tbuckley/cabot-search huggingface dataset:
Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation
Authors: Susanne S. Pedersen, Pedro A. Lemos, Priya R. van Vooren, Tommy K.K. Liu, Joost Daemen, Ruud A.M. Erdman, Pieter C. Smits, Patrick W.J.C. Serruys, Ron T. van Domburg
Journal: Journal of the American College of Cardiology (2004)
On the Origin of Darwin's Finches
Authors: A Sato, H Tichy, C O'hUigin, P R Grant, B R Grant, J Klein
Journal: Molecular Biology and Evolution (2001)

Darwin's finches comprise a group of 15 species endemic to the Galápagos (14 species) and Cocos (1 species) Islands in the Pacific Ocean. The group is monophyletic and originated from an ancestral species that reached the Galápagos Archipelago from Central or South America. Descendants of this ancestor on the Archipelago then colonized Cocos Island. In the present study, we used sequences of two mitochondrial (mt) DNA segments (922 bp of the cytochrome b gene and 1,082 bp of the control region), as well as two nuclear markers (830 bp of numt2, consisting of 140 bp of mtDNA control region and 690 bp of flanking nuclear DNA; and 740 bp of numt3, consisting of 420 bp of mt cytochrome b sequence flanked by 320 bp of nuclear DNA) to identify the species group most closely related to the Darwin's finches. To this end, we analyzed the sequences of 28 species representing the main groups (tribes) of the family Fringillidae, as well as 2 outgroup species and 13 species of Darwin's finches. In addition, we used mtDNA cytochrome b sequences of some 180 additional Fringillidae species from the database for phylogeny reconstruction by maximum-parsimony, maximum-likelihood, minimum-evolution, and neighbor-joining methods. The study identifies the grassquit genus Tiaris, and specifically the species Tiaris obscura, as the nearest living relative of Darwin's finches among the species surveyed. Darwin's finches diverged from the Tiaris group shortly after the various extant species of Tiaris diverged from one another. The initial adaptive radiation of the Tiaris group apparently occurred on the Caribbean islands and then spread to Central and South America, from where the ancestors of Darwin's finches departed for the Galápagos Islands approximately 2.3 MYA, at the time of the dramatic climatic changes associated with the closure of the Panamanian isthmus and the onset of Pleistocene glaciation.
Long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the RAPID 1 trial and open-label extension
Authors: Edward Keystone, Robert Landewé, Ronald van Vollenhoven, Bernard Combe, Vibeke Strand, Philip Mease, Laura Shaughnessy, Brenda VanLunen, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

To examine the safety and efficacy of 5-year administration of certolizumab pegol (CZP)+methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Eligible patients from the Rheumatoid Arthritis Prevention of Structural Damage (RAPID)1 randomised controlled trial (RCT) were treated in open-label extension (OLE) with CZP 400 mg every other week (Q2W), reduced to 200 mg Q2W after ≥6 months, +MTX. Combined safety data from RCT and OLE are presented from initiation of CZP treatment to 12 wks post last visit in patients receiving ≥1 dose of CZP (Safety population, N=958). Efficacy data are presented to start of first site closure (wk 256 of CZP treatment: 52 wks in RCT+204 wks in OLE) for all patients randomised to receive CZP (intent-to-treat (ITT) population, N=783) and CZP patients who completed the 52 wk RCT and enrolled into OLE (wk 52 CZP completers, N=508). Disease Activity Score (DAS)28 (Erythrocyte Sedimentation Rate (ESR)), American College of Rheumatology Criteria (ACR) 20/50/70, Health Assessment Questionnaire - Disability Index (HAQ-DI), and patient retention (Kaplan-Meier analysis) were assessed.Overall event rate per 100 patient-years (ER) of adverse events (AEs) was 290.4, most frequently: urinary tract infections (ER=7.9), nasopharyngitis (ER=7.3) and upper respiratory tract infections (ER=7.3). ER of serious AEs was 20.3 (infections=5.9, malignancies=1.2). 21 patients (2.2%) experienced an AE resulting in death (incidence rate=0.6). At wk 256 of treatment, 55.3% of the CZP ITT population were estimated to remain on treatment (68.7% if solely withdrawals due to AE or lack of efficacy were considered). In wk 52 CZP completers and CZP ITT population, DAS28 (ESR) remission rates and improvements from baseline were sustained to wk 256.CZP+MTX treatment provided a favourable risk-benefit profile over 5 years in patients with active RA. No new safety signals were identified.
Ultrastructural lesions on the surface of platelets associated with either blood coagulation or with antibody-mediated immune injury.
Authors: M J Polley, R L Nachman
Journal: The Journal of Experimental Medicine (1975)

During blood coagulation ultrastructural lesions were produced on the platelet membrane. They were dependent on the presence of both thrombin and complement (C) and were morphologically identical to the C-dependent ultrastructural lesions (type II) seen in red cells subsequent to activation of C by the alternate mechanismmthough similar in shape they differed in size from ultrastructural lesions (type I) PRODUCED BY ACTIVATION OF C via the classic mechanismmlesions of type I were seen on the platelet surface subsequent to antibody-dependent activation of the C system.
Excitotoxicity increases the release of 24S-hydroxycholesterol via CYP46A1 activation
Authors: Alejandro Sodero, Joris Vriens, Debapriya Ghosh, David Stegner, Anna Brachet, Marta Pallotto, Marco Sassoe-Pognetto, Jos Brouwers, Bernd Helms, Bernard Nieswandt, Thomas Voets, Carlos Dotti
Journal: Molecular Neurodegeneration (2013)

Background Excitotoxicity, a common hallmark of different neurological disorders including Alzheimer’s disease (AD), is the consequence of exacerbated neuronal stimulation and leads to a high influx of calcium trough membrane glutamate receptors [1]. On the other hand, high levels of the cholesterol metabolite 24S-hydroxycholesterol (24-HC) have been found in cerebral spinal fluid (CSF) from AD patients [2,3]. Brain cholesterol homeostasis is an essential, tightly-regulated process that ensures neuronal integrity, viability, and function. One of the mechanisms that neurons put to work to regulate the amount of cellular cholesterol is its conversion into the metabolite 24-HC by the 24-cholesterol hydroxylase CYP46A1 [4]. In this work, we explored the possibility that excitotoxicity, a common process that precedes neurodegeneration, could be a direct modulator of the 24-HC production via a CYP46A1-mediated hydroxylation of cholesterol.
Influence of Coffee Drinking on Subsequent Risk of Hepatocellular Carcinoma: A Prospective Study in Japan
Authors: M. Inoue, I. Yoshimi, T. Sobue, S. Tsugane
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Methods: Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90 452 middle-aged and elderly Japanese subjects (43 109 men and 47 343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Results: Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1–2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3–4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for ≥5 cups per day = 0.24 [95% CI = 0.08 to 0.77], Ptrend < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100 000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). Conclusions: In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.
Influence of Deflated and Anaerobic Conditions During Cold Storage on Rat Lungs
Authors: TATSUO FUKUSE, TOSHIKI HIRATA, TAKAYUKI NAKAMURA, MASAHIRO KAWASHIMA, SHIGEKI HITOMI, HIROMI WADA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Energy depletion closely correlates with ischemia–reperfusion (I-R) injury in solid organs, but there has been no conclusion about the lungs that contain air. We investigated the alveolar state during cold storage and its relation to energy metabolism and I-R injury in an ex vivo rat lung model. The lung was deflated (DEF group) or inflated with either room air (RA group) or nitrogen (N2 group) for 6 h at 4 ° C, and reperfusion samples of buffer and bronchoalveolar lavage fluid (BALF) was collected (n = 6, each). Furthermore, the static lung compliance, the intrapulmonary high-energy phosphates, lactate, and pyruvate were measured. The pulmonary functions of the DEF and N2 groups were significantly worse than those of the RA group. In the N2 group, the intrapulmonary levels of energy charge and pyruvate/lactate ratio were significantly lower than those in the DEF and RA groups, whereas there were no significant differences between the DEF and RA groups. In the DEF group, total protein and lactate dehydrogenase (LDH) in the BALF were significantly higher whereas the static lung compliance was significantly lower compared with the N2 and RA groups. We concluded that aerobic metabolism would be essential for attenuating I-R injury of the lung, and inflation of the alveoli would be necessary for avoiding mechanical damage during reexpansion.
Global and Regional CpG Methylation in Pheochromocytomas and Abdominal Paragangliomas: Association to Malignant Behavior
Authors: Janos Geli, Nimrod Kiss, Mohsen Karimi, Jia-Jing Lee, Martin Bäckdahl, Tomas J. Ekström, Catharina Larsson
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aims to quantitatively assess promoter and global methylation changes in pheochromocytomas and abdominal paragangliomas and its relation to tumor phenotypes. Experimental Design: A panel of 53 primary tumors (42 benign, 11 malignant) was analyzed by quantitative bisulfite pyrosequencing. Based on methylation levels in the tumor suppressor genes, p16INK4A, CDH1, DCR2, RARB, RASSF1A, NORE1A, TP73, APC, DAPK1, p14ARF, and PTEN, a CpG island methylator phenotype (CIMP) was defined as concerted hypermethylation in three or more genes. Mean Z scores for the hypermethylated promoters were calculated to characterize overall promoter methylation. Global DNA methylation was quantified for LINE-1 promoter sequences and by using luminescent methylation analysis. Results: Five primary tumors (9.4%) exhibited a CIMP phenotype, four of which were malignant paragangliomas. CIMP was significantly associated with malignant behavior (P = 0.005) and younger age at presentation (P &amp;lt; 0.007) but did not result from BRAF V600E mutation. Global hypomethylation of LINE-1 elements was observed in tumors compared with normal adrenal samples (P &amp;lt; 0.02). Conclusion: We here describe the identification of CIMP in abdominal paragangliomas and a strong association of this phenotype with malignant behavior, as well as young age at presentation. The findings raise a prospective for potential benefits of epigenetically acting drugs for a subgroup of young abdominal paraganglioma patients with adverse prognosis.
Biological significance of endogenous methylarginines that inhibit nitric oxide synthases
Authors: J Leiper
Journal: Cardiovascular Research (1999)

The guanidino-methylated arginine analogue NG monomethyl-l-arginine (l-NMMA) has been the standard nitric oxide synthase inhibitor used to evaluate the role of the l-arginine:nitric oxide pathway. However, l-NMMA and other methylated arginine residues are also synthesised in vivo by the action of a family of enzymes known as protein arginine methyltransferases. Proteolysis of proteins containing methylated arginine residues releases free methylarginine residues into the cytosol from where they may pass out of the cell into plasma. Of the three known methylarginine residues produced in mammals only asymmetrically methylated forms (l-NMMA and asymmetric dimethylarginine (ADMA)) but not symmetrically methylated arginine (symmetric dimethylarginine (SDMA)) inhibit nitric oxide synthase (NOS). We and others have proposed that endogenously produced asymmetrically methylated arginines may modulate NO production and that the accumulation of these residues in disease states may contribute to pathology. The activity of the enzyme dimethylarginine dimethylaminohydrolase that metabolises asymmetric methylarginines may be of critical importance in affecting NO pathways in health or disease.
The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia
Authors: Anthony M. McElligott, Elaina N. Maginn, Lisa M. Greene, Siobhan McGuckin, Amjad Hayat, Paul V. Browne, Stefania Butini, Giuseppe Campiani, Mark A. Catherwood, Elisabeth Vandenberghe, D. Clive Williams, Daniela M. Zisterer, Mark Lawler
Journal: Cancer Research (2009)

Abstract Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity of PBOX-15 in samples taken from a cohort of CLL patients (n = 55) representing both high-risk and low-risk disease. PBOX-15 exhibited cytotoxicity in CLL cells (n = 19) in a dose-dependent manner, with mean IC50 of 0.55 μmol/L. PBOX-15 significantly induced apoptosis in CLL cells (n = 46) including cells with poor prognostic markers: unmutated IgVH genes, CD38 and zeta-associated protein 70 (ZAP-70) expression, and fludarabine-resistant cells with chromosomal deletions in 17p. In addition, PBOX-15 was more potent than fludarabine in inducing apoptosis in fludarabine-sensitive cells. Pharmacologic inhibition and small interfering RNA knockdown of caspase-8 significantly inhibited PBOX-15–induced apoptosis. Pharmacologic inhibition of c-jun NH2-terminal kinase inhibited PBOX-15–induced apoptosis in mutated IgVH and ZAP-70− CLL cells but not in unmutated IgVH and ZAP-70+ cells. PBOX-15 exhibited selective cytotoxicity in CLL cells compared with normal hematopoietic cells. Our data suggest that PBOX-15 represents a novel class of agents that are toxic toward both high-risk and low-risk CLL cells. The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential. [Cancer Res 2009;69(21):8366–75]
The distribution of a receptor for IgM (μFcR) on haemic cells
Authors: G. F. Burns, J. C. Cawley, C. P. Worman, C. R. Barker, F. G. J. Hayhoe
Journal: American Journal of Hematology (1979)

Abstract A range of normal and malignant haemic cells is examined for expression of receptors of the Fc of IgM (μFcR) in order to establish the distribution and possible nosological significance of this receptor. It is shown that μFcR expression by freshly isolated cells is restricted to a small population of normal lymphocytes and to the pathological B cells of most of 45 cases of chronic lymphocytic leukaemia (CLL) and all 23 cases of hairy‐cell leukaemia (HCL) examined. The pathological cells of acute lymphoblastic leukaemia (eight cases), prolymphocytic leukaemia (two cases), a variety of non‐Hodgkin lymphomata (eight cases) and immunoproliferative disorders (25 cases), Hodgkin disease (three cases), and a range of myeloid and histiocytic proliferations (22 cases) were all negative for the μFcR. The pathological cells of the Sezary syndrome were also shown to possess a μFcR, but this required a period of in vitro incubation in RPMI medium containing foetal calf serum for its demonstration. This and other differences between μFcR expression by T‐ and B‐cells are discussed. The possible immunological, nosological, and diagnostic significance of the observed restriction of μFcR expression is considered.
Incidence and specificities of IgA and IgM anti-AgG autoantibodies in various mouse strains and colonies.
Authors: J L van Snick, P L Masson
Journal: The Journal of Experimental Medicine (1980)

Mice, greater than 20 wk old, were tested for the presence of anti-IgG autoantibodies by agglutination and radioimmunoassay. IgA and IgM anti-IgG were found in the 129/Sv, C57BL/6, and DBA/2 strains from the local colony at the International Institute of Cellular and Molecular Pathology (ICP), at the Institut Pasteur de Paris (IP), and in the endotoxin-resistant C3H/He strain of ICP. These strains were negative at Iffa Credo (IC), and at The Jackson Laboratory (JL). Among 33 strains from the latter colony, 129/J, AKR/J, CBA/J, C57L/J, and NZB/BinJ were positive. All were specific pathogen-free and, excepting the NZB/BinJ, are not known to develop systemic autoimmune disorders. These differences between colonies suggest an influence of the environment on the production of anti-IgG. Evidence for the role of an infectious agent was provided by the fact that germ-free DBA/2 were negative in contrast to their SPF relatives. Strains which were positive at ICP and IP for anti-IgG had four-times higher serum levels of total IgA and two-times higher levels of total IgG than the corresponding negative strains from IC and JL. The anti-IgG titers differed markedly from one strain to the other in the same environment; e.g., in mice from ICP, BALB/c mice produced 40-times less anti-IgG than 129/Sv. IgA anti-IgG occurred only in high producers of anti-IgG. In these animals, the proportion of IgA vs. IgM anti-IgG was very different from one group to the other; C57BL/6 had mainly IgM anti-IgG, DBA/2 mainly IgA anti-IgG, and 129/Sv both IgM and IgA anti-IgG. The IgA anti-IgG from 129/Sv, 129/J, NZB/BinJ, C57L/J, DBA/2, and C3H/He had restricted hetero-, iso-, and allotypic specificities. It reacted only with mouse IgGa2, but not with the Ig-1b allotype. C57BL/6 also had IgA anti-IgG with a narrow specificity, but directed against IgG1 without allotypic restriction. In contrast to the specificity of IgA anti-IgG, the antibody activity of IgM anti-IgG was much broader, except in the 129/Sv and 129/J strains where IgM anti-IgG shared the same narrow specificity with IgA.
Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children
Authors: Muhammad T. Salam, Hyang-Min Byun, Fred Lurmann, Carrie V. Breton, Xinhui Wang, Sandrah P. Eckel, Frank D. Gilliland
Journal: Journal of Allergy and Clinical Immunology (2011)
CAN ANTIGLIADIN ANTIBODY DETECT SYMPTOMLESS COELIAC DISEASE IN CHILDREN WITH SHORT STATURE?
Authors: E. Cacciari, U. Volta, R. Lazzari, M. Feliciani, S. Partesotti, P. Tassoni, F.B. Bianchi, S. Salardi, G. Biasco, G.R. Corazza, A. Cicognani, D. Azzaroni, P. Pirazzoli, E. Pisi
Journal: The Lancet (1985)
Perioperative Influenza Vaccination Reduces Postoperative Metastatic Disease by Reversing Surgery-Induced Dysfunction in Natural Killer Cells
Authors: Lee-Hwa Tai, Jiqing Zhang, Karen J. Scott, Christiano Tanese de Souza, Almohanad A. Alkayyal, Anu Abhirami Ananth, Shalini Sahi, Robert A. Adair, Ahmad B. Mahmoud, Subash Sad, John C. Bell, Andrew P. Makrigiannis, Alan A. Melcher, Rebecca C. Auer
Journal: Clinical Cancer Research (2013)

Surgical removal of solid primary tumors is an essential component of cancer treatment. Surgery-induced dysfunction in natural killer (NK) cells has been linked to the development of metastases in animal models and patients with cancer. We investigated the activation of NK cells using influenza vaccine in the perioperative period to eradicate micrometastatic disease.Both the B16lacZ and 4T1 tumor models in immunocompetent mice were used to assess the in vivo efficacy of perioperative influenza vaccine administration. In healthy human donors and cancer surgery patients, we assessed NK cell function pre- and post-influenza vaccination using both in vivo and ex vivo assays.Using the TLR3 agonist poly(I:C), we showed as proof-of-principle that perioperative administration of a nonspecific innate immune stimulant can inhibit surgery-induced dysfunction in NK cells and attenuate metastases. Next, we assessed a panel of prophylactic vaccines for NK cell activation and determined that inactivated influenza vaccine was the best candidate for perioperative administration. Perioperative influenza vaccine significantly reduced tumor metastases and improved NK cytotoxicity in preclinical tumor models. Significantly, IFNα is the main cytokine mediator for the therapeutic effect of influenza vaccination. In human studies, influenza vaccine significantly enhanced NK cell activity in healthy human donors and cancer surgery patients.These results provide the preclinical rationale to pursue future clinical trials of perioperative NK cell activation, using vaccination in cancer surgery patients. Research into perioperative immune therapy is warranted to prevent immune dysfunction following surgery and eradicate metastatic disease.
Ontogeny of B cells in CBA/N mice. Evidence for a stage of responsiveness to thymus-independent antigens during development.
Authors: T Lindsten, B Andersson
Journal: The Journal of Experimental Medicine (1979)

This paper deals with the CBA/N mice, a strain bearing a genetic defect in their B-cell compartment. By using a previously described system we have been able to show that the immature cells of CBA/N mice are functionally indistinguishable from normal immature cells, in that both can be triggered to respond to thymus-independent (TI) antigens, provided they are supplied with helper T cells. When the maturation is completed, CBA/N B cells are unable to respond to TI antigens (like lipopolysaccharide and polyvinyl pyrrolidine) irrespective of the presence of helper T cells, whereas normal mature B cells have grown able to respond without any help. These data allow us to reject the hypothesis that CBA/N mice are arrested at an immature stage and clearly support the idea that they have deviated during development so that only thymus-dependent B cells develop.
Elevated Maternal C-Reactive Protein and Increased Risk of Schizophrenia in a National Birth Cohort
Authors: Sarah Canetta, Andre Sourander, Heljä-Marja Surcel, Susanna Hinkka-Yli-Salomäki, Jaana Leiviskä, Christoph Kellendonk, Ian W. McKeague, Alan S. Brown
Journal: American Journal of Psychiatry (2014)

Maternal inflammation level during pregnancy was related to risk of schizophrenia in offspring, adding new evidence for the association of infection and immune activation with the development of the disorder.