Biomedical subjects

W Wu

Publications and source records attributed to W Wu.

At least 127 records · Page 7Linked to original sources

PubMed2000

Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1.

Sphingosylphosphorylcholine (SPC) is a bioactive lipid that acts as an intracellular and extracellular signalling molecule in numerous biological processes. Many of the cellular actions of SPC are believed to be mediated by the activation of unidentified G-protein-coupled receptors. Here we show that SPC is a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1). In OGR1-transfected cells, SPC binds to OGR1 with high affinity (Kd = 33.3 nM) and high specificity and transiently increases intracellular calcium. The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation. In addition, SPC causes internalization of OGR1 in a structurally specific manner.

Calcium↗

PubMed2000

Correction of severe congenital epicanthus using the modified square-flap method.

The square-flap method has been gradually adopted for the correction of cicatricial contracture because it effectively relieves the longitudinal shortness in the deformity. Since 1990, the authors have slightly modified the design and employed it for the correction of severe congenital epicanthus. Forty-six cases (23 patients) have been treated by using this modified square flap. Good functional and cosmetic results were obtained. The authors consider it an effective technique with the advantages of rational design, simple operation and fewer incisions. This paper describes the operation design and discusses the advantages and key points of the surgery.

Adolescent↗

PubMed2000

HIV-1 gp41 by N-domain binds the potential receptor protein P45.

Recent crystal structure analysis of HIV-1 gp41 revealed that two domains (N- and C-domains) on gp41 play an important role in mediating membrane fusion and HIV-1 entry. The experimental evidence that gp41 by N-domain bound the potential receptor protein P45 could help to understand the mechanism of HIV entry. A recombinant soluble gp41 (rsgp41: Env aa539-684) could bind to P45 in the affinity capillary electrophoresis analysis and the surface plasmon resonance assay. In a blockade assay, peptide P1 (Env aa583-599) could inhibit interaction between rsgp41 and P45, while a control peptide could not. Direct binding of rsgp41, rgp41DP (aa567-648), P1 peptide and (P1)(2) peptide [(aa586-596)(2)] to P45 was examined in an ELISA assay. Rsgp41 bound the potential receptor protein P45 strongly, while rgp41DP and P1 as well as (P1)(2) could all weakly bind to P45, indicating that gp41 by N-domain weakly binds P45 and the region RILAVERYLKD located in the N-domain is defined as the binding site for P45 binding.

Amino Acid Motifs↗

PubMed2000

Development of hypertension induced by subpressor infusion of angiotensin II: role of sensory nerves.

Long-term administration of a subpressor dose of angiotensin II (Ang II) leads to pressor hyperresponsiveness and slow development of hypertension. Our preliminary data show that mRNA expression for calcitonin-gene related peptide in dorsal root ganglia was significantly increased by subpressor infusion of Ang II. To determine the role of sensory nerves in the development of hypertension induced by subpressor infusion of Ang II, newborn Wistar rats were given 50 mg/kg SC capsaicin on the 1st and 2nd days of life. After the weaning period, male rats were divided into 4 groups and subjected to the following treatments for 2 weeks: capsaicin+Ang II (150 ng. kg(-1). min(-1) SC by osmotic pumps, CAP-AII), capsaicin+vehicle (CAP), control+Ang II (CON-AII), and control+vehicle (CON). The results show that mean arterial pressure was significantly elevated in both Ang II-infused rats compared with non-Ang II-treated rats (P<0.05), and it was higher in CAP-AII than in CON-AII rats (P<0.05). The 24-hour urinary and sodium excretions were lower in CAP-AII than in CON-AII, CAP, and CON rats (P<0.05). These data demonstrated that sensory denervation exacerbates the development of hypertension and impairs renal excretory function when a subpressor dose of Ang II is given. These results indicate that activation of sensory nerves, either by Ang II or by other hormonal or hemodynamic factors, plays a compensatory role in promoting urine and sodium excretion and attenuating elevated blood pressure initiated by Ang II.

Angiotensin II↗

PubMed2000

Eosinophils generate brominating oxidants in allergen-induced asthma.

Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific "molecular fingerprint" for proteins modified through the eosinophil peroxidase-H(2)O(2) system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase. Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.

Allergens↗

PubMed2000

Long-term survey of outcome in acute promyelocytic leukemia.

OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event-free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post-remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL.

Adolescent↗

PubMed2000

Prognostic implication of microsatellite alteration profiles in early-stage non-small cell lung cancer.

Development of non-small cell lung cancer (NSCLC) is a result of multiple accumulated genetic abnormalities. Profiles of genetic abnormalities may determine tumor behavior and impact on patient outcome. We used microsatellite markers at 3p14, 9p21, and 10q24 to analyze tumor samples from 91 patients with pathologically confirmed stage I NSCLC for microsatellite alterations. Loss of heterozygosity at any single locus was not significantly associated with length of survival. However, patients whose tumors had microsatellite instability (MI) at 10q24 had shortened disease-specific survival. Among 31 such patients, 32% (10 of 31 patients) had died of the disease within 5 years after surgery compared with 16% (9 of 58 patients) without MI at 10q24 (P = 0.07). Interestingly, in the adenocarcinoma subtype, 71% (5 of 7 patients) of the patients with MI at 10q24 succumbed to the disease as compared with only 12% (3 of 26) of the adenocarcinoma patients without such MI (P < 0.001), suggesting the presence of distinct mechanisms in tumorigenesis among different subtypes of lung cancer. It has been noticed that certain microsatellite alteration profiles provide additional values for risk assessment. Of 23 patients who had MI at 10q24 and an alteration at 3p14, 39% (9 of 23 patients) died of the disease within 5 years as compared with only 15% (10 of 66 patients) of the patients without such a profile (P = 0.02). Strikingly, among the 22 patients with no alteration at any loci tested or with loss of heterozygosity at 10q24 and retention of at least one of the other two loci, none died of lung cancer within 5 years after surgery, whereas 28% (19 of 67 patients) of the patients outside these profiles did so (P = 0.01). Our results support the hypothesis that microsatellite alterations can be used as biomarkers for the genetic classification of pathological stage I NSCLC, which may in turn influence treatment decisions dependent on an accurate forecast of patient survival time.

Adenocarcinoma↗

PubMed2000

[Therapeutic efficacy of microsphere-entrapped curcuma aromatica oil infused via hepatic artery against transplanted hepatoma in rats].

OBJECTIVE: To observe the therapeutic efficacy of microsphere-entrapped Curcuma aromatica oil (MS-CAO) infused via hepatic artery against transplanted hepatoma in rats. METHODS: One hundred duplicated rats bearing transplanted hepatoma were randomly divided into control group, CAO group, blank microsphere (B-MS) group, high-dose and low-dose MS-CAO groups. Each group included twenty rats. Normal saline (0.2-0.3 ml), CAO (10mg/kg), B-MS (10mg/kg) and MS-CAO (10mg/kg, 5mg/kg) were infused from gastroduodenal artery into hepatic artery, in five groups of rats respectively. The survival periods and the tumor growth rates and necrosis grades were compared in rats among five groups. RESULTS: Compared with the control group of rats, the tumor growth rates were significantly inhibited (1.23% +/- 0.66%, 4.86% +/- 1.47% vs 22.44% +/- 17.81%, F=10.21, P<0.01), the tumor necrosis grades were more extensive (Hc=23.63, P<0.01) and the survival periods were also prolonged (25.50 d +/- 3.89 d, 22.70 d +/- 3.92 d vs 11.70 d +/- 1.89 d, F=36.53, P<0.01) in either high-dose or low-dose MS-CAO group. The therapeutic effects of MS-CAO were superior to either CAO or B-MS. CONCLUSION: The therapeutic efficacy of MS-CAO infused via hepatic artery against hepatoma was much better than that of CAO or B-MS in the rats bearing transplanted hepatoma.

Animals↗

PubMed2000

Design, synthesis, and pharmacological evaluation of soft glycopyrrolate and its analog.

Glycopyrrolate is a quaternary anticholinergic drug. Like for other anticholinergics, the usefulness of this agent is limited by its side effects. In this study, based on the structure of glycopyrrolate, we designed a soft drug, methoxycarbonylphenyl-cyclopentylacetoxy-N,N-dimethyl-3-p yrrolidinium methyl sulfate (SG), and its analog, methoxycarbonylphenylcyclopentyl-acetoxyethyl-N,N,N-trimethylammon ium methyl sulfate (SGA). These soft drugs are expected to be locally active, but systemically inactive in order to increase therapeutic index. SG and SGA were synthesized by (i) carboxylation of methyl phenylcyclopentylacetate, (ii) esterification with N-methyl-3-pyrrolidinol (for SG) or 2-chloro-N,N-dimethylaminoethane (for SGA), and (iii) quarternization with dimethyl sulfate. Receptor binding studies demonstrate that SG has muscarinic subtype selectivity (m3/m2). Guinea pig ileum pA2 assay indicates that activity of SG is moderate, and SG is about ten times more potent than SGA. The in vivo characterization of SG and SGA, both in mydriasis tests and in prevention of carbachol induced bradycardia, supported its soft nature. Applying SG or SGA into rabbit eyes, the dilation of the contralateral (water-treated) pupils was not observed. Glycopyrrolate application, however, caused dilation of the contralateral pupil, indicating a systemic effect of this drug. Cardiac studies were carried out by evaluating the protective effect of soft anticholinergics against carbachol induced bradycardia. The results indicate that SG and SGA were as potent as atropine-MeBr in preventing carbachol induced bradycardia in the rat; however, their durations of action were significantly shorter. In conclusion, the newly synthesized SG and SGA showed soft nature in the body. They are anticholinergics with subtype selectivity and moderate potency, and can be used as topical antiperspirants.

Administration, Topical↗

PubMed2000

Effect of cyclodextrins on the solubility and stability of a novel soft corticosteroid, loteprednol etabonate.

To increase the aqueous solubility and stability of the soft corticosteroid loteprednol etabonate (LE), drug complexation using various cyclodextrins (CDs), such as gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HPBCD), maltosyl-beta-cyclodextrin (MBCD), mixture of glucosyl/maltosyl-alpha-, beta-, and gamma-cyclodextrin (GMCD), and heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD), were attempted. The solubilizing and stabilizing effects of CD by itself or combined with various co-solvents were also investigated. Micronized (5 micron) LE was mixed in various aqueous CD or CD with cosolvent solutions. After equilibration and filtration at 23 degrees C, the solubility of LE was determined by HPLC. Subsequently, the stability of LE in the solutions was also determined by following the LE concentration change in the solution for an appropriate period. CD complexation significantly increased the aqueous solubility and stability of LE. The increase in solubility displayed a concentration dependency on CDs (0-50%). Among the five CDs used, DMCD showed the highest effects on the solubility (4.2-18.3 mg/ml in 10-50% DMCD) and stability (t90 > 4 years at 4 degrees C, when LE 0.5 mg/ml was dissolved in 10% DMCD solution) of LE. By adding co-solvents, such as glycerol, propylene glycol (PG), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP-10), the solubility of LE in DMCD solutions was further increased. Degradation of LE to the corresponding metabolites, delta 1-cortienic acid etabonate (AE) and delta 1-cortienic acid (A), in aqueous CD solutions appeared to be a predicted, two-step kinetics. Differential Scanning Calorimetry (DSC) was used to assist explaining the solubilizing and stabilizing activity differences between CDs. LE/CD mixture or lyophilized LE/CD complex was scanned at a rate of 20 degrees C/min. The exothermic peak found in the DSC diagram with LE/DMCD sample, but not with LE/HPBCD samples, suggests a stronger complex formed between LE and DMCD, resulting in higher solubility and stability of LE in DMCD than in HPBCD.

Androstadienes↗

PubMed2000

Toxigenic strains of Fusarium moniliforme and Fusarium proliferatum isolated from dairy cattle feed produce fumonisins, moniliformin and a new C21H38N2O6 metabolite phytotoxic to Lemna minor L.

Corn samples suspected of causing refusal-to-eat syndrome in dairy cattle were examined mycologically. Fusarium moniliforme (14 isolates) and F. proliferatum (12 isolates) were the predominant fungi present. These isolates were tested for mycotoxin production on rice at 25 degrees C. Each strain of F. moniliforme produced fumonisin B1 (FB1: 378-15,600 ppm) and fumonisin B2 (FB2: 2-1050 ppm). Each strain of F. proliferatum produced moniliformin (45-16,000 ppm), FB1 (27-6140 ppm), and FB2 (5-1550 ppm). In addition, a new Fusarium metabolite of molecular composition C21H38N2O6 was produced by 10 of the F. moniliforme isolates and 7 of the F. proliferatum isolates. The metabolite's 1H- and 13C-NMR, HRFAB/MS and IR spectra indicate an alpha amino acid. It is toxic to Lemna minor L. duckweed (LD50 100 micrograms/mL).

Animal Feed↗

PubMed2000

Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin.

The coupling of apoptosis (programmed cell death) to the cell division cycle is essential for homeostasis and genomic integrity. Here, we report the crystal structure of survivin, an inhibitor of apoptosis, which has been implicated in both control of cell death and regulation of cell division. In addition to a conserved N-terminal Zn finger baculovirus IAP repeat, survivin forms a dimer through a symmetric interaction with an intermolecularly bound Zn atom located along the molecular dyad axis. The interaction of the dimer-related C-terminal alpha helices forms an extended surface of approximately 70 A in length. Mutagenesis analysis revealed that survivin dimerization and an extended negatively charged surface surrounding Asp-71 are required to counteract apoptosis and preserve ploidy. These findings may provide a structural basis for a dual role of survivin in inhibition of apoptosis and regulation of cell division.

Amino Acid Motifs↗

PubMed2000

Efficacy and effect of SI17 therapy on pancreatic polypeptide in vascular and tension-type headache.

BACKGROUND AND PURPOSE: Vascular and tension-type headache is most commonly encountered, and SI17 therapy has been tested to treat headache with good results. The efficacy of SI17 therapy for vascular and tension-type headache was compared and the effect of SI17 therapy on pancreatic polypeptide (PP) was studied. MATERIALS AND METHODS: 29 cases of vascular headache (20 cases in acute attack during the trial) and 27 cases of tension-type headache (19 cases in acute attack) were enrolled in the study. Plasma PP level before and 4th day after treatment was measured by radioimmunoassay. RESULTS: SI17 therapy is better for the treatment of vascular headache. Vascular headache with higher PP level and tension-type headache with normal PP level had good therapeutic results. CONCLUSION: The clinical efficacy is better for vascular headache with the increase of vagus tension and for tension-type headache with normal vagus tension.

Acupuncture Points↗

PubMed2000

Effect of batroxobin on expression of c-Jun in left temporal ischemic rats with spatial learning and memory disorder.

The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.

Animals↗

PubMed2000

[The change of serum melatonin and diagnosis value in hepatic encephalopathy].

OBJECTIVE: To explore the change of serum melatonin (MT) and its diagnosis value in hepatic encephalopathy (HE). METHODS: The change of MT in serum in cirrhotic patients with HE and without HE was determined by ELISA, and normal serum served as control. The change of serum MT during exacerbation and remission stage of HE was also determined. RESULTS: The level of MT in patients with HE was higher than that without (P<0.01). Both groups were higher than normal group (312.7 +/- 77.4) ng/L, (149.8 +/- 38.4) ng/L, and (77.3 +/- 28.4)ng/L, respectively, P<0.01. The level of serum MT was higher in exacerbation stage than remission stage, (308.5 +/- 59.1) ng/L and (147.8 +/- 23.3) ng/L, respectively, P<0.01. CONCLUSION: The elevation of MT in serum may be one of pathogenic factors for HE. Dynamic measurement of MT in serum is conducive to the diagnosis of HE.

Adult↗

PubMed2000

Fertilization triggers activation of Fyn kinase in the zebrafish egg.

Fertilization results in the tyrosine phosphorylation of several egg proteins and studies have shown that tyrosine protein kinase activity is required for successful fertilization. The Fyn protein kinase has been detected in eggs of the sea urchin, frog and rat, although measurement of fertilization-induced changes in Fyn kinase activity have only been successful in the sea urchin system. The present study demonstrates the presence of Fyn kinase in the zebrafish egg and the stimulation of this enzyme at fertilization. Activation of Fyn was detected as early as 30 seconds post-fertilization and increased approximately six-fold by 2 minutes post-insemination. The activation of Fyn in the zebrafish egg required sperm and was not observed in spontaneously activated eggs.

Animals↗

PubMed2000

Effects of batroxobin on spatial learning and memory disorder of rats with temporal ischemia and the expression of HSP32 and HSP70.

The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.

Animals↗

PubMed2000

[Measure of vibration protection effect of driver's corset and analysis of its biomechanical effect].

The purpose of this study was to evaluate the vibration protection and biomechanical effect of driver's corset. The frequencies of vertfical and horizontal vibrations were measured at low back of driver. The vehicle driven was ISUZU truck (loading capacity 8 tons). Vibration of the driver's lumbar back was measured real time with wear corset and without wear corset when the truck loaded with 6 tons was driven at the spead of ten, thirty and sixty kilometers an hour on the asphalt road. The results showed: 1. Vibration frequencies at driver's low back was under 10 Hz. It is a low frequency vibration. 2. The value of vertical vibration was higher than the value of horizontal (back and forth) vibration. 3. The vibration value of wear corset was higher than un-wear corset. These indicate the driver's corset is effective for protecting lumbar spine by means of change in the biomechanical characteristics and the resonace requencies of lumbar spine. So the driver's corset is one of the good methods for preventing the back pain of drivers.

Automobile Driving↗