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Biomedical subjects

Y F Chen

Publications and source records attributed to Y F Chen.

At least 19 recordsLinked to original sources
PubMed2001

On-line microdialysis coupled with microbore liquid chromatography with ultraviolet detection for continuous monitoring of free cefsulodin in rat blood.

A microdialysis method followed by a microbore liquid chromatographic ultraviolet detection procedure has been performed for the assay of unbound cefsulodin in rat blood. A microdialysis probe was inserted into the jugular vein for blood sampling. This method involves an on-line design for submitting dialysate into the liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (10:90, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 265 nm. Microdialysis probes, being laboratory-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of cefsulodin in the blood following intravenous administration of cefsulodin (20 mg/kg) in rats. Pharmacokinetics were calculated from the corrected data for dialysate concentrations of cefsulodin versus time. Based on pharmacokinetic calculation, cefsulodin best fitted to a two-exponential disposition. This study provided specific pharmacokinetic information for protein-unbound cefsulodin and demonstrated the applicability of this continuous sampling method for pharmacokinetic study.

Animals↗
PubMed2001

Catalytic growth and characterization of gallium nitride nanowires.

The preparation of high-purity and -quality gallium nitride nanowires is accomplished by a catalytic growth using gallium and ammonium. A series of catalysts and different reaction parameters were applied to systematically optimize and control the vapor-liquid-solid (VLS) growth of the nanowires. The resulting nanowires show predominantly wurtzite phase; they were up to several micrometers in length, typically with diameters of 10-50 nm. A minimum nanowire diameter of 6 nm has been achieved. Temperature dependence of photoluminescence spectra of the nanowires revealed that the emission mainly comes from wurtzite GaN with little contribution from the cubic phase. Moreover, the thermal quenching of photoluminescence was much reduced in the GaN nanowires. The Raman spectra showed five first-order phonon modes. The frequencies of these peaks were close to those of the bulk GaN, but the modes were significantly broadened, which is indicative of the phonon confinement effects associated with the nanoscale dimensions of the system. Additional Raman modes, not observed in the bulk GaN, were found in the nanowires. The field emission study showing notable emission current with low turn-on field suggests potential of the GaN nanowires in field emission applications. This work opens a wide route toward detailed studies of the fundamental properties and potential applications of semiconductor nanowires.

Journal Article↗
PubMed2001

Genetic variation in angiotensin-converting enzyme does not prevent development of cardiac hypertrophy or upregulation of angiotensin II in response to aortocaval fistula.

BACKGROUND: Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload. METHODS AND RESULTS: Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF (P<0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice. CONCLUSIONS: ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.

Angiotensin II↗
PubMed2001

Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity.

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.

Animals↗
PubMed2001

Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest.

BACKGROUND: Because there is no smooth muscle cell surrounding the capillary endothelial cells, the effect of coronary microcirculation at the capillary level following cardioplegic arrest and reperfusion would be much different from that of resistant arterioles. We therefore studied the effect of hypothermic blood cardioplegic arrest and subsequent reperfusion on the myocardial capillaries in cardiac operation patients. METHODS: Twenty-seven patients who underwent cardiac operations were included in this study. Three sequential biopsies (preischemia, ischemia, and reperfusion) were obtained from the right atrium. This study was restricted to blood vessels with a diameter of less than 8 microns. Ten randomly selected capillaries from each biopsy were measured for luminal surface area, endothelial cytoplasmic surface area, and total cross-sectional surface area of capillaries. RESULTS: From stereologic morphometric studies, the serial changes in total cross-sectional surface area were not statistically significant (p = 0.152). However, there was a significant swelling of endothelial cytoplasm following ischemia and reperfusion (p = 0.0007). Meanwhile, changes in luminal surface area of capillaries following ischemia and reperfusion were also remarkable (p = 0.0008). CONCLUSIONS: The most striking finding of this study was the progressive decrease in capillary lumen during ischemia and after reperfusion. The swelling of endothelial cells is a major determinant of luminal narrowing of capillaries in patients receiving cardioplegic arrest.

Adolescent↗
PubMed2001

Effects of paeoniflorin on the formalin-induced nociceptive behaviour in mice.

In this study, we attempted to identify the mechanisms of paeoniflorin on antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.) showed dose-related antinociception both on the early and late phases of formalin test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test. However, the antinociceptive effects of paeoniflorin were not potentiated by L-arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10 microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block the paeoniflorin-induced antinociception on the early phase of formalin test. These results suggested that the central antinociceptive effects of paeoniflorin on formalin test in mice were mediated by the activation of kappa-opioid receptor and not related to the increase of intracellular calcium.

Animals↗
PubMed2001

Self-reported medication use for older people in England and Wales.

OBJECTIVES: To describe the patterns of self-reported medication use, including both prescription and non-prescription drugs, for older people in five areas in England and Wales, and to identify the effects of socio-demographic features on medication use. DESIGN: A cross-sectional survey on population random samples of people aged 65 and over. The survey is a part of the screening interviews at the first stage of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) carried out between 1991 and 1994. The sample was stratified to provide equal numbers in the 65-74 years and 75 years and over age groups. SETTING: Three urban (Newcastle, Nottingham and Oxford) and two rural (Cambridgeshire and Gwynedd) centres. Older people living in both the general community and institutions were included. PARTICIPANTS: 12489 older people whose medication data were collected among the 13009 participants of the CFAS, of which the participation rate is 80%. RESULTS: Overall prevalence of medication use was 75% (95% confidence interval 74-76%) for people aged 65-74 and 84% (83-85%) for people aged 75 and over, with a mean number of 2.03 (standard deviation 1.95) and 2.47 (2.02) drugs reported per respondent in each group, respectively. Concurrent use of five or more drugs (polypharmacy) was found in 11% (10-12%) of people in the 65-74 age group and in 15% (14-16%) in the 75 and over age group. People aged 75 and over were more likely to be taking at least one drug than people aged 65-74 (OR=1.69, 1.54-1.85), and women were more likely to be so compared with men (OR=1.43, 1.30-1.56). Centre variation was found but none of the centres consistently showed higher or lower usage of medications across the major drug categories. People living in institutions were more likely to be taking gastrointestinal drugs, central nervous system drugs and experience polypharmacy. The use of respiratory and central nervous system drugs (except hypnotics and anxiolytics) increased in lower social class and decreased in people attending full-time education for 10 years or more. The use of haematology/dietetic drugs (85% of which were vitamin and mineral preparations) decreased in lower social class. CONCLUSION: This study provides representative estimates of medication usage among older people in England and Wales and identified associated factors and regional variations for medication use in a category-specific manner. The findings, suggesting the existence of centre variation and the association between type of accommodation, social class and medication use warrant further investigation.

Age Factors↗
PubMed2001

Increased dietary salt accelerates chronic allograft nephropathy in rats.

BACKGROUND: Chronic allograft nephropathy (CAN), a major problem in renal transplantation, is related to both alloantigen-dependent and -independent processes. Because dietary salt intake modulated glomerular production of transforming growth factor-beta, which has been shown to play an important role in CAN, we hypothesized that dietary salt would directly enhance renal injury in a rodent model of CAN. METHODS: Dietary NaCl was increased from 1.0% (normal) to 8.0% in a group of Fisher/Lewis rats 25 days following orthotopic renal transplantation and was continued until 16 weeks after transplantation. RESULTS: Blood pressure, which was recorded using radiotelemetry in the first eight-weeks post-transplantation, did not differ between the groups, but allograft recipients on the 8.0% NaCl diet rapidly demonstrated increased urinary albumin excretion. Renal function determined by dynamic functional imaging was worse in allograft recipients on the 8.0% NaCl diet by six weeks following transplantation. Histologic examination at 16 weeks confirmed a significant increase in allograft damage in the 8.0% NaCl group compared with allografts from rats on 1.0% NaCl diet. These findings included glomerulosclerosis and tubulointerstitial injury that consisted of fibrosis, tubular atrophy and dilation, intratubular casts, and tubular epithelial cell damage. Small arteries and arterioles did not show evidence of damage from hypertension or other abnormality. CONCLUSIONS: In this model of CAN, renal allograft dysfunction preceded hypertension and was accelerated significantly by an increase in dietary salt.

Albuminuria↗
PubMed2001

Tyrosine kinase receptor activation inhibits NPR-C in lung arterial smooth muscle cells.

We have previously demonstrated that expression of the atrial natriuretic peptide (ANP) clearance receptor (NPR-C) is reduced selectively in the lung of rats and mice exposed to hypoxia but not in pulmonary arterial smooth muscle cells (PASMCs) cultured under hypoxic conditions. The current study tested the hypothesis that hypoxia-responsive growth factors, fibroblast growth factors (FGF-1 and FGF-2) and platelet-derived growth factor-BB (PDGF-BB), that activate tyrosine kinase receptors can reduce expression of NPR-C in PASMCs independent of environmental oxygen tension. Growth-arrested rat PASMCs were incubated under hypoxic conditions (1% O2) for 24 h; with FGF-1, FGF-2, or PDGF-BB (0.1-20 ng/ml for 1-24 h); or with ANG II (1-100 nM), endothelin-1 (ET-1, 0.1 microM), ANP (0.1 microM), sodium nitroprusside (SNP, 0.1 microM), or 8-bromo-cGMP (0.1 mM) for 24 h under normoxic conditions. Steady-state NPR-C mRNA levels were assessed by Northern blot analysis. FGF-1, FGF-2, and PDGF-BB induced dose- and time-dependent reduction of NPR-C mRNA expression within 1 h at a threshold concentration of 1 ng/ml; hypoxia, ANG II, ET-1, ANP, SNP, or cGMP did not decrease NPR-C mRNA levels in PASMCs under the above conditions. Downregulation of NPR-C expression by FGF-1, FGF-2, and PDGF-BB was inhibited by the selective FGF-1 receptor tyrosine kinase inhibitor PD-166866 and mitogen-activated protein/extracellular signal-regulated kinase inhibitors U-0126 and PD-98059. These results indicate that activation of tyrosine kinase receptors by hypoxia-responsive growth factors, but neither hypoxia per se nor activation of G protein-coupled receptors, inhibits NPR-C gene expression in PASMCs. These results suggest that FGF-1, FGF-2, and PDGF-BB play a role in the signal transduction pathway linking hypoxia to altered NPR-C expression in lung.

Animals↗
PubMed2001

Absence of cocaine- and amphetamine-regulated transcript results in obesity in mice fed a high caloric diet.

Cart (cocaine- and amphetamine-regulated transcript) was first identified to be a major brain mRNA up-regulated by cocaine and amphetamine. The CART protein has been established as a satiety factor closely associated with the action of leptin. To assess CART's role as an anorexigenic signal, we have generated CART-deficient mice by gene targeting. On a high fat diet, CART-deficient and female heterozygous mice, but not male heterozygous mice, showed statistically significant increases in weekly food consumption, body weight, and fat mass compared with their wild-type littermates. Furthermore, CART-deficient and female heterozygous mice were significantly heavier when fed a high fat diet than on a regular chow diet at 17 wk of age and at the 14th wk of the feeding studies. However, wild-type or male heterozygous mice showed no weight variations attributable to caloric contents of the diet at that age. Contrary to the obese phenotypes shown in MC4R-, proopiomelanocortin-, or leptin-deficient mice, our results showed that CART deficiency predisposed mice to become obese on a calorically dense diet. The results also show that CART may not be a major anorectic signal compared with proopiomelanocortin or leptin in the regulation of energy homeostasis.

Animals↗
PubMed2001

[High expression of rabbit sperm membrane protein rSP10 in Escherichia coli and preparation of its specific antisera].

To study the position and immunogenicity of rSP10, the rabbit rsp10 gene which did not include sequences coding for signal peptides was inserted into expression vector pET30a. An in-frame fusion protein was made such that a His6 stretch was produced at the N terminus of re-rSP10. High expression was obtained, the amount of re-rSP10 up to 67% in the total bacterial protein. The re-rSP10 was purified by DEAE chromatography and the yield of purified re-rSP10 was approximately 50 micrograms/mL of culture. Western blotting analysis of re-rSP10 with rabbit polyclonal sera raised against rabbit sperm membrane protein showed that the synthesized antigen possessed immunogenicity of rSP10. Specific antisera against re-rSP10 was induced using purified re-rSP10 as an antigen. The motility of capacitated sperms were affected but no aggregation was observed.

Animals↗
PubMed2001

[Exogenous pGH gene localization on chromosomes of the transgenic pigs].

The pUC19-OMT plasmids were cut by Ssp 1 and the products in 900 bp were recovered from low-melting agarose gel and used as probes which were labeled by Digoxigenin. After being denatured, the probes were dropped on the chromosome samples which were also denatured to anneal with them. The anti-digoxigenin antibodies labeled with colloidal gold were used to act with the chromosome samples. In order to localize the exogenous pGH genes(porcine growth hormone gene) on chromosomes detected with optical microscope and improve the sensitivity, digoxigen gold signals are amplified by silver precipitation. After calculating the number of silver grains on every chromosome under the optical microscope, we analyzed the data with statistical methods. The results show that the integrating sites of exogenous pGH genes are very different among the positives. However, it is clear that the exogenous genes in one are always of the tendency to integrate in one specific site on a certain chromosome. These data are of great significance for studying the site-specific integration and the expression efficiency of exogenous genes in the future research.

Animals↗
PubMed2000

Estrogen attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of osteopontin production in vascular smooth muscle cells.

BACKGROUND: Previous in vitro studies have suggested that estrogen attenuates the vascular injury response by modulating vascular smooth muscle cell (VSMC) expression of soluble factor(s) directing migration of adventitial fibroblasts. Previous in vivo studies have established a role for osteopontin (OPN) and its integrin receptors after vascular injury. In this study, we examined OPN expression in activated VSMCs, its modulation by estrogen, and its effects on adventitial fibroblast migration. In addition, the relative functional roles of beta(1)- and beta(3)-integrin-matrix interactions were examined. METHODS AND RESULTS: Primary cultures of VSMCs and adventitial fibroblasts were derived from female Sprague-Dawley rats. Serum-activated VSMCs expressed high levels of OPN mRNA and secreted protein that was effectively inhibited by estrogen treatment (10(-7) mol/L). Compared with VSMCs, fibroblasts expressed similar levels of integrins alphanu and beta(1) and higher levels of integrin-beta(3). Exogenous OPN (5.0 to 40 microg/mL) directed fibroblast migration in a dose-dependent fashion. Anti-beta(3)-integrin antibody (F11) pretreatment markedly inhibited adventitial fibroblast migration directed by exogenous OPN or VSMC-conditioned medium in a dose-dependent manner. In contrast, anti-beta(1)-integrin antibody (Ha2/5) did not affect fibroblast migration. Similarly, pretreatment with either linear or cyclic RGD peptides (10 to 1000 micromol/L) inhibited fibroblast migration directed by OPN or VSMC-conditioned medium in a dose-dependent manner. CONCLUSIONS: These observations suggest that estrogen indirectly attenuates integrin-beta(3)-dependent adventitial fibroblast migration after inhibition of OPN expression in VSMCs.

Animals↗
PubMed2000

A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.

Amino Acid Sequence↗
PubMed2000

Determination of unbound cephalothin in rat blood by on-line microdialysis and microbore liquid chromatography.

A method of analysis for the determination of unbound cephalothin in rat blood has been developed. The method was fully automated using an on-line microdialysis procedure. A microdialysis probe was inserted into the jugular vein/right atrium of male Sprague-Dawley rats to examine the unbound cephalothin level in the rat blood after cephalothin administration (50 mg/kg, i.v.). Dialysates were directly input to a liquid chromatographic system using an on-line injector. Samples were eluted with a mobile phase containing methanol-acetonitrile-100 mM monosodium phosphate (pH 5.0) (20:20:60, v/v). The UV wavelength was set at 254 nm for monitoring the analyte. Using the retrograde method, at infusion concentrations of 1 and 5 microg/ml of cephalothin, the in vivo microdialysis recoveries were 48.4+/-4.5% and 52.9+/-4.7% for the rat blood (n=6). Intra- and inter-assay accuracy and precision of the analyses were < or = 10% in the range of 0.01 through 10 microg/ml. Pharmacokinetic parameters were calculated from the recovery corrected dialysate concentrations of cephalothin versus time data. The results suggest that the pharmacokinetics of unbound cephalothin in blood fitted best to the two-compartmental model following cephalothin administration (50 mg/kg, i.v.).

Animals↗
PubMed2000

Estrogen-induced vasoprotection is estrogen receptor dependent: evidence from the balloon-injured rat carotid artery model.

BACKGROUND: Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the alpha or beta isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated. METHODS AND RESULTS: Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg. kg(-1). d(-1), subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17beta estradiol (E2) (20 microgram. kg(-1). d(-1), S.C.) alone or combined with ICI 5 mg. kg(-1). d(-1), S.C.; with ICI 5 mg. kg(-1). d(-1) alone; or with vehicle according to a similar protocol. Two weeks after injury, rats were killed, and the carotid arteries were evaluated for neointima formation using morphometric analysis. ICI 182,780 blunted the E2-related protective effect and increased neointima formation in injured carotid arteries of intact female rats in a dose-dependent fashion. ICI had no effect on neointima formation in OVX, but addition of ICI to E2 in OVX blocked the inhibitory effect of exogenous E2 on neointima formation. CONCLUSIONS: These results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.

Animals↗