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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 73 records · Page 4Linked to original sources
PubMed2000

Reversible suppression of in vitro biomineralization by activation of protein kinase A.

Parathyroid hormone (PTH-(1-34)) potently suppresses apatite deposition in osteoblastic cultures. These inhibitory effects are mediated through signaling events following PTH receptor binding. Using both selective inhibitors and activators of protein kinase A (PKA), this study shows that a transient activation of PKA is sufficient to account for PTH's inhibition of apatite deposition. This inhibition is not a result of reduced cell proliferation, reduced alkaline phosphatase activity, increased collagenase production, or lowering medium pH. Rather, data suggest a functional relationship between matrix assembly and apatite deposition in vitro. Bone sialoprotein (BSP) and apatite co-localize in the extracellular matrix of mineralizing cultures, with matrix deposition of BSP temporally preceding that of apatite. Transient activation of PKA by either PTH-(1-34) or short term cAMP analog treatment blocks the deposition of BSP in the extracellular matrix without a significant reduction in the total amount of BSP synthesized and secreted. This effect is reversible after allowing the cultures to recover in the absence of PKA activators for several days. Thus, a transient activation of PKA may suppress mineral deposition in vitro as a consequence of altering the assembly of an extracellular matrix permissive for apatite formation.

Alkaline Phosphatase↗
PubMed2000

Subcellular localization and PKC-dependent regulation of the human lysophospholipase A/acyl-protein thioesterase in WISH cells.

Lysophospholipases play essential roles in keeping their multi-functional substrates, the lysophospholipids, at safe levels. Recently, a 25 kDa human lysophospholipase A (hLysoPLA I) that is highly conserved among rat, mouse, human and rabbit has been cloned, expressed and characterized and appears to hydrolyze only lysophospholipids among the various lipid substrates. Interestingly, this enzyme also displays acyl-protein thioesterase activity towards a G protein alpha subunit. To target the subcellular location of this hLysoPLA I, we have carried out immunocytochemical studies and report here that hLysoPLA I appears to be associated with the endoplasmic reticulum (ER) and nuclear envelope in human amnionic WISH cells and not the plasma membrane. In addition, we found that the hLysoPLA I can be up-regulated by phorbol 12-myristate 13-acetate (PMA) stimulation, a process in which phospholipase A(2) is activated and lysophospholipids are generated in WISH cells. Furthermore, the PMA-induced hLysoPLA I expression can be blocked by the protein kinase C (PKC) inhibitor Gö6976. The regulated expression of the LysoPLA/acyl-protein thioesterase by PKC may have important implications for signal transduction processes.

Cell Line↗
PubMed2000

Antileukemic activity of Flt3 ligand in murine leukemia.

Flt3-ligand (Flt3-L) is an early acting costimulatory cytokine that has been shown to possess antitumor properties in murine solid tumor models. Flt3-L is a trans-membrane protein (tm) but can be proteolytically cleaved to a soluble form, which is also biologically active. In this study, the antitumor effect of both soluble and tmFlt3-L was evaluated in a mouse leukemia model. To mimic the multiorgan involvement characteristic of human leukemia, a factor-dependent cell line FDC.P1 was made leukemogenic by transfection with the human BCR/ABL gene. The resulting cell line, AW, expresses BCR/ABL RNA and protein. It maintains a similar in vitro growth rate as the parent cell line, but unlike the parent cell line, AW cells are factor independent and tumorigenic. Growth of FDC.P1 and AW cells are unaffected by the addition of soluble human Flt3-L to the culture medium. Also, AW growth is unaltered after transduction with a retroviral vector expressing the tm isoform of human Flt3-L (AW/tmFlt3-L). When 10(5) AW cells were i.v. injected into syngeneic DBA/2 mice, fatal leukemia developed in nine of nine (100%) mice within 4-6 weeks with involvement of the blood, bone marrow, spleen, and thymus. Systematic administration of soluble human Flt3-L (500 microg/kg/day) for 10 days protected mice from leukemia, with 11 of 17 mice tumor free at week 8 (64.7%) The tm isoform of Flt3-L also was protective. When 10(4) AW/tmFlt3-L cells were injected i.v. into mice, only 35.7% (5 of 14) developed leukemia versus 100% in control groups. Adoptive transfer of immunity was also demonstrated; T cells obtained from tumor-free animals conferred protection to 87% (seven of eight) naive mice challenged with AW cells. These results demonstrate that both soluble and membrane-bound human Flt3-L has antitumor activity in this leukemia model.

Animals↗
PubMed2000

Regulation of BRCA1 expression by the Rb-E2F pathway.

Inheritance of a mutant allele of the breast cancer susceptibility gene BRCA1 confers increased risk of developing breast and ovarian cancers. Likewise, inheritance of a mutant allele of the retinoblastoma susceptibility gene (RB1) results in the development of retinoblastoma and/or osteosarcoma, and both alleles are often mutated or inactivated in sporadic forms of these and other cancers. We now demonstrate that the product of the RB1 gene, Rb, regulates the expression of the murine Brca1 and human BRCA1 genes through its ability to modulate E2F transcriptional activity. The Brca1 gene is identified as an in vivo target of E2F1 in a transgenic mouse model. The Brca1 promoter contains E2F DNA-binding sites that mediate transcriptional activation by E2F1 and repression by Rb. Moreover, ectopic expression of cyclin D1 and Cdk4 can stimulate the Brca1 promoter in an E2F-dependent manner, and this is inhibited by coexpression of the p16(INK4a) cyclin-dependent kinase inhibitor. The human BRCA1 promoter also contains a conserved E2F site and is similarly regulated by E2F1 and Rb. This functional link between the BRCA1 and Rb tumor suppressors may provide insight into the mechanism by which BRCA1 inactivation contributes to cancer development.

Animals↗
PubMed2000

Recombinant human interleukin-11 synergizes with steel factor and interleukin-3 to promote directly the early stages of murine megakaryocyte development in vitro.

The authors studied the role that interleukin (IL)-11 plays during the early stages of megakaryocyte (MK) development by investigating its in vitro effects on cell subpopulations enriched for bone marrow primitive progenitor cells and early and late committed progenitor cells. Progenitor subpopulations were isolated from bone marrow of normal or 5-fluorouracil (5FU)-treated mice and separated by sorting based on the surface antigens Sca-1, c-kit, and CD34. Functional analysis of the cell subpopulations, 5FU Lin(-)Sca-1(+)c-kit(+) or normal bone marrow (NBM) Lin(-)Sca-1(+)c-kit(+)CD34(-)cells, indicated that exposure of these cells to recombinant human (rh)IL-11 in combination with steel factor (SF) stimulates the formation of colonies in methylcellulose and their proliferation in single cell-containing liquid cultures. Kinetic studies of MK progenitor generation, in response to SF and rhIL-11, demonstrated that a significant number of the progenitors produced are committed to the MK lineage. RhIL-11 also synergized with both SF and IL-3 to stimulate MK colony growth from NBM Lin(-)Sca-1(+)c-kit(+) cells (early progenitors) and NBM Lin(-)Sca-1(-)c-kit(+) cells (committed late progenitors). In the presence of IL-3, NBM, Lin(-)Sca-1(-)c-kit(+) cells responded more strongly to rhIL-11 than SF. Consistent with these results is the observation that IL-11 receptor alpha chain mRNA is present in all the progenitor cells from which the MKs are derived. This cell culture and RNA analysis suggest that murine bone marrow primitive progenitor cells and early and late progenitor cells are direct targets of rhIL-11 and that rhIL-11 has the potential to promote megakaryocyte development at several very early stages. (Blood, 2000;95:503-509) (Blood. 2000;95:503-509)

Animals↗
PubMed2000

Applications of capillary electrophoresis with electrochemical detection in pharmaceutical and biomedical analyses.

As a high efficiency separation technique, capillary electrophoresis has been widely used in various fields of analytical science. This review discusses the applications of electrochemical detection systems combined with capillary electrophoresis in pharmaceutical and biomedical analysis. These detection methods mainly involve amperometric detection but also include conductivity detection and potentiometric detection. Its applications in the field are divided into six parts, including catechol compounds, thiols, amino acids and peptides, carbohydrates, general pharmaceuticals, and other related compounds. A relatively detailed discussion is described for each compound under the current studied. On this basis, we have suggested several conceivable directions for capillary electrophoresis with electrochemical detection in the future.

Electrochemistry↗
PubMed2000

Congenital agenesis of the right pulmonary artery.

A 44-year-old woman with recurrent pulmonary infections developed severe hemoptysis. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery, a very rare congenital anomaly, was demonstrated by computed tomography and cardiac catheterization. Severe pulmonary hypertension in the contralateral lung precluded right pneumonectomy but percutaneous embolization of a large systemic arterial collateral to the right lung provided palliative relief of hemoptysis.

Adult↗
PubMed2000

Effect of coriaria lactone on membrane potential of hippocampal neurons in rats.

Intracellular recording method of electrophysiology was used to study the effect of microinjection of coriaria lactone (CL) into hippocampus on membrane potential of hippocampal neurons in rats. The membrane potential in 34 neurons of 12 rats were recorded. The results showed that CL induced depolarization of all of 34 neurons examined. Among the 34 neurons, 15 had paroxysmal depolarization accompanied by spike discharge in cluster and spike discharge in cluster ceased when membrane was hyperpolarized, 7 showed continuous depolarization accompanied by continuous spike discharge and 12 had only depolarizing response. The results suggest that injection of CL into hippocampus may lead to an increase of excitability of local neurons accompanied by different patterns of epileptioform discharge.

Animals↗
PubMed2000

Platelet fibrinogen in the patients with idiopathic bleeding platelet disorder.

The changes of platelet fibrinogen in patients with obscure cutaneous mucosal bleeding and their relation with disease were evaluated. By using flow cytometry and Western blot, the platelet binding site of fibrinogen and the expression of platelet fibrinogen in 8 cases of obscure bleeding were detected. The results showed that platelet surface binding sites of fibrinogen were 65.38 +/- 3.62 in the resting state and 65.25 +/- 5.78 after activated by adenosine diphosphate, showing no significant difference as compared with control group (P > 0.05). The expression of platelet fibrinogen was obviously decreased in 4 patients and increased in one case as compared with control group. It was concluded that the binding sites of fibrinogen on the platelet surface were normal in the patients with idiopathic bleeding platelet disorder. The abnormal of platelet fibrinogen might be one of hemorrhagic reasons in partial patients.

Adult↗
PubMed2000

The effect of coriaria lactone on NMDA receptor mediated currents in rat hippocampal CA1 neurons.

To investigate the exact mechanism of epileptogenesis induced by coriaria lactone (CL), the effect of CL on NMDA receptor mediated current (IAsp) in rat hippocampal CA1 neurons was investigated by using nystatin perforated whole-cell patch clamp. 10(-6)-10(-4) mol/L Asp acted on NMDA receptors and elicited an inward current (IAsp) at a holding potential (VH) of -40 mV in presence of 10(-6) mol/L glycine and absence of Mg2+ extracellularly. CL enhanced NMDA receptor mediated current induced by Asp, but had no effect on threshold concentration, EC50, Hill coefficient as well as maximal-effect concentration and reversal potential of IAsp. The effect had no relationship with holding potential. These results showed that CL could enhance NMDA receptor mediated current to increase [Ca2+]i of neurons by acting on Gly site, thereby inducing epilepsy.

Animals↗
PubMed2000

Photokinetic voltammetric method for the determination of thiocyanate.

Thiocyanate traces have a strong inhibitory effect on the oxidation of Neutral Red by potassium bromate under UV irradiation in diluted phosphoric acid. Neutral Red exhibits a sensitive second derivative oscillopolarographic wave at -0.6 V(vs. SCE) in diluted phosphoric acid and sodium acetate solution. The oscillopolarographic behavior of Neutral Red was selected as indicator component for its photo-activated oxidation. The photochemical reaction rate equation was determined. A detection limit of 0.3 ng mL(-1) (3sigma/k) and a linear calibration curve from 2.0-48.0 ng mL(-1) thiocyanate were obtained. The method was applied to the determination of thiocyanate in urine, saliva and serum with satisfactory results.

Journal Article↗
PubMed2000

Effects of hepatocellular iron imbalance on nitric oxide and reactive oxygen intermediates production in a model of sepsis.

BACKGROUND/AIMS: In mammals iron homeostasis is most important, as imbalance of iron such as iron overload may lead to severe diseases. Recently, it has been shown that the iron regulatory protein-1 is partially controlled by nitric oxide and reactive oxygen intermediates, molecules frequently seen in inflammatory events. The aim of the present study was to investigate the effects of impaired iron homeostasis on the interaction of nitric oxide, and reactive oxygen intermediate formation in hepatocytes in a model of acute inflammation. METHODS: Hepatocytes isolated from Corynebacterium parvum (C parvum)-injected rats were used to examine the formation of nitrogen and oxygen intermediates by iron deprivation and iron overload in the presence of lipopolysaccharide. In addition, we investigated the RNA binding and aconitase activity of iron regulatory protein-1. RESULTS: In the present study we show that iron overload in lipopolysaccharide-treated C. parvum-primed hepatocytes downregulated the RNA binding of iron regulatory protein-1 and aconitase activity. Subsequently, we observed a reduced formation of nitrite/nitrate and S-nitrosothiols but an increased production of reactive oxygen species, and hepatocellular damage. Moreover, the addition of iron to cell cultures caused a further increase in cellular damage, a drop in the cellular glutathione pool, and an increase in peroxynitrite and hydroxyl-like radicals. In contrast, addition of deferoxamine (an iron chelator) to lipopolysaccharide-treated C. parvum-primed hepatocytes protected cells by stabilizing the GSH content, maintaining the nitric oxide formation, and by reducing Fenton oxidants. CONCLUSIONS: Our results show that the antioxidative effects of iron chelators prevent the formation of toxic Fenton oxidants in severe inflammatory events, which should be considered in the treatment of disorders characterized by an iron imbalance.

Animals↗
PubMed2000

Inhaled nitric oxide selectively dilates pulmonary vasculature in adult patients with pulmonary hypertension, irrespective of etiology.

OBJECTIVES: We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory. BACKGROUND: Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH. METHODS: Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of > or =20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). RESULTS: Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO. CONCLUSIONS: Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.

Administration, Inhalation↗
PubMed2000

Sorption and desorption of Eu and Yb on alumina: mechanisms and effect of fulvic acid.

The effects of pH, ionic strength and FA (fulvic acid) on the sorption and desorption of Eu(III) and Yb(III) on alumina were respectively investigated by using batch technique and radiotracers 152 + 154Eu and 169Yb. The distribution coefficients for sorption and desorption of Eu on alumina at pH 4.4, 4.6 and 5.7 in 1 mol/l NaCl solutions as a function of solid phase concentration were determined in the presence or absence of FA. The effects of pH, FA and ionic strength on the distribution coefficients for sorption and desorption of Yb on alumina were determined in 0.01-2.0 mol/l NaNO3. It was found that pH and FA influenced the sorption of Eu(III) and Yb(III) on alumina greatly. A surface hydrolysis model can satisfactorily and qualitatively explain the observations on bare alumina. The competition among the complexations of surface free hydroxyl groups, soluble and sorbed fulvic acids can satisfactorily and qualitatively explain the observations on the coated alumina.

Adsorption↗
PubMed2000

Prevalence of childhood asthma, allergic rhinitis and eczema in Urumqi and Beijing.

OBJECTIVE: To assess the prevalence of asthma and other allergies in children in Urumqi and Beijing, compared with that in Hong Kong. METHODS: A total of 7754 primary school students were randomly selected to participate in the study. Data were collected in 1995-96 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol for 6- and 7-year-olds. The study design and data quality assurance in all aspects followed the protocol, including the double entry of data. RESULTS: The questionnaire response rate was high (98.9%). Beijing children reported significantly more asthma than those living in Urumqi in three categories: wheezing or whistling in the chest in the past year (6.0%, 95% confidence interval (CI): 5.1-6.9% vs 2.9%, 2.3-3.5%, P < 0.001), sleeping disturbed due to wheezing (1.3%, 0.9-1.7% vs 0.6%, 0.3-0.9%, P < 0. 03) and having experienced asthma ever (10.7%, 9.6-11.8% vs 7.6%, 6. 6-8.6%, P < 0.001). The prevalence of allergic rhinitis (30.0% vs 31. 1% estimated as 12-month nasal symptoms in Beijing and Urumqi, respectively) and eczema (2.8% vs 2.0% recorded as 12-month itchy rash) in the two cities were not significantly different. A similar study was also performed in Hong Kong in 1995 using the same ISAAC protocol. The children in Urumqi and Beijing had fewer (P < 0.05) allergic symptoms compared to those living in Hong Kong (n = 3618). The 12-month prevalence of wheezing, nasal symptoms and itchy rash found in Hong Kong were 9.2% (95% CI: 8.2-10.2%), 35.1% (33.5-36.7%) and 4.2% (3.5-4.9%), respectively. CONCLUSION: : Urumqi, Beijing and Hong Kong represent communities at different stages of westernization and the results from these three cities reflect a worldwide trend for an increasing prevalence of allergies along with westernization. These three cities could assist in identifying risk factors involved in the increase in asthma, allergic rhinitis and eczema.

Asthma↗
PubMed2000

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.

Aged↗
PubMed2000

Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.

It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.

Adolescent↗