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Biomedical subjects

G X Wang

Publications and source records attributed to G X Wang.

At least 37 records · Page 2Linked to original sources

BK(Ca) channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy.

We investigated the influence of pregnancy on large-conductance calcium-activated potassium channel (BK(Ca)) activity (NP(o)) and on channel expression in membranes of isolated human myometrial smooth muscle cells. NP(o) in inside-out patches was higher in pregnant myometria (PM) compared with nonpregnant myometria (NPM), and the half-maximal activation potential was shifted by 39 mV to more negative potentials. This effect was not due to an enhanced BK(Ca) channel expression. In the presence of cAMP kinase (PKA) or cGMP kinase (PKG), NP(o) increased in patches from PM but decreased in those from NPM. Western blot analysis and use of a specific PKG inhibitor (1 microM KT-5823) verified the existence of a partially active membrane-associated PKG. Inhibition of PKA by 100 nM PKI, the inhibitory peptide of PKA, had no effect on NP(o). 8-p-Chlorophenylthio-cGMP (8-pCPT-cGMP) hyperpolarized cells from PM. This effect was abolished by iberiotoxin, a specific blocker of BK(Ca) channels. It is concluded that an endogenous, membrane-bound PKG in myometrial cells specifically enhances BK(Ca) channel activity during pregnancy and thus may contribute to uterine quiescence during pregnancy.

Alkaloids↗

Effects of mitoxantrone on excitation-contraction coupling in guinea pig ventricular myocytes.

The mechanisms of the inotropic effect of mitoxantrone (MTO), a synthetic dihydroxyanthracenedione derivative with antineoplastic activity, was investigated in guinea pig ventricular myocytes using whole-cell patch-clamp methods combined with fura-2 fluorescence and cell-edge tracking techniques. In right ventricular papillary muscles, 30 microM MTO increased isometric force of contraction as well as action potential duration (APD) in a time-dependent manner. The force of contraction was increased approximately 3-fold within 4 h. This positive inotropic effect was accompanied by a prolongation of time to peak force and relaxation time. In current-clamped single myocytes treated with 30 microM MTO for 30 min, an increase of cell shortening by 77% and a prolongation of APD by 19% was observed. Peak amplitude of the intracellular Ca(2+) transients was also increased by 10%. The contribution of APD prolongation to the enhancement of cell shortening induced by MTO was assessed by clamping control myocytes with action potentials of various duration. Prolongation of APD(90) (ADP measured at 90% of repolarization) by 24% led to an increase of cell shortening by 13%. When the cells were clamped by an action potential with constant APD, MTO still caused an increase of cell shortening by 59% within 30 min. No increase of the peak intracellular Ca(2+) transients, however, was observed under this condition. We conclude that both the APD prolongation and a direct interaction with the contractile proteins contributed to the positive inotropic effect of MTO.

Action Potentials↗

Effects of mitoxantrone on action potential and membrane currents in isolated cardiac myocytes.

1. The effects of mitoxantrone (MTO), an anticancer drug, on the membrane electrical properties of cardiac myocytes were investigated using the whole-cell clamp technique. 2. In isolated guinea-pig ventricular myocytes, 30 microM MTO induced a time-dependent prolongation of action potential duration (APD) which was occasionally accompanied by early afterdepolarizations. APD prolongation was preserved in the presence of 10 microM tetrodotoxin and showed reverse rate-dependence. 3. Both the inward rectifier K+ current (I(KI)) and the delayed rectifier K+ current (I(K)) of guinea-pig ventricular myocytes were significantly depressed by 30 microM MTO. The rapidly activating component of I(k) (I(Kr)) seemed to be preferentially blocked by MTO. The transient outward current was not affected by MTO in rat ventricular myocytes. 4. Thirty microM MTO had no direct effect on the L-type Ca2+ current (I(Ca(L))), but reversed the inhibitory effect of 1 microM carbamylcholine but not the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (1 microM) on I(Ca(L)) enhanced by 50 nM isoprenaline in guinea-pig ventricular myocytes. In guinea-pig atrial mycotyes, 30 microM MTO inhibited by 93% the muscarinic receptor gated K+ current (I(K,ACh)) evoked by 1 microM carbamylcholine, whereas I(K,ACh) elicited by 100 microM GTPgammaS, a nonhydrolysable GTP analogue, was only decreased by 12%. 5. The specific binding of [3H]QNB, a muscarinic receptor ligand, to human atrial membranes was concentration-dependently displaced by MTO (1-1000 microM). 6. In conclusion, MTO blocks cardiac muscarinic receptors and prolongs APD by inhibition of I(KI) and I(Kr). The occasionally observed early afterdepolarizations may signify a potential cardiac hazard of the drug.

Action Potentials↗

Detection of circulating antigens and antibodies in Toxocara canis infection among children in Chengdu, China.

In order to determine the seroprevalence of Toxocara spp. infection in children from Chengdu, we performed an enzyme-linked immunosorbent assay (ELISA) and sandwich ELISA (S-ELISA) with excretory-secretory antigens isolated from second-stage larvae of Toxocara canis (TES-Ag ELISA). The seroprevalences of T. canis antibodies in the children from rural areas, urban districts, and urban districts with recent Ascaris lumbricoides infection were 17.7% (59/333), 2.1% (4/186), and 2.6% (1/38), respectively. Among 63 suspected patients with symptoms of T. canis infection, 31 had positive antibodies. The inhibition assay showed an apparent inhibiting capacity of TES-Ag for the antibody against T. canis larvae. The result of S-ELISA demonstrated that circulating antigens of T. canis larvae could be detected in part of the serum with positive antibodies and that the detection rate for circulating antigens in the sera could be improved by polyethylene glycol-acid treatment. This is the first epidemiological study to confirm the existence of T. canis infection and Toxocara-larvae migrans in Chengdu by the combination of TES-Ag ELISA and S-ELISA.

Animals↗

Defective smooth muscle regulation in cGMP kinase I-deficient mice.

Regulation of smooth muscle contractility is essential for many important biological processes such as tissue perfusion, cardiovascular haemostasis and gastrointestinal motility. While an increase in calcium initiates smooth muscle contraction, relaxation can be induced by cGMP or cAMP. cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides. To study the biological role of cGKI and its postulated cross-activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting in severe vascular and intestinal dysfunctions. However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.

Animals↗

Spinocerebellar ataxia type 2 in China: molecular analysis and genotype-phenotype correlation in nine families.

Sixteen patients from nine Chinese families with spinocerebellar ataxia type 2 (SCA2) were heterozygous for a CAG repeat expansion in the SCA2 gene containing 37 to 56 repeats, whereas the normal alleles carried 14 to 28 repeats. One or two CAA triplets within the CAG tract were seen in normal, but not in the expanded alleles. A strong inverse correlation was established between the number of CAG repeats and the age of disease onset. SCA2 accounted for 12% of the known Chinese families with spinocerebellar ataxia.

Adolescent↗

Machado-Joseph disease in four Chinese pedigrees: molecular analysis of 15 patients including two juvenile cases and clinical correlations.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD families and 18 Chinese normal control subjects and confirmed that the (CAG)n array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no subjects with (CAG)n array sizes intermediate between those of normal and MJD affected groups. Meanwhile, we found a significant negative correlation between the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of 86 repeat units was in the youngest patient, whose age of onset was 5 years. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.

Adolescent↗

[Synthesis of S-9-(2,3-dihydroxypropyl)adenine (DHPA) analogs and their inhibition of S-adenosyl-L-homocysteine (SAH) hydrolase].

In order to search for new antiviral agents with high potency and low toxicity, eleven new acyclonucleosides were synthesized. Nucleic-acid bases were condensed with 3-chloro-2-methylpropene to give 5-8a. b, which were oxidized by N-methylmorpholine-N-oxide in the presence of OsO4 to give vicinal dihydroxy acyclonucleosides 1-4a.b. Four DHPA analogs have been tested for the inhibitory activities on s-adenosyl-L-homocysteine hydrolase (SAH). Only compound 1 showed some enzyme inhibitory effect with IC50 of 1.1 mmol.L-1.

Adenine↗

Analysis and estimates of attributable risk factors for lung cancer in Nanjing, China.

A case-control study was performed on 83 cases of primary pulmonary squamous cell carcinoma and 180 cases of primary pulmonary adenocarcinoma in Nanjing. Multivariate conditional logistic regression analysis showed five risk factors for pulmonary squamous carcinoma. These were: smoking, indoor air pollution due to cooking fumes, family tumor history, type of fuel used in the home, and use of coal stoves for heating in winter. The relative risks (RR) for these five risk factors were: 1.03 (95% CI, 1.00-1.06), 3.81 (95% CI, 1.06-13.73), 5.61 (95% CI, 1.23-15.79), 4.97 (95% CI, 0.8-30.88) and 3.72 (95% CI, 0.88-15.71), respectively. The respective population attributable risks (PAR) were: 68%, 52%, 28%, 55% and 36%. The four risk factors for pulmonary adenocarcinoma were smoking, cooking fumes, chronic bronchitis and family tumor history. The respective RRs were: 1.01 (95% CI, 1.00-1.03), 2.99 (95% CI, 1.68-5.34), 2.49 (95% CI, 1.68-5.34) and 4.77 (95% CI, 1.93-11.83). The respective PARs were: 20%, 47%, 18% and 18%. The combined PAR for the five risk factors for pulmonary squamous cell carcinoma was 94% and the combined PAR for the risk factors for pulmonary adenocarcinoma was 79%.

Air Pollution, Indoor↗

Intergenerational instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n-GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter-allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.

Chromosomes, Human, Pair 14↗

Prophylactic effects of taurine and diltiazem, alone or combined, on reperfusion arrhythmias in rats.

AIM: To study the effects of taurine (Tau) and diltiazem (Dil), alone or in combination, on reperfusion arrhythmias in anesthetized rats. METHODS: The arrhythmias were produced by coronary artery ligation for 15 min followed by reperfusion. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured by thiobarbituric acid fluorescence assay and colorimetric determination. RESULTS: Tau 70 mg.kg-1 in combination with Dil 1 mg.kg-1 were more effective on prevention of the reperfusion arrhythmias than each drug alone. The combination of both drugs not only decreased the content of MDA, but also increased the activity of SOD in reperfusion myocardium. CONCLUSION: The inhibition of lipoperoxides formation as well as the inhibition of the calcium influx was involved in the anti-arrhythmic effect of both Tau and Dil.

Animals↗

[Synthesis of optically active (R)- and (S)-tai-ding-an(TDA) and their anti-HSV activity evaluation].

Tai-Ding-An (3-phthalimido-2-oxo-n-butyraldehyde bisthiosemicarbazone, TDA) is an antiviral drug first synthesized in this institute. In order to clarify the difference between the two enantiomeric isomers of TDA, (R)- and (S)-TDA were synthesized from (R)- and (S)-alanine, respectively, via the following steps: fusing with phthalic anhydride gave 2-phthalimido alanine(2a or 2b). The resulting acid was reacted with thionyl chloride to offer the corresponding acid chloride(3a or 3b), which was treated with diazomethane to give the diazoketone(4a or 4b). Bromination of the ketone with hydrobromic acid gave the key intermediate 3-phthalimido-2-oxo-1-bromobutanone (5a or 5b). Compound 5a or 5b was oxidized with DMSO to give 6a or 6b, which was directly condensed with thiosemicarbazide to afford the desired (R)- or (S)-TDA. (R)-TDA, (S)-TDA and (RS)-TDA have been tested in cell culture for anti-Herpes simplex virus I (HSV-1) and HSV-2 activities by plaque reducing method. All of them showed inhibitory effects on HSV-1 and HSV-2 replication with IC50 of 0.0296 mmol.L-1, 0.0359 mmol.L-1 and 0.0418 mmol.L-1 for HSV-1 and 0.88 mmol.L-1, 1.04 mmol.L-1 and 1.06 mmol.L-1 for HSV-2. Not much difference was found among these compounds either on IC50 or on therapeutic indexes.

Animals↗

Effects of taurine on slow action potentials in papillary muscles of guinea pig.

AIM: To examine the effects of taurine on the slow action potentials induced by KCl 24 mmol.L(-1) or tetrodotoxin 40 mumol.L(-1) in guinea pig papillary muscles. METHODS: The transmembrane AP was recorded by a conventional glass microelectrode filled with KCl 3 mmol.L(-1). The muscles were exposed to high K(+)-Tyrode's solution or perfused with Tyrode's solution containing tetrodotoxin. Ouabain was added in order to induce oscillatory afterpotentials. RESULTS: Taurine 20 mmol.L(-1) decreased the maximal upstroke velocity of slow action potential and prolonged the action potential duration at 50% of repolarization. The amplitude of slow action potential and the maximal upstroke velocity both increased by CaCl(2)3 mmol.L(-1) were antagonized by taurine. Taurine increased the concentration of ouabain for oscillatory afterpotential and prolonged the onset time of oscillatory afterpotential. CONCLUSION: Taurine possesses a calcium antagonistic property.

Action Potentials↗

Depressant effect of taurine on triggered activity induced by cesium chloride in rabbit hearts in vivo.

AIM: To study the effects of taurine (Tau) and tetrodotoxin (Tet) on cesium chloride (CsCl)-induced triggered activity and arrhythmia in anesthetized rabbits. METHODS: With a cuffed endotracheal tube, the rabbit ventilation was maintained by a respirator. A Franzy's contact electrode catheter was advanced into the right ventricle through the right external jugular vein and positioned against the anteroapical endocardial surface to record the monophasic action potential (MAP). A catheter was placed into femoral vein for systemic drug administration. RESULTS: CsCl (1 mmol L-1 iv) produced a decrease in the amplitude of MAP from 42.2 +/- 2.1 to 37.0 +/- 3.8 mV (P < 0.01), a prolongation of MAPD50 (156 +/- 22 to 209 +/- 26 ms, P < 0.01) or MAPD90 (205 +/- 25 to 250 +/- 20 ms, P < 0.01) and an early afterdepolarization (EAD) developed within 30 s after CsCl injection. The ventricular premature (VP) resulted from EAD triggered by CsCl. In the Tau (100 mg kg-1)- or Tet (10 micrograms kg-1)-pretreated group, not only was the amplitude of EAD decreased (Tau, 4.2 +/- 2.7; or Tet, 5.2 +/- 2.6, respectively vs 16.1 +/- 8.3 mv, P < 0.01), but also the duration of EAD was shortened (Tau, 695 +/- 164; or Tet, 492 +/- 172, respectively, vs 1068 +/- 166 ms, P < 0.01). The severity of triggered arrhythmia (TA) was alleviated and the incidence of TA was lowered within 30 min after iv CsCl by either Tau or Tet. CONCLUSION: The depressant effects of Tau and Tet on EAD and VP induced by CsCl were involved in an increase of outward current or a decrease of an inward current.

Action Potentials↗

Duodenogastric reflux demonstrated by cholescintigraphy in peptic ulcer disease and chronic gastritis.

Duodenogastric (D-G) reflux is commonly associated with peptic ulcer disease and chronic gastritis. To determine D-G reflux in association with each disease entity, we studied 43 chronic gastritis patients and 21 peptic ulcer patients with cholescintigraphy. Scoring (0 to 3+) was judged by the amount of Tc-99m diethylacetanitanilido-IDA (EHIDA) in the stomach. In the chronic gastritis group, 5, 16, 10, and 12 patients scored 3+, 2+, 1+, and 0, respectively. In the peptic ulcer disease group 6, 2, and 13 patients scored 2+, 1+, and 0, respectively. Thirty-nine of the 64 patients (60.9%) were positive for D-G reflux. D-G reflux occurred in 31 of 43 (72.09%) of chronic gastritis patients and in 8 of 21 (38.1%) patients with peptic ulcer disease. D-G reflux was significantly higher in the chronic gastritis group (P = 0.0009). Chronic gastritis patients were more likely to have more marked D-G reflux than peptic ulcer disease (P = 0.048). The authors conclude that cholescintigraphy is noninvasive and objectively demonstrates D-G reflux in chronic gastritis and peptic ulcer disease and that chronic gastritis is more closely associated with D-G reflux than peptic ulcer disease.

Adult↗

[The pathology of Joseph's disease in a Chinese family: a report of two autopsy cases].

This is the first pathology report on Joseph's disease in China, based on autopsies of 2 members of the Huang family. The main pathological changes were chiefly located in the central nervous system including globus pallidus and Luy's body, cerebellar dentate nucleus, cranial nerve motor nuclei of brain stem, substantia nigra and red nuclei, and also there were severe loss of neurons in the anterior horn and Clarke's nuclei; severe demyelinization of cerebellospinal tract and degeneration with demyelinization of the peripheral nerves accompanied by neurogenic skeletal muscular atrophy. It is concluded that the pathologic characteristics were similar to those found in Europe, United States and Japan.

Adult↗

Ultrastructural observation on macrophage-lymphocyte interactions in semen from Tripterygium wilfordii Hook.f. takers.

Sixty-nine specimens from Tripterygium Wilfordii Hook.f. (TWH) users were investigated by electron microscopy. No macrophages were demonstrated in the 21 specimens collected prior to the administration of TWH. However, it was found in 23 out of the 48 semen specimens obtained following the TWH administration. The macrophages were functionally active as shown by the presence of a large number of cytoplasmic processes and pseudopodia on the surface, and primary and secondary lysosomes in the cytoplasm. The macrophages phagocytized sperm debris and degenerated or dead spermatids with formation of specific phagosomes. Around those macrophages, lymphocytes were commonly noted. The cytoplasmic processes of the two cell types could come into contact or even fuse with each other, leading to tight junction-like structure; in some of the contacts, the plasma membranes were found dissolved so as to form direct cytoplasmic linkage.

Adolescent↗