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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 181 records · Page 10Linked to original sources
PubMed2000

Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83.

Early reports indicated that ECV304 was a spontaneously-transformed line derived from a Japanese human umbilical vein endothelial cells (HUVEC) culture. Many morphological, immunochemical, and genetic studies provided further evidence that ECV304 was a valuable biomedical research tool and could be used to study processes that include angiogenesis in vitro and signal transduction by a variety of G protein-coupled receptors. However, several distinct differences between ECV304 and HUVEC are now apparent and recent reports have indicated genetic similarity between ECV304 and T24/83, a human bladder cancer cell line. To further assess the utility of ECV304 as a human endothelial cell model, we compared the functional responses of ECV304 and T24/83 to a range of G protein-coupled receptor agonists. We also used DNA fingerprinting to karyotype both ECV304 and T24/83. Both ATP and uridine triphosphate (UTP) stimulated inositol phosphate metabolism in ECV304 without alteration of cAMP levels. Comparative data using selective P2Y receptor agonists indicated that this response, leading to calcium mobilization from intracellular stores, was predominantly mediated by the activation of P2Y2 receptors. Similar responses were recorded from both ECV304 and T24/83 cells. ECV304 expressed a relatively high basal activity of NOS that was reduced by L-NAME and stimulated by P2Y2 receptor agonists. In contrast, P2Y2 receptor activation did not induce prostaglandin synthesis in ECV304. Both ECV304 and T24/83 express receptors for adenosine, adrenaline, and calcitonin, which stimulate adenylate cyclase. Proliferation of ECV304 and T24/83 cells, measured by the incorporation of [3H]thymidine into DNA, was largely serum-independent. This was in contrast to parallel experiments with porcine and bovine aortic endothelial cells that indicated a marked serum-dependent increase in DNA synthesis. Genetic analysis confirmed that ECV304 and T24/83 are identical. ECV304 displays some endothelial characteristics and is useful for the study of receptor pharmacology. However, ECV304 is not of HUVEC origin and is therefore an inappropriate cell line to study endothelial cell biology.

Adenylyl Cyclases↗
PubMed2000

Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients.

In contrast to primary central nervous system lymphomas (PCNSLs) that occur in immunocompetent patients, most of those that occur in immunosuppressed patients are associated with Epstein-Barr virus (EBV). BCL-2-related proteins either block or promote cell death, forming homo- or heterodimers with each other. LMP-1, EBV latent protein, has been shown to upregulate BCL-2 and BCL-XL. This observation suggests that these proteins may be involved in the transformation process of EBV-infected cells. Twenty-three cases of PCNSLs were studied: 12 of the patients were immunosuppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the presence of EBV (EBER-1, LMP-1). Apoptosis was assessed by the TdT-mediated dUTP-biotin nick-end labeling method and quantified by image analysis. In three cases, electron microscopy was performed. The BCL-2 family proteins (BCL-2, BCL-X, MCL1, and BAX) and p53 expression were studied by immunohistochemistry on paraffin slides. All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immunosuppressed patients were characterized by EBV association, necrosis, important gliosis, and numerous macrophages. There was no significant difference between the two groups regarding the TdT-mediated dUTP-biotin nick-end labeling staining (P = .08). In contrast, PCNSLs in immunosuppressed patients were shown to express high levels of BCL-2, BCL-X, and BAX in more than 80% of tumor cells in 7, 10, and 11 cases, respectively. In immunocompetent patients, only one case showed a high level of BCL-2 expression in more than 80% of the cells, whereas BCL-X and BAX were overexpressed in two cases. These differences are significant (P < .05). In contrast, there was no significant difference between the two groups in MCL-1 expression. Besides EBV association and necrosis, PCNSLs related to immunosuppression are characterized by an overexpression of BCL-2-related proteins, without dramatically modifying their susceptibility for apoptosis.

Adult↗
PubMed2000

Role of erythropoietin in cortisol-induced hypertension.

The mechanism of cortisol-induced hypertension remains unknown. We investigated a possible role of erythropoietin (EPO) as a mediator of hypertension in healthy male subjects treated with cortisol. In Study 1, blood pressure (BP) and serum EPO concentrations were measured on alternate days in nine subjects treated with 80 mg of cortisol per day for 5 days. In Study 2 the same parameters were measured in eight subjects randomised to cortisol (80 mg/day) or placebo and 10 subjects randomised to cortisol (200 mg/day) or placebo for 5 days. In Study 1, cortisol caused a significant increase in systolic BP (SBP) (115 +/- 2 vs 126 +/- 2 mm Hg, control vs day 5, P < 0.001) and serum EPO concentrations (14.5 +/- 2.7 vs 24.3 +/- 2.7 mU/mL, P < 0.001). In Study 2 both doses of cortisol increased SBP (118 +/- 2 vs 113 +/- 2 mm Hg, 80 mg cortisol vs placebo, P < 0.05 and 129 +/- 3 vs 113 +/- 2 mm Hg, 200 mg cortisol vs placebo, P < 0.001). Serum EPO concentrations were significantly increased at 200 mg cortisol (25.2 +/- 11.9 vs 15.9 +/- 3.5 mU/mL, P < 0.01) but not 80 mg cortisol (21.3 +/- 2.9 vs 14.9 +/- 3.1 mU/mL). In the 200 mg group there was a positive correlation between the change in SBP and the change in serum EPO concentration (r2 = 0.43, P < 0.05). These results point to a possible role for EPO as the mediator of cortisol-induced hypertension. Journal of Human Hypertension (2000) 14, 195-198.

Blood Pressure↗
PubMed2000

General Summary.

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Journal Article↗
PubMed2000

General summary.

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Journal Article↗
PubMed2000

The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killing.

The lic1 locus of Haemophilus influenzae controls the incorporation of environmental choline into lipopolysaccharide (LPS) as phosphorylcholine (ChoP) as well as the phase variation of this structure. ChoP is the target of an acute phase reactant in serum, C-reactive protein (CRP), which mediates killing through the activation of complement when bound to the organism. Structural analysis of the oligosaccharide region of the H. influenzae LPS showed that ChoP is linked to different hexose residues on different chain extensions in strains Rd and Eagan. Differences in the molecular environment of ChoP affect the epitope defined by monoclonal antibody 12D9 and were associated with polymorphisms within LicD, a putative diphosphonucleoside choline transferase. Exchanging the licD genes between the two strains with ChoP on different chain extensions was sufficient to switch its position. Allelic variants with ChoP on a hexose on heptose III rather than heptose I were sensitive to CRP-mediated serum bactericidal activity regardless of the genetic background. Differences in CRP-mediated killing correlated with differences in the binding of CRP from human serum to whole bacteria. This suggests that, in addition to the mechanism involving phase variation, the structural rearrangements within the oligosaccharide contribute to evasion of innate and acquired immunity.

Alleles↗
PubMed2000

Characterization of the phosphocholine-substituted oligosaccharide in lipopolysaccharides of type b Haemophilus influenzae.

Haemophilus influenzae expresses heterogeneous populations of short-chain lipopolysaccharide (LPS) which exhibit extensive antigenic diversity among multiple oligosaccharide epitopes. These LPS oligosaccharide epitopes can carry phosphocholine (PCho) substituents, the expression of which is subject to high frequency phase variation mediated by genes in the lic1 genetic locus. The location and site of attachment of PCho substituents were determined by structural analysis of LPS from two type b H. influenzae strains, Eagan and RM7004. The lic2 locus is involved in phase variation of oligosaccharide expression. LPS obtained from the parent strains, from mutants generated by insertion of antibiotic resistance cassettes in the lic2 genetic locus, and from phase-variants showing high levels of PCho expression was characterized by electrospray ionization-mass spectrometry (ESI-MS) and 1H NMR spectroscopy of derived O-deacylated samples. ESI-MS of O-deacylated LPS from wild-type strains revealed mixtures of related glycoform structures differing in the number of hexose residues. Analysis of LPS from PCho-expressing phase-variants revealed similar mixtures of glycoforms, each containing a single PCho substituent. O-Deacylated LPS preparations from the lic2 mutants were much less complex than their respective parent strains, consisting only of Hex3 and/or Hex2 glycoforms, were examined in detail by high-field NMR techniques. It was found that the LPS samples contain the phosphoethanolamine (PEtn) substituted inner-core element, L-alpha-D-Hepp-(1-->2)-[PEtn-->6]-L-alpha-D-Hepp-(1--> 3)-L-alpha-D-He pp-(1-->5)-alpha-Kdo in which the major glycoforms carry a beta-D-Glcp or beta-D-Glcp-(1-->4)-beta-D-Glcp at the O-4 position of the 3-substituted heptose (HepI) and a beta-D-Galp at the O-2 position of the terminal heptose (HepIII). LPS from the lic2 mutants of both type b strains were found to carry PCho groups at the O-6 position of the terminal beta-D-Galp residue attached to HepIII. In the parent strains, the central heptose (HepII) of the LPS inner-core element is also substituted by hexose containing oligosaccharides. The expression of the galabiose epitope in LPS of H. influenzae type b strains has previously been linked to genes comprising the lic2 locus. The present study provides definitive evidence for the role of lic2 genes in initiating chain extension from HepII. From the analysis of core oligosaccharide samples, LPS from the lic2 mutant strain of RM7004 was also found to carry O-acetyl substituents. Mono-, di-, and tri-O-acetylated LPS oligosaccharides were identified. The major O-acetylated glycoforms were found to be substituted at the O-3 position of HepIII. A di-O-acetylated species was characterized which was also substituted at the O-6 postion of the terminal beta-D-Glc in the Hex3 glycoform. This is the first report pointing to the occurrence of O-acetyl groups in the inner-core region of H. influenzae LPS. We have previously shown that in H. influenzae strain Rd, a capsule-deficient type d strain, PCho groups are expressed in a different molecular environment, being attached at the O-6 position of a beta-D-Glcp, which is in turn attached to HepI.

Acetylation↗
PubMed2000

Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.

A simple and sensitive HPLC method has been developed to measure trimebutine (CAS 39133-31-8, maleate: CAS 34140-59-5) and its main metabolite desmethyl-trimebutine in human plasma. The method was validated according to the Washington Consensus Conference on the Validation of Analytical Methods. It involved extraction of the plasma with n-hexane containing 2-pentanol, followed by reversed-phase HPLC using a Partisil ODS2 10 microns column and UV detection at 265 nm. The retention times of the internal standard (procaine), desmethyl-trimebutine and trimebutine were 2.4, 4.3 and 6.5 min, respectively. The standard curves were linear from 20 ng.ml-1 (limit of quantitation) to 5000 ng.ml-1 for both compounds. The coefficient of variation for all the criteria of validation were less than 15%. The extraction recoveries obtained for trimebutine and desmethyl-trimebutine were about 90%. Both compounds were very stable upon storage in plasma. The method was tested by measuring the plasma concentrations following oral administration to humans during a bioequivalence study and was shown suitable for pharmacokinetic studies.

Calibration↗
PubMed2000

Pharmacokinetics and bioequivalence of two trimebutine formulations in healthy volunteers using desmethyl-trimebutine levels.

Trimebutine tablets (dimethylamino-2-phenyl-2-n-butyl-3,4,5- trimethoxybenzoate maleate, CAS 34140-59-5, reference) and a new tablet formulation (Eurogalena, test) were administered in 24 healthy volunteers of both sexes according to a cross-over design, in a single dose of one 100 mg tablet of each formulation. Blood samples were drawn off over a 24-h period, before (time 0) and after each administration at specific intervals. Trimebutine and its main active metabolite, desmethyl-trimebutine, were measured in plasma using a validated HPLC method with UV detection. For both compounds, the sensitivity was 20 ng.ml-1 and the analytical method was proved to be linear for concentrations between 20 ng.ml-1 and 5000 ng.ml-1, with a variability less than 11%. The non-compartmental method was used for pharmacokinetic analysis. The confidence interval approach was used for comparison of the formulations according to the EU guidance note on bioavailability and bioequivalence on Cmax, AUC0-t and AUC0-infinity, log transformed. Tmax values were statistically compared using the Friedman non-parametric test. No trimebutine concentration was measured in the plasma samples. The obtained data with desmethyl-trimebutine proved the bioequivalence of the two tested formulations.

Adult↗
PubMed2000

The effects of a prolonged running exercise on strength characteristics.

The aim of this study was to examine concentric, isometric, and eccentric strength reductions in the quadriceps muscle following a prolonged running exercise. Before and after a 2 h run (28.4+/-1.4 km) peak torque (PT) of the knee extensors at angular velocities of -120, -90, -60, 0, 60, 120, 180, 240 degrees x s(-1) using an isokinetic dynamometer, electromyographic (EMG) activity of the vastus lateralis (VL) and vastus medialis (VM) muscles and height of a counter movement jump were recorded in twelve well-trained triathletes. Counter movement jump performances decreased by 10% and PT values were all significantly lower (p < 0.01) at each angular velocity following the run. The torque loss was significantly (p < 0.01) greater under eccentric contractions (from 18 to 21%) than under concentric ones (from 11 to 14%). EMG activity (RMS) was lower in both VL and VM muscles after the 2 h run but no difference existed in RMS losses between concentric and eccentric contractions. The present results demonstrate that 1) a prolonged running exercise more greatly affects eccentric force production in the quadriceps muscle, and 2) this specificity seems to be due to an impairment of the muscular contractile mechanism rather than a modification to the neural input.

Adult↗
PubMed2000

The effects of electromyostimulation training and basketball practice on muscle strength and jumping ability.

The aim of this study was to investigate the influence of a 4-week electromyostimulation training program on the strength of the knee extensors and the vertical jump performance of 10 basketball players. Electromyostimulation sessions were carried out 3 times weekly; each session consisted of 48 contractions. Testing was carried out before and after the electromyostimulation training program (week 4) and once more after 4 weeks of normal basketball training (week 8). At week 4, isokinetic strength increased significantly (p < 0.05) at eccentric and high concentric velocities (between 180 and 360 x s(-1)); this was not the case for low concentric velocities (60 and 120 degrees x s(-1)). Electromyostimulation training increased also isometric strength at the two angles adjacent to the training angle (p < 0.01). Squat jump increased significantly by 14% at week 4 (p < 0.01), whereas counter movement-jump showed no change. At week 8, gains in isokinetic, isometric strength and squat-jump performance were maintained and the counter movement jump performance increased significantly by 17% (p<0.01). Electromyostimulation as part of a short strength-training program enhanced knee extensor strength and squat jump performance of basketball players.

Adult↗
PubMed2000

Re-examination of training effects by electrostimulation in the human elbow musculoskeletal system.

This study examines the effects of a 7 weeks sub-maximal training period of electrostimulation on the maximal isometric, concentric, eccentric voluntary torque and muscle contractile properties of the elbow flexor muscles of nine subjects. The daily program consisted of five series of six 6-s isometric actions (60 to 70% of maximal isometric voluntary action) at an elbow angle of 90 . After training the maximal voluntary isometric flexion torque increased significantly whereas the maximal voluntary isometric extension torque decreased significantly. Increases in isometric flexion torque were linked to an increase of the myoelectrical activity of the biceps brachii muscle. Under dynamic conditions flexion torque was significantly increased throughout the whole spectrum of angular velocities. These changes were accompanied by an increase in the myoelectrical activity of the agonist muscle under eccentric conditions and at two fast concentric angular velocities, without modifications of the myoelectrical activity of the antagonist muscle. The analysis of the electrical and mechanical twitches indicated that modifications of the muscle membrane electrical activity were also present at the muscle level. These results indicate that torque gains were attributed to neural adaptations and/or to a modification of the relative part of agonist and antagonist muscles in elbow flexion torque production.

Adaptation, Physiological↗
PubMed2000

Antiproteinuric effect of calcium antagonists on puromycin-induced experimental nephrosis.

Calcium antagonists have a potential for beneficial effects on kidney function unrelated to their antihypertensive action. In this study we have investigated the efficacy of calcium antagonists compounds (verapamil, nifedipine and diltiazem) on reversible acute renal insufficiency, proteinuria and interstitial nephritis induced by the puromycin ammonucleoside (PAN). An increase in blood pressure (BP) was detected on day 14, with no statistical differences in the response to calcium antagonists. Serum creatinine concentration increased to 1.2 mg/dL on day 7 after PAN and decreased to 0.7 mg/dL at 14 days, calcium antagonists shortened the time required to reach baseline or control levels. Calcium antagonists also reduced proteinuria in the PAN-treated animals, in both day 7 and day 14. Differential effects of the antagonists were observed. Verapamil caused a greater reduction (p < 0.01) in proteinuria than nifedipine or diltiazem in day 7. Moreover, verapamil (p < 0.01) and nifedipine (p < 0.01) reduced the total number of interstitial infiltrating leukocytes from 690 to 120 and 425 positive cells/20 high power fields (x63) respectively, by contrast, diltiazem had no effect. We conclude that in this model of PAN nephropathy verapamil is more effective in reducing both proteinuria and the severity of acute interstitial nephritis than either nifedipine or diltiazem. The possible clinical implications of these results remain to be elucidated.

Animals↗
PubMed2000

Risperidone-associated weight gain in children and adolescents: a retrospective chart review.

OBJECTIVE: Risperidone use has been associated with substantial weight gain in children and adolescents. Reports available to date have consisted of small case series evaluated without standardized indices of developmentally normative weight increase. The purpose of this study was to evaluate age- and gender-adjusted weight changes linked to risperidone use in a juvenile psychiatric inpatient population. METHOD: Thirty-seven child and adolescent inpatients treated with risperidone for 6 consecutive months were compared to a group of 33 psychiatric inpatients with no atypical neuroleptic exposure. Weight, height, and body mass index (BMI) were recorded on at least a monthly basis, and Tanner staging was completed on admission. Percent change from baseline weight, changes in standardized z scores of weight for age and gender, and proportion of subjects experiencing a < or = 7% weight increase from baseline were compared among groups. RESULTS: Subjects in both groups were comparable at baseline except for gender distribution (more males were in the risperidone group, p < 0.05). Risperidone-treated children and adolescents experienced significant weight gain between baseline and endpoint (paired t test, p < 0.001) that was first evident within 2 months of starting treatment, progressed steadily at an average rate of 1.2 kg/month, and did not reach a clear plateau during 6 months of observation. Significant increases in standardized weight were noted at 3 and 6 months for risperidone-treated subjects. Risperidone use conferred a substantial risk of gaining over 7% from baseline weight (odds ratio = 3.5, 95% confidence interval = 1.8-6.6, p < 0.001). CONCLUSIONS: Six-month exposure to risperidone was associated with clinically significant weight gain in 78% of treated children and adolescents (as opposed to 24% of those in the comparison group, p < 0.001). Risperidone dosage, concomitant medication use, and other demographic characteristics such as age, pubertal status, gender, and baseline weight and BMI were not associated with an increased risk of morbid weight gain. Standardized z scores offer advantages for the assessment of weight change among developing children and adolescents.

Adolescent↗
PubMed2000

Thyroid organoid formation in simulated microgravity: influence of keratinocyte growth factor.

The generation of artificial human thyroid tissues in suspension (low-shear environment, present in simulated microgravity [MG] and generated by a rotary cell culture system [RCCS]), was enhanced by increasing medium kinematic viscosity with a (3% v/v) suspension of extracellular matrix (basement membrane extract [BME]) in serum-free medium to generate artificial human thyroid organoids. Recombinant human keratinocyte growth factor (KGF, 7 ng/mL) facilitated human thyrocyte aggregation and three-dimensional (3-D) differentiation. There was an MG-associated decrease in extractable DNA that was reversed after addition of keratinocyte growth factor (KGF). In simulated MG, the increase in extractable DNA after KGF addition was up to 170% over non-KGF control cultures. In contrast, monolayer cultures in unit gravity showed a maximum DNA increase of 39% after KGF addition. Morphologically, differentiated thyroid neofollicles displayed polarization and were located in close proximity after 2 weeks of culture. Immunogold labeling with antibody to human thyroglobulin (Tg) revealed staining of follicular lumina and secretory vesicles, and a time-dependent increase in human Tg was detected in the culture media. Culture under simulated MG thus allowed direct visualization of KGF-facilitated thyrocyte/extracellular matrix interaction. Such artificial human thyroid organoids-generated in MG and in the presence of KGF-structurally resembled natural thyroid tissue. The above findings may have implications for autoimmune thyroid disease where KGF (if, for example, secreted locally by intraepithelial gammadelta T cells among other cells) may contribute to thyroid cell growth.

Cell Adhesion Molecules↗
PubMed2000

Effect of fruits, vegetables, or vitamin E--rich diet on vitamins E and C distribution in peripheral and brain tissues: implications for brain function.

Age-related neurodegenerative conditions are the principal cause of declining cognitive and motor function during aging. Evidence support that fruits and vegetables containing generous amounts of antioxidant nutrients are important for neurological function. We investigated the effect of diets enriched with fruits or vegetables but low in vitamin E and a diet high in vitamin E on the distribution of vitamins C and E in the brain and dopamine release of Fischer 344 rat model, over an 8-month period. The low-vitamin E diet resulted in lowered alpha-tocopherol levels in brain and peripheral tissues, whereas the animals that received a diet enriched in vitamin E showed a significant increase, between 500-900%. Vitamin C concentration in plasma, heart, and liver was reduced in the vitamin E-supplemented group. It is concluded that supplementation or depletion of alpha-tocopherol for 8 months results in marked changes in vitamin E levels in brain tissue and peripheral tissues, and varied distribution of alpha-tocopherol throughout the different brain regions examined. In addition, compared to control group, rats supplemented with strawberry, spinach, or vitamin E showed a significant enhancement in striatal dopamine release. These findings suggest that other nutrients present in fruits and vegetables, in addition to the well-known antioxidants, may be important for brain function.

Aging↗
PubMed2000

Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance.

A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (-35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/ kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.

Adaptation, Physiological↗