tbuckley/cabot-search huggingface dataset:
Cirrhosis of undefined pathogenesis: Absence of evidence for unknown viruses or autoimmune processes
Authors: Martina Greeve, Linda Ferrell, Michael Kim, Connie Combs, John Roberts, Nancy Ascher, Teresa L. Wright
Journal: Hepatology (1993)

To examine whether unknown viruses or autoimmune processes contribute to the development of cryptogenic liver disease, we studied 48 patients undergoing liver transplantation who had non-A, non-B cirrhosis; non-blood-borne cirrhosis of unknown etiology; or autoimmune cirrhosis. After the diagnosis of hepatitis C virus infection was established by the presence of viral antibodies or viral RNA, patients were reclassified into three groups: hepatitis C virus infection, autoimmune cirrhosis and cryptogenic cirrhosis. Explant histological appearance, incidence of posttransplant hepatitis and immunological features were compared in the three groups. Thirty-one percent of patients had neither hepatitis C virus infection nor classical autoimmune cirrhosis and were classified as having cryptogenic cirrhosis. Unlike histological appearance in hepatitis C virus infection but similar to that in autoimmune cirrhosis, explant histological appearance of cryptogenic cirrhosis showed inactive cirrhosis with little inflammation. After transplantation, histological hepatitis of the allograft was demonstrated in 44% of patients with hepatitis C infection but in no patient with autoimmune or cryptogenic cirrhosis. The autoimmune score, developed from clinical criteria associated with autoimmune liver disease, was significantly lower in cryptogenic cirrhosis and hepatitis C virus infection than in autoimmune cirrhosis. Autoantibodies–including antinuclear antibodies, smooth muscle antibodies and liver-kidney microsomal antibodies–were not commonly present in serum of patients with cryptogenic cirrhosis, whereas antibodies to soluble liver antigens were found with increased frequency in this entity. We conclude that in many patients with liver disease, no pathogenesis can be identified. The mild inflammation of the explant on histological study and the low incidence of posttransplant hepatitis in cryptogenic cirrhosis suggest that chronic active viral infection is unlikely to be implicated in the pathogenesis. Although the presence of antibodies to soluble liver antigens implies an immune component to the pathogenesis of this disease, low autoimmune score and infrequent presence of other autoantibodies suggest that cryptogenic cirrhosis is distinct from classical autoimmune liver disease. (HEPATOLOGY 1993;17:593–598.)
Anticoagulant and Antiplatelet Usage Associates with Mortality among Hemodialysis Patients
Authors: Kevin E. Chan, J. Michael Lazarus, Ravi Thadhani, Raymond M. Hakim
Journal: Journal of the American Society of Nephrology (2009)

Many prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. This retrospective cohort study examined whether use of warfarin, clopidogrel, and/or aspirin affected survival in 41,425 incident hemodialysis patients during 5 yr of follow-up. The prescription frequencies for warfarin, clopidogrel, and aspirin were 8.3, 10.0, and 30.4%, respectively, during the first 90 d of initiating chronic hemodialysis. Compared with the 24,740 patients receiving none of these medications, Cox proportional hazards analysis suggested that exposure to these medications was associated with increased risk for mortality (warfarin hazard ratio [HR] 1.27 [95% confidence interval (CI) 1.18 to 1.37]; clopidogrel HR 1.24 [95% CI 1.13 to 1.35]; and aspirin HR 1.06 [95% CI 1.01 to 1.11]). The increased mortality associated with warfarin or clopidogrel use remained in stratified analyses. A covariate- and propensity-adjusted time-varying analysis, which accounted for longitudinal changes in prescription, produced similar results. In addition, matching for treatment facility and attending physician revealed similar associations between prescription and mortality. We conclude that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients. Given the possibility of confounding by indication, randomized trials are needed to determine definitively the risk and benefit of these medications.
Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group (IBCSG) trials
Authors: J. Huober, S. Gelber, A. Goldhirsch, A.S. Coates, G. Viale, C. Öhlschlegel, K.N. Price, R.D. Gelber, M.M. Regan, B. Thürlimann
Journal: Annals of Oncology (2012)
SINGLE NUCLEOTIDE POLYMORPHISMS THAT INFLUENCE LIPID METABOLISM: Interaction with Dietary Factors
Authors: Dolores Corella, Jose M. Ordovas
Journal: Annual Review of Nutrition (2005)

Cardiovascular disease (CVD) risk is the result of complex interactions between genetic and environmental factors. During the past few decades, much attention has focused on plasma lipoproteins as CVD risk factors. The current evidence supports the concept that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been highly promising. Several loci (i.e., APOA1, APOA4, APOE, and LIPC) are providing proof-of-concept for the potential application of genetics in the context of personalized nutritional recommendations for CVD prevention. However, the incorporation of these findings to the clinical environment is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (i.e., one single dietary component, single nucleotide polymorphism, and risk factor) to more realistic situations involving interactions between multiple genes, dietary components, and risk factors. In summary, there is need for both large population studies and well-standardized intervention studies.
Complete Plasmodium falciparum liver-stage development in liver-chimeric mice
Authors: Ashley M. Vaughan, Sebastian A. Mikolajczak, Elizabeth M. Wilson, Markus Grompe, Alexis Kaushansky, Nelly Camargo, John Bial, Alexander Ploss, Stefan H.I. Kappe
Journal: Journal of Clinical Investigation (2012)

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.
THE CYCLE CAR AND MOTOR CYCLE SHOW AT KENSINGTON
Authors: H. M. Buist
Journal: BMJ (1912)

THE Motor Exhibition which closed at Olympia, Ken- sington, on November 16tll contained such a multitude of novelties, all chiefly of a minor character, that it has been almost impossible to make acquaintance with all in the eiglht days during which the display has been open to the public.But the first and last impression is still that the miiain advance has been the tendency to fit self-starters and the further growth of the use of electric lighting systems, for plant are now being made on a smaller scale to suit middle and low-powered cars and slender.
Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma: Oncologic Marker of Radiologic Response, Progression, and Survival
Authors: Ahsun Riaz, Robert K. Ryu, Laura M. Kulik, Mary F. Mulcahy, Robert J. Lewandowski, Jeet Minocha, Saad M. Ibrahim, Kent T. Sato, Talia Baker, Frank H. Miller, Steven Newman, Reed Omary, Michael Abecassis, Al B. Benson, Riad Salem
Journal: Journal of Clinical Oncology (2009)

Alpha-fetoprotein (AFP) is considered to be an indicator of tumor activity in hepatocellular carcinoma (HCC). We present a novel correlation of AFP response to radiologic response, time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) in patients treated with locoregional therapies.Four hundred sixty-three patients with HCC were treated with chemoembolization or radioembolization at our institution. One hundred twenty-five patients with baseline AFP higher than 200 ng/mL were studied for this analysis. AFP response was defined as more than 50% decrease from baseline. One hundred nineteen patients with follow-up imaging were studied for the AFP imaging correlation analysis. AFP response was correlated to radiologic response, TTP, PFS, and OS. Multivariate analyses were performed.Eighty-one patients (65%) showed AFP response. AFP response was seen in 26 (55%) of 47 and 55 (70%) of 78 of patients treated with chemoembolization and radioembolization, respectively (P = .12). WHO response was seen in 41 (53%) of 77 and 10 (24%) of 42 of AFP responders and nonresponders, respectively (P = .002). The hazard ratio (HR) for TTP in AFP nonresponders compared with responders was 2.8 (95% CI, 1.5 to 5.1). The HR for PFS was 4.2 (95% CI, 2.4 to 7.2) in AFP nonresponders compared with responders. The HR for OS in AFP nonresponders compared with responders was 5.5 (95% CI, 3.1 to 9.9) and 2.7 (95% CI, 1.6 to 4.6) on univariate and multivariate analyses, respectively.The data presented support the use of AFP response seen after locoregional therapy as an ancillary method of assessing tumor response and survival, as well as an early objective screening tool for progression by imaging.
Intratumoral injection of STING ligand promotes abscopal effect
Authors: Jason R Baird, Thomas W Dubensky, David B Kanne, David J Friedman, Benjamin Cottam, Shelly Bambina, Keith S Bahjat, Marka Crittenden, Michael Gough
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The abscopal effect is a phenomenon that occurs when radiation of disease at one-site leads to regression of distant, untreated tumors. Historically, the abscopal effect caused by conventional radiation therapy has been rare. However, the combination of radiation and immunotherapy
A Phylogenomic Approach to Resolve the Arthropod Tree of Life
Authors: K. Meusemann, B. M. von Reumont, S. Simon, F. Roeding, S. Strauss, P. Kuck, I. Ebersberger, M. Walzl, G. Pass, S. Breuers, V. Achter, A. von Haeseler, T. Burmester, H. Hadrys, J. W. Wagele, B. Misof
Journal: Molecular Biology and Evolution (2010)

Arthropods were the first animals to conquer land and air. They encompass more than three quarters of all described living species. This extraordinary evolutionary success is based on an astoundingly wide array of highly adaptive body organizations. A lack of robustly resolved phylogenetic relationships, however, currently impedes the reliable reconstruction of the underlying evolutionary processes. Here, we show that phylogenomic data can substantially advance our understanding of arthropod evolution and resolve several conflicts among existing hypotheses. We assembled a data set of 233 taxa and 775 genes from which an optimally informative data set of 117 taxa and 129 genes was finally selected using new heuristics and compared with the unreduced data set. We included novel expressed sequence tag (EST) data for 11 species and all published phylogenomic data augmented by recently published EST data on taxonomically important arthropod taxa. This thorough sampling reduces the chance of obtaining spurious results due to stochastic effects of undersampling taxa and genes. Orthology prediction of genes, alignment masking tools, and selection of most informative genes due to a balanced taxa–gene ratio using new heuristics were established. Our optimized data set robustly resolves major arthropod relationships. We received strong support for a sister group relationship of onychophorans and euarthropods and strong support for a close association of tardigrades and cycloneuralia. Within pancrustaceans, our analyses yielded paraphyletic crustaceans and monophyletic hexapods and robustly resolved monophyletic endopterygote insects. However, our analyses also showed for few deep splits that were recently thought to be resolved, for example, the position of myriapods, a remarkable sensitivity to methods of analyses.
Reaction of antibodies to rheumatoid arthritis nuclear antigen with a synthetic peptide corresponding to part of Epstein-Barr nuclear antigen 1.
Authors: P J Venables, T Pawlowski, P A Mumford, C Brown, D H Crawford, R N Maini
Journal: Annals of the Rheumatic Diseases (1988)

Antibodies to rheumatoid arthritis nuclear antigen (RANA) are detected by immunodiffusion (ID) and immunofluorescence (IF), though reports of the identity of the antigen(s) have been conflicting. In this study it is shown conclusively that ID and IF anti-RANA react with epitopes on Epstein-Barr nuclear antigen 1 (EBNA-1) and that the major epitope detected by immunofluorescence is represented by a synthetic peptide, P62, corresponding to part of EBNA-1. In an enzyme linked immunosorbent assay (ELISA) anti-P62 antibodies in 35 rheumatoid arthritis sera were threefold higher than those of 35 age and sex matched controls, with the highest levels occurring in young patients with active joint disease.
Meta-Analysis Of Gene Expression Microarrays Reveals Novel Biomarkers Consistent With Altered Functionality Of Mucosal Barrier In Patients With Chronic Rhinosinusitis
Authors: Sergejs Berdnikovs, Atsushi Kato, James Norton, Lydia Suh, Robert C. Kern, David Conley, Rakesh Chandra, Anju T. Peters, Leslie C. Grammer, Kathleen E. Harris, Michael Platt, Ralph Metson, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2014)
Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia.
Authors: M L Myers, R Bolli, R F Lekich, C J Hartley, R Roberts
Journal: Circulation (1985)

Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 +/- 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 +/- 1.2% of the left ventricle in the control group and 26.5 +/- 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 +/- 14.3 vs 12.8 +/- 11.6) and 2 hr of reperfusion (74.2 +/- 8.4 vs 31.6 +/- 9.8, p less than .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia.
Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole
Authors: T.O. Kiljander, E.R.M. Salomaa, E.K Hietanen, E.O Terho
Journal: European Respiratory Journal (2000)

Gastro-oesophageal reflux (GOR) is an important cause of chronic cough. There has been a lack of placebo-controlled trials treating GOR related chronic cough with antireflux therapy. The aim of this study was to determine the efficacy of omeprazole on GOR related chronic cough. After excluding other common causes of cough, oesophageal pH monitoring was performed on 48 patients with chronic cough. Twenty-nine patients found to have GOR were randomized in a double-blind fashion to receive omeprazole 40 mg o.d. or placebo for 8 weeks. After a 2-week washout period, patients were crossed over to the other treatment. Symptoms were recorded daily in a diary. Twenty-one patients completed both treatment periods. Cough (p=0.02) and gastric symptoms (p=0.003) improved significantly during the omeprazole treatment in twelve patients who received placebo during the first and omeprazole during the second 8-week period. In nine patients who received omeprazole during the first 8-week period, amelioration in cough reached statistical significance only after cessation of omeprazole. Gastric symptoms also remained minor during placebo in these nine patients. Omeprazole 40 mg o.d. seems to improve chronic cough in patients with gastrooesophageal reflux and the effect of omeprazole in ameliorating both cough and reflux symptoms continues after treatment ceases.
Is general practice in need of a career structure?
Authors: G. J Elwyn, S. A Smail, A. G K Edwards
Journal: BMJ (1998)

With nearly 1000 vacancies for general practitioners in the United Kingdom in 1998, 1 the recruitment problem-exacerbated by early retirement by doctors keen to leave a discipline under pressure-is high on the professional agenda.Recruitment to general practice depends on acceptable and appropriate training.Bain has suggested that role models for the training of general practitioners in Britain are still stuck in a time warp of the 1970s, when the first training scheme started. 2 The government, however, has deemed that primary care is to become the steering force of the NHS again.An imbalance exists therefore between the strength needed to steer the NHS and the potential lack of structure in general practice training.
Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis
Authors: A. S. Nayak, E. Schenkel
Journal: Allergy (2001)

Nasal congestion is among the most bothersome of the symptoms of intermittent allergic rhinitis (IAR). Decongestants such as pseudoephedrine are often accompanied by adverse effects and should be avoided by patients with hypertension, arrhythmia, and other medical conditions. Most of the currently available antihistamines are ineffective for nasal congestion. Oral desloratadine, a new, potent H 1 ‐receptor antagonist, was examined for its ability to relieve nasal congestion/stuffiness in 346 patients (172 in the desloratadine group and 174 in the placebo group) with IAR. Desloratadine, administered once daily at a dose of 5 mg, demonstrated significant improvement in nasal congestion/stuffiness at all time points assessed in the study. This benefit was observed as early as the first patient evaluation on day 2 and continued throughout the 2 weeks of the study. Desloratadine is a new treatment option for patients with IAR and nasal congestion.
Molecular Basis for Leukocyte Integrin αEβ7 Adhesion to Epithelial (E)-Cadherin
Authors: Karen S. Taraszka, Jonathan M.G. Higgins, Kemin Tan, Didier A. Mandelbrot, Jia-huai Wang, Michael B. Brenner
Journal: The Journal of Experimental Medicine (2000)

Cadherins are expressed in tissue-restricted patterns and typically mediate homophilic adhesion. Cadherins also mediate lymphocyte adhesion, providing the opportunity for lymphocyte attachment to parenchymal cells. The best characterized example of lymphocyte adhesion to a tissue-specific cell adhesion molecule, as opposed to a vascular endothelial adhesion molecule, is the interaction between integrin αEβ7 on intraepithelial lymphocytes and E-cadherin on epithelial cells. However, the molecular basis for an integrin–cadherin interaction is not well defined. Realization that the cadherin domain adopts a topology similar to the immunoglobulin (Ig) fold suggested that integrin recognition of E-cadherin might be similar to recognition of Ig superfamily ligands. Thus, we modeled domain 1 of human E-cadherin and studied the role of solvent-exposed loops that connect Ig-like core-forming β strands. Mutational analyses localized the integrin αEβ7 recognition site to the top of domain 1 at the face formed by the BC and FG loops, a site distinct from the region recognized in intercellular adhesion molecule (ICAM)-1, -2, and -3, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), vascular cell adhesion molecule 1 (VCAM-1), and fibronectin by their integrin ligands. Moreover, the integrin αEβ7 binding site is distinct from the homophilic binding site on E-cadherin. These studies provide a conceptual basis for integrin–cadherin binding and extend the model that an Ig-like fold can serve as a scaffold for recognition.
Identification of an HLA-A*0201–restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein
Authors: Baomei Wang, Huabiao Chen, Xiaodong Jiang, Minghui Zhang, Tao Wan, Nan Li, Xiangyang Zhou, Yanfeng Wu, Feng Yang, Yizhi Yu, Xiaoning Wang, Ruifu Yang, Xuetao Cao
Journal: Blood (2004)