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Articles by K. Y Wu
Total Records ( 7 ) for K. Y Wu
  M. S Kim , K. Y Wu , V Auyeung , Q Chen , P. A Gruppuso and C. Phornphutkul

Linear growth in children is sensitive to nutritional status. Amino acids, in particular leucine, have been shown to regulate cell growth, proliferation, and differentiation through the mammalian target of rapamycin (mTOR), a nutrient-sensing protein kinase. Having recently demonstrated a role for mTOR in chondrogenesis, we hypothesized that leucine restriction, acting through mTOR, would inhibit growth plate chondrocyte proliferation and differentiation. The effect of leucine restriction was compared with that of the specific mTOR inhibitor, rapamycin. Leucine restriction produced a dose-dependent inhibition of fetal rat metatarsal explant growth. This was accounted by reduced cell proliferation and hypertrophy but not apoptosis. mTOR activity, as reflected by ribosomal protein S6 phosphorylation, was only partially inhibited by leucine restriction, whereas rapamycin abolished S6 phosphorylation. In chondrogenic ATDC5 cells, leucine restriction inhibited cell number, proteoglycan accumulation, and collagen X expression despite minimal inhibition of mTOR. Microarray analysis demonstrated that the effect of leucine restriction on ATDC5 cell gene expression differed from that of rapamycin. Out of 1,571 genes affected by leucine restriction and 535 genes affected by rapamycin, only 176 genes were affected by both. These findings indicate that the decreased chondrocyte growth and differentiation associated with leucine restriction is only partly attributable to inhibition of mTOR signaling. Thus nutrient restriction appears to directly modulate bone growth through unidentified mTOR-independent mechanisms in addition to the well-characterized mTOR nutrient-sensing pathway.

  T. M Temu , K. Y Wu , P. A Gruppuso and C. Phornphutkul

The ATDC5 cell line exhibits a multistep process of chondrogenic differentiation analogous to that observed during endochondral bone formation. Previous investigators have induced ATDC5 cells to differentiate by exposing them to insulin at high concentrations. We have observed spontaneous differentiation of ATDC5 cells maintained in ascorbic acid-containing -MEM. A comparison of the differentiation events in response to high-dose insulin vs. ascorbic acid showed similar expression patterns of key genes, including collagen II, Runx2, Sox9, Indian hedgehog, and collagen X. We took advantage of the action of ascorbic acid to examine signaling events associated with differentiation. In contrast to high-dose insulin, which downregulates both IGF-I and insulin receptors, there were only minimal changes in the abundance of these receptors during ascorbic acid-induced differentiation. Furthermore, ascorbic acid exposure was associated with ERK activation, and ERK inhibition attenuated ascorbic acid-induced differentiation. This was in contrast to the inhibitory effect of ERK activation during IGF-I-induced differentiation. Inhibition of collagen formation with a proline analog markedly attenuated the differentiating effect of ascorbic acid on ATDC5 cells. When plates were conditioned with ATDC5 cells exposed to ascorbic acid, ATDC5 cells were able to differentiate in the absence of ascorbic acid. Our results indicate that matrix formation early in the differentiation process is essential for ascorbic acid-induced ATDC5 differentiation. We conclude that ascorbic acid can promote the differentiation of ATDC5 cells by promoting the formation of collagenous matrix and that matrix formation mediates activation of the ERK signaling pathway, which promotes the differentiation program.

  C. C Chen , C. L Chuang , K. Y Wu and C. C. Chan

Objectives: Occupational exposure assessment is a major task in industrial hygiene studies. Although statistical analyses for magnitudes and variations of exposures to various types of working populations based on existing data sets are extensive, relatively few discussions on study designs appear in the literature, especially for sample size determination and number of repeated measurements.

Methods: In this paper, we propose a general framework of sampling strategies on sample size requirement together with the number of repeated measurements using the mixed-effects generalized linear model (GLM). As illustrative examples, we discuss sampling strategies separately under the log-normal assumption for hypotheses testing on (i) mean exposure differences of multiple worker groups and (ii) presence of a long-term exposure trend.

Results: Given a specified alternative hypothesis, the desired significance level and statistical power, the number of repeated measurements, within-worker and between-worker variances, and a correlation structure, we have derived and tabulated an explicit sample size requirement of the two hypothetical cases under log-normal distribution assumption.

Conclusions: On the basis of the tabulated outcomes, the sample size requirement is much more dominant than the number of repeated measurements for a group exposure comparison. Thus, in this case, recruiting more workers with fewer repeated measurements may be more economical than the opposite approach. For testing the presence of a long-term exposure trend, the sample size required decreases substantially with the number of repeated measurements. Also, equally spaced sampling times would be optimal because the effect of between-worker variance is algebraically cancelled out in sample size calculations.

  K. Y Wu , Y. F Huang , M. F Chen , T. S Shih , S. N Uang , I. F Mao and M. L. Chen

Objectives: To develop a highly sensitive analytical method for very low acrylamide (AA) exposure and to conduct an occupational exposure assessment by the developed method.

Methods: Seventy-five air samples from four plants were collected and analyzed using an isotope-dilution gas chromatography coupled with mass spectrometry (GC/MS).

Results: This isotope-dilution GC–MS method is sufficiently sensitive for assessing very low AA level as 4.37 ng m–3, which is 10- to 7500-fold lower than the current analytical method. Field study showed that most airborne AA was gaseous rather than particulate. The personal exposure levels in workers ranged from 4.37 x 10–3 µg m–3 to 94.90 µg m–3 with a mean of 12.08 µg m–3. Fifty percent of personal 8-h time-weighted average (TWA) concentrations in the AA production plant exceeded the threshold limit value of 30 µg m–3 set by American Conference of Governmental Industrial Hygienists.

Conclusions: The field study indicated that 8-h TWA concentrations in workers varied by two orders of magnitude. The highly sensitive method can be used in future health risk assessment of AA exposure, such as those in fast-food restaurants.

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