Biomedical subjects

C H Wang

Publications and source records attributed to C H Wang.

At least 91 records · Page 5Linked to original sources

PubMed2000

Chronic morphine treatment inhibits oxytocin synthesis in rats.

The changes of oxytocin content and mRNA expression in some nuclei were investigated in morphine-dependent rats using radioimmunoassay (RIA) and in situ hybridization (ISH). After chronic administration of morphine, the oxytocin content in supraoptic nucleus (SON) and nucleus accumbens (NAc) decreased, and increased in the ventral tegment area (VTA) and locus coeruleus (LC), but did not change in other nuclei including the paraventricular nucleus (PVN), lateral septum (SEPTUM), raphe magnus nucleus (NRM) and periaquaductal gray (PAG). In morphine-L dependent rats, naloxone increased the levels of oxytocin in SON and PVN, but decreased that in LC. ISH first showed that chronic morphine treatment inhibited the oxytocin synthesis in SON but not in PVN. The present study demonstrates that chronic morphine treatment alters the brain oxytocin system, suggesting that oxytocin might contribute to the behavioral and neuroendocrine responses to morphine.

Animals↗

PubMed2000

[Role of nitric oxide in pathogenesis of pregnancy induced hypertension].

OBJECTIVE: We attempted to investigate the role of nitric oxide(NO) in pathogenesis of pregnancy-induced hypertension(PIH). METHODS: No-nitro-L-arginine-methyl ester(L-NAME) was used to inhibit nitric oxide synthase(NOS) in pregnant rats. Indices including blood pressure, urine protein concentration, pup weight, serum NO level and plasma ET-1 level were measured. Nitroglycerin, a nitric oxide donor, was used to observe its impact on the effect of L-NAME at the same time. RESULTS: Infusion of L-NAME elevated blood pressure, increased urine protein concentration, decreased pup weight, decreased serum NO level and raised plasma ET-1 level(P < 0.01, respectively); However in the L-NAME-treated animals nitroglycerin significantly lowered blood pressure, decreased urine protein concentration, increased pup weight, increased serum NO level and decreased plasma ET-1 level(P < 0.01, respectively). CONCLUSIONS: 1. Infusion of L-NAME, an inhibitor of NOS, causes decreased serum NO level and some signs similar to preeclampsia such as hypertension, proteinuria and intrauterine growth retardation(IUGR). Nitroglycerin can reverse the lesions induced by the treatment of L-NAME. These findings indicate that reduced level of NO may be a factor responsible for PIH. 2. NO can decrease the plasma ET-1 level. NO may regulate the process of PIH via ET-1 pathway. It may be one mechanism for NO. 3. An useful animal model for PIH is provided to test novel therapeutic and preventive strategies.

Animals↗

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

Comparing the performance of two indices for spatial model selection: application to two mortality data.

The statistical analysis of spatially correlated data has become an important scientific research topic lately. The analysis of the mortality or morbidity rates observed at different areas may help to decide if people living in certain locations are considered at higher risk than others. Once the statistical model for the data of interest has been chosen, further effort can be devoted to identifying the areas under higher risks. Many scientists, including statisticians, have tried the conditional autoregressive (CAR) model to describe the spatial autocorrelation among the observed data. This model has greater smoothing effect than the exchangeable models, such as the Poisson gamma model for spatial data. This paper focuses on comparing the two types of models using the index LG, the ratio of local to global variability. Two applications, Taiwan asthma mortality and Scotland lip cancer, are considered and the use of LG is illustrated. The estimated values for both data sets are small, implying a Poisson gamma model may be favoured over the CAR model. We discuss the implications for the two applications respectively. To evaluate the performance of the index LG, we also compute the Bayes factor, a Bayesian model selection criterion, to see which model is preferred for the two applications and simulation data. To derive the value of LG, we estimate its posterior mode based on samples derived from the BUGS program, while for Bayes factor we use the double Laplace-Metropolis method, Schwarz criterion, and a modified harmonic mean for approximations. The results of LG and Bayes factor are consistent. We conclude that LG is fairly accurate as an index for selection between Poisson gamma and CAR model. When easy and fast computation is of concern, we recommend using LG as the first and less costly index.

Asthma↗

PubMed2000

Ultrastructure of white spot syndrome virus development in primary lymphoid organ cell cultures.

Primary cell cultures from the lymphoid organ of Penaeus monodon were used to investigate in vitro propagation and morphogenesis of white spot syndrome virus (WSSV). Double-strength Leibovitz's L15 supplemented with 20% fetal bovine serum, pH 7.5, with a final osmolarity of 530 +/- 5 mOsm kg-1 was identified as the most suitable culture medium. In this medium, the lymphoid cells remained viable for more than 1 wk. Migrating cells were inoculated with WSSV, and the consequent cytopathic effects documented by light and electron microscopy. WSSV appears capable of following 2 alternative assembly sequences, one similar to the morphogenesis of the Oryctes rhinocerus virus and another which is more typical of baculoviral assembly. Possible relationships between WSSV, Oryctes virus, and baculoviruses are discussed.

Animals↗

PubMed2000

Degradation of DNA topoisomerase I by a novel trypsin-like serine protease in proliferating human T lymphocytes.

DNA topoisomerase I (Topo I) contributes to various important biological functions, and its activity is therefore likely regulated in response to different physiological conditions. Increases in both the synthesis and degradation of Topo I were previously shown to accompany phytohemagglutinin stimulation of proliferation in human peripheral T lymphocytes. The mechanism of this degradation of Topo I has now been investigated with both in vivo and in vitro assays. The activity of a nuclear protease that specifically degrades Topo I was induced in proliferating T lymphocytes. The full-length Topo I protein (100 kDa) was sequentially degraded to 97- and 82-kDa fragments both in vivo and in vitro. The initial site of proteolytic cleavage was mapped to the NH(2)-terminal region of the enzyme. The degradation of Topo I in vitro was inhibited by aprotinin or soybean trypsin inhibitor, suggesting that the enzyme responsible is a trypsin-like serine protease. Furthermore, Topo I degradation by this protease was Mg(2+)-dependent. The Topo I-specific protease activity induced during T lymphocytes proliferation was not detected in Jurkat (human T cell leukemia) cells and various other tested human cancer cell lines, possibly explaining why the abundance of Topo I is increased in tumor cells.

Acetylcysteine↗

PubMed2000

Transcriptional repression of p21((Waf1/Cip1/Sdi1)) gene by c-jun through Sp1 site.

Previously, we found that c-jun represses the tumor suppressor p21((Waf1/Cip1/Sdi1)) (p21) gene expression. In this study, we further investigated the mechanism of the inhibitory effect of c-jun on p21. After analysis of a series of deletion and point mutants of p21 promoter, we found that Sp1-3 site (-77 and -83) relative to the transcription start site played an important role for c-jun-repressing-responsive element in the p21 promoter. Both Sp1 and Sp3 transcription factors were the key factors for this event. However, the data from electrophoretic mobility shift assay indicated that c-jun did not change the Sp1 DNA-binding affinity, suggesting that additional factors may be involved in the repression of p21 by c-jun. Furthermore, c-jun could inhibit butyrate-inducing p21 gene expression through Sp1, indicating at least one common pathway whereby p21 expression is affected by c-jun and butyrate in opposing actions. Moreover, the hyperphosphorylated retinoblastoma protein (Rb) increased in c-jun expressing cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to repress p21 expression. This is the first demonstration of how housekeeping factors and oncogene product counteract the function of tumor suppressor genes to control cell cycle progression.

Binding Sites↗

PubMed2000

Diagnosis of Penaeus monodon-type baculovirus by PCR and by ELISA of occlusion bodies.

The black tiger prawn Penaeus monodon is a valuable aquaculture product in Taiwan. Two specific diagnostic methods were established for P. monodon-type baculovirus, one using polymerase chain reaction (PCR) technology and the other enzyme-linked immunosorbent assay (ELISA) technology. Monodon-type baculovirus (MBV) was purified by sucrose gradient centrifugation from occlusion bodies of MBV-infected postlarvae of P. monodon. MBV DNA was subsequently purified from the occlusion bodies and its presence was confirmed by PCR using primers of the polyhedrin gene. Based on conserved sequences of the DNA polymerase genes of Autographa californica nuclear polyhedrosis virus (AcMNPV) and Lymantria dispar nuclear polyhedrosis virus (LdMNPV), primers were designed and synthesized to yield a 714 bp PCR fragment from MBV. However, the sequence of this fragment revealed low homology with that of LdMNPV and AcMNPV. From the DNA sequence of this fragment, a second set of primers was designed, and using these primers, a 511 bp DNA fragment was amplified only when MBV DNA was the template. DNA templates from AcMNPV, white spot syndrome diseased shrimp, or PMO cells (a cell line derived from the Oka organ of Penaeus monodon) did not give any amplified DNA fragment. Therefore, this primer pair was specific for the diagnosis of MBV. By using intraspleenic immunization of rabbits with purified MBV occlusion bodies, a polyclonal rabbit antiserum against MBV was obtained. This antiserum could detect nanogram levels of MBV, but did not cross react with white spot syndrome virus (WSSV), homogenates of PMO cells, postlarvae, hepatopancreatic tissue or intestinal tissue of black tiger prawns by competitive ELISA. This sensitive method could detect MBV even in tissue homogenates.

Animals↗

PubMed2000

Relationship between serotypes and genotypes based on the hypervariable region of the S1 gene of infectious bronchitis virus.

To group infectious bronchitis virus (IBV) isolates, a genetic grouping method based on hypervariable region 1 (HVR 1, nucleotides 168 to 197) was compared with that based on the whole S1 gene. Both methods resulted in the same grouping data. So the grouping method based on HVR 1 could represent the grouping method based on the whole S1 gene. Taiwan isolates could not be placed within the existing groups. In order to test the correlation between genotype and serotype, a one-way neutralization test was used to compare 9 Taiwan isolates selected from different genotypes with Massachusetts (Mass) (H120) and Connecticut (Conn) standard strains. In addition, a two-way cross-neutralization test was performed in embryonated eggs with the beta method (constant-virus, diluted-serum) and the reciprocal neutralization titers were calculated to give the relatedness (r) values. The results of two kinds of neutralizing tests showed that the serotypes of 9 isolates were different from Mass or Conn. Based on the r-values, 9 isolates were divided into two serotypes which were correlated with their genotypes. From pathogenicity tests, IBV Taiwan isolates could be divided into high, intermediate, and low pathogenicity according to their pathogenicity indexes. However, no relationship exists between pathotype and genotype. In conclusion, the genetic typing method based on HVR 1 can be used for typing IBV isolates.

Animals↗

PubMed2000

Sequence variants and functional analysis of human papillomavirus type 16 E5 gene in clinical specimens.

Previously, we found that the E5 protein can be expressed in HPV-16 infected precancerous lesions and cervical cancer. In this study, we investigated the presence of sequence variants of E5 in HPV-16 infected tissues. Toward this end, we amplified the E5 gene by polymerase chain reaction from 29 HPV-16 infected tissues including eight normal tissues, seven high grade neoplastic tissues (high grade squamous intraepithelial lesions (HSIL) and 14 cervical cancer tissues. Sequence analysis demonstrated that there were three mutational hot spots at positions 3979, 4042, and 4077 of the HPV-16 DNA; these and other mutations resulted in six variants in the E5 sequence. This resulted in four E5 protein mutants, named WTE5 [wild type E5 protein], 14E5, 21E5 and 56E5. Functional analysis of these four mutant proteins revealed that the transforming activities of 14E5, 21E5 and 56E5 were 0.95, 0.59, and 0.89 fold of WTE5, respectively. Although E5 was expressed in all of the HSIL and cervical cancer tissues, but in only one of the eight normal tissues tested, only WT E5 protein was found in HSIL while in cervical cancer tissues both WT and mutant E5 proteins were detected. Since these E5 proteins exhibited the same in vitro transforming activity, these data suggest that expression of E5 is important in development and progression toward malignancy but mutation of E5 does not affect the transformation process.

Base Sequence↗

PubMed2000

Trends in severity of hospitalized myocardial infarction: the atherosclerosis risk in communities (ARIC) study, 1987-1994.

BACKGROUND: Declining mortality rates of coronary heart disease in the United States could be attributable to declining incidence, declining severity, and/or improvements in treatment. METHODS: We examined trends in severity of patients hospitalized for myocardial infarction to characterize its contribution to this decline by using data from the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: No significant change in the proportion having systolic blood pressure <100 mm Hg or an abnormal pulse at presentation was noted. The proportion with ST-segment elevation on the initial electrocardiogram increased 10% per year (P <.001), and the proportion with a diagnostic or evolving diagnostic electrocardiogram abnormality increased 4% per year (P <.01); the proportion that had a new Q-wave infarction develop remained unchanged. The mean peak creatine kinase level decreased 5% per year (P <.001), the proportion with abnormal enzyme levels decreased 10% per year (P <.001), and the proportion that met criteria for definite myocardial infarction decreased 4% per year (P <.05). The proportion that had cardiogenic shock decreased 10.9% per year (P <. 01), but the proportion that had an acute episode of congestive heart failure was stable. CONCLUSIONS: With stable hemodynamic indicators, worsening electrocardiographic indicators, and improving enzymatic indicators, these results provide mixed support for decreases in the severity of myocardial infarction.

Adult↗

PubMed2000

Nested polymerase chain reaction and in situ hybridization for detection of nucleopolyhedrosis.

A nested polymerase chain reaction (PCR) and in situ hybridization were developed for detection of baculoviruses in insects or other arthropods with nucleopolyhedrosis. The nested PCR was based on the sequences of polyhedrin genes from baculoviruses. Two sets of primers were designed, primers set, 35/36, was for the first step of amplification and yielded a product of around 680 bp, the second primer, 35-1/36-1, was designed to yield a product of around 335bp from the fragment amplified by the first primer set. The sensitivity of this two-step amplification was 100 to 1000 times higher than that of the one-step amplification by primer set (35/36). Samples which contained baculovirus DNA yielded an amplification product showing the expected DNA fragment mobility, whereas nucleic acid extracted from tissue samples of clinically healthy insects or uninfected cells showed no such DNA fragment, thereby confirming the specificity of the primers. Using the 35/36 amplicon as a probe, the PenuNPV-infected cells show positive reaction by in situ hybridization. Two-step DNA amplification and in situ hybridization with the DNA probe developed in the present paper provide effective detection and diagnostic tools for screening insects or other arthropods, especially crustacean species, crabs and shrimps, for baculovirus infections, and may be important in preventing (and/or controlling/enhancing) the infection of baculoviruses.

Animals↗

PubMed2000

Locally recurrent nasopharyngeal carcinoma.

PURPOSE: To assess the outcome of and determine prognostic factors for locally recurrent nasopharyngeal carcinoma (NPC) in patients treated with a second course of radiotherapy (RT). MATERIALS AND METHODS: From 1982 to 1995, 186 NPC patients, who had initially been treated in the Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou, developed local recurrence in the nasopharynx and were re-treated with RT (>/=20 Gy). The time from the initial RT to re-treatment ranged from 8 to 136 months (median: 23 months). All patients were treated with external RT and conformal radiotherapy was used in 35 patients after 1993. Fifteen received radiosurgery as a boost treatment. The RT dose at the nasopharyngeal tumor area ranged from 20 to 67.2 Gy (median 50 Gy). Eighty-two patients received one to eight courses of cisplatin-based chemotherapy in addition to RT. RESULTS: The 1-, 3- and 5-year survival was 54.9, 22. 1 and 12.4%, respectively. Patients whose tumor relapsed later than 2 years after the first treatment had a better survival than those with earlier relapse (3-year survival: 30.1 vs. 10.8%; P=0.015), but the difference became insignificant in patients who received >/=50 Gy. Patients without evidence of intracranial invasion or cranial nerve palsy had better survival than those with such lesions (3-year survival: 30.9 vs. 3.7%; P=0.006). A re-treatment dose >/=50 Gy yielded better survival (3-year survival: 22.8 vs. 18.5%; P=0.003). Addition use of radiosurgery may improve survival. The use of chemotherapy did not improve survival. Conformal radiotherapy resulted in significantly fewer severe complications than conventional RT. CONCLUSIONS: A repeat course of RT for locally recurrent NPC successfully prolongs survival in a significant number of patients. Intracranial invasion and/or cranial nerve palsy and re-treatment dose affect the prognosis, with a dose of >/=50 Gy significantly improving survival. Radiosurgery boost may also improve survival. Our preliminary data indicates that conformal radiotherapy may decrease the severity of radiation-induced complications. However; longer follow-up and larger sample size is necessary to document the findings.

Adult↗

PubMed2000

Characterization of acute myeloid leukemia with MLL rearrangements--no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts.

MLL gene rearrangements are associated with coexpression of myeloid- and lymphoid-associated antigens on leukemic blasts and a dismal outcome in acute lymphoblastic leukemia (ALL). Whether the same conditions can apply to acute myeloid leukemia (AML) is not quite clear. Rearrangements of the MLL gene were analyzed on 113 patients with newly diagnosed de novo AML in a single institution. Sixteen (14%) of them showed rearranged bands by Southern blot analysis, including three (50%) of six infants, three (14%) of 21 children between 1 and 15 years and 10 (12%) of 86 adults. MLL rearrangements were not only detected in M5 (four of 12 patients, 33%) and M4 (six of 31, 19%) subtypes but also in other non-M4-M5 AML (six of 70, 9%), including M1, M2 and M7, but not M3 subtype. Seven patients had chromosomal abnormalities involving 11q23, but nine did not. The latter comprised three (6%) of 48 patients with normal karyotype, one with t(8;21), none with t(15;17), inv(16) or t(9;22), and four (15%) of 27 with cytogenetic aberrations other than those specific structural abnormalities. In contrast to ALL, AML patients with MLL rearrangements did not tend to coexpress lymphoid- and myeloid-associated antigens simultaneously on leukemic blasts and have similar outcome as those without the gene rearrangements.

Acute Disease↗

PubMed2000

Erythromycin inhibits beta2-integrins (CD11b/CD18) expression, interleukin-8 release and intracellular oxidative metabolism in neutrophils.

Macrolides have therapeutic benefits on chronic inflammatory airway diseases. Thus, macrolides are supposed to have variable biological effects apart from antimicrobial activity. Neutrophil adherence and influx with oxidants and cytokines production implicates involvement in airway inflammation. To investigate whether erythromycin (EM) affects neutrophil activity in vitro, lipopolysaccharide (LPS)-treated neutrophils were continuously incubated for 4 h in the absence or presence of increasing doses of EM from 1 microg ml(-1) to 100 microg ml(-1) in the last 2 h. Leukocyte adhesion molecules Mac-1 and intracellular H2O2(DCFH) were determined by flowcytometric assay. IL-8 and TNFalpha in supernatant was measured by ELISA method. The expression of Mac-1 and mean intracellular DCF fluorescence intensity (DCFH) of neutrophils significantly increased after stimulation with LPS. Pretreatment with EM significantly decreased LPS induced Mac-1 expression on neutrophils compared with LPS stimulation only. EM alone (100 microg ml(-1)) also decreased Mac-1 expression on neutrophils. EM significantly reduced the LPS-increased DCFH. EM alone (100 microg ml(-1)) also caused a decrease in DCFH. Increasing doses of EM also significantly decreased the IL-8 released by LPS-stimulated neutrophils. In conclusion, EM exerts a direct effect on the neutrophils by downregulating the expression of beta2-integrin on neutrophils, thus leading to a decrease in the intracellular H2O2, as well as the production of IL-8. Our conclusion provides an explanation for the clinical efficacy of erythromycin in neutrophil-mediated airway inflammation.

Anti-Bacterial Agents↗

PubMed2000

Control of cisplatin-induced emesis with intravenous ondansetron plus intravenous dexamethasone: a crossover study of triple 8-mg dose of ondansetron.

Two hundred seventy-five patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron intravenous (IV) were given at 4-hour intervals plus dexamethasone 20 mg IV from the start of chemotherapy followed by dexamethasone 5 mg IV every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron IV were given at 24-hour intervals substituted for ondansetron IV given at 4-hour intervals. There were 237 patients in arm A and 223 patients in arm B. Complete protection from acute and delayed vomiting/nausea obtained in arm A was 94.5%/90.3% and 71.3%/57.8%, respectively; protection obtained in arm B was 92.7%/91.0% and 71.7%/60.5%, respectively. No differences were observed in control of acute emesis after the addition of dexamethasone to ondansetron, given as either a triple 8-mg dose at 4-hour intervals or a single 8-mg dose. The triple dose of ondansetron given at 24-hour intervals was also not more effective than ondansetron given at 4-hour intervals in preventing delayed emesis when dexamethasone was added. However, the former improved control of delayed nausea on day 2. Adverse events tended to be minor, with constipation and hiccup the most common.

Adolescent↗

PubMed2000

Single-agent docetaxel in metastatic breast cancer patients pre-treated with anthracyclines and paclitaxel: partial cross-resistance between paclitaxel and docetaxel.

The purpose of this study was a retrospective analysis of docetaxel in a cohort of anthracyclines and paclitaxel pretreated patients with metastatic breast cancer. From July 1998 to June 1999, 24 consecutive patients were included for this study. The regimen consisted of docetaxel 75 mg/m2 in combination with a 3-day schedule of dexamethasone every 3 weeks until disease progression or unacceptable toxicity. The median age of patients was 53 (ranged 32-67) years with a median performance status of 2. Twenty of the 24 patients (84%) had measurable disease. The median number of organs involved was 2 (range 1-4). A total of 146 cycles chemotherapy were given with a mean of 6. There was a 25% (six of 24) overall response rate including one complete response, 37.5% stable disease and 37.5% progressive disease. The major toxicity included grade 3-4 leukopenia (41.7%) and eight episodes of infection. No treatment-related death was observed. The responders included patients refractory to or resistant to prior paclitaxel treatment. The median survival and median time to disease progression was 12 and 9 months, respectively. We conclude that docetaxel has a modest activity in breast cancer patients pre-treated with anthracyclines and paclitaxel, indicating a partial cross-resistance between paclitaxel and docetaxel.

Adult↗

PubMed2000

Cardiopulmonary resuscitation during coronary vasospasm induced by tilt table testing.

A 65-year-old man presented to our institution with recurrent episodes of early morning chest discomfort and near syncope. An ergonovine provocation test documented a diagnosis of coronary vasospastic angina. Using our investigation of the syncope, a head-up tilt table test provoked a severe episode of coronary vasospasm that resulted in a life-threatening cardiac event. The present case reminds us that an elevation of ST segments on the electrocardiogram during tilt testing should be promptly managed as an attack of coronary vasospasm.

Aged↗