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Biomedical subjects

W H Kao

Publications and source records attributed to W H Kao.

9 recordsLinked to original sources
PubMed2001

Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study.

Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the Atherosclerosis Risk in Communities Study (1990-1998), who were followed between 3 and 6 years. Alcohol consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of various levels. Incident diabetes was determined by blood glucose measurements and self-report. After adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21 drinks/week when compared with men who drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were current drinkers but reported no regular use of spirits, beer, or wine were 1.82 (95% confidence interval: 1.14, 2.92). Results of this study support the hypothesis that high alcohol intake increases diabetes risk among middle-aged men. However, more moderate levels of alcohol consumption do not increase risk of type 2 diabetes in either middle-aged men or women.

Alcohol Drinking↗
PubMed2000

Incident type 2 diabetes mellitus in African American and white adults: the Atherosclerosis Risk in Communities Study.

CONTEXT: Although the excess prevalence of type 2 diabetes mellitus in African Americans is well established, few studies have compared incident diabetes in African American and white persons. OBJECTIVES: To compare risk of incident diabetes in African American vs white adults and to identify explanatory factors for racial disparities. DESIGN: Prospective cohort study using baseline data collected from 1986 to 1989 from the ongoing Atherosclerosis Risk in Communities (ARIC) Study, with 9 years of follow-up. SETTING AND PARTICIPANTS: A total of 2646 African American and 9461 white adults aged 45 to 64 years without diabetes at baseline, sampled from 4 US communities. MAIN OUTCOME MEASURES: Incident type 2 diabetes, ascertained by self-report of physician diagnosis, use of diabetes medications, or fasting glucose level of at least 7.0 mmol/L (126 mg/dL), compared among white and African American subjects and by presence of potentially modifiable risk factors. RESULTS: Diabetes incidence per 1000 person-years was about 2.4-fold greater in African American women (25.1 [95% confidence interval [CI], 22.4-28.1] vs 10.4 [95% CI, 9.4-11.4]) and about 1.5-fold greater in men (23.4 [95% CI, 19.9-27.2] vs 15.9 [95% CI, 14.6-17.2]) than in their white counterparts (P<.001). Results from proportional hazards regression models indicated that racial differences in potentially modifiable risk factors, particularly adiposity, accounted for 47.8% of the excess risk in African American women but accounted for little excess risk in African American men. Compared with their white counterparts, African American men and women had higher blood pressures before diabetes onset (diastolic blood pressure difference=5.6 mm Hg in women and 8.4 mm Hg in men; P=.005). CONCLUSIONS: Our data indicate that compared with their white counterparts, middle-aged African Americans are at greater risk of developing type 2 diabetes and have higher blood pressure prior to development of diabetes. In women, almost 50% of this excess risk might be related to potentially modifiable factors.

Black People↗
PubMed2000

Human papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase.

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells.

Blotting, Western↗
PubMed1999

Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes; however, this association has not been examined prospectively. METHODS: We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults (N = 12,128) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up. Fasting serum magnesium level, categorized into 6 levels, and dietary magnesium intake, categorized into quartiles, were measured at the baseline examination. Incident type 2 diabetes was defined by self-report of physician diagnosis, use of diabetic medication, fasting glucose level of at least 7.0 mmol/L (126 mg/dL), or nonfasting glucose level of at least 11.1 mmol/L (200 mg/dL). RESULTS: Among white participants, a graded inverse relationship between serum magnesium levels and incident type 2 diabetes was observed. From the highest to the lowest serum magnesium levels, there was an approximate 2-fold increase in incidence rate (11.1, 12.2, 13.6, 12.8, 15.8, and 22.8 per 1000 person-years; P = .001). This graded association remained significant after simultaneous adjustment for potential confounders, including diuretic use. Compared with individuals with serum magnesium levels of 0.95 mmol/L (1.90 mEq/L) or greater, the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories: 1.13 (95% CI, 0.79-1.61), 1.20 (95% CI, 0.86-1.68), 1.11 (95% CI, 0.80-1.56), 1.24 (95% CI, 0.86-1.78), and 1.76 (95% CI, 1.18-2.61) (for trend, P = .01). In contrast, little or no association was observed in black participants. No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in black or white participants. CONCLUSIONS: Among white participants, low serum magnesium level is a strong, independent predictor of incident type 2 diabetes. That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal handling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes.

Adult↗
PubMed1999

Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.

OBJECTIVE: Although hyperglycemia is hypothesized to increase the short-term risk of infection, this hypothesis has not been well tested in a clinical setting. This study was designed to assess the relationship of perioperative glycemic control to the subsequent risk of infectious complications. RESEARCH DESIGN AND METHODS: A total of 411 adults with diabetes who underwent coronary artery surgery from 1990 to 1995 in the cardiac surgery service of an urban university hospital were included in a nonconcurrent prospective cohort study based on chart review. Perioperative glycemic control was characterized by the mean of six capillary glucose measurements taken during the 36-h interval following surgery. The major outcomes studied were infections of leg and chest wounds, pneumonia, and urinary tract infections. RESULTS: Mean postoperative glucose levels ranged from 121 to 352 mg/dl and were divided into quartiles: quartile 1 (121-206 mg/dl), quartile 2 (207-229 mg/dl), quartile 3 (230-252 mg/dl), and quartile 4 (253352 mg/dl). After simultaneous adjustment for age, sex, race, underlying comorbidity, acute severity of illness, and the length of the stay in the surgical intensive care unit, patients with higher mean capillary glucose readings were at increased risk of developing infections. Compared with people in the lowest quartile of postoperative glucose, those in quartiles 2 (relative odds of infection [95% CI] = 1.17 [0.57-2.40]), 3 (1.86 [0.94-3.68]), and 4 (1.78 [0.86-3.47]) were at progressively higher risk for infection (P = 0.05 for trend). CONCLUSIONS: In patients with diabetes who undergo coronary artery surgery, postoperative hyperglycemia is an independent predictor of short-term infectious complications. Physicians should consider a glucose concentration target of < or =200 mg/dl to reduce the risk of infection.

Blood Glucose↗
PubMed1997

Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity.

The cellular protein E6AP functions as an E3 ubiquitin protein ligase in the E6-dependent ubiquitination of p53. E6AP is a member of a family of functionally related E3 proteins that share a conserved carboxyl-terminal region called the Hect domain. Although several different E2 ubiquitin-conjugating enzymes have been shown to function with E6AP in the E6-dependent ubiquitination of p53 in vitro, the E2s that cooperate with E6AP in the ubiquitination of its normal substrates are presently unknown. Moreover, the basis of functional cooperativity between specific E2 and Hect E3 proteins has not yet been determined. Here we report the cloning of a new human E2, designated UbcH8, that was identified in a two-hybrid screen through specific interaction with E6AP. We demonstrate that UbcH7, an E2 closely related to UbcH8, can also bind to E6AP. The region of E6AP involved in complex formation with UbcH8 and UbcH7 was mapped to its Hect domain. Furthermore, we show that UbcH5 and UbcH6, two highly homologous E2s that were deficient for interaction with E6AP, could associate efficiently with another Hect-E3 protein, RSP5. Finally, only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP, whereas the noninteracting E2s could not. Taken together, these studies demonstrate for the first time complex formation between specific human E2s and the Hect domain family of E3 proteins and suggest that selective physical interaction between E2 and E3 enzymes forms the basis of specificity for functionally distinct E2:E3 combinations.

Amino Acid Sequence↗
PubMed1996

Loss of the p16INK4a and p15INK4b genes, as well as neighboring 9p21 markers, in sporadic melanoma.

Although homozygous deletions of the cyclin-dependent kinase inhibitor 2 gene p16INK4a on 9p21 have been reported frequently in metastatic melanoma cell lines, and intragenic mutations within the p16INK4a gene have been detected in familial melanoma kindreds, specific targeting of this gene in the development of sporadic melanoma in vivo remains controversial. Southern analyses were performed in this study to initially assess the frequency of hemi- or homozygous losses of p16INK4a, as well as its neighboring family member, p15INK4b, and other candidate regions within 9p21, in sporadic melanoma. Overall, 22 of 40 (55%) uncultured sporadic melanoma DNAs were determined to harbor deletions of 1-11 markers/genes located on 9p21. This included 10 tumors (25%; 10 of 40) with homozygous deletions limited to either the p16INK4a gene only (20%; 2 of 10), both the p16INK4a and p15INK4b genes (10%; 1 of 10), another novel 9p21 gene, FB19 (10%; 1 of 10), or all three of these genes plus surrounding markers (60%; 6 of 10). In subsequent single-strand conformation polymorphism and sequencing analyses, intragenic mutations in the p16INK4a gene were also revealed in two (10%; 2 of 21) melanoma DNAs that retained one copy of this locus. By comparison, the frequency of pl6INK4a and p15INK4b homozygous deletions, as well as p16INK4a mutations, in melanoma cell lines (analyzed in parallel) was 2-3-fold higher at 61 (23 of 38) and 24% (9 of 38), respectively. These findings indicate that (a) p16INK4a is inactivated in vivo in over one-fourth (27.5%; 11 of 40) of sporadic melanomas; (b) mutation/deletion of p16INK4a may confer a selective growth advantage in vitro; and (c) other 9p21 tumor suppressor genes could be targeted during the development of melanoma.

Carrier Proteins↗