Biomedical subjects

Q Wang

Publications and source records attributed to Q Wang.

At least 325 records · Page 18Linked to original sources

PubMed2000

HLA-DRB1 gene polymorphism in patients with dilated cardiomyopathy.

To probe into the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM), HLA-DRB1 gene polymorphism in 68 patients with DCM and 175 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) techniques. It was found that the frequencies of HLA-DRB1* 15 and HLA-DRB1* 03 alleles were significantly lower in DCM patients than those in normal controls (14.71% vs 29.71% and 4.41% vs 15.43%, respectively), the relative risks (RR) in the DCM patients being 0.41 and 0.25, respectively, all P < 0.05. However, the frequencies of HLA-DRB1* 11 and HLA-DRB1* 12 alleles were significantly higher in the DCM patients than in controls (29.4% vs 12.00% and 36.76% vs 12.57%, respectively) with the RR in the DCM patients being 3.06 and 4.04, respectively, all P < 0.01. These findings further demonstrated that immunogenetics might play a predominant pathogenetic role in partial DCM patients.

Adult↗

PubMed2000

Androgen receptor polymorphisms and mutations in male infertility.

Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor (AR) gene was examined for mutations and polymorphisms in a large cohort of infertile men. Genetic screening of over 400 patients and controls showed that defects in the AR gene lead to the production of dysfunctional receptor protein in up to 10% of males with abnormally low sperm production and male infertility. The dozens of mutations and polymorphisms uncovered were associated with subtly reduced intrinsic AR activity, and are of two main categories: polymorphic changes in length of a trinucleotide CAG tract in the N-terminal transactivation domain, and missense mutations in the C-terminal ligand-binding domain. These polymorphisms and mutations are associated with reduced AR function due to defective intermolecular protein-protein interactions with coactivator molecules. Genetic screening for AR mutations and polymorphism should be offered to severely oligospermic and azoospermic patients. These traits can be transmitted to progeny, and counseling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.

Humans↗

PubMed2000

Expression of cadherins and catenins in paired tumor and non-neoplastic primary prostate cultures and corresponding prostatectomy specimens.

Cadherins are a family of transmembrane proteins that play a crucial role in cell differentiation, cell migration, and intercellular adhesion. Cadherins are associated with catenins through their highly conserved cytoplasmic domain. Down-regulation of E-cadherin protein has been shown in various human cancers. This study examined the expression of cadherins and associated catenins at the mRNA level. Paired tumor and nonneoplastic primary prostate cultures were obtained from surgical specimens. Quantitative multiplex fluorescence reverse transcriptase-polymerase chain reaction (QMF RT-PCR) and quantitative analysis were performed and correlated with immunostain results. Six of seven cases of neoplastic cultures showed moderately-to-markedly decreased levels of E-cadherin and P-cadherin mRNA. Similar losses of alpha-catenin and beta-catenin mRNA were also observed. The results of QMF RT-PCR showed good correlation with the results of immunohistochemical studies based on corresponding formalin-fixed sections. In conclusion, this paper presents a coordinated down-regulation in the expression of E-cadherin and associated catenins at the mRNA and protein level in most of the cases studied. This down-regulation may play an important role in the pathogenesis of prostate cancer.

Adenocarcinoma↗

PubMed2000

Modulation of a cloned human A-type voltage-gated potassium channel (hKv1.4) by the protein tyrosine kinase inhibitor genistein.

A cloned, human, A-type, voltage-gated potassium channel (hKv1.4) was expressed transiently in Chinese hamster ovary cells and the effects of the broad-spectrum tyrosine kinase inhibitor genistein on hKv1.4 were studied using the whole-cell patch-clamp recording method. Genistein (up to 50 microM) reversibly reduced the peak currents of hKv1.4 by 44.9+/-12%. In addition, genistein markedly slowed the activation kinetics (time constant tau(a)) of hKv1.4. At +50 mV, tau(a) increased from 1.8+/-0.3 to 5.0+/-0.6 ms (P<0.01). The effect of genistein on the channel inactivation kinetics (time constant tau(i)) was more complex, in that tau(i) was increased significantly at lower step potentials but unaltered at +50 mV or more depolarized potentials. Tail current analysis showed that genistein had no effect on the kinetics of deactivation (time constant tau(d)), but shifted the steady-state activation curve significantly to the right by about 15 mV (potential for half-maximal activation, V1/2, changed from -7.4+/-4.4 to +7.7+/-2.7 mV) with a moderate change in the slope (k) of the curve (from 17.4+/-2.2 to 23+/-1.0 mV, P<0.05). Genistein slightly altered the slope of the steady-state inactivation curve from -5.5+/-0.4 to -7.5+/-0.4 mV (P<0.01). The recovery rate from inactivation was not altered by genistein. The tyrosine phosphatase inhibitor orthovanadate (1 mM) alone had little impact on current amplitude or channel kinetics. However, orthovanadate significantly, but not completely, blocked the effect of genistein on current amplitude (by 25.5%) and kinetics (by 67.1%). Daidzein (up to 50 microM), an inactive analogue of genistein, had no effect on current amplitude or kinetics. In contrast to genistein, another tyrosine kinase inhibitor, herbimycin A, had little effect on the channel peak amplitude or kinetics. In addition, genistein had a similar impact on the channel peak current amplitude and kinetics in cells with or without pre-treatment with herbimycin A (10 microM). The data suggest that genistein-induced inhibition of tyrosine phosphorylation may not be the exclusive mechanism by which hKv1.4 is down-regulated and channel gating affected. Genistein may produce a non-catalytic blockade of this channel.

Animals↗

PubMed2000

Expression patterns of two putative odorant-binding proteins in the olfactory organs of Drosophila melanogaster have different implications for their functions.

The aqueous medium bathing the dendrites of olfactory neurons contains high concentrations of odorant-binding proteins (OBPs) whose role is still unclear. OBPs may facilitate interactions between odorants and their membrane-bound receptors, perhaps by increasing the water solubility of hydrophobic molecules. Alternatively, OBPs may be involved in the inactivation of odorants and other volatile molecules, preventing desensitization and/or protecting olfactory neurons from toxic chemicals. We report here novel features of the localization of two putative OBPs, PBPRP2 and PBPRP5, that have important and different implications for their role in olfaction. Unlike several other putative OBPs of Drosophila melanogaster that are only found in adult olfactory organs, PBPRP5 is also expressed in the larval olfactory organs, suggesting that it plays a common role in olfaction at both stages. In the adult, PBPRP5 expression is restricted to the sensillum lymph that bathes the olfactory dendrites of a subset of olfactory hairs, the basiconic sensilla. Since individual basiconic sensilla differ in olfactory specificity, PBPRP5 may be able to bind to and mediate olfactory responses to a wide range of odorants. In contrast, PBPRP2 is present in the space immediately below the antennal cuticle and in the outer cavity of approximately 30% of the double-walled coeloconic sensilla on the antennal surface. In neither case is PBPRP2 in contact with the dendritic membranes of olfactory neurons, making a carrier function unlikely for this protein. Instead, PBPRP2 may act as a sink, binding to odorants and other volatile chemicals and limiting their interactions with olfactory neurons.

Animal Structures↗

PubMed2000

Protein analysis of geographic isolates of shrimp white spot syndrome virus.

Six geographic isolates of the white spot syndrome virus (WSSV) of penaeid shrimp, from China, India, Thailand, South Carolina, Texas, as well as from crayfish kept at the US National Zoo in Washington D. C, were compared by electron microscopy and sodium sulfate polyacrylamine gel electrophoresis (SDS-PAGE). Amino acid compositions of four of the major structural polypeptides of the South Carolina WSSV were analyzed, and three of the four polypeptides were partially sequenced from their NH2 termini. The morphologies of purified virions of the six geographic isolates of WSSV were indistinguishable by transmission electron microscopy. By SDS-PAGE, the protein profiles of the six isolates were very similar, but not identical. They all contained three major polypeptides with sizes of approximately 25, 23 and 19 kDa. A fourth major polypeptide at the 14.5 kDa position was observed in four of the geographic isolates. The WSSV isolated from crayfish presented a slightly different structural protein profile, particularly with regard to the protein in the 19 kDa range that appeared larger in size than those of the other isolates. The NH2 terminal amino acids of the 25, 23 and 14.5 kDa polypeptides of the South Carolina WSSV were sequenced as MDLSFTLSVVTA, MEFGNLTNLDVA, and VARGGKTKGRRG, respectively. No significant homologous sequence was found in the GenBank. These protein sequences have been submitted to the SWISS-PROT Protein Data Bank and assigned the accession numbers P82004, P82005 and P82006.

Amino Acid Sequence↗

PubMed2000

Pulmonary artery perfusion with protective solution reduces lung injury after cardiopulmonary bypass.

BACKGROUND: The inflammatory response and higher temperature of lung tissue during cardiopulmonary bypass can result in lung injury. This study was to evaluate the protective effect of pulmonary perfusion with hypothermic antiinflammatory solution on lung function after cardiopulmonary bypass. METHODS: Twelve adult mongrel dogs were randomly divided into two groups. The procedure was carried out through a midline sternotomy, cardiopulmonary bypass was established using cannulas placed in the ascending aorta, superior vena cava, and right atrium near the entrance of the inferior vena cava. After the ascending aorta was clamped and cardioplegic solution infused, the right lung was perfused through a cannula placed in the right pulmonary artery with 4 degrees C lactated Ringer's solution in the control group (n = 6) and with 4 degrees C protective solution in the antiinflammation group (n = 6). Antiinflammatory solution consisted of anisodamine, L-arginine, aprotinin, glucose-insulin-potassium, and phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung function were measured at different time point before and after cardiopulmonary bypass; lung biopsies were also taken. RESULTS: Peak airway pressure increased dramatically in the control group after cardiopulmonary bypass when compared with the antiinflammation group at four different time points (24 +/- 1, 25 +/- 2, 26 +/- 2, 27 +/- 2 cm H2O versus 17 +/- 2, 18 +/- 1, 17 +/- 1, 18 +/- 1 cm H2O; all p < 0.01). Pulmonary vascular resistance increased significantly in the control group than in the antiinflammation group at 5 and 60 minutes after cardiopulmonary bypass (1,282 +/- 62 dynes x s x cm(-5) versus 845 +/- 86 dynes x s x cm(-5) and 1,269 +/- 124 dynes x s x cm(-5) versus 852 +/- 149 dynes x s x cm(-5), p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the antiinflammation group was higher than in the control group at 60 minutes after cardiopulmonary bypass (628 +/- 33.3 mm Hg versus 393 +/- 85.9 mm Hg, p < 0.05). The ratio of white blood cells in the right atrial and the right pulmonary venous blood was lower in the antiinflammation group than in the control group at 5 minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01 and p < 0.05, respectively). Histologic examination revealed that the left lung from both groups had marked intraalveolar edema and abundant intraalveolar neutrophils, whereas the right lung in the control group showed moderate injury and the antiinflammation group had normal pulmonary parenchyma. CONCLUSIONS: Pulmonary artery perfusion using hypothermic protective solution can reduce lung injury after cardiopulmonary bypass.

Animals↗

PubMed2000

Lignans from Mosla scabra.

Two new cyclobutane-type lignans, named moslolignans A and B, together with two known ones, andamanicin and magnosalin, were isolated from the whole plant of Mosla scabra. Their structures were established as 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(3- methoxy-4,5-methylene-dioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cycl obutane and 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(2, 5-dimethoxy-3,4-methylenedioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cyclobu tane by spectroscopic methods. This is the first report of naturally-occurring cyclobutane-type lignans with asymmetrical substitutions.

Alkenes↗

PubMed2000

HIV-2 transmembrane protein gp36 binds to the putative cellular receptor proteins P45 and P62.

Based on the findings that two cellular proteins of 45 kDa (P45) and 62 kDa (P62) serve as the putative receptor molecules for binding of HIV-1 transmembrane protein gp41 to human T, B lymphocytes and monocytes, we examined whether HIV-2 gp36 and HIV-1 gp41 share the putative receptor proteins P45 and P62. In SPR-assay (SPR: surface plasmon resonance), the recombinant soluble gp36 (rsgp36: Env aa518-678 from clone ROD) like the recombinant soluble gp41 (rsgp41: Env aa539-684 from clone BH10) was binding to P45 and P62. By affinity capillary electrophoresis (ACE)-analysis, formation of stable rsgp36-P45 and rsgp36-P62 complexes were confirmed, and the interactions of rsgp36 with P45 and P62 is quite strong with a fast association rate and a slow dissociation rate. These results indicate that HIV-2 gp36 and HIV-1 gp41 have the common putative cellular receptor proteins P45 and P62, and the binding of gp36 to human lymphocytes and monocytes could be based on the interaction between gp36 and P45 and P62.

Amino Acid Sequence↗

PubMed2000

Purine requirements for the expression of Cape buffalo serum trypanocidal activity.

Cape buffalo serum contains xanthine oxidase which generates trypanocidal H(2)O(2) during the catabolism of hypoxanthine and xanthine. The present studies show that xanthine oxidase-dependent trypanocidal activity in Cape buffalo serum was also elicited by purine nucleotides, nucleosides, and bases even though xanthine oxidase did not catabolize those purines. The paradox was explained in part, by the presence in serum of purine nucleoside phosphorylase and adenosine deaminase, that, together with xanthine oxidase, catabolized adenosine, inosine, hypoxanthine, and xanthine to uric acid yielding trypanocidal H(2)O(2). In addition, purine catabolism by trypanosomes provided substrates for serum xanthine oxidase and was implicated in the triggering of xanthine oxidase-dependent trypanocidal activity by purines that were not directly catabolized to uric acid in Cape buffalo serum, namely guanosine, guanine, adenine monophosphate, guanosine diphosphate, adenosine 3':5-cyclic monophosphate, and 1-methylinosine. The concentrations of guanosine and guanine that elicited xanthine oxidase-dependent trypanocidal activity were 30-270-fold lower than those of other purines requiring trypanosome-processing which suggests differential processing by the parasites.

Animals↗

PubMed2000

Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses.

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting basal synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of synaptic plasticity.

Animals↗

PubMed2000

Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.

Fibroblast growth factors (FGFs) 11-14 comprise a subfamily of FGFs with poorly defined biological function. Here we characterize two isoforms of FGF14 (FGF14-1a and FGF14-1b) that result from the alternative usage of two different first exons. We demonstrate that these isoforms have differential subcellular localization and that they are differentially expressed in various adult tissues. Using in situ hybridization we show that Fgf14 is widely expressed in brain, spinal cord, major arteries and thymus between 12.5 and 14.5 days of mouse embryonic development. We also show that during cerebellar development, Fgf14 is first observed at postnatal day 1 in post mitotic granule cells, and later in development, in migrating and post migratory granule cells. The developmental expression pattern of Fgf14 in the cerebellum is complementary to that of Math1, a marker for proliferating granule cells in the external germinal layer.

3T3 Cells↗

PubMed2000

Potentiation of brain acetylcholine neurons by Kami-Untan-To (KUT) in aged mice: implications for a possible antidementia drug.

The effects of a traditional Japanese herbal medicine, Kami-Untan-To (KUT), on brain choline (Ch) and Acetylcholine (ACh) levels in aged mice were examined. Further, the expression of choline acetyltransferase (ChAT) in the medial septum (MS), the vertical limbs of the diagonal band of Broca (VDB), and the nucleus basalis Meynert (NBM) was examined by immunohistochemistry. Following an oral administration of KUT to the aged mice for 3 months, ACh levels in the cortex, striatum and hippocampus were increased significantly. The density of ChAT-immunoreactive cells located in MS, VDB, and NBM in the KUT-treated group was increased significantly as compared to the non-treatment group. The survival rate of aged mice was significantly higher in the KUT-treated group as compared to that in the nontreated group. Our results suggest that KUT potentiates the brain acetylcholinergic system, and may become a possible anti-dementia drug.

Acetylcholine↗

PubMed2000

The effects of the traditional chinese medicine, "Banxia Houpo Tang (Hange-Koboku To)" on the swallowing reflex in Parkinson's disease.

Swallowing disorder is common in Parkinson's disease (PD). We studied the swallowing disorder in PD, and tested the efficacy of Banxia Houpo Tang (BHT, a Chinese traditional medicine) in improving the swallowing reflex of PD patients. The Swallowing reflex test is a simple method used to detect swallowing disorders in patients with cerebrovascular disease. Because we observed previously that BHT significantly improved the swallowing reflex in cerebrovascular patients, we studied whether BHT was also effective in improving the swallowing disorder in patients with PD. 23 PD patients (13 males, 10 females, mean age 66.0+/-9.3, Hoehn & Yahr (H-Y) mean score = 2.8) were evaluated for swallowing reflex and the concentration of substance-P in their saliva before and after 4 weeks of BHT treatment. The swallowing reflex before treatment was significantly delayed, according to the H-Y score (Spearman's p = 0.014, R2 = 0.463). The swallowing reflex before BHT treatment was 3.66+/-0.98 sec, and after BHT treatment, it improved significantly, to 2.27+/-0.54 sec (p < 0.0001). Substance-P concentration in PD patients saliva before treatment was significantly lower than in healthy controls (p = 0.007), but showed no significant change after BHT treatment. Our research shows that the swallowing reflex is an effective method to evaluate the swallowing disorder in PD. BHT can significantly improved the swallowing reflex in PD patients, and therefore can be a hopeful candidate for preventing aspiration pneumonia in PD.

Aged↗

PubMed2000

Effects of the hydrophobicity of taxoids on their interaction with tubulin.

Modifications of the hydrophobic character at the 7 and 10 positions of the taxoids greatly modified the effect of these drugs on the tubulin microtubule system. The presence of an alkyl chain at these positions decreased the activity while their corresponding more polar analogues restored the activity of these molecules. It appears that the recognition of taxoids by tubulin depends on the location of the most important hydrophobic area.

Alkaloids↗

PubMed2000

A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains.

Members of the double-stranded RNA- (dsRNA) specific adenosine deaminase gene family convert adenosine residues into inosines in dsRNA and are involved in A-to-I RNA editing of transcripts of glutamate receptor (GluR) subunits and serotonin receptor subtype 2C (5-HT(2C)R). We have isolated hADAR3, the third member of this class of human enzyme and investigated its editing site selectivity using in vitro RNA editing assay systems. As originally reported for rat ADAR3 or RED2, purified ADAR3 proteins could not edit GluR-B RNA at the "Q/R" site, the "R/G" site, and the intronic "hot spot" site. In addition, ADAR3 did not edit any of five sites discovered recently within the intracellular loop II region of 5-HT(2C)R RNAs, confirming its total lack of editing activity for currently known substrate RNAs. Filter-binding analyses revealed that ADAR3 is capable of binding not only to dsRNA but also to single-stranded RNA (ssRNA). Deletion mutagenesis identified a region rich in arginine residues located in the N-terminus that is responsible for binding of ADAR3 to ssRNA. The presence of this ssRNA-binding domain as well as its expression in restricted brain regions and postmitotic neurons make ADAR3 distinct from the other two ADAR gene family members, editing competent ADAR1 and ADAR2. ADAR3 inhibited in vitro the activities of RNA editing enzymes of the ADAR gene family, raising the possibility of a regulatory role in RNA editing.

Adenosine Deaminase↗

PubMed2000

Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo.

Monoclonal antibodies specific for the p185HER2/neu growth factor receptor represent a significant advance in receptor-based therapy for p185HER2/neu-expressing human cancers. We have used a structure-based approach to develop a small (1.5 kDa) exocyclic anti-HER2/neu peptide mimic (AHNP) functionally similar to an anti-p185HER2/neu monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185HER2/neu with high affinity (KD=300 nM). This results in inhibition of proliferation of p185HER2/neu-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185HER2/neu-expressing tumors in athymic mice. In addition, the mimetic sensitizes the tumor cells to apoptosis when used in conjunction with ionizing radiation or chemotherapeutic agents. A comparison of the molar quantities of the Herceptin antibody and the AHNP mimetic required for inhibiting cell growth and anchorage-independent growth showed generally similar activities. The structure-based derivation of the AHNP represents a novel strategy for the design of receptor-specific tumor therapies.

Animals↗

PubMed2000

Sucrose transport into barley seeds: molecular characterization of two transporters and implications for seed development and starch accumulation.

In order to understand sucrose transport in developing seeds of cereals at the molecular level, we cloned from a caryopses library two cDNAs encoding sucrose transporters, designated HvSUT1 and HvSUT2. Sucrose uptake activity was confirmed by heterologous expression in yeast. Both transporter genes are expressed in maternal as well as filial tissues. In a series of in situ hybridizations we analysed the cell type-specific expression in developing seeds. HvSUT1 is preferentially expressed in caryopses in the cells of the nucellar projection and the endospermal transfer layer, which represent the sites of sucrose exchange between the maternal and the filial generation and are characterized by transfer cell formation. HvSUT2 is expressed in all sink and source tissues analysed and may have a general housekeeping role. The rapid induction of HvSUT1 gene expression in caryopses at approximately 5-6 days after fertilization coincides with increasing levels of sucrose as well as sucrose synthase mRNA and activity, and occurs immediately before the onset of rapid starch accumulation within the endosperm. Starch biosynthesis requires sucrose to be imported into the endosperm, as direct precursor for starch synthesis and to promote storage-associated processes. We discuss the possible role of HvSUT1 as a control element for the endospermal sucrose concentration.

Base Sequence↗