bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic ACE Inhibition Enhances the Endothelial Control of Arterial Mechanics and Flow-Dependent Vasodilatation in Heart Failure
Authors: Joannides Robinson , Bizet-Nafeh Catherine , Costentin Agathe , Iacob Michaela , Derumeaux Geneviève , Cribier Alain , Thuillez Christian
Published: September 2007

Reduced conduit arteries flow-dependent dilatation and altered compliance have been described during heart failure. However, the role of shear stress, the relation between endothelial dysfunction and mechanics, and the effect of chronic ACE inhibition on this relationship have not been investigated. The present study was designed to evaluate in heart failure patients the relationship between flow-dependent dilatation and radial artery mechanics at known shear stress levels and to assess the effect of chronic ACE inhibition. Sixteen stable congestive heart failure patients, who had never been treated with ACE inhibitors, participated in the study. Arterial pressure, cardiac output (bioimpedance), radial artery diameter (echo tracking) and flow (Doppler), total blood viscosity, and mean artery wall shear stress were assessed before and during a gradual increase in the forearm blood flow in response to gradual distal hand skin heating. Cross-sectional radial artery compliance and distensibility indexes were calculated at 34°C, 40°C, and 44°C. The endothelium-independent vasodilatation was evaluated by use of glyceryl trinitrate. All parameters were assessed before and 24 hours after the last administration of perindopril (4 mg once daily) or placebo in a 2-month double-blind randomized study. Before treatment, there was no difference between the 2 groups for all parameters. After chronic ACE inhibition, systolic arterial pressure decreased at baseline from 126±11 to 118±10 mm Hg (
P
<0.05). During heating, the increase in diameter in response to shear stress was higher after ACE inhibition than after placebo (time/treatment interaction,
P
<0.05). Moreover, in contrast to placebo, at the same shear stress, there was a significant increase in compliance (3.23±0.79×10
−7
to 6.82±2.47×10
−7
m
2
/kPa,
P
<0.05) and distensibility (5.71±1.35×10
−3
to 8.87±1.88×10
−3
/kPa,
P
<0.05) during heating after ACE inhibition. The effect of glyceryl trinitrate did not change. The present study demonstrates that chronic administration of the ACE inhibitor perindopril increases the magnitude of the flow-dependent dilatation and restores the flow-dependent increase in compliance and distensibility of the radial artery evaluated at stable shear stress. In addition, the decrease in baseline systolic arterial pressure after ACE inhibitor suggests an associated increase in the distensibility of the proximal elastic conduit arteries.
Pulse Pressure, Endothelium Function, and Arterial Stiffness in Spontaneously Hypertensive Rats
Authors: Safar Michel , Chamiot-Clerc Philippe , Dagher Georges , Renaud Jean François
Published: September 2007

In rats, removal of the carotid arterial or abdominal aortic endothelium results in an acute increase of diameter and compliance. In humans, acute local administration of a specific NO synthase inhibitor increases radial artery compliance but not the diameter. The purpose of this review is to determine whether in spontaneously hypertensive rats (SHR), a cause-and-effect relationship may be observed between endothelial function and arterial stiffness with possible consequences on pulse pressure (PP) control. The study is based on a comparative time-dependent analysis of the following in young and old SHR: aortic blood pressure measurements and reactivity, ultrasonographic arterial stiffness assessment, aortic histomorphometry and staining, and molecular biology with evaluation of endothelium function. In young SHR, aortic mean blood pressure and PP increase proportionally, whereas isobaric arterial stiffness is unchanged or poorly modified. The endothelial NO response to norepinephrine is normal or upregulated as a response to predominant vasoconstrictive influences. In contrast, in old SHR, PP and mean blood pressure change disproportionately with age, together with an enhanced isobaric arterial stiffness. The endothelial NO response to norepinephrine is abolished, in association with endothelium-dependent heightened norepinephrine reactivity and enhanced accumulation of vessel extracellular matrix. In this latter case, exogenous NO acutely and selectively lowers the increased PP. Thus, during SHR aging, a negative feedback may be observed between NO bioactivity and PP through changes in arterial structure and function. Whether this alteration contributes to the development of systolic hypertension in old populations remains to be determined.
Angiotensinogen Gene Core Promoter Variants and Non-Modulating Hypertension
Authors: Hilgers Karl F. , Delles Christian , Veelken Roland , Schmieder Roland E.
Published: September 2007

Non-modulation has been suggested as a possible intermediate phenotype defining a subgroup of genetic hypertension. The trait is characterized by an attenuated response of renal blood flow and/or aldosterone to angiotensin (Ang) II. We tested the hypothesis that functional polymorphisms of the core promoter of the angiotensinogen gene are associated with non-modulation. Fifty-six young, white, male, untreated hypertensive patients and 65 age-matched normotensive volunteers were genotyped for 3 known functional variants of the angiotensinogen core promoter. All subjects were infused with 2 doses (0.5 and 3 ng/kg per minute) of Ang II while they were on a high sodium diet (250 mmol/d). The blood pressure, renal plasma flow, and aldosterone responses to Ang II were not affected by the −6 G/A polymorphism. The −20 A/C variant had no significant effects on the blood pressure or renal hemodynamic response to Ang II. However, the aldosterone response to both doses of Ang II was significantly decreased in −20 C allele carriers compared with −20 AA homozygotes in a multivariate analysis. The −18 T allele was not detected in our population, and there was a linkage dysequilibrium between −20 C and −6 A: −20 C almost exclusively occurred on the −6 A allele. Haplotype analysis indicated that the −20 C/−6 A haplotype but not the −20 A/−6 A haplotype was associated with a decreased aldosterone response to Ang II. We conclude that the −20 C variant or the −20 C/−6 A haplotype of the angiotensinogen core promoter is associated with a blunted aldosterone response to Ang II and may thus contribute to the non-modulating phenotype.
Role of the B2Receptor of Bradykinin in Insulin Sensitivity
Authors: Duka Irena , Shenouda Sherene , Johns Conrado , Kintsurashvili Ekaterina , Gavras Irene , Gavras Haralambos
Published: September 2007

The biological actions of bradykinin (BK) are attributed to its B2type receptor (B2R), whereas the B1R is constitutively absent, inducible by inflammation and toxins. Previous studies in B2R gene knockout mice showed that the B1R is overexpressed, is further upregulated by hypertensive maneuvers, and assumes some of the hemodynamic functions of the B2R. The current experiments were designed to further clarify the metabolic function of the B2R and to explore whether the upregulated B1R can also assume the metabolic function of the missing B2R. One group of B2R−/− mice (n=9) and one of B2R+/+ controls (n=8) were treated for 3 days with captopril (which produced a similar blood pressure-lowering response in both groups) and studied with the hyperinsulinemic euglycemic clamp. The knockout mice had fasting and steady-state blood glucose levels similar to those of the wild-type mice but a had tendency to higher fasting insulin levels (at 27.8±5.2 versus 18±2.9 mU/L, respectively). However, they had significantly higher steady-state insulin levels (749±127.2 versus 429.1±31.5 mU/L,P<0.05) and a significantly lower glucose uptake rate (31±2.4 versus 41±2.3 mg/kg per minute,P<0.05) and insulin sensitivity index (4.6±0.9 versus 10±0.7P<0.001). Analysis of B1R and B2R gene expression by reverse transcription-polymerase chain reaction in cardiac muscle, skeletal muscle, and adipose tissues revealed significantly higher B1R mRNA level in the knockouts versus wild-type (P<0.05) at baseline and a further significant upregulation in mRNA by 1.8- to 3.2-fold (P<0.05) after insulin infusion. We conclude that absence of B2R confers a state of insulin resistance because it results in impaired insulin-dependent glucose transport; this is probably a direct B2R effect because, unlike the hemodynamic autacoid-mediated effects, it cannot be assumed by the upregulated B1R.
Arterial Epidermal Growth Factor Receptor Expression in Deoxycorticosterone Acetate–Salt Hypertension
Authors: Northcott Carrie , Florian Jennifer A. , Dorrance Anne , Watts Stephanie W.
Published: September 2007

Epidermal growth factor (EGF) causes contraction in arteries from deoxycorticosterone acetate (DOCA)–salt hypertensive rats but not in normotensive sham rats. We hypothesized that an increase in the number of EGF receptors (EGFRs) in arteries from DOCA-salt rats enables the observed contraction to EGF to occur. DOCA-salt rats had a systolic blood pressure >170 mm Hg, whereas all sham rats had a systolic blood pressure <125 mm Hg. Thoracic aorta were removed for measurement of isometric force, EGFR mRNA levels, and EGFR protein levels. EGF caused a significant contraction in endothelium-denuded aorta from DOCA-salt rats (38±7% of maximal phenylephrine-induced [10 μmol/L] contraction) compared with aorta from sham rats (4±2%). The EGFR tyrosine kinase–specific inhibitors 4,5-dianilinophthalimide (10 μmol/L) and AG1478 (250 nmol/L) reduced contraction in aorta from DOCA-salt by 85±14% and 65±10%, respectively. EGFR mRNA in DOCA-salt aorta was increased 4.2-fold compared with that in sham aorta. However, Western analyses of membrane-enriched and whole-tissue lysate of aorta from sham and DOCA-salt revealed no statistical difference in the density of EGFR protein between sham and DOCA-salt aorta. These data refute our hypothesis and suggest that a change downstream of EGFR is responsible for enabling EGF-induced contraction in hypertension.
Office Blood Pressures, Arterial Compliance Characteristics, and Estimated Cardiac Load
Authors: Izzo Jr Joseph L. , Manning Timothy S. , Shykoff Barbara E.
Published: September 2007

Because of rising interest in new methods to detect arterial diseases, we compared data from 3 different compliance-related techniques to measure arterial stiffness: systolic pulse contour analysis, diastolic pulse contour analysis (modified Windkessel model), and muscular (brachial) artery compliance by cuff plethysmography. Variables measured in the sitting position were compared with each other, with clinic blood pressures (BPs), and with the cardiac time-tension integral (CTTI) in 63 established hypertensive and 28 age-matched normotensive subjects. Hypertensives demonstrated marginal reductions in C
1
(thought to represent reduced large vessel compliance) and increased central systolic BP augmentation. In contrast, muscular artery compliance tended to be greater in the hypertensives despite normal brachial arterial diameters. C
2
, suggested to be an indicator of small artery properties, was similar in both groups. CTTI was strongly related to systolic pressure (
r
=0.81), integrated mean arterial pressure (
r
=0.83), and systolic pressure-heart rate product (
r
=0.85) and was less strongly related to diastolic (
r
=0.71) or pulse pressure (
r
=0.57). Weak correlations were observed between CTTI and measured compliance-related variables, which also showed absent or weak correlations among themselves. We conclude that the weak relationships among BP and compliance-related variables could be due to intrinsic differences in the properties of large and small arteries, theoretical methodological weaknesses, measurement artifacts, or intrinsic hemodynamic differences of the sitting position. At present, compliance-related variables provide little additional advantage over cuff BP in the office estimation of cardiac work.
Pulsatile Hemodynamics in Congestive Heart Failure
Authors: Mitchell Gary F. , Tardif Jean-Claude , Arnold J. Malcolm O. , Marchiori Gordon , O’Brien Terrence X. , Dunlap Mark E. , Pfeffer Marc A.
Published: September 2007

Pulse pressure, an indirect measure of vascular stiffness and pulsatile load, predicts clinical events in congestive heart failure (CHF), suggesting that abnormal pulsatile load may contribute to CHF. This study was designed to assess more direct measures of central pulsatile load in CHF. Noninvasive hemodynamic evaluations were performed in 28 subjects with CHF and 40 controls using calibrated tonometry of the brachial, radial, femoral, and carotid arteries along with echocardiographic assessment of left ventricular outflow tract (LVOT) diameter and Doppler flow. Characteristic impedance (Z
c
) was calculated as the ratio of ΔP (carotid) and ΔQ (LVOT flow) in early systole. Carotid-radial (CR-PWV) and carotid-femoral (CF-PWV) pulse wave velocities were calculated from tonometry. Augmentation index was assessed from the carotid waveform. Total arterial compliance (TAC) was calculated using the area method. Brachial pulse pressure was elevated (62±16 versus 53±15 mm Hg,
P
=0.015) in CHF because of lower diastolic pressure (66±10 versus 73±9 mm Hg,
P
=0.003). CHF had higher Z
c
(225±76 versus 184±66 dyne · sec · cm
−5
,
P
=0.020). CF-PWV did not differ (9.7±2.7 versus 9.2±2.0,
P
=0.337), whereas CR-PWV was lower in CHF (8.6±1.4 versus 9.4±1.5,
P
=0.038). There was no difference in TAC (1.4±0.5 versus 1.4±0.6 mL/mmHg,
P
=0.685), and augmentation index was lower in CHF (8±17 versus 21±13%,
P
=0.001). CHF subjects have elevated central pulsatile load (Z
c
), which is not apparent in global measures such as augmentation index or TAC, possibly because of contrasting changes in central and peripheral conduit vessels. This increased pulsatile load represents an important therapeutic target in CHF.
Heart Failure, Redox Alterations, and Endothelial Dysfunction
Authors: Farré Antonio López , Casado Santos
Published: September 2007

Heart failure is characterized by neurohumoral alterations, such as activation of the sympathetic nervous system, stimulation of the renin-angiotensin system, increased activity of the endothelin system, increased production of norepinephrine, and increased circulating levels of cytokines. Oxidative stress is associated with the formation of reactive oxygen species (ROS). The myocardium has enzymes that stimulate ROS generation and enzymes with antioxidant effects. Several studies have suggested that ROS are increased in the failing heart. ROS may contribute to the pathophysiology of heart failure by initiating myocyte apoptosis and exerting direct negatively inotropic effects through the reduction of cytosolic intracellular free calcium. However, mechanisms such as endothelial dysfunction and inflammation have also been involved in the progression of heart failure. Antioxidants (eg, vitamin C) seem to improve endothelial functionality and reduce the inflammatory response in patients with heart failure. Therefore, in this review, we analyzed the involvement of ROS in the cellular and molecular mechanisms associated with endothelial dysfunction in heart failure.
Regeneration of the Myocardium
Authors: Hagège Albert A. , Vilquin Jean-Thomas , Bruneval Patrick , Menasché Philippe
Published: September 2007

Intramyocardial cell grafting aims to limit the consequences of the loss of contractile function of a damaged left ventricle. Its functional efficacy is suggested by a wealth of experimental data using multiple evaluation techniques in different animal species. Intramyocardial injections of cultured fetal cardiomyocytes after infarction increase the ejection fraction. Cultured autologous skeletal myoblasts, which do not raise immunologic, ethical, tumorigenesis, or donor availability problems, improve ventricular function to a similar extent. The presence of connexin-43 is demonstrated between fetal (but not myoblast) grafted cells and host myocytes. Thus, the mechanisms of this beneficial effect (direct systolic effect, paracrine factors, passive girdling effect, and decrease in wall stress) remain controversial. These encouraging results have opened the way to the first clinical trial in patients with low ejection fractions, akinetic and nonviable postinfarction scars, and indications for coronary artery bypasses in remote, viable, and ischemic areas. Large-scale cell expansion allows a yield of >10
9
myoblasts from a single human muscular biopsy. Cultured autologous myoblasts are directly administered by multiple injections within and around the infarcted area during open-chest surgery. Preliminary postoperative observations show an improvement in ejection fraction, reappearance of a systolic thickening of the grafted scars, and a new-onset metabolic viability within this area. Thus, this new procedure might become a useful adjunct to current treatments of severe ischemic heart failure.
Carotid Atherosclerosis Is a Stronger Predictor of Myocardial Infarction in Women Than in Men
Authors: Johnsen Stein Harald , Mathiesen Ellisiv B. , Joakimsen Oddmund , Stensland Eva , Wilsgaard Tom , Løchen Maja-Lisa , Njølstad Inger , Arnesen Egil
Published: September 2007

Background and Purpose—

Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI).

Methods—

IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered.

Results—

During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex.

Conclusions—

In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.
Facilities Available in European Hospitals Treating Stroke Patients
Authors: Leys Didier , Ringelstein E. Bernd , Kaste Markku , Hacke Werner
Published: September 2007

Background and Purpose—

Stroke units decrease mortality and need for institutional care, but they are not widely available. The objective of the study was to determine, among European hospitals admitting acute stroke patients, how many are able to provide an appropriate level of care.

Method—

We randomly selected 886 hospitals in 25 countries. We used definitions derived from a European expert survey for comprehensive stroke centers (CSC), primary stroke centers (PSC), and minimum level required for any hospital ward (AHW) admitting stroke patients. We determined the proportion of hospitals meeting criteria for each category, and which facilities were not available.

Results—

Participating hospitals treated approximately one-third of all strokes supposed to have occurred in these countries in 2005. Forty-three (4.9%) met criteria for CSC, 32 (3.6%) for PSC, 356 (40.2%) for AHW, and 455 (51.4%) provided a lower level of care. In 2005, hospitals meeting criteria for CSC, PSC, AHW, and none of them admitted 27 644 (8.3%), 17 365 (5.2%), 146 175 (44.1%), and 140 306 (42.3%) patients. There was no 24-hour availability for brain CT scan in 25% of hospitals not meeting criteria for AHW. Of 448 hospitals admitting at least 1 stroke per day, 51 (11.4%) met criteria for PSC or CSC, and 227 (50.7%) for AHW.

Conclusions—

Less than 10% of European hospitals admitting acute stroke patients have optimal facilities, and in 40% even the minimum level is not available. Because the availability of facilities does not grant their use, our study suggests that only few acute stroke patients are treated in appropriate centers in Europe.
Association of Leukocyte Count With Progression of Aortic Atheroma in Stroke/Transient Ischemic Attack Patients
Authors: Sen Souvik , Hinderliter Alan , Sen Pranab K. , Simmons Jennifer , LeGrys Vicky A. , Beck James , Offenbacher Steven , Moss Kevin , Oppenheimer Stephen M.
Published: September 2007

Background and Purpose—

Leukocyte count is an independent predictor of stroke. We investigated the association between leukocyte count and progression of aortic atheroma over 12 months in stroke/transient ischemic attack (TIA) patients.

Methods—

Consecutive ischemic stroke and transient ischemic attack patients underwent 12-month sequential transesophageal echocardiography and were assessed for total and differential leukocyte counts on admission. Paired aortic plaque images were assessed for several parameters, including changes in grade, intimal-medial thickness (IMT), and cross-sectional area. Multivariate linear and logistic regressions were used to calculate the effect of leukocyte count on the change in aortic atheromas over 12 months.

Results—

Of the 115 participants (mean±SD age, 64.6±11.9 years; 53.1% men; 73.4% white, 24.2% black, and 2.3% Asian), 45 (35%) showed clinically significant progression of aortic atheromas (maximal change in IMT >0.70 mm over 12 months). The mean admission leukocyte count was higher in the progression group compared with the no-progression group (8.6±2.2 vs 7.3±2.2×10
9
/L respectively,
P
=0.002). Each unit increase in leukocyte count was associated with a 0.26-mm increase in aortic arch IMT over 12 months (
P
=0.006). After adjustment for other atherosclerosis risk factors, the relation persisted (mean increase in aortic arch IMT per unit increase in leukocyte count=0.27 mm,
P
=0.007). Each unit increase in leukocyte count was associated with an increased risk of significant progression of aortic atheromas (adjusted odds ratio=1.33; 95% CI, 1.09 to 1.61).

Conclusions—

In stroke/transient ischemic attack patients, leukocyte count is independently associated with the progression of aortic atheroma over 12 months (>0.70 mm), which is associated with cardiovascular risk.
Analysis of Calcium in Carotid Plaques With Agatston Scores for Appropriate Selection of Surgical Intervention
Authors: Katano Hiroyuki , Yamada Kazuo
Published: September 2007

Background and Purpose—

The aim of the study was to determine whether the Agatston calcium score might be applied as a useful tool for evaluation of carotid stenosis.

Methods—

A total of 124 carotid bifurcations were examined with multidetector row CT. Calcium scores were determined according to the method described by Agatston et al.

Results—

Agatston scores generally appear appropriate for evaluation of calcified plaques. Calcified lesions with bigger differences between mean and peak Hounsfield unit (HU) in single cases accounted for only 34.3% of those with volume scores under 500 mm
3
, whereas 81.3% (
P
<0.001) for those sized >500 mm
3
.

Conclusions—

The Agatston calcium score is useful in evaluating carotid plaques with calcium. We recommend, however, individual analyses for quality (hardness) and quantity (volume) of each large calcified focus (>500 mm
3
) by multidetector row CT lesions in order to provide indications for surgical treatment of carotid stenosis, carotid endarterectomy or carotid artery stenting.
Neuroprotective Effects of Adenosine Monophosphate- Activated Protein Kinase Inhibition and Gene Deletion in Stroke
Authors: Li Jun , Zeng Zhiyuan , Viollet Benoit , Ronnett Gabriele V. , McCullough Louise D.
Published: September 2007

Background and Purpose—

5′ adenosine monophosphate-dependent protein kinase (AMPK) acts as a metabolic sensor. AMPK is elevated under ischemic conditions, but the role of AMPK in ischemic brain remains controversial. In this study, we examined the effects of AMPK inhibition using both pharmacological and genetic approaches in an in vivo stroke model.

Methods—

Focal stroke was induced by reversible middle cerebral artery occlusion in male wild-type mice as well as mice deficient in one of the isoforms of the catalytic subunit of AMPK, AMPK α-1 or α-2.

Results—

AMPK inhibition was neuroprotective after focal stroke. Mice deficient in AMPK α-2 demonstrated significantly smaller infarct volumes compared with wild-type littermates, whereas deletion of AMPK α-1 had no effect. Phosphorylation of a major upstream regulator of AMPK, LKB1, was also induced in stroke brain.

Conclusions—

AMPK activation is detrimental in a model of focal stroke. The AMPK catalytic isoform α-2 contributes to the deleterious effects of AMPK activation. AMPK inhibition leads to neuroprotection even when these agents are administered poststroke.
Polymorphisms in MMP Family and TIMP Genes and Carotid Artery Intima-Media Thickness
Authors: Armstrong Christine , Abilleira Sonia , Sitzer Matthias , Markus Hugh S. , Bevan Steve
Published: September 2007

Background and Purpose—

Genetic variation in a number of
MMP
and
TIMP
genes have been implicated as risk factors for atherosclerosis, although such studies have been generally small and produced conflicting results. We have therefore sought to address this issue in a large, well-phenotyped community population to assess the effect of a number of polymorphisms in both
MMP
and
TIMP
genes on carotid artery intima-media thickness (IMT).

Methods—

In a community population (n=1000), IMT was determined using ultrasound in the common carotid artery, carotid bulb, and bifurcation. Eight polymorphisms in 6
MMP
genes were genotyped (MMP1 A-519G, MMP2 C-1306T, MMP2 C-735T, MMP3 -1171 5A/6A, MMP9 R279Q, TIMP2 G853A, TIMP3 A-915G, and T-1296C) and assessed for their effect on carotid IMT alone and by interaction with common cardiovascular risk factors.

Results—

An association was found between MMP9 R279Q and internal carotid artery bulb IMT (
P
=0.002), but there was no linear trend between allele number and IMT and no association with common carotid artery or bulb IMT. In addition, 3 interactions were found between polymorphisms and hypertension (MMP1 A-519G, MMP3 5A/6A, TIMP3 T-1296C), the latter 2 of which showed a significant trend test for linearity with increasing copy number and increased internal carotid artery bulb IMT. All remained significant after correction for multiple testing.

Conclusions—

Our findings provide little support for genetic variants of
MMP
as direct risk factors for IMT. However, the interaction findings between
MMP
variants and hypertension suggest that hypertensive carriers of these alleles may be at greater risk for increased IMT and future cardiovascular disease. These findings need replication in hypertensive populations to assess their effects more fully.
Geoelectric Monitoring of Wind-Driven Barotropic Transports in the Baltic Sea
Authors: Nilsson Jenny A. U. , Sigray Peter , Tyler Robert H.
Published: September 2007

The possibility of using data from a cable-based observational system for long-term monitoring of barotropic flow in the Baltic Sea was investigated. Measurements were made of the induced potential differences between Visby on the island of Gotland and Västervik on the Swedish mainland and a yearlong period was studied in order to ensure the presence of seasonal fluctuations. The predictions from a 2D electric-potential model, forced by velocity fields from a shallow-water circulation model, proved to be well correlated with the observations. A winter and a summer period were selected for a thorough analysis, the results of which indicated a stronger correlation during winter. This implies that the relative importance of the barotropic forcing tends to weaken during summer. The spatial coverage of the induced potential differences for the cable region was found to encompass a considerable part of the Baltic proper. The correlation study indicated that the winter circulation in the Baltic proper showed “broad-scale” motion, whereas summer conditions were characterized by a barotropic gyre. An overall result of the investigation is that geoelectric monitoring is capable of providing useful data for oceanographic purposes.
Assessing NOAA-16 HIRS Radiance Accuracy Using Simultaneous Nadir Overpass Observations from AIRS
Authors: Wang Likun , Cao Changyong , Ciren Pubu
Published: September 2007

The High-Resolution Infrared Radiation Sounder (HIRS) has been carried on NOAA satellites for more than two decades, and the HIRS data have been widely used for geophysical retrievals, climate studies, and radiance assimilation for numerical weather prediction models. However, given the legacy of the filter-wheel radiometer originally designed in the 1970s, the HIRS measurement accuracy is neither well documented nor well understood, despite the importance of this information for data users, instrument manufacturers, and calibration scientists. The advent of hyperspectral sounders, such as the Atmospheric Infrared Sounder (AIRS), and intersatellite calibration techniques makes it possible to independently assess the accuracy of the HIRS radiances. This study independently assesses the data quality and calibration accuracy of HIRS by comparing the radiances between HIRS on NOAA-16 and AIRS on Aqua with simultaneous nadir overpass (SNO) observations for the year 2004. The results suggest that the HIRS radiometric bias relative to the AIRS-convolved HIRS radiance is on the order of ∼0.5 K, except channel 16, which has a bias of 0.8 K. For all eight spectrally overlapped channels, the observations by HIRS are warmer than the corresponding AIRS-convolved HIRS channel. Other than channel 16, the biases are temperature dependent. The root causes of the bias can be traced to a combination of the HIRS blackbody emissivity, nonlinearity, and spectral uncertainties. This study further demonstrates the utility of high-spectral-resolution radiance measurements for high-accuracy assessments of broadband radiometer calibration with the SNO observations.
A Marine Radar Wind Sensor
Authors: Dankert Heiko , Horstmann Jochen
Published: September 2007

A new method for retrieving the wind vector from radar-image sequences is presented. This method, called WiRAR, uses a marine X-band radar to analyze the backscatter of the ocean surface in space and time with respect to surface winds. Wind direction is found using wind-induced streaks, which are very well aligned with the mean surface wind direction and have a typical spacing above 50 m. Wind speeds are derived using a neural network by parameterizing the relationship between the wind vector and the normalized radar cross section (NRCS). To improve performance, it is also considered how the NRCS depends on sea state and atmospheric parameters such as air–sea temperature and humidity. Since the signal-to-noise ratio in the radar sequences is directly related to the significant wave height, this ratio is used to obtain sea state parameters. All radar datasets were acquired in the German Bight of the North Sea from the research platform FINO-I, which provides environmental data such as wind measurements at different heights, sea state, air–sea temperatures, humidity, and other meteorological and oceanographic parameters. The radar-image sequences were recorded by a marine X-band radar installed aboard FINO-I, which operates at grazing incidence and horizontal polarization in transmit and receive. For validation WiRAR is applied to the radar data and compared to the in situ wind measurements from FINO-I. The comparison of wind directions resulted in a correlation coefficient of 0.99 with a standard deviation of 12.8°, and that of wind speeds resulted in a correlation coefficient of 0.99 with a standard deviation of 0.41 m s−1. In contrast to traditional offshore wind sensors, the retrieval of the wind vector from the NRCS of the ocean surface makes the system independent of the sensors’ motion and installation height as well as the effects due to platform-induced turbulence.
An Integrated Glucose‐Insulin Model to Describe Oral Glucose Tolerance Test Data in Type 2 Diabetics
Authors: Jauslin Petra M. , Silber Hanna E. , Frey Nicolas , Gieschke Ronald , Simonsson Ulrika S. H. , Jorga Karin , Karlsson Mats O.
Published: September 2007

An integrated model for the glucose‐insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose‐insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.
Institutionalizing Support for Nonprofit Management Education: Developing a Case for State Investment
Authors: Donnelly-Cox Gemma , McGee Siobhán
Published: September 2007

This article argues that the institutionalization of nonprofit management education must be considered in national societal and education establishment contexts. The article examines the case for the institutionalization of nonprofit management education within the Irish societal context. Drawing on relevant literature and profiling the evolution of thinking on this subject within one education center, the article develops a case for state investment in institutionalization. The article concludes with a series of observations on the requirements for and implications of case development.
Hundholmenite-(Y) from Norway – a new mineral species in the vicanite group:
descriptive data and crystal structure
Authors: Raade G. , Johnsen O. , Erambert M. , Petersen O. V.
Published: September 2007

Hundholmenite-(Y) occurs as pale brown, subhedral crystals up to 1 mm across,
embedded in REE–bearing fluorite, in a granitic
pegmatite at Hundholmen, Tysfjord, Nordland County, north Norway. Two other
occurrences in the same area are the granitic pegmatites at Stetind and
Lagmannsvik. The simplified formula, obtained from wavelength-dispersive EMP
analyses and boron determination by ICP-AES, is
(Y,REE,Ca,Na)15(Al,Fe3+)CaxAs1–x3+
(Si,As5+)Si6B3(O,F)48
(x = 0.78). The mineral is trigonal, R3m, with a =
10.675(6), c = 27.02(2) Å , V = 2667(5) Å 3, Z = 3. The
crystal structure was refined to R1 = 0.037 for 1720
observed reflections. Hundholmenite-(Y) is isostructural with okanoganite-(Y) and
vicanite-(Ce), and the differences in site populations are discussed. The
strongest seven reflections of the X-ray powder-diffraction pattern
[dobs in Å , (I)
(hkl)] are: 4.38 (33) (202), 3.114 (43) (214), 2.972
(100) (027), 2.947 (76) (125), 2.924 (66) (303, 033), 2.681 (36) (220) and 1.978
(37) (235). The mineral is optically uniaxial (–) with o 1.7578(5) and e
1.7487(5). The Mohs hardness is ~5–6; Dcalc = 5.206(9)
g/cm3.
Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu
Authors: Tai Yu-Tzu , Dillon Myles , Song Weihua , Leiba Merav , Li Xian-Feng , Burger Peter , Lee Alfred I. , Podar Klaus , Hideshima Teru , Rice Audie G. , van Abbema Anne , Jesaitis Lynne , Caras Ingrid , Law Debbie , Weller Edie , Xie Wanling , Richardson Paul , Munshi Nikhil C. , Mathiot Claire , Avet-Loiseau Hervé , Afar Daniel E. H. , Anderson Kenneth C.
Published: September 2007

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.
Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers
Authors: Navarro-Costa Paulo , Pereira Luísa , Alves Cíntia , Gusmão Leonor , Proença Carmen , Marques-Vidal Pedro , Rocha Tiago , Correia Sónia C , Jorge Sónia , Neves António , Soares Ana P , Nunes Joaquim , Calhaz-Jorge Carlos , Amorim António , Plancha Carlos E , Gonçalves João
Published: September 2007

Background

The AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility.

Results

The amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6–30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles.

Conclusion

Although partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator.
Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families
Authors: Enomoto Hisako , Noguchi Emiko , Iijima Shigeruko , Takahashi Takenori , Hayakawa Kazuhito , Ito Mikako , Kano Toshiyuki , Aoki Takeshi , Suzuki Yoichi , Koga Minori , Tamari Mayumi , Shiohara Tetsuo , Otsuka Fujio , Arinami Tadao
Published: September 2007

Background

Atopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population.

Methods

We used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis.

Results

We found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87,P= .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44,P= .008).

Conclusion

We report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.
Hospital quality reports in Germany: patient and physician opinion of the reported quality indicators
Authors: Geraedts Max , Schwartze David , Molzahn Tanja
Published: September 2007

Background

Starting in 2005, Germany's health law required hospital quality reports to be published every two years by all acute care hospitals. The reports were intended to help patients and physicians make informed choices of hospitals. However, while establishing the quality indicators that form the content of the reports, the information needs of the target groups were not explicitly taken into account. Therefore, the aim of our study was to determine patient and physician opinion of the relevance of the reported quality indicators for choosing or referring to a hospital.

Methods

Convenience samples of 50 patients and 50 physicians were asked to rate the understandability (patients), suitability (physicians) and relevance (both groups) of a set of 29 quality indicators. The set was drawn from the reports (24 indicators) and supplemented by five indicators commonly used in hospital quality reports. We analysed the differences in patient and physician ratings of relevance of all indicators by applying descriptive statistics, t-tests and Wilcoxon tests.

Results

Only three indicators were considered not understandable by the interviewed patients and unsuitable by the interviewed physicians. The patients rated 19 indicators as highly or very relevant, whereas the physicians chose 15 indicators. The most relevant indicator for the patients was "qualification of doctors", and for the physicians "volume of specified surgical procedures". Patient and physician rankings of individual indicators differed for 25 indicators. However, three groups of indicators could be differentiated, in which the relevance ratings of patients and physicians differed only within the groups. Four of the five indicators that were added to the existing set of reported indicators ranked in the first or second group ("kindness of staff", "patient satisfaction", "recommendation", and "distance to place of living").

Conclusion

Most of the content of Germany's hospital quality reports seems to be useful for patients and physicians and influence their choice of hospitals. However, the target groups revealed that approximately one third of the indicators (mostly hospital structural characteristics), were not useful and hence could have been omitted from the reports. To enhance the usefulness of the reports, indicators on patient experiences should be added.
Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity
Authors: Abdurahman Samir , Youssefi Masoud , Höglund Stefan , Vahlne Anders
Published: September 2007

Background

The mature HIV-1 conical core formation proceeds through highly regulated protease cleavage of the Gag precursor, which ultimately leads to substantial rearrangements of the capsid (CAp24) molecule involving both inter- and intra-molecular contacts of the CAp24 molecules. In this aspect, Asp51 which is located in the N-terminal domain of HIV-1 CAp24 plays an important role by forming a salt-bridge with the free imino terminus Pro1 following proteolytic cleavage and liberation of the CAp24 protein from the Pr55Gag precursor. Thus, previous substitution mutation of Asp51 to alanine (D51A) has shown to be lethal and that this invariable residue was found essential for tube formation in vitro, virus replication and virus capsid formation.

Results

We extended the above investigation by introducing three different D51 substitution mutations (D51N, D51E, and D51Q) into both prokaryotic and eukaryotic expression systems and studied their effects on in vitro capsid assembly and virus infectivity. Two substitution mutations (D51E and D51N) had no substantial effect on in vitro capsid assembly, yet they impaired viral infectivity and particle production. In contrast, the D51Q mutant was defective both for in vitro capsid assembly and for virus replication in cell culture.

Conclusion

These results show that substitutions of D51 with glutamate, glutamine, or asparagine, three amino acid residues that are structurally related to aspartate, could partially rescue both in vitro capsid assembly and intra-cellular CAp24 production but not replication of the virus in cultured cells.
Comparison of fertility results after vaginal insemination using different thawing procedures and packages for frozen ram semen
Authors: Paulenz Heiko , Ådnøy Tormod , Söderquist Lennart
Published: September 2007

Background

The effect of different thawing procedures for ram semen frozen in minitubes and mini straws on the fertility of sheep was tested in a field trial.

Methods

Altogether, 719 Norwegian Crossbred ewes, aged between six months and six-and-a-half years from 8 farms, were inseminated vaginally in natural oestrus with frozen-thawed semen. Minitubes were thawed at 70°C for 8 sec (T70) and mini straws either at 50°C for 9 sec (S50) or at 35°C for 12 sec (S35).

Results

Vaginal insemination with 200 × 106 spermatozoa resulted in 25-days non-return rates of 63.2, 59.6, and 62.5% (overall 61.8%), respectively, and lambing rates of 56.8, 55.0, and 59.2% (overall 57.0%), respectively. No significant effect on fertility (as 25-days non-return- or lambing rate) was seen for straw type/thawing temperature (P = 0.5/0.5), but semen filled in mini straws and thawed at 35°C resulted numerically in the highest lambing rate (59.2%). A significant effect was, however, seen for farmer (P = >0.0001/>0.0001) and ram (P = 0.009/0.002). Moreover, age of the ewes had a significant effect on the NR rate (0.007), but not on lambing rate (P = 0.2).

Conclusion

A vaginal deposition of frozen ram semen containing approximately 200 × 106 spermatozoa, filled in mini straws and thawed at 35°C is a simplified technique that under field conditions and used on a do-it-yourself regime gives acceptable lambing rates in Norway.