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Biomedical subjects

C J Chen

Publications and source records attributed to C J Chen.

At least 19 recordsLinked to original sources

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Humans

Prevalence and risk factors of diabetic retinopathy among noninsulin-dependent diabetic subjects.

In a population-based study in Taiwan, 11,478 subjects aged 40 years or older were screened for diabetes in one urban and five rural areas. Among the 715 subjects proven to have diabetes, 527 subjects underwent ophthalmoscopy. Diabetic retinopathy was present in 184 of the 527 subjects (35.0%), including background diabetic retinopathy in 157 subjects (30.0%), preproliferative diabetic retinopathy in 15 subjects (2.8%), and proliferative diabetic retinopathy in 12 subjects (2.2%). Diabetic retinopathy was correlated with the duration of diabetes and age at onset of diabetes, type of diabetes treatment, higher serum creatinine levels, and lower serum cholesterol levels. Several other factors, including gender, age, residential area, family income, educational level, control and family history of diabetes, body mass index, physical activity, exercise, cigarette smoking, stroke, ischemic heart disease, leg vessel disease, hypertension, and proteinuria, had no significant association with retinopathy. By multiple logistic regression analysis, duration of diabetes was the most important risk factor related to retinopathy. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control (relative risk, 1.57; .05 < P < .10). The univariate analysis disclosed that proliferative diabetic retinopathy was related to older age at examination, older age at onset of diabetes, type of diabetes treatment, and presence of leg vessel disease. Insulin-treated diabetic subjects also had a higher risk of proliferative diabetic retinopathy than patients in whom diabetes was controlled by diet, with a relative risk of 2.51 (.05 < P < .10) in the multiple logistic regression analysis.

Adult

Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates.

Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.

Base Sequence

The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study.

To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case-control study of 128 patients with HCC and 384 age-matched and sex-matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti-HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P less than 0.001). Both HBsAg and anti-HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti-HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC.

Adult

Determinants on simian virus 40 large T antigen are important for recognition and phosphorylation by casein kinase I.

Casein kinase I has been shown to phosphorylate Ser123 and possibly Thr124, in simian virus 40 (SV40) large T antigen; the same sites are also modified in cultured cells incubated with 32Pi [Friedrich A. Grässer, Karl H. Scheidtmann, Polygena T. Tuazon, Jolinda A. Traugh & Gernot Walter (1988) Virology 165, 13-22]. The peptide, A-D-S-Q-H-S-T-P-P, which corresponds to the amino acid sequence 118-125 of SV40 large T antigen, was synthesized together with peptides containing changes in specific amino acid residues on either side of Ser123. These peptides were used as model substrates to determine the amino acids in the SV40 large T antigen important for recognition by casein kinase I. The native peptide identified above, with aspartate at the -4 position, was a poor substrate for casein kinase I in vitro. Peptides with acidic residues added at the -2 and -3 positions, preceding Ser123, were phosphorylated by casein kinase I with apparent Km values around 2 mM and Vmax values up to 500 pmol.min-1.ml-1. When acidic residues were added at both sides of the phosphorylatable serine, the peptide had a first-order rate constant over 20-fold higher than peptides with acidic amino acid residues at the N-terminus only; the apparent Km value was 0.65 mM with a Vmax of 2900 pmol.min-1.ml-1. The effects of modifying Ser120 to phosphoserine were examined by addition of a recognition sequence for the cAMP-dependent protein kinase prior to Ser120. Prior phosphorylation of the peptide at Ser120 lowered the apparent Km to 0.061 mM and increased the Vmax to 360 pmol.min-1.ml-1, a 50-fold decrease in Km for casein kinase I and a 6-fold increase in Vmax as compared to the non-phosphorylated peptide. This indicates that Ser120, which has been shown to be phosphorylated in vivo, provides an appropriate recognition determinant for casein kinase I.

Amino Acid Sequence

Current seroepidemiology of hepatitis D virus infection among hepatitis B surface antigen carriers of general and high-risk populations in Taiwan.

In order to assess the current seroepidemiology of hepatitis D virus (HDV) infection in Taiwan where hepatitis B virus (HBV) is hyperendemic, a total of 756 voluntary blood donors, 641 prostitutes, 1,014 patients with sexually transmitted diseases (STDs), and 628 drug abusers were studied. Radioimmunoassays were used for testing HBV infection markers and antibody against HDV (anti-HDV) among HBsAg carriers. The anti-HDV prevalence among HBsAg carriers was significantly higher in STD patients (9.6%), prostitutes (33.1%), and drug abusers (68.1%) than in blood donors from the general population (2.2%). The prevalence gradually increased with age in blood donors and STD patients, but reached a plateau at a young age in prostitutes and drug abusers. Males had a higher prevalence than females in blood donors (2.7% vs. 0), STD patients (8.2% vs. 7.5%), and drug abusers (69.0% vs. 57.1%), but the difference was not statistically significant. STD patients with syphilis had a higher prevalence (19.5%) than those affected with non-ulcerating STDs (5.3%). While unlicensed prostitutes had a lower prevalence (13.6%) than licensed prostitutes (44.9%), intravenous drug abusers had a higher prevalence (73.1%) than non-intravenous drug abusers (34.6%). There was a twofold increase in anti-HDV prevalence from 1986 to 1989 among prostitutes, but the prevalence remained unchanged in the general population and drug abusers. HDV infection remains limited to the high-risk groups and spread mainly by promiscuity and needle sharing in Taiwan.

Adult

Correlation of contractile function and passive properties of rabbit urinary bladder subjected to outlet obstruction--an in vitro whole bladder study.

The present study investigated the correlation between contractile function and passive properties of rabbit urinary bladder subjected to outlet obstruction. Mild bladder outlet obstruction was induced by placing silicone rings (7 mm. diameter) around the bladder necks of male New Zealand rabbits. The animals were sacrificed after 2 weeks of obstruction. Contractile function was evaluated by measuring the response of the in vitro whole bladder to 500 microM bethanechol administration. Passive properties was assessed by performing in vitro cystometry and stress-relaxation techniques utilizing six different infusion rates. When the intravesical pressure reached 30 cm. H2O the infusion was stopped, allowing the bladder to relax and intravesical pressure to drop to a steady state level. The results can be summarized as follows: 1) Although the intravesical pressure response to bethanechol was about the same in control (13.3 cm. H2O) and obstructed (12.4 cm. H2O) bladder, the obstructed bladder emptied significantly less than control (20.4 vs 89.3%); 2) the results of the passive properties study showed that bladder stiffness was significantly higher at all infusion rates in the obstructed bladder, 3) the obstructed bladder showed significantly less relaxation after rapid stretching of the whole bladder by high speed fluid infusion; 4) histological examination of obstructed bladders revealed marked fibrous thickening of the serosal layer, interstitial fibrosis of the muscle layers, and hypertrophic and/or degenerative changes of the muscle fibers. In summary, 2 weeks after mild outlet obstruction of the urinary bladder the emptying ability, but not pressure generation, was reduced along with increased bladder stiffness and diminished capacity for stress-relaxation. Interstitial fibrosis and changing the properties of the smooth muscle cells might be involved in the functional impairment and deranged viscoelasticity of the urinary bladder after outlet obstruction.

Animals

Use of perfluoroperhydrophenanthrene in the management of suprachoroidal hemorrhages.

BACKGROUND: Suprachoroidal hemorrhage may cause the expulsion of intraocular contents. Generally, cases of nonexpulsive suprachoroidal hemorrhage have a better outcome than their expulsive counterparts. Those cases with massive nonexpulsive suprachoroidal hemorrhage do better with treatment than without. Treatment modalities have included suprachoroidal hemorrhage drainage with or without intraocular volume reformation, and vitrectomy. METHODS: The authors used the liquid perfluorocarbon perfluoroperhydrophenanthrene in the treatment of three patients with nonexpulsive suprachoroidal hemorrhage. The perfluorocarbon was injected into the vitreous cavity while the suprachoroidal blood was drained through anterior sclerotomies. RESULTS: With 5 months of follow-up, complete resolution of the suprachoroidal blood was noted in all patients. All three patients had attached retinas, and postoperative visual acuities were improved over preoperative visual acuities. CONCLUSION: Perfluoroperhydrophenanthrene and other perfluorocarbon liquids may be beneficial in the treatment of certain cases of nonexpulsive suprachoroidal hemorrhages.

Aged

Perinatal mortality and prevalence of major congenital malformations of twins in Taipei city.

In order to examine perinatal mortality and prevalence of major congenital malformations in twins, deliveries in four teaching hospitals in Taipei City were studied. Among a total of 73,264 deliveries from October 1985 to June 1989, there were 844 pairs of twins. The zygosity of the twin pairs was determined by sex, placentation and 12 red blood cell antigens. There were 482 MZ and 252 DZ twin pairs identified, but the zygosity of a further 110 twin pairs was indeterminable due to lack of information on plancentation and/or blood types. A total of 4,573 singletons delivered in one study hospital from July 1986 to June 1987 were also studied as controls. The perinatal mortality rate was 7.5% for MZ twins, 1.4% for DZ twins, and 0.7% for singletons. The concordance rate of perinatal death was significantly higher in MZ (60%) than in DZ (0%) twins. The prevalence of major congenital malformations was 2.7% for MZ twins, 1.0% for DZ twins, and 0.6% for singletons. The concordance rate of major congenital malformations was 18% for MZ twins, but no DZ pair was concordant in any major congenital malformation. The concordance rate of facial clefts was 29% for MZ twins. There were 2 sets of conjoined twins giving a prevalence rate of 2.7 per 100,000 deliveries. These findings showing the prevalence of perinatal mortality and major congenital malformation to be highest in MZ twins, intermediate in DZ twins and lowest in singletons, suggest the importance of intrauterine environments in the determination of perinatal mortality and congenital malformations.

Congenital Abnormalities

Secular trend and associated factors of twinning in Taiwan.

Delivery records of public hospitals and local health centers were analyzed to investigate the secular trend of multiple births from 1955 to 1990 in Taiwan. Twinning rates decreased gradually from the late 1950s to 1973, slightly increased and remained stable from 1974 to 1980, and then increased strikingly from 1981 to 1990. During the study period, MZ rates were consistently higher than DZ rates except in 1986 when a higher DZ rate was observed. The highest MZ rate of 7.7 per 1,000 deliveries was observed in 1985, while the highest DZ rate of 4.6 per 1,000 deliveries was observed in 1986. The triplet incidence rate also declined from the early 1960s to 1973 and then increased markedly from 1974 to 1990. A case-control study including 482 MZ and 252 DZ twin pairs and 1,496 singletons was carried out in four teaching hospitals in Taipei City between October 1985 and June 1989 to examine factors related to twinning. The zygosity of twin pairs was determined by sex, placentation and red blood cell antigens. Multiple logistic regression analysis showed that the higher the maternal age, the lower the MZ and DZ rates, while the higher the parity, the higher the rates. There was no association of paternal age or of maternal educational level with twinning rates.

Adult

Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water.

In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.

Adult

Association of body build with non-insulin-dependent diabetes mellitus and hypertension among Chinese adults: a 4-year follow-up study.

Both cross-sectional and longitudinal studies on the association of body build with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension were conducted in Taiwan during the period 1986-1990. The cross-sectional study, was carried out in 1986 in Ta-An District of Taipei City and five rural areas evenly distributed in Taiwan Province. A total of 11,478 randomly selected subjects aged 40 years or over were surveyed. World Health Organization designations of diabetes and hypertension were followed. The longitudinal observation was made in 1990 for the cohort living in Taipei City who had neither diabetes nor hypertension in 1986. Of 2822 subjects, 1873 individuals participated in the follow-up study and 52 had died, giving a response rate of 67.6%. In comparison with Caucasian or Polynesian populations, Chinese adults have a much lower prevalence of obesity (body mass index [BMI] greater than 30 kg/m2). Univariate and multivariate analyses revealed both diabetes and hypertension increased as body build became heavier. The age-adjusted prevalence ratio and relative risk for the fourth quartile of BMI compared to the first quartile were 2.72 and 2.87, respectively, for diabetes as well as 2.96 and 2.24, respectively, for hypertension. Multiple logistic regression analyses revealed a slightly higher increase in prevalence of hypertension than that of diabetes for every 1 kg/m2 increase in BMI (1.16-fold and 1.12-fold, respectively), while a similar increase in BMI resulted in a slightly higher relative risk of diabetes than that of hypertension (1.14-fold and 1.11-fold, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Association between glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice: interaction with multiple risk factors.

This nonconcurrent cohort study was carried out to evaluate the association of neonatal jaundice with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and its interactions with other risk factors. The G-6-PD enzyme activity of 12,379 neonates was screened by a semi-quantitative fluorometric assay and double-checked by a quantitative method to identify a G-6-PD deficient cohort of 333 neonates. Matched with these on birth date, sex and delivery hospital were a G-6-PD normal cohort of 653 neonates. Neonatal jaundice was defined by a peak serum bilirubin (PSB) level of > or = 15 mg/dl. A significant association between G-6-PD deficiency and neonatal jaundice was observed in male but not female neonates. There was an inverse dose-response relation between G-6-PD activity and neonatal jaundice among male neonates. Both hypoxia/asphyxia and maternal hepatitis B surface antigen (HBsAg) carrier status were associated with an increased risk of neonatal jaundice among G-6-PD deficient but not G-6-PD normal male neonates. Based on multiple regression analyses, an additively synergistic effect on PSB level and severe jaundice (PSB > or = 20 mg/dl) was observed for G-6-PD deficiency and maternal HBsAg carrier status.

Cohort Studies

Seroepidemiology and evaluation of passive surveillance during 1988-1989 measles outbreak in Taiwan.

A seroepidemiological study was carried out to explore the risk factors of a measles outbreak that occurred among school children at a rural village (Li-Tse) in Taiwan. Among the 1166 participants, the percentage susceptible before the outbreak was 10.5% (122/1158) which was estimated as the sum of measles IgG-negative (29/1158) and IgM-positive (93/1166) individuals. Among 340 vaccinated children, 16 (4.7%) were measles IgM-positive and 10 (2.9%) were measles IgG-negative; therefore the vaccine failure rate was estimated to be 7.6% (26/340) and vaccine efficacy was 79.7% (95% confidence interval [CI] : 65.0-88.5). The most important risk factors for acquiring measles infection were the presence of other measles cases in the family (Odds Ratio [OR] = 32.5, P = 0.002) and the presence of more than two cases in a class (OR = 29.1, P = 0.003). The physician reporting rate was 6.1% (4/66), and the sensitivity of passive measles surveillance was only 4.3% (4/93) by active serosurvey. A concomitant rubella epidemic also amplified the inaccuracy of a passive reporting system based only on clinical diagnosis. Five children developed measles IgM but did not experience any symptoms, indicating that asymptomatic measles infection can occur. Our experience has highlighted three important areas for future measles elimination: (1) the need for serological evaluation of vaccinees, particularly those who were born during the introduction of mass immunization; (2) improvement in measles vaccine efficacy; and (3) further investigations on the role of asymptomatic transmission and susceptibles who remain after mass immunization.

Adolescent

Numerical simulation of steady flow in a two-dimensional total artificial heart model.

In this paper, a numerical simulation of steady laminar and turbulent flow in a two-dimensional model for the total artificial heart is presented. A trileaflet polyurethane valve was simulated at the outflow orifice while the inflow orifice had a trileaflet or a flap valve. The finite analytic numerical method was employed to obtain solutions to the governing equations in the Cartesian coordinates. The closure for turbulence model was achieved by employing the k-epsilon-E model. The SIMPLER algorithm was used to solve the problem in primitive variables. The numerical solutions of the simulated model show that regions of relative stasis and trapped vortices were smaller within the ventricular chamber with the flap valve at the inflow orifice than that with the trileaflet valve. The predicted Reynolds stresses distal to the inflow valve within the ventricular chamber were also found to be smaller with the flap valve than with the trileaflet valve. These results also suggest a correlation between high turbulent stresses and the presence of thrombus in the vicinity of the valves in the total artificial hearts. The computed velocity vectors and turbulent stresses were comparable with previously reported in vitro measurements in artificial heart chambers. Analysis of the numerical solutions suggests that geometries similar to the flap valve (or a tilting disk valve) results in a better flow dynamics within the total artificial heart chamber compared to a trileaflet valve.

Biomechanical Phenomena

Effect of histamine treatment on dopamine tachyphylaxis of canine tracheal smooth muscle.

In order to understand how histamine-sensitized airways may react to exogenous dopamine, we investigated the effect of histamine treatment on the dopamine-induced contractions of canine tracheal smooth muscle. The results showed that preconstricting muscle strips with histamine (10(-6) M to 10(-4) M) not only increased the amplitude of dopamine-induced contraction, but also lowered the concentration of dopamine required to provoke contraction from 10(-4) M to 10(-6) M. In muscle strips desensitized by repeated challenges of 10(-3) M dopamine, a 15-min treatment with 10(-4) M histamine transiently restored the response. The restored contractions were decreased by the dopaminergic antagonist, domperidone, and the alpha 2-adrenoceptor antagonist, yohimbine, and increased by the beta 1-adrenoceptor antagonist, atenolol. It is concluded that in addition to its role in mediating airway constriction, histamine can promote and enhance the contractile response of canine tracheal smooth muscle to dopamine. Histamine treatment restored the dopamine response of desensitized tracheal muscle with resensitization of the adrenoceptors.

Animals