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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 109 records · Page 6Linked to original sources
PubMed2000

Melanoma peptide vaccines: from preclinical background to clinical trials.

The discovery that immune T-cells recognize intracellularly processed peptides associated with major histocompatibility locus molecules has revolutionized the cancer vaccine field by providing new reagents for the generation of immune responses against cancer. The cloning of tumor antigen genes has proceeded most rapidly in melanoma because of the ease with which melanoma-specific T-cells can be propagated in vitro. The cloning and identification of tumor regression antigens and data from the initial clinical trials with peptides vaccines derived from those antigens are presented here.

Antigens, Neoplasm↗
PubMed2000

[Evoked mechanical and electrical anal sphincter responses after cortical and lumbar magnetic stimulation].

In 13 healthy volunteers we recorded electrical and mechanical anal sphincter (AS) evoked responses. Electrical responses were obtained with surface electrodes, and mechanical responses by anal manometry; all responses were compared with those of anterior tibialis. Mechanical evoked responses' latency and amplitude were calculated. The mean total conduction time of the electrical responses was 26.07 ms at rest and 23.31 ms with mild contraction (p < 0.003). After lumbar magnetic stimulations, because of stimulation artefact, electrical responses couldn't be correctly measured. The mean central conduction time calculated with mechanical responses was 21.44 ms at rest and 18.81 ms with mild contraction (p < 0.003). The mean central conduction time to the anterior tibialis was shorter (14.38 ms; p < 0.003). Evoked mechanical responses', amplitudes were respectively 128.2 cm H2O (cortical stimulations at rest), 138.8 cm H2O (cortical stimulations with mild contraction) and 133.1 cm H2O (lumbar stimulations at rest) (NS). Evoked mechanical responses amplitudes were correlated with the AS maximal voluntary contraction amplitude (p < 10(-4)). Mechanical motor evoked responses after cortical and lumbar magnetic stimulations can be recorded and quantified. In anorectal disorders, this technique could be of major interest for the diagnosis of neurologic lesions versus behavioural problems.

Adult↗
PubMed2000

Leptin: an essential regulator of lipid metabolism.

This paper reviews the general mechanisms by which leptin acts as a regulator of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid metabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. As well, normal decreases in energy expenditures (e.g. with diurnal cycles or reduced caloric intake) do not occur. This is probably caused by an increase in mitochondrial proton leak mediated by leptin via increases in sympathetic nervous system stimulation and thyroid hormone release. The decrease in caloric input coupled with relatively higher energy expenditure, therefore, leads to negative energy balance. Leptin also changes the fuel source from which ATP is generated. Fuel preference switches from carbohydrate (glucose) to lipid (fatty acids). This effect arises through stimulation of triacylglycerol catabolism by leptin. In vitro studies show that leptin is a potent stimulator of lipolysis and fatty acid oxidation in adipocytes and other cell types. Consequently, leptin is also a regulator of cellular triacylglycerol content. Hormonal regulation of leptin, as well as its role in fasting and seasonal weight gain and energy expenditure are also briefly discussed.

Adipocytes↗
PubMed2000

The catalytic transition state in ATP synthase.

The catalytic transition state of ATP synthase has been characterized and modeled by combined use of (1) Mg-ADP-fluoroaluminate, Mg-ADP-fluoroscandium, and corresponding Mg-IDP-fluorometals as transition-state analogs; (2) fluorescence signals of beta-Trp331 and beta-Trp148 as optical probes to assess formation of the transition state; (3) mutations of critical catalytic residues to determine side-chain ligands required to stabilize the transition state. Rate acceleration by positive catalytic site cooperativity is explained as due to mobility of alpha-Arg376, acting as an "arginine finger" residue, which interacts with nucleotide specifically at the transition state step of catalysis, not with Mg-ATP- or Mg-ADP-bound ground states. We speculate that formation and collapse of the transition state may engender catalytic site alpha/beta subunit-interface conformational movement, which is linked to gamma-subunit rotation.

Animals↗
PubMed2000

Efficacy of etodolac on gait in hip osteoarthritis as assessed by Bessou's locometer: a randomized, crossover, double-blind study versus placebo. Groupe de Recherche sur le Handicap de L'appareil Locomoteur.

OBJECTIVES: To assess the efficacy of a single, oral dose of etodolac (300 mg), a nonsteroidal antiinflammatory drug, on gait and pain in patients with unilateral hip osteoarthritis (hOA). DESIGN: Sixteen patients (8 F, 8 M; mean age: 61+/-11.2 years) with painful hOA were included in a randomized, crossover, double-blind study versus placebo. Space and time parameters were assessed using Bessou's locometer and pain was evaluated using the visual analog scale (VAS) at t0 (before taking the drug), t60 (min), t120, and t180 after taking a 300-mg tablet of etodolac. RESULTS: Walking speed was significantly faster only between t0 and t180 under etodolac versus placebo (P< 0.02). Walking speed increased between t0, t60, t120 and t180 with etodolac (P< 0.003), but not with placebo. Stride length increased (P< 0.0001) only on the hOA side, while the time parameters of gait for etodolac- and placebo-treated patients did not differ. VAS values differed significantly at t0 (P< 0.01) between etodolac and placebo groups, but no significant difference was observed at t60, t120 and t180. CONCLUSIONS: Bessou's locometer was able to demonstrate the efficacy of 300 mg of etodolac on gait in hOA. Walking speed was faster 3 h after taking the drug, essentially due to a greater stride length. Pain reduction in the etodolac group contributed to gait improvement. It was concluded that gait performances improved because of less hip pain and thus a greater range of motion after etodolac intake.

Adult↗
PubMed2000

Endovascular treatment of a giant aneurysm of the internal carotid artery in a child with visual loss: case report.

We report on a case of a giant aneurysm of the internal carotid artery in a 11-year old boy presenting with gradual unilateral visual loss, combined with slight headache and retro-orbital pain. Endovascular balloon occlusion of the internal carotid artery combined with monitoring of somatosensory evoked potentials was performed. Follow-up MR imaging six months after balloon occlusion revealed complete thrombosis and considerable retraction of the aneurysm. However, visual loss persisted, since therapy was initiated too late and optic nerve atrophy had already occurred. It is important to emphasize that visual disturbance should be considered as an emergency, and, although rare, aneurysms do occur in the pediatric population.

Balloon Occlusion↗
PubMed2000

Spatial and temporal gait variable differences between basketball, swimming and soccer players.

The gait variables of 10 swimmers, 10 basketball players, and 16 soccer players were compared. They were all male and right-handed. There was no statistical difference between the three groups in age, weight and height. Spatial and temporal gait variables were measured with the Bessou gait analyzer. In the swimmers group, the gait variables of the right side were not statistically different from those of the left side. The right propulsion double support duration, right cycle duration, and right late swing phase duration were respectively longer than those on the left side for the basketball players. The right propulsion double support duration, right step length, and right late swing phase duration were higher than those on the left side for the soccer players. Moreover, a discriminant analysis performed with the gait variables permitted significant differentiation between the three groups. In conclusion, both basketball and soccer players presented asymmetrical gait variables, that have never been previously reported in normal subjects, or in swimmers. These results suggest that the anticipatory postural adjustments programmed to be used just before a jump or a shoot influence the motor program of the spontaneous locomotion. These gait asymmetries could also be due to asymmetric muscle development.

Adult↗
PubMed2000

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease.

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype.

Aged↗
PubMed2000

Detection of chromosomal aberrations by a whole-genome microsatellite screen.

Chromosomal aberrations are a common cause of multiple anomaly syndromes that include developmental and growth retardation. Current microscopic techniques are useful for the detection of such aberrations but have a limit of resolution that is above the threshold for phenotypic effect. We hypothesized that a genomewide microsatellite screen could detect chromosomal aberrations that were not detected by standard cytogenetic techniques in a portion of these individuals. To test this hypothesis, we performed a genomewide microsatellite screen of patients, by use of a currently available genetic-marker panel that was originally designed for meiotic mapping of Mendelian traits. We genotyped approximately 400 markers on 17 pairs of parents and their children who had normal karyotypes. By using this approach, we detected and confirmed two cases of segmental aneusomy among 11 children with multiple congenital anomalies. These data demonstrate that a genomewide microsatellite scan can be used to detect chromosomal aberrations that are not detected by microscopic techniques.

Abnormalities, Multiple↗
PubMed2000

Respiratory efficacy of subglottic low-frequency, subglottic combined-frequency, and supraglottic combined-frequency jet ventilation during microlaryngeal surgery.

UNLABELLED: We tested the respiratory efficacy of different jet ventilation techniques (subglottic low-frequency versus subglottic combined-frequency and subglottic combined-frequency versus supraglottic combined frequency) in patients undergoing microlaryngeal surgery. The PaCO(2) and the quotient of arterial oxygen tension (PaO(2)) over FIO(2) were measured. After anesthetic induction (propofol, remifentanil, vecuronium), an endotracheal Mon-Jet catheter (Xomed, Jacksonville, FL) for subglottic jet ventilation and a laryngoscope for supraglottic jet ventilation (Carl Reiner G.m.b.H., Vienna, Austria) were inserted. In Group 1 (n = 18), subglottic low-frequency (15 breaths/min), combined-frequency (600 and 15 breaths/min), and low-frequency jet ventilation was subsequently performed (15 min each). In Group 2 (n = 19), the sequence was supraglottic, subglottic, and supraglottic combined-frequency jet ventilation. The driving pressures were initially adjusted to achieve normocapnia and were not changed during the entire study period. The FIO(2) was measured endotracheally. The Wilcoxon's signed rank test was applied. In Group 1, PaCO(2) and PaO(2)/FIO(2) improved significantly after switching from subglottic low-frequency to subglottic combined-frequency jet ventilation (PaCO(2), from 46.6 +/-8.3 to 42.1+/-8.1 mm Hg; PaO(2)/FIO(2), from 311+/-144 to 361+/-141 mm Hg; P<0.05). In Group 2, PaCO(2) increased and PaO(2)/FIO(2) decreased significantly after switching from supraglottic to subglottic combined-frequency jet ventilation (PaCO(2), from 39.4+/-7.1 to 45.9+/-7.5 mm Hg; PaO(2)/FIO(2), from 415+/-114 to 351+/-129 mm Hg; P<0.05). We conclude that subglottic combined-frequency jet ventilation is less effective than supraglottic combined-frequency ventilation, but more effective than subglottic low-frequency jet ventilation. IMPLICATIONS: The combination of high and low respiratory frequencies (600 and 15 breaths/min) improves pulmonary gas exchange during subglottic jet ventilation via an endotracheal catheter. However, subglottic combined-frequency jet ventilation is less effective than supraglottic combined-frequency jet ventilation via a jet ventilation laryngoscope.

Adult↗
PubMed2000

A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women.

BACKGROUND: Although the male condom provides a reliable means of preventing HIV transmission, a broader choice of methods is required particularly in circumstances where the negotiation of condom use is difficult. Development of new products that may be effective as topical vaginal microbicides is the focus of a great deal of research activity currently. The novel agent PRO 2000, a naphthalene sulphonate derivative with in vitro activity against HIV and other sexually transmissible pathogens, is one such compound. We have studied the local and systemic safety and tolerance of a vaginal gel formulation of this agent at two concentrations (0.5% and 4%) over a 2 week period of daily exposure in two cohorts of healthy sexually abstinent women (one in London, UK, and the other in Antwerp, Belgium). METHODS: This was a randomised, placebo controlled, double blind, three arm clinical trial conducted on two sites. Macroscopic evidence of genital epithelial changes was sought using colposcopy and evidence of microscopic inflammation was acquired using high vaginal biopsy from predetermined sites (UK cohort only). Blood levels of PRO 2000 were measured and laboratory safety tests, including coagulation screens, were performed. The impact on vaginal ecology was also assessed. RESULTS: 73 women were enrolled across both sites (36 UK, 37 Belgium); 24, 24, 25 in the 4%, 0.5%, and placebo groups respectively. Of these, 70 completed 2 weeks' exposure to the study gel. Three (all in the 4% group) withdrew owing to adverse events which were possibly or probably gel related. Cervicovaginal abrasion was seen colposcopically in three subjects after 14 days of gel use (two in the 4% group and one in the placebo group). Genital ulceration was not seen during gel use in any of the subjects who completed the study. Histological evaluation of vaginal biopsy samples (36 women only) showed evidence of increased inflammatory signs in one participant of the 4.0% group. One volunteer in the placebo group had moderate inflammation at screening and at follow up. Severe inflammation was not seen among any of the subjects tested. Plasma levels of PRO 2000 and laboratory safety tests showed no evidence of systemic absorption. No impact was seen on normal vaginal ecology in the UK cohort where samples were taken 12 hours after the last gel application. CONCLUSION: In this phase I study PRO 2000 gel was found to be generally well tolerated with promising local and systemic safety profiles. The 0.5% gel was better tolerated than the 4% gel as fewer genital epithelial adverse events were seen in the former. Phase II studies are about to begin in sexually active women.

Administration, Intravaginal↗
PubMed2000

Pulmonary embolism: comprehensive diagnosis by using electron-beam CT for detection of emboli and assessment of pulmonary blood flow.

PURPOSE: To comprehensively assess thoracic anatomy and pulmonary microcirculation in pulmonary embolism by using computed tomographic (CT) angiography of the pulmonary arteries combined with functional CT imaging of blood flow. MATERIALS AND METHODS: Twenty-two patients suspected of having acute pulmonary embolism underwent contrast material-enhanced thin-section electron-beam CT angiography of the pulmonary arteries. In addition, in each patient, a dynamic multisection blood flow CT study was performed on a 7.6-cm lung volume with electrocardiographic gating. Pulmonary blood flow was calculated, and perfusion parameters were visualized on color-coded maps. The color-coded maps and CT angiograms were independently evaluated, segment by segment, by two readers for perfusion deficits and the presence of clots, respectively. The results were compared. RESULTS: Mean pulmonary blood flow was 0.63 mL/min/mL in the occluded segments versus 2.27 mL/min/mL in the nonoccluded segments (P: =.001). The sensitivity and specificity of perfusion maps for the presence of segmental pulmonary embolism compared with those of CT angiography were 75.4% and 82.3%, respectively, with positive and negative predictive values of 79.6% and 84.7%, respectively. The false-negative findings were caused mainly by partial occlusion of vessels. In eight patients, a substantial alternative or additional pathologic entity was diagnosed. CONCLUSION: By combining CT angiography and dynamic CT imaging, a comprehensive and noninvasive diagnosis of thoracic structure and function is feasible with a single modality.

Acute Disease↗
PubMed2000

Initial experience of an objective structured clinical examination in evaluating urology residents.

OBJECTIVES: Objective Structured Clinical Examination (OSCE) is now generally considered as the new gold standard for evaluating clinical competence. The objective of this study was to assess the feasibility of OSCE in evaluating urology residents. MATERIAL AND METHODS: 20 urology residents rotated through a circuit of five standardized patient-based OSCE stations of 10 min duration. The selection of problems was based on educational objectives of urology residency programs. Written questionnaires based on Likert-type scales were used to measure OSCE feasibility. The mean score was arbitrarily used as a passing score. Student t test was only used to compare the performance between junior and senior residents. RESULTS: Senior residents performed globally better, but without significant differences (51.3+/-7.8 vs. 45.03+/-5.1, p>0.05). Senior resident scores regarding outpatient problems were significantly higher (p = 0.04), more senior residents reached the passing score (75 vs. 16% junior residents). All the participants agreed that the clinical situations were realistic and that the simulated patients were believable. Most participants agreed that the sampling of cases were representative of urology practice. CONCLUSIONS: This is the first reported OSCE applied to urology residency. The results of this pilot study support the feasibility of an OSCE in assessing the performance of urology residents. Our data raises questions regarding the training of outpatient consultation skills to residents. This experiment warrants further series to explore the study's psychometrics features.

Clinical Competence↗
PubMed2000

Rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthase.

The rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthase is of the order of 10(11)-fold. We present a cyclic enzyme mechanism for the reaction, relate it to known F(1) X-ray structure and speculate on the linkage between enzyme reaction intermediates and subunit rotation. Next, we describe five factors known to be important in the Escherichia coli enzyme for the rate acceleration. First, the provision of substrate binding energy by residues lining the catalytic site is substantial; beta-Lys155 and beta-Arg182 are specific examples, both of which differentially support substrate MgATP versus product MgADP binding. Second, octahedral coordination of the Mg(2+) in MgATP is crucial for both catalysis and catalytic site asymmetry. The residues involved are beta-Thr156, beta-Glu185 and beta-Asp242. Third, there is stabilization of a pentacoordinate phosphorus catalytic transition state by residues beta-Lys155, beta-Arg182 and alpha-Arg376. Fourth, residue beta-Glu181 binds the substrate water and stabilizes the catalytic transition state. Fifth, there is strong positive catalytic cooperativity, with binding of MgATP at all three sites yielding the maximum rate (V(max)); the molecular basis of this factor remains to be elucidated.

Adenosine Triphosphate↗
PubMed2000

Analysis of point mutation in exon 2 of CYP2E1 gene in renal cell/urothelial cancer patients in comparison with control population.

OBJECTIVE: Genetic polymorphisms of human cytochrome P450s have been implicated to be of importance for susceptibility to different cancers. Recently, a point mutation was found in the exon 2 of the CYP2E1 gene (CYP2E1*2) [Hu et al. 1997]. In order to evaluate a possible link between the point mutation in exon 2 of the CYP2E1 gene and the susceptibility to renal cell/urothelial cancer, we developed a screening method based on the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). MATERIAL: DNA of peripheral white blood cells was isolated from 158 renal cell/urothelial cancer patients as well as from 150 controls. METHOD: Primers for PCR were designed by the Primer 3 release 0.1 program. The PCR yield a product of 215 base pairs (bp), which was digested with the restriction enzyme Hha I. The DNA fragments were separated on a 3% agarose gel stained with ethidium bromide. Restriction enzyme digestion of the PCR product obtained from the wild-type DNA resulted in the appearance of a 66 bp, a 43 bp, a 40 bp, a 39 bp and a 28 bp DNA fragment. In contrast to the wild-type, the digestion of the PCR product from DNA carrying the point mutation resulted in the loss of the 39 bp and 40 bp fragments and the appearance of an additional 79 bp fragment. Therefore, the loss of one Hha I restriction site caused by a single nucleotide exchange is suitable for the identification of the point mutation in exon 2 of CYP2E1 gene. RESULTS: However, we could not detect any point mutation in any of the 158 renal cell/urothelial cancer patients or the 150 controls. The distribution of the point mutation in exon 2 of CYP2E1 gene did not show any difference in renal cell/urothelial cancer patients and controls. CONCLUSION: This might indicate a lack of association between this CYP2E polymorphism (CYP2E1*2) and renal cell/urothelial cancer.

Base Sequence↗