Gene expression profiling in biliary atresia.
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Biliary Atresia↗
Biomedical subjects
J H Wang
Publications and source records attributed to J H Wang.
Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers.
BACKGROUND: Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. METHODS AND RESULTS: Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. CONCLUSIONS: These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.
Adult↗
Adenovirus-mediated interleukin-2 gene therapy of nociception.
The effect of adenovirus-mediated interleukin-2 (IL-2) gene on rat basal nociceptive response and chronic neuropathic pain was explored. The paw withdrawal latency induced by radiant heat was used to evaluate the antinociceptive effect of adenovirus type 5 (Ad5) and Ad5-IL-2. The results showed that intrathecal delivery of Ad5-IL-2 exhibited obvious antinociceptive effects on basal nociceptive response and chronic neuropathic pain, which were maintained for 3 and 4 weeks, respectively. This suggested that the antinociceptive effect of Ad5-IL-2 on chronic neuropathic pain was greater than its effect on basal nociceptive response. Human IL-2 mRNA was detected by in situ hybridization in the spinal pia mater and parenchyma of the lumbar, sacral, thoracic and cervical regions, and gray matter had higher level of IL-2 expression than white matter. These data demonstrated that the IL-2 gene was transfected into spinal cord regions relevant to pain modulation. The expressed IL-2 protein profile in spinal cord detected by enzyme-linked immunosorbent assay coincided almost exactly with its antinociceptive effect. This supported the hypothesis that the therapeutic effect of IL-2 gene was related to IL-2 protein expression. The study indicates that intrathecal delivery of adenovirus-mediated IL-2 gene has a relatively long antinociceptive effect.
Adenoviridae↗
Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan.
BACKGROUND: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. METHODS: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. RESULTS: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0: F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (<50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P < 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. CONCLUSIONS: These results suggest that genotype C is associated with more severe liver diseases than the B variant.
Adolescent↗
Different excitation and reception distributions with a single-loop transmit-receive surface coil near a head-sized spherical phantom at 300 MHz.
Calculations and experiments were used to examine the B(1) field behavior and signal intensity distribution in a 16-cm diameter spherical phantom excited by a 10-cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B(1) field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head-sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution.
Head↗
Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?
The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.
Cell Adhesion↗
Role of the neutrophil in the development of systemic inflammatory response syndrome and sepsis following abdominal aortic surgery (Br J Surg 2001; 88: 1583-9).
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Aortic Aneurysm, Abdominal↗
Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis.
Lamivudine therapy for chronic hepatitis and decompensated liver cirrhosis related to the hepatitis B virus (HBV) resulted in improvement of liver function and inhibition of viral replication. Despite emergence of the HBV mutant, e-antigen seroconversion and improvement of liver function may be achieved with continuation of lamivudine therapy. Although hepatic decompensation has been reported in a few cases after the emergence of lamivudine-resistant mutants, fatal cases of non-transplant patients have only rarely been reported in the literature. Here, we describe a patient with HBV-related liver cirrhosis who died after a breakthrough infection with a lamivudine-resistant mutant. Hepatic failure and mortality developed after flare-up of severe hepatitis after 13 months of lamivudine treatment. Emergence of the HBV mutant with substitution of isoleucine for leucine at residue 426 (L4261) in combination with isoleucine for methionine at residue 550 (M5501) was observed at 10 and 13 months of treatment.
Base Sequence↗
Characteristics of community-acquired methicillin-resistant Staphylococcus aureus in infants and children without known risk factors.
This retrospective study sought to determine the characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in patients younger than 18 years without known risk factors who were treated at a teaching hospital in central Taiwan. Epidemiological and clinical data were collected from medical charts. Possible risk factors included hospitalization within the past 6 months, transfer from other hospitals or nursing homes, and having underlying illness. A total of 173 isolates of community-acquired S. aureus were analyzed. Seventeen (9.8%) of these 173 isolates were methicillin-resistant S. aureus collected from patients without risk factors, 31 (17.9%) were methicillin-resistant S. aureus from patients with risk factors, and the other 125 (72.3%) were methicillin-susceptible S. aureus. Most isolates of community-acquired methicillin-resistant S. aureus collected from patients without risk factors (14/17, 82.4%) were obtained from the infected wounds of skin or soft tissues. Only 4 (23.5%) in 17 patients with isolates resistant to methicillin were prescribed antimicrobial therapy with glycopeptides. Nevertheless, all patients recovered without any long-term sequelae. These results highlight the fact that community-acquired methicillin-resistant S. aureus infections occur frequently in Taiwan among patients who have no established risk factors for this infection.
Adolescent↗
Phosphorylation of human N-myristoyltransferase by N-myristoylated SRC family tyrosine kinase members.
N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational and/or posttranslational transfer of myristate to the amino terminal glycine residue of a number of important proteins especially the non-receptor tyrosine kinases whose activity is important for tumorigenesis. Human NMT was found to be phosphorylated by non-receptor tyrosine kinase family members of Lyn, Fyn and Lck and dephosphorylated by the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin. Deletion of 149 amino acids from the N-terminal end resulted in the absence of phosphorylation suggesting that the phosphorylation sites are located in the N-terminal end of NMT. Furthermore, a site-directed mutagenesis study indicated that substitution of tyrosine 100 with phenylalanine served NMT as a poor substrate for the Lyn kinase. A synthetic peptide corresponding to the amino-terminal region encompassing tyrosine 100 of NMT served as a good substrate for the Lyn and Fyn kinases. Our studies also indicated that NMT was found to interact with Lyn through its N-terminal end in a phosphorylation-dependent manner. This is the first study demonstrating the cross-talk between NMT and their myristoylated protein substrates in signaling pathways.
Acyltransferases↗
Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule.
The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha 2 and beta 2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to immunodeficiency.
Amino Acid Sequence↗
Is immunohistochemical analysis an appropriate diagnostic technique for bone marrow micrometastases?
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Bone Marrow Neoplasms↗
Structural Insights into Cdk5 activation by a neuronal Cdk5 activator.
Although Cdk5 shows high sequence identity to Cdk1 and Cdk2, it can be fully activated by its neuronal activators p35/p25(nck5a) and p39(nck5ai) in a phosphorylation-independent manner. To understand structural basis of the Cdk5/p25(nck5a) activation, the complex is modelled to assume either an obstructed or an opened conformation based on X-ray structures of the unphosphorylated or the phosphorylated Cdk2/cyclin A complex, respectively. Comparison and analysis of the two models, along with mutagenesis studies of p25(nck5a), suggest that the opened form represents more closely the structure of active Cdk5/p25(nck5a). The results provide a rationale basis for understanding the phosphorylation-independent activation of Cdk5/p25(nck5a).
Amino Acid Sequence↗
Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?
INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.
Adolescent↗
Role of hypothalamic-pituitary axis in morphine-induced alteration in thymic cell distribution using mu-opioid receptor knockout mice.
Mu-opioid receptor knockout mice (MORKO), were used to address two questions: (1) if morphine induced decrease in thymic weight and cell distribution is mediated by the mu-opioid receptor and (2) the role of corticosteroids in morphine mediated alteration in thymic cell distribution. Our result show that morphine mediated increase in plasma corticosterone is mediated by the mu-opioid receptor since morphine at doses as high as 25 mg/kg-body weight does not increase plasma corticosterone levels in the MORKO. In addition, we have also shown that morphine treatment results in the differentiation of CD4+CD8+ (double positive cells) to single positive CD4+ cells while dexamethasone treatment results in the deletion of CD4+CD8+ (double positive) cells.
Adrenocorticotropic Hormone↗
Calcium-calmodulin signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal, fast spiking rat hippocampal CA1 neurons.
1. The role of Ca(2+)-calmodulin (CaM) signalling cascades in modulating glutamatergic synaptic transmission on CA1 non-pyramidal fast-spiking neurons was investigated using whole-cell recording and perfusion in rat hippocampal slices. 2. Paired stimuli (PS), consisting of postsynaptic depolarization to 0 mV and presynaptic stimulation at 1 Hz for 30 s, enhanced excitatory postsynaptic currents (EPSCs) on non-pyramidal neurons in the stratum pyramidale (SP). The potentiation was reduced by the extracellular application of D-amino-5-phosphonovaleric acid (DAP-5, 40 microM), and blocked by the postsynaptic perfusion of 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM), a CaM-binding peptide (100 microM) or CaMKII (281-301) (an autoinhibitory peptide of CaM-dependent protein kinases, 100 microM). 3. The application of adenophostin, an agonist of inositol trisphosphate receptors (IP(3)Rs) that evokes Ca(2+) release, into SP non-pyramidal neurons via the patch pipette (1 microM) enhanced EPSCs and occluded PS-induced synaptic potentiation. The co-application of BAPTA (10 mM) with adenophostin blocked synaptic potentiation. In addition, Ca(2+)-CaM (40:10 microM) induced synaptic potentiation, which occluded PS-induced potentiation and was attenuated by introducing CaMKII (281-301) (100 microM). EPSCs were sensitive to an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR). 4. Application of Ca(2+)-CaM into SP non-pyramidal neurons induced the emergence of AMPAR-mediated EPSCs that were not evoked by low stimulus intensity before perfusion. Ca(2+)-CaM also increased the amplitude and frequency of spontaneous EPSCs. A scavenger of nitric oxide, carboxy-PTIO (30 microM in slice-perfusion solution), did not affect these increases in sEPSCs. 5. The magnitude of PS-, adenophostin- or Ca(2+)-CaM-induced synaptic potentiation in SP non-pyramidal neurons increased during postnatal development. 6. These results indicate that Ca(2+)-CaM signalling pathways in CA1 SP non-pyramidal neurons up-regulate glutamatergic synaptic transmission probably through the conversion of inactive-to-active synapses.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Determination of three nitroimidazole residues in poultry meat by gas chromatography with nitrogen-phosphorus detection.
A method was developed for the determination of the nitroimidazole compounds dimetridazole (DMZ), ronidazole (RNZ) and metronidazole (MNZ) by gas chromatography with nitrogen phosphorus detection. Nitroimidazole compounds were extracted with acetonitrile, followed by acidification using acetic acid and cleanup using strong cation-exchange (SCX) SPE column. Validation in chicken muscle fortified at a concentration of 5 microg/kg gave mean recoveries of 85% DMZ, 90% RNZ, 80% MNZ with RSDs of 13.0, 14.3, 11.2%, respectively (n=6). The method is suitable for statutory residue testing and is used as a quick screening method in the National Residue Surveillance Plan in China.
Antiprotozoal Agents↗
Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.
BACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.
Cell Adhesion↗