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Biomedical subjects

A Leber

Publications and source records attributed to A Leber.

At least 19 recordsLinked to original sources
PubMed2005

[Prediction of serious cardiovascular events by determining coronary artery calcification measured by multi-slice computed tomography].

BACKGROUND: The efficacious prophylaxis of myocardial infarction requires an accurate identification of patients at risk. Conventional risk stratification is often insufficient for this. We therefore examined the predictive value of coronary calcifications for future cardiovascular events. METHODS: We determined the extent of coronary calcification by multi-slice computed tomography in 924 patients (443 men, 481 women, aged 59.4 +/- 18.7 years) after coronary artery disease had been excluded by coronary angiography. To quantify coronary calcifications the volume score was calculated. After an observation period of 36 months was calculated the incidence of coronary revascularisation, myocardial infarction, and cardiac death. RESULTS: During the observation period the event rates for coronary revascularization (5.4 %/ year vs. 2.9 %/ year), myocardial infarction (3.8 %/ year vs. 1.8 %/ year), and cardiac death (2.1 %/ year vs. 1.0 %/ year) in patients with volume scores above the 75th percentile were significantly higher compared to the total study group. Correspondingly the scores in patients with revascularization (397 +/- 187), myocardial infarction (412 +/- 176), and cardiac death (422 +/- 184) were significantly higher compared to patients without cardiovascular events (218 +/- 167). In addition future cardiovascular events were excluded in patients without coronary calcifications. CONCLUSIONS: By determining coronary calcifications it was possible to identify patients at risk for myocardial infarction could be identified. Future cardiovascular events could not be observed in patients without coronary calcifications.

Calcinosis↗
PubMed2004

[Technique and possibilities of cardiac computed tomography].

Electron beam computed tomography no longer has a role to play in Germany. In contrast, multidetector spiral CT has great potential for replacing some coronary catheter studies, in particular for the exclusion of coronary artery disease, and this in particular since the forthcoming introduction of a 64-slice MDCT scanner promises a further improvement in temporal and special resolution. Currently, however it is no alternative to invasive angiography, since quantification of coronary stenoses is not possible; nor can a diagnostic evaluation be made in the presence of coronary calcifications or intracoronary stents. In particular, however, before applying CT angiography to the heart, the patient groups that can benefit from this method must be defined, especially in light of the fact that radiation exposure is three times as high as with diagnostic coronary catheterization.

Coronary Angiography↗
PubMed2004

[Coronary calcifications and the diagnosis of coronary artery disease].

Coronary calcium is a sensitive marker of coronary atherosclerosis, even at an early stage. With the aid of multislice computed tomography, noninvasive visualization of the microcalcification is possible. This enables the identification of asymptomatic patients at risk of developing future cardiovascular disease, and the initiation of effective preventive measures. In addition, in symptomatic patients, CT angiography with calcium scoring is of high negative predictive value in the exclusion of coronary artery disease.

Calcinosis↗
PubMed2004

[Evaluating multislice computed tomography for imaging coronary atherosclerosis].

PURPOSE: The purpose of this study was the evaluation of multidetector-row computed tomography (MDCT) for the assessment of atherosclerotic coronary artery vessel wall changes. METHODS: In an ex vivo study, 17 human hearts were scanned with MDCT and results were compared to histopathology. Morphologic imaging criteria of MDCT for various plaque-types were developed. In a following in vivo study, 94 coronary MDCT angiograms (MDCTA) of patients with suspected coronary artery disease (CAD) were reviewed retrospectively, assessing the diagnostic value of the coronary MDCTA, and determining the number and correlations of the various plaques types as described in the ex vivo study. Additionally, volumetry of calcified and noncalcified plaque components was performed. RESULTS: In the ex vivo study, MDCT showed a high sensitivity for calcified and non-calcified plaques. Comparing the results with histopathology, characteristic image criteria could be determined for lipid-rich, fibrous and calcified plaque components. Reviewing the contrastenhanced in-vivo MDCT coronary angiographies, presence of noncalcified plaques was proven in 38% of the patients. In 5 patients with a calcium score of 0, presence of coronary atherosclerosis was proven in the contrastenhanced scan. CONCLUSIONS: MDCT is able to differentiate various plaque components in an ex vivo setting as well as invivo. Contrastenhanced MDCT of the coronary arteries allows for the detection of noncalcified plaques. In vivo volumetry of noncalcified plaques is feasible.

Adult↗
PubMed2002

[Detection of coronary calcinosis with multislice spiral computerized tomography: an alternative to electron beam tomography].

Electron-beam CT (EBT) has been used for years as the gold standard to quantify coronary artery calcification as a marker of coronary atherosclerosis. With the introduction of Multi-Slice Spiral CT (MSCT) technology in 1999, EBT is now challenged in the determination of coronary calcium. The aim of this study was to determine the diagnostic accuracy of MSCT for the assessment of coronary calcium, comparing this new technique to EBT. The study population consisted of 54 male patients, aged 58 +/- 11 years with suspected coronary artery disease. For EBT, 40 axial slices (scan time = 100 ms, slice thickness = 3 mm) were acquired in one breath-hold (35 +/- 5 s) using an ECG-trigger at 80% of the RR interval. For MSCT, simultaneous acquisition of four axial slices (scan time = 250 ms, slice thickness = 2.5 mm) allowed the entire heart (40 slices) to be covered in one breath-hold (25 +/- 5 s) using a prospective ECG-trigger (R--450 ms). For quantification of coronary calcium the Agatston and the Volumetric calcium score (VCS) were applied. Mean Agatston score of the study group was calculated as 88 +/- 111 (median = 45), which is between the 25th and 75th age-corrected percentile of asymptomatic patients. For the Volumetric calcium score, number of lesions, calcium mass and density, no statistical difference was found between both imaging modalities. Agatston and Volumetric calcium score were statistically different between and within both scans. Mean variability of VCS of the two methods was calculated as 24% and was in the range of repeated EBT studies (14-44.9%). The Multi-Slice Spiral CT scanner is equivalent to EBT for the determination of coronary calcium and can, therefore, be used for calcium screening. Using a prospective ECG-trigger technique, the application of the Agatston method delivers statistically different results in comparison to EBT. With the application of the spiral mode technique, retrospective ECG-trigger and thinner slice thickness, further improvement in variability can be expected, thus allowing for follow-up studies to determine progression or regression of atherosclerosis with high accuracy.

Aged↗
PubMed2001

[Angiography with multi-slice spiral CT. Detecting plaque, before it causes symptoms].

The short imaging time of 1/4 second, renders the new generation of multiple-slice spiral CT devices with ECG gating enables the investigation of the heart without disturbing motion artefacts. With this method, calcifications of the coronary arteries can be detected or excluded. Certain amounts of coronary "chalk" in asymptomatic patients with risk factors point to coronary artery disease and thus a need to modulate the risk factors. With the aid of intravenous injection of contrast medium during the examination, non-calcified plaques in the coronary arteries can also be visualized. A limiting factor is that the patient's heart rate should not exceed 60 beats per minute. Indications for this examination are visualization of coronary vessels with the aim of excluding coronary artery disease, pre-operative planning and monitoring of bypass vessels, and non-invasive follow-up after PTCA and stenting.

Coronary Angiography↗
PubMed2001

[Exclusion of coronary calcium with electron beam tomography: an effective filter before invasive diagnosis in symptomatic patients?].

Electron beam computed tomography (EBCT) is the most sensitive and accurate method of measuring coronary calcium which indicates coronary atherosclerosis. We performed a prospective study in 1764 symptomatic patients who were referred to our hospital for coronary angiography because of suspected coronary artery disease. In all of these patients cardiac catheterization and coronary calcium scanning was performed within 3.2 +/- 4 days. 454/1225 men (37.0%) and 165/539 women (30.6%) had significant coronary stenoses > or = 75%. Only two men (0.4%) and no single woman (0.0%) with stenoses > or = 75% and only 3/323 patients (0.9%) with moderate stenoses (50-75%) did not exhibit coronary calcium. Coronary angiography excluded stenoses in 822 patients. Of these patients 261 (29.4%) did not reveal coronary calcium. In younger patients (< 60 years) without stenosis exclusion of coronary calcium was a frequent finding: 31% of men and 55.8% of women were free of coronary calcium. Thus, exclusion of coronary calcium with electron beam tomography defines a substantial subgroup of patients who have an extremely low risk of significant coronary stenosis despite suspected coronary artery disease in history and non-invasive testing. Determination of coronary calcium might, therefore, be an effective filter before invasive angiography in selected groups of symptomatic patients.

Adult↗
PubMed2001

Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients.

OBJECTIVES: This study correlated the electron beam computed tomographic (EBCT) calcium scores with the results of coronary angiography in symptomatic patients in order to assess its value to predict or exclude significant coronary artery disease (CAD). BACKGROUND: Electron beam computed tomography is a sensitive method to detect coronary calcium. However, it is unclear whether it may play a role as a filter before invasive procedures in symptomatic patients. METHODS: A total of 1,764 patients (1,225 men and 539 women) with suspected CAD from a single center were included in our study. All patients underwent calcium screening with EBCT (C150XP Imatron) and conventional coronary angiography. RESULTS: Fifty-six percent of men and 47% of women revealed significant coronary stenoses (> or =50%). Total exclusion of coronary calcium (14% of the study group) was associated with an extremely low probability of stenosis (<1%). With calcium scores > or =20th, > or =100th or > or =75th percentile of age groups, the sensitivity to detect stenoses decreased to 97%, 93% and 81%, respectively, in men and to 98%, 82% and 76%, respectively, in women. At the same time, the specificity increased up to 77% in men and women. There was a significant difference in coronary calcium between men and women in all age groups; however, receiver-operating characteristic curves indicated that the test can be performed with equal accuracy in all of these subgroups. CONCLUSIONS: Calcium screening with EBCT is a highly sensitive and moderately specific test to predict stenotic disease. Exclusion of coronary calcium defines a substantial subgroup of patients, albeit symptomatic, with a very low probability of significant stenoses.

Adult↗
PubMed2000

Interaction of endothelial and neuronal nitric-oxide synthases with the bradykinin B2 receptor. Binding of an inhibitory peptide to the oxygenase domain blocks uncoupled NADPH oxidation.

Endothelial nitric-oxide synthase (type III) (eNOS) was reported to form an inhibitory complex with the bradykinin receptor B2 (B2R) from which the enzyme is released in an active form upon receptor activation (Ju, H., Venema, V. J., Marrero, M. B., and Venema, R. C. (1998) J. Biol. Chem. 273, 24025-24029). Using a synthetic peptide derived from the known inhibitory sequence of the B2R (residues 310-329) we studied the interaction of the receptor with purified eNOS and neuronal nitric-oxide synthase (type I) (nNOS). The peptide inhibited formation of L-citrulline by eNOS and nNOS with IC(50) values of 10.6 +/- 0.4 microM and 7.1 +/- 0.6 microM, respectively. Inhibition was not due to an interference of the peptide with L-arginine or tetrahydrobiopterin binding. The NADPH oxidase activity of nNOS measured in the absence of L-arginine was inhibited by the peptide with an IC(50) of 3.7 +/- 0.6 microM, but the cytochrome c reductase activity of the enzyme was much less susceptible to inhibition (IC(50) >0.1 mM). Steady-state absorbance spectra of nNOS recorded during uncoupled NADPH oxidation showed that the heme remained oxidized in the presence of the synthetic peptide consisting of amino acids 310-329 of the B2R, whereas the reduced oxyferrous heme complex was accumulated in its absence. These data suggest that binding of the B2R 310-329 peptide blocks flavin to heme electron transfer. Co-immunoprecipitation of B2R and nNOS from human embryonic kidney cells stably transfected with human nNOS suggests that the B2R may functionally interact with nNOS in vivo. This interaction of nNOS with the B2R may recruit the enzyme to allow for the effective coupling of bradykinin signaling to the nitric oxide pathway.

Animals↗
PubMed2000

[Diagnostic imaging in cardiac diagnosis].

PURPOSE: Cardiac imaging includes determination of the size and structure of the cardiac chambers, valves, great vessels and the coronary arteries, chamber and valvular function, myocardial perfusion, viability and metabolism. MATERIAL AND METHODS: Chest roentgenography, angiography, echocardiography and nuclear imaging are commonly used but computed tomography and magnetic resonance imaging also offer a promising potential. RESULTS: Coronary angiography is the gold standard in assessing coronary anatomy. Fast CT technologies such as electron-beam and multi-low-CT are promising non-invasive imaging modalities in the assessment of coronary artery disease. With intravascular ultrasound early stages of coronary atherosclerosis can be detected. For the assessment of myocardial perfusion and viability as well as cardiac function, scintigraphic methods are widely accepted. However, MRI methods have also reached a high degree of accuracy. Evaluation of chamber and valvular function is, due to its wide availability, the field of echocardiography. CONCLUSIONS: In clinical routine chest roentgenography, angiography, echocardiography and nuclear imaging are well established. The value of computed tomography and magnetic resonance imaging in the evaluation of coronary artery disease, myocardial perfusion, viability and metabolism is yet to be defined.

Coronary Disease↗
PubMed2000

[Initial experiences with multi-slice detector spiral CT in diagnosis of arteriosclerosis of coronary vessels].

PURPOSE: Multi-row-detector-spiral-CT (MSCT) allows for 250 ms effective exposure time. The purpose of this study was to demonstrate the possibilities and limitations of this CT technology for non enhanced and contrast enhanced investigation of the coronary arteries. METHODS: Investigation of the coronary arteries without contrast medium for quantification of coronary calcifications was performed in an obese patient (140 kg) with MSCT and electron beam CT (EBCT). In 56 patients contrast enhanced CT angiography of the coronary arteries was performed to determine image quality depending on the heart rate. RESULTS: In the obese patient superior image quality could be achieved with MSCT allowing for reliable quantification of coronary calcifications. With MSCT angiography of the coronary arteries good image quality was achieved in patients with a heart rate of 59 +/- 8 beats per minute. CONCLUSION: Even if there are limitations in patients with higher heart rates with an effective exposure time of 250 ms MSCT has clear advantage of image quality in the assessment of non enhanced and contrast enhanced coronary arteries.

Adult↗
PubMed1999

Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris.

Human endothelial nitric-oxide synthase (eNOS) was expressed in the methylotrophic yeast Pichia pastoris, making use of the highly inducible alcohol oxidase promoter. The recombinant protein constituted approximately 3% of total protein and was largely soluble (>75%). About 1 mg of purified eNOS was obtained from 100-ml yeast cell cultures by affinity chromatography of crude cell supernatants. The purified enzyme had a V(max) of 192 +/- 18 nmol of L-citrulline x mg(-1) x min(-1), had a K(m) for L-arginine of 3.9 +/- 0.2 microM, and showed an absolute requirement for tetrahydrobiopterin (H(4)biopterin). NADPH oxidase activity was 136 +/- 9 and 342 +/- 24 nmol x mg(-1) x min(-1) in the absence and presence of 0.1 mM L-arginine, respectively, and not affected by H(4)biopterin. The protein contained 0.56 +/- 0.06 equivalents of FAD and 0.79 +/- 0.08 equivalents of FMN. On-line gel filtration/inductively coupled plasma mass spectrometry analysis confirmed that both iron (0.80 +/- 0.09 mol/subunit) and zinc (0.43 +/- 0.03 mol/subunit) were bound to the enzyme. Graphite furnace-atomic absorption spectroscopy yielded a value for bound iron of 0.84 +/- 0.04 mol/subunit. The absorbance of the enzyme at 398 nm implied a heme content of 0.85 +/- 0.09 mol/subunit, and the high pressure liquid chromatography heme assay gave an estimate of 0.71 +/- 0.02 mol heme/subunit. Gel permeation chromatography yielded one single peak with a Stokes radius of 6.62 +/- 0.7 nm, indicating that the native protein is dimeric. Upon low temperature gel electrophoresis the untreated protein appeared mainly as a monomer (88 +/- 3%), but pretreatment with H(4)biopterin and L-arginine led to a pronounced shift toward dimers (77 +/- 4%). Thus, in contrast to bovine eNOS (List, B. M., Klösch, B., Völker, C., Gorren, A. C. F., Sessa, W. C., Werner, E. R., Kukovetz, W. R., Schmidt, K., and Mayer, B. (1997) Biochem. J. 323, 159-165; Rodriguez-Crespo, I., Gerber, N. C., and Ortiz de Montellano, P. R. (1996) J. Biol. Chem. 271, 11462-11467), the human eNOS appears to be markedly stabilized by H(4)biopterin.

Animals↗
PubMed1999

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane.

Nano-electrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) was employed to determine qualitative differences in the lipid molecular species composition of a comprehensive set of organellar membranes, isolated from a single culture of Saccharomyces cerevisiae cells. Remarkable differences in the acyl chain composition of biosynthetically related phospholipid classes were observed. Acyl chain saturation was lowest in phosphatidylcholine (15.4%) and phosphatidylethanolamine (PE; 16.2%), followed by phosphatidylserine (PS; 29.4%), and highest in phosphatidylinositol (53.1%). The lipid molecular species profiles of the various membranes were generally similar, with a deviation from a calculated average profile of approximately +/- 20%. Nevertheless, clear distinctions between the molecular species profiles of different membranes were observed, suggesting that lipid sorting mechanisms are operating at the level of individual molecular species to maintain the specific lipid composition of a given membrane. Most notably, the plasma membrane is enriched in saturated species of PS and PE. The nature of the sorting mechanism that determines the lipid composition of the plasma membrane was investigated further. The accumulation of monounsaturated species of PS at the expense of diunsaturated species in the plasma membrane of wild-type cells was reversed in elo3Delta mutant cells, which synthesize C24 fatty acid-substituted sphingolipids instead of the normal C26 fatty acid-substituted species. This observation suggests that acyl chain-based sorting and/or remodeling mechanisms are operating to maintain the specific lipid molecular species composition of the yeast plasma membrane.

Acetyltransferases↗
PubMed1997

The yeast mic2 mutant is defective in the formation of mannosyl-diinositolphosphorylceramide.

The mic2 mutation dominantly blocks formation of mannosyl-diinositolphosphorylceramide, the most abundant sphingolipid of the yeast, Saccharomyces cerevisiae. Interestingly, lack of mannosyl-diinositolphosphorylceramide is not lethal but is compensated for by increased amounts of inositolphosphorylceramide and mannosyl-inositolphosphorylceramide in the plasma membrane and Golgi of the mutant. The level of negatively charged phospholipids in the plasma membrane of the mic2 strain is markedly reduced; the sterol composition is not altered. In spite of dramatic changes of its lipid composition the mutant grows like wild type on complex and minimal media, under osmotic stress conditions, at low pH, and in the presence of high ionic strength. While sensitivity to several drugs is not altered, the mic2 mutant strain becomes resistant to the polyene antibiotic nystatin.

Cell Membrane↗
PubMed1995

Phospholipid-synthesizing enzymes in Golgi membranes of the yeast, Saccharomyces cerevisiae.

Golgi membranes of the yeast, Saccharomyces cerevisiae, were isolated by a method similar to the procedure described by Cleves et al. [Cell 64 (1991) 789-800]. Marker proteins of the Golgi, such as Kex2 protease and GDPase, are highly enriched in these preparations. The phospholipid and ergosterol content of Golgi membranes is low. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol are the major phospholipids of this compartment. The amount of phosphatidylserine in the Golgi is significantly higher than in yeast bulk membranes. Inositol-containing sphingolipids, especially inositolphosphorylceramide, are highly enriched in Golgi membranes. Two phospholipid-synthesizing enzymes, namely phosphatidylinositol synthase and sn-1,2-diacylglycerol cholinephosphotransferase, are detected in the Golgi at a specific activity which exceeds that of the endoplasmic reticulum.

CDP-Diacylglycerol-Inositol 3-Phosphatidyltransfer↗
PubMed1994

Import of phosphatidylinositol and phosphatidylcholine into mitochondria of the yeast, Saccharomyces cerevisiae.

An in vitro assay was designed to study the import of 3H-labeled phosphatidylinositol and phosphatidylcholine, respectively, from unilamellar vesicles into isolated mitochondria of the yeast, Saccharomyces cerevisiae. Both phospholipids reached the inner mitochondrial membrane. During import they were detected in contact sites between the outer and the inner mitochondrial membrane, supporting the notion that these zones are sites of intramitochondrial phospholipid transport. The uncoupler CCCP, the antibiotic adriamycin, and energy depletion caused by oligomycin and apyrase did not inhibit the transport of phosphatidylinositol and phosphatidylcholine into mitochondria.

Biological Transport↗
PubMed1991

Kinetics of uptake and effects of topical indomethacin application on protein concentration in the aqueous humor of dogs.

The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗