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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 145 records · Page 8Linked to original sources

Up-regulation of p27Kip1, p21WAF1/Cip1 and p16Ink4a is associated with, but not sufficient for, induction of squamous differentiation.

Irreversible growth arrest is an early and integral part of squamous cell differentiation in normal human epidermal keratinocytes (NHEKs) and is assumed to be linked to the control of expression of differentiation-specific genes. In this study, we examine the link between the molecular events associated with growth arrest and the expression of differentiation genes. NHEKs that have been induced to undergo growth arrest and differentiation by suspension culture contain populations in both G1 and G2/M of the cell cycle. The irreversible growth arrest state in NHEKs is characterized by an accumulation of the hypophosphorylated forms of Rb and p130, with subsequent down-regulation of levels of Rb, up-regulation of p130 and associated down-regulation of E2F-regulated genes such as cyclin A. These events correlate with an inhibition of G1 cdk activity, mediated in part by an increase in the cdk inhibitors p21(WAF1/Cip1), p27(Kip1) and p16(Ink4a). Flow cytometric and immunoblot analysis demonstrated that the timing of the up-regulation of p27, p16 and p130 corresponds closely with the induction of the squamous-specific genes cornifin alpha (SPRR-1) and transglutaminase type I, suggesting a close link between control of growth arrest and differentiation. However, growth arrest induced by over-expression of p27, p21 or p16 by recombinant adenovirus is not sufficient to induce expression of the differentiation genes, or to invoke the pattern of cell cycle regulatory protein expression characteristic of the differentiation-specific irreversible growth arrest. We conclude that growth arrest mediated by activation of the Rb pathway is not sufficient to trigger terminal squamous differentiation and additional signals which can be generated during suspension culture are required to promote the complete differentiation program.

Cell Cycle↗

Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension associated with fibrotic occlusion of the smaller pulmonary veins. Although vasodilator therapy is effective in many patients with primary pulmonary hypertension, the role of vasodilators in PVOD is unclear because of concerns about precipitating pulmonary edema. Recently, however, there have been reports of successful therapy with oral vasodilators or intravenous administration of prostacyclin in patients with PVOD. In contrast, a patient with PVOD is described who developed acute pulmonary edema and respiratory failure during low-dose prostacyclin infusion, leading to death. This report suggests that vasodilators, especially prostacyclin, must be used with extreme caution in patients with known PVOD.

Adult↗

[An experimental study on effects of antimony on anti-oxidase system on liver mitochondria in mice].

OBJECTIVE: To explore the mechanisms of toxic liver damage caused by antimony. METHODS: Experimental mice were injected peritoneally 40 mg/kg of antimony trioxide daily for 28 days to observe the effects of it on the anti-oxidase system in their liver mitochondria. RESULTS: Activities of aspartate aminotransferase and alanine aminotransferase increased obviously in the experimental animals, and those of superoxide dismutase and glutathione peroxidase in liver mitochondria lowered, as compared to those in the control animals with statistical significance. Content of malonyl dialdehyde in the liver mitochondria was 47.27 +/- 1.21 mumol/L in the experimental animals, significantly higher than that in controls. CONCLUSION: It suggested that the mechanism of liver damage caused by antimony associated with injury to the ability of anti-oxidation and lipid peroxidation in the liver mitochondria.

Animals↗

[Role of hyperinsulinemia in pathogenesis of polycystic ovary syndrome and treatment by reduction of insulin secretion].

OBJECTIVE: To investigate the role of insulin in the polycystic ovary syndrome (PCOS) pathogenesis and application of Metformin in the treatment of PCOS. METHODS: Serum androgen, luteinizing hormone (LH) and sex hormone-binding globulin(SHBG) concentration during fasting and serum 17 alpha-hydroxyprogesterone (17-OHP), LH level in response to gonadotropin-releasing hormone agonist (GnRH-a) stimulation were determined. Oral glucose-tolerance tests(OGTT) before and after oral administration of metoformin for 8-12 weeks were performed in 12 obese and 11 lean women with PCOS. RESULTS: After oral administration of metformin for 8-12 weeks, fasting insulin concentration in obese group and area under curve (AUC) after OGTT in lean group decreased significantly. There were significant decrease in basal 17 alpha-hydroprogesterone, androstenedione, testosterone concentration, and increase in serum SHBG concentration in obese and lean groups. Basal LH and the response of serum 17-OHP, LH to GnRHa were not significantly changed. CONCLUSIONS: Hyperinsulinemia may play an important role in hyperandrogenism GnRH-a of PCOS, and metformin may be used in the treatment of PCOS.

Adult↗

[The effects of FSH,LH and insulin on steroids production by granulosa cells from polycystic ovaries syndrome].

OBJECTIVES: To investigate steroids production of granulosa cells obtained from normal ovaries and polycystic ovaries from polycystic ovary syndrome (PCOS) patients under FSH, LH and insulin stimulation. METHODS: Granulosa cells of 33 folicles from 18 pairs of normal ovaries and about 100 folicles from 8 pairs of PCOS were cultured. Estrodial (E2) and progesterone (P) accumulation in the medium was determined under different incubated conditions by RIA. RESULTS: Granulosa cells from PCOS produced more E2(P < 0.05-0.01) under basal, FSH and insulin stimulation and more P (P < 0.05-0.01) under FSH, LH and insulin stimulation than controls. Insulin markedly augmented FSH and LH-stimulated steroid accumulation by two groups of granulosa cells. Granulosa cells from PCOS with peripheral insulin resistance also responded to insulin. CONCLUSION: Enzymes for steroids synthesis in granulosa cells from PCOS may be activated in vivo, and hyperinsulinisma and elevated LH levels in PCOS may be contributable.

Adult↗

Activity of platelet in patients with high level of LDL and the effect of LDL on platelet glycoproteins.

OBJECTIVE: To investigate the activity of platelet in patients with high level of low density lipoproteins (LDL) and the effect of LDL on platelet glycoproteins (GP). METHODS: Platelet glycoproteins, whose platelet were activated or unactivated, were measured by flow cytometry. RESULTS: The amount of the platelet membrane GP II b/III a in patients was not significantly different from that of the control when platelet was unactivated (P > 0.05); when platelet was activated by adenosine diphosphate (ADP), the amount of patients' platelet GP II b/III a was increased markedly in comparison with that in the control (P < 0.01). Having been preincubated with LDL, the platelets were activated by ADP and the amounts of GP II b/III a of patients group and the control were all increased obviously as compared with those in the platelets which were not incubated with LDL (P < 0.01; P < 0.01). There was no significant difference of the amount of granule membrane protein-140 (GMP-140) between patients and the control when platelet was activated by thrombin (P > 0.05). Having been preincubated with LDL, platelet was activated by thrombin, the amounts of GMP-140 on patients' and control platelet were all increased markedly (P < 0.01, P < 0.01). CONCLUSION: The activity of platelet in patients with high level of LDL is increased significantly. LDL can increase the expression of platelet glycoproteins.

Adult↗

Protective effect of recombinant human augmenter of liver regeneration on CCl4-induced hepatitis in mice.

OBJECTIVE: To observe the anti-injury role of recombinant human augmenter of liver regeneration. METHODS: To establish liver injury models induced by CCl4 in vivo and in vitro, cell survival rates and LDH release rates served as observing index in experiments in vitro. Survival rates of liver failure animals, serum concentration of ALT, LDH, DNA and pathological examination were selected as parameters in experiment in vivo. RESULTS: rhALR could increase the survival rates and decrease the LDH release rates of injured hepatocytes in vitro. rhALR could also increase the survival rates of liver failure animal, promote hepatocyte proliferation and decrease the serum level of ALT and LDH in vivo. CONCLUSION: ALR is an important stimulator for liver regeneration and may play important role in liver damage repair.

Animals↗

[Development of the LCY-3E intelligent intracranial pressure monitor].

The LCY-3E intelligent intracranial pressure (ICP) monitor uses a microcomputer system for measurement and control. The ICP is transmitted by an air capsule, and detected by an universal high precision transducer. The problem of zero point drift during continuous ICP measurement was successfully solved and the electric safety of the instrument was greatly improved.

Aerospace Medicine↗

[Distal spleno-caval shunt in 66 patients with portal hypertension].

OBJECTIVE: To evaluate the long-term results and operative experience of distal splenocaval shunt. METHOD: 66 patients with portal hypertension were treated by distal spleno-caval shunt. Of these patients 57 were males and 9 females with a mean age of 39 years. All the patients were followed up. RESULT: The operative mortality rate was 7.58%. Only 5 patients experienced recurrent bleeding (7.58%). None of the patients had clinical hepatic encephalopathy. Five-year survival rate was 70.45%. CONCLUSION: Distal splenocaval shunt is suitable for portal hypertension patients with hepatopetal portal flow.

Adult↗

[Endovascular treatment of intracranial aneurysms with GDC: report of 8 cases].

OBJECTIVE: To assess the usefulness and practical experience in intracranial aneurysm embolization with guglielmi detachable coil (GDC) applied firstly in China. METHOD: Under general anesthesia and systematic anticoagulation, eight cases of intracranial aneurysms were embolized with GDC which was introduced by tracker micro-catheter, combined remodeling technique (RT) if necessary. RESULT: 100% occlusion was achieved in 5 cases, 95% in 2 and 90% in 1, without any complication. Among these cases, 4 failed in the previous attempts of endovascular treatment with mechanical detachable system (MDS), because MDS could not be safely and totally placed inside the aneurysms and Mag 3F/2F micro-catheter could not be navigated into the aneurysms. CONCLUSION: Embolization of intracranial aneurysms with GDC is safe, effective and reliable, and it may offer the cure opportunity to those enearysms which are very dangerous to embolize or can not be embolized with MDS.

Adult↗

[Determination of captopril plus its disulfide metabolites in human plasma].

A new and sensitive HPLC method has been developed for the determination of captopril plus its disulfide metabolites (total captopril) in human plasma. Captopril disulfides and the drug covalently bound to protein were reduced with sodium borohydride to captopril. After liquid-liquid extraction, captopril was treated with o-phthalaldehyde in the presence of D-phenylalanine. The fluorescent derivative of captopril was measured by HPLC using a C-18 reversed phase column with fluorescence detection at the excitation and emission wavelengths of 235 nm and 440 nm, respectively. The mobile phase consisted of a methanol-acetonitrile-phosphate buffer (0.02 mol.L-1, pH 6.4) mixture (30:30:135, v/v), and was set at a flow rate of 1 ml.min-1. The linear range of the assay was between 5 ng.ml-1 (lower limit of quantitation) and 300 ng.ml-1 for total captopril in plasma. The method was successfully applied to determine plasma concentrations of captopril plus its disulfide metabolites in hypertensive patients and was demonstrated to be suitable for the therapeutic drug monitoring.

Antihypertensive Agents↗

[Comparison of roxithromycin bioavailability of a conventional and a dispersible tablet formulation].

Following oral administrations of a single dose of 150 mg roxithromycin dispersible tablet (formulation A, a new formulation for clinical trial) and conventional tablet (formulation B, purchased from the market) to each of 10 healthy male volunteers in a randomized crossover design, the plasma levels of active drug at different times were determined by a microbial assay with Micrococcus luteus CMCC (B) 28001 and the plasma concentration-time profiles were obtained. The Tmax values of formulation A and B obtained were 1.7 +/- 0.9 and 3.7 +/- 1.6 h, the Cmax values were 4.97 +/- 1.17 and 2.04 +/- 1.26 micrograms.ml-1 and the AUC0-->infinity values were 62.2 +/- 11.9 and 35.0 +/- 16.9 micrograms.h.ml-1, respectively. Surprisingly, the relative bioavailability of formulation B was found to be only 59.8% +/- 32.6% (P < 0.01). The low bioavailability of the latter formulation was attributed to poor release of roxithromycin in the gastric site, which was proposed as a key factor to influence drug absorption. Other related factors were also discussed.

Adult↗

[Establishment of germinal cell line of Echinococcus granulosus].

AIM: To establish a cell line of Echinococcus granulosus. METHODS: The proliferating membranes striped from liver cysts in a naturally infected sheep from Urumq were released to monodispersed germinal cells by grinding. The germinal cells were cultivated in the RPMI 1640 medium supplemented with 10%-20% calf serum on collagen-coated 24-well culture plate alternately from passage 1 to passage 14, and then continued. The morphological feature and growth situation were observed by light microscopy. The cultured cells were inoculated into BALB/c mice to identify the infectivity. ELISA was used to determine the immunogenicity of the cells. RESULTS: The germinal cells have been cultivated continuously up to passage 75. The subcultured cells were circular in shape with smooth surface and had the tendency to form syncytia and tissue-like masses. The cells from this cell line could be stored for at least 15 days in refrigerator at 4 degrees C and 10 months in liquid nitrogen. No cyst materials were detected in the mice inoculated with cells. The antigens from cell line could react with positive sera from mice infected with protoscoleces and sera against secreted antigens of cyst membrane, soluble antigens from cyst membrane, soluble antigens from protoscoleces and SHF. CONCLUSION: A germinal cell line of Echinococcus granulosus was successfully established.

Animals↗

The use of technetium-labeled erythrocyte scintigraphy in the evaluation and treatment of lower gastrointestinal hemorrhage.

The percentage of incorrect operations performed as a result of technetium-labeled erythrocyte scintigraphy has been reported as high as 42 per cent. Recent studies have found scintigraphy to be superior to angiography and propose that it be used as the primary diagnostic test in patients with lower gastrointestinal (GI) bleeding. A retrospective analysis was conducted of 105 patients with the symptoms of lower GI hemorrhage to determine the effect of erythrocyte scintigraphy on surgical management. Operative and pathology results were analyzed to determine the accuracy of the scintigraphy for localization of the bleeding source. In addition to tagged erythrocyte scans, 95 of 105 patients had additional diagnostic procedures: colonoscopy (78), upper endoscopy (47), and angiography (9). Scintigraphy localized a site of bleeding in 42 patients (colon, 29; jejunum/ileum, 10; duodenum, 2; esophagus, 1). Surgical intervention was required in 25 patients, and the site of bleeding was correctly determined by scintigraphy in 22 of these patients (88%). The scans were negative in two patients, and the bleeding site was incorrectly reported in another. The patients who had operations were significantly more likely to have positive scintigraphy than the nonoperative group (P < 0.05). Preoperative localization of GI hemorrhage is possible in most patients with technetium-labeled erythrocyte scans (88% of operative patients). When combined with other tests to exclude upper GI bleeding, scintigraphy is a reliable means of guiding surgical intervention.

Angiography↗

Recombinant human interleukin-11 directly promotes megakaryocytopoiesis in vitro.

We have investigated the mechanism of action of the thrombopoietic cytokine, recombinant human interleukin-11 (rhIL-11), on megakaryocytopoiesis in vitro. We have shown that rhIL-11-induced murine and human megakaryocytopoiesis are not mediated by thrombopoietin (Tpo). Murine megakaryocytes (MKs) were produced from bone marrow (BM) mononuclear cells cultured with rhIL-11, IL-3, and a combination of the two cytokines. Conditioned media (CM) were collected and assayed for the presence of biologically active Tpo. Tpo activity was not detected in any of the CMs tested. Next, human BM CD34+ cells were cultured in serum-free fibrin clot medium with rhIL-11, IL-3, or rhIL-11 plus IL-3 and an antibody that neutralizes human Tpo activity. No inhibition of either burst-forming unit-MK- or colony-forming unit-MK-derived colony formation was observed. The antibody did partially inhibit steel factor-induced MK-colony formation, suggesting that the actions of this cytokine are mediated, in part, by Tpo. We determined that MKs can be direct targets of rhIL-11 by showing the expression of functional IL-11 receptor on these cells. Total RNA was prepared from cultured human BM CD41+CD14- cells (MKs) and IL-11 receptor alpha chain mRNA was detected in the MKs by reverse transcription-polymerase chain reaction. Analysis of single-sorted CD41+CD14- cells confirmed that the observed IL-11 receptor expression was not due to contaminating CD41- cells in the pool. The presence of rhIL-11 receptor alpha chain protein in the cells was established by Western blot analysis. After a short exposure of purified BM MKs to rhIL-11, enhanced phosphorylation of both its signal transduction subunit, gp130, and the transcription factor, STAT3 was detected, showing a direct activation of receptor signaling by the cytokine. Consistent with the lack of effect of rhIL-11 on platelets in vivo, IL-11 receptor alpha chain mRNA and protein were not detected in isolated human platelets. These data indicate that rhIL-11 acts directly on MKs and MK progenitors but not on platelets.

Animals↗

Regiospecificity and catalytic triad of lysophospholipase I.

A 25-kDa murine lysophospholipase (LysoPLA I) has been cloned and expressed, and Ser-119 has been shown to be essential for the enzyme activity (Wang, A., Deems, R. A., and Dennis, E. A. (1997) J. Biol. Chem. 272, 12723-12729). In the present study, we show that LysoPLA I represents a new member of the serine hydrolase family with Ser-119, Asp-174, and His-208 composing the catalytic triad. The Asp-174 and His-208 are conserved among several esterases and are demonstrated herein to be essential for LysoPLA I activity as the mutation of either residue to Ala abolished LysoPLA I activity, whereas the global conformation of the mutants remained unchanged. Furthermore, the predicted secondary structure of LysoPLA I resembles that of the alpha/beta-hydrolase fold, with Ser-119, Asp-174, and His-208 occupying the conserved topological location of the catalytic triad in the alpha/beta-hydrolases. Structural modeling of LysoPLA I also indicates that the above three residues orient in such a manner that they would comprise a charge-relay network necessary for catalysis. In addition, the regiospecificity of LysoPLA I was studied using 31P NMR, and the result shows that LysoPLA I has similar LysoPLA1 and LysoPLA2 activity. This finding suggests that LysoPLA I may play an important role in removing lysophospholipids produced by both phospholipase A1 and A2 in vivo.

Amino Acid Sequence↗