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Biomedical subjects

Shu Zhang

Publications and source records attributed to Shu Zhang.

At least 55 records · Page 3Linked to original sources

Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study.

BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. METHODS: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma ( z = -2.444; P = .015) and asthma severity ( z = -2.615; P = .009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores ( P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.

Adult↗

Elicitation of immunity in mice after immunization with the S2 subunit of the severe acute respiratory syndrome coronavirus.

The S2 domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein is responsible for fusion between virus and target cell membranes, and is expected to be immungenic. In this study, we investigated the immune responses against the S2 subunit in BALB/c mice, which were vaccinated either with plasmid DNA encoding the S2 domain (residues 681-1120), the recombinant S2 fragment (residues 681-980) in incomplete Freund's adjuvant, or with inactivated SARS-CoV. The increased number of specific cytotoxic cells (CTLs) and the high titer of specific antibody showed stimulation of both arms of the immune system in these groups. The shift in cytokines suggested that Th1-polarized immune response was induced by plasmid pCoVS2, meanwhile the Th2-dominant response was induced by recombinant S2 fragment and inactivated vaccine. However, the titer of neutralizing antibodies was only detectable in mice immunized with inactivated virus, but not with pCoVS2 plasmid. Taken together, the S2 domain could induce specific cellular immune response and a high level of total IgG but little neutralizing antibodies against infection by SARSCoV.

Animals↗

Protective effects of low respiratory frequency in experimental ventilator-associated lung injury.

OBJECTIVE: To determine whether ventilator-associated lung hyperinflation injury can be attenuated by a reduction in respiratory frequency. DESIGN: Prospective comparative laboratory investigation. SETTING: University medical center research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Eight groups of isolated, perfused rat lungs were exposed to cyclic ventilation at different respiratory frequencies and tidal volumes. Each group of six to eight lung preparations was assigned to one of four respiratory frequencies (10, 20, 40, or 80 breaths/min) and one of two tidal volumes (5 or 20 mL.kg). Measurement of capillary filtration coefficient (Kf,c), a sensitive index of lung microvascular permeability and injury, was made at baseline and at 30, 60, and 90 mins of the experimental conditions. MEASUREMENTS AND MAIN RESULTS: Lungs exposed to 5 mL.kg tidal volume had no elevation in Kf,c at any time point regardless of respiratory frequency. Lungs exposed to 20 mL. kg tidal volume and a respiratory frequency of 80 had significant elevations in Kf,c at all times after baseline compared with lungs exposed to respiratory frequencies of 10, 20, or 40 (0.14 +/- 0.03, 0.16 +/- 0.02, 0.31 +/- 0.05 vs. 0.76 +/- 0.16). Furthermore, the Kf,c at 90 mins was significantly higher than permeability at baseline in this group (1.53 +/- 0.45 vs. 0.12 +/- 0.02 mL.min.cm H2O.100 g of lung tissue). CONCLUSIONS: Reduction in respiratory frequency to values much lower than normal ameliorated experimental ventilator-induced hyperinflation lung injury as determined by pulmonary capillary filtration coefficient.

Animals↗

Synergistic effects of matrine and 5-fluorouracil on tumor growth of the implanted gastric cancer in nude mice.

OBJECTIVE: To investigate the inhibitive effects of matrine and 5-fluorouracil (5-FU) on the growth of human gastric adenocarcinoma cell line SGC-7901 when transplanted into nude mice and to investigate the bone marrow toxicity of these compounds. METHODS: 50 mg/kg and 100 mg/kg matrine with 50 mg/kg 5-FU, and 50 mg/kg matrine only, 50 mg/kg 5-FU only were intraperitoneally injected to observe their inhibitive effects by calculating the relative tumor volume (RTV) and tumor inhibition rates (IR%) as shown by the number of nucleated cells and bone marrow cell colony culture. RESULTS: The tumor inhibitive effect of the combined 100 mg/kg matrine and 50 mg/kg 5-FU group was stronger than that of the combined 50 mg/kg matrine and 50 mg/kg 5-FU groups (P < 0.05), and were also much stronger than that of the control group (50 mg/kg matrine only, 50 mg/kg 5-FU only, P < 0.01). As for the bone marrow inhibition effect, there was no significant statistical difference between the combination group and 5-FU alone group. In the cultured bone marrow cell colony, exuberant growth was seen in the combination group, but not in the control group. CONCLUSIONS: The inhibitive effect of combined matrine and 5-FU on the growth of transplanted human gastric cancer in nude mice is superior to that of matrine or 5-FU alone. Combined matrine and 5-FU can increase the inhibitive effect on proliferative hemopoietic bone marrow cells in nude mice and does not affect the resting bone marrow stem cells.

Adenocarcinoma↗

Preparation and characterization of a novel pH-sensitive ion exchange resin.

Methylacrylic acid/styrene cross-linked with divinylbenzene is a novel pH-sensitive ion exchange resin. Microspheres of this resin were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The microspheres showed a pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with salbutamol sulfate and the drug-release characteristics were studied under both simulated gastric and intestinal pH conditions. The results obtained showed that the drug release also depended on the pH of the release media.

Hydrogen-Ion Concentration↗

[Effects of high +Gx during simulated spaceship emergency return on learning and memory in rats].

OBJECTIVE: To observe the effects of high +Gx during simulated spaceship emergency return on learning and memory in rats. METHOD: Thirty two male SD rats were randomly divided into control group, 7 d simulated weightlessness group, +15 Gx/180 s group and +15 Gx/180 s exposure after 7 d simulated weightlessness group, with 8 rats in each group. The changes of learning and memory in rats were measured after stresses by means of Y-maze test and step-through test. RESULT: In Y-maze test, as compared with control group, percentage of correct reactions decreased significantly (P<0.01) and reaction time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at all time after stress; as compared with +15 Gx group or simulated weightlessness group, percentage of correct reactions decreased significantly (P< 0.05) and reaction time increased significantly (P< 0.05) immediately after stress. In step-through test, as compared with control group, total time increased significantly (P<0.01) in hypergravity after simulated weightlessness group at 1 d after stress; latent time decreased significantly (P<0.01) and number of errors increased significantly (P< 0.01) at all the time after stress. As compared with +15 Gx group, total time increased significantly (P<0.05) immediately, 1 d after stress. As compared with simulated weightlessness group, total time and number of errors increased significantly (P<0.05) immediately after stress. CONCLUSION: It is suggested that +15 Gx/180 s and simulated weightlessness may affect the ability of learning and memory of rats. Simulated weightlessness for 7 d can aggravate the effect of +Gx on learning and memory ability in rats.

Animals↗

Changes of hippocampus somatostatin and learning ability in rats after +Gz exposure.

OBJECTIVE: To investigate changes of learning ability and somatostatin (SS) changes after positive acceleration (+Gz) exposures. METHOD: Eighty male SD rats were randomly divided into 3 groups: control group (Con), +6 Gz/3 min group (+6 Gz), and +10 Gz/3 min group (+10 Gz), 8 rats in each group. Changes of learning ability in rats were observed at 0 d, 2 d, 4 d and 6 d after +Gz exposure. SS in hippocampus was measured by RIA at 0 d, 2 d and 4 d after +Gz exposures (there were 8 rats every time, in each group). RESULT: In Y-maze test, number of correct response decreased significantly (P<0.01), and total reaction time increased significantly (P<0.01) in +6 Gz and +10 Gz groups as compared with control group; number of correct response and total reaction time in +10 Gz group changed significantly at 0 d (P<0.01 or P<0.05) as compared with +6 Gz group. RIA showed that, content of SS in hippocampus declined at 0 d and 2 d (P<0.05 or P<0.01) in +6 Gz and +10 Gz groups as compared with control group. CONCLUSION: +Gz exposure could impair learning ability of rats, and inhibit expression of SS in hippocampus.

Acceleration↗

[Flow cytometry and its application in andrological studies].

As an advanced technology, flow cytometry has its unique advantages in detecting single cells quantitatively and rapidly. So it has been used more and more widely in clinical examination. FCM offers a powerful tool and exciting opportunities for accurately evaluation of semen quality and sperm functions. And it's a new idea to apply this technology in andrological studies. This review introduces its basic principles, summaries its present and potential application in andrology studies, including separating and identifying spermatozoa, analyzing spermids structure and function, examining the biological active substances in semen and on the surface of spermids.

Andrology↗

[Clinical study on 29 pacemaker and defibrillator lead fractures].

OBJECTIVE: To analyze major probable causes, locations and remedies of lead fractures in implanted pacemaker and implanted cardioverter defibrillator (ICD) . METHODS: From January 1982 to November 2004, on all the pacemakers and ICDs implanted at this hospital, lead fractures were detected timely by regular telemetric programmed testing, chest radiography and electrocardiography. Appropriate remedial actions were given and follow up visits were done to verify the results. RESULTS: Of all the 4698 pacemakers and 161 ICDs, there were 29 lead fractures on 31 leads with an incidence rate of 0.6%. The incidence rate of lead fracture was 0.9% for pacemakers/defibrillators implanted by subclavian venipuncture, while it was 0.4% for pacemakers/defibrillators implanted by cephalic venotomy (P = 0.04). Fracture locations: 22 cases at the sub clavicle, 6 cases in the pacemaker pocket, and 1 case in the right ventricle. Among the 29 cases, 24 were implanted with additional new leads, 3 cases whose atrial leads were fractured were switched from DDD mode to VVI. All the patients were followed up for an average of 5.6 months +/- 16.1 months. In one patient, the lead was removed through thoracotomy due to infection of exposed lead. CONCLUSIONS: Cephalic venotomy is the first choice for pacemaker and ICD implantation, and the second choice is subclavian venipuncture in the outer part of subclavian vein, which has a higher incidence rate of lead fracture. Most lead fractures are detected at the region of medial subclavian. Regular follow-up can help timely detect fractures, so that the cases can be dealt with properly.

Adult↗

[The association of single nucleotide polymorphism of slow delayed rectifier K+ channel genes with atrial fibrillation in Han nationality Chinese].

OBJECTIVE: To investigate the association between atrial fibrillation and the single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel (I(Ks)) genes in Han nationality Chinese. METHODS: Three hundred and eighty of Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out-hospital control) were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP. RESULTS: The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects. CONCLUSIONS: None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on the function of I(Ks) channel is to be determined.

Aged↗

Protection of pigs against Taenia solium cysticercosis using recombinant antigen or in combination with DNA vaccine.

In the present study, we investigated the duration of protection afforded to pigs immunized in two different prime-boost regimens: one is homologus priming and boosting with a protein vaccine, and the other is priming with a DNA vaccine and boosting with the protein vaccine. Groups of pigs that received the same vaccination regimen were then challenged with Taenia solium eggs at 6, 12 or 20 weeks post-immunization (wpi), respectively. The results showed that all vaccinated pigs challenged at 6 or 12 wpi showed significant (P < 0.05) reduction in the development of cysts. When challenged at 20 wpi, pigs primed with the DNA vaccine (pcDNA3-cC1) followed by two boosters of the protein vaccine (GST-cC1) showed significant (P < 0.05) protection against the challenge of T. solium eggs, whereas pigs receiving three injections of the protein vaccine showed no significant protection compared to non-vaccinated controls (P > 0.05). Antibody isotype assays showed that DNA prime-protein boost regimen induced a predominantly IgG2 response, compared to an IgG1 biased response for the protein prime-protein boost regimen. In addition, peripheral blood mononuclear cells (PBMC) obtained from the DNA prime-protein boost group proliferated strongly in response to GST-cC1 protein, and this responsiveness persisted until 20 wpi. Taken together, our data suggest that the use of a prime-boost strategy combining DNA and protein vaccines may be better than protein alone for the longevity of protection against the challenge of T. solium eggs.

Animals↗

Clinical significance of serum IGF-I, IGF-II and IGFBP-3 in liver cirrhosis.

AIM: To investigate the relationship between insulin-like growth factor-I, -II (IGF-I and IGF-II), IGF-binding protein 3 (IGFBP-3) and Child-Pugh score in patients with liver cirrhosis, and to search for potential clinical markers of liver function. METHODS: Forty-four patients with advanced liver cirrhosis of viral origin were divided into 3 groups according to severity of cirrhosis (Child-Pugh score) and 38 healthy subjects served as controls. Serum levels of IGF-I, IGF-II and IGFBP-3 were measured by immunoradiometric assay. RESULTS: Serum IGF-I, IGF-II and IGFBP-3 levels were significantly lower in patients with cirrhosis than in controls, and serum concentrations of IGF-I, IGF-II and IGFBP-3 were associated with the severity of liver dysfunction, and dropped sharply during the progression of liver failure. Among these 3 parameters, serum IGF-II was the most sensitive and effective indicator for liver dysfunction. Concentrations of IGF-I <30 ng/mL, IGF-II <200 ng/mL and IGFBP-3 <6 ng/mL implied a negative prognosis for patients with liver cirrhosis. CONCLUSION: Serum IGF-I, IGF-II and IGFBP-3 may provide a new dimension in the assessment of liver dysfunction. Combined detection of serum IGF-I, IGF-II and IGFBP-3 with Child-Pugh score is more effective in predicting prognosis than Child-Pugh score alone.

Adult↗

Heterodimeric interaction and interfaces of S100A1 and S100P.

With the widespread use of yeast two-hybrid systems, many heterodimeric forms of S100 proteins have been found, although their biological significance is unknown. In the present study, S100A1 was found to interact with another S100 protein, S100P, by using the yeast two-hybrid system. The binding parameters of the interaction were obtained using an optical biosensor and show that S100P has a slightly higher affinity for S100A1 (K(d)=10-20 nM) when compared with that for self-association (K(d)=40-120 nM). The physical interaction of S100A1 and S100P was also demonstrated in living mammalian cells using a fluorescence resonance energy transfer technique. Preincubation of recombinant S100P with S100A1, before the biosensor assay, reduced by up to 50% the binding of S100P to a recombinant C-terminal fragment of non-muscle myosin A, one of its target molecules. Site-specific mutations of S100P and S100A1, combined with homology modelling of an S100P/S100A1 heterodimer using known S100P and S100A1 structures, allowed the hydrophobic interactions at the dimeric interface of the heterodimer to be defined and provide an explanation for the heterodimerization of S100P and S100A1 at the molecular level. These results have revealed the similarities and the differences between the S100P homodimer and the S100A1/S100P heterodimer.

B-Lymphocytes↗

Interaction of metastasis-inducing S100A4 protein in vivo by fluorescence lifetime imaging microscopy.

Elevated levels of the calcium-binding regulatory protein, S100A4, have been shown to be causative of a metastatic phenotype in models of cancer metastasis and to be associated with reduced patient survival in breast cancer patients. Recombinant S100A4 protein interacts in vitro in a calcium-dependent manner with the heavy chain of non-muscle myosin isoform A at a protein kinase C phosphorylation site. At present, the mechanism of metastasis induction by S100A4 in vivo is almost completely unknown. The binding of S100A4 to a C-terminal recombinant fragment of non-muscle myosin heavy chain in living HeLa cells has now been shown using confocal microscopy, fluorescence lifetime imaging microscopy and time-correlated single-photon counting. The association between S100A4 and non-muscle myosin heavy chain was studied by determining fluorescence resonance energy transfer-derived changes in the fluorescence lifetime of enhanced cyan fluorescent protein fused to S100A4 in the presence of a recombinant fragment of the C-terminal region of non-muscle myosin heavy chain (rNMMHCIIA) fused to enhanced yellow fluorescent protein. There was no interaction between the non-muscle myosin heavy chain fragment and a calcium-binding-deficient mutant of S100A4 protein which has been shown to be defective in the induction of metastasis in model systems in vivo. The results demonstrate, for the first time, not only direct interaction between S100A4 and a target rNMMHCIIA in live mammalian cells, but also that the interaction between S100A4 and the non-muscle myosin heavy chain in vivo could contribute to the mechanism of metastasis induction by a high level of S100A4 protein.

Binding Sites↗

Near-infrared spectroscopy: a tool to monitor cerebral hemodynamic and metabolic changes after cardiac arrest in rats.

INTRODUCTION: Cardiac arrest (CA) is associated with poor neurological outcome and is associated with a poor understanding of the cerebral hemodynamic and metabolic changes. The objective of this study was to determine the applicability of near-infrared spectroscopy (NIRS), to observe the changes in cerebral total hemoglobin (T-Hb) reflecting cerebral blood volume, oxygenation state of Hb, oxidized cytochrome oxidase (Cyto-C), and brain water content following CA. METHODS: Fourteen rats were subjected to normothermic (37.5 degrees C) or hypothermic (34 degrees C) CA induced by 8 min of asphyxiation. Animals were resuscitated with ventilation, cardiopulmonary resuscitation (CPR), and epinephrine (adrenaline). Hypothermia was induced before CA. NIRS was applied to the animal head to measure T-Hb with a wavelength of 808 nm (n = 10) and oxygenated/deoxygenated Hb, Cyto-C, and brain water content with wavelengths of 620-1120 nm (n = 4). RESULTS: There were no technical difficulties in applying NIRS to the animal, and the signals were strong and consistent. Normothermic CA caused post-resuscitation hyperemia followed by hypoperfusion determined by the level of T-Hb. Hypothermic CA blunted post-resuscitation hyperemia and resulted in more prominent post-resuscitation hypoperfusion. Both, normothermic and hypothermic CA resulted in a sharp decrease in oxygenated Hb and Cyto-C, and the level of oxygenated Hb was higher in hypothermic CA after resuscitation. There was a rapid increase in brain water signals following CA. Hypothermic CA attenuated increased water signals in normothermic CA following resuscitation. CONCLUSION: NIRS can be applied to monitor cerebral blood volume, oxygenation state of Hb, Cyto-C, and water content following CA in rats.

Animals↗

Aortic eNOS expression and phosphorylation in Apo-E knockout mice: differing effects of rapamycin and simvastatin.

BACKGROUND: The inhibition of nitric oxide (NO) by hypercholesterolemia may be mediated, in part, by interactions with caveolin-1 (Cav-1). Because of the facilitatory effects of statins on endothelial function and the adverse effects of rapamycin (RAPA) on plasma lipids, we compared the effects of simvastatin (SMV) and RAPA on endothelial NO synthase (eNOS) and Cav-1 protein expression and phosphorylation in the aortas of apolipoprotein E (Apo-E) knockout (-/-) mice. METHODS: Apo-E -/- mice (n = 38) fed a high-cholesterol diet were given SMV (100 mg/kg/day po), RAPA (3 mg/kg/day ip), or no treatment for 10 weeks. Blood was drawn for serum lipid analysis, and protein was extracted for Western immunoblotting. Selected aortic specimens from 2 animals in each group were examined by histology and immunohistochemistry. The data are expressed as the mean +/- SEM and compared by the Student t test and ANOVA. Significance was established as P < .05. RESULTS: Lipid levels at 10 weeks were similar in the 3 groups except for higher triglyceride levels in RAPA-treated animals. eNOS expression was highest in RAPA-treated mice, but the p-eNOS to eNOS protein expression ratio was significantly greater in the SMV treatment group compared to both RAPA and controls (P < .05). Both Cav-1 and p-Cav-1 expression was significantly lower in the SMV-treated animals (P < .05) compared to mice treated with RAPA. CONCLUSIONS: Although eNOS expression was greatest in the RAPA-treated mice, the expression of p-eNOS was similar in the RAPA- and SMV-treated animals. The increase in eNOS induced by RAPA and the inverse relationship between p-eNOS and Cav-1 protein expression observed with SMV treatment suggest different mechanisms for the regulation of aortic eNOS expression in Apo-E mice by these 2 agents.

Animals↗