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Biomedical subjects

M Y Tsai

Publications and source records attributed to M Y Tsai.

At least 19 recordsLinked to original sources
PubMed2001

Surface characterization and platelet adhesion studies of self-assembled monolayer with phosphonate ester and phosphonic acid functionalities.

Because of its well-defined surface configuration and creative chemical structure, an alkanethiol self-assembled monolayer (SAM) on gold is a model surface for a blood compatibility investigation. In this study two laboratory-synthesized long-chain alkanethiols, HS(CH(2))(10)PO(3)-(C(2)H(5))(2) and HS(CH(2))(10)PO(3)H(2), were employed for the direct preparation of SAMs with nonionic and ionic functional groups. Various instrumental analyses confirmed the high purity of the phosphonate ester and phosphonic acid terminated alkanethiols. The surface characterization results showed the -PO(3)H(2) terminated SAM was more hydrophilic than the -PO(3)(C(2)H(5))(2) one. Higher hysteresis values for the -PO(3)(C(2)H(5))(2) and -PO(3)H(2) terminated SAMs were noted, which were possibly due to the steric hindrance of the bulky terminal groups. In addition, the O(2) plasma + EtOH-rinse pretreated Au sample was hydrophilic because of the residual gold oxide on the surface. This finding was supported by electron spectroscopy for chemical analysis (ESCA) as well. The ESCA analysis also indicated bulky and polar terminal groups [-PO(3)(C(2)H(5))(2) and -PO(3)H(2)] were situated in the outermost layer of its monolayer. The platelet reactivity on the SAM with the nonionic group -PO(3)(C(2)H(5))(2) was less than those of the ionic terminated SAMs -COOH and -PO(3)H(2). The O(2) plasma + EtOH-rinse pretreated gold substrate exhibited the least platelet-activating surface among the different pretreated Au substrates studied.

Biocompatible Materials↗
PubMed2001

A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study.

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk=1.60, 95% CI 0.9-2.9). After adjusting for other confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and triglycerides), the association became stronger (relative risk=2.70, 95% CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.

Cohort Studies↗
PubMed2001

Short-term variability in the measurement of plasma homocysteine, fasting and post-methionine loading.

OBJECTIVES: Hyperhomocysteinemia is associated with premature cerebral, peripheral and coronary vascular disease. Evaluation of the significance of changes in plasma total homocysteine (tHcy) results obtained by analysis of serial specimens may be accomplished only by taking into account biologic (between-person and within-person) as well as analytical variation. Since the repeatability of a measurement significantly determines our ability to associate tHcy level with the presence of disease, this study was performed to evaluate various components of variation in tHcy values. DESIGN AND METHODS: We report the within-person, between-person, and methodological variability of tHcy, both fasting and postmethionine load (PML) values, in 20 healthy volunteers from whom samples were drawn weekly for 4 weeks. RESULTS: The short-term reliability coefficient (R) was 0.72 for fasting tHcy and 0.83 for PML tHcy. CONCLUSIONS: The current study demonstrates for the first time that the short-term reliability coefficient for PML tHcy is relatively high (0.83), suggesting that an individual's PML tHcy, like fasting tHcy, is relatively constant over at least one month, and that a single measurement should provide a reasonable characterization of an individual's PML tHcy concentration.

Adult↗
PubMed2001

Determination of the efficiency of controlled ovarian hyperstimulation in the gonadotropin-releasing hormone agonist-suppression cycle using the initial follicle count during gonadotropin stimulation.

PURPOSE: Our purpose was to evaluate the relationship between the initial follicle count during gonadotropin stimulation after gonadotropin-releasing hormone (GnRH) agonist suppression and the efficiency of controlled ovarian hyperstimulation (COH) in patients receiving treatment with assisted reproductive technologies (ARTs). METHODS: A total of 338 COH procedures in 291 couples was performed with cycles that reached the stage of oocyte retrieval. The ovarian antral follicle number was measured using transvaginal ultrasonography at the folliculometry during gonadotropin stimulation by GnRH agonist suppression in patients undergoing ARTs. Controlled ovarian hyperstimulation was accomplished using GnRH agonist down-regulation combined with FSH and menotropin stimulation. The characteristics of oocytes after retrieval and embryos after in vitro culture and the pregnancy rates were assessed. RESULTS: The procedures performed included 195 ET cycles, 129 TET cycles, and 14 incomplete cycles. The treatment cycles were divided into four categories according to the antral follicle number (i.e., < or = 5, 6-10, 11-15, and > or = 16) at the first folliculometry to evaluate the influence of various factors. The antral follicle count correlated significantly with the patient age, dosage of gonadotropins, serum estradiol concentration, number of antral follicles (> or = 13 mm) while receiving hCG injections, number of oocytes retrieved, and, later, number of embryos transferred. There was a trend toward an increasing number of pregnancies per cycle as the number of antral follicles increased (14.7, 26.5, 44, and 45%, respectively). CONCLUSIONS: We were able to predict the efficiency of COH and outcome of ARTs based on the follicle count during the first folliculometry during gonadotropin stimulation after GnRH agonist suppression. The results of the folliculometry significantly predicted the ovarian response to COH and the outcome of ARTs in the current treatment cycle.

Adult↗
PubMed2001

Effect of retinoic acid on implantation and post-implantation development of mouse embryos in vitro.

BACKGROUND: This study was designed to examine the embryotoxic potential of retinoic acid (RA) at the blastocyst stage and during early post-implantation development of mouse embryos in vitro. METHODS AND RESULTS: All-trans retinoic acid (t-RA) was administered to ICR mice embryos at a dose level of 0, 0.001 micromol/l, 0.1 micromol/l and 10 micromol/l throughout in-vitro culture. A total of 404 embryos was randomly assigned to all different dose groups. The percentage of embryos in later stages of development changed depending upon the dose of RA used. Exposure to 10 micromol/l of t-RA at the blastocyst stage, implanted blastocyst stage or early oocyte stage was also found to cause different degrees of retardation of embryo development and embryo death. These findings demonstrate, for the first time, that RA exerts an adverse effect on embryo growth during the early post-implantation stages of development, in comparison with day 3 to day 8 of gestation in vivo. CONCLUSIONS: Although isotretinoin (13-cis-retinoic acid) is effective for the therapy of cystic acne and other dermatological disorders, retinoid treatment should be avoided at the early post-implantation stage of gestation.

Animals↗
PubMed2001

C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease.

BACKGROUND: Moderately increased plasma concentrations of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia. METHODS: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of the C677T and A1298C MTHFR genotypes and the combined effect of these polymorphisms on plasma tHcy concentrations, as measured by HPLC with fluorometric detection, both fasting and post-methionine load (PML), in 1238 individuals. RESULTS: The prevalences of the C677T and A1298C genotypes did not differ significantly in 772 individuals with documented coronary artery disease (CAD), 137 individuals with deep-vein thrombosis (DVT), and 329 individuals without documented vascular disease. Individuals homozygous for the 677T allele had significantly increased fasting tHcy, particularly in the presence of low folate, compared with individuals homozygous for the wild-type allele. Neither the 1298AC nor the 1298CC genotype was associated with significantly increased fasting or PML tHcy concentrations irrespective of serum folate. Of the nine combined MTHFR genotypes, six were present in >10% of the population. Of these, the difference in mean fasting tHcy reached statistical significance (P<0.005) only in individuals with the 677TT/1298AA genotype compared with individuals with the wild-type 677CC/1298AA genotype. Differences in mean fasting tHcy did not reach statistical significance in individuals heterozygous for both MTHFR variants. We detected two 677CT/1298CC and three 677TT/1298AC individuals; only one, an 677TT/1298AC individual, had increased tHcy (both fasting and PML). No individuals had the 677TT/1298CC genotype. CONCLUSIONS: The prevalences of the C677T and A1298C polymorphisms did not differ among individuals with CAD, DVT, or those without documented vascular disease. In contrast to the C677T polymorphism, the A1298C polymorphism is not associated with increased fasting tHcy. Although the two polymorphisms usually exist in trans configuration, crossover may occur rarely to form recombinant chromosomes.

Adult↗
PubMed2001

Cystatin C is an independent predictor of fasting and post-methionine load total homocysteine concentrations among stable renal transplant recipients.

BACKGROUND: An increased prevalence of hyperhomocysteinemia with an increased incidence of cardiovascular disease events has been reported among stable renal transplant recipients (RTRs). Preliminary studies in a small number of these individuals have shown that serum creatinine and cystatin C, both markers of kidney function and glomerular filtration rate, are independent determinants of fasting tHcy concentrations; however, determinants of tHcy concentrations after a methionine load have not been studied. METHODS: We determined the prevalence of both fasting and 4-h post-methionine load (PML) tHcy concentrations in 78 stable RTRs and compared the role of cystatin C with the role of serum creatinine as determinants of fasting and PML tHcy. RESULTS: Of the 78 RTRs, 21 (26.9%) had fasting and PML tHcy within the respective reference intervals, and 57 (73.1%) had increased plasma tHcy. Of these 57 RTRs, 22 had fasting hyperhomocysteinemia, 9 had PML hyperhomocysteinemia, and 26 had combined hyperhomocysteinemia (both fasting and PML). Unadjusted Pearson correlations showed that fasting plasma tHcy correlated with both cystatin C (r = 0.564; P <0.001) and creatinine (r = 0.519; P <0.001) and that increases in PML tHcy modestly correlated with cystatin (r = 0.205; P = 0.072), but not creatinine (r = 0.057; P = 0.624). General linear regression modeling with stepwise analysis of covariance showed that both cystatin C (partial R = 0.554; P <0.001) and creatinine (partial R = 0.535; P <0.001) were independent predictors of fasting tHcy, but of the two, only cystatin C (partial R = 0.242; P = 0.035) was an independent predictor of increased PML tHcy. CONCLUSIONS: Clinically stable RTRs have an excess prevalence of moderate hyperhomocysteinemia, and additional cases can be detected by methionine loading. Both creatinine and cystatin C are independent predictors of fasting tHcy in these individuals; however, only cystatin C is a determinant of tHcy concentration after a methionine load, probably because cystatin C is a more sensitive marker of glomerular filtration rate than serum creatinine.

Adult↗
PubMed2000

Variable number tandem repeat in exon/intron border of the cystathionine beta-synthase gene: a single nucleotide substitution in the second repeat prevents multiple alternate splicing.

We studied a large number of individuals with respect to the 31-bp variable number tandem repeat (VNTR) in the cystathionine beta-synthase (CBS) gene. The number of repeats varies from 15-20, with 17 repeats the most common allele. Significantly, we found that the first repeat of the 31-bp VNTR originates 12 bp from the 5' end of exon 13 and extends 19 bp into intron 13. Since this VNTR spans across the exon-intron border, it can theoretically create multiple alternate splice sites. However, a substitution of g-->a at the exon-intron border is uniquely present in the second repeat, preventing alternate splicing at that site. While the g-->a substitution is absent from all subsequent 31-bp repeats, alternate splicing probably does not occur at those distal sites due to the lack of exon 13 sequences not contained in the repeats but needed for the binding of spliceosomes. Investigation of five individuals with normal plasma total homocysteine (tHcy) and five individuals with mild hyper-homocysteinemia shows that all have the g-->a substitution in the second repeat. Nonetheless, we speculate that the absence of this substitution may be found in rare individuals with normal CBS cDNA and unexplained hyperhomocysteinemia. Gene scanning and direct nucleotide sequencing were used to characterize the VNTR in 398 patients with premature coronary artery disease and 137 controls. Five alleles and 10 genotypes were found; 17/17 is the most prevalent genotype in our study population. The two other prevalent genotypes, 16/17 and 17/18, are associated with significantly decreased tHcy levels as compared to the 17/ 17 genotype, suggesting that the 16 and 18 repeats haplotype may be in linkage disequilibrium with regulatory elements which upregulate CBS gene transcription.

Adolescent↗
PubMed2000

Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

BACKGROUND: We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. METHODS: We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. RESULTS: Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. CONCLUSIONS: Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

Airway Resistance↗
PubMed2000

The expression of DAZL1 in the ovary of the human female fetus.

OBJECTIVE: To determine whether DAZL1 is expressed in human fetal ovarian tissue. DESIGN: The presence of DAZL1 expression was determined by reverse transcriptase polymerase chain reaction (RT-PCR). SETTING: Academic tertiary care medical center and research unit of university. PATIENT(S): Five female abortuses between the 19th and 22nd week of gestational age. INTERVENTION(S): Fetal ovarian tissues were collected immediately after the cessation of the heart beat. MAIN OUTCOME MEASURE(S): The product of RT-PCR. RESULT(S): DAZL1 expression was detected in all five samples. CONCLUSION(S): DAZL1 is not only expressed in human testes but also in ovaries. It may play a role in germ cell survival and gonad development in both sexes.

Abortion, Induced↗
PubMed2000

Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels.

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

Plasma homocysteine and its association with carotid intimal-medial wall thickness and prevalent coronary heart disease: NHLBI Family Heart Study.

Mildly elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of coronary heart disease (CHD). Carotid artery intimal-medial wall thickening is a predictor of cardiovascular disease and has been previously shown to be positively associated with plasma tHcy in studies of asymptomatic subjects. In the current study we examined 1467 subjects with regard to their fasting plasma tHcy levels and intimal-medial wall thickness as measured by B-mode ultrasound and early onset CHD. The results showed that there is a significant positive association between plasma tHcy levels and carotid-artery wall thickness in participants 55 years or older even after the tHcy levels are adjusted for age, smoking and anti-hypertensive medication. The direction and magnitude of the relationship is similar although the result was not statistically significant in younger participants ( < 55 years). Early onset CHD at any age was not significantly different across the tHcy quintiles. The lack of an association of tHcy and CHD in the presence of a positive association with intimal-medial wall thickening may be a reflection of increased statistical power of quantitative versus qualitative traits. We conclude that the present finding of a positive association between tHcy and intimal-medial wall thickness strengthens the in vitro finding of the stimulating effect of homocysteine on vascular smooth muscle cell growth. Vascular smooth muscle cell proliferation may be an important mechanism through which mildly elevated plasma tHcy promotes atherosclerosis.

Aged↗
PubMed2000

Two different timings of intrauterine insemination for non-male infertility.

PURPOSE: Our purpose was to assess the simplicity and convenience of treatment scheduled not on weekends, by comparing two different timings of intrauterine insemination (IUI) protocol. METHODS: A prospective observational study of two different protocols of intrauterine insemination was designed. Two hundred and ten infertile couples with normal spermiograms were included in this study. Fifty-eight couples were treated with IUI 26 to 28 h after human chorionic gonadotropin (hCG) injection plus timed intercourse within a 12- to 18-hr period and 147 couples had IUI 36 to 38 hr after hCG injection and timed intercourse within a 12- to 18-hour period. Pregnancy rates were compared with two different protocols of IUI. RESULTS: The mean age, duration, and causes of infertility and the cycle characteristics following follicular stimulation were similar between the two groups. The cycle characteristics of follicular stimulation in the two treatment groups were not different. There also were no significant differences between the groups in the type of sperm concentration, sperm motility, and the percentage of sperm with normal morphology per insemination. The number of follicles greater than 17 mm per patient was not significantly different between the two groups. The pregnancy rate per cycle also was similar between the two groups in men with lower motile sperm numbers (< 40 x 10(6)) (23.6% vs. 23.4%) and in men with higher sperm numbers (> or = 40 x 10(6)) (25% vs. 24.4%). CONCLUSIONS: The different timing but similar efficacy of these two IUI protocols provides a practical choice to clinicians. The availability of both protocols may avoid unnecessary scheduling of clinical and laboratory work on weekends and holidays in women participating in controlled ovarian hyperstimulation and IUI programs for treatment of non-male infertility.

Adult↗
PubMed2000

Influence of 699C-->T and 1080C-->T polymorphisms of the cystathionine beta-synthase gene on plasma homocysteine levels.

The association of moderately elevated total homocysteine (tHcy) levels with coronary artery disease is increasingly being recognized. However, the role of genetic influence on plasma tHcy levels is not completely understood. We studied 1,055 individuals with respect to the effect of two silent polymorphisms, the 699C--> T and the 1080C-->T, of the cystathionine beta-synthase (CBS) gene on plasma tHcy levels. Individuals who were heterozygous or homozygous for the T699 allele had lower post-methionine load (PML) tHcy levels when compared to individuals with the C/C genotype. This association was statistically significant (p = 0.005) for the T/T genotype compared to the C/C genotype and became even more significant (p = 0.000002) when individuals carrying the 68-bp insertion (844ins68) and the T1080 allele were excluded from the analysis. With regard to the 1080C-->T polymorphism, the T1080 allele was associated with significantly lower PML tHcy levels only when individuals carrying the 844ins68 and T699 allele were excluded from the study (p = 0.01 for 1080T/T genotype compared to 1080C/C genotype). We speculate that the 699C-->T and 1080C-->T polymorphisms may be in linkage disequilibrium with regulatory elements that upregulate CBS gene transcription.

Adult↗
PubMed2000

Release of kinesin from vesicles by hsc70 and regulation of fast axonal transport.

The nature of kinesin interactions with membrane-bound organelles and mechanisms for regulation of kinesin-based motility have both been surprisingly difficult to define. Most kinesin is recovered in supernatants with standard protocols for purification of motor proteins, but kinesin recovered on membrane-bound organelles is tightly bound. Partitioning of kinesin between vesicle and cytosolic fractions is highly sensitive to buffer composition. Addition of either N-ethylmaleimide or EDTA to homogenization buffers significantly increased the fraction of kinesin bound to organelles. Given that an antibody against kinesin light chain tandem repeats also releases kinesin from vesicles, these observations indicated that specific cytoplasmic factors may regulate kinesin release from membranes. Kinesin light tandem repeats contain DnaJ-like motifs, so the effects of hsp70 chaperones were evaluated. Hsc70 released kinesin from vesicles in an MgATP-dependent and N-ethylmaleimide-sensitive manner. Recombinant kinesin light chains inhibited kinesin release by hsc70 and stimulated the hsc70 ATPase. Hsc70 actions may provide a mechanism to regulate kinesin function by releasing kinesin from cargo in specific subcellular domains, thereby effecting delivery of axonally transported materials.

3T3 Cells↗
PubMed2000

Codon-54 polymorphism of the fatty acid-binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes.

Patients with type 2 diabetes are frequently dyslipidemic or hypertriglyceridemic. To assess whether increased intestinal triglyceride input leads to elevated fasting and postprandial triglycerides in type 2 diabetes, we used the codon 54 polymorphism of the fatty acid-binding protein 2 gene, which results in the substitution of threonine (Thr) for alanine and is associated with increased intestinal input of triglyceride. Of the 287 diabetic patients screened, 108 (37.6%) were heterozygous and 31 (10.8%) were homozygous for the Thr-54 allele. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild-type (n = 80), those heterozygous for the Thr-54 allele (n = 57), and those homozygous for it (n = 18) were 2.0 +/- 0.09, 2.7 +/- 0.20, and 3.8 +/- 0.43 mmol/L, respectively. A linear relationship of mean fasting plasma triglyceride levels (r2 = 0.97) between the 3 groups was found. After fat ingestion, the postprandial area under the curve of plasma triglyceride (P = 0.025) and chylomicrons (Sf > 400, P = 0.013) was higher in the Thr-54/Thr-54 (n = 6) than in the wild-type (n = 9). Our results are consistent with the hypothesis that, in type 2 diabetes, increased intestinal input of triglyceride can lead to elevated fasting and postprandial plasma triglycerides.

Alleles↗