tbuckley/cabot-search huggingface dataset:
International variations in associations of allergic markers and diseases in children: ISAAC Phase Two
Authors: G. Weinmayr, J. Genuneit, G. Nagel, B. Björkstén, M. Van Hage, A. Priftanji, P. Cooper, M.‐A. Rijkjärv, E. Von Mutius, J. Tsanakas, F. Forastiere, G. Doekes, J. B. Garrido, M. M. Suarez‐Varela, L. Bråbäck, D. P. Strachan
Journal: Allergy (2009)

To cite this article: Weinmayr G, Genuneit J, Nagel G, Björkstén B, van Hage M, Priftanji A, Cooper P, Rijkjärv M‐A, von Mutius E, Tsanakas J, Forastiere F, Doekes G, Garrido JB, Suarez‐Varela MM, Bråbäck L, Strachan DP, the ISAAC Phase Two Study Group. International variations in associations of allergic markers and diseases in children: ISAAC Phase Two. Allergy 2010; 65 : 766–775. Abstract Background: Circulating allergen‐specific IgE (sIgE) and skin prick tests (SPT) are used to define atopy. Downregulation of local inflammatory responsiveness has been proposed to explain a low prevalence of positive SPTs in less affluent countries. We analysed the association between SPTs, total and allergen‐specific IgE and their relationships to allergic symptoms in centres with diverse living conditions. Methods: Cross‐sectional studies of stratified random samples of 8 to 12‐year‐old children ( n = 7461) used the standardized methodology of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema were ascertained by parental questionnaires. Skin examination, hypertonic saline bronchial challenge, six aeroallergen SPTs and measurements of serum total IgE and sIgE were performed. Results: In nonaffluent countries, a higher proportion of children with positive SPT had no detectable sIgE (range 37–61%) than in affluent countries (0–37%). Total serum IgE was associated with all disease outcomes among children with both positive SPT and sIgE ( P &lt; 0.001), but only with self‐reported eczema in children with negative SPTs and negative sIgE. Conclusions: The international pattern of discordance between SPT and sIgE results did not support the downregulation hypothesis. Among children with no evidence of sensitization to common aeroallergens, increased total IgE contributes little to the risk of wheeze and rhinitis in the general population but may play a role in eczema.
Spark-Induced Sparks As a Mechanism of Intracellular Calcium Alternans in Cardiac Myocytes
Authors: Robert Rovetti, Xiaohua Cui, Alan Garfinkel, James N. Weiss, Zhilin Qu
Journal: Circulation Research (2010)

Intracellular calcium (Ca) alternans has been widely studied in cardiac myocytes and tissue, yet the underlying mechanism remains controversial.In this study, we used computational modeling and simulation to study how randomly occurring Ca sparks interact collectively to result in whole-cell Ca alternans.We developed a spatially distributed intracellular Ca cycling model in which Ca release units (CRUs) are locally coupled by Ca diffusion throughout the myoplasm and sarcoplasmic reticulum (SR) network. Ca sparks occur randomly in the CRU network when periodically paced with a clamped voltage waveform, but Ca alternans develops as the pacing speeds up. Combining computational simulation with theoretical analysis, we show that Ca alternans emerges as a collective behavior of Ca sparks, determined by 3 critical properties of the CRU network from which Ca sparks arise: "randomness" (of Ca spark activation), "refractoriness" (of a CRU after a Ca spark), and "recruitment" (Ca sparks inducing Ca sparks in adjacent CRUs). We also show that the steep nonlinear relationship between fractional SR Ca release and SR Ca load arises naturally as a collective behavior of Ca sparks, and Ca alternans can occur even when SR Ca is held constant.We present a general theory for the mechanisms of intracellular Ca alternans, which mechanistically links Ca sparks to whole-cell Ca alternans, and is applicable to Ca alternans in both physiological and pathophysiological conditions.
Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia/reperfusion in rats
Authors: J. E. Baker, J. Su, A. Hsu, Y. Shi, M. Zhao, J. L. Strande, X. Fu, H. Xu, A. Eis, R. Komorowski, E. S. Jensen, J. S. Tweddell, P. Rafiee, G. J. Gross
Journal: Cardiovascular Research (2007)

AimsThrombopoietin (Tpo) is known for its ability to stimulate platelet production. However, it is currently unknown whether Tpo plays a physiological function in the heart.
Allogeneic hematopoietic stem cell transplantation for myelofibrosis
Authors: H. Joachim Deeg, Theodore A. Gooley, Mary E. D. Flowers, George E. Sale, John T. Slattery, Claudio Anasetti, Thomas R. Chauncey, Kristine Doney, George E. Georges, Hans-Peter Kiem, Paul J. Martin, Effie W. Petersdorf, Jerald Radich, Jean E. Sanders, Brenda M. Sandmaier, E. Houston Warren, Robert P. Witherspoon, Rainer Storb, Frederick R. Appelbaum
Journal: Blood (2003)
Evidence for Homologous Recombination in Intracellular Chemosynthetic Clam Symbionts
Authors: F. J. Stewart, C. R. Young, C. M. Cavanaugh
Journal: Molecular Biology and Evolution (2009)

Homologous recombination is a fundamental mechanism for the genetic diversification of free-living bacteria. However, recombination may be limited in endosymbiotic bacteria, as these taxa are locked into an intracellular niche and may rarely encounter sources of foreign DNA. This study tested the hypothesis that vertically transmitted endosymbionts of deep-sea clams (Bivalvia: Vesicomyidae) show little or no evidence of recombination. Phylogenetic analysis of 13 loci distributed across the genomes of 14 vesicomyid symbionts revealed multiple, well-supported inconsistencies among gene tree topologies, and maximum likelihood–based tests rejected a hypothesis of shared evolutionary history (linkage) among loci. Further, multiple statistical methods confirmed the presence of recombination by detecting intragenic breakpoints in two symbiont loci. Recombination may be confined to a subset of vesicomyid symbionts, as some clades showed high levels of genomic stability, whereas others showed clear patterns of homologous exchange. Notably, a mosaic genome is present in symB, a symbiont lineage shown to have been acquired laterally (i.e., nonvertically) by Vesicomya sp. JdF clams. The majority of loci analyzed here supported a tight sister clustering of symB with the symbiont of a host species from the Mid-Atlantic Ridge, whereas others placed symB in a clade with symA, the dominant phylotype of V. sp. JdF clams. This result raises the hypothesis that lateral symbiont transfer between hosts may facilitate recombination by bringing divergent symbiont lineages into contact. Together, the data show that homologous recombination contributes to the diversification of vesicomyid clam symbionts, despite the intracellular lifestyle of these bacteria.
Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort
Authors: R. Cathomas, D. Klingbiel, T.R. Geldart, G.M. Mead, S. Ellis, M. Wheater, P. Simmonds, N. Nagaraj, R. von Moos, M. Fehr
Journal: Annals of Oncology (2014)
Serum Amyloid A, C-Reactive Protein, and Retinal Microvascular Changes in Hypertensive Diabetic and Nondiabetic Individuals
Authors: Christoph Stettler, Nicholas Witt, Robyn J. Tapp, Simon Thom, Sabin Allemann, Therese Tillin, Alice Stanton, Eoin O'Brien, Neil Poulter, J. Ruth Gallimore, Alun D. Hughes, Nish Chaturvedi
Journal: Diabetes Care (2009)

To study the association of the inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) with retinal microvascular parameters in hypertensive individuals with and without type 2 diabetes.This cross-sectional analysis was a substudy in 711 patients (159 with and 552 without diabetes) of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) based on digital 30-degree images of superior and inferior temporal retinal fields.SAA was associated with arteriolar length-to-diameter ratio positively in nondiabetic patients (P(trend)= 0.028) but negatively in diabetic patients (P(trend)= 0.005). The difference was unlikely to be a chance finding (P = 0.007 for interaction). Similar results were found for the association of SAA with arteriolar tortuosity (P = 0.05 for interaction). Associations were less pronounced for CRP and retinal parameters.Inflammatory processes are differentially involved in retinal microvascular disease in diabetic compared with nondiabetic hypertensive individuals.
Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes.
Authors: C Fernandez, G Möller
Journal: The Journal of Experimental Medicine (1978)

Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.
Efficacy and Safety of Ibandronate in the Treatment of Opioid-Resistant Bone Pain Associated With Metastatic Bone Disease: A Pilot Study
Authors: Isabelle Mancini, Jean-Claude Dumon, Jean-Jacques Body
Journal: Journal of Clinical Oncology (2004)

Bone metastases are associated with severe and sometimes intractable pain, compromising patient quality of life (QOL). This open-label pilot study investigated the effects of short-term intensive treatment with intravenous (i.v.) ibandronate on opioid-resistant bone pain in patients with skeletal metastases.Eighteen patients with advanced tumors and metastatic bone disease received nonstandard treatment with 4 mg of ibandronate administered i.v. (2-hour infusion) for 4 consecutive days (16-mg total dose). Baseline opioid analgesic use was equivalent to 400 mg/d of morphine. Patients were assessed for 6 weeks or until death. Changes from baseline were determined for bone pain, opioid consumption, patient functioning, QOL, performance status, and biochemical markers of calcium metabolism and bone turnover. Renal function was assessed by serum urea and creatinine measurement.Short-term, intensive ibandronate treatment significantly reduced bone pain scores within 7 days (P <.001). Pain reductions were sustained over the study period. Ibandronate significantly improved QOL, patient functioning, and performance status (P <.05). Mean values of the urinary cross-links pyridinoline and deoxypyridinoline tended to increase after day 21, returning close to baseline values by day 42. There was no correlation between the change in crosslinks values and the change in pain scores after ibandronate treatment. Ibandronate was well tolerated, with no evidence of renal toxicity.Nonstandard, intensive treatment with i.v. ibandronate seems to have a marked analgesic effect in patients with opioid-resistant bone pain from metastatic bone disease. Further investigation is warranted.
In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction
Authors: Dara L. Kraitchman, Alan W. Heldman, Ergin Atalar, Luciano C. Amado, Bradley J. Martin, Mark F. Pittenger, Joshua M. Hare, Jeff W.M. Bulte
Journal: Circulation (2003)

We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model.Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16x107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals.MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.
Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial
Authors: Shinjini Bhatnagar, Nitya Wadhwa, Satinder Aneja, Rakesh Lodha, Sushil Kumar Kabra, Uma Chandra Mouli Natchu, Halvor Sommerfelt, Ashok Kumar Dutta, Jagdish Chandra, Bimbadhar Rath, Mamta Sharma, Vinod Kumar Sharma, Mohini Kumari, Tor A Strand
Journal: The Lancet (2012)
Acute exacerbation of idiopathic pulmonary fibrosis
Authors: R. Dallari, M. Foglia, M. Paci, A. Cavazza
Journal: European Respiratory Journal (2004)

Background IV Aminophylline is commonly used in patients presenting with acute exacerbations of COPD (AECOPD). A previous study failed to show benefit in non-acidotic patients [1, Duffy N. et al. Thorax 2005, 60(9):713-7] albeit showing improvements in pH and pCO2. Side effects of methylxanthines are common and potentially serious. Aim We aimed to evaluate the use and side-effects of IV aminophylline in AECOPD presenting with acidotic T2RF who also received NIV. Methods Prospective data collected on 24 patients admitted to the Royal Liverpool Hospital with acidotic AECOPD. Results 20/24 (83%) were current or ex-smokers with Mean (SD) 43 (32) pack years. Mean [SD] pH 7.22 [0.10]. 12 (50%) patients were previously on oral theophylline. IV aminophylline was commenced in the emergency department in 62.5%. Only 14 (58.3%) patients were weighed prior to maintenance dose prescription. 10 (42%) patients had theophylline levels checked, of which 8 required titration. Mean (SD) duration of infusion was 2.7 [2.2] days. In 7 patients (29.1%), infusion was stopped due to side effects. Mean (SD) duration of NIV was 1.7 (1.3) days and mean (SD) length of stay 13.4 [10.5] days. 5 (20%) patients died during admission; 1 due to acute coronary syndrome where Aminophylline may have been contributary. Discussion The role for IV aminophylline in AECOPD is not clear, although current guidance allows its use [2, NICE CG 101, June 2010]. IV aminophylline requires careful titration and monitoring which does not always happen and may lead to adverse effects. Further evidence of benefit, especially in acidotic AECOPD is required.
Noninvasive ventilation in chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis
Authors: J.A. Wedzicha, J-F. Muir
Journal: European Respiratory Journal (2002)

Although long-term oxygen therapy (LTOT) improves survival, it has little effect on hypoventilation and other outcomes in patients with hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD). Recent studies have shown that the use of noninvasive positive-pressure ventilation, when used in combination with LTOT in selected stable COPD patients, controls hypoventilation and improves daytime arterial blood gases, sleep quality, health status and may have a benefit in reducing exacerbation frequency and severity. Patients who show the greatest reduction in overnight carbon dioxide tension in arterial blood with ventilation are most likely to benefit from long-term ventilatory support. Some benefits have also been shown in patients with chronic respiratory failure due to bronchiectasis and cystic fibrosis, though survival is inferior in this patient group. As most studies of noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease have been relatively short term, large multicentre studies with survival, exacerbations and hospital admissions as the primary end points are required to evaluate longer term effects.
Contribution of individual superficial nephron segments to ammonium handling in chronic metabolic acidosis in the rat. Evidence for ammonia disequilibrium in the renal cortex.
Authors: E Simon, D Martin, J Buerkert
Journal: Journal of Clinical Investigation (1985)

Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled. As anticipated, the ammonium concentration (TFNH+4) was significantly higher in proximal tubule fluid during acidosis, and ammonium delivery to end proximal sites increased from 19.4 +/- 2.3 to 34.0 +/- 3.2 pmol/min (P less than 0.001). Although chronic acidosis did not affect TFNH+4 at the beginning of the distal tubule, ammonium delivery to the end of the distal tubule increased from 5.72 +/- 0.97 to 9.88 +/- 0.97 pmol/min. In both control and acidotic groups ammonium delivery was lower (P less than 0.001) to end distal sites than to end proximal sites, indicating net loss in the intervening segment. This loss was greater during chronic metabolic acidosis (23.9 +/- 3.3 vs. 13.6 +/- 2.0 pmol/min in controls, P less than 0.025). In both groups net entry of ammonia, in similar amounts, occurred along the distal tubule (P less than 0.05). In situ pH averaged 6.80 +/- 0.05 at end proximal tubule sites and fell to 6.54 +/- 0.08 at the beginning of the distal tubule (P less than 0.005). Chronic metabolic acidosis did not affect these measurements. The calculated free ammonia at the end of the proximal tubule rose from 9.3 +/- 2.2 to 21 +/- 9 microM (P less than 0.005) during chronic metabolic acidosis, and was also higher at beginning distal sites during acidosis (8.8 +/- 2.4 vs. 2.7 +/- 0.7 microM in controls, P less than 0.05). In both groups ammonia values for the beginning distal tubule fluid were lower than for end proximal tubule fluid. Thus, loss of ammonium in the loop segment is enhanced by chronic metabolic acidosis. Distal entry of ammonia is markedly less than along the proximal tubule and does not change in chronic metabolic acidosis, and ammonia permeabilities for the proximal and distal segments of surface nephrons seem different.
Characterization of the 4C8 Antigen Involved in Transendothelial Migration of CD26hi T Cells after Tight Adhesion to Human Umbilical Vein Endothelial Cell Monolayers
Authors: Jun-ichi Masuyama, Taku Yoshio, Kenichi Suzuki, Seiichi Kitagawa, Masahiro Iwamoto, Takeshi Kamimura, Daisuke Hirata, Akira Takeda, Shogo Kano, Seiji Minota
Journal: The Journal of Experimental Medicine (1999)

In extravasation of T cells, little is known about the mechanisms of transendothelial migration subsequent to the T cells' tight adhesion to endothelium. To investigate these mechanisms, we developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26–expressing (CD26hi) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. Anti-4C8 reacted with all CD3+ T cells and monocytes but not neutrophils or HUVECs. The structure defined by this antibody was an 80-kD molecule. The mAb at 1 μg/ml inhibited 80–90% of migration of CD3+ T cells through unstimulated and interferon γ–stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase–contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 μg/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26hi. Second, solid-phase–immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26hi T cells when added to T cells at a high dose of 10 μg/ml. Finally, both anti-4C8–induced chemokinetic migration and transendothelial migration were inhibited by pretreatment of T cells with pertussis toxin. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26hi cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26hi cells adherent to HUVECs.
Systems medicine and the integration of bioinformatic tools for the diagnosis of alzheimer's disease
Authors: Matej Orešič, Jyrki Lötjönen, Hilkka Soininen
Journal: Genome Medicine (2010)

Because of the changes in demographic structure, the prevalence of Alzheimer's disease is expected to rise dramatically over the next decades. The progression of this degenerative and terminal disease is gradual, with the subclinical stage of illness believed to span several decades. Despite this, no therapy to prevent or cure Alzheimer's disease is currently available. Early disease detection is still important for delaying the onset of the disease with pharmacological treatment and/or lifestyle changes, assessing the efficacy of potential therapeutic agents, or monitoring disease progression more closely using medical imaging. Sensitive cerebrospinal-fluid-derived marker candidates exist, but given the invasiveness of sample collection their use in routine diagnostics may be limited. The pathogenesis of Alzheimer's disease is complex and poorly understood. There is thus a strong case for integrating information across multiple physiological levels, from molecular profiling (metabolomics, lipidomics, proteomics and transcriptomics) and brain imaging to cognitive assessments. To facilitate the integration of heterogeneous data, such as molecular and image data, sophisticated statistical approaches are needed to segment the image data and study their dependencies on molecular changes in the same individuals. Molecular profiling, combined with biophysical modeling of molecular assemblies associated with the disease, offer an opportunity to link the molecular pathway changes with cell- and tissue-level physiology and structure. Given that data acquired at different levels can carry complementary information about early Alzheimer's disease pathology, it is expected that their integration will improve early detection as well as our understanding of the disease.