tbuckley/cabot-search huggingface dataset:
Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies
Authors: Li Xuan, Fen Huang, Zhiping Fan, Hongsheng Zhou, Xian Zhang, Guopan Yu, Yu Zhang, Can Liu, Jing Sun, Qifa Liu
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Intensified conditioning regimens (increasing the intensity of standard myeloablative conditioning) for hematological malignancies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) could reduce the relapse rate of the underlying disease, but it might simultaneously increase the transplant-related mortality including the mortality of infections. To explore whether intensified conditioning affected Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, 185 patients undergoing allo-HSCT were enrolled. Methods A total of 104 cases received standard and 81 intensified conditioning. Cyclosporine A (CsA) withdrawal and/or donor lymphocyte infusion (DLI) were conducted in high-risk patients. The EBV-DNA and CMV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR) and immune reconstitution of recipients were analyzed by flow cytometry. Results The 3-year cumulative incidence of EBV viremia, EBV-associated diseases and mortality of EBV-associated diseases were 25.3% ± 4.6%, 10.5% ± 3.4% and 0.0% ± 0.0% in the standard group, compared with 45.6% ± 6.5%, 26.0% ±5.3% and 7.3% ± 3.1% in the intensified group ( P = 0.002, P = 0.002, P = 0.008). The 3-year cumulative incidence of CMV viremia and CMV-associated diseases, mortality of CMV-associated diseases and incidence of bacterial and fungal infections were similar between the two groups ( P = 0.855, P = 0.581, P = 0.933, P = 0.142, P = 0.182, respectively). Multivariate analysis showed that intensified conditioning was one of the risk factors for EBV viremia and EBV-associated diseases ( P = 0.037, P = 0.037), but it had no effects on CMV infections. The percentage of CD4 + T cells and CD4 + /CD8 + ratio at 3 months post-transplantation were lower in the intensified group ( P = 0.032, P = 0.022). The 3-year OS and DFS in the standard group were 62.2% ± 5.8% and 60.6% ± 5.6%, compared with 51.6% ± 6.2% and 51.1% ± 5.9% in the intensified group ( P = 0.029, P = 0.063). Conclusions Intensified conditioning represents a promising approach for high-risk hematological malignancies, although it affects early immune reconstitution of recipients and increases the incidence and mortality of EBV infections.
House‐dust mite hypersensitivity, eczema, and other nonpulmonary manifestations of allergy
Authors: R. A. Tupker, J. G. R. de Monchy, P.‐J. Coenraads
Journal: Allergy (1998)

The pathogenetic role of house‐dust mites (HDM) in atopic dermatitis (AD) remains controversial, mainly because there is no common agreement on a provocation test that mimics ordinary exposure to HDM. This is related to the lack of knowledge of the mechanism of how HDM allergens enter the body. Theoretically, there are two possible routes: directly through the epidermis, or by inhalation. In “atopy patch testing”, a concentrated HDM suspension is tested on the skin under occlusion. This method is frequently used as a model of the epidermal route. The clinical relevance of this method as a provocation test for AD is discussed. As opposed to atopy patch testing, we describe another method, namely, “allergen inhalation testing”, as a model of the respiratory route. Twenty patients with AD underwent bronchial provocations with HDM extract in a double‐blind, randomized, placebo‐controlled study. In nine out of 20 AD patients, bronchial challenge with HDM evoked skin symptoms. All patients with HDM‐induced dermatitis had a history of asthma, and as a group they had a higher mean total log‐transformed IgE level than the “negative skin responders”. Thus, the respiratory route may be relevant in the provocation of AD in a subset of AD patients and may represent an appropriate model of provocation in these patients. Furthermore, the role of HDM in urticaria and allergic rhinitis is discussed.
Thyroid-Hormone–Disrupting Chemicals: Evidence for Dose-Dependent Additivity or Synergism
Authors: Kevin M. Crofton, Elena S. Craft, Joan M. Hedge, Chris Gennings, Jane E. Simmons, Richard A. Carchman, W. Hans Carter, Michael J. DeVito
Journal: Environmental Health Perspectives (2005)

Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T4) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T4 was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose-response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED30), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs.
Global Reality of Type 1 Diabetes Care in 2013
Authors: David Beran, John S. Yudkin, Mark A. Atkinson
Journal: Diabetes Care (2013)

In his first editorial of the year, the Editor in Chief of Diabetes Care affirmed that the “state of Diabetes Care ” is strong (1). We agree and are congratulatory regarding his noting of the benefits that improved management has brought to many with the disease. Clearly, advances in insulin delivery, blood glucose monitoring, patient education, and health care worker training have the potential to be quite impacting in this regard.

However, this positive situation is not the reality for many with the condition living in resource-poor settings. Indeed, from a global perspective, the most common cause of death for a child with type 1 diabetes is lack of access to insulin (2). Yet, this is not just a …
Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1
Authors: T RUI, Q FENG, M LEI, T PENG, J ZHANG, M XU, E DALEABEL, A XENOCOSTAS, P KVIETYS
Journal: Cardiovascular Research (2005)

Objective: Erythropoietin (EPO) prevents the myocardial dysfunction induced by ischemia/reperfusion (I/R). Since I/R-induced myocardial dysfunction is associated with an acute inflammatory response, we assessed the anti-inflammatory properties of EPO using in vitro and in vivo models of I/R.
1108-116 Cardiac power output is the only independent hemodynamic predictor of outcome in acute heart failure
Authors: Gad Cotter, Nir Uriel, Loic Perchenet, Edo Kaluski, Isaac Kobrin, Aline Frey, Olga Milo, Alex Blatt, Shoshana Kaplan, Zvi Vered, Guillermo Torre-Amione
Journal: Journal of the American College of Cardiology (2004)
From Genome-Wide Association Studies to Next-Generation Sequencing
Authors: Manu Sharma, Rejko Krüger, Thomas Gasser
Journal: JAMA Neurology (2013)

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Pulmonary arterial hypertension in familial hemiplegic migraine with ATP1A2 channelopathy
Authors: David Montani, Barbara Girerd, Sven Günther, Florence Riant, Elisabeth Tournier-Lasserve, Laurent Magy, Nizar Maazi, Christophe Guignabert, Laurent Savale, Olivier Sitbon, Gérald Simonneau, Florent Soubrier, Marc Humbert
Journal: European Respiratory Journal (2013)

To the Editor: 

Pulmonary arterial hypertension (PAH) has been the focus of major research in recent years [1]. Involvement of mutations in genes encoding for members of the transforming growth factor-β signalling pathway ( BMPR2 , ACVRL1 , ENG and SMAD8 ) has been demonstrated in the development of heritable PAH, allowing novel experimental and clinical approaches [2–4]. However, ∼30% of familial forms of PAH remain without any identification of genetic mutations. Recently, mutations of the KCNK3 gene (encoding K+ channel subfamily K member 3) have been reported in patients with familial and sporadic PAH [5]. KCNK3 belongs to a family of mammalian K+ channels, and are involved in the regulation of resting membrane potential, pulmonary vascular tone and in vascular remodelling. This result paves the way to the involvement of novel signalling pathways in the development of heritable PAH. Herein, we describe a novel association of PAH and a channelopathy due to mutation in ATP1A2 (encoding the α2-subunit of the Na+/K+-ATPase), a mutation known to cause familial hemiplegic migraine (FHM), a rare autosomal dominant disease [6].

A 24-year-old male was referred with a 1-year history of progressive exertional dyspnoea. Since the age of 8 years, he has reported recurrent episodes of hemiplegic migraine associated with muscle weakness and pain. The proband’s mother (II4) (fig. 1) and two of his brothers (III6 and III7) had recurrent hemiplegic migraine with aura. There was no familial history of PAH. On admission, the patient was in New York Heart Association (NYHA) functional class III. His 6-min …
Sex Is an Independent Prognostic Indicator for Survival and Relapse/Progression-Free Survival in Metastasized Stage III to IV Melanoma: A Pooled Analysis of Five European Organisation for Research and Treatment of Cancer Randomized Controlled Trials
Authors: Arjen Joosse, Sandra Collette, Stefan Suciu, Tamar Nijsten, Poulam M. Patel, Ulrich Keilholz, Alexander M.M. Eggermont, Jan Willem W. Coebergh, Esther de Vries
Journal: Journal of Clinical Oncology (2013)

To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature.Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively.In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load.The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.
Control of the Simian Fetal Hemoglobin Switch at the Progenitor Cell Level
Authors: Blanche P. Alter, Benjamin T. Jackson, Jeffrey M. Lipton, George J. Piasecki, Pamela L. Jackson, Michele Kudisch, David G. Nathan
Journal: Journal of Clinical Investigation (1981)

This investigation was designed to define the cellular level at which the gamma to beta globin switch is established in the developing simian fetus in order to determine whether the switch is controlled by environmental influences within differentiating erythroid precursors or predetermined by the genetic program of erythroid progenitors. Samples of marrow and liver were obtained from rhesus fetuses throughout the switch period, and marrow was obtained from adult rhesus monkeys. Globin chain synthesis was then measured in differentiated erythroblasts and in erythroid progenitor-derived colonies grown in semisolid media. The relative rates of synthesis of gamma and beta chains were determined by the uptake of [3H]leucine into the respective chains separated by Triton gel electrophoresis and in some cases by urea carboxymethyl cellulose chromatography. Four periods of the switch were defined during fetal development. In the preswitch period both erythroblasts and progenitor-derived colonies produced <5% beta globin. In the early switch erythroblasts produced 5-15% beta globin, while progenitor-derived colonies produced 10-35% beta globin. In mid-switch erythroblasts synthesized 50% beta globin, whereas progenitor-derived colonies produced only 15-35% beta. At the completion of the switch erythroblasts produced 100% beta globin, while progenitor-derived colonies produced as little as 40% beta chains. We conclude that the program of globin synthesis that characterizes the fetal switch is established at the level of erythroid progenitors. Fetal erythroid burst-forming units (BFU-E) dominate the marrow prior to the switch. The early switch period is heralded by the appearances of adult erythroid burst-forming units programmed to express increasing beta chain synthesis in colonies. By mid-switch a second class of adult erythroid progenitors capable of giving rise to fetal and adult hemoglobin synthesis in in vitro colonies becomes apparent. These shifting populations of erythroid progenitors with unique globin synthesis programs give rise to the erythroblasts that create the sigmoid pattern of the fetal to adult hemoglobin switch in the developing simian fetus.
Dry tap marrow aspiration
Authors: M. M. Reid
Journal: American Journal of Hematology (1991)

Dry Tap Marrow AspirationDr. Humphries [l] confirms the impression of those experienced in obtaining bone marrow aspirates that dry taps are usually associated with abnormal marrow and should not simply (or scornfully) be attributed to faulty technique on the part of the operator, whether experienced or in training.The point could have been strengthened by showing that a larger proportion of the successful aspirates than the dry taps were accompanied by biopsies with normal cellularity and reticulin content."Touch' or "roll" preparations made from the biopsy core are valuable, though not simply because of the delay in processing the core.A significant proportion of the dry taps in his report were from patients with acute leukemia.Good cytology (as opposed to histology) is of paramount importance in the diagnosis of acute leukemia, particularly if there are few circulating blasts.One of the traps into which the unwary hematologist/pathologist may fall when faced with a dry tap and no cytology is to misdiagnose megaloblastic anemia as leukaemia, as recently exemplified [2] and emphasized [3] by others.The principles of enzyme digestion of tissue biopsies to obtain single cell suspensions are long established.Mononen and Jansson [4] described in detail this approach to the handling of marrow biopsy cores well before Gibson et al. [ 5 ] .Finally, how hard should one try before accepting a dry tap?The first thing to do is try again.I have had to accept only one dry tap at diagnosis in more than 100 children with acute leukemia over the past 6 years.Many have had intense fibrosis [6] and all were hypercellular.I have been similarly lucky in children presenting with neuroblastoma and other non-haemopoietic malignancies in-
Immunotherapy of established tumors using bone marrow transplantation with antigen gene–modified hematopoietic stem cells
Authors: Yan Cui, Erin Kelleher, Erin Straley, Ephraim Fuchs, Kevin Gorski, Hyam Levitsky, Ivan Borrello, Curt I Civin, Stephen P Schoenberger, Linzhao Cheng, Drew M Pardoll, Katharine A Whartenby
Journal: Nature Medicine (2003)
Serum IgE clearance is facilitated by human FcεRI internalization
Authors: Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin
Journal: Journal of Clinical Investigation (2014)

The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1–positive (BDCA1+) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1+ DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance.
Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs
Authors: Chiara Dell'Agnola, Zejing Wang, Rainer Storb, Stephen J. Tapscott, Christian S. Kuhr, Stephen D. Hauschka, Richard S. Lee, George E. Sale, Eustacia Zellmer, Serina Gisburne, Janet Bogan, Joe N. Kornegay, Barry J. Cooper, Theodore A. Gooley, Marie-Térèse Little
Journal: Blood (2004)
Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents
Authors: Gilad Twig, Avi Livneh, Asaf Vivante, Arnon Afek, Ari Shamiss, Estela Derazne, Dorit Tzur, Ilan Ben-Zvi, Amir Tirosh, Micha Barchana, Tamy Shohat, Eliezer Golan, Howard Amital
Journal: Annals of the Rheumatic Diseases (2013)

There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF.
Sarcoidosis: an underrecognised cause for bullous lung disease?
Authors: V. Jeebun, I. A. Forrest
Journal: European Respiratory Journal (2009)

Sarcoidosis: an under-recognised cause for bullous lung disease?To the Editors:A 35-yr-old Caucasian female was admitted with a 2-week history of rapidly progressive dyspnoea on minimal exertion.She denied any associated cough, chest pain or systemic symptoms.She gave a background of a 5-yr history of dyspnoea on moderate exertion, with intermittent cough, but no diurnal variation.This had been previously attributed to asthma and she had been maintained on inhaled corticosteroids and short-acting b-agonists.She had no symptoms suggestive of any connective tissue disease.She had no family history of respiratory disease.She was a heavy smoker, having accrued a 10-pack-yr history of smoking, but denied any illicit drug use.She was unemployed.There was no history of exposure to hazardous dusts.
MIRA-Assisted Microarray Analysis, a New Technology for the Determination of DNA Methylation Patterns, Identifies Frequent Methylation of Homeodomain-Containing Genes in Lung Cancer Cells
Authors: Tibor Rauch, Hongwei Li, Xiwei Wu, Gerd P. Pfeifer
Journal: Cancer Research (2006)

Abstract We present a straightforward and comprehensive approach for DNA methylation analysis in mammalian genomes. The methylated-CpG island recovery assay (MIRA), which is based on the high affinity of the MBD2/MBD3L1 complex for methylated DNA, has been used to detect cell type–dependent differences in DNA methylation on a microarray platform. The procedure has been verified and applied to identify a series of novel candidate lung tumor suppressor genes and potential DNA methylation markers that contain methylated CpG islands. One gene of particular interest was DLEC1, located at a commonly deleted area on chromosome 3p22-p21.3, which was frequently methylated in primary lung cancers and melanomas. Among the identified methylated genes, homeodomain-containing genes were unusually frequent (11 of the top 50 hits) and were targeted on different chromosomes. These genes included LHX2, LHX4, PAX7, HOXB13, LBX1, SIX2, HOXD3, DLX1, HOXD1, ONECUT2, and PAX9. The data show that MIRA-assisted microarray analysis has a low false-positive rate and has the capacity to catalogue methylated CpG islands on a genome-wide basis. The results support the hypothesis that cancer-associated DNA methylation events do not occur randomly throughout the genome but at least some are targeted by specific mechanisms. (Cancer Res 2006; 66(16): 7939-47)
Zurich 2012: our cohort of ‘concussionologists‘ – conveying consensus
Authors: Jonathan Speridon Patricios, Robert Collins, Craig Roberts
Journal: British Journal of Sports Medicine (2012)

Zurich 2012: our cohort of 'concussionologists' -conveying consensusclinicians to be in what seems like an 'observer status' in relation to the patient.Current management consists of monitoring physical and cognitive rest as the concussed patient recovers; it wou ld be ideal