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N Wang

Publications and source records attributed to N Wang.

At least 73 records · Page 4Linked to original sources
PubMed2001

Statistical evaluation of the regulatory guidelines for use of furosemide in race horses.

The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulting estimators compared. Their numerical performances were further evaluated through simulations. Finally, we applied these methods to a furosemide concentration profile data set and used our findings to address certain important practical issues.

Animals↗
PubMed2001

Treatment with sheng-mai-san reduces myocardial infarct size through activation of protein kinase C and opening of mitochondrial KATP channel.

Sheng-mei-san (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700 years for patients with coronary heart disease. We attempted to clarify 1) whether SMS reduces myocardial infarct size, and 2) whether the infarct size-reducing effect of SMS is related to activation of protein kinase C and the opening of the mitochondrial KATP channels in Japanese white rabbits without collateral circulation. The results indicate that three days treatment but not acute treatment with SMS reduces myocardial infarct size through activation of protein kinase C and opening of the mitochondrial KATP channels.

Analysis of Variance↗
PubMed2001

X-linked lymphoproliferative disease: a progressive immunodeficiency.

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells.

A magnetic twisting stimulator was developed based on the previously published technique of magnetic twisting cytometry. Using ligand-coated ferromagnetic microbeads, this device can apply mechanical stresses with varying amplitudes, duration, frequencies, and waveforms to specific cell surface receptors. Biochemical and biological responses of the cells to the mechanical stimulation can be assayed. Twisting integrin receptors with RGD (Arg-Gly-Asp)-containing peptide-coated beads increased endothelin-1 (ET-1) gene expression by >100%. In contrast, twisting scavenger receptors with acetylated low-density lipoprotein-coated beads or twisting HLA antigen with anti-HLA antibody-coated beads did not lead to alterations in ET-1 gene expression. In situ hybridization showed that the increase in ET-1 mRNA was localized in the cells that were stressed with the RGD-coated beads. Blocking stretch-activated ion channels with gadolinium, chelating Ca2+ with EGTA, or inhibiting tyrosine phosphorylation with genistein abolished twist-induced ET-1 mRNA elevation. Abolishing cytoskeletal tension with an inhibitor of the myosin ATPase, with an inhibitor of myosin light chain kinase, or with an actin microfilament disrupter blocked twisted-induced increases in ET-1 expression. Our results are consistent with the hypothesis that the molecular structural linkage of integrin-cytoskeleton is an important pathway for stress-induced ET-1 gene expression.

Actins↗
PubMed2001

Investigation on cell proliferation with a new antibody against thymidine kinase 1.

The cytosolic thymidine kinase 1 (TK1) is one of the enzymes involved in DNA replication. Based on biochemical studies, TK1 is activated at late G1 of cell cycle, and its activity correlates with the cell proliferation. We have developed a polyclonal anti-TK1 antibody against a synthetic peptide from the C-terminus of human TK1. Using this antibody, here we demonstrate the exclusive location of TK1 in the cytoplasm of cells. Cell cycle dependent TK1 expression was studied by simultaneous fluorescence staining for TK1 and bromodeoxyuridine, by using elutriated cells, and by quantitation of the amount TK1 in relation to the cellular DNA content. TK1, which was strongly expressed in the cells in S+G2 period, raised at late G1 and decreased during mitosis. The amount of TK1 increased three folds from late G1 to G2. TK1 positive cells were demonstrated in areas of proliferation activity of various normal and malignant tissues. The new anti-TK1 antibody works in archival specimens and is a specific marker of cell proliferation.

Animals↗
PubMed2001

LDL-activated p38 in endothelial cells is mediated by Ras.

Endothelial dysfunction is a major atherogenic proinflammatory event. LDL causes the activation and phenotypic changes of cultured vascular endothelial cells (ECs). We previously reported that LDL activates c-Jun and AP-1 in ECs. In this study, we demonstrated that p38-ATF-2 is activated by LDL in human ECs and that this activation is mediated by Ras. When ECs are incubated with LDL in pathophysiological concentrations, the p38-mediated ATF-2 phosphorylation and ATF-2 transactivation are increased in a time- and dose-dependent manner. To elucidate the upstream mechanism in LDL-activated p38 in ECs, we demonstrate that LDL increases Ras translocation from the cytoplasm to the cellular membrane, with concurrent increases in Ras binding activity to GST-Raf-1. Overexpression of RasN17, a dominant negative mutant of Ras, attenuates the LDL-induced increases in (1) phosphorylation of ATF-2, (2) phosphorylation of c-Jun, (3) AP-1 binding, and (4) AP-1-driven luciferase activity. To study the effect of p38 in the regulation of an LDL targeting gene, we show that a specific p38 inhibitor attenuates LDL-induced E-selectin at the mRNA level. Thus, LDL activates both p38 and JNK signaling pathways through Ras activation, and furthermore, these events may play an important role in LDL-induced endothelial activation.

Activating Transcription Factor 2↗
PubMed2001

Adenovirus-mediated overexpression of dominant-negative mutant of c-Jun prevents intercellular adhesion molecule-1 induction by LDL: a critical role for activator protein-1 in endothelial activation.

Low density lipoprotein (LDL) induces intercellular adhesion molecule-1 (ICAM-1) gene expression and leads to endothelial cell (EC) leukocyte adhesion. However, the transcriptional mechanism for LDL-induced EC perturbation remains to be fully explained. Activator protein-1 (AP-1) is induced after the exposure of ECs to LDL. In the present study, a regulated adenovirus expressing a dominant-negative mutant of c-Jun (TAM-67) was used to examine the role of AP-1 in the LDL-induced ICAM-1 activation. Overexpression of TAM-67 specifically inhibited AP-1 activation and prevented the LDL-activated surface expression of ICAM-1 protein in human umbilical vein ECs and human coronary artery ECs. Northern analyses and promoter transactivation assays indicated that this effect of TAM-67 was likely mediated through a suppression of the transcriptional regulation of the ICAM-1 gene. Functionally, TAM-67 attenuated leukocyte adherence to ECs in response to LDL. Furthermore, electrophoresis mobility shift assays and site-directed mutagenesis suggested that an AP-1-like motif in the promoter region of the human ICAM-1 gene was a critical cis element for LDL induction. These results, for the first time, provide evidence suggesting that AP-1 is a major regulatory mechanism leading to endothelial activation.

Adenoviridae↗
PubMed2001

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers. Part II: biodegradation.

A series of previously-synthesized lactic/glycolic acid polymers (PLGA) with various molar ratios of lactic to glycolic acid and various molecular weights were further studied with regard to their biodegradation behavior, and in particular, the factors affecting the biodegradation rate. The biodegradation of PLGA is affected by many factors including polymer composition, molecular weight, and nature of the incubating media. The biodegradation rate of PLGA containing higher content of lactic acid moiety is lower than those containing a lower content of lactic acid moiety. PLGAs with a higher molecular weight, degrade faster than those with a lower molecular weight, i.e. the molecular weight decreases more rapidly for higher molecular weight PLGAs than their lower molecular weight counterparts. Nature or properties of the hydrolysis/incubating media may have an effect on the biodegradation of PLGAs. A basic medium may slow down the biodegradation of PLGA in comparison with samples in an acidic medium. The rate of pH reduction for the incubating medium can be divided into three deferent phases, giving an inverted S-type pH profile for the non-buffered incubating media.

Biocompatible Materials↗
PubMed2001

Antiallergic agents from natural sources. 3. Structures and inhibitory effects on nitric oxide production and histamine release of five novel polyacetylene glucosides from Bidens parviflora WILLD.

Five new polyacetylene glucosides, bidensyneosides A1, A2, B, C (1-4), and 3-deoxybidensyneoside B (5), have been isolated from the air-dried whole plant of Bidens parviflora WILLD. The structures were identified based on spectroscopic analysis, physicochemical properties, and application of the modified Mosher method to be 3(R),8(E)-8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside (1), deca-3(R),8(Z) 8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside (2), 3(R)-deca-4,6,8-triyne-1,3-diol 1-O-beta-D-glucopyranoside (3), 3(R),8(E)-8-decene-4,6-diyne-1,3,10-triol 1-O-beta-D-glucopyranoside (4), and 8(E)-8-decene-4,6-diyne-1,10-diol 1-O-beta-D-glucopyranoside (5), respectively. These compounds inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-gamma activated murine macrophages (RAW264.7) and also inhibited histamine release from rat mast cells stimulated by the antigen-antibody reaction.

Acetylene↗
PubMed2001

Combination of N-methyl-1-deoxynojirimycin and ischemic preconditioning markedly reduces the size of myocardial infarcts in rabbits.

N-methyl-1-deoxynojirimycin (NMDN), an a-glucosidase inhibitor, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Ischemic preconditioning (PC), which markedly reduces the size of the myocardial infarct, is known to reduce the activity of phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized that a combination of pharmacological inhibition of glycogenolysis by an alpha-1,6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial infarct size more than NMDN or PC alone. Japanese white rabbits without collateral circulation were subjected to a 30-min coronary occlusion followed by 48-h reperfusion. The infarct sizes as a percentage of area at risk were significantly reduced by pre-ischemic treatment with either 100mg/kg of NMDN or PC of 5 min ischemia and 5 min reperfusion alone (15.9+/-2.0%, n=8, and 10.3+/-1.2%, n=8, respectively) as compared with the control (43.9+/-2.2%, n=8). However, the combination of 100mg/kg of NMDN and PC significantly reduced the infarct size (4.9+/-1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given 100mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved the glycogen content and attenuated the lactate accumulation, respectively, as compared with the control. However, the combination of NMDN and PC preserved significantly more glycogen and significantly reduced lactate accumulation than either NMDN or PC alone. The combination of NMDN and PC markedly reduced the myocardial infarct size more than either process alone. The marked preservation of glycogen and marked attenuation of lactate accumulation by the combination of NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to the inhibition of glycogenolysis.

1-Deoxynojirimycin↗
PubMed2001

Caspase-dependent and serine protease-dependent DNA fragmentation of myocytes in the ischemia-reperfused rabbit heart: these inhibitors do not reduce infarct size.

Some infarcted myocytes undergo caspase-dependent DNA fragmentation, but serine protease-dependent DNA fragmentation may also be involved. There is controversy regarding whether caspase inhibitors can reduce infarct size, so the present study investigated whether serine protease inhibitor can reduce the DNA fragmentation of infarcted myocytes and whether serine protease or caspase inhibitors attenuates myocardial infarct size in Japanese white rabbits without collateral circulation. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. A vehicle (dimethylsulfoxide, control group, n=8) or Z-Val-Ala-Asp(Ome)-CH2F (ZVAD-fmk, a caspase inhibitor, ZVAD group, 0.8 mg/kg iv at 20 min before coronary occlusion and 0.8 mg/kg at 90 min after reperfusion, n=8) or 3,4-dichloroisocoumarin (DCI, a serine protease inhibitor, 2 mg/kg iv at 20 min before coronary occlusion, DCI group, n=8) was administered. Animals were killed at 48h after reperfusion for the detection of myocardial infarct size and at 4h after reperfusion for the detection of dUTP nick end-labeling (TUNEL)-positive myocytes, the electrophoretic pattern of DNA fragmentation and ultrastructural analysis. The left ventricle (LV) was excised and sliced. The myocardial infarct size as a percentage of the area at risk was assessed by triphenyltetrazolium chloride staining. DNA fragmentation was assessed by in situ TUNEL at the light microscopic level. ZVAD and DCI significantly reduced the mean blood pressure during reperfusion without affecting heart rate. There was no significant difference in the % area at risk (AAR) of LV among the 3 groups (control: 26.3+/-3.0%; ZVAD: 25.6+/-2.6%; DCI: 25.6+/-2.0%). The % infarct size as a percentage of the AAR in the ZVAD group (41.3+/-4.5%) and the DCI group (50.4+/-3.8%) was not significantly different from the control group (43.5+/-4.5%). However, the percent DNA fragmentation in the infarcted area in the ZVAD (3.5+/-0.8%) and DCI groups (4.2+/-0.9%) was significantly reduced compared with the control group (10.7+/-1.9%). The DNA ladder pattern observed in the control group was attenuated in both the ZVAD and DCI groups. There was no difference in electron microscopic changes among the 3 groups. Serine protease-dependent DNA fragmentation is present in infarcted myocytes, in addition to caspase-dependent DNA fragmentation, but an infarct-size reducing effect was not observed with either of these inhibitors.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Absorption spectra of the 4f electron transitions of the praseodymium complex with 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(4-ethyl-1-piperazinyl) -4-oxo-3-quinoline carboxylic acid hydrochloride and its analytical application.

The absorption spectra of the praseodymium complex with 1-cyclopropyl-6-fluoro-1,4-dihydro-7-(4-ethyl-1-piperazinyl)-4-oxo-3- quinoline carboxylic acid hydrochloride (NNFX) has been studied by normal and derivative spectrophotometry. The complex showed maximum absorption at 350 nm at pH 6.0. The stoichiometry of the Pr-NNFX complex was calculated by the molar ratio and continuous variation methods. The ratio of Pr to NNFX was 1:3. The absorption bands of the 4f electron transitions of the praseodymium complex with NNFX are enhanced markedly, especially the wavelength at 481 nm. Using the third-derivative spectrum, the calibration graph is linear over the range 2.5 x 10(-5)-3.5 x 10(-4) mol dm-3 for praseodymium. The detection limits (signal-to-noise ratio of 2) is 1.4 x 10(-6) mol dm-3. The relative standard deviation is 1.2% for 7.0 x 10(-5) mol dm-3 of praseodymium. A method for the direct determination of praseodymium in rare earth mixtures with good accuracy and selectivity is described.

Journal Article↗
PubMed2001

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.

Animals↗
PubMed2001

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.

Animals↗
PubMed2001

[Identification of traditional Chinese medicine Baizhi with near-infrared spectrum].

In this paper, 8 kinds of traditional Chinese medicines Baizhi were identified by near-infrared spectrum, coping with pattern recognition. The results showed that near-infrared spectrum method in identifying traditional Chinese medicines Baizhi was not only simple, rapid, but also using few examples, noninvasion. This method provided referential information for identifying these traditional Chinese medicines.

Angelica↗
PubMed2001

Increased human scleral permeability with prostaglandin exposure.

PURPOSE: To investigate the effect of prostaglandins (PGs) on the permeability of human sclera in vitro. METHODS: Twenty-three pairs of human eye bank eyes were studied. Circular pieces of sclera were cultured in low-serum DMEM/F-12 media. Scleral hydration was assessed by measuring wet and dry weight of scleral cultures incubated with medium for 3 days and with Hanks' buffered saline solution (HBSS) for 4 hours. To assess scleral permeability, organ-cultured scleral tissues were exposed to 100 to 500 nM PGF(2alpha), 17-phenyltrinor PGF(2alpha), or PhXA85 (the active form of latanoprost) for 1, 2, and 3 days. Scleral permeability was measured using a two-chamber Ussing apparatus and rhodamine-dextran polymers dissolved in HBSS (MW = 10,000, 40,000, and 70,000). The movement of each rhodamine-dextran across the cultured sclera was measured using a spectrofluorometer. To understand the biological basis of the permeability change, the media were collected from the treated cultures, and the concentration of MMP-1, 2, and 3 was measured using an enzyme-linked immunosorbent assay. RESULTS: There was no difference in scleral hydration among fresh sclera and sclera incubated with medium for 3 days, with HBSS for 4 hours, or with medium for 3 days followed by HBSS for 4 hours. Compared to tracer movement across untreated scleral cultures (1.5 x 10(-6) cm/sec for 10 kDa dextran, 0.7 x 10(-6) cm/sec for 40 kDa dextran, and 0.4 x 10(-6) cm/sec for 70 kDa dextran), exposure to PGF(2alpha), 17-phenyltrinor PGF(2alpha), or PhXA85 each increased scleral permeability in a dose- and time-dependent manner. Increases in permeability were greater with the10 kDa dextran than with the 40 or 70 kDa dextran. The magnitude of these effects was greatest with exposure to PhXA85 and similar with exposure to PGF(2alpha) or 17-phenyltrinor-PGF(2alpha). MMP expression also was significantly increased after PG exposure. These increases were generally time and dose dependent and greater with MMP-2 and -3 than with MMP-1. CONCLUSIONS: There is increased permeability of human sclera exposed to various PGs in organ culture. This increased permeability is accompanied by increased expression of MMPS:

Aged↗
PubMed2001

[VP7 typing of rotavirus from children with diarrhea in Chongqing Region].

OBJECTIVE: To study VP7 type of rotavirus from children with diarrhea in Chongqing area from 1998 to 2000. METHODS: Double-strand RNA of rotavirus extracted from stool samples was used as the template for reverse transcription of gene VP7, which was followed by nested PCR for VP7 typing. Nucleotide sequence analysis was used for VP7 typing. RESULTS: Among the 130 fecal specimens from pediatric patients with acute gastroenteritis during the epidemic season of 1998-1999, fifty specimens (38.46%) were identified as rotavirus-positive by RT-PCR. Of these, serotype G1 was found to be largely predominant and accounted for 88% (44/50), while serotype G3 accounted for 8% (4/50), coinfection of G1 and G3 accounted for 4% (2/50) respectively. While during the next epidemic season from 1999 to 2000, thirty-eight (33.93%) rotavirus positive specimens were detected from 112 stool samples by RT-PCR. Serotype G3 increased significantly-up to 78.95% (30/38) and became the most prevalent serotype in that season. It was found that only 13.16% (5/38) were serotype G1, 7.89% (3/38) were G1 and G3 mixture. The nucleotide sequence analysis results agreed with the RT-PCR typing assay. CONCLUSIONS: Serotype G1 and G3 were the prevalent VP7 types in Chongqing, China from 1998 to 2000. A shift from G1 to G3 was observed in the last two successive epidemic seasons of rotavirus epidemics.

Amino Acid Sequence↗