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Biomedical subjects

Z Wu

Publications and source records attributed to Z Wu.

At least 307 records · Page 17Linked to original sources

Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5' leader sequence of the receptor mRNA.

Two of the most highly recognized factors implicated in the pathogenesis of hypertension, atherosclerosis, congestive heart failure and associated cardiovascular disease are the renin angiotensin system (RAS) and estrogen. A major effect of estrogen results from its influence on the RAS. Beta-estradiol (E2) replacement in ovariectomized (OVX) rats significantly decreased type 1 angiotensin (AT1) receptor expression in the pituitary and adrenal, whereas it significantly increased receptor expression in the uterus when compared to OVX controls. Additional evidence demonstrated an important influence of estrogen on a recently discovered post-transcriptional mechanism for regulating expression of the AT1 receptor. This mechanism consists of cytosolic RNA binding proteins (BPs) that recognize the 5' leader sequence (5'LS) of the receptor mRNA. The activities of these 5'LS BPs were modulated by estrogen in an inverse manner to AT1 receptor regulation. Moreover, in vitro translation assays in wheat germ lysates suggested that the 5'LS BPs inhibited AT1 receptor translation. Our data therefore indicate that hormonal regulation of AT1 receptors involves modulation of 5'LS BPs by estrogen. These findings may in part account for the observed protective effects of estrogen on cardiovascular disease.

Adrenal Glands↗

Growth hormone (GH) and prolactin receptors in human peripheral blood mononuclear cells: relation with age and GH-binding protein.

GH receptors (GHRs) and PRL receptors (PRLRs) were studied in human peripheral blood mononuclear cells (PBMC) using flow cytometry, biotinylated anti-GH receptor monoclonal antibody 10B8, and biotinylated human PRL. Variations of GHR and PRLR expression and the relationship of plasma GHBP and GH receptor in PBMC subsets were examined as a function of age and sex. By double immunofluorescence staining, we show that about 30% of total cells express GH receptors, with a low expression in T cells, whereas almost all B cells and monocytes are GH receptor positive. Four age groups were defined among the 64 normal volunteers, aged 12 to 85 yr, who were included in the study. The percentage of PBMC expressing GH receptors is significantly lower in group 2 (20-40 yr) than in group 1 (12-20 yr) and group 4 (>60 yr). In T cells, monocytes and B cells, no significant changes are detected in either the percentage of GH receptor positive cells or in the GH receptor level per cell. The level of PRLRs expressed in PBMC is significantly higher in age group 2 than in age group 4. A negative correlation is observed between plasma GHBP and the percentage of PBMC expressing GH receptors. These results suggest that regulation of GH receptors in lymphocytes and in other target cells could be different.

Adolescent↗

Growth hormone (GH) receptor blockade with a PEG-modified GH (B2036-PEG) lowers serum insulin-like growth factor-I but does not acutely stimulate serum GH.

B2036-PEG, a GH receptor (GH-R) antagonist, is an analog of GH that is PEG-modified to prolong its action. Nine mutations alter the binding properties of this molecule, preventing GH-R dimerization and GH action. A potential therapeutic role of B2036-PEG is to block GH action, e.g. in refractory acromegaly. A phase I, placebo-controlled, single rising-dose study was performed in 36 normal young men (ages, 18-37 yr; within 15% ideal body weight). Four groups received a single s.c. injection of either placebo (n = 3 in each group, total n = 12) or B2036-PEG (0.03, 0.1, 0.3, or 1.0 mg/kg; n = 6 each dose). B2036-PEG and GH concentrations were measured 0, 0.25, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 120, and 144 h after dosing. Serum insulin-like growth factor-I was measured before and 1-7 days after dosing. All doses were well tolerated, with no serious or severe adverse reactions. B2036-PEG, at 1.0 mg/kg, reduced insulin-like growth factor-I by 49 +/- 6% on day 5 (P < 0.001 vs. placebo). GH was measured by two independent methods: 1) modified Nichols chemiluminescence assay (empirically corrected for B2036-PEG cross-reactivity); and 2) direct GH two-site immunoassay, using monoclonal antibodies that did not react with B2036-PEG. There was good agreement between the two methods. GH did not change substantially at any B2036-PEG dose, suggesting that B2036-PEG does not interact with hypothalamic GH-Rs to block short-loop feedback. B2036-PEG may thus block peripheral GH action without enhancing its secretion.

Adolescent↗

Dominant effects of RET receptor misexpression and ligand-independent RET signaling on ureteric bud development.

During kidney development, factors from the metanephric mesenchyme induce the growth and repeated branching of the ureteric bud, which gives rise to the collecting duct system and also induces nephrogenesis. One signaling pathway known to be required for this process includes the receptor tyrosine kinase RET and co-receptor GFR(&agr;)-1, which are expressed in the ureteric bud, and the secreted ligand GDNF produced in the mesenchyme. To examine the role of RET signaling in ureteric bud morphogenesis, we produced transgenic mice in which the pattern of RET expression was altered, or in which a ligand-independent form of RET kinase was expressed. The Hoxb7 promoter was used to express RET throughout the ureteric bud branches, in contrast to its normal expression only at the bud tips. This caused a variable inhibition of ureteric bud growth and branching reminiscent of, but less severe than, the RET knockout phenotype. Manipulation of the level of GDNF, in vitro or in vivo, suggested that this defect was due to insufficient rather than excessive RET signaling. We propose that RET receptors expressed ectopically on ureteric bud trunk cells sequester GDNF, reducing its availability to the normal target cells at the bud tips. When crossed to RET knockout mice, the Hoxb7/RET transgene, which encoded the RET9 isoform, supported normal kidney development in some RET-/- animals, indicating that the other major isoform, RET51, is not required in this organ. Expression of a Hoxb7/RET-PTC2 transgene, encoding a ligand-independent form of RET kinase, caused the development of abnormal nodules, outside the kidney or at its periphery, containing branched epithelial tubules apparently formed by deregulated growth of the ureteric bud. This suggests that RET signaling is not only necessary but is sufficient to induce ureteric bud growth, and that the orderly, centripetal growth of the bud tips is controlled by the spatially and temporally regulated expression of GDNF and RET.

Animals↗

The effects of tetrandrine on the contractile function and microvascular permeability in the stunned myocardium of rats.

The effects of tetrandrine (Tet) on the contractile function and microvascular permeability in stunned rat myocardium in vivo were studied. Stunned myocardium was induced by 15 (MS(15) group) or 20 (MS(20) group) min of myocardial ischemia plus 60 min of reperfusion. The following was shown. (1) FITC-BSA concentration was 166.0 +/- 7. 9 microg/g myocardium in the control group. The concentrations in ischemic myocardium increased by 35.4 and 45.6% in MS(15) and MS(20) groups respectively (p<0.05). (2) Administration of Tet (64.2 and 96. 3 micromol/kg, I.P.) 20 min before ischemia not only ameliorated the contractile function, but also reduced the FITC-BSA concentrations in ischemic myocardium. At 60 min after reperfusion, the contractile function parameters in Tet-treated groups were significantly superior to those in corresponding stunning groups. FITC-BSA concentrations in Tet-treated groups were lower than those in stunning groups. Then, there was already no significant difference in FITC-BSA concentrations between Tet-treated groups and the control group. The FITC-BSA concentrations at the end of experiments were correlated negatively with dp/dt(max) (r = -0.83, p<0.01). (3) Tet inhibited KCl-induced calcium influx in isolated cardiomyocytes. The results suggest that Tet given before ischemia may be involved in the reduction of microvascular permeability in stunned myocardium, which might be associated with its calcium channel blocking effect.

Alkaloids↗

[Missense mutations of exons 14 and 18 of Wilson's disease gene in Chinese patients].

OBJECTIVE: To investigate the characteristics of mutations of exons 14 and 18 of Wilson's disease (WD) gene in Chinese patients. METHODS: The subjects of study included 60 unrelated normal controls and 44 unrelated WD patients. Genomic DNA was prepared from peripheral blood leukocytes by a salt-out method. Mutations of exons 14 and 18 in these subjects were screened by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and further confirmed by sequencing. RESULTS: One patient was homozygous for Arg1041Pro mutation of exon 14 and another patient was heterozygous for Asn1270Ser mutation of exon 18. CONCLUSION: The mutations of exons 14 and 18 of WD gene in Chinese patients were confirmed by sequencing for the first time in China. Arg1041Pro was identified as a novel missense mutation. In addition, an Asn1270Ser, previously described mutation, was detected in this study. But exons 14 and 18 are not the hot point mutations of WD gene in Chinese patients.

Adolescent↗

Knowledge of HIV/AIDS among health care workers in China.

This study was designed to assess knowledge of AIDS among health professionals in China via a cross-sectional survey. A self-administered questionnaire requesting demographic characteristics and basic AIDS knowledge was given to health professionals in 11 provinces, cities, and autonomous regions. Questionnaires were completed by 1,400 of 1,500 (93%) health professionals surveyed. The percentages of correct answers ranged from 3% to 68%. Findings included that public health workers had more knowledge than clinicians; having attended training workshops was not associated with an adequate levels of knowledge; and knowledge differed by professional level and by the geographic region in which they worked. Although most health professionals questioned knew that AIDS is caused by an infectious agents, their knowledge of transmission routes, the "window period" and the length of the incubation period is still inadequate. Thus, health professionals in China urgently need both more training and more effective training. The effectiveness of future HIV/AIDS workshops should be evaluated.

Acquired Immunodeficiency Syndrome↗

Selective in vivo mobilization with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF as compared to G-CSF alone of dendritic cell progenitors from peripheral blood progenitor cells in patients with advanced breast cancer undergoing autologous transplantation.

Dendritic cells (DCs) are potent antigen-presenting cells that are essential for the initiation of T cell-mediated immunity. DCs develop from myeloid progenitor populations under the influence of granulocyte macrophage colony-stimulating factor (GM-CSF) and pass through an intermediate stage of maturation that is characterized by CD14 expression. Interest has focused on generating human-derived DCs for antigen-specific tumor vaccines to be used as adjuvant immunotherapy in minimal disease settings, such as after autologous transplantation. In the present study, mobilized peripheral blood progenitor cells (PBPCs) were obtained from 18 patients with locally advanced or metastatic breast cancer preparing to undergo autologous stem cell transplantation. PBPCs mobilized in 10 patients with GM-CSF for 1 week, followed by the combination of GM-CSF and G-CSF, were compared with those obtained from patients receiving G-CSF alone with respect to the presence of DC progenitors and the capacity to generate functionally active mature DCs. PBPCs mobilized with GM-CSF/G-CSF were markedly enriched for CD14+ DC progenitor cells as compared with those mobilized with G-CSF alone. Consistent with an immature progenitor population, the CD14+ cells express Ki-67 antigen but not nonspecific esterase. CD14+ cells purified by fluorescence-activated cell sorting from PBPCs mobilized with either regimen and cultured for 1 week in GM-CSF and interleukin-4 generated nearly pure populations of cells with characteristic DC phenotype and function. The addition of GM-CSF to the mobilization regimen resulted in greater yields of functionally active DCs for potential use in posttransplant immunotherapy.

Breast Neoplasms↗

Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1.

Oxysterol 7alpha-hydroxylase has broad substrate specificity for sterol metabolites and may be involved in many metabolic processes including bile acid synthesis and neurosteroid metabolism. The cloned human oxysterol 7alpha-hydroxylase (CYP7B1) cDNA encodes a polypeptide of 506 amino acid residues that shares 40% sequence identity to human cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In contrast to the liver-specific expression of CYP7A1, CYP7B1 mRNA transcripts were detected in human tissues involved in steroid genesis (brain, testes, ovary, and prostate) and in bile acid synthesis (liver) and reabsorption (colon, kidney, and small intestine). The human oxysterol 7alpha-hydroxylase transiently expressed in 293/T cells was able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone (DHEA). The human CYP7A1 and CYP7B1 both contain six exons and five introns. However, CYP7B1 spans at least 65 kb of the genome and is about 6-fold longer than CYP7A1. The transcription start site (+1) was localized 204 bp upstream of the initiation codon. No TATA box-like sequence was found near the transcription start site. Transient transfection assays of CYP7B1 promoter/luciferase reporter constructs in HepG2 cells revealed that the promoter was highly active. The 5' upstream region from nt -83 to +189 is the core promoter of the gene.

Animals↗

Effects of oxidative damage of membrane protein thiol groups on erythrocyte membrane viscoelasticities.

In three oxidative damaging systems: the diamide-mercaptoethanol redox modification system (DM), the pyrogallol oxygen free radicals system (PG) and the hypoxanthine-xanthine oxidase oxygen free radical system (HXO), the effect of erythrocyte membrane oxidative damage on membrane viscoelasticities was investigated with micropipette aspiration method. The experimental results indicated that erythrocyte membrane oxidative damage has a great influence upon the membrane mechanical properties. The oxidative damage led to decrease of contents of membrane protein thiol radical. The scanning of SDS-PAGE presented that membrane proteins form the higher molecular weight component (HMP) by the cross-linking of membrane protein thiol radicals that might hinder the conformational change of membrane protein. This might be the reason for the increased membrane elastic modulus and viscous coefficient upon treating erythrocytes with the oxidative damaging systems. A significant negative logarithm regression relation was found between the membrane elastic modulus, mu, or viscoefficient, eta, and the contents of membrane protein thiol radicals. These experimental results suggested that thiol radicals oxidative damage reaction due to the superoxides anions (*O2-) may be an important molecular mechanism inducing changes of membrane viscoelasticities or whole cell deformability of erythrocyte under physiological and pathological oxidative stress.

Blood Viscosity↗

Influence of dosing vehicles on the preclinical pharmacokinetics of phenolic antioxidants.

Phenolic antioxidants, such as butylated hydroxyanisole (BHA) and propyl gallate (PG), have demonstrated paradoxical cancer initiating and preventive actions in animals. Studies examining the disposition and biological effects of these agents have used solutions in ethanol-saline, PEG400-saline, corn oil, or DMSO. The aim of this study was to compare the pharmacokinetics of BHA and PG in mice following dosing in either a "control" dosing vehicle (ethanol-saline, 2:3) or a solution of an inclusion complex of each agent with hydroxypropyl-beta-cyclodextrin (HPB) in saline. Results demonstrate that BHA or PG are rapidly absorbed and eliminated in mice following i.p. or p.o. dosing in either dosing vehicle. Pharmacokinetic parameters of BHA estimated in mice correlated with those reported for other species, including humans ("Interspecies Scaling"), suggesting that exposures are proportional to body weight across species. Therefore, rodents are appropriate animal models to study these phenolic antioxidants. The oral absorption of PG was influenced by dosing vehicle in mice, suggesting the need for cautious selection of traditional nonaqueous vehicles (such as DMSO, ethanol, etc.) in the investigation of biological activities of these xenobiotics. Indeed, DMSO elevated plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) concentrations following subchronic i.p. administration of various blank vehicles to mice. Such elevations in plasma concentrations of these enzymes are considered biomarkers of hepatotoxicity. The absolute oral bioavailability of PG (administered as an HPB complex) in rats was low (5%) suggesting extensive metabolism or incomplete absorption. The low oral bioavailability of these phenolic antioxidants in rodents suggests that the risk assessment of these antioxidants should include an evaluation of their metabolites as well.

Administration, Oral↗

[Risk factors for initiation of drug use among young males in Longchuan, Yunnan].

OBJECTIVE: To identify the risk factors for drug use among young males in Longchuan, Yunnan. METHODS: A non-concurrent cohort study was carried out based on a cross-sectional survey. Demographic, behavioral, and drug-using related information were collected using an anonymous questionnaire. The non-concurrent cohort included the period January 1, 1991 to August 1, 1994. Risk factors were assessed by univariate and multivariate analysis. RESULTS: The annual incidence of drug use increased between 1991 and 1993. Multivariate analysis identified the following risk factors for drug use: being born to Jingpo ethnic group (OR = 1.8, 95% C.I. 1.2-2.5), being divorced/ widowed/separated (OR = 8.9, 95% C.I. 1.8-43.3), smoking cigarettes (OR = 2.4,95% C.I. 1,6-3.8), having had pre-/extra-marital sex (OR = 1.5, 95% C.I. 1.1-2.2), having been encouraged by friends to try drugs (OR = 8.8, 95% C.I. 6.1-12.9) and having a family member who used drugs in 1991 (OR = 1.5, 95% C.I. 1.0-2.3). More than six years of education was a protective factor for drug use (OR = 0.6, 95% C.I. 0.4-0.98). The population attributable fractions were 70.8% for being encouraged by friends or others to try drugs, 50% for smoking cigarettes and 24% for being Jingpo ethnic group. CONCLUSION: Results suggested that community based programs to change attitudes towards smoking cigarettes and drug use could dramatically reduce the incidence of new drug users in Longchuan County. We, therefore, recommend a community-based intervention program targeting adolescent.

Adolescent↗

[Analysis on characteristics and risk factors of acute myocardial infarction in younger adults].

OBJECTIVE: To investigate the risk factors and characteristics related to acute myocardial infarction (AMI) in younger adults. METHODS: Clinical data were analyzed in 55 patients under 40 years old with AMI and compared with 1,097 controls of older age group (> or = 40 years). RESULTS: Results showed that the family history of coronary heart disease, smoking and alcohol intake were more frequently seen in younger age group than those in control group with odds ratios OR = 1.4, OR = 1.6 and OR = 1.6, respectively. Younger age group had a higher rate of noticeable inducing cause and the major causes were exhaustion and physically over-hurdened. A higher percentage of typical chest pain was found in younger patients. CONCLUSION: Smoking, alcohol drinking and genetic factor made up major risk factors of coronary heart disease in younger adults in this study, however reducing the amount of smoking and alcohol drinking, prevention of fatigue and over excitement might have some preventive impact on the prevalence of AMI in younger population.

Adolescent↗

Clinical study on manipulative treatment of derangement of the atlantoaxial joint.

The derangement of the atlantoaxial joint is one of main cervical sources of dizziness and headache, which were based on the observation on the anatomy of the upper cervical vertebrae, analysis of X-ray film of the atlantoaxial joint, and the manipulative treatment in 35 patients with cervical spondylosis. The clinical diagnosis of derangement consists of: dizziness, headache, prominence and tenderness on one side of the affected vertebra, deviation of the dens for 1 mm-4 mm on the open-mouth X-ray film, abnormal movement of the atlantoaxial joint on head-rotated open-mouth X-ray film. An accurate and delicate adjustment is the most effective treatment.

Adult↗

[The effect of intradermal injection of collagenase in implanted hypertrophic scar in nude mice].

OBJECTIVE: Effects of collagen degradation in hypertrophic scar by intradermal injection of collagenase were observed. METHODS: Hypertrophic scar was implanted into nude mice and collagenase was injected locally. Light and electron microscopic observations were carried out. RESULTS: Collagen degradation in hypertrophic scar by intradermal injection of collagenase was observed. The implanted scars became soft, thin and small. CONCLUSION: These results suggested that local injection of collagenase may be a useful therapeutic tool for hypertrophic scar.

Animals↗

Endovascular embolization of traumatic carotid cavernous fistulas.

OBJECTIVE: To analyze the effectiveness of endovascular embolization on treatment of traumatic carotid-cavernous fistula (TCCF). METHODS: From 1986 to 1997, 482 cases of traumatic carotid-cavernous fistula were treated by endovascular embolization in the Beijing Neurosurgical Institute. Several kinds of balloon-catheter were used for embolization. External carotid-cavernous fistulas and rare carotid-cavernous fistulas (CCF) with minute leakage were treated by cyanoacrylate or coils. Although artery approach was applied in most cases (477 cases), vein approach showed its own advantages in some special cases. RESULTS: We found a special "bileakage sign" indicating multileakage of TCCF, which was never mentioned before. All 482 cases were embolized successfully, and 405 cases maintained the patency of internal carotid artery (ICA). No treatment-related deaths occurred and the symptoms and signs of 462 cases were relieved after embolization. Emergency embolization was needed in some conditions such as serious epistaxis, delayed or repeated subdural hematoma, and rapid visual impairment. CONCLUSION: Endovascular embolization of TCCF is a safe and efficient method. Carefully selected operation time, operative approach, and materials are the essential factors to reach a best result.

Accidents, Traffic↗

Diagnosis and treatment of splanchnic artery aneurysms: a report of 57 cases.

OBJECTIVE: To evaluate the diagnosis and treatment of splanchnic artery aneurysms. METHODS: A retrospective study of our case records from 1957 to 1997 was carried out. Fifty-seven patients with splanchnic artery aneurysms were involved in this study with 62 aneurysms, including hepatic aneurysm (14 patients), gastric and pancreaticoduodenal aneurysm (13), splenic aneurysm (14), renal aneurysm (6), superior mesenteric aneurysm (3), inferior mesenteric aneurysm (1), truncus coeliacus (3) and epiploic arterial aneurysm (3). Among them, 5 patients had multiple aneurysms; 29 had massive bleeding of spontaneous rupture into the biliary tract (14 patients), the upper gastrointestinal tract (10), and the peritoneal and retroperitoneal cavity (5). RESULTS: Preoperative diagnosis was confirmed by arteriography in 37 patients, digital subtraction angiography (DSA) in 2, and magnetic resonance angiography (MRA) in 2. Among the 46 patients who underwent surgical intervention, 9 died. Splanchnic arterial embolotherapy was performed in 6 patients. CONCLUSION: Splanchnic artery aneurysms have a potential for rupture with life-threatening hemorrhage. Clinical assessment of these lesions before operation is very difficult. The most valuable examination is selective arteriography of the splanchnic artery (including DSA). Surgical treatment is a safe and effective procedure. Embolic therapy may be the method of choice for selected splanchnic artery aneurysms. Prognosis of this disorder depends on the anatomic location of aneurysms, primary disease and general condition of patients.

Adolescent↗

Non-invasive assessment of myocardial risk and infarct area in canine model of myocardial reperfusion by intravenous contrast echocardiography.

OBJECTIVE: To evaluate the newly developed perfluoropropene-filled echo-contrast agent (FCT-188) in non-invasive assessment of risk areas (RA) and infarct areas (IA) with intravenous myocardial contrast echocardiography (MCE) in canine model of ischemia followed by reperfusion. METHODS: Eight chest-opened Beagle dogs with a 90-minute ischemia followed by a 240-minute reperfusion were studied. MCE was performed after a bolus injection of FCT-188 (0.025 ml/kg, i.v.) into a superficial vein of the forelimb at baseline, 20 minutes after occlusion, and 4 h after reperfusion to non-invasively assess the left ventricular myocardium area (LVMA), myocardial ischemic risk area (RA), and infarct area (IA) in a short-axis view of left ventricle. The accuracy of detecting myocardial perfusion with intravenous MCE was further assessed by in vitro myocardial staining of the matched cross-sections. Both RA and IA were expressed as percent of LVMA. RESULTS: LVMA, RA, IA, and IA/RA ratio were accurately assessed by MCE (LVMA: 6.60 cm2 +/- 0.76 cm2; RA: 35.7% +/- 6.68%; IA: 21.0% +/- 13.2%; IA/RA: 60.3% +/- 31.4%; n = 7) as compared with those of the matched cross-section (LVMA: 6.81 cm2 +/- 0.73 cm2, P = 0.062; RA: 35.3% +/- 9.9%, P = 0.84; IA: 25.10% +/- 14.5%, P = 0.07; IA/RA: 68.0% +/- 22.2%, P = 0.28, respectively). There was a significant correlation of MCE-assessed IA/RA ratio and its corresponding pathologically determined finding in vitro (Y = 1.21 x -21.6, r = 0.73, P = 0.015). No significant changes of electrocardiogram (ECG), mean artery pressures (MAP), pulmonary artery pressures (PAP), and pulmonary artery wedge pressures (PAWP) were found between pre- and post-intravenous injection of FCT-188 at each time point. CONCLUSION: These indicate that FCT-188 can be used to assess risk areas and infarct areas accurately and non-invasively with intravenous MCE in the canine model of a 90-minute ischemia followed by a 240-minute reperfusion and might have potential significance for non-invasive assessment of myocardial reperfusion clinically.

Animals↗