Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 109 records · Page 6Linked to original sources

PubMed2002

Gastric bypass model in the obese rat to study metabolic mechanisms of weight loss.

A rat model replicating gastric bypass with Roux-en-Y (GB) as used in morbidly obese patients, evolved in our laboratory in stages, using the Zucker rat as an obese model (GB) is presented. In the final model, a 20% gastric fundic pouch to limit the gastric reservoir was created using two staple lines (Ethicon). A 4- to 5-mm end-to-side gastrojejunostomy and a 6- to 8-mm jejunojejunostomy, at 10 cm length of the Roux-en-Y limb, placed 16 cm below the ligament of Treitz, was hand sewn to create a limited area of nutrient digestion and absorption. Controls underwent sham operation. Rats were divided into: (i) sham-op ad lib-fed (Control); (ii) GB; and (iii) sham-op pair fed (PF) in two experiments. In Experiment 1, 24 Zuckers (control n = 8; GB n = 8; PF n = 8) were studied to assess the effectiveness of the model for weight loss. In Experiment 2, 24 Zuckers (8/group) were studied to confirm the effects of the operation on weight loss and on metabolic parameters. Boost was given for 4 days starting 24 h postop and then ground chow was given. Daily food intake (FI), meal size (MZ), meal number (MN), and body weight (BW) were measured. Rats were sacrificed on Day 20 in Experiment 1 and on Day 10 in Experiment 2. Serum metabolites and body fat weight were measured. Data were evaluated using Student's t test. Controls steadily gained BW (5.2-6.1 g/day), reaching approximately 500 g. In GB: FI, MZ, MN, BW, glucose, free fatty acids, insulin, and body fat decreased (P < 0.05). In PF: BW, insulin, triglycerides, and body fat decreased. A dependable, reproducible gastric bypass with Roux-en-Y obesity model was developed. This permits the study of biochemical and eventually molecular mechanism(s) of weight loss resulting from the operation.

Adipose Tissue↗

PubMed2002

Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.

The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.

Animals↗

PubMed2002

Development and evaluation of a novel decellularized vascular xenograft.

Although autogenous saphenous vein remains the standard for coronary and infrapopliteal bypass, many patients do not have a suitable vein. Attempts at developing a small-caliber vascular graft have failed largely due to occlusion, neointimal hyperplasia, or aneurismal degradation. We have designed and characterized a novel small-caliber vascular xenograft that may overcome these failure modes. To reduce immune reactions, porcine common carotid arteries were decellularized by enzymatic and detergent treatments. Histology and electron microscopic examination showed complete removal of cellular components while the extracellular matrix structure remained intact. To reduce thrombogeneity, decellularized vascular grafts were covalently linked with heparin. The efficiency of heparin linkage was demonstrated with toluidine blue staining and the antithrombogeneity of the heparin-treated grafts was demonstrated with a clot time test. Mechanical testing of the graft was performed. Decellularized-heparin-treated grafts were similar in compliance to fresh vessels and burst testing showed grafts to withstand pressures exceeding 10 times physiologic blood pressure. There was no difference in suture retention strength between fresh vessels and decellularized-heparin-treated grafts. Decellularized, heparinized grafts were implanted in dogs as carotid artery bypass grafts and showed smooth muscle cells densely populating the wall, and endothelial cells lining the lumen by two months. This study provides a new strategy to develop a small-caliber vascular graft with excellent mechanical properties, antithrombogeneity, and tissue compatibility.

Animals↗

PubMed2002

Novel peptide inhibitors for Grb2 SH2 domain and their detection by surface plasmon resonance.

One of the critical intracellular signal transduction pathways involves the binding of the Grb2 SH2 domain to the phosphotyrosine (pTyr) motifs on growth factor receptors, such as epidermal growth factor receptor (EGFR) and erbB2, leading to downstream activation of the oncogenic Ras signaling pathway. Therefore, the Grb2 SH2 domain has been chosen as our target for the development of potential anticancer agents. As a continuation of our earlier work, herein we report the design and synthesis of new peptide analogs, and their inhibitory effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology. These novel agents do not contain phosphotyrosine or phosphotyrosine mimics. Binding interactions between these peptides and the Grb2 SH2 domain were measured and analyzed using a BIAcore X instrument, which provides detailed information on the real-time detection of the binding interaction. The results of this study should provide important information for the further development of peptides or peptidomimetics with high affinity for the Grb2 SH2 domain.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Application of actinomycetes to soil to ameliorate water repellency.

AIMS: The aim of this study was to develop a novel isolation technique using a mixture of Bacillus and Streptomyces phages to selectively isolate wax-utilizing non-streptomycete actinomycetes effective in ameliorating water repellency in a problem soil. METHODS AND RESULTS: Phages added to a soil suspension reduced the dominance of Bacillus and Streptomyces isolates and significantly increased the number of non-streptomycete actinomycetes on isolation plates. Promising isolates, grown on a medium containing beeswax as sole carbon source, were selected for application to water repellent soil. Their addition significantly reduced water repellency. CONCLUSIONS: Phage application significantly increased the isolation of non-streptomycete actinomycetes. Wax-utilizing isolates were found to significantly reduce water repellency in a problem soil. SIGNIFICANCE AND IMPACT OF THE STUDY: The phage technique can be used for the routine isolation of non-streptomycete actinomycetes. Beeswax medium can be used to selectively isolate wax-utilizing micro-organisms with the potential to ameliorate water repellency in soil.

Actinobacteria↗

PubMed2002

Reliability of serial urine HCG as a biomarker to detect early pregnancy loss.

BACKGROUND: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented 'no conception,' a 'continuing conception' or a 'conception lost.' METHODS: Urine samples were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. RESULTS: Pairwise agreement among the assessors for any of the three options ranged from 78-89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. CONCLUSION: The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women.

Abortion, Spontaneous↗

PubMed2002

Pain as a factor complicating recovery and discharge after ambulatory surgery.

UNLABELLED: Pain complicates the recovery process after ambulatory surgery. We surveyed 175 ambulatory surgery patients to determine pain severity, analgesic use, relationship of pain to duration of recovery, and the relative importance of various factors to predicting these outcomes. Multivariate regression analysis was used to determine unique contributions of predictor variables to outcome. Surgical procedures included knee arthroscopy (n = 50), hernia surgery (n = 25), pelvic laparoscopy (n = 25), transvaginal uterine surgery (n = 25), surgery for breast disease (n = 25), and plastic surgery (n = 25). Maximum pain (on a scale of 0-10) varied from 2.3 +/- 0.5 to 5.1 +/- 0.5 (mean +/- SE), depending on surgical procedure; 24% of patients had pain scores of > or =7, and 24% were delayed in Phase 1 recovery by pain. Pain scores were lower if local anesthetic or ketorolac was administered intraoperatively (22% and 26% respectively). Fentanyl dose during recovery correlated with maximum pain scores; fentanyl dose was 42% less if ketorolac was administered intraoperatively. In females, the recovery fentanyl dose increased in proportion to the intraoperative fentanyl dose. The maximum pain score was predictive of total recovery time (135, 172, and 212 min of recovery for maximum pain scores of 0-3, 4-6, and 7-10, respectively; P < 0.001). We conclude that improvements in pain therapy are warranted to improve patient comfort and to expedite recovery. IMPLICATIONS: Moderate to severe pain is common after ambulatory surgery and is a frequent cause of delayed discharge. Postoperative pain, opioid-related side effects, and time to discharge were less when nonsteroidal antiinflammatory drugs or local anesthetics were used intraoperatively to prevent pain before patient awakening.

Adult↗

PubMed2002

Effects of aryl substituents on the anti-HIV activity of the arylphosphoramidate derivatives of stavudine.

We compared the anti-HIV activity of 13 phenyl phosphate derivatives of stavudine (2',3'-didehydro-2',3'-dideoxythymidine/d4T) by examining their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells. Our results show that the introduction of electron-withdrawing substituents enhances the activity of these phosphoramidate derivatives. The rate of chemical hydrolysis under alkaline conditions (but not the lipophilicity) predicted the potency of the compounds.

Anti-HIV Agents↗

PubMed2002

Sequential genotyping of Pseudomonas aeruginosa from upper and lower airways of cystic fibrosis patients.

A controversy exists concerning the adequate specimen to characterise colonisation of cystic fibrosis (CF) airways by Pseudomonas aeruginosa. Oropharyngeal, sputum and bronchoalveolar lavage samples were evaluated from 38 stable CF patients for the detection of P. aeruginosa, genetically different isolates within the same host and longitudinal variations in the genotype during repeated examinations. Bacterial isolates were typed by pulsed-field gel electrophoresis of deoxyribonucleic acid macrorestriction fragments. Sensitivity, negative and positive predictive values and specificity to detect P. aeruginosa were 35.7, 73.5, 83.3 and 96.2% for oropharyngeal cultures in nonexpectorating patients and 91.7, 94.1, 100 and 100% for sputum cultures from expectorating patients, respectively. Genotypes of Pseudomonas isolates recovered from oropharyngeal swabs and sputum differed to the strains recovered by bronchoscopy in 55% and 40%, respectively. In 62% longitudinal variations in the genotype occurred. One-half of these alterations were detectable by bronchoscopy only. In conclusion, sputum samples were of equal value as specimens from bronchoalveolar lavage to detect Pseudomonas aeruginosa colonisation. Cultures from the oropharynx are not suitable for characterising bacterial conditions in the cystic fibrosis lung. Different genotypes within the same host and longitudinal genetic alterations are common and may be detectable in the bronchoalveolar lavage fluid exclusively.

Adolescent↗

PubMed2002

Diffusion weighted MR imaging in acute stroke: the SGH experience.

Cerebrovascular accident (CVA) is a leading cause of death and disability in many countries. Diffusion-weighted (DW) magnetic resonance (MR) imaging has been reported to be useful in the detection of acute strokes and as an investigative tool evaluating the therapeutic effects of neuroprotective and thrombolytic agents. The objectives of this study are to share our experience using the commercially available isotropic DW scan in imaging of acute stroke, assess its usefulness over conventional T2-weighted (T2W) scans in a busy clinical radiology unit and highlight it pitfalls. We found the rapid sub-minute DW technique well suited for ill and restless stroke patients and superior to T2W scans in many ways. It was highly sensitive to acute ischaemic lesions, made lesions easily identifiable and readily differentiated the acute lesion from a background of multiple chronic infarcts. However, there are potential pitfalls in the evaluation of small hyperacute posterior fossa strokes and venous infarcts. The major strength of this MR technique lies in its ability to diagnose hyperacute strokes and thence the potential for therapeutic thrombolysis, but unfortunately patients qualifying for the "therapeutic window" were a minority. More efforts need to be focused on public education in order for this powerful imaging modality to find its true value and contribute to viability of an effective thrombolytic programme.

Adult↗

PubMed2002

Cerebral infarct mimicking glioma in Sjogren's syndrome.

A 50-year-old Chinese woman with a chronic 20-year history of ataxic gait associated with dry eyes and mouth, was admitted to hospital after a single episode of syncope. Magnetic resonance imaging scans showed a large left frontal hypodense lesion suggestive of a glioma. Craniotomy was performed and the lesion excised, with histology showing only infarcted tissue and no malignant cells. Further diagnostic evaluation revealed that the patient had primary Sjogren's syndrome, with demyelinating polyneuropathy. In the absence of risk factors for stroke, it was considered likely that the cerebral infarct was secondary to autoimmune-related vasculitis. Functional neuroimaging, such as magnetic resonance spectroscopy, should be considered in evaluating doubtful or unusual brain lesions in patients with autoimmune disease.

Brain↗

PubMed2002

Over-expression of beta-1,4-galactosyltransferase V increases the growth of astrocytoma cell line.

Our previous study showed that the gene expression of beta-1,4-galactosyltransferase V (beta-1,4-GalT V), preferentially galactosylating GlcNAc1-->6Man of oligosaccharides, increased in the process of astrocytoma progress, with the highest level in grade IV astrocytoma. To investigate the function of this beta-1,4-GalT in cell proliferation, the sense and antisense cDNA of beta-1,4-GalT V was constructed as pcDNA3-HA-GalT V and pcDNA3-anti-GalT V respectively and transfected into SHG cell, a kind of human astrocytoma cell line. The transfection was confirmed with Northern and Western blot assay. It was found that the growth of SHG/HA-GalT V in serum-containing medium was faster than that of mock-transfectant with the vector pcDNA3, whereas the growth of SHG/GalTV-AS was slower than that of mock-transfectant. GalTV-HA/SHG showed a stronger capability for colony formation than that of GalTV-AS/SHG as evaluated by anchorage-independent growth in soft agar assay. This result was consistent with that of the growth curve. By RCA-1 lectin assay, the galactosylation on the surface of GalTV-HA/SHG and SHG/GalTV-AS was stained stronger (P<0.001) and weaker (P<0.05) respectively compared with the mock transfectant. This indicates that beta-1,4-GalT V was involved in the malignant phenotype of astrocytoma cells, possibly causing the high galactosylation on the cell surface.

Astrocytoma↗

PubMed2001

1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities.

Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF(1) receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF(1) receptor (K(i)=9 nM).

Humans↗

PubMed2001

Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII.

The coagulation factor VIII (FVIII) is the coagulation factor deficient in the X-chromosome-linked bleeding disorder hemophilia A. Previous transfection studies demonstrated that factor VIII was 10-100-fold less efficiently expressed than the homologous coagulation factor, factor V. To investigate the regulatory mechanisms of FVIII synthesis and secretion, we used the yeast two-hybrid system as an approach to search for proteins that associated with FVIII. The A2 domain (337-740 amino acids) of factor VIII (FVIII-A2) was used as a bait and phytanoyl-CoA alpha-hydroxylase (PAHX) was identified as a binding protein of FVIII-A2. PAHX had potential to interact with the residues 373-508 within the A2 domain, but not with A1 and A3 (the homologous domains of A2). The interaction between the A2 domain and PAHX was independent of the type 2 peroxisomal targeting signal (PTS2) of PAHX. Overexpression of PAHX in FVIII-produced cells decreased the expression of FVIII by about 70%. The elevated expression of von Willebrand factor had no effect on the suppression of FVIII secretion by PAHX. Expression of the green fluorescent PAHX fusion protein in SMMC-7721 cells affected the intracellular trafficking of FVIII-A2. These results suggested that the interaction between PAHX and FVIII-A2 was in part responsible for the low-level expression of factor VIII.

Animals↗

PubMed2001

Search for gluinos and squarks using like-sign dileptons in pp macro collisions at square root of s = 1.8 TeV.

We present results of the first search for like-sign dilepton ( e(+/-)e(+/-), e(+/-)mu(+/-), mu(+/-)mu(+/-)) events associated with multijets and large missing energy using 106 pb(-1) of data in pp macro collisions at square root of s = 1.8 TeV collected during 1992-1995 by the CDF experiment. Finding no events that pass our selection, we examine pair production of gluinos (tilde g) and squarks (tilde q) in a constrained framework of the minimal supersymmetric standard model. At tan beta = 2 and mu = -800 GeV/c(2), we set 95% confidence level limits of M(tilde g)>221 GeV/c(2) for M(tilde g) approximately M(tilde q), and M(tilde q)>168 GeV/c(2) for M(tilde q)>>M(tilde g), both with small variation as a function of mu.

Journal Article↗

PubMed2001

Observation of diffractive J/psi production at the Fermilab Tevatron.

We report the first observation of diffractive J/psi(--> mu+mu-) production in pp collisions at root square[s] = 1.8 TeV. Diffractive events are identified by their rapidity gap signature. In a sample of events with two muons of transverse momentum p(mu)T>2 GeV/c within the pseudorapidity region /eta/ < 1.0, the ratio of diffractive to total J/psi production rates is found to be R(J/psi) = [1.45 +/- 0.25]%. The ratio R(J/psi)(x) is presented as a function of x-Bjorken. By combining it with our previously measured corresponding ratio R(jj)(x) for diffractive dijet production, we extract a value of 0.59 +/- 0.15 for the gluon fraction of the diffractive structure function of the proton.

Journal Article↗

PubMed2001

Charged-particle multiplicity pp collisions at square root of (s) = 1.8 TeV.

We report on a measurement of the mean charged-particle multiplicity of jets in dijet events with dijet masses in the range 80-630 GeV/c(2), produced at the Tevatron in pp collisions with square root (s) = 1.8 TeV and recorded by the Collider Detector at Fermilab. The data are fit to perturbative-QCD calculations carried out in the framework of the modified leading log approximation and the hypothesis of local parton-hadron duality. The fit yields values for two parameters in that framework: the ratio of parton multiplicities in gluon and quark jets, r identical withN(g-jet)(partons)/N(q-jet)(partons) = 1.7+/-0.3, and the ratio of the number of charged hadrons to the number of partons in a jet, K(charged)(LPHD) identical with N(charged)(hadrons)/N(partons) = 0.57+/-0.11.

Journal Article↗

PubMed2001

Search for quark-lepton compositeness and a heavy W' Boson using the enu channel in p p macro collisions at square root of [s] = 1.8 TeV.

We present searches for quark-lepton compositeness and a heavy W' boson at high electron-neutrino transverse mass. We use approximately 110 pb(-1) of data collected in p p macro collisions at square root of [s] = 1.8 TeV by the CDF Collaboration during 1992-1995. The data are consistent with standard model expectations. Limits are set on the quark-lepton compositeness scale Lambda, the ratio of partial cross sections sigma(W'-->enu)/sigma(W-->enu), and the mass of a W' boson with standard model couplings. We exclude Lambda<2.81 TeV and a W' boson with mass below 754 GeV/c(2) at the 95% confidence level. Combining with our previously published limit obtained using the muon channel, we exclude a W' boson with mass below 786 GeV/c(2) at the 95% confidence level.

Journal Article↗