Biomedical subjects
Publications and source records attributed to Q Wang.
We derive the quantum kinetic equation for a pure gluon plasma, applying the background field and closed-time-path method. The derivation is more general and transparent than earlier works. A term in the equation is found which, as in the classical case, corresponds to the color charge precession for partons moving in the gauge field.
Detection of courtship-activating female pheromones by contact chemoreceptors on the front legs of male Drosophila melanogaster is thought to play an important role in triggering courtship behavior. However, the chemosensory organs, cells, and molecules responsible are not known. We have isolated two genes, CheA29a and CheB42a, expressed in nonneuronal auxiliary cells within two nested subsets of chemosensory sensilla on the front legs of sexually mature, adult males. The proteins encoded by the CheA29a and CheB42a genes have no sequence similarity to each other or any other known protein, but they belong to two novel families of proteins encoded by the D. melanogaster genome. Members of the two families are predicted to have a single transmembrane domain at their amino terminus, probably to serve as a signal peptide, suggesting that they are soluble and secreted. Finally, in addition to CheA29a and CheB42a, other genes within each family are expressed preferentially in appendages where chemosensory organs are concentrated, in several cases in a male-specific manner. Our data suggest that CheA29a and CheB42a and other members of these two protein families are involved in male-specific chemical senses, perhaps pheromone response.
UNLABELLED: Microcirculation viviperception and fluorescent tracer techniques were used and digital image analysis applied for quantitative measurement of fluorescein sodium (FiNa) permeability in microvessels of the cerebral pia mater. The diffusion permeation equations of FiNa within the blood vessels and through the vessel walls into the perivascular tissue of normal rats and ischemic rats were established with two vessels as study object, thus the permeation speed equations under different ischemic conditions were deduced. Based on analysis of the results, we deduced the relation between the permeability and the intersection angle of two vessels. RESULT: logarithm model showed a good fit of the experiment data. The permeation equation showed logarithmic distribution and then tended towards stability. FiNa could pass through microvessel walls with the highest speed in the one-hour ischemic rat group, and the permeation speed of FiNa in rats receiving reperfusion after twelve hours of ischemia was much faster than that in normal rats. CONCLUSION: the method can be useful for quantitative analysis of cerebral pia mater microvascular permeability
The effects of aminoguanidine (AG), a specific inhibitor of inducible nitric oxide synthase, on the bleomycin (BL)-induced lung fibrosis was evaluated in mice. The animals were placed into five groups: saline (SA)-instilled drinking water (SA+H(2)O), saline-instilled drinking water containing 0.5%AG (SA+0.5%AG), BL-instilled drinking water (BL+H(2)O), BL-instilled drinking water containing 0.2%AG (BL+0.2%AG), and BL-instilled drinking water containing 0.5%AG (BL+0.5%AG). The mice had free access to H(2)O or H(2)O containing AG and lab chow ad lib 2 days prior to intratracheal (IT) instillation of BL (0.07U/mouse/100 microL) or an equivalent volume of sterile isotonic saline. The mice in the SA+0.5%AG group consumed the greatest amount of AG without any ill effects than the mice in any other group. There were no differences in any of the measured biochemical determinants between the SA+H(2)O and SA+0.5%AG control groups. The IT instillation of BL in the BL+H(2)O group caused significant increases in the lipid peroxidation, hydroxyproline content, and prolyl hydroxylase activity of lungs and influx of inflammatory cells in the broncheoalveolar lavage fluid (BALF) as compared to both control groups. The intake of aminoguanidine by mice in the BL+0.5%AG group caused significant reductions in the BL-induced increases in all measured biochemical indices of lung fibrosis without any effects on the influx of inflammatory cells in the BALF. In fact, AG in both BL-treated groups additionally increased the total cell counts in the BALF from mice in the BL+0.2%AG and BL+0.5%AG groups as compared to the BL+H(2)O group. Histopathological evaluation of the lungs revealed that the mice in the BL+0.5%AG group had markedly fewer fibrotic lesions than mice in the BL+H(2)O group. These results demonstrate that aminoguanidine minimizes the BL-induced lung fibrosis at both the biochemical and the morphological level and support our earlier hypothesis that the production of nitric oxide plays a significant role in the pathogenesis lung fibrosis caused by BL.
Lymphotactin (Lptn) is a C chemokine that attracts T cells and NK cells. Dendritic cells (DC) are highly efficient, specialized antigen-presenting cells and antigen-pulsed DC has been regarded as promising vaccines in cancer immunotherapy. The aim of our present study is to improve the therapeutic efficacy of DC-based tumor vaccine by increasing the preferential chemotaxis of DC to T cells. In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model. Immunization of C57BL/6 mice with DC adenovirally cotransfected with Lptn and gp100 (Lptn/gp100-DC) could enhance the cytotoxicities of CTL and NK cells, increase the production of IL-2 and interferon-gamma significantly, as compared with immunization with gp100-DC, Lptn-DC, LacZ-DC, DC or PBS counterparts. The Lptn/gp100-DC immunized mice exhibited resistance to tumor challenge most effectively. It was found that the tumor mass of mice vaccinated by Lptn/gp100-DC showed obvious necrosis and inflammatory cell infiltration. In vivo depletion analysis demonstrated that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of Lptn/gp100-DC and CD4(+) T cells were necessary in the induction phase of tumor rejection, while NK cells were less important although they participated in the antitumor response either in the induction phase or in the effector phase. In the murine model with the pre-established subcutaneous B16 melanoma, immunization with Lptn/gp100-DC inhibited the tumor growth most significantly when compared with other counterparts. These findings provide a potential strategy to improve the efficacy of DC-based tumor vaccines.
AIMS: To investigate the occurrence of Erysipelothrix rhusiopathiae and other Erysipelothrix spp. in abattoir and meat samples in Western Australia. METHODS AND RESULTS: Samples were collected from various parts of pig and sheep carcasses, as well as different sections of slaughtering line, pen soil and effluent. Previously evaluated culture methods were applied for the isolation of Erysipelothrix spp., in conjunction with phenotypic and genotypic detection and identification procedures. Of 109 samples from the two abattoirs, 35 (32.1%) were Erysipelothrix genus-specific PCR-positive. These came from swabs of animal exterior surfaces and joints, slaughtering areas, pig pen soil and abattoir effluent. Four samples (3.7%) from sheep arthritic joints and pig abattoir effluent were also E. rhusiopathiae species-specific PCR-positive. Of 123 carcass washing samples, 12 (9.8%) were genus-specific PCR-positive, and these came from all five kinds of meat samples tested, including beef, lamb, mutton, pork and chicken. Four of them (3.3%) were also species-specific PCR-positive. A total of 25 isolates was recovered from the samples, of which seven were identified as E. rhusiopathiae, seven were consistent with E. tonsillarum, and the remaining 11 were other species of Erysipelothrix. CONCLUSIONS: Erysipelothrix spp. can still be isolated and identified from specimens of animal origin with relative ease, provided that appropriate cultural and molecular procedures are used. Clinical microbiology laboratories may need to improve their diagnostic protocols. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms that E. rhusiopathiae and other species of Erysipelothrix continue to colonize and contaminate farmed animals and animal products. Erysipelothrix infection still poses a potential threat to the economy of the farmed animal industry, as well as being a potential human public health hazard.
AIMS: To find a yeast strain that can overproduce pyruvate and to investigate the effect of nutrients on pyruvate production. METHODS AND RESULTS: Trichosporon cutaneum PD70, a yeast strain that can overproduce pyruvate, was isolated from shake-flask cultures of 132 yeast strains. Pyruvate was measured by the HPLC or DNP method (see Materials and methods). Pyruvate production reached approximately 30.0 +/- 1.0 g l(-1) in basal fermentation medium. Different nutrient supplements had great effects on pyruvate production. Some of the conditions that gave the highest yield are described. CONCLUSIONS: Exogenous thiamine supplement caused a decrease in pyruvate yield. Some amino acids, such as L-arginine, L-isoleucine and L-valine, caused a minor increase in pyruvate yield. Soybean peptone was the most suitable nitrogen source for pyruvate production. A glucose concentration of 15% in fermentation medium gave the highest yield (34.6 g l(-1)) and the highest yield against consumed glucose (0.429 g g(-1)). SIGNIFICANCE AND IMPACT OF THE STUDY: Nutrients have significant impacts on pyruvate production. As a pyruvate overproducing yeast strain independent of exogenous vitamins or amino acids, T. cutaneum PD70 provides an advantage for commercial pyruvate production.
We characterized the effects of i.v. and s.c. zolpidem (1-8 mg/kg) under a differential reinforcement of low-rate schedule (i.e. DRL 45 s) in 3-hour sessions. Both behavioral and pharmacokinetic-pharmacodynamic analyses were used with the intent to compare the effects of zolpidem with those of benzodiazepines reported previously under the same behavioral paradigm. Zolpidem increased the shorter-response [inter-response times (IRTs)<45 s] rate and decreased the reinforcement rate in a dose- and time-related fashion. The behavioral profiles of zolpidem were mainly similar to those of benzodiazepines, except zolpidem produced far fewer shorter IRT responses. Pharmacokinetically, zolpidem decays biexponentially with distributional and terminal elimination half-lives of 5.2 and 42 min, respectively. The absorption rate constant and absolute bioavailability for s.c. zolpidem were 0.083/min and of 84.1%, respectively. The pharmacodynamic parameters for the reinforcement rate, an index of timing performance, were determined by integration of behavioral and pharmacokinetic profiles in a between-subject design using the effect-linked inhibitory sigmoidal E(max) model. The pharmacokinetic-pharmacodynamic analysis revealed that the potency of zolpidem (concentration required to produce 50% maximal effects, IC(50)) in disrupting the timing performance was 0.129 microg/ml. The pharmacodynamic estimates of zolpidem were compared to our previous results for benzodiazepines.
BACKGROUND: The transcription factor encoded by the intestinal Cdx2 homeobox gene and treatment with sodium butyrate (NaB), a byproduct of fibre fermentation by colonic bacteria, exert similar effects on colon cancer cell lines as they both inhibit cell growth and stimulate cell differentiation and apoptosis. AIM: To investigate whether NaB regulates expression of the Cdx2 gene in colon cancer cell lines. METHODS: Human adenocarcinoma cell lines Caco2 and HT29 were grown in the presence or absence of NaB. Cells were analysed for Cdx2 mRNA expression by reverse transcription-polymerase chain reaction, for protein expression by western blotting and electromobility shift assays, and for transcriptional activity of the Cdx2 promoter by transfection with luciferase reporter plasmids. RESULTS: In HT29 and Caco2 cells, NaB stimulated Cdx2 mRNA and protein expression as well as transcriptional activity of the Cdx2 promoter. Stimulation of the activity of the Cdx2 promoter by NaB was dose and time dependent. The Cdx2 promoter contains discrete regions that participate in or inversely that blunt the stimulatory effect exerted by NaB. In addition, NaB stimulated the transcriptional activity of the Cdx2 promoter downregulated by oncogenic ras. CONCLUSION: This study is the first report of an intestine specific transcription factor, Cdx2, stimulated by butyrate. Thus it provides a new mechanism whereby butyrate controls proliferation and differentiation of colon cancer cells.
Cardiac arrhythmias cause 400 000 sudden deaths annually in the United States alone. Mutations in the cardiac sodium channel gene SCN5A on chromosome 3p21 cause cardiac arrhythmias and sudden death. In this study, we define an SCN5A mutation, S1103Y, in a white family associated with syncope, ventricular fibrillation, and sudden death. A very recent study reported the same mutation in 13.2% of African Americans, but not in the white population. Our study shows that mutation S1103Y does exist in the white population, and it is associated with a considerable risk of syncope, ventricular arrhythmia, ventricular fibrillation, and sudden death in this population.
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Protein tyrosine phosphatases (PTPases) are signal-transducing enzymes that dephosphorylate intracellular proteins that have phosphorylated tyrosine residues. It has been demonstrated that protein tyrosine phosphatase 1B (PTP1B) is an attractive therapeutic target because of its involvement in regulating insulin sensitivity (Elcheby et al. Science 1999, 283, 1544-1548). The identification of a second binding site in PTP1B (Puius et al., Proc. Natl. Acad. Sci. U.S.A.1997, 94, 13420-13425) suggests a new strategy for inhibitor design, where appropriate compounds may be made to simultaneously occupy both binding sites to gain much higher affinity and selectivity. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have determined the crystal structure of PTP1B complexed with two non-peptidyl inhibitors, 4 and 5, both of which contain two aryl difluoromethylenephosphonic acid groups, a nonhydrolyzable phosphate mimetic. The structures were determined and refined to 2.35 and 2.50 A resolution, respectively. Although one of the inhibitors seems to have satisfied the perceived requirement for dual binding, it did not bind both the active site and the adjacent noncatalytic binding site as expected. The second or distal phosphonate group instead extends into the solvent and makes water-mediated interactions with Arg-47. The selectivity of the more potent of these two inhibitors, as well as four other inhibitors bearing two such phosphate mimetics for PTP1B versus seven other PTPases, was examined. In general, selectivity was modest to good when compared to PTPases Cdc25a, PTPmeg-1, PTPbeta, and CD45. However, selectivity was generally poor when compared to other PTPases such as SHP-1, SHP-2, and especially TCPTP, for which almost no selectivity was found. The implications these results have concerning the utility of dual-binding inhibitors are discussed.
From July 1999 to January 2000, we determined the particulate mercury [Hg(p)] concentration in the atmosphere of five function sites and one contrast site in the city of Changchun, China. During non-heating season, the Hg(p) concentration in air in urban areas ranged from 0.022 to 0.398 ng m(-3) with an average of 0.145 ng m(-3), and at the contrast site with an average of 0.084 ng m(-3). During the heating season, the Hg(p) concentration in urban areas was in the range of 0.148-1.984 ng m(-3) with an average of 0.461 ng m(-3) and with an average of 0.211 ng m(-3) at the contrast site. The Hg(p) concentration during heating season is two times higher than that during non-heating time. Coal burning and wind-blown soil material are the two important sources of Hg(p). Wind-blown soil material contributes 7.9-38.5% to the Hg(p) with an average of 24.1% in urban area. A theoretical model was used to estimate the dry deposition flux, with results of 43.06 microg m(-2) a(-1) in the urban area and 21.28 microg m(-2) a(-1) at the contrast site.
Absence of CD4 impairs the efficiency of T cell receptor (TCR) signaling in response to major histocompatibility complex (MHC) class II-presented peptides. Here we use mice carrying a conditional Cd4 allele to study the consequences of impaired TCR signaling after the completion of thymocyte development. We show that loss of CD4 decreases the steady-state proliferation of T cells as monitored by in vivo labeling with bromo-deoxyuridine. Moreover, T cells lacking CD4 compete poorly with CD4-expressing T cells during proliferative expansion after transfer into lymphopenic recipients. The data suggest that T cells compete with one another during homeostatic proliferation, and indicate that the basis of this competition is TCR signaling.
Bacteria and their ubiquitous cell wall component peptidoglycan (PGN) activate the innate immune system of the host and induce the release of inflammatory molecules. TNF-alpha is one of the highest induced cytokines in macrophages stimulated with PGN; however, the regulation of tnf-alpha expression in PGN-activated cells is poorly understood. This study was done to identify some of the transcription factors that regulate the expression of the tnf-alpha gene in macrophages stimulated with PGN. Our results demonstrated that PGN-induced expression of human tnf-alpha gene is regulated by sequences proximal to -182 bp of the promoter. Mutations within the binding sites for cAMP response element, early growth response (Egr)-1, and kappaB3 significantly reduced this induction. The transcription factor c-Jun bound the cAMP response element site, Egr-1 bound the Egr-1 motif, and NF-kappaB p50 and p65 bound to the kappaB3 site on the tnf-alpha promoter. PGN rapidly induced transcription of egr-1 gene and this induction was significantly reduced by specific mutations within the serum response element-1 domain of the egr-1 promoter. PGN also induced phosphorylation and activation of Elk-1, a member of the Ets family of transcription factors. Elk-1 and serum response factor proteins bound the serum response element-1 domain on the egr-1 promoter, and PGN-induced expression of the egr-1 was inhibited by dominant-negative Elk-1. These results indicate that PGN induces activation of the transcription factors Egr-1 and Elk-1, and that PGN-induced expression of tnf-alpha is directly mediated through the transcription factors c-Jun, Egr-1, and NF-kappaB, and indirectly through the transcription factor Elk-1.
The coagulation factor VIII (FVIII) is the coagulation factor deficient in the X-chromosome-linked bleeding disorder hemophilia A. Previous transfection studies demonstrated that factor VIII was 10-100-fold less efficiently expressed than the homologous coagulation factor, factor V. To investigate the regulatory mechanisms of FVIII synthesis and secretion, we used the yeast two-hybrid system as an approach to search for proteins that associated with FVIII. The A2 domain (337-740 amino acids) of factor VIII (FVIII-A2) was used as a bait and phytanoyl-CoA alpha-hydroxylase (PAHX) was identified as a binding protein of FVIII-A2. PAHX had potential to interact with the residues 373-508 within the A2 domain, but not with A1 and A3 (the homologous domains of A2). The interaction between the A2 domain and PAHX was independent of the type 2 peroxisomal targeting signal (PTS2) of PAHX. Overexpression of PAHX in FVIII-produced cells decreased the expression of FVIII by about 70%. The elevated expression of von Willebrand factor had no effect on the suppression of FVIII secretion by PAHX. Expression of the green fluorescent PAHX fusion protein in SMMC-7721 cells affected the intracellular trafficking of FVIII-A2. These results suggested that the interaction between PAHX and FVIII-A2 was in part responsible for the low-level expression of factor VIII.
Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), and the administration of pharmacological PPARgamma agonists attenuates vascular lesion formation. The factors that regulate PPARgamma expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPARgamma by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPARgamma mRNA and protein were increased by 2- to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20 ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50 micromol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10 micromol/L), but not affected by a p38 kinase inhibitor (SB202190, 10 micromol/L). In addition, overexpression of the dominant-negative p85 subunit of PI3-kinase or Akt proteins blocked the PDGF-induced PPARgamma expression. Taken together, our results suggest that PDGF induces PPARgamma expression in VSMCs by a PI3-kinase/Akt signaling pathway. The characterization of factors and signaling pathways that modulate PPARgamma expression in VSMCs may have important implications for understanding the pathogenesis of vascular diseases.
Intermolecular dipole-dipole interactions were once thought to average to zero in gases and liquids as a result of rapid molecular motion that leads to sharp nuclear magnetic resonance lines. Recent papers have shown that small residual couplings survive the motional averaging if the magnetization is nonuniform or nonspherical. Here, we show that a much larger, qualitatively different intermolecular dipolar interaction remains in nanogases and nanoliquids as an effect of confinement. The dipolar coupling that characterizes such interactions is identical for all spin pairs and depends on the shape, orientation (with respect to the external magnetic field), and volume of the gas/liquid container. This nanoscale effect is useful in the determination of nanostructures and could have unique applications in the exploration of quantum space.