tbuckley/cabot-search huggingface dataset:
Congenic Fine-Mapping Identifies a Major Causal Locus for Variation in the Native Collateral Circulation and Ischemic Injury in Brain and Lower Extremity
Authors: Robert Sealock, Hua Zhang, Jennifer L. Lucitti, Scott M. Moore, James E. Faber
Journal: Circulation Research (2013)

Rationale : Severity of tissue injury in occlusive disease is dependent on the extent (number and diameter) of collateral vessels, which varies widely among healthy mice and humans. However, the causative genetic elements are unknown. Recently, much of the variation among different mouse strains, including C57Bl/6J (B6, high extent) and BALB/cByJ (Bc, low extent), was linked to a quantitative trait locus on chromosome 7 ( Candq1 ). Objective : We used congenic mapping to refine Candq1 and its candidate genes to create an isogenic strain set with large differences in collateral extent to assess their impact and the impact of Candq1 , alone, on ischemic injury. Methods and Results : Six congenic strains possessing portions of Candq1 introgressed from B6 into Bc were generated and phenotyped. Candq1 was refined from 27 to 0.737 Mb with full retention of effect, that is, return or rescue of phenotypes from the poor values in Bc to nearly those of wild-type B6 in the B6/B6 congenic mice as follows: 83% rescue of low pial collateral extent and 4.5-fold increase in blood flow and 85% reduction of infarct volume after middle cerebral artery occlusion; 54% rescue of low skeletal muscle collaterals and augmented recovery of perfusion (83%) and function after femoral artery ligation. Gene deletion and in silico analysis further delineated the candidate genes. Conclusions : We have significantly refined Candq1 (now designated determinant of collateral extent 1; Dce1 ), demonstrated that genetic background–dependent variation in collaterals is a major factor underlying differences in ischemic tissue injury, and generated a congenic strain set with wide allele dose–dependent variation in collateral extent for use in investigations of the collateral circulation.
Demographic and clinical differences between unilateral and bilateral forms of naevoid telangiectasia: a retrospective study with review of the literature
Authors: E.J. Kim, H.S. Park, H.S. Yoon, K.H. Kim, S. Cho
Journal: British Journal of Dermatology (2014)

Journal Article Demographic and clinical differences between unilateral and bilateral forms of naevoid telangiectasia: a retrospective study with review of the literature Get access E.J. Kim, E.J. Kim Department of Dermatology Seoul National University Boramae Hospital 20 Boramae Road 5‐gil Dongjak‐gu Seoul 156‐707 Korea Search for other works by this author on: Oxford Academic Google Scholar H.S. Park, H.S. Park Department of Dermatology Seoul National University Boramae Hospital 20 Boramae Road 5‐gil Dongjak‐gu Seoul 156‐707 Korea Search for other works by this author on: Oxford Academic Google Scholar H.S. Yoon, H.S. Yoon Department of Dermatology Seoul National University Boramae Hospital 20 Boramae Road 5‐gil Dongjak‐gu Seoul 156‐707 Korea Search for other works by this author on: Oxford Academic Google Scholar K.H. Kim, K.H. Kim Department of Dermatology Seoul National University Hospital 101 Daehak‐ro Jongno‐gu 2 Seoul 110‐744 Korea Search for other works by this author on: Oxford Academic Google Scholar S. Cho S. Cho Department of Dermatology Seoul National University Boramae Hospital 20 Boramae Road 5‐gil Dongjak‐gu Seoul 156‐707 Korea Correspondence: Soyun Cho E‐mail: sycho@snu.ac.kr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 6, 1 June 2015, Pages 1651–1653, https://doi.org/10.1111/bjd.13615 Published: 01 June 2015
Panniculitis associated with cutaneous T-cell lymphoma and cytophagocytic histiocytosis
Authors: IRIS K. ARONSON, D.P. WEST, D. VARIAKOJIS, S.G. RONAN, I. IOSSIFIDES, H.J. ZEITZ
Journal: British Journal of Dermatology (1985)

A 36‐year‐old woman had a 6‐year history of recurrent panniculitis with development of an angiocentric and angiodestructive cutaneous T‐cell lymphoma (CTCL) of the helper cell phenotype. She subsequently developed a rapidly progressive fatal syndrome characterized by cytophagocytic histiocytosis and hyperlipidaemia. Cytophagocytic histiocytosis has previously been reported in association with panniculitis, malignancy and infection, but not with CTCL and the precise relationship between panniculitis, CTCL, cytophagocytic histiocytosis and hyperlipidemia is unclear.
Optimal Use of Blood Tests for Assessment of Thyroid Function
Authors: David V. Becker
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The American Thyroid Association (ATA) in 1990 and 1991 issued guidelines for use of laboratory tests in thyroid disorders.<sup>1,2</sup>These ATA position papers update previous recommendations because of the development and availability of improved thyrotropin (thyroid-stimulating hormone [TSH]) methods capable of clearly separating normal from subnormal serum TSH levels. The highly sensitive TSH assay constitutes a practical, useful, and significant laboratory advance in clinical thyroidology. There is agreement among thyroid specialists that measurement of serum TSH level, complemented by an appropriate free thyroxine (FT<sub>4</sub>) estimate, represents the best and most efficient combination of blood tests for diagnosis and follow-up of most patients with thyroid disorders. Currently in the investigation of thyroid disease there is a trend to replace a combination of tests (eg, total T<sub>4</sub>+ triiodothyronine resin uptake + FT<sub>4</sub>+ total T<sub>3</sub>+ TSH) by a discriminating single thyroid function test. This trend reflects
No lung cancer at resection of PET positive lesions: an audit of the lung cancer multidisciplinary team
Authors: I. J. Clifton, A. F. Scarsbrook, M. F. Muers
Journal: European Respiratory Journal (2009)

To the Editors: 

An essential role of the lung cancer multidisciplinary team (MDT) is to provide an accurate and prompt diagnosis enabling resection of malignant disease where appropriate, while minimising the risk of unnecessary surgical intervention. Since 2005, 18F-deoxy-d-glucose positron emission tomography–computed tomography (18FDG PET-CT) has been recommended for all patients with potentially radically treatable disease as part of the routine lung cancer staging process 1. The Leeds Teaching Hospital (Leeds, UK) lung cancer MDT is a regional centre with an approximate workload of 500 patients with lung cancer per year. Within the lung cancer MDT, concern was raised regarding a series of patients referred for surgical resection who had a nonmalignant diagnosis at lung resection. It was decided to audit patients referred for surgical resection to determine the frequency of a benign diagnosis at resection. Standard practice within the lung cancer MDT …
Augmented Antitumor Activity against B-Cell Lymphoma by a Combination of Monoclonal Antibodies Targeting TRAIL-R1 and CD20
Authors: Sreeram Maddipatla, Francisco J. Hernandez-Ilizaliturri, Joy Knight, Myron S. Czuczman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Mapatumumab and lexatumumab are fully humanized, high-affinity immunoglobulin G1λ monoclonal antibodies (mAb) that target/activate the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2), respectively, triggering the extrinsic apoptotic pathway. Theoretically, synergistic antitumor activity should be observed by combining TRAIL-R mAbs with agents (e.g., rituximab) that activate the intrinsic apoptotic pathway. Experimental Design: To this end, targeted antigen expression in a NHL-cell panel was evaluated by flow cytometry. NHL cells were exposed to mapatumumab or lexatumumab followed by rituximab, isotype, or RPMI. DNA synthesis was quantified by [3H]-thymidine incorporation assays. Induction of apoptosis was detected by flow-cytometric analysis. For antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) studies, standardized 51Cr-release assays were done. We inoculated severe combined immunodeficiency (SCID) mouse with Raji cells i.v. The animals then were treated with various combinations of rituximab, mapatumumab, lexatumumab, and isotype alone or in combination. Results: In vitro exposure to mapatumumab resulted in significant apoptosis (30-50%) and decreased DNA synthesis in sensitive lymphoma cells. Mapatumumab/rituximab combination resulted in a significant inhibition of cell proliferation (90% reduction) when compared with mapatumumab (60% reduction) or rituximab (5% reduction). In vivo, the median survival time of animals treated with mapatumumab and rituximab was longer (not reached) than those treated with rituximab monotherapy [33 days (95% confidence interval, 29-37), log-rank test, P = 0.05]. Conclusions: Mapatumumab induces apoptosis, cell growth arrest, ADCC, and CMC. The combination of mapatumumab plus rituximab is more effective in controlling lymphoma growth in vivo than either antibody. Rituximab and mapatumumab warrant further evaluation against B-cell lymphoma.
Natural killer and interleukin‐2 induced cytotoxicity in asthmatics
Authors: M. Jira, E. Antosova, V. Vondra, J. Strejcek, H. Mazakova, J. Prazakova
Journal: Allergy (1988)

Natural killer (NK) cell activity and interleukin-2 (IL-2) induced cytotoxicity to NK-resistant targets T24 in a group of patients with grass pollen seasonal asthma were investigated. Acute bronchial provocation with this antigen was also performed and blood samples were taken before and 15 min after the maximal clinical response. NK activity was elevated in this group but there was a significant decrease after acute challenge. IL-2 induced cytotoxicity was also increased and declined after antigen challenge. Limiting dilution analysis for minimal frequencies of precursors of the IL-2 induced killer cells was introduced and showed increased numbers of lymphokine-activated killing precursors in this group of patients. These data might indicate the aberrations of the IL-2 system in immediate type allergy but the clinical significance of these findings remains to be determined.
Classification of stillbirth by relevant condition at death (ReCoDe): population based cohort study
Authors: Jason Gardosi, Sue M Kady, Pat McGeown, Andre Francis, Ann Tonks
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To develop and test a new classification system for stillbirths to help improve understanding of the main causes and conditions associated with fetal death. <b>Design</b> Population based cohort study. <b>Setting</b> West Midlands region. <b>Subjects</b> 2625 stillbirths from 1997 to 2003. <b>Main outcome measures</b> Categories of death according to conventional classification methods and a newly developed system (ReCoDe, relevant condition at death). <b>Results</b> By the conventional Wigglesworth classification, 66.2% of the stillbirths (1738 of 2625) were unexplained. The median gestational age of the unexplained group was 237 days, significantly higher than the stillbirths in the other categories (210 days; P &lt; 0.001). The proportion of stillbirths that were unexplained was high regardless of whether a postmortem examination had been carried out or not (67% and 65%; P = 0.3). By the ReCoDe classification, the most common condition was fetal growth restriction (43.0%), and only 15.2% of stillbirths remained unexplained. ReCoDe identified 57.7% of the Wigglesworth unexplained stillbirths as growth restricted. The size of the category for intrapartum asphyxia was reduced from 11.7% (Wigglesworth) to 3.4% (ReCoDe). <b>Conclusion</b> The new ReCoDe classification system reduces the predominance of stillbirths currently categorised as unexplained. Fetal growth restriction is a common antecedent of stillbirth, but its high prevalence is hidden by current classification systems. This finding has profound implications for maternity services, and raises the question whether some hitherto "unexplained" stillbirths may be avoidable.
Opposing Effects of 60% Oxygen and Neutrophil Influx on Alveologenesis in the Neonatal Rat
Authors: Man Yi, Robert P. Jankov, Rosetta Belcastro, Daryl Humes, Ian Copland, Samuel Shek, Neil B. Sweezey, Martin Post, Kurt H. Albertine, Richard L. Auten, A. Keith Tanswell
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced neutrophil chemoattractant-1, which signals through the neutrophil CXC chemokine receptor-2, is increased in the lung tissue of newborn rats exposed to 60% oxygen. The purpose of this study was to explore the role of neutrophils in the rat model of BPD by inhibiting neutrophil influx using SB265610, a selective CXC chemokine receptor-2 antagonist. SB265610, administered to 60% oxygen-exposed newborn rats from birth to 14 days, completely inhibited neutrophil influx. It also attenuated increased production of reactive oxygen species in newborn rat lung tissue after exposure to 60% oxygen for 4 days. Lung morphometric analysis revealed that 60% oxygen for 14 days, when accompanied by treatment with SB265610 to prevent neutrophil accumulation, increased alveolar formation over that seen in newborn rats exposed to air. These data suggest that exposure of the neonatal lung to moderate hyperoxia may enhance postnatal lung growth, provided postnatal pulmonary inflammation is suppressed.
Divergent Regulation of Ryanodine Receptor 2 Calcium Release Channels by Arrhythmogenic Human Calmodulin Missense Mutants
Authors: Hyun Seok Hwang, Florentin R. Nitu, Yi Yang, Kafa Walweel, Laetitia Pereira, Christopher N. Johnson, Michela Faggioni, Walter J. Chazin, Derek Laver, Alfred L. George, Razvan L. Cornea, Donald M. Bers, Björn C. Knollmann
Journal: Circulation Research (2014)

Calmodulin (CaM) mutations are associated with an autosomal dominant syndrome of ventricular arrhythmia and sudden death that can present with divergent clinical features of catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome (LQTS). CaM binds to and inhibits ryanodine receptor (RyR2) Ca release channels in the heart, but whether arrhythmogenic CaM mutants alter RyR2 function is not known.To gain mechanistic insight into how human CaM mutations affect RyR2 Ca channels.We studied recombinant CaM mutants associated with CPVT (N54I and N98S) or LQTS (D96V, D130G, and F142L). As a group, all LQTS-associated CaM mutants (LQTS-CaMs) exhibited reduced Ca affinity, whereas CPVT-associated CaM mutants (CPVT-CaMs) had either normal or modestly lower Ca affinity. In permeabilized ventricular myocytes, CPVT-CaMs at a physiological intracellular concentration (100 nmol/L) promoted significantly higher spontaneous Ca wave and spark activity, a typical cellular phenotype of CPVT. Compared with wild-type CaM, CPVT-CaMs caused greater RyR2 single-channel open probability and showed enhanced binding affinity to RyR2. Even a 1:8 mixture of CPVT-CaM:wild-type-CaM activated Ca waves, demonstrating functional dominance. In contrast, LQTS-CaMs did not promote Ca waves and exhibited either normal regulation of RyR2 single channels (D96V) or lower RyR2-binding affinity (D130G and F142L). None of the CaM mutants altered Ca/CaM binding to CaM-kinase II.A small proportion of CPVT-CaM is sufficient to evoke arrhythmogenic Ca disturbances, whereas LQTS-CaMs do not. Our findings explain the clinical presentation and autosomal dominant inheritance of CPVT-CaM mutations and suggest that RyR2 interactions are unlikely to explain arrhythmogenicity of LQTS-CaM mutations.
MicroRNA-494 Targeting Both Proapoptotic and Antiapoptotic Proteins Protects Against Ischemia/Reperfusion-Induced Cardiac Injury
Authors: Xiaohong Wang, Xiaowei Zhang, Xiao-Ping Ren, Jing Chen, Hongzhu Liu, Junqi Yang, Mario Medvedovic, Zhuowei Hu, Guo-Chang Fan
Journal: Circulation (2010)

MicroRNAs (miRs) participate in many cardiac pathophysiological processes, including ischemia/reperfusion (I/R)-induced cardiac injury. Recently, we and others observed that miR-494 was downregulated in murine I/R-injured and human infarcted hearts. However, the functional consequence of miR-494 in response to I/R remains unknown.We generated a mouse model with cardiac-specific overexpression of miR-494. Transgenic hearts and wild-type hearts from multiple lines were subjected to global no-flow I/R with the Langendorff system. Transgenic hearts exhibited improved recovery of contractile performance over the reperfusion period. This improvement was accompanied by remarkable decreases in both lactate dehydrogenase release and the extent of apoptosis in transgenic hearts compared with wild-type hearts. In addition, myocardial infarction size was significantly reduced in transgenic hearts on I/R in vivo compared with wild-type hearts. Similarly, short-term overexpression of miR-494 in cultured adult cardiomyocytes demonstrated an inhibition of caspase-3 activity and reduced cell death on simulated I/R. In vivo treatment with antisense oligonucleotide miR-494 increased I/R-triggered cardiac injury relative to the administration of mutant antisense oligonucleotide miR-494 and saline controls. We further identified that 3 proapoptotic proteins (PTEN, ROCK1, and CaMKIIδ) and 2 antiapoptotic proteins (FGFR2 and LIF) were authentic targets for miR-494. Importantly, the Akt-mitochondrial signaling pathway was activated in miR-494-overexpressing myocytes.Our findings suggest that although miR-494 targets both proapoptotic and antiapoptotic proteins, the ultimate consequence is activation of the Akt pathway, leading to cardioprotective effects against I/R-induced injury. Thus, miR-494 may constitute a new therapeutic agent for the treatment of ischemic heart disease.
One-day treatment for lobar pneumonia
Authors: D. R. Sutton, A. C. B. Wicks, L. Davidson
Journal: Thorax (1970)

An investigation was undertaken to discover whether a single intramuscular dose of long-acting (or mixed long-acting and crystalline) penicillin or a single day9s therapy with oral penicillin was satisfactory treatment for lobar pneumonia. These treatments were compared with standard hospital oral and injection therapies. All the experimental treatment regimes were found to be satisfactory. They provide justification for treating lobar pneumonia on an out-patient basis in order to save hospital admissions.
Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Catherine Van Poznak, Mark R. Somerfield, Robert C. Bast, Massimo Cristofanilli, Matthew P. Goetz, Ana M. Gonzalez-Angulo, David G. Hicks, Elizabeth G. Hill, Minetta C. Liu, Wanda Lucas, Ingrid A. Mayer, Robert G. Mennel, William F. Symmans, Daniel F. Hayes, Lyndsay N. Harris
Journal: Journal of Clinical Oncology (2015)

To provide recommendations on the appropriate use of breast tumor biomarker assay results to guide decisions on systemic therapy for metastatic breast cancer.A literature search and prospectively defined study selection identified systematic reviews, meta-analyses, randomized controlled trials (RCTs), prospective-retrospective studies, and prospective comparative observational studies published from 2006 through September 2014.The literature search revealed 17 articles that met criteria for further review: 11 studies reporting discordances between primary tumors and metastases in expression of hormone receptors or human epidermal growth factor receptor 2 (HER2), one RCT that addressed the use of a biomarker to decide whether to change or continue a treatment regimen, and five prospective-retrospective studies that evaluated the clinical utility of biomarkers.In patients with accessible metastases, biopsy for confirmation of disease process and retesting of estrogen receptor, progesterone receptor, and HER2 status should be offered, but evidence is lacking to determine whether changing anticancer treatment on the basis of change in receptor status affects clinical outcomes. With discordance of results between primary and metastatic tissues, the Panel consensus is to use preferentially the estrogen receptor, progesterone receptor, and HER2 status of the metastasis to direct therapy if supported by the clinical scenario and patient's goals for care. Carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 may be used as adjunctive assessments, but not alone, to contribute to decisions regarding therapy. Recommendations for tumor rebiopsy and use of circulating tumor markers are based on clinical experience and Panel informal consensus in the absence of studies designed to evaluate the clinical utility of the markers. As such, it is also reasonable for clinicians to not use these markers as adjunctive assessments.
Effects of proportional assist ventilation on exercise tolerance in COPD patients with chronic hypercapnia
Authors: L Bianchi, K Foglio, M Pagani, M Vitacca, A Rossi, N Ambrosino
Journal: European Respiratory Journal (1998)

This study investigates the impact of proportional assist ventilation (PAV), a new mode of partial ventilatory support, on exercise tolerance and breathlessness in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients. We also examined the effects of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV). On two consecutive days, 15 stable hypercapnic COPD patients underwent four endurance tests on a cycle ergometer at 80% of their maximal workrate, receiving, via a nasal mask in random order, either: 1) sham ventilation (CPAP: 1 cmH2O); 2) CPAP (6 cmH2O); 3) PSV (inspiratory pressure support: 12-16 cmH2O; expiratory positive airway pressure (EPAP): 1 cmH2O); or 4) PAV (8.6+/-3.6 cmH2O x L(-1) and 3+/-1.3 cmH2O x L(-1)x s(-1) of volume and flow assistance, respectively plus EPAP: 1 cmH2O). Oxygen supply was standardized to maintain an arterial oxygen saturation (Sa,O2) of 92-93%. Breathing pattern and minute ventilation (by respiratory inductive plethysmography), pulse oximetry, end tidal partial pressure of CO2, cardiac frequency and sensations of dyspnoea and leg discomfort (by Borg scale) were monitored. In comparison to sham ventilation, PAV, PSV and CPAP were able to increase the endurance time (from 7.2+/-4.4 to 12+/-5.6, 10+/-5.2 and 9.6+/-4.6 min, respectively) and to reduce dyspnoea and oxygen flow to the nasal mask. However, the greatest improvement was observed with PAV. We conclude that PAV delivered by nasal mask can im-prove exercise tolerance and dyspnoea in stable hypercapnic COPD patients and hence this mode of ventilatory support may be useful in respiratory rehabilitation programmes.
A Different Method of Evaluation of the ERSPC Trial Confirms That Prostate-specific Antigen Testing Has a Significant Impact on Prostate Cancer Mortality
Authors: Marco Zappa, Donella Puliti, Jonas Hugosson, Fritz H. Schröder, Pim J. van Leeuwen, Ries Kranse, Anssi Auvinen, Sigrid Carlsson, Maciej Kwiatkowski, Vera Nelen, Alvaro Paez Borda, Monique J. Roobol, Arnauld Villers
Journal: European Urology (2014)