tbuckley/cabot-search huggingface dataset:
Relapsing necrotising sarcoid granulomatosis in a young patient
Authors: G. P. Currie, K. M. Kerr, J. S. Legge
Journal: European Respiratory Journal (2007)

To the Editors: 

The recent case of necrotising sarcoid granulomatosis described by Aliberti et al. 1 provides clinicians with an interesting insight into this rare condition. We would like to supplement the paucity of literature surrounding necrotising sarcoid granulomatosis and illustrate a case of our own. This was also in a young patient but did require treatment with oral corticosteroids at initial presentation and for a subsequent relapse.

A previously well 15-yr-old nonsmoking Caucasian female was referred to …
Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study
Authors: Richard K Burt, Yvonne Loh, Bruce Cohen, Dusan Stefosky, Roumen Balabanov, George Katsamakis, Yu Oyama, Eric J Russell, Jessica Stern, Paolo Muraro, John Rose, Alessandro Testori, Jurate Bucha, Borko Jovanovic, Francesca Milanetti, Jan Storek, Julio C Voltarelli, William H Burns
Journal: The Lancet Neurology (2009)
Identification of a New Subset of Myeloid Suppressor Cells in Peripheral Blood of Melanoma Patients With Modulation by a Granulocyte-Macrophage Colony-Stimulation Factor–Based Antitumor Vaccine
Authors: Paola Filipazzi, Roberta Valenti, Veronica Huber, Lorenzo Pilla, Paola Canese, Manuela Iero, Chiara Castelli, Luigi Mariani, Giorgio Parmiani, Licia Rivoltini
Journal: Journal of Clinical Oncology (2007)

Phenotypic and functional features of myeloid suppressor cells (MSC), which are known to serve as critical regulators of antitumor T-cell responses in tumor-bearing mice, are still poorly defined in human cancers. Here, we analyzed myeloid subsets with suppressive activity present in peripheral blood of metastatic melanoma patients and evaluated their modulation by a granulocyte-macrophage colony-stimulating factor (GM-CSF)--based antitumor vaccine.Stage IV metastatic melanoma patients (n = 16) vaccinated with autologous tumor-derived heat shock protein peptide complex gp96 (HSPPC-96) and low-dose GM-CSF provided pre- and post-treatment whole blood specimens. Peripheral-blood mononuclear cells (PBMCs) were analyzed by flow cytometry, separated into cellular subsets, and used for in vitro proliferation assays. PBMCs from stage-matched metastatic melanoma patients (n = 12) treated with non-GM-CSF-based vaccines (ie, HSPPC-96 alone or interferon alfa/melanoma-derived peptides) or sex- and age-matched healthy donors (n = 16) were also analyzed for comparison.The lack of or low HLA-DR expression was found to identify a CD14+ cell subset highly suppressive of lymphocyte functions. CD14+HLA-DR-/lo cells were significantly expanded in all metastatic melanoma patients, whereas they were undetectable in healthy donors. Suppressive activity was mediated by transforming growth factor beta (TGF-beta), whereas no involvement of the arginase and inducible nitric oxide synthase pathways could be detected. CD14+HLA-DR-/lo cells, as well as spontaneous ex vivo release and plasma levels of TGF-beta, were augmented after administration of the HSPPC-96/GM-CSF vaccine. No enhancement of the CD14+-mediated suppressive activity was found in patients receiving non-GM-CSF-based vaccines.CD14+HLA-DR-/lo cells exerting TGF-beta-mediated immune suppression represent a new subset of MSC potentially expandable by the administration of GM-CSF-based vaccines in metastatic melanoma patients.
SHP-1 phosphatase activity counteracts increased T cell receptor affinity
Authors: Michael Hebeisen, Lukas Baitsch, Danilo Presotto, Petra Baumgaertner, Pedro Romero, Olivier Michielin, Daniel E. Speiser, Nathalie Rufer
Journal: Journal of Clinical Investigation (2013)

Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (Kd < 1 μM) lead to drastic functional declines. Using human CD8+ T cells engineered with TCRs of incremental affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity–associated loss of function. As compared with cells expressing TCR affinities generating optimal function (Kd = 5 to 1 μM), those with supraphysiological affinity (Kd = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8+ T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity–dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8+ T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell–mediated immunity.
Estimation of Glomerular Podocyte Number
Authors: Kevin V. Lemley, John F. Bertram, Susanne B. Nicholas, Kathryn White
Journal: Journal of the American Society of Nephrology (2013)

The podocyte depletion hypothesis has emerged as an important unifying concept in glomerular pathology. The estimation of podocyte number is therefore often a critical component of studies of progressive renal diseases. Despite this, there is little uniformity in the biomedical literature with regard to the methods used to estimate this important parameter. Here we review a selection of valid methods for estimating podocyte number: exhaustive enumeration method, Weibel and Gomez method, disector/Cavalieri combination, disector/fractionator combination, and thick-and-thin section method. We propose the use of the disector/fractionator method for studies in which controlled sectioning of tissue is feasible, reserving the Weibel and Gomez method for studies based on archival or routine pathology material.
Origin and Diversification of Basic-Helix-Loop-Helix Proteins in Plants
Authors: N. Pires, L. Dolan
Journal: Molecular Biology and Evolution (2009)

Basic helix-loop-helix (bHLH) proteins are a class of transcription factors found throughout eukaryotic organisms. Classification of the complete sets of bHLH proteins in the sequenced genomes of Arabidopsis thaliana and Oryza sativa (rice) has defined the diversity of these proteins among flowering plants. However, the evolutionary relationships of different plant bHLH groups and the diversity of bHLH proteins in more ancestral groups of plants are currently unknown. In this study, we use whole-genome sequences from nine species of land plants and algae to define the relationships between these proteins in plants. We show that few (less than 5) bHLH proteins are encoded in the genomes of chlorophytes and red algae. In contrast, many bHLH proteins (100–170) are encoded in the genomes of land plants (embryophytes). Phylogenetic analyses suggest that plant bHLH proteins are monophyletic and constitute 26 subfamilies. Twenty of these subfamilies existed in the common ancestors of extant mosses and vascular plants, whereas six further subfamilies evolved among the vascular plants. In addition to the conserved bHLH domains, most subfamilies are characterized by the presence of highly conserved short amino acid motifs. We conclude that much of the diversity of plant bHLH proteins was established in early land plants, over 440 million years ago.
Novel Oral Factor Xa and Thrombin Inhibitors in the Management of Thromboembolism
Authors: Bengt I. Eriksson, Daniel J. Quinlan, John W. Eikelboom
Journal: Annual Review of Medicine (2010)

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice.
Synthesis of subcellular protein fractions in the rat heart in vivo in response to chronic ethanol feeding
Authors: V. R PREEDY, T. J PETERS
Journal: Cardiovascular Research (1989)

Journal Article Synthesis of subcellular protein fractions in the rat heart in vivo in response to chronic ethanol feeding Get access VICTOR R PREEDY, VICTOR R PREEDY From the Department of Clinical Biochemistry, Kings College School of Medicine and Dentistry London Address for correspondence and reprints: Dr Victor R Preedy. Department of Clinical Biochemistry, Kings College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar TIMOTHY J PETERS TIMOTHY J PETERS From the Department of Clinical Biochemistry, Kings College School of Medicine and Dentistry London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 8, August 1989, Pages 730–736, https://doi.org/10.1093/cvr/23.8.730 Published: 01 August 1989 Article history Accepted: 05 April 1989 Published: 01 August 1989
Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort
Authors: Rupert C M Jones, David Price, Dermot Ryan, Erika J Sims, Julie von Ziegenweidt, Laurence Mascarenhas, Anne Burden, David M G Halpin, Robert Winter, Sue Hill, Matt Kearney, Kevin Holton, Anne Moger, Daryl Freeman, Alison Chisholm, Eric D Bateman
Journal: The Lancet Respiratory Medicine (2014)

Patterns of health-care use and comorbidities present in patients in the period before diagnosis of chronic obstructive pulmonary disease (COPD) are unknown. We investigated these factors to inform future case-finding strategies.We did a retrospective analysis of a clinical cohort in the UK with data from Jan 1, 1990 to Dec 31, 2009 (General Practice Research Database and Optimum Patient Care Research Database). We assessed patients aged 40 years or older who had an electronically coded diagnosis of COPD in their primary care records and had a minimum of 3 years of continuous practice data for COPD (2 years before diagnosis up to a maximum of 20 years, and 1 year after diagnosis) and at least two prescriptions for COPD since diagnosis. We identified missed opportunites to diagnose COPD from routinely collected patient data by reviewing patterns of health-care use and comorbidities present before diagnosis. We assessed patterns of health-care use in terms of lower respiratory consultations (infective and non-infective), lower respiratory consultations with a course of antibiotics or oral steroids, and chest radiography. If these events did not lead to a diagnosis of COPD, they were deemed to be missed opportunities. This study is registered with ClinicalTrials.gov, number NCT01655667.We assessed data for 38,859 patients. Opportunities for diagnosis were missed in 32,900 (85%) of 38,859 patients in the 5 years immediately preceding diagnosis of COPD; in 12,856 (58%) of 22,286 in the 6-10 years before diagnosis, in 3943 (42%) of 9351 in the 11-15 years before diagnosis; and in 95 (8%) of 1167 in the 16-20 years before diagnosis. Between 1990 and 2009, we noted decreases in the age at diagnosis (0·05 years of age per year, 95% CI 0·03-0·07) and yearly frequency of lower respiratory prescribing consultations (rate ratio 0·982 opportunities per year, 95% CI 0·979-0·985). Prevalence of all comorbidities present at COPD diagnosis increased except for asthma and bronchiectasis, which decreased between 1990 and 2007, from 281 (33·4%) of 842 patients to 451 of 1465 (30·8%) for asthma, and from 53 of 842 (6·3%) to 53 of 1465 (3·6%) for bronchiectasis. In the 2 years before diagnosis, of 6897 patients who had had a chest radiography, only 2296 (33%) also had spirometry.Opportunities to diagnose COPD at an earlier stage are being missed, and could be improved by case-finding in patients with lower respiratory tract symptoms and concordant long-term comorbidities.UK Department of Health, Research in Real Life.
Increased Risk of Myocardial Infarction in Depressed Patients With Type 2 Diabetes
Authors: Jeffrey F. Scherrer, Lauren D. Garfield, Timothy Chrusciel, Paul J. Hauptman, Robert M. Carney, Kenneth E. Freedland, Richard Owen, William R. True, Patrick J. Lustman
Journal: Diabetes Care (2011)

To investigate major depressive disorder (MDD), which complicates the course of type 2 diabetes and is associated with an increased risk of cardiovascular disease and death. This risk may be due to a greater susceptibility for myocardial infarction (MI) in depressed patients with type 2 diabetes compared with nondepressed patients with type 2 diabetes.Veterans Administration electronic medical records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25 to 80 years. ICD-9-CM codes were used to create a four-level risk group indicating 1) neither diabetes nor MDD (n = 214,749), 2) MDD alone (n = 77,568), 3) type 2 diabetes alone (n = 40,953), and 4) comorbid MDD and type 2 diabetes (n = 12,679). Age-adjusted Cox proportional hazards models were computed before and after adjusting for baseline sociodemographic and time-dependent covariates.After adjusting for covariates, patients with type 2 diabetes alone and patients with MDD alone were at ∼30% increased risk for MI, and patients with type 2 diabetes and MDD were at 82% increased risk for MI (hazard ratio 1.82 [95% CI 1.69-1.97]) compared with patients without either condition.Compared with patients with only diabetes or only MDD, individuals with type 2 diabetes and MDD are at increased risk for new-onset MI. Monitoring cardiovascular health in depressed patients with type 2 diabetes may reduce the risk of MI in this especially high-risk group.
DIVERSE FUNCTIONS OF IL-2, IL-15, AND IL-7 IN LYMPHOID HOMEOSTASIS
Authors: Averil Ma, Rima Koka, Patrick Burkett
Journal: Annual Review of Immunology (2006)

IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis. These cytokines stimulate similar responses from lymphocytes in vitro, but play markedly divergent roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by proprietary cytokine receptor chains, differential expression patterns of the cytokines or their receptor chains, and/or signals occurring in distinct physiological contexts. Recently, the discovery of a novel mechanism of cytokine signaling, trans-presentation, has provided further insights into the different ways these cytokines function. Trans-presentation also raises several novel cell biological and cellular implications concerning how cytokines support lymphoid homeostasis.
Modern treatment of warts: cure rates at 3 and 6 months
Authors: J. BERTH-JONES, P.E. HUTCHINSON
Journal: British Journal of Dermatology (1992)

Journal Article Modern treatment of warts: cure rates at 3 and 6 months Get access J. BERTH‐JONES, J. BERTH‐JONES Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Dr J. Berth‐Jones. Search for other works by this author on: Oxford Academic Google Scholar P.E. HUTCHINSON P.E. HUTCHINSON Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 3, 1 September 1992, Pages 262–265, https://doi.org/10.1111/j.1365-2133.1992.tb00125.x Published: 01 September 1992
BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads
Authors: Lewis Z Hong, Shuzhen Hong, Han Teng Wong, Pauline PK Aw, Yan Cheng, Andreas Wilm, Paola F de Sessions, Seng Gee Lim, Niranjan Nagarajan, Martin L Hibberd, Stephen R Quake, William F Burkholder
Journal: Genome biology (2014)

Abstract We present a method for obtaining long haplotypes, of over 3 kb in length, using a short-read sequencer, Barcode-directed Assembly for Extra-long Sequences (BAsE-Seq). BAsE-Seq relies on transposing a template-specific barcode onto random segments of the template molecule and assembling the barcoded short reads into complete haplotypes. We applied BAsE-Seq on mixed clones of hepatitis B virus and accurately identified haplotypes occurring at frequencies greater than or equal to 0.4%, with &gt;99.9% specificity. Applying BAsE-Seq to a clinical sample, we obtained over 9,000 viral haplotypes, which provided an unprecedented view of hepatitis B virus population structure during chronic infection. BAsE-Seq is readily applicable for monitoring quasispecies evolution in viral diseases.
Remote Ischemic Preconditioning and Renoprotection
Authors: Natig Gassanov, Amir M. Nia, Evren Caglayan, Fikret Er
Journal: Journal of the American Society of Nephrology (2013)

There is currently no effective prophylactic regimen available to prevent contrast-induced AKI (CI-AKI), a frequent and life-threatening complication after cardiac catheterization. Therefore, novel treatment strategies are required to decrease CI-AKI incidence and to improve clinical outcomes in these patients. Remote ischemic preconditioning (rIPC), defined as transient brief episodes of ischemia at a remote site before a subsequent prolonged ischemia/reperfusion injury of the target organ, is an adaptational response that protects against ischemic and reperfusion insult. Indeed, several studies demonstrated the tissue-protective effects of rIPC in various target organs, including the kidneys. In this regard, rIPC may offer a novel noninvasive and virtually cost-free treatment strategy for decreasing CI-AKI incidence. This review evaluates the current experimental and clinical evidence for rIPC as a potential renoprotective strategy, and discusses the underlying mechanisms and key areas for future research.
RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors
Authors: Yingjun Su, Anna E. Vilgelm, Mark C. Kelley, Oriana E. Hawkins, Yan Liu, Kelli L. Boyd, Sara Kantrow, Ryan C. Splittgerber, Sarah P. Short, Tammy Sobolik, Snjezana Zaja-Milatovic, Kimberly Brown Dahlman, Katayoun I. Amiri, Aixiang Jiang, Pengcheng Lu, Yu Shyr, Darrin D. Stuart, Shawn Levy, Jeffrey A. Sosman, Ann Richmond
Journal: Clinical Cancer Research (2012)

The purpose of this preclinical study was to determine the effectiveness of RAF265, a multikinase inhibitor, for treatment of human metastatic melanoma and to characterize traits associated with drug response.Advanced metastatic melanoma tumors from 34 patients were orthotopically implanted to nude mice. Tumors that grew in mice (17 of 34) were evaluated for response to RAF265 (40 mg/kg, every day) over 30 days. The relation between patient characteristics, gene mutation profile, global gene expression profile, and RAF265 effects on tumor growth, mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation, proliferation, and apoptosis markers was evaluated.Nine of the 17 tumors that successfully implanted (53%) were mutant BRAF (BRAF(V600E/K)), whereas eight of 17 (47%) tumors were BRAF wild type (BRAF(WT)). Tumor implants from 7 of 17 patients (41%) responded to RAF265 treatment with more than 50% reduction in tumor growth. Five of the 7 (71%) responders were BRAF(WT), of which 1 carried c-KIT(L576P) and another N-RAS(Q61R) mutation, while only 2 (29%) of the responding tumors were BRAF(V600E/K). Gene expression microarray data from nonimplanted tumors revealed that responders exhibited enriched expression of genes involved in cell growth, proliferation, development, cell signaling, gene expression, and cancer pathways. Although response to RAF265 did not correlate with pERK1/2 reduction, RAF265 responders did exhibit reduced pMEK1, reduced proliferation based upon reduced Ki-67, cyclin D1 and polo-like kinase1 levels, and induction of the apoptosis mediator BCL2-like 11.Orthotopic implants of patient tumors in mice may predict prognosis and treatment response for melanoma patients. A subpopulation of human melanoma tumors responds to RAF265 and can be characterized by gene mutation and gene expression profiles.
Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation
Authors: Brandon Hayes‐Lattin, Timothy J. Seipel, Ken Gatter, Michael C. Heinrich, Richard T. Maziarz
Journal: American Journal of Hematology (2004)

Abstract Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed. Am. J. Hematol. 75:142–145, 2004. © 2004 Wiley‐Liss, Inc.
Measurement of blood pressure using a portable recorder operated by the patient
Authors: N. Conway, D. Rubenstein, R. Emanuel, D. Gibbons
Journal: Cardiovascular Research (1970)

Journal Article Measurement of blood pressure using a portable recorder operated by the patient Get access Neville Conway, Neville Conway From the Departments of Cardiology and Medicine, Middlesex Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar David Rubenstein, David Rubenstein From the Departments of Cardiology and Medicine, Middlesex Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Emanuel, Richard Emanuel From the Departments of Cardiology and Medicine, Middlesex Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar David Gibbons David Gibbons From the Departments of Cardiology and Medicine, Middlesex Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 4, Issue 4, October 1970, Pages 537–544, https://doi.org/10.1093/cvr/4.4.537 Published: 01 October 1970 Article history Accepted: 19 March 1970 Published: 01 October 1970