tbuckley/cabot-search huggingface dataset:
Insulin-like growth factor-II delays myocardial infarction in experimental coronary artery occlusion
Authors: Achim M Vogt, Patrik Htun, Angelika Kluge, René Zimmermann, Wolfgang Schaper
Journal: Cardiovascular Research (1997)

We have previously shown that short pulses of myocardial ischemia cause increased mRNA expression of the insulin-like growth factor II (IGF-II) gene. The expression of IGF-II precedes the expression of its binding protein 5 (IGFBP-5). The cardioprotective actions of the IGF-II peptide and of its binding protein 5 as well as the underlying mechanisms were investigated in this study.Human recombinant IGF-II (0.25 microgram/ml) was applied by means of direct intramyocardial infusion (IM) for 60 min prior to a 60 min LAD occlusion and 120 min reperfusion. Myocardial infarction, compared to the region at risk, was significantly decreased by IGF-II treatment, whereas infusion of Krebs-Henseleit buffer did not show any protective effect (IGF-II, 78.75 +/- 1.51%; control, 100%; P < 0.005). A comparable degree of cardioprotection was observed after infusion of an equipotent concentration of recombinant human insulin (0.02 IU/ml; 88.25 +/- 1.45%; P < 0.05). Lavendustin A (100 microM), an inhibitor of protein tyrosine kinases, prevented the observed cardioprotection. The protective effect of IGF-II was lost when IGFBP-5 was simultaneously infused.IGF-II, a peptide that binds to the insulin receptor and whose mRNA is rapidly transcribed by cardiac myocytes following ischemic stress, is cardioprotective and mimics ischemic preconditioning. Its observed actions are probably based on its metabolic effects and are mediated by the insulin or the IGF-I receptor. IGFBP-5, whose expression follows IGF-II's expression with a short delay, inhibits the cardioprotection afforded by IGF-II and may thus account for the limited temporal duration of ischemic preconditioning.
A specific role for TLR1 in protective TH17 immunity during mucosal infection
Authors: R. William DePaolo, Karishma Kamdar, Samira Khakpour, Yui Sugiura, Wenxia Wang, Bana Jabri
Journal: The Journal of Experimental Medicine (2012)

The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes TH17 immunity, whereas systemic infection promotes TH1 immunity. Furthermore, induction of TH17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-β in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in TH1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10+ regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal TH17 immunity.
Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck
Authors: A. De Paoli, G. Bertola, G. Boz, F. Gherlinzoni, S. Frustaci, G. Fumo, R. Innocente, M.G. Trovò, C. Rossi, A. Carbone, S. Morassut
Journal: Annals of Oncology (1992)
THE ANTIGENIC STRUCTURE OF THE POLYPEPTIDE CHAINS OF HUMAN γ-GLOBULIN
Authors: D. E. Olins, G. M. Edelman
Journal: The Journal of Experimental Medicine (1962)

The antigenic properties of the polypeptide chains of human 7S γ-globulin have been related to two major non-cross-reacting antigenic determinants of the whole molecule. These determinants, called S and F, were obtained by hydrolysis of γ-globulin with papain. Antisera against whole γ-globulin and against S and F fragments were used in techniques of immune diffusion. Light (L) chains of γ-globulin showed reactions of partial identity with S fragments, and thus are antigenically deficient with respect to these fragments. Antisera directed against F determinants did not react with L chains but did react with heavy (H) polypeptide chain preparations. In addition, the major component of H chain fractions did not appear to contain determinants in common with the S fragments. L chains of a γ-myeloma protein were shown to be antigenically deficient with respect to the whole myeloma molecule, and antigenically identical with the Bence-Jones protein of the same patient. Correlation of these results with those of previous investigations have led to the conclusions that the S fragment which is known to contain the combining region of antibody molecules, consists in part of L chains or portions of L chains, and that the F fragment, which mediates several other functions of the whole molecule, is composed in part of portions of H chains.
The UK postmortem organ retention crisis: a qualitative study of its impact on parents
Authors: Magi Sque, Tracy Long, Sheila Payne, William R Roche, Peter Speck
Journal: Journal of the Royal Society of Medicine (2008)

Objective: To explore the impact of postmortem organ retention on parents who made enquires about their babies and children when the retention of hearts and other organs removed at postmortem and stored without explicit knowledge or consent of the next-of-kin came to public attention in the UK during 1999-2004. Design: Qualitative study conducted 2003-2004. Data were collected via semi-structured, qualitative interviews and focus groups. Participants: 39 parents who had been affected by organ retention. Setting: Participants were recruited via three parental peer support groups and two NHS Hospital Trusts. Results: Transcripts of the interviews and focus groups were analysed using a thematic approach that sought patterns within the data and highlighted important similarities and differences between participants' accounts. Participants reported the distressing impact organ retention had on their lives; their need for information about the retention of their babies' or children's organs; and the difficulties in their decision making about disposal of retained body parts and tissue blocks and slides. Analysis indicated that organ retention had evoked unresolved bereavement issues and a renewal of grief as well as an opportunity for some parents to resolve ongoing bereavement concerns. Conclusions: Parents in this study wanted NHS teams to appreciate the difficulties organ retention had caused them, deal with their enquires proactively with openness and honesty, and facilitate an environment where they felt supported and could gain the answers to their questions and concerns that were provoked by postmortem organ retention. Such issues may also have implications for the care of other parents and relatives of deceased children.
Protein Kinase C θ (PKCθ) Expression and Constitutive Activation in Gastrointestinal Stromal Tumors (GISTs)
Authors: Anette Duensing, Nora E. Joseph, Fabiola Medeiros, Felicity Smith, Jason L. Hornick, Michael C. Heinrich, Christopher L. Corless, George D. Demetri, Christopher D. M. Fletcher, Jonathan A. Fletcher
Journal: Cancer Research (2004)

KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C theta (PKCtheta) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.
A Study of 183 Road Deaths in and Around Birmingham in 1960
Authors: W. Gissane, J. Bull
Journal: BMJ (1961)

This study is of 149 persons who died as the result of road accidents in Birmingham during 1960, and 34 others who died from road accidents outside the city but who were brought to city hospitals and came under the jurisdiction of the city's coroner. It may be of interest that a further three drivers (all males) of motor cars died from natural causes. One, a taxi-driver aged 61, known to have suffered from cardiac trouble for a considerable time, had a heart attack while driving his taxi, collided with the rear end of a corporation bus, and died from coronary thrombosis. Another, aged 46, when driving his car braked suddenly to avoid hitting a pedestrian on a pedestrian-crossing ; his car then collided with a motor-scooter. He left his car to 'phone his wife and was about to light a cigarette when he collapsed and died from coronary thrombosis. The third, aged 60, was driving his car when he lost control and collided with a stationary motor-van, which in turn struck another stationary car ; necropsy revealed that death resulted from cerebral haemorrhage caused
Prevalence of Nontuberculous Mycobacterial Lung Disease in U.S. Medicare Beneficiaries
Authors: Jennifer Adjemian, Kenneth N. Olivier, Amy E. Seitz, Steven M. Holland, D. Rebecca Prevots
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Pulmonary nontuberculous mycobacteria (PNTM) are an important cause of morbidity among older adults in the United States, but national prevalence estimates are lacking.Objectives: To describe the prevalence and trends of PNTM disease among adults aged 65 years or older throughout the United States.Methods: A nationally representative 5% sample of Medicare Part B beneficiaries was analyzed from 1997 to 2007. Demographic and medical claims data were compiled and prevalence estimates for PNTM and selected comorbidities were calculated and trends over time evaluated. Logistic regression was used to identify demographic and geographic factors associated with PNTM.Measurements and Main Results: From 1997 to 2007, the annual prevalence significantly increased from 20 to 47 cases/100,000 persons, or 8.2% per year. The period prevalence was 112 cases/100,000 persons, although prevalence was twofold higher among Asians/Pacific Islanders than among whites (228 vs. 116 cases/100,000 persons). Western states had the highest period prevalence at 149 cases/100,000 persons, with Hawaii having the highest prevalence at 396 cases/100,000 persons, followed by southeastern states, which had a period prevalence of 131 cases/100,000 persons. PNTM cases had more comorbid conditions than noncases and were 40% more likely to die than noncases. Women were 1.4 times more likely to be a PNTM case than men. Relative to whites, Asians/Pacific Islanders were twice as likely to be a case, whereas blacks were half as likely.Conclusions: The prevalence of PNTM is increasing across all regions of the United States and among both men and women. Significant racial/ethnic and geographic differences suggest important gene–environment interactions.
Enthesis erosion in spondyloarthritis is not a persistent structural lesion
Authors: E. de Miguel, S. Falcao, C. Castillo, C. Plasencia, M. Garcia, J. C. Branco, E. Martin-Mola
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To evaluate the ability of ultrasound (US) to detect the presence and change of Achilles erosions in spondyloarthritis (SpA). <h3>Methods</h3> A blind prospective two-dimensional (2D) and three-dimensional (3D) US study of Achilles enthesis erosions in early SpA was undertaken. US examinations were performed at baseline and at 6 and 12 months of follow-up. Clinical outcomes measures were collected. <h3>Results</h3> Bilateral Achilles entheses of 68 patients (35 women) were investigated. The mean Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (CRP) levels were 4.58±2.05 and 5.97±9.91 mg/l, respectively. The κ values for intrareader agreement for 2D and 3D images were 0.84 and 0.85 for two readers. 2D US visualised 10 erosions (7.4%) and 3D US visualised 13 erosions (9.6%) in 10 patients (14.7%). At 6 and 12 months of follow-up, 25% and 50% of basal erosions had disappeared, respectively and, of the new erosions that appeared at 6 months, 40% had disappeared 6 months later. A statistically significant association between erosion and CRP levels, entheseal Doppler signals and the number of tender and swollen joints was found. <h3>Conclusions</h3> US examination of Achilles erosions is reliable and sensitive to change. An association was found between Achilles erosions and objective activity-based measurements of SpA outcomes.
Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells.
Authors: M S Simonson, S Wann, P Mené, G R Dubyak, M Kester, Y Nakazato, J R Sedor, M J Dunn
Journal: Journal of Clinical Investigation (1989)

A recently described peptide hormone, endothelin, is a potent vasoconstrictor, but it is unclear whether endothelin has other biological actions. These experiments extend the range of biological actions of endothelin to stimulation of mitogenesis. Endothelin at low concentrations (0.1-10 nM) induced mitogenesis by quiescent rat glomerular mesangial cells in culture. Mitogenesis induced by endothelin was accompanied by activation of phospholipase C with increased inositol phosphate turnover and increments of intracellular [Ca2+]. Endothelin also activated Na+/H+ exchange, causing cytosolic alkalinization, and enhanced transcription of the c-fos protooncogene, additional biochemical signals closely linked to proliferation. In addition to being a vasoconstrictor, endothelin thus also functions as a mitogen, presumably through activation of phospholipase C.
Capillary Exchange Modeling
Authors: CARL A. GORESKY, WILFRED H. ZIEGLER, GLEN G. BACH, Brita wangel
Journal: Circulation Research (1970)

In the well-perfused visceral organs, active flow occurs in most capillaries, and they are packed closely. In this situation, lateral diffusion equilibration is relatively rapid and the distribution of exchanging materials is governed chiefly by the permeability of the capillary walls. We modeled extravascular distribution of exchanging substances from this kind of capillary and illustrated the changes expected in the outflow profile with increasing permeability, the evolution from the barrier-limited to the flow-limited case. We then examined the two extremes of the assemblies of such capillaries in an organ. In one, the large-vessel transit times are constant and the capillary transit times account for the outflow distribution of the vascular reference substance; in the other, the capillary transit times are constant but the large-vessel transit times vary. The barrier-limited and flow-limited cases corresponding to these are very different. In the case intermediate between these two extremes, the transit times in both the large vessels and the capillaries in the organs vary. If the organ is functionally homogeneous, the distribution of capillaries supplied by each large vessel is the same, and the situation may be described by a product distribution. The formulation for this intermediate case may then be used both to quantify capillary permeability and to describe the distributions of large-vessel and capillary transit times.
Pharmacological treatment of asthma today
Authors: K.F. Rabe, D.T. Schmidt
Journal: European Respiratory Journal (2001)

The current concept of asthma therapy is based on a stepwise approach, depending on disease severity, and the aim is to reduce the symptoms that result from airway obstruction and inflammation, to prevent exacerbations and to maintain normal lung function. Beta2-adrenoceptor agonists and glucocorticoids are at present the most effective drugs for the treatment of airway obstruction and inflammation, with theophylline, leukotriene receptor antagonists and anticholinergics as second- or third-line therapy. There are, to date, no additional or newly developed drugs available that add substantially to the current strategies or even replace beta2-adrenoceptor agonists or glucocorticoids. New approaches in asthma therapy recommend drug combinations of inhaled steroids, primarily with long-acting beta2-adrenoceptor agonists, based on their improved efficacy and the potential for a steroid-sparing effect. Although existing drug entities are able to control the vast majority of patients with mild and moderate asthma, patients' (and doctors') adherence to guidelines and treatment strategies falls well short of the desired standards. Treatment choices, however, differ between countries and should take into account convenience to the patient and the occurrence of side-effects. Additionally, the cost of therapy and reimbursement policies also influences therapeutic strategies.
Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study
Authors: Stephen D Lawn, Andrew D Kerkhoff, Monica Vogt, Robin Wood
Journal: The Lancet Infectious Diseases (2011)

BackgroundThe diagnostic accuracy of sputum smear microscopy and routine chest radiology for HIV-associated tuberculosis is poor, and culture-based diagnosis is slow, expensive, and is unavailable in most resource-limited settings. We assessed the diagnostic accuracy of a urine antigen test Determine TB-LAM Ag (Determine TB-LAM; Alere, Waltham, MA, USA) for screening for HIV-associated pulmonary tuberculosis before antiretroviral therapy (ART).MethodsIn this descriptive study, consecutive adults referred to a community-based ART clinic in Gugulethu township, South Africa, were all screened for tuberculosis by obtaining sputum samples for fluorescence microscopy, automated liquid culture (gold-standard test), and Xpert MTB/RIF assays (Cepheid, Sunnyvale, CA, USA) and urine samples for the Clearview TB-ELISA (TB-ELISA; Alere, Waltham, MA, USA) and Determine TB-LAM test. Patients with Mycobacterium tuberculosis cultured from one or more sputum samples were defined as cases of tuberculosis. The diagnostic accuracy of Determine TB-LAM used alone or combined with sputum smear microscopy was compared with that of sputum culture and the Xpert MTB/RIF assay for all patients and subgroups of patients stratified by CD4 cell count.FindingsPatients were recruited between March 12, 2010, and April 20, 2011. Of 602 patients enrolled, 542 were able to provide one or more sputum samples, and 94 had culture-positive tuberculosis (prevalence 17·4%, 95% CI 14·2–20·8). Complete results from all tests were available for 516 patients (median CD4 count, 169·5 cells per μL; IQR 100–233), including 85 culture-positive tuberculosis, 24 of whom (28·2%, 95% CI 19·0–39·0) had sputum smear-positive disease. Determine TB-LAM test strips provided results within 30 min. Agreement was very high between two independent readers of the test strips (κ=0·97) and between the test strips and TB-ELISA (κ=0·84). Determine TB-LAM had highest sensitivity at low CD4 cell counts: 66·7% (95% CI 41·0–86·7) at <50 cells per μL, 51·7% (32·5–70·6) at <100 cells per μL, and 39·0% (26·5–52·6) at <200 cells per μL; specificity was greater than 98% for all strata. When combined with smear microscopy (either test positive), sensitivity was 72·2% (95% CI 46·5–90·3) at CD4 counts less than 50 cells per μL, 65·5% (45·7–82·1) at less than 100 cells per μL, and 52·5% (39·1–65·7) at less than 200 cells per μL, which did not differ statistically from the sensitivities obtained by testing a single sputum sample with the Xpert MTB/RIF assay.InterpretationDetermine TB-LAM is a simple, low-cost, alternative to existing diagnostic assays for tuberculosis screening in HIV-infected patients with very low CD4 cell counts and provides important incremental yield when combined with sputum smear microscopy.FundingWellcome Trust.
Effect of fluticasone propionate/salmeterol plus tiotropium<i>versus</i>tiotropium on walking endurance in COPD
Authors: François Maltais, Donald A. Mahler, Véronique Pepin, Eric Nadreau, Glenn D. Crater, Andrea N. Morris, Amanda H. Emmett, Thomas J. Ferro
Journal: European Respiratory Journal (2013)

To the Editor: 

Exercise intolerance is a hallmark feature of chronic obstructive pulmonary disease (COPD) and is associated with premature mortality [1]. Tiotropium (TIO) is effective in improving cycling exercise tolerance [2, 3] and walking endurance time in COPD [4]; these properties are thought to be associated with reductions in operating lung volume and the perception of dyspnoea during exercise [2, 3, 5]. What is less certain, however, is the extent to which these benefits of TIO on exercise duration can be further improved with the use of additional inhalational therapy.

We examined whether the addition of fluticasone propionate/salmeterol combination (FSC) to TIO improved endurance time during the endurance shuttle walking test (ESWT) more than TIO alone in patients with COPD. Our specific objectives were to compare endurance time during the ESWT and evaluate the impact on lung function of TIO alone or in combination with FSC. We hypothesised that the addition of FSC to TIO would improve endurance time during the ESWT compared to TIO alone. This was an 8-week, multicentre, placebo-controlled, double-blind, randomised, parallel group study. Patients received either FSC (Advair/Seretide; GlaxoSmithKline, Research Triangle Park, NC, USA) 250/50 μg administered via DISKUS twice daily plus TIO (Spiriva; Boehringer Ingelheim GmbH and Co.KG, Ingelheim, Germany) 18 μg administered via Handihaler once daily or placebo DISKUS twice daily plus TIO 18 μg once daily. The study was conducted at 24 sites in the USA and Canada between July 19, 2010 and May 2, 2011. Eligible patients were aged ≥40 years and …
Primary airway epithelial cell culture from lung transplant recipients
Authors: I. A. Forrest, D. M. Murphy, C. Ward, D. Jones, G. E. Johnson, L. Archer, F. K. Gould, T. E. Cawston, J. L. Lordan, P. A. Corris
Journal: European Respiratory Journal (2005)

Long-term survival in lung transplantation is limited by the development of obliterative bronchiolitis, a condition characterised by inflammation, epithelial injury, fibroproliferation and obliteration of bronchioles leading to airflow obstruction. To investigate the role of the bronchial epithelium in the pathogenesis of obliterative bronchiolitis the current study aimed to establish primary bronchial epithelial cell cultures (PBEC) from lung allografts. Four to six bronchial brushings were obtained from sub-segmental bronchi of lung allografts. Cells were seeded onto collagen-coated plates and grown to confluence in bronchial epithelial growth medium. Bronchial brushings (n=33) were obtained from 27 patients. PBECs were grown to confluence from 12 out of 33 (39%) brushings. Failure to reach confluence was due to early innate infection. Bacteria were usually isolated from both bronchoalveolar lavage and culture media, but a separate population was identified in culture media only. Primary culture of bronchial epithelial cells from lung transplant recipients is feasible, despite a high rate of early, patient-derived infection. Latent infection of the allograft, identified only by bronchial brushings, may itself be a persistent stimulus for epithelial injury. This technique facilitates future mechanistic studies of airway epithelial responses in the pathogenesis of obliterative bronchiolitis.