tbuckley/cabot-search huggingface dataset:
Quality of life and use of red cell transfusion in patients with myelodysplastic syndromes. A systematic review
Authors: Deborah J. Pinchon, Simon J. Stanworth, Carolyn Dorée, Susan Brunskill, Derek R. Norfolk
Journal: American Journal of Hematology (2009)

The main treatment for many patients with Myelodysplastic Syndromes (MDS) remains red cell transfusion to attenuate the symptoms of chronic anemia. Fatigue can reduce a patient's health related quality of life (HRQoL), but there is little understanding of the optimal use of transfusions to improve this. A systematic review was performed to identify and appraise publications reporting the use of HRQoL instruments in patients with MDS. A total of 17 separate studies were identified that used 14 HRQoL instruments, but only one MDS disease specific HRQoL instrument (QOL-E) was reported. Two well established HRQoL instruments were most often used in MDS research (variants of the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30)). Several common problems were identified in the published literature including a lack of power calculations to detect clinically relevant changes, small sample sizes and significant attrition rates for completion of HRQoL assessments, all of which limit the strength of any conclusions. There is no consensus on the optimal transfusion regimen to improve HRQoL in transfusion-dependent MDS. Future research into HRQoL within MDS is a pressing requirement. Studies should focus on the domains that are of most clinical importance to the patient as well as traditional quantitative changes of hemoglobin concentration.
Reactive Oxygen Species and Matrix Remodeling in Diabetic Kidney
Authors: Hunjoo Ha, Hi Bahl Lee
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Excessive deposition of extracellular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Although the amount of ECM deposited in the kidney depends on the balance between the synthesis and degradation of ECM, the role of ECM degradation in matrix remodeling has been less well appreciated. High glucose, advanced glycation end products, angiotensin II, and TGF-β1 all increase intracellular reactive oxygen species (ROS) in renal cells and contribute to the development and progression of diabetic renal injury. The role of ROS in increased ECM synthesis has been well documented. ROS may also play a critical role in decreased ECM degradation by mediating high glucose- and TGF-β1-induced inhibition of the proteolytic system, plasmin, and matrix metalloproteinases in the glomeruli. A recent observation suggests that ROS play an important role in tubulointerstitial fibrosis by mediating TGF-β1-induced epithelial-mesenchymal transition (EMT). Accelerated ECM degradation is required to disrupt tubular basement membrane and complete EMT. ROS thus seem to be involved in both decreased and increased ECM degradation. It is not clear how cells determine when and where to increase or decrease ECM degradation in response to ROS. Precise definition of ROS-activated signaling pathways leading to ECM remodeling in the kidney will provide new strategies to prevent or treat diabetic renal injury. E-mail: ha@hkl.ac.kr
Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995-9
Authors: M E J Callister
Journal: Thorax (2002)

Over 50% of cases of tuberculosis (TB) in the UK occur in people born overseas, and new entrants to the country are screened for TB. A study was undertaken to determine the prevalence and disease characteristics of pulmonary TB in new entrants to the UK seeking political asylum.A retrospective analysis of the results of screening 53 911 political asylum seekers arriving at Heathrow Airport between 1995 and 1999 was performed by studying Airport Health Control Unit records and hospital medical records. Outcome measures were chest radiograph abnormalities, sputum smear, culture, and drug resistance data for Mycobacterium tuberculosis.The overall prevalence of active TB in political asylum seekers was 241 per 100 000. There were large variations in prevalences of TB between asylum seekers from different regions, with low rates from the Middle East and high rates from the Indian subcontinent and sub-Saharan Africa. The frequency of drug resistance was high; 22.6% of culture positive cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both isoniazid and rifampicin), and 4% of cases diagnosed with active disease had multidrug resistant TB.The prevalence rate of TB in political asylum seekers entering the UK through Heathrow Airport is high and more M tuberculosis isolates from asylum seekers are drug resistant than in the UK population. Extrapolating these figures, it is estimated that 101 political asylum seekers with active pulmonary TB enter the UK every year, of whom about 25 would have smear positive disease.
Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study
Authors: Jing Chen, Dongfeng Gu, Jianfeng Huang, Dabeeru C Rao, Cashell E Jaquish, James E Hixson, Chung-Shiuan Chen, Jichun Chen, Fanghong Lu, Dongsheng Hu, Treva Rice, Tanika N Kelly, L Lee Hamm, Paul K Whelton, Jiang He
Journal: The Lancet (2009)
Survival of Patients With Newly Diagnosed Glioblastoma Multiforme Treated With RSR13 and Radiotherapy: Results of a Phase II New Approaches to Brain Tumor Therapy CNS Consortium Safety and Efficacy Study
Authors: L. Kleinberg, S.A. Grossman, K. Carson, G. Lesser, A. O’Neill, J. Pearlman, P. Phillips, T. Herman, M. Gerber
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The objectives of this phase II study were to determine survival, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 2,4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid (RSR13, efaproxiral) 100 mg/kg per day administered with standard cranial radiotherapy (RT) for the treatment of glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin, is a radiation-enhancing agent that noncovalently binds to hemoglobin, reduces oxygen-binding affinity, and increases oxygen unloading to hypoxic tissue. PATIENTS AND METHODS: Fifty patients with newly diagnosed GBM (Karnofsky performance status ≥ 60) were enrolled onto this multicenter phase II study. Patients received daily RSR13 100 mg/kg intravenously infused for 30 minutes immediately before cranial RT (60 Gy in 30 fractions). Supplemental oxygen was given during RSR13 infusion and continued until after the RT treatment was completed. RT was given within 30 minutes of the end of RSR13 infusion. PK and PD determinations were performed. RESULTS: The median survival for the RSR13-treated patients was 12.3 months with 1-year and 18-month survival rates of 54% and 24%, respectively. Twenty-four percent of patients had greater than grade 2 toxicity, which was generally transient and self-limited. A significant PD effect on hemoglobin-oxygen binding affinity was demonstrated for most patients. CONCLUSION: RSR13 (100 mg/kg) administered immediately before cranial RT is well tolerated and is pharmacodynamically active. Median survival in excess of 1 year is favorable.
Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients
Authors: Qing Ouyang, Xueyang Gong, Hualiang Xiao, Ji Zhou, Minhui Xu, Yun Dai, Lunshan Xu, Hua Feng, Hongjuan Cui, Liang Yi
Journal: Molecular Cancer (2015)

The poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) overexpression induces neoplastic growth and predicts the poor prognosis in various malignancies. Whether NTS can promote the glioma progression and its prognostic significance for glioma patients remains unclear. NTS precursor (ProNTS), NTS and NTSR1 expression levels in glioma were detected by immunobloting Elisa and immunohistochemistry assay. The prognostic analysis was conducted from internet by R2 microarray platform. Glioma cell proliferation was evaluated by CCK8 and BrdU incorporation assay. Wound healing model and Matrigel transwell assay were utilized to test cellular migration and invasion. The orthotopic glioma implantations were established to analyze the role of NTS and NTSR1 in glioma progression in vivo. Positive correlations were shown between the expression levels of NTS and NTSR1 with the pathological grade of gliomas. The high expression levels of NTS and NTSR1 indicate a worse prognosis in glioma patients. The proliferation and invasiveness of glioma cells could be enhanced by NTS stimulation and impaired by the inhibition of NTSR1. NTS stimulated Erk1/2 phosphorylation in glioma cells, which could be reversed by SR48692 or NTSR1-siRNA. In vivo experiments showed that SR48692 significantly prolonged the survival length of glioma-bearing mice and inhibited glioma cell invasiveness. NTS promotes the proliferation and invasion of glioma via the activation of NTSR1. High expression levels of NTS and NTSR1 predict a poor prognosis in glioma patients.
Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial
Authors: Djillali Annane, Philippe Vignon, Alain Renault, Pierre-Edouard Bollaert, Claire Charpentier, Claude Martin, Gilles Troché, Jean-Damien Ricard, Gérard Nitenberg, Laurent Papazian, Elie Azoulay, Eric Bellissant
Journal: The Lancet (2007)
Evidence-ranked motif identification
Authors: Stoyan Georgiev, Alan P Boyle, Karthik Jayasurya, Xuan Ding, Sayan Mukherjee, Uwe Ohler
Journal: Genome biology (2010)

cERMIT is a computationally efficient motif discovery tool based on analyzing genome-wide quantitative regulatory evidence. Instead of pre-selecting promising candidate sequences, it utilizes information across all sequence regions to search for high-scoring motifs. We apply cERMIT on a range of direct binding and overexpression datasets; it substantially outperforms state-of-the-art approaches on curated ChIP-chip datasets, and easily scales to current mammalian ChIP-seq experiments with data on thousands of non-coding regions.
Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide
Authors: Takamasa Oono, Yoshinori Fukui, Sadahiko Masuko, Osamu Hashimoto, Takato Ueno, Terukazu Sanui, Ayumi Inayoshi, Mayuko Noda, Michio Sata, Takehiko Sasazuki
Journal: Journal of Clinical Investigation (2001)

Organ-specific autoimmune diseases have been postulated to be the result of T cell response against organ-specific self-peptides bound to MHC molecules. Contrary to this paradigm, we report here that transgenic mice lacking MHC class I expression and expressing an MHC class II I-A(b) molecule that presents only a single peptide (E alpha 52-68) spontaneously develops peripheral nervous system-specific autoimmune disease with many of the histopathological features found in experimental allergic neuritis. Reciprocal bone marrow chimeras produced using susceptible and resistant lines revealed that bone marrow-derived cells determined disease susceptibility. While the expression of the I-A(b)-E alpha 52-68 complex in the periphery was readily detectable in both lines, its expression on thymic dendritic cells responsible for tolerance induction was markedly lower in the susceptible line than in the resistant line. Consistent with this, CD4(+) T cells that can be activated by the I-A(b)-E alpha 52-68 complex were found in the susceptible line, but not in the resistant line. Such CD4(+) T cells conferred the disease to the resistant line by adoptive transfer, and administration of Ab specific for the I-A(b)-E alpha 52-68 complex inhibited disease manifestation in the susceptible line. These results indicate that disease development involves systemic T cell reactivity to I-A(b)-E alpha 52-68 complex, probably caused by incomplete negative thymocyte selection.
Replication of association of 3p21.1 with susceptibility to bipolar disorder but not major depression
Authors: Gerome Breen, Cathryn M Lewis, Evangelos Vassos, Michele L Pergadia, Douglas H R Blackwood, Dorret I Boomsma, Brenda Penninx, Patrick F Sullivan, Inti Pedroso, David Collier, Peter McGuffin
Journal: Nature Genetics (2010)
Effects of Gestational Diabetes on Diurnal Profiles of Plasma Glucose, Lipids, and Individual Amino Acids
Authors: Boyd E Metzger, Richard L Phelps, Norbert Freinkel, Irene A Navickas
Journal: Diabetes Care (1980)

To assess the effects of gestational diabetes mellitus (GDM) on intermediary metabolism in late pregnancy, circulating levels of glucose, FFA, triglycerides, cholesterol, and individual amino acids were monitored for 24 h while subjects received a liquid formula diet (containing 2110 cal and 275 g carbohydrate) in three equal feedings at 0800, 1300, and 1800. Attempts were made to distinguish between varying degrees of severity of gestational diabetes by subdividing the population into those with fasting plasma glucose within the normal range for pregnancy, i.e., below 105 mg/dl (GDM &amp;lt; 105), and those with fasting plasma glucose of 105 mg/dl or greater (GDM ≥ 105). Both groups were compared with pregnant women with normal carbohydrate metabolism (NM). The diurnal profiles indicated that premeal, postprandial averages, and integrated 24-h values for plasma glucose were consistently higher in GDM ≥ 105 than in GDM &amp;lt; 105; both GDM groups uniformly exceeded the values in NM. Plasma FFA tended to be higher in all GDM, with maximal increments occurring in the early hours before breakfast and assuming greatest significance in GDM ≥ 105. The elevations in circulating cholesterol that occur in pregnancy were not significantly different at any time point in NM, GDM &amp;lt; 105, and GDM ≥ 105. However, the increases in plasma triglycerides were greater in GDM &amp;lt; 105 and GDM ≥ 105 than in NM and most marked in GDM ≥ 105. Diurnal profiles for a number of individual amino acids (phenylalanine, tyrosine, alanine, serine, proline) were not affected by gestational diabetes. However, certain other amino acids, particularly the branched chain (leucine, isoleucine, valine), tended to be elevated in subjects with GDM and to the most significant extent in GDM ≥ 105. Although the GDM subjects tended to be heavier than the NM, the progressively more pronounced metabolic abnormalities in GDM ≥ 105 than in GDM &amp;lt; 105 would suggest that relative insulinopenia rather than obesity contributed to the differences. Our findings indicate that gestational diabetes is attended by disturbances of varying degrees in all major classes of insulin-dependent foodstuffs and must be viewed as a disorder of multiple fuels.
Hip flexibility and strength measures: reliability and association with athletic groin pain
Authors: P Malliaras, A Hogan, A Nawrocki, K Crossley, A Schache
Journal: British Journal of Sports Medicine (2009)

Groin pain commonly affects football players and can be associated with prolonged recovery periods. Understanding the relationship between groin pain and reliable measures of hip flexibility and strength may facilitate the development of optimal rehabilitation and prevention strategies. In this study, the reliability and association with athletic groin pain of hip flexibility and strength measures were investigated.A cohort of 29 football players (15-21 years) participating in junior elite competitions (Australian Rules football and soccer) were recruited. The intra-rater reliability (n=13) and inter-rater reliability (n=12) of various hip flexibility (bent knee fall out test, hip internal rotation, hip external rotation) and strength (hip abduction, hip internal rotation, hip external rotation, hip adduction (squeeze test)) measures were investigated using intraclass correlation coefficients (ICC). Reliable hip flexibility and strength measures were compared between football players with (n=10) and without (n=19) groin pain.The bent knee fall out test, hip internal rotation flexibility and the squeeze test demonstrated acceptable (ICC>0.75) intra-rater and inter-rater reliability, while hip external rotation flexibility and hip abduction strength demonstrated acceptable intra-rater but not inter-rater reliability. Hip internal and external rotation strength tests were not found to be reliable. Football players with groin pain had significantly reduced force production on the squeeze test (p>0.05).Several hip flexibility and strength measures were found to be reliable. Only the squeeze test discriminated between football players with and without groin pain.
Pulmonary arterial hypertension prototype for national protocol and registry
Authors: Majid Malekmohammad, Fanak Fahimi, Babak Sharifkashani, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2012)

Background: Pulmonary Hypertension (PH) has been defined as an increase in mean pulmonary arterial pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization.  The idiopathic form so called idiopathic pulmonary arterial hypertension iPAH is a fatal disorder with a prevalence of 8.6 per million of population.  In the current report we introduced a registry site for iPAH patients, named www.pah.ir for better delivery of subsidized antihypertensive medications (now only Bosentan).  Methods: The registry was opened since November 2009. The first step of this action is to add iPAH patient9s information with a username and password in the site. Data entry is only available to the physicians and healthcare organizations via internet that are given a personalized username & password for entry. Following the patient9s profile submission in the site, a scientific committee composed of a cardiologist and a pulmonologist who are selected by Ministry of Health (MOH), would then evaluate the data. The eligibility of the patient to receive the medications is announced in the site after evaluation. If a patient is eligible, 82% of bosentan cost is paid by MOH.  Results: Till now, one hundred and sixteen patients (82 females, 34 males) are registered. Measured mean pulmonary artery pressure by right heart catheterization was 69.24±17 mmHg (ranging from 35 to 110 mmHg).  Conclusion: The first online Iranian registry program for iPAH patients has recently been started and it is believed that this national program will supply essential information for health care providers in the field.
Major histocompatibility complex class II-restricted antigen presentation across a species barrier: conservation of restriction determinants in evolution.
Authors: R E Bontrop, D G Elferink, N Otting, M Jonker, R R de Vries
Journal: The Journal of Experimental Medicine (1990)

The existence of at least three alleles of the HLA-DRB3 gene within the human population is evident. These alleles express DRw52 determinants and react with monoclonal antibody (mAb) 7.3.19.1. The polymorphic epitope recognized by 7.3.19.1 is not only present on human cells but is also expressed on chimpanzee (Pan troglodytes) class II-positive cells. The 7.3.19.1 determinant already existed before speciation of man and chimpanzee, and is at least 5,000,000 yr old. Two-dimensional gel electrophoresis demonstrated that the various HLA- and Patr-DRw52 molecules that are reactive with 7.3.19.1 exhibit isoelectric point differences due to primary amino acid heterogeneity, as was confirmed by sequencing data. Sequence comparison allowed us to map the binding site of mAb 7.3.19.1 to the alpha helix of the major histocompatibility complex (MHC) class II DRB1 domain surrounding the antigen-binding cleft. Despite MHC sequence variation, chimpanzee antigen-presenting cells can present antigen (purified protein derivative) to human T cell lines and vice versa. Only the HLA- and Patr-DRw52 molecules were shown to function as restriction elements for antigen presentation across this species barrier. It is concluded that these particular restriction determinants probably have been conserved in evolution. The HLA- and Patr-DRw52 molecules represent alleles displaying polymorphism that has been selected for in evolution. Such "biomutants" may thus be more useful to study the biological significance of MHC molecules than MHC variants that have been generated by in vitro mutagenesis experiments.
PHAGOCYTIN: A BACTERICIDAL SUBSTANCE FROM POLYMORPHONUCLEAR LEUCOCYTES
Authors: James G. Hirsch
Journal: The Journal of Experimental Medicine (1956)

A technique has been developed for collecting large numbers of polymorphonuclear leucocytes from peritoneal exudates in rabbits. These cells are obtained essentially free from other cell types and from debris. When microphages so procured are disrupted by physical methods and extracted with aqueous salt solutions, the soluble fraction manifests striking bactericidal activity, especially on Gram-negative enteric bacilli. The susceptible microorganisms are not lysed. This bactericidal substance, which has been called phagocytin, appears to be limited in distribution mainly to the polymorphonuclear leucocyte. No phagocytin is present in extracts of rabbit heart, kidney, or skeletal muscle, and rabbit liver and spleen contain much less than do packed leucocytes. Extracts of human and of guinea pig microphages show less bactericidal activity than rabbit cell preparations. Similar extracts of rat and mouse polymorphonuclear leucocytes contain no demonstrable phagocytin. As indicated by its behavior on dialysis, on exposure to proteolytic enzymes, and on salt fractionation, phagocytin appears to be a protein with general properties characteristic of a globulin. It is clearly different from lysozyme and from properdin. Although phagocytin is reasonably stable at temperatures of 65 degrees C. and lower for several hours, solutions of it gradually lose bactericidal activity on standing for prolonged periods at 4 degrees C. This instability, and also the ease with which phagocytin is inactivated, presumably by adsorption, on exposure to a variety of materials, have thus far rendered fruitless efforts to isolate it.
Mimicking of Estradiol Binding by Flame Retardants and Their Metabolites: A Crystallographic Analysis
Authors: Rajendrakumar A. Gosavi, Gabriel A. Knudsen, Linda S. Birnbaum, Lars C. Pedersen
Journal: Environmental Health Perspectives (2013)

Brominated flame retardants (BFRs), used in many types of consumer goods, are being studied because of concerns about possible health effects related to endocrine disruption, immunotoxicity, reproductive toxicity, and neurotoxicity. Tetrabromobisphenol A (TBBPA), the most widely used BFR, and human metabolites of certain congeners of polybrominated diphenyl ether (e.g., 3-OH-BDE-47) have been suggested to inhibit estrogen sulfotransferase, potentially affecting estrogen metabolism.Our primary goal was to understand the structural mechanism for inhibition of the hormone-metabolizing enzyme estrogen sulfotransferase by certain BFRs. We also sought to understand various factors that facilitate the binding of flame retardants in the enzyme binding pocket.We used X-ray crystallography to obtain atomic detail of the binding modes of TBBPA and 3-OH-BDE-47 to estrogen sulfotransferase for comparison with binding of the endogenous substrate estradiol.The crystal structures reveal how BFRs mimic estradiol binding as well as the various interactions between the compounds and protein residues that facilitate its binding. In addition, the structures provide insights into the ability of the sulfotransferase substrate binding pocket to accommodate a range of halogenated compounds that satisfy minimal structural criteria.Our results show how BFRs or their metabolites can bind to and inhibit a key hormone-metabolizing enzyme, potentially causing endocrine disruption.