tbuckley/cabot-search huggingface dataset:
Effects of β <sup>–</sup> -Emitting <sup>188</sup> Re Balloon in Stented Porcine Coronary Arteries
Authors: Raj Makkar, James Whiting, Alex Li, Hidehiko Honda, Michael C. Fishbein, F.F. (Russ) Knapp, Jörg Hausleiter, Frank Litvack, Neal L. Eigler
Journal: Circulation (2000)

Background —Restenosis within stents may be prevented by ionizing radiation from an intravascular source. Methods and Results —A liquid β − radiation ( 188 Re) balloon was evaluated in a randomized and blinded porcine coronary model of stent restenosis. Group A pigs (n=17) received 0,16, 22, or 29 Gy at 0.5-mm depth, followed by stenting. Restenosis was quantified by angiography, ultrasound, and histomorphometry at 30 days. Group B (n=7) was stented first and then treated with 0 or 29 Gy with follow-up at 60 days. There was a measurable effect at 16 Gy, which improved with increasing doses. At 29 Gy, the histological stenotic area was reduced by 67% (22% versus 66% in controls, P &lt;0.001). Radiation after stenting was equally effective; the stenotic area was reduced (21% versus 65%, P &lt;0.001). At 16 Gy, the vessel just distal to the stent was significantly smaller than control vessels because of intimal thickening ( P =0.003). Radiated vessels had distinctive histology consisting of neointimal fibrin and reduced smooth muscle cells and matrix ( P &lt;0.0001). Conclusions — 188 Re balloon brachytherapy in porcine coronary arteries results in dose-dependent and injury-independent inhibition of stent restenosis for up to 60 days. Restenosis at the borders of the irradiated zone is a potential limitation and may be related to underdosing. Brachytherapy with the 188 Re balloon appears to be safe and feasible for clinical studies.
Immunology of Reactive Arthritides
Authors: G. R. Burmester, A. Daser, T. Kamradt, A. Krause, N. A. Mitchison, J. Sieper, N. Wolf
Journal: Annual Review of Immunology (1995)

Reactive arthritis (ReA) and Lyme arthritis together comprise a pair of chronic inflammatory diseases of the joints. Although differing in detail, these relatively rare diseases are related in their immunopathology to the much commoner rheumatoid arthritis (RA), for which they serve as both model and control. The trigger for rheumatoid arthritis is unknown, but for these rarer diseases triggering occurs by certain well-defined bacterial infections. Arthritis is an uncommon outcome of these infections, for reasons unknown, and the development of chronic, as distinct from brief, arthritis is even rarer; again, the reasons are unknown. Not only does knowing the trigger greatly assist us in understanding these diseases, so also does knowing the contrasting pattern of Th1 versus Th2 cytokines observed in RA and ReA. ReA and Lyme arthritis are here considered in the wider setting of infections where chronic morbidity arises first from hypersensitivity, and perhaps finally from autoimmunity, such as occurs in some of the major tropical diseases. The immunology of ReA and Lyme disease is surveyed in detail, concentrating on T cells and including an update on the Lyme vaccine(s). Additional sections deal with the enigma of HLA B27, with epidemiological findings relevant to the chronicity of ReA and to the need for enlarged prospective studies of ReA in the setting of a developing country.
Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells.
Authors: C Clayberger, R H Dekruyff, J Aisenberg, H Cantor
Journal: The Journal of Experimental Medicine (1983)

Hapten-reactive inducer T cell clones can be divided into two groups based on their activation specificity. The first and largest group is conjugate specific. These clones are activated only by hapten coupled to the same carrier protein used for in vitro selection. The second group, which is quite rare, is hapten specific. Clones of this type are activated by hapten coupled to all foreign and autologus proteins tested. Both types of clones corecognize soluble antigen in association with products of the I-A locus. The hapten-specific cells were used to analyze the molecular basis of I-A vs. I-E gene control. The physiologic significance of hapten- and carrier-specific inducer T cells in the response to foreign antigens and autoantigens is discussed.
Patient Safety Is Not Enough: Targeting Quality Improvements To Optimize the Health of the Population
Authors: Steven H. Woolf
Journal: Annals of Internal Medicine (2004)

Ensuring patient safety is essential for better health care, but preoccupation with niches of medicine, such as patient safety, can inadvertently compromise outcomes if it distracts from other problems that pose a greater threat to health. The greatest benefit for the population comes from a comprehensive view of population needs and making improvements in proportion with their potential effect on public health; anything less subjects an excess of people to morbidity and death. Patient safety, in context, is a subset of health problems affecting Americans. Safety is a subcategory of medical errors, which also includes mistakes in health promotion and chronic disease management that cost lives but do not affect "safety." These errors are a subset of lapses in quality, which result not only from errors but also from systemic problems, such as lack of access, inequity, and flawed system designs. Lapses in quality are a subset of deficient caring, which encompasses gaps in therapeutics, respect, and compassion that are undetected by normative quality indicators. These larger problems arguably cost hundreds of thousands more lives than do lapses in safety, and the system redesigns to correct them should receive proportionately greater emphasis. Ensuring such rational prioritization requires policy and medical leaders to eschew parochialism and take a global perspective in gauging health problems. The public's well-being requires policymakers to view the system as a whole and consider the potential effect on overall population health when prioritizing care improvements and system redesigns.
PWE-096 Is there an Association Between Parkinson’S Disease and Inflammatory Bowel Disease ?
Authors: M W Johnson, K Lithgo, T Price
Journal: Gut (2013)

<h3>Introduction</h3> The BRAAK theory of Parkinson’s disease believes that the aetiology may all start in the bowel with a “slow virus” entering the central nervous system after passing through the intestinal mucosa {Hawkes C.H., 2007}. There is already work confirming an increased frequency of H. pylori infections (requiring treatment) in the 5 years prior to Parkinson’s disease being diagnosed {Nielsen H.H. 2012}. Recently a gene associated with the inherited form of Parkinson’s disease (leucine-rich repeat kinase 2 - LRRK2), has been shown to regulate the transcription factor NFAT1 (nuclear factor of activated T cells 1), which in turn appears to regulate cells in the immune system, including macrophages, dendritic cells and T cells. Higher quantities of NFAT1 activity are seen in the colonic mucosa of Crohn’s patients, where the total quantity directly correlates to the severity of the disease {Liu Z., 2011}. Objective: With these theories in mind, we aimed to assess whether a higher than expected association between inflammatory bowel disease (IBD) and Parkinson’s disease (PD) could be found. <h3>Methods</h3> A cross correlation analysis was performed using the IBD and PD databases at the Luton &amp; Dunstable University Hospital. A retrospective analysis was also performed using medical notes and the internal electronic results system to assess the disease severity of these two conditions. <h3>Results</h3> The prevalence of IBD and PD within the UK population is said to be 225/100,000 (UC 150/100,000 + CrD 75/100,000) and 140/100,000, respectively. The L&amp;D catchment area covers 330,000 and so one would have expected approximately 742 IBD and 462 PD patients, respectively. The databases had 2783 IBD patients (median age = 51) and 350 PD patients (median age = 79) listed. Probability analysis predicted that we would find just 1 patient with concomitant PK and IBD, however, we found 6 subjects with these conditions concomitantly. This translates into 0.2% of IBD patients having PD and 1.72% of PD patients having IBD. Mild-to-moderate PD was noted in 3 patients, and all 3 had mild-to-moderate IBD. Three of the PD patients were scored as having moderate-to-severe disease, and 2 of these also had moderate-to-severe IBD. <h3>Conclusion</h3> The proportion of PD patients having concomitant IBD is considerably higher than one would have expected by chance. This raises possible issues around genetic association, but also lends some credence to theories that PD may owe its origins to the bowel and infective translocation across bowel mucosa. Those patients with more significant IBD also appeared to have more severe PD. <h3>Disclosure of Interest</h3> None Declared.
Physical Activity for Health: What Kind? How Much? How Intense? On Top of What?
Authors: Kenneth E. Powell, Amanda E. Paluch, Steven N. Blair
Journal: Annual Review of Public Health (2011)

Physical activity improves health. Different types of activity promote different types of physiologic changes and different health outcomes. A curvilinear reduction in risk occurs for a variety of diseases and conditions across volume of activity, with the steepest gradient at the lowest end of the activity scale. Some activity is better than none, and more is better than some. Even light-intensity activity appears to provide benefit and is preferable to sitting still. When increasing physical activity toward a desired level, small and well-spaced increments will reduce the incidence of adverse events and improve adherence. Prior research on the relationship between activity and health has focused on the value of moderate to vigorous activity on top of an indefinite and shifting baseline. Given emerging evidence that light activities have health benefits and with advances in tools for measuring activities of all intensities, it may be time to shift to zero activity as the conceptual starting point for study.
Influence of Lifestyle Modifications on Age-Related Free Radical Injury to Brain
Authors: Elaine R. Peskind, Ge Li, Jane B. Shofer, Steven P. Millard, James B. Leverenz, Chang-En Yu, Murray A. Raskind, Joseph F. Quinn, Douglas R. Galasko, Thomas J. Montine
Journal: JAMA Neurology (2014)

The Healthy Brain Initiative 2013-2018 seeks to optimize brain health as we age. Free radical injury is an important effector of molecular and cellular stress in the aging brain that derives from multiple sources.To identify potentially modifiable risk factors associated with increased markers of brain oxidative stress.This cross-sectional, academic multicenter study consisted of 320 research volunteers (172 women) aged 21 to 100 years who were medically healthy and cognitively normal.Free radical injury to the brain was assessed using cerebrospinal fluid (CSF) F2-isoprostane (F2-IsoP) concentrations correlated with age, sex, race, cigarette smoking, body mass index, inheritance of the ε4 allele of the apolipoprotein E gene (APOE), and CSF biomarkers of Alzheimer disease.The concentration of CSF F2-IsoP increased with age by approximately 3 pg/mL (approximately 10%) from age 45 to 71 years in medically healthy, cognitively normal adults (P < .001). The CSF F2-IsoP concentration increased by approximately more than 10% for every 5-U increase in body mass index (P < .001). Current smoking had an approximately 3-fold greater effect on CSF F2-IsoPs compared with age (P < .001). Women had greater mean CSF F2-IsoP concentrations than men at all ages after adjusting for other factors (P = .02). Neither the concentration of CSF Alzheimer disease biomarkers nor inheritance of the APOE ε4 allele was associated with the CSF F2-IsoP concentration in this group of medically healthy, cognitively normal adults (P > .05). The association between CSF F2-IsoP concentrations and race was not significant after controlling for the effect of current smoking status (P = .45).Our results are consistent with an age-related increase in free radical injury in the human brain and uniquely suggest that this form of injury may be greater in women than in men. Our results also highlighted 2 lifestyle modifications (ie, body mass index and smoking) that would have an even greater effect on suppressing free radical injury to the brain than would suppressing the processes of aging. These results inform efforts to achieve success in the Healthy Brain Initiative 2013-2018.
Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction
Authors: Shuang Zhou, Hou-Zao Chen, Yan-zhen Wan, Qing-Jun Zhang, Yu-Sheng Wei, Shuai Huang, Jin-Jing Liu, Yun-Biao Lu, Zhu-Qin Zhang, Rui-Feng Yang, Ran Zhang, Hua Cai, De-Pei Liu, Chih-Chuan Liang
Journal: Circulation Research (2011)

Inactivation of the p66Shc adaptor protein confers resistance to oxidative stress and protects mice from aging-associated vascular diseases. However, there is limited information about the negative regulating mechanisms of p66Shc expression in the vascular system.In this study, we investigated the role of SIRT1, a class III histone deacetylase, in the regulation of p66Shc expression and hyperglycemia-induced endothelial dysfunction.Expressions of p66Shc gene transcript and protein were significantly increased by different kinds of class III histone deacetylase (sirtuin) inhibitors in human umbilical vein endothelial cells and 293A cells. Adenoviral overexpression of SIRT1 inhibited high-glucose-induced p66Shc upregulation in human umbilical vein endothelial cells. Knockdown of SIRT1 increased p66Shc expression and also increased the expression levels of plasminogen activator inhibitor-1 expression, but decreased manganese superoxide dismutase expression in high-glucose conditions. However, knockdown of p66Shc significantly reversed the effects of SIRT1 knockdown. In addition, p66Shc overexpression significantly decreased manganese superoxide dismutase expression and increased plasminogen activator inhibitor-1 expression in high-glucose conditions, which were recovered by SIRT1 overexpression. Moreover, compared to streptozotocin-induced wild-type diabetic mice, endothelium-specific SIRT1 transgenic diabetic mice had decreased p66Shc expression at both the mRNA and the protein levels, improved endothelial function, and reduced accumulation of nitrotyrosine and 8-OHdG (markers of oxidative stress). We further found that SIRT1 was able to bind to the p66Shc promoter (-508 bp to -250 bp), resulting in a decrease in the acetylation of histone H3 bound to the p66Shc promoter region.Our findings indicate that repression of p66Shc expression by SIRT1 contributes to the protection of hyperglycemia-induced endothelial dysfunction.
S51 Efficacy of Aclidinium Bromide Compared with Tiotropium and Placebo in Patients with Moderate to Severe COPD: A Phase IIIb Study: Abstract S51 Table 1
Authors: Jutta Beier, Anne Marie Kirsten, Robert Mroz, Rosa Segarra, Ferran Chuecos, Cynthia Caracta, Esther Garcia Gil
Journal: Thorax (2012)

<h3>Introduction and Objective</h3> Aclidinium bromide is a novel, long-acting, muscarinic antagonist indicated as a maintenance treatment for chronic obstructive pulmonary disease (COPD). Maintaining significant bronchodilation throughout the 24-hour day is important to improve outcomes for patients with COPD. This study evaluated daily bronchodilatory symptom control with twice-daily (BID) aclidinium in patients with stable, moderate-to-severe COPD. <h3>Methods</h3> In this 6-week, randomised, double-blind, Phase IIIb study, patients received aclidinium 400 µg (metered dose; equivalent to aclidinium 322 µg delivered dose) BID, tiotropium bromide 18 µg once daily or placebo. Change from baseline in normalised forced expiratory volume in 1 second (FEV1) area under the curve over the 24-hour period immediately following morning treatment (AUC0–24) at Week 6 was the primary endpoint. Other endpoints included change from baseline in normalised FEV1 AUC12–24 and AUC0–12, pre-dose (trough) FEV1 and peak FEV1. Daily symptoms were recorded each evening using the 11-item EXAcerbations of Chronic pulmonary disease Tool-Respiratory Symptoms (EXACT-RS) and a total score was calculated (range 040: more severe symptoms indicated by higher score). Additional daily symptoms, including presence of morning symptoms and night-time symptom severity (5point scale: 0=none; 4=very severe), were recorded using electronic diaries. <h3>Results</h3> In total, 414 patients were randomised: mean age was 62.3±8.1 years (mean±SD); 54.1% were current smokers; baseline FEV1 was 1.484±0.51 L At Week 6, aclidinium 400 µg BID and tiotropium 18 µg QD significantly improved lung function from baseline compared with placebo (Table). Compared with placebo, aclidinium and tiotropium significantly reduced EXACT-RS total scores from baseline (–2.1 and –1.3 versus –0.1; p&lt;0.0001 and p&lt;0.05, respectively), and increased percentage of days without morning symptoms from baseline (6.7% and 3.4%, respectively, versus 2.2%; p&lt;0.05 for both) at Week 6. Night-time symptom severity scores were significantly reduced from baseline with aclidinium (–0.16) versus placebo (–0.02) at Week 6 (p&lt;0.05) but improvements with tiotropium (–0.09) did not reach statistical significance. <h3>Conclusions</h3> Aclidinium 400 µg BID provided significant 24-hour bronchodilation and daily symptom improvement throughout the study. The bronchodilatory effect of aclidinium was similar to tiotropium, with numerically greater improvement in morning and night-time symptoms among aclidinium-treated patients.
Attachment of Meandering Reentrant Wave Fronts to Anatomic Obstacles in the Atrium
Authors: Takanori Ikeda, Masaaki Yashima, Takumi Uchida, Dustan Hough, Michael C. Fishbein, William J. Mandel, Peng-Sheng Chen, Hrayr S. Karagueuzian
Journal: Circulation Research (1997)

Abstract Acetylcholine chloride (ACh) induces nonstationary meandering reentrant wave fronts in the atrium. We hypothesized that an anatomic obstacle of a suitable size prevents meandering by causing attachment of the reentrant wave front tip to the obstacle. Eight isolated canine right atrial tissues (area, 3.8×3.2 cm) were mounted in a tissue bath and superfused with Tyrode’s solution containing 10 to 15 μmol/L ACh. Holes with 2- to 10-mm diameters were sequentially created in the center of the tissue with biopsy punches. Reentry was induced by a premature stimulus after eight regular stimuli at 400-ms cycle length. The endocardial activation maps and the motion of the induced reentry were visualized dynamically before and after each test lesion using 509 bipolar electrodes. In the absence of a lesion (n=8), the induced single reentrant wave front, in the form of a spiral wave, meandered irregularly from one site to another before terminating at the tissue border. Holes with 2- to 4-mm diameters (n=6) had no effect on meandering. However, when the hole diameters were increased to 6 mm (n=8), 8 mm (n=8), and 10 mm (n=6), the tip of the spiral wave attached to the holes, and reentry became stationary. Transition from meandering to an attached state converted the irregular and polymorphic electrogram to a periodic and monomorphic activity with longer cycle lengths (101±11 versus 131±9 ms for no hole versus 10-mm hole, respectively; P &lt;.001). Regression analysis showed a significant positive linear correlation between the cycle length of the reentry and the hole diameter ( r =.89, P &lt;.01) and between the cycle length of the reentry and the excitable gap ( r =.89, P &lt;.05). We conclude that a critically sized anatomic obstacle converts a nonstationary meandering reentrant wave front to a stationary one. This transition converts an irregular “fibrillation-like” activity into regular monomorphic activity.
NF-κB Regulates Fas-Mediated Apoptosis in HIV-Associated Nephropathy
Authors: Michael J. Ross, Scott Martinka, Vivette D. D’Agati, Leslie A. Bruggeman
Journal: Journal of the American Society of Nephrology (2005)

Renal parenchymal injury in HIV-associated nephropathy (HIVAN) is characterized by epithelial proliferation, dedifferentiation, and apoptosis along the entire length of the nephron. Although apoptotic cell death in HIVAN has been well documented, the mechanism for HIV-induced apoptosis is poorly understood. Whether the epithelial apoptosis in HIVAN is mediated by NF-kappaB-activated Fas ligand expression was investigated here. In human HIVAN and HIV-1 transgenic mouse kidney specimens, the expression of Fas receptor and ligand proteins were markedly upregulated on epithelium in diseased glomerular and tubulointerstitial compartments when compared with normal. Podocyte cell lines that were derived from HIV-1 transgenic mice showed a similar upregulation of Fas receptor expression and de novo expression of Fas ligand by semiquantitative reverse transcription-PCR and Western blotting. In cultured podocytes, cross-linking of the Fas receptor to mimic ligand binding induced caspase 8 activity and apoptosis in both normal and HIVAN podocytes. Because constitutive NF-kappaB activity has been demonstrated in HIVAN epithelia, evidence for transcriptional control of the Fas ligand expression by NF-kappaB was sought. With the use of cultured podocytes, expression of a Fas ligand promoter reporter plasmid was higher in HIVAN podocytes, indicating increased transcriptional activity. In addition, chromatin immunoprecipitation assays were performed to demonstrate that p65-containing (RelA) complexes bound the Fas ligand promoter and that suppression of activated NF-kappaB with a peptide inhibitor could reduce the expression of Fas ligand mRNA in HIVAN podocytes. These results suggest that NF-kappaB may regulate Fas-mediated apoptosis in HIVAN by controlling the expression of Fas ligand in renal epithelium.
Fatal variceal haemorrhage after paracetamol overdose.
Authors: J R Thornton, M S Losowsky
Journal: Gut (1989)

A patient is described where oesophageal varices developed and bled 13 days after a paracetamol overdose. The bleeding was unresponsive to medical management and proved fatal. There was no evidence that the patient had pre-existing liver disease. At necropsy the liver showed severe acute parenchymal necrosis but chronic lesions were absent. The portal vein and hepatic veins were patent.
How tonicity regulates gene expression.
Authors: M B Burg, A Garcia-Perez
Journal: Journal of the American Society of Nephrology (1992)

The expression of a number of different mammalian genes is directly affected by hypertonicity. At present, the list of their products includes aldose reductase, heat shock proteins, early response factors, and transporters for betaine, inositol, and taurine. Hypertonicity increases the abundance of the mRNAs for all of them. Aldose reductase mRNA levels increase because of increased transcription with little change in the stability of its mRNA. Transcription of the betaine transporter also increases. The mechanisms by which hypertonicity increases the transcription of these mammalian genes remain speculative. However, the consideration of transcriptional control of betaine transport in bacteria and of heat shock proteins in many organisms provides interesting insight into this question.