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Biomedical subjects

Zhao Chen

Publications and source records attributed to Zhao Chen.

At least 19 recordsLinked to original sources
PubMed2006

Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2.

Megakaryocyte (MK) differentiation is well described in morphologic terms but its molecular counterparts and the basis for platelet release are incompletely understood. We profiled mRNA expression in populations of primary mouse MKs representing successive differentiation stages. Genes associated with DNA replication are highly expressed in young MKs, in parallel with endomitosis. Intermediate stages are characterized by disproportionate expression of genes associated with the cytoskeleton, cell migration, and G-protein signaling, whereas terminally mature MKs accumulate hemostatic factors, including many membrane proteins. We used these expression profiles to extract a reliable panel of molecular markers for MKs of early, intermediate, or advanced differentiation and establish the value of this marker panel using mouse models of defective thrombopoiesis resulting from absence of GATA1, NF-E2, or tubulin beta1. Computational analysis of the promoters of late-expressed MK genes identified new candidate targets for NF-E2, a critical transcriptional regulator of platelet release. One such gene encodes the kinase adaptor protein LIMS1/PINCH1, which is highly expressed in MKs and platelets and significantly reduced in NF-E2-deficient cells. Transactivation studies and chromatin immunoprecipitation implicate Lims1 as a direct target of NF-E2 regulation. Attribution of stage-specific genes, in combination with various applications, thus constitutes a powerful way to study MK differentiation and platelet biogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Ethnic and geographic differences in mammographic density and their association with breast cancer incidence.

The objective of this pooled analysis was to compare differences in dense areas and percent mammographic densities to breast cancer incidence in populations at different breast cancer risk. The data set included 1,327 women aged 40-80: Caucasians from Norway, Arizona, and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. One reader performed computer-assisted quantitative density assessment for all mammographic films. Multiple linear regression models evaluated the influence of the covariates on breast density. Spearman correlation coefficients (r (s)) estimated the association between breast density and breast cancer incidence for the seven populations. After adjustment for covariates, ethnicity, but not location, was significantly associated with breast density. In the full model, 19% of the variation in the dense areas and 46% in the variation of percent densities were explained by measured risk factors. Native Hawaiians had the largest dense areas and women in Japan the smallest, whereas percent densities were highest among Native Hawaiians and Japanese in Hawaii and lowest among Norwegian women. The mean age-adjusted dense area had the strongest association with breast cancer incidence (r (s) = 0.93, P = 0.003); the relation with percent density was considerably weaker (r (s) = 0.32, P = 0.48). The correlation between age-adjusted dense area and breast cancer incidence remained strong after selectively removing individual data points. This comparison of mammographic densities suggests that, on a group level, age-adjusted dense areas may reflect breast cancer incidence better than percent densities.

Adult↗
PubMed2006

Potential solution processible phosphorescent iridium complexes toward applications in doped light-emitting diodes: rapid syntheses and optical and morphological characterizations.

A series of carbazol-9-yl end-capped red-emitting heteroleptic iridium complexes was readily synthesized using post Suzuki coupling. The appealing solubility, photoluminescent characteristics, and morphological stability enabled the current heteroleptic iridium complexes to be highly desirable phosphorescent dopant emitters in doped light-emitting diodes for the purpose of resisting molecular aggregations in the doped emitting layers.

Journal Article↗
PubMed2006

Metabolically active portion of fat-free mass: a cellular body composition level modeling analysis.

The proportion of fat-free mass (FFM) as body cell mass (BCM) is highly related to whole body resting energy expenditure. However, the magnitude of BCM/FFM may have been underestimated in previous studies. This is because Moore's equation [BCM (kg) = 0.00833 x total body potassium (in mmol)], which was used to predict BCM, underestimates BCM by approximately 11%. The aims of the present study were to develop a theoretical BCM/FFM model at the cellular level and to explore the influences of sex, age, and adiposity on the BCM/FFM. Subjects were 112 adults who had the following measurements: total body water by (2)H(2)O or (3)H(2)O dilution; extracellular water by NaBr dilution; total body nitrogen by in vivo neutron activation analysis; and bone mineral by dual-energy X-ray absorptiometry. FFM was calculated using a multicomponent model and BCM as the difference between FFM and the sum of extracellular fluid and solids. The developed theoretical model revealed that the proportion of BCM to FFM is mainly determined by water distribution (i.e., E/I, the ratio of extracellular to intracellular water). A significant correlation (r = 0.90, P < 0.001) was present between measured and model-predicted BCM/FFM for all subjects pooled. Measured BCM/FFM [mean (SD)] was 0.584 +/- 0.041 and 0.529 +/- 0.041 for adult men and women (P < 0.001), respectively. A multiple linear regression model showed that there are independent significant associations of sex, age, and fat mass with BCM/FFM.

Adult↗
PubMed2006

Computerized analysis of tissue density effect on missed cancer detection in digital mammography.

This paper presents a study of the analysis of breast density in missed cancer cases and the effect of tissue density on cancer detection. A total of 100 missed cancer cases were collected. The breast density tissue was segmented with a statistical-based method. A set of tests was then applied to examine: (1) the differences in density between the mammograms at the detected stage and that at missed stage; (2) the density difference between the cancerous mammograms and their contra-lateral normal mammograms in the missed cancer cases; (3) the effect of breast density on CAD cancer detection. The results demonstrate that breast density is an important factor affecting not only radiologist's reading but also CAD performance. In order to improve early detection of breast cancer, a special effort should be directed to the high dense breast cases in CAD system design.

Breast Neoplasms↗
PubMed2006

The evolution from asparagine or threonine to cysteine in position 146 contributes to generation of a more efficient and stable form of muscle creatine kinase in higher vertebrates.

Creatine kinase, a key enzyme in vertebrate excitable tissues that require large energy fluxes, catalyzes the reversible transfer of phosphate between adenosine triphosphate and creatine. Sequence alignment indicated that the 146th amino acid is cysteine in the muscle creatine kinase of higher vertebrates including Amphibia, Reptilia, Aves and Mammalia. In fishes, it is cysteine in Agnatha and Chondrichthyes, and asparagine or threonine in Osteichthyes, which is the ancestor of Amphibia, Reptilia, Aves and Mammalia. To explore the structural and functional role of this special residue, a series of site-directed mutants of rabbit muscle creatine kinase were constructed, including C146S, C146N, C146T, C146G, C146A, C146D and C146R. A detailed comparison was made between wild-type creatine kinase and the mutants in catalytic activity, physico-chemical properties and structural stability against thermal inactivation and guanidine hydrochloride denaturation. It was found that except for C146S, the mutants had relatively lower catalytic activity and structural stability than Wt-CK. Wt-CK and C146S were the most stable ones, followed by C146N and C146T, and then C146G and C146A, and C146D and C146R were the least stable mutants. These results suggested that the 146th residue plays a crucial role in maintaining the structural stability of creatine kinase, and that the evolution in this amino acid from asparagine or threonine to cysteine contributes to the generation of a more efficient and more stable form of creatine kinase in higher vertebrates.

Amino Acid Sequence↗
PubMed2006

High-level expression, purification, and characterization of non-tagged Aspergillus flavus urate oxidase in Escherichia coli.

The entire encoding region for Aspergillus flavus uricase was cloned into pET-32a and expressed in Escherichia coli BL21 (DE3). The uricase was expressed in the E. coli cytoplasm in a completely soluble, biologically active form. A scalable process aimed to produce and purify multi-gram quantities of highly pure, recombinant urate oxidase (rUox) from E. coli was developed. The rUox protein was produced in a 30 L fermentor containing 25 L of 2x YT medium and purified to >99% purity using hydrophobic interaction, anion-exchange, and gel filtered chromatography. The final yield of purified rUox from fermentation resulted in approximately 27 g of highly pure, biologically active rUox per kg of cell paste (approximately 238 mg/8.8 g cell paste/L). The results presented here exhibit the ability to generate multi-gram quantities of rUox from E. coli that may be used for the development of pharmaceutics of reducing the hyperuricemia.

Aspergillus flavus↗
PubMed2006

Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate.

Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-Ras(V12) or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.

Animals↗
PubMed2005

Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancer.

BACKGROUND: Breast cancer diagnosis and treatment may put women at higher risk for osteoporosis in later life. METHODS: In a subgroup of participants in the Women's Health Initiative Observational Study, authors of the current study investigated differences in bone mineral density (BMD, measured by dual-energy x-ray absorptiometry) between breast cancer survivors (n = 209) and a noncancer reference group (n = 5759). RESULTS: In comparison to the reference group, breast cancer survivors had significantly lower total body BMD value (0.989 vs. 1.013 g/cm(2), P = 0.001) and total hip BMD value (0.823 vs. 0.845 g/cm(2), P = 0.02) at baseline after adjustment for age, race/ethnicity, years since menopause, and clinical center. These lower BMD levels were largely explained by lower usage of hormone therapy (HT) among survivors: after additional statistical adjustment for HT, hip BMD values were 0.834 versus 0.844 g/cm(2) (P = 0.26), and total body values were 1.005 versus 1.013 g/cm(2) (P = 0.33) for survivors and reference women, respectively. More than 77% of survivors with osteoporosis were undiagnosed by their healthcare providers, and this was similar to the undiagnosed rate in the reference group (85.7%). Longitudinally, breast cancer survivors in this study did not demonstrate an accelerated rate of bone loss compared with the reference population. CONCLUSIONS: Associated with lower HT usage, postmenopausal survivors of breast cancer were more likely to have low BMD in comparison to other women of the same age; and many of these survivors with osteoporosis were undiagnosed.

Absorptiometry, Photon↗
PubMed2005

Bone mineral density of American Indian and Alaska Native women compared with non-Hispanic white women: results from the Women's Health Initiative Study.

OBJECTIVE: To compare bone mineral density (BMD) of American Indian/Alaska Native (AI/AN) women with that of non-Hispanic white women. DESIGN: This cross-sectional study compared mean BMD between AI/AN women and a random sample of non-Hispanic white women matched on geographic region in the Women's Health Initiative Study, a prospective study of postmenopausal women. We analyzed baseline BMD measurements for the total hip, spine, and whole body from 139 AI/AN women and 1,431 non-Hispanic white women. RESULTS: Unadjusted mean spine and whole body BMDs were not significantly different between the two races. Controlling for age, education, and hormone therapy use, adjusted mean BMD was similar by race among women who were underweight, normal, or obese. We found a significant interaction of race by body mass index on spine (P = 0.003) and whole body (P = 0.0003) BMD; thus, analyses were stratified by body mass index. Overweight AI/AN women had slightly lower adjusted mean whole body and spine BMD than overweight non-Hispanic white women (whole body: 0.97 vs 1.03 g/cm, P = 0.02; spine: 0.96 versus 1.03 g/cm, P = 0.001). Among extremely obese (body mass index: > or =40.0 kg/m) women, adjusted mean total hip BMD was higher in the AI/AN women (1.07 vs 0.97 g/cm, respectively, P = 0.03). CONCLUSIONS: Overall, AI/AN and non-Hispanic white women had similar BMDs. This study suggests that extremely obese AI/AN women may have higher BMD at certain skeletal sites compared with extremely obese non-Hispanic white women. However, these results need to be confirmed by additional research.

Absorptiometry, Photon↗
PubMed2005

Ethnicity and breast cancer: factors influencing differences in incidence and outcome.

BACKGROUND: The lower breast cancer incidence in minority women and the higher breast cancer mortality in African American women than in white women are largely unexplained. The influence of breast cancer risk factors on these differences has received little attention. METHODS: Racial/ethnic differences in breast cancer incidence and outcome were examined in 156,570 postmenopausal women participating in the Women's Health Initiative. Detailed information on breast cancer risk factors including mammography was collected, and participants were followed prospectively for breast cancer incidence, pathological breast cancer characteristics, and breast cancer mortality. Comparisons of breast cancer incidence and mortality across racial/ethnic groups were estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models. Tumor characteristics were compared as odds ratios (ORs) and 95% confidence intervals in logistic regression models. RESULTS: After median follow-up of 6.3 years, 3938 breast cancers were diagnosed. Age-adjusted incidences for all minority groups (i.e., African American, Hispanic, American Indian/Alaskan Native, and Asian/Pacific Islander) were lower than for white women, but adjustment for breast cancer risk factors accounted for the differences for all but African Americans (HR = 0.75, 95% CI = 0.61 to 0.92) corresponding to 29 cases and 44 cases per 10,000 person years for African American and white women, respectively. Breast cancers in African American women had unfavorable characteristics; 32% of those in African Americans but only 10% in whites were both high grade and estrogen receptor negative (adjusted OR = 4.70, 95% CI = 3.12 to 7.09). Moreover, after adjustment for prognostic factors, African American women had higher mortality after breast cancer than white women (HR = 1.79, 95% CI = 1.05 to 3.05) corresponding to nine and six deaths per 10 000 person-years from diagnosis in African American and white women, respectively. CONCLUSION: Differences in breast cancer incidence rates between most racial/ethnic groups were largely explained by risk factor distribution except in African Americans. However, breast cancers in African American women more commonly had characteristics of poor prognosis, which may contribute to their increased mortality after diagnosis.

Adult↗
PubMed2005

Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study.

BACKGROUND: Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history. METHODS: A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records. RESULTS: After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25). CONCLUSIONS: Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.

Aged↗
PubMed2005

Evidence for common machinery utilized by the early and late RNA localization pathways in Xenopus oocytes.

In Xenopus, an early and a late pathway exist for the selective localization of RNAs to the vegetal cortex during oogenesis. Previous work has suggested that distinct cellular mechanisms mediate localization during these pathways. Here, we provide several independent lines of evidence supporting the existence of common machinery for RNA localization during the early and late pathways. Data from RNA microinjection assays show that early and late pathway RNAs compete for common localization factors in vivo, and that the same short RNA sequence motifs are required for localization during both pathways. In addition, quantitative filter binding assays demonstrate that the late localization factor Vg RBP/Vera binds specifically to several early pathway RNA localization elements. Finally, confocal imaging shows that early pathway RNAs associate with a perinuclear microtubule network that connects to the mitochondrial cloud of stage I oocytes suggesting that motor driven transport plays a role during the early pathway as it does during the late pathway. Taken together, our data indicate that common machinery functions during the early and late pathways. Thus, RNA localization to the vegetal cortex may be a regulated process such that differential interactions with basal factors determine when distinct RNAs are localized during oogenesis.

Animals↗
PubMed2005

Postmenopausal hormone therapy and body composition--a substudy of the estrogen plus progestin trial of the Women's Health Initiative.

BACKGROUND: It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women. OBJECTIVE: This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women. DESIGN: The substudy was composed of 835 women from the estrogen plus progestin trial of the Women's Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed. RESULTS: After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (-0.04 kg) than did the women who received placebo (-0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: -0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took > or = 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis. CONCLUSIONS: A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.

Absorptiometry, Photon↗
PubMed2004

Wheat bran fiber supplementation and bone loss among older people.

OBJECTIVE: The purpose of this study was to investigate the effect of wheat bran fiber (WBF) supplementation on bone loss in older people. METHODS: Two hundred thirty-seven men and women ages 40 to 80 y were included in this study. They constituted a subgroup of participants from a 3-y WBF intervention trial for preventing recurrence of colorectal adenomas. These participants were randomized into a high (13.5 g/d) or a low (2 g/d) WBF supplementation group. Bone mineral density at the forearm was measured by single photon absorptiometry at baseline and yearly during the intervention to monitor possible toxic effects of fiber supplementation on bone metabolism. RESULTS: Baseline characteristics of this subgroup of participants from the WBF trial were similar between the high and low supplementation groups. The annual amounts of bone loss at the radial third site were -0.017 +/- 0.018 g/cm2 and -0.013 +/- 0.021 g/cm2, respectively, for the low and high WBF groups; and the annual bone losses at the ultra-distal site were was -0.005 +/- 0.020 g/cm2 and -0.006 +/- 0.027 g/cm2, respectively, for the low and high WBF groups. After controlling for confounding factors, we found no significant differences in bone loss between groups (P > 0.05). CONCLUSION: WBF supplementation at the level given in this study may not have a significant effect on bone loss among older people.

Absorptiometry, Photon↗
PubMed2004

Simple subtyping assay for human immunodeficiency virus type 1 subtypes B, C, CRF01-AE, CRF07-BC, and CRF08-BC.

After the initial development of a human immunodeficiency virus type 1 (HIV-1) subtype-screening tool by nested multiplex PCR, we further improve it through the redesign of subtype-specific primers based on subtype signature pattern (SSP) analyses and optimization of the PCR conditions. Extracted RNA from plasma samples was used in reverse transcription and the cDNA products were added to the first round PCR, in which universal primers in the gag region were used to detect HIV-1 M group isolates. In the second round of PCR, three pairs of subtype-specific primers, detecting subtypes B, C, and CRF01-AE, were added in one tube. Subtype determination was based on the different size of PCR products on the agarose gel electrophoresis. An additional set of primers detecting only the prevalent recombinant strains CRF07-BC and CRF08-BC was used to discriminate CRF07- and CRF08-BC from pure subtype C. Testing for all kinds of HIV subtype reference strains indicated that this assay was applicable. A panel of 252 HIV-positive samples and 30 HIV-negative samples was further used to evaluate and validate this assay. Compared to the assay of sequence-based phylogenetic analysis, the newly developed assay has an adequate designated subtype sensitivity, 93.2% (69 of 74) for subtype B, 95.1% (117 of 123) for subtype C, 94.0% (47 of 50) for CRF01-AE, and 95.0% (115 of 121) for CRF07-BC and CRF08-BC. Most importantly, the intersubtype specificity of the assay was found to be 100%. The assay specificity was also found to be 100% when used to test 30 HIV-negative samples. The average reproducibility was 96.0% for subtype B, 96.7% for subtype C, and 95.0% for CRF01-AE. We have developed a simple, rapid, and low cost assay for screening subtypes B, C, CRF01-AE, CRF07-BC, and CRF08-BC in China.

Acquired Immunodeficiency Syndrome↗
PubMed2004

[The current status of schistosomiasis epidemics in China].

OBJECTIVE: To analyze the change of tendency on schistosomiasis epidemics in China in the last 5 years. METHODS: Data on schistosomiasis epidemics in the history and particularly in the last 5 years were collected. Tendency and the re-emerging status after 1998 were analyzed. RESULTS: Data in 2003 showed that in 42%, 40% and 53% of the provinces, counties and townships with epidemics, the transmission of the disease has been interrupted or controlled. The number of estimated patients of schistosomiasis and areas with snails were also reduced by 92.74% and 73.56%, in 2003. The annual estimated number of chronic cases was around 800 000 and 31 321.5 hectare of snail infested areas were newly identified in recent 5 years. Among 20 national villages under longitudinal surveillance, 30%, 70% and 35% of the villages were presented a tendency of increase in the rates of human infection, bovine infection and Oncomelania snails infection, respectively. A total of 38 counties from 7 provinces have re-emerged in schistosomiasis transmission after those counties having reached criteria of transmission under control or interrupted. In 6 non-endemic counties, snails were presented, and 16 marshlands in Xan river were found with appearance of acute cases of schistosomiasis. More snail infested areas were found in Shanghai, Zhejiang, and Fujian. Both snail infested areas and newly infected cases were occurred in urban areas along the Yangtze River. CONCLUSION: The tendency of increase was presented in focal areas along the Yangtze River, due to changes of environmental, ecological, societal and economic status, as well as on the forces of control.

Animals↗