tbuckley/cabot-search huggingface dataset:
Allergic burden and the risk of venous thromboembolism
Authors: Daniel P. Potaczek, Anetta Undas
Journal: European Respiratory Journal (2013)

To the Editor: 

We read with keen interest a recent article by Majoor et al . [1], who studied the relationship between asthma and venous thromboembolism (VTE). They provided evidence for the increased risk of VTE, specifically pulmonary embolism (PE), among asthmatics. In final regression models, after adjustment for potential confounders, Majoor et al . [1] found that body mass index was the sole independent predictor of deep vein thrombosis (DVT) risk, while only severe asthma and oral corticosteroid use independently predicted PE.

Mechanisms underlying the intriguing association of asthma with VTE remain unclear. However, several previous papers published by us and other investigators [2–5] showed that allergic diseases are associated with a number of prothrombotic alterations involving enhanced platelet activation, formation of dense fibrin clots …
HIV Seroconversion in Health Care Workers
Authors: Dietmar Fuchs
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Human immunodeficiency virus (HIV) seroconversion has occurred in three health care workers who have been exposed to blood but not via needle-stick injury.<sup>1</sup> It is now well established that activation of T lymphocytes regulates HIV reproduction. It is likely that macrophages activated with gamma interferon contribute to HIV production also. We have concluded that activation of T lymphocytes by foreign or modified histocompatibility complex determinants represents a crucial event in HIV infection.<sup>2,3</sup>We have demonstrated a high frequency of elevated neopterin levels in all high-incidence groups for acquired immunodeficiency syndrome (AIDS), even in HIV-seronegative individuals.<sup>2</sup>Since neopterin is produced specifically from human macrophages on stimulation with gamma interferon, we concluded that early steps in the activation cascade of cellular immunity are induced in those individuals.<sup>4</sup>Moreover, this status was found to parallel progressive HIV infection, eg, patients with AIDS have the highest neopterin
A total of 58 million Americans lack health insurance
Authors: C. Marwick
Journal: BMJ (2002)

At some point in their lives, one in five members of American families lack health insurance for a year or more—a total of some 58 million people—and this threatens the health and financial stability of the entire household.

This is the principal finding from the third report of an investigation by the US Institute of Medicine on the effects of lack of health insurance on health.

Earlier reports had shown that people without insurance had poorer health than those who had insurance. The latest report, Health Insurance is a Family Matter ,deals …
Atlas of pain injection techniques
Authors: A Nicol
Journal: British Journal of Sports Medicine (2005)

Edited by T O’Connor, S Abram. London: Published by Harcourt Publishers Ltd, 2003, £49.99, hardcover, pp 141. ISBN 044306380X

Injections have a well recognised role to play in managing pain in many musculoskeletal conditions. Joint injections are commonly used now by a variety of medical practitioners from GPs to rheumatologists and orthopaedic surgeons. Muscle injections into myofascial trigger points are also gaining favour, with many practitioners now utilising both injections and dry needling techniques. This book therefore had great potential.

One major change in current practice with regard to injection techniques is that many are now “guided”. Ultrasound, fluoroscopy, and computed …
Abstract 2469: Increased cathepsin B expression in cultured tuberous sclerosis skin tumor cells and patient tumor tissues
Authors: Shaowei Li, Ying Liu, Ji-an Wang, Joel Moss, Thomas N. Darling
Journal: Cancer Research (2012)

Abstract Skin hamartomas in tuberous sclerosis complex (TSC) are disfiguring red tumors that contain fibroblast-like cells, vessels, fibrous tissue, and elongated hair follicles. Our recent studies show that TSC skin tumor cells induce angiogenesis and hair follicle neogenesis in a xenograft mouse model. These morphogenic changes are likely caused by altered expression of proteins involved in tissue remodeling. To identify such factors, we carried out 2-D gel analysis of cell extracts of TSC2-null fibroblasts derived from a TSC periungual fibroma (PF) compared to fibroblasts from patient normal-appearing skin (NL). PF cells had greater levels of all three forms of cathepsin B than TSC normal fibroblasts. Cathepsin B, a member of the lysosomal cysteine proteases family that has been implicated in angiogenesis and extracellular matrix remodeling, exists in pro-, single chain and double chain forms, and these were increased in PF cells by 1.6-, 2.3- and 8.3-fold, respectively. Western blot analysis of TSC skin tumor fibroblasts from 5 patients showed dramatically greater levels of active cathepsin B than in paired patient NL fibroblasts. Tumor cells from PFs showed greater intracellular cathepsin B enzyme activity than NL controls. Western blot and ELISA analysis showed that media conditioned by TSC skin tumor cells from 5 different patients contained 4.1- to 36-fold more procathepsin B than media conditioned by NL fibroblasts. Immunohistochemical staining of TSC patient angiofibromas and PFs showed greater numbers of cathepsin B-positive cells than patient normal-appearing skin. These results suggest that TSC skin tumor cells may induce hamartoma morphogenesis through expressing and releasing high level of cathepsin B. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2469. doi:1538-7445.AM2012-2469
Aetiology of Ankylosing Spondylitis
Authors: H. F. West
Journal: Annals of the Rheumatic Diseases (1949)

An attempt is here made to add to our knowledge of the aetiology of ankylosing spondylitis by marshal- ling what appear to be the relevant facts and by adding certain observations that have resulted from a detailed study of one hundred cases that have been under treatment or observation for from two to ten years. Geographical DistributionThe geographical distribution appears to be world- wide.Reports of series of cases have come from all parts of Europe and America, from Syria, South Africa, India, Australia, Japan, the Argentine, Brazil, and Chile.Seventy-four cases living within the City of Bristol have been found to be evenly distributed between the various suburbs.Incidence Few attempts have been made to estimate the frequency of the disease in the general population.Clausen and Kober (1936) accepted an incidence of 1 in 1,000, based on the autopsy findings of Schmorl and Junghanns (1932), who found six or eight definite cases among 10,000 bodies coming to necropsy at the city hospital of Dresden.More than half the spines were only examined in situ by palpation.Other figures relate to highly Age of patients E Patients known 1 Patients missing, presumed InactiveFIGURE.-Estimate of the number of cases of ankylosing spondylitis in Bristol.
Could microchimerism be a source of disease-associated HLA alleles in patients with scleroderma?
Authors: D. Azzouz, M. Martin, J. Roudier, N. C. Lambert
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Systemic sclerosis (SSc) is an autoimmune disease divided in two subsets, diffuse cutaneous and limited cutaneous SSc (dcSSc and lcSSc), affecting mostly women. We, and others showed that patients with dcSSc are associated with particular HLA-DRB1*11 and *15 alleles, having in common an amino acid sequence (<sup>67</sup>FLEDR<sup>71</sup>). In parallel, cells and/or DNA, originating from bi-directional traffic of cells during pregnancy, referred as maternal or fetal microchimerism (Mc) persist for decades in healthy women and could trigger to SSc under particular circumstances. The aim of our study was to examine whether patients with dcSSc have more often a mother carrying the HLA susceptibility alleles and whether Mc may be a source of FLEDR among patients with dcSSc, as previously described by us and others in patients with RA for RA-associated HLA alleles.12 <h3>Methods</h3> Thirty five patients with dcSSc and 54 healthy women were HLA-DRB1 typed by SSOP methods as well as their mothers (N=89). Among the 35 patients, 13 did not carry the SSc-associated HLA-DRB1*15 alleles and were tested for DRB1*15 Mc by HLA specific quantitative PCR assays in their peripheral blood mononuclear cells and compared to 32 healthy controls who also did not carry HLA-DRB1*15 alleles. <h3>Results</h3> Initial results, show that women with dcSSc had a tendency to have more often a mother carrying HLA DRB1*15 alleles (non-inherited maternal antigen, NIMA), than healthy controls (22.9% vs 11.1%, p=0.07). However HLA-DRB1*15 Mc levels and frequencies were not different between patients and controls with respectively 4/13 (30.7%) and 9/32 (28.1%) women positive for Mc. HLA-DRB1*11 NIMAs were at similar frequencies for patients and controls and not yet tested for maternal Mc. <h3>Conclusions</h3> Contrary to our recent publication in RA, patients with SSc do not acquire more often than controls HLA-DRB1*15 susceptibility alleles through Mc. Several mechanisms may explain this negative result as we recently showed that immunosuppressive treatments could decrease Mc levels. Moreover the marginal increase of mothers carrying HLA-DRB1 susceptibility alleles (NIMA) is intriguing and merits further analyses.
The Adrenal Cortex in Internal Medicine
Authors: J. P. Thomas, A. H. El-Shaboury
Journal: BMJ (1966)

Dr. Cope dismhses the method developed by Peterson et al.' using the Porter-Silber reaget for measuring plasma 17-hydroxy- .orticosteroidsas being non-specific and little *coepted clinically.This we find surprising, s:nce Peterson and his colleagues established .hattheir method was highly specific, accu- rate, and reliable for cortisol.In fact, Dr.Cope himself in an earlier review' wrote, ...the great value of the Peterson method -is thiat its simplicity is associated with a prooved seability under almost all clinical condskxis. . . .It is probably one of 'the :mo carefully checked and reliable methods= suitable for semi-roudne or routine clinical ,use at the present time."We have used
Fractal correlation properties of R‐R interval dynamics in asymptomatic relatives of patients with dilated cardiomyopathy☆
Authors: Niall G. Mahon, Antti E. Hedman, Mina Padula, Yi Gang, Irina Savelieva, Johan E.P. Waktare, Marek M. Malik, Heikki V. Huikuri, William J. McKenna
Journal: European Journal of Heart Failure (2002)
Understanding and Addressing the Epidemic of Obesity: An Energy Balance Perspective
Authors: James O. Hill
Journal: Endocrine Reviews (2006)

The intent of this paper is to address the obesity epidemic, which is a term used to describe the sudden and rapid increase in obesity rates that began in the 1980s and continues unabated today. Since 1980, the entire population, regardless of starting weight, is gradually gaining weight. This has led to escalating obesity rates and to obesity being considered one of the most serious public health challenges facing the world. At one level, the obesity epidemic is a classic gene-environment interaction where the human genotype is susceptible to environmental influences that affect energy intake and energy expenditure. It is also a problem of energy balance. Understanding the etiology of obesity requires the study of how behavioral and environmental factors have interacted to produce positive energy balance and weight gain. Reversing the epidemic of obesity will require modifying some combination of these factors to help the population achieve energy balance at a healthy body weight. While body weight is strongly influenced by biological and behavioral factors, changes in the environment promoting positive energy balance have been most responsible for the obesity epidemic. Our best strategy for reversing the obesity epidemic is to focus on preventing positive energy balance in the population through small changes in diet and physical activity that take advantage of our biological systems for regulating energy balance. Simultaneously, we must address the environment to make it easier to make better food and physical activity choices. This is a very long-term strategy for first stopping and then reversing the escalating obesity rates, but one that can, over time, return obesity rates to pre-1980s levels.
Abstract 4241: Isozyme-selective intracellular binding assay for histone deacetylases .
Authors: Carolyn C. Woodroofe, Matthew B. Robers, Thomas A. Kirkland, Kevin Kupcho, Andrew L. Niles, Mei Cong, Keith V. Wood
Journal: Cancer Research (2013)

Abstract The precise modulation of histone acetylation is crucial to cellular survival and control of reproduction.Misregulation of acetylation is often correlated with uncontrolled cellular proliferation, and general inhibition of histone deacetylases has proven to be an effective strategy in the treatment of some cancers. The underlying biology of histone deacetylases is however quite complex, with four classes of isozymes and a large number of interacting proteins that modulate the activity of each. The general scarcity of potent isozyme-selective HDAC inhibitors further complicates the task of deciphering individual isozyme activity in a cellular context. We now report a novel approach to monitoring the intracellular inhibition of single isozymes based on bioluminescence resonance energy transfer from NanoLucTM, a small and exceedingly bright bioluminescent reporter. In our approach, a NanoLucTM fusion of the isozyme of interest is used in combination with an optimized fluorescent tracer. When bound, energy transfer occurs from the bioluminescent enzyme to the fluorescent probe. Displacement of the probe by a competitive inhibitor is then measured as a decrease in the energy transfer ratio, yielding IC50 data specific to the chosen isozyme. We demonstrate the ability to measure intracellular IC50 values of inhibitors against individual isozymes of class I and class IIb based on choice of the NanoLucTM fusion. Citation Format: Carolyn C. Woodroofe, Matthew B. Robers, Thomas A. Kirkland, Kevin Kupcho, Andrew L. Niles, Mei Cong, Keith V. Wood. Isozyme-selective intracellular binding assay for histone deacetylases . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2013-4241
Rapid Ventricular Pacing Produces Myocardial Protection by Nonischemic Activation of K <sub>ATP</sub> <sup>+</sup> Channels
Authors: Monique M.G. Koning, Ben C.G. Gho, Erik van Klaarwater, René L.J. Opstal, Dirk J. Duncker, Pieter D. Verdouw
Journal: Circulation (1996)

Background Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of K ATP + channels in the protection afforded by ventricular pacing. Methods and Results Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79±3% of the area at risk, mean±SEM) was not different from control infarct size (84±2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71±2%, P &lt;.05 versus control). Thirty minutes of pacing immediately preceding the occlusion without intervening sinus rhythm resulted in considerable limitation of infarct size (63±4%, P &lt;.05), which was abolished by pretreatment with the K ATP + channel blocker glibenclamide (78±4%, P =NS). K ATP + channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07±0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and P co 2 were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73±3%, P &lt;.05 versus control), suggesting that K ATP + channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing. Conclusions Rapid ventricular pacing protects the myocardium against infarction via nonischemic K ATP + channel activation. Continued activation of K ATP + channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.
Atrial Arrhythmias in Adults With Congenital Heart Disease
Authors: Judith Bouchardy, Judith Therrien, Louise Pilote, Raluca Ionescu-Ittu, Giuseppe Martucci, Natalie Bottega, Ariane J. Marelli
Journal: Circulation (2009)

Background— Atrial arrhythmias increase disease burden in the general adult population. Adults with congenital heart lesions constitute a rapidly growing group of patients with cardiovascular disease. We hypothesized that atrial arrhythmias increase with age and impair health outcomes in this population. Methods and Results— We conducted a population-based analysis of prevalence, lifetime risk, mortality, and morbidity associated with atrial arrhythmias in adults with congenital heart disease from l983 to 2005. In 38 428 adults with congenital heart disease in 2005, 5812 had atrial arrhythmias. Overall, the 20-year risk of developing atrial arrhythmia was 7% in a 20-year-old subject and 38% in a 50-year-old subject. More than 50% of patients with severe congenital heart disease reaching age 18 years developed atrial arrhythmias by age 65 years. In patients with congenital heart disease, the hazard ratio of any adverse event in those with atrial arrhythmias compared with those without was 2.50 (95% confidence interval, 2.38 to 2.62; P &lt;0.0001), with a near 50% increase in mortality (hazard ratio, 1.47; 95% confidence interval, 1.37 to 1.58; P &lt;0.001), more than double the risk of morbidity (stroke or heart failure) (hazard ratio, 2.21; 95% confidence interval, 2.07 to 2.36; P &lt;0.001), and 3 times the risk of cardiac interventions (hazard ratio, 3.00; 95% confidence interval, 2.81 to 3.20; P &lt;0.001). Conclusions— Atrial arrhythmias occurred in 15% of adults with congenital heart disease. The lifetime incidence increased steadily with age and was associated with a doubling of the risk of adverse events. An increase in resource allocation should be anticipated to deal with this increasing burden.
Chaperones for genital examination
Authors: C J Bignell
Journal: BMJ (1999)

Papers p 159 

Never, sometimes, or always characterise the wide variation in individual doctors' practice of using chaperones during genital and rectal examination. This variation is not confined to general practice.1 In this week's issue Torrance et al report a survey of chaperone policy in genitourinary medicine clinics (p 159).2 Some clinics would appear to allow male doctors to examine female patients without the presence or offer of a chaperone. Such practice is surely beyond justification.

Some may argue that the use of chaperones is an area where physician discretion is more relevant than policy. Certainly not all patients choose to have a chaperone present during intimate examinations, and it may be difficult to provide chaperones in some settings. However, in this area of quality and clinical risk guidelines rather than discretion need to dictate practice.

What considerations should direct the use of chaperones? Several studies have sought patient preferences in primary and secondary healthcare settings,3–7 although not in genitourinary medicine. The …
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia
Authors: Teresa Palomero, Maria Luisa Sulis, Maria Cortina, Pedro J Real, Kelly Barnes, Maria Ciofani, Esther Caparros, Jean Buteau, Kristy Brown, Sherrie L Perkins, Govind Bhagat, Archana M Agarwal, Giuseppe Basso, Mireia Castillo, Satoru Nagase, Carlos Cordon-Cardo, Ramon Parsons, Juan Carlos Zúñiga-Pflücker, Maria Dominguez, Adolfo A Ferrando
Journal: Nature Medicine (2007)
Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model
Authors: Hainan Piao, Jin-Sook Kwon, Shuguang Piao, Ju-Hee Sohn, Yeong-Shin Lee, Jang-Whan Bae, Kyung-Kuk Hwang, Dong-Woon Kim, Oju Jeon, Byung-Soo Kim, Young-Bae Park, Myeong-Chan Cho
Journal: Biomaterials (2006)
Stable Gene Transfer to Muscle Using Non-integrating Lentiviral Vectors
Authors: Luis Apolonia, Simon N Waddington, Carolina Fernandes, Natalie J Ward, Gerben Bouma, Michael P Blundell, Adrian J Thrasher, Mary K Collins, Nicola J Philpott
Journal: Molecular Therapy (2007)

Human immunodeficiency virus (HIV)-based lentiviral vectors (LVs) hold immense promise for gene delivery applications because of their relatively large packaging capacity and their ability to infect a range of cell types. The genome of HIV non-specifically integrates into the host genome, and this promotes efficient, stable transgene expression in dividing cells. However, integration can also be problematic because of variations in gene expression among cells, possible gene silencing and, most importantly, insertional mutagenesis which can lead to undesirable effects such as malignant transformation. In order to alleviate these problems, we have developed a range of non-integrating LVs (NILVs) by introducing point mutations into the catalytic site, chromosome binding site, and viral DNA binding site of the viral integrase (IN). In addition, we have mutated the IN attachment (att) sites within the HIV long terminal repeats (LTRs). All of the vectors produced show efficient reverse transcription and transgene expression in dividing cells and prolonged expression in non-dividing myotubes. Finally, we show that NILV can be used for achieving highly effective gene transfer and expression in muscle in vivo.