tbuckley/cabot-search huggingface dataset:
Regulator of calcineurin 1 mediates pathological vascular wall remodeling
Authors: Vanesa Esteban, Nerea Méndez-Barbero, Luis Jesús Jiménez-Borreguero, Mercè Roqué, Laura Novensá, Ana Belén García-Redondo, Mercedes Salaices, Luis Vila, María L. Arbonés, Miguel R. Campanero, Juan Miguel Redondo
Journal: The Journal of Experimental Medicine (2011)

Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed &amp;gt;1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression.
Baroreflex Gain in Children with Obstructive Sleep Apnea
Authors: Keith McConnell, Virend K. Somers, Thomas Kimball, Stephen Daniels, Rhonda VanDyke, Matthew Fenchel, Aliza Cohen, Paul Willging, Abu Shamsuzzaman, Raouf Amin
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage.Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea.A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (+/-2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains.Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index.Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.
Should doctors recommend automated external defibrillators for use at home after myocardial infarction? Yes
Authors: M. F O'Rourke
Journal: BMJ (2009)

Should people who risk of reinfarction have defibrillators available at home? Michael F O’Rourke thinks that enthusiasm is an important factor (doi:10.1136/bmj.b874); Mathew Hutchinson and David Callans say at home defibrillators do not save additional lives (doi:10.1136/bmj.b876)
Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis
Authors: R Knevel, M Schoels, T W J Huizinga, D Aletaha, G R Burmester, B Combe, R B Landewé, J S Smolen, T Sokka, D M F M van der Heijde
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA). Methods As part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA. Results The search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms (‘steering strategies’, n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments (‘medication strategies’, n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA. Conclusion Intensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.
Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders
Authors: Kristi M Anderson, Katherine E Olson, Katherine A Estes, Ken Flanagan, Howard E Gendelman, R Lee Mosley
Journal: Translational Neurodegeneration (2014)

Inappropriate T cell responses in the central nervous system (CNS) affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include, but are not limited to, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. On the one hand immune responses can exacerbate neurotoxic responses; while on the other hand, they can lead to neuroprotective outcomes. The temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent attention. Spatially, immune responses that affect neurodegeneration may occur within or outside the CNS. Migration of antigen-specific CD4+ T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal survival. The destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T cells. Temporally, immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the CNS. Immune responses with predominate T cell subtypes may differentially manifest migratory, regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific stimuli. The final result is altered glial and neuronal behaviors that influence the disease course. Thus, discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.
Drug survival for ciclosporin A in a long-term daily practice cohort of adult patients with atopic dermatitis
Authors: J. van der Schaft, K. Politiek, J.M.P.A. van den Reek, W.A. Christoffers, W. Kievit, E.M.G.J. de Jong, C.A.F.M. Bruijnzeel-Koomen, M.L.A. Schuttelaar, M.S. de Bruin-Weller
Journal: British Journal of Dermatology (2015)

Long-term data of ciclosporin A (CsA) treatment in daily practice in patients with severe atopic dermatitis (AD) are lacking.To perform a detailed analysis of drug survival, which is the length of time a patient continues to take a drug, for CsA in a long-term daily practice cohort of patients with AD. The secondary objective was to identify determinants of drug survival.Data were extracted from a retrospective cohort of patients treated with CsA for AD. Drug survival was analysed using Kaplan-Meier survival curves. Determinants of drug survival were analysed using uni- and multivariate Cox regression analyses with backward selection.In total, 356 adult patients were analysed (386 patient-years). The overall drug survival rates were 34%, 18%, 12% and 4% after 1, 2, 3 and 6 years, respectively. Reasons for discontinuation were controlled AD (26·4%), side-effects (22·2%), ineffectiveness (16·3%), side-effects plus ineffectiveness (6·2%) or other reasons (11·0%). Older age was associated with a decreased drug survival related to controlled AD [hazard ratio (HR) 0·91]. Older age was also associated with a decreased drug survival related to side-effects (HR 1·14). An intermediate-to-high starting dose (> 3·5-5·0 mg kg(-1) daily) was associated with an increased drug survival related to ineffectiveness (HR 0·63).This is the first study on drug survival for CsA treatment in AD. Older age was associated with decreased drug survival related to controlled AD and side-effects. An intermediate-to-high starting dose was associated with an increased drug survival related to ineffectiveness.
Press: Mystery of the imported plagues
Authors: T. Jackson
Journal: BMJ (2003)

Prime minister Tony Blair may be responsible for a lot of things, but the importation of killer plagues does not sound like one of them. However, one British tabloid Sunday newspaper thinks otherwise. On 26 January the Mail on Sunday ran a story headlined “Madness of Blair's imported plagues.” This claimed that “by importing mass Third World immigration the Government has also been bringing in killer diseases—and it has tried to hide what is happening from the public …”

After weeks of linking asylum seekers with terrorism, the British tabloids now claimed to have made a more lethal connection: between immigration and HIV infection, tuberculosis, and hepatitis. “The diseases that mass immigration is bringing to Britain will probably claim more British lives in the long run than any terrorist acts.” So, according to tabloid thinking not only are asylum seekers said to be …
Dichloralphenazone and breast milk.
Authors: J H Lacey
Journal: BMJ (1971)

from several laboratories and the method of Prince.4 484 (6-05%) of the donors were carriers of Au(I), while 13 (0.16%) had the antibody.There was a monthly variation in the prevalence of Au(I) antigenaemia, varying from 3-8% in May to 10-1% in April (see Table ).There was no correlation between the Au(l) carrier state and ABO blood group or haemoglobin genotype.Au(I) was prevalent in all age groups but commonest in the second and third decades.Among 423 school children aged between 4 and 20 years who lived in two boarding houses in Ibadan Au(I) was present in 29 (6.7%) and the antibody in 1 (0 24%).There were 208 girls and 215 boys in the study population; 11 (5.3%) of the girls and 18 (8 4%) of the boys had the antigen.The only student with anti- body was a 17-year-old girl.
Classification of Human Breast Cancer Using Gene Expression Profiling as a Component of the Survival Predictor Algorithm
Authors: Gennadi V. Glinsky, Takuya Higashiyama, Anna B. Glinskii
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Selection of treatment options with the highest likelihood of successful outcome for individual breast cancer patients is based to a large degree on accurate classification into subgroups with poor and good prognosis reflecting a different probability of disease recurrence and survival after therapy. Here we propose a breast cancer classification algorithm taking into account three main prognostic features determined at the time of diagnosis: estrogen receptor (ER) status; lymph node (LN) status; and gene expression signatures associated with distinct therapy outcome. Experimental Design: Using microarray expression profiling and quantitative reverse transcription-PCR analyses, we compared expression profiles of the 70-gene breast cancer survival signature in established breast cancer cell lines and primary breast carcinomas from cancer patients. We classified 295 breast cancer patients using 14-, 13-, 6-, and 4-gene survival predictor signatures into subgroups having statistically distinct probability of therapy failure (P &amp;lt; 0.0001). We evaluated the prognostic power of breast cancer survival predictor signatures alone and in combination with ER and LN status using Kaplan-Meier analysis. Results: The breast cancer survival predictor algorithm allowed highly accurate classification into subgroups with dramatically distinct 5- and 10-year survival after therapy of a large cohort of 295 breast cancer patients with either ER+ or ER− tumors as well as LN+ or LN− disease (P &amp;lt; 0.0001, log-rank test). Conclusions: Our data imply that quantitative laboratory tests measuring expression profiles of a limited set of identified small gene clusters may be useful in stratification of breast cancer patients at the time of diagnosis into subgroups with statistically distinct probability of positive outcome after therapy and assisting in selection of optimal treatment strategies. The estimated increase in survival due to the optimization of treatment protocols may reach many thousands of breast cancer survivors every year at the 10-year follow-up check point.
Benefits and harms of roflumilast in moderate to severe COPD
Authors: Tsung Yu, Kevin Fain, Cynthia M Boyd, Sonal Singh, Carlos O Weiss, Tianjing Li, Ravi Varadhan, Milo A Puhan
Journal: Thorax (2013)

<h3>Background</h3> Roflumilast, a phosphodiesterase 4 inhibitor, has been approved for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It is unclear which patients will have a favourable benefit–harm balance with roflumilast. Our aim was to quantitatively assess the benefits and harms of roflumilast (500 µg/day) compared with placebo. <h3>Methods</h3> We used summary data released by the US Food and Drug Administration to estimate the treatment effects of roflumilast. Data from trials and observational studies were used to estimate the baseline risks for COPD exacerbations and gastrointestinal, neurological and psychiatric harms associated with roflumilast. Using simulation, we calculated the probability that roflumilast provides net benefit. We examined the impacts of different baseline risks for exacerbations and the severity of exacerbations, and varied weights (ie, relative importance) for outcomes and treated death as a competing risk in the analyses. <h3>Results</h3> The probability that roflumilast provides net benefit approximates 0% across different age categories of men and women with varying baseline risks for exacerbations. Using different weights for outcomes did not change the probability that roflumilast provides a net benefit. Only in the sensitivity analysis restricted to the prevention of severe exacerbations was there a probability of &gt;50% that roflumilast provides a net benefit if the baseline risk of having at least one severe exacerbation per year exceeds 22%. <h3>Conclusions</h3> Our results suggest that roflumilast only provides a net benefit to patients at a high risk of severe exacerbations. Guideline developers should consider different recommendations for patients with COPD at different baseline risks for exacerbations.
Effect of mechanical boundary conditions on orientation of angiogenic microvessels
Authors: L. Krishnan, C. J. Underwood, S. Maas, B. J. Ellis, T. C. Kode, J. B. Hoying, J. A. Weiss
Journal: Cardiovascular Research (2008)

AimMechanical forces are important regulators of cell and tissue phenotype. We hypothesized that mechanical loading and boundary conditions would influence neovessel activity during angiogenesis.
Tuberculosis outbreak among students in a boarding school
Authors: C. Stein-Zamir, I. Volovik, S. Rishpon, A. Atamna, A. Lavy, D. Weiler-Ravell
Journal: European Respiratory Journal (2006)

Tuberculosis (TB) outbreaks present a public health challenge. Six cases of active TB emerged in a boarding school in Israel during 1 yr. An epidemiological outbreak investigation was performed, followed by implementation of control measures. The investigation included interviews, tuberculin skin test (TST) and chest radiographs of the students. Close contact (n = 155) was defined as being in the same class or dormitory with a patient. Remote contact (n = 246) was defined as being in the school. An epidemiological association was detected among five of the cases and a distinct pattern was found in molecular analysis. TST was performed in 398 (99.2%) students. Repeated (two-step) TST was applied to the close contacts. The degree of contact, country of origin and previous bacille Calmette-Guérin vaccination were significantly associated with TST reactions. Preventive directly observed therapy was completed by 157 (91.3%) students. During 5 yrs follow-up, no additional cases emerged. While investigating a tuberculosis outbreak, the definition of degree of contact is a significant predictor for detecting positive tuberculin test. Immigration from an endemic country, as well as previous bacille Calmette-Guérin vaccination have a major effect on tuberculin skin-test results. The directly observed therapy approach was found to be successful in preventing further morbidity.
Biological function of unannotated transcription during the early development of Drosophila melanogaster
Authors: J Robert Manak, Sujit Dike, Victor Sementchenko, Philipp Kapranov, Frederic Biemar, Jeff Long, Jill Cheng, Ian Bell, Srinka Ghosh, Antonio Piccolboni, Thomas R Gingeras
Journal: Nature Genetics (2006)
Molecular size of secreted and cell-associated plasminogen activators from cultured epidermal cells
Authors: K. HASHIMOTO, KAY H.SINGER, G. S. LAZARUS
Journal: British Journal of Dermatology (1983)

Journal Article Molecular size of secreted and cell‐associated plasminogen activators from cultured epidermal cells Get access K. HASHIMOTO, K. HASHIMOTO Division of Dermatology, Department of Medicine and Division of Immunology, Department of Microbiology and Immunology, Duke University Medical Center, Durhatn, North Carolina 27710, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar KAY H.SINGER, KAY H.SINGER Division of Dermatology, Department of Medicine and Division of Immunology, Department of Microbiology and Immunology, Duke University Medical Center, Durhatn, North Carolina 27710, U.S.A. Dr Kay H.Singer, Box 2987, Duke University Medical Center, Durham, NC 27710, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar G. S. LAZARUS G. S. LAZARUS Division of Dermatology, Department of Medicine and Division of Immunology, Department of Microbiology and Immunology, Duke University Medical Center, Durhatn, North Carolina 27710, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 1, 1 July 1983, Pages 15–20, https://doi.org/10.1111/j.1365-2133.1983.tb03986.x Published: 01 July 1983 Article history Accepted: 10 November 1982 Published: 01 July 1983
On the Role of the Innate Immunity in Autoimmune Disease
Authors: Martin F. Bachmann, Manfred Kopf
Journal: The Journal of Experimental Medicine (2001)

The essence of the immune system is built on two separate foundation pillars: one is specific or adaptive immunity which is characterized by relatively slow response kinetics and the ability to remember. The other is nonspecific or innate immunity exhibiting rapid response kinetics but lacking memory. Lymphocytes are the key players of the adaptive immune system. Each lymphocyte expresses antigen receptors of unique specificity. Upon recognizing an antigen via the receptor, lymphocytes proliferate and develop effector function. Few lymphocytes exhibit specificity for a given antigen or pathogen and massive proliferation is usually required before an effector response can be measured. Hence, the slow kinetics of the adaptive immune system. Because a significant proportion of the expanded lymphocytes survive and may maintain some effector function after elimination of the antigen, the adaptive immune system reacts faster when encountering the antigen a second time. This is the basis of its ability to remember. In contrast to the situation with lymphocytes, where specificity for a pathogen is confined to few cells that must expand to gain function, the cells and molecules of the innate immune system are usually present in massive numbers and recognize a limited number of invariant features associated with pathogens (1). Examples of such patterns include LPS, nonmethylated CG-rich DNA (CpG), or double-stranded RNA, which are specific for bacterial and viral infections, respectively. Most research in immunology has focused on the adaptive immune system and only recently has the innate immune system entered the focus of interest. Historically, the adaptive and innate immune system were treated and analyzed as two separate entities that had little in common. Such was the disparity that few researchers wondered why antigens were much more immunogenic for the specific immune system when applied with adjuvants that stimulated innate immunity (2‐4). However, the answer posed by this question is critical to our understanding of the immune system and for comprehending the balance between protective immunity and autoimmunity. This commentary tries to highlight a few important links between the innate and adaptive immune systems and how those may impinge on the course of autoimmune diseases. Association of Autoimmunity with Infection: Molecular Mimicry versus Aberrant Presentation of Self-Antigens. It has long been suspected that infections may be responsible for the in