Biomedical subjects

Jeng-Min Chiou

Publications and source records attributed to Jeng-Min Chiou.

6 recordsLinked to original sources

PubMed2005

Arsenic ingestion and increased microvascular disease risk: observations from the south-western arseniasis-endemic area in Taiwan.

BACKGROUND: We established the association between arsenic ingestion and increased risk of vascular diseases associated with diabetes. However, the specific microvascular diseases in relation to arsenic exposure level have not been well reported. METHODS: The study population was obtained through national health database linkage. A total of 28 499 subjects living in the study area were successfully linked with their medical records from the National Health Insurance database in 1999-2000. The arsenic concentrations of artesian well water in the villages of the study area were utilized as indices of previous ingestion level. Both stratified analysis and unconditional logistic regression were used to examine mainly neurological and renal disease in relation to the arsenic exposure taking into account diabetes status. RESULTS: The age-adjusted and gender-adjusted prevalence of microvascular diseases was 7.51% [95% confidence interval (CI) 7.50-7.51] for arsenic level of <0.1 mg/litre, and then increased from 6.59% (6.59-6.60) for the arsenic concentrations of 0.1-0.29 mg/litre to 8.02% (8.02-8.03) and 11.82% (11.81-11.83) for those of 0.3-0.59 mg/litre and > or =0.6 mg/litre in non-diabetic subjects. For diabetic patients, the prevalence was 16.41% (95% CI 16.37-16.45), 15.85% (15.8-15.9), 21.69% (21.6-21.8), and 28.31% (28.2-28.4) for arsenic levels <0.1, 0.1-0.29, 0.3-0.59, and > or =0.6 mg/litre, respectively. The prevalence of microvascular diseases increased significantly with arsenic exposure, especially at higher levels, and the relationship is stronger in diabetics than in non-diabetic subjects. The results for neurological disease are very similar, and the patterns are the same for renal disease. CONCLUSIONS: The increased prevalence of microvascular diseases, including neurological and renal disorders, is associated with arsenic ingestion. This excess risk was further elevated in diabetic subjects. Further studies are necessary to verify the hypotheses of threshold or dose-response relationships.

Adult↗

PubMed2005

Multipoint linkage mapping using sibpairs: non-parametric estimation of trait effects with quantitative covariates.

Multipoint linkage analysis using sibpair designs remains a common approach to help investigators to narrow chromosomal regions for traits (either qualitative or quantitative) of interest. Despite its popularity, the success of this approach depends heavily on how issues such as genetic heterogeneity, gene-gene, and gene-environment interactions are properly handled. If addressed properly, the likelihood of detecting genetic linkage and of efficiently estimating the location of the trait locus would be enhanced, sometimes drastically. Previously, we have proposed an approach to deal with these issues by modeling the genetic effect of the target trait locus as a function of covariates pertained to the sibpairs. Here the genetic effect is simply the probability that a sibpair shares the same allele at the trait locus from their parents. Such modeling helps to divide the sibpairs into more homogeneous subgroups, which in turn helps to enhance the chance to detect linkage. One limitation of this approach is the need to categorize the covariates so that a small and fixed number of genetic effect parameters are introduced. In this report, we take advantage of the fact that nowadays multiple markers are readily available for genotyping simultaneously. This suggests that one could estimate the dependence of the generic effect on the covariates nonparametrically. We present an iterative procedure to estimate (1) the genetic effect nonparametrically and (2) the location of the trait locus through estimating functions developed by Liang et al. ([2001a] Hum Hered 51:67-76). We apply this new method to the linkage study of schizophrenia to illustrate how the onset ages of each sibpair may help to address the issue of genetic heterogeneity. This analysis sheds new light on the dependence of the trait effect on onset ages from affected sibpairs, an observation not revealed previously. In addition, we have carried out some simulation work, which suggests that this method provides accurate inference for estimating the location of quantitative trait loci.

Algorithms↗

PubMed2005

Neutralizing antibody response and SARS severity.

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

Adult↗

PubMed2004

Inhibition of hepatitis C virus replication by arsenic trioxide.

Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that As2O3 at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC50) of As2O3 required to inhibit HCV replication was 0.35 microM when it was determined by a reporter-based HCV replication assay, and the EC50 was below 0.2 microM when it was determined by quantitative reverse transcription-PCR analysis. As2O3 did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of As2O3 and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, As2O3 at 0.3 microM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of As2O3 may lead to the development of agents with potent activities against HCV or related viruses.

Antiviral Agents↗

PubMed2003

Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan.

There is evidence indicating that ingestion of arsenic may predispose the development of diabetes mellitus in arsenic-endemic areas in Taiwan. However, the prevalence of diabetes and related vascular diseases in the entire southwestern arseniasis-endemic and nonendemic areas remains to be elucidated. We used the National Health Insurance Database for 1999-2000 to derive the prevalence of non-insulin-dependent diabetes and related vascular diseases by age and sex among residents in southwestern arseniasis-endemic and nonendemic areas in Taiwan. The study included 66,667 residents living in endemic areas and 639,667 in nonendemic areas, all greater than or equal to 25 years of age. The status of diabetes and vascular diseases was ascertained through disease diagnosis and treatment prescription included in the reimbursement claims of clinics and hospitals. The prevalence of non-insulin-dependent diabetes, age- and gender-adjusted to the general population in Taiwan, was 7.5% (95% confidence interval, 7.4-7.7%) in the arseniasis-endemic areas and 3.5% (3.5-3.6%) in the nonendemic areas. Among both diabetics and nondiabetics, higher prevalence of microvascular and macrovascular diseases was observed in arseniasis-endemic than in the nonendemic areas. Age- and gender-adjusted prevalence of microvascular disease in endemic and nonendemic areas was 20.0% and 6.0%, respectively, for diabetics, and 8.6% and 1.0%, respectively, for nondiabetics. The corresponding prevalence of macrovascular disease was 25.3% and 13.7% for diabetics, and 12.3% and 5.5% for nondiabetics. Arsenic has been suggested to increase the risk of non-insulin-dependent diabetes mellitus and its related micro- and macrovascular diseases.

Adult↗

PubMed2002

Fertility and life span: late children enhance female longevity.

The relation between fertility and postmenopausal longevity is investigated for a sample of 1635 women from a historical (17th to 18th century) French-Canadian cohort who lived past the age of 50 years. We find that increased fertility is linked to increased rather than decreased postreproductive survival. Postreproductive life expectancy extension is found to be tied to late births. This finding sheds new light on the cost of reproduction and may be viewed as supporting a new paradigm that states that reproductive potential drives remaining longevity. The emerging reproductive potential concept complements the well-established cost of reproduction hypothesis. Alternative explanations for the observed association are also explored. A specific finding is that the degree to which mortality increases for 50-year-old mothers as a result of senescence is closely tied to the logarithm of the age of their youngest child. For example, 50-year-old mothers experience a mortality decrease of 38% and an increase of remaining lifetime of 3.93 years for every 10-fold decrease in the age of their youngest child. This amount of gain in remaining life expectancy would apply to a mother with a two-year-old child as compared with a mother with a 20-year-old offspring. We also find evidence for the existence of vulnerable periods in human life history that are characterized by phases of heightened mortality and are found to be tied to reproduction and senescence.

Child, Preschool↗