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Biomedical subjects

W Lan

Publications and source records attributed to W Lan.

12 recordsLinked to original sources
PubMed2005

Effect of aprotinin on in vitro cerebral endothelial ICAM-1 expression induced by astrocyte-conditioned medium.

BACKGROUND AND OBJECTIVE: Aprotinin administration may decrease the incidence of stroke associated with coronary artery bypass surgery by an unknown mechanism. Astrocytes exposed to hypoxia produce proinflammatory cytokines and upregulate intercellular adhesion molecule (ICAM)-1 on cerebral endothelium. This study investigated the effects of aprotinin on cerebral endothelial activation by hypoxic astrocytes in vitro. METHODS: Mouse astrocytes were exposed to hypoxia in an anaerobic chamber for 4 h followed by reoxygenation for 24 h. Astrocyte-conditioned medium (ACM) collected from mouse astrocytes subjected to hypoxia/reoxygenation (HR) or normoxia were applied to mouse cerebral endothelial cell (MCEC) cultures for 4 and 24 h in normoxia. Endothelial cells were preincubated for 1 h with aprotinin (1600 KIU mL(-1)) prior to exposure to ACM. Flow cytometry was used to estimate endothelial ICAM-1 expression. Interleukin (IL)-1beta space concentrations in ACM were estimated with enzyme-linked immunosorbent assay (ELISA). Repeated comparisons were made using analysis of variance (ANOVA) and post hoc Tukey test as appropriate. P < 0.05 was considered significant. Data is presented as mean (standard deviation, SD). RESULTS: MCEC ICAM-1 expression was greater after 24 h exposure to HR-ACM compared to normoxic-ACM (mean channel flouresence (MCF) 107.5 (4.5) vs. 74.3 (4.5), respectively, P < 0.001). ICAM-1 expression was decreased by aprotinin preincubation compared to control (MCF 91.0 (1.1) vs. 107.5 (2.1), P = 0.006). Supernatant IL-1beta concentrations in astrocytes exposed to HR were greater than those exposed to normoxia (7.1 (0.2) vs. 4.1 (0.2), P = 0.01). CONCLUSIONS: This may be a neuroprotective mechanism associated with aprotinin administration.

Anaerobiosis↗
PubMed2004

The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion.

BACKGROUND: Changes in neutrophil and endothelial adhesion molecule expression occur during perioperative ischaemia and reperfusion (I/R) injury. We investigated the effects of lidocaine on neutrophil-independent changes in neutrophil and endothelial adhesion molecule expression associated with tourniquet-induced I/R. METHODS: Plasma was obtained from venous blood samples (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24 h following tourniquet release in seven patients undergoing elective upper limb surgery with tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1) for 1 h, and then incubated with I/R plasma for 2 h. Human umbilical vein endothelial cells (HUVECs) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)) for 1 h, and then incubated with the plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry. Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. RESULTS: I/R plasma (withdrawn 15 min following tourniquet release) increased isolated neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b, CD18 and ICAM-1 expression on lidocaine (0.005 mg mL(-1)) treated neutrophils was similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002) expression on lidocaine (0.05 mg mL(-1)) treated neutrophils and HUVECs was less than that on controls. CONCLUSION: Increased in vitro neutrophil and endothelial cell adhesion molecule expression on exposure to plasma obtained during the early reperfusion phase is diminished by lidocaine at greater than clinically relevant plasma concentrations.

Adolescent↗
PubMed2004

The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1 expression and IL-1beta concentrations induced by hypoxia-reoxygenation.

BACKGROUND: Lidocaine has actions potentially of benefit during ischaemia-reperfusion. Neutrophils and endothelial cells have an important role in ischaemia-reperfusion injury. METHODS: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1beta concentrations in response to hypoxia-reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)). Adhesion molecule expression was quantified by flow cytometry and IL- 1beta concentrations by ELISA. Differences were assessed with analysis of variance and Student-Newman-Keuls as appropriate. Data are presented as mean+/-SD. RESULTS: Exposure to hypoxia-reoxygenation increased neutrophil CD11b (94.33+/-40.65 vs. 34.32+/-6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84+/-35.44 vs. 59.05+/-6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62+/-16.78 vs. 47.29+/-9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (71.07+/-10.14 vs. 109.84+/-35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (133.25+/-16.05 vs. 146.62+/-16.78 MCF, P = 0.03). Hypoxia-reoxygenation increased HUVEC supernatant IL-1beta concentrations compared to normoxia (3.41+/-0.36 vs. 2.65+/-0.21 pg mL(-1), P = 0.02). Endothelial supernatant IL-1beta concentrations in lidocaine-treated HUVECs were similar to controls. CONCLUSIONS: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1beta concentrations.

Analysis of Variance↗
PubMed2004

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+/-46% vs. 91+/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+/-46% vs. 129+/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+/-3.7 vs. 43+/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+/-0.4 vs. 2.6+/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+/-3.3 vs. 116+/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+/-0.3 vs. 2.6+/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.

Analysis of Variance↗
PubMed2003

The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

UNLABELLED: Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

Acid-Base Equilibrium↗
PubMed2001

How well tolerated are lipid-lowering drugs?

It has been clearly established that lipid-lowering treatments [such as 3-hydroxyl-3-methylglutamyl coenzyme A reductase inhibitors ('statins') or fibrates] can reduce cardiovascular events, and with one of the statins even total mortality, in high-risk populations. Intervention studies have not included the very old, but it is generally assumed that this patient group would benefit from these treatments to an extent similar to younger patients. Worries about the associations seen in observational studies between low cholesterol levels and cancer, cerebral haemorrhage or mood and behaviour change have been largely overcome by findings from the latest large drug intervention trials, which do not show any increase in these conditions with statin or fibrate treatments. The common adverse effects associated with these drugs are relatively mild and often transient in nature. Potentially more serious adverse effects, which are more clearly related to drug treatment and are probably dose-dependent, include elevations in hepatic transaminase levels and myopathy; however, these effects are uncommon and generally resolve rapidly when treatment is stopped. The risk of myopathy with fibrate treatment is increased in patients with renal impairment, and the risk of myopathy with statin treatment increases with co-administration of drugs that inhibit statin metabolism or transport. Other adverse effects are related to specific drugs, for example, clofibrate is associated with an increased risk of gallstones. Studies in elderly patients have not shown an increased risk of adverse effects with lipid-lowering drugs compared with younger patients, but in clinical practice there may be some increased risk, particularly with regards to drug interactions. Therefore, lipid-lowering drugs should be administered with extra caution to elderly patients.

Age Factors↗
PubMed1998

Adolescents' perceptions of their parents' academic expectations: comparison of American, Chinese-American, and Chinese high school students.

Cultural background not only influences family beliefs about the value of education, but may affect how academic expectations are communicated by parents and perceived by their children. This study examined differences in willingness to conform to parents' expectations of academic achievement as perceived by American, Chinese-American, and Chinese high school students. Findings indicated that Chinese students were more willing to accept their parents' advice and cared more about fulfilling academic expectations than did American students. Students in all three groups had similar feelings of independence. The views of Chinese-American students reflected the influence of both their Chinese heritage and the American culture in which they resided.

Acculturation↗
PubMed1997

Studies on the mutagenicity of mild gasification products of coal and their subfractions by the Salmonella/microsomal assay.

Mild gasification of coal is a technology being developed in the United States in order to upgrade lower rank coals and facilitate their use in coal-burning electric generation plants. Thirteen coal-derived mild gasification products from different coal sources and processing conditions have been examined for their potential biohazards. The mutagenicity of these samples was tested with the Ames Salmonella/microsomal assay. Two solvents, dimethyl sulfoxide (DMSO) and polyoxyethylene-sorbitan monooleate (Tween 80), were used to dissolve samples in a manner to facilitate their interaction with the test organisms. The results showed that 9 of the 13 samples displayed mutagenic activity in test strains TA98 and/or TA100 with or without metabolic activation, whether dissolved in Tween 80 or DMSO. Five mutagenic and two nonmutagenic samples were class-fractionated into basic, acidic, nonpolar, and polar neutral subfractions to examine their class-related mutagenic activities. Results of the testing of subfractions of the five mutagenic and one nonmutagenic samples showed mutagenic activity in at least the nonpolar neutral fraction. The subfractions of the another nonmutagenic sample did not display any mutagenic activity. Chemical characterization of the subfractions revealed the existence of aromatic hydrocarbons in certain subfractions, which may be responsible for the mutagenic activity of the coal-derived mild gasification products.

Animals↗
PubMed1994

Mutagenicity of mild gasification products in Salmonella typhimurium.

Mild gasification is a coal-conversion technology that is currently under development in order to help meet future energy needs. 7 products from this process were assayed for mutagenic activity in the pre-incubation variant of the Salmonella assay (Ames test) using both DMSO and Tween 80 as sample solvents. Significant mutagenic activity was detected only in the wide-boiling-point composite materials, and the amount of this activity was found to be dependent on the solvent utilized. The highest number of revertants detected were on TA98 and its O-acetyltransferase over-producing derivative, YG1024, in the presence of the S9 microsomal fraction. Aromatic amines were suggested as a possible source of the mutagenic activity elicited. An examination of the liquid and tar phases of one composite material (MG-120) indicated that the mutagenic activity was restricted to the tar phase.

Coal↗
PubMed1992

Energetics of folding subtilisin BPN'.

Subtilisin is an unusual example of a monomeric protein with a substantial kinetic barrier to folding and unfolding. Here we document for the first time the in vitro folding of the mature form of subtilisin. Subtilisin was modified by site-directed mutagenesis to be proteolytically inactive, allowing the impediments to folding to be systematically examined. First, the thermodynamics and kinetics of calcium binding to the high-affinity calcium A-site have been measured by microcalorimetry and fluorescence spectroscopy. Binding is an enthalpically driven process with an association constant (Ka) equal to 7 x 10(6) M-1. Furthermore, the kinetic barrier to calcium removal from the A-site (23 kcal/mol) is substantially larger than the standard free energy of binding (9.3 kcal/mol). The kinetics of calcium dissociation from subtilisin (e.g., in excess EDTA) are accordingly very slow (t1/2 = 1.3 h at 25 degrees C). Second, to measure the kinetics of subtilisin folding independent of calcium binding, the high-affinity calcium binding site was deleted from the protein. At low ionic strength (I = 0.01) refolding of this mutant requires several days. The folding rate is accelerated almost 100-fold by a 10-fold increase in ionic strength, indicating that part of the free energy of activation may be electrostatic. At relatively high ionic strength (I = 0.5) refolding of the mutant subtilisin is complete in less than 1 h at 25 degrees C. We suggest that part of the electrostatic contribution to the activation free energy for folding subtilisin is related to the highly charged region of the protein comprising the weak ion binding site (site B).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗
PubMedDate not supplied

Differences between learning disability subtypes classified using the revised Woodcock-Johnson Psycho-Educational Battery.

This study examined the characteristics of students with specific learning disabilities in either reading and spelling or arithmetic. Based on scores obtained using the revised Woodcock-Johnson Psycho-Educational Battery, students with a marked weakness in arithmetic relative to reading and spelling were designated as Group A. Group R-S showed the opposite pattern. Each group included 30 participants ranging in age from 7 to 16 years, with a mean age of 10 years. The boy-to-girl ratios were 16:14 and 19:11 in Group A and Group R-S, respectively. Comparisons using measures from the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) indicated that Group A was weaker in nonverbal skills than Group R-S, despite equivalent overall IQ scores between the two groups. Group R-S showed a within-group strength in nonverbal versus verbal skills. Group A students were more likely than Group R-S students to have counseling provided as part of their Individualized Education Program, suggesting greater socioemotional difficulty among Group A students. The present study supports the connection between nonverbal skills and socioemotional functioning noted by previous researchers, and generalizes findings from earlier studies to more current test editions.

Adolescent↗