Search PubMed⌕ Search

Biomedical subjects

Q Chen

Publications and source records attributed to Q Chen.

At least 163 records · Page 9Linked to original sources
PubMed2001

Ca2+-induced contraction of cat esophageal circular smooth muscle cells.

ACh-induced contraction of esophageal circular muscle (ESO) depends on Ca2+ influx and activation of protein kinase Cepsilon (PKCepsilon). PKCepsilon, however, is known to be Ca2+ independent. To determine where Ca2+ is needed in this PKCepsilon-mediated contractile pathway, we examined successive steps in Ca2+-induced contraction of ESO muscle cells permeabilized by saponin. Ca2+ (0.2-1.0 microM) produced a concentration-dependent contraction that was antagonized by antibodies against PKCepsilon (but not by PKCbetaII or PKCgamma antibodies), by a calmodulin inhibitor, by MLCK inhibitors, or by GDPbetas. Addition of 1 microM Ca2+ to permeable cells caused myosin light chain (MLC) phosphorylation, which was inhibited by the PKC inhibitor chelerythrine, by D609 [phosphatidylcholine-specific phospholipase C inhibitor], and by propranolol (phosphatidic acid phosphohydrolase inhibitor). Ca2+-induced contraction and diacylglycerol (DAG) production were reduced by D609 and by propranolol, alone or in combination. In addition, contraction was reduced by AACOCF(3) (cytosolic phospholipase A(2) inhibitor). These data suggest that Ca2+ may directly activate phospholipases, producing DAG and arachidonic acid (AA), and PKCepsilon, which may indirectly cause phosphorylation of MLC. In addition, direct G protein activation by GTPgammaS augmented Ca2+-induced contraction and caused dose-dependent production of DAG, which was antagonized by D609 and propranolol. We conclude that agonist (ACh)-induced contraction may be mediated by activation of phospholipase through two distinct mechanisms (increased intracellular Ca2+ and G protein activation), producing DAG and AA, and activating PKCepsilon-dependent mechanisms to cause contraction.

Adrenergic beta-Antagonists↗
PubMed2001

Abnormalities of gallbladder muscle associated with acute inflammation in guinea pigs.

Muscle strips from experimental acute cholecystitis (AC) exhibit a defective contraction. The mechanisms responsible for this impaired contraction are not known. The present studies investigated the nature of these abnormalities. AC was induced by ligating the common bile duct of guinea pigs for 3 days. Contraction was studied in enzymatic dissociated muscle cells. Cholecystokinin (CCK) and prostaglandin E2 (PGE2) receptor binding studies were performed by radioreceptor assay. The levels of lipid peroxidation, cholesterol, phospholipid, and H2O2 as well as the catalase and superoxide dismutase (SOD) activities were determined. PGE2 content was measured by radioimmunoassay. Muscle contraction induced by CCK, ACh, or KCl was significantly reduced in AC, but PGE2-induced contraction remained normal. GTPgammaS, diacyglycerol (DAG), and 1,4,5-trisphosphate (IP3), which bypass the plasma membrane, caused a normal contraction in AC. The number of functional receptors for CCK was significantly decreased, whereas those for PGE2 remained unchanged in AC. There was a reduction in the phospholipid content and increase in the level of lipid peroxidation as well as H2O2 content in the plasma membrane in AC. The PGE2 content and the activities of catalase and SOD were also elevated. These data suggest that AC cause damage to the constituents of the plasma membrane of muscle cells. The preservation of the PGE2 receptors may be the result of muscle cytoprotection.

Acetylcholine↗
PubMed2001

Blocking Na(+)/H(+) exchange reduces [Na(+)](i) and [Ca(2+)](i) load after ischemia and improves function in intact hearts.

We determined in intact hearts whether inhibition of Na(+)/H(+) exchange (NHE) decreases intracellular Na(+) and Ca(2+) during ischemia and reperfusion, improves function during reperfusion, and reduces infarct size. Guinea pig isolated hearts were perfused with Krebs-Ringer solution at 37 degrees C. Left ventricular (LV) free wall intracellular Na(+) concentration ([Na(+)](i)) and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured using fluorescence dyes. Hearts were exposed to 30 min of ischemia with or without 10 microM of benzamide (BIIB-513), a selective NHE-1 inhibitor, infused for 10 min just before ischemia or for 10 min immediately on reperfusion. At 2 min of reperfusion, BIIB-513 given before ischemia decreased peak increases in [Na(+)](i) and [Ca(2+)](i), respectively, from 2.5 and 2.3 times (controls) to 1.6 and 1.3 times pre-ischemia values. At 30 min of reperfusion, BIIB-513 increased systolic-diastolic LV pressure (LVP) from 49 +/- 2% (controls) to 80 +/- 2% of pre-ischemia values. BIIB-513 reduced ventricular fibrillation by 54% and reduced infarct size from 64 +/- 1% to 20 +/- 3%. First derivative of the LVP, O(2) consumption, and cardiac efficiency were also improved by BIIB-513. Similar results were obtained with BIIB-513 given on reperfusion. These data show that Na(+) loading is a marker of reperfusion injury in intact hearts in that inhibiting NHE reduces Na(+) and Ca(2+) loading during reperfusion while improving function. These results clearly implicate the ionic basis by which inhibiting NHE protects the guinea pig intact heart from ischemia-reperfusion injury.

Animals↗
PubMed2001

Fasting downregulates renal water channel AQP2 and causes polyuria.

Starvation causes impairment in the urinary concentrating ability. The mechanism of this defect, however, remains unknown. We tested the possibility that food deprivation might affect the expression and activity of aquaporins (AQP1, 2), thereby impairing renal water reabsorption in the kidney. Rats fasted for 24 h exhibited severe polyuria (urine volume increased from 11 before fasting to 29 ml/24 h after fasting, P < 0.0001) along with failure to concentrate their urine (urine osmolality decreased from 1,485 before fasting to 495 mosmol/kgH(2)O after fasting, P < 0.0001). Refeeding for 24 h returned the urinary concentrating ability back to normal. Northern hybridization and immunoblot analysis demonstrated that fasting was associated with a decrease in AQP2 protein (-80%, P </= 0.002) and mRNA levels (-69%, P </= 0.003) in the outer medulla. In the cortex, fasting decreased AQP2 protein abundance by 60% (P </= 0.004) but did not alter its mRNA expression. During the recovery phase, AQP2 expression returned to normal level in both tissues. In the inner medulla, the expression of AQP2 was not altered in fasting, but was increased significantly at both protein ( +/- 92%) and mRNA ( +/- 43%) levels during the recovery from fasting. The proximal nephron water channel (AQP1) was not affected in response to fasting or recovery from fasting. We conclude that 1) fasting impairs the urinary concentrating ability in rats, and 2) the renal water-handling defect in fasting results specifically from the downregulation of AQP2 in the cortical and outer medullary collecting duct.

Animals↗
PubMed2001

Three-dimensional micropatterns of well-aligned carbon nanotubes produced by photolithography.

Three-dimensional micropatterns of well-aligned carbon nanotubes were prepared on photolithographically prepatterned substrates by pyrolysis of iron(II) phthalocyanine (FePc) under an Ar/H2 atmosphere at 800-1100 degrees C. The photopatterning was achieved by photolithographic cross-linking of a chemically amplified photoresist layer spin-cast on a quartz plate or a silicon wafer, coupled with solution development. Owing to an appropriate surface characteristic, the patterned photoresist layer was found in this case to support aligned carbon nanotube growth by pyrolysis of FePc, as were the photoresist-free substrate surfaces. The difference in chemical nature between the surface areas covered and uncovered by the photoresist film, however, caused a region-specific growth of the nanotubes with different tubular lengths and packing densities, leading to the formation of three-dimensional aligned nanotube patterns suitable for various device applications.

Crystallization↗
PubMed2001

Multiple effects of artemin on sympathetic neurone generation, survival and growth.

To define the role of artemin in sympathetic neurone development, we have studied the effect of artemin on the generation, survival and growth of sympathetic neurones in low-density dissociated cultures of mouse cervical and thoracic paravertebral sympathetic ganglia at stages throughout embryonic and postnatal development. Artemin promoted the proliferation of sympathetic neuroblasts and increased the generation of new neurones in cultures established from E12 to E14 ganglia. Artemin also exerted a transient survival-promoting action on newly generated neurones during these early stages of development. Between E16 and P8, artemin exerted no effect on survival, but by P12, as sympathetic neurones begin to acquire neurotrophic factor independent survival, artemin once again enhanced survival, and by P20 it promoted survival as effectively as nerve growth factor (NGF). During this late period of development, artemin also enhanced the growth of neurites from cultured neurones more effectively than NGF. Confirming the physiological relevance of the mitogenic action of artemin on cultured neuroblasts, there was a marked reduction in the rate of neuroblast proliferation in the sympathetic ganglia of mice lacking the GFRalpha3 subunit of the artemin receptor. These results indicate that artemin exerts several distinct effects on the generation, survival and growth of sympathetic neurones at different stages of development.

Animals↗
PubMed2001

Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates.

Platelet-endothelial cell adhesion molecule-1 or CD31 (PECAM-1/CD31) is a receptor recognized by Plasmodium falciparum-parasitized erythrocytes (pRBCs). Fluorescence-labeled soluble recombinant PECAM-1/CD31 (sPECAM-1/CD31) is shown to bind to the surface of P. falciparum-infected erythrocytes on up to 70% of the cells. Binding is blocked by the addition of the unlabeled receptor in a dose-dependent fashion, but not by unrelated receptor-proteins. A significant correlation was found between the binding of sPECAM-1/CD31 to pRBCs and the binding to transfected L cells expressing the receptor as seen with six different P. falciparum lines or clones. Panning of cultures on PECAM-1/CD31 transfected L cells was paralleled by an increase in the binding of sPECAM-1/CD31. The pRBCs of 54% of fresh patient-isolates bound sPECAM-1/CD31 with a mean rate of 12.9% (range = 1.1-44%). The data suggest that PECAM-1/CD31 is a common receptor recognized by wild isolates and that the soluble PECAM-1/CD31 suspension assay is a sensitive and reliable way to study PECAM-1/CD31 binding.

Animals↗
PubMed2001

Regulation of hepatic cytochrome P450 2C11 via cAMP: implications for down-regulation in diabetes, fasting, and inflammation.

The effect of glucagon and its second messenger cAMP on cytochrome P450 2C11 (CYP2C11) expression was investigated in primary hepatocytes cultured on Matrigel. Glucagon, epinephrine, forskolin, and the cAMP derivatives dibutyryl cAMP, (S(p))-adenosine 3',5' cyclic monophosphothioate (S(p)-cAMPS), and 8-(4-chlorophenylthio)-cAMP, but not dideoxyforskolin, all down-regulated CYP2C11 mRNA expression to approximately 20% of control levels in a concentration-dependent manner. Using the transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, CYP2C11 mRNA was found to have a half-life of 9.8 h. The kinetics of suppression of CYP2C11 mRNA by glucagon and forskolin was similar to that obtained with the transcriptional inhibitor, suggesting that glucagon and forskolin act at the transcriptional level. CYP2C11 expression was more sensitive to suppression by glucagon at low insulin concentrations than at higher concentrations. (R(p))-Adenosine 3',5' cyclic monophosphothioate inhibited the down-regulation of CYP2C11 by S(p)-cAMPS, consistent with a competitive blockade of protein kinase A activation. These results suggest a role for glucagon in the down-regulation of CYP2C11 in diabetic rats, and provide a possible explanation for the known sensitivity of this cytochrome P450 to suppression in various stress and disease models.

Animals↗
PubMed2001

Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.

Actins↗
PubMed2001

[Comparison of seminal vitamin B12, folate, reactive oxygen species and various sperm parameters between fertile and infertile males].

Vitamin B12(VB12), folate and reactive oxygen species(ROS) in human semen from both fertile and infertile males, and their relationships with other parameters were observed. Semen samples from 44 infertile and 176 fentile control subjects were collected and measured based on the guidelines issued by WHO. The results showed that no significant differences on semen VB12 and folate were observed between fertile and infertile groups(P > 0.05). However, the levels of ROS in infertile group were significantly higher than those in fertile group(P < 0.01). The morphological defects and low motility of sperm in infertile group was significantly higher than those in fertile group(P < 0.01). A positive relation was observed between the levels of ROS production and the morphological defect of sperm(P < 0.01). There was a significant negative correlation between the levels of VB12, folate and ROS(P < 0.01) in semen. It is interesting to note that the values of ROS also show a significantly positive correlation with sperm motility (P < 0.01). A significant differences of ROS levels between fertile and infertile group with negative white blood cells in sperm was also observed. It is concluded that the increase of ROS on the morphological defect of sperm is one of the most important factors related to poor sperm quality and human infertility.

Adult↗
PubMed2001

[The numerical simulation of the dynamic stress field from impacting head].

In order to study the mechanism of impact injury to the head, we have simulated the development of the stress field by using the numerical simulation method. The process of the head having been impacted vertically by an impactor can be described as a 2D problem, and the reactions of the head subjected to impacted force can be simulated and analyzed by the method based on the finite difference method (FDM). The model is subjected to applied force by an impactor with the initial velocity of 25 m/s (90 km/h). The pre-processing for the model is done on the microcomputer software. Once imported to the software, the nodes and elements are generated and material characteristics are assigned. The results demonstrate that the high resolution computer graphics can provide the dynamic distribution of the stress field, which can clearly show how the stress is developed, and how many its value is. The results are helpful to understanding the mechanism of impact injury to head.

Craniocerebral Trauma↗
PubMed2001

In vitro stimulation of warfarin metabolism by quinidine: increases in the formation of 4'- and 10-hydroxywarfarin.

It has been demonstrated that the activity of cytochrome P450 (CYP)3A4 in certain cases is stimulated by quinidine (positive heterotropic cooperativity). We report herein that the 4'- and 10-hydroxylation of S- and R-warfarin are enhanced in human liver microsomal incubations containing quinidine. These reactions were catalyzed by CYP3A4, based on data derived from immunoinhibitory studies, with 4'-hydroxylation being preferentially associated with S-warfarin and 10-hydroxylation with R-warfarin. The 4'-hydroxylation of S-warfarin and 10-hydroxylation of R-warfarin increased with increasing quinidine concentrations and maximized at ~3- and 5-fold the values of controls, respectively. Stimulatory effects of quinidine also were observed with recombinant CYP3A4, suggesting that increases in warfarin metabolism were due to quinidine-mediated enhancement of CYP3A4 activity. This positive cooperativity of CYP3A4 was characterized by a 2.5-fold increase in V(max) for the 4'-hydroxylation of S-warfarin and a 5-fold increase in V(max) for the 10-hydroxylation of R-warfarin, with little change in K(m) values. Conversely, V(max) for the 3-hydroxylation of quinidine was not influenced by the presence of warfarin. These results are consistent with previous findings suggesting the existence of more than one binding site in CYP3A4 through which interactions may occur between substrate and effector at the active site of the enzyme. Such interactions were subsequently illustrated by a kinetic model containing two binding domains, and a good regression fit was obtained for the experimental data. Finally, stimulation of warfarin metabolism by quinidine was investigated in suspensions of human hepatocytes, and increases in the formation of 4'- and 10-hydroxywarfarin again were observed in the presence of quinidine, indicating that this type of drug-drug interaction occurs in intact cells.

Cytochrome P-450 CYP3A↗
PubMed2001

Correlation between the expression of cyclin A protein and p53 activity in oral squamous cell carcinomas.

Cyclins and wild-type p53 protein are prime cell cycle regulators and may be involved in tumorigenesis. Cyclin A is a late S cyclin and its abnormalities have been reported in several cancers, including oral squamous cell carcinomas. To explore whether aberrant G1/S in p53 mutant tumours leads to increased cyclin A protein in oral squamous cell carcinomas (OSCC), a total of 39 samples were evaluated for the expression of cyclin A and p53 protein by an immunohistochemical method using a labelled polymer assay. These samples comprised two hyperkeratotic and three oral premalignant lesions (two moderate and one severe dysplastic lesions), and 27 OSCC, together with seven healthy controls. The results demonstrated that the cyclin A protein was localized and highly expressed in the nuclei of the tumour cells. Although there was no correlation between cyclin A detection and the local lymph node involvement, a positive correlation was noted between the positivity of cyclin A and p53 protein (p <0.05). The results suggested that cyclin A may contribute to the progression of oral cancer and correlated to some degree with that of the p53 gene activity.

Carcinoma, Squamous Cell↗
PubMed2001

An association between genetic polymorphisms in the ileal sodium-dependent bile acid transporter gene and the risk of colorectal adenomas.

Epidemiological and experimental studies have implicated bile acids (particularly secondary bile acids) as important factors in the development of colorectal cancer. The ileal sodium-dependent bile acid transporter (ISBT) is a crucial player in the enterohepatic circulation of bile acids. Genetic defects in ISBT may result in malabsorption of bile acids and a loss of bile acids into the large intestine, with a resultant increase in the cytotoxic secondary bile acids in the colon. In a case-control study, we investigated the association between two sequence variations in SLC10A2, the gene encoding ISBT, and colorectal adenomas, a precursor lesion of colorectal cancer. The frequency of the missense mutation in codon 171 of exon 3 (a nucleotide transversion from G to T resulting in an alanine to serine substitution) was not significantly different between cases and controls. However, we found a 2-fold higher risk of colorectal adenomas associated with a C-->T nucleotide transition in codon 169 of exon 3 (odds ratio = 2.06; 95% confidence interval: 1.10-3.83). Logistic regression analysis using A171S/169 C-->T haplotypes as the allelic markers showed that among AA wild-type homozygotes for A171S mutation, this C-->T nucleotide transition in codon 169 was associated with a 2.42 times increased risk (odds ratio = 2.42; 95% confidence interval: 1.26-4.63). This initial observation of an association between a polymorphism in the SLC10A2 gene and the risk of colorectal adenomatous polyps would, if confirmed by other studies, support the role of bile acids in the carcinogenesis of colorectal cancer.

Adenoma↗
PubMed2001

Effect of Cr(VI) exposure on sperm quality: human and animal studies.

The semen status of male workers occupationally exposed to hexavalent chromium(VI) was investigated. Sperm counts from exposed workers were 47.05+/-2.13 x 10(6)/ml and those from control group 88.96+/-3.40 x 10(6)/ml. Sperm motility decreased from 81.92+/-0.41% for the control group to 69.71+/-0.93% for the exposed workers. The levels of zinc, lactate dehydrogenase (LDH), and lactate dehydrogenase C4 isoenzyme (LDH-x) in seminal plasma for the exposed workers were 1.48+/-0.07 micromol/ml, 1.05+/-0.02 x 10(3) U, and 0.47+/-0.01 x 10(3) U, respectively, which were significantly lower than those of 5.72+/-0.15 micromol/ml, 1.49+/-0.02 x 10(3) U, and 0.78+/-0.15 x 10(3) U for the control group, respectively. Follicle stimulating hormone (FSH) (7.34+/-0.34 x 10(-3) IU/ml) in serum from the exposed workers was significantly higher than that (2.41+/-0.08 x 10(-3) IU/ml) from the control group. On the other hand, there were no significant differences in semen volume, semen liquefaction time, luteinizing hormone (LH) level in serum, and Cr concentration in both serum and seminal plasma between the exposed workers and the control group. Feeding Cr(VI) to rats significantly reduced the epididymal sperm counts from 87.40+/-3.85 x 10(6)/g epididymis in control group to 21.40+/-1.20 x 10(6)/g epididymis at a CrO(3) dose of 10 mg/kg body weight and to 17.48+/-1.04 x 10(6)/g epididymis at a CrO(3) dose of 20 mg/kg body weight. Exposure of rats to Cr(VI) also significantly increased the sperm abnormality from 2.75+/-0.06% in the control group to 6.68+/-0.32% in the exposed group at a CrO(3) dose of 10 mg/kg body and to 7.6+/-0.15% at a CrO(3) dose of 20 mg/kg body weight. In exposed rats, there was visible disruption in germ cell arrangement near the walls of the seminiferous tubules. The diameters of seminiferous tubules in exposed rats were smaller. These results suggest that occupational exposure to chromium(VI) leads to alteration of semen status and may affect the reproductive success of exposed workers.

Animals↗
PubMed2001

[The effects of ZMS on learning and memory ability and brain choline acetyltransferase in scopolamine-induced mouse model].

OBJECTIVE: To observe the effects of ZMS on learning and memory ability and on brain choline acetyltransferase activity. METHODS: A single intraperitoneal injection of scopolamine was used to establish a dementia mouse model. The learning and memory ability was detected by step-through and sted-down tests. And the choline acetyltransferase activity in brain was determined by 3H-acetyl-CoA incorporation analysis. RESULTS: ZMS could significantly reduce wrongness frequences, prolong incubation period of scopolamine-induced dementia mice in step-through and step-down tests (P < 0.01). ZMS could also significantly improve the activity of brain choline acetyltransferase (ChAT) (P < 0.01). CONCLUSION: ZMS could improve the learning and memory ability and the activity of brain ChAT in scopolamine-induced dementia mice. However, ZMS had no significant dose-response effect on improving the activity of brain ChAT, and the effect of Tacrine was similar to that of ZMS, it seemed unlikely that ZMS had a direct action on the ChAT. More probably, ZMS exerted its effect on ChAT activity and on learning and memory ability via elevating brain M receptor density.

Animals↗
PubMed2001

Surgical ostioplasty for isolated ostial stenosis of the left main stem coronary artery.

We report the cases of 4 patients in whom surgical ostioplasty was performed for isolated severe ostial stenosis of the left main stem coronary artery. No perioperative death or myocardial infarction occurred. One patient required reoperation for symptomatic recurrent ostial stenosis after 6 months. The others remained angina free after a mean follow-up of 23 months. The literature associated with this procedure is briefly reviewed.

Adult↗