Biomedical subjects

Ya-Hui Chang

Publications and source records attributed to Ya-Hui Chang.

9 recordsLinked to original sources

PubMed2006

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.

Adenocarcinoma↗

PubMed2005

Genomewide loss of heterozygosity and its clinical associations in non small cell lung cancer.

We extensively allelotyped a panel of 71 microdissected primary surgically resected non small cell lung cancer (NSCLC) tumors to identify chromosomal regions that are likely to contain tumor suppressor genes (TSGs) or associated with clinicopathologic and prognostic effects. Loss of heterozygosity (LOH) was detected by genotyping of 177 microsatellite markers and correlation of LOH with clinicopathologic parameters and prognosis was analyzed. Twenty markers showed an LOH frequency greater than 48%, and 8 of them (2p23.3, 2p24.3, 2q35, 6p22.2, 7p14.3, 7p22.2, 17q24.3 and 21q22.3) were novel in NSCLC. The high LOH regions were confirmed by further aligning continuous LOH regions from another set of 24 NSCLC tissues and defining 7 minimal deletion regions ranging from 1.29 to 12.26 cM. The aberrations of 8 markers showed a significant correlation with alteration of p16 and Rb proteins, suggesting the gene(s) located in the chromosomal loss that may interact with p16/Rb pathway. In addition, markers specifically associated with smoking, histology types and tumor stages were identified and the linked candidate TSGs were suggested. For example, marker D1S1612 closely linked with Mig-6 gene was associated with smoking patients, squamous cell carcinoma patients and late-stage patients. Furthermore, 3 markers, D2S2968, D6S2439 and D7S1818, were significantly associated with poor prognosis of NSCLC patients using both univariate and multivariate Cox's regression analyses (p = 0.035, 0.022 and 0.006, respectively). These markers can potentially be used for early lung cancer detection, outcome measurement and the positional cloning of new TSGs whose loss of function contributes to NSCLC tumorigenesis.

Aged↗

PubMed2005

Type II collagen gene variants and inherited osteonecrosis of the femoral head.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) causes disability that often requires surgical intervention. Most cases of ANFH are sporadic, but we identified three families in which there was autosomal dominant inheritance of the disease and mapped the chromosomal position of the gene to 12q13. METHODS: We carried out haplotype analysis in the families, selected candidate genes from the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1) from persons with inherited and sporadic forms of ANFH. RESULTS: We identified a G-->A transition in exon 50 of COL2A1 in affected members of a four-generation family with ANFH. This transition predicts the replacement of glycine with serine at codon 1170 in a GXY repeat of type II collagen. Another pedigree was shown to harbor the same transition, but the mutant allele occurred on a different haplotype background. In a third family, a G-->A transition in exon 33 of the gene, causing a glycine-to-serine change at codon 717, was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH. CONCLUSIONS: All the patients with familial ANFH whom we studied carried COL2A1 mutations. In families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease.

Adult↗

PubMed2005

TPMD: a database and resources of microsatellite marker genotyped in Taiwanese populations.

Taiwan Polymorphic Marker Database (TPMD) (http://tpmd.nhri.org.tw/) is a marker database designed to provide experimental details and useful marker information allelotyped in Taiwanese populations accompanied by resources and technical supports. The current version deposited more than 372,000 allelotyping data from 1425 frequently used and fluorescent-labeled microsatellite markers with variation types of dinucleotide, trinucleotide and tetranucleotide. TPMD contains text and map displays with searchable and retrievable options for marker names, chromosomal location in various human genome maps and marker heterozygosity in populations of Taiwanese, Japanese and Caucasian. The integration of marker information in map display is useful for the selection of high heterozygosity and commonly used microsatellite markers to refine mapping of diseases locus followed by identification of disease gene by positional candidate cloning. In addition, our results indicated that the number of markers with heterozygosity over 0.7 in Asian populations is lower than that in Caucasian. To increase accuracy and facilitate genetic studies using microsatellite markers, we also list markers with genotyping difficulty due to ambiguity of allele calling and recommend an optimal set of microsatellite markers for genotyping in Taiwanese, and possible extension of genotyping in other Mongoloid populations.

Alleles↗

PubMed2005

Elderly Nutrition and Health Survey in Taiwan (1999-2000): research design, methodology and content.

The purpose of the Elderly Nutrition and Health Survey in Taiwan (1999-2000) was to assess the diet, nutrition and health of persons aged 65 and above in Taiwan. A multi-staged, stratified, clustered probability sampling scheme was used in the survey. The survey population was stratified into a total of 13 strata. The four strata of "Hakka areas", "Mountain areas", " Eastern areas", and "PengHu islands" were unique in their ethnicity or geographic locations. The remaining areas of Taiwan were stratified into "Northern", "Central", and "Southern" parts with these 3 strata, then each subdivided into a further 3 strata based on population density. The household interview of the survey was arranged such that effect of seasonal variation was taken into account. A total of 1,937 persons completed the interview and 2,432 persons completed the health exam. The following data were collected: (1) Interview data : household information, basic demographics, 24 hour dietary recall, food frequency and habit, knowledge, attitudes and practice, medical history, 36-item Short Form for generic health status, and physical activity. (2) Health exam data: blood sample for measurement of nutritional biochemical indicators and complete clinical chemistry profile, urine sample for urinary electrolytes, anthropometric measurements, ECG, blood pressure, body temperature, pulmonary function, and an osteoporosis assessment. Data from the survey were analyzed using SUDAAN to adjust for the design effect and to obtain unbiased estimates of the mean, standard error and confidence intervals. Survey respondents were slightly younger compared to non-respondents; however, after weighting and adjustment with SUDAAN, the education levels and ethnicity of respondents and non-respondents were similar indicating lack of bias. We anticipate that the results of this survey will be of benefit in understanding the nutritional status of the elderly, the relationship between nutrition and health, and factors influencing elderly persons' nutritional status. Furthermore, this information could be used in the development of public health nutrition policy aimed at improving the nutrition and health of the elderly in Taiwan.

Aged↗

PubMed2005

Intake levels and major food sources of energy and nutrients in the Taiwanese elderly.

The purpose of this article is to examine dietary intake levels and major food sources of energy and nutrients for the Taiwanese elderly in order to relate nutrient intakes to food choices and to provide suggestions for dietary improvement. The data were derived from the 24-hour recalls from 1,911 subjects (955 males and 956 females) aged 65 and above, who participated in the Elderly NAHSIT carried out from 1999 to 2000. The differences in food consumption patterns between the elderly and younger adults (aged 19 to 64) were also evaluated by comparison with data obtained from NAHSIT 1993-1996. The results revealed that cereals/roots, meat, other protein-rich foods and fats/oils contributed most to daily energy intake. The energy contributions from fats/oils, poultry, meat, other protein-rich foods, refreshments/snacks, alcoholic beverages, and miscellaneous food groups were lower in elderly diets compared with those of younger adults. Meat and cereals/roots were the major food sources of protein. The main carbohydrate-contributing food group was cereals/roots, while primary lipid sources were meat and fats/oils for the elderly. The food groups with a high contribution to vitamin intake were the following: vegetables for vitamin A; meat and cereals/roots for vitamin B1; dairy products, vegetables, cereals/roots and meat for vitamin B2; cereals/roots, seafood and meat for niacin; meat, vegetables and cereals/roots for vitamin B6; plant oils for vitamin E; and vegetables and fruit for vitamin C. The highest ranked food sources for minerals are listed as follows: dairy products, vegetables and seafood for calcium; dairy products and cereals/roots for phosphorous; vegetables and meat for iron; and vegetables, cereals/ roots, other protein-rich foods and seafood for magnesium. The elderly were found to consume more salt, dairy products and vegetables, but less poultry and meat than their younger counterparts. In summary, differences in consumption patterns between the elderly and younger adults was reflected in differences in common food sources of energy and specific nutrients. The dietary patterns of the elderly are in general "healthier" than that of younger adults except for higher salt intake among the elderly. Nonetheless, our elderly population needs to increase their intake of calcium, magnesium, vitamins E and B6, and dietary fiber, and decrease their consumption of salt. Promoting the ingestion of whole-grain and nut products may be a useful strategy to improve the nutritional status of the Taiwanese elderly, aiming at increasing the percentage of energy obtained from carbohydrates and the daily intake of vitamins E and B6, magnesium, and dietary fiber. Suitable strategies are also needed to improve the calcium status of Taiwanese elderly, particularly as a high proportion of them are either lactose intolerant or dislike dairy products.

Aged↗

PubMed2004

Clustering of minimal deleted regions reveals distinct genetic pathways of human hepatocellular carcinoma.

Systematic scan and statistical analysis of loss of heterozygosity (LOH) has been widely used to define chromosomal aberrations in various cancers for cloning of tumor suppressor genes and for development of prognostic markers. However, the establishment of novel strategies is needed, so that the nonrandom but heterogeneous chromosomal aberration data could provide significant insights into our understanding of molecular pathogenesis of cancers. After comprehensive allelotyping of recurrent allelic losses with 441 highly informative microsatellite markers and overlapping LOH regions on human hepatocellular carcinoma (HCC) chromosomes, 33 minimal deleted regions (MDRs) were revealed. Five and 15 of the 33 MDRs have physical intervals in less than 5 and 10 Mb, respectively, with the smallest MDR9p1 of 2.2 Mb located at 9p21.3-p21.2. Statistical and Kaplan-Meier survival analysis revealed a significant association between the loss of MDR15q1 (15q21.1-q22.2) and the HCC patient survival (adjusted P = 0.033). After cluster analysis of 33 MDRs that represented LOH profiles of each HCC tissue based on clinicopathological features and p53 mutations, two major genetic pathways, low-stage and advanced-stage HCC, were uncovered based on high concordance of MDR clusters. We propose that the definition of genome-wide MDRs on the cancer genome not only narrows down the location of existing tumor suppressor genes to facilitate positional candidate cloning and develop potential prognostic markers after statistical association of MDRs with clinicopathological features but also dissects genetic interactions and pathways of chromosomal aberrations in tumorigenesis.

Carcinoma, Hepatocellular↗

PubMed2003

Characterization of rifampicin-resistant Mycobacterium tuberculosis in Taiwan.

Sixty-three rifampicin-resistant (Rif(r)) isolates of Mycobacterium tuberculosis from Kaohsiung, Taiwan, were analysed for mutations in the core region (69 bp, codons 511-533) of the rpoB gene. Some 84.1 % (53/63) of the resistant isolates showed mutations in this region, especially in codons 531 (41.5 %), 526 (18.9 %), 516 (15.1 %) and 533 (7.5 %). Five novel alleles of a total of 16 different types of mutations were identified in Rif(r) isolates. Ten Rif(r) isolates (15.9 %) exhibited no mutations in the core region of rpoB. Also, they did not show mutations in another 365 bp fragment (codons 99-220) of rpoB. The agar proportion method was used to determine the relationship between the degree of rifampicin resistance and alterations in the core region of rpoB. The results revealed that the mean MIC was 92.38 micro g ml(-1) for the 53 isolates with a mutation in the core region, whereas the mean MIC of the other 10 isolates without mutations was only 24.8 micro g ml(-1). This indicates that the isolates with mutations in the core region had higher levels of resistance than those without mutations in this region. IS6110 restriction fragment length polymorphism (RFLP) was used for typing of 55 Rif(r) M. tuberculosis isolates. Isolates contained two to 19 copies of IS6110, with sizes ranging from 600 to 16 000 bp. The majority (85 %) contained six to 16 copies. No strains lacking IS6110 were found. A total of 54 of 55 RFLP types were defined at the 90 % similarity level. The observation of varied IS6110-associated banding patterns indicates that an outbreak of drug-resistant tuberculosis did not occur in this area.

Base Sequence↗

PubMed2002

Prevalence of dyslipidemia and mean blood lipid values in Taiwan: results from the Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996).

This paper reports the blood lipid status of people aged 4 years and older in Taiwan. The data is based on the Nutrition and Health Survey in Taiwan (NAHSIT: 1993-1996), which adopted a multi-stage, stratified clustering sampling scheme. Altogether, 5097 subjects (2451 males and 2646 females) had data on triglyceride and 5643 subjects (2736 males and 2907 females) had data on cholesterol. We found that (a) cholesterol levels of males were lower than females in mid-to old age group (> or = 45 years old); (b) triglyceride values of females were lower than males in young adulthood (19-44 years), but higher than males after the age of 45 years, and (c) adult females had higher HDL-C value and lower ratio of total cholesterol to HDL-C than males. The prevalence of hypercholesterolemia was 10.2% in adult males and 12.6% in mid-to-old aged men, and that in females was 11.2% and 24.4%, respectively. The prevalence of hypertriglyceridemia was 13.4% and 6.1% in adult males and females (> or = 19 years as a whole), respectively. It was 12.3% in mid-to-old aged men (> or = 45 years), and 11.9% in women. The mean cholesterol values were similar to values of several previous surveys in different areas of Taiwan. But it was higher than those in some areas of Mainland China, and lower than those of western countries. People in metropolitan cities had a higher level of blood cholesterol than other areas. The average triglyceride values of males and females were higher than those of previous studies in Taiwan and of people in Mainland China. Mountainous stratum with predominantly aboriginal residents had higher level of triglycerides and body mass index (BMI) than other strata. The associations between dietary intakes of men and women and blood lipids were examined controlling for age and BMI. Result showed that Keys score, which was derived from saturated fat, polyunsaturated fat and dietary cholesterol of a 24-hour recall, was positively related to blood cholesterol and LDL-C in men, but not in women. Average alcohol intakes per day were related to HDL-C positively, but LDL-C negatively in men and women. The regional differences in blood lipid profiles in Taiwan are consistent with the dietary and life-style variations island-wide.

Adolescent↗