Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 379 records · Page 21Linked to original sources

PubMed2001

Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells.

Although cardiac Purkinje cells (PCs) are believed to be the source of early afterdepolarizations generating ventricular tachyarrhythmias in long Q-T syndromes (LQTS), the ionic determinants of PC repolarization are incompletely known. To evaluate the role of the slow delayed rectifier current (I(Ks)) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37 degrees C). Typical I(Ks) voltage- and time-dependent properties were noted. Isoproterenol enhanced I(Ks) in a concentration-dependent fashion (EC(50) approximately 30 nM), negatively shifted I(Ks) activation voltage dependence, and accelerated I(Ks) activation. Block of I(Ks) with 293B did not alter PC action potential duration (APD) in the absence of isoproterenol; however, in the presence of isoproterenol, 293B significantly prolonged APD. We conclude that, without beta-adrenergic stimulation, I(Ks) contributes little to PC repolarization; however, beta-adrenergic stimulation increases the contribution of I(Ks) by increasing current amplitude, accelerating I(Ks) activation, and shifting activation voltage toward the PC plateau voltage range. I(Ks) may therefore provide an important "braking" function to limit PC APD prolongation in the presence of beta-adrenergic stimulation.

Acetamides↗

PubMed2001

Influence of permeating ions on Kv1.5 channel block by nifedipine.

Nifedipine can block K(+) currents through Kv1.5 channels in an open-channel manner (32). Replacement of internal and external K(+) with equimolar Rb(+) or Cs(+) reduced the potency of nifedipine block of Kv1.5 from an IC(50) of 7.3 microM (K(+)) to 16.0 microM (Rb(+)) and 26.9 microM (Cs(+)). The voltage dependence of block was unaffected, and a single binding site block model was used to describe block for all three ions. By varying ion species at the intra- and extracellular mouth of the channel and by using a nonconducting W472F-Kv1.5 mutant, we demonstrated that block was conditioned by the ion permeating the pore and, to a lesser extent, by the extracellular ion species alone. In Kv1.5, the outer pore mutations R487V and R487Y reduced nifedipine potency close to that of Kv4.2 and other Kv channels with an equivalent valine. Although changing this residue can affect C-type inactivation of Kv channels, the normalized reduction and time course of currents blocked by nifedipine in 5, 135, and 300 mM extracellular K(+) concentration was the same. Similarly, a mean recovery time constant from nifedipine block of 316 ms was unchanged (332 ms) after 5-s prepulses to allow C-type inactivation. This is consistent with the conclusion that nifedipine block and C-type inactivation in the Kv1.5 channel can coexist but are mediated by distinct mechanisms coordinated by outer pore conformation.

Calcium Channel Blockers↗

PubMed2001

Endotoxin stimulated cytokine production in rat vascular smooth muscle cells.

Because inflammatory processes may promote the development of atherosclerosis, we examined the activation of cytokine genes in rat vascular smooth muscle cells in vitro after treatment with bacterial lipopolysaccharide (LPS). Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) mRNA increased in response to LPS. Activation of nuclear factor-kappaB (NF-kappaB) presumably results in NF-kappaB binding to regulatory regions of target genes and activating transcription. We therefore compared the kinetics of NF-kappaB activation, cytokine message production, and TNF-alpha secretion. Maximum active NF-kappaB was found at 30 min after the addition of LPS and decreased thereafter. Increased IL-6 mRNA was detected at 30 min, increased TNF-alpha mRNA at 60 min, and increased IL-1 mRNA at 120 min. Secretion of TNF-alpha was dependent on LPS concentration and was first detected 120 min after LPS addition. Aspirin, which has been shown to inhibit NF-kappaB activation and cytokine secretion in other cell types, did not inhibit NF-kappaB activation or TNF-alpha secretion. However, aspirin reduced the amount of both TNF-alpha and IL-6 mRNA present 30 min after LPS addition by half (P < 0.05).

Animals↗

PubMed2001

Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex.

The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange.

Analysis of Variance↗

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

Study on concretions developed around urinary catheters and mechanisms of renal calculi development.

AIMS: To study the structure and composition of encrustation and concretions developed on urinary catheters to better understand their formation mechanism to be able to prevent them. METHODS: The surface of catheters was studied by direct and scanning electron microscopy observation. In vitro formation of encrustations was performed in synthetic urine. RESULTS: The surface of catheters was covered by a continuous layer of organic matter, on which a thin scale consisting of crystals of calcium oxalate monohydrate (COM), uric acid anhydrous or calcium phosphate developed. Encrustations observed on catheters generally exhibited the same composition as the previously developed renal calculi. In catheters collected from patients without previous episodes of renal calculi or with previous episodes of infected renal calculi in which infection was afterwards eradicated, on the first organic layer, in that case plate-like COM crystals forming a columnar layer were observed. In vitro experiments demonstrated that COM columnar structures were only formed when normocalciuric urine containing organic matter was used, and the presence of crystallization inhibitors, as phytate, notably delayed their formation. CONCLUSION: Calcium oxalate was the main crystalline phase developed on catheters inserted in patients, specially in the absence of urinary infection or urinary pH values <5.5 and high urinary uric acid levels. Thus, prophylaxis of encrustations may consist of preventive measures usually applied in cases of recurrent idiopathic calcium oxalate urolithiasis.

Adult↗

PubMed2001

Association of asthma with beta(2)-adrenergic receptor gene polymorphism and cigarette smoking.

Recent studies have suggested that two polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) gene at codons 16 (arginine to glycine) and 27 (glutamine to glutamate) affect an individual's airway responsiveness, or response to acute or chronic beta(2)-agonist therapy but are not risk factors for asthma. We hypothesize that there is an interaction effect on asthma between the beta(2)AR gene polymorphisms and cigarette smoking. A case-control study was conducted in 128 asthma cases and 136 control individuals identified from 10,014 studied subjects in rural Anqing, China. Allele-specific polymerase chain reaction (PCR) was used to genotype beta(2)AR gene polymorphisms. Multiple logistic regression was used to adjust for potential confounding factors. We found a marginally significant interaction between cigarette smoking and beta(2)AR-16 genotype after adjusting for important confounding factors (p = 0.06). Specifically, we found that compared with never-smoking Gly-16 homozygotes, those ever-smokers who are Arg-16 homozygotes had a significantly increased risk of asthma (odds ratio [OR] = 7.81; 95% confidence interval [CI]: 2.07 to 29.5). This association showed a clear dose-response relationship with the number of cigarettes smoked. However, there was no significant association of asthma with polymorphisms of the beta(2)AR at position 27 (OR = 1.38; 95% CI: 0.69 to 2.73). Our study suggests a gene-environment interaction between the Arg-16 genotype and ever cigarette smoking with respect to the susceptibility of an individual to asthma.

Adult↗

PubMed2001

Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction.

Rho-associated serine/threonine kinase (Rho-kinase) is a downstream effector of small GTPase RhoA that has recently been shown to play an important role in regulating smooth muscle contraction. The present study investigated the role of Rho/ Rho-kinase in hypoxia-induced pulmonary vasoconstriction (HPV). Small pulmonary resistance vessels and cultured pulmonary arterial smooth muscle cells (PASMCs) from the rat were used. PASMCs exposed to hypoxia (PO(2) = 26 +/- 2 mm Hg) showed a significant increase in Rho-kinase activity. Exposure to hypoxia for 20, 40, 60, 90, and 120 min also resulted in a significant increase in myosin light chain (MLC) phosphorylation at all time points in PASMCs. Hypoxia-induced MLC phosphorylation was inhibited by Y-27632 (a Rho-kinase inhibitor), exoenzyme C3 (a specific Rho inhibitor), or toxin B (an inhibitor for Rho proteins). In addition, hypoxia-induced Rho-kinase activation was blocked by C3 and toxin B. Small rat intrapulmonary arterial rings, which were made hypoxic (PO(2) = 30 +/- 3 mm Hg), showed a slow sustained contraction, and Y-27632 caused a significant relaxation during the sustained phase of HPV in a concentration-dependent manner. In summary, the data show that Rho-kinase is activated by hypoxia in PASMCs, and Rho/Rho-kinase is functionally linked to hypoxia-induced MLC phosphorylation and plays a role in the sustained phase of HPV.

Animals↗

PubMed2001

Anterior window laryngoplasty: a new anatomic approach for posterior glottic and subglottic stensosis.

This study explores the feasibility of an anterior thyroid window as a new approach for posterior glottic stenosis. An anterior window was made on the thyroid cartilage of human cadaver larynges, with its superior edge below the level of the vocal cords and an inferior pedicle composed of the inferior border of the thyroid cartilage attached to the cricothyroid membrane, which was left intact. By obtaining direct exposure of the posterior glottis and cricoarytenoid joints, mucosal graft suturing and exploration of the joints were easily achieved with an operating microscope. This study demonstrates the anatomic feasibility of an anterior window laryngoplasty as an alternative approach to treating posterior glottic stenosis while preserving the cartilage framework and avoiding the anterior commissure. This technique may improve endolaryngeal manipulation by providing a closer and more direct exposure than do endoscopic techniques, and by having fewer possible complications than traditional open techniques.

Feasibility Studies↗

PubMed2001

Spontaneous platelet aggregation with congenital giant platelet containing large granules and thick membrane.

Inherited giant platelet disorders are a heterogeneous group of disorders. In the current study, a patient was reported with moderate bleeding tendency, giant platelets, and spontaneous platelet aggregation, which were not affected by the administration of aspirin or ticlopidine. The electron microscopy of platelets showed a black and thick plasma membrane with crystal-like fine hairs in the exterior coat and more large and variously shaped granules in the cytoplasm. The expression of glycoprotein (GP) Ib, GP IIb, and GP IIIa on platelet surface was normal, and no mutations in genes for GP Ib alpha, GP Ib beta, and GP IX were detected. These phenomena are so distinguishable from those of Mondreal platelet syndrome and other hereditary giant platelet disorders, that we propose that this patient probably has a novel platelet disorder, which has not yet been reported.

Blood Platelet Disorders↗

PubMed2001

Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division.

Tumorigenic pituitary tumor transforming gene (PTTG) is a mammalian homolog of Xenopus securin that inhibits chromatid separation, is overexpressed in many human tumor types, and mediates transcriptional activation. Loss of yeast securin Pds1p or Drosophila securin pimples is lethal. Here we show that mice lacking PTTG (PTTG -/-) are, surprisingly, viable and fertile; but they have testicular and splenic hypoplasia, thymic hyperplasia, and thrombocytopenia. PTTG -/- mouse embryo fibroblasts exhibited aberrant cell cycle progression with prolonged G2-M phase and binucleated and multinucleated nuclei with increased aneuploidy. PTTG -/- mouse embryo fibroblast metaphases contained quadriradial, triradial, and chromosome breaks, as well as premature centromere division. The results show that PTTG functions to maintain chromosome stability, cell cycle progression, and appropriate cell division. Moreover, mammalian sister chromatid separation, an important transition in the cell cycle, is likely regulated by mechanisms in addition to securin.

Animals↗

PubMed2001

Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.

Thyroid hormone governs a diverse repertoire of physiological functions through receptors encoded in the receptor genes alpha and beta, which each generate variant proteins. In mammals, the alpha gene generates, in addition to the normal receptor TRalpha1, a non-hormone-binding variant TRalpha2 whose exact function is unclear. Here, we present the phenotype associated with the targeted ablation of TRalpha2 expression. Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1. Both TRalpha2 +/- and -/- mice show a complex phenotype with low levels of free T3 and free T4, and have inappropriately normal levels of TSH. The thyroid glands exhibit mild morphological signs of dysfunction and respond poorly to TSH, suggesting that the genetic changes affect the ability of the gland to release thyroid hormones. However, the phenotype of the mutant mice also has features of hyperthyroidism, including decreased body weight, elevated heart rate, and a raised body temperature. Furthermore, TRalpha2-/- and TRalpha2+/- mice are obese and exhibit skeletal alterations, associated with a late-onset growth retardation. The results thus suggest that the overexpression of TRalpha1 and the concomitant decrease in TRalpha2 expression lead to a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied. The phenotypes suggest that the balance of TRalpha1:TRalpha2 expressed from the TRalpha gene provides an additional level of tuning the control of growth and homeostasis in mammalian species.

Animals↗

PubMed2001

Distinct tissue-specific roles for thyroid hormone receptors beta and alpha1 in regulation of type 1 deiodinase expression.

Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control levels of T3, the active ligand for thyroid hormone receptors (TR). The D1 gene is itself T3-inducible and here, the regulation of D1 expression by TRalpha1 and TRbeta, which act as T3-dependent transcription factors, was investigated in receptor-deficient mice. Liver and kidney D1 mRNA and activity levels were reduced in TRbeta(-/-) but not TRalpha1(-/-) mice. Liver D1 remained weakly T3 inducible in TRbeta(-/-) mice whereas induction was abolished in double mutant TRalpha1(-/-)TRbeta(-/-) mice. This indicates that TRbeta is primarily responsible for regulating D1 expression whereas TRalpha1 has only a minor role. In kidney, despite the expression of both TRalpha1 and TRbeta, regulation relied solely on TRbeta, thus revealing a marked tissue restriction in TR isotype utilization. Although TRbeta and TRalpha1 mediate similar functions in vitro, these results demonstrate differential roles in regulating D1 expression in vivo and suggest that tissue-specific factors and structural distinctions between TR isotypes contribute to functional specificity. Remarkably, there was an obligatory requirement for a TR, whether TRbeta or TRalpha1, for any detectable D1 expression in liver. This suggests a novel paradigm of gene regulation in which the TR sets both basal expression and the spectrum of induced states. Physiologically, these findings suggest a critical role for TRbeta in regulating the thyroid hormone status through D1-mediated metabolism.

Animals↗

PubMed2001

Regulation of imprinted X-chromosome inactivation in mice by Tsix.

In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRESbetageo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.

Animals↗

PubMed2001

Potential role for laminin 5 in hypoxia-mediated apoptosis of human corneal epithelial cells.

Laminin 5 functions to promote cell-matrix adhesion and therefore is hypothesized to abrogate apoptosis initiated through the loss of epithelial cell contact with extracellular matrix. Laminin 5 levels are decreased in epithelial cells cultured in a hypoxic environment. Exposure of epithelial cells to hypoxia may induce apoptotic pathways transmitted through changes in mitochondrial membrane potential. Using an apoptosis assay based on mitochondrial membrane integrity, the effect of hypoxia (2% oxygen) on human corneal epithelial cell viability was determined. Both a virally transformed corneal epithelial cell line and third passage corneal epithelial cells were resistant to hypoxia-mediated apoptosis for up to 5 days in culture. However, at 7 days in culture, a statistically significant increase in apoptosis was noted in hypoxic corneal epithelial cells compared to normoxic (20% oxygen) controls. Increased apoptosis in hypoxic epithelium at 7 days in culture correlated with decreased deposition of laminin 5 into the extracellular matrix, as determined by western blot analysis and immunofluorescence microscopy. Additionally, the extracellular processing of the alpha3 and gamma2 chains of laminin 5 was negatively impacted by corneal epithelial cell exposure to hypoxia for 7 days. Treatment of human corneal epithelial cells cultured in 20% oxygen with function-inhibiting antibodies to laminin 5 for 2 or 3 days resulted in a statistically significant decrease in proliferation, and concomitant increase in apoptosis, compared with untreated normoxic controls. Based on these results, it appears that mechanisms of hypoxia-mediated apoptosis in human corneal epithelial cells may be initiated by the loss of processed laminin 5 in the extracellular matrix or by the loss of laminin 5-epithelial cell communication and transmitted through mitochondria.

Apoptosis↗

PubMed2001

Effects of two saponins extracted from the polygonatum Zanlanscianense pamp on the human leukemia (HL-60) cells.

Two saponins, methyl protodioscin and dioscin, were extracted from the root of Polygonatum Zanlanscianense Pamp. One of them, dioscin exerted significant inhibitory effects on the growth of the human leukemia cell HL-60, inducing differentiation and apoptosis. HL60 cells were induced mainly along the granulocytic lineage. In addition, we have found that dioscin affects many cancer cells. These studies may have important significance in treating related cancers.

Apoptosis↗

PubMed2001

Differences in knowledge, attitude and behavior with respect to hypertension among cardiologists, neurologists and other physicians in internal medicine.

It is known that the knowledge, attitude and behavior (KAB) of physicians with respect to hypertension directly affect the prevention of hypertension and associated cardiovascular diseases. To investigate the differences in KAB among cardiologists, neurologists and other physicians, 1,722 potential participants were selected by stratified random sampling. Among these, 1,609 participants took part in the present survey, and 948 of this group were eligible for the present analysis. The data were collected using a self-administrated questionnaire. Results showed that, with respect to knowledge and attitude regarding hypertension, 15.3% of cardiologists, 15.2% of neurologists and 7.2% of other internals selected the correct answers to all questions (p<0.05). The criteria of hypertension were not correctly understood by about two-thirds of physicians, including both cardiologists and neurologists. With regard to behavior, 16.5% of cardiologists, 17.9% of neurologists and 9.6% of other internals selected the correct answers to all questions (p<0.05). A majority of physicians considered that routine blood pressure measurements were not necessary in cases uncomplicated by cardiovascular disease and other disease, such as nephrotic disease, or diabetes mellitus. One-half to two-thirds of physicians did not believe that life style modifications reduce blood pressure. For each question, cardiologists showed the highest, and other internals the lowest, percentage of correct responses to all items in the questionnaire. These findings indicate that cardiovascular health education must be strengthened for all physicians, and not only for specialists.

Cardiology↗

PubMed2001

Tartary buckwheat flavonoid activates caspase 3 and induces HL-60 cell apoptosis.

It has been proposed that flavonoids may have potential as anticancer agents. In this study, we showed that tartary buckwheat flavonoid (TBF) obviously inhibits the growth of human acute myelogenous leukemia (AML) HL-60 cells by MTT assay. The inhibitory effect of TBF on the proliferation of HL-60 cells is related to the induction of apoptosis, which is confirmed by DNA ladder formation on gel electrophoresis and apoptosis morphological changes under light microscope. Furthermore, HL-60 cells undergo rapid apoptosis upon treatment with TBF, as indicated by increased annexin V binding capacity and caspase 3 activation with flow cytometric analysis. Thus, our data provide a potential mechanism for the chemopreventive activity of tartary buckwheat flavonoid and suggest that it may have a potentially therapeutic role for human leukemia.

Annexin A5↗