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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 145 records · Page 8Linked to original sources
PubMed2002

The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Adult↗
PubMed2002

Reconstructing the mechanics of quadrupedalism in an extinct hominoid.

Traditionally, analogising comparative anatomical approaches, working on features of individual bony elements, have led to the Miocene hominoids Proconsul heseloni and P. nyanzae being described as arboreal, with a variety of possible locomotion modes. Whilst most researchers seemingly agree that quadrupedal was one of the most frequently adopted modes, any deeper knowledge about the kinematical characteristics of such quadrupedalism is very limited. Based on the previous studies and a computer simulation technique developed in our laboratory, a set of alternative models for Proconsul quadrupedalism was created. The body measurements and initial properties for the different models were held constant, using data from published literature if available, or otherwise estimated from data for Pan. Judged by the power output of joints, the results of computer simulation indicate that the style of quadrupedal locomotion typical of living macaques fits the body proportions of Proconsul better than that of Canis domesticus, Varecia variegata, Cebus albifrons or Pan troglodytes. It may reasonably be assumed that Proconsul's quadrupedal mode was similar to that of living macaques.

Animals↗
PubMed2002

Parallel-plate flow chamber for studies of 3D flow-endothelium interaction.

Flow induced shear stress influences vascular cellular biology and pathophysiology in numerous ways. Previous in vitro studies on interactions between flow and endothelial cells using parallel-plate flow chambers involve two-dimensional flows, whereas flows in larger vessels are commonly three-dimensional. We have constructed a parallel plate flow chamber with a backward facing step aligned oblique to the axis of the chamber. Flow visualisation by steady injection of ink through a hypodermic tube reveals swirling flow in the recirculation region downstream of the step. At given angles of the step, theta; (to the axis of the chamber), the pitch of the swirl and the width of the separation region, as measured in the direction perpendicular to the step, increase with the Reynolds number (Re). On the other hand, at given values of Re, reduction of theta; results in increases in the swirl pitch but decreases in the width of the separation zone. Furthermore, clearance time of ink from the separation region is shorter with an oblique step than a perpendicular one at given Re. Computer simulation confirms the 3D swirling flow created by the oblique step and provides detailed distribution of wall shear stresses in the flow chamber.

Arteries↗
PubMed2001

Photochemical incorporation of silver quantum dots in monodisperse silica colloids for photonic crystal applications.

We developed a novel method to fabricate nanocomposite monodisperse SiO2 spheres (approximately 100 nm) containing homogeneously dispersed Ag quantum dots (approximately 2 to 5 nm). The inclusion morphology is controlled through the timing of the photochemical reduction of silver ions during hydrolysis of tetraethoxysilane in a microemulsion. Depending on the timing, Ag quantum dots can be directed to different annuli within the SiO2 spheres, as well as onto the SiO2 sphere surfaces. The embedded Ag quantum dots show a plasmon resonance absorption band at 438 nm. These Ag@SiO2 particles have significant surface charge and readily self-assemble into crystalline colloidal array (CCA) photonic crystals which Bragg-diffract light in the visible region. The magnitude of the plasmon resonance absorption depends on the CCA Bragg diffraction condition. The negative dielectric constant of the silver nanoparticles may be decreasing the silica-silver nanodot composite refractive index below that of the water medium. We may be observing an analogue of the Borrmann effect previously observed in X-ray scattering, where the incident and diffracted electric field standing wave becomes localized in regions of small CCA crystal absorption.

Journal Article↗
PubMed2001

Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance.

Drug resistance has sharply limited the effectiveness of HIV-1 protease inhibitors in AIDS therapy. It is critically important to understand the basis of this resistance for designing new drugs. We have evaluated the free energy contribution of each residue in the HIV protease in binding to one of its substrates and to the five FDA-approved protease drugs. Analysis of these free energy profiles and the variability at each sequence position suggests: (i) single drug resistance mutations are likely to occur at not well conserved residues if they interact more favorably with drugs than with the substrate; and (ii) resistance-evading drugs should have a free energy profile similar to the substrate and interact most favorably with well conserved residues. We also propose an empirical parameter, called the free energy/variability value, which combines free energy calculation and sequence analysis to suggest possible drug resistance mutations on the protease. The free energy/variability value is defined as the product of one residue's contribution to the binding free energy and the variability of that residue. This parameter can assist in designing resistance-evading drugs for any target.

Drug Resistance, Microbial↗
PubMed2001

[The prevalence and mechanism of Helicobacter pylori resistance to clarithromycin in Beijing].

OBJECTIVE: (1) To determine the prevalence of Helicobacter pylori strains resistant to clarithromycin in Peking. (2) To determine the genetic mutation in relation to clarithromycin resistance. METHODS: Helicobacter pylori were cultured from gastric biopsies obtained from 89 patients during upper endoscopy. Minimal inhibitory concentrations of clarithromycin were determined by Etest method. Genomic DNA was prepared by the hexadecyltrimethylammonium bromide (CTAB)-phenol extraction method. Mutations in clarithromycin-resistant strains were identified by polymerase chain reaction and restrictions analysis. RESULTS: (1) The prevalence of Helicobacter pylori strains resistant to clarithromycin was 13.5% in Beijing. (2) All twelve clarithromycin-resistant strains had the new BsaI site which is characteristic of the A2143G point mutation in 23S rRNA gene, none of the tested twenty-four susceptible strains had the A2142G or A2143G mutation. CONCLUSION: The prevalence of clarithromycin-resistant strains was not rare in Beijing. Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori.

Anti-Bacterial Agents↗
PubMed2001

Synthesis and preliminary testing of molecular wires and devices.

Presented here are several convergent synthetic routes to conjugated oligo(phenylene ethynylene)s. Some of these oligomers are free of functional groups, while others possess donor groups, acceptor groups, porphyrin interiors, and other heterocyclic interiors for various potential transmission and digital device applications. The syntheses of oligo(phenylene ethynylene)s with a variety of end groups for attachment to numerous metal probes and surfaces are presented. Some of the functionalized molecular systems showed linear, wire-like, current versus voltage (I(V)) responses, while others exhibited nonlinear I(V) curves for negative differential resistance (NDR) and molecular random access memory effects. Finally, the syntheses of functionalized oligomers are described that can form self-assembled monolayers on metallic electrodes that reduce the Schottky barriers. Information from the Schottky barrier studies can provide useful insight into molecular alligator clip optimizations for molecular electronics.

Journal Article↗
PubMed2001

Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii.

Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide (PZA) to ammonia and pyrazinoic acid, which is active against Mycobacterium tuberculosis. Loss of PZAase activity is the major mechanism of pyrazinamide-resistance by M. tuberculosis. We have determined the crystal structure of the gene product of Pyrococcus horikoshii 999 (PH999), a PZAase, and its complex with zinc ion by X-ray crystallography. The overall fold of PH999 is similar to that of N-carbamoylsarcosine amidohydrolase (CSHase) of Arthrobacter sp. and YcaC of Escherichia coli, a protein with unknown physiological function. The active site of PH999 was identified by structural features that are also present in the active sites of CSHase and YcaC: a triad (D10, K94, and C133) and a cis-peptide (between V128 and A129). Surprisingly, a metal ion-binding site was revealed in the active site and subsequently confirmed by crystal structure of PH999 in complex with Zn(2+). The roles of the triad, cis-peptide, and metal ion in the catalysis are proposed. Because of extensive homology between PH999 and PZAase of M. tuberculosis (37% sequence identity), the structure of PH999 provides a structural basis for understanding PZA-resistance by M. tuberculosis harboring PZAase mutations.

Amidohydrolases↗
PubMed2001

Phosphorylation of tau by glycogen synthase kinase 3beta in intact mammalian cells influences the stability of microtubules.

Tau is a neuronal microtubule-associated protein found predominantly in axons. Hyperphosphorylation of tau reduces the stability of microtubules, which may be a pathogenic mechanism in Alzheimer's disease. To understand the different effects between tau and glycogen synthase kinase 3beta (GSK-3beta) phosphorylated tau on the organization and stability of microtubules, we performed transfection studies on 3T3 cells using EGFP-tau (Enhanced Green Fluorescence Protein-tau) and GSK-3beta to quantify the stability of microtubules. Laser confocal microscope observation revealed that thick and thin microtubule bundles could be induced by tau and GSK-3beta phosphorylated tau. The bundles appeared either to be relatively straight or to form a ring around the circumference of the cell. Both the thick and thin microtubule bundles were resistant to colchicine-induced dissociation, with thick bundles more resistant than thin bundles. The bundles induced by GSK-3beta phosphorylated tau were sensitive to colchicine, and could be reversed by the addition of LiCl, an inhibitor of GSK-3beta.

3T3 Cells↗
PubMed2001

[Clinical analysis of pulmonary lymphangioleiomyomatosis].

OBJECTIVE: To study the clinical features, treatment, and prognosis of pulmonary lymphangioleiomyomatosis (LAM). METHODS: A retrospective analysis of 16 cases of LAM was made, among which two were diagnosed and treated in the Chinese PLA General Hospital, and the clinical data of the other fourteen cases were studied by literature review. RESULTS: Among the 16 patients, 15 were female (94%) and 1 was male (6%). The age of onset ranged 5 - 69 years, with an average age of onset of 35 +/- 15 years. Thirteen patients (81%) were women of childbearing age. The main clinical menifestations included dyspnea (15 cases, 94%), hemoptysis (10 cases, 62%), pneumothorax (7 cases, 44%), and chylothorax (7 cases, 44%). High-resolution computerized tomography conducted in 14 cases showed thin-walled air-filled cysts throughout both lungs. Seven patients took pulmonary function test with the results of obstructive ventilatory disturbance in 5 cases, mixed ventilatory disturbance in 2 cases, and reduction of carbon dioxide duffusing capacity in all cases. Arterial blood gas analysis was made among 11 patients and showed hypoxemia (blood oxygen < 80 mm Hg) in 8 cases and respiratory failure in 5 cases. All of the patients were misdiagnosed as other diseases at the first visit. The time between onset of symptoms and confirmation of diagnosis ranged 2 - 276 months (median 28 months). Six patients were treated with medroxyprogesterone for 6-50 months. Among them two patient' condition remained stable, two patients' condition was worsened, and two died. Six out of the 16 patients (38%) died of respiratory failure, pneumothorax, or lung infection 1.5 to 26 years after the onset. CONCLUSION: The main clinical manifestations of LAM are dyspnea, hemoptysis, pneumothorax, and chylothorax. Medroxyprogesterone is of little curative effect on LAM. The main task in LAM research is to find out its etiology and effective treatment.

Adolescent↗
PubMed2001

Total synthesis of bafilomycin A(1) relying on iterative 1,2-induction in acyclic precursors.

The macrolide bafilomycin A(1) was synthesized starting from D-valine and D-mannitol as chiral progenitors of propionate units. Acyclic subunits corresponding to different parts of the molecule were constructed based on an iterative 1,2-asymmetric induction protocol as a distinctive feature of the synthesis. The assembly of two segments encompassing the entire carbon framework of the macrolide was achieved by using a Stille coupling. The resulting seco-ester was further manipulated to provide crystalline bafilomycin A(1) via a conventional carbodiimide-mediated Keck-type macrolactonization.

Anti-Bacterial Agents↗
PubMed2001

Interaction of 3,4-dienoyl-CoA thioesters with medium chain acyl-CoA dehydrogenase: stereochemistry of inactivation of a flavoenzyme.

The medium chain acyl-CoA dehydrogenase is rapidly inhibited by racemic 3,4-dienoyl-CoA derivatives with a stoichiometry of two molecules of racemate per enzyme flavin. Synthesis of R- and S-3,4-decadienoyl-CoA shows that the R-enantiomer is a potent, stoichiometric, inhibitor of the enzyme. alpha-Proton abstraction yields an enolate to oxidized flavin charge-transfer intermediate prior to adduct formation. The crystal structure of the reduced, inactive enzyme shows a single covalent bond linking the C-4 carbon of the 2,4-dienoyl-CoA moiety and the N5 locus of reduced flavin. The kinetics of reversal of adduct formation by release of the conjugated 2,4-diene were evaluated as a function of both acyl chain length and truncation of the CoA moiety. The adduct is most stable with medium chain length allenic inhibitors. However, the adducts with R-3,4-decadienoyl-pantetheine and -N-acetylcysteamine are some 9- and >100-fold more kinetically stable than the full-length CoA thioester. Crystal structures of these reduced enzyme species, determined to 2.4 A, suggest that the placement of H-bonds to the inhibitor carbonyl oxygen and the positioning of the catalytic base are important determinants of adduct stability. The S-3,4-decadienoyl-CoA is not a significant inhibitor of the medium chain dehydrogenase and does not form a detectable flavin adduct. However, the S-isomer is rapidly isomerized to the trans-trans-2,4-conjugated diene. Protein modeling studies suggest that the S-enantiomer cannot approach close enough to the isoalloxazine ring to form a flavin adduct, but can be facilely reprotonated by the catalytic base. These studies show that truncation of CoA thioesters may allow the design of unexpectedly potent lipophilic inhibitors of fatty acid oxidation.

Acyl Coenzyme A↗
PubMed2001

Characterization of regulatory elements on the promoter region of p16(INK4a) that contribute to overexpression of p16 in senescent fibroblasts.

Cyclin-dependent kinase inhibitor p16(INK4a) is implicated in replicative senescence, cell immortalization, and tumor generation. However, the mechanism regulating its overexpression in senescent cells is unknown. We used the enhanced green fluorescent protein reporter system to scan regulatory elements in the upstream region of p16(INK4a). The results of 5'-deletion studies indicated that the transcription regulatory elements contributing to overexpression of p16(INK4a) in senescent cells were located in the region of the p16(INK4a) promoter from -622 to -280 bp. According to the results of in vitro DNase I footprinting, EMSA, and Southwestern blotting, we found a novel negative regulatory element, the INK4a transcription silence element (ITSE), at -491 to -485 bp of the p16(INK4a) promoter. A 24-kDa protein that was highly expressed in young cells may inhibit the expression of p16(INK4a) by interacting with the ITSE. The activity of the p16(INK4a) promoter increased significantly in young cells when the ITSE was deleted. The GC-rich region of the p16(INK4a) promoter from -466 to -451 was a positive transcription regulatory element. Deletion of this region showed 91.4% loss of p16(INK4a) promoter activity in senescent cells, and the promoter activity decreased by 41.2% in young cells comparably.

Base Sequence↗
PubMed2001

Reversed-phase high-performance liquid chromatography procedure for the simultaneous determination of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine in mouse liver and the effect of methionine on their concentrations.

An improved reversed-phase high-performance liquid chromatography (HPLC) procedure with ultraviolet detection is described for the simultaneous determination of S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) in mouse tissue. The method provides rapid resolution of both compounds in a 25-microl perchloric acid extract of the tissue. The limits of detection in 25-microl injection volumes were 22 and 20 pmol for SAM and SAH, respectively. The limits of quantitation in 25-microl injection volumes were 55 and 50 pmol for SAM and SAH, respectively, with recovery consistently >98%. The assay was validated over linear ranges of 55-11000 pmol for SAM and 50-10000 pmol for SAH. The intra-day precision and accuracy were < or =6.4% relative standard deviation (RSD) and 99.9-100.0% for SAH and < or =6.7% RSD and 100.0-100.1% for SAM. The inter-day precision and accuracy were < or =5.9% RSD and 99.9-100.6% for SAH and < or =7.0% RSD and 99.5-100.1% for SAM. Compared to earlier procedures, the HPLC method demonstrated significantly better separation, detection limit and linear range for SAM and SAH determination. The assay demonstrated applicability to monitoring in mice the time-course of the effect of methionine on SAM and SAH levels in the liver. Administering methionine to mice increased by 10-fold the liver concentration of SAM and SAH within 2 h, which then rapidly decreased to the control levels by 8 h. This indicated that methionine was promptly converted to SAM and then rapidly catabolized into SAH. Thus, the metabolism of methionine to SAM should be considered in the supplementation of methionine to maintain SAM levels in the body.

Animals↗
PubMed2001

Self-assembled bismuth nanocrystallites.

Using a high-temperature organic solution reduction method, highly crystalline and single domain bismuth nanoparticles have been synthesized and self-assembled.

Journal Article↗
PubMed2001

Modeling two-state cooperativity in protein folding.

A protein model with the pairwise interaction energies varying as the local environment changes, i.e., including some kind of collective effect between the contacts, is proposed. Lattice Monte Carlo simulations on the thermodynamical characteristics and free energy profile show a well-defined two-state behavior and cooperativity of folding for such a model. As a comparison, related simulations for the usual G&o model, where the interaction energies are independent of the local conformation, are also made. Our results indicate that the evolution of interactions during the folding process plays an important role in the two-state cooperativity in protein folding.

Biophysics↗
PubMed2001

[MRI-guided transcutaneous aspiration biopsy of liver lesions].

OBJECTIVE: To evaluate the clinical application of MR-guided aspiration biopsy of liver lesions. METHODS: MR-guided aspiration biopsy of liver lesions with 0.5 T Conventional MR system and 19 gauge MRI-compatible aspiration needle was performed in 13 patients. For MR guidance, fast gradient echo sequence or fast spin echo sequence was used. RESULTS: MR-guided aspiration liver biopsy was performed successfully without any complication on all patients. The accurate needle puncture rate was 100%, accurate diagnosis rate 92.3%, and false negative rate 7.7%. CONCLUSION: MR-guided transcutaneous aspiration biopsy of liver lesions is a safe, accurate and effective method for diagnosis and differential diagnosis.

Adult↗