bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiponectin Is Associated with Brain Natriuretic Peptide and Left Ventricular Hypertrophy in Hemodialysis Patients with Type 2 Diabetes Mellitus
Authors: Komaba Hirotaka , Igaki Naoya , Goto Shunsuke , Yokota Kazuki , Takemoto Toshiyuki , Hirosue Yoshiaki , Goto Takeo
Published: September 2007

Background: Adiponectin, an adipocyte-derived hormone, has been shown to prevent the progression of left ventricular hypertrophy (LVH). However, recent studies have demonstrated increased levels of adiponectin according to the severity of chronic heart failure. We therefore investigated the relationships between adiponectin, brain natriuretic peptide (BNP), and LVH in type 2 diabetic patients on hemodialysis. Methods: The study population comprised 41 type 2 diabetic patients on hemodialysis. Left ventricular mass index (LVMI) and criteria for LVH were determined on the basis of echocardiographic findings. Serum adiponectin and plasma BNP levels were assayed with a commercially available kit. Results: Serum adiponectin levels significantly correlated with BMI (r = –0.49, p < 0.01), HDL-C (r = 0.36, p < 0.05) and TG (r = –0.49, p < 0.01). In addition, serum adiponectin levels correlated significantly and positively with plasma BNP levels (r = 0.36, p < 0.05). This relationship remained significant after adjustment for age, gender, and BMI (r = 0.34, p < 0.05). Serum adiponectin levels as well as plasma BNP levels were significantly higher than in patients without LVH (p < 0.05; p < 0.01, respectively), accompanied by a positive correlation between these levels and LVMI (r = 0.42, p < 0.01; r = 0.32, p < 0.05, respectively). Conclusion: Increased levels of adiponectin were associated with elevated BNP levels and LVH in hemodialysis patients with type 2 diabetes mellitus. It is speculated that adiponectin levels may be modulated by chronic hypervolemic state in this population.
Puromycin Induces Reversible Proteinuric Injury in Transgenic Mice Expressing Cyclooxygenase-2 in Podocytes
Authors: Jo Young-Il , Cheng Huifang , Wang Suwan , Moeckel Gilbert W. , Harris Raymond C.
Published: September 2007

Previous studies from our own group and others have demonstrated that cyclooxygenase-2 (COX-2) inhibitors could reduce proteinuria in some experimental models of progressive renal disease. To investigate a possible role of COX-2 in podocytes during the course of self-limited glomerular injury, we administered puromycin nucleoside (PAN) on day 1 (15 mg/100 g BW) and day 3 (30 mg/100 g BW) to wild-type and transgenic mice with podocyte-specific COX-2 expression driven by a nephrin promoter. An additional group received both PAN and the COX-2-specific inhibitor, SC58236 (6 mg/l in drinking water). There was no significant difference in the albumin (µg)/creatinine (mg) ratio between wild-type (26.3 ± 4.2, n = 8) and transgenic (28.9 ± 2.3, n = 8) mice under baseline conditions. PAN induced significant albuminuria only in the transgenic mice with a peak at day 3: 72.1 ± 8.9 µg/mg creatinine (n = 12, p < 0.05, compared with basal level), which remitted by day 10 (37.4 ± 4.4 µg/mg, n = 7, p < 0.05, compared with day 3). Electron microscopy demonstrated that PAN caused 56.7 ± 4.2% foot process effacement in transgenic mice compared with 38.8 ± 4.1% in wild type at day 3. PAN increased immunoreactive COX-2 in glomeruli from transgenic mice (day 3: 1.47 ± 0.08 fold; day 10: 1.25 ± 0.16 fold, n = 5–9, p < 0.05 compared with basal level), which was restricted to podocytes. Real time PCR indicated that endogenous COX-2 mRNA increased (2.6 ± 0.1 fold of wild-type control at day 3 and 2.2 ± 0.2 at day 10, n = 4, p < 0.05), while the nephrin-driven COX-2 mRNA was unchanged. Nephrin mRNA and protein expression were decreased by PAN in the transgenic mice. The COX-2-specific inhibitor, SC58236, reduced foot process effacement in transgenic mice administered PAN to 21.7 ± 5.2% and significantly reduced the albuminuria at day 3 (42.2 ± 3.8, n = 13, p < 0.05 compared with untreated) without significantly altering COX-2 expression. In summary, in transgenic mice with podocyte COX-2 overexpression, PAN increased albuminuria and induced foot process fusion. Thus, increased COX-2 expression increased podocyte susceptibility to further injury.
Malignant Struma Ovarii – A Case Report and Review of the Literature
Authors: Hatami Mehrangiz , Breining Dwayne , Owers Ricky L. , Del Priore Giuseppe , Goldberg Gary L.
Published: September 2007

Background: Struma ovarii is a rare monodermal ovarian teratoma composed predominantly of mature thyroid tissue. Of these cases, 5–8% are clinically hyperthyroid and 5–10% of these tumors are malignant. Case Report: A 53-year-old female presented with a 19 × 5 × 5 cm pelvic mass that was treated with bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node sampling, omentectomy and appendectomy and staging for an ovarian tumor. There was no evidence of distant metastases or lymph node invasion. Re-evaluation of the patient after surgery revealed that she was clinically euthyroid and there was no thyroid malignancy. Histopathology revealed papillary thyroid carcinoma arising in struma ovarii (malignant struma ovarii). Conclusion: Malignant struma ovarii is a very rare malignant ovarian teratoma. In young patients unilateral oophorectomy and complete surgical staging should be considered when the tumor is confined to the one ovary (stage Ia). Long-term follow-up for the detection of metastases or tumor recurrence by serial serum thyroglobulin and 131I scan or positron emission tomography/computed tomography may be required in selected patients with this rare tumor.
Vasopressin Receptor mRNA Expression in the Human Gastrointestinal Tract
Authors: Monstein H.-J. , Truedsson M. , Ryberg A. , Ohlsson B.
Published: September 2007

Background/Aim: Vasopressin and oxytocin are closely related peptides, and both exert effects on the gastrointestinal function. In the present study, we wanted to map the expression of vasopressin receptor mRNAs (V1a, V1b/V3, and V2) in nontumorous tissue biopsy specimens of human gastrointestinal tract and surrounding tissues. Methods: Total and polyA+ RNAs were isolated from human tissue biopsy specimens using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA. Seminested PCR amplifications were carried out, using gene-specific V1a, V1b/V3, and V2 receptor primers. The PCR amplicons were partially sequenced to confirm their identity. Results: The present study demonstrated the expression of vasopressin receptor mRNAs in human gastrointestinal tract, pancreas, kidney, lung, brain, and ovary. The expression pattern varied between different parts of the gastrointestinal tract. In the colon ascendens, V1a receptor mRNA expression could not be detected in 3 out of 4 analyzed tissue biopsy specimens. On the other hand, all the vasopressin receptor mRNAs were expressed in all colon transversum biopsy samples. Conclusions: V1a, V1b/V3, and V2 receptor mRNAs are widely expressed throughout human gastrointestinal tract and surrounding tissues. The data obtained provide information for further mapping and determination of the physiological role of the vasopressin receptor mRNA expression in normal and tumorous tissues.
Effects of Advanced Glycation End Product Modification on Proximal Tubule Epithelial Cell Processing of Albumin
Authors: Ozdemir Aylin M. , Hopfer Ulrich , Rosca Mariana V. , Fan Xing-Jun , Monnier Vincent M. , Weiss Miriam F.
Published: September 2007

Aim: The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells. Background: A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs. Therefore in diabetes, plasma proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs. Methods: The model system was electrically resistant polarized renal proximal tubular epithelial cells in monolayer culture. The model proteins comprise a well-characterized AGE, methylglyoxal-modified bovine serum albumin (MGO-BSA), and unmodified BSA. Results: Renal proximal tubular cells handle MGO-BSA and native BSA in markedly disparate ways, including differences in: (1) kinetics of binding, uptake, and intracellular accumulation, (2) processing and fragmentation, and (3) patterns of electrical conductance paralleling temporal changes in binding, uptake and processing. Conclusion: These differences support the idea that abnormal protein processing by the renal tubule can be caused by abnormal proteins, thereby forging a conceptual link between the pathogenic role of AGEs and early changes in tubular function that can lead to hypertrophy and nephropathy in diabetes.
The Selective TP Receptor Antagonist, S18886 (Terutroban), Attenuates Renal Damage in the Double Transgenic Rat Model of Hypertension
Authors: Šebeková Katarína , Ramuscak Anika , Boor Peter , Heidland August , Amann Kerstin
Published: September 2007

Background/Aims: Thromboxane receptors play a decisive role in the renovascular actions of angiotensin II. We studied the efficacy of the selective thromboxane receptor antagonist, S18886, in the retardation of renal damage in the double transgenic rats (dTGR), harboring human renin and angiotensinogen genes. Methods: dTGR were gavaged daily with either S18886 (30 mg/kg/day, n = 12), or placebo (dTGR-Plac, tap water, n = 14) for 3 weeks. Matched Sprague-Dawley rats (n = 10) served as controls. Results: The dTGR-Plac had higher systolic blood pressure (1.7-fold) than controls, and developed profound renal damage with significantly higher proteinuria (6.9-fold), polyuria (2.3-fold), index of glomerulosclerosis (+58%), and tubulointerstitial (+47%) and vascular damage scores (+19%). Creatinine concentration and the mesangiolysis index remained unchanged. In dTGR, S18886 slightly lowered the blood pressure (162 ± 15 vs. 149 ± 13 mm Hg, not significant) and improved proteinuria (558 ± 218 vs. 136 ± 71 mg/µmol creatinine, p < 0.01), polyuria and renal morphology (glomerulosclerosis index: 0.79 ± 0.05 vs. 0.66 ± 0.13, p < 0.01; tubulointerstitial damage index: 1.82 ± 0.22 vs. 1.49 ± 0.27, p < 0.05; mesangiolysis index: 1.31 ± 0.18 vs. 0.36 ± 0.09, p < 0.01). Vascular damage score and plasma creatinine were not influenced. S18886 did not alter measured markers of oxidative stress. Conclusion: The data present the first evidence that thromboxane receptor inhibition ameliorates angiotensin II-induced nephropathy.
Zinc Protection against Pneumolysin Toxicity on Rat Cochlear Hair Cells
Authors: Franco-Vidal Valérie , Beurg Maryline , Darrouzet Vincent , Bébéar Jean-Pierre , Skinner Liam J. , Dulon Didier
Published: September 2007

Streptococcus pneumoniae can induce local and systemic diseases such as meningitis, otitis media, and pneumonia. One third of these meningitis cases can be associated with irreversible sensorineural hearing loss whose mechanisms likely involves the exotoxin pneumolysin (PLY) that irreversibly damages cochlear hair cells (HCs). In the respiratory system and in neuron it has been demonstrated that zinc deficiency increases severity and mortality of such infections in animal models and in children. Moreover, zinc supplementation can decrease the severity of pneumococcal respiratory infections. The aim of our study was to assess the potential protective effect of zinc against PLY toxicity on HCs in culture. Our results showed that in the presence of zinc at concentration as low as 1 µM, the toxicity of PLY was largely reduced by about 50% for both inner and outer HCs. At 300 µM of zinc, protection significantly increased with 62 and 55.2% for IHCs and OHCs, respectively. Our results suggest that the protective effect of zinc is likely due to an inhibition of the toxin incorporation and aggregation into the plasma membrane, thus preventing calcium influx through the toxin pores. Our findings raise the possibility that treatments with zinc may help to prevent debilitating otological sequelae from pneumococcal infection.
A Systematic Review and Meta-Analysis of a Brief Delay in Clamping the Umbilical Cord of Preterm Infants
Authors: Rabe Heike , Reynolds Graham , Diaz-Rossello Jose
Published: September 2007

Background: The optimal timing of clamping the umbilical cord in preterm infants at birth is the subject of continuing debate. Objective: To investigate the effects of a brief delay in cord clamping on the outcome of babies born prematurely. Methods: A retrospective meta-analysis of randomised trials in preterm infants was conducted. Data were collected from published studies identified by a structured literature search in EMBASE, PubMed, CINAHL and the Cochrane Library. All infants born below 37 weeks gestation and enrolled into a randomised study of delayed cord clamping (30 s or more) versus immediate cord clamping (less than 20 s) after birth were included. Systematic search and analysis of the data were done according to the methodology of the Cochrane collaboration. Results: Ten studies describing a total of 454 preterm infants were identified which met the inclusion and assessment criteria. Major benefits of the intervention were higher circulating blood volume during the first 24 h of life, less need for blood transfusions (p = 0.004) and less incidence of intraventricular hemorrhage (p = 0.002). Conclusions: The procedure of a delayed cord clamping time of at least 30 s is safe to use and does not compromise the preterm infant in the initial post-partum adaptation phase.
A New Surgical Model for Hepatectomy in Pigs
Authors: Knubben K. , Thiel C. , Schenk M. , Etspüler A. , Schenk T. , Morgalla M.H. , Königsrainer A.
Published: September 2007

Background: Anhepatic animal models are suitable for simulating acute liver failure. Hepatectomy in pigs includes en bloc resection of the vena cava, and therefore, a temporary extracorporeal bypass and total clamping of the inferior vena cava are needed. These steps cause severe depression of circulation with impaired survival. Methods: Previous to en bloc hepatectomy including retrohepatic vena cava in 20 female pigs, a Y-shaped bypass was implanted starting with end-to-side anastomosis between the vena cava and the portal vein, followed by anastomosis to the intrathoracic vena cava. Results: Blood flow was constant during and after hepatectomy because vessels were only partially clamped. No venous stasis of intestinal organs was observed. Hemodynamic parameters like heart rate, mean arterial pressure, central venous pressure, pulse oximetry and intracranial pressure remained extremely stabile during and after hepatectomy. Postoperative survival time was 100% after 12 h. Maximum survival time was 84.9 h and mean survival time 51.2 ± 18.7 h. All animals died from multiple organ failure. Intracranial pressure remained stable during the surgical procedure and rose continuously until death. The autopsy showed massive brain edema. Conclusions: This new surgical technique is safe and easy to perform and permits total hepatectomy with minimal blood loss under stable circulation without requiring an extracorporeal bypass.
RamB Is an Activator of the Pyruvate Dehydrogenase Complex Subunit E1p Gene in Corynebacterium glutamicum
Authors: Blombach Bastian , Cramer Annette , Eikmanns Bernhard J. , Schreiner Mark
Published: September 2007

In Corynebacterium glutamicum, the transcriptional regulator RamB negatively controls the expression of genes involved in acetate metabolism. Here we show that during growth in media containing glucose and in complex medium without glucose RamB activates expression of the aceE gene, encoding the E1p subunit of the pyruvate dehydrogenase complex. Thus, RamB functions both as repressor and as activator in C. glutamicum.
Tracheal Compression in a Patient with Marfan’s Syndrome-Associated Tracheomegaly Treated by an XXL Stent: The Largest Diameter Airway Stent Ever Placed in a Previously Undescribed Airway Condition
Authors: Dutau Hervé , Cavailles Arnaud , Fernandez-Navamuel Iker , Breen David P.
Published: September 2007

A 43-year-old man was referred to our institution with severe extrinsic compression of the trachea at the level of the main carina secondary to an aortic aneurysm, causing respiratory distress and requiring mechanical ventilation. The patient had a past history of Marfan’s syndrome and tracheomegaly (the estimated tracheal diameter bronchoscopically was 28 mm). Palliation of the compression was successfully achieved by a custom-made, self-expandable, fully covered metallic stent with a diameter of 28 mm and a length of 60 mm. The patient was weaned off ventilation. The stent stayed in place for 2 years without major complications. This case represents the first stent ever inserted in a very rare condition combining tracheomegaly and extrinsic compression in Marfan’s syndrome. It is also the first report of successful placement of the largest tracheal stent which was manufactured exclusively for the airway.
Nitric Oxide and Mitochondrial Signaling
Authors: Erusalimsky Jorge D. , Moncada Salvador
Published: September 2007

Nitric oxide (NO) has been known for many years to bind to cytochrome C oxidase, the terminal acceptor in the mitochondrial electron transport chain, in competition with oxygen. This interaction may be significant in vivo and explain some of the biological actions of NO. In this article we review the evidence showing that binding of NO to cytochrome C oxidase elicits intracellular signaling events, including the diversion of oxygen to nonrespiratory substrates and the generation of reactive oxygen species. We discuss findings indicating that these NO-elicited events act as triggers by which mitochondria modulate signal transduction cascades involved in the induction of cellular defense mechanisms and adaptive responses. We also discuss instances in which the effects of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology.
USF1 Gene Variants, Cardiovascular Risk, and Mortality in European Americans
Authors: Reiner Alexander P. , Carlson Christopher S. , Jenny Nancy S. , Durda J. Peter , Siscovick David S. , Nickerson Deborah A. , Tracy Russell P.
Published: September 2007

Objective—

A common haplotype of the upstream transcription factor 1 gene (
USF1
) has been associated with decreased susceptibility to familial combined hyperlipidemia (FCHL) and, paradoxically, with increased risk of cardiovascular disease (CVD) and all-cause mortality.

Methods and Results—

We assessed associations between
USF1
tagSNPs, CVD risk factors, and aging-related phenotypes using data from 2 large population-based cohorts, Coronary Artery Risk Development in Young Adults (CARDIA) and the Cardiovascular Health Study (CHS), comprising younger and older adults, respectively. In CARDIA, each additional copy of the FCHL low-risk allele was associated with 2.4 mg/dL lower levels of LDL cholesterol (
P
=0.01) and decreased risk of subclinical atherosclerosis as assessed by coronary artery calcium (odds ratio 0.79; 95%CI 0.63 to 0.98). Whereas there was little association between
USF1
genotype and metabolic or CVD traits in older adults from CHS, the
USF1
low-risk dyslipidemia allele was associated with higher plasma C-reactive protein and interleukin (IL)-6 levels and with increased risk of mortality, particularly attributable to noncardiovascular causes.

Conclusions—

There appears to be a complex and possibly age-dependent relationship between
USF1
genotype, atherosclerosis phenotypes, and CVD risk. USF1 may influence mortality through pathways distinct from atherosclerosis. Alternatively, linkage disequilibrium with neighboring polymorphisms in other genes such as
F11R
may be responsible for the observed
USF1
genotype–phenotype associations in older adults.
Local Delivery of Anti-Monocyte Chemoattractant Protein-1 by Gene-Eluting Stents Attenuates In-Stent Stenosis in Rabbits and Monkeys
Authors: Egashira Kensuke , Nakano Kaku , Ohtani Kisho , Funakoshi Kouta , Zhao Gang , Ihara Yoshiko , Koga Jun-ichiro , Kimura Satoshi , Tominaga Ryuji , Sunagawa Kenji
Published: September 2007

Objective—

We have previously shown that the intramuscular transfer of the anti–monocyte chemoattractant protein-1 (MCP-1) gene (called 7ND) is able to prevent experimental restenosis. The aim of this study was to determine the in vivo efficacy and safety of local delivery of 7ND gene via the gene-eluting stent in reducing in-stent neointima formation in rabbits and in cynomolgus monkeys.

Methods and Results—

We here found that in vitro, 7ND effectively inhibited the chemotaxis of mononuclear leukocytes and also inhibited the proliferation/migration of vascular smooth muscle cells. We then coated stents with a biocompatible polymer containing a plasmid bearing the 7ND gene, and deployed these stents in the iliac arteries of rabbits and monkeys. 7ND gene-eluting stents attenuated stent-associated monocyte infiltration and neointima formation after one month in rabbits, and showed long-term inhibitory effects on neointima formation when assessments were carried out at 1, 3, and 6 months in monkeys.

Conclusions—

Strategy of inhibiting the action of MCP-1 with a 7ND gene-eluting stent reduced in-stent neointima formation with no evidence of adverse effects in rabbits and monkeys. The 7ND gene-eluting stent could be a promising therapy for treatment of restenosis in humans.
Regression of Abdominal Aortic Aneurysms by Simultaneous Inhibition of Nuclear Factor κB and Ets in a Rabbit Model
Authors: Miyake Takashi , Aoki Motokuni , Masaki Hisao , Kawasaki Tomio , Oishi Masako , Kataoka Kazusaburo , Ogihara Toshio , Kaneda Yasufumi , Morishita Ryuichi
Published: September 2007

Because current therapy to treat abdominal aortic aneurysm (AAA), and particularly to manage small AAA, is limited to elective surgical repair, we explored less invasive molecular therapy by simultaneous inhibition of the transcription factors nuclear factor (NF)κB and ets using a decoy strategy. Both NFκB and ets were shown to be markedly activated in human AAA. In addition, NFκB- and ets-positive cells were increased in the aneurysm wall, and a part of the expression of NFκB and ets was detected in migrating macrophages. Thus, we used chimeric decoy oligodeoxynucleotides (ODNs) containing consensus sequences of both NFκB and ets binding sites to treat AAA. Inhibitory effects of chimeric decoy ODNs on matrix metalloproteinase-1 and -9 expression were confirmed by ex vivo experiments using a human aorta organ culture. To examine the regressive effect in a rabbit already-formed AAA model, transfection by wrapping a delivery sheet containing chimeric decoy ODNs around the aneurysm was performed 1 week after incubation with elastase. Importantly, treatment with chimeric decoy ODNs significantly decreased the size of AAA. Interestingly, significant preservation of elastic fibers was observed with chimeric decoy ODN treatment, accompanied by a reduction of matrix metalloproteinase-2 and -9 and induction of macrophage apoptosis. Regression of AAA was also associated with an increase in elastin and collagen type I and III synthesis in the aneurysm wall. Minimally invasive molecular therapy targeted to the inhibition of NFκB and ets is expected to be useful for AAA through the rebalance of matrix synthesis and degradation.
Systemic Deficiency of the MAP Kinase–Activated Protein Kinase 2 Reduces Atherosclerosis in Hypercholesterolemic Mice
Authors: Jagavelu Kumaravelu , Tietge Uwe J.F. , Gaestel Matthias , Drexler Helmut , Schieffer Bernhard , Bavendiek Udo
Published: September 2007

Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. A critical regulator of inflammatory processes represents the mitogen-activated protein kinase–activated protein kinase-2 (MK2). Therefore, we investigated the functional role of MK2 in atherogenesis in hypercholesterolemic mice as well as potentially underlying mechanisms in vivo and in vitro. Activation of MK2 (phospho-MK2) was predominantly detected in the endothelium and macrophage-rich plaque areas within aortas of hypercholesterolemic LDL receptor–deficient mice (
ldlr
−/−
). Systemic MK2 deficiency of hypercholesterolemic
ldlr
−/−
mice (
ldlr
−/−
/mk2
−/−
) significantly decreased the accumulation of lipids and macrophages in the aorta after feeding an atherogenic diet for 8 and 16 weeks despite a significant increase in proatherogenic plasma lipoproteins compared with
ldlr
−/−
mice. Deficiency of MK2 significantly decreased oxLDL-induced foam cell formation in vitro, diet-induced foam cell formation in vivo, and expression of scavenger receptor A in primary macrophages. In addition, systemic MK2 deficiency of hypercholesterolemic
ldlr
−/−
mice significantly decreased the aortic expression of the adhesion molecule VCAM-1 and the chemokine MCP-1, key mediators of macrophage recruitment into the vessel wall. Furthermore, silencing of MK2 in endothelial cells by siRNA reduced the IL-1β–induced expression of VCAM-1 and MCP-1. MK2 critically promotes atherogenesis by fostering foam cell formation and recruitment of monocytes/macrophages into the vessel wall. Therefore, MK2 might represent an attractive novel target for the treatment of atherosclerotic cardiovascular disease.
Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Authors: Ripplinger Crystal M. , Li Wenwen , Hadley Jennifer , Chen Junjie , Rothenberg Florence , Lombardi Raffaella , Wickline Samuel A. , Marian Ali J. , Efimov Igor R.
Published: September 2007

Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (β-myosin heavy chain–Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n=6) and wild-type (WT) rabbits (n=6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3±2.1 versus 7.4±2.3 V/cm;
P
=3.2e
−5
), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6±10.9° versus 79.2±7.8°;
P
=0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46±2.44% versus 2.68±0.77%;
P
=0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy.
High-Sensitivity C-Reactive Protein Is Independently Associated With Early Carotid Artery Progression in Women But Not in Men
Authors: Sander Kerstin , Schulze Horn Carla , Briesenick Claus , Sander Dirk
Published: September 2007

Background and Purpose—

High-sensitivity C-reactive protein (hsCRP) is known to be associated with atherosclerosis and cardiovascular events. Limited information exists regarding the importance of sex differences for the association between hsCRP and the progression of early stages of atherosclerosis. Therefore, we investigated the effect of hsCRP on early carotid atherosclerosis progression and major vascular risk factors in men and women.

Methods—

We analyzed the data of INVADE (intervention project on cerebrovascular diseases and dementia in the community of Ebersberg, Bavaria), a prospective, population-based study. In addition to common risk factors, measurements of carotid intima-media-thickness and hsCRP were performed at baseline and after 2 years.

Results—

Complete baseline data were available for 3387 subjects including 2001 women, and complete follow-up data were available for 2346 subjects. Within this study population, women were older and had higher systolic blood pressure and cholesterol levels. The prevalence of smoking and ischemic heart disease was more frequent in men. The baseline carotid intima-media-thickness was significantly higher in men compared with women (0.82 mm; 95% CI, 0.812 to 0.834 mm versus 0.77 mm; 95% CI, 0.763 to 0.779 mm;
P
<0.0001). Carotid intima-media-thickness progression after risk factor adjustment was significantly associated with hsCRP in women (
P
=0.006) but not in men (
P
=0.39).

Conclusions—

The association between hsCRP and progression of early carotid atherosclerosis shows sex differences. In further studies analyzing the role of inflammation for cardiovascular diseases and atherosclerosis, these sex differences should be considered.
Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure
Authors: Nakamura Taishi , Yamamoto Eiichiro , Kataoka Keiichiro , Yamashita Takuro , Tokutomi Yoshiko , Dong Yi-Fei , Matsuba Shinji , Ogawa Hisao , Kim-Mitsuyama Shokei
Published: September 2007

Background and Purpose—

Very recent subgroup analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events has shown that pioglitazone reduces the risk of recurrent stroke in type 2 diabetic patients. However, the underlying mechanism of stroke prevention by pioglitazone is unknown. Our aim was to examine the effect of pioglitazone on hypertension-based stroke in rats.

Methods—

Pioglitazone (1 mg · kg
−1
· d
−1
) was orally administered to stroke-prone spontaneously hypertensive rats (SHRSP) to examine the effect on incidental stroke, cerebrovascular injury, brain inflammation, oxidative stress, and vascular endothelial dysfunction induced by hypertension.

Results—

Treatment of SHRSP with pioglitazone for 4 weeks, without affecting blood pressure and blood glucose values, improved vascular endothelial dysfunction (
P
<0.05), suppressed remodeling of the middle cerebral artery (
P
<0.05) and brain microvessels (
P
<0.05), and inhibited brain macrophage infiltration (
P
<0.05) and the upregulation of brain monocyte chemoattractant protein-1 and tumor necrosis factor-α expression (
P
<0.01). Furthermore, pioglitazone treatment significantly delayed the onset of stroke signs and death in SHRSP (
P
<0.05). These beneficial effects of pioglitazone on cerebrovascular injury and stroke in SHRSP were associated with a reduction of brain and vascular superoxide via the inhibition of NADPH oxidase activity.

Conclusions—

Our work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress. These beneficial effects of pioglitazone were independent of blood pressure or blood sugar values. Thus, pioglitazone appears to be a potential therapeutic agent for stroke in type 2 diabetes with hypertension.
Direct Thrombin Inhibition and Stroke Prevention in Elderly Patients With Atrial Fibrillation
Authors: Ford Gary A. , Choy Anna Maria , Deedwania Prakash , Karalis Dean G. , Lindholm Carl-Johan , Pluta Wladyslaw , Frison Lars , Olsson S. Bertil
Published: September 2007

Background and Purpose—

Warfarin prevents stroke in atrial fibrillation (AF); however, concerns regarding international normalized ratio control and hemorrhage limit its use in the elderly. The oral direct thrombin inhibitors (DTIs) are potential alternatives to warfarin, offering fixed dosing without drug and dietary interactions and the need for international normalized ratio monitoring. Although ximelagatran, a DTI studied in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation trials, has been withdrawn, development of other DTIs continues. We report our experience in elderly high-risk AF patients on ximelagatran compared with warfarin therapy.

Methods—

Data from patients with AF and stroke risk factors randomized in Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation III and V trials to ximelagatran or warfarin were analyzed for stroke/systemic emboli, bleeding, and raised alanine aminotransferase levels in those ≥75 (n=2804) and <75 (n=4525) years.

Results—

Ximelagatran was as effective as warfarin in reducing stroke/systemic emboli in the elderly (2.23%/y with ximelagatran vs 2.27%/y with warfarin) as in younger patients (1.25%/y vs 1.28%/y). Total bleeds were significantly lower with ximelagatran compared with warfarin in elderly (40% vs 45%,
P
=0.01) and younger (27% vs 35%,
P
<0.001) patients. Raised alanine aminotransferase values (>3-fold elevation) among ximelagatran patients were more common in older (7.5% old vs 5.3% young) patients, particularly women (9.5% elderly women vs 6.1% elderly men).

Conclusions—

In high-risk elderly AF patients, ximelagatran is as effective as warfarin with less bleeding, but alanine aminotransferase elevations are common, particularly in elderly women. Oral DTIs for stroke prevention show promise in elderly patients.
Subcortical Hyperintensities Are Associated With Cognitive Decline in Patients With Mild Cognitive Impairment
Authors: Debette Stéphanie , Bombois Stéphanie , Bruandet Amélie , Delbeuck Xavier , Lepoittevin Samuel , Delmaire Christine , Leys Didier , Pasquier Florence
Published: September 2007

Background and Purpose—

It has been suggested that subcortical lesions may influence cognitive performances at early stages of cognitive impairment but not in late stages of dementia. We aimed to test whether cognitive decline is associated with subcortical hyperintensities in patients with mild cognitive impairment (MCI).

Methods—

We included 170 consecutive MCI patients (mean follow-up, 3.8±1.6 years). We assessed subcortical hyperintensities on a baseline magnetic resonance imaging scan with a semiquantitative rating scale. The mean annual cognitive decline was calculated with the Mini-Mental State Examination and the Dementia Rating Scale at baseline and the end of follow-up.

Results—

Compared with patients whose cognitive performances remained stable or improved during follow-up, patients whose cognitive performances declined often had a larger amount (greater than the median of the distribution) of periventricular (PVH) (
P
=0.0005) and white-matter (
P
=0.02) hyperintensities. The rate of cognitive decline was higher with increasing PVH: mean change in the Mini-Mental State Examination score=0.16 vs −0.66 points/year in patients with PVH in the first versus third tertile (
P
=0.0002). The rate of decline in executive functioning was also higher with increasing PVH: mean change in the Dementia Rating Scale initiation subscore=−0.05 vs −1.42 points/year in patients with PVH in the first versus third tertile (
P
=0.04). These associations were independent of vascular risk factors, temporal lobe atrophy, and MCI subtype and were stronger in patients with baseline executive dysfunction.

Conclusion—

White-matter hyperintensities and especially PVH were significantly associated with cognitive decline in MCI patients. This result was independent of the MCI subtype but stronger in cases of executive dysfunction at baseline.
Mixed Layer Instabilities and Restratification
Authors: Boccaletti Giulio , Ferrari Raffaele , Fox-Kemper Baylor
Published: September 2007

The restratification of the oceanic surface mixed layer that results from lateral gradients in the surface density field is studied. The lateral gradients are shown to be unstable to ageostrophic baroclinic instabilities and slump from the horizontal to the vertical. These instabilities, which are referred to as mixed layer instabilities (MLIs), differ from instabilities in the ocean interior because of the weak surface stratification. Spatial scales are O(1–10) km, and growth time scales are on the order of a day. Linear stability analysis and fully nonlinear simulations are used to study MLIs and their impact on mixed layer restratification. The main result is that MLIs are a leading-order process in the ML heat budget acting to constantly restratify the surface ocean. Climate and regional ocean models do not resolve the scales associated with MLIs and are likely to underestimate the rate of ML restratification and consequently suffer from a bias in sea surface temperatures and ML depths. In a forthcoming paper, the authors discuss a parameterization scheme to include the effect of MLIs in ocean models.
The Propagation Mechanism of a Vortex on the β Plane
Authors: van Leeuwen Peter Jan
Published: September 2007

The propagation velocity and propagation mechanism for vortices on a β plane are determined for a reduced-gravity model by integrating the momentum equations over the β plane. Isolated vortices, vortices in a background current, and initial vortex propagation from rest are studied. The propagation mechanism for isolated anticyclones as well as cyclones, which has been lacking up to now, is presented. It is shown that, to first order, the vortex moves to generate a Coriolis force on the mass anomaly of the vortex to compensate for the force on the vortex due to the variation of the Coriolis parameter. Only the mass anomaly of the vortex is of importance, because the Coriolis force due to the motion of the bulk of the layer moving with the vortex is almost fully compensated by the Coriolis force on the motion of the exterior flow. Because the mass anomaly of a cyclone is negative the force and acceleration have opposite sign. The role of dipolar structures in steadily moving vortices is discussed, and it is shown that their overall structure is fixed by the steady westward motion of the mass anomaly. Furthermore, it is shown that reduced-gravity vortices are not advected with a background flow. The reason for this behavior is that the background flow changes the ambient vorticity gradient such that the vortex obtains an extra self-propagation term that exactly cancels the advection by the background flow. Last, it is shown that a vortex initially at rest will accelerate equatorward first, after which a westward motion is generated. This result is independent of the sign of the vortex.
Fast Northward Energy Transfer in the Atlantic due to Agulhas Rings
Authors: van Sebille Erik , van Leeuwen Peter Jan
Published: September 2007

The adiabatic transit time of wave energy radiated by an Agulhas ring released in the South Atlantic Ocean to the North Atlantic Ocean is investigated in a two-layer ocean model. Of particular interest is the arrival time of baroclinic energy in the northern part of the Atlantic, because it is related to variations in the meridional overturning circulation. The influence of the Mid-Atlantic Ridge is also studied, because it allows for the conversion from barotropic to baroclinic wave energy and the generation of topographic waves. Barotropic energy from the ring is present in the northern part of the model basin within 10 days. From that time, the barotropic energy keeps rising to attain a maximum 500 days after initiation. This is independent of the presence or absence of a ridge in the model basin. Without a ridge in the model, the travel time of the baroclinic signal is 1300 days. This time is similar to the transit time of the ring from the eastern to the western coast of the model basin. In the presence of the ridge, the baroclinic signal arrives in the northern part of the model basin after approximately 10 days, which is the same time scale as that of the barotropic signal. It is apparent that the ridge can facilitate the energy conversion from barotropic to baroclinic waves and the slow baroclinic adjustment can be bypassed. The meridional overturning circulation, parameterized in two ways as either a purely barotropic or a purely baroclinic phenomenon, also responds after 1300 days. The ring temporarily increases the overturning strength. The presence of the ridge does not alter the time scales.
The Influence of Diapycnal Mixing on Quasi-Steady Overturning States in the Indian Ocean
Authors: Palmer Matthew D. , Garabato Alberto C. Naveira , Stark John D. , Hirschi Joël J-M. , Marotzke Jochem
Published: September 2007

A regional general circulation model (GCM) of the Indian Ocean is used to investigate the influence of prescribed diapycnal diffusivity (Kd) on quasi-steady states of the meridional overturning circulation (MOC). The model has open boundaries at 35°S and 123°E where velocity, temperature, and salinity are prescribed at each time step. The results suggest that quasi-steady overturning states in the Indian Ocean are reached on centennial time scales. The size and structure of the MOC are controlled by the distribution of Kd and the southern boundary conditions. The distribution of Kd required to support an overturning circulation in the model interior of a magnitude equal to that prescribed at the southern boundary is estimated using a 1D advection–diffusion balance in isopycnal layers. Implementing this approach, 70%–90% of the prescribed deep inflow can be supported in quasi-steady state. Thus one is able to address the systematic discrepancy between past estimates of the deep MOC based on hydrographic sections and those based on GCM results. However, the Kd values required to support a substantial MOC in the model are much larger than current observation-based estimates, particularly for the upper 3000 m. The two estimates of the flow field near 32°S used to force the southern boundary imply a highly nonuniform distribution of Kd, as do recent estimates of Kd based on hydrographic observations. This work highlights the need to improve and implement realistic estimates of (nonuniform) Kd in ocean and coupled ocean–atmosphere GCMs when investigating quasi-equilibrium model states.
Ocean and Atmosphere Storm Tracks: The Role of Eddy Vorticity Forcing
Authors: Williams Richard G. , Wilson Chris , Hughes Chris W.
Published: September 2007

Signatures of eddy variability and vorticity forcing are diagnosed in the atmosphere and ocean from weather center reanalysis and altimetric data broadly covering the same period, 1992–2002. In the atmosphere, there are localized regions of eddy variability referred to as storm tracks. At the entrance of the storm track the eddies grow, providing a downgradient heat flux and accelerating the mean flow eastward. At the exit and downstream of the storm track, the eddies decay and instead provide a westward acceleration. In the ocean, there are similar regions of enhanced eddy variability along the extension of midlatitude boundary currents and the Antarctic Circumpolar Current. Within these regions of high eddy kinetic energy, there are more localized signals of high Eady growth rate and downgradient eddy heat fluxes. As in the atmosphere, there are localized regions in the Southern Ocean where ocean eddies provide statistically significant vorticity forcing, which acts to accelerate the mean flow eastward, provide torques to shift the jet, or decelerate the mean flow. These regions of significant eddy vorticity forcing are often associated with gaps in the topography, suggesting that the ocean jets are being locally steered by topography. The eddy forcing may also act to assist in the separation of boundary currents, although the diagnostics of this study suggest that this contribution is relatively small when compared with the advection of planetary vorticity by the time-mean flow.
Group-Level Organizational Citizenship Behavior in the Education System: A Scale Reconstruction and Validation
Authors: Vigoda-Gadot Eran , Beeri Itai , Birman-Shemesh Taly , Somech Anit
Published: September 2007

Purpose: Most writings on Organizational Citizenship Behavior (OCB) to date have focused on analysis at the individual level and paid less attention to other analytical frameworks at the group level (i.e., team, unit, or organization). This article approaches OCB from the less conventional perspective of group-level activities and uses it to develop and validate a scale of Group-level Organizational Citizenship Behavior (GOCB) in the education system.

Data Collection: Data were collected from a survey of 206 Israeli teachers and their principals at 13 schools.

Findings: The scores were found to be statistically valid and demonstrated a high degree of reliability. In addition, two intra-factors (GOCB-I [group-level OCB toward individuals] and GOCB-O [group-level OCB toward the organization]) that are quite similar to those suggested in previous OCB literature emerged as key components.

Conclusions: The advantages of the group-level scale over other individual-level scales are explored and discussed in detail. The article ends with theoretical and practical implications for future studies that may focus on the “good platoon syndrome” of educational and other administrative systems rather than merely on the “good soldier syndrome.” The authors elaborate on the potential reconstruction of group-level measures of OCB that can enrich studies on organizational climate, culture, and social norms. Finally, the authors argue that their results as well as those suggested in previous research may direct future studies to develop the idea of “organizational citizenship climate” in the educational system and beyond.
Assessing Influence on the Field: An Analysis of Citations to Educational Administration Quarterly, 1979—2003
Authors: Haas Eric , Wilson Glen Yahola , Cobb Casey D. , Hyle Adrienne E. , Jordan Kitty , Kearney Kerri S.
Published: September 2007

Study Purpose: This article examines the influence of Educational Administration Quarterly (EAQ) on the scholarly literature in education during the 25-year period 1979 to 2003. This article continues part of the first critique of EAQ conducted by Roald Campbell in 1979.

Study Methods: Two citation measures are used in this study to assess EAQ influence: (a) citation frequency, the total citations counts to EAQ articles found in the Web of Science database and (b) the impact factor, a ratio of citations to articles published that is calculated as part of the Journal Citation Reports .

Study Findings: The findings point to three conclusions: (a) EAQ's substantive, ongoing influence on the scholarly education literature is limited to a small percentage of its published articles, which are cited predominantly by subsequent articles in EAQ; (b) this level of influence, though perhaps not the form, appears to be generally comparable to the level of other scholarly education journals with a solid academic reputation; and (c) EAQ appears to be statistically among the top tier of influential scholarly journals in education, but below the most influential. Overall, EAQ's influence on the scholarly education literature has improved since the first critique published in 1979.