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Biomedical subjects

P Wu

Publications and source records attributed to P Wu.

At least 109 records · Page 6Linked to original sources

The inhibitory guanine nucleotide-binding protein Gi2alpha induces and potentiates adipocyte differentiation.

The present study further elucidates the involvement of the alpha-subunit of the GTP-binding protein Gi2 in the differentiation of murine 3T3-L1 cells. Control and vector-transfected cells attained a fully differentiated adipocyte phenotype showing ample lipid droplets. Cells expressing wild type (WT)-Gi2alpha or the constitutively active R179E-Gi2alpha, however, became enlarged, less confluent, and produced large amounts of lipids. Differentiation consistently increased the triglyceride (TAG) content in control cells. In both WT-Gi2alpha and R179E-Gi2alpha clones, a marked increase in TAG could be detected even prior to insulin/dexamethasone/isobutyl methylxanthine exposure. The activity of palmitoyl-CoA synthetase (PCS) and glycerophosphate acyltransferase (GPAT) also increased upon differentiation. WT-Gi2alpha and R179E-Gi2alpha overexpression also enhanced PCS and GPAT activities even before differentiation medium was added. The total amount of phospholipids (PL) generally increased upon differentiation; however, pre- and postdifferentiation values were insignificantly different in cells expressing WT-Gi2alpha and R179E-Gi2alpha. Differentiation altered the PL profile with a relative shift from phosphatidylcholine and phosphatidylethanolamine to phosphatidylinositol (PI) in differentiated cells. Finally, differentiation yielded a general increase in the activity of basal PI-phospholipase-C activity. Again, cells expressing WT-Gi2alpha and R179E-Gi2alpha demonstrated elevated enzyme activity and enhanced second messenger accumulation subsequent to differentiation. In summary, cells with the R179E-mutants of Gi2alpha exhibited stimulated lipid turnover and accumulation in both undifferentiated and differentiated cells.

3T3 Cells↗

Effects of cholic acid on blood pressure and production of vascular aldosterone and corticosterone.

The aims of this study were to search for the role of cholic acid in the regulation blood pressure of humans and rats and to investigate the effects of cholic acid on the production of vascular aldosterone and corticosterone in rats. Levels of serum total bile acids were measured by an enzymic spectrophotometeric method in normal controls, patients with essential hypertension, and in Wistar and spontaneously hypertensive rats. Levels in essential hypertension (7.3+/-3.4 micromol/l, n = 88) were higher than those of normal subjects (4.9+/-3.3 micromol/l, n = 86), and levels in SHR (13.9+/-3.8 micromol/l, n = 11) were slightly increased, but not significantly different from Wistar rats (10.4+/-5.1 micromol/l, n = 12). Male Wistar rats received cholic acid 80 mg/kg/day, orally, for 30 days, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with cholic acid compared to control rats. Mesenteric artery perfusion ex vivo was performed, and pressor responses to norepinephrine were determined in Wistar rats. The pressor responses to norepinephrine in mesenteric arteries treated with cholic acid were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high performance liquid chromatography, and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with cholic acid. Reverse transcriptase polymerase chain reaction showed that cholic acid inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenases↗

Chronic ethanol exposure alters MK-801 binding sites in the cerebral cortex of the near-term fetal guinea pig.

The mechanism of ethanol central nervous system (CNS) teratogenesis, resulting from chronic maternal ingestion of high-dose ethanol during pregnancy, is not clearly understood. One of the target sites for ethanol-induced damage in the developing brain is the cerebral cortex. It has been proposed that chronic prenatal ethanol exposure alters NMDA receptors in the developing cerebral cortex. To test this hypothesis, timed pregnant guinea pigs were administered one of the following oral treatments throughout gestation: 4 g ethanol/kg maternal body weight/day; isocaloric sucrose/pair-feeding; water; or no treatment (ad lib). Near-term fetuses were studied at gestational day (GD) 63 (term, about GD 68). This ethanol regimen produced a maternal blood ethanol concentration of 66+/-4 mM (304+/-19 mg/dl) at 1 h after the daily dose on GD 58. The chronic ethanol regimen decreased near-term fetal body weight (12-26% decrease), brain weight (23% decrease), and cerebral cortical weight (21% decrease), compared with the isocaloric sucrose/pair-feeding, and combined water/ad lib experimental groups. Saturation analysis of near-term fetal cerebral cortical membranes using a [3H]MK-801 radioligand binding assay demonstrated a decreased affinity and increased number of MK-801 binding sites for the chronic ethanol regimen compared with the control treatments. These data support the suggestion that upregulation of NMDA receptors in the cerebral cortex after chronic prenatal ethanol exposure could lead to NMDA receptor-mediated excitotoxicity in this brain region.

Animals↗

Functional assessment of the shoulder following latissimus dorsi muscle donation in the handicapped.

The latissimus dorsi muscle, one of the largest muscles in the human body, has gained widespread popularity in microsurgical reconstruction. Because the latissimus serves to adduct and medially rotate the upper extremity, caution in its use has been advocated in handicapped and non-ambulatory patients, although a paucity of information exists in the literature. The purpose of this reported project was to determine whether the loss of the latissimus dorsi could be documented objectively or subjectively, either in the preoperative condition or post-harvesting in the handicapped patients. Two paraplegic patients were studied. Results indicate a lack of objective functional deficit; this includes both the nerve-blocked state and the postoperative condition. In addition, both patients failed to demonstrate the need to change any activities of daily living. This evidence suggests that, although careful decisions must be made on a case-by-case basis, the use of the latissimus dorsi muscle is not necessarily contraindicated in this group of patients.

Abdominal Neoplasms↗

Perinatal brain iron deficiency increases the vulnerability of rat hippocampus to hypoxic ischemic insult.

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain.

Animals↗

Depressive and disruptive disorders and mental health service utilization in children and adolescents.

OBJECTIVE: To examine the relationship of depressive and disruptive disorders with patterns of mental health services utilization in a community sample of children and adolescents. METHOD: Data were from the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. The sample consisted of 1,285 child (ages 9-17 years) and parent/guardian pairs. Data included child psychopathology (assessed by the Diagnostic Interview Schedule for Children), impairment, child need and use of mental health services, and family socioeconomic status. RESULTS: After adjusting for potential confounding factors, disruptive disorder was significantly associated with children's use of mental health services, but depressive disorder was not. For school-based services, no difference was found between the 2 types of disorders. Parents perceived greater need for mental health services for children with disruptive disorders than for those with depression. Conversely, depression was more related to children's perception of mental health service need than was disruptive disorder. CONCLUSIONS: The findings highlight the need for more effective ways to identify and refer depressed children to mental health professionals, the importance of improving school-based services to meet children's needs, and the necessity to better educate parents and teachers regarding the identification of psychiatric disorders, especially depression.

Adolescent↗

Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes.

There are four different genes encoding the cAMP-specific phosphodiesterase (PDE4) isozymes (A, B, C, and D). cAMP has been the only agent known to induce PDE4 gene expression. In the present study, we demonstrate, for the first time, that lipopolysaccharide (LPS) significantly and selectively stimulated PDE4B mRNA production in human monocytes. The LPS stimulation occurred very rapidly (in 30-45 min) and in a dose-dependent manner (0.01-100 ng/ml). We also demonstrate that LPS induction of PDE4B mRNA expression was inhibited strongly by interleukin (IL)-10. The inhibition with IL-10 was dose-dependent (0.1-10 ng/ml). IL-4 also inhibited the LPS induction, but to a lesser extent than IL-10. PDE4B mRNA expression was also stimulated by dibutyryl-cAMP. Interestingly, unlike LPS induction, the dibutyryl-cAMP induction of PDE4B mRNA expression was not inhibited by IL-10. By performing nuclear run-on and mRNA stability assays, we demonstrate further that IL-10 inhibited LPS-stimulated PDE4B mRNA synthesis by abolishing the gene transcription rather than by enhancing mRNA degradation. The present study suggests that PDE4B, as the only LPS-inducible PDE4 subtype, may be an appropriate target for discovering anti-inflammatory drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils.

The type 4 phosphodiesterase (PDE4) is the predominant PDE isozyme in various leukocytes and plays a key role in the regulation of inflammatory cell activation. There are four PDE4 subtypes (A, B, C, and D), and within each subtype, there are multiple variants. Very recently, we found in monocytes that PDE4B gene expression is selectively induced by lipopolysaccharide (LPS) and that the induction is inhibited by interleukin (IL)-10 and IL-4. In this study, we show that the PDE4B gene is constitutively expressed in neutrophils and that this expression remains unaffected by LPS or IL-10. PDE4B is the predominant subtype in neutrophils and in unstimulated or LPS-stimulated monocytes, and in these cells, the PDE4B2 variant is the only detectable molecular species of PDE4B. Therefore, PDE4B2 is the predominant PDE isoform in human neutrophils and monocytes, and its expression is regulated differently by these two cell types. Furthermore, leukocytes are the most dominant source of PDE4B2, suggesting that PDE4B2 is a relatively specific target for discovering anti-inflammatory drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Prospective comparison of whole-blood- and plasma-based hepatitis C virus RNA detection systems: improved detection using whole blood as the source of viral RNA.

We previously demonstrated that whole blood contains significantly more hepatitis C virus (HCV) RNA than plasma. To validate the whole-blood-based HCV RNA detection method, a prospective comparison of HCV RNA detection in whole blood and plasma from 50 patients with chronic liver disease was undertaken. Whole-blood and plasma aliquots were independently tested for HCV RNA by reverse transcriptase (RT) PCR assay, and plasma was tested by the Roche Amplicor assay. HCV RNA was detected in 35 of 50 (70%) whole-blood samples by RT-PCR but in only 26 of 50 (52%) plasma samples tested by the Amplicor assay (P < 0.01). HCV RNA was detected in 85% of HCV antibody-positive patients by the whole-blood method compared with 74% of plasma samples by the Amplicor method. The five HCV antibody-positive subjects who were negative by whole-blood-based RT-PCR assay were all receiving interferon therapy and had normal transaminases at the time of testing. HCV RNA was detected in 38% of HCV antibody-negative subjects by the whole-blood-based RT-PCR assay compared with 6.25% of these patients by the Amplicor assay (P < 0. 05). There were nine samples in which HCV RNA was detected in whole blood but the Amplicor test was negative. Eight of the nine RNAs prepared from these whole-blood samples tested positive in the Amplicor assay, thus confirming the specificity of our results. This study demonstrates that whole-blood-based HCV RNA detection is more sensitive than currently available commercial tests and that whole-blood RNA is suitable for use in commercial assays.

Cloning, Molecular↗

Effects of glycyrrhizin on production of vascular aldosterone and corticosterone.

This study is to confirm the role of glycyrrhizin on blood pressure and to test the effects of glycyrrhizin on production of vascular aldosterone and corticosterone in rats. Male Wistar rats received glycyrrhizin (Sigma) 200 mg/kg/day p.o. for 5 weeks, and blood pressure was monitored by a pressure transducer. Systolic blood pressure significantly increased in Wistar rats treated with glycyrrhizin compared to that without glycyrrhizin. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column, used for reverse-phase high-performance liquid chromatography, and measured for both aldosterone and corticosterone by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in perfusate from arteries treated with glycyrrhizin. RT-PCR showed that glycyrrhizin inhibited the expression of 11beta- HSD2 and CYP11B2 mRNA in mesenteric arteries. These results confirm that glycyrrhizin is able to induce hypertension, and provide evidence that it inhibits the transcriptions of both 11beta-HSD2 and CYP11B2 in the vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenases↗

Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes.

Regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis. Activation of the complex promotes disposal of glucose, whereas inactivation conserves substrates for hepatic glucose production. Starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex. The present study shows that these metabolic conditions induce a large increase in the expression of PDK4, one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues, in the mitochondria of gastrocnemius muscle. Refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in PDK4 protein in gastrocnemius muscle mitochondria. Starvation and diabetes also increased the abundance of PDK4 mRNA in gastrocnemius muscle, and refeeding and insulin treatment again reversed the effects of starvation and diabetes. These findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions. It was further found that feeding rats WY-14,643, a selective agonist for the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), also induced large increases in pyruvate dehydrogenase kinase activity, PDK4 protein, and PDK4 mRNA in gastrocnemius muscle. Since long-chain fatty acids activate PPAR-alpha endogenously, increased levels of these compounds in starvation and diabetes may signal increased expression of PDK4 in skeletal muscle.

Animals↗

Aldosterone biosynthesis in extraadrenal tissues.

OBJECTIVE: To determine whether extraadrenal tissues synthesize aldosterone in addition to vascular tissue and brain. METHODS: Ex vivo kidney perfusion was performed in normal Wistar rats, ACEI pretreated and adrenalectomized rats prior to the perfusion experiment. After equilibration for 30 minutes, 120 ml of perfusate was collected and subjected to reverse-phase HPLC and then aldosterone was measured by RIA. By RT-PCR and Southern blot the expression of aldosterone synthase gene-CYP11B2 mRNA was studied in both kidney tissue and cultured renal tubular epithelial cell, lung and liver tissues. In situ hybridization was used to identify the cell types of liver and lung expressing CYP11B2 mRNA. RESULTS: Production of aldosterone in the kidney perfusate was not changed in adrenalectomized rats although it was decreased in the group pretreated with ACEI perindopril. By RT-PCR and Southern blot the expression of CYP11B2 mRNA was demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We have also identified CYP11B2 mRNA expression in liver and lung of rats. In situ hybridization showed that CYP11B2 mRNA was localized in the endoplasm of liver fat-storing cell (Ito cells) and type II alveolar cells of lung. CONCLUSIONS: These studies prove that kidney, liver and lung are able to produce aldosterone.

Aldosterone↗

[Intervention treatment with percutaneous trans-arterial implantation of port-catheter system for advanced cancer patients].

OBJECTIVE: To examine the feasibility, clinical efficacy and complications of percutaneous trans-arterial implantation of port-catheter system (PCS) for intervention treatment of advanced malignant tumors. METHODS: Fifty-three cases with advanced malignant tumors were treated by infusion of chemotherapeutic drugs and/or chemo-embolization through PCS. Patients received one course of treatment every 4-6 weeks. RESULTS: In this series of treated patients, the survival period was 5-18 months with a mean survival time of 13.5 months. The overall response rate (CR + PR) was 62.3%. Detachment of the catheter tip occurred in 2 cases. Disruption of wound after removal of stitches occurred in one case and skin necrosis at the port occurred in another. CONCLUSION: Long-term intervention treatment with PCS is simple and safe. It is a treatment of choice for patients with advanced malignancy.

Adult↗

[The value of spiral CT in CT arterial portography and CT hepatic arteriography].

OBJECTIVE: To evaluate the usefulness of spiral CT in CT arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHODS: The CTAP and CTHA manifestations in 50 patients with small hepatocellular carcinoma (< 3 cm in diameter) were analyzed and compared with those in bi-phase enhanced CT. RESULTS: The detection rate of CTAP and CTHA was 92.2% and 90.1%, respectively. They could reveal tumors of 0.2 cm-0.5 cm in diameter. Both CTAP and CTHA gave false-positive findings, such as perfusion defects in 13.0% of CTAP and non-pathologic enhancement in 19.1% of CTHA. CONCLUSION: With the use of spiral CT technique, the quantity of contrast material administrated in CTAP and CTHA can be considerably reduced, and the quality of CT images significantly improved. The detection rate of CTAP and CTHA is higher than that of biphase enhanced CT. Simultaneous use of both procedures may help decrease the false-positive rate, and increase the sensitivity of diagnosis for small hepatocellular carcinoma.

Adult↗

[Dynamic enhanced spiral CT characteristics of recurrent nasopharyngeal carcinoma and radiofibrosis].

OBJECTIVE: To study the characteristics of dynamic enhanced density-time curves of recurrent nasopharyngeal carcinoma(RNPC) and radiofibrosis(RF) in spiral CT. METHODS: Fifty cases of RF and 46 cases of RNPC were examined both before and after contrasting in spiral CT. The CT values of the regions of interest (ROI) at various acquisition time (0, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, and 300 sec after the beginning of the contrast injection) were collected. The difference in CT value of various acquisition time was analysed statisticaly and the dynamic enhanced density-time curves were established. RESULTS: The typical curve in RF group was a slowly ascending-slowly descending one. Its peak CT value as seen at 210 sec postcontrast and measured 60.1 +/- 2.57 Hu. That of the RNPC was of rapidly ascending-slowly ascending-slowly descending one. Its peak CT valne was seen at 150 sec postcontrst and measured 75.4 +/- 7.2 Hu. The differences of CT values were significant between RNPC and RF from 40 to 300 sec postcontrast (P < 0.001). CONCLUSION: The different characteristics of the dynamic enhanced desity-time curves and CT values of the ROI may provide important informations for differential diagnosis of RNPC and RF.

Adult↗

[Effects of glycyrrhizin on blood pressure and its mechanisms].

OBJECTIVE: To confirm the action of glycyrrhizin on blood pressure by inhibiting the activity of 11beta-hydroxysteroid dehydrogenase type II (11betaHSD 2) and to test its mechanism. METHODS: Male Wistar rats and SHRs (weighing 150 - 220 g) were given glycyrrhizin (Sigma) 200 mg/kg/day, orally for 5 weeks and 3 months. The blood pressure was monitored by means of a pressure transducer connected to a polygraph and recorded. Histological pathological changes of the nutrient arteries of the heart and aorta were studied with light microscope. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The perfusate from the mesenteric arteries was collected and used for reverse phase high performance liquid chromatography to measure aldosterone and corticosterone level. RT-PCR was used to measure the expression of 11betaHSD 2 and aldosterone synthase (CYP11B2) mRNA. RESULTS: The results showed that the systolic blood pressure was significantly increased in Wistar rats treated with glycyrrhizin compared with those not treated. Hyperplasia of smooth muscle cells and hypertrophy in arterioles were observed under microscope. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The level of aldosterone was decreased but that of corticosterone was increased in perfusate treated with glycyrrhizin. RT-PCR showed that glycyrrhizin inhibited the expression of 11beta-HSD2and CYP11B2 mRNA in aorta. CONCLUSION: These results confirm that glycyrrhizin is able to induce hypertension. There is evidence that it inhibits the enzymes of both 11beta-HSD2 and CYP11B2 in vasculature and leads to higher corticosterone and lower aldosterone production in vessels as well as an increase in vascular responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenases↗

[A comparative study of different neuromuscular pedicle embedded in posterior cricoarytenoid muscle].

OBJECTIVE: To compare the results and effect of different neuromuscular pedicle (NMP) embedded in posterior cricoarytenoid muscle. METHOD: In 22 dogs, combined vocal cord paralysis models were made. The first group (10 dogs) were embedded by sternohyoid muscle pedicle of ansa cervicalis, the second (10 dogs), accessory sternocleidomastoid neuromuscular pedicle, the third (2 dogs), control group. RESULT: Evaluation was possible in 19 dogs. Reinnervation of the left posterior cricoarytenoid muscle occurred in 17 dogs following NMP. Return of spontaneous abduction in the operated side with NMP was noted after 4 months postoperatively. There was little difference between the two NMP groups. CONCLUSION: NMP was successful to reinnervate the posterior cricoarytenoid muscle.

Accessory Nerve↗