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C Chen

Publications and source records attributed to C Chen.

At least 685 records · Page 38Linked to original sources

Phosphorylcholine coating of ePTFE grafts reduces neointimal hyperplasia in canine model.

This study attempts to prevent neointimal hyperplasia by coating the graft luminal surface with a derivative of phosphorylcholine (PC), thereby providing a biocompatible surface with the assumption of limiting pannus tissue ingrowth from the graft anastomoses. Bilateral carotid artery bypass grafts were placed in six dogs using expanded polytetrafluoroethylene (ePTFE). In each animal, one carotid arterial-arterial conduit was constructed using a graft having a PC coating over the entire luminal surface of the graft. On the contralateral side, uncoated graft served as a control. The processed specimens were analyzed for graft neointimal area and neointimal thickness. Cell proliferation was assessed by staining for bromodeoxyuridine (BrdU) incorporation. All grafts were patent except one control graft that was occluded at 4 weeks. There was a significant reduction in the anastomotic graft neointimal area between the treated and control groups (0.27 +/- 0.17 mm2 versus 0.53 +/- 0.13 mm2, respectively; p = 0.008). Furthermore, the BrdU labeling index in the graft neointimal tissues was significantly smaller (p < 0.001) in the treated group (2.64 +/- 0.77%) as compared with the control group (5.07 +/- 0.83%). These data demonstrate that PC coating of ePTFE significantly reduces graft neointimal hyperplasia and cell proliferation in a canine carotid artery bypass model. The application of PC within the ePTFE graft effectively blocks tissue ingrowth from the adjacent native vessel, thereby preserving the anastomosis luminal diameter.

Animals↗

Irreversible binding of N-methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl-3,4 -dichlorophenylacetamide to the cloned rat kappa opioid receptor.

N-Methyl-N-[(1S)-1-(4-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl-3,4- dichlorophenylacetamide (MITPD), is an isothiocyanate derivative of the kappa agonist ICI-199,441. In this study, interaction of MITPD with cloned mu, delta, and kappa opioid receptors was characterized. MITPD inhibited [3H]diprenorphine binding to kappa receptors with high affinity and with approximately 700- and approximately 870-fold selectivity over mu and delta receptors. Pretreatment with MITPD followed by extensive washing reduced kappa receptor binding with an IC50 value of 3.7 nM, but did not affect mu or delta binding at < or = 0.1 microM. Preincubation with 1 microM MITPD abolished [3H]diprenorphine binding, while pretreatment with 1 microM ICI-199,441 increased Kd of [3H]diprenorphine binding with no change in Bmax. Thus, MITPD is a selective kappa irreversible ligand. The region of the kappa receptor that conferred selectivity for MITPD was determined by examining its binding to four mu/kappa chimeras. IC50 values of MITPD for inhibition of [3H]diprenorphine binding were determined to be 430 nM for Chimera III (kappa1-141/mu151-398), 1.8 nM for Chimera IV (mu1-150/kappa142-380), 40 nM for Chimera XI (mu1-268/kappa263-380) and 14 nM for Chimera XII (kappa1-262/mu269-398). Pretreatment with MITPD followed by extensive washing reduced binding to chimera IV with an IC50 value of 75 nM, but did not affect III, XI or XII binding (IC50 >1 microM). Thus, the region from the third transmembrane helix to the C-terminus of the kappa receptor is important for the binding of MITPD.

Acetamides↗

Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity.

OBJECTIVES: Because the large increase in luteinizing hormone secretion induced by flutamide in the intact rat is not found in men, we have used castrated rats and mice supplemented with androstenedione (4-dione) instead of intact animals to measure the activity of the pure antiandrogens flutamide and Casodex. METHODS: We first compared the effect of different schedules of administration of various doses of the two antiandrogens on prostate and seminal vesicle weights in the castrated rat and mice models. RESULTS: For both flutamide and Casodex, no consistent difference was found between the effects of once daily and thrice daily oral dosing in the rat. It was observed, however, that flutamide, especially at the high and therapeutically more effective doses, is about three times more potent than Casodex under both schedules of dosing. When flutamide was administered subcutaneously three times a day, twice a day, once a day, or once every second day in rats and mice, no difference was observed in the degree of inhibition achieved on prostate and seminal vesicle weights. CONCLUSIONS: The present data show that Casodex is about three times less potent than flutamide on the well-recognized parameters of androgen responsiveness in the rat, namely prostate and seminal vesicle weights. Another finding is that once daily dosing with flutamide exhibits an effectiveness comparable to thrice daily dosing; such data may have potential significance in facilitating compliance by administration of flutamide once daily instead of the current thrice daily schedule in men. Moreover, these data, if obtained in a reliable in vivo model, should be helpful in determining the choice of an appropriate dose of Casodex for the treatment of prostate cancer.

Androgen Antagonists↗

Bilateral hypothalamic dopamine infusion in male Zucker rat suppresses feeding due to reduced meal size.

Lateral hypothalamic area dopamine activity (LHA-DA) appears to play a contributory role in regulating food intake, in particular, meal size. In this study we examined our hypothesis that bilateral LHA-DA injection induced depression of food intake via reduced meal size. Dopamine (11 mg/ml) or vehicle was infused into bilateral LHA at 0.5 microliter/h via two osmotic minipumps in six study or six control obese male Zucker rats for 13 days, respectively. Meal size, meal number, as well as food intake were continuously measured before, during, and after dopamine infusion. Intra-LHA-DA infusion significantly depressed food intake. The decreased food intake was solely caused by a significant and profound reduction in meal size. There was a modest compensatory rise in meal number that gradually increased food intake so that it reached control level on 10th dopamine infusion day. However, feeding pattern did not normalize until dopamine infusion ceased. The findings support our hypothesis that LHA-DA may participate in regulating meal size. Data also demonstrate that meal size and meal number are regulated in a reciprocal and independent manner to compensate for each other.

Animals↗

Fumonisins as a possible contributory risk factor for primary liver cancer: a 3-year study of corn harvested in Haimen, China, by HPLC and ELISA.

Employing HPLC fluorometry, gas-liquid chromatography (GLC) and a novel enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody, 40 corn samples, each collected in 1993 from agricultural stocks for human consumption in Haimen (Jiangsu County) and Penlai (Shandong Province), high- and low-risk areas for primary liver cancer (PLC) in China, respectively, were analysed for fumonisins (FBs), aflatoxins (AFs) and trichothecenes. Levels and positive rates of FBs and deoxynivalenol (DON) were significantly higher in Haimen than in Penlai. ELISA of the 40 corn samples harvested in the two areas in 1994 revealed that FB contamination levels and rates in these areas were comparable to those observed in 1993 in Haimen. ELISA analysis of 1993 and 1994 products revealed a wide occurrence of AFB1 but the positive rates as well as levels were not significantly different between these areas. ELISA of the same sample number of corn harvested in 1995 revealed that FB contamination in Haimen was significantly higher than in Penlai. These 3-yearly surveys of corn samples (240 in total) demonstrated that corn harvested in Haimen was highly contaminated with FBs and that the contamination level, as well as positive rate in 1993 and 1995, were 10-50-fold higher than those in Penlai, suggesting FBs as a risk factor for promotion of PLC in endemic areas, along with the trichothecene DON. Co-contamination with AFs, potent hepatocarcinogens, was assumed to play an important role in the initiation of hepatocarcinogenesis.

Aflatoxins↗

Differences in the distribution of responses to ATP and acetylcholine between outer hair cells of rat and guinea pig.

Adenosine 5' triphosphate (ATP) and acetylcholine (ACh) are neurotransmitters (ACh) and/or modulators (ATP) in the mammalian cochlea. In guinea pig, it appears that both neurotransmitters have a similar response distribution, with larger responses being evoked by the ligands in short hair cells compared to long hair cells (e.g., Chen et al., 1995b. Noise exposure alters the response of outer hair cells to ATP. Hear. Res. 88, 215-221.; Erostegui et al., 1994. In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells. Hear. Res. 74, 135 147). The purpose of the present study was to test whether the distribution of responses to ACh and ATP in the OHCs of rat is the same as guinea pig. The ligand-induced current was monitored using the whole-cell configuration of the patch-clamp technique. Results show that in guinea pig OHCs, extracellular application of 100 microM ATP induced a current response in a majority of the same cells that responded to the application of 100 microM ACh. In contrast in rat OHCs, 100 microM ATP did not induce a current in the majority of cells that responded to the application of 100 microM ACh. N-methyl-glucamine (NMG+) substituted for K+ in the pipette solution failed to unmask an ATP-evoked inward current in rat OHCs. In addition, no response was produced in rat or guinea pig OHCs by adenosine, adenosine 5'-monophosphate (AMP) or adenosine 5'-diphosphate (ADP) at 100 microM. Results suggest that in guinea pig ACh-gated channels are present on most of the same OHCs that have ATP-gated ion channels, whereas in rat ACh-gated ion channels are present without ATP-gated channels on some OHCs.

Acetylcholine↗

Hyperpolarization-activated current (Ih) in primary auditory neurons.

A hyperpolarization-activated current (termed I[h]) is believed to provide a pacemaker depolarization in sinoatrial node cells and in some central and peripheral neurons. In the present study, we examined if such an inward cation current exists in primary auditory neurons using the whole-cell patch-clamp technique. A large inward, non-inactivating current was seen during hyperpolarizing steps negative to the resting potential. A depolarizing sag occurred during hyperpolarizing current injection, and upon termination of the current injection there was an overshoot, or a rebound firing. A low concentration of Cs+, but not Ba2+, reversibly blocked the inward current and depolarizing sag. The activation of the current showed voltage dependence with half-activation occurring at -101 +/- 1 mV. The time course of I(h) activation was fitted by double exponential function and was voltage-dependent (time constants: tau1 and tau2 = 480 and 3125 ms at -100 mV, and 66 and 404 ms at -160 mV). The reversal potential of the current was -36 mV measured from tail currents. The conductance of the current was decreased in Na+-free solution, and increased in high K+ solution. Increases in the levels of intracellular cAMP or cGMP enhanced the current. The results suggest that there exists a hyperpolarization-activated inward cation current in mammalian primary auditory neurons. This current may provide a depolarizing current during the membrane hyperpolarization following each firing of the primary auditory nerve.

Animals↗

Pharmacological evidence that endogenous ATP modulates cochlear mechanics.

In the cochlea, outer hair cells (OHCs) and Deiters' cells most likely contribute to the generation of active cochlear mechanics. The presence of ATP receptors on these cells indicates that endogenous ATP may have a role in cochlear mechanics. To explore this possibility, the effects of ATP antagonists were studied both in vivo on distortion product otoacoustic emissions (DPOAEs) using cochlear perfusion and in vitro on isolated OHCs and Deiters' cells using the whole-cell configuration of the patch-clamp technique. Results show that extracellular application of 5-10 microM ATP to OHCs and Deiters' cells induced an inward current that was reduced by both suramin (100 microM) and cibacron (100 microM). Cibacron reduced the voltage gated currents in Deiters' cells and increased them in OHCs, while suramin had no effect. In addition, cibacron induced a hyperpolarizing shift of the half activation voltage of the whole cell currents in Deiters' cells. Suramin (0.1-1 mM) reversibly suppressed the 'slow decline' in the quadratic DPOAE that occurs during continuous stimulation with moderate level primaries. This effect of suramin may be evidence that endogenous ATP alters active cochlear mechanics.

Acoustic Stimulation↗

In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin.

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clarithromycin. These compounds have demonstrated excellent in vitro activity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combination, was examined against 41 Legionella organisms. The activity of clarithromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciprofloxacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory concentration index. An agar dilution method using buffered charcoal yeast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 degrees C for 48 h. The MIC90 for clarithromycin or 14-hydroxy clarithromycin alone was 0.5, versus 0.25 microgram/mL for the combination. Additive effects were observed with clarithromycin and its hydroxy metabolite for 61% of the Legionella species, with fractional inhibitory concentration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite significantly increased the activity of both fluoroquinolone/clarithromycin combinations. Based on these data, in vitro susceptibility testing of agents such as clarithromycin should be reevaluated to account for the activity of active metabolites.

Anti-Bacterial Agents↗

Anti-VLA-4 antibody reduces intimal hyperplasia in the endarterectomized carotid artery in nonhuman primates.

PURPOSE: Recently, very late antigen-4 (VLA-4) has been shown to mediate initial monocyte adhesion and migration to the injured artery. We hypothesized that blocking monocyte adhesion using a specific monoclonal antibody against VLA-4 may reduce intimal hyperplasia. METHODS: Bilateral carotid endarterectomies were performed in eight adult baboons. Among them, five animals received an intravenous bolus injection of anti-VLA-4 antibody (3 mg/kg) during surgery and again after 2 weeks. Three animals underwent bilateral carotid endarterectomies and served as untreated control subjects. Specimens were harvested at 4 weeks and subjected to morphometric analysis, cell proliferation assay, and immunostaining for macrophages. RESULTS: All of the endarterectomized arteries were patent except for one in the treated group. The number of macrophages in the intimal tissues was significantly reduced in the treated arteries compared with that in the control vessels (15.78 +/- 3.05 cells/section versus 33.50 +/- 6.13 cells/section; p < 0.001). The cell proliferation rate was significantly lower (p < 0.001) in the treated vessels (2.88% +/- 1.07%) compared with the control vessels (4.89% +/- 0.77%). The intimal area at the endarterectomized sites of carotid arteries was significantly less (p < 0.05) in the group treated with the anti-VLA-4 antibody (1.10 +/- 0.68 mm2) than in the control group (2.00 +/- 0.52 mm2). CONCLUSION: These data show that blocking monocyte adhesion by use of an anti-VLA-4 antibody significantly reduces the number of intimal macrophages, intimal cell proliferation, and intimal hyperplasia in injured carotid arteries in baboons. This study supports a central role for macrophages in the development of intimal hyperplasia and may suggest a new therapeutic strategy to prevent clinical restenosis.

Animals↗

Reduced blood flow accelerates intimal hyperplasia in endarterectomized canine arteries.

The purpose of this study was to evaluate a technique that accelerates intimal hyperplasia by reduction of blood flow. Bilateral endarterectomies were performed in both femoral and carotid arteries in six dogs. One week later, all animals underwent banding of an artery distal to the injured region to reduce the blood flow by 50%. The contralateral injured arteries served as controls. At 11 weeks, the specimens were harvested and analyzed. Five of 12 (42%) of the flow-restricted arteries and nine of 12 (75%) of the non-flow-restricted arteries were patent at 11 weeks (P<0.05). Marked stenotic intimal hyperplastic lesions developed in the flow-restricted arteries (69% stenosis) as compared with the non-flow-restricted arteries (37% stenosis). Mean(s.d.) intimal thickness, intimal areas, and intimal/medial area ratio were 0.52(0.19) mm, 3.17(1.11) mm2, and 1.12(0.33)%, respectively, in the flow-restricted arteries. Their counterparts in the non-flow-restricted arteries were 0.21(0.09) mm, 1.70(1.09) mm2, and 0.58(0.14)%, respectively (P<0.05). Extracellular matrix comprised 48% of total intimal volumes in the flow-restricted arteries. Cell proliferation and occluded arteries were also characterized. These data demonstrate that reduction of blood flow significantly accelerated intimal hyperplasia and occlusion rates in endarterectomized arteries. Advanced intimal hyperplastic lesions (>50% stenosis) possess a high extracellular matrix content. This new animal model is a reliable generator of advanced stenotic lesions in a relatively short time period and can be used to study biologic mechanisms of stenosis and evaluate therapeutic interventions.

Animals↗

Perioperative risk factors affecting hospital stay and hospital costs in open heart surgery for patients > or = 65 years old.

OBJECTIVE: Demographic changes, associated with increased demands for open heart surgery in the elderly, place increased burden on financial resources. To evaluate perioperative risk factors affecting incidence of hospital events and estimation of hospital charges, 2577 patients > or = 65 years (range 65-91), operated on from January 1991 to December 1994, were compared with a concurrent cohort of 2642 younger patients. METHODS: Statistical analysis, by surgical procedure, focused on hospital mortality, key postoperative complications affecting length of hospital stay and hospital charges. RESULTS: Overall hospital mortality was 4.7%, 3.5% in younger patients versus 6.1% in the older group (P << 0.01). Mortality was significantly lower in patients less than 65 years undergoing coronary artery bypass grafting (3% versus 5%, P < 0.01) and valve replacement (4% versus 9%, P = 0.01). Significant risk factors for hospital death in the elderly: diabetes (P < 0.01), hypertension (P < 0.01), myocardial infarction (P < 0.01) and congestive heart failure (P < 0.01). Significant postoperative events, more common in older patients, included prolonged ventilation (P << 0.01), congestive heart failure (P << 0.01), infection (P << 0.01), cerebrovascular accident (P < 0.01), and intra aortic balloon pump (P < 0.01). Incremental risk factors for morbidity in the elderly were: higher New York Heart Association class, congestive heart failure, emergent operation, and female gender. Mean length of hospital stay for the < 65 group was 15.3 versus > 19.5 days for the > 65 group (P << 0.01). Length of stay over 18 days positively correlated with increased morbidity in both age groups. For patients > or = 65 years of age, the average hospital charge for open heart surgery was 172% higher for patients with a length of stay greater than 18 days compared with 165% for patients less than 65 years of age. CONCLUSIONS: Higher operative mortality and longer length of stay in elderly patients, resulting in increased health care costs, was associated with more co-morbidities. These results suggest interventions designed to reduce congestive heart failure and other co-morbidities may improve patient's recovery and reduce costs.

Adult↗

Environmental and occupational determinants of blood pressure in rural communities in China.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Adolescent↗

Editing disease-associated autoantibodies.

We have generated site-directed transgenic mice whose transgenes code for anti-DNA antibodies. These antibodies are representative of the lupus-associated anti-DNAs seen in mouse models of autoimmunity and human SLE, and have the usual characteristics of pathogenic autoantibodies. As conventional transgenics in nonautoimmune mice, anti-DNA B cells have been shown to be deleted or inactivated. Autoreactive B cells can also escape negative regulation by a process called receptor editing. Here we describe two combined immunoglobulin H and L chain site-directed transgenic mouse models and characterize their editing phenotypes. One model, 3H9R/Vkappa4R, has a deletion-prone phenotype and undergoes editing, primarily by inactivation of the light chain by leap-frogging events. In the other model, 3H9R/Vkappa8R, B cells are susceptible to anergy and maintain most of their HR and LR chains. These studies clarify the relationship between editing and other mechanisms of tolerance.

Alleles↗

Extensive biliary excretion of the model opioid peptide [D-PEN2,5] enkephalin in rats.

PURPOSE: This study was designed to test the hypothesis that the enzymatically stable opioid peptide, [D-pen2,5] enkephalin (DPDPE), is excreted extensively into bile. METHODS: Following an i.v. bolus dose of DPDPE (10 mg/kg) to rats, concentrations of DPDPE in serum, bile, liver homogenate and urine were measured by a novel capillary zone electrophoresis method. Data were analyzed to recover the fundamental pharmacokinetic parameters (volumes of distribution; distribution and elimination rate constants governing DPDPE systemic and biliary disposition). Parallel in vitro experiments were performed to evaluate the partitioning of DPDPE between erythrocytes and plasma, as well as to assess the degree of binding of DPDPE to serum proteins. RESULTS: The majority of the administered dose (approximately 80%) was recovered from bile as intact peptide. DPDPE disposition was best described by a two-compartment model with Michaelis-Menten elimination (Km: 37.5 +/- 11 micrograms/ml; Vmax: 1143 +/- 368 micrograms/min/kg) from the central compartment into bile, suggestive of an active hepatic transport system. DPDPE was associated with a distributional space of 486 +/- 62 ml/kg. In vitro incubation of DPDPE with whole blood showed that approximately 65% of the peptide was associated with erythrocytes. The difference between concentrations of DPDPE in erythrocytes and plasma was statistically significant (29.2 +/- 4.9 vs. 18.1 +/- 3.1 micrograms/ml, p < 0.05), but not between whole blood and plasma (21.3 +/- 2.8 vs. 18.1 +/- 3.1 micrograms/ml, p > 0.05). Concentration-independent binding of DPDPE to serum proteins was evidenced between 10 and 100 micrograms/ml, with an unbound fraction of 0.517 +/- 0.182. CONCLUSIONS: DPDPE undergoes extensive biliary excretion after i.v. administration in rats. The apparent nonlinearity in the biliary excretion of DPDPE revealed by the pharmacokinetic modeling strongly suggests the existence of an active transport system(s) in hepatocytes which may mediate the rapid disappearance of DPDPE from the systemic circulation.

Analgesics↗

Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMM) is a disease characterized by bone marrow megakaryocyte hyperplasia and clusters of megakaryocytes, in which many of the megakaryocytes are atypical. In order to elucidate the mechanisms of megakaryocytosis, ELISA assays of blood levels of thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11) were done in 45 patients with AMM and compared with normal volunteer controls. Higher blood TPO levels were found in AMM than in controls (P < 0.0001), and blood TPO levels were correlated with the degree of marrow fibrosis (P = 0.0078). Blood levels of IL-6 were also significantly higher in AMM, when compared with controls (P < 0.0001). However, no correlation was found between blood IL-6 levels and degree of marrow fibrosis. No correlation was found between either TPO or IL-6 and the number of blood platelet counts, the number of marrow megakaryocytes, WBC counts, or the degree of splenomegaly. Blood IL-11 levels were undetectable in most patients and no significant difference was found in AMM as compared to controls. The present study demonstrated that, while in idiopathic thrombocytopenic purpura (ITP) or aplastic anemia, blood TPO levels are relatively correlated with the numbers of platelet and/or megakaryocyte mass, blood TPO levels do not correlate with blood platelet counts, or marrow megakaryocyte mass in AMM. Therefore, in AMM, other mechanisms such as the number of TPO receptors on platelets or megakaryocytes, c-MPL receptor abnormalities, abnormal production of TPO mRNA and so on, will have to be studied. Furthermore, TPO may play a significant role in the pathogenesis of marrow fibrosis; IL-6 may be a factor in the development of marrow megakaryocytosis but its elevated blood levels may represent a secondary immune phenomenon; and IL-11 probably does not play a significant role in causing marrow megakaryocytosis in this disease.

Biomarkers↗