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B Y Chan

Publications and source records attributed to B Y Chan.

10 recordsLinked to original sources

Improved statistical inference from DNA microarray data using analysis of variance and a Bayesian statistical framework. Analysis of global gene expression in Escherichia coli K12.

We describe statistical methods based on the t test that can be conveniently used on high density array data to test for statistically significant differences between treatments. These t tests employ either the observed variance among replicates within treatments or a Bayesian estimate of the variance among replicates within treatments based on a prior estimate obtained from a local estimate of the standard deviation. The Bayesian prior allows statistical inference to be made from microarray data even when experiments are only replicated at nominal levels. We apply these new statistical tests to a data set that examined differential gene expression patterns in IHF(+) and IHF(-) Escherichia coli cells (Arfin, S. M., Long, A. D., Ito, E. T., Tolleri, L., Riehle, M. M., Paegle, E. S., and Hatfield, G. W. (2000) J. Biol. Chem. 275, 29672-29684). These analyses identify a more biologically reasonable set of candidate genes than those identified using statistical tests not incorporating a Bayesian prior. We also show that statistical tests based on analysis of variance and a Bayesian prior identify genes that are up- or down-regulated following an experimental manipulation more reliably than approaches based only on a t test or fold change. All the described tests are implemented in a simple-to-use web interface called Cyber-T that is located on the University of California at Irvine genomics web site.

Bayes Theorem↗

The effect of N-methyl-N'-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cells.

Normal dog gallbladder epithelial cells in long-term culture were used as a model to study the morphologic, genetic, and secretory processes associated with the progression to cancer formation. Dog gallbladder epithelial cells cultured on collagen-coated plates grew into polarized monolayers, could be passaged repeatedly, and showed the typical morphological profile of well-differentiated columnar epithelial cells. After cells were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 10(-5) mol/L for 48 hours, the treated cells grew on plastic and could be cloned. Flow cytometry revealed emergence of an aneuploid cell subpopulation. In organotypic culture, treated cells showed a pseudostratified appearance, with cellular and nuclear pleomorphism. Large and hyperchromatic nuclei were present as well as increased mitotic rate. The proteins of MNNG-treated dog gallbladder epithelial cells showed increased phosphorylation of tyrosine residues. Treated cells showed a decrease in mucin secretion in response to prostaglandin E2, manifesting an altered pattern of mucin secretion. Transforming growth factor-beta failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibition in normal cells. Together, the data reflected changes representing preliminary steps on the pathway to develop cancer cells. Our results indicate that carcinogenic chemicals can cause measurable chromosomal and cellular modifications to normal biliary epithelial cells in vitro. This model may be useful in understanding the sequential steps in carcinogenesis and affords an opportunity to study chromosomal damage, cytokinetics, changes in molecular genetic markers, and expression, as well as cell biological function during cellular transformation.

Animals↗

Urban/rural differences in home health patients and services.

Using data from the Wisconsin Annual Survey of Home Health Agencies, we describe urban/rural differences for home health care patients. Our findings indicate that urban dwellers are more likely to be home health patients than are rural residents. Urban home health patients are more apt to be nonelderly, male, and have "other conditions" as their primary diagnosis. They are also likely to be more physically dependent and to receive home care longer. Urban home health patients are more typical of long-term care patients, whereas rural patients may be better described as recipients of postacute care, often recovering from diabetes and heart attacks. Possible problems with rural access to home health care are discussed.

Activities of Daily Living↗

Analytical and clinical performance of six sensitive thyrotrophin kits.

We have evaluated the analytical and clinical performance of six sensitive thyrotrophin (TSH) assay kits. The detection limits of the assay kits ranged from 0.02 mIU/L to 0.18 mIU/L. Except for one assay kit, the precision of the assays (coefficients of variation) at different concentrations was below or around 10%. Although results obtained from different kits showed good correlations (r = 0.82 to 0.95), large discrepancies were found when aliquots of the same control sera were assayed by different kits. Results from 33 hyperthyroid patients were all below the lower limit of reference ranges. However, 2 healthy subjects had low TSH results clearly distinguishable from the other 69 healthy subjects. Out of 31 hyperthyroid patients who had recovered after treatment, suppressed TSH values were found in 20% of patients. These results indicate that although TSH is a good test for the detection of hyperthyroidism, low TSH may be found in some euthyroid subjects and diagnosis of hyperthyroidism cannot be based on a suppressed TSH result alone.

Adolescent↗

Cyclic nucleotide phosphodiesterase activity in human peripheral blood lymphocytes and monocytes.

cAMP and cGMP phosphodiesterase (PDE) activity was assayed in human peripheral blood lymphocytes purified by isopycnic centrifugation as well as in lymphocyte preparations further purified to remove contaminating platelets and monocytes. The 16,000 X G supernatant from sonicates of each of these cell preparations contained two hydrolytic activities for cAMP with apparent Km of 1.1 to 2.5 microM and 33 to 66 microM, and a single hydrolytic activity for cGMP with an apparent Km of 6 to 25 microM. When lymphocytes were disrupted by Dounce homogenization, there was only a single, low Km cAMP PDE activity in the homogenate; however, the 16,000 X G supernatant demonstrated 2 Km similar to that seen in sonicated lymphocytes. Treatment of the Dounce preparations with 0.5% Triton X-100 or 1.0% NP-40 converted these preparations to activities similar to those seen in sonicated preparations. cGMP hydrolytic activity was low or absent in the Dounce preparations and was not altered by centrifugation; however, it was markedly enhanced by detergent extraction. These data indicate that human peripheral blood lymphocytes and monocytes have PDE activities similar to those seen in other tissues.

3',5'-Cyclic-AMP Phosphodiesterases↗