tbuckley/cabot-search huggingface dataset:
Antibody against interleukin-6 receptor attenuates left ventricular remodelling after myocardial infarction in mice
Authors: M. Kobara, K. Noda, M. Kitamura, A. Okamoto, T. Shiraishi, H. Toba, H. Matsubara, T. Nakata
Journal: Cardiovascular Research (2010)

The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI. Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 µg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region. Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.
Hailey-Hailey disease: a widespread abnormality of cell adhesion
Authors: S. M. BURGE, P. R. MILLARD, F. WOJNAROWSKA
Journal: British Journal of Dermatology (1991)

Journal Article Hailey‐Hailey disease: a widespread abnormality of cell adhesion Get access S. M. BURGE, S. M. BURGE Department of Dermatology, The Slade Hospital, Oxford, U. K. Dr S. M. Burge, Department of Dermatology, Slade Hospital, Oxford OX3 7JH, U. K. Search for other works by this author on: Oxford Academic Google Scholar P. R. MILLARD, P. R. MILLARD Department of Histopathology, John Radcliffe Hospital, Oxford, U. K. Search for other works by this author on: Oxford Academic Google Scholar F. WOJNAROWSKA F. WOJNAROWSKA Department of Dermatology, The Slade Hospital, Oxford, U. K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 4, 1 April 1991, Pages 329–332, https://doi.org/10.1111/j.1365-2133.1991.tb00592.x Published: 01 April 1991
Abnormal Nasal Nitric Oxide Production, Ciliary Beat Frequency, and Toll-like Receptor Response in Pulmonary Nontuberculous Mycobacterial Disease Epithelium
Authors: Cedar J. Fowler, Kenneth N. Olivier, Janice M. Leung, Caroline C. Smith, Andrea G. Huth, Heather Root, Douglas B. Kuhns, Carolea Logun, Adrian Zelazny, Cathleen A. Frein, Janine Daub, Carissa Haney, James H. Shelhamer, Clare E. Bryant, Steven M. Holland
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Pulmonary nontuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Despite extensive investigation, no consistent immunological abnormalities have been found. Using evidence from diseases such as cystic fibrosis and primary ciliary dyskinesia, in which mucociliary dysfunction predisposes subjects to high rates of nontuberculous mycobacterial disease that increase with age, we investigated correlates of mucociliary function in subjects with PNTM infections and healthy control subjects.Objectives: To define ex vivo characteristics of PNTM disease.Methods: From 2009 to 2012, 58 subjects with PNTM infections and 40 control subjects were recruited. Nasal nitric oxide (nNO) was determined at the time of respiratory epithelial collection. Ciliary beat frequency at rest and in response to Toll-like receptor (TLR) and other agonists was determined using high-speed video microscopy.Measurements and Main Results: We found decreased nNO production, abnormally low resting ciliary beat frequency, and abnormal responses to agonists of TLR2, -3, -5, -7/8, and -9 in subjects with PNTM compared with healthy control subjects. The low ciliary beat frequency in subjects with PNTM was normalized ex vivo by augmentation of the NO–cyclic guanosine monophosphate pathway without normalization of their TLR agonist responses.Conclusions: Impaired nNO, ciliary beat frequency, and TLR responses in PNTM disease epithelium identify possible underlying susceptibility mechanisms as well as possible avenues for directed investigation and therapy.
Portosplenomesenteric Venous Thrombosis in Patients With Acute Pancreatitis Is Associated With Pancreatic Necrosis and Usually Has a Benign Course
Authors: Jeffrey Easler, Venkata Muddana, Alessandro Furlan, Anil Dasyam, Kishore Vipperla, Adam Slivka, David C Whitcomb, Georgios I Papachristou, Dhiraj Yadav
Journal: Clinical Gastroenterology and Hepatology (2013)
Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial
Authors: Marius M. Hoeper, Michael Halank, Heinrike Wilkens, Andreas Günther, Gerrit Weimann, Irmingard Gebert, Hanno H. Leuchte, Jürgen Behr
Journal: European Respiratory Journal (2012)

We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. Secondary end-points included haemodynamic changes and 6-min walk distance (6MWD). Overall, 104 adverse events were reported, of which 25 were serious; eight of the latter were considered drug-related. After 12 weeks of therapy, mean cardiac output increased (4.4 ± 1.5 L · min(-1) to 5.5 ± 1.8 L · min(-1)), pulmonary vascular resistance (PVR) decreased (648 ± 207 dyn · s(-1) · cm(-5) to 528 ± 181 dyn · s(-1) · cm(-5)) and mean pulmonary artery pressure (mPAP) remained unchanged compared with baseline. Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased. The 6MWD increased from 325 ± 96 m at baseline to 351 ± 111 m after 12 weeks. Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.
Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis
Authors: Joachim Sieper, Désirée van der Heijde, Maxime Dougados, L Steve Brown, Frederic Lavie, Aileen L Pangan
Journal: Annals of the Rheumatic Diseases (2011)

To describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission.Patients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan-Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥ 6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses.Of the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety.In patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.
Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)
Authors: Kim De Keersmaecker, Carlos Graux, Maria D. Odero, Nicole Mentens, Riet Somers, Johan Maertens, Iwona Wlodarska, Peter Vandenberghe, Anne Hagemeijer, Peter Marynen, Jan Cools
Journal: Blood (2005)
Deficiency of Endothelium-Specific Transcription Factor <i>Sox17</i> Induces Intracranial Aneurysm
Authors: Seungjoo Lee, Il-Kug Kim, Jae Sung Ahn, Dong-Cheol Woo, Sang-Tae Kim, Sukhyun Song, Gou Young Koh, Hyung-Seok Kim, Byeong Hwa Jeon, Injune Kim
Journal: Circulation (2015)

Background— Intracranial aneurysm (IA) is a common vascular disorder that frequently leads to fatal vascular rupture. Although various acquired risk factors associated with IA have been identified, the hereditary basis of IA remains poorly understood. As a result, genetically modified animals accurately modeling IA and related pathogenesis have been lacking, and subsequent drug development has been delayed. Methods and Results— The transcription factor Sox17 is robustly expressed in endothelial cells of normal intracerebral arteries. The combination of Sox17 deficiency and angiotensin II infusion in mice induces vascular abnormalities closely resembling the cardinal features of IA such as luminal dilation, wall thinning, tortuosity, and subarachnoid hemorrhages. This combination impairs junctional assembly, cell-matrix adhesion, regeneration capacity, and paracrine secretion in endothelial cells of intracerebral arteries, highlighting key endothelial dysfunctions that lead to IA pathogenesis. Moreover, human IA samples showed reduced Sox17 expression and impaired endothelial integrity, further strengthening the applicability of this animal model to clinical settings. Conclusions— Our findings demonstrate that Sox17 deficiency in mouse can induce IA under hypertensive conditions, suggesting Sox17 deficiency as a potential genetic factor for IA formation. The Sox17 -deficient mouse model provides a novel platform to develop therapeutics for incurable IA.
Lipoatrophy in a Girl With Type 1 Diabetes: Beneficial Effects of Treatment With a Glucocorticoid Added to an Insulin Analog
Authors: Hester T. Swelheim, Ciska Westerlaken, Evelyn van Pinxteren-Nagler, Gianni Bocca
Journal: Diabetes Care (2012)

Lipoatrophy has been reported in association with the use of human insulin analogs (1). We report on a girl with severe lipoatrophy who was treated with betamethasone added to the insulin analog, after which the areas of lipoatrophy improved.

A 7-year-old girl with type 1 diabetes, treated with insulin-aspart by continuous subcutaneous insulin infusion, developed areas of lipoatrophy at her insulin infusion sites, which initially only involved the buttocks. A few months later, areas of lipoatrophy were also seen on her thighs. The areas of lipoatrophy on her left and right buttocks measured 7 × 7 cm and 7 × 6 cm, respectively. Laboratory investigation excluded the presence of insulin antibodies. A skin biopsy was not performed.

Initially, insulin-aspart was substituted with insulin-lispro. Because …
siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake
Authors: Thierry Galvez, Mary N Teruel, Won Do Heo, Joshua T Jones, Man Lyang Kim, Jen Liou, Jason W Myers, Tobias Meyer
Journal: Genome biology (2007)

Abstract Background Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth, viability and proliferation in tumor cells as well as non-transformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not yet been identified. Results We surveyed the human signaling proteome for regulators that increase or decrease transferrin uptake by screening 1,804 dicer-generated signaling small interfering RNAs using automated quantitative imaging. In addition to known transport proteins, we identified 11 signaling proteins that included a striking signature set for the phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3)-target of rapamycin (mTOR) signaling pathway. We show that the PI3K-mTOR signaling pathway is a positive regulator of transferrin uptake that increases the number of transferrin receptors per endocytic vesicle without affecting endocytosis or recycling rates. Conclusion Our study identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake and serves as a proof-of-concept that targeted RNA interference screens of the signaling proteome provide a powerful and unbiased approach to discover or rank signaling pathways that regulate a particular cell function.
Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension
Authors: O Sitbon, M Humbert, JL Jagot, O Taravella, M Fartoukh, F Parent, P Herve, G Simonneau
Journal: European Respiratory Journal (1998)

In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by &gt;20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.
Are speed/accuracy trade-offs caused by neuromotor noise, or not?
Authors: Willem P. De Jong, Gerard P. Van Galen
Journal: Behavioral and Brain Sciences (1997)

Notwithstanding its overwhelming descriptive power for existing data, it is not clear whether the kinematic theory of Plamondon &amp; Alimi could generate new insights into biomechanical constraints and psychological processes underlying the way organisms trade off speed for accuracy. The kinematic model should elaborate on the role of neuromotor noise and on biomechanical strategies for reducing endpoint variability related to such noise.
Depressive Symptoms and the Risk of Type 2 Diabetes
Authors: Sherita Hill Golden, Janice E. Williams, Daniel E. Ford, Hsin-Chieh Yeh, Catherine Paton Sanford, F. Javier Nieto, Frederick L. Brancati
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to determine whether depressive symptoms predict type 2 diabetes. RESEARCH DESIGN AND METHODS—We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48–67 years, who were subsequently followed for 6 years for the development of type 2 diabetes. RESULTS—At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P &amp;lt; 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31–2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02–1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10–1.73). CONCLUSIONS—In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.
Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block
Authors: Yu-Feng Hu, James Frederick Dawkins, Hee Cheol Cho, Eduardo Marbán, Eugenio Cingolani
Journal: Science Translational Medicine (2014)

TBX18 gene therapy reprogrammed cardiomyocytes to become pacemaker cells in a pig model of heart block.
Gas cooking and respiratory disease
Authors: D. JARVIS
Journal: Thorax (1999)

More than half of British homes use gas as their cooking fuel and even a small risk associated with either acute or chronic inhalation of the by-products of gas combustion—such as other nitrogen containing species, formaldehyde, sulphur dioxide and particulates—would have a substantial influence on public health. Surveys have been performed to assess these risks, variably defining exposure by the presence of a gas cooker in the home or by direct measures of related pollutants. Results from these surveys are remarkable by their lack of consistency. While some large and powerful cross sectional studies have found no association of the presence of a gas cooker1 2or level of indoor nitrogen dioxide3 with respiratory disease in children, others report an increased risk of lower respiratory illness.4-6Those who use the cooker the most—arguably adult women—may be the group at greatest risk. The European Community Respiratory Health Survey (ECRHS) which analysed data collected from young adults aged 20–44 years living in 23 …
IgG4-Related Skin Disease Successfully Treated by Thalidomide
Authors: Saskia Ingen-Housz-Oro, Nicolas Ortonne, Muriel Elhai, Yannick Allanore, Pierre Aucouturier, Olivier Chosidow
Journal: JAMA Dermatology (2013)

In IgG4-related disease (IgG4-RD), skin involvement is rare and associated especially with systemic disease. We report 2 cases of isolated skin IgG4-RD successfully treated with thalidomide and investigated their phenotypic characteristics.Two men had cephalic nodules. Skin biopsies revealed dense lymphocytic infiltrates with numerous plasma cells and fibrosis. IgG4-RD was confirmed by very high IgG4+ to IgG+ plasma cells ratios of 76% (patient 1) and 100% (patient 2). The serum IgG4 level was normal. There was no other organ involvement. Thalidomide therapy was introduced. After 6 months, lesions were in remission. Patient 1 required long-term, low-dose thalidomide, whereas patient 2 stopped treatment and showed no relapse. Immunostaining revealed numerous FoxP3+ cells in the interfollicular areas, which decreased with treatment in patient 2, and numerous follicular helper T lymphocytes (TFH) within the follicular germinal centers. There were numerous mast cells; some stained for interleukin (IL)-6, and expression of phospho-Smad2/3 was demonstrated.IgG4-RD may be skin limited. Cutaneous infiltrates comprise numerous FoxP3+ cells that may interact with mast cells to produce IL-6 and stimulate fibrosis synthesis via the transforming growth factor β/phospho-Smad2/3 pathway. The role of TFH cells remains to be studied. IgG4-RD should be added to the causes of cutaneous pseudolymphomas. Thalidomide could be considered as a therapeutic option in IgG4-RD.
A High-Frequency Regulatory Polymorphism in the p53 Pathway Accelerates Tumor Development
Authors: Sean M. Post, Alfonso Quintás-Cardama, Vinod Pant, Tomoo Iwakuma, Amir Hamir, James G. Jackson, Daniela R. Maccio, Gareth L. Bond, David G. Johnson, Arnold J. Levine, Guillermina Lozano
Journal: Cancer Cell (2010)
Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule.
Authors: T K van den Berg, J J Brevé, J G Damoiseaux, E A Döpp, S Kelm, P R Crocker, C D Dijkstra, G Kraal
Journal: The Journal of Experimental Medicine (1992)

In this study we present evidence that the mouse and rat sialoadhesin (originally named sheep erythrocyte receptor) on macrophages can function as a lymphocyte adhesion molecule. Lymphocytes were shown to bind to the splenic marginal zone, and lymph node subcapsular sinus and medulla in a frozen section assay. Selective depletion experiments showed that binding was mediated by macrophages. Adhesion was blocked by preincubation of the sections with monoclonal antibodies against mouse or rat sialoadhesin. Binding was temperature dependent, divalent cation independent, and involved sialic acid residues on the lymphocyte, as it could be inhibited by prior neuraminidase treatment or addition of the ganglioside GD1a. Binding to sialoadhesin was confirmed using the purified receptor and was observed among T cells, T blasts, B cells, and B blasts. Isolated macrophages or dendritic cells showed little binding. Sialoadhesin provides the first example of a macrophage-restricted lymphocyte adhesion molecule.