bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal characterization of the development of renal injury in FHH rats and FHH.1BNcongenic strains
Authors: Williams Jan Michael , Burke Marilyn , Lazar Jozef , Jacob Howard J. , Roman Richard J.
Published: November 2010

The present study examined the effect of transfer of portions of chromosome 1 that includes (FHH.1BNAR+strain) or excludes (control FHH.1BNAR−strain) a 4.3-Mb region from the Brown Norway (BN) rat that restores the autoregulation (AR) of renal blood flow (RBF) on the development of hypertension and renal injury in congenic strains of Fawn Hooded Hypertensive (FHH) rats. FHH and control AR−rats exhibited poor autoregulation of RBF, and glomerular capillary pressure (Pgc) rose by 19 ± 2 mmHg in FHH rats when renal perfusion pressure (RPP) was increased from 100 to 150 mmHg. In contrast, RBF was well autoregulated in the AR+strain, and Pgc only increased by 3 ± 1 mmHg when RPP was increased over this range. Baseline mean arterial pressure (MAP) at 12 wk of age was similar in all strains and averaged 122 mmHg. MAP increased significantly in FHH rats and was significantly higher by 12 mmHg in 21-wk-old FHH rats than in the FHH.1BNcongenic strains. Protein excretion rose from 5 ± 1 to 397 ± 29 mg/day in 6- vs. 21-wk-old FHH rats. In contrast, protein excretion only increased to 139 ± 21 mg/day in the control AR−strain, and it did not increase significantly in the AR+strain. Glomerular permeability to albumin was similar in all strains at 6 wk of age. It increased significantly in 9-wk-old FHH and control AR−rats, but not in the AR+strain. The levels of matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-β2 protein were significantly higher in the renal cortex of 9-wk-old FHH rats compared with the levels seen in the AR+strain. These data indicate that transfer of a 4.3-Mb region of BN chromosome 1 into the FHH genetic background improves autoregulation of RBF, normalizes Pgc, and slows the progression of renal disease.
Dual sources of vitronectin in the human lower urinary tract: synthesis by urothelium vs. extravasation from the bloodstream
Authors: Zhang Dianzhong , Hudson Amber E. , Delostrinos Catherine F. , Carmean Nicole , Eastman Rocky , Hicks Bryson , Hurst Robert E. , Bassuk James A.
Published: November 2010

Vitronectin (VN), secreted into the bloodstream by liver hepatocytes, is known to anchor epithelial cells to basement membranes through interactions with cell surface integrin receptors. We report here that VN is also synthesized by urothelial cells of urothelium in vivo and in vitro. In situ hybridization, dideoxy sequencing, immunohistochemistry, and ELISA of urothelial cell mRNA, cDNA, tissue, and protein extracts demonstrated that the VN gene is active in vivo and in vitro. The expression of VN by urothelium is hypothesized to constitute one of several pathways that anchor basal cells to an underlying substratum and explains why urothelial cells adhere to glass and propagate under serum-free conditions. Therefore, two sources of VN in the human urinary bladder are recognized: 1) localized synthesis by urothelial cells and 2) extravasation of liver VN through fenestrated capillaries. When human plasma was fractionated by denaturing heparin affinity chromatography, VN was isolated in a biologically active form that supported rapid spreading of urothelial cells in vitro under serum-free conditions. This activity was inhibited by the matricellular protein SPARC via direct binding of VN to SPARC through a Ca+2-dependent mechanism. A novel form of VN, isolated from the same heparin affinity chromatography column and designated as the VN(c) chromatomer, also supported cell spreading but failed to interact with SPARC. Therefore, the steady-state balance among urothelial cells, their extracellular milieu, and matricellular proteins constitutes a principal mechanism by which urothelia are anchored to an underlying substrata in the face of constant bladder cycling.
Role of NH3and NH4+transporters in renal acid-base transport
Authors: Weiner I. David , Verlander Jill W.
Published: November 2010

Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3movement coupled with NH4+“trapping” is being replaced by a model in which specific proteins mediate regulated transport of NH3and NH4+across plasma membranes. In the proximal tubule, the apical Na+/H+exchanger, NHE-3, is a major mechanism of preferential NH4+secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl−cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+exchanger, NHE-4, appears to be important for basolateral NH4+exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+secretion and NH3secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+transport. The role and mechanisms of these proteins are discussed in depth in this review.
GAD67-GFP+ Neurons in the Nucleus of Roller: A Possible Source of Inhibitory Input to Hypoglossal Motoneurons. I. Morphology and Firing Properties
Authors: van Brederode J.F.M. , Yanagawa Y. , Berger A. J.
Published: November 2010

In this study we examined the electrophysiological and morphological properties of inhibitory neurons located just ventrolateral to the hypoglossal motor (XII) nucleus in the Nucleus of Roller (NR). In vitro experiments were performed on medullary slices derived from postnatal day 5 (P5) to P15 GAD67-GFP knock-in mouse pups. on cell recordings from GFP+ cells in NR in rhythmic slices revealed that these neurons are spontaneously active, although their spiking activity does not exhibit inspiratory phase modulation. Morphologically, GFP+ cells were bi- or multipolar cells with small- to medium-sized cell bodies and small dendritic trees that were often oriented parallel to the border of the XII nucleus. GFP+ cells were classified as either tonic or phasic based on their firing responses to depolarizing step current stimulation in whole cell current clamp. Tonic GFP+ cells fired a regular train of action potentials (APs) throughout the duration of the pulse and often showed rebound spikes after a hyperpolarizing step. In contrast, phasic GFP+ neurons did not fire throughout the depolarizing current step but instead fired fewer than four APs at the onset of the pulse or fired multiple APs, but only after a marked delay. Phasic cells had a significantly smaller input resistance and shorter membrane time constant than tonic GFP+ cells. In addition, phasic GFP+ cells differed from tonic cells in the shape and time course of their spike afterpotentials, the minimum firing frequency at threshold current amplitude, and the slope of their current–frequency relationship. These results suggest that GABAergic neurons in the NR are morphologically and electrophysiologically heterogeneous cells that could provide tonic inhibitory synaptic input to HMs.
On Invariant Tori of Nearly Integrable Hamiltonian Systems with Quasiperiodic Perturbation
Authors: Zhang Dongfeng , Cheng Rong
Published: November 2010

We are concerned with the persistence of frequency of invariant tori for analytic integrable Hamiltonian system with quasiperiodic perturbation. It is proved that if the unperturbed system satisfies the Rüssmann's nondegeneracy condition and has nonzero Brouwer's topological degree at some Diophantine frequency; the perturbed system satisfies the colinked nonresonant condition, then the invariant torus with this frequency persists under quasiperiodic perturbation.
Interleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation
Authors: Tawara Isao , Koyama Motoko , Liu Chen , Toubai Tomomi , Thomas Dafydd , Evers Rebecca , Chockley Peter , Nieves Evelyn , Sun Yaping , Lowler Kathleen P. , Malter Chelsea , Nishimoto Norihiro , Hill Geoffrey R. , Reddy Pavan
Published: November 2010

Purpose: The graft-versus-tumor (GVT) effect is a potent form of immunotherapy against many hematologic malignancies and some solid tumors. The beneficial GVT effect after allogeneic bone marrow transplantation (BMT) is tightly linked to its most significant complication, graft-versus-host disease (GVHD). The role of interleukin-6 (IL-6) after allogeneic BMT is not well understood. This study used a series of complementary knockout and antibody blockade strategies to analyze the impact of IL-6 in multiple clinically relevant murine models of GVHD and GVT.

Experimental Design: We examined the effect of the source of IL-6 by analyzing the role IL-6 deficiency in donor T cells, donor bone marrow or in host tissues. We confirmed and extended the relevance of IL-6 deficiency on GVHD and GVT by treating BMT recipients with anti-mouse IL-6 receptor (IL-6R), MR16-1.

Results: Deficiency of IL-6 in donor T cells led to prolongation of survival. Total inhibition of IL-6 with MR16-1 caused an even greater reduction in GVHD-induced mortality. The reduction in GVHD was independent of the direct effects on T effector cell expansion or donor regulatory T cells. GVT responses were preserved after treatment with MR16-1.

Conclusion: MR16-1 treatment reduced GVHD and preserved sufficient GVT. Tocilizumab, a humanized anti–IL-6R monoclonal antibody (mAb), is approved in several countries including the United States and European Union for the treatment of rheumatoid arthritis and other inflammatory diseases. Blockade of IL-6 with anti–IL-6R mAb therapy may be testable in clinical trials as an adjunct to prevent GVHD in BMT patients without a significant loss of GVT. Clin Cancer Res; 17(1); 77–88. ©2010 AACR.
From Evidence to Rationale: Cardiovascular Protection by Angiotensin II Receptor Blockers Compared with Angiotensin-Converting Enzyme Inhibitors
Authors: Böhm Michael , Baumhäkel Magnus , Mahfoud Felix , Werner Christian
Published: November 2010

Clinical trials have shown the efficacy of angiotensin II receptor blockers (ARBs) in patients with hypertension and have suggested that ARBs are noninferior to angiotensin-converting enzyme (ACE) inhibitors in patients with ischemic heart disease and heart failure. The Heart Outcomes Prevention Evaluation (HOPE), a landmark study in high cardiovascular risk management, demonstrated the cardioprotection of the ACE inhibitor ramipril. Thus, in the recent Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET®) ramipril was selected as a comparator when exploring the cardioprotective potential of telmisartan in the first head-to-head comparison of an ACE inhibitor and an ARB in a broad cross-sectional cohort of cardiovascular high-risk patients. ONTARGET showed that telmisartan is as effective as ramipril in the management of these patients but is better tolerated. The combination of ramipril and telmisartan did not confer a further benefit but did bring about an increased rate of adverse events such as renal dysfunction. In previous ARB outcome trials, cardiovascular risk profile, nature and severity of the underlying cardiovascular disease, dosing regimens and concomitant therapies, follow-up, and endpoints have varied greatly so that caution is warranted in extrapolating evidence gained from high-risk patients to other conditions such as acute myocardial infarction or chronic heart failure.
Localization of Progenitor/Stem Cells in the Human Tympanic Membrane
Authors: Knutsson Johan , von Unge Magnus , Rask-Andersen Helge
Published: November 2010

Background: The outer epithelium of the tympanic membrane (TM) initiates the closure of a perforation. Embryonic stem cells have been used in attempts to enhance the healing capacity of induced perforations in experimental animals. More knowledge about epithelial cell proliferation and cell migration is needed for a better understanding of the TM healing process. This includes the identification of regenerative zones within the outer epithelial layer of the TM where progenitor cells may be present. Methods: Normal human TMs from translabyrinthine surgery were investigated using immunohistochemistry and immunofluorescence to detect the progenitor/stem cell markers α6-integrin, β1-integrin and cytokeratin 19 (CK19). Results: α6-Integrin was detected in the basal layer of the keratinizing epithelium in the umbo, in the annular region and along the malleus but not in the intermediate portion of the pars tensa. β1-Integrin and CK19 were found in the same locations not only in the basal layer but also in the suprabasal layers of the keratinizing epithelium. Conclusions: Possible progenitor cells are found in the umbo, the annular region and along the malleus. Further studies are needed to identify the source of these cells.
Acute Effects of Blood Transfusion on Growth Hormone and Insulin-Like Growth Factor-1 Levels in Children with Thalassemia
Authors: Mahachoklertwattana Pat , Yimsumruay Titiya , Poomthavorn Preamrudee , Chuansumrit Ampaiwan , Khlairit Patcharin
Published: November 2010

Background/Aim: Children with β-thalassemia have chronic anemia and growth retardation. Impaired growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis function has been demonstrated. Growth improvement has been demonstrated following optimal blood transfusion. Whether correction of anemia by blood transfusion augments GH-IGF-1 axis function has not been established. Methods: Twenty children with thalassemia aged 11.7 years (5.3–16.3 years) were recruited. GH provocative tests were performed twice, before and 1 week after blood transfusion. IGF-1, IGF-binding protein-3 (IGFBP-3) and hematocrit were measured. Results: Median IGF-1 and IGFBP-3 concentrations were significantly increased at 1 week following transfusion: pre- versus posttransfused concentrations: 86.4 versus 143.5 ng/ml (p < 0.001) and 2.95 versus 3.75 mg/l (p < 0.001), respectively. However, median peak GH levels and areas under the curve of GH during GH testing between pre- and posttransfusion periods were not different. The pretransfused hematocrit level was correlated with pretransfused IGF-1 (r = 0.662, p < 0.001) and IGFBP-3 (r = 0.691, p < 0.001) levels. Conclusions: In thalassemics, correction of anemia by blood transfusion rapidly enhanced GH-mediated IGF-1 and IGFBP-3 secretion. This suggests thatanemia may be one of the factors causing partial GH insensitivity.
Exposure to Secondhand Tobacco Smoke Enhances Respiratory Symptoms and Responses to Animals in 8,819 Children in Kindergarten: Results from 25 Districts in Northeast China
Authors: Dong Guang-Hui , Ren Wan-Hui , Wang Da , Yang Zong-Hua , Zhang Peng-Fei , Zhao Ya-Dong , He Qin-Cheng
Published: November 2010

Background: Experimental data suggest that asthma exacerbation by allergens is enhanced by exposure to environmental tobacco smoke (ETS); however, there is little supporting epidemiologic evidence. To our knowledge, few studies have assessed respiratory symptoms and allergies in this context. Objectives: To evaluate whether the association of exposure to animals (indicators of allergen and endotoxin exposure) with asthma-related symptoms is modified by ETS exposure in Chinese children. Methods: A cross-sectional study of 8,819 children in kindergarten was conducted in 25 districts in northern China. Information on respiratory health and exposure to indoor allergens was obtained using a standard questionnaire from the American Thoracic Society. Results: Among the children with ETS exposure in utero, the effects of exposure to animals were significant with respect to persistent cough [adjusted odds ratio (OR) 1.83; 95% confidence interval (CI) 1.12–2.99] and persistent phlegm (adjusted OR 2.40; 95% CI 1.28–4.54). The combined effect of in utero ETS exposure and animal exposure on doctor-diagnosed asthma was approximately as expected on the basis of their independent effects on an additive scale. There was no interaction between animal exposure and ETS exposure in the first 2 years of life or current ETS exposure. Conclusions: This study provides evidence that animal and ETS exposure increases the risk of asthma-related symptoms in children in kindergarten. ETS exposure in utero did modify the effect of animal exposure on persistent phlegm and persistent cough but not on doctor-diagnosed asthma among children.
Temporal updating during phonotaxis in male túngara frogs (Physalaemus pustulosus)
Authors: Baugh Alexander , Ryan Michael
Published: November 2010

In acoustically advertising anurans the male courtship call elicits species-typical responses from conspecifics – usually phonotactic approach and mate choice in gravid females and an evoked vocal response in adult males. Males in several species, however, are also known to perform phonotaxis, sometimes with the same acoustic preferences as females. Female túngara frogs are known to update their phonotactic approach as male advertisement signals change dynamically in attractiveness. Here we show that males also perform such temporal updating during phonotaxis in response to dynamic playbacks. While males exhibit slower phonotactic approaches than females, their responsiveness to dynamic changes in call complexity does not differ significantly compared to females. These results demonstrate that males are sensitive to the location of preferred call types on a moment-to-moment basis and suggest that similarities between male and female sexual behaviour in anurans might often be overlooked. We suggest that anuran phonotaxis is more widespread and serves different functions in reproductive females and males. Lastly, these temporal updating results suggest that male frogs are highly selective about site selection in a chorus.
Skeletochronological analysis of age structure in populations of four species of Malagasy poisonous frogs, genus Mantella
Authors: Jovanovic Olga , Vences Miguel
Published: November 2010

Age structure of populations of four species of endemic Malagasy frogs of the genus Mantella (M. aurantiaca, M. baroni, M. bernhardi, M. madagascariensis) was examined by skeletochronology based on 96 specimens from nine different localities. In more than half of these (57%), no lines of arrested growth (LAGs) were found, and the number of LAGs recognized in the remaining specimens was mostly one, and probably two in three specimens. It is generally considered that each LAG corresponds to one year of life; our results therefore confirm that in Mantella populations almost all specimens are in their first or second year of life.
Cohabitation patterns of the San Marcos salamander (Eurycea nana)
Authors: Thaker Maria , Gabor Caitlin , Fries Joe , Epp Kristen
Published: November 2010

Social interactions of conspecifics are a function of complex relationships involving resource defense, antipredatory tactics, and mate acquisition. Consequently, individuals often associate non-randomly with conspecifics in their habitats, with spatial distributions of adults ranging from territorial spacing to aggregations. Site tenacity and cohabitation patterns have been well studied in many species of terrestrial salamander; however, less is understood about these behaviors in aquatic species. We examined the cohabitation patterns of intrasexual and intersexual pairs of the federally threatened, paedomorphic San Marcos salamander (Eurycea nana) under artificial shelters in a laboratory setting over a 20-day period. We found that intrasexual female pairs and intersexual pairs were found cohabiting more often than intrasexual male pairs. We also assessed site tenacity by examining shelter affinity and found that both males and females inhabited one of the two shelters more often than expected from random habitation, regardless of whether they were in intersexual or intrasexual pairings. Our results indicate that although both sexes of Eurycea nana exhibit site affinity, the sex of individuals is an important determinant of cohabitation patterns.
Estimation of Near-Ground Propagation Conditions Using Radar Ground Echo Coverage
Authors: Park Shinju , Fabry Frédéric
Published: November 2010

The vertical gradient of refractivity (dN/dh) determines the path of the radar beam; namely, the larger the negative values of the refractivity gradient, the more the beam bends toward the ground. The variability of the propagation conditions significantly affects the coverage of the ground echoes and, thus, the quality of the scanning radar measurements. The information about the vertical gradient of refractivity is usually obtained from radiosonde soundings whose use, however, is limited by their coarse temporal and spatial resolution. Because radar ground echo coverage provides clues about how severe the beam bending can be, we have investigated a method that uses radar observations to infer propagation conditions with better temporal resolution than the usual soundings.

Using the data collected during the International H2O Project (IHOP_2002), this simple method has shown some skill in capturing the propagation conditions similar to these estimated from soundings. However, the evaluation of the method has been challenging because of 1) the limited resolution of the conventional soundings in time and space, 2) the lack of other sources of data with which to compare the results, and 3) the ambiguity in the separation of ground from weather echoes.
Using a Stochastic Kinetic Energy Backscatter Scheme to Improve MOGREPS Probabilistic Forecast Skill
Authors: Tennant Warren J. , Shutts Glenn J. , Arribas Alberto , Thompson Simon A.
Published: November 2010

An improved stochastic kinetic energy backscatter scheme, version 2 (SKEB2) has been developed for the Met Office Global and Regional Ensemble Prediction System (MOGREPS). Wind increments at each model time step are derived from a streamfunction forcing pattern that is modulated by a locally diagnosed field of likely energy loss due to numerical smoothing and unrepresented convective sources of kinetic energy near the grid scale. The scheme has a positive impact on the root-mean-square error of the ensemble mean and spread of the ensemble. An improved growth rate of spread results in a better match with ensemble-mean forecast error at all forecast lead times, with a corresponding improvement in probabilistic forecast skill from a more realistic representation of model error. Other examples of positive impact include improved forecast blocking frequency and reduced forecast jumpiness. The paper describes the formulation of the SKEB2 and its assessment in various experiments.
Stab and cut resistance of knitted structures: a comparative study
Authors: Alpyildiz Tuba , Rochery Maryline , Kurbak Arif , Flambard Xavier
Published: November 2010

A new double-face knitted structure has been developed which is composed of tuck stitches and has the same back and front faces. The newly derived structure, manufactured from p-aramid fibers with and without inlay yarns, has been compared with jersey and plush structures of these same fibers in terms of cut and stab performances. Not only have new structures been proposed, but the effect of the inlay yarns has been investigated also. In order to manufacture the plush structure on a V-bed Flat Knitting Machine instead of a traditional circular knitting machine a new design has been developed. The results show that the newly derived structure with inlay yarns has the best cut and stab performances when a comparison is made between samples of different structures with the same mass per unit area and thickness values.
Physical properties of the functional bamboo charcoal/stainless steel core-sheath yarns and knitted fabrics
Authors: Lin Jia-Horng , Chen An-Pang , Hsieh Chien-Teng , Lin Ching-Wen , Lin Chin-Mei , Lou Ching-Wen
Published: November 2010

In this study, bamboo charcoal/stainless steel (B/S) core-sheath yarns were made of stainless steel wires and bamboo charcoal polyester textured yarn using a rotor twister machine. The speed of rotor twister was from 7000 to 11000 rpm and the wrapped amount varied from 2 to 7 turns/cm. The tenacity of 3.08 g/d was obtained when the speed of rotor twister was 8000 rpm and wrapped amount was 4.0 turns/cm. The tensile strain of 24.9% was yielded when the speed of the rotor twister was 7000 rpm and the wrapped amount was 5.0 turns/cm. The laminated amount of the knitted fabrics varied from 1 to 6 layers. The far infrared ray emissivity of the knitted fabrics was 0.934 when the laminated amount was 2 layers and wrapped amount was 6 turns/cm. Finally, the optimum anion density of the knitted fabrics was 610 ions/cm3.
Towards global convergence: Emerging economies, the rise of China and western sunset?
Authors: Dunford Michael , Yeung Godfrey
Published: November 2010

The financial crisis indicates the underlying bankruptcy of the last of a series of attempts to restore sustained growth in advanced countries since the end of the post-war Golden Age: Italian flexible specialization, Japanese and Rhine-style lean production, the new economy and Anglo-American financialization. Over the same period a number of emerging economies and in particular China have sustained high rates of growth. In the years to come, developed country growth is likely to remain slow because no alternative high-growth model is on the horizon. A country such as China conversely has the potential to continue to grow relatively fast provided it can profoundly alter its model of development in ways that address global and national imbalances. If it and other large emerging economies do achieve further sustained growth, this will in effect reverse the gap created by industrial revolution, colonialism and imperialism. The aim of this paper is to explain the reasons for and the possibilities of such global convergence, paying particular attention to the reasons for and implications of the financial crisis and the extent to which China’s fiscal stimulus contributes to a new model of Chinese development.
Do Family Interventions Improve Health?
Authors: Chesla Catherine A.
Published: November 2010

The central aim of this article is to examine the evidence that family interventions improve health in persons with chronic illness and their family members, across the life span. The review focuses on recent meta-analyses of randomized controlled trials of family intervention research. In adults, evidence supports the salutary effects of family interventions versus usual medical care for patient health and mental health, and for family member health. In children, robust evidence supports family-based multimodal interventions for obesity treatment. Reasonable evidence supports family approaches to type 1 diabetes treatment in children. Nurses led the research or were members of interdisciplinary research teams in several of these literatures, representing one quarter to one third of the research cited, but were absent in other literatures, such as family treatment of childhood obesity.
Bound to follow? The Anglosphere and US-led coalitions of the willing, 1950–2001
Authors: Vucetic Srdjan
Published: November 2010

This article addresses the question whether membership in the ‘Anglosphere’ — a grouping of English-speaking states/nations — impacts the likelihood of participation in US-led coalitions of the willing. I translate the Anglosphere into International Relations (IR) theory using a tripartite division of realism, liberalism and constructivism. In a quantitative empirical analysis of a sample of US-led military coalitions between 1950 and 2001, I find robust evidence of what can be seen as the Anglosphere effect: all else constant, English-speaking states/nations tend to be more willing to join US-led military coalitions than states/nations selected at random. I conclude with a discussion of future research avenues in the Anglosphere agenda in IR.
Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers
Authors: Pillozzi Serena , Masselli Marika , De Lorenzo Emanuele , Accordi Benedetta , Cilia Emanuele , Crociani Olivia , Amedei Amedeo , Veltroni Marinella , D'Amico Massimo , Basso Giuseppe , Becchetti Andrea , Campana Dario , Arcangeli Annarosa
Published: November 2010

Bone marrow mesenchymal cells (MSCs) can protect leukemic cells from chemotherapy, thus increasing their survival rate. We studied the potential molecular mechanisms underlying this effect in acute lymphoblastic leukemia (ALL) cells. Coculture of ALL cells with MSCs induced on the lymphoblast plasma membrane the expression of a signaling complex formed by hERG1 (human ether-à-go-go-related gene 1) channels, the β1-integrin subunit, and the chemokine receptor CXC chemokine receptor-4. The assembly of such a protein complex activated both the extracellular signal-related kinase 1/2 (ERK1/2) and the phosphoinositide 3-kinase (PI3K)/Akt prosurvival signaling pathways. At the same time, ALL cells became markedly resistant to chemotherapy-induced apoptosis. hERG1 channel function appeared to be important for both the initiation of prosurvival signals and the development of drug resistance, because specific channel blockers decreased the protective effect of MSCs. NOD/SCID mice engrafted with ALL cells and treated with channel blockers showed reduced leukemic infiltration and had higher survival rates. Moreover, hERG1 blockade enhanced the therapeutic effect produced by corticosteroids. Our findings provide a rationale for clinical testing of hERG1 blockers in the context of antileukemic therapy for patients with ALL.
Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia
Authors: Shanafelt Tait D. , Drake Matthew T. , Maurer Matthew J. , Allmer Cristine , Rabe Kari G. , Slager Susan L. , Weiner George J. , Call Timothy G. , Link Brian K. , Zent Clive S. , Kay Neil E. , Hanson Curtis A. , Witzig Thomas E. , Cerhan James R.
Published: November 2010

Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratio[HR] = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.
Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia
Authors: Akech Samuel O , Karisa Japhet , Nakamya Phellister , Boga Mwanamvua , Maitland Kathryn
Published: November 2010

Background

Children with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution.

Methods

A Phase II randomised controlled, safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock (non-diarrhoeal shock). Eligible children were randomised to HSD/5D or Ringer's Lactate (RL). A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours (as recommended by guidelines) while those randomised to RL received 10 ml/kg aliquots half hourly (maximum 40 ml/kg). Primary endpoint was resolution of shock at 8 and 24 hours. Secondary outcomes included resolution of acidosis, adverse events and mortality.

Results

61 children were enrolled: 41 had shock and severe dehydrating diarrhoea, 20 had presumptive septic shock; 69% had decompensated shock. By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 (68%) and RL14/25 (52%), p = 0.39. Oliguria was more prevalent at 8 hours in the HSD/5D group, 9/22 (41%), compared to RL-3/25 (12%), p = 0.02. Mortality was high, HSD/5D-15/26(58%) and RL 13/29(45%); p = 0.42. Most deaths occurred within 48 hours of admission. Neither pulmonary oedema nor cardiogenic failure was detected.

Conclusions

Outcome was universally poor characterised by persistence of shock, oliguria and high case fatality. Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy. Although isotonic fluid resuscitation did not result in cardiogenic heart failure, as previously feared, we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock. The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock, defining rate and volumes required to inform future guidelines.

Trial Registration

The trial is registered as ISCRTN: 61146418
Retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus A16 circulated wildly in central and southern China before large-scale outbreaks from 2008
Authors: Zhu Zhen , Zhu Shuangli , Guo Xuebin , Wang Jitao , Wang Dongyan , Yan Dongmei , Tan Xiaojuan , Tang Liuying , Zhu Hui , Yang Zhaohui , Jiang Xiaohong , Ji Yixin , Zhang Yong , Xu Wenbo
Published: November 2010

Background

Large nationwide outbreaks of hand, foot, and mouth disease (HFMD) occurred in China from 2008; most of the cases were in children under 5 years. This study aims to identify the situation of natural human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) infections in children before 2008 in China.

Results

Retrospective seroepidemiologic studies of HEV71 and CVA16 were performed with 900 serum samples collected from children ≤5 years of age in 2005. The samples were collected from 6 different geographical areas (Anhui, Guangdong, Hunan, Xinjiang, Yunnan, and Heilongjiang provinces) in mainland China. Of the 900 samples, 288 were positive for HEV71; the total positive rate was 32.0% and the geometric mean titer (GMT) was 1:8.5. Guangdong (43.7% and 1:10.8), Xinjiang (45.4% and 1:11.1), and Yunnan (43.4% and 1:12.0) provinces had relatively high rates of infection, while Heilongjiang province (8.1% and 1:4.9) had the lowest rate of infection. On the other hand, 390 samples were positive for CVA16; the total positive rate was 43.4% and the GMT was 1:9.5. Anhui (62.2% and 1:16.0) and Hunan (61.1% and 1:23.1) had relatively high rates, while Heilongjiang (8.0% and 1:4.6) had the lowest rate. Although there is a geographical difference in HEV71 and CVA16 infections, low neutralizing antibody positive rate and titer of both viruses were found in all 6 provinces.

Conclusions

This report confirmed that HEV71 and CVA16 had wildly circulated in a couple provinces in China before the large-scale outbreaks from 2008. This finding also suggests that public health measures to control the spread of HEV71 and CVA16 should be devised according to the different regional characteristics.
Unilateral or bilateral V-Y fasciocutaneous flaps for the coverage of soft tissue defects following total knee arthroplasty
Authors: Papaioannou Konstantinos , Lallos Stergios , Mavrogenis Andreas , Vasiliadis Elias , Savvidou Olga , Efstathopoulos Nikolaos
Published: November 2010

Background

Soft tissue necrosis following total knee arthroplasty (TKA) may be the cause of the devastating complication of deep infection. It necessitates an immediate operative intervention because it could potentially jeopardise the arthroplasty or even the limb.

Methods

Sixteen consecutive patients with a mean age of 73,8 years (range 47 to76 years) over a 6-year period (January 2003 to December 2008) with wound dehiscence after TKA were enrolled in the present study. Unilateral or bilateral fasciocutaneous V-Y flaps that are differently oriented, depending on the local conditions of the tissues were used to reconstruct the soft tissues defects.

Results

In 15 of the 16 cases studied, the wound was successfully covered with the presented technique while in 1 patient a partial flap loss occurred, which was healed after surgical debridement and the application of vacuum system. No other complications occurred. Knee prosthesis was salvaged in all the patients with a good functional and esthetical outcome.

Conclusions

The presented reconstructive technique is a simple, quick, versatile and reliable solution for the coverage of soft tissue defects following TKA, more than 2 cm width and grade 1 and 2 according to Laing classification, provided the V-Y flaps are applied early in the postoperative period and no complex defects are involved.
CD4+ T cell reconstitution, T cell activation, and memory T cell subset composition in blood and gut of HIV‐negative and ART‐suppressed HIV‐positive patients: implications for HIV persistence in the gut
Authors: Yukl S , Sinclair E , Epling L , Li Q , Shergill A , McQuaid K , Duan L , Hare B , Lampiris H , Haase A , Havlir D , Wong J
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
LEDGF/p75 is critical but not essential for multiple‐round HIV 1 replication
Authors: Schrijvers RLG , De Rijck J , Gijsbers R , Ronen K , Bushman FD , Debyser Z
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
Effect of 24 weeks of intensification with a CCR5‐antagonist on the decay of the HIV‐1 latent reservoir
Authors: Díaz L , Gutiérrez C , Page C , Lorente R , Hernández‐Novoa B , Vallejo A , Domínguez E , Abad M , Madrid N , Moreno A , Pérez‐Elías MJ , Rubio R , Muñoz‐Fernández MA , Moreno S
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
Epigenetic drug Gar1041 in combination with antiretroviral therapy transiently reduces the proviral DNA reservoir in SIVmac251‐infected macaques
Authors: Lewis MG , Norelli S , Chomont N , De Fonseca S , Sgarbanti M , Collins M , Chirullo B , Yalley‐Ogunro J , Greenhouse J , Palamara AT , Garaci E , Savarino A
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
Homeostatic proliferation of memory T cells and expansion of the HIV‐1 latent reservoir
Authors: Bosque A , Planelles V
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
The role of the ubiquitin‐proteasome pathway in rhTRIM5α restriction of HIV‐1
Authors: Danielson CM , Hope TJ
Published: November 2010

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria
Sex-specific modification of progesterone receptor expression by 17β-oestradiol in human cardiac tissues
Authors: Kararigas Georgios , Becher Eva , Mahmoodzadeh Shokoufeh , Knosalla Christoph , Hetzer Roland , Regitz-Zagrosek Vera
Published: November 2010

Background

Although circulating levels of sexual hormones in elderly men and women are low and quite similar, the adaptation of the elderly heart to stress differs between the sexes. We have hypothesized that the effects of sexual hormones in the heart may differ in men and women. Here, we assessed whether 17β-oestradiol regulates gene expression in the human heart in a sex-dependent manner. We selected the progesterone receptor as a well studied 17β-oestradiol target that may be pathologically linked to cardiac remodelling.

Methods

In order to assess the ex vivo effects of 17β-oestradiol in intact human cardiac tissues, we developed a 24-h model for the culture of human atrial myocardium. We verified tissue viability after 24 h in culture with two standard assays to determine the degree of apoptosis and metabolic activity of cardiac tissues. Progesterone receptor mRNA and protein level were measured after 24-h treatment of tissues with 17β-oestradiol. Statistical analysis was performed by the Mann-Whitney U test and two-way ANOVA.

Results

We established a tissue culture model that allows for the study of viable human cardiac tissue over a 24-h period. After 24 h, cultured cardiac tissues revealed low apoptosis, retained their metabolic activity and, therefore, remained viable. Treatment with 17β-oestradiol led to an induction of the progesterone receptor mRNA level in female (P = 0.001) but not in male tissues. Similarly, there was an increase in the level of progesterone receptor protein in female tissues (P = 0.03), while a decreasing trend was observed in male tissues (P = 0.079) exposed to 17β-oestradiol.

Conclusions

Our novel finding may offer a molecular explanation for the sex-specific differences observed in cardiac remodelling. The culture model we established for human cardiac tissue will facilitate the study of cellular processes in health and disease and will be of use for pharmacological testing.
Collaborative effects of bystander-initiated cardiopulmonary resuscitation and prehospital advanced cardiac life support by physicians on survival of out-of-hospital cardiac arrest: a nationwide population-based observational study
Authors: Yasunaga Hideo , Horiguchi Hiromasa , Tanabe Seizan , Akahane Manabu , Ogawa Toshio , Koike Soichi , Imamura Tomoaki
Published: November 2010

Introduction

There are inconsistent data about the effectiveness of prehospital physician-staffed advanced cardiac life support (ACLS) on the outcomes of out-of-hospital cardiac arrest (OHCA). Furthermore, the relative importance of bystander-initiated cardiopulmonary resuscitation (BCPR) and ACLS and the effectiveness of their combination have not been clearly demonstrated.

Methods

Using a prospective, nationwide, population-based registry of all OHCA patients in Japan, we enrolled 95,072 patients whose arrests were witnessed by bystanders and 23,127 patients witnessed by emergency medical service providers between 2005 and 2007. We divided the bystander-witnessed arrest patients into Group A (ACLS by emergency life-saving technicians without BCPR), Group B (ACLS by emergency life-saving technicians with BCPR), Group C (ACLS by physicians without BCPR) and Group D (ACLS by physicians with BCPR). The outcome data included 1-month survival and neurological outcomes determined by the cerebral performance category.

Results

Among the 95,072 bystander-witnessed arrest patients, 7,722 (8.1%) were alive at 1 month, including 2,754 (2.9%) with good performance and 3,171 (3.3%) with vegetative status or worse. BCPR occurred in 42% of bystander-witnessed arrests. In comparison with Group A, the rates of good-performance survival were significantly higher in Group B (odds ratio (OR), 2.23; 95% confidence interval, 2.05 to 2.42; P < 0.01) and Group D (OR, 2.80; 95% confidence interval, 2.28 to 3.43; P < 0.01), while no significant difference was seen for Group C (OR, 1.18; 95% confidence interval, 0.86 to 1.61; P = 0.32). The occurrence of vegetative status or worse at 1 month was highest in Group C (OR, 1.92; 95% confidence interval, 1.55 to 2.37; P < 0.01).

Conclusions

In this registry-based study, BCPR significantly improved the survival of OHCA with good cerebral outcome. The groups with BCPR and ACLS by physicians had the best outcomes. However, receiving ACLS by physicians without preceding BCPR significantly increased the number of patients with neurologically unfavorable outcomes.
Minireview: Steroid Receptor Coactivator-3: A Multifarious Coregulator in Mammary Gland Metastasis
Authors: Lydon John P. , O'Malley Bert W.
Published: November 2010

A member of the steroid receptor coactivator (SRC)/p160 family, SRC-3 acts as a coregulator for nuclear receptor (NR) and non-NR transcription factors. Such coregulator pleiotropy enables SRC-3 to influence a myriad of signaling networks that are essential for normal physiology and pathophysiology. Although SRC-3’s proliferative role in primary tumor formation in the mammary gland is well established, a role for this oncogenic coregulator in tumor cell motility and invasion has only recently been elucidated. In the nucleus, SRC-3 is required for the execution of the epithelial–mesenchymal transition, a programming step which endows an immotile cancer cell with motile and invasive characteristics. Nuclear SRC-3 is also essential for proteolytic breakdown of the extracellular matrix by matrix-metalloproteinases, a process which enables primary tumor cell invasion into the surrounding stroma. At the plasma membrane, however, a truncated isoform of SRC-3 (SRC-3Δ4) serves as a signaling adaptor for the epidermal growth factor→focal adhesion kinase→c-Src signal transduction pathway, a signaling cascade that is central to growth factor–induced cell migration and invasion. Together, these studies underscore a pivotal role for SRC-3 not only as a proto-oncogene but also as a prometastatic factor during the early steps in the invasion-metastasis cascade. Beyond furnishing critical mechanistic insights into SRC-3’s involvement in mammary tumor progression, these findings provide opportunities to develop new approaches for breast cancer diagnosis and intervention.