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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 145 records · Page 8Linked to original sources
PubMed2000

Ursolic acid triggers calcium-dependent apoptosis in human Daudi cells.

Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs naturally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in human lymphoma Daudi cells in a dose-dependent manner. UA also induced morphological changes in cells as well as loss of membrane asymmetry, DNA fragmentation and nuclei condensation, indicating that the mechanism by which UA induced cell death was through apoptosis. Treatment with UA increased intracellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induced constituted the first steps of apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Structures of nanometre-size crystals determined from selected-area electron diffraction data.

The structure of a new modification of Ti2Se, the beta-phase, and several related inorganic crystal structures containing elements with atomic numbers between 16 and 40 have been solved by quasi-automatic direct methods from single-crystal electron diffraction patterns of nanometre-size crystals, using the kinematical approximation. The crystals were several thousand times smaller than the minimum size required for single-crystal X-ray diffraction. Atomic coordinates were found with an average accuracy of 0.2 A or better. Experimental data were obtained by standardized techniques for recording and quantifying electron diffraction patterns. The SIR97 program for solving crystal structures from three-dimensional X-ray diffraction data by direct methods was modified to work also with two-dimensional electron diffraction data.

Journal Article↗
PubMed2000

Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction.

The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5'-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 control subjects recruited into the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde) and in 717 healthy individuals with echographically assessed arterial calcification and atherosclerosis who were participating in the AXA Study. In the ECTIM Study, alleles and genotypes were distributed similarly in patients and controls in the whole study group; in only 1 subgroup of subjects defined as being at low risk for MI were the concordant A-7 and Ala 83 alleles more frequent in patients with MI than in controls (P<0.003). In the AXA Study among subjects with femoral atherosclerosis, the same alleles were more common in the presence than the absence of plaque calcification (P<0.025). The other MGP polymorphisms were not associated with any investigated clinical phenotype. Transient transfection experiments with allelic promoter-reporter gene constructs and DNA-protein interaction assays were carried out to assess possible in vitro functionality of the promoter variants detected at positions -814, -138, and -7 relative to the start of transcription. When compared with the -138 T allele, the minor -138 C: allele consistently conferred a reduced promoter activity of -20% (P<0.0001) in rat vascular smooth muscle cells and of -50% (P<0.004) in a human fibroblast cell line, whereas the other polymorphisms, including -7, displayed no evidence of in vitro functionality. We conclude that the A-7 or Ala 83 alleles of the MGP gene may confer an increased risk of plaque calcification and MI; however, the observed relationships are weak or limited to subgroups of patients and therefore need confirmation.

Adolescent↗
PubMed2000

Feasibility and reliability of ankle/arm blood pressure index in preventive medicine.

Despite its potential usefulness for assessing preclinical atherosclerosis and cardiovascular risk, the ankle/arm blood pressure index (AAI) has not yet been the matter of study evaluating its feasibility and reliability by nonspecialist doctors in a general population. This study was planned for two steps. In step 1, the measurement of AAI, (ratio between Doppler systolic pressure at the ankle for each lower limb and the highest value of Doppler systolic pressure of the two upper limbs), should be performed by 50 general practitioners (GPs), 50 social security center physicians, and 50 occupational health physicians in 3,000 male smokers, 40 to 59 years, without clinical cardiovascular disease. In step 2, AAI measurement, coupled with echography-Doppler of iliofemoral arteries, should be repeated by a specialist in all subjects with decreased AAI (<0.90) and the first two subjects with normal AAI recruited in step 1 by each nonspecialist. The number of physicians and subjects participating in step 1 was lower than planned (80 physicians and 962 subjects) with the greatest defect for GPs (six physicians and 35 subjects) and the prevalence of decreased AAI was low (28 subjects). AAI measurement was repeated in step 2 in only 12 subjects with decreased AAI in step 1 and in 124 subjects with normal AAI in step 1. Five of the six subjects with decreased AAI in step 2 also had decreased AAI in step 1 and 123 of the 130 subjects with normal AAI in step 2 also had normal AAI in step 1. As regards echographic stenosis, decreased AAI had a sensitivity of 44% and a specificity of 98%. AAI seems more feasible for occupational health physicians and social security center physicians and AAI is also reliable for nonspecialists previously trained, but its predictive value as regards echographic stenosis is poor in asymptomatic subjects, which may limit its usefulness for detecting preclinical atherosclerosis.

Adult↗
PubMed2000

Two years' clinical experience with a quadrileaflet stentless bioprosthesis in the mitral position.

BACKGROUND AND AIMS OF THE STUDY: Currently available bioprosthetic mitral valves do not provide sufficient durability. A new stentless pericardial prosthesis was designed for better hemodynamic performance and reduction of stress load compared with current stented bioprostheses. METHODS: Between September 1997 and August 1999, the Quadrileaflet mitral valve (QMV) was implanted in 17 patients at our institution. Four patients had minimally invasive mitral valve replacement. Mean patient age was 62.2 +/- 16.3 years; preoperative NYHA class was 3.06 +/- 0.2; ejection fraction was 64.1 +/- 14.7%. Echocardiography was performed pre-, intra- and postoperatively, and at 3-6, 12 and 24 months follow up. RESULTS: Fifteen patients had an uneventful intra- and postoperative course. Two patients died, one from acute left heart failure at 6 h after surgery, and one on the first postoperative day after resuscitation for ventricular fibrillation. A small-sized prosthesis was implanted in four patients, medium-sized in eight and large-sized in five. The mean duration of cardiopulmonary bypass was 138.3 +/- 37.0 min; mean cross-clamp time was 91.3 +/- 26.3 min. Postoperative control echocardiography showed a mean valve orifice area of 2.5 +/- 0.4 cm2, transvalvular velocity (Vmax) was 1.6 +/- 0.4 m/s, and mean pressure gradient 3.6 +/- 2.0 mmHg. Echocardiographic evaluation after 3, 6 and 12 months showed no significant difference compared with the intraoperative data. Three patients had a minor mitral regurgitation (grade I-II). At 12 months all patients were in NYHA class I or II. CONCLUSION: The implantation technique of the QMV is more demanding, but the prosthesis is a promising alternative to conventional biological mitral valve replacement. Further follow up is needed to confirm these favorable mid-term results.

Adult↗
PubMed2000

[Blood and arterial wall rheology and cardiovascular risk factors].

The vascular endothelium and circulating blood cells are exposed to a hemodynamic environment related to the pulsatile nature of the pressure and blood flow which influence the morphology, the physical properties and the metabolism of the cells. Among these mechanical forces, shear stresses, related to the speed gradients and to the blood viscosity, control vascular vasomotor tone and thrombogenecity, stimulating the production of the endothelial factors of relaxation or contraction, of the coagulation factors or activating erythrocyte and platelet aggregation or disaggregation phenomena. Low shear stress is considered to be a critical factor in the causation of thickening of the arterial wall and in the formation of atheromatous plaques. These plaques develop predominantly in specific parts of the arterial tree where asymmetries in the velocity profiles occur. A close relationship has been found in a large general population between plasma viscosity and thickening of the carotid bifurcation. The blood cells share the same environment as the endothelial cells. Thus, the shear stresses to which the erythrocytes are submitted is a major determinant of the blood viscosity. Shear is also an important physiological parameter regulating platelet aggregation in flowing suspensions. However, in vivo, the response of platelets depends on the balance between activation of the platelets by shear and the same rheological forces acting on the endothelial cells which produce mediators which inhibit this activation in order to maintain blood fluidity.

Arteries↗
PubMed1999

[Preclinical detection of atherosclerosis].

Several markers of preclinical atherosclerosis are currently available, such as: wall thickening and stiffening and endothelial dysfunction of large peripheral arteries detected by ultrasonography, or coronary calcification detected by ultrafast computed tomography. They reflect the integrated effects over time of multiple risk factors, traditional and emerging, and some of them (wall thickening and coronary calcification) have demonstrated a powerful predictive value as regards subsequent clinical events. Also these markers are invaluable targets for testing the effects of preventive treatments. Their detection should help selecting those asymptomatic subjects at risk for cardiovascular disease in whom prevention is justified.

Arteriosclerosis↗
PubMed1999

Altered development of dopaminergic cells in the retina of weaver mice.

Postnatal degeneration of dopaminergic (DA) cells is known to occur in mesencephalic nuclei of mutant weaver mice, whereas retinal DA content is reported to be unchanged in the adult animal. To determine whether morphological changes occur in the weaver retinal DA system, we compared weaver and control developing and adult retinas after tyrosine hydroxylase (TH) immunohistochemistry. The density and distribution of DA cells were analyzed using Dirichlet tessellation. Not only was no DA cell loss found in adult weaver retinas, but we even observed an increase in DA cells in weaver compared to control retinas between postnatal days 14 and 30. Furthermore, some unusual features were found during the latter period: atypical cells (representing a maximum of 12% of the whole DA cell population) were observed, and these differed from typical DA cells in terms of both location (slightly more external within the inner nuclear layer) and appearance (flat somata, round and clear nuclei, thick dendritic trunks emerging laterally and giving rise to horizontal processes). Some of the atypical cells were intermingled in a delicate network lying in a more outer focal plane than the main DA plexus. The expression of GIRK2, a G protein-related inward rectifying K(+) channel responsible for the weaver syndrome, was investigated. Although no GIRK2 labeling was demonstrated in DA cells, its possible involvement in the transient disturbances observed in the weaver DA retinal system is discussed.

Animals↗
PubMed1999

Recombinant growth hormone's effects on the strength and thickness of radiation-injured ileal anastomoses: a rat model.

BACKGROUND: Small bowel resections following radiotherapy for gynecologic cancers have resulted in significant rates of morbidity and mortality. The objective of this study was to evaluate the effect of rGH on the breaking strength and thickness of radiation-injured ileal anastomoses in an animal model. MATERIALS AND METHODS: Sprague-Dawley rats were treated with 1800 cGy of pelvic irradiation in a single fractionation. Seventeen weeks following pelvic teletherapy an ileo-ileostomy was performed. The rats were randomized to receive 2.0 mg/kg/day of rGH for 7 days or placebo. On the seventh postoperative day a segment of ileum surrounding the anastomosis was resected. The segments were tested for breaking strength or were histologically measured for anastomotic thickness. RESULTS: The ileal anastomotic breaking strength in the rGH group was 181 +/- 8.4 g (mean +/- standard error). The breaking strength of ileal anastomoses in the placebo group was 133 +/- 6.9 g (P < 0.05). The rGH group demonstrated a greater anastomotic thickness (1.65 +/- 0.116 mm) than the placebo group (1.17 +/- 0.113 mm, P < 0.05). Of placebo rats 14.7% developed anastomotic leaks compared to 0% of rGH-treated animals (P < 0.05). CONCLUSIONS: RGH increased the ileal anastomotic breaking strength by 36% in radiated rats. The anastomotic leak rate was reduced from 14.7% in the placebo group to 0% in the rGH group. These findings correlated with a 41% increase in the thickness of the anastomotic connective tissue in the rGH group. Clinical investigation in selected patients is warranted.

Anastomosis, Surgical↗
PubMed1999

A flexible protocol for artificial preparation of the endometrium without prior gonadotropin-releasing hormone agonist suppression in women with functioning ovaries undergoing frozen-thawed embryo transfer cycles.

OBJECTIVE: To present our experience with a flexible and convenient protocol for artificial endometrial preparation without prior GnRH agonist suppression in patients with functioning ovaries undergoing frozen ET. DESIGN: Case series. SETTING: An IVF unit in a university hospital. PATIENT(S): All patients who underwent IVF with embryo cryopreservation from December 1997 to June 1998 and requested transfer of their frozen-thawed embryos. INTERVENTION(S): Controlled endometrial preparation for ET entailed the use of a fixed dose of 6 mg/d of micronized E2 started on day 1 of the cycle, followed by concomitant administration of micronized P placed in the vagina. MAIN OUTCOME MEASURE(S): Hormonal and endometrial profiles throughout the cycle, pregnancy rate per ET, implantation rate, and pregnancy outcome. RESULT(S): Of 185 treatment cycles in 140 patients, 8 cycles (4.3%) were canceled. In another 2 cycles, no embryos were suitable for transfer. For the remaining 175 ET cycles, the calculated pregnancy rate and implantation rate were 21.7% and 9%, respectively. The proliferative phase could be extended up to 20 days but was a mean (+/-SD) of 15+/-1.9 days. CONCLUSION(S): For patients with functioning ovaries, controlled endometrial preparation for the transfer of frozen-thawed embryos can be done successfully by using oral E2 from day 1 of the cycle followed by P preparation. Prior suppression with GnRH agonist is not necessary.

Adult↗
PubMed1999

Influence of hypercholesterolemia and endothelin-3 pre-treatment on the effects of shear forces on platelet aggregation and cyclic GMP content.

Shear forces induce platelet aggregation and stimulate the endothelial production of anti-aggregatory factors. Among them, endothelin-3 (ET-3) has been reported to reduce aggregation and to increase platelet cyclic GMP (cGMP) content. Since hypercholesterolemia modifies both platelet aggregability and endothelial function, we compared in 14 hypercholesterolemic and 15 normocholesterolemic subjects the influences of shear forces (240 and 650 s(-1)) on platelet aggregation and cGMP content, and their modulation by ET-3. Spontaneous maximal aggregation occurred earlier and at a greater extent in hypercholesterolemic than in normocholesterolemic subjects (63+/-2 vs 46+/-6% P < 0.01). Pre-treatment with ET-3 abolished the shear-induced facilitation of maximal aggregation in platelets of normocholesterolemic (from 70+/-2 to 52+2% at 240 s(-1) and from 73+/-1 to 59+/-2S at 650s(-1); P < 0.05) and hypercholesterolemic (from 78+/-3 to 64+/-2 at 240 s(-1) and from 78+/-2 to 66+/-3 at 650 s(-1); P < 0.05) subjects. cGMP content did not significantly differ between normocholesterolemic and hypercholesterolemic subjects (6.1+/-0.5 vs 6.9+/-0.7 pmol/10(9) platelets). It was reduced in platelets submitted to shear forces (P < 0.05). This shear-dependent reduction was suppressed by ET-3 pre-treatment. These results demonstrate that shear forces enhance platelet aggregation and diminish their cGMP content. ET-3 reduces the pro-aggregating effects of shear, suggesting a rise in cGMP content as a dynamic associated mechanism.

Blood Platelets↗
PubMed1999

Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing.

A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.

Animals↗
PubMed1999

A new gypsogenin saponin from arenaria filicaulis

The structure elucidation of a new saponin from Arenaria filicaulis (Boiss.), Caryophyllaceae, Snatzkein F (1), containing gypsogenin with a tetrasaccharide moiety was accomplished by use of 1D and 2D NMR methods.

Journal Article↗
PubMed1999

Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus.

The metabolic pathways that produce 11-cis retinal are important for vision because this retinoid is the chromophore residing in rhodopsin and the cone opsins. The all-trans retinal that is generated after cone and rod photopigments absorb photons of light is recycled back to 11-cis retinal by the retinal pigment epithelium and Müller cells of the retina. Several of the enzymes involved have recently been purified and molecularly cloned; here we focus on 11-cis retinol dehydrogenase (encoded by the gene RDH5; chromosome 12q13-14; ref. 4), the first cloned enzyme in this pathway. This microsomal enzyme is abundant in the retinal pigment epithelium, where it has been proposed to catalyse the conversion of 11-cis retinol to 11-cis retinal. We evaluated patients with hereditary retinal diseases featuring subretinal spots (retinitis punctata albescens and fundus albipunctatus) and patients with typical dominant or recessive retinitis pigmentosa for mutations in RDH5. Mutations were found only in two unrelated patients, both with fundus albipunctatus; they segregated with disease in the respective families. Recombinant mutant 11-cis retinol dehydrogenases had reduced activity compared with recombinant enzyme with wild-type sequence. Our results suggest that mutant alleles in RDH5 are a cause of fundus albipunctatus, a rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments.

Adaptation, Ocular↗
PubMed1999

Predictive value of waist-to-hip ratio on cardiovascular risk events.

BACKGROUND: A central distribution of adipose tissue is frequently associated with cardiovascular disease (CVD) and its risk factors. METHODS: Clinical usefulness of waist-to-hip ratio (WHR) for predicting the risk of cardiovascular events, estimated with models based on data from the Framingham and Prospective Cardiovascular Münster (PROCAM) studies was evaluated. SUBJECTS: These were 552 men and 160 women, asymptomatic and at risk for CVD, aged 30-74 y, recruited from an ongoing risk factor screening program conducted at worksites. RESULTS: Abdominal fatness was a strong predictor of cardiovascular complications in subjects whose WHR was in the top quintile (> 0.98 for men and > 0.91 for women). The estimated percentage rate of coronary heart disease (CHD, P <0.01) and death (P < 0.01), myocardial infarction (P < 0.01), stroke (P < 0.01), total CVD (P < 0.001) and death (P < 0.01) increased with increasing quintile of WHR in men and women. In the highest WHR, the number of subjects exceeding a 15% risk of developing a coronary event over the next 10 y was more than two-fold greater (odds ratio (OR) 2.60 (confidence intervals (CI) 1.09-6.54) than in the lowest WHR quintiles. Similar six-year myocardial infarction (MI) risks at each quintile of WHR were observed in men in both Framingham and PROCAM models. In the overall population, CHD estimates increased with increasing quintiles of WHR with the Framingham model and an adapted model for estimating probabilities of disease in the French population of the Prevention Cardiovasculaire en Médecine du Travail (PCV-METRA) group. CONCLUSION: Abdominal deposition of fat assessed by WHR may be of strong clinical value for predicting high risk of cardiovascular events.

Adult↗
PubMed1999

UVB increases urokinase-type plasminogen activator receptor (uPAR) expression.

Keratinocytes synthesize and secrete urokinase-type plasminogen activator, which binds to its specific receptor on keratinocytes. When bound to urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator proteolytically converts surface bound plasminogen to plasmin, which in turn cleaves many extracellular components leading to pericellular proteolysis. The activation of the urokinase system has been observed during re-epithelialization of skin wounds and in lesions of the autoimmune blistering skin disease pemphigus. As pemphigus is photoinducible, we investigated the effect of ultraviolet B on urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor expression in the epidermal keratinocyte cell line A431. Ultraviolet B increased cellular and secreted urokinase-type plasminogen activator protein (enzyme-linked immunosorbent assay) and urokinase-type plasminogen activator receptor cell surface expression (flow cytometry) 24 h postirradiation. Northern blot analysis indicated that ultraviolet B increased urokinase-type plasminogen activator receptor mRNA. Compared with a more rapid mRNA induction by epidermal growth factor (maximal after 4 h) the ultraviolet B response was maximal after 24 h and prolonged up to 36 h. The mRNA induction was not dependent on protein synthesis as judged by cycloheximide incubation. Ultraviolet B did not influence urokinase-type plasminogen activator receptor mRNA stability (actinomycin D incubation). A transiently transfected chloramphenicol acetyltransferase-reporter construct containing a -398/+51 urokinase-type plasminogen activator receptor promoter fragment was activated when cells were exposed to ultraviolet B. This induction was almost completely abolished by mutating a -182/-176 AP-1 binding sequence. Ultraviolet B increased the binding capacity at this AP-1 motif in electrophoretic mobility shift assays. These data identify a distinct transcriptional mechanism by which ultraviolet B induces urokinase-type plasminogen activator receptor. The epidermal induction of components of the proteolytic urokinase system by ultraviolet B may help explain the photoinducibility of pemphigus lesions.

Binding Sites↗
PubMed1999

Carotid wall inertial index increase is related to intima-media thickening in hypertensive patients.

OBJECTIVE: The aim of this study is to evaluate the relationship between carotid intima-media thickness (IMT) and arterial wall inertial behaviour. METHODS: The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. The common carotid artery of eleven normotensive subjects (NTA) and eleven mild-to-moderate essential hypertensive patients (HTA) were measured noninvasively using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure (P) and diameter (D) loops. A linear discrete time model was used to estimate the inertial index (K(M)) using a system modelling-identification approach. RESULTS: In NTA K(M) was 0.333+/-0.256 (mmHg x s2/mm) and IMT 0.643+/-0.061 (mm), whereas in HTA K(M) was 0.798+/-0.590 (P < 0.05) and IMT 0.760+/-0.034 (P < 0.025). When all data of K(M) versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r = 0.61 (P < 0.05) was obtained. CONCLUSION: Wall inertia increase was associated with a higher IMT, suggesting that the intima-media thickening might be partially related to vascular hypertrophy manifested as increase of inertial behaviour.

Adult↗