus (DM). Nesidioblastosis has been reported to cause 'reversal' of Type 1 DM and insulinoma causing 'reversal' of Type 2 disease. We therefore hypothesize that our patient might have had an undiagnosed DM in the past, which resulted in the typical diabetic nodular glomerulosclerosis. The nesidioblastosis caused a 'reversal' of DM and even the ultimate development of hyperinsulinaemic hypoglycaemia.

Aged↗
PubMed1999

Protein kinase C isoforms in the epidermal tissues of normal and postburn human skin.

Because the expression of the isoforms of protein kinase C (PKC) in human basal keratinocytes is not understood, the expression of PKC isoforms were screened in specimens of epidermal tissue from postburn skin and the normal locations for skin grafts in patients with second or higher degrees of flame injury. The expression of individual isoform was determined by Western blot technique. Only PKC alpha and zeta were detected in the epidermal tissues of normal and postburn skin and translocation occurred in PKC alpha. Patients without antibiotic treatment after flame injury had higher expressions of PKC alpha and zeta. These findings indicate that the mechanisms of cellular differentiation and growth in postburn epidermal tissue may be related to the expression and translocation of PKC alpha induced by intra- and extracellular stimulation. These changes in PKC alpha further activate the DAG/PKC signal transduction pathways.

Adult↗
PubMed1999

No association between alpha-1-antichymotrypsin polymorphism and Alzheimer's disease in Chinese.

A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) confers a significant risk for Alzheimer's disease (AD). Furthermore, the apolipoprotein E epsilon4 allele (APOE*4) effect associated with AD risk is modified by the ACT polymorphisms. To evaluate the role of ACT polymorphism in AD, we conducted an association study of ACT polymorphisms in Chinese AD patients and normal controls. We found that the ACT polymorphism had no effect on the development of AD either alone or in combination with the APOE*4 allele.

Aged↗