Acute administration of 17beta-estradiol improves endothelium-dependent vasodilation in postmenopausal women.

Objectives: Estrogen's effect on endothelial function in postmenopausal women with mild hypertension but no other cardiovascular risk factors remains unclear. This study investigated the effect of an acutely administered therapeutic/low dose of 17beta-estradiol on vasodilation in this patient population.

Methods: Forearm blood flow (FBF) was measured in seven white, hypertensive (blood pressure 144 +/- 8/93 +/- 5 mmHg), postmenopausal (mean age: 54.

High wall shear stress measured by magnetic resonance is a predictor of restenosis in the femoral-artery after balloon angioplasty.

Aim: Wall shear stress (WSS) has been implied in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTA). Aims of the present study were to calculate WSS in the superficial femoral artery (SFA) from magnetic resonance imaging (MRI) and from duplex sonography in healthy controls and in patients after PTA of the SFA to evaluate the predictive value of WSS for restenosis.

Methods: WSS was assessed by calculating the slope of velocity profiles at the vessel wall from data obtained with velocity encoded cine MR and with duplex using the formula: Shear stress=4xblood viscosityxpeak blood velocity/internal diameter.

Blood fluidity and outcome after femoropopliteal percutaneous transluminal angioplasty (PTA): role of plasma viscosity and low platelet count in predicting restenosis.

Rheological abnormalities are well known in patients with peripheral arterial occlusive disease (PAOD). We wanted to determine whether rheological variables are related to restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). In 114 patients (62 men; median age 70 years) undergoing femoropopliteal PTA for symptomatic peripheral arterial occlusive disease (PAOD) plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, fibrinogen, platelet count, leukocytes and C-reactive protein were determined the day after the procedure and at 1, 3, and 12 months.

Endothelial function is preserved in Chagas' heart disease patients without heart failure.

Endothelium may be damaged, especially at the coronary microcirculation, in animal models of Chagas' disease by several mechanisms. Endothelial dysfunction has been reported in chronic Chagas' heart disease patients with heart failure. Nevertheless, peripheral endothelial function has never been studied in patients with Chagas' heart disease without heart failure and other conditions that could per se alter the endothelial function.

[Cardiovascular disease and risk factors in candidates for renal transplantation].

Objective: To determine the prevalence of cardiovascular disease (CVD) and traditional risk factors in patients with chronic renal failure undergoing evaluation for inclusion on the renal transplantation list.

Methods: One hundred ninety-five patients with dialytic chronic renal failure underwent clinical evaluation and complementary tests and were compared with a group of 334 hypertensive patients paired for age. The Framingham equations were used for calculating the absolute risk (AR).

Asn792 participates in the hydrogen bond network around the K+-binding pocket of gastric H,K-ATPase.

Asn792 present in M5 of gastric H,K-ATPase is highly conserved within the P-type ATPase family. A direct role in K+ binding was postulated for Na,K-ATPase but was not found in a recent model for gastric H,K-ATPase (Koenderink, J. B.

Acute reduction of ventricular volume decreases QT interval dispersion in elderly subjects with and without heart failure.

To evaluate the effects of acute reduction in ventricular volume (VV) on QT interval dispersion (QTd), 14 men with heart failure (HF; 74.5 +/- 2 yr of age) and 11 healthy male control subjects (68 +/- 2 yr of age) were studied. For 15 min, lower body negative pressure (LBNP) was applied at -15 and -40 mmHg to reduce venous return.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy.

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.

C-reactive protein and red cell aggregation correlate with late venous function after acute deep venous thrombosis.

Objective: Risk factors leading to development and subsequent progression of chronic venous insufficiency after acute deep venous thrombosis (DVT) are only partially identified. Inflammation and rheologic abnormalities might have a causative role. The purpose of this study was to investigate C-reactive protein (CRP), D -dimer, and blood rheologic parameters in patients after acute DVT in relation to clinical outcome.

Making optimal use of empirical energy functions: force-field parameterization in crystal space.

Today's energy functions are not able yet to distinguish reliably between correct and almost correct protein models. Improving these near-native models is currently a major bottle-neck in homology modeling or experimental structure determination at low resolution. Increasingly accurate energy functions are required to complete the "last mile of the protein folding problem," for example during a molecular dynamics simulation.

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant hearing impairment that clinically resembles the previously published DFNA11 family. The affected family members show a flat audiogram at young ages and only modest progression, most clearly at the high frequencies.

A structural and dynamic model for the interaction of interleukin-8 and glycosaminoglycans: support from isothermal fluorescence titrations.

Binding of interleukin-8 (IL-8) to glycosaminoglycans (GAGs) on the surface of endothelial cells is crucial for the recruitment of neutrophils to an inflammatory site. Deriving structural knowledge about this interaction from in silico docking experiments has proved difficult because of the high flexibility and the size of GAGs. Therefore, we developed a docking method that takes into account ligand and protein flexibility by running approximately 15,000 molecular dynamics simulations of the docking event with different initial orientations of the binding partners.

A conformation-specific interhelical salt bridge in the K+ binding site of gastric H,K-ATPase.

Homology modeling of gastric H,K-ATPase based on the E2 model of sarcoplasmic reticulum Ca2+-ATPase (Toyoshima, C., and Nomura, H. (2002) Nature 392, 835-839) revealed the presence of a single high-affinity binding site for K+ and an E2 form-specific salt bridge between Glu820 (M6) and Lys791 (M5).

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk).

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26).

Linkage analysis in a multigenerational family with autosomal dominant hearing loss yielded a chromosomal localisation of the underlying genetic defect in the DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the gamma-1-actin (ACTG1) gene, which was considered an attractive candidate gene because actins are important structural elements of the inner ear hair cells. In this study, a Thr278Ile mutation was identified in helix 9 of the modelled protein structure.

Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p.

Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p.

DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism.

Four chromosomal loci ( PARK2, PARK6, PARK7, and PARK9) associated with autosomal recessive, early onset parkinsonism are known. We mapped the PARK7 locus to chromosome 1p36 in a large family from a genetically isolated population in the Netherlands, and confirmed this linkage in an Italian family. By positional cloning within the refined PARK7 critical region we recently identified mutations in the DJ-1 gene in the two PARK7-linked families.

Quantitative evaluation of experimental NMR restraints.

Nuclear Overhauser effect (NOE) data are an indispensable source of structural information in biomolecular structure determination by NMR spectroscopy. The number and type of experimental restraints used in the structure calculation and the RMS deviation of the restraints are usually reported. We present a new method for quantifying the information contained in the experimental NMR restraints.

The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial.

Objectives: The goal of this study was to test the hypothesis that exercise training reduces resting sympathetic neural activation in patients with chronic advanced heart failure.

Background: Exercise training in heart failure has been shown to be beneficial, but its mechanisms of benefit remain unknown.

Methods: Sixteen New York Heart Association class II to III heart failure patients, age 35 to 60 years, ejection fraction < or =40% were divided into two groups: 1) exercise-trained (n = 7), and 2) sedentary control (n = 9).

Coronary angiography is the best predictor of events in renal transplant candidates compared with noninvasive testing.

Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (>or=70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (>or=50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months.

The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser-Asp catalytic dyad.

Patatin is a nonspecific lipid acyl hydrolase that accounts for approximately 40% of the total soluble protein in mature potato tubers, and it has potent insecticidal activity against the corn rootworm. We determined the X-ray crystal structure of a His-tagged variant of an isozyme of patatin, Pat17, to 2.2 A resolution, employing SeMet multiwavelength anomalous dispersion (MAD) phasing methods.

The precision of NMR structure ensembles revisited.

Biomolecular structures provide the basis for many studies in research areas such as structure-based drug design and homology modeling. In order to use molecular coordinates it is important that they are reliable in terms of accurate description of the experimental data and in terms of the overall and local geometry. Besides these primary quality criteria an indication is needed for the uncertainty in the atomic coordinates that may arise from the dynamic behavior of the considered molecules as well as from experimental- and computational procedures.