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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 19 recordsLinked to original sources

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

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

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

Intracellular localization and membrane topology of 11-cis retinol dehydrogenase in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis retinaldehyde.

11-cis retinol dehydrogenase (EC 1.1.1.105) catalyses the last step in the biosynthetic pathway generating 11-cis retinaldehyde, the common chromophore of all visual pigments in higher animals. The enzyme is abundantly expressed in retinal pigment epithelium of the eye and is a member of the short chain dehydrogenase/reductase superfamily. In this work we demonstrate that a majority of 11-cis retinol dehydrogenase is associated with the smooth ER in retinal pigment epithelial cells and that the enzyme is an integral membrane protein, anchored to membranes by two hydrophobic peptide segments. The catalytic domain of the enzyme is confined to a lumenal compartment and is not present on the cytosolic aspect of membranes. Thus, the subcellular localization and the membrane topology of 11-cis retinol dehydrogenase suggest that generation of 11-cis retinaldehyde is a compartmentalized process.

Alcohol Oxidoreductases

[Therapeutic management of hypercholesterolemia].

FUNDAMENTAL PRINCIPLES: Therapeutic management of hypercholesterolemia requires information on two fundamental aspects: the patient's lipid profile and his/her risk of coronary artery disease. RISK EVALUATION: The latest therapeutic trials have partially confirmed the LDL-cholesterol levels retained for the different guidelines, including those proposed by the ANDEM. It is clear however, that the assessment of the individual beneficial effect of primary prevention must be based on a multifactorial evaluation of risk. But there is no standardization of methodologies currently used to evaluate risk. Briefly, these methodologies use mathematical equations deducted from statistical models or noninvasive quantification of preclinical atherosclerosis. PERSPECTIVES: In the future, this strategy based on quantification of cardiovascular risk should be evaluated in a prospective study.

Anticholesteremic Agents

Evidence of carotid artery wall hypertrophy in homozygous homocystinuria.

BACKGROUND: We aimed to determine whether intima-media thickness (IMT) was increased in the carotid artery of subjects with homocystinuria to better understand the in vivo contribution of homocysteine to early atherogenesis. METHODS AND RESULTS: We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocystinuria aged 3 to 34 years (mean, 13 years) and in 15 of their heterozygous parents aged 32 to 47 years (mean, 41 years) by comparison with 2 control groups of 15 healthy subjects of the same age. Far-wall IMT and lumen diameter were measured with a computerized program, and the cross-sectional area of the intima-media complex (CSA-IMC) was calculated from IMT and diameter. Comparison with their respective controls, adjusted for body surface area or height, showed that homozygotes had greater IMT (P<0.001) and CSA-IMC (P<0.05) and smaller diameter (P<0.05), whereas heterozygotes had values similar to their controls. Multivariate analysis of the arterial parameters with age, body surface area (or height), and plasma total homocysteine in the homozygous and heterozygous groups combined showed that IMT was related to age (P<0.05) and homocysteine (P<0.01), diameter was related to body surface area (P<0.001) or height (P<0.05), and CSA-IMC was related to age (P<0.05), body surface area (P<0.05) (but not height), and homocysteine (P<0.05). CONCLUSIONS: Homozygous homocystinuria was associated with common carotid wall hypertrophy, whereas heterozygous disease was not. Such hypertrophy may reflect a smooth muscle proliferation induced by hyperhomocysteinemia and represent a promising target for testing vascular effects of therapeutic measures to lower homocysteine.

Adolescent

Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships.

Curcumin, demethoxycurcumin and bisdemethoxycurcumin are the yellow coloring phenolic compounds isolated from the spice turmeric. This study was part of a program correlating the biological activity and molecular structure of antitumor agents; the effect of these curcuminoids and cyclocurcumin (Cyclocur) was examined on the proliferation of MCF-7 human breast tumor cells. Curcuminoids appeared to be potent inhibitors, whereas Cyclocur was less inhibitory. To contribute to our understanding of the mechanism of antiproliferative activity of curcumin, cell cycle analysis was performed by propidium iodide staining and a flow cytometry technique. Curcumin exerts a cytostatic effect at G2/M which explains its antiproliferative activity. The presence of the diketone moiety in the curcumin molecule seems to be essential for the inhibitory activity.

Anticarcinogenic Agents

The identification of a 9-cis retinol dehydrogenase in the mouse embryo reveals a pathway for synthesis of 9-cis retinoic acid.

The ligand-controlled retinoic acid (RA) receptors and retinoid X receptors are important for several physiological processes, including normal embryonic development, but little is known about how their ligands, all-trans and 9-cis RA, are generated. Here we report the identification of a stereo-specific 9-cis retinol dehydrogenase, which is abundantly expressed in embryonic tissues known to be targets in the retinoid signaling pathway. The membrane-bound enzyme is a member of the short-chain alcohol dehydrogenase/reductase superfamily, able to oxidize 9-cis retinol into 9-cis retinaldehyde, an intermediate in 9-cis RA biosynthesis. Analysis by nonradioactive in situ hybridization in mouse embryos shows that expression of the enzyme is temporally and spatially well controlled during embryogenesis with prominent expression in parts of the developing central nervous system, sensory organs, somites and myotomes, and several tissues of endodermal origin. The identification of this enzyme reveals a pathway in RA biosynthesis, where 9-cis retinol is generated for subsequent oxidation to 9-cis RA.

Alcohol Oxidoreductases

Comparison of cryopreservation outcome following intracytoplasmic sperm injection and conventional in vitro fertilization.

PURPOSE: Our purpose was to compare the success rate of transferring frozen-thawed embryos generated from either intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (IVF). METHODS: A retrospective review of all frozen-thawed embryo transfer (ET) cycles between January 1995 and April 1997 was performed. There were 83 and 204 transfer cycles of frozen-thawed multicellular embryos generated from conventional IVF (group A) and ICSI (group B), respectively. The survival rate of frozen-thawed embryos and the outcome following ET in both groups were assessed. RESULTS: The groups did not differ in age (31.7 +/- 4.6 and 30.6 +/- 6.0; mean +/- SD) or number of embryos transferred (3.5 +/- 1.1 and 3.8 +/- 1.3 for groups A and B, respectively). An acceptable pregnancy rate per ET was achieved in both groups, but the rate was significantly higher (P = 0.04) for group A than group B, 32.5 and 20%, respectively. Group A included frozen embryos of a higher quality than those of group B, but the proportion of embryos surviving after thawing was significantly higher for group B than group A (92.5 and 85.6%, respectively; P = 0.0004). The abortion rate did not differ between the two groups: 22 and 26.8% for groups A and B, respectively. CONCLUSIONS: Although an overall high pregnancy rate was achieved following frozen-thawed ET, it was lower for cycles in which embryos had been generated from ICSI. This difference may be attributed to a lower prefreezing embryo quality in the ICSI group. Embryos originating from ICSI were not vulnerable to cryopreservation and, when implanted, resulted in a comparable abortion rate to thawed embryos of conventional IVF.

Abortion, Spontaneous

Young low responders protected from untoward effects of reduced ovarian response.

OBJECTIVE(S): To correlate fertilization and clinical pregnancy rates (PRs) in low responders with their E2 levels (<500, 500-800, >800-1,000 pg/mL), age (20-30, 31-40, >40 years), number of follicles, and number of oocytes retrieved. DESIGN: A retrospective study. SETTING: The IVF unit of an academic hospital. PATIENT(S): One hundred forty-three women who failed to attain E2 levels of 1,000 pg/mL on the day of hCG administration. INTERVENTION(S): Controlled ovarian hyperstimulation, blood E2 and progesterone measurements, ultrasonographic scanning of ovarian follicles, oocyte retrieval after hCG administration, and ET. MAIN OUTCOME MEASURE: Clinical PR. RESULT(S): Although E2 levels, fertilization rates, age, and number of oocytes did not differ significantly between the three age groups, the PR achieved in the youngest group was approximately three times as high (19.3%) as that achieved in the two older groups. CONCLUSION: Young low responders represent a unique subset in that their age protects them from the deleterious effects of poor ovarian response.

Adult

Erythrocyte antioxidant status in asymptomatic hypercholesterolemic men.

An imbalance between antioxidant and oxidant-generating systems leading to an oxidative stress has already been proposed in the pathogenesis of atherosclerosis. In the present study we investigated the antioxidant status in 60 asymptomatic hypercholesterolemic (HC) men compared with 48 normocholesterolemic (NC) men. Hypercholesterolemic subjects had a significantly lower red blood cell vitamin E (vit E-RBC) content in spite of their normal total plasma and HDL vitamin E concentrations. Activities of erythrocyte superoxide dismutase and glutathione peroxidase were not significantly different between groups. We also determined the resistance of RBCs to an oxidative stress by determining the extent of hemolysis induced by a water-soluble azo-compound. This resistance was significantly decreased in HC men compared with NC subjects. These results demonstrate an altered antioxidant status of RBC in asymptomatic HC men associated with an increased erythrocyte susceptibility to an oxidative stress. The measure of the vitamin E content in RBC might be the most sensitive parameter for evidencing early oxidative stress which does not need an adaptation of enzymatic protective systems.

Adult

Cardiac valve endothelial cells: relevance in the long-term function of biologic valve prostheses.

OBJECTIVE: For reasons that are still unclear, biologic heart valve prostheses undergo degeneration after implantation. We studied the possible role of the immune system in this process. METHODS: We examined the expression of immunologically relevant molecules by human cardiac valve endothelium in situ and in vitro and studied re-endothelialization of implanted allogeneic and xenogeneic valvular surfaces using explanted bioprostheses and valves obtained from donor hearts at cardiac retransplantation. RESULTS: We demonstrate that human cardiac valve endothelial cells express molecules capable of initiating immune responses and might therefore play a role in the degeneration of viable cardiac valve prostheses. Also, we show evidence of re-endothelialization on the surfaces of xenografts and allografts but not on valves obtained from previously transplanted hearts. CONCLUSION: Inasmuch as valves from previously transplanted hearts seem to be free from degeneration, we conclude that reduction of the immunogenicity of allograft valve prostheses by HLA matching or immunosuppressive treatment might further improve long-term results after allograft valve replacement.

Antigens, CD

Two triterpene saponins from Arenaria filicaulis.

Two novel triterpenoid saponins, Snatzkein C, (3beta, 20-dihydroxylupan-28-oic acid 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucopyranosyl-28- O-beta-D-glucopyranoside) and Snatzkein D, (3beta, 20-dihydroxylupan-28-oic acid 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-28-O-beta-D-++ +glucopyranoside), have been isolated from Arenaria filicaulis. Their structure and conformational behaviour were elucidated by one- and two-dimensional 1H NMR and 13C NMR spectroscopy.

Carbohydrate Conformation

Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk for cardiovascular disease.

Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with Ci before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with Ci. In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.

Adult

Utility of electrocardiogram for predicting increased left ventricular mass in asymptomatic men at risk for cardiovascular disease.

The objective of this study was to test the value of electrocardiogram for predicting left ventricular mass (LVM), assessed echographically in 136 asymptomatic men with at least one major cardiovascular risk factor. We measured the Sokolow-Lyon and Cornell voltages, as well as the ratio of Cornell voltage to QRS voltage in lead II. The prevalence of left ventricular hypertrophy (LVH), defined as LVM of > or = 125 g/m2, was 6%, whereas that of increased LVM, defined as LVM of > or = 99 g/m2, the 90th upper percentile of a control group, was 29%. Receiver operating characteristics curves showed that for predicting LVH at 80% specificity, the Cornell/QRS(II) voltage ratio had a sensitivity of 75%, whereas those of the Cornell and Sokolow-Lyon voltages were 50% and 12.5%, respectively. For predicting increased LVM at 80% specificity, the Cornell/QRS(II) voltage ratio had a sensitivity of 56%, whereas the sensitivities of the Cornell and Sokolow-Lyon voltages were 36% and 22%, respectively. We conclude that, in constrast with the Sokolow-Lyon voltage, the new dimensionless Cornell/QRS(II) voltage shows a sensitivity at a high specificity value at least as acceptable as that of the Cornell voltage for predicting borderline-high LVM in a population with a low prevalence of LVH.

Adult