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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 163 records · Page 9Linked to original sources

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↗

Benchmarking cardiac catheterization laboratories: the impact of patient age, gender and risk factors on variable costs, device costs, total time and procedural time in 53 catheterization laboratories.

Coronary catheterization laboratories (CCLs) are the cornerstones of the delivery system for many cardiovascular procedures performed in the United States. However, few comprehensive data exist benchmarking physician activities in CCLs. This study benchmarks cost and time data on 82,548 consecutive patient encounters in 53 CCLs for the 18-month period of January 1997 through June 1998. The data are compiled from the OEP program, a relational database developed by Boston Scientific/Scimed (Maple Grove, Minnesota) for use in CCLs. CCL productivity (total time and procedure time) and cost (variable costs and device costs) benchmarks are created for: 1) left heart catheterization; 2) right and left heart catheterization; 3) percutaneous transluminal coronary balloon angioplasty (PTCA); 4) atherectomy; and 5) coronary stents. Results show the variable costs (those costs that vary in direct proportion to changes in CCL activities) for the five procedures are: $308, left heart catheterization; $395, right and left heart catheterization; $841, PTCA; $2,768, atherectomy; and $3,186, coronary stent. These variable costs are lower than the typical average costs reported for these procedures because they do not include hospital, laboratory, and physician costs, only the procedure-specific activity-related costs most directly controlled and/or influenced by CCL physicians or administrators. The total time for the left heart catheterization averaged 64 minutes and 84 minutes for the right and left heart catheterization, respectively, and procedural times averaged 25 and 32 minutes, respectively. For the major interventional procedures N PTCA, atherectomy, and coronary stents, total times averages were 102, 135, and 117 minutes, respectively. Procedural times for these procedures averaged between 60 and 65 percent of the total time. The major implications of these findings are discussed and limitations noted.

Age Factors↗

[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↗