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Q M Chen

Publications and source records attributed to Q M Chen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibition of nitric oxide synthase by straight chain and cyclic alcohols.

Nitric oxide appears to mediate some of the central effects of alcohols. However, the direct effects of alcohols on brain nitric oxide synthase have not been determined. In the present study, we tested on purified nitric oxide synthase from rat brain n-alkan-1-ols, n-alkan-2-ol enantiomers, cycloalkanols, and cycloalkanemethanols. In general, the alcohols inhibited nitric oxide synthase activity noncompetitively. Enzyme inhibitory potencies increased with increasing lipophilicity (increasing carbon number) up to the point of 'cutoff', which was C7 for n-alkan-1-ols and C13 for cycloalkanemethanols, indicating that the alcohol binding site on nitric oxide synthase accommodates a maximum chain length of 6-7 carbon atoms. Before the point of 'cutoff', Ki values for the cyclic alcohols and short chain n-alkanols on nitric oxide synthase were less than their respective anesthetic EC50 values. As reported for tadpole anesthesia, there was no stereoselectivity between enantiomeric pairs of secondary alcohols for inhibition of nitric oxide synthase. These results indicate that the nitric oxide synthase inhibitory potency of alcohols of diverse structure is directly related to lipophilicity and length of the alcohols and that direct inhibition of nitric oxide synthase mediates some of the effects of alcohols even at subanesthetic concentrations.

Alcohols↗
PubMed1997

Treatment of recurrent malignant supratentorial gliomas with the association of carboplatin and etoposide: a phase II study.

Thirty one patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of carboplatin (CBDCA) and etoposide (VP16) at tumor progression. Carboplatin and etoposide (CE) were given, each at a dose of 100 mg/m2/day from day 1 to 3. The response was evaluated at each course and a minimum of three course was required to definite stable patient. Tolerance was evaluated in 31 patients. None had renal or auditory toxicity. Side effects consisted of grade III hematologic toxicity in 6 patients (19%), and grade III hepatic toxicity in one patient. No grade IV WHO toxicity was observed. All 31 patients could be evaluated for therapeutic response. A partial response was noted in 4 patients during 13, 34 +, 35 + and 51 + weeks. Ten patients had stable disease after a minimum of 3 courses (19 to 37 weeks). The rate of partial response (PR) and stabilisation (S) was 45% (14/31). The median time to tumor progression (MTTP) for responding and stable patients was 28 weeks. The median survival time (ST) for the entire group was 45 weeks and over 51 weeks for PR and S patients.

Adult↗
PubMed1997

The site of general anaesthesia and cytochrome P450 oxygenases: similarities defined by straight chain and cyclic alcohols.

1. General anaesthetics disrupt normal cell receptivity and responsiveness while sparing vital respiratory processes. Ultimate elucidation of the molecular basis of general anaesthesia presumes the identification of one or more subcellular components with appropriate sensitivity to the entire array of anaesthetics. 2. Previously, we showed the universal cellular enzymes, cytochrome P450 mono-oxygenases, to be sensitive at relevant concentrations to all anaesthetics tested. The potential significance of P450 inhibition by anaesthetics resides in the contribution of this enzyme family, in conjunction with that of cyclo-oxygenases and lipoxygenases, to the generation from arachidonic acid of lipid second messengers, the eicosanoids. 3. We have shown that P450 enzymes model the site of general anaesthesia in the tadpole with respect to (a) an absolute sensitivity to increasing chain-length series of flexible, straight chain primary and secondary alcohols and straight chain diols, (b) an absolute sensitivity to increasing molecular weight series of rigid cyclic alkanols and cyclic alkanemethanols, (c) the points of abrupt change and of reversal (cut-off) in the linear relationship between increasing anaesthetic potency with increasing carbon chain length, and (d) non-differentiation between secondary alkanol enantiomers. These findings reveal the P450 enzyme family as the most relevant biomolecular counterpart of the site of general anaesthesia, thus far identified.

Alcohols↗
PubMed1995

Radiation-induced cognitive dysfunction: an experimental model in the old rat.

PURPOSE: To develop a model of radiation-induced behavioral dysfunction. METHODS AND MATERIALS: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. RESULTS: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p < or = 0.001) and two-way avoidance (18% vs. 40%, p < or = 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p < or = 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. CONCLUSION: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Aging↗
PubMed1994

Intrathecal synthesis of the anti-Hu antibody in patients with paraneoplastic encephalomyelitis or sensory neuronopathy: clinical-immunologic correlation.

We studied the intrathecal synthesis of the anti-Hu antibody (also called type 1 antineuronal nuclear autoantibody) in 14 patients with isolated paraneoplastic subacute sensory neuronopathy (SSN) and 16 with paraneoplastic encephalomyelitis (PEM). Patients with PEM had higher anti-Hu titers in the CSF (p = 0.003) but not in the serum than those with SSN. Only one patient (7%) with SSN had a positive intrathecal anti-Hu antibody synthesis whereas this was present in 14 (88%) of the 16 patients with PEM (p < 0.0001). The correlation between the intrathecal production of anti-Hu antibodies and PEM supports the role of autoimmune mechanisms in the pathogenesis of PEM. The absent intrathecal synthesis of anti-Hu antibodies in patients with SSN suggests easier accessibility of the systemic immune reaction to the sensory neurons probably due to the partial absence of blood-nerve barrier in the dorsal root ganglia.

Aged↗
PubMed1994

[Paraneoplastic cerebellar degeneration].

Paraneoplastic cerebellar degeneration (PCD) is a rare complication of systemic cancer. PCD may present as a "pure", severe pan-cerebellar syndrome of subacute progression or be only one clinical feature in the setting of extensive CNS disease. The most characteristic form of "pure" PCD is associated with the presence of an anti-Purkinje cell antibody (AB), called anti-Yo, in patients with breast or ovarian cancer. The primary tumor is very often unknown when the cerebellar signs occur, and extensive investigations, including laparotomy or prolonged follow-up may be required to demonstrate its presence. More rarely, others AB than anti-Yo are discovered during PCD. Almost 50% of patients with "pure" PCD do not have circulating anti-neuronal AB. In the cases, the primary cancer is more often known and the clinical course of the cerebellar syndrome may be slower. Cerebellar degeneration may also occur during paraneoplastic encephalomyelitis. In this setting, the cerebellar signs which may be isolated at the onset, become associated with other signs of neuraxis involvement (limbic encephalitis, brainstem encephalitis, myelitis and particularly, subacute sensory neuronopathy) during the course of the disease. When a paraneoplastic encephalomyelitis is associated with a small cell lung cancer, an antineuronal AB called anti-Hu is frequently found. Finally PCD may be associated with the opsoclonus-myoclonus syndrome with the Lambert-Eaton syndrome.

Adult↗
PubMed1994

Chlorotyrosine exerts renal effects and antagonizes renal and gastric responses to atrial natriuretic peptide.

3-Chloro-L-tyrosine (3CT) is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis. In vivo inhibition of tyrosine hydroxylase results in lower catecholamine levels. 3CT (0.5 mg/kg), administered as a bolus i.v. to anesthetized uninephrectomized rats, elicited increases of 72% and 44% in urinary sodium concentration and volume, respectively, whereas a dose of 1 mg/kg caused increases of 27% and 29%. 3CT, 1 mg/kg, resulted in a 2-fold increase in plasma aldosterone (ALD); 0.5 mg/kg was without significant effect. At a dose of 1 mg/kg 3CT significantly antagonized the renal effects of atrial natriuretic peptide (ANP) (1.5 micrograms kg-1 min-1 by intrarenal infusion), expressed as an enhanced excretion of urine volume (102 +/- 14 vs. 70 +/- 11 microliters/min) and sodium (16.1 +/- 1.8 vs. 11.5 +/- 1.7 microEq/min) and increased osmolar clearance (171 +/- 12 vs. 144 +/- 13 microliters/min). A dose of 0.5 mg/kg of 3CT did not produce these same responses to ANP. The increased urine flow caused by 3CT may reflect reduced norepinephrine synthesis. The inverse dose-effect relationship of 3CT on urine flow rate may result from concomitant depletion of dopamine (DA) and elevated circulating ALD. The antagonism of 3CT on responses to ANP is not at the receptor level, because 3CT did not compete for [125I] ANP binding or inhibit ANP-stimulated guanylate cyclase in kidney cell membranes. It was proposed that the reduced basal sympathetic and renal DA tone, together with the elevated ALD level, account for this antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sequence of the gene coding for ribosomal protein S8 of Xenopus laevis.

We present here the cloning and the entire sequence of one of the two gene copies coding for ribosomal protein (r-protein) S8 in Xenopus laevis (corresponding to r-protein S7 in rat) and its flanking regions. The S8a gene contains seven exons and six introns for a total length of about 12,700 bp coding for a mRNA of 663 nucleotides (nt) plus a poly(A) tail. Mapping of the 5' end of the gene has shown that the transcription start point is located in a pyrimidine-rich tract, as has been observed for all r-protein-encoding genes of X. laevis and other vertebrates so far characterized. A computer analysis of the S8a sequence has revealed the presence of a 220-nt sequence repeated, with some variations, once in each of the six introns. RNA analysis by hybridization with oligo probes specific for the two gene copies coding for r-protein S8 has demonstrated that the two of them are expressed at similar levels both in oocytes and in embryos.

Animals↗
PubMed1993

Treatment of recurrent malignant supratentorial gliomas with the association of procarbazine, thiotepa and vincristine: a phase II study.

Twenty patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of procarbazine, thiotepa and vincristine (P.T.V.) at tumor recurrence. Procarbazine was given at a dose of 100 mg/m2 per os from day 1 (D1) to day 15 (D15), thiotepa was administered i.v. at a dose of 35-45 mg/m2 at D1, and vincristine at a dose of 1.4 mg/m2 at D1 and D8. Courses of therapy were repeated every four weeks. Tolerance was evaluated in 20 patients. Three patients developed peripheral neuropathy after 2 or 3 courses of vincristine which was then discontinued. Blood toxicity over grade I occurred in 8 patients (40%). One patient developed a grade i.v. pancytopenia. All 20 patients could be evaluated for therapeutic response. A partial response was noted in 3 patients (15%): 1 glioblastoma multiforme, 1 anaplastic oligodendroglioma and 1 anaplastic astrocytoma. In these three patients time to tumor progression was 10, 11+ and 5 months, respectively. Stabilization lasting 4 months was observed in one patient (anaplastic astrocytoma). Estimated median duration of survival for the entire group was 4.5 months following the onset of PTV (13 months following the date of histology).

Adult↗
PubMed1993

Pharmacological characterization of the activity of endogenous inotropic factor from porcine left ventricle.

We report some of the unique pharmacological properties of a semipurified endogenous inotropic factor (EIF) present in the extract of the porcine left ventricle. EIF produced the following effects: (a) increase in isometric contractile force developed by electrically driven canine right ventricular trabecula, reaching a maximum with 60-100 microliters/ml concentration; (b) inhibition of Na-pump activity in canine portal vein; (c) no digitalis-like cardiac toxicity, e.g., increased diastolic tension or spontaneous diastolic mechanical oscillatory activity, despite inhibition of the sodium pump; (d) a small increase in sarcoplasmic reticular Ca release from the heart but a large increase in transsarcolemmal Ca influx as seen in biphasic contractions, an action similar to that produced by digitalis-like substances; and (e) prolongation of the action potential duration and refractory period of the canine isolated trabeculae. This latter action may confer a unique antiarrhythmic property to EIF.

Action Potentials↗
PubMed1993

[Effect of salidroside on cultured myocardial cells anoxia/reoxygenation injuries].

The effects of salidroside (p-hydroxyphenethyl glucoside, Sal, first isolated and synthesized in China) on reoxygenation damages were studied on cultured myocytes from neonatal rat hearts. At least 80% of cells in the form of monolayer contracted spontaneously on cultured 72 h, then the cells were used in the contractility experiment. After anoxia 3 h and reoxygenation for 1 h the beating of myocardial cells was slowed down and the lactate dehydrogenase (LDH) liberated by myocardial cells was increased. Electron microscopy of myocardial cells revealed localized defects of cell membrane, dilatation of endoplasmic reticulum, and swelling of mitochondria. One h before anoxia, addition of Sal 10 and 30 micrograms.ml-1 increased the beat rate of myocardial cells, depressed the release LDH of from myocytes, and the myocardial ultrastructure was normal during anoxia and reoxygenation. Hence Sal may provide some protective effects on the anoxia/reoxygenation damages upon myocardium.

Animals↗
PubMed1992

The pyrimidine sequence encompassing the transcription start point of Xenopus laevis ribosomal-protein-encoding genes is not obligatory for activity in oocytes.

The genes coding for ribosomal proteins (r-proteins) in Xenopus laevis have a stretch of about 20 pyrimidines (Y) at their 5' end, in the middle of which is localized the main transcription start point (tsp). To obtain information about its possible functional significance, we have introduced by site-directed mutagenesis one or more purines at various positions within the oligo(Y) tract present at the 5' end of the gene coding for r-protein S19 of X. laevis. The effect of these mutations on transcription and translation of a reporter-coding sequence has been evaluated by DNA microinjection in X. laevis oocytes. We show that an uninterrupted stretch of pyrimidines is not necessary for efficient transcription and translation of the reporter gene in the X. laevis oocyte. This finding does not exclude the possibility that this sequence is involved in transcription and/or translation regulation in some developmental situations different from oogenesis.

Animals↗
PubMed1991

[Protoscolicidal effect of some chemical agents and drugs against Echinococcus granulosus].

The present paper reports the protoscolicidal action of hydrastine, ether-acetic acid-ethanol admixture, H2O2, pyquiton and albendazole through in vitro or in vivo exposure, for 15 minutes and transplantation studies. The mortality of protoscolices in vitro and in vivo were 70.2% and 68.9% for 0.3% hydrastine, 56.8% and 56.2% for 10% ether-acetic acid-ethanol admixture, 6.0% and 8.8% for 0.3% H2O2; 6.1% for 0.004% pyquiton in vitro and 5.0% were 10% and 25% for 0.3% hydrastine, 30% and for 0.004% albendazole in vitro. The survival rates after transplantation of protoscolices 37.5% for 10% ether-acetic acid-ethanol admixture, 100% and 95% for 0.3% H2O2 respectively. Disruption of external plasma membrane, hook detachment, sucker deformity of protoscolices exposed to hydrastine were demonstrated by scanning electron microscopy. It is suggested that hydrastine exerts a profound intracellular effect on the protoscolex of E. granulosus of sheep and man, and might be a promising protoscolicide as adjuvant to hydatid surgery.

Acetates↗
PubMed1989

Development of calcitonin gene-related peptide (CGRP) immunoreactivity in relationship to the formation of neuromuscular junctions in Xenopus myotomal muscle.

Immunoreactivity (IR) to calcitonin gene-related peptide (CGRP) has recently been found in chick motoneurons. Bath application of this peptide causes an increase in surface acetylcholine receptor (AChR) density and cAMP level in cultured chick muscle cells. These results suggest a role for this peptide in the formation of synaptic specializations. In this study, we examined the development of CGRP IR in larval Xenopus myotomal muscle in relation to synaptogenesis. Using an antiserum against CGRP, a monoclonal antibody against the p65 synaptic vesicle antigen and a fluorescence conjugate of alpha-bungarotoxin, we followed the development of synaptic specializations with fluorescence microscopy in whole-mount specimens. We found that the postsynaptic specialization in the form of AChR clusters was first detected in stage 22 (24 hour) embryos. The presynaptic specializations, including the synaptic vesicle clusters as evidenced by p65 antibody staining and CGRP IR, were first detected at stage 32 (40 hours). The appearance of these two presynaptic specializations followed the same time course. Subsequently, all three structures, the AChR clusters, CGRP IR, and synaptic vesicle clusters, were colocalized at the neuromuscular junction (NMJ). This shows that CGRP is unlikely to be involved in signaling the development of the postsynaptic apparatus. This premise is further examined in cultures of Xenopus myotomal muscle cells. CGRP at concentrations up to 1 microM did not affect the number of AChR clusters, nor did it interfere with the formation of clusters induced by polycation-coated beads. In contrast, an extract from the basement membrane of Torpedo electric organ promoted the formation of AChR clusters and interfered with the clustering activity of the beads. These results suggest that CGRP, an integral component of the presynaptic specialization, is not involved in signaling synaptogenesis at the NMJ.

Animals↗
PubMed1989

The relationship between talin and acetylcholine receptor clusters in Xenopus muscle cells.

Talin is involved in mediating the cytoskeleton-extracellular matrix interaction at focal contacts in cultured fibroblasts. Recently this protein has been localized at both the myotendinous junction (MTJ) and the neuromuscular junction (NMJ) in skeletal muscle. At the MTJ, talin may mediate the insertion of myofibrils into the plasma membrane, thus serving a function similar to that seen at focal contacts. However, the function of talin at the NMJ is unknown. In this study, we examined its distribution at both mature and developing acetylcholine receptor (AChR) clusters in Xenopus muscle cells both in vivo and in vitro with immunofluorescence. At the NMJs of both myotomal and submaxillaris muscles, talin was absent from the AChR clusters. In cultured myotomal muscle cells, it was absent from 40% of both the nerve-associated AChR patches and the spontaneously formed AChR clusters located on the top surface of the cells. We therefore conclude that this protein is not essential for maintenance of AChR clusters at the NMJ. In addition to MTJs, talin was invariably associated with AChR clusters induced by polyornithine-coated beads, and, to a large extent, with spontaneously formed clusters on the ventral side of cultured cells. A common feature of these talin-positive domains is the deep membrane infoldings, where bundles of actin filaments are inserted into the membrane. Thus, talin may be involved in the formation and maintenance of these structures. The deep membrane infoldings, though prominent at most NMJs, are absent from the two muscles under study in vivo. Our work thus suggests that the postjunctional membrane at the NMJ is heterogeneous, consisting of an AChR cluster domain and, often but not always, a domain for proteins involved in cytoskeleton-membrane linkage as exemplified by talin.

Animals↗
PubMed1989

[The hypoglycemic effect of clausenacoumarine].

Clausenacoumarine is a compound isolated from the leaves of Clausena lansium (Lour.) Skeels which grows widely in South China. The studies show that clausenacoumarine can lower blood glucose level in normal mice and alloxan diabetic mice at 200 mg/kg.d for three days orally, and antagonize the elevation of blood glucose caused by injecting adrenaline in normal mice. No effect on blood lactic acid was observed.

Alloxan↗
PubMed1989

[Study on Bacillus pumilus as a recipient strain for genetic engineering of Bacillus].

Bacillus pumilus 289 can be transformed easily by plasmid pUB110 through protoplast transformation with the frequency of 10(-5)--10(-3), similar to B. subtilis AS 1.1176, a derivative strain of B. subtilis 168. The regeneration frequency of its protoplast is only slightly lower than B. subtilis AS1.1176 (0.3-12.0% compare to 1.53--24.16%). Plasmid pUB110 can be maintained in both bacterial strains stably. The frequency of loss of the plasmid in both strains is lower than 3% after 45 generations in LB medium. But it is quite different that the hybrid plasmid (pUB110 with 3.9 kb foreign DNA fragment) can be maintained much more stably in B. pumilus 289 than in B. subtilis AS1.1176. The frequency of loss of the plasmid is lower than 5% in B. pumilus 289 and 24% in B. subtilis AS1.1176 after 25 generations when they grown in SH medium. The expression level of foreign gene in B. pumilus 289 is also much higher than that in B. subtilis AS1.1176. Therefore B. pumilus 289 is valuable to be exploited as recipient strain for genetic engineering of Bacillus in the future.

Bacillus↗