tbuckley/cabot-search huggingface dataset:
Single vs Weekly Courses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery
Authors: D A Guinn, M W Atkinson, L Sullivan, M Lee, S MacGregor, B V Parilla, J Davies, K Hanlon-Lundberg, L Simpson, J Stone, D Wing, K Ogasawara, J Muraskas
Journal: JAMA (2001)

ContextThe practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice.ObjectivesTo evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment.Design and SettingRandomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000.ParticipantsA total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery.InterventionAll patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246).Main Outcome MeasureComposite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death).ResultsComposite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity.ConclusionsWeekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.
Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation
Authors: F Lacaille, N Vass, F Sauvat, D Canioni, V Colomb, C Talbotec, N P.-M. De Serre, J Salomon, J-P Hugot, J-P Cezard, Y Revillon, F M Ruemme, O Goulet
Journal: Gut (2007)

<h3>Objective:</h3> Small bowel (SB) transplantation (Tx), long considered a rescue therapy for patients with intestinal failure, is now a well recognised alternative treatment strategy to parental nutrition (PN). In this retrospective study, we analysed graft functions in 31 children after SBTx with a follow-up of 2–18 years (median 7 years). <h3>Patients:</h3> Twelve children had isolated SBTx, 19 had combined liver–SBTx and 17 received an additional colon graft. Growth, nutritional markers, stool balance studies, endoscopy and graft histology were recorded every 2–3 years post-Tx. <h3>Results:</h3> All children were weaned from PN after Tx and 26 children remained PN-free. Enteral nutrition was required for 14/31 (45%) patients at 2 years post-Tx. All children had high dietary energy intakes. The degree of steatorrhoea was fairly constant, with fat and energy absorption rates of 84–89%. Growth parameters revealed at transplantation a mean height Z-score of –1.17. After Tx, two-thirds of children had normal growth, whereas in one-third, Z-scores remained lower than –2, concomitant to a delayed puberty. Adult height was normal in 5/6. Endoscopy and histology analyses were normal in asymptomatic patients. Chronic rejection occurred only in non-compliant patients. Five intestinal grafts were removed 2.5–8 years post-Tx for acute or chronic rejection. <h3>Conclusions:</h3> This series indicates that long-term intestinal autonomy for up to 18 years is possible in the majority of patients after SBTx. Subnormal energy absorption and moderate steatorrhoea were often compensated for by hyperphagia, allowing normal growth and attainment of adult height. Long-term compliance is an important pre-requisite for long-term graft function.
A Study of Hsp90 Inhibitor At13387 Alone and in Combination with Crizotinib (Czt) in the Treatment of Non-Small Cell Lung Cancer (Nsclc)
Authors: B. Besse, E. Bertino, N.A. Pennell, A. Wozniak, D. Mahadevan, A. Spira, A. Oganesian, L. Manlapaz-Espiritu, H. Keer, J-C. Soria, D.R. Camidge
Journal: Annals of Oncology (2014)
Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells
Authors: Mübeccel Akdis, Johan Verhagen, Alison Taylor, Fariba Karamloo, Christian Karagiannidis, Reto Crameri, Sarah Thunberg, Günnur Deniz, Rudolf Valenta, Helmut Fiebig, Christian Kegel, Rainer Disch, Carsten B. Schmidt-Weber, Kurt Blaser, Cezmi A. Akdis
Journal: The Journal of Experimental Medicine (2004)

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.
Are circulating proinflammatory cytokines associated with lower birth weight of newborns from women with rheumatoid arthritis?
Authors: F D O de Steenwinkel, J M W Hazes, Y A de Man, A C S Hokken, Y B de Rijke, R J E M Dolhain
Journal: Annals of the Rheumatic Diseases (2010)

Recent studies have shown that high disease activity during pregnancy in women with rheumatoid arthritis (RA) is associated with lower birth weight of the child, even after adjustment for gestational age and medication. Lower birth weight, even within the normal range, has been linked with cardiovascular diseases and metabolic syndromes in adulthood. In studies on a limited number of healthy pregnant women, a role for interleukin 6 (IL6) and tumour necrosis factor α (TNFα) in intrauterine growth restriction has been …
[569] RELATIONSHIP OF FIBROGENIC POLYMORPHISMS (TGF-BETA, PAI-1, AT) AND PIRFENIDONE TREATMENT IN MEXICAN CIRRHOTIC PATIENTS WITH HCV
Authors: I. Armendariz-Borunda, M. Bueno-Topete, A.R. Rincon, M.C. Islas-Carbajal, J.F. Munoz-Valle, E. Oregon-Romero, A. Alvarez-Rodriguez, R. Troyo-Sanroman
Journal: Journal of Hepatology (2007)
A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four α-Fetoprotein Peptides
Authors: Lisa H. Butterfield, Antoni Ribas, Vivian B. Dissette, Yohan Lee, Jin Quan Yang, Pilar De la Rocha, Sonia D. Duran, Jackie Hernandez, Elisabeth Seja, Douglas M. Potter, William H. McBride, Richard Finn, John A. Glaspy, James S. Economou
Journal: Clinical Cancer Research (2006)

Abstract α-Fetoprotein (AFP) is a self protein expressed by fetal liver at high levels, but is transcriptionally repressed at birth. AFP is up-regulated in hepatocellular carcinomas, and patients with active disease could have plasma levels as high as 1 mg/mL. We previously identified four immunodominant HLA-A*0201-restricted peptides [hAFP137-145 (PLFQVPEPV), hAFP158-166 (FMNKFIYEI), hAFP325-334 (GLSPNLNRFL), and hAFP542-550 (GVALQTMKQ)] derived from human AFP that could stimulate specific T cell responses in healthy donor peripheral blood lymphocytes in vitro. We conducted a phase I/II clinical trial in which HLA-A*0201 patients with AFP-positive hepatocellular carcinoma were immunized with three biweekly intradermal vaccinations of the four AFP peptides pulsed onto autologous dendritic cells (DC). DCs were prepared from adherent peripheral blood mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. Sixteen subjects were enrolled and 10 were treated. Peripheral blood lymphocytes were isolated from these patients before, during, and after AFP peptide/DC immunization and were tested ex vivo with MHC tetramer and IFNγ ELISPOT analysis. Six of 10 subjects expanded statistically significant levels of AFP-specific T cells postvaccine to at least one peptide by MHC tetramer. Also, 6 of 10 subjects increased IFNγ producing AFP-specific T cell responses to at least one of the peptides postvaccination, by ELISPOT. We conclude that the human T cell repertoire is capable of responding to the AFP self antigen after the administration of AFP peptide-pulsed DC even in an environment of high circulating levels of this oncofetal antigen.
Bringing non-human primate research into the post-genomic era: how monkeys are teaching us about elite controllers of HIV/AIDS
Authors: Eric J Vallender
Journal: Genome biology (2014)

Whole-genome sequencing of Mauritian cynomolgus macaques reveals novel candidate loci for controlling simian immunodeficiency virus replication. See related Research, http://genomebiology.com/2014/15/11/478
Specific serum IgE levels and FcɛRIβ genetic polymorphism in patients with penicillins allergy
Authors: H.‐L. Qiao, J. Yang, Y.‐W. Zhang
Journal: Allergy (2004)

Background: Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. Methods: Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcɛRIβ polymorphism. Results: The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE ( P = 0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)‐, phenoxomethylpenicilloyl (PVO)‐ or ampicilloyl (APO)‐IgE and control group ( P = 0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA‐, PVO‐ as well as APO‐IgE patients ( P = 0.014, 0.02, and 0.011, respectively). Conclusions: The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcɛRIβ gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.
Diaphragm Length and Neural Drive after Lung Volume Reduction Surgery
Authors: Robert B. Gorman, David K. McKenzie, Jane E. Butler, Jane F. Tolman, Simon C. Gandevia
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Patients with chronic obstructive pulmonary disease have shorter inspiratory muscles and higher motor unit firing rates during quiet breathing than do age-matched healthy subjects. Lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease improves lung function, exercise capacity, and quality of life.We studied the effect of LVRS on length and motor unit firing rates of diaphragm and scalene muscles.Diaphragm length was estimated by ultrasound and magnetometers, and firing rates were recorded with needle electrodes in patients (five females and seven males) with severe chronic obstructive pulmonary disease, before and after surgery.Pre-LVRS total lung capacity was 135 +/- 10% predicted (mean +/- SD), and FEV1 was 30 +/- 12% predicted. After surgery, median firing frequency of diaphragmatic motor units fell from 17.3 +/- 4.2 to 14.5 +/- 3.4 Hz (p < 0.001), and scalene motor unit firing rates were reduced from 15.3 +/- 6.9 to 13.4 +/- 3.8 Hz (p < 0.001). Tidal volume and diaphragm length change during quiet breathing did not change, but at end expiration, the zone of apposition length of diaphragm against the rib cage (L(Zapp)) increased (30 +/- 28%, p = 0.004). Improvements in quality-of-life measures and exercise performance after surgery were related to increased forced vital capacity and L(Zapp).Increased diaphragm length resulted in lower motor unit firing rates and reduced breathing effort, and this is likely to contribute to improved quality of life and exercise performance after LVRS.
Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Christoph Schmid, Michael Schleuning, Georg Ledderose, Johanna Tischer, Hans-Jochem Kolb
Journal: Journal of Clinical Oncology (2005)

To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD).Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD.Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.
Lineage-specific compaction of <i>Tcrb</i> requires a chromatin barrier to protect the function of a long-range tethering element
Authors: Kinjal Majumder, Olivia I. Koues, Elizabeth A.W. Chan, Katherine E. Kyle, Julie E. Horowitz, Katherine Yang-Iott, Craig H. Bassing, Ichiro Taniuchi, Michael S. Krangel, Eugene M. Oltz
Journal: The Journal of Experimental Medicine (2014)

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers.
Improving hepatitis C services across the UK: response to a walk-in HCV testing service
Authors: R F C D'Souza
Journal: Gut (2004)

The Department of Health (DH) estimates that approximately 0.4% of the UK population are chronically infected with hepatitis C virus (HCV) (that is, 200 000 people). As few as 10% of these individuals, who are at risk of end stage liver disease, are thought to be aware of their infection. Clearly action is required to identify and treat these patients with current drugs (pegylated interferons …
Identification of Bacterial DNA in the Peripheral Blood of Patients With Active Psoriasis
Authors: Ana Ramírez-Boscá, Vicente Navarro-López, Asunción Martínez-Andrés, José Such, Rubén Francés, José Horga de la Parte, Manuel Asín-Llorca
Journal: JAMA Dermatology (2015)

Article Tables References Comments Psoriasis is a systemic autoimmune inflammatory disease that shares some immunological aspects with other inflammatory-based diseases, such as Crohn disease.1 Bacterial DNA (bactDNA) fragments have been shown to induce a systemic immunological response in Crohn disease and other settings.2,3 Although the results of most blood bacterial cultures are negative in patients with psoriasis, we hypothesized that the presence of bactDNA in the blood might act as a molecular trigger in disease outbreaks and induce a systemic inflammatory response in these patients.
Two-Step Approach for the Prediction of Future Type 2 Diabetes Risk
Authors: Muhammad A. Abdul-Ghani, Tamam Abdul-Ghani, Michael P. Stern, Jasmina Karavic, Tiinamaija Tuomi, Insoma Bo, Ralph A. DeFronzo, Leif Groop
Journal: Diabetes Care (2011)

To develop a model for the prediction of type 2 diabetes mellitus (T2DM) risk on the basis of a multivariate logistic model and 1-h plasma glucose concentration (1-h PG).
Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury
Authors: Y. Gushima, K. Ichikado, M. Suga, T. Okamoto, K. Iyonaga, K. Sato, H. Miyakawa, M. Ando
Journal: European Respiratory Journal (2001)

The aim of this study was to determine the role of matrix metalloproteinases (MMPs) in the pathogenesis of acute lung injury induced by hyperoxia. Twenty-three pigs were exposed in sealed cages to &gt;80% oxygen (for 24–120 h) or room air. Correlation between MMP-;2/MMP-;9 activity, measured by gelatin zymography in bronchoalveolar lavage fluid (BALF), and the histological findings and pathological parameters were examined in detail. Sources of these MMPs in the hyperoxic lung were analysed by immunohistochemistry. The histological progression of acute lung injury in this model ranged from the early exudative to the early proliferative phase of diffuse alveolar damage (DAD). MMP-;2 and -;9 activities were elevated under prolonged hyperoxic exposure. MMP-;9 activity correlated significantly with the oxygen tension in arterial blood/inspiratory oxygen fraction, the lung wet-to-dry weight ratio, and the number of neutrophils in BALF, whereas MMP-;2 activity did not correlate at all with these factors. MMP-;9 activity correlated more closely with the pathological findings of DAD than did MMP-;2 activity. Strong MMP-;9 expression was observed in neutrophils, alveolar macrophages as well as alveolar lining epithelial cells. These results suggest that matrix metalloproteinase, which may derive from neutrophils recruited into airspaces, plays an important role in the pathogenesis of hyperoxic diffuse alveolar damage.
An evaluation of oxygen therapy equipment: Experimental study of various devices on the human subject
Authors: D. W. Bethune, J. M. Collis
Journal: Thorax (1967)

Six commercially available devices were tested to determine the alveolar oxygen concentration that is achieved and the volume of rebreathing that can occur in conditions simulating clinical use. All were tested at zero oxygen flow, since failure and interruption of the oxygen supply to such devices can occur in clinical use. In patients whose cardiorespiratory reserve is exhausted, any increase in dead space will be detrimental; for such patients devices should be selected which cannot cause rebreathing under any circumstances. Three of the devices tested could cause appreciable rebreathing, <i>i.e.,</i> Oxyaire (B.L.B. pattern), Pneumask, and the M.C. mask. Claims made for the Pneumask and the M.C. mask were not substantiated in this study. With administration by nasal catheter changes in alveolar oxygen concentrations were found to be dependent on the percentage of mouth breathing by the subject. The Ventimask produced a consistent elevation of the alveolar oxygen percentage and did not cause any increase in the dead space.