bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Missing and Erroneous Genotypes on Tagging SNP Selection and Power of Subsequent Association Tests
Authors: Liu Wenlei , Zhao Wei , Chase Gary A.
Published: March 2006

Objective: Single nucleotide polymorphisms (SNPs) serve as effective markers for localizing disease susceptibility genes, but current genotyping technologies are inadequate for genotyping all available SNP markers in a typical linkage/association study. Much attention has recently been paid to methods for selecting the minimal informative subset of SNPs in identifying haplotypes, but there has been little investigation of the effect of missing or erroneous genotypes on the performance of these SNP selection algorithms and subsequent association tests using the selected tagging SNPs. The purpose of this study is to explore the effect of missing genotype or genotyping error on tagging SNP selection and subsequent single marker and haplotype association tests using the selected tagging SNPs. Methods: Through two sets of simulations, we evaluated the performance of three tagging SNP selection programs in the presence of missing or erroneous genotypes: Clayton’s diversity based program htstep, Carlson’s linkage disequilibrium (LD) based program ldSelect, and Stram’s coefficient of determination based program tagsnp.exe. Results: When randomly selected known loci were relabeled as ‘missing’, we found that the average number of tagging SNPs selected by all three algorithms changed very little and the power of subsequent single marker and haplotype association tests using the selected tagging SNPs remained close to the power of these tests in the absence of missing genotype. When random genotyping errors were introduced, we found that the average number of tagging SNPs selected by all three algorithms increased. In data sets simulated according to the haplotype frequecies in the CYP19 region, Stram’s program had larger increase than Carlson’s and Clayton’s programs. In data sets simulated under the coalescent model, Carlson’s program had the largest increase and Clayton’s program had the smallest increase. In both sets of simulations, with the presence of genotyping errors, the power of the haplotype tests from all three programs decreased quickly, but there was not much reduction in power of the single marker tests. Conclusions: Missing genotypes do not seem to have much impact on tagging SNP selection and subsequent single marker and haplotype association tests. In contrast, genotyping errors could have severe impact on tagging SNP selection and haplotype tests, but not on single marker tests.
Transcallosal Inhibition in Patients with and without Alexithymia
Authors: Richter Jan , Möller Bertram , Spitzer Carsten , Letzel Susanne , Bartols Susanne , Barnow Sven , Willert Carsten , Freyberger Harald Jürgen , Grabe Hans Jörgen
Published: March 2006

Objective: Previous results indicated a facilitated transcallosal inhibition via the corpus callosum (CC) in alexithymic male students. This study investigates transcallosal inhibition in alexithymic and nonalexithymic psychiatric inpatients. Method: Transcallosal inhibition was elicited by means of transcranial magnetic stimulation (TMS) of the primary motor cortex. Seven right-handed male and 12 female psychiatric patients with Toronto Alexithymia Scale (TAS-20) scores of ≧61 and 12 patients with TAS-20 scores of <51 were investigated. The transcallosal conduction time (TCT) reflects the TMS-induced inhibitory cortical activity that is mediated via the CC. Results: There was a significant effect of alexithymia on TCT (Wilks λ = 0.76; F = 4.1; d.f. = 2, 26; p = 0.027) indicating that alexithymic patients had shorter bidirectional TCTs than nonalexithymic patients. The in-between models showed a significant impact of alexithymia on both right to left TCT (F = 4.8; d.f. = 1; p = 0.038) and left to right TCT (F = 5.0; d.f. = 1; p = 0.033). Neither gender nor scores of depression (Montgomery-Asberg Depression Rating Scale) had any significant effects on TCT. Conclusion: Our results confirm and extend the previous findings of a facilitated, bidirectional transcallosal inhibition in alexithymia to male and female psychiatric inpatients. Facilitated transcallosal inhibition should be considered as a neurobiological correlate of alexithymia.
Changing Electrolyte and Acido-Basic Profile in HIV-Infected Patients in the HAART Era
Authors: Isnard Bagnis Corinne , Tezenas Du Montcel Sophie , Fonfrede Michele , Jaudon Marie Chantal , Thibault Vincent , Carcelain Guislaine , Valantin Marc Antoine , Izzedine Hassan , Servais Aude , Katlama Christine , Deray Gilbert
Published: March 2006

Background: HIV-infected patients may develop a variety of underreported metabolic abnormalities that may be classified into HIVAN, specific HIV abnormalities, coincidental renal disorders and anti-retroviral-treatment-induced side effects. Methods: Our descriptive cross-sectional study evaluates the prevalence of electrolyte and acid base disorders in HIV patients in the HAART era in a tertiary care teaching hospital. All consecutive HIV-infected patients (n = 1,232) presenting at our Department of Infectious Disease over 3 months were included. Measurements: All available biochemical data obtained at admission or on the day of the visit were analyzed. We identified risk factors for electrolyte and acid base disorders with univariate regression analysis and multivariate stepwise regression analysis. Variables tested for significance included age, sex, absolute CD4 and CD8 counts, hepatitis B and C antibodies, and use and type of anti-retroviral medication. Results: Most frequent and clinically relevant abnormalities were hyperuricemia in 41.3%, hypophosphatemia in 17.2% and low bicarbonate level in 13.6% of HIV-tested patients. Plasma magnesium was out of the normal range in 38.9% and blood glucose in 25.3% of the tested patients. When CD4 count was below 200/mm3, 9.2% of tested patients experienced low serum calcium (vs. 0.5% if CD4 count >200/mm3, p < 0.002), 11.4% increased creatinine plasma level (vs. 2.3% if CD4 count >200/mm3, p < 0.0001) and 24.5% low serum bicarbonate (vs. 13.7% if CD4 count >200/mm3, p < 0.0001). Protease inhibitor treatment was a significant risk factor of hyperuricemia (p < 0.003). Non-nucleoside reverse transcriptase inhibitor therapy was significantly associated with less hyperuricemia (OR = 0.6, 95% CI 0.38–0.96) and with hypophosphatemia (OR = 2.0, 95% CI 1.1–3.4). Conclusions: The profile of biochemical abnormalities in HIV-infected patients has changed, hyperuricemia and hypophosphatemia being the most prevalent. Causes are poorly understood. Interpretation of drug-induced side effects in the HIV patient is only meaningful if performed versus a control group of patients.
Subtle Immunodeficiency in Severe Asthma: IgA and IgG2 Correlate with Lung Function and Symptoms
Authors: Balzar Silvana , Strand Matthew , Nakano Takanari , Wenzel Sally E.
Published: March 2006

Background: Atopy, increased serum IgE and eosinophilic airway inflammation are common in asthma and may indicate aberrant immune responses, but the cause(s) are unknown. It was hypothesized that differences in serum immunoglobulins, immunoglobulin free light chains (FLC) and secretory IgA (sIgA) would exist between subjects with asthma of varying severity and normal subjects, and the levels would correlate with lung function, symptoms and airway inflammation. Methods: Serum IgG, IgA, IgE and IgM, IgG subclasses and FLC, and bronchoalveolar lavage sIgA were evaluated from 15 normal subjects, 9 mild and 22 severe asthmatics with similar atopic status. Asthma symptoms were obtained by questionnaire, and airway inflammation was assessed by immunostaining for five inflammatory cell types. Results: Immunoglobulin levels in all groups were generally within the normal range. However, IgA and IgG were lower in severe asthmatics than normal subjects (overall p = 0.006 and 0.02, respectively). IgA, but not IgG, correlated with lung function and asthma symptoms (r-values >0.58; p-values <0.009). Although similar among the groups, higher sIgA and IgG2 also positively correlated with lung function and negatively with asthma symptoms (r-values >0.63; p-values <0.009). IgA and IgG/IgG1 positively correlated with tissue mast cells. Conclusions: Subtle alterations in IgA- and IgG2-mediated responses in asthma may be disease-related. As their levels are generally normal, it is possible that the quality/repertoire of immune protection provided by these isotypes, perhaps against carbohydrate epitopes, may be altered in asthma.
Serum Adiponectin Levels Increase after Human Chorionic Gonadotropin Treatment during in vitro Fertilization
Authors: Liu Yung-Hsien , Tsai Eing-Mei , Chen Yi-Ling , Chen Hung-Sheng , Chen Yu-Chieh , Wu Lee-Chen , Lee Chien-Hung , Jong Shiang-Bin , Chan Te-Fu
Published: March 2006

Aims: To determine whether or not serum adiponectin concentrations are influenced by ovarian hyperstimulation during in vitro fertilization (IVF). Methods: This study involved 52 women who were participating in IVF-ET cycles. Adiponectin levels in serum were determined by radioimmunoassay and compared. Results: Serum adiponectin levels fell from Day-basal to Day-hCG (p = 0.047), and then rose on Day-OR and again on Day-7ET (p < 0.001; p < 0.001). Estradiol levels on Day-hCG were significantly and positively correlated with serum adiponectin levels on Day-OR and Day-7ET (r = 0.325, p = 0.019; r = 0.372, p = 0.007). Progesterone levels on Day-OR positively correlated with serum adiponectin levels on Day-basal (r = 0.278, p = 0.046). There was also a positive correlation between progesterone levels on Day-7ET and serum adiponectin levels on Day-OR (r = 0.289, p = 0.038). Multiple linear regression analysis revealed that adiponectin levels on Day-OR and Day-7ET were negatively correlated with age and body mass index after adjustment was made for concomitant diseases. Conclusions: To sum up, following gonadotropin treatment, serum adiponectin levels decrease as a result of the negative effect of high estradiol levels on adiponectin production. Conversely, serum adiponectin levels increase following human chorionic gonadotropin treatment.
The Predictive Value of C-Reactive Protein in End-Stage Renal Disease: Is It Clinically Significant?
Authors: van der Sande Frank M. , Kooman Jeroen P. , Leunissen Karel M.L.
Published: March 2006

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Besides traditional risk factors, disturbances in mineral and bone metabolism and inflammation are thought to be responsible for the increased risk of death. In the last years C-reactive protein (CRP) has gained a lot of attention in the general population, especially with regard to its link with atherosclerosis. Although several studies suggest that CRP may be useful as a parameter in predicting future cardiovascular events in both the general population and in patients with end-stage renal disease, there is doubt about the clinical evidence of this assumption. A statistical association between CRP and cardiovascular disease was observed in various studies, but the predictive power of this association is markedly diminished when adjusted for other risk factors. The relative contributions of CRP as a marker, as a causative agent, or as a consequence of atherosclerotic vascular disease are unclear, both in the general population and in the dialysis population. The CRP levels are highly variable and influenced by intercurrent events in dialysis patients. In dialysis patients, it is possible to reduce the CRP levels by statins, although these agents do not reduce the cardiovascular mortality in diabetic dialysis patients.
A Population-Based Assessment of the Familial Component of Chronic Kidney Disease Mortality
Authors: Goldfarb-Rumyantzev Alexander S. , Cheung Alfred K. , Habib Arsalan N. , Wang Ben-Jr , Lin Shih-jui , Baird Bradley C. , Naiman Natalie , Cannon-Albright Lisa
Published: March 2006

Background/Aim: While the familial nature of chronic kidney disease (CKD) has been recognized, it has primarily been defined from studies of first-degree relatives of selected sets of cases. The goal of this study is an evaluation of the familial clustering of end-stage renal disease (ESRD) and CKD mortality using a population-based genealogy of Utah. This is the first population-based analysis of the familial component of ESRD and non-ESRD CKD. Methods: We have defined two distinct patient groups for this analysis, using individuals with death certificates in the Utah Population Database indicating ESRD (n = 192) and non-ESRD CKD (n = 335) as the cause of death. Two measures of familiality were used: (1) relative risk (RR) of CKD or ESRD death in relatives of cases and (2) an average relatedness statistic, i.e., the Genealogical Index of Familiality. Results: The RR for dying with ESRD among the first-degree relatives of individuals dying with ESRD is estimated to be 10.1 (p = 0.0007, 95% confidence interval CI 2.76–25.95), but is not significantly elevated among second-degree relatives. The RR for dying with non-ESRD CKD among first- and second-degree relatives of individuals dying with non-ESRD CKD was 3.89 (p = 0.0051, 95% CI 1.43–8.46) and 3.11 (p = 0.04, 95% CI 0.85–7.95), respectively. The Genealogical Index of Familiality statistic demonstrated that the individuals dying with ESRD are significantly more related than expected in this population (p = 0.013); significant excess relatedness was also observed for individuals dying with non-ESRD CKD (p = 0.006), suggesting a familial component for both, with evidence for common environmental and genetic effects. Conclusion: The results of this analysis of individuals dying with ESRD and non-ESRD CKD supports a significant and independent familial component to both conditions, suggesting a heritable factor playing a role.
Effects of Lazaroid U-74389G on Acute Necrotizing Pancreatitis in Rats
Authors: Alhan E. , Türkyılmaz S. , Erçin C. , Kural B.V.
Published: March 2006

The aim of this study was to investigate the influence of U-74389G on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in mortality rate, pancreatic necrosis, and serum levels of amylase, alanine aminotransferase, interleukin-6, tumor necrosis factor alpha, and urea, in lactate dehydrogenase levels in bronchoalveolar lavage fluid, and in the activities of myeloperoxidase and malondialdehyde in pancreas and lung tissue; a significant decrease was observed in serum calcium levels, blood pressure, urine output, and pO2. The use of U-74389G inhibited the changes in serum urea, pO2, and tissue levels of myeloperoxidase and malondialdehyde in pancreas and lungs. Moreover, it indicated a limited effect on the course of ANP in the rats and did not reduce mortality and pancreatic damage. Therefore, it may be used in the treatment of lung injury during acute pancreatitis.
Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts via Formyl-Peptide Receptors
Authors: Tjabringa G. Sandra , Ninaber Dennis K. , Drijfhout Jan Wouter , Rabe Klaus F. , Hiemstra Pieter S.
Published: March 2006

Background: Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by the presence of eosinophils and neutrophils. However, the mechanisms that mediate the influx of these cells are incompletely understood. Neutrophil products, including neutrophil elastase and antimicrobial peptides such as neutrophil defensins and LL-37, have been demonstrated to display chemotactic activity towards cells from both innate and adaptive immunity. However, chemotactic activity of LL-37 towards eosinophils has not been reported. Therefore, the aim of the present study was to investigate the chemotactic activity of LL-37 for eosinophils and to explore the mechanisms involved in LL-37-mediated attraction of neutrophils and eosinophils. Methods: Neutrophils and eosinophils were obtained from venous blood of healthy donors. Chemotaxis was studied using a modified Boyden chamber technique. Involvement of formyl-peptide receptors (FPRs) was studied using the antagonistic peptide tBoc-MLP. Activation of the mitogen-activated protein kinase (MAPK) ERK1/2 was studied by Western blotting using antibodies directed against phosphorylated ERK1/2. Results: Our results show that LL-37 chemoattracts both eosinophils and neutrophils. The FPR antagonistic peptide tBoc-MLP inhibited LL-37-induced chemotaxis. Whereas the FPR agonist fMLP activated ERK1/2 in neutrophils, LL-37 did not, indicating that fMLP and LL-37 deliver different signals through FPRs. Conclusions: LL-37 displays chemotactic activity for eosinophils and neutrophils, and this activity is mediated via an FPR. These results suggest that LL-37 may play a role in inflammatory lung diseases such as asthma and COPD.
Epilepsy and Obstructive Sleep Apnea
Authors: Höllinger Peter , Khatami Ramin , Gugger Matthias , Hess Christian W. , Bassetti Claudio L.
Published: March 2006

A few publications documented the coexistence of epilepsy and obstructive sleep apnea (OSA). The extent, nature, and clinical relevance of this association remain poorly understood. We retrospectively reviewed the database of our sleep center to identify patients with both sleep apnea and epilepsy. Characteristics of epilepsy, sleep history, presence of excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)] and polysomnographic data were assessed. The effect of continuous positive airway pressure (CPAP) on seizure reduction was prospectively analyzed after a median interval of 26 months (range: 2–116 months) from the diagnosis of OSA. OSA was found in 29 epilepsy patients (25 men and 4 women) with a median age of 56 years (range: 37–79). The median apnea hypopnea index was 33 (range: 10–85), the oxygen desaturation index was 12 (range 0–92), and 52% of the patients had an ESS score >10. In 27 patients, epilepsy appeared 1 month to 44 years prior to the diagnosis of OSA. In 21 patients, the appearance of OSA symptoms coincided with a clear increase in seizure frequency or the first appearance of a status epilepticus. Treatment with CPAP was continued with good compliance in 12 patients and led to a significant reduction of both ESS scores and seizure frequency in 4 patients. Our data suggest the importance of considering diagnosis and treatment of OSA in epilepsy patients with poor seizure control and/or reappearance of seizures after a seizure-free interval.
The Retina of Tyrant Flycatchers: Topographic Organization of Neuronal Density and Size in the Ganglion Cell Layer of the Great Kiskadee Pitangus sulphuratus and the Rusty Margined Flycatcher Myiozetetes cayanensis (Aves: Tyrannidae)
Authors: Coimbra João Paulo , Marceliano Maria Luiza Videira , Andrade-da-Costa Belmira Lara da Silveira , Yamada Elizabeth Sumi
Published: March 2006

Tyrant flycatchers comprise the largest group of passerine birds of the Neotropical region but their retinal organization is unknown. The great kiskadee, Pitangus sulphuratus, is categorized as a supreme generalist and utilizes a variety of foraging strategies. The rusty margined flycatcher, Myiozetetes cayanensis, is partially frugivorous and captures insects in the air. Using retinal wholemounts, we described the topographic distribution of density and size of neurons lying in the retinal ganglion cell layer in those two species of tyrant flycatchers. Maps of neuron distribution showing isodensity contours revealed the presence of a pronounced central fovea and a temporal area in both species. Both retinal specializations were circumscribed by an inconspicuous horizontal visual streak. The highest foveal densities ranged from 48,000 to 55,000 cells/mm2 for Pitangus sulphuratus and between 62,000 and 65,000 cells/mm2 for Myiozetetes cayanensis. The peak density in the temporal area was around 40,000 cells/mm2 for Pitangus sulphuratus and 46,000 cells/mm2 for Myiozetetes cayanensis. At central, mid-peripheral and peripheral eccentricities, perikaryon size varied quite similarly in both species. A cohort of giant retinal ganglion cells with perikaryon size > 300 µm2 was observed at the temporal periphery and defines an ‘area giganto cellularis’ described previously in procellariiform seabirds. This specialization is thought to be involved in movement detection and could aid the tyrant flycatchers to capture moving prey. Functionally, the presence of a fovea associated with a temporal area would allow high spatial resolution for capturing insects by the tyrant flycatchers. Nonetheless, even though both species exhibit different foraging strategies, they shared a similar topographic arrangement of neuronal density in the ganglion cell layer. This suggests that the retinal topography did not accompany changes in the foraging ecology throughout evolutionary history for these species of tyrant flycatchers.
Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia
Authors: Junyent Mireia , Cofán Montserrat , Núñez Isabel , Gilabert Rosa , Zambón Daniel , Ros Emilio
Published: March 2006

Objective—

The effect of risk factors on carotid atherosclerosis in heterozygous familial hypercholesterolemia (FH) is unclear. We evaluated carotid intima-media thickness (IMT) by sonography in relation to classical and emergent risk factors in a large FH cohort.

Methods and Results—

Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged ≥25 years fulfilling strict diagnostic criteria for clinical FH who were either undertreated or treatment-naive. Conventional risk factors, but not lipoprotein(a), homocysteine, or apolipoprotein E (apoE) genotypes were univariately related to IMT. Age-adjusted and gender-adjusted IMT increased with increasing low-density lipoprotein (LDL) cholesterol and decreased with increasing high-density lipoprotein (HDL) cholesterol. Compared with a total cholesterol/HDL ratio >5.0, a ratio ≤5.0 was associated with a lower adjusted IMT, with a mean difference of −0. 09 mm (95% confidence interval, −0.13 to −0.04). By multivariate analysis, age, HDL cholesterol (negatively), physical exercise, family history of early-onset coronary heart disease, LDL cholesterol, and leukocyte count, in this order, were independent associations of IMT (r
2
=0.429,
P
<0.001).

Conclusions—

Traditional risk factors account for a sizeable proportion of variation in carotid IMT in FH. Because the HDL cholesterol level and the total cholesterol/HDL ratio are strong predictors of preclinical carotid atherosclerosis, HDL cholesterol-raising strategies should have an important therapeutic role in FH.
Apelin Stimulates Myosin Light Chain Phosphorylation in Vascular Smooth Muscle Cells
Authors: Hashimoto Tatsuo , Kihara Minoru , Ishida Junji , Imai Nozomi , Yoshida Shin-ichiro , Toya Yoshiyuki , Fukamizu Akiyoshi , Kitamura Hitoshi , Umemura Satoshi
Published: March 2006

Objective—

Physiological roles of apelin and its specific receptor APJ signaling were investigated in vascular smooth muscle cells (VSMCs). The present study determined whether apelin activates myosin light chain (MLC), a major regulatory event in initiating smooth muscle contraction.

Methods and Results—

To assess MLC activation, we performed Western blot and immunohistochemical studies using an antibody against the phospho-MLC. In VSMCs, apelin induces the phosphorylation of MLC in a concentration-dependent manner with a peak at 2 minutes. Pretreatment of VSMCs with pertussis toxin abolishes the apelin-induced phosphorylation of MLC. Inhibition of protein kinase C (PKC) with GF-109203X markedly attenuated the apelin-induced MLC phosphorylation. In addition, methylisobutyl amiloride, a specific inhibitor of the Na
+
/H
+
exchanger (NHE), and KB-R7943, a potent inhibitor for the reverse mode of the Na
+
/Ca
2+
exchanger (NCX), significantly suppressed the action of apelin. In wild-type mice, apelin phosphorylates MLC in vascular tissue, whereas it had no response in APJ-deficient mice by Western blot and immunohistochemistry. Apelin-induced phosphorylation of MLC was accompanied with myosin phosphatase target subunit phosphorylation.

Conclusions—

These results provide the first evidence to our knowledge for apelin-mediated MLC phosphorylation in vitro and in vivo, which is a potential mechanism of apelin-mediated vasoconstriction.
Activation of Peroxisome Proliferator-Activated Receptor γ Suppresses Telomerase Activity in Vascular Smooth Muscle Cells
Authors: Ogawa Daisuke , Nomiyama Takashi , Nakamachi Takafumi , Heywood Elizabeth B. , Stone Jeffrey F. , Berger Joel P. , Law Ronald E. , Bruemmer Dennis
Published: March 2006

Activation of the peroxisome proliferator-activated receptor (PPAR) γ, the molecular target for insulin sensitizing thiazolidinediones used in patients with type 2 diabetes, inhibits vascular smooth muscle cell (VSMC) proliferation and prevents atherosclerosis and neointima formation. Emerging evidence indicates that telomerase controls key cellular functions including replicative lifespan, differentiation, and cell proliferation. In the present study, we demonstrate that ligand-induced and constitutive PPARγ activation inhibits telomerase activity in VSMCs. Telomerase reverse transcriptase (TERT) confers the catalytic activity of telomerase, and PPARγ ligands inhibit TERT expression through a receptor-dependent suppression of the TERT promoter. 5′-deletion analysis, site-directed mutagenesis, and transactivation studies using overexpression of Ets-1 revealed that suppression of TERT transcription by PPARγ is mediated through negative cross-talk with Ets-1–dependent transactivation of the TERT promoter. Chromatin immunoprecipitation assays further demonstrated that PPARγ ligands inhibit Ets-1 binding to the TERT promoter, which is mediated at least in part through an inhibition of Ets-1 expression by PPARγ ligands. In VSMCs overexpressing TERT, the efficacy of PPARγ ligands to inhibit cell proliferation is lost, indicating that TERT constitutes an important molecular target for the antiproliferative effects of PPARγ ligands. Finally, we demonstrate that telomerase activation during the proliferative response after vascular injury is effectively inhibited by PPARγ ligands. These findings provide a previously unrecognized mechanism for the antiproliferative effects of PPARγ ligands and support the concept that PPARγ ligands may constitute a novel therapeutic approach for the treatment of proliferative cardiovascular diseases.
Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function
Authors: Dawn Buddhadeb , Guo Yiru , Rezazadeh Arash , Huang Yiming , Stein Adam B. , Hunt Greg , Tiwari Sumit , Varma Jai , Gu Yan , Prabhu Sumanth D. , Kajstura Jan , Anversa Piero , Ildstad Suzanne T. , Bolli Roberto
Published: March 2006

We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL– and G-CSF+SCF–treated but not in G-CSF–treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF–treated mice. G-CSF+FL therapy mobilized bone marrow–derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective
.
Hypercholesterolemia Suppresses Inwardly Rectifying K
+
Channels in Aortic Endothelium In Vitro and In Vivo
Authors: Fang Yun , Mohler Emile R. , Hsieh Esther , Osman Hashim , Hashemi Seyed M. , Davies Peter F. , Rothblat George H. , Wilensky Robert L. , Levitan Irena
Published: March 2006

Inwardly rectifying K
+
(Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia in vivo. Specifically, exposing human aortic endothelial cells to acetylated low-density lipoprotein or very low density lipoprotein resulted in a time- and concentration-dependent decrease in Kir current that correlated with the degree of cholesterol loading. The suppression was fully reversible by cholesterol depletion. Furthermore, a decrease in Kir current resulted in depolarization of endothelial membrane potential. Most important, the flow sensitivity of Kir currents was also impaired by cholesterol loading. Specifically, flow-induced increase in Kir current was suppressed by 70%, and flow-induced hyperpolarization was almost completely abrogated. Furthermore, we show that hypercholesterolemia in vivo also strongly suppresses endothelial Kir currents and causes a shift in endothelial membrane potential, as determined by comparing the currents in aortic endothelial cells freshly isolated from healthy or hypercholesterolemic pigs. Therefore, we suggest that suppression of Kir current is one of the important factors in hypercholesterolemia-induced endothelial dysfunction.
Myocardin Induces Cardiomyocyte Hypertrophy
Authors: Xing Weibing , Zhang Tong-Cun , Cao Dongsun , Wang Zhigao , Antos Christopher L. , Li Shijie , Wang Yibin , Olson Eric N. , Wang Da-Zhi
Published: March 2006

In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly of sarcomeres, and cellular enlargement. We show that hypertrophic signals stimulate the expression and transcriptional activity of myocardin, a cardiac and smooth muscle–specific coactivator of serum response factor (SRF). Consistent with a role for myocardin as a transducer of hypertrophic signals, forced expression of myocardin in cardiomyocytes is sufficient to substitute for hypertrophic signals and induce cardiomyocyte hypertrophy and the fetal cardiac gene program. Conversely, a dominant-negative mutant form of myocardin, which retains the ability to associate with SRF but is defective in transcriptional activation, blocks cardiomyocyte hypertrophy induced by hypertrophic agonists such as phenylephrine and leukemia inhibitory factor. Myocardin-dependent hypertrophy can also be partially repressed by histone deacetylase 5, a transcriptional repressor of myocardin. These findings identify myocardin as a nuclear effector of hypertrophic signaling pathways that couples stress signals to a transcriptional program for postnatal cardiac growth and remodeling.
Angiotensin II and Stretch Activate NADPH Oxidase to Destabilize Cardiac Kv4.3 Channel mRNA
Authors: Zhou Chaoming , Ziegler Chandra , Birder Lori A. , Stewart Alexandre F.R. , Levitan Edwin S.
Published: March 2006

Pathological and physiological hypertrophy of the heart is associated with decreased expression of the Kv4.3 transient outward current (
I
to
) channel. The downregulation of channel mRNA and protein, which may be proarrhythmic, is recapitulated with cultured neonatal rat ventricular myocytes treated with angiotensin II (Ang II). Here we show that the 4.9 kb 3′ untranslated region (3′ UTR) of the Kv4.3 channel transcript confers Ang II sensitivity to a promoter-reporter construct. In contrast, Kv4.2 and Kv1.5 3′-UTR sequences are insensitive to Ang II. Both Kv4.3 3′-UTR reporter mRNA and activity are decreased in Ang II–treated cardiac myocytes, in accordance with a decrease in mRNA stability. This regulation is mediated by Ang II type 1 (AT
1
) receptors and abolished by NADPH oxidase inhibitors and dominant negative rac. The Ang II effect is also blocked by expression of superoxide dismutase (SOD), but not catalase, showing that superoxide is required. Dominant negative subunits, enzyme inhibitors and hydrogen peroxide experiments show that the apoptosis signal-regulating kinase 1 (ASK1)–p38 kinase pathway mediates downstream signaling from NADPH oxidase. Mechanical stretch also downregulates Kv4.3 3′-UTR reporter activity and this requires AT
1
receptors and NADPH oxidase. Thus, activation of AT
1
receptors by Ang II or stretch specifically destabilizes cardiac myocyte Kv4.3 channel mRNA by activating NADPH oxidase. These results link long-term control of cardiac K
+
channel gene expression to a physiological reactive oxygen species signaling pathway.
Comparison of Ischemic Lesion Evolution in Embolic Versus Mechanical Middle Cerebral Artery Occlusion in Sprague Dawley Rats Using Diffusion and Perfusion Imaging
Authors: Henninger Nils , Sicard Kenneth M. , Schmidt Karl F. , Bardutzky Jürgen , Fisher Marc
Published: March 2006

Background and Purpose—

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague Dawley rats after permanent suture MCAO (sMCAO; n=8) and embolic MCAO (eMCAO; n=8).

Methods—

Serial measurements of quantitative cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed up to 180 minutes after MCAO. ADC and CBF values within 5 different brain regions were analyzed. ADC and CBF lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO.

Results—

Compared with sMCAO animals, the threshold-derived CBF lesion volume was significantly larger in eMCAO at all time points (
P
<0.01), remained relatively constant over time, and was highly correlated with the 2,3,5-triphenyltetrazolium chloride–defined infarct size. The ADC lesion volume did not differ between models at any time point. A diffusion/perfusion mismatch was present significantly longer in eMCAO animals (
P
<0.05), and these rats demonstrated larger absolute mismatch volumes that were statistically significant at 30, 60, and 90 minutes (
P
<0.05). In both models, CBF and ADC declines were highly correlated.

Conclusion—

This study demonstrated substantial differences in acute ischemic lesion evolution between the eMCAO and sMCAO models.
Evidence for Involvement of Both IK
Ca
and SK
Ca
Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery
Authors: McNeish Alister J. , Sandow Shaun L. , Neylon Craig B. , Chen Mark X. , Dora Kim A. , Garland Christopher J.
Published: March 2006

Background and Purpose—

Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IK
Ca
channels alone, contrasting with peripheral vessels where block of both IK
Ca
and SK
Ca
is required. As the contribution of IK
Ca
and SK
Ca
to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SK
Ca
might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions.

Methods—

Rat middle cerebral arteries (≈175 μm) were mounted in a wire myograph. The effect of K
Ca
channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 μmol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial K
Ca
channels revealed with immunohistochemistry.

Results—

SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IK
Ca
(TRAM-34, 1 μmol/L) or SK
Ca
(apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SK
Ca
and IK
Ca
within the endothelium.

Conclusions—

In the absence of NO, IK
Ca
underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SK
Ca
contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SK
Ca
expression may be altered.
Hyperbaric Oxygen Suppresses NADPH Oxidase in a Rat Subarachnoid Hemorrhage Model
Authors: Ostrowski Robert P. , Tang Jiping , Zhang John H.
Published: March 2006

Background and Purpose—

One of the major contributors to brain injury after subarachnoid hemorrhage (SAH) is oxidative stress, and 1 of the major enzymatic sources of superoxide anion production in the brain is NADPH oxidase. Therefore, we studied whether hyperbaric oxygen (HBO) suppresses neuronal NADPH oxidase in a rat model of SAH.

Methods—

Eighty-three Sprague-Dawley male rats were assigned to sham, SAH, and SAH treated with HBO groups. SAH was induced by endovascular perforation. HBO (2.8 atmospheres absolutes for 2 hours) was started at 1 hour after perforation. Rats were euthanized at 6 or 24 hours, and brains were collected for histology, biochemistry, and molecular biology studies including NADPH oxidase activity, gp91
phox
mRNA expression, and lipid peroxidation assays. Mortality and neurological scores were evaluated.

Results—

We observed an increased neuronal immunoreactivity of gp91
phox
at 24 hours after SAH. The upregulation of gp91
phox
mRNA was associated with increased oxidative stress. HBO decreased NADPH oxidase expression, activity, and the level of oxidative stress at 24 hours after SAH. HBO reduced neuronal injury and improved functional performance throughout the observation period.

Conclusion—

HBO suppresses NADPH oxidase and oxidative stress in cerebral tissues at 24 hours after SAH.
Leaving Children Behind: How "Texas-Style" Accountability Fails Latino Youth
Authors: Maxcy Brendan D.
Published: March 2006

Background: Leaving Children Behind: How “Texas-Style” Accountability Fails Latino Youth, edited by Angela Valenzuela, presents federal-, state-, district-, and school-level research on the effects of performance accountability systems featuring high-stakes testing on Latina/Latino students. Drawing on empirical work from studies in Texas and California, the authors argue forcefully that the state policy systems purported to eliminate longstanding inequities in educational services provided poor and minority students are instead creating perverse incentives that exacerbate the achievement gap for language minority students and others.

Purpose: In this book review and policy commentary, the reviewer examines the evidence provided in various chapters, offering an array of perspectives on the policy, politics, and effects on practice of what the authors term “Texas-style accountability.”

Analysis and Findings: Reconsidering the portrayal of this type of system as a Texas phenomenon foisted on the nation through the No Child Left Behind legislation, performance accountability is situated in a broader public-sector reform movement, termed New Public Management (NPM) by Hood (1991).

Conclusions: The reviewer suggests that Leaving Children Behind is important reading for practicing administrators, those who prepare them, and those who make and research educational policy.
The Influence of School Social Composition on Teachers’ Collective Efficacy Beliefs
Authors: Goddard Roger D. , Skrla Linda
Published: March 2006

Purpose: The purpose of this study was to determine how school social composition is related to perceived collective efficacy. Several hypotheses tested in this research were derived from social cognitive theory and based on the extant literature.

Participants: Data were drawn from 1,981 teachers in 41 K-8 schools in a diverse urban school district in the southwestern United States.

Findings: The results of two-level hierarchical linear models indicated that a school’s past academic achievement, rate of special program placement for gifted children, and faculty ethnic composition explained 46% of the variation among schools in perceived collective efficacy. The article also reports a much smaller but statistically significant relationship between collective efficacy beliefs and teacher race and experience. Teachers of color and those with more than 10 years experience reported slightly higher levels of perceived collective efficacy.

Conclusions: The article concludes with a discussion of the theoretical and practical implications of these findings.
A New Method for Predicting the Fatigue Life of Fiber-reinforced Plastic Laminates
Authors: Momenkhani Kourosh , Sarkani Shahram
Published: March 2006

This article introduces a new methodology for predicting the fatigue life of fiber-reinforced plastic (FRP) laminates at various stress levels. This method is based on the evolution of the center of gravity (CG) of the hysteresis loops (HL), and is termed the CG method. The CG method provides precise information regarding the fatigue behavior and damage situation within FRPs, offering highly accurate predictability of fatigue failure. Furthermore, the CG method can be constructed by tests performed on only one specimen by utilizing a new periodic function that represents the response of FRP specimens under dynamic loading fatigue tests - either in displacement control mode or load control mode. The authors originated the CG method in (Momenkhani, K. (2003). Using Geometric Properties of Hysteresis Loops for Predicting Fatigue Damage Accumulation in Fiber Reinforced Plastic Laminates, Doctoral Dissertation, The George Washington University, pp. 49-130), and published it in (Momenkhani, K., Sarkani, S. and Jones, D.L. (2005). Development and Application of a Model Using Center of Gravity of Hysteresis Loops to Predict Fatigue Damage Accumulation in Fiber Reinforced Plastic Laminates, Journal of Composite Materials, 39(6): 557-575). The present article applies the CG method as an alternative model to replace and supersede S-N curve methods for fatigue life predictions of FRPs.
Effect of Hygrothermal History on Water and Mechanical Properties of Glass/Vinylester Composites
Authors: De La Osa O. , Alvarez V. , Avazquez A
Published: March 2006

The effects of hygrothermal aging on the mechanical and viscoelastic properties of vinylester (VE)/unidirectional glass-fiber composites are reported. The studies are done by means of a dynamometer (INSTRON) and a dynamic mechanical thermal analyzer (Perkin Elmer). The studies are carried out at three different temperatures: 20, 40, and 60 C. The adhesion between the fibers and matrix is studied by scanning electron microscopy (SEM) microphotographs. Flexural strength, flexural modulus, storage modulus in the glass state (Tg - 50 K), in rubber state (Tg + 50 K), and the glass transition temperatures are also investigated. These parameters are determined in the case of the matrix and composites materials, for the initial and final states. The diffusion coefficients are calculated by using the simplest Fick's equation.
Discrete Cohesive Zone Model to Simulate Static Fracture in 2D Triaxially Braided Carbon Fiber Composites
Authors: Xie De , Salvi Amit G. , Sun Ce , Waas Anthony M. , Caliskan Ari
Published: March 2006

A discrete cohesive zone model (DCZM) is implemented to simulate the mode I fracture of two dimensional triaxially braided carbon (2DTBC) fiber composites. The 2DTBC is modeled as an elastic-one-parameter (a66) plastic continuum. The plastic behavior of the 2DTBC was characterized by measuring a66. Mode I fracture tests are carried out by using a modified single edge notch bend (SENB) configuration. Fracture toughness (GIC) as a function of crack extension is measured by a compliance approach. The fracture tests are then simulated by using the DCZM based interface element in conjunction with the commercial software ABAQUS® through a user subroutine UEL. The simulated results, carried out under conditions of plane stress, are compared with the experimental results and also verified for mesh sensitivity. The results presented provide guidelines and a basic understanding to model structural response of non-homogeneous materials, incorporating fracture as a damage mechanism and using constituent level material properties, geometry, and fracture toughness (GIC) as input.
Parametric Optmisation of Pin-assisted-melt Impregnation of Glass Fiber/Polypropylene by Taguchi Method
Authors: Xian Guijun , Pu Hong-Ting , Yi Xiao-Su , Pan Yi
Published: March 2006

A continuous glass fiber (GF) roving reinforced polypropylene (PP) tape is prepared with a pin-assisted-melt impregnation set-up. This study originally applied the Taguchi method to statistically assess the effect of selected impregnation parameters on the impregnation process, and to optimize the parameters to realize a high quality impregnated tape. The quality of the impregnated tape is characterized by the degree of impregnation, ratio of the impregnated fiber number to the total fiber number. According to the Taguchi method, impregnation experiments are designed and the experimental results are analyzed. An optimal parameter combination is determined, which led to a degree of impregnation more than 94%. Analysis of variance (ANOVA) was performed on the measured data and S/N (signal to noise) ratios. The results indicated that pulling speed, melt temperature, and the number of impregnation pins are the significant factors in a declining sequence affecting the impregnation process.
Testing and Evaluation of Rubber-base Composites Reinforced with Silica Sand
Authors: Jalham Issam S. , Maita Ibrahim J.
Published: March 2006

In this study, natural rubber (NR) was reinforced with the unique composition of Jordanian silica sand at different loadings (10, 30, 50, and 75 pphr) and different particle sizes (10, 25, 45, and 75 μm). Several tests, such as hardness, tensile strength, elongation at break, compression set, compression stress-strain, and density are conducted to evaluate this composite according to the international standards. The results showed that, although the particle size for each loading is directly proportional to the hardness, the worst results are observed for the products of 75 pphr loading and 75 μm particle size. The tensile strength is inversely related to the particle size of the filler and gives the highest strength when filling with 10 pphr among other filling loadings. The elongation at break of natural rubber reduced by increasing the loading and decreasing the particle size. The results of compression set showed that the best behavior was for the product of 10 pphr and 10 μm particle size. The compression stress is directly related to the loading, especially for small particle sizes. The elastic modulus increased with the increase of loading and the increase of particle size. The density test showed that the silica filler has no significant increase in the density of rubber especially for small particle size fillers. Comparing the studies of properties of the manufactured rubber-base composites in this investigation with those achieved in other research works, it is found that they are superior especially for hardness, tensile strength, and compression set properties and density.