Biomedical subjects

Y M Chen

Publications and source records attributed to Y M Chen.

At least 73 records · Page 4Linked to original sources

PubMed1999

Influences of chloropazine, nimodipine and their combination on the toxic effects of cadmium in liver and kidney of mice.

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A series of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca(2+)-Mg2+ ATPase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination 1 h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that CPZ could protect kidney tissue against Cd-induced damage, as the urinary gamma-glutamyl-traspeptidase (gamma-GT) and N-acetyl-beta-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effect of CPZ and NIMO. Both CPZ and NIMO showed a considerable protective effect against the decrease in Ca(2+)-Mg2+ ATPase activity, and a synergistic action was observed. Cd content in blood was reduced significantly by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO considerably increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevant to the function of MT.

Animals↗

PubMed1999

[Abdominal bipedicled subepidermal vascular-network flap in repair of degloving injury of hand].

OBJECTIVE: To evaluate the clinical result of repairing degloving injury of hand with abdominal bipedicled subdermal vascular-network flap in emergence. METHODS: From 1994 to 1997, 19 cases with degloving injury of hand were treated with two flaps, one flaps with the inferior epigastric artery as pedicle, another with superficial epigastric artery. The two skin flaps were designed oppositely to cover the injured hands. RESULTS: All the flaps survived. Followed up for 1 to 3 years, the contour of hands were fine. Extension of fingers was normal and opponers of thumbs was good. Range of flexion of metacarpo-phalangeal joints was from 45 to 60 degrees, and the proximal interphalangeal joints was from 10 to 25 degrees. CONCLUSION: For the subdermal vascular network, the bipedicled flaps of abdomen in repair of degloving injury of hand have sufficient blood supply, strong resistance to infection, high survival rate, and good contour.

Adolescent↗

PubMed1998

Molecular epidemiology and trends of HIV-1 subtypes in Taiwan.

To understand the trends of distribution and risk factors associated with different HIV-1 subtypes in different populations in Taiwan, blood samples and questionnaires were collected from 267 male and 21 female HIV-1-infected people in a multicenter survey from 1993 to 1996. This group represented about one quarter of the total registered HIV-1 cases in Taiwan. The HIV-1 subtypes were determined using V3-based peptide-enzyme immunoassays complemented by heteroduplex mobility assay and phylogenetic tree analysis. The results showed that in Taiwan, men were primarily infected with HIV-1B (68.2%) and HIV-1E (27.3%), whereas women were mainly infected with non-B subtypes (4.8% A, 4.8% C, 71.4% E, and 9.5% G). In addition, 71.4% of men with HIV-1B were homosexual or bisexual, whereas 56.2% of men with HIV-1E were heterosexual (p < .001). Although HIV-1E subtype came to Taiwan later than HIV-1B, it has become a major subtype in the heterosexual population.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Surveys of HIV-1, HTLV-I, and other sexually transmitted diseases in female sex workers in Taipei City, Taiwan, from 1993 to 1996.

Between 1993 and 1996 in Taipei, Taiwan, we studied the prevalences of HIV-1, HTLV-I, HSV-2, Chlamydia trachomatis, and syphilis infection in female commercial sex workers (CSW) and the pathogens' associated risk factors. Female CSW from nine massage parlors, two karaoke bars (KB), and 22 brothels in Taipei city participated in this study. Two of 557 (0.4%) KB CSWs from those who participated during the period from 1993 to 1994 had HIV-1 infection, whereas no KB CSWs in the periods 1994 to 1995 or 1995 to 1996 had HIV-1 infection. None of the 725 MP CSWs or 291 brothel CSWs who participated in the study between 1993 and 1996 had HIV-1 infection. In contrast, CSWs from brothels had elevated rates of both HTLV-I and active chlamydia infections compared with KB and MP CSWs (p < .05 and p < .005, respectively). KB CSWs showed an elevated rate of HSV-2 infection in the years 1993 and 1994 when compared with CSWs employed by brothels and MPs (p < .005). The prevalence rates of syphilis for CSWs from brothels dropped from 42.8% in the year 1993 to 1994 to 26.3% in the 1995 to 1996 period, whereas for KB and MP CSWs, the rates were < 6% in each of year studied.

Adult↗

PubMed1998

Molecular mimics of insulin-like growth factor 1 (IGF-1) for inhibiting IGF-1: IGF-binding protein interactions.

IGF-1 (insulin-like growth factor 1) is a 70-residue protein hormone which has both metabolic and mitogenic activities mediated through IGF-1 binding to cell surface receptors. However, an unrelated class of proteins, the IGF-binding proteins (IGFBPs) also bind IGF-1 in the serum and tissues and block or modulate its activity in vivo. Therefore, inhibitors of the IGFBPs can alter the distribution between free and bound IGF-1 [Loddick, S. A., Liu, X.-J., Lu, Z.-X., Liu, C., Behan, D. P., Chalmers, D. C., Foster, A. C., Vale, W. W., Ling, N., and De Souza, E. B. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 1894-1898] and potentially affect the distribution of IGF-1 among body tissues. We report here that phage-displayed peptide libraries have yielded a peptide that binds IGFBP-1 and produces IGF-like activity at sub-micromolar concentrations. The 14-residue peptide has an extremely well-defined solution conformation that can aid in the design of smaller, orally active compounds. Interestingly, the peptide structure contains a helix, as does one region of IGF-1 previously implicated in IGFBP binding, yet displays side chains different from those of the IGF-1 helix I. Furthermore, an IGF-1 variant lacking receptor-signaling activity in vitro is shown here to produce IGF-like mitogenic and metabolic activity in vivo. These results suggest that small antagonist mimetics of protein ligands, identified by binding selection to otherwise inhibitory factors, may be useful as indirect agonists for a variety of therapeutic applications.

Amino Acid Sequence↗

PubMed1998

Characterization of glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma.

Messenger RNA differential display was used to study liver-gene expression in paired tumor and non-tumor tissues from hepatocellular carcinoma (HCC) patients. mRNA differential display and Northern-blot analyses showed that a 0.8-kb cDNA fragment was diminished or absent from the tumorous tissues of 7 HCC patients. The cDNA fragment was sequenced and found to have 98.7% nucleotide sequence homology with human glycine-N-methyltransferase cDNA (GNMT). In addition, there was no detectable level of GNMT expression in 4 human HCC cell lines, SK-Hep1, Hep 3B, HuH-7 and HA22T, examined by Northern-blot assay. A full-length GNMT cDNA clone-9-1-2 was obtained by screening a Taiwanese liver cDNA library. In comparison with the GNMT cDNA sequence reported elsewhere, clone 9-1-2 had 4 nucleotide differences resulting in 1 amino-acid change. Immunohistochemical staining with rabbit anti-recombinant GNMT serum showed that GNMT protein almost completely disappeared in liver-cancer cells, while it was abundant in the non-tumorous liver cells. Down-regulation of GNMT gene expression may be involved in the pathogenesis of liver cancer.

Amino Acid Sequence↗

PubMed1998

Oxidized lipoproteins activate NF-kappaB binding activity and apoptosis in PC12 cells.

Oxidative stress in the central nervous system may cause oxidation of lipoproteins. The oxidized lipoproteins may in turn damage cellular and subcellular membranes and other biomolecules, leading to tissue injury and cell death. Recently, we have demonstrated that oxidized LDL and VLDL induced cell death in a dose-dependent manner. The present study examined the possible signal transduction cascade leading to cell death by oxLDL and oxVLDL in PC12 cells. Using the electrophoretic mobility shift assay, we found that both oxLDL and oxVLDL activated the binding of NF-kappaB to the consensus sequence in the promoter region of the target genes, followed by apopototic cell death. Resveratrol protects the cells from both the activation of NF-kappa-B/ DNA binding activity and apoptotic cell death. Results indicated that oxidized lipoproteins may serve as an oxidative mediator and may activate apoptosis through a nuclear signalling pathway contributing to the pathology in Alzheimer's disease.

Animals↗

PubMed1998

Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors.

The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM-CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S-phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findings suggest that transduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site.

3T3 Cells↗

PubMed1998

Extracellular ATP-induced apoptosis in PC12 cells.

Studies in our laboratory indicate that extracellular ATP (ATP)o may induce cell death by reactive oxygen insults. We have also shown that the Ca(2+)-induced oxidative stress as elicited by ATP may lead to an activation of a specific AP-1 activity. Since early impairment of mitochondria constitutes a critical event of the apoptotic cell death, we have examined whether (ATP)o will affect mitochondrial damage and cell injury by using mitochondrial specific probes, dihydrorhodamine and 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). We have found that (ATP)o induced cell death in a concentration dependent manner by MTT assay. The (ATP)o induced cell death correlated well with the reactive oxygen species (ROS) generation in mitochondria, since (ATP)o enhanced both cell death and ROS production and antioxidant blocked both of these processes. We found (ATP)o treatment led to apoptotic cell death by examining DNA laddering and the TUNEL assay. Interestingly, vitamin C and vitamin E combined treatment appeared to attenuate the (ATP)o-induced apoptosis. Results indicated that (ATP)o may cause oxidative damage of mitochondria leading to apoptotic cell death. Antioxidants may be useful in preventing apoptosis by preventing ROS formation in mitochondria.

Adenosine Triphosphate↗

PubMed1998

Hepatitis C virus variants circumventing cytotoxic T lymphocyte activity as a mechanism of chronicity.

BACKGROUND & AIMS: High rate of chronicity after acute hepatitis C virus (HCV) infection cannot be explained in the presence of a multispecific cytotoxic T lymphocyte (CTL) response. The aim of this study was to investigate the effect of virus variants on CTL activity in patients in whom chronicity developed. METHODS: CTL clones specific to a decapeptide epitope derived from hypervariable region 1 were generated from 5 HLA-A2-positive patients with acute hepatitis C by in vitro stimulation with synthetic peptides. The sequential change of this CTL epitope and its influence on the CTL recognition were examined. RESULTS: Virus variants did not appear in 3 patients with recovery, whereas variants with altered peptide ligands capable of antagonizing CTL activity emerged rapidly in the remaining 2 patients in whom chronicity developed. Importantly, these HLA-A2-restricted, hypervariable region 1-specific CTL clones shared the use of T-cell receptor (TCR) genes AV6 and BV17. CONCLUSIONS: These data suggest that there is only a narrow T-cell repertoire responding to a single viral peptide/HLA ligand. The emergence of HCV variants with altered peptide ligands as TCR antagonists accompanied by a limited TCR repertoire may provide a mechanism for HCV chronicity.

Acute Disease↗

PubMed1998

First report of microcystins in Taiwan.

This is the first report on microcystins from Microcystis aeruginosa Kützing in Taiwan. A total of nine strains of cyanobacteria have been isolated from eutrophic aquaculture ponds and water reservoirs. By mouse toxicity assay, six of the nine strains had LD100 in the range of 25-100 mg per kg mouse for dried bacterial mass. Microcystin-LR and -RR were found in all toxic strains and their contents ranged from 0.11-10.06 microg and 0.08 2.21 microg per mg of dried bacteria, respectively. Microcystin-RA, a minor component found only in M. TN-2 and M. CY-1 strains, was identified as a new microcystin. All three toxins were isolated by a serial separation on an LH-20 column, Si-flash column chromatography and reverse phase HPLC. Toxins were further identified by comparing their FABMS, 1H and 1H-1H COSY NMR spectra with the authentic microcystin-LR. Several other microcystin-like compounds were also found in the cultured strains and their structures are being determined.

Amino Acids↗

PubMed1998

Phase II trial of intrapleural paclitaxel injection for non-small-cell lung cancer patients with malignant pleural effusions.

A phase II clinical trial of intrapleural paclitaxel injection for malignant effusions of non-small-cell lung cancer (NSCLC) was conducted in order to evaluate the efficacy and toxicity profile of paclitaxel pleurodesis in patients with malignant effusions. From February to May of 1996, 15 NSCLC patients with malignant pleural effusions were enrolled on study. After adequate drainage and assurance of lung re-expansion, paclitaxel 125 mg m-2 diluted in normal saline was infused through a preinserted pig-tail catheter which was removed 2 h later. Chest radiography and sonography were scheduled 4 days later; depending on whether there remained a significant amount of pleural effusion, further drainage by needle thoracentesis or by a pig-tail catheter was performed. All patients were assessable for toxicity. Ipsilateral chest and/or shoulder pain, fever, facial flushing and nausea were the most frequent side-effects. Grade 4 neutropenia, grade 3 anaemia, and grade 3 renal impairment occurred in one patient each. Fourteen patients were evaluable for response at the end of the fourth week. Overall response rate of pleural effusion in evaluable patients was 92.9%, with a complete response rate of 28.6%. There was one out of 14 evaluable patients whose measurable tumour lesion decreased by more than 50% (partial response). No disease progression was noted among evaluable patients at the end of the fourth week. It is concluded that paclitaxel is a useful agent for the treatment of malignant pleural effusions. Because of its relatively low systemic toxicity, intrapleural paclitaxel injection in combination with systemic chemotherapy or radiotherapy can be considered in treating NSCLC patients with malignant pleural effusions.

Aged↗

PubMed1998

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections.

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.

Adult↗

PubMed1998

Nonlinear system analysis of renal autoregulation in normotensive and hypertensive rats.

We compared the dynamic characteristics in renal autoregulation of blood flow of normotensive Sprague-Dawley rats (SDR) and spontaneously hypertensive rats (SHR), using both linear and nonlinear systems analysis. Linear analysis yielded only limited information about the differences in dynamics between SDR and SHR. The predictive ability, as determined by normalized mean-square errors (NMSE), of a third-order Volterra model is better than for a linear model. This decrease in NMSE with a third-order model from that of a linear model is especially evident at frequencies below 0.2 Hz. Furthermore, NMSE are significantly higher in SHR than SDR, suggesting a more complex nonlinear system in SHR. The contribution of the third-order kernel in describing the dynamics of renal autoregulation in arterial blood pressure and blood flow was found to be important. Moreover, we have identified the presence of nonlinear interactions between the oscillatory components of the myogenic mechanism and tubuloglomerular feedback (TGF) at the level of whole kidney blood flow in SDR. An interaction between these two mechanisms had previously been revealed for SDR only at the single nephron level. However, nonlinear interactions between the myogenic and TGF mechanisms are not detected for SHR.

Animals↗

PubMed1998

Assessing the relationship between dental disease and coronary heart disease in elderly U.S. veterans.

Several recent studies have shown a link between dental disease and coronary heart disease. The authors studied 320 U.S. veterans in a convenience sample to assess the relationship between oral health and systemic diseases among older people. They present cross-sectional data confirming that a statistically significant association exists between a diagnosis of coronary heart disease and certain oral health parameters, such as the number of missing teeth, plaque benzoyl-DL-arginine-naphthylamide test scores, salivary levels of Streptococcus sanguis and complaints of xerostomia. The oral parameters in these subjects were independent of and more strongly associated with coronary heart disease than were recognized risk factors, such as serum cholesterol levels, body mass index, diabetes and smoking status. However, because of the convenience sample studied, these findings cannot be generalized to other populations.

Aged↗

PubMed1998

The relationship between dental disease and cerebral vascular accident in elderly United States veterans.

We report here information obtained from a cross-sectional study of 401 veterans, who were at least 60 years of age, which showed that several dental/oral conditions can be significantly associated with the diagnosis of a cerebral vascular accident (CVA), when included in a multivariate logistic regression model with and without many of the known risk factors for a CVA. The dental findings relative to the prevalence of dental caries and periodontal disease were not distinctly different between the subjects with and without a CVA in the bivariate analysis. A higher stimulated salivary flow was negatively associated with a CVA in the multivariate models. The plaque index and oral hygiene habits relating to brushing, flossing, and frequency of having teeth cleaned by a dentist/hygienist were significantly associated with a CVA in the bivariate analysis. Among these oral hygiene parameters, *needing help in brushing one's teeth" and the reported annual visit to the dentist/hygienist for teeth cleaning remained significant in the multivariate models involving the dependent-living subjects. The need for help in brushing one's teeth could reflect the fact that many subjects had reduced manual dexterity as a result of the CVA and required this extra care. However, the finding that those dependent-living individuals who reported that they did not have their teeth cleaned at least once a year were 4.76 times more likely to have had a CVA, suggests that a pattern of oral neglect might be associated with developing a CVA. The implications of this in terms of an intervention strategy for CVA warrants further consideration. However, caution is recommended because the data were obtained from a convenience sampling of older veterans and may not be generalizable to other populations.

Aged↗

PubMed1998

Quantitative analysis of CDKN2, p53 and retinoblastoma mRNA in human gastric carcinoma.

The mRNA level of CDKN2 (p16), retinoblastoma (Rb) and p53 in cancerous and non-cancerous tissue samples were compared using a semi-quantitative reverse-transcription-polymerase chain reaction method. The mean CDKN2 mRNA level of 10 gastric cancer specimens was significantly higher than that of their non-cancerous tissue samples (p=0.039). In contrast, the mRNA levels of Rb and p53 in gastric cancer tissues were both significantly lower than those in their non-cancerous tissue samples. Furthermore, both mRNA ratios of Rb/CDKN2 and p53/CDKN2 were significantly decreased in gastric cancer tissues. Therefore, suppression of both Rb and p53 and overexpression of CDKN2 may be associated with the tumorigenesis of gastric cancer.

Adolescent↗

PubMed1998

Ifosfamide-based chemotherapy for previously treated lung cancer patients.

BACKGROUND: Ifosfamide-based chemotherapy has already been the basis of three separate clinical trials. In this study, ifosfamide was administered to lung cancer patients who had failed to respond to previous chemotherapy, to assess its response rate and toxicity. METHODS: From January 1993 to December 1996, 21 patients were treated, including eight patients with small cell lung cancer (SCLC) and 13 with non-small cell lung cancer (NSCLC). Patients who had histocytologically confirmed lung cancer, were previously treated with chemotherapy, had a measurable lesion(s), were younger than 75 years of age, had an Eastern Cooperative Oncology Group performance status of 0-3 and adequate marrow, renal and liver function were eligible for inclusion in this study. For SCLC patients, ifosfamide 2.4 g/m2 intravenous (i.v.) infusion was given over 30 minutes on days 1-3 every four weeks. For NSCLC two regimens were used: IFL (ifosfamide 2 g/m2, 5-fluorouracil (FU) 600 mg/m2 and leucovorin 50 mg/m2 i.v. infusion on days 1-3 every four weeks) and LIFE (leucovorin 50 mg/m2, ifosfamide 1 g/m2, 5-FU 400 mg/m2 and epirubicin 12 mg/m2 i.v. infusion on days 1-3 every four weeks). For NSCLC patients, IFL was used for the first two years of treatment and LIFE was used in the last two treatment years. All patients were evaluated for treatment response and toxicity. RESULTS: The major toxic effect, myelosuppression (grade 3 or 4 leukopenia), occurred in 62.5% of SCLC patients and 23.1% of NSCLC patients during treatment, and in 62.5% and 10% of SCLC and NSCLC patients, respectively, throughout the course. Only one SCLC and one NSCLC patient experienced febrile neutropenia. One toxic death, attributed to febrile neutropenia, was documented in a patient with SCLC. Alopecia was ubiquitous. Other toxicities were uncommon and mild. The overall response rate was 50% in SCLC and 7.7% in NSCLC. The median time to disease progression was 61 days in SCLC and 47 days in NSCLC. Median survival was 172 days in SCLC and 173 days in NSCLC. CONCLUSIONS: The study results suggest that ifosfamide chemotherapy is active with an acceptable toxicity profile in previously treated SCLC patients. However, it lacks efficacy in NSCLC patients who have been previously treated.

Adult↗