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Biomedical subjects

G Chen

Publications and source records attributed to G Chen.

At least 631 records · Page 35Linked to original sources
PubMed1996

Chitinase activity of Xenorhabdus and Photorhabdus species, bacterial associates of entomopathogenic nematodes.

Xenorhabdus nematophilus (three strains), Xenorhabdus bovienii (one strain), and Photorhabdus luminescens (one strain) showed both exo- and endochitinase activity using p-nitrophenyl-N-acetyl-beta-D-glucosaminide and p-nitrophenyl-beta-D-N,N',N'-triacetylchitotriose, respectively, as substrates. One to three bands were detected on PAGE gel with glycol chitin after electrophoresis. Variation in exo- and endochitinase activity among different species and strains was detected with the strongest activity in X. nematophilus and the weakest in P. luminescens. The primary form of X. bovienii had significantly greater chitinase activity than the secondary form, whereas their growth rate and total protein released into culture medium were similar. The partially purified chitinase of X. bovienii showed significant antimycotic activity against conidial germination and germ tube elongation of Botrytis cinerea.

Animals↗
PubMed1996

Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease.

UNLABELLED: The effect of verapamil treatment on the myocardial beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection with T. cruzi reduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of the beta-adrenergic receptor complex were characterized. INFECTION: (1) increased right ventricular (RV) beta-adrenergic receptor (beta AR) density five-fold; (2) decreased left ventricle beta AR density by 20%; (3) reduced the proportion of high-affinity beta AR receptors to the same extent in both left and right ventricles; (4) reduced alpha s by 50% as determined by Western blot analysis, increased alpha 11-3 but did not change alpha 0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in alpha 0. Verapamil treatment of infected animals restored RV beta AR receptor density, alpha s and alpha i1-3 to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increased beta-adrenergic adenylyl cyclase activity; (2) increased beta AR density in the RV but not the LV; (3) reduced high- to low-affinity beta-adrenergic receptors; and (4) affected only alpha i2 (50% decrease). The results indicate that the major actions of verapamil on the beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardioprotective effects.

Adenylyl Cyclases↗
PubMed1996

Controlling the dynamical behavior of a circle map model of the human heart.

One-dimensional circle maps are good models for describing the nonlinear dynamical behavior of two interacting oscillators. They have been employed to characterize the interaction between a periodic external forcing stimulus and an in vitro preparation of chick embryonic cardiac cells. They have also been used to model some human cardiac arrythmias such as modulated ventricular parasystole. In this paper, we describe several techniques involving engineering feedback control theory applied to a circle map model of human heart parasystole. Through simulations of the mathematical model, we demonstrate that a desired target phase relationship between the normal sinus rhythm and an abnormal ectopic pacemaker can be achieved rapidly with low-level external stimulation applied to the system. Specifically, we elucidate the linear, self-tuning, and nonlinear feedback approaches to control. The nonlinear methods are the fastest and most accurate, yet the most complex and computationally expensive to implement of the three types. The linear approach is the easiest to implement but may not be accurate enough in real applications, and the self-tuning methods are a compromise between the other two. The latter was successful in tracking a variety of period-1, period-2, and period-3 target phase trajectories of the heart model.

Biological Clocks↗
PubMed1996

Transforming growth factor-beta in in vivo resistance.

The potential role of transforming growth factor-beta in in vivo resistance was examined by administration of transforming growth factor-beta-neutralizing antibodies to animals bearing the EMT-6/Parent tumor or the antitumor alkylating resistance tumors, EMT-6/CTX or EMT-6/CDDP. Treatment of tumor bearing animals with anti-TGF-beta antibodies by intraperitoneal injection daily on days 0-8 post-tumor cell implantation increased the sensitivity of the EMT-6/Parent tumor to cyclophosphamide (CTX) and cisplatin (CDDP) and markedly increased the sensitivity of the EMT-6/CTX tumor to CTX and the EMT6/CDDP tumor to CDDP, as determined by tumor cell survival assay. Bone marrow granulocyte-macrophage colony-forming units (CFU-GM) survival was determined from these same animals. The increase in the sensitivity in the tumors upon treatment with the anti-TGF-beta antibodies was also observed in increased sensitivity of the bone marrow CFU-GM to CTX and CDDP. Treatment of non-tumor-bearing animals with the anti-TGF-beta regimen did not alter blood ATP or serum glucose level but did decrease serum lactate levels. This treatment also decreased hepatic glutathione, glutathione S-transferase, glutathione reductase, and glutathione peroxidase in non-tumor bearing animals by 40-60% but increased hepatic cytochrome P450 reductase in these normal animals. Animals bearing the EMT-6/CTX and EMT-6/CDDP tumors had higher serum lactate levels than normal or EMT-6/Parent tumor-bearing animals; these were decreased by the anti-TGF-beta regimen. Treatment of animals bearing any of the three tumors with the anti-TGF-beta regimen decreased by 30-50% the activity of hepatic glutathione S-transferase and glutathione peroxidase, and increased by 35-80% the activity of hepatic cytochrome P450 reductase. In conclusion, treatment with transforming growth factor-beta-neutralizing antibodies restored drug sensitivity in the alkylating agent-resistant tumors, altering both the tumor and host metabolic states.

Animals↗
PubMed1996

Effect of ethanol and cocaine treatment of the immune system of v-Ha-ras-transgenic mice.

The objective was to investigate if the presence of the v-Ha-ras oncogene could induce immune changes different to the ones observed in normal mice. Therefore, we decided to use Oncomice, the transgenic mice with an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus-promoter, and their normal inbred counterparts, FVB mice. Both strains of mice were fed the Lieber-DeCarli liquid diet with ethanol or the isocaloric control diet and were injected daily with cocaine or saline. The percentage and absolute number of T and B lymphocytes in the spleen and thymus were determined. The in vitro production of TNF-alpha (tumor necrosis factor-alpha), IL-2 (interleukin-2) and IFN-gamma (interferon-gamma) by spleen cells, and the levels of serum sIL-2R (soluble IL-2 receptor) were also measured. Oncomice fed the Lieber-DeCarli ethanol diet or receiving either saline or cocaine injections presented a higher tumor incidence than Oncomice receiving the control diet. A reduced total number of thymocytes as well as absolute number of cells in all the subsets was found in Oncomice. Moreover, a decreased percentage of CD8+ cells was also observed in Oncomouse spleens. These features were even more marked in ethanol-treated Oncomice. Higher serum sIL-2R levels were observed in Oncomice, especially in mice treated with ethanol or cocaine. The results suggest that the oncogene product, P21ras, plays an important role in dysregulating the immune system and hence in favoring tumorigenesis.

Animals↗
PubMed1996

G-protein level quantification in platelets and leukocytes from patients with panic disorder.

The objective of our study was to investigate if there are abnormalities in signal transducing G proteins in patients with panic disorder. We utilized selective antibodies to quantitate the levels of the G protein alpha subunits that regulate adenylyl cyclase activity (G alpha s and G alpha i2) and phosphoinositide turnover (G alpha q/11) in platelet membranes (and leukocyte membranes for G alpha s), and also carried out pertussis toxin (PT) catalyzed [32P]ADP-ribosylation in platelet membranes from a group of 13 untreated panic disorder patients, 10 untreated social phobia patients, and 12 healthy subjects. There were no significant differences among the three groups in the immunolabeling of G alpha s in platelets or leukocytes, or in the immunolabeling of G alpha i1/2, G alpha q/11, or PT-catalyzed [32P]ADP-ribosylation in platelets. Within the constraints imposed by using peripheral blood cells to reflect brain composition, our results do not provide support for G protein abnormalities in patients with panic disorder. These results contrast with those obtained using identical methodology in bipolar affective disorder, where elevated G alpha s in leukocytes has been reported (Manji et al. 1995).

Adenosine Diphosphate Ribose↗
PubMed1996

Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells.

Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. In the present study, we found that chronic exposure of rat C6 glioma cells to VPA induces a coordinate decrease in multiple components of the beta-adrenergic receptor- (beta-AR) coupled cyclic adenosine 3'-5'monophosphate (cAMP) generating system. Chronic VPA decreased the number of beta-ARs in a time- and concentration-dependent manner; the decrease of beta-ARs was largely beta 1-AR selective and affected beta-ARs in both the high- and low-affinity states. Chronic VPA also significantly attenuated receptor- and postreceptor-stimulated cAMP production, [3H]forskolin binding sites, immunolabeling of G alpha s 45, and cholera toxin catalyzed ADP-ribosylation of G alpha s 52 and 45. Although the precise underlying mechanisms remain to be elucidated, such profound long-term changes in the functioning of this key signaling pathway may help explain the antimanic effects of chronic VPA treatment and are worthy of further study.

Adenylyl Cyclases↗
PubMed1996

Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol.

Lithium is the most effective treatment for reducing both the frequency and severity of recurrent affective episodes, but despite extensive research, the molecular mechanisms underlying its therapeutic actions have not been fully elucidated. Signal transduction pathways are in a pivotal position in the central nervous system, able to affect the functional balance between neurotransmitter systems and have clearly been demonstrated to be targets of lithium's actions. We investigate the hypothesis that the action of chronic lithium on PKC isozymes and substrates may be secondary to its potent effect in inhibiting the recycling of inositol. Rats received lithium for 3 weeks and also myo-inositol or saline twice daily via intracerebroventricular (ICV) injections. There was a significant interaction between chronic lithium and myo-inositol administration, with the chronic ICV administration of myo-inositol attenuating lithium's effects on PKC alpha, PKC epsilon, and on pertussis toxin-catalyzed [32P]ADP-ribosylation. These results suggest that the effects of chronic lithium on signal transduction pathways may stem initially from its inhibition of inositol-1-phosphatase. Given the critical role of PKC isozymes and G proteins in modulating intracellular cross-talk between neurotransmitter systems and thereby the integrative functions of the CNS, future studies using other inhibitors of inositol monophosphatases are warranted, and offer the hope for the development of more potent and more rapidly acting mood-stabilizing drugs.

Animals↗
PubMed1996

Distance between phosphine-sulfide sidechains of a disubstituted peptide by DRAMA 31P NMR.

Dipolar restoration at the magic angle (DRAMA) has been used to measure the 31P-31P internuclear distance between phosphine-sulfide substituted sidechanins on the fourth and eighth residues of a 12-residue helical peptide. The 7.4 A distance is the same for the peptide lyophilized in bulk or isolated in a cryo- and lyoprotected matrix of poly(ethylene glycol) and sucrose. However, the 31P linewidth for the undiluted peptide is an order of magnitude greater than for the matrix-isolated peptide indicating charge and hydration heterogeneity in the bulk state.

Chemical Phenomena↗
PubMed1996

Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.

Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.

Adult↗
PubMed1996

Attenuation of cyclic AMP production by carbamazepine.

The anticonvulsant carbamazepine is an effective treatment both for epilepsy and for bipolar affective disorder, but the molecular mechanism(s) underlying its therapeutic effects have not been identified. We have found that carbamazepine exerts significant inhibitory effects on the cyclic AMP (cAMP) generating system. Within the clinical therapeutic range (approximately 50 microM), carbamazepine inhibited both basal and forskolin-stimulated cAMP production, without having any significant effects on phosphodiesterase activity. Carbamazepine also exerted its inhibitory effects on the cAMP generating system in pertussis toxin-treated cells, suggesting that the action of carbamazepine was likely mediated through an inhibitory guanine nucleotide binding protein-independent mechanism. A forskolin affinity purification column was used to purify adenylyl cyclases from rat cerebral cortex, and we found that carbamazepine inhibited both basal and forskolin-stimulated activity of purified adenylyl cyclase. We also investigated the effects of carbamazepine on the levels of the transcription factor, cAMP response element binding protein in the phosphorylated (active) state, and found that carbamazepine significantly inhibited forskolin-induced phosphorylation of the cAMP response element binding protein. The data indicate that carbamazepine inhibits adenylyl cyclase activity as well as the downstream effects of activation of adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Interleukin-8 inhibits non-small cell lung cancer proliferation: a possible role for regulation of tumor growth by autocrine and paracrine pathways.

Interleukin-8 (IL-8) is an 8 kD chemokine and angiogenic factor produced by alveolar macrophages, endothelial cells, monocytes, fibroblasts, T lymphocytes, and epithelial cells in response to a variety of stimuli, including LPS, TNF-alpha, IL-1, IL-7, and hypoxia. Pulmonary tumors produce a variety of growth factors and cytokines that may act in both autocrine and paracrine fashion. A549, a well-characterized human lung adenocarcinoma line, was cloned for different levels of IL-8 production by limiting dilution. Clone 3B4 produced 361 +/- 73 pg/ml, and clone 2B2 produced 7818 +/- 614 pg/ml of IL-8 (p = 0.003). Clone 3B4 proliferated at 1.7 times the rate of 2B2. Anti-IL-8 reversed the decrement in proliferation of clone 2B2 by 50%, but recombinant IL-8 decreased the proliferation of 3B4 by 40-55% compared with control. In addition to A549, three other non-small cell lung cancer (NSCLC) lines showed significantly decreased proliferation in response to exogenous recombinant IL-8 (5-30 ng/ml; p < 0.05). These findings suggest that in addition to its chemotactic and angiogenic activities, IL-8 may inhibit lung tumor proliferation by both autocrine and paracrine pathways.

Antigens, CD↗
PubMed1996

Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay.

An epidemiological survey for the causes of a high incidence of primary liver cancer (PLC) in Haimen city, Jian-Su province and Fusui county, Guangxi province in China, found a close correlation between the incidence of PLC and the drinking of pond and ditch water. With an aim to clarify whether microcystins (MC), a hepatotoxic peptide produced by water bloom algae, contaminate the drinking water in the endemic areas of PLC in China, a highly sensitive enzyme-linked immunosorbent assay with a detection limit of 50 pg/ml, was introduced to monitor the MC. Three trials to survey the drinking water were carried out in 1993-1994. Samples, 1135 in total, were collected from different sources such as: ponds, ditches, rivers, shallow wells and deep wells in Haimen city. The first survey in September 1993 found that three out of 14 ditch water specimens were positive for MC, with a range of 90-460 pg/ml. Several toxic algae such as Oscillatoria agardhii were present in some of the ditches. In the second trial, samples were collected from five ponds/ditches, two rivers, two shallow wells and two deep wells monthly for the whole year of 1994. These data showed that MC was highest in June to September, with a range of 62-296 pg/ml. A third trial on the 989 different water samples collected from the different types of water sources in July 1994 revealed that 17% of the pond/ditch water, 32% of the river water, and 4% of the shallow-well water were positive for MC, with averages of 101, 160 and 68 pg/ml respectively. No MC was detected in deep well water. A similar survey on 26 drinking water samples in Fusui, Guangxi province, demonstrated a high contamination frequency of MC in the water of ponds/ditches and rivers but no MC in shallow and deep wells. These data support a hypothesis that the blue-green algal toxin MC in the drinking water of ponds/ditches and rivers, or both, is one of the risk factors for the high incidence of PLC in China. Based on previous findings on the epidemiology of PLC and the present results from the mass screening of MC in the drinking water, an advisory level of MC in drinking water was proposed to below 0.01 microg/l. The combined effect of a potent hepatocarcinogen AFB1 and an intermittent intake of MC in drinking water in the summer season was discussed as an etiology of PLC.

Antibodies, Monoclonal↗
PubMed1996

Efficient transcription from the rice tungro bacilliform virus promoter requires elements downstream of the transcription start site.

Elements downstream of the transcription start site enhance the activity of the rice tungro bacilliform virus (RTBV) promoter in protoplasts derived from cultured rice cells. This enhancer region was located to the first 90 nucleotides of the RTBV leader sequence. Within this region, at least two components which act together to enhance expression from the RTBV promoter could be identified. One is a position- and orientation-independent DNA element within a CT-rich region, and the other is a position-dependent element. Either element was found to be capable of acting independently on a heterologous promoter. The enhancer activity of the DNA element correlates with specific binding of nuclear proteins. Nuclear proteins also recognize an RNA transcript covering the first 90 nucleotides of the RTBV leader.

Badnavirus↗
PubMed1996

Functional parasagittal compartments in the rat cerebellar cortex: an in vivo optical imaging study using neutral red.

1. The spatial patterns of activation in the rat cerebellar cortex evoked by peripheral stimulation were studied in vivo using optical imaging techniques. 2. Crus I and Crus II were stained with the pH sensitive dye, neutral red. Electrical stimulation of the vibrissae area of the ipsilateral face evoked optical responses consisting of parasagittal bands. The bands were 100-300 microns in width, elongated in the anterior-posterior direction, commonly extended across at least two folia, and varied in number from 1 to 7. 3. The optical responses were dependent on activation of postsynaptic elements since they were decreased substantially by the non-N-methyl-D-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. The optical bands were shown to correspond anatomically with the parasagittal compartments revealed by immunostaining with anti-zebrin II. 4. The present study demonstrates that functional parasagittal compartments exist in the rat cerebellar cortex and suggests that zebrin-positive Purkinje cell subgroups are anatomically related to this functional organization.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Modulation of endothelium-dependent hyperpolarization and relaxation to acetylcholine in rat mesenteric artery by cytochrome P450 enzyme activity.

Acetylcholine (ACh) induced hyperpolarization and relaxation in rat mesenteric arteries contracted with norepinephrine, as indicated from studies with simultaneous microelectrode and tension recordings. We tested whether the hyperpolarization to ACh was modified by induction and depletion of cytochrome P450 enzymes. Enzyme induction by treating the animals with 3-methylcholanthrene and beta-naphthoflavone for 3 days resulted in a significant increase in the endothelium-dependent hyperpolarization to a maximum of 22.7 +/- 1.0 mV from 13.9 +/- 0.4 mV in arteries from untreated animals. Enzyme depletion by treating the animals with CoCl2 for 2 days resulted in a significant reduction in the maximum hyperpolarization to 9.9 +/- 0.7 mV. When NO synthesis was inhibited by N omega-nitro-L-arginine, the relaxation was correlated to hyperpolarization. The N omega-nitro-L-arginine-resistant responses were significantly inhibited by clotrimazole. The relaxation to ACh was not altered by enzyme induction but was significantly reduced by enzyme depletion. In KCI-contracted arteries, modification of cytochrome P450 enzyme activity had no significant effect on the relaxation to ACh. Similarly, hyperpolarization and relaxation to pinacidil were not significantly affected. These results suggest that the hyperpolarization response to ACh is closely regulated by cytochrome P450-dependent enzymes.

Acetylcholine↗
PubMed1996

Comparative attributes of effective health services managers and definitions of organizational effectiveness in Australia, the UK and the USA.

This paper explores and contrasts the perceptions of 855, mainly health services managers and 1452 students from three major English-speaking countries regarding the attributes needed for becoming effective managers in their country. Also addressed are country differences and similarities in the perceived relevance of particular indicators of organizational effectiveness. Despite Australia's British heritage, respondents from this country were found to be more similar to those from the USA, than those from the UK, in their views regarding the attributes of effective managers. Australian and American respondents rated 'nurturing' personality skills relatively highly, as they did 'classical' management skills. UK respondents rated 'classical' management skills as more important than 'political' skills.

Administrative Personnel↗