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Biomedical subjects

M Wei

Publications and source records attributed to M Wei.

At least 37 records · Page 2Linked to original sources

Cross-axis adaptation of the translational vestibulo-ocular reflex.

The adaptive plasticity of the translational vestibulo-ocular reflex (VOR) was investigated in rhesus monkeys after 2-h exposure to either vertical or torsional optic flow stimulation accompanied by lateral translation stimuli (0.5 Hz). Because of the inherent ambiguity in the otolith system for the detection of gravitoinertial accelerations, we hypothesized that cross-axis adaptation of the translational VOR during lateral motion would be preferentially selective for a torsional optic flow stimulus that would mimic a roll tilt movement. However, we found that both vertical and torsional adaptation was possible. Furthermore, there was no significant preference for whether the torsional adaptation was in phase or out of phase with the apparent tilt induced by the motion stimulus. These results suggest that, at least at 0.5 Hz, there seems to be no preferential, visually induced adaptive capacity of the otolith system for tilt/translation reinterpretation during motion. Like the rotational VOR, translational VOR appears to exhibit a general form of cross-axis adaptation that operates for different directions of optic flow stimulation.

Adaptation, Physiological↗

LF15-0195 prevents the induction and inhibits the progression of rat anti-GBM disease.

BACKGROUND: LF15-0195 is a novel immunosuppressant that is currently in phase II clinical trials for the treatment of vasculitis. This study examined whether LF15-0195 could suppress the induction and progression of rat anti-glomerular basement membrane (anti-GBM) glomerulonephritis. METHODS: Rapidly progressive glomerulonephritis was induced in primed rats by the administration of anti-GBM serum. In the first experiment, LF15-0195 was given daily by subcutaneous injection (days 0 to 14) to treat the induction of anti-GBM disease analyzed at day 14. In a second experiment, rats received LF15-0195 as an intervention treatment from days 7 to 28 (continuous therapy) or days 7 to 12 (pulse therapy) to treat the progression of disease assessed at day 28. RESULTS: Continuous LF15-0195 treatment during the induction of anti-GBM disease (experiment 1) prevented proteinuria and loss of renal function, and markedly reduced histological kidney lesions and renal fibrosis. LF15-0195 also reduced kidney leukocyte infiltrate, urine excretion of interleukin-1beta (IL-1beta) and transforming growth factor-beta (TGF-beta), and the serum antibody response, but not kidney deposition of Ig and C3. When LF15-0195 treatment was initiated at day 7, both continuous and pulse therapy partially inhibited disease progression by suppressing the loss of renal function, interstitial macrophage and T-cell accumulation, tubular cell proliferation, and renal fibrosis. CONCLUSION: LF15-0195 prevents the induction and suppresses the progression of rat anti-GBM disease through multiple mechanisms of action, suggesting that this drug may have significant therapeutic potential in human glomerulonephritis. The similar efficacy of continuous and pulse intervention treatment in this model indicates that short-term LF15-0195 treatment may achieve optimal benefit without prolonged bone marrow suppression.

Animals↗

Anti-inflammatory effects of 17beta-estradiol pretreatment in men after coronary artery surgery.

OBJECTIVE: To investigate the anti-inflammatory and hemodynamic effects of 17beta-estradiol in men undergoing elective coronary artery bypass graft surgery (CABG). DESIGN: Prospective, randomized, controlled. SETTING: Operating room and intensive care unit in a university hospital. PARTICIPANTS: Twenty-one men undergoing primary, elective CABG surgery. INTERVENTION: 17beta-estradiol, 2mg, was given orally twice in 14 hours before the operation. MEASUREMENTS AND MAIN RESULTS: Leukocyte counts, plasma myeloperoxidase, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured perioperatively. Leukocyte counts were lower in the 17beta-estradiol group than in controls at 6 hours (11.4 +/- 2.0 hours v 15.5 +/- 4.7 hours x 10(9)/L) and 20 hours (11.6 +/- 1.9 hours v 13.6 +/- 2.5 hours x 10(9)/L) after reperfusion (p = 0.03). The release of myeloperoxidase was lower in the 17beta-estradiol group than in controls (5 minutes; 634.4 +/- 213.1 microg/mL v 773.1 +/- 209.3 microg/mL; 4 hours, 305.0 +/- 108.0 microg/mL v 441.3 +/- 191.6 microg/mL; p = 0.02). Systemic vascular resistance index was lower just after cardiopulmonary bypass, and cardiac index was higher postoperatively in the 17beta-estradiol group as compared with controls. CONCLUSION: Pretreatment with 17beta-estradiol can limit leukocyte activation in men after CABG surgery.

Administration, Oral↗

Cytokine responses and myocardial injury in coronary artery bypass grafting.

OBJECTIVE: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation. RESULTS: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values. CONCLUSION: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.

Aged↗

Pump prime aprotinin fails to limit proinflammatory cytokine release after coronary artery bypass surgery.

BACKGROUND: The purpose of this study was to establish whether pump prime aprotinin could limit the cytokine responses in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-one patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg aprotinin in the pump prime. Leukocyte count, creatine kinase cardiac isoenzyme (CK-MB), cytokine production and postoperative blood loss were analyzed perioperatively and compared with preoperative values. RESULTS: The peak level of leukocyte count was lower in the aprotinin group than in controls (9.3 +/- 0.58 vs 11.2 +/- 0.68 x 10(9)/L, p = 0.01). Interleukin (IL)-6 and IL-8 did not differ significantly between the groups throughout the study period. Plasma IL-10 levels were higher in the controls than in the aprotinin group at 5 min (49.6 +/- 24.9 vs 8.13 +/- 2.8 pg/ml, p = 0.01) after reperfusion. CONCLUSION: Pump prime aprotinin fails to limit proinflammatory cytokine response in circulating blood.

Aged↗

Cytokine responses in patients undergoing coronary artery bypass surgery after ischemic preconditioning.

OBJECTIVE: The release of proinflammatory cytokines has been shown to be associated with the development of complications after coronary artery bypass grafting with cardiopulmonary bypass. The purpose of the present study was to establish whether ischemic preconditioning (IP) could limit inflammatory cytokines release in patients undergoing elective coronary artery bypass surgery. METHODS: Twenty-two patients with multiple-vessel coronary artery disease and stable angina admitted for first-time elective coronary artery bypass surgery were randomized into control or ischemic preconditioning groups. Patients in the IP group were exposed to two cycles of two-minute myocardial ischemia, followed by three minutes of reperfusion, at the beginning of the revascularization operation, before the cross-clamping and ischemic period used for coronary artery bypass graft anastomosis. Peripheral plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 were measured perioperatively. RESULTS: Significant elevation of IL-6, IL-8 and IL-10 were observed in both groups after reperfusion. Ischemic preconditioning has no effect on cytokine release in the early stage after reperfusion. Arterial blood IL-6 levels in the preconditioning group were significantly lower than in controls at 20 h after declamping (52.93 +/- 9.79 vs 96.04 +/- 17.56 pg/ml, p < 0.05). CONCLUSIONS: The results indicate that ischemic preconditioning results in no effect on systemic inflammatory cytokine release in the early stage but a delayed reduction in IL-6 levels at 20 h after reperfusion.

Aged↗

Vestibular discrimination of gravity and translational acceleration.

According to Einstein's equivalence principle, linear accelerations experienced during translational motion are physically indistinguishable from changes in orientation relative to gravity experienced during tilting movements. Nevertheless, despite these ambiguous sensory cues provided by the primary otolith afferents, perceptual and motor responses discriminate between gravity and translational acceleration. There is growing evidence to suggest that the brain resolves this ambiguity primarily by combining signals from multiple sensors, the semicircular canals being a main extra otolith contributor. Here, we summarize the experimental evidence in support of the canal influences on the neural processing of otolith cues, provide specific experimental results in rhesus monkeys, and discuss and compare previously proposed models that combine otolith and semicircular-canal signals in order to provide neural estimates of gravity and linear acceleration.

Animals↗

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

Adenosine↗

OxLDL upregulates growth-regulation oncogene alpha expression in human endothelial cells.

OBJECTIVE: To explore the effect of oxLDL on CXC chemokine growth-regulated oncogene alpha (GRO alpha) expression in human endothelial cells and the possible functional significance of the effect. METHODS: LDL was isolated by sequential ultracentrifugation and oxidized to oxLDL. Reverse transcription-polymerase chain reaction with GAPDH as internal standard was applied and CXC chemokine GRO alpha mRNA in endothelial ECV304 cells was examined. ELISA was used to determine GRO alpha protein expression on ECV304 cells surface and in the medium. With static cell adhesion assays, the physiological significance of elevated GRO alpha expression was tested. RESULTS: OxLDL, not LDL, treatment of ECV304 cells significantly induced the expression of GRO alpha mRNA that was not detectable in untreated cells. Induction of expression was first evident at 1 h, became maximal at 2 h, and was substantially decreased by 4 h. In a concentration- and time-dependent manner, oxLDL, and not LDL, induced a significant upregulation of GRO alpha surface expression in ECV304 cells that was at a barely detectable level in unstimulated ECV304 cells. GRO alpha protein in the medium did not change significantly. Exposure of ECV304 cells to 40 micrograms protein/ml oxLDL for 24 h resulted in a marked increase in the number of U937 cells bound to ECV304 cells and antibodies to GRO alpha inhibited adhesion. CONCLUSION: OxLDL functionally upregulated GRO alpha expression in endothelial cells.

Cell Adhesion↗

[Experimental study on effect of bushen huoxue xiezhuo decoction in treating minimal change nephropathy].

OBJECTIVE: To explore the therapeutic effect and mechanism of Bushen Huoxue Xiezhuo Decoction (BHXD) in treating minimal change nephropathy (MCN) in rats. METHODS: The MCN model rats established by a single intravenous injection of Adriamycin were divided into the model, BHXD group, and a normal group was set up for control. The effect of treatment on renal function, hemorrheologic parameters, renal tissue TGF-beta 1 expression and polyanion sites on glomerular basement membrane were observed dynamically. RESULTS: After treatment, all the parameters between the BHXD group and the model group were significantly different respectively, morphological observation also showed the pathological changes in the BHXD group were milder than those in the model group. CONCLUSION: BHXD treatment could markedly improve the renal function, alleviate blood hypercoagulability and hyperviscosity, protect the anion barrier and delay the progression of glomerular fibrosis and sclerosis.

Animals↗

[Subtotal laryngectomy reconstructed by platysma myocutaneous flaps].

OBJECTIVE: To study the feasibility, surgical techniques and the results of laryngeal function preservation during subtotal laryngectomy in laryngeal carcinoma. METHODS: A retrospective review was made of 13 patients treated by subtotal laryngectomy and laryngeal reconstruction from 1991 to 1996. Eleven patients were male and 2 were female. The age ranged from 46 to 72 years, with a mean of 53.25. All cases were of stage IV. The essence of this operation is to reconstruct the new larynx with two platysma myocutaneous flaps following subtotal laryngectomy. RESULTS: The success rate of voice rehabilitation was 100%. Among them, the acceptability rating scores in 11 cases were 7 and the intelligibility scores ranged from 95% to 98%. The other two cases had acceptability 5 and intelligibility form 90% to 94%. The three-year survival rate was 84.6% (11/13), 5-year survival rate was 76.9% (10/13). CONCLUSION: This form of laryngeal reconstruction in subtotal laryngectomy is helpful to restore laryngeal function and decrease the rate of total laryngectomy. The procedure is easy, safe and applicable to patients treated by subtotal laryngectomy.

Aged↗

[Study on high-efficiency gene transfer of pseudotyped HIV vector].

OBJECTIVE: To investigate the high-efficiency of pseudotyped HIV as gene transfer vector. METHODS: Three plasmids of pseudotyped HIV gene transfer vector system were transferred into packaging cell line 293T by Ca3 (PO4)2 precipitation method. GFP (Green Fluorescence Protein) or HSV-tk gene was constructed in the plasmid pHR'CS respectively (pHR'CS.GFP or pHR'CS.HSV-tk). The pseudotyped HIV particles were observed through electronic microscopy and were measured through spectrofluorophotometer. High titer pseudotyped HIV was harvested from volume of virus-producing cell supernatant and concentrated. Ovarian epithelial cancer cell line SKOV3 and normal human gingival fibroblast cell GF were infected by pseudotyped HIV. PCR and RT-PCR were resorted to demonstrate the successful transduction and transcription of the HSV-tk gene. After administration of GCV, the changes of those cells and apoptosis were observed through optical microscopy. The cytotoxicity efficacy of HSV-tk/GCV system was evaluated by MTT method. The growth inhibition rate (GIR) of cells and inhibition concentration 50 (IC50) were counted. RESULTS: The above plasmids were effectively transferred into 293T cell. A lot of pseudotyped HIV particles were observed through electronic microscopy. The virus supernatant had a high absorbing value at 510 nm through spectrofluorophotometer, which proved the existence of virus. After pseudotyped HIV infection, SKOV3 and GF had remarkable infection rate. 600 bp strand was seen through PCR and RT-PCR. Changes and apoptosis of cells followed by administration of GCV were observed. The MTT method showed that the cytotoxicity efficacy of GCV was high to SKOV3 and GF cell. CONCLUSIONS: The pseudotyped HIV is a high-efficiency gene transfer vector.

Cell Line, Tumor↗

Identification of domain-domain docking sites within Clostridium symbiosum pyruvate phosphate dikinase by amino acid replacement.

Potential domain-domain docking residues, identified from the x-ray structure of the Clostridium symbiosum apoPPDK, were replaced by site-directed mutagenesis. The steady-state and transient kinetic properties of the mutant enzymes were determined as a way of evaluating docking efficiency. PPDK mutants, in which one of two stringently conserved docking residues located on the N-terminal domain (Arg(219) and Glu(271)) was substituted, displayed largely unimpeded catalysis of the phosphoenolpyruvate partial reaction at the C-terminal domain, but significantly impaired catalysis (>10(4)) of the ATP pyrophosphorylation of His(455) at the N-terminal domain. In contrast, alanine mutants of two potential docking residues located on the N-terminal domain (Ser(262) and Lys(149)), which are not conserved among the PPDKs, exhibited essentially normal catalytic turnover. Arg(219) and Glu(271) were thus proposed to play an important role in guiding the central domain and, hence, the catalytic His(455) into position for catalysis. Substitution of central domain residues Glu(434)/Glu(437) and Thr(453), the respective docking partners of Arg(219) and Glu(271), resulted in mutants impaired in catalysis at the ATP active site. The x-ray crystal structure of the apo-T453A PPDK mutant was determined to test for possible misalignment of residues at the N-terminal domain-central domain interface that might result from loss of the Thr(453)-Glu(271) binding interaction. With the exception of the mutation site, the structure of T453A PPDK was found to be identical to that of the wild-type enzyme. It is hypothesized that the two Glu(271) interfacial binding sites that remain in the T453A PPDK mutant, Thr(453) backbone NH and Met(452) backbone NH, are sufficient to stabilize the native conformation as observed in the crystalline state but may be less effective in populating the reactive conformation in solution.

Adenosine Triphosphate↗

Chemopreventive effects of S-methylcysteine on rat hepatocarcinogenesis induced by concurrent administration of sodium nitrite and morpholine.

The aim of the present study was to examine the chemopreventive efficacy of S-methylcysteine (SMC) on rat hepatocarcinogenesis induced by concurrent administration of sodium nitrite (NaNO(2)) and morpholine (Mor) using a medium-term rat liver carcinogenesis bioassay (Ito test). Administration of SMC caused significant reduction in the areas of glutathione S-transferase placental form positive foci along with a significant decrease of hepatocyte 5-bromo-2'-deoxyuridine (BrdU) labeling indices. These results demonstrated potent chemopreventive effects of SMC against hepatocarcinogenesis due to concurrent administration of Mor and NaNO(2). SMC could thus be an effective chemopreventive agent for decreasing the risk of carcinogenicity from environmental precursors of N-nitroso compounds.

Animals↗

Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men.

Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease (CHD). Previous studies on asymptomatic subjects, however, may not have been large enough or long enough to provide reliable outcome measures. This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men. This is a prospective longitudinal study performed between 1970 and 1989, with an average follow-up of 8.4 years. The subjects are 25,927 healthy men, 20 to 82 years of age at baseline (mean 42.9 years) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic. The main outcome measures are CHD mortality and all-cause mortality. During follow-up there were 612 deaths from all causes and 158 deaths from CHD. The sensitivity of an abnormal exercise test to predict coronary death was 61%. The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 (6.9 to 63.3) in those with no risk factors, 27 (10.7 to 68.8) in those with 1 risk factor, 54 (21.5 to 133.7) in those with 2 risk factors, and 80 (30.0 to 212. 5) in those with >/=3 factors. A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death. An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors.

Adult↗

Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality.

BACKGROUND: Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS: We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS: Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.

Adult↗

Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes.

BACKGROUND: Although physical activity is recommended as a basic treatment for patients with diabetes, its long-term association with mortality in these patients is unknown. OBJECTIVE: To evaluate the association of low cardiorespiratory fitness and physical inactivity with mortality in men with type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Preventive medicine clinic. PATIENTS: 1263 men (50+/-10 years of age) with type 2 diabetes who received a thorough medical examination between 1970 and 1993 and were followed for mortality up to 31 December 1994. MEASUREMENTS: Cardiorespiratory fitness measured by a maximal exercise test, self-reported physical inactivity at baseline, and subsequent death determined by using the National Death Index. RESULTS: During an average follow-up of 12 years, 180 patients died. After adjustment for age, baseline cardiovascular disease, fasting plasma glucose level, high cholesterol level, overweight, current smoking, high blood pressure, and parental history of cardiovascular disease, men in the low-fitness group had an adjusted risk for all-cause mortality of 2.1 (95% CI, 1.5 to 2.9) compared with fit men. Men who reported being physically inactive had an adjusted risk for mortality that was 1.7-fold (CI, 1.2-fold to 2.3-fold) higher than that in men who reported being physically active. CONCLUSIONS: Low cardiorespiratory fitness and physical inactivity are independent predictors of all-cause mortality in men with type 2 diabetes. Physicians should encourage patients with type 2 diabetes to participate in regular physical activity and improve cardiorespiratory fitness.

Adult↗