tbuckley/cabot-search huggingface dataset:
Lung allograft transplantation: indications, preoperative assessment and postoperative management
Authors: F Heritier, B Madden, ME Hodson, M Yacoub
Journal: European Respiratory Journal (1992)

In spite of a shortage of available donors, an increasing number of heart-lung transplantations have been performed within the last decade. This procedure, first limited to patients with pulmonary vascular disease, has been successfully extended to patients with end stage lung disease, including cystic fibrosis. More recently, single lung, double-lung and bilateral single lung transplantation have become other therapeutic options. Better selection of patients and donors as well as improvements in surgical techniques and immunosuppression regimens have contributed to the reduction in the high perioperative mortality experienced in the early stages. Moreover, the introduction of daily spirometry and transbronchial lung biopsies have permitted early and reliable diagnosis of opportunistic infection and rejection. The most serious late complication of lung transplantation is obliterative bronchiolitis and further research is urgently required to improve diagnosis and management of this condition.
A 5-Year Follow-up of Rituximab Treatment in Patients With Neuromyelitis Optica Spectrum Disorder
Authors: Su-Hyun Kim, So-Young Huh, Sun Ju Lee, AeRan Joung, Ho Jin Kim
Journal: JAMA Neurology (2013)

A previous 2-year analysis of repeated rituximab treatment in patients with neuromyelitis optica (NMO) revealed significant improvements in relapse rates and disability. We report the findings from the longest follow-up of rituximab treatment in NMO, which provide reassurance regarding the long-term efficacy and safety of rituximab in NMO.To report the results of rituximab treatment in patients with relapsing NMO or NMO spectrum disorder (NMOSD) for a median of 60 months.Retrospective case series in an institutional referral center for multiple sclerosis, including 30 patients with relapsing NMO or NMOSD.After induction therapy, a single infusion of rituximab (375 mg/m2) as maintenance therapy was administered whenever the frequency of reemerging CD27+ memory B cells in peripheral blood mononuclear cells, as measured with flow cytometry, exceeded 0.05%in the first 2 years and 0.1% thereafter.Annualized relapse rate (ARR), disability (Expanded Disability Status Scale score), change in anti–aquaporin 4 antibody, and safety of rituximab treatment.Of 30 patients, 26 (87%) exhibited a marked reduction in ARR over 5 years (mean [SD] pretreatment vs posttreatment ARR, 2.4 [1.5] vs 0.3 [1.0]). Eighteen patients (60%) became relapse free after rituximab treatment. In 28 patients (93%), the disability was either improved or stabilized after rituximab treatment. No serious adverse events leading to discontinuation were observed during follow-up.Repeated treatment with rituximab in patients with NMOSD over a 5-period, using an individualized dosing schedule according to the frequency of reemerging CD27+ memory B cells, leads to a sustained clinical response with no new adverse events.
The stunned myocardium: prolonged, postischemic ventricular dysfunction.
Authors: E Braunwald, R A Kloner
Journal: Circulation (1982)

Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of myocardial ischemia should be expanded. According to this formulation, an ischemic insult not of sufficient severity of duration to produce myocardial necrosis may acutely affect myocardial repolarization and cause angina (hit); but these changes wane rapidly (run), when the balance between myocardial oxygen supply and demand has been reestablished. However, the ischemia may interfere with normal myocardial function, biochemical processes and ultrastructure for prolonged periods (stun). The severity and duration of these postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode. Furthermore, it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, an ill-defined condition. If prolonged, chronic postischemic left ventricular dysfunction can progress to myocardial scarring and ischemic cardiomyopathy, it may be important to determine how often it can be ameliorated by permanent improvement of myocardial perfusion by surgical treatment.
Medicare's Physician Value-Based Payment Modifier — Will the Tectonic Shift Create Waves?
Authors: Alyna T. Chien, Meredith B. Rosenthal
Journal: New England Journal of Medicine (2013)

Medicare's new Physician Value-Based Payment Modifier will financially reward physicians who provide high-quality, low-cost health care. Will this tectonic shift in physician payment set off a new wave of efforts to improve quality and cost performance?
Preferential Expression and Function of Voltage-Gated, O <sub>2</sub> -Sensitive K <sup>+</sup> Channels in Resistance Pulmonary Arteries Explains Regional Heterogeneity in Hypoxic Pulmonary Vasoconstriction
Authors: Stephen L. Archer, Xi-Chen Wu, Bernard Thébaud, Ali Nsair, Sebastien Bonnet, Ben Tyrrell, M. Sean McMurtry, Kyoko Hashimoto, Gwyneth Harry, Evangelos D. Michelakis
Journal: Circulation Research (2004)

Hypoxic pulmonary vasoconstriction (HPV) is initiated by inhibition of O 2 -sensitive, voltage-gated (Kv) channels in pulmonary arterial smooth muscle cells (PASMCs). Kv inhibition depolarizes membrane potential (E M ), thereby activating Ca 2+ influx via voltage-gated Ca 2+ channels. HPV is weak in extrapulmonary, conduit pulmonary arteries (PA) and strong in precapillary resistance arteries. We hypothesized that regional heterogeneity in HPV reflects a longitudinal gradient in the function/expression of PASMC O 2 -sensitive Kv channels. In adult male Sprague Dawley rats, constrictions to hypoxia, the Kv blocker 4-aminopyridine (4-AP), and correolide, a Kv1.x channel inhibitor, were endothelium-independent and greater in resistance versus conduit PAs. Moreover, HPV was dependent on Kv-inhibition, being completely inhibited by pretreatment with 4-AP. Kv1.2, 1.5, Kv2.1, Kv3.1b, Kv4.3, and Kv9.3. mRNA increased as arterial caliber decreased; however, only Kv1.5 protein expression was greater in resistance PAs. Resistance PASMCs had greater K + current (I K ) and a more hyperpolarized E M and were uniquely O 2 − and correolide-sensitive. The O 2 -sensitive current (active at −65 mV) was resistant to iberiotoxin, with minimal tityustoxin sensitivity. In resistance PASMCs, 4-AP and hypoxia inhibited I K 57% and 49%, respectively, versus 34% for correolide. Intracellular administration of anti-Kv1.5 antibodies inhibited correolide’s effects. The hypoxia-sensitive, correolide-insensitive I K (15%) was conducted by Kv2.1. Anti-Kv1.5 and anti-Kv2.1 caused additive depolarization in resistance PASMCs (Kv1.5&gt;Kv2.1) and inhibited hypoxic depolarization. Heterologously expressed human PASMC Kv1.5 generated an O 2 − and correolide-sensitive I K like that in resistance PASMCs. In conclusion, Kv1.5 and Kv2.1 account for virtually all the O 2 -sensitive current. HPV occurs in a Kv-enriched resistance zone because resistance PASMCs preferentially express O 2 -sensitive Kv-channels.
Phylogenetic Distributions and Histories of Proteins Involved in Anaerobic Pyruvate Metabolism in Eukaryotes
Authors: L. A. Hug, A. Stechmann, A. J. Roger
Journal: Molecular Biology and Evolution (2009)

Protists that live in low oxygen conditions often oxidize pyruvate to acetate via anaerobic ATP-generating pathways. Key enzymes that commonly occur in these pathways are pyruvate:ferredoxin oxidoreductase (PFO) and [FeFe]-hydrogenase (H2ase) as well as the associated [FeFe]-H2ase maturase proteins HydE, HydF, and HydG. Determining the origins of these proteins in eukaryotes is of key importance to understanding the origins of anaerobic energy metabolism in microbial eukaryotes. We conducted a comprehensive search for genes encoding these proteins in available whole genomes and expressed sequence tag data from diverse eukaryotes. Our analyses of the presence/absence of eukaryotic PFO, [FeFe]-H2ase, and H2ase maturase sequences across eukaryotic diversity reveal orthologs of these proteins encoded in the genomes of a variety of protists previously not known to contain them. Our phylogenetic analyses revealed: 1) extensive lateral gene transfers of both PFO and [FeFe]-H2ase in eubacteria, 2) decreased support for the monophyly of eukaryote PFO domains, and 3) that eukaryotic [FeFe]-H2ases are not monophyletic. Although there are few eukaryote [FeFe]-H2ase maturase orthologs characterized, phylogenies of these proteins do recover eukaryote monophyly, although a consistent eubacterial sister group for eukaryotic homologs could not be determined. An exhaustive search for these five genes in diverse genomes from two representative eubacterial groups, the Clostridiales and the α-proteobacteria, shows that although these enzymes are nearly universally present within the former group, they are very rare in the latter. No α-proteobacterial genome sequenced to date encodes all five proteins. Molecular phylogenies and the extremely restricted distribution of PFO, [FeFe]-H2ases, and their associated maturases within the α-proteobacteria do not support a mitochondrial origin for these enzymes in eukaryotes. However, the unexpected prevalence of PFO, pyruvate:NADP oxidoreductase, [FeFe]-H2ase, and the maturase proteins encoded in genomes of diverse eukaryotes indicates that these enzymes have an important role in the evolution of microbial eukaryote energy metabolism.
Radiological correlates and clinical implications of the paradoxical lung function response to β2 agonists: an observational study
Authors: Surya P Bhatt, James M Wells, Victor Kim, Gerard J Criner, Craig P Hersh, Megan Hardin, William C Bailey, Hrudaya Nath, Young-il Kim, Marilyn G Foreman, Douglas S Stinson, Carla G Wilson, Stephen I Rennard, Edwin K Silverman, Barry J Make, Mark T Dransfield
Journal: The Lancet Respiratory Medicine (2014)
Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse.
Authors: W I Rosenblum, G H Nelson, J T Povlishock
Journal: Circulation Research (1987)

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.
What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort
Authors: K Takase, S C Horton, A Ganesha, S Das, A McHugh, P Emery, S Savic, M H Buch
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To determine whether serial ANA testing predicts biological disease modifying antirheumatic drugs (bDMARD)-associated ANA/dsDNA production in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Serial autoantibody profiles, bDMARD treatment sequences and clinical data were collected from patients identified from our database that since 2005 received (i) a first bDMARD (tumour necrosis factor inhibitor (TNFi)) and (ii) tocilizumab and/or abatacept. <h3>Results</h3> Of over 1000 patients, 454 RA patients received a first TNFi. Infliximab group demonstrated higher ANA seroconversion rates (31.2%) compared with etanercept (11.8%) and adalimumab (16.1%) (p&lt;0.001). Median (range) treatment duration prior to ANA seroconversion was 10.9 (1.3–80.0) months. Positive anti-dsDNA titres of IgG class (median (range) of 77 IU/mL (65–109)) were noted in six (7.2%) patients, within a median (range) of 2.0 (0.8–4.2) years. Three patients developed classifiable lupus. 4 of 74 (5.4%) primary non-responders and 24 of 111 (21.6%) secondary non-responders developed positive ANA antibodies after TNFi initiation (p=0.003). Seven (9.5%) tocilizumab-treated patients changed to positive ANA; five (8.6%) abatacept-treated patients changed to positive ANA status. <h3>Conclusions</h3> This study demonstrates no utility of serial ANA/dsDNA testing that could be used to predict onset of seroconversion and therefore the development of lupus/vasculitis. An association however between seroconversion and the development of a secondary non-response to bDMARD therapy is suggested.
Growth of B-lymphocyte colonies in vitro.
Authors: D Metcalf, G J Nossal, N L Warner, J F Miller, T E Mandel, J E Layton, G A Gutman
Journal: The Journal of Experimental Medicine (1975)

In semisolid agar cultures containing mercaptoethanol, cells from the spleen, lymph nodes, marrow, peritoneal cavity, thoracic duct, and blood of normal mice generated clusters and colonies of up to 3,000 cells. Colony numbers and growth were markedly enhanced by the addition of sheep red cells. The frequency of colony-forming cells in the spleen or lymph nodes was 0.5-2.0%, and cluster forming cells were approximately five times more numerous. The mononuclear cells comprising these colonies had the electronmicroscopic morphology of immature lymphoid and plasma cells. The majority of the cells possessed Fc receptors, 61-69% reacted with anti-mu-serum and 4-11% with anti-gamma2-serum. Analysis of single cells from individual colonies indicated a higher frequency of the cells with membrane immunoglobulin and a clonal pattern of anti-mu or anti-gamma-reactivity. The clonal nature of colonies was supported by an analysis of NIP-binding cells in colonies grown from CBA spleen cells enriched for NIP-binding cells. Mass-harvested colony cells synthesized immunoglobulin in short-term liquid cultures. It is concluded that the colonies are clones of functionally active B-lymphoid cells.
Battle of the clotbusters.
Authors: M O'Donnell
Journal: BMJ (1991)

Coordinated by Dr Rory Collins from Oxford, the data for the third international study of infarct survival (ISIS-3) came from investigators in nearly 1 000 hospitals in Europe, North America, and Australasia who had treated over 46 000 patients suffering an acute myocardial infarction with one of three randomly assigned fibrinolytic agents : streptokinase, anistreplase, or tissue plasminogen activator (tPA)
Transient Ventricular Conduction Disturbances Produced by Intra-atrial Injection of Single Doses of KCI
Authors: JAOK HAN, ANNA MAE MALOZZI, GORDON K. MOE
Journal: Circulation Research (1967)

In dogs under pentobarbital anesthesia, the administration of KCl in single intra-atrial doses of 1 mg/kg produced varying effects on intraventricular conduction depending upon the initial potassium concentration of systemic blood. At normal and moderately increased systemic K concentrations, single injections of KCl improved intraventricular conduction, but at higher systemic K concentrations a negative dromotropic effect appeared. Following injection into the right atrium, the effect appeared immediately in the right ventricle, followed after some delay by an appreciably lesser effect in the left ventricle. Injection of potassium into the left atrium altered conduction in the left ventricle without affecting the right ventricle. The results indicate that transient alterations of [K] in the blood of the ventricular cavity can act directly on the specialized conduction network to alter the rate of intraventricular conduction.
Lack of association of T cell receptor V beta 8 polymorphism with rheumatoid arthritis in United Kingdom and Italian white patients.
Authors: C Lunardi, M Ibberson, S Zeminian, G De Sandre, A K So
Journal: Annals of the Rheumatic Diseases (1994)

To study if the reported association of a BamH I 2kb RFLP of the T cell receptor V beta 8 gene with DR4+ rheumatoid arthritis patients is found in non-American white populations.The frequency of this RFLP in two different populations was analysed. Eighty one northern Italians were studied for HLA-DR genotypes and V beta 8 polymorphism, and 29 DR4+ British white patients were studied for V beta 8 polymorphism.No association between the V beta 8 RFLP and DR4 was found with rheumatoid arthritis in both groups.The reported V beta 8-DR4 association is not generally applicable. The lack of association in our populations may be due to genetic differences, or to differences in factors which shaped the T cell repertoire.
THE ABSORPTION OF PROTEIN SOLUTIONS FROM THE PULMONARY ALVEOLI
Authors: Cecil K. Drinker, Madeleine Field Warren, Margaret MacLanahan
Journal: The Journal of Experimental Medicine (1937)

Horse serum, crystallized hemoglobin, and crystallized egg albumin have been injected into the lung alveoli of dogs in which the entrances of the right lymphatics have been tied and the thoracic duct cannulated. Samples of blood and lymph have been taken following this injection. Only after several hours in the case of the horse serum and hemoglobin have these proteins been detected by immunological methods and invariably they have appeared first in the blood. Egg albumin also enters the blood capillaries, but much more rapidly than the other two proteins, due probably to the smaller molecular size.
Circumferential Hyperechogenecity as an Ultrasound Sign of Infected Abdominal Aortic Aneurysm
Authors: Tsuyoshi Yoshimuta, Toshiya Okajima, Hatsue Ishibashi-Ueda, Mika Mori, Masahiro Higashi, Kenshi Hayashi, Masa-aki Kawashiri, Masakazu Yamagishi
Journal: Circulation (2013)
A transcriptional timetable of autumn senescence
Authors: Anders Andersson, Johanna Keskitalo, Andreas Sjödin, Rupali Bhalerao, Fredrik Sterky, Kirsten Wissel, Karolina Tandre, Henrik Aspeborg, Richard Moyle, Yasunori Ohmiya, Rishikesh Bhalerao, Amy Brunner, Petter Gustafsson, Jan Karlsson, Joakim Lundeberg, Ove Nilsson, Göran Sandberg, Steven Strauss, Björn Sundberg, Mathias Uhlen, Stefan Jansson, Peter Nilsson
Journal: Genome biology (2004)
Role of Transforming Growth Factor Beta in Human Cancer
Authors: Rebecca L. Elliott, Gerard C. Blobe
Journal: Journal of Clinical Oncology (2005)

Transforming growth factor beta (TGF-beta) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-beta signaling pathway, including mutation or deletion of members of the signaling pathway and resistance to TGF-beta-mediated inhibition of proliferation are frequently observed in human cancers. Although these alterations define a tumor suppressor role for the TGF-beta pathway in human cancer, TGF-beta also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through a fundamental alteration in the TGF-beta responsiveness of the tumor cells themselves. TGF-beta and members of the TGF-beta signaling pathway are being evaluated as prognostic or predictive markers for cancer patients. Ongoing advances in understanding the TGF-beta signaling pathway will enable targeting of this pathway for the chemoprevention and treatment of human cancers.
The cost‐effectiveness of immunotherapy for respiratory allergy: a review
Authors: S. Simoens
Journal: Allergy (2012)

Abstract This article reviews the international literature on the cost‐effectiveness of immunotherapy for respiratory allergy. Included studies conducted an economic evaluation of immunotherapy for allergic rhinoconjunctivitis, allergic conjunctivitis, allergic rhinitis, asthma or allergic rhinitis in combination with asthma. Although there were few economic evaluations and these suffered from methodological shortcomings, the evidence appears to support the cost‐effectiveness of immunotherapy as compared with pharmacotherapy for allergic rhinoconjunctivitis, subcutaneous immunotherapy as compared with pharmacotherapy for allergic rhinitis and immunotherapy as compared with pharmacotherapy for allergic rhinitis and asthma. One economic evaluation suggested that immunotherapy as compared with pharmacotherapy is unlikely to be cost‐effective for asthma. The questions of the cost‐effectiveness of sublingual vs subcutaneous immunotherapy and of the cost‐effectiveness of immunotherapy for allergic conjunctivitis have not been resolved to date. The cost‐effectiveness of immunotherapy depends on the duration of the clinical benefit of immunotherapy following treatment cessation, and on the break‐even point of cumulative costs between immunotherapy and pharmacotherapy. There is a need for economic evaluations based on high‐quality prospective and long‐term clinical studies comparing immunotherapy with pharmacotherapy in real‐life practice and comparing sublingual with subcutaneous immunotherapy.
Response to Preiksaitis and Limaye
Authors: Pierre-Olivier Bridevaux, J-D Aubert, T Rochat, L Nicod, Laurent Kaiser
Journal: Thorax (2013)

We thank Preiksaitis and Limaye for their comments on our paper1 and their interest and we attempt to provide herewith responses to their questions. First, they correctly note that we did not find an association between viral infection and acute rejection in our lung transplant recipient (LTR) cohort.2 However, this finding does not preclude a possible association between viral infection and bronchiolitis obliterans syndrome (BOS). While the temporal association between viral infection and acute rejection is expected to be short, the BOS inflammatory process and lung function decline may develop months after infection. In our study, follow-up was too short in many LTRs at this stage to allow for an adequate analysis of factors associated with incident BOS. Analyses pertaining to such are currently ongoing.

We agree with Preiksaitis and Limaye that respiratory viral infections have been under-recognised thus far. They raise the criticism that surveillance testing …