Biomedical subjects

Shibing Deng

Publications and source records attributed to Shibing Deng.

8 recordsLinked to original sources

PubMed2006

Struggles for equivalence: in vitro developmental toxicity model evolution in pharmaceuticals in 2006.

Our group has been using the ECVAM Embryonic Stem Cell assay to predict developmental toxicity. In order to improve the separation of non-teratogens from weak teratogens, we have employed measures of gene expression, and different statistical methods from those originally used to develop the test. These approaches have fundamentally not improved the discrimination of 'weaks' from 'nons'. A realization that a very low value for cytotoxicity IC50 would drive a final result for the test in ways that were inappropriate for pharmaceuticals has led us to re-examine the cytotoxicity component. Our current efforts are focused on other, perhaps more sensitive, measures of cytotoxicity, combined with gene expression changes in mouse stem cells in an attempt to correctly identify weak teratogens and non-teratogens.

Animal Testing Alternatives↗

PubMed2005

Standardizing global gene expression analysis between laboratories and across platforms.

To facilitate collaborative research efforts between multi-investigator teams using DNA microarrays, we identified sources of error and data variability between laboratories and across microarray platforms, and methods to accommodate this variability. RNA expression data were generated in seven laboratories, which compared two standard RNA samples using 12 microarray platforms. At least two standard microarray types (one spotted, one commercial) were used by all laboratories. Reproducibility for most platforms within any laboratory was typically good, but reproducibility between platforms and across laboratories was generally poor. Reproducibility between laboratories increased markedly when standardized protocols were implemented for RNA labeling, hybridization, microarray processing, data acquisition and data normalization. Reproducibility was highest when analysis was based on biological themes defined by enriched Gene Ontology (GO) categories. These findings indicate that microarray results can be comparable across multiple laboratories, especially when a common platform and set of procedures are used.

Gene Expression Profiling↗

PubMed2004

Cross-site comparison of gene expression data reveals high similarity.

Consistency and coherence of gene expression data across multiple sites depends on several factors such as platform (oligo, cDNA, etc.), environmental conditions at each laboratory, and data quality. The Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute consortium on the application of genomics to mechanism-based risk assessment is investigating these factors by comparing high-density gene expression data sets generated on two sets of RNA from methapyrilene (MP) experiments conducted at Abbott Laboratories and Boehringer-Ingelheim Pharmaceuticals, Inc. using a single platform (Affymetrix Rat Genome U34A GeneChip) at seven different sites. This article focuses on the evaluation of data quality and statistical models that facilitate the comparison of such data sets at the probe level. We present methods for exploring and quantitatively assessing differences in the data, with the principal goal being the generation of lists of site-insensitive genes responsive to low and high doses of MP. A combination of numerical and graphical techniques reveals important patterns and partitions of variability in the data, including the magnitude of the site effects. Although the site effects are significantly large in the analysis results, they appear to be primarily additive and therefore can be adjusted in the statistical calculations in a way that does not bias conclusions regarding treatment differences.

Animals↗

PubMed2003

Repeated observation of breast tumor subtypes in independent gene expression data sets.

Characteristic patterns of gene expression measured by DNA microarrays have been used to classify tumors into clinically relevant subgroups. In this study, we have refined the previously defined subtypes of breast tumors that could be distinguished by their distinct patterns of gene expression. A total of 115 malignant breast tumors were analyzed by hierarchical clustering based on patterns of expression of 534 "intrinsic" genes and shown to subdivide into one basal-like, one ERBB2-overexpressing, two luminal-like, and one normal breast tissue-like subgroup. The genes used for classification were selected based on their similar expression levels between pairs of consecutive samples taken from the same tumor separated by 15 weeks of neoadjuvant treatment. Similar cluster analyses of two published, independent data sets representing different patient cohorts from different laboratories, uncovered some of the same breast cancer subtypes. In the one data set that included information on time to development of distant metastasis, subtypes were associated with significant differences in this clinical feature. By including a group of tumors from BRCA1 carriers in the analysis, we found that this genotype predisposes to the basal tumor subtype. Our results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.

Breast Neoplasms↗

PubMed2003

Gender and ethnic changes in physical work capacity from childhood through adolescence.

This study determined gender and ethnic differences in physical work capacity (PWC170) of 8-16-year-old American youth as they progress from elementary to high school. A multicohort group of 2,540 youth participated 50.4% girls (21.4% African Americans, and 78.6% Caucasians). PWC170 was predicted from cycle ergometer testing six times over a 7-year period. The absolute PWC170 of girls stabilized in early adolescence, while boys increased with each trial. The PWC170 relative to body weight of girls decreased steadily, whereas the boys remained stable. African Americans had greater absolute PWC170 values than Caucasians (p = .0001). The relative PWC170 was lower for African American girls than Caucasian girls (p = .0001), but there were no ethnic differences for boys (p > .05). Although correlations and grouping suggested moderate tracking; girls with high relative PWC170 tended to migrate to lower levels as they aged, where as high-peforming boys maintained their PWC170 as they aged.

Adolescent↗

PubMed2002

A school-based intervention can reduce body fat and blood pressure in young adolescents.

PURPOSE: To determine the effect of increasing the aerobic component of the school's physical activity program and improving the knowledge about weight control and blood pressure on the blood pressure and body fat of early adolescents. METHODS: The subjects were 1140 youth aged 11 to 14 years (630 females, 510 males; 64% white, 24.4% African-American, and 11.6% "other"), who were randomly assigned by school into four treatment groups: exercise only, education only, exercise and education combined, and control group. Heights, weights, and skinfold thicknesses were measured, and body mass index (BMI) was computed kg/m(2). Blood pressure was obtained in duplicate using a random-zero mercury sphygmomanometer. Maximal oxygen uptake was predicted from a submaximal cycle ergometer test. Data were analyzed using analysis of covariance statistics, adjusting for gender, ethnicity, age, socioeconomic status, and initial baseline characteristics. RESULTS: Systolic and diastolic blood pressures increased more in the control group than in the intervention groups (p =.001). The BMI did not change significantly (p =.709), but the sum of skinfolds increased less in subjects in the exercise intervention groups than the education only or control groups (p =.0001). The small increase in (p)VO(2)max of the combined exercise and education group was significantly greater than the education only group (p =.0001). CONCLUSION: An exercise program for youth can have a positive effect on blood pressure independent of body weight loss.

Adolescent↗

PubMed2002

Predicted maximal aerobic power in youth is related to age, gender, and ethnicity.

PURPOSE: To determine the effects of age, gender, and ethnicity on the predicted aerobic power of youth as they age from 8 to 16 yr. METHODS: The sample was a multicohort group of 2540 African Americans (N = 543) and Caucasians (N = 1997), 1279 (50.4%) girls and 1261 (49.6%) boys. Heights, weights, and sum of skin folds (triceps + subscapular) were measured. Aerobic power ((p)VO(2max)), expressed in relative (mL x kg(-1) x min(-1)) or absolute (L x min(-1)) terms, was predicted from a three-stage cycle ergometry test. RESULTS: Quadratic mixed-model analysis indicated that boys had higher relative and absolute (p)VO(2max) than the girls (P = 0.0004). The African American subjects had a higher absolute (p)VO(2max) (L x min(-1)) than the Caucasians, but their relative (p)VO(2max) was lower than the Caucasians (P = 0.031). Finally, age had a significant effect on (p)VO(2max) (P = 0.0001). The absolute (p)VO(2max) of the girls increased 9%.yr(-1) until age 14; but their relative (p)VO(2max) declined approximately 1.2 mL x kg(-1) x min(-1) x yr(-1). The absolute (p)VO(2max) for the boys increased yearly by approximately 14% from ages 8 to 16 yr, but the relative (p)VO(2max) of the African American males was stable from ages 8 to 11, then dropped, and stabilized again between ages 12 and 16 yr. The relative (p)VO(2max) of the Caucasian boys declined from ages 8 to 10, but then increased slightly from age 12 to 16 yr. In addition, the interactions of age and gender, and age squared and gender were significant (P < 0.02). CONCLUSION: These data indicate that although absolute (p)VO(2max) (L x min(-1)) increases from age 8 to 16 yr, relative (p)VO(2max) (mL x kg(-1) x min(-1)) declines. The decline appears to be related to increased fat mass. Similarly, the higher relative (p)VO(2max) (mL x kg(-1) x min(-1)) of the Caucasian youth compared with the African American youth was related to lower weights and skin folds of the Caucasian youth.

Adolescent↗

PubMedDate not supplied

Racial and socioeconomic differences in risk factors for cardiovascular disease among Southern rural women.

BACKGROUND: African American women living in the Southeast experience a higher mortality due to cardiovascular (CV) disease than their White counterparts. It is unclear if this vulnerability to CV disease is due to race, socioeconomic status, or health behaviors. OBJECTIVES: To examine the disparities in cardiovascular health between Southern rural, African American and White women to determine if a CV Risk-Index differed by race, education, or income levels and if differences persisted when controlling for body mass index (BMI). METHODS: Subjects were 1,110 women (27% African American, 73% White) residing in rural North Carolina. Data were collected by mailed questionnaire and analyzed using analysis of variance (ANOVA) and analysis of covariance (ANCOVA). RESULTS: African American women had significantly lower education and lower income than Whites, higher BMI, and a much greater prevalence of hypertension, angina, and diabetes. In a three-way ANOVA including race, income, and education, education and race were significant predictors of the CV Risk Index, but when adjusted for BMI race was no longer significant (p =.3039); the only significant predictors were BMI and educational level. DISCUSSION: Women with the least education had the highest CV Risk-Index, regardless of race. These findings suggest the need to focus risk reduction interventions on all Southern rural women with limited education, not only African American women. This supports the current literature that suggests race should be viewed as a risk marker rather than a risk factor.

Adult↗