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Biomedical subjects

W J Chen

Publications and source records attributed to W J Chen.

At least 19 recordsLinked to original sources

Painless Prinzmetal's ST elevation related to propranolol: a case report.

Previous studies have shown that propranolol, an effective mainstay for angina pectoris and unstable angina, can induce coronary arterial spasm in patients with variant angina. However, no report has yet associated it with painless Prinzmetal's ST elevation in patients without a history of variant angina. The present communication describes such an unusual and negligible case after propranolol overdose. Coronary arterial spasm can be induced by beta-blocker, not only in patients with variant angina but also in normal persons.

Administration, Oral

Clinical symptom dimensions and deficits on the Continuous Performance Test in schizophrenia.

We examined the relationships between symptom dimensions derived from factor analytic studies of schizophrenic symptoms and sustained attention deficits. Four factors, negative, delusion/hallucination, disorganization, and excitement, were yielded from factor analysis on 14 items of the Positive and Negative Syndrome Scale (PANSS) among 60 Chinese inpatients with acute schizophrenia. The negative dimension was associated with lower sensitivity index (d') while the excitement dimension was associated with higher d' on the Continuous Performance Test (CPT) after sex, age and education were adjusted for in multiple linear regressions. The positive dimension affected only response criterion (ln beta) and was not associated with the d' on the CPT. In contrast, the summed scores of PANSS Positive and Negative scales did not have significant correlations with d' on the CPT. Thus, the discriminant validity of these symptom dimensions of schizophrenia is supported by their correlations with CPT performance indices.

Acute Disease

Cocaethylene exposure during the brain growth spurt period: brain growth restrictions and neurochemistry studies.

The concurrent use of alcohol and cocaine has recently attracted attention in the medical research field due to the prevalence of this drug abuse pattern and the exclusive formation of a pharmacologically active substance, cocaethylene (CE). This is the first study to examine the neuroteratogenic effects of cocaethylene exposure during the brain growth spurt (part of the third trimester equivalent) on brain growth restrictions and neurochemical profiles. For the brain growth restrictions study, three groups of artificially reared rat pups were given daily injections of 0, 10 or 20 mg/kg cocaethylene (s.c.) from postnatal days (PDs) 4 through 9. One group of normally reared pups (suckle control) also was used. These pups were perfused on PD 10 and the brains were removed and weighed (forebrain, cerebellum and brainstem). For the neurochemistry study, five groups of artificially reared pups were used and were treated identically to those in the brain growth restrictions study, with the exceptions that animals assigned to acute cocaethylene treatment groups did not receive cocaethylene from PDs 4 through 8 and all animals in this study were sacrificed on PD 9 by decapitation. One suckle control group was included to control the possible artificial rearing effects on the neurochemical measures. Blood and fresh brain tissues (cortex, subcortical structures, cerebellum and brainstem) were collected for blood cocaethylene concentration and neurochemical analyses using GC/MS and HPLC techniques, respectively. The statistical analyses indicated that daily administration of 10 or 20 mg/kg cocaethylene, but not 0 mg/kg cocaethylene, significantly restricted the brain growth (brain weights) in all three brain regions assessed. Furthermore, cocaethylene administration from PDs 4 through 9 produced region-specific alterations in various neurotransmitter concentrations. The changes in neurotransmitter levels were not a function of the responses to the last cocaethylene injection on PD 9, since the outcomes between six days of cocaethylene treatment (PDs 4 to 9) and one day acute treatment (PD 9) were notably different. Furthermore, the artificial rearing procedure appeared to produce significant alterations in various neurotransmitter levels when compared with normally reared (suckle) controls. Collectively, these results suggest that cocaethylene is neuroteratogenic to the developing brain during the third trimester equivalent and the unique formation of cocaethylene resulting from the concurrent use of alcohol and cocaine may represent an increased risk to the developing brain beyond the intrinsic neuroteratogenic effects of cocaine and alcohol individually.

Animals

Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan.

Previous studies examining the putative association between DRD2 TaqI A1 and alcoholism have produced conflicting results. Major critiques of such studies include potential confounding arising from population admixture by inappropriate selection of controls, failure to screen out substance abusers from controls, and the failure to assess the severity of alcoholics. To address these issues, we compared the allelic frequency of two polymorphisms of DRD2, TaqI A and NcoI, among severe alcoholics and their ethnically matched nonalcoholic controls within four major aboriginal groups and Han (Chinese) in Taiwan. The sample of alcoholics and controls examined for the five groups included 36 and 31 (Atayal), 24 and 23 (Ami), 58 and 58 (Bunun), 35 and 35 (Paiwan), and 50 and 66 (Han). A borderline association between TaqI A1 and alcoholism among the Ami (P = 0.08) and an association between NcoI N1 and alcoholism among Han (P = 0.01) were found. Results of haplotype analysis further confirm that the frequency of haplotype A1N1 was higher in alcoholics than in controls for the Ami (P = 0.01) and Han (P = 0.03). If controls with tobacco abuse were excluded from the analysis, the results remained unchanged. Severity in medical complications of alcohol dependence with withdrawal symptoms was not associated with higher prevalence of DRD2 TaqI A1 or NcoI N1 alleles. The absence of an association between DRD2 and alcoholism among the three aboriginal groups suggests either a higher rate of phenocopies among aboriginal alcoholics or genetic heterogeneity in the susceptibility to alcoholism.

Alcoholism

Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines.

Previous population association studies have indicated that certain alleles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes may reduce the risk of alcoholism in Oriental populations. In this report we determined the genotypes for three genes, ADH2, ADH3, and ALDH2 among subjects with alcohol dependence (n = 159) and ethnically matched normal controls (n = 149) for the four largest aboriginal groups (Atayal, Ami, Bunun, and Paiwan) in Taiwan. The ethnicity matching used in this study was feasible because there are still few intergroup marriages between these aboriginal groups. On a group level, the rare frequencies of ALDH2*2, the inactive allele of ALDH2, among these aborigines may account partially for their vulnerability to alcohol use disorders. On an individual level, however, the genotypes controlling alcohol metabolism did not account for intragroup differences in vulnerability to alcoholism except in the case of ADH2 for the Ami ethnic group.

Adult

Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors.

Several mutations that cause ectopic expression of the agouti gene result in obesity, hyperinsulinemia, and yellow coat color. A candidate pathway for agouti induced obesity and hyperinsulinemia is through altered signaling by melanocortin receptors, as agouti normally regulates coat coloration through antagonism of melanocortin receptor 1. Furthermore, melanocortin peptides mediate functions including steroidogenesis, lipolysis, and thermoregulation. We report apparent inhibition dissociation constants for mouse and human agouti protein inhibition of ligand binding to the melanocortin receptors, to determine which of these receptors might be involved in agouti induced diabetes. The similarity in the apparent K(I) values for agouti inhibition of ligand binding to the brain melanocortin receptors 3 and 4 (mouse: K(I) app = 190 +/- 74 and 54 +/- 18 nM; human: K(I) app = 140 +/- 56 and 70 +/- 18 nM, respectively) suggests that the MC3-R is a potential candidate for a receptor mediating the effects of agouti protein overexpression. Agouti residues important for melanocortin receptor inhibition were identified through the analysis of deletion constructs and site-specific variants. Val83 is important for inhibition of binding to MC1-R (K(I) app for Val83Ala agouti increased 13-fold relative to wild-type protein). Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R.

Agouti Signaling Protein

Concordance of positive and negative symptoms in coaffected sib-pairs with schizophrenia.

Positive and negative symptom (NGS) dimensions were examined for their concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and thought disorganization (TDS) could be formulated. Discrete genetic endowment of these three symptom dimensions was not found as shown by the low concordance in sib pair analysis (kappa = 0.20-0.30). Thirty-seven pairs (80.4%) and 21 pairs (45.7%) had liability, defined by the presence of NGS in any one member of the coaffected sib-pairs, of NGS of "any degree", and of "severe degree" in 46 sib-pairs, respectively. Both groups had high prevalence (59.1-81.0%) of positive symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of "any degree" or of "severe degree" out of 46 sib-pairs, respectively. These two groups had high concordance (kappa = 0.45-1.00) of TDS or DHS between coaffected sib-pairs. Based on the results, it is hypothesized that schizophrenia, as defined by DSM-III-R, may consist of two subtypes: one has liability of NGS and a high prevalence of positive symptoms, while the other has only positive symptoms.

Delusions

Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.

Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a variety of inflammatory disease states. The protein exists as a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA. TACE is a membrane-bound disintegrin metalloproteinase. Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development. The expression of recombinant TACE (rTACE) results in the production of functional enzyme that correctly processes precursor TNF-alpha to the mature form. The rTACE provides a readily available source of enzyme to help in the search for new anti-inflammatory agents that target the final processing stage of TNF-alpha production.

ADAM Proteins

The prognostic significance of proliferating cell nuclear antigen in patients with lymph node-positive breast cancer.

OBJECTIVE: To evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) in patients with lymph node-positive primary breast cancer. DESIGN: A retrospective study. SETTING: A tertiary care hospital. STUDY PARTICIPANTS: A consecutive series of 123 patients with lymph node-positive primary breast cancer. INTERVENTION: The PCNA-labeling index [(PCNA-positive cells/1000 cells) x 100] was quantified in paraffin-embedded tissue specimens from 123 patients with lymph node-positive primary breast cancer by immunohistochemical staining. Other important clinicopathological variables, including estrogen receptor status, histological grade, lymph node status, primary tumor status, ploidy pattern, S-phase fraction, and TNM staging, were also identified and evaluated. MAIN OUTCOME MEASURES: The influence of the PCNA-labeling index on the disease-free survival rate and overall survival rate. RESULTS: The PCNA-labeling index of the tissue specimens tested from 123 patients ranged from 11% to 82%. The PCNA-labeling index was closely related to primary tumor status, histological grade, TNM staging, and S-phase fraction. Between patients with a high PCNA-labeling index (> 35%) and those with a low PCNA-labeling index (< or = 35%), there were significant (P < .01) differences in both 5-year disease-free survival rates (2% vs 85%) and 5-year overall survival rates (2% vs 92%). When the PCNA-labeling index and all the clinicopathologic variables were entered into a multivariate analysis for either disease-free survival or overall survival by the Cox proportional hazards model, the PCNA-labeling index emerged as an independent prognostic factor. CONCLUSION: Based on our results, the PCNA-labeling index potentially is a useful prognostic factor for lymph node-positive primary breast cancer.

Adult

Decrease in myocardial Na(+)-K(+)-ATPase activity and ouabain binding sites in hypercholesterolemic rabbits.

OBJECTIVES: The purpose of this study was to explore the effect of high dietary cholesterol on the lipid composition, Na(+)-K(+)-ATPase activity and ouabain receptor property of the myocardial sarcolemma. METHODS: Male New Zealand white rabbits were fed with standard chow or standard chow supplemented with 0.5% (w/w) cholesterol and 10% (w/w) coconut oil to induce hypercholesterolemia. After 8 weeks, the rabbits were sacrificed; a myocardial sarcolemma fraction was then prepared from the left ventricular myocardium and analyzed for lipid composition. Assay of Na(+)-K(+)-ATPase activity and 3H-ouabain binding studies were performed in the myocardial sarcolemma from the control and cholesterol-fed rabbits. RESULTS: The cholesterol content, but not the phospholipid content, of the sarcolemma was significantly greater in the cholesterol-fed group, thus, resulting in an increased cholesterol/phospholipid molar ratio in the cholesterol-fed group. In addition, a decrease in Na(+)-K(+)-ATPase activity was also found in this group. The decrease in Na(+)-K(+)-ATPase activity was selective, since the Mg(++)-ATPase and 5'-nucleotidase activities remained unchanged. In the 3H-ouabain binding study, a decrease in the number of maximum binding sites, but not the binding affinity, for 3H-ouabain was found in the cholesterol-fed group. CONCLUSIONS: High dietary cholesterol induces higher levels of cholesterol not only in the plasma, but also in the myocardial sarcolemma. These changes result in decreased myocardial Na(+)-K(+)-ATPase activity mediated by a reduction in the maximum number of binding sites for ouabain but not a change in binding affinity.

5'-Nucleotidase

Accessory hepatic duct associated with a choledochal cyst.

This case report describes an accessory hepatic duct (AHD) identified by intraoperative cholangiography during excisional surgery of a choledochal cyst (CC). The accessory duct was divided and reconstructed successfully to the Roux-en-Y jejunal loop. The postoperative course was uneventful, and follow-up abdominal sonography revealed neither evidence of biliary tract obstruction nor atrophic changes of the liver. It is advocated that an AHD should be meticulously reconstructed if it is divided during excisional surgery of a CC.

Anastomosis, Roux-en-Y

Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese.

The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE) gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported to be correlated with an increased prevalence of coronary artery disease (CAD) and myocardial infarction (MI). The importance of the DD genotype and T235 homozygote as genetic risk factors for CAD in Chinese remains uncertain. This study included 426 patients who underwent coronary angiography and 180 healthy subjects without clinical evidence of CAD. Coronary angiography identified 268 patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects and patients without angiographic evidence of CAD constituted the control group. Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association was found between any of the three studied polymorphisms and the risk of CAD or MI in Chinese using univariate or multivariate analysis. In multivariate analysis, the relative risks were 1.20 (95% confidence interval = 0.91-1.61, P = 0.20) for the DD genotype, 1.05 (95% CI = 0.82-1.35, P = 0.69) for the T174 homozygote, and 1.19 (95% CI = 0.91-1.55, P = 0.20) for the T235 homozygote. Similarly, no significant difference was found in the frequencies of the DD genotype and the T174 and T235 homozygotes between the control group, the CAD group, the non-MI group, and the MI group when analyzed according to sex, age, or degree of risk. Our data suggest that neither the DD genotype of the ACE I/D polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant risk for CAD or MI in Chinese.

Angiotensinogen

Structural features and biochemical properties of TNF-alpha converting enzyme (TACE).

Tumor necrosis factor-alpha is a potent cytokine, secreted primarily by activated monocytes and macrophages, that possesses a broad range of immunomodulating properties. Involvement of this cytokine has been validated in disease states such as arthritis and Crohn's disease and implicated in diverse neuroimmunological pathologies such as multiple sclerosis, Alzheimers and stroke. TNF-alpha is initially synthesized as a 26 kDa precursor molecule that is subsequently processed to the mature form by cleavage of the Ala76 Val77 bond. The 17 kDa carboxy-terminal protein is then secreted to function in a paracrine manner. The enzyme that processes precursor TNF-alpha has previously been identified as a microsomal metalloprotease called TNF-alpha converting enzyme (TACE). We have now purified and partially cloned the enzyme. TACE represents a novel target for therapeutic intervention in a variety of inflammatory and neuroimmunological diseases.

ADAM Proteins

MR imaging of thoracic neurilemmomas.

Magnetic resonance (MR) imaging features of 15 thoracic neurilemmomas were analyzed. Morphologically, five tumor patterns could be identified on MR imaging including: inhomogeneous masses (n = 8), thick-walled multiloculated masses (n = 2), thick-walled central cystic masses (n = 2), homogeneous cystic masses (n = 2) and a target pattern mass (n = 1). The signal characterization of thoracic neurilemmomas was variable, usually brighter on T2-weighted images, hyper- to hypo-intense on T1-weighted images and always enhancing. Histopathologically, the inhomogeneous masses were characterized by irregular distribution of hypercellular Antoni A and hypocellular Antoni B tissues with variable degrees of cystic, hemorrhagic, myxoid and hyaline degenerative changes. Enlargement of the cystic areas led to the development of thick-walled multiloculated masses while confluence of these cystic areas produced a central cystic pattern. Extensive myxoid or hyaline degeneration yielded homogeneous cystic tumors. Peripheral fibrinous changes and central Antoni B stroma contributed to a target pattern. Appreciation of the protean MR manifestations and understanding of the underlying histopathological changes of thoracic neurilemmomas are helpful in the diagnosis of this tumor.

Adult

Effects of n-3 and n-6 fatty acids on plasma eicosanoids and liver antioxidant enzymes in rats receiving total parenteral nutrition.

The effect of total parenteral nutrition (TPN) enriched with n-3 or n-6 fatty acids on the concentration of plasma eicosanoids was evaluated in rats. Rats were divided into three groups: the control group (n = 6) was fed a chow diet and infused with saline only. Two experimental groups (n = 11, 13) received TPN solutions at an energy level of 30 kcal/100g body weight with 40% energy provided as fat. The experimental groups were maintained on TPN for a period of 7 d. The basal TPN solutions were isonitrogenous and identical in nutrient composition except for differences in lipid source. One experimental group received a safflower oil emulsion, whereas the other group received a fish oil emulsion. At the end of the experimental period, plasma 6-keto prostaglandin F1 alpha, thromboxane B2, bleeding time, lipid peroxidation products, and antioxidant enzymes of liver were analyzed. The results demonstrated that the fish oil group had lower 6-keto prostaglandin F1 alpha concentration than the safflower oil group. Also, plasma thromboxane B2 was the lowest in the fish oil group among the three groups. There was no difference in bleeding time among the groups. With regard to liver lipid peroxidation products, malondialdehyde concentration was not higher in the fish oil group, whereas superoxide dismutase and glutathione peroxidase activities were lower in the fish oil group compared with the control and safflower oil groups. The results suggest that TPN prepared with fish oil fat emulsion causes less accumulation of lipid peroxidation products in the liver of rats, and may be beneficial in preventing platelet aggregation.

6-Ketoprostaglandin F1 alpha

Assessment of neutralizing antibodies elicited by a vaccine (Nakayama) strain of Japanese encephalitis virus in Taiwan.

A total of 368 blood specimens were resampled from a serum collection containing 2914 blood samples which were collected by a random sampling in Taiwan in 1991. The plaque reduction neutralization test was applied to evaluate the neutralizing ability to two strains of Japanese encephalitis viruses, i.e. Nakayama (the present vaccine strain) and JE5 (a Taiwan isolate). The result revealed that antibodies against JE virus were present in each stratified age group. Antibody positive rates were both highest in the group older than 70 years although the lowest rates were located in different groups. In addition, the result showed that the immunogenicity potency of the antibody induced by the vaccine strain did not have a good coverage against JE5. The rate of neutralizing antibodies above the level of protective efficacy of the present vaccine was limited as low as 37.93%. Efficacy of the vaccine used at present was apparently not efficient. Consideration of a more promising vaccine may be necessary.

Adolescent

Serum concentration of tumor necrosis factor in patients with breast cancer.

BACKGROUND: The outcome of breast cancer is usually determined by multiple factors. Serum tumor necrosis factor alpha concentration has been found to be increased in the circulation of patients with malignancy. This study was designed with the aim to investigate any correlation between the serum tumor necrosis factor alpha and the clinicopathological features and furthermore evaluate the prognostic significance of serum tumor necrosis factor alpha concentration in breast cancer. METHODS: Forty consecutive patients with invasive breast cancer undergoing modified radical mastectomy were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C until assayed. The control group consisted 30 healthy, age-matched subjects. Serum concentrations of tumor necrosis factor alpha were measured by the quantitative sandwich enzyme immunoassay technique. The data on tumor size, age, estrogen receptor status, lymph node status and TNM staging were reviewed and recorded. RESULTS: The mean value of serum tumor necrosis factor alpha in patients with invasive breast cancer was 1.47 +/- 0.58 pg/ml and that of the control group was 0.98 +/- 0.37 pg/ml, and the difference was significant (P < 0.01). With univariable analysis, patients with maximum tumor size of 5 cm or larger (P = 0.03), more advanced TNM staging (P < 0.01); and more advanced lymph node status (P < 0.01) were shown to have significantly higher serum concentrations of tumor necrosis factor alpha. However, with multivariable analysis, TNM staging appeared as the only independent factor (P < 0.01) predicting the significant, higher serum concentrations of tumor necrosis factor alpha. CONCLUSION: Preoperative evaluation of serum tumor necrosis factor alpha concentrations may be a valuable parameter for reflecting the severity of staging for invasive breast cancer.

Adult