bluuebunny/crossref_metadata_2025 huggingface dataset:
Micellar Phytosterols Effectively Reduce Cholesterol Absorption at Low Doses
Authors: Shin Min-Jeong , Lee Jong Ho , Jang Yangsoo , Lee-Kim Yang Cha , Park Eunju , Kim Kyung Mee , Chung Bong Chul , Chung Namsik
Published: August 2005

Background: The objective of this study was to evaluate the effects of micellar phytosterols on cholesterol absorption in humans. Methods: 24 healthy adults (mean age 37 years, 16 women and 8 men) underwent four cholesterol-absorption tests to compare the effects of micellar phytosterols supplement containing 500, 300, 200 mg phytosterols and placebo on cholesterol absorption in a cross-over design. Individual absorption tests were separated by 2 weeks. Using the single oral isotope method, inhibition of cholesterol absorption was determined by gas-chromatography mass spectrometry measurement of the differences in plasma hexadeuterated cholesterol enrichment 4 days after test meals with or without phytosterols. Each test meal provided 500 kcal and 89 mg cholesterol including 40 mg tracer cholesterol. We used a general linear mixed model with SAS to test the significance of treatment effect. Results: Micellar phytosterols had a significant overall effect on cholesterol absorption (p = 0.0002), reduced cholesterol absorption by 23.3% at a dose of 300 mg phytosterols (p = 0.0004) and by 32.0% at a dose of 500 mg phytosterols (p = 0.0001) compared with the placebo. The effect of 200 mg treatment did not reach statistical significance but there was a tendency (p = 0.052). Conclusion: Water-dispersible, micellar phytosterols reduced cholesterol absorption effectively at very low doses.
Analysis of Sequence Variations in the ABCC6 Gene among Patients with Abdominal Aortic Aneurysm and Pseudoxanthoma Elasticum
Authors: Schulz Veronika , Hendig Doris , Schillinger Martin , Exner Markus , Domanovits Hans , Raith Marianne , Szliska Christiane , Kleesiek Knut , Götting Christian
Published: August 2005

Abdominal aortic aneurysm (AAA) is characterized by dilatation of arterial walls, which is accompanied by degradation of elastin and collagen molecules. Biochemical and environmental factors are known to be relevant for AAA development, and familial predisposition is well recognized. A connective tissue disorder that is also associated with fragmentation of elastic fibers is Pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the ABCC6 gene and mainly affects dermal, ocular and all vascular tissues. To investigate whether variations in ABCC6 are found in AAA patients and to determine mutations in PXE patients, we analyzed seven selected ABCC6 exons of 133 AAA and 54 PXE patients subjected to mutational analysis. In our cohort of AAA patients, we found five ABCC6 alterations, which result in missense or silent amino acid variants. The allelic frequencies of these sequence variations were not significantly different between AAA patients and healthy controls. Therefore, we suggest that alterations in ABCC6 are not a genetic risk factor for AAA. Mutational screening of the PXE patients revealed 19 different ABCC6 variations, including two novel PXE-causing mutations. These results expand the ABCC6 mutation database in PXE.
Attenuated Noradrenaline-Induced Contraction of Pulmonary Arteries from Rats Treated with Monocrotaline: Role of Rho Kinase
Authors: Khan Islam , Oriowo Mabayoje A. , Chandrasekhar Bindu , Kadavil Elizabeth A.
Published: August 2005

Noradrenaline-induced pulmonary artery contraction was reduced in monocrotaline-treated rats. The possibility that this could be due to alterations in the rho kinase pathway was examined in this study. A combination of nifedipine (10–6 M) and thapsigargin (10–6 M) attenuated noradrenaline-induced contraction significantly more in artery segments from monocrotaline-treated rats than in artery segments from control rats indicating a reduced role for calcium sensitization in artery segments from monocrotaline-treated rats. In artery segments permeabilized with ionomycin, CaCl2 (1.25 mmol/l) produced significantly greater contraction in monocrotaline treated rats compared with control rats. Addition of noradrenaline (10–5 M) to the bath produced further contractions in both groups. However, noradrenaline-induced contraction was less in monocrotaline-treated rats compared with controls. Y-27632 concentration dependently relaxed ring segments of pulmonary artery pre-contracted with noradrenaline (10–5M). The pIC50 values were 6.46 ± 0.09 (n = 5) 5.81 ± 0.06 (n = 5) in control and pulmonary hypertensive rings, respectively. The maximum relaxation to Y-27632 was significantly higher in monocrotaline-treated rats. ROCK II was the predominant isoform of rho kinase expressed in the pulmonary artery. The level of expression was increased in rats treated with monocrotaline. These results would suggest that while basal rho kinase activity was elevated in monocrotaline-induced pulmonary hypertension, noradrenaline-induced contraction was attenuated, suggesting poor coupling of the receptor activation to rho kinase activation.
Phase I Study of Weekly Docetaxel and Liposomal Doxorubicin in Patients with Advanced Solid Tumors
Authors: Kouroussis Ch. , Androulakis N. , Vamvakas L. , Kalykaki A. , Spiridonakou S. , Kentepozidis N. , Saridaki Z. , Xiropoulou El. , Georgoulias V.
Published: August 2005

Purpose: To determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities (DLTs) of the weekly administration of docetaxel and pegylated liposomal doxorubicin (PEG-LD) in patients with advanced solid tumors. Patients and Methods: Forty-eight patients with solid tumors were enrolled in the study. Dose escalations of both drugs were given on a weekly basis for 3 consecutive weeks in cycles of 4 weeks. The starting dose for docetaxel was 20 mg/m2/week and for PEG-LD 6 mg/m2/week. Results: The MTD was 35 mg/m2/week for docetaxel and 14 mg/m2/week for PEG-LD. The DLTs at this level were grade 3 diarrhea (n = 1 patient) and grade 3 mucositis (n = 2 patients). There was no grade 4 hematologic or non-hematologic toxicity. Grade 3 neutropenia and thrombocytopenia occurred only in 1 and 2 patients, respectively. The non-hematologic toxicity was also mild with grade 2/3 fatigue in 8 patients, grade 2/3 neurotoxicity in 4, grade 2/3 mucositis in 8, grade 2/3 diarrhea in 4 and grade 2/3 nausea and vomiting in 5 patients. Two (5.7%) complete and 6 (17%) partial responses (overall response rate = 22.7%; 95% confidence interval 9.6–32.4%) were observed among 35 evaluable patients. In 12 (63%) of 19 patients with hormone-refractory prostate cancer, a decline in serum levels of prostate-specific antigen of >50% was observed. Conclusions: The weekly administration of docetaxel with PEG-LD is a well-tolerated regimen that merits further evaluation.
The Effect of Treatment Interruptions in the Postoperative Irradiation of Breast Cancer
Authors: Bese Nuran Senel , Sut Pelin Altinok , Ober Ahmet
Published: August 2005

Objective: There is much evidence for the detrimental effect of treatment interruptions on tumor control, particularly in head and neck cancer. In order to determine the outcome of the treatment interruptions in postoperative irradiation of breast cancer, 853 female patients treated between 1990 and 1999 inclusive were retrospectively analyzed. Methods: Locally advanced breast cancer patients who received neoadjuvant chemotherapy were not included in the study. Five hundred and forty-six patients (64%) treated with mastectomy and 307 patients (36%) with breast-conserving surgery were analyzed. A total dose of 50 Gy (46–54 Gy) was given to the chest wall/breast and regional lymph nodes in 1.8- to 2-Gy daily fractions, 5 times per week. A 14-Gy (10- to 20-Gy) photon or electron boost was given to the tumor bed of the patients with breast-conserving surgery. Unplanned treatment interruptions occurred in 741 (87%) of the patients and the median duration of the gaps was 13 days (1–91 days). A total of 348 patients (41%) had no treatment break or interruptions of 1 week or less, whereas 505 patients (59%) had treatment interruptions of more than 1 week. The locoregional control (LC) and overall survival (OS) rates were estimated with the Kaplan-Meier method. A Cox proportional hazard regression model was used to evaluate the influence of host- and treatment-related factors on LC and OS (age, menopausal status, histological subtype, grade, hormonal receptor status, pT stage, pN stage, type of surgery, adjuvant treatment, number of gaps and duration of gaps). Results:For all patients LC rates for 5 and 10 years were 95 and 87%, respectively, and OS rates were 78% for 5 years and 62% for 10 years. LC rates for the group of patients with no treatment break or interruptions of 1 week or less, for 5 and 10 years were 94 and 90%, whereas the LC rates for 5 and 10 years were 89 and 86%, for the group of patients with interruptions of more than 1 week (p = 0.019). Treatment interruptions of more than 1 week and premenopausal status appeared to be independent adverse prognostic factors in multivariate analyses affecting the LC (p = 0.043 and p = 0.005, respectively). The OS rates for the patients without treatment interruptions or interruptions of 1 week or less were also significantly better than for the patients with treatment interruptions of more than 1 week (p = 0.026) in multivariate analyses. Conclusion:Interruptions more than 1 week during postoperative irradiation of breast cancer adversely affect the treatment outcome.
C-Reactive Protein Induces NF-κB Activation through Intracellular Calcium and ROS in Human Mesangial Cells
Authors: Chang Jai Won , Kim Choung Soo , Kim Soon Bae , Park Su Kil , Park Jung Sik , Lee Sang Koo
Published: August 2005

Background: C-reactive protein (CRP) is known to have a direct proinflammatory effect in endothelial cells. However, little is known about the effect of CRP in intrinsic renal cells. We investigated the effects of CRP on the nuclear factor-ĸB (NF-ĸB) activation and monocyte chemoattractant protein-1 (MCP-1) gene expression in human mesangial cells and also examined whether intracellular calcium and reactive oxygen species (ROS) were involved in the CRP- induced NF-ĸB activation. Methods: NF-ĸB binding activity and MCP-1 mRNA expression were measured by electrophoretic mobility shift assay and Northern blot analysis, respectively.Intracellular calcium was monitored by confocal microscopy using calcium sensitive dye, Fluo-3 and intracellular ROS production was determined, using 2′,7′-dichlorofluorescin diacetate. Results: CRP increased NF-ĸB binding activity in a dose-dependent manner (12.5–100 µg/ml), which was induced within 1 h after incubation and peaked around 3 h. CRP also increased the MCP-1 mRNA expression via activation of NF-ĸB. Both intracellular calcium and ROS was induced by CRP. Calcium chelator, BAPTA-AM and anti-oxidants such as N-acetylcysteine and tiron suppressed CRP-induced NF-ĸB activation. Conclusion: CRP exerted a proinflammatory effect in human mesangial cells by inducing MCP-1 gene expression via NF-ĸB activation, which was mediated, at least in part, through intracellular calcium and ROS.
Cholesteryl Ester Transfer Protein Directly Mediates Selective Uptake of High Density Lipoprotein Cholesteryl Esters by the Liver
Authors: Gauthier Andre , Lau Paulina , Zha Xiaohui , Milne Ross , McPherson Ruth
Published: August 2005

Objective—

To determine whether cholesteryl ester transfer protein (CETP) directly mediates selective uptake of high-density lipoprotein (HDL)-cholesteryl ester (CE) by hepatocytes and to quantify the effects of the CETP inhibitor, torcetrapib, on this process.

Methods and Results—

Using adenovirus-mediated CETP (ad-CETP) expression in primary mouse hepatocytes from either wild-type, low-density lipoprotein (LDL) receptor−/− or SR-BI−/− mice, we demonstrate that CETP enhances the selective accumulation of HDL-derived
3
H-CE independently of known lipoprotein receptors. Addition of torcetrapib to the media did not impair the ability of cell-associated CETP to enhance CE uptake but reduced the ability of exogenously added CETP to increase selective uptake by up to 80%. When mice were infected with ad-CETP or ad-Luciferase and treated with daily intravenous injections of torcetrapib or vehicle, hepatic CETP expression resulted in a 50% decrease in HDL cholesterol in vehicle-treated animals versus a 33% decrease in HDL cholesterol in mice treated with torcetrapib.

Conclusions—

CETP mediates selective uptake of HDL-CE by hepatocytes by both torcetrapib-sensitive (exogenous CETP) and torcetrapib-insensitive (cell-associated CETP) mechanisms. Hepatic expression of CETP in vivo results in a marked decrease in cholesterol in particles in the HDL density range, consistent with a physiological role for hepatocyte CETP in selective uptake.
Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial
Authors: Asztalos Bela F. , Collins Dorothea , Cupples L. Adrienne , Demissie Serkalem , Horvath Katalin V. , Bloomfield Hanna E. , Robins Sander J. , Schaefer Ernst J.
Published: August 2005

Objective—

To test the hypothesis whether determination of high-density lipoprotein (HDL) subpopulations provides more power to predict recurrent cardiovascular disease (CVD) events (nonfatal myocardial infarction, coronary heart disease death, and stroke) than traditional risk factors in the Veterans Affairs HDL Intervention Trial (VA-HIT).

Methods and Results—

Apolipoprotein A-I (apoA-I)–containing HDL subpopulations were quantitatively determined by nondenaturing 2D gel electrophoresis. Hazard ratios of recurrent CVD events were calculated by comparing VA-HIT subjects with (n=398) and without (n=1097) such events. Subjects with new CVD events had significantly lower HDL-C, apoA-I, and large cholesterol-rich HDL particle (α-1, α-2, pre–α-1, and pre–α-2) levels, significantly higher triglyceride, and small poorly lipidated HDL particle (pre–β-1 and α-3) levels than subjects without such events. Multivariate analyses indicated that α-1 and α-2 particle levels were significant negative risk factors, whereas α-3 level was a significant positive risk factor for new CVD events. Pre–β-1 level was a significant risk factor for new CVD events only in univariate analysis. A forward selection model indicated that α-1 was the most significant risk factor for recurrent CVD events among HDL particles.

Conclusions—

An altered HDL subpopulation profile marked with low α-1 and α-2 levels and a high α-3 level in coronary heart disease patients indicated an elevated risk for new CVD events. Moreover, α-1 and α-2 levels were superior to HDL-C levels in risk assessment in patients with low HDL-C in VA-HIT.
An Unsuspected Metabolic Role for Atrial Natriuretic Peptides
Authors: Lafontan Max , Moro Cédric , Sengenes Coralie , Galitzky Jean , Crampes François , Berlan Michel
Published: August 2005

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3′, 5′-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral β-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.
Lifecourse Socioeconomic Position, C-Reactive Protein, and Carotid Intima-Media Thickness in Young Adults
Authors: Kivimäki Mika , Lawlor Debbie A. , Juonala Markus , Davey Smith George , Elovainio Marko , Keltikangas-Järvinen Liisa , Vahtera Jussi , Viikari Jorma S.A. , Raitakari Olli T.
Published: August 2005

Objective—

It has been suggested that confounding by socioeconomic position from across the lifecourse together with adult risk factors explain the association between C-reactive protein (CRP) and coronary heart disease, but the evidence for this is limited to elderly subjects. We examined associations between socioeconomic position in childhood and adulthood, adult CRP, and carotid intima-media thickness (IMT), a presymptomatic predictor of coronary heart disease, in a population of young adults.

Methods and Results—

The association of socioeconomic indicators at age 3 to 18 and in adulthood with CRP and IMT at age 24 to 39 were examined in a prospective cohort study of 2290 (1030 men and 1260 women) participants in the Young Finns Study. After adjustment for age and sex, both childhood and adulthood socioeconomic position were inversely associated with CRP (
p
s≤0.02). There was also a direct correlation between CRP and IMT (
P
<0.008). However, both the association between socioeconomic position and CRP and that between CRP and IMT attenuated to the null with adjustment for BMI and waist-to-hip ratio. Controlling for other risk factors had little effect on these associations.

Conclusions—

In young adults, the interrelations between socioeconomic position, CRP, and carotid atherosclerosis are accounted for by adiposity.
Vascular Neointimal Formation and Signaling Pathway Activation in Response to Stent Injury in Insulin-Resistant and Diabetic Animals
Authors: Jonas Michael , Edelman Elazer R. , Groothuis Adam , Baker Aaron B. , Seifert Philip , Rogers Campbell
Published: August 2005

Diabetes and insulin resistance are associated with increased disease risk and poor outcomes from cardiovascular interventions. Even drug-eluting stents exhibit reduced efficacy in patients with diabetes. We now report the first study of vascular response to stent injury in insulin-resistant and diabetic animal models. Endovascular stents were expanded in the aortae of obese insulin-resistant and type 2 diabetic Zucker rats, in streptozotocin-induced type 1 diabetic Sprague-Dawley rats, and in matched controls. Insulin-resistant rats developed thicker neointima (0.46±0.08 versus 0.37±0.06 mm
2
,
P
=0.05), with decreased lumen area (2.95±0.26 versus 3.29±0.15 mm
2
,
P
=0.03) 14 days after stenting compared with controls, but without increased vascular inflammation (ED1+ tissue macrophages). Insulin-resistant and diabetic rat vessels did exhibit markedly altered signaling pathway activation 1 and 2 weeks after stenting, with up to a 98% increase in p-ERK (anti-phospho ERK) and a 54% reduction in p-Akt (anti-phospho Akt) stained cells. Western blotting confirmed a profound effect of insulin resistance and diabetes on Akt and ERK signaling in stented segments. p-ERK/p-Akt ratio in stented segments uniquely correlated with neointimal response (
R
2
=0.888,
P
=0.04) in insulin-resistant and type 1 and 2 diabetic rats, but not in lean controls. Transfemoral aortic stenting in rats provides insight into vascular responses in insulin resistance and diabetes. Shifts in ERK and Akt signaling related to insulin resistance may reflect altered tissue repair in diabetes accompanied by a shift in metabolic:proliferative balance. These findings may help explain the increased vascular morbidity in diabetes and suggest specific therapies for patients with insulin resistance and diabetes.
The Role of the Multidrug Resistance Protein-1 in Modulation of Endothelial Cell Oxidative Stress
Authors: Mueller Cornelius F.H. , Widder Julian D. , McNally Joseph S. , McCann Louise , Jones Dean P. , Harrison David G.
Published: August 2005

Glutathione (GSH) is the major source of intracellular sulfhydryl groups. Oxidized GSH (GSSG) can be recycled to GSH by the GSH reductase or exported from the cell. The mechanism by which GSSG is exported and the consequence of its export from endothelial cells has not been defined previously. We found that human endothelial cells express the multidrug resistance protein-1 (MRP1) and use this as their major exporter of GSSG. Oscillatory shear stress, which is known to stimulate endothelial cell production of reactive oxygen species, decreased intracellular GSH. In contrast, laminar shear significantly increased intracellular GSH. Oscillatory shear also caused a robust export of GSSG that was prevented by the MRP1 inhibitor MK571 and by MRP1 small interfering RNA. MRP1 inhibition prevented the decline in intracellular GSH, preserved the intracellular GSH Nernst potential, and reduced apoptosis caused by oscillatory shear. In aortas of hypertensive mice, endothelial disulfide export was doubled, and this was prevented by MK571 and was not observed in aortas of hypertensive MRP1
−/−
mice. Further, the altered endothelium-dependent vasodilatation caused by hypertension was ameliorated in MRP1
−/−
mice. GSSG export by MRP1 leads to a perturbation of endothelial redox state and ultimately endothelial cell apoptosis. Endothelial MRP1 may provide a novel therapeutic target for prevention of vascular disease.
A Myocardial Nox2 Containing NAD(P)H Oxidase Contributes to Oxidative Stress in Human Atrial Fibrillation
Authors: Kim Young M. , Guzik Tomasz J. , Zhang Yin Hua , Zhang Mei Hua , Kattach Hassan , Ratnatunga Chandi , Pillai Ravi , Channon Keith M. , Casadei Barbara
Published: August 2005

Human atrial fibrillation (AF) has been associated with increased atrial oxidative stress. In animal models, inhibition of reactive oxygen species prevents atrial remodeling induced by rapid pacing, suggesting that oxidative stress may play an important role in the pathophysiology of AF. NAD(P)H oxidase is a major source of superoxide in the cardiovascular system; however, whether this enzyme contributes to atrial oxidative stress in AF remains to be elucidated. We investigated the sources of superoxide production (using inhibitors and substrates of a range of oxidases, RT-PCR, immunofluorescence, and immunoblotting) in tissue homogenates and isolated atrial myocytes from the right atrial appendage (RAA) of patients undergoing cardiac surgery (n=54 in sinus rhythm [SR] and 15 in AF). A membrane-bound gp91phox containing NAD(P)H oxidase in atrial myocytes was the main source of atrial superoxide production in SR and in AF. NADPH-stimulated superoxide release from RAA homogenates was significantly increased in patients with AF in the absence of changes in mRNA expression of the p22phox and gp91phox subunits of the NAD(P)H oxidase. In contrast with findings in SR patients, NO synthases (NOSs) contributed significantly to atrial superoxide production in fibrillating atria, suggesting that increased oxidative stress in AF may lead to NOS “uncoupling.” These findings indicate that a myocardial NAD(P)H oxidase and, to a lesser extent, dysfunctional NOS contribute significantly to superoxide production in the fibrillating human atrial myocardium and may play an important role in the atrial oxidative injury and electrophysiological remodeling observed in patients with AF.
Birth Weight Is Inversely Associated With Incident Coronary Heart Disease and Stroke Among Individuals Born in the 1950s
Authors: Lawlor Debbie A. , Ronalds Georgina , Clark Heather , Davey Smith George , Leon David A.
Published: August 2005

Background—

Birth weight is inversely associated with cardiovascular disease risk factors, but few studies have examined the association with disease end points, in particular with stroke risk. Furthermore, previous studies demonstrating an inverse association between birth weight and coronary heart disease (CHD) risk have been conducted on populations born in the early part of the 20th century, when infant mortality rates were high. If the environmental factors associated with improvements in infant mortality rates over the last century explain the inverse association between birth weight and CHD risk, one would expect weaker associations in more contemporary birth cohorts.

Methods and Results—

We have examined the association in a large birth cohort of 10 803 (with an average of 239 000 person-years of follow-up) singleton births that occurred between 1950 and 1956. Our outcomes were hospital admissions for, and fatalities from, CHD (n=296) and stroke (n=107). Birth weight was inversely associated with CHD and stroke. The age-adjusted hazards ratio for a 1-kg increase in birth weight was 0.62 (95% CI 0.50 to 0.78) for CHD and 0.38 (95% CI 0.24 to 0.60) for stroke. Adjustment for gestational age, social class at birth, height and body mass index at school entry, gravidity, maternal age at birth, pregnancy-induced hypertension, antepartum hemorrhage, and maternal height did not alter the association with CHD but attenuated the association with stroke to 0.48 (95% CI 0.30 to 0.76). This attenuation resulted largely from adjustment for gestational age, which was linearly inversely related to stroke risk. Adjusted hazard ratios per sex and gestational age standardized
z
score of birth weight were 0.85 (95% CI 0.73 to 0.97) for CHD and 0.74 (95% CI 0.71 to 0.88) for stroke.

Conclusions—

Birth weight is inversely associated with CHD and stroke in a population born at a time when environmental circumstances, as indexed by low infant mortality rates, were relatively advantageous for infants.
Randomized Evaluation of the Effects of Filter-Based Distal Protection on Myocardial Perfusion and Infarct Size After Primary Percutaneous Catheter Intervention in Myocardial Infarction With and Without ST-Segment Elevation
Authors: Gick Michael , Jander Nikolaus , Bestehorn Hans-Peter , Kienzle Rolf-Peter , Ferenc Miroslaw , Werner Klaus , Comberg Thomas , Peitz Kristhild , Zohlnhöfer Dietlind , Bassignana Valerio , Buettner Heinz Joachim , Neumann Franz-Josef
Published: August 2005

Background—

In acute myocardial infarction, distal embolization of debris during primary percutaneous catheter intervention may curtail microvascular reperfusion of the infarct region. Our randomized trial investigated whether distal protection with a filter device can improve microvascular perfusion and reduce infarct size after primary percutaneous catheter intervention.

Methods and Results—

We enrolled 200 patients who had angina within 48 hours after onset of pain plus at least 1 of 3 additional criteria: ST-segment elevation, elevated myocardial marker proteins, and angiographic evidence of thrombotic occlusion. Among the patients included (83% men; mean age, 62±12 years), 100 were randomly assigned to the filter-wire group and 100 to the control group. The primary end point was the maximal adenosine-induced Doppler flow velocity in the recanalized infarct artery; the secondary end point was infarct size estimated by the volume of delayed enhancement on nuclear MRI. ST-segment elevation myocardial infarction was present in 68.5% of the patients; the median time from onset of pain was 6.9 hours. In the filter-wire group, maximal adenosine-induced flow velocity was 34±17 compared with 36±20 cm/s in the control group (
P
=0.46). Infarct sizes, assessed in 82 patients in the filter-wire group and 78 patients in the control group, were 11.8±9.3% of the left ventricular mass in the filter-wire group and 10.4±9.4% in the control group (
P
=0.33). Thirty-day mortality was 2% in filter-wire group and 3% in the control group.

Conclusions—

The filter wire as an adjunct to primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation did not improve reperfusion or reduce infarct size.
The Giant Sucking Sound: Is China Diverting Foreign Direct Investment from Other Asian Economies?
Authors: Chantasasawat Busakorn , Fung K. C. , Iizaka Hitomi , Siu Alan
Published: August 2005

This paper attempts to determine empirically whether China is taking foreign direct investment (FDI) away from other Asian economies (the “China effect”). A random-effects simultaneous equation model, controlling for the determinants of inward FDI of eight East and Southeast Asian economies over 1985–2001 and using China's inward FDI as an indicator of the China effect, indicates that China's FDI level is positively related to these economies' FDI levels and negatively related to their shares in FDI in Asia. Moreover, openness, corporate tax rates, and corruption can exert a greater influence on these countries' FDI than China's FDI.
Regional Versus Global Risk Sharing in East Asia
Authors: Kim Soyoung , Kim Sunghyun H. , Wang Yunjong
Published: August 2005

This paper estimates the degree of risk sharing for each of 10 East Asian countries with countries in the region and with OECD countries by using cross-country consumption correlations and formal regression analysis. Risk sharing is found to be far from complete and quite low for most of the countries. Taiwan and Singapore have the highest risk sharing. Indonesia and Malaysia have the lowest (and significantly negative) risk sharing. The degree of risk sharing does not increase in most countries over 1970–2000. For the less-developed countries, potential gains from risk sharing would be larger with OECD countries than with East Asian countries.
Can the Strategy of Western Development Narrow Down China's Regional Disparity?
Authors: Zhang Wei
Published: August 2005

The main causes of the faster growth in China's eastern coastal area, and thus for the rise in income disparity between eastern and western regions, are the rapid increases in foreign trade and foreign investment resulting not only from the government's coastal development strategy but also from inherent advantages of the eastern coastal area. Since 1999, the development strategy for western China has focused on the injection of large amounts of capital, but fiscal constraints make this strategy unsustainable. China's government should allow mobility of the labor force across regions to play a bigger role in solving the income disparity problem.
With a Little Help from my Friends
Authors: Murillo M. Victoria , Schrank Andrew
Published: August 2005

Why did Latin American governments adopt potentially costly, union-friendly labor reforms in the cost-sensitive 1980s and 1990s? The authors answer the question by exploring the relationship between trade unions and two of their most important allies: labor-backed parties at home and labor rights activists overseas. While labor-backed parties in Latin America have locked in the support of their core constituencies by adopting relatively union-friendly labor laws in an otherwise uncertain political and economic environment, labor rights activists in the United States have demonstrated their support for their Latin American allies by asking the U.S. government to treat the protection of labor rights as the price of access to the U.S. market. The former trajectory is the norm in traditionally labor-mobilizing polities, where industrialization encouraged the growth of labor-backed parties in the postwar era; the latter is more common in more labor-repressive environments, where vulnerable unions tend to look for allies overseas.
Cost-Benefit Analysis in Social Care for Elderly People
Authors: Dutrénit Jean-Marc
Published: August 2005

Social care at home for elderly people is now growing rapidly in France. A new question is, What are better forms of care for the different partners concerned? The research presented here, and made for the Comity of Lille Employment Area with cooperation of the Caisse Primaire d’Assurance Maladiede Lille (the local board of the national social security system), offers some answers to that question. Ceteris paribus, cultural activities—in a group or at home—versus others appear to produce more interest for elderly, professional caregivers, and the rest of society.
General Child Benefit Fund Experiments in Providing Differentiated Services
Authors: Serres Anne-Marie
Published: August 2005

Populations not autonomous in their administrative relations has difficulties with access to social benefits of the Caisses d’Allocations Familiales (CAFs). These difficulties, whether rooted in cultural, educational, social, or other issues, disrupt the management of their documents of social benefits and thereby weigh on their economic situations. From 1998 to 2000, five CAFs tested suitable solutions to situations of beneficiaries for whom standardized procedures have shown their limits, in the areas of housing, compensatory allocations of revenues, and given territories. They have defined goals, methods, and indicators for complex situations and have regular assessments of the management of the project as the project is going on. These results concern a better understanding of the beneficiaries, understanding of the services to provide them with, and the benefits for the beneficiaries, for the agents, for the CAF, and for its relations with the partners associated with their missions.
Facilitating Self-Determination in Adolescents with Intellectual Disabilities
Authors: Haelewyck Marie-Claire , Bara Mélanie , Lachapelle Yves
Published: August 2005

Taking an active part and responsibilities in one’s own life is not always easy, particularly at adolescence, which is a very important period in which people progressively find their identity and life project. This article describes the social validation analyses of a Belgian self-determination curriculum that was adapted from a French-Canadian curriculum. It was done with the participation of adolescents with intellectual disabilities, teachers, and experts from the field. Overall, results indicate a satisfying to very satisfying appreciation of the social utility of the training manual. The findings also highlighted that the curriculum actually supports the conceptual framework of self-determination.
Partial-Thickness Rotator Cuff Tears
Authors: Matava Matthew J. , Purcell Derek B. , Rudzki Jonas R.
Published: August 2005

Partial-thickness tears of the rotator cuff have been diagnosed with increased frequency because of a heightened awareness of the condition by clinicians and improved diagnostic methods. Research into the causes, natural history, and optimal treatment of this condition lags behind that of full-thickness tears. However, despite the limitations in the existing literature, there has emerged a consensus among shoulder experts that partial-thickness rotator cuff tears should be aggressively treated in the active athlete because of the unfavorable natural history of these lesions and success of accepted surgical algorithms. This review will provide an overview of the theories regarding the origins of partial-thickness rotator cuff tears, discuss the relative accuracy of accepted diagnostic techniques, and summarize the indications and methods of operative repair with an emphasis on the results of various treatment approaches.
MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10
Authors: Nakagawa Masao , Hosokawa Yoshitaka , Yonezumi Masakatsu , Izumiyama Koh , Suzuki Ritsuro , Tsuzuki Shinobu , Asaka Masahiro , Seto Masao
Published: August 2005

MALT1, BCL10 (B-cell lymphoma 10), and API2 (apoptosis inhibitor 2)-MALT1 are key molecules in mucosa-associated lymphoid tissue (MALT) lymphomagenesis. We previously reported that MALT1 and API2-MALT1 were localized only in cytoplasm, where we suggested that both molecules were likely to be active. In the study presented here, we further examined the localization-determining region by generating various mutants and were able to demonstrate that there were nuclear export signal (NES)-containing domains in the MALT1 C-terminal region. The use of leptomycin B, an NES-specific inhibitor, demonstrated that both MALT1 and API2-MALT1 were predominantly retained in the nuclei, indicating that these molecules were shuttling between nucleus and cytoplasm in an NES-dependent manner. It was also found that MALT1 was involved in the nuclear export of BCL10, which is originally localized in both nucleus and cytoplasm. These results correlate well with the nuclear BCL10 expression pattern in both t(1;14) and t(11;18) MALT lymphomas. The nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor κB (NF-κB) pathway but also in other biologic functions in lymphocytes.
Multitarget inhibition of drug-resistant multiple myeloma cell lines by dimethyl-celecoxib (DMC), a non–COX-2 inhibitory analog of celecoxib
Authors: Kardosh Adel , Soriano Nathaniel , Liu Yen-Ting , Uddin Jasim , Petasis Nicos A. , Hofman Florence M. , Chen Thomas C. , Schönthal Axel H.
Published: August 2005

2,5-dimethyl-celecoxib (DMC) is a close structural analog of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib that lacks COX-2 inhibitory function. We and others have demonstrated that DMC, despite its inability to block COX-2, is able to potently mimic the antitumor effects of celecoxib in vitro and in vivo. In this current study, we investigated whether DMC would also be able to inhibit the growth of highly drug-resistant tumor cell variants. We focused on human multiple myeloma (MM) cells, as patients with MM frequently develop drug-resistant disease and ultimately succumb to death. Here we show that DMC (and celecoxib) inhibits the proliferation of various multiple myeloma cell lines, including several (multi) drug-resistant variants. Growth inhibition in drug-sensitive and drug-resistant cells is mediated via multiple effects, which include diminished signal transducer and activator of transcription 3 (STAT-3) and mitogen-activated protein (MAP) kinase kinase (MEK) activity, reduced expression of survivin and various cyclins, and is followed by apoptotic cell death. Thus, our study demonstrates that inhibition of proliferation and induction of apoptosis by DMC (and celecoxib) can be accomplished even in highly drug-resistant multiple myeloma cells, and that this effect is achieved via the blockage of multiple targets that are critical for multiple myeloma cell growth and survival.
Surfactant Protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses
Authors: Scanlon Seth Thomas , Milovanova Tatyana , Kierstein Sonja , Cao Yang , Atochina Elena N , Tomer Yaniv , Russo Scott J , Beers Michael F , Haczku Angela
Published: August 2005

Background

The pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown.

Methods

We studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals.

Results

SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1–10 μg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function.

Conclusion

We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.
Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis
Authors: Ekberg-Aronsson Marie , Pehrsson Kerstin , Nilsson Jan-Åke , Nilsson Peter M , Löfdahl Claes-Göran
Published: August 2005

Background

The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function. The aims of this study were to investigate total mortality risks in GOLD stages 0–4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1–4.

Method

Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits. Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses. Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0–4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group. HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1–4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.

Results

The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively. The proportion of smokers among men was 50% and among women 40%. Self reported comorbidity was present in 4.6% of the men and 6.6% of the women. Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32–2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31–1.70). The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98–1.29). Among male smokers with stage 1; HR: 2.04 (1.34–3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38–7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.

Conclusion

Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2).
A comparative study of discriminating human heart failure etiology using gene expression profiles
Authors: Huang Xiaohong , Pan Wei , Grindle Suzanne , Han Xinqiang , Chen Yingjie , Park Soon J , Miller Leslie W , Hall Jennifer
Published: August 2005

Background

Human heart failure is a complex disease that manifests from multiple genetic and environmental factors. Although ischemic and non-ischemic heart disease present clinically with many similar decreases in ventricular function, emerging work suggests that they are distinct diseases with different responses to therapy. The ability to distinguish between ischemic and non-ischemic heart failure may be essential to guide appropriate therapy and determine prognosis for successful treatment. In this paper we consider discriminating the etiologies of heart failure using gene expression libraries from two separate institutions.

Results

We apply five new statistical methods, including partial least squares, penalized partial least squares, LASSO, nearest shrunken centroids and random forest, to two real datasets and compare their performance for multiclass classification. It is found that the five statistical methods perform similarly on each of the two datasets: it is difficult to correctly distinguish the etiologies of heart failure in one dataset whereas it is easy for the other one. In a simulation study, it is confirmed that the five methods tend to have close performance, though the random forest seems to have a slight edge.

Conclusions

For some gene expression data, several recently developed discriminant methods may perform similarly. More importantly, one must remain cautious when assessing the discriminating performance using gene expression profiles based on a small dataset; our analysis suggests the importance of utilizing multiple or larger datasets.
Genomes are covered with ubiquitous 11 bp periodic patterns, the "class A flexible patterns"
Authors: Larsabal Etienne , Danchin Antoine
Published: August 2005

Background

The genomes of prokaryotes and lower eukaryotes display a very strong 11 bp periodic bias in the distribution of their nucleotides. This bias is present throughout a given genome, both in coding and non-coding sequences. Until now this bias remained of unknown origin.

Results

Using a technique for analysis of auto-correlations based on linear projection, we identified the sequences responsible for the bias. Prokaryotic and lower eukaryotic genomes are covered with ubiquitous patterns that we termed "class A flexible patterns". Each pattern is composed of up to ten conserved nucleotides or dinucleotides distributed into a discontinuous motif. Each occurrence spans a region up to 50 bp in length. They belong to what we named the "flexible pattern" type, in that there is some limited fluctuation in the distances between the nucleotides composing each occurrence of a given pattern. When taken together, these patterns cover up to half of the genome in the majority of prokaryotes. They generate the previously recognized 11 bp periodic bias.

Conclusion

Judging from the structure of the patterns, we suggest that they may define a dense network of protein interaction sites in chromosomes.
A protein domain interaction interface database: InterPare
Authors: Gong Sungsam , Park Changbum , Choi Hansol , Ko Junsu , Jang Insoo , Lee Jungsul , Bolser Dan M , Oh Donghoon , Kim Deok-Soo , Bhak Jong
Published: August 2005

Background

Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently.

Description

We introduce a large-scale protein domain interaction interface database called InterPare http://interpare.net. It contains both inter-chain (between chains) interfaces and intra-chain (within chain) interfaces. InterPare uses three methods to detect interfaces: 1) the geometric distance method for checking the distance between atoms that belong to different domains, 2) Accessible Surface Area (ASA), a method for detecting the buried region of a protein that is detached from a solvent when forming multimers or complexes, and 3) the Voronoi diagram, a computational geometry method that uses a mathematical definition of interface regions. InterPare includes visualization tools to display protein interior, surface, and interaction interfaces. It also provides statistics such as the amino acid propensities of queried protein according to its interior, surface, and interface region. The atom coordinates that belong to interface, surface, and interior regions can be downloaded from the website.

Conclusion

InterPare is an open and public database server for protein interaction interface information. It contains the large-scale interface data for proteins whose 3D-structures are known. As of November 2004, there were 10,583 (Geometric distance), 10,431 (ASA), and 11,010 (Voronoi diagram) entries in the Protein Data Bank (PDB) containing interfaces, according to the above three methods. In the case of the geometric distance method, there are 31,620 inter-chain domain-domain interaction interfaces and 12,758 intra-chain domain-domain interfaces.