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Biomedical subjects

Wei Zhu

Publications and source records attributed to Wei Zhu.

At least 145 records · Page 8Linked to original sources

Expression of recombinant human ICOS and in vitro characterization of its bioactivity on B lymphocytes.

Inducible costimulator (ICOS) is a novel costimulatory molecule expressed in activated T cell and has critical regulation effect on special immune response. In this study, the cDNA encoding human ICOS was cloned from activated tonsil cells via RT-PCR, and was expressed in E. coli on pET28 expression vector. The recombinant ICOS protein expressed from E. coli showed a molecular weight of 14 kD on SDS-polyacrylamide gel electrophoresis and was further confirmed by Western blot. In presence of IL-10, the purified rhICOS significantly increased in vitro B cell growth stimulated by pokeweed mitogen (PWM), and enhanced the secretion of IgG from B cells.

Antigens, Differentiation, T-Lymphocyte↗

Cyclic exercise induces anti-inflammatory signal molecule increases in the plasma of Parkinson's patients.

It has been known for many years that immune system alterations occur with Parkinson's disease (PD). Changes in lymphocyte populations in cerebrospinal fluid and blood, immunoglobulin synthesis, and cytokine and acute phase protein production have been observed in patients with PD. Hence, there is evidence for inflammation. In this report we demonstrate that cyclic exercise over months results in a significant increase in the rise of plasma anti-inflammatory signal molecules, such as interleukin-10 and adrenocorticotropin. Additionally, endogenous plasma morphine levels increase with the duration of the cyclic exercise protocol. Morphine is identified and quantified by high performance liquid chromatography coupled to electrochemical detection and nano electro-spray ionization double quadrupole orthogonal acceleration time of flight mass spectrometry. Proinflammatory cytokine, i.e., interleukin-1, interleukin-6, plasma levels did not increase. These results matched with those reported previously, demonstrating enhanced motor skills and mood elevation with this cyclic exercise protocol, suggest that this protocol induces the formation of anti-inflammatory signal molecules, which appear to be associated with alleviation of some of the clinical characteristics of PD.

Adrenocorticotropic Hormone↗

The value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications.

OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring normal orthotopic liver transplantation and postoperative complications. METHODS: Forty-one patients after orthotopic liver transplantation were examined by using color Doppler flow imaging to observe the hepatic blood flow and change of ultrasonography of the hepatic parenchyma and bile duct. The measured indexes included maximum blood flow velocity, time-average blood flow velocity (TAV), resistance index (RI) and diameter of the bile duct. RESULTS: Among 41 patients, 17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13 (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude single-phase serrated wave or negative biphasic wave of the hepatic vein, 9 (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct. Sonography showed disappearance of the hepatic artery blood flow around the portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the postoperative period. Slight dilatation of the intrahepatic bile duct was found in 3 (7.3%) of the 41 patients in the early postoperational period and it normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a visible dilatation of the intrahepatic bile duct, which was worsening gradually. The causes of bile duct dilatation included biliary stricture in 2 patients (10%), stone in 15 patients (75%) and others in 3 patients (15%). CONCLUSIONS: Color Doppler ultrasonography is valuable for monitoring normal liver transplantation and postoperative complications.

Bile Duct Diseases↗

Interventional therapy of malignant obstructive jaundice.

OBJECTIVE: To assess the short-term results of interventional therapy for malignant obstructive jaundice. METHODS: In 82 patients with malignant obstructive jaundice, hepatocellular carcinoma was detected in 10 patients, carcinoma of gallbladder in 14, hilar biliary carcinoma in 22, pancreatic carcinoma in 20, and hilar metastatic carcinoma in 16. Percutaneous transhepatic biliary internal and/or external drainage (PTBIED) was performed in 61 patients and percutaneous transhepatic insertion of biliary stent (PTIBS) in 21. RESULTS: The level of total serum bilirubin (TSB) was reduced in 71 patients and less markedly in others. The level of TSB of the 61 patients was reduced from 450.12+/-113.51 micromol/L before operation to 240.25+/-107.81 micromol/L and 90.91+/-101.72 micromol/L 1 and 2 weeks after operation respectively. The TSB level of the 21 patients was reduced from 410.53+/-98.13 micromol/L to 270.23+/-115.64 micromol/L and 105.43+/-97.85 micromol/L 1 and 2 weeks after operation, respectively. No significant difference was found in the effect between PTBIED and PTIBS. Short-term complications developed in 33 patients. Seven patients died 30 days after operation. CONCLUSION: Interventional therapy may be simple, safe and effective in the treatment of malignant obstructive jaundice.

Adult↗

Protective effects of alpha 1-antitrypsin on acute lung injury in rabbits induced by endotoxin.

OBJECTIVE: To investigate whether pretreatment with alpha(1)-antitrypsin (AAT) can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. METHODS: Thirty-two healthy adult New Zealand rabbits were anaesthetized, tracheotomized and mechanically ventilated. They were then randomly divided into four groups (n = 8): (1) Infusion of Escherichia coli endotoxin [Lipopolysaccharide (LPS) 500 microg/kg] without AAT (Group LPS). (2) Infusion of AAT 120 mg/kg at 15 minutes after LPS (Group LAV). (3) Infusion of AAT 120 mg/kg without endotoxin (Group AAT). (4) Infusion of saline 4 ml/kg as control (Group NS). Arterial blood gases, peripheral leukocyte counts and airway pressure were recorded every hour for eight hours. Physiologic intrapulmonary shunting (Qs/Qt) was measured every four hours. After eight hours, blood samples were collected for measurement of plasma concentration and activity of AAT. Then, the animals were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected for measurement of concentrations of total protein (TP), interleukin-8 (IL-8), tumor necrosis factor (TNF alpha, the activities of NE and AAT, total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC). In addition, the wet-to-dry lung weight ratio (W/D) was measured. RESULTS: The infusion of endotoxin induced decreases in arterial oxygen pressure (PaO(2)), peripheral leukocyte counts, total respiratory compliance (TLC) and the increases in peak pressure (P(peak)), Qs/Qt compared with the baseline values (P < 0.05). The increased plasma concentration but reduced activity of AAT was also found in contrast to that in Group NS (P < 0.05). In the BALF, the activity of AAT, TPL, DSPC/TPL were lower than those in Group NS (P < 0.05), but the concentrations of albumin, IL-8, TNF alpha, the activity of NE and the ratio of W/D were higher than those in Group NS (P < 0.05). The pretreatment of AAT attenuated the deterioration of oxygenation, the reduction of compliance and the deterioration of other physiological and biochemical parameters mentioned above. CONCLUSION: Pretreatment with AAT could attenuate endotoxin-induced lung injury in rabbits. Those beneficial effects of AAT might be due, in part, to reduction in the levels of mediators that could activate neutrophils, in addition to the direct inhibitory effect on neutrophil elastase.

Animals↗

[Effects of jing'an capsule on rat sperm quality].

OBJECTIVE: The effects of Jing'an capsule on the quality of rat sperm were studied to supply data for its safe clinical use. METHODS: Eighty SD male rats were evenly and randomly divided into three test groups and one control group. Then the test groups were continuously given Jing'an capsule at different dosages: 557.1 mg/kg, 5,571 mg/kg or 11,420 mg/kg and the control group was given starch (20 g/L). Sixty days later, one of the epididymides, the sperm density was made and the sperm motility and morphology were investigated. The data obtained were analyzed by ANOVA, chi 2 test and Kruskal-Wallis test. RESULTS: The sperm density, motility and morphology were variable at different dosages. Compared with the control, the sperm density increased significantly at the dosage of 557.1 mg/kg(P < 0.05), and a significant decrease was observed in the sperm density and motility (P < 0.05) at the dosage of 11,420 mg/kg. Although the rate of abnormal sperm morphology decreased at the dosage of 557.1 mg/kg and increased at the dosage of 5,571 mg/kg or 11,420 mg/kg compared with the control, there was no statistic significance(P < 0.05). CONCLUSIONS: A low dosage of Jing'an capsule might ameliorate the quality of sperm, while a high dosage could do damage to sperm.

Animals↗

Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase.

Transcriptional induction by interferons requires the tyrosine and serine phosphorylation of the STAT1 transcription factor as well as its amino-terminal arginine methylation. Here we show that arginine methylation of STAT1 controls the rate of STAT1 dephosphorylation by modulating its interaction with PIAS1 and the nuclear tyrosine phosphatase TcPTP. Inhibition of STAT1 arginine methylation, or mutation of STAT1 Arg-31, results in a prolonged half-life of STAT1 tyrosine phosphorylation. This effect appears to be mediated by an increased binding of PIAS1 to STAT1 in the absence of STAT1 arginine methylation and a concomitant decrease in the association of STAT1 with TcPTP. Furthermore, inhibitors of arginine methylation require the presence of PIAS1 to exert their negative regulatory effect on the dephosphorylation of STAT1.

Animals↗

Enhanced resting activity of the oral somatosensory cortex in obese subjects.

The cerebral mechanisms underlying excess food intake in obese subjects are poorly understood. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to assess differences in regional brain metabolism between obese and lean subjects at rest. Brain metabolic images were analyzed using statistical parameter maps. We found that obese subjects have significantly higher metabolic activity in the bilateral parietal somatosensory cortex in the regions where sensation to the mouth, lips and tongue are located. The enhanced activity in somatosensory regions involved with sensory processing of food in the obese subjects could make them more sensitive to the rewarding properties of food related to palatability and could be one of the variables contributing to their excess food consumption.

Adult↗

Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications.

Methylphenidate (Ritalin) is an effective drug in the treatment of attention deficit hyperactivity disorder. However, the doses required therapeutically vary significantly between subjects and it is not understood what determines these differences. Since methylphenidate's therapeutic effects are in part due to increases in extracellular DA secondary to blockade of dopamine transporters (DAT), the variability could reflect differences in levels of DAT blockade. Here we used PET to assess if for a given dose of methylphenidate the differences in DAT blockade account for the variability in methylphenidate-induced increases in extracellular DA. Ten healthy adult subjects were tested before and 60 min after oral methylphenidate (60 mg) with PET to estimate DAT occupancy (with [(11)C]cocaine as the radioligand) and levels of extracellular DA (with [(11)C]raclopride as the D2 receptor radioligand that competes with endogenous DA for binding to the receptor). Methylphenidate significantly blocked DAT (60 +/- 11%) and increased extracellular DA in brain (16 +/- 8% reduction in [(11)C]raclopride binding in striatum). However, the correlation between methylphenidate-induced DAT blockade and DA increases was not significant. These results indicate that for a given dose of methylphenidate, individual differences in DAT blockade are not the main source for the intersubject variability in MP-induced increases in DA. This finding suggests that individual differences in response to MP are due in part to individual differences in DA release, so that for an equivalent level of DAT blockade, MP would induce smaller DA changes in subjects with low than with high DA cell activity.

Administration, Oral↗

Cold stress alters Mytilus edulis pedal ganglia expression of mu opiate receptor transcripts determined by real-time RT-PCR and morphine levels.

Previous pharmacological, biochemical and molecular evidence prove that mu-subtype opiate receptors and opiate alkaloids, i.e. morphine, are present in the ganglionic nervous system of the mollusk Mytilus edulis (bivalve). We now present molecular evidence on the effect of rapid temperature changes on mu opiate receptor expression and morphine levels. Using primers, a labeled Taq-Man probe derived from the human neuronal mu1 opiate receptor, and real-time RT-PCR to measure the expression of mu transcripts from Mytilus pedal ganglia, we observe, in animals placed in cold water from room temperature, an enhanced morphine and morphine 6 glucuronide level in addition to a decrease in mu opiate receptor gene expression. This study provides further evidence that mu-type opiate receptors and morphine are expressed in mollusk ganglia and appear to be involved in physiological processes responding to thermal stress.

Animals↗

Changes in brain functional homogeneity in subjects with Alzheimer's disease.

Imaging studies have reported marked reductions in brain glucose metabolism in Alzheimer's Disease (AD). However, less is known about disruptions in the patterns of brain metabolic activity. Here we questioned whether AD affects the patterns of homogeneity/heterogeneity in brain metabolism. PET images of 35 AD subjects were compared with those of 35 controls. A template was applied to extract a cortical rim, which was partitioned into 990 contiguous regions. Estimates of metabolic homogeneity were obtained using the coefficient of variation (CV). The CV of the entire cortex was found to be significantly larger in AD, suggesting increased heterogeneity at the whole brain level. In contrast, regional CV was significantly lower in AD in temporal and parietal cortices, which were the regions that along with the precuneus had the largest metabolic decrements, though the precuneus had increased CV. The enhanced heterogeneity for the global cortical pattern most likely reflects variability in the degree of pathology among brain regions as well as neuroanatomical disconnection. The enhanced homogeneity in parietal and temporal cortices is likely to reflect loss of regional differentiation (i.e. macrocolumnar disorganization). The enhanced CV in precuneus, despite its marked reductions in metabolism, suggests that increases in regional homogeneity in parietal and temporal cortices are not a mere reflection of the decrement in metabolism.

Aged↗

Regulation of fetal versus embryonic gamma globin genes: appropriate developmental stage expression patterns in the presence of HS2 of the locus control region.

The gamma genes provide the major contribution to beta-like globin chain production in the fetal liver of humans. However, the expression of gamma genes in the fetus is a recent evolutionary trend seen only in the primate lineage. In a previous study, it was shown that galago and human gamma genes retain their characteristic stage-specific expression patterns in transgenic mice (galago gamma is expressed exclusively in the embryo, whereas human gamma is expressed in the fetus). In that experiment, human and galago gamma genes were linked to hypersensitive site 3 (HS3) of the locus control region. To rule out the possibility that HS3 is required for these differential expression profiles, additional transgenic lines were tested in which human or galago gamma genes were linked to HS2. Once again, the galago gamma gene was embryonic and the human gamma gene was fetal, indicating that the stage specificity of these genes is driven by elements located within the 4-kb fragments that contain the human and galago gamma genes proper.

Age Factors↗

Effects of estrogen on cardiac electrophysiology in female mice.

INTRODUCTION: Understanding the molecular mechanisms that underlie gender- and hormonal-related differences in susceptibility to cardiac arrhythmias has been hampered by the lack of a suitable animal model. We examined the effect of hormonal status on the electrophysiologic (EP) properties of the mouse heart in an in vivo, closed chest model. METHODS AND RESULTS: Fifty-three female C57/J mice aged 10 to 12 weeks were studied. Thirty-six mice underwent bilateral ovariectomies; 18 received estrogen (OVX+E) and 18 received placebo (OVX). Seventeen female mice underwent only sham surgery. All animals underwent in vivo EP studies. Select EP parameters were measured after quinidine treatment. Data were analyzed by a blinded observer. Compared with the intact female mice, the PR and AH intervals were significantly shorter in the OVX mice, and these parameters normalized with estrogen replacement (PR = 45.9+/-4.5 msec in the intact mice, 42.1+/-4.3 msec in the OVX group, and 46.9+/-3.5 msec in the OVX+E group, P < 0.005; AH = 36.5+/-4.9 msec in the intact mice, 34.4+/-4.7 msec in the OVX group, and 38.8+/-2.7 msec in the OVX+E group, P = 0.03). The right ventricular effective refractory period was significantly shorter in the OVX mice versus the intact mice, and this also normalized with estrogen replacement. Hormonal status did not significantly affect any other EP variable, including QT interval. CONCLUSION: In female mice, estrogen prolongs AV nodal conduction and the right ventricular effective refractory period. Taken together, these data suggest that hormonal status affects aspects of cardiac EP function. Future application of this mouse model will be helpful in determining the molecular pathways that mediate hormonal differences in cardiac EP.

Analysis of Variance↗

Gene structure identification with MyGV using cDNA evidence and protein homologs to improve ab initio predictions.

UNLABELLED: MyGV is an application to visualize (potentially genome-scale) gene structure annotation and prediction. The output of any external gene prediction program can be easily converted to a generalized format for input into MyGV. The application displays all input simultaneously in graphical representation, with a toggle option for a text-based view. Zooming capabilities allow detailed comparisons for specific genome locations. The tool is particularly helpful for refinement of ab initio predicted gene structures by spliced alignment with cDNA or protein homologs. AVAILABILITY: The program was written in Java and is freely available to non-commercial users by electronic download from http://bioinformatics.iastate.edu/bioinformatics2go/MyGV.

Animals↗

Identification of a nuclear Stat1 protein tyrosine phosphatase.

Upon interferon (IFN) stimulation, Stat1 becomes tyrosine phosphorylated and translocates into the nucleus, where it binds to DNA to activate transcription. The activity of Stat1 is dependent on tyrosine phosphorylation, and its inactivation in the nucleus is accomplished by a previously unknown protein tyrosine phosphatase (PTP). We have now purified a Stat1 PTP activity from HeLa cell nuclear extract and identified it as TC45, the nuclear isoform of the T-cell PTP (TC-PTP). TC45 can dephosphorylate Stat1 both in vitro and in vivo. Nuclear extracts lacking TC45 fail to dephosphorylate Stat1. Furthermore, the dephosphorylation of IFN-induced tyrosine-phosphorylated Stat1 is defective in TC-PTP-null mouse embryonic fibroblasts (MEFs) and primary thymocytes. Reconstitution of TC-PTP-null MEFs with TC45, but not the endoplasmic reticulum (ER)-associated isoform TC48, rescues the defect in Stat1 dephosphorylation. The dephosphorylation of Stat3, but not Stat5 or Stat6, is also affected in TC-PTP-null cells. Our results identify TC45 as a PTP responsible for the dephosphorylation of Stat1 in the nucleus.

Animals↗

Localization of nitric oxide synthases during fracture healing.

Previously, we have reported that nitric oxide synthases (NOSs), which generate NO, modulate fracture healing. However, the cellular sources of the NOS isoforms during the course of fracture healing have not been studied systematically. The purpose of this study was to localize the cellular distribution of NOS isoforms (inducible NOS [iNOS], endothelial NOS [eNOS], and neuronal NOS [bNOS]) by in situ hybridization and immunohistology after femoral fractures in rats. The iNOS signal was detected during the initial stages (on day 4 and day 7) of fracture healing in 52 +/- 2% (mean +/- SE, n = 7) of cells within the intramembranous region, along the edge of the periosteal callus. The iNOS signal in callus cells declined to an undetectable level on day 14. eNOS was detected during the middle stages (on day 7 and day 14) of fracture healing in cells lining the blood vessels and also in 49 +/- 3% of cells in the chondral region. The bNOS signal was found to be increased at the later stages (day 14 and day 21) of fracture healing in 51 +/- 3% of cells at the junction between fibrous tissue and cartilage within the fibrochondral region. In summary, the,expression of NOS isoforms during fracture healing was time dependent and cellular distinctive.

Animals↗

Tonal nitric oxide and health--a free radical and a scavenger of free radicals.

Basal/tonal nitric oxide (NO) production helps maintain particular microenvironments, i.e., vascular. Besides NO's function in controlling the activation state of various tissues such as immune cells, its presence appears to modulate other free radical levels, i.e., H2O2, in these same tissues and indeed these processes may be one and the same. Thus, by being a free radical, along with the ability to scavenge other free radicals, NO is placed in a pivotal regulatory position. We surmise that in the absence of adequate NO release other free radicals may go 'unchecked' and, therefore, initiate tissue damage. Furthermore, under these circumstances, proinflammatory events will occur due to heightened cell sensitivity and a diminished control of NF-kappaB. In an excess situation, and one without an appropriate circumstance, i.e., microbial action, NO may become the harmful agent. Hence, balancing basal NO production in body compartments may represent a fundamental process in maintaining general, long-term health.

Animals↗

Tonal nitric oxide and health: anti-bacterial and -viral actions and implications for HIV.

Nitric oxide has been shown to have important physiological regulatory roles, i. e, vasodilation, neurotransmitter release, etc. Now, we review its role as an antibacterial and antiviral agent. Nitric oxide has also been identified as an important factor in the development of non-specific immunity. And accordingly, nitric oxide synthase (NOS), the catalytic enzyme producing nitric oxide, is a key element in the protective activities of nitric oxide. The expression of inducible (i) NOS is regulated by cytokines. iNOS-derived nitric oxide was found to contribute to both early and late phases of antibacterial activity. Enzymes, such as proteases (reverse transciptases, and ribonucleotide reductase, etc.) containing cysteine residues, appear to be targets for nitric oxide nitrosylation, as well as viral-encoded transcription factors that are involved in viral replication. It would appear that this multifunctional signaling molecule is not only involved with signaling between cells, it also appears to maintain the immediate environment free of microbial agents.

Animals↗