Biomedical subjects

Jau-Tsuen Kao

Publications and source records attributed to Jau-Tsuen Kao.

15 recordsLinked to original sources

PubMed2006

Comparison of three automated urinalysis systems--Bayer Clinitek Atlas, Roche Urisys 2400 and Arkray Aution Max for testing urine chemistry and detection of bacteriuria.

BACKGROUND: Our study is aimed to determine the performance of 3 automated urinalysis systems-Clinitek Atlas, Urisys 2400 and Aution Max. METHODS: One thousand urine specimens were analyzed with the 3 automated systems. The results of the 3 assays were compared for testing urine chemistry and evaluating the capacity of leukocyte esterase and nitrite to detect bacteriuria. RESULTS: The correlation between the 3 instruments represented as within 1 grading difference was better between the Atlas and Aution Max systems for pH, blood, glucose, urobilinogen, ketone and specific gravity. For protein and nitrite, better correlation was observed between the Atlas and Urisys 2400, while the Aution Max and Urisys 2400 conveyed better correlation for bilirubin and white blood cells. The sensitivity and specificity of both the leukocyte esterase and nitrite in screening for significant bacteriuria were 71.7, 58.9, 70.8% and 99.1, 99.1 and 97.2%, for the Clinitek Atlas, Aution Max and Urisys 2400, respectively. CONCLUSIONS: The automated urinalysis systems demonstrate acceptable correlations with each other in urine chemistries, especially between the Clinitek Atlas and Aution Max systems on the majority of items. The specificity and negative predictive value of leukocyte esterase and nitrite of the 3 instruments for screening of significant bacteriuria were sufficient to avoid unnecessary urine culture.

Bacteriuria↗

PubMed2006

Multinomial logistic regression approach to haplotype association analysis in population-based case-control studies.

BACKGROUND: The genetic association analysis using haplotypes as basic genetic units is anticipated to be a powerful strategy towards the discovery of genes predisposing human complex diseases. In particular, the increasing availability of high-resolution genetic markers such as the single-nucleotide polymorphisms (SNPs) has made haplotype-based association analysis an attractive alternative to single marker analysis. RESULTS: We consider haplotype association analysis under the population-based case-control study design. A multinomial logistic model is proposed for haplotype analysis with unphased genotype data, which can be decomposed into a prospective logistic model for disease risk as well as a model for the haplotype-pair distribution in the control population. Environmental factors can be readily incorporated and hence the haplotype-environment interaction can be assessed in the proposed model. The maximum likelihood estimation with unphased genotype data can be conveniently implemented in the proposed model by applying the EM algorithm to a prospective multinomial logistic regression model and ignoring the case-control design. We apply the proposed method to the hypertriglyceridemia study and identifies 3 haplotypes in the apolipoprotein A5 gene that are associated with increased risk for hypertriglyceridemia. A haplotype-age interaction effect is also identified. Simulation studies show that the proposed estimator has satisfactory finite-sample performances. CONCLUSION: Our results suggest that the proposed method can serve as a useful alternative to existing methods and a reliable tool for the case-control haplotype-based association analysis.

Algorithms↗

PubMed2006

Association between the apolipoprotein E genotypes and breast cancer patients in Taiwanese.

To display the association between the apolipoprotein E (APOE) genotypes and breast cancer patients, a cross sectional study including 291 patients and 148 controls was performed. The APOE genotypes were measured in all participants, and the pathological diagnosis, estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER-2) among breast cancer patients were collected. The results showed the APOE allele frequency in breast cancer patients was 11.7% epsilon2 carriers, 74.6% epsilon3 carriers and 13.7% epsilon4 carriers, and there was no significant difference when they were compared with those of the control group (15.5% epsilon2 carriers, 74.3% epsilon3 carriers and 10.1% epsilon4 carriers; p=0.342). Among the patients in pre-menopause, showed a higher frequency of epsilon2 carriers had the cancer site on the left than that of the epsilon3 carriers (78.6% versus 40.3%; p=0.019). Among breast cancer patients, there was no significant association between the APOE genotypes and menopausal status, pathological diagnosis, estrogen receptor, progesterone receptor, and HER-2. Our findings demonstrated that the APOE genotypes were not associated with breast cancer patients, and epsilon2 allele tended to induce breast cancer on the left site among those patients in pre-menopause.

Adult↗

PubMed2006

A two-stage design for multiple testing in large-scale association studies.

Modern association studies often involve a large number of markers and hence may encounter the problem of testing multiple hypotheses. Traditional procedures are usually over-conservative and with low power to detect mild genetic effects. From the design perspective, we propose a two-stage selection procedure to address this concern. Our main principle is to reduce the total number of tests by removing clearly unassociated markers in the first-stage test. Next, conditional on the findings of the first stage, which uses a less stringent nominal level, a more conservative test is conducted in the second stage using the augmented data and the data from the first stage. Previous studies have suggested using independent samples to avoid inflated errors. However, we found that, after accounting for the dependence between these two samples, the true discovery rate increases substantially. In addition, the cost of genotyping can be greatly reduced via this approach. Results from a study of hypertriglyceridemia and simulations suggest the two-stage method has a higher overall true positive rate (TPR) with a controlled overall false positive rate (FPR) when compared with single-stage approaches. We also report the analytical form of its overall FPR, which may be useful in guiding study design to achieve a high TPR while retaining the desired FPR.

Cost-Benefit Analysis↗

PubMed2006

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP.

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). METHODS: We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. RESULTS: The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP=7.23xAxSYM BNP+2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 degrees Celsius or 25 degrees Celsius for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. CONCLUSIONS: Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.

Enzyme-Linked Immunosorbent Assay↗

PubMed2005

Regression-based association analysis with clustered haplotypes through use of genotypes.

Haplotype-based association analysis has been recognized as a tool with high resolution and potentially great power for identifying modest etiological effects of genes. However, in practice, its efficacy has not been as successfully reproduced as expected in theory. One primary cause is that such analysis tends to require a large number of parameters to capture the abundant haplotype varieties, and many of those are expended on rare haplotypes for which studies would have insufficient power to detect association even if it existed. To concentrate statistical power on more-relevant inferences, in this study, we developed a regression-based approach using clustered haplotypes to assess haplotype-phenotype association. Specifically, we generalized the probabilistic clustering methods of Tzeng to the generalized linear model (GLM) framework established by Schaid et al. The proposed method uses unphased genotypes and incorporates both phase uncertainty and clustering uncertainty. Its GLM framework allows adjustment of covariates and can model qualitative and quantitative traits. It can also evaluate the overall haplotype association or the individual haplotype effects. We applied the proposed approach to study the association between hypertriglyceridemia and the apolipoprotein A5 gene. Through simulation studies, we assessed the performance of the proposed approach and demonstrate its validity and power in testing for haplotype-trait association.

Apolipoprotein A-V↗

PubMed2005

Nick-directed repair of palindromic loop mismatches in human cell extracts.

Palindromic sequences present in DNA may form secondary structures that block DNA replication and transcription causing adverse effects on genome stability. It has been suggested that hairpin structures containing mispaired bases could stimulate the repair systems in human cells. In this study, processing of variable length of palindromic loops in the presence or absence of single-base mismatches was investigated in human cell extracts. Our results showed that hairpin structures were efficiently processed through a nick-directed mechanism. In a similar sequence context, mismatch-containing hairpins have higher repair efficiencies. We also found that shorter hairpins are generally better repaired. A strand break located either 3' or 5' to the loop is sufficient to activate hairpin repair on the nicked strand. The reaction requires Mg(2+), the four dNTPs and hydrolysis of ATP for efficient repair on both palindromic loop insertions and deletions. Correction of each of these heteroduplexes was abolished by aphidicolin but was relatively insensitive to the presence of ddTTP, suggesting involvement of polymerase(s) alpha and/or delta. These findings are most consistent with the nick-directed loop repair pathway being responsible for processing hairpin heterologies in human cells.

Bacteriophages↗

PubMed2004

Interaction of nick-directed DNA mismatch repair and loop repair in human cells.

In human cells, large DNA loop heterologies are repaired through a nick-directed pathway independent of mismatch repair. However, a 3'-nick generated by bacteriophage fd gene II protein heterology is not capable of stimulating loop repair. To evaluate the possibility that a mismatch near a loop could induce both repair types in human cell extracts, we constructed and tested a set of DNA heteroduplexes, each of which contains a combination of mismatches and loops. We have demonstrated that a strand break generated by restriction endonucleases 3' to a large loop is capable of provoking and directing loop repair. The repair of 3'-heteroduplexes in human cell extracts is very similar to that of 5'-heteroduplex repair, being strand-specific and highly biased to the nicked strand. This observation suggests that the loop repair pathway possesses bidirectional repair capability similar to that of the bacterial loop repair system. We also found that a nick 5' to a coincident mismatch and loop can apparently stimulate the repair of both. In contrast, 3'-nick-directed repair of a G-G mismatch was reduced when in the vicinity of a loop (33 or 46 bp between two sites). Increasing the distance separating the G-G mismatch and loop by 325 bp restored the efficiency of repair to the level of a single base-base mismatch. This observation suggests interference between 3'-nick-directed large loop repair and conventional mismatch repair systems when a mispair is near a loop. We propose a model in which DNA repair systems avoid simultaneous repair at adjacent sites to avoid the creation of double-stranded DNA breaks.

Base Pair Mismatch↗

PubMed2004

Method for testing for human papillomavirus infection in patients with cervical intraepithelial disease.

To determine whether DNA detection of high-risk human papillomavirus could represent a reliable screening technique and a useful follow-up method, we investigated the performance of the Hybrid Capture II assay in detecting high-grade cervical lesions. The test positivity at 1.86 pg/ml had a high sensitivity (94.7%) and improved specificity. It was also a suitable follow-up method for detecting the recurrence of cervical intraepithelial disease in patients.

Adolescent↗

PubMed2004

Association of apolipoprotein E genotypes with serum lipid profiles in a healthy population of Taiwan.

Apolipoprotein E (apoE, protein; APOE, gene) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described associations between apoE genotypes, coronary artery disease (CAD), and other risk factors. The aim of this study was to investigate the association between apoE genotypes and serum lipid profiles in a healthy population of 220 volunteers at Kaohsiung in Taiwan. Other CAD risk factors such as serum levels of apolipoprotein A-I (apoA-I), apolipoprotein B, (apoB), homocysteine (Hcy), folate, and vitamin B12 were also measured. ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the study population, the frequency of apoE allele epsilon3 was greatest (85.2%); the frequency of epsilon2 was 8.4%; and that of epsilon4 was 6.4%. The serum apoA-1/apoB ratio showed significant difference among the 3 apoE genotype groups (p 0.0001); the apoA-1/apoB ratio was 1.9 +/- 0.1 (mean +/- SD) in the epsilon2 group, vs 1.4 +/- 0.04 and 1.5 +/- 0.12 in the epsilon3 and epsilon4 groups, respectively. No significant associations were found between APOE alleles and the serum levels of the various lipids or other CHD risk factors.

Apolipoproteins E↗

PubMed2003

A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia.

The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-coding regions of the gene, this variant occurs within the coding region and causes the change of amino acid sequence (a substitution of a cysteine for a glycine residue). The minor allele frequencies were 0.042 and 0.27 (P<0.001) for control and hypertriglyceridemic patients, respectively. The serum triglyceride level was significantly different among the genotypic groups (G/G 92.5+/-37.8 mg/dl, G/T 106.6+/-34.8 mg/dl, T/T 183.0 mg/dl, P=0.014) in control subjects. Multiple logistic regression revealed individuals carrying the minor allele had age, gender and BMI (body mass index)-adjusted odds ratio of 11.73 (95% confidence interval of 6.617-20.793; P<0.0001) for developing hypertriglyceridemia in comparison to individuals without that allele. These findings suggest the possible use of c.553G>T polymorphisms in APOA5 as prognostic indicators for hypertriglyceridemia susceptibility in Chinese.

Age Factors↗

PubMed2003

Apolipoprotein epsilon 2/3 genotype and type III hyperlipoproteinemia among Taiwanese.

BACKGROUND: Type III hyperlipoproteinemia (HLP) is a genetic disorder of lipid metabolism in humans that predisposes affected subjects to the premature development of atherosclerosis. Most type III HLP occurs in homozygous carriers of apolipoprotein (apo) E2. The aims of this study were to determine the frequencies of different apo E genotypes in type III HLP in Taiwanese and to assess the possibility of apo E mutants in these patients. MATERIALS AND METHODS: Four hundred and seven patients with hyperlipoproteinemia were recruited. Electrophoresis, apo E genotyping and sequencing were performed. RESULTS: Of the 407 hyperlipoproteinemia, 8 were identified as type III HLP. In contrast to reports of high apo epsilon 2/2 genotype prevalence, only two of the type III HLP subjects were of the apo epsilon 2/2 genotype (25%). Fifty percent of the type III HLP were of apo epsilon 2/3 genotype. This observation was further reflected in a lower frequency of the epsilon 2 allele (0.563) and higher epsilon 3 allele (0.375) frequency. No rare apo E variant was found by direct sequencing. CONCLUSION: The most common genotype of type III HLP in Taiwan was apo epsilon 2/3 instead of apo epsilon 2/2.

Aged↗

PubMed2003

Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3.

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.

Aged↗

PubMed2003

Interference caused by the contents of serum separator tubes in the Vitros CRP assay.

BACKGROUND: We have observed discrepancies between C-reactive protein (CRP) measured in serum prepared from a serum separator tube (SST) and that obtained from a plain tube, when using the Vitros CRP assay. Our study aimed at elucidating the cause of these discrepancies. METHODS: Eighty-seven specimens from hospitalized patients with various types of inflammatory disease were analysed using a fixed-point immuno-rate method on a Vitros CRP slide. The serum was prepared simultaneously in both vacuum and SSTs. We also performed mixing tests by adding 47 samples of serum prepared from plain tubes to SSTs and incubating for 15 min before CRP analysis. RESULTS: Lower values of CRP were found in serum prepared from plain tubes than in serum from SSTs. Addition of serum prepared from plain tubes to SSTs and incubating for 15 min increased the CRP values significantly. The ratio of CRP measured in serum prepared from plain tubes and from SSTs did not differ significantly from the ratio obtained when serum was prepared in a plain tube then added to an SST. DISCUSSION: We propose that SSTs can adsorb some macromolecules that form complexes with CRP. The addition of SST gel to serum results in the release of CRP molecules from these complexes, which enhances the antigen-antibody reaction on the Vitros CRP slide and increases the measured CRP concentrations.

Antibodies, Monoclonal↗

PubMed2002

Characterization of apolipoprotein E genetic variations in Taiwanese: association with coronary heart disease and plasma lipid levels.

Apolipoprotein E (apoE, protein; APOE, gene) is important in lipoprotein metabolism. Three isoforms, apoE2 (Cys112 Cys158), apoE3 (Cys112 Arg158), and apoE4 (Arg112 Arg158), are present in the general population. This report investigates the frequency distribution of apoE isoforms and the association of APOE genotypes with plasma lipid profile and coronary heart disease (CHD) in a population of Taiwan. ApoE isoforms were determined genetically by polymerase chain reaction and HhaI restriction enzyme digestion in control and coronary heart disease (CHD) patients. Plasma lipid and lipoprotein concentrations were also determined. The control group exhibited frequencies of 84.6% APOE3, 7.9% APOE4, 7.5% APOE2, 70.6% APOE3E3, 14.4% APOE3E4, 13.6% APOE2E3, and 1.4% APOE2E4. Comparable frequencies were observed in the CHD group. In both APOE2 carrier and APOE3E3 groups, the CHD patients expressed abnormal lipid profiles while the control group expressed normal lipid profiles. The APOE4 carriers, however, expressed abnormal lipid profiles in both normal control and CHD groups. Extremely high apoE levels in the hypertriglyceridemic group (TG > 400 mg/dL) seemed to be undesirable and were often observed in CHD patients.

Adult↗