Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 181 records · Page 10Linked to original sources

PubMed2001

Heart disease and diabetes risk factors in Pacific Islands communities and associations with measures of body fat.

AIMS: To describe the prevalence of obesity and other coronary heart disease and Type 2 diabetes risk factors by age and ethnic group in Pacific Island communities and to determine the associations between these risk factors and body mass index. METHODS: Cross-sectional data from commuity-based intervention projects were combined to provide anthropometric, blood sample and blood pressure data on 1,175 Pacific Islands people (467 men, 708 women) aged 20 years and over from church communities in South, Central and West Auckland. Self-reported data on diabetes status and leisure-time physical activity were also collected. RESULTS: Based on an ethnic-specific mass index (BMI) cut-off (> 32 kg/m2), 45% of men and 66% of women were obese. The age-standardised prevalence of known diabetes was 12%. Men and women aged 40-60 years had the highest risk factor levels and were the most sedentary. Tongans had higher risk factor levels than Samoans. In men, BMI and waist circumference were associated (p<0.05), in the direction of greater disease risk, with blood pressure and concentrations of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and blood glucose. In women, these associations were similar but less consistent. CONCLUSIONS: While these data are not representative for all Pacific people living in New Zealand, they do show an extremely high prevalence of obesity and significant associations between obesity and other cardiovascular risk factors. These communities warrant a very high priority as part of public health efforts to address New Zealand's growing obesity epidemic.

Adolescent↗

PubMed2001

An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations, and sequence analysis.

The Src-homology-3 (SH3) domain of the Caenorhabditis elegans protein Sem-5 binds proline-rich sequences. It is reported that the SH3 domains broadly accept amide N-substituted residues instead of only recognizing prolines on the basis of side chain shape or rigidity. We have studied the interactions between Sem-5 and its ligands using molecular dynamics (MD), free energy calculations, and sequence analysis. Relative binding free energies, estimated by a method called MM/PBSA, between different substitutions at sites -1, 0, and +2 of the peptide are consistent with the experimental data. A new method to calculate atomic partial charges, AM1-BCC method, is also used in the binding free energy calculations for different N-substitutions at site -1. The results are very similar to those obtained from widely used RESP charges in the AMBER force field. AM1-BCC charges can be calculated more rapidly for any organic molecule than can the RESP charges. Therefore, their use can enable a broader and more efficient application of the MM/PBSA method in drug design. Examination of each component of the free energy leads to the construction of van der Waals interaction energy profiles for each ligand as well as for wild-type and mutant Sem-5 proteins. The profiles and free energy calculations indicate that the van der Waals interactions between the ligands and the receptor determine whether an N- or a Calpha-substituted residue is favored at each site. A VC value (defined as a product of the conservation percentage of each residue and its van der Waals interaction energy with the ligand) is used to identify several residues on the receptor that are critical for specificity and binding affinity. This VC value may have a potential use in identifying crucial residues for any ligand-protein or protein-protein system. Mutations at two of those crucial residues, N190 and N206, are examined. One mutation, N190I, is predicted to reduce the selectivity of the N-substituted residue at site -1 of the ligand and is shown to bind similarly with N- and Calpha-substituted residues at that site.

Animals↗

PubMed2001

Enhancement of antigen-presenting ability of B lymphoma cells by immunostimulatory CpG-oligonucleotides and anti-CD40 antibody.

Immunostimulatory oligodeoxynucleotides containing the CpG motifs (CpG-ODN) can activate antigen-presenting cells including dendritic cells, macrophages, B cells, and enhance production of Thl cytokines. So, CpG-ODN has been regarded as a promising immune adjuvant. Using the A20 B lymphoma cell model, we investigated the effect of CpG-ODN on the immunogenicity of B lymphoma cells and whether CpG-ODN could enhance the antigen-presenting ability of B lymphoma cells. After incubation with CpG-ODN, proliferation of A20 cells remained unchanged. But CpG-ODN stimulation up-regulated the expression of MHC-I, MHC-II, CD40, ICAM-1 molecules in A20 cells, enhanced the antigen uptake ability of A20 cells, and promoted A20 cell production of IgM and IgG. More importantly, A20 cells activated by CpG-ODN could stimulate allogeneic T cells in MLR and antigen-primed T cells to proliferate more efficiently, suggesting the antigen-presenting ability of A20 B lymphoma cells could be enhanced by CpG-ODN stimulation and CpG-ODN-activated B lymphoma cells might be used as a potent cellular vaccine. Although anti-CD40 mAb was as effective as CpG-ODN at activating A20 cells and A20 cells expressed more CD40 molecules after CpG-ODN stimulation, a combination of CpG-ODN and anti-CD40 mAb had no synergistic effect on A20 cell activation. Our data expanded the potential application of CpG-ODN as an immunotherapeutic agent in cancer treatment.

Animals↗

PubMed2001

The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells.

TNF-alpha-related apoptosis-inducing ligand (TRAIL) is characterized by its preferential induction of apoptosis of tumor cells but not normal cells. Dendritic cells (DCs), besides their role as APCs, now have been demonstrated to exert cytotoxicity or cytostasis on some tumor cells. Here, we report that both human CD34(+) stem cell-derived DCs (CD34DCs) and human CD14(+) monocyte-derived DCs (MoDCs) express TRAIL and exhibit cytotoxicity to some types of tumor cells partially through TRAIL. Moderate expression of TRAIL appeared on CD34DCs from the 8th day of culture and was also seen on freshly isolated monocytes. The level of TRAIL expression remained constant until DC maturation. TRAIL expression on immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation. Moreover, IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to kill TRAIL-sensitive tumor cells, but LPS did not have such an effect. The up-regulation of TRAIL on IFN-beta-stimulated DCs partially contributed to the increased cytotoxicity of DCS: Pretreatment of TRAIL-sensitive tumor cells with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of IFN-beta-stimulated DCS: In contrast, NF-kappaB inhibitor could significantly increase the sensitivity of tumor cells to the killing by nonstimulated or LPS-stimulated DCS: Our studies demonstrate that IFN-beta-stimulated DCs are functionally cytotoxic. Thus, an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors to directly kill tumor cells partially via TRAIL. Subsequently, DCs act as APCs involved in the uptake, processing, and presentation of apoptotic tumor Ags to cross-prime CD8(+) CTL cells.

Adjuvants, Immunologic↗

PubMed2001

Signal-to-noise ratio gain in neuronal systems.

We explore the possibility of a signal-to-noise ratio (SNR) gain both in a single neuron and a neuronal network. In the presence of a weak sinusoidal or pulse signal and Gaussian noise, the output SNR can exceed the input SNR over a wide range of noise intensities. The high output SNR and SNR gain can be acquired coincidentally at optimal noise levels. The results further verify that noise can play a constructive role in sensory processing in neuronal systems.

Animals↗

PubMed2001

Synergistic activity of STAT3 and c-Jun at a specific array of DNA elements in the alpha 2-macroglobulin promoter.

The transcriptional activity of natural promoters is sensitive to the precise spatial arrangement of DNA elements and their incorporation into higher order DNA-protein complexes. STAT3 and c-Jun form a specific ternary complex in vitro with a synthetic DNA element containing AP1 and SIE sites. These associations are critical for synergistic activation of transcription from a synthetic promoter by STAT3 and c-Jun. Expression of the acute phase protein alpha(2)-macroglobulin is induced in vivo by interleukin-6 (IL-6)-related cytokines; we demonstrate that coordinate interactions among STAT3, c-Jun, and a specific array of DNA elements contribute to activation of the alpha(2)-macroglobulin promoter in response to IL-6 family members. At least five promoter elements are involved in activation: two AP1 sites at -113 to -107 and -152 to -140, an acute phase response element (APRE (SIE)) at -171 to -163, and two AT-rich regions at -143 to -138 and -128 to -123. Synergism between STAT3 or STAT3-C and c-Jun is impaired by mutation of the APRE (SIE) or either AP1 site, as well as by mutations that alter the AT-rich regions or their phasing. Mutations of STAT3 previously shown to disrupt physical and functional interactions with c-Jun do not impair synergy between STAT3-C and c-Jun at the alpha(2)-macroglobulin promoter in HepG2 cells, suggesting that STAT3-C and STAT3 differ with respect to their precise contacts with c-Jun.

Base Sequence↗

PubMed2001

Transgenic expression of IL-10 in T cells facilitates development of experimental myasthenia gravis.

Ab to the acetylcholine receptor (AChR) cause experimental myasthenia gravis (EMG). Th1 cytokines facilitate EMG, whereas Th2 cytokines might be protective. IL-10 inhibits Th1 responses but facilitates B cell proliferation and Ig production. We examined the role of IL-10 in EMG by using wild-type (WT) C57BL/6 mice and transgenic (TG) C57BL/6 mice that express IL-10 under control of the IL-2 promoter. We immunized the mice with doses of AChR that cause EMG in WT mice or with low doses ineffective at causing EMG in WT mice. After low-dose AChR immunization, WT mice did not develop EMG and had very little anti-AChR serum Ab, which were mainly IgG1, whereas TG mice developed EMG and had higher levels of anti-AChR serum Ab, which were mainly IgG2, in addition to IgG1. At the higher doses, TG mice developed EMG earlier and more frequently than WT mice and had more serum anti-AChR Ab. Both strains had similar relative serum concentrations of anti-AChR IgG subclasses and IgG and complement at the muscle synapses. CD8(+)-depleted splenocytes from all AChR-immunized mice proliferated in the presence of AChR and recognized a similar epitope repertoire. CD8(+)-depleted splenocytes from AChR-immunized TG mice stimulated in vitro with AChR secreted significantly more IL-10, but less of the prototypic Th1 cytokine IFN-gamma, than those from WT mice. They secreted comparable amounts of IL-4 and slightly but not significantly reduced amounts of IL-2. This suggests that TG mice had reduced activation of anti-Torpedo AChR Th1 cells, but increased anti-AChR Ab synthesis, that likely resulted from IL-10-mediated stimulation of anti-AChR B cells. Thus, EMG development is not strictly dependent on Th1 cell activity.

Animals↗

PubMed2001

GABA transaminase inhibition induces spontaneous and enhances depolarization-evoked GABA efflux via reversal of the GABA transporter.

The GABA transporter can reverse with depolarization, causing nonvesicular GABA release. However, this is thought to occur only under pathological conditions. Patch-clamp recordings were made from rat hippocampal neurons in primary cell cultures. Inhibition of GABA transaminase with the anticonvulsant gamma-vinyl GABA (vigabatrin; 0.05-100 microm) resulted in a large leak current that was blocked by bicuculline (50 microm). This leak current occurred in the absence of extracellular calcium and was blocked by the GABA transporter antagonist SKF-89976a (5 microm). These results indicate that vigabatrin induces spontaneous GABA efflux from neighboring cells via reversal of GABA transporters, subsequently leading to the stimulation of GABA(A) receptors on the recorded neuron. The leak current increased slowly over 4 d of treatment with 100 microm vigabatrin, at which time it reached an equivalent conductance of 9.0 +/- 4.9 nS. Blockade of glutamic acid decarboxylase with semicarbazide (2 mm) decreased the leak current that was induced by vigabatrin by 47%. In untreated cells, carrier-mediated GABA efflux did not occur spontaneously but was induced by an increase in [K(+)](o) from 3 to as little as 6 mm. Vigabatrin enhanced this depolarization-evoked nonvesicular GABA release and also enhanced the heteroexchange release of GABA induced by nipecotate. Thus, the GABA transporter normally operates near its equilibrium and can be easily induced to reverse by an increase in cytosolic [GABA] or mild depolarization. We propose that this transporter-mediated nonvesicular GABA release plays an important role in neuronal inhibition under both physiological and pathophysiological conditions and is the target of some anticonvulsants.

4-Aminobutyrate Transaminase↗

PubMed2001

Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice.

We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu et al., 1998). To further evaluate the functional significance of the Ki-ras proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-ras gene dosage on tumor progression. The lack of one normal Ki-ras allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas. However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles. The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-ras affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis.

Animals↗

PubMed2001

A simple automated continuous-flow-equilibration method for measuring carbon monoxide in seawater.

A simple, robust, low-maintenance method using air-segmented continuous-flow equilibration was developed and automated to measure carbon monoxide (CO) in natural waters precisely and accurately. Finely regulated flows of CO-free air and of seawater or standard water were pumped into a glass coil, forming discrete gas/liquid segments. The partially CO-equilibrated gas effluent was injected into a Trace Analytical reduction analyzer for CO detection. A semiempirical mass-balance model was established for predicting and optimizing the performance of the CO extractor. The optimized gas and water flow rates were approximately 1.2 and approximately 14 mL min(-1), respectively, giving a response time of less than 15 min and a CO-extraction yield of approximately 80%. The analytical blank, precision, and accuracy were, respectively, 0.02 nM, +/-2.5% (at the approximately 1 nM level), and better than 5%. Two extractors can be interfaced to one detector at 4-6 samples per hour for each extractor. Coupled with a continuous surface-water sampler, the system was successfully applied to monitoring the diurnal variation of CO concentration in Sargasso Sea surface waters.

Automation↗

PubMed2001

Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function.

Cyclin A1 is tissue-specifically expressed during spermatogenesis, but it is also highly expressed in acute myeloid leukemia (AML). Its pathogenetic role in AML and in the cell cycle of leukemic blasts is unknown. B-myb is essential for G1/S transition and has been shown to be phosphorylated by the cyclin A2/cdk2 complex. Here it is demonstrated that cyclin A1 interacts with the C-terminal portion of B-myb as shown by glutathione S-transferase (GST) precipitation. This interaction is confined to cyclin A1 because binding could not be detected between cyclin A2 and B-myb. Also, cdk2 was not pulled down by GST-B-myb from U937 lysates. In addition, co-immunoprecipitation of cyclin A1 and B-myb in leukemic cells evidenced protein interaction in vivo. Baculovirus-expressed cyclin A1/cdk2 complexes were able to phosphorylate human as well as murine B-myb in vitro. Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. These phosphorylation sites have been demonstrated to be important for the enhancement of B-myb transcriptional activity. Further studies showed that cyclin A1 cooperated with B-myb to transactivate myb binding site containing promoters including the promoter of the human cyclin A1 gene. Taken together, the data suggest that cyclin A1 is a tissue-specific regulator of B-myb function and activates B-myb in leukemic blasts. (Blood. 2001;97:2091-2097)

Animals↗

PubMed2001

Self-assembled monolayers from a designed combinatorial library of de novo beta-sheet proteins.

A variety of naturally occurring biomaterials owe their unusual structural and mechanical properties to layers of beta-sheet proteins laminated between layers of inorganic mineral. To explore the possibility of fabricating novel two-dimensional protein layers, we studied the self-assembly properties of de novo proteins from a designed combinatorial library. Each protein in the library has a distinct 63 amino acid sequence, yet they all share an identical binary pattern of polar and nonpolar residues, which was designed to favor the formation of six-stranded amphiphilic beta-sheets. Characterization of proteins isolated from the library demonstrates that (i) they self assemble into monolayers at an air/water interface; (ii) the monolayers are dominated by beta-sheet secondary structure, as shown by both circular dichroism and infrared spectroscopies; and (iii) the measured areas (500- 600 A(2)) of individual protein molecules in the monolayers match those expected for proteins folded into amphiphilic beta-sheets. The finding that similar structures are formed by distinctly different protein sequences suggests that assembly into beta-sheet monolayers can be encoded by binary patterning of polar and nonpolar amino acids. Moreover, because the designed binary pattern is compatible with a wide variety of different sequences, it may be possible to fabricate beta-sheet monolayers by using combinations of side chains that are explicitly designed to favor particular applications of novel biomaterials.

Air↗

PubMed2001

Biomarker risk assessment and bladder cancer detection in a cohort exposed to benzidine.

BACKGROUND: Cancer screening with highly sensitive, specific biomarkers that reflect molecular phenotypic alterations is an attractive strategy for cancer control. We examined whether biomarker profiles could be used for risk assessment and cancer detection in a cohort of Chinese workers occupationally exposed to benzidine and at risk for bladder cancer. METHODS: The cohort consisted of 1788 exposed and 373 nonexposed workers, followed from 1991 through 1997. We assayed urothelial cells from voided urine samples for DNA ploidy (expressed as the 5C-exceeding rate [DNA 5CER]), the bladder tumor-associated antigen p300, and a cytoskeletal protein (G-actin). Workers were stratified into different risk groups (high, moderate, and low risk) at each examination based on a predefined biomarker profile. For workers who developed bladder cancer, tumor risk assessment was analyzed from samples collected 6-12 months before the cancer diagnosis. The associations between risk group and subsequent development of bladder cancer were analyzed by Cox proportional hazards regression analysis and logistic analysis, after adjustment. All statistical tests were two-sided. RESULTS: Twenty-eight bladder cancers were diagnosed in exposed workers and two in nonexposed workers. For risk assessment, DNA 5CER had 87.5% sensitivity, 86.5% specificity, an odds ratio (OR) of 46.2 (95% confidence interval [CI] = 8.1 to 867.0), and a risk ratio (RR) of 16.2 (95% CI = 7.1 to 37.0); p300 had 50.0% sensitivity, 97.9% specificity, an OR of 40.0 (95% CI = 9.0 to 177.8), and an RR of 37.9 (95% CI = 16.8 to 85.3). The risk of developing bladder cancer was 19.6 (95% CI = 8.0 to 47.9) times higher in workers positive for either the DNA 5CER or p300 biomarkers than in workers negative for both biomarkers and 81.4 (95% CI = 33.3 to 199.3) times higher in workers positive for both biomarkers. G-actin was a poor marker of individual risk. CONCLUSIONS: Occupationally exposed workers at risk for bladder cancer can be individually stratified, screened, monitored, and diagnosed based on predefined molecular biomarker profiles.

Actins↗

PubMed2001

Molecular cloning, mapping and characterization of the human neurocalcin delta gene (NCALD).

We identified a new human gene that encodes a cognate of the bovine neurocalcin delta from a human fetal brain cDNA library; hence we named it human neurocalcin delta (NCALD) gene. The deduced polypeptide product of the cDNA is 22 kDa in size, and its amino acid sequence is 100% and 99% identical to that of the bovine and chicken neurocalcin, respectively. Northern blots showed that the NCALD gene is more abundantly expressed in brain, testis, ovary and small intestine. Tissue in situ hybridization confirmed the existence of the NCALD mRNA in the adult human testis. Radiation hybrid panel mapping localized the gene to chromosome 8 between molecular markers D8S270 and D8S257.

Adult↗

PubMed2001

Differentially expressed genes in zona reticularis cells of the human adrenal cortex.

The zona reticularis (ZR) cell in the human adrenal cortex is responsible for the secretion of dehydroepiandrosterone, but its biology, origin, and putative decrease in number during aging are poorly understood. In the present experiments, we investigated to what extent ZR and zona fasciculata (ZF) cells differ in patterns of gene expression. Both cell types were purified by microdissection from adult adrenal cortex specimens. After a brief period in culture, RNA was harvested from the cells and used to prepare radioactively labeled probes following amplification by PCR. Probes were used in hybridizations of arrays of cDNAs on nylon membranes (PCR products or plasmids obtained from an adrenal cDNA library). Analysis of hybridization intensities showed that 17 of the 750 genes studied differed in expression by more than 2-fold. Several genes expressed at higher levels in ZR cells encode components of the major histocompatibility complex or enzymes involved in peroxide metabolism. Members of the tubulin gene family were expressed at higher levels in ZF cells. Differential expression of four of the genes was confirmed by Northern blotting. These differences show that although ZR and ZF cells are similar in gene expression, ZR cells have a gene expression pattern related to the unique biology of this cell type.

Adult↗

PubMed2001

Effects of correlated and independent noise on signal processing in neuronal systems.

Stochastic resonance has recently received considerable attention demonstrating that noise can play a constructive role in signal processing. We investigate the effects of input noise on sensory processing via numerical simulation when they are independent of each other or spatially correlated in a globally coupled neuronal network. The network exhibits a coherent behavior in the absence of stimulation. Such ongoing activity has a remarkable influence on neuronal responses to stimuli. In the presence of a subthreshold periodic signal, the activity averaged over neurons can convey precise information about the stimulus in the case of independent noise. On the other hand, when the noise is correlated among the neurons, the average response is nearly as noisy and variable as the responses of the individual neurons. Thus, the spatially correlated noise diminishes the beneficial effects of pooling, although it can evoke synchronous firings of neurons. These suggest that response variability in cortical activity may be closely related to the correlation in input noise.

Action Potentials↗

PubMed2001

Approach to energy eigenvalues and eigenfunctions from nonperturbative regions of eigenfunctions.

We study the approach to energy eigenvalues and eigenfunctions of Hamiltonian matrices with band structure from diagonalization of their truncated matrices. Making use of a generalization of Brillouin-Wigner perturbation theory, it is shown that in order to obtain approximate energy eigenvalues and eigenfunctions the sizes of truncated matrices should be larger than the nonperturbative regions of the eigenfunctions by several band width of the Hamiltonian matrix, with the nonperturbative regions being able to be estimated before the eigenfunctions are known. This prediction is checked numerically by the Wigner-band random-matrix model, which shows that 99% of eigenfunctions can be obtained when the sizes of truncated matrices are larger than those of the nonperturbative regions of the eigenfunctions by three band widths of the Hamiltonian matrix, on average.

Journal Article↗

PubMed2001

Enhancement of T helper2 response in the absence of interleukin (IL-)6; an inhibition of IL-4-mediated T helper2 cell differentiation by IL-6.

Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice deficient in IL-6 and wild mice were immunized with antigens (myelin oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover, polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal stimulation and by antigen-primed spleen T cells in response to re-challenge with the antigen. In contrast, the induction of spleen CD4-positive T cells into Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3 plus IL-12 was not inhibited by the presence of IL-6. Thus, these results indicate that IL-6 physiologically could modulate qualitative T cell response and suggest that it augments Th(1)responses partly through its inhibitory capability of IL-4-induced Th(2)differentiation of naive T cells.

Adjuvants, Immunologic↗