bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic and Gender Inequities in the Evaluation of Referred Short Children
Authors: Yardeni David , Loewenthal Neta , Limony Yehuda , Hershkovitz Eli
Published: June 2011

Aims: To examine ethnicity and gender differences in the evaluation of referred children with short stature and to investigate adherence of the primary care evaluation to published guidelines. Methods: Cross-sectional study in a referral center. 371 short patients aged 2–18 years were included. Outcome measures were patient’s growth characteristics, final diagnosis, and prevalence of pre-referral patient data. Results: The study population was composed of 239 Bedouin children and 132 Jewish children (p < 0.0001). More males (61%) than females were evaluated (p < 0.0001). There were no significant differences between males and females in age and growth parameters at the time of referral. Bedouins, males and females, were significantly shorter than their Jewish counterparts at the time of referral: height SD –2.44 ± 0.73 and –2.62 ± 1.05 versus –2.13 ± 0.55 and –2.21 ± 0.57, respectively (p < 0.05). There were no significant ethnic or gender differences in the final diagnosis. Significant deficiencies in the primary care evaluation of referred short children were found. Conclusions: We demonstrated novel ethnic- and gender-based inequities in the evaluation of referred short children. We found that the current evaluation of short stature in our area does not comply with existing guidelines.
Dental Erosion – An Overview with Emphasis on Chemical and Histopathological Aspects
Authors: Lussi A. , Schlueter N. , Rakhmatullina E. , Ganss C.
Published: June 2011

The quality of dental care and modern achievements in dental science depend strongly on understanding the properties of teeth and the basic principles and mechanisms involved in their interaction with surrounding media. Erosion is a disorder to which such properties as structural features of tooth, physiological properties of saliva, and extrinsic and intrinsic acidic sources and habits contribute, and all must be carefully considered. The degree of saturation in the surrounding solution, which is determined by pH and calcium and phosphate concentrations, is the driving force for dissolution of dental hard tissue. In relation to caries, with the calcium and phosphate concentrations in plaque fluid, the ‘critical pH’ below which enamel dissolves is about 5.5. For erosion, the critical pH is lower in products (e.g. yoghurt) containing more calcium and phosphate than plaque fluid and higher when the concentrations are lower. Dental erosion starts by initial softening of the enamel surface followed by loss of volume with a softened layer persisting at the surface of the remaining tissue. Dentine erosion is not clearly understood, so further in vivo studies, including histopathological aspects, are needed. Clinical reports show that exposure to acids combined with an insufficient salivary flow rate results in enhanced dissolution. The effects of these and other interactions result in a permanent ion/substance exchange and reorganisation within the tooth material or at its interface, thus altering its strength and structure. The rate and severity of erosion are determined by the susceptibility of the dental tissues towards dissolution. Because enamel contains less soluble mineral than dentine, it tends to erode more slowly. The chemical mechanisms of erosion are also summarised in this review. Special attention is given to the microscopic and macroscopic histopathology of erosion.
Screening and Prediction of Erosive Potential
Authors: Barbour M.E. , Lussi A. , Shellis R.P.
Published: June 2011

The literature on the erosive potential of drinks and other products is summarised, and aspects of the conduct of screening tests as well as possible correlations of the erosive potential with various solution parameters are discussed. The solution parameters that have been suggested as important include pH, acid concentration (with respect to buffer capacity and concentration of undissociated acid), degree of saturation, calcium and phosphate concentrations, and inhibitors of erosion. Based on the available data, it is concluded that the dominant factor in erosion is pH. The effect of buffer capacity seems to be pH dependent. The degree of saturation probably has a non-linear relationship with erosion. While calcium at elevated concentrations is known to reduce erosion effectively, it is not known whether it is important at naturally occurring concentrations. Fluoride at naturally occurring concentrations is inversely correlated with erosive potential, but phosphate is probably not. Natural plant gums, notably pectin, do not inhibit erosion, so they are unlikely to interfere with the prediction of erosive potential. The non-linearity of some solution factors and interactions with pH need to be taken into account when developing multivariate models for predicting the erosive potential of different solutions. Finally, the erosive potential of solutions towards enamel and dentine might differ.
Initial Erosion Models
Authors: Young A. , Tenuta L.M.A.
Published: June 2011

Initial dental erosion – the very first tooth surface changes caused by short-term acidic exposures before any tissue loss is observed – has been studied using in vitro and in situ/in vivo protocols. This paper describes the events that should be considered when modelling initial erosion, the available protocols and their strengths and limitations. In vitro initial erosion models can provide relevant information about the erosive outcome. However, the published studies vary considerably regarding the erosive parameters used, and few of these studies have been validated. On the other hand, relevant in situ/in vivo studies are available that have studied the effect of salivary pellicle and preventive treatments on initial erosion, as well as the changes in salivary pH following exposure to acid solutions. Guidelines for good methodology in modelling initial erosion are proposed.
In vitro and in situ Erosion Models for Evaluating Tooth Substance Loss
Authors: West N.X. , Davies M. , Amaechi B.T.
Published: June 2011

Because of the difficulties in measuring erosion in vivo, a number of in vitro and in situ models have been developed and validated. These models are flexible and informative, allowing single as well as multiple variables to be examined under specific conditions using accurate measurement techniques over defined timelines, thus yielding useful data without harmful effects on individuals. This information, together with clinical findings, is essential for clinicians advising susceptible patients appropriately regarding the management of their condition. Little guidance is available, however, on the standardisation of in vitro and in situ protocols for erosive tooth wear studies, so it is difficult to make meaningful comparisons between investigations as experimental variables differ widely from study to study. The aim of this review was to collate the available data on models designed to assess erosive challenges which are severe enough to cause tissue loss as opposed to just softening of the surface structure. The different types of models, with their merits and pitfalls, are documented. Test substrates, disinfecting regimens and ethical considerations are discussed. The aims of this paper are to give guidance to the researcher on evidence-based in vitro and in situ erosive tooth wear methodology and to suggest best practice given current knowledge.
Methodology and Models in Erosion Research: Discussion and Conclusions
Authors: Shellis R.P. , Ganss C. , Ren Y. , Zero D.T. , Lussi A.
Published: June 2011

This paper summarises the discussions which took place at the Workshop on Methodology in Erosion Research in Zürich, 2010, and aims, where possible, to offer guidance for the development and application of both in vitro and in situ models for erosion research. The prospects for clinical trials are also discussed. All models in erosion research require a number of choices regarding experimental conditions, study design and measurement techniques, and these general aspects are discussed first. Among in vitro models, simple (single- or multiple-exposure) models can be used for screening products regarding their erosive potential, while more elaborate pH cycling models can be used to simulate erosion in vivo. However, in vitro models provide limited information on intra-oral erosion. In situ models allow the effect of an erosive challenge to be evaluated under intra-oral conditions and are currently the method of choice for short-term testing of low-erosive products or preventive therapeutic products. In the future, clinical trials will allow longer-term testing. Possible methodologies for such trials are discussed.
Impact of Intravitreal Injection of Tissue Plasminogen Activator on Full-Field Electroretinogram in Patients with Macular Oedema Secondary to Retinal Vein Occlusion
Authors: Tagami Mizuki , Kusuhara Sentaro , Imai Hisanori , Honda Shigeru , Tsukahara Yasutomo , Negi Akira
Published: June 2011

Purpose: To evaluate the retinal toxicity of intravitreal tissue plasminogen activator (tPA) injection for branch and central retinal vein occlusion (BRVO and CRVO) using the electroretinogram (ERG). Procedures: Ten BRVO patients and 5 CRVO patients were enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT), and evaluation of systemic and ocular complications was performed before and after intravitreal tPA injection. Results: No significant differences were found in the amplitude or implicit time of any ERG component after tPA injection, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at month 3 in the BRVO group (p < 0.05) but not in the CRVO group. CRT significantly decreased over the course of 3 months in both groups (p < 0.01). Conclusion: Intravitreal tPA injection seems to be a safe and effective treatment option for macular oedema caused by retinal vein occlusions.
T Cell Subsets Related with a Sex Difference in IL-5 Production
Authors: Okuyama Kaori , Hamanaka Yuka , Kawano Tasuku , Ohkawara Yuichi , Takayanagi Motoaki , Kikuchi Toshiaki , Ohno Isao
Published: June 2011

Background: Before puberty, the prevalence and severity of asthma are higher in boys than in girls, but this pattern is reversed after puberty. The underlying mechanisms of these gender differences in asthma are not fully understood. Using murine models of allergic asthma, a sex difference in Th2 cytokine production has been suggested to contribute to the gender differences in asthma. Therefore, we determined which subsets of T cells are involved in the sex difference in Th2 cytokine production. Methods: Splenocytes from wild-type mice and CD4+ T cell-, CD8+ T cell-, and iNKT cell-deficient mice were stimulated with anti-CD3/CD28 antibodies for 3 days, and the concentrations of IL-4, IL-5, IL-13, and IFN-γ in the cultures were measured by ELISA. Results: IL-5, but not IL-4 and IL-13, concentrations in culture derived from female wild-type mice were significantly higher than those in male wild-type mice. The sex difference in IL-5 concentrations was not observed in the cultures of splenocytes from CD4+ and CD8+ T cell-deficient mice. The disappearance of the sex differences in CD4+ and CD8+ T cell-deficient mice was attributable to a decrease in IL-5 concentration in female mice and an increase in IL-5 concentration in male mice. In iNKT cell-deficient mice, the sex difference was still observed. There was no significant difference between the sexes in any type of mice with respect to IFN-γ production. Conclusions: There was a sex difference in IL-5 production by splenocytes stimulated by TCR activation. The difference might be attributable to sex differences in CD4+ and CD8+ T cell functions.
Peripheral Blood Mononuclear Cells from Patients with Bronchial Asthma Show Impaired Innate Immune Responses to Rhinovirus in vitro
Authors: Iikura Katsuhito , Katsunuma Toshio , Saika Shizuko , Saito Saburo , Ichinohe Sadato , Ida Hiroyuki , Saito Hirohisa , Matsumoto Kenji
Published: June 2011

Background: Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients’ peripheral blood mononuclear cells (PBMCs) to RV exposure. Methods: PBMCs obtained from 3 different age groups (2–6 years: young-children group; 7–19 years: youth group; ≧20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA. Results: When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze. Conclusions: These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients’ PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.
Human Eosinophils Produce and Release a Novel Chemokine, CCL23, in vitro
Authors: Matsumoto Kenji , Fukuda Shuhei , Hashimoto Noriko , Saito Hirohisa
Published: June 2011

Background: CCL23 (MPIF1/CK-BETA-8) is a novel CC chemokine that plays important roles in the inhibition of myeloid progenitor cell development, the selective recruitment of resting T lymphocytes and monocytes, and the potentiation of VEGF-induced proliferation and migration of human endothelial cells. Since eosinophils participate in the pathogenesis of airway remodeling, we examined CCL23 production and release by human eosinophils in vitro. Methods: Using Ficoll and antibody-coated immunomagnetic beads, eosinophils and other blood cells were purified from peripheral blood samples obtained from normal subjects and mildly allergic patients. Eosinophils were cultured in the presence of 10 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF), 10 ng/ml IL-5, 100 ng/ml IFN-γ, 100 ng/ml IFN-α, or immobilized secretory IgA (sIgA). Total mRNA was extracted after 6 h of culture, and mRNA expression was measured using a microarray and RT-PCR. The CCL23 concentrations in the supernatants and cell lysates after 24 and 48 h of culture were measured by ELISA. Results: CCL23 mRNAs (both CK-β8-1 and CK-β8) were constitutively expressed in fresh eosinophils, and their expression levels were higher than in other types of blood cells. CCL23 mRNAs were significantly increased by stimulation with GM-CSF and IL-5 and slightly by IFN-α and immobilized sIgA. Fresh eosinophils contained trace amounts of CCL23 protein. CCL23 was significantly released into the supernatant when the eosinophils were stimulated with GM-CSF or IL-5 but not with IFN-γ or immobilized sIgA. Conclusion: Our data suggest that eosinophils produce and release CCL23 and may be involved in some in vivo physiological and pathological conditions.
Eosinophilic Gastrointestinal Disorders in Infants: A Japanese Case Series
Authors: Yamada Yoshiyuki , Nishi Akira , Ebara Yoshifumi , Kato Masahiko , Yamamoto Hideki , Morita Hideaki , Nomura Ichiro , Matsumoto Kenji , Hirato Junko , Hatakeyama Shin-itsu , Suzuki Norio , Hayashi Yasuhide
Published: June 2011

Background: Eosinophilic gastrointestinal disorders (EGIDs) are disorders characterized by primary eosinophil inflammation in the gastrointestinal tract. There are a small number of reports of eosinophil infiltration in gastrointestinal tracts presenting as EGIDs in infants. In this study, we present Japanese cases of EGIDs in infants. Methods: Five patients diagnosed with or strongly suspected to have EGIDs in our hospital from 2008 to 2010 were reviewed. Radiographic contrast enema examinations and/or endoscopies were performed in 4 and 3 patients, respectively. Results: There were patients with eosinophilic colitis (1 suspected and 2 biopsy-proven), a patient who was suspected of having allergic eosinophilic enterocolitis, and a patient with eosinophilic gastroenteritis associated with pediatric hypereosinophilic syndrome. Conclusions: The causes and clinical findings of patients with intestinal eosinophil inflammation vary. Therefore, deliberate examination and observation are important for patients with infantile EGID.
Peroxisome Proliferator-Activated Receptor-γ Is Expressed in Eosinophils in Nasal Polyps
Authors: Asaka Chikara , Honda Kohei , Ito Eiko , Fukui Naoko , Chihara Junichi , Ishikawa Kazuo
Published: June 2011

Background: Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear receptors, which regulate fatty acid metabolites. One of the natural ligands for PPARγ is 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a major metabolite of prostaglandin D2 (PGD2). Recently, PPARγ has been shown to play an important role in anti-inflammatory reactions, including within-airway allergic diseases, in a mouse model. Our aim was to clarify the expression and localization of PPARγ and PGD2 synthase, which produces ligands of PPARγ, in nasal polyps by immunohistochemical analysis. Methods: Nasal polyps of chronic rhinosinusitis patients (6 asthmatic patients and 6 nonasthmatic patients) were obtained during surgery. May-Grünwald-Giemsa staining was performed to evaluate the eosinophil infiltration of the polyps. To identify the cells expressing PPARγ protein and PGD2 synthase, double immunostaining was performed using anti-PPARγ antibody, monoclonal antileukocyte antibodies, and PGD2 synthase antibody. Results: The number of eosinophils and the number of PPARγ-positive cells in the nasal polyps of the asthmatic patients were significantly higher than those in the nonasthmatic patients. PPARγ was expressed on eosinophils and T cells of the infiltrating cells in the nasal polyps. PGD2 synthase was also expressed on PPARγ-positive cells. Conclusion: PPARγ is involved in nasal polyposis pathogenesis, acting on eosinophils and T cells.
The in vitro Effects of Advanced Glycation End Products on Basophil Functions
Authors: Han Kaiyu , Suzukawa Maho , Yamaguchi Masao , Sugimoto Naoya , Nakase Yuko , Toda Takako , Nagase Hiroyuki , Ohta Ken
Published: June 2011

Background: Basophils are thought to play pivotal roles in the pathogenesis of allergic reactions, but their roles in inflammation associated with systemic abnormalities such as metabolic disorders remain largely unknown. Advanced glycation end products (AGEs) are potentially important substances produced in high-glucose disease conditions. In this in vitro study, we investigated whether the biological functions of human basophils can be influenced by AGEs. Methods: We analyzed the effects of AGEs on various functions and markers of human basophils, including CD11b expression, apoptosis, degranulation, and cytokine production. Results: Flow cytometric analysis indicated that the level of the receptor for AGEs (RAGE) on the surface of freshly isolated basophils was very low but was clearly upregulated by IL-3. Apoptosis of basophils was induced by high concentrations of glycated albumin. Although glycated albumin failed to affect the level of surface CD11b expression or to trigger degranulation or production of IL-4 and IL-13 in basophils, it dose-dependently induced IL-6 and IL-8 secretion. Conclusions: AGEs seem to act on human basophils; they suppress the cells’ longevity but elicit secretion of inflammatory cytokines. Through these biological changes, basophils might play some roles in inflammatory conditions associated with metabolic disorders presenting elevated levels of AGEs.
STAT4 Is Required for IFN-β-Induced MCP-1 mRNA Expression in Murine Mast Cells
Authors: Iida Kazuma , Suzuki Kotaro , Yokota Masaya , Nakagomi Daiki , Wakashin Hidefumi , Iwata Arifumi , Kawashima Hirotoshi , Takatori Hiroaki , Nakajima Hiroshi
Published: June 2011

Background: Mast cells are immunocompetent cells that are found in almost all tissues and function as sentinels of immune responses. Recently, it has been shown that mast cells play significant roles in innate immune responses. However, it is still largely unknown whether signal transducers and activators of transcription 4 (STAT4), one of the STAT proteins under type I IFN signaling, is involved in type I IFN-mediated gene expression in mast cells. Methods: We investigated the role of STAT4 in IFN-β-induced gene expression in mast cells by using STAT4-deficient (STAT4–/–) bone marrow-derived mast cells (BMMCs). Results: STAT4 was expressed in BMMCs and activated in response to IFN-β but not to IL-12 or IL-23. The development of BMMCs as well as IgE-induced degranulation of BMMCs was normal in STAT4–/– mice. On the other hand, while IFN-β-induced mRNA expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1), protein kinase interferon-inducible double stranded RNA dependent (PKR), and myxovirus resistance 1 (Mx1) was similar between STAT4–/– BMMCs and wild-type (WT) BMMCs, IFN-β-induced MCP-1 mRNA expression was severely diminished in STAT4–/– BMMCs as compared with WT BMMCs. Conclusions: STAT4 plays an essential role in IFN-β-induced MCP-1 mRNA expression in mast cells.
Effects of a Cysteinyl Leukotriene Dual 1/2 Receptor Antagonist on Antigen-Induced Airway Hypersensitivity and Airway Inflammation in a Guinea Pig Asthma Model
Authors: Muraki Masato , Imbe Shu , Santo Hiroshi , Sato Ryuji , Sano Hiroyuki , Iwanaga Takashi , Tohda Yuji
Published: June 2011

Background: Little is known about the role of the cysteinyl leukotriene (cysLT) 2 receptor in the pathophysiology of asthma. The aim of this study is to investigate the effects of a cysLT1 receptor antagonist (montelukast) and a dual cysLT1/2 receptor antagonist (BAY-u9773) on airway hypersensitivity and airway inflammation induced by antigen challenge in ovalbumin (OVA)-sensitized guinea pigs. Methods: Male Hartley guinea pigs sensitized with OVA were intraperitoneally administered 0.1, 1, or 10 mg/kg of montelukast or 0.1 mg/kg of BAY-u9773 and then challenged with inhaled OVA. Airway reactivity to acetylcholine, inflammatory cells in bronchoalveolar lavage (BAL) fluid, and eosinophil infiltration in airway walls after OVA challenge were evaluated. Results: Pretreatment with 1 or 10 mg/kg, but not 0.1 mg/kg, of montelukast significantly suppressed airway hypersensitivity and eosinophil infiltration into the BAL fluid. Moreover, 0.1 mg/kg of BAY-u9773 significantly suppressed the development of these markers. The suppressive effects of BAY-u9773, although not significantly different, trended toward being greater than those of montelukast. Although all of the doses of montelukast tested and 0.1 mg/kg of BAY-u9773 significantly suppressed eosinophil infiltration in airway walls, the suppressive effect of BAY-u9773 was significantly greater than that of 0.1 mg/kg of montelukast. Conclusion: Signaling may contribute to the pathophysiology of asthma via the cysLT1/2 receptor.
Protease-Mediated House Dust Mite Allergen-Induced Reactive Oxygen Species Production by Neutrophils
Authors: Fukunaga Makiko , Gon Yasuhiro , Nunomura Satoshi , Inoue Toshio , Yoshioka Mino , Hashimoto Shu , Ra Chisei
Published: June 2011

A growing body of evidence indicates that neutrophils may play an important role in the pathogenesis of asthma. However, the involvement of the house dust mite (HDM) in neutrophil activation associated with the pathogenesis of asthma is not fully understood yet. To address this situation, we harvested neutrophils isolated from 15 HDM-sensitized asthmatic subjects and 18 HDM-sensitized nonasthmatic subjects and measured the amounts of neutrophil reactive oxygen species (ROS) production in response to the major HDM allergens Der-f and Der-f1. Der-f and Der-f1 significantly increased ROS production in neutrophils isolated from asthmatic subjects versus nonasthmatic subjects. To assess the involvement of Der-f-specific IgE antibodies binding to their receptors in HDM allergen-induced ROS production, we examined whether neutrophils produce ROS by cross-linking of cell-bound IgE antibodies with anti-IgE. Treatment with anti-IgE antibodies did not induce ROS production by neutrophils isolated from 6 asthmatic subjects. On the other hand, pretreatment of Der-f with E-64, a cysteine protease inhibitor, eliminated Der-f-induced ROS production. These results suggest that HDM-allergen exposure may result in greater production of ROS in asthmatic patients and may be involved in the pathogenesis of asthma.
Human Eosinophil Innate Response to Alternaria Fungus through Protease-Activated Receptor-2
Authors: Matsuwaki Yoshinori , Wada Kota , Moriyama Hiroshi , Kita Hirohito
Published: June 2011

Eosinophils are multifunctional leukocytes implicated in the pathogenesis of allergic diseases. An association between eosinophilic inflammation and infection or colonization by fungi has also been long recognized. However, the mechanisms underlying how eosinophils are activated and how they release proinflammatory and immunomodulatory mediators such as major basic protein (MBP) and eosinophil-derived neurotoxin remain largely unknown. We used a fungus, i.e. Alternaria, as a model microbe relevant to human asthma and chronic rhinosinusitis (CRS) to investigate the molecular mechanisms involved in the immune recognition of ubiquitous environmental allergens. Human eosinophils are activated by live Alternaria alternata organisms, release their granule proteins, and kill the fungi. Eosinophils, but not neutrophils, respond to secreted products from A. alternata. We found that eosinophils are equipped with innate cellular activation machinery that responds to an extracellular aspartate protease secreted by Alternaria. Aspartate protease activation of protease-activated receptor (PAR)-2 probably involves a novel mechanism different from that for serine protease activation of PAR-2. Thus, human eosinophils may recognize certain danger signals or virulence factors produced by fungi and provoke inflammatory responses against these organisms. Dysregulation of such an innate immune mechanism may be involved in the pathophysiology of certain human inflammatory diseases, including asthma and CRS.
Thioredoxin in Allergic Inflammation
Authors: Ito Wataru , Kobayashi Noriko , Takeda Masahide , Ueki Shigeharu , Kayaba Hiroyuki , Nakamura Hajime , Yodoi Junji , Chihara Junichi
Published: June 2011

Thioredoxin (TRX) is a redox-active protein that regulates reactive oxidative metabolism and plays a crucial role in the antioxidant system in regulating the reduction/oxidation balance by scavenging reactive oxygen species, which is implicated in the mechanism of asthma. As for the mechanisms by which TRX exerts its beneficial effects, some studies have shown that TRX suppresses allergic inflammation in animal models of asthma. Recently, we reported that TRX directly modulated the chemotaxis of eosinophils, which have been shown to play a pivotal role in the mechanism of allergic airway inflammation, in the absence of T helper (Th)1 or Th2 cytokines. Further, serum TRX levels in patients with asthma were significantly increased in patients with attacks compared with those in the asymptomatic period. This review focuses on TRX in allergic reactions and discusses the physiological role of TRX.
Interactions between Dietary Fat Intake and FASN Genetic Variation Influence LDL Peak Particle Diameter
Authors: Dolley G. , Boisclair M.E. , Lamarche B. , Després J.P. , Bouchard C. , Pérusse L. , Vohl M.C.
Published: June 2011

Background: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on the Quebec Family Study (QFS) revealed a quantitative trait locus for LDL peak particle diameter (LDL-PPD) on the 17q21 region. A positional candidate gene – the fatty acid synthase gene (FASN) – encodes a key enzyme in the biogenesis of membrane lipids. FASN may play a role in the regulation of feeding and may be a potential therapeutic target for obesity and insulin resistance. Methods: Analyses were performed on 592 subjects of the QFS. Dietary fat was estimated by a 3-day food record. LDL-PPD was measured by gradient gel electrophoresis on polyacrylamide gradient gels. Results: Five single nucleotide polymorphisms were genotyped in FASN gene. FASN rs4246444 was associated with LDL-PPD, but only when fat intake was taken into account (p = 0.001). High and low lipid consumers were defined using a cutoff of 35% of dietary fat intake. Carriers of the variant allele showed smaller LDL-PPD only when consuming a high amount of fat. This association remained significant after adjustments for age, sex, body mass index and plasma triglyceride levels. Conclusion: The results suggest that dietary fat intake may modify the effect of the FASN rs4246444 polymorphism on LDL-PPD.
Mechanisms of Growth Plate Maturation and Epiphyseal Fusion
Authors: Emons Joyce , Chagin Andrei S. , Sävendahl Lars , Karperien Marcel , Wit Jan M.
Published: June 2011

Longitudinal growth occurs within the long bones at the growth plate. During childhood, the growth plate matures, its total width decreases and eventually it disappears at the end of puberty with complete replacement by bone along with cessation of longitudinal growth. The exact mechanism of epiphyseal fusion is still not completely understood and experimental studies are complicated by the fact that there is a species difference between humans and rabbits that do fuse their growth plates and rodents that do not. This mini review summarizes hypotheses and theories postulated in the literature regarding growth plate maturation and epiphyseal fusion. Growth factors, local regulators and hormones involved in growth plate maturation are described as well as four postulated hypotheses and theories regarding the final steps in epiphyseal fusion: apoptosis, autophagy, transdifferentiation and hypoxia. A better insight into the mechanisms of epiphyseal fusion may ultimately help to develop new strategies for the treatment of cartilage and growth disorders.
An Exploratory Study on Facial Emotion Recognition Capacity in Beginning Alzheimer’s Disease
Authors: Wiechetek Ostos Marzanna , Schenk Françoise , Baenziger Tania , von Gunten Armin
Published: June 2011

Objective: It was the aim of this study to investigate facial emotion recognition (FER) in the elderly with cognitive impairment. Method: Twelve patients with Alzheimer’s disease (AD) and 12 healthy control subjects were asked to name dynamic or static pictures of basic facial emotions using the Multimodal Emotion Recognition Test and to assess the degree of their difficulty in the recognition task, while their electrodermal conductance was registered as an unconscious processing measure. Results: AD patients had lower objective recognition performances for disgust and fear, but only disgust was accompanied by decreased subjective FER in AD patients. The electrodermal response was similar in all groups. No significant effect of dynamic versus static emotion presentation on FER was found. Conclusion: Selective impairment in recognizing facial expressions of disgust and fear may indicate a nonlinear decline in FER capacity with increasing cognitive impairment and result from progressive though specific damage to neural structures engaged in emotional processing and facial emotion identification. Although our results suggest unchanged unconscious FER processing with increasing cognitive impairment, further investigations on unconscious FER and self-awareness of FER capacity in neurodegenerative disorders are required.
Visual Rating versus Volumetry to Detect Frontotemporal Dementia
Authors: Chow T.W. , Gao F. , Links K.A. , Ween J.E. , Tang-Wai D.F. , Ramirez J. , Scott C.J.M. , Freedman M. , Stuss D.T. , Black S.E.
Published: June 2011

Background/Aims: Automated, volumetrically defined atrophy in the left anterior cingulate (LAC) and anterior temporal regions (LAT) on MRI can be used to distinguish most patients with frontotemporal dementia (FTD) from controls. FTD and Alzheimer’s disease (AD) can differ in the degree of anterior temporal atrophy. We explored whether clinicians can visually detect this atrophy pattern and whether they can use it to classify the 2 groups of dementia patients with the same accuracy. Methods: Four neurologists rated atrophy in the LAC and LAT regions on MRI slices from 21 FTD, 21 controls, and 14 AD participants. Inter-rater reliability and diagnostic accuracy were assessed. Results: All 4 raters agreed on the presence of clinically significant atrophy, and their atrophy scoring correlated with the volumes, but without translation into high inter-rater diagnostic agreement. Conclusions: Volumetric analyses are difficult to translate into routine clinical practice.
Plaque Vulnerability in Internal Carotid Arteries with Positive Remodeling
Authors: Miura Toshiyasu , Matsukawa Noriyuki , Sakurai Keita , Katano Hiroyuki , Ueki Yoshino , Okita Kenji , Yamada Kazuo , Ojika Kosei
Published: June 2011

Background: This study aimed to evaluate the efficacy of assessing positive remodeling for predicting future stroke events in the internal carotid artery. We therefore assessed narrowing of the carotid artery lumen using multidetector-row computer tomography (MDCT) angiography and carotid plaque characteristics using black-blood (BB) magnetic resonance (MR). Methods: We retrospectively selected 17 symptomatic and 11 asymptomatic lesions with luminal narrowing >50%. We compared remodeling parameters of luminal stenosis (remodeling ratio, RR/remodeling index, RI) using MDCT and MR intensities of atherosclerotic plaque contents using the BB technique (relative signal intensity, rSI). We also confirmed the validity of the relationship between MR intensity and atherosclerotic plaque contents by histology. The levels of biological markers related to vessel atherosclerosis were measured. Results: Plaque lesions with positive remodeling in carotid arteries were associated with a significantly higher prevalence of stroke compared with plaques with negative remodeling (p < 0.05). Radiologic and histologic analyses determined that plaques with positive remodeling had higher signal intensities (with respect to their lipid-rich content or to hemorrhage) compared with negative remodeling (correlation coefficients: RI and rSI, r = 0.41, p < 0.05; RR and rSI, r = 0.50, p < 0.05). Levels of biological markers, including high-sensitivity C-reactive protein, hemoglobin A1C, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were not useful for predicting stroke events. Conclusions: The results of this study suggest that the combined analysis of RR, RI and rSI could potentially help to predict future stroke events.
Validity of an Information and Communication Technology System for Data Capture in Epidemiological Studies
Authors: Carvalho J.C. , Bottenberg P. , Declerck D. , van Nieuwenhuysen J.P. , Vanobbergen J. , Nyssen M.
Published: June 2011

The Belgian National Institute of Health Insurance is implementing an oral health data registration and surveillance system. This study aimed to develop and validate a system of electronic data capture for oral health surveys at a national level – Oral Survey-B – and to identify the advantages and disadvantages of the electronic system in comparison with the traditional handwritten data capture. Six series of full-mouth recordings simulating the clinical examination of 6 patients were set up in a Powerpoint presentation. The validation was undertaken by 52 general practitioners. A randomized one-period crossover design was used with two formats of data capture, i.e. electronic followed by handwritten or handwritten followed by electronic system. Further, 6 benchmarked handwritten forms were transferred to the electronic format. For the electronic data capture, 86.5% of the practitioners had a correct completion rate of ≧95%. The corresponding value for the handwritten data capture and transfer was 78.8% (p = 0.25, McNemar test). The overall accuracy of forms without any error was 73.4% for the electronic and 62.5% for the handwritten data capture (p < 0.001, signed-rank test). Significantly lower percentages of errors and less time were observed for the electronic data capture (p < 0.001, signed-rank test). Practitioners considered the electronic data capture as being much more difficult to carry out (p < 0.001). As information technology has turned into an ever more necessary working tool in epidemiology, there should be an important potential for uptake of further improvements in electronic data capture in the future.
Impact of Leukocyte Count on Mortality and Bleeding in Patients With Myocardial Infarction Undergoing Primary Percutaneous Coronary Interventions
Authors: Palmerini Tullio , Mehran Roxana , Dangas George , Nikolsky Eugenia , Witzenbichler Bernhard , Guagliumi Giulio , Dudek Darius , Genereux Philippe , Caixeta Adriano , Rabbani LeRoy , Weisz Giora , Parise Helen , Fahy Martin , Xu Ke , Brodie Bruce , Lansky Alexandra , Stone Gregg W.
Published: June 2011

Background—

The relationship between white blood cell count (WBCc) and mortality in patients with ST-segment–elevation acute myocardial infarction treated with percutaneous coronary intervention is poorly understood. Furthermore, whether there is a relationship between WBCc and risk of noncardiac mortality and bleeding after percutaneous coronary intervention is unknown.

Methods and Results—

The baseline WBCc was available in 3193 of 3345 patients (95.5%) who underwent percutaneous coronary intervention in the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial. In a propensity-adjusted multivariable analysis, WBCc was an independent predictor of 1-year cardiac mortality (hazard ratio, 1.15; 95% confidence interval, 1.09 to 1.22), noncardiac mortality (hazard ratio, 1.19; 95% confidence interval, 1.10 to 1.29), and major bleeding (hazard ratio, 1.08; 95% confidence interval, 1.04 to 1.12). After adjustment for baseline creatinine phosphokinase levels and left ventricular ejection fraction, WBCc remained an independent predictor of 1-year all-cause mortality and cardiac mortality. In patients matched for baseline creatinine phosphokinase levels at hospital admission, the median peak creatinine phosphokinase level was significantly higher in patients with high WBCc (>11 000 per 1 mm
3
) compared with low WBCc (1851 U/L [range, 880-3307 U/L] versus 1241 U/L [range, 540 to 2,78], respectively;
P
<0.0001). In this subgroup of patients, WBCc was an independent correlate of peak creatinine phosphokinase level, and remained an independent predictor of 1-year mortality.

Conclusions—

In patients with ST-segment–elevation acute myocardial infarction undergoing percutaneous coronary intervention, elevated baseline WBCc is an independent predictor of infarct size, as assessed by peak creatinine phosphokinase level, and of 1-year cardiac mortality, noncardiac mortality, and major bleeding.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00433966.
Elimination of Severe Albuminuria in Aging Hypertensive Rats by Exchange of 2 Chromosomes in Double-Consomic Rats
Authors: van Es Nicole , Schulz Angela , IJpelaar Daphne , van der Wal Annemieke , Kuhn Kristina , Schütten Sabrina , Kossmehl Peter , Nyengaard Jens R. , de Heer Emile , Kreutz Reinhold
Published: June 2011

The inherited nephron deficit and progressive albuminuria development observed in hypertensive Munich Wistar Frömter (MWF) rats are influenced by quantitative trait loci on rat chromosome (RNO) 6 and RNO8. Previous studies in young MWF rats suggested that the nephron deficit represents a cause for glomerular hypertrophy preceding onset of albuminuria at 8 weeks and demonstrated a simultaneous induction of the podocyte stress marker desmin and podoplanin loss in podocytes. Here we investigated the separate genetic influence of RNO6 and RNO8 on early glomerular changes and subsequent albuminuria in single-consomic MWF rats in which RNO6 (MWF-6
SHR
) and RNO8 (MWF-8
SHR
) were replaced by the respective spontaneously hypertensive rat (SHR) chromosome. Furthermore, we tested the role of synergistic effects between both chromosomes in a double-consomic MWF-6
SHR
8
SHR
strain. Increased glomerular, extramesangial desmin expressions at 6 and albuminuria at 8 weeks were significantly reduced in single- and double-consomics (
P
<0.05 versus MWF, respectively). MWF-6
SHR
8
SHR
rats demonstrated the lowest desmin expression and glomerular volume (
P
<0.05 versus MWF, MWF-6
SHR
, and MWF-8
SHR
, respectively), indicating synergistic effects between RNO6 and RNO8. A significant and similar loss of podoplanin was only seen in MWF and MWF-6
SHR
rats but not in MWF-8
SHR
and MWF-6
SHR
8
SHR
rats (
P
<0.02, respectively); this refutes a mandatory coupling of desmin induction and podoplanin loss in podocytes preceding albuminuria and reveals a genetic link between RNO8 and loss of podoplanin protein. Long-term follow up in MWF-6
SHR
8
SHR
rats demonstrates the relevance of the absence of glomerular changes in young animals, because double-consomics demonstrate a complete suppression of progressive albuminuria and kidney damage compared with MWF rats despite similar blood pressures.
Diurnal Variation in the Mechanical and Neural Components of the Baroreflex
Authors: Taylor Chloe E. , Atkinson Greg , Willie Christopher K. , Jones Helen , Ainslie Philip N. , Tzeng Yu-Chieh
Published: June 2011

Diminished baroreflex sensitivity in the morning negatively influences morning coronary blood flow and blood pressure control in hypertensive patients. Our aim was to determine the contribution of the mechanical and neural components of the cardiac baroreflex to diurnal variation in blood pressure control. In 12 healthy participants, we used the modified Oxford method to quantify baroreflex sensitivity for rising (G
up
) and falling (G
down
) pressures in the morning (7:00
am
) and afternoon (4:00
pm
). Beat-to-beat blood pressure, R-R intervals, and carotid artery diameter measurements were recorded. Integrated sensitivity was determined by plotting R-R intervals against systolic blood pressure. The mechanical component was carotid artery diameter plotted against systolic blood pressure, and the neural component was R-R intervals plotted against carotid artery diameter. Linear mixed models were used to compare the integrated, mechanical, and neural sensitivities between morning and afternoon. We found significant diurnal variation in integrated sensitivity, with an attenuated response in the morning (G
up
=13.0±0.6; G
down
=6.3±0.4 ms/mm Hg) when compared with the afternoon (G
up
=15.1±0.6; G
down
=12.6±0.4 ms/mm Hg). For rising pressures, the diminished integrated sensitivity in the morning was caused by a reduction in mechanical sensitivity, whereas for falling pressures it was caused by a reduction in neural sensitivity. Our findings explicate the mechanisms underlying diurnal variation in baroreflex function. Pharmacological and lifestyle interventions targeted specifically at the diminished component of the cardiac baroreflex in the morning may lead to better management of hypertension.
Dynamics and Thermodynamics of the Regional Response to the Indian Monsoon Onset
Authors: Saini Roop , Barlow Mathew , Hoell Andrew
Published: June 2011

The regional influence of the Indian monsoon onset is examined though observational analysis focusing on the Rodwell–Hoskins “monsoon-desert” hypothesis, which proposes that the strong diabatic heating associated with the monsoon produces a Gill-like Rossby wave response that thermodynamically interacts with the midlatitude westerly jet to produce subsidence and reduced rainfall to the west of the monsoon. Here, the authors analyze this proposed mechanism in terms of changes to the thermodynamic energy equation, regional circulation, and precipitation between the 10-day periods before and after the monsoon onset, for all onset dates in the 1958–2000 period. A Rossby-like response to the monsoon onset is clear in the observational data and is associated with horizontal temperature advection at midlevels as the westerlies intersect the warm temperature anomalies of the Rossby wave. Analysis of the thermodynamic equation verifies that the horizontal temperature advection is indeed balanced by subsidence over areas of North Africa, the Mediterranean, and the Middle East, and there is an associated decrease in precipitation over those regions. Despite the increased subsidence, diabatic heating changes are small in these regions so diabatic enhancement does not appear to be a primary factor in the response to the onset. This analysis also shows that the same processes that favor subsidence to the west of the monsoon also force rising motion over northern India and appear to be an important factor for the inland development of the monsoon. Comparison of strong and weak onsets further validates these relationships.
Reliability Analysis of Climate Change of Tropical Cyclone Activity over the Western North Pacific
Authors: Ren Fumin , Liang Jin , Wu Guoxiong , Dong Wenjie , Yang Xiuqun
Published: June 2011

Data homogeneity has become a significant issue in the study of tropical cyclones (TCs) and climate change. In this study, three historical datasets for the western North Pacific TCs from the Joint Typhoon Warning Center (JTWC), Japan Meteorological Agency (JMA), and China Meteorological Administration (CMA) are compared with a focus on TC intensity. Over the past 55 years (1951–2005), significant discrepancies are found among the three datasets, especially between the CMA and JTWC datasets.

The TC intensity in the CMA dataset was evidently overestimated in the 1950s and from the late 1960s to the early 1970s, while it was overestimated after 1988 in the JTWC dataset, especially during 1993–2003. Large discrepancies in TC tracks exist in two periods of 1951–early 1960s and 1988–1990s. Further analysis reveals that the discrepancies are obviously related to the TC observational techniques. Before the era of meteorological satellites (1951–the early 1960s), and after the termination of aircraft reconnaissance (since 1988), large discrepancies exist in both TC intensity and track. That the intensity discrepancy was smallest during the period (1973–87) when aircraft reconnaissance data and the Dvorak technique were both available suggests that availability of the aircraft reconnaissance and the Dvorak method helps in reducing the TC intensity discrepancy. For those TCs that were included in all the three datasets, no significant increasing or decreasing trend was found over the past 50 years. Each of the three TC datasets has individual characteristics that make it difficult to tell which one is the best. For TCs that affect China, the CMA dataset has obvious advantages such as more complete and more accurate information.