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Biomedical subjects

J S Chen

Publications and source records attributed to J S Chen.

At least 19 recordsLinked to original sources

Stereospecific blocking effects of naloxone against hemodynamic compromise and ventricular dysfunction due to myocardial ischemia and reperfusion.

Endogenous opioid peptides subserve regulatory roles in cardiovascular function and are released upon myocardial ischemia contributing to the development of ischemic arrhythmias and cardiogenic shock, which are reversed by the opioid antagonist naloxone. Since the hallmark of myocardial infarction is the impairment of hemodynamics and ventricular function, we evaluated further if blockade of opioids reverses the ischemia induced hemodynamic compromise, and if the effects are mediated by opioid receptors. Thirty-two mongrel dogs were anesthetized and artificially ventilated. Median thoracotomy was performed, the heart exposed, and the left anterior descending coronary artery isolated for subsequent occlusion and reperfusion. All cardiac parameters were recorded on an Electronics for Medicine recorder through the intracardiac catheters advanced from femoral vessels. Results indicate that naloxone significantly reversed the ischemic and reperfusion induced reduction in aortic, left ventricular and pulmonary arterial pressures, and left ventricular dp/dt. The inactive (+) stereoisomer of naloxone was without effect. These data demonstrate that opioids may have a role in the pathophysiology of myocardial infarction, mediated by opioid receptors, and provide new insight and strategies for the understanding and treatment of ischemic heart disease.

Animals

Regression of left ventricular aneurysm after delayed percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction.

Two weeks after acute myocardial infarction (AMI), 23 patients received delayed percutaneous transluminal coronary angioplasty (PTCA) and 14 consecutive randomized selected patients received conservative treatment as a control group. Follow up intravenous and/or intraventricular left cine-ventriculography, as well as radionuclide ejection fraction were performed 6-24 months (mean 11.2 months) after the acute phase. The results showed no significant statistical differences between the two groups for age, sex, Killip class, left ventricular end-diastolic pressure, and medication. The PTCA group showed a significant increase in radionuclide left ventricular ejection fraction, when compared to the control group (20.4 +/- 0.3 vs. 2.05 +/- 1.2; P < 0.05), as well as in the cine-global ejection fraction (32.1 +/- 0.4 vs. 3.44 +/- 1.1; P < 0.05). The dyskinetic area and volume were found also to have greater reduction in the PTCA group than in the control group (-84.7 +/- 1.2 vs. -10.5 +/- 1.1 and -86.1 +/- 1.1 vs. -15.4 +/- 0.9; P < 0.05). There were no significant changes in diastolic or systolic circumferences for both group. In conclusion, delayed PTCA after AMI can reduce the left ventricular dyskinetic area, and improve cine-global ejection fraction. Intravenous first pass left ventriculography is a safe, simple, and reproducible method for evaluating left ventricular remodeling after acute myocardial infarction.

Aged

Cholelithiasis in Taiwan. Gallstone characteristics, surgical incidence, bile lipid composition, and role of beta-glucuronidase.

The nature and occurrence of gallstones in Taiwan and their etiologic factors might not be the same as in Western countries and warranted a systematic investigation. Gallbladder biles and gallstones were obtained at surgery from 100 and 74 patients, respectively. Common duct bile and stones were either drained through an indwelling common duct T-tube or aspirated through a nasobiliary catheter in 108 patients. Gallstones were analyzed for bilirubin, cholesterol, bile acid, calcium, and residue, and biles for bile acid, cholesterol, phospholipid, bilirubin, and beta-glucuronidase. There were four major kinds of gallstones in Taiwan: cholesterol/mixed stones, high-residue black formed pigment stones, low-residue brown formed pigment stones, and muddy pigment stones. The surgical incidence of all types of stones increased steadily during the past four decades. During the past 15 years the relative frequencies for mixed, formed pigment, and muddy pigment stones had been roughly 40, 40, and 20%, respectively, with a further increase in the mixed stones and a decrease in the muddy pigment stones in recent years. Improvement of nutritional status and living standards might contribute to such changes. Cholesterol content in the common duct and gallbladder biles was higher in the mixed stone group than in other groups. Bacterial beta-glucuronidase activity was detected in 53% of patients with muddy pigment stones. Endogenous beta-glucuronidase activity and concentration were also highest in this group, intermediate in the formed pigment and mixed stone group, and lowest in the control. We concluded that hypercholesterobilia was responsible for increasing incidence of mixed stones during the past two decades, while both bacterial and human beta-glucuronidase might contribute to pigment cholelithiasis.

Bile

Stable high expression of human gamma-aminobutyric acidA receptors composed of alpha and beta subunits.

Multiple classes of pharmacological agents including benzodiazepines, cage convulsants like t-butylbicyclophosphorothionate (TBPS), barbiturates and neuroactive steroids allosterically modulate the gamma-aminobutyric acidA receptor-chloride ionophore complex (GRC). The function of benzodiazepines requires a GRC comprised of alpha, beta and gamma subunits, while TBPS, barbiturates and neuroactive steroids will allosterically modulate GRCs comprised of only alpha and beta subunits. Binary alpha beta complexes are still hypothesized to be expressed in the mammalian brain particularly during development and could contribute to the pharmacological action of neuroactive steroids and barbiturates. In order to examine binary alpha beta complexes we report here the establishment of stable cell lines that express high levels of human GABAA receptors comprised of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 subunit combinations. The apparent potencies for allosteric modulation of [35S]TBPS for most naturally occurring neuroactive steroids for the binary subunit combinations was similar to that of the gamma-containing subunit combinations. Also discussed is the usefulness of these cell lines for the biophysical analysis of the GABAA receptor stoichiometry.

Animals

Indirect control of yolk protein genes by 20-hydroxyecdysone in the fat body of the mosquito, Aedes aegypti.

In response to a blood meal, the fat body of the female mosquito, Aedes aegypti, begins massive production of several yolk proteins which are subsequently stored in the developing oocytes. Although 20-hydroxyecdysone (20E) is important for initiation and maintenance of expression of the yolk protein genes encoding vitellogenin (Vg) and vitellogenic carboxypeptidase (VCP), the exact nature of 20E action has not been clearly defined. A primary question is whether this hormone directly stimulates expression of the genes for Vg and VCP or if it acts indirectly through a hormone response cascade. We have demonstrated that 10(-4) M cycloheximide (Chx) reversibly inhibits > 98% of protein synthesis in in vitro fat body culture. 10(-5) M 20E stimulates high levels of the mRNAs for Vg and VCP in previtellogenic fat bodies cultured in vitro, but initiation of this expression is eliminated by Chx. Thus, our results indicate that protein synthesis is required in response to 20E before increased levels of yolk protein mRNAs can be measured. We therefore conclude that the action of 20E is indirect.

Aedes

Differential effects of 4'-chlorodiazepam on expressed human GABAA receptors.

The interactions of the atypical benzodiazepine 4'-chlorodiazepam (Ro 5-4864) with functionally expressed human GABAA receptor cDNAs were determined. Cotransfection of human alpha 2, beta 1, and gamma 2 subunits was capable of reconstituting a 4'-chlorodiazepam recognition site as revealed by a dose-dependent potentiation of t-[35S]butylbicyclophosphorothionate ([35S]-TBPS) binding to the GABA-activated chloride channel. This site is found on GABAA receptor complexes containing sites for GABA agonist-like benzodiazepines and neuroactive steroids. The importance of the alpha subunit was further demonstrated as substitution of either alpha 1 or alpha 3 for the alpha 2 subunit did not reconstitute a 4'-chlorodiazepam recognition site that was capable of modulating [35S]TBPS binding under the same experimental conditions. The 4'-chlorodiazepam modulatory site was shown to be distinct from the benzodiazepine site, but the phenylquinolines PK 8165 and PK 9084 produced effects similar to 4'-chlorodiazepam, consistent with the previous analysis of the 4'-chlorodiazepam site in brain homogenates. Further analysis of the subunit requirements revealed that coexpression of alpha 2 and beta 1 alone reconstituted a 4'-chlorodiazepam recognition site. It is interesting, however, that the 4'-chlorodiazepam site was found to inhibit [35S]TBPS binding to the GABA-activated chloride channel. Thus, the 4'-chlorodiazepam site may be reconstituted with only the alpha and beta polypeptides.

Benzodiazepinones

Acquired genital smooth-muscle hamartoma. A case report.

Smooth-muscle hamartoma is an uncommon, usually congenital malformation of smooth-muscle origin. When it is acquired, it may be confused with Becker's nevus with a prominent smooth-muscle component. Over the past 3 decades, only two cases of acquired smooth-muscle hamartoma without the concomitant appearance of hairy-pigmented lesions have been reported. We describe a third case. To the best of our knowledge, this is the first case of smooth-muscle hamartoma to occur in the scrotum.

Adult

Familial acanthosis nigricans with madarosis.

We report familial acanthosis nigricans affecting a 35-year-old woman, her 7-year-old son and 5-year-old daughter. Absence of the eyebrows and eyelashes was noted in this family. The mother had no axillary hair and her pubic hair was sparse. The boy also suffered from congenital heart disease and a congenital cataract in the left eye. The combination of acanthosis nigricans and ectodermal defects in this family may represent a distinct nosological entity.

Acanthosis Nigricans

Alcohol dehydrogenase: multiplicity and relatedness in the solvent-producing clostridia.

Alcohol dehydrogenase (ADH) is a key enzyme for the production of butanol, ethanol, and isopropanol by the solvent-producing clostridia. Initial studies of ADH in extracts of several strains of Clostridium acetobutylicum and C. beijerinckii gave conflicting molecular properties. A more coherent picture has emerged because of the following results: (i) identification of ADHs with different coenzyme specificities in these species; (ii) discovery of structurally conserved ADHs (type 3) in three solvent-producing species; (iii) isolation of mutants with deficiencies in butanol production and restoration of butanol production with a cloned alcohol/aldehyde dehydrogenase gene; and (iv) resolution of various 'C. acetobutylicum' cultures into four species. The three ADH isozymes of C. beijerinckii NRRL B592 have high sequence similarities to ADH-1 of Clostridium sp. NCP 262 (formerly C. acetobutylicum P262) and to the ADH domain of the alcohol/aldehyde dehydrogenase of C. acetobutylicum ATCC 824/DSM 792. The NADH-dependent activity of the ADHs from C. beijerinckii NRRL B592 and the BDHs from C. acetobutylicum ATCC 824 is profoundly affected by the pH of the assay, and the relative importance of NADH and NADPH to butanol production may be misappraised when NAD(P)H-dependent activities were measured at different pH values. The primary/secondary ADH of isopropanol-producing C. beijerinckii is a type-1 enzyme and is highly conserved in Thermoanaerobacter brockii (formerly Thermoanaerobium brockii) and Entamoeba histolytica. Several solvent-forming enzymes (primary ADH, aldehyde dehydrogenase, and 3-hydroxybutyryl-CoA dehydrogenase) are very similar between C. beijerinckii and the species represented by Clostridium sp. NCP 262 and NRRL B643. The realization of such relationships will facilitate the elucidation of the roles of different ADHs because each type of ADH can now be studied in an organism most amenable to experimental manipulations.

Alcohol Dehydrogenase

Application of natural and amplification-created restriction sites in prenatal and preimplantation diagnosis of beta-thalassemia.

We attempted the strategy of natural and amplification-created restriction sites for early prenatal and preimplantation diagnosis of Chinese beta-thalassemia. Mutagenesis primers were designed for 11 mutations reported for the Chinese population. The diagnosis was established after polymerase chain reaction and digestion of products by specific enzymes. The results were confirmed by direct sequencing of enzymatically amplified double-stranded DNA. The beta-globin gene was amplified from triploid embryos and isolated blastomeres using mismatched primers. The mutant and normal alleles can be distinguished clearly by this new method. Early prenatal diagnosis was successfully achieved in 9 cases. The beta-globin gene was successfully amplified from single blastomeres and tripronuclear embryos with mismatched primers. Natural and amplification-created restriction sites are a reliable method for rapid prenatal diagnosis of beta-thalassemia. Furthermore, the strategy provides a possible approach for the preimplantation diagnosis of beta-thalassemia.

Base Sequence

Zygomycotic lung abscess: a case report.

Zygomycosis is an uncommon, but frequently fatal, fungal infection caused by members of the class Zygomycetes. The risk factors include diabetes mellitus, uremia, leukemia and use of deferoxamine as an iron-chelating agent; healthy persons also are occasionally infected. Those fungi, spread by their ubiquitous spores, most frequently involve the respiratory system. Rhinocerebral zygomycosis occurs predominantly in patients with uncontrolled diabetic ketoacidosis. Pulmonary zygomycosis most frequently is observed in granulocytopenic and corticosteroid-treated patients. Other clinical manifestations are gastrointestinal, cutaneous, disseminated and miscellaneous. This report concerns a previously robust farmer who suffered from left upper lung abscess caused by Rhizopus spp.-one member of the order Mucorales. Initially, it was intended to administer amphotericin B to a total dose of 2,000 mg; however, the patient could not tolerate such side effects as nausea, vomiting and refused further management when the cumulative dose was 948 mg. However, he did recover without further fever and cough. Chest X-ray, followed every three months, disclosed satisfactory improvement.

Amphotericin B

The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age.

To investigate the significance of spontaneous hepatitis B e antigen (HBeAg) seroconversion during childhood, 415 hepatitis B surface antigen (HBsAg) carrier children (ages 0 to 15 years) were prospectively followed for 7.1 +/- 2.9 years. Hepatitis B virus (HBV) markers and liver function profiles of each child were tested at least once every 6 months. Among them, 50 were initially anti-HBe positive and 140 seroconverted from HBeAg to anti-HBe during follow-up. Before HBeAg seroconversion, jaundice occurred in 9 and alanine transaminase (ALT) activities elevated in 99 of the 140 seroconverters. Serum ALT returned to normal in all patients within 1 to 5 years of seroconversion. Six had reelevated ALT later after seroconversion. Only 7 (9.7%) of the 72 carrier infants seroconverted before 3 years of age. The peak ALT levels in five of them exceeded 100 IU/L, and two had jaundice before HBeAg seroconversion. One of the early seroconverters developed hepatocellular carcinoma (HCC) at 11 years of age, although his liver function profiles remained normal after HBeAg seroconversion. Liver biopsy specimens from 30 children during the anti-HBe-positive stag e showed inactive cirrhosis in 2 (including one with HCC), chronic hepatitis with marked fibrosis in 1, mild activity and moderate fibrosis in 2, mild activity and mild fibrosis in 9, and minimal histologic changes in the remaining 16. Although most will achieve a normalization of ALT and inactive liver histologic changes, the seroconversion of HBsAg carrier children from HBeAg to anti-HBe is not necessarily an indicator of favorable prognosis; a small proportion of children will develop cirrhosis or even HCC.

Adolescent

Cisplatin and 5-fluorouracil as neoadjuvant chemotherapy: predicting response in head and neck squamous cell cancer.

In order to prospectively evaluate the efficacy, toxicity and predictive factors of response to neoadjuvant chemotherapy, a total of 120 patients with head and neck squamous cell cancer diagnosed from January 1992 to November 1993 were enrolled in this study. There were 118 male and 2 female patients, with a median age of 51 years (range 30-74 years). The primary sites were the oral cavity (77), oropharynx (15), hypopharynx (25) and larynx (3). Betel quid chewing was habitual in 91% of patients. All patients were previously untreated, and 94% had stage III or IV disease. Chemotherapy was given in two or three courses to 96 patients who were then assessed for response rate and predictive factors. The chemotherapy regimen consisted of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1 g/m2/day intravenous infusion continuously for 4 to 5 days for 4 weeks. The overall chemotherapy response rate was 56%, with a 3% complete response. By univariate analysis, both the T-stage and tumor volume were significant for predicting the response of the primary site. The age, histologic differentiation, tumor location and N-stage were unpredictive for response. The nodal response (43%) was less than that of the primary site (68%). By multivariate analysis, only the tumor volume (> or = 50 cm3) and the presence of nodal metastases were predictive for the combined TN response. Based on the World Health Organization toxicity criteria, 49 patients experienced grade 3 to 4 mucositis, and 24 patients had grade 3 to 4 vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Prevalence of permanent primary congenital hypothyroidism in Taiwan.

The purpose of this study was to find the prevalence of permanent primary congenital hypothyroidism in Taiwan. From January 1988 to December 1990, there were 991,132 live births in Taiwan. Of these, 329,891 neonates were screened for primary congenital hypothyroidism. Fifty-seven cases of permanent primary congenital hypothyroidism were confirmed. Hence, the prevalence of permanent primary congenital hypothyroidism in that period in Taiwan was 1 in every 5,788 live births. There was a female preponderance with a female to male ratio of 1.7. Of 54 infants who had a thyroid scan, 36 were found to have an ectopic thyroid gland, while 11 were found to have dyshormonogenesis. Among the 57 infants, one case with a delayed rise in the serum thyrotropin level was missed on initial screening. When compared with other studies, these data suggest that the prevalence of permanent primary congenital hypothyroidism varies in different ethnic groups throughout the world.

Congenital Hypothyroidism

Survival impact of lymph node metastasis in TNM stage III carcinoma of the colon and rectum.

BACKGROUND: Node-positive (TNM stage III) adenocarcinoma of the colon and rectum consists of tumors with a widely variable prognosis. To predict the outcome of patients with stage III carcinoma, we assessed the survival impact of the number and level of lymph node metastasis and other clinicopathological variables. STUDY DESIGN: A retrospective study was performed on 538 patients with stage III carcinoma of the colon and rectum who underwent curative resection at Chang Gung Memorial Hospital between 1980 and 1989. Ten or more lymph nodes in each resected specimen were identified microscopically. Multivariate analysis was used to determine the independent variables. RESULTS: The relative survival rates at five and ten years were 52 and 42 percent, respectively. Tumor morphology, depth or tumor penetration, histologic grade, and the status (number and level) of nodal involvement were significant in the univariate analyses. Only grade and nodal status remained significant in the multivariate analysis. Based on the nodal status, these patients were separated into three groups: stage IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more nodes or presence of pN3). The five-year survival rates for patients with stages IIIA, IIIB, and IIIC disease were 69, 44, and 29 percent, respectively. Compared with patients with stage IIIA disease, the odds of death for patients with stages IIIB and IIIC carcinoma were 2.1 (95 percent confidence interval: 1.5 to 2.8, p = 0.0001) and 3.3 (95 percent confidence interval 2.4 to 4.5, p = 0.001), respectively. CONCLUSIONS: We suggest that stage III adenocarcinoma of the colon and rectum be divided into three substages: IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more positive nodes or presence of pN3.

Adenocarcinoma

Use of a low profile Doppler angioplasty guidewire to evaluate the effect of percutaneous coronary angioplasty on coronary artery flow velocity.

BACKGROUND: The intracoronary Doppler flow velocity measurement is widely used. The Doppler flow catheter, used in many studies, still cannot always measure distal portions of coronary artery stenosis. However, three years ago, a low profile Doppler angioplasty guide wire (0.018-inch) was started by apply for measurement of changes in proximal and distal flow velocity during coronary angioplasty. METHODS: Blood flow velocity and diastolic/systolic velocity ratio (DSVR) on both proximal and distal portions of the coronary artery were measured with a low profile Doppler angioplasty guide wire in 13 patients with stenosis of the left anterior descending artery (LAD) during coronary angioplasty. RESULTS: Non-significant improvement in maximal peak velocity was noted in the distal portion of the coronary artery immediately after angioplasty (before, 36 +/- 12 cm/s; after, 41 +/- 12 cm/s; p > 0.05); but significant improvement was found after removal of the balloon (from 41 +/- 12 cm/s to 49.5 +/- 15 cm/s, p < 0.01). Increases in proximal maximal peak velocity after angioplasty were less remarkable (before, 38.5 +/- 15 cm/s; after, 45 +/- 13 cm/s; p > 0.05), and there was a significant increase of DSVR on the distal portion of the left anterior descending artery after angioplasty (before, 2.18 +/- 0.51; after, 2.98 +/- 0.44; p < 0.05). However, there was no significant increase of DSVR on the proximal portion of LAD (before, 2.19 +/- 0.16; after, 2.44 +/- 0.1; p > 0.05). The coronary flow reserve ratio showed no significant increase on the distal portion of the LAD (before, 1.03 +/- 0.3; after, 1.02 +/- 0.3) and proximal portion of LAD (before, 1.05 +/- 0.2; after, 1.03 +/- 0.3). CONCLUSIONS: Increase in peak velocity and DSVR of the distal portion of the coronary artery after angioplasty was more significant after removal of the balloon catheter than as if it were assessed immediately, without removing the balloon catheter. No significant increase in flow velocity of the proximal portion of the coronary artery after angioplasty was observed. No significant increase of the coronary flow reserve of the distal and proximal portion of the coronary artery occurred after successful angioplasty.

Adult

Selective actions of certain neuroactive pregnanediols at the gamma-aminobutyric acid type A receptor complex in rat brain.

Certain endogenous pregnanediols (5 alpha-pregnan-3 alpha,20 alpha-diol and 5 beta-pregnan-3 alpha,20 beta-diol) were observed to have limited efficacy as allosteric modulators of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to sites on the gamma-aminobutyric acid (GABA)A receptor complex in rat brain. In contrast, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha,5 beta-P) have full efficacy. Moreover, 3 alpha,5 beta-P but not 3 alpha,5 alpha-P recognizes high (nanomolar) and low (micromolar) affinity neuroactive steroid sites in these allosteric modulatory assays. The concentration-response curve for 3 alpha,5 alpha-P modulation of [35S]TBPS binding was shifted rightward in the presence of these pregnanediols and GABA. The maximum shift produced by these pregnanediols never exceeded the concentration-response curve obtained with 3 alpha,5 alpha-P alone in the absence of GABA. Additionally, neither 5 alpha-pregnan-3 alpha,20 alpha-diol nor 5 beta-pregnan-3 alpha,20 beta-diol had any effect on the site recognized by 3 alpha,5 alpha-P in the absence of GABA. The difference in the affinities of the two apparent sites (29 nM versus 152 nM in the presence and absence of GABA, respectively) recognized by 3 alpha,5 alpha-P is only approximately 5-fold. In contrast, the difference between the high (30 nM) and low (7 microM) affinity sites discriminated by 3 alpha,5 beta-P is > 200-fold. Thus, the selective interaction between the high affinity site recognized by 3 alpha,5 beta-P and these pregnanediols can be clearly observed. A saturating concentration of 5 beta-pregnan-3 alpha,20 beta-diol selectively eliminated the high affinity component recognized by 3 alpha,5 beta-P, whereas 5 alpha-pregnan-3 alpha,20 alpha-diol did not completely abolish the high affinity site. 5 alpha-Pregnan-3 alpha,20 alpha-diol recognized only a portion of the high affinity sites discriminated by 3 alpha,5 beta-P, relative to 5 beta-pregnan-3 alpha,20 beta-diol, whereas the two pregnanediols recognized a similar population of sites mediating 3 alpha,5 alpha-P inhibition of [35S]TBPS binding. Collectively, these studies provide evidence that the limited efficacy of certain pregnanediols as allosteric modulators of [35S]TBPS binding may be explained in part by selectivity for the high affinity site recognized by 3 alpha,5 beta-P.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals