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Biomedical subjects

B Zheng

Publications and source records attributed to B Zheng.

At least 73 records · Page 4Linked to original sources
PubMed2000

Summarizing the predictive power of a generalized linear model.

This paper studies summary measures of the predictive power of a generalized linear model, paying special attention to a generalization of the multiple correlation coefficient from ordinary linear regression. The population value is the correlation between the response and its conditional expectation given the predictors, and the sample value is the correlation between the observed response and the model predicted value. We compare four estimators of the measure in terms of bias, mean squared error and behaviour in the presence of overparameterization. The sample estimator and a jack-knife estimator usually behave adequately, but a cross-validation estimator has a large negative bias with large mean squared error. One can use bootstrap methods to construct confidence intervals for the population value of the correlation measure and to estimate the degree to which a model selection procedure may provide an overly optimistic measure of the actual predictive power.

Bias↗
PubMed2000

Summarizing the goodness of fit of generalized linear models for longitudinal data.

This paper extends four goodness-of-fit measures of a generalized linear model (GLM) to random effects and marginal models for longitudinal data. The four measures are the proportional reduction in entropy measure, the proportional reduction in deviance measure, the concordance correlation coefficient and the concordance index. The extended measures satisfy the basic requirements for measures of association. Two examples illustrate their use in model selection.

Adolescent↗
PubMed2000

DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.

The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.

Adult↗
PubMed2000

Interacting molecular loops in the mammalian circadian clock.

We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.

ARNTL Transcription Factors↗
PubMed2000

MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16.

We have identified the protein MIR16 (for Membrane Interacting protein of RGS16) from a yeast two-hybrid screen by using RGS16 as bait. MIR16 shares strong homology with bacterial glycerophosphodiester phosphodiesterases. It interacts with RGS16 and, more weakly, with several other selected RGS proteins. Analysis of deletion mutants showed that the N-terminal region of the RGS domain in RGS16 is required for its interaction with MIR16. MIR16 is an integral membrane glycoprotein, because it remained associated with membrane fractions after alkaline treatment and because, in some cells, it is sensitive to digestion with endoglycosidase H. By immunofluorescence and immunoelectron microscopy, MIR16 was localized on the plasma membrane in liver and kidney and on intracellular membranes in rat pituitary and cultured pituitary cells. MIR16 represents the only integral membrane protein identified thus far to interact with an RGS domain and, to our knowledge, is the only mammalian glycerophosphodiester phosphodiesterase that has been cloned. The putative enzymatic activity of MIR16 and its interaction with RGS16 suggest that it may play important roles in lipid metabolism and in G protein signaling.

Amino Acid Sequence↗
PubMed2000

Applying computer-assisted detection schemes to digitized mammograms after JPEG data compression: an assessment.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of Joint Photographic Experts Group (JPEG) image data compression on the performance of computer-assisted detection (CAD) schemes for the detection of masses and microcalcification clusters on digitized mammograms. MATERIALS AND METHODS: This study included 952 mammograms that were digitized and compressed with a JPEG-compatible image-compression scheme. A CAD scheme, previously developed in the authors' laboratory and optimized for noncompressed images, was applied to reconstructed images after compression at five levels. The performance was compared with that obtained with the original noncompressed digitized images. RESULTS: For mass detection, there were no significant differences in performance between noncompressed and compressed images for true-positive regions (P = .25) or false-positive regions (P = .40). In all six modes the scheme identified 80% of masses with less than one false-positive region per image. For the detection of microcalcification clusters, there was significant performance degradation (P < .001) at all compression levels. Detection sensitivity was reduced by 4%-10% as compression ratios increased from 17:1 to 62:1. At the same time, the false-positive detection rate was increased by 91%-140%. CONCLUSION: The JPEG algorithm did not adversely affect the performance of the CAD scheme for detecting masses, but it did significantly affect the detection of microcalcification clusters.

Algorithms↗
PubMed2000

Direct analysis and identification of triterpene glycosides by LC/MS in black cohosh, Cimicifuga racemosa, and in several commercially available black cohosh products.

A method to directly identify triterpene glycosides using reversed-phase liquid chromatography with positive atmospheric pressure chemical ionization mass spectrometry (LC/(+)APCIMS) was developed. Based on the analysis of the molecular weight, fragment ions, selected ion chromatograms, a number of triterpene glycosides, including actein, 27-deoxyactein, cimicfugoside M, and cimicifugoside, from Cimicifuga racemosa were studied. A chromone, cimifugin, from C. foetida was also identified. Cimicifugoside M and cimifugin can specifically serve as indicators for species identification. The method can, therefore, be used to distinguish black cohosh products from among different plant species for quality control purposes.

Chromatography, Liquid↗
PubMed2000

High versus low basal cortisol secretion in asymptomatic, medication-free HIV-infected men: differential effects of severe life stress on parameters of immune status.

The authors hypothesized that HIV-infected men with high basal cortisol secretion would exhibit greater stress-related reductions in the ratio of Th1/Th2 cell-derived cytokines and numbers of CD8+ T and NK lymphocytes than low basal cortisol secretors. A semistructured interview was used to assess life stress during the preceding 6 months of 94 HIV-infected men classified as high and low cortisol secretors (n = 47/group). Increased levels of severe life stress were highly correlated with lower numbers of CD8+ T cells, CD16+ and CD56+ NK cells, CD57+ cells, and higher DHEA-S concentrations in the high cortisol group. Conversely, no significant correlations were found in the low cortisol group. No correlations were found between stress and CD4+ T helper/inducer cell counts, cytokine production, or testosterone levels in either participating group. These data suggest that severe stress in combination with high glucocorticoid activity may modify select parameters of immune status in HIV-infected men.

Adaptation, Psychological↗
PubMed2000

Low levels of expression of cytochromes P-450 in normal and cancerous fetal pancreatic tissues of hamsters treated with NNK and/or ethanol.

Previous studies from this laboratory have demonstrated that administration of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to pregnant hamsters results in tumors in the offspring. Whereas treatment with NNK alone caused mainly tumors in the respiratory tract of the treated offspring, cotreatment with ethanol (EtOH) and NNK shifted the site of tumor formation to the pancreas. In order to determine potential mechanisms for the cocarcinogenic effects of EtOH, the levels of NNK metabolites and expression of various CYPs implicated in the metabolic activation of NNK were determined in fetal liver and pancreas. NNK and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), were detected at low and variable levels in the fetal liver and pancreas, with an NNAL to NNK ratio greater than 20 in both organs. EtOH had no effect on the amount of metabolites found in either organ. Results obtained with the fetal liver samples, which served as a positive control, correlated very well with our previous studies demonstrating low levels of expression of several CYP isozymes at both the protein and RNA level. Western blot analysis showed low but detectable levels of CYP1A1, barely detectable levels of CYP2E1, and an absence of CYP1A2 and 2B family members in the fetal pancreas. RNA transcripts were undetectable by ribonuclease protection in the fetal pancreas, although readily seen in fetal liver samples. Treatment with NNK, EtOH, or both NNK and EtOH had small and variable effects on the levels of metabolism of NNK and expression of the isozymes. These findings suggest that alternative mechanisms may be responsible for transplacentally induced tumors in this model system.

Animals↗
PubMed2000

Deterministic equations of motion and phase ordering dynamics

We numerically solve microscopic deterministic equations of motion for the two-dimensional straight phi(4) theory with random initial states. Phase ordering dynamics is investigated. Dynamic scaling is found and it is dominated by a fixed point corresponding to the minimum energy of random initial states.

Journal Article↗
PubMed2000

Dynamic approach to weak first-order phase transitions

A short-time dynamic approach to weak first-order phase transitions is proposed. Taking the two-dimensional Potts models as examples, from short-time behavior of nonequilibrium relaxational processes starting from high temperature and zero temperature states, pseudo-critical-points K* and K** are determined. A clear difference of the values for K* and K** distinguishes a weak first-order transition from a second-order one.

Journal Article↗
PubMed2000

Sequence requirements for trafficking of the CRAM transmembrane protein to the flagellar pocket of African trypanosomes.

CRAM is a cysteine-rich acidic transmembrane protein, highly expressed in the procyclic form of Trypanosoma brucei. Cell surface expression of CRAM is restricted to the flagellar pocket of trypanosomes, the only place where receptor mediated endocytosis takes place in the parasite. CRAM can function as a receptor and was hypothesized to be a lipoprotein receptor of trypanosomes. We study mechanisms involved in the presentation and routing of CRAM to the flagellar pocket of insect- and bloodstream-form trypanosomes. By deletional mutagenesis, we found that deleting up to four amino acids from the C terminus of CRAM did not affect the localization of CRAM at the flagellar pocket. Shortening the CRAM protein by 8 and 19 amino acids from the C terminus resulted in the distribution of the CRAM protein in the endoplasmic reticulum (ER) (the CRAM protein is no longer uniquely sequestered at the flagellar pocket). This result indicates that the truncation of the CRAM C terminus affected the transport efficiency of CRAM from the ER to the flagellar pocket. However, when CRAM was truncated between 29 and 40 amino acids from the C terminus, CRAM was not only distributed in the ER but also located to the flagellar pocket and spread to the cell surface and the flagellum. Replacing the CRAM transmembrane domain with the invariant surface glycoprotein 65-derived transmembrane region did not affect the flagellar pocket location of CRAM. These results indicate that the CRAM cytoplasmic extension may exhibit two functional domains: one domain near the C terminus is important for efficient export of CRAM from the ER, while the second domain is of importance for confining CRAM to the flagellar pocket membrane.

Amino Acid Sequence↗
PubMed2000

Engineering mouse chromosomes with Cre-loxP: range, efficiency, and somatic applications.

Chromosomal rearrangements are important resources for genetic studies. Recently, a Cre-loxP-based method to introduce defined chromosomal rearrangements (deletions, duplications, and inversions) into the mouse genome (chromosome engineering) has been established. To explore the limits of this technology systematically, we have evaluated this strategy on mouse chromosome 11. Although the efficiency of Cre-loxP-mediated recombination decreases with increasing genetic distance when the two endpoints are on the same chromosome, the efficiency is not limiting even when the genetic distance is maximized. Rearrangements encompassing up to three quarters of chromosome 11 have been constructed in mouse embryonic stem (ES) cells. While larger deletions may lead to ES cell lethality, smaller deletions can be produced very efficiently both in ES cells and in vivo in a tissue- or cell-type-specific manner. We conclude that any chromosomal rearrangement can be made in ES cells with the Cre-loxP strategy provided that it does not affect cell viability. In vivo chromosome engineering can be potentially used to achieve somatic losses of heterozygosity in creating mouse models of human cancers.

Amino Acid Sequence↗
PubMed2000

The regulator of G protein signaling family.

Regulator of G protein signaling (RGS) proteins are responsible for the rapid turnoff of G protein-coupled receptor signaling pathways. The major mechanism whereby RGS proteins negatively regulate G proteins is via the GTPase activating protein activity of their RGS domain. Structural and mutational analyses have characterized the RGS/G alpha interaction in detail, explaining the molecular mechanisms of the GTPase activating protein activity of RGS proteins. More than 20 RGS proteins have been isolated, and there are indications that specific RGS proteins regulate specific G protein-coupled receptor pathways. This specificity is probably created by a combination of cell type-specific expression, tissue distribution, intracellular localization, posttranslational modifications, and domains other than the RGS domain that link them to other signaling pathways. In this review we discuss what has been learned so far about the role of RGS proteins in regulating G protein-coupled receptor signaling and point out areas that may be fruitful for future research.

Amino Acid Sequence↗
PubMed2000

Determination of monomethylarsonous acid, a key arsenic methylation intermediate, in human urine.

In this study we report on the finding of monomethylarsonous acid [MMA(III)] in human urine. This newly identified arsenic species is a key intermediate in the metabolic pathway of arsenic biomethylation, which involves stepwise reduction of pentavalent to trivalent arsenic species followed by oxidative addition of a methyl group. Arsenic speciation was carried out using ion-pair chromatographic separation of arsenic compounds with hydride generation atomic fluorescence spectrometry detection. Speciation of the inorganic arsenite [As(III)], inorganic arsenate [As(V)], monomethylarsonic acid [MMA(V)], dimethylarsinic acid [DMA(V)], and MMA(III) in a urine sample was complete in 5 min. Urine samples collected from humans before and after a single oral administration of 300 mg sodium 2,3-dimercapto-1-propane sulfonate (DMPS) were analyzed for arsenic species. MMA(III) was found in 51 out of 123 urine samples collected from 41 people in inner Mongolia 0-6 hr after the administration of DMPS. MMA(III )in urine samples did not arise from the reduction of MMA(V) by DMPS. DMPS probably assisted the release of MMA(III) that was formed in the body. Along with the presence of MMA(III), there was an increase in the relative concentration of MMA(V) and a decrease in DMA(V) in the urine samples collected after the DMPS ingestion.

Arsenic↗
PubMed2000

[Construction of recombinant BCG bearing Schistosoma japonicum 26Ku antigen gene and study on its immunogenicity on mice].

OBJECTIVE: To construct recombinant BCG vaccine bearing Schistosoma japonicum 26Ku glutathione S-transferase (Sj26GST) gene and determine its immunogenicity on BALB/c mice. METHODS: Using techniques of molecular biology, human mycobacterium tuberculosis HSP70 promoter and Sj26GST gene were linked to produce a fused gene. The fused gene was cloned into an E. coli-Mycobacterium shuttle plasmid pBCG-2000 to construct an E. coli-Mycobacterium expression shuttle plasmid pBCG-Sj26 that could express Sj26GST gene. Then, the pBCG-Sj26 was introduced by electroporation into mycobacterium bovis BCG to construct a recombinant BCG vaccine bearing Sj26GST gene (rBCG- Sj26GST). The expression of Sj26GST gene in BCG was induced by heating. The lymphocyte stimulating index (SI), macrophage activity and IL-2, IFN-gamma levels of the serum and culture supernatant of spleen lymphocytes were tested after immunization of BALB/c mice with rBCG-Sj26GST vaccine. RESULTS: The fused gene of HSP70 promoter and Sj26GST cDNA was inserted into an E. coli-Mycobacterium shuttle expression plasmid by analysing electrophoresis results on PCR products using plasmid pBCG-Sj26 as a templet. The content of rSj26GST contained 15% of total bacterial protein of BCG. The SI of the experimental group was 2.26 +/- 0.43, which was significantly higher than those in the control group (1.61 +/- 0.28, P < 0.05), vector group (1.48 +/- 0.30, P < 0.05) and BCG group (1.42 +/- 0.26, P < 0.05). The macrophage NO level of the experimental group was (357.42 +/- 84.11) nmol/ml which was significantly higher than those in the control group (183 nmol/ml +/- 33 nmol/ml, P < 0.01) and vector group (203 nmol/ml +/- 56 nmol/ml, P < 0.01). The serum IL-2 level of the experimental group was (267 pg/ml +/- 130 pg/ml), which was significantly higher than those in the control group (45 pg/ml +/- 15 pg/ml, P < 0.01) and vector group (52 pg/ml +/- 29 pg/ml, P < 0.05. Compared with the control group, the serum IFN-gamma level increased by 20%, the IL-2 level of the culture supernatant of spleen lymphocytes increased by 44%. CONCLUSIONS: The foreign gene encoding Sj26 GST can be expressed in BCG. rBCG Sj26GST vaccine may induce stronger immune response in BALB/c mice than in control, vector and BCG groups.

Animals↗
PubMed2000

[The histogenesis, clinical features and histopathological analysis on 52 cases of ciliary body neoplasms].

OBJECTIVE: To analyze the histogenesis, classification, incidence, clinical feature, the key point of differential diagnosis and histopathologic characteristics of ciliary body neoplasms to provide the basis for clinical diagnosis and treatment. METHOD: 52 specimens of ciliary body neoplasms on file were analyzed and studied for the characteristics of clinical presentation and histopathology. RESULTS: Of the 52 specimens, 38 were located in the ciliary body (73.1%), and 14 lesions involved the iris (26.9%). According to the results of histogenetic classification, the tumors of ciliary sensory epithelium were ranked the first place (20 cases, 38.5%) while malignant melanoma, the second one (14 cases, 26.9%) followed by melanocytoma (9 cases, 17.3%) and granulomatous lesions (5 cases, 9.6%). CONCLUSION: The clinical features and histopathologic characteristics of ciliary body neoplasms are systemically and deeply recognized, that may help clinical ophthalmologists to make correct diagnosis and proper treatment.

Adolescent↗