tbuckley/cabot-search huggingface dataset:
Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease
Authors: Shuhua Han, Micheal Tredger, Germana V. Gregorio, Giorgina Mieli-Vergani, Diego Vergani
Journal: Hepatology (1995)

Antibodies to liver cytosol antigen type 1 (anti-LC1), which recognize a 60-kd peptide contained in the liver cytosolic fraction, have been reported to define a subset of autoimmune hepatitis (AIH) either negative for other autoantibodies or positive for anti-liver kidney microsomal antibody type 1 (LKM-1) and to be best detected in immunodiffusion. To analyze the prevalence of anti-LC1 in childhood liver disease, we have tested the sera of 95 patients using immunoblot, indirect immunofluorescence, and immunodiffusion. Fifteen children had smooth muscle antibody (SMA) and/or anti-nuclear antibody (ANA)-positive AIH, 13 had anti-LKM-1-positive AIH, 14 had autoimmune sclerosing cholangitis (ASC) (all SMA and/or ANA positive), and 53 had non-autoimmune liver disease (10 had alpha 1-anti-trypsin deficiency [alpha 1-ATD], 11 had Wilson's disease [WD], 14 had Alagille's syndrome, and 18 had chronic hepatitis B virus [HBV] infection). Twenty healthy children were studied as controls. Anti-LC1 positivity in immunodiffusion and strong reactivity in immunoblot were found in 4 LKM-1- and 2 SMA/ANA-positive patients with AIH and in 1 patient with ASC, but in none of the patients with other liver diseases nor in controls. A weak 60-kd band was detected by immunoblot in 6 more patients with AIH (2 were LKM-1- and 4 were SMA/ANA-positive) and 6 patients with ASC, all anti-LC1-negative by immunofluorescence and immunodiffusion. No distinct clinical features characterized the anti-LC1-positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Early Intervention in Low-Birth-Weight Premature Infants
Authors: Jeanne Brooks-Gunn
Journal: JAMA (1994)

To evaluate the persistence of effects on health and development at age 5 years of the Infant Health and Development Program, an early childhood intervention that was provided to low-birth-weight (LBW) premature infants from neonatal discharge through age 3 years.Randomized, controlled, multicenter trial, stratified by two LBW groups: lighter (< or = 2000 g) and heavier (2001 to 2500 g).Eight socioeconomically heterogeneous clinical sites.Of 985 eligible infants weighing 2500 g or less and at 37 weeks' or less gestational age, 377 infants were randomly assigned to the intervention group and 608 to the follow-up only group. About two thirds of the infants in each group were in the lighter LBW stratum, and one third were in the heavier LBW stratum.The intervention group received home visits (from neonatal discharge through age 3 years) as well as center-based schooling (from 1 to 3 years of age). Children in both groups received pediatric surveillance.Cognitive development, behavioral competence, and health status.At age 5 years, the intervention group had full-scale IQ scores similar to children in the follow-up only group. However, in the heavier LBW stratum, children in the intervention group had higher full-scale IQ scores (3.7 points higher; P = .03) and higher verbal IQ scores (4.2 points higher; P = .02). No significant differences between intervention and follow-up only groups in cognitive measures at age 5 years were noted in the lighter LBW infants. The intervention and follow-up groups were similar in behavior and health measures regardless of LBW stratum.The early childhood intervention provided in the first 3 years of life had effects on heavier LBW premature infants' IQ and verbal performance at age 5 years that were not observed for lighter LBW premature infants. The intervention did not affect health or behavior at age 5 years in either LBW stratum.
Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial
Authors: Andreas Münch, Johan Bohr, Stephan Miehlke, Cecilia Benoni, Martin Olesen, Åke Öst, Lars Strandberg, Per M Hellström, Erik Hertervig, Peter Armerding, Jiri Stehlik, Greger Lindberg, Jan Björk, Annika Lapidus, Robert Löfberg, Ole Bonderup, Sören Avnström, Martin Rössle, Karin Dilger, Ralph Mueller, Roland Greinwald, Curt Tysk, Magnus Ström
Journal: Gut (2014)

<h3>Objective</h3> This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. <h3>Design</h3> A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. <h3>Results</h3> Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p&lt;0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. <h3>Conclusions</h3> Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. <h3>Trial registration numbers</h3> http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).
IL-17 in Severe Asthma. Where Do We Stand?
Authors: Julie Chesné, Faouzi Braza, Guillaume Mahay, Sophie Brouard, Marc Aronica, Antoine Magnan
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Asthma is a major chronic disease ranging from mild to severe refractory disease and is classified into various clinical phenotypes. Severe asthma is difficult to treat and frequently requires high doses of systemic steroids. In some cases, severe asthma even responds poorly to steroids. Several studies have suggested a central role of IL-17 (also called IL-17A) in severe asthma. Indeed, high levels of IL-17 are found in induced sputum and bronchial biopsies obtained from patients with severe asthma. The recent identification of a steroid-insensitive pathogenic Th17 pathway is therefore of major interest. In addition, IL-17A has been described in multiple aspects of asthma pathogenesis, including structural alterations of epithelial cells and smooth muscle contraction. In this perspective article, we frame the topic of IL-17A effects in severe asthma by reviewing updated information from human studies. We summarize and discuss the implications of IL-17 in the induction of neutrophilic airway inflammation, steroid insensitivity, the epithelial cell profile, and airway remodeling.
Cost-effectiveness of tiotropium<i>versus</i>salmeterol: the POET-COPD trial
Authors: Martine Hoogendoorn, Maiwenn J. Al, Kai-Michael Beeh, David Bowles, J. Matthias Graf von der Schulenburg, Juliane Lungershausen, Brigitta U. Monz, Hendrik Schmidt, Claus Vogelmeier, Maureen P.M.H. Rutten-van Mölken
Journal: European Respiratory Journal (2012)

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55–195) and €170 (95% UI €77–260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010–0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19–157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.
Quantification of electrical remodeling in human atrial fibrillation
Authors: Andreas Bollmann
Journal: Cardiovascular Research (2000)

See article by Manios et al. [10] (pages 244–253) in this issue. 

Mapping of the atrial electrical activation pattern during human Atrial Fibrillation (AF) has provided evidence supporting Moe's hypothesis that AF is based on the continuous propagation of multiple wavelets wandering throughout the atria in the majority of cases [1]. Since the average size of reentry pathways during AF is dependent on atrial wavelength (conduction velocity×refractory period) it is not surprising that different complex atrial activation patterns with different numbers and dimensions of the reentry circuits were found. While long wavelengths are associated with larger and fewer wavefronts, short wavelengths result in a greater number of smaller circuits. A numerical index for quantification of spatial AF organization was proposed and applied to different AF patterns by Botteron and Smith [2]. These authors, by calculating a so-called activation space constant from five bipolar right atrial recordings illustrated that the spatial organisation was smaller in patients with chronic AF, whereas a group of patients with induced AF and no AF history exhibited the highest degree of AF organisation. An intermediate value was observed in patients with paroxysmal AF. From a pathophysiological point of view it can therefore be concluded that AF is not a homogenous arrhythmia.

From animal models it is known that atrial effective refractory period (AERP) shortening and the loss of its normal rate adaptation are associated with an increase in AF stability and duration of AF paroxysms leading to the concept that ‘AF begets AF’ [3]. In humans, these findings of this so-called electrical remodeling process were replicated in induced AF [4,5] and confirmed in chronic AF [6,7]. Daoud et al. have … 

* Tel.: +49-391-671-3203; fax: +49-391-671-3202 andreas.bollmann{at}medizin.uni-magdeburg.de
Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis
Authors: Suzanne R. Hayman, Richard J. Bailey, Syed M. Jalal, Gregory J. Ahmann, Angela Dispenzieri, Morie A. Gertz, Philip R. Greipp, Robert A. Kyle, Martha Q. Lacy, S. Vincent Rajkumar, Thomas E. Witzig, John A. Lust, Rafael Fonseca
Journal: Blood (2001)
Identification of a Novel Homozygous Deletion Region at 6q23.1 in Medulloblastomas Using High-Resolution Array Comparative Genomic Hybridization Analysis
Authors: Angela B.Y. Hui, Hirokuni Takano, Kwok-Wai Lo, Wen-Lin Kuo, Cleo N.Y. Lam, Carol Y.K. Tong, Qing Chang, Joe W. Gray, Ho-Keung Ng
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of this study is to comprehensively characterize genome copy number aberrations in medulloblastomas using high-resolution array comparative genomic hybridization. Experimental Design: High-density genomic arrays containing 1,803 BAC clones were used to define recurrent chromosomal regions of gains or losses throughout the whole genome of medulloblastoma. A series of 3 medulloblastoma cell lines and 16 primary tumors were investigated. Results: The detected consistent chromosomal aberrations included gains of 1q21.3-q23.1 (36.8%), 1q32.1 (47.4%), 2p23.1-p25.3 (52.6%), 7 (57.9%), 9q34.13-q34.3 (47.4%), 17p11.2-q25.3 (89.5%), and 20q13.31-q13.33 (42.1%), as well as losses of 3q26.1 (57.9%), 4q31.23-q32.3 (42.1%), 6q23.1-25.3 (57.9%), 8p22-23.3 (79%), 10q24.32-26.2 (57.9%), and 16q23.2-q24.3 (63.2%). One of the most notable aberrations was a homozygous deletion on chromosome 6q23 in the cell line DAOY, and single copy loss on 30.3% primary tumors. Further analyses defined a 0.887 Mbp minimal region of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was reduced in cell lines D283 and D384, and in 50% and 70% of primary tumors, respectively. Conclusion: Current array comparative genomic hybridization analysis generates a comprehensive pattern of chromosomal aberrations in medulloblastomas. This information will lead to a better understanding of medulloblastoma tumorigenesis. The delineated regions of gains or losses will indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous deletion region was newly identified at 6q23.1. Frequent detection of reduced expression of AK091351 and KIAA1913 genes implicates them as suppressors of medulloblastoma tumorigenesis.
Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors
Authors: S.N. Holden, S.G. Eckhardt, R. Basser, R. de Boer, D. Rischin, M. Green, M.A. Rosenthal, C. Wheeler, A. Barge, H.I. Hurwitz
Journal: Annals of Oncology (2005)
Functional Pairing of Class B1 Ligand-GPCR in Cephalochordate Provides Evidence of the Origin of PTH and PACAP/Glucagon Receptor Family
Authors: Jason S.W. On, Cumming Duan, Billy K.C. Chow, Leo T.O. Lee
Journal: Molecular Biology and Evolution (2015)

Several hypotheses have been proposed regarding the origin and evolution of the secretin family of peptides and receptors. However, identification of homologous ligand–receptor pairs in invertebrates and vertebrates is difficult because of the low levels of sequence identity between orthologs of distant species. In this study, five receptors structurally related to the vertebrate class B1 G protein-coupled receptor (GPCR) family were characterized from amphioxus (Branchiostoma floridae). Phylogenetic analysis showed that they clustered with vertebrate parathyroid hormone receptors (PTHR) and pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon receptors. These PTHR-like receptors shared synteny with several PTH and PACAP/glucagon receptors identified in spotted gar, Xenopus, and human, indicating that amphioxus preserves the ancestral chordate genomic organization of these receptor subfamilies. According to recent data by Mirabeau and Joly, amphioxus also expresses putative peptide ligands including homologs of PTH (bfPTH1 and 2) and PACAP/GLUC-like peptides (bfPACAP/GLUCs) that may interact with these receptors. Functional analyses showed that bfPTH1 and bfPTH2 activated one of the amphioxus receptors (bf98C) whereas bfPACAP/GLUCs strongly interacted with bf95. In summary, our data confirm the presence of PTH and PACAP/GLUC ligand–receptor pairs in amphioxus, demonstrating that functional homologs of vertebrate PTH and PACAP/glucagon GPCR subfamilies arose before the cephalochordate divergence from the ancestor of tunicates and vertebrates.
Allergenicity and cross‐reactivity of Russian olive pollen (<i>Eleagnus angustifolia</i>)
Authors: J. Sastre, M. Lluch‐Bernal, A. M. G. Bustillo, J. Carnés, F. Marañón, M. Casanovas, E. Fernández‐Caldas
Journal: Allergy (2004)

Background: The purposes of this study were: to determine the prevalence of sensitization and immunochemical characterization of Eleagnus angustifolia pollen (Russian olive) that belongs to the family Eleagnaceae. Methods: A total of 134 patients with rhinoconjunctivitis and/or asthma were studied. Its allergenicity, cross‐reactivity with olive pollen and the presence of Ole e 1 and Ole e 4‐like molecules were evaluated. Results: Eleagnus angustifolia pollen was detected from May to June. Seventy‐three of 134 (30.5%) had positive skin test to E. angustifolia , all of them were positive to olive. There was a good correlation between specific immunoglobulin (Ig)E levels to E. angustifolia and Olea europaea ( r = 0.77, P = 0.002). Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) immunoblots revealed major IgE‐binding bands in the E. angustifolia extract of 43 and 63.7 kDa. The E. angustifolia extract was not able to inhibit olive, whereas O. europaea inhibited E. angustifolia up to 41%. The presence of Ole e 1‐ and Ole e 4‐like allergens in E. angustifolia extract was confirmed by enzyme‐linked immunosorbent (ELISA) inhibition assays. Nasal challenge with E. angustifolia was positive in three of six patients with positive skin test to both pollens and negative in five patients with positive skin test only to O. europaea . Conclusions: This study confirms that E. angustifolia is capable of sensitizing individuals in Madrid. A minimal‐to‐moderate cross‐reactivity with olive pollen was established, suggesting some cross‐reactivity but not excluding co‐sensitization.
Projecting Individualized Absolute Invasive Breast Cancer Risk in African American Women
Authors: M. H. Gail, J. P. Costantino, D. Pee, M. Bondy, L. Newman, M. Selvan, G. L. Anderson, K. E. Malone, P. A. Marchbanks, W. McCaskill-Stevens, S. A. Norman, M. S. Simon, R. Spirtas, G. Ursin, L. Bernstein
Journal: JNCI Journal of the National Cancer Institute (2007)

The Breast Cancer Risk Assessment Tool of the National Cancer Institute (NCI) is widely used for counseling and determining eligibility for breast cancer prevention trials, although its validity for projecting risk in African American women is uncertain. We developed a model for projecting absolute risk of invasive breast cancer in African American women and compared its projections with those from the Breast Cancer Risk Assessment Tool.Data from 1607 African American women with invasive breast cancer and 1647 African American control subjects in the Women's Contraceptive and Reproductive Experiences (CARE) Study were used to compute relative and attributable risks that were based on age at menarche, number of affected mother or sisters, and number of previous benign biopsy examinations. Absolute risks were obtained by combining this information with data on invasive breast cancer incidence in African American women from the NCI's Surveillance, Epidemiology and End Results Program and with national mortality data. Eligibility screening data from the Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new model would affect eligibility, and independent data from the Women's Health Initiative (WHI) were used to assess how well numbers of invasive breast cancers predicted by the new model agreed with observed cancers.Tables and graphs for estimating relative risks and projecting absolute invasive breast cancer risk with confidence intervals were developed for African American women. Relative risks for family history and number of biopsies and attributable risks estimated from the CARE population were lower than those from the Breast Cancer Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance). Using eligibility screening data from the STAR trial, we estimated that 30.3% of African American women would have had 5-year invasive breast cancer risks of at least 1.66% by use of the CARE model, compared with only 14.5% by use of the Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE model agreed well with observed numbers of cancers (i.e., it was well calibrated) in data from the WHI, except that it underestimated risk in African American women with breast biopsy examinations.The CARE model usually gave higher risk estimates for African American women than the Breast Cancer Risk Assessment Tool and is recommended for counseling African American women regarding their risk of breast cancer.
Actin-Containing Sera From Patients With Adult Respiratory Distress Syndrome Are Toxic to Sheep Pulmonary Endothelial Cells
Authors: JEFFREY A. ERUKHIMOV, ZI-LUE TANG, BRUCE A. JOHNSON, MICHAEL P. DONAHOE, JAMAL A. RAZZACK, KEVIN F. GIBSON, WILLIAM M. LEE, KARLA J. WASSERLOOS, SIMON A. WATKINS, BRUCE R. PITT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism and pulmonary vascular angiopathy have been noted in rats. It remains to be determined whether this injury is a result of a direct toxic effect or occurs indirectly via platelet activation or fibrin interactions. We examined the effect of sera from patients with adult respiratory distress syndrome (ARDS), as well as G-actin added to normal serum, on the viability, morphology, and function of cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and normal sera to which actin was added were toxic in the cell culture model; this toxicity could be abrogated, at least partially, by preincubation with gelsolin, which is known to complex with actin. A significant portion of the toxicity of sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an important role of complement. Sera from patients with ARDS were shown to contain filaments of F-actin by immunoblot and rhodamine phalloidin staining after ultracentrifugation. Thus, saturation of the actin-scavenging system by addition of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury. Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is toxic to SPAEC, and a small but significant contributory role of actin is apparent in these studies.
High body iron stores predisposes to early carotid atherosclerotic changes in B-thalassemia major patients
Authors: I.E. Kallikazaros, C.P. Tsioufis, I.G. Malliaros, C.G. Stratos, C.I. Stefanadis, C.G. Pitsavos, P.K. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
HIV-1–specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon-γ and tumor necrosis factor–α
Authors: Mathias Lichterfeld, Xu G. Yu, Michael T. Waring, Stanley K. Mui, Mary N. Johnston, Daniel Cohen, Marylyn M. Addo, John Zaunders, Galit Alter, Eunice Pae, Daryld Strick, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, Marcus Altfeld
Journal: Blood (2004)