tbuckley/cabot-search huggingface dataset:
Percutaneous visceral pleural biopsy with fenestrated cup biopsy forceps.
Authors: P P Prabhudesai, A A Mahashur, S N Murudkar, R Ajay
Journal: Thorax (1992)

When there is an exudative pleural effusion often both the parietal and the visceral pleura are affected, but the usual practice is to perform a percutaneous parietal pleural biopsy alone for diagnosis. Percutaneous visceral pleural biopsy was carried out in 20 patients with exudative pleural effusions with fenestrated cup biopsy forceps. In all 20 biopsies pleural tissue was obtained and it was diagnostic in 19 cases. The procedure is painless and appears safe.
Early biochemical signals arise from low affinity TCR-ligand reactions at the cell-cell interface.
Authors: C Beeson, J Rabinowitz, K Tate, I Gütgemann, Y H Chien, P P Jones, M M Davis, H M McConnell
Journal: The Journal of Experimental Medicine (1996)

The kinetics of acid release by a mixture of T cells and antigen presenting cells were measured with a microphysiometer during a brief exposure to antigenic peptides. We find that some of the early biochemical events that lead to cellular proliferation cause a specific increase in the rate of acid release. The duration of this increase in acid release reflects the life-time of the peptide-MHC complexes. Peptides that form long-lived complexes produce a response that is stable for more than an hour. Serial TCR engagement is suggested by the observation that the amplitude of this stable response can be rapidly shifted up or down with additional agonist peptide or with antibodies that block T cell receptor binding. Cells briefly exposed to a peptide that forms short-lived peptide-MHC complexes produce a response that decays rapidly as peptide is washed away. A quantitative analysis of the kinetics of this decay in acidification demonstrates that intercellular TCR-ligand reactions are rapid, reversible, and of low apparent affinity with &amp;lt; 20% of peptide-MHC ligand bound to a TCR at any one time. These results demonstrate that the fraction of peptide-MHC ligands bound to TCRs at the cell-cell interface is no higher than anticipated from the affinities observed in solution for isolated TCRs and ligands.
An Evidence-Based Approach to Interactive Health Communication&lt;SUBTITLE&gt;A Challenge to Medicine in the Information Age&lt;/SUBTITLE&gt;
Authors: Thomas N. Robinson
Journal: JAMA (1998)

To examine the current status of interactive health communication (IHC) and propose evidence-based approaches to improve the quality of such applications.The Science Panel on Interactive Communication and Health, a 14-member, nonfederal panel with expertise in clinical medicine and nursing, public health, media and instructional design, health systems engineering, decision sciences, computer and communication technologies, and health communication, convened by the Office of Disease Prevention and Health Promotion, US Department of Health and Human Services.Published studies, online resources, expert panel opinions, and opinions from outside experts in fields related to IHC.The panel met 9 times during more than 2 years. Government agencies and private-sector experts provided review and feedback on the panel's work.Interactive health communication applications have great potential to improve health, but they may also cause harm. To date, few applications have been adequately evaluated. Physicians and other health professionals should promote and participate in an evidence-based approach to the development and diffusion of IHC applications and endorse efforts to rigorously evaluate the safety, quality, and utility of these resources. A standardized reporting template is proposed to help developers and evaluators of IHC applications conduct evaluations and disclose their results and to help clinicians, purchasers, and consumers judge the quality of IHC applications.
Stenting versus thrombolysis in acute myocardial infarction trial (STAT)
Authors: Michel R Le May, Marino Labinaz, Richard F Davies, Jean-François Marquis, Louise A Laramée, Edward R O’Brien, William L Williams, Rob S Beanlands, Graham Nichol, Lyall A Higginson
Journal: Journal of the American College of Cardiology (2001)
Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior
Authors: Jeffery D. Steketee, Peter W. Kalivas
Journal: Pharmacological Reviews (2011)

Repeated exposure to drugs of abuse enhances the motor-stimulant response to these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse to drug, conditioned cue, or stress priming. The involvement of sensitization in reinstated drug-seeking behavior remains controversial. This review describes sensitization and reinstated drug seeking as behavioral events, and the neural circuitry, neurochemistry, and neuropharmacology underlying both behavioral models will be described, compared, and contrasted. It seems that although sensitization and reinstatement involve overlapping circuitry and neurotransmitter and receptor systems, the role of sensitization in reinstatement remains ill-defined. Nevertheless, it is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts.
Low-avidity anticitrullinated protein antibodies (ACPA) are associated with a higher rate of joint destruction in rheumatoid arthritis
Authors: Parawee Suwannalai, Karin Britsemmer, Rachel Knevel, Hans Ulrich Scherer, E W Nivine Levarht, Annette H van der Helm-van Mil, Dirkjan van Schaardenburg, Tom W J Huizinga, René E M Toes, L A Trouw
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Anticitrullinated protein antibodies (ACPA) are specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Previously we have shown that ACPA display a considerably lower avidity as compared with antibodies against recall antigens. Nonetheless, ACPA-avidity did vary between patients. As antibody mediated effects are influenced by antibody-avidity, we now investigated ACPA-avidity in relation to biological activity and clinical outcome. <h3>Methods</h3> We determined the avidity of ACPA and related this with severity of joint damage in two Dutch early-RA cohorts containing 199 and 132 patients respectively. Differences in effector functions of low- and high-avidity ACPA were studied. <h3>Results</h3> Extensive variation in ACPA-avidity between patients was observed. This allowed the analysis of the relationship between avidity and severity. The presence of low-avidity ACPA is associated with a higher rate of joint destruction. This finding was replicated in an independent cohort. Analysis of the properties of low-versus high-avidity ACPA revealed that low-avidity ACPA are less hampered in their ability to bind 'new' citrullinated antigens. Although no differences could be observed regarding cellular activation via Fc-γ receptors, low-avidity ACPA were more potent in activating the complement system. <h3>Conclusions</h3> Patients with low-avidity ACPA display a higher rate of joint destruction. Low-avidity ACPA display a higher potency to interact with more citrullinated antigens in time and show that low-avidity ACPA are more potent in complement activation. These data indicate that (low) avidity impacts on the biological activity of ACPA and associates with a worse radiological outcome.
Vascular Bioactivation of Nitroglycerin Is Catalyzed by Cytosolic Aldehyde Dehydrogenase-2
Authors: Matteo Beretta, Gerald Wölkart, Michaela Schernthaner, Martina Griesberger, Regina Neubauer, Kurt Schmidt, Michael Sacherer, Frank R. Heinzel, Sepp D. Kohlwein, Bernd Mayer
Journal: Circulation Research (2011)

According to general view, aldehyde dehydrogenase-2 (ALDH2) catalyzes the high-affinity pathway of vascular nitroglycerin (GTN) bioactivation in smooth muscle mitochondria. Despite having wide implications to GTN pharmacology and raising many questions that are still unresolved, mitochondrial bioactivation of GTN in blood vessels is still lacking experimental support.In the present study, we investigated whether bioactivation of GTN is affected by the subcellular localization of ALDH2 using immortalized ALDH2-deficient aortic smooth muscle cells and mouse aortas with selective overexpression of the enzyme in either cytosol or mitochondria.Quantitative Western blotting revealed that ALDH2 is mainly cytosolic in mouse aorta and human coronary arteries, with only approximately 15% (mouse) and approximately 5% (human) of the enzyme being localized in mitochondria. Infection of ALDH2-deficient aortic smooth muscle cells or isolated aortas with adenovirus containing ALDH2 cDNA with or without the mitochondrial signal peptide sequence led to selective expression of the protein in mitochondria and cytosol, respectively. Cytosolic overexpression of ALDH2 restored GTN-induced relaxation and GTN denitration to wild-type levels, whereas overexpression in mitochondria (6-fold vs wild-type) had no effect on relaxation. Overexpression of ALDH2 in the cytosol of ALDH2-deficient aortic smooth muscle cells led to a significant increase in GTN denitration and cyclic GMP accumulation, whereas mitochondrial overexpression had no effect.The data indicate that vascular bioactivation of GTN is catalyzed by cytosolic ALDH2. Mitochondrial GTN metabolism may contribute to oxidative stress-related adverse effects of nitrate therapy and the development of nitrate tolerance.
Secretion of a specific collagenase by stimulated macrophages.
Authors: Z Werb, S Gordon
Journal: The Journal of Experimental Medicine (1975)

Thioglycollate-stimulated mouse macrophages release a specific collagenase into their medium during in vitro culture. The macrophage collagenase has been characterized as a typical metal proteinase which catalyzes the cleavage of the native collagen molecule into three and one-quarter fragments. The extracellular accumulation and low activity in cell lysates suggest that collagenase is a secretion product of the stimulated macrophage. Prolonged secretion of the enzyme at a constant rate for more than 7 days in culture and its inhibition by cycloheximide provide evidence for biosynthesis in vitro. In contrast, secretion of collagenase is barely detectable from unstimulated macrophages which can, however, be stimulated to secret the enzyme by ingestion and intralysosomal storage of latex particles or dextran sulfate. Macrophages laden with latex, an undigestable particle, continue to release collagenase for at least 20 days. Several established mouse cell lines have also been examined for their capacity to secrete collagenase. Collagenase is one of a class of inducible neutral proteinases by which the activated macrophage can modify its extracellular environment.
Syndromic management of sexually-transmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial
Authors: A Kamali, M Quigley, J Nakiyingi, J Kinsman, J Kengeya-Kayondo, R Gopal, A Ojwiya, P Hughes, LM Carpenter, J Whitworth
Journal: The Lancet (2003)
Osteomyelitis presenting as a swollen elbow in a patient with the acquired immune deficiency syndrome.
Authors: B T Goh, A S Jawad, D Chapman, S J Winceslaus, G E Forster, J D Perry
Journal: Annals of the Rheumatic Diseases (1988)

A patient suffering from the acquired immune deficiency syndrome (AIDS), who developed swelling of the left elbow four weeks after Staphylococcus aureus septicaemia is reported. The cause was osteomyelitis of the olecranon process.
Syncope due to Brugada syndrome in a young athlete
Authors: Hans D Esperer, Olaf Hoos, Kuno Hottenrott
Journal: British Journal of Sports Medicine (2006)

A 30-year-old male athlete with exercise-related syncopal symptoms spontaneously exhibited a type 1 Brugada ECG and was inducible during electrophysiology study. He was diagnosed with symptomatic Brugada syndrome and deemed at high risk of sudden cardiac death. Thus, he received a cardioverter/defibrillator and was advised to abstain from further competitive sports activities. This case points to a role of the ECG in pre-participation screening. It also demonstrates that, in athletes with Brugada syndrome, repolarisation anomalies may be markedly attenuated during vigorous exercise and considerably increased immediately after exercise. The observed J-wave amplitude dynamics suggests enhancement of pre-existing autonomic dysfunction through heavy exertion.
Theranostic cRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy
Authors: Manfred Wiessler, Ute Hennrich, Rüdiger Pipkorn, Waldemar Waldeck, Liji Cao, Jörg Peter, Volker Ehemann, Wolfhard Semmler, Twan Lammers, Klaus Braun
Journal: Theranostics (2011)

Innovative and personalized therapeutic approaches result from the identification and control of individual aberrantly expressed genes at the transcriptional and post-transcriptional level.Therefore, it is of high interest to establish diagnostic, therapeutic and theranostic strategies at these levels.In the present study, we used the Diels-Alder Reaction with inverse electron demand (DAR inv ) click chemistry to prepare a series of cyclic RGD-BioShuttle constructs.These constructs carry the near-infrared (NIR) imaging agent Cy7 and the chemotherapeutic agent temozolomide (TMZ).We evaluated their uptake by and their efficacy against integrin α v β 3 -expressing MCF7 human breast carcinoma cells.In addition, using a mouse phantom, we analyzed the suitability of this targeted theranostic agent for NIR optical imaging.We observed that the cyclic RGD-based carriers containing TMZ and/or Cy7 were effectively taken up by α v β 3 -expressing cells, that they were more effective than free TMZ in inducing cell death, and that they could be quantitatively visualized using NIR fluorescence imaging.Therefore, these targeted theranostic agents are considered to be highly suitable systems for improving disease diagnosis and therapy.
Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis
Authors: Wu-Shiun Hou, Dieter Brömme, Yingming Zhao, Ernest Mehler, Craig Dushey, Harel Weinstein, Clara Sa Miranda, Claudia Fraga, Fenella Greig, John Carey, David L. Rimoin, Robert J. Desnick, Bruce D. Gelb
Journal: Journal of Clinical Investigation (1999)

Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.
eNOS Activity Is Reduced in Senescent Human Endothelial Cells
Authors: Hidetsugu Matsushita, Edwin Chang, Alexander J. Glassford, John P. Cooke, Choy-Pik Chiu, Philip S. Tsao
Journal: Circulation Research (2001)

Advanced age is associated with endothelial dysfunction and increased risk for atherosclerosis. However, the mechanisms for these observed effects are not clear. To clarify the association between aging and loss of endothelial function, young human aortic endothelial cells (HAECs), senescent HAECs transfected with control vector, and immortalized HAECs containing human telomerase reverse transcriptase (hTERT) were compared for expression of endothelial nitric oxide synthase (eNOS) and production of NO. To investigate a specific function modulated by endothelial NO, adhesion of monocytes under basal conditions as well as after exposure to TNF-α was assessed. A decrease in eNOS mRNA, protein, and activity was observed in endothelial cells at senescence as compared with young HAEC; this effect was blunted in hTERT cells. In all cells, shear stress induced a greater increase in the expression of eNOS protein with the final result being higher levels in hTERT compared with senescent cells. Basal monocyte binding was significantly elevated on aged endothelial cells compared with parental and hTERT cells. Exposure of TNF-α resulted in a 2-fold increase in monocyte adhesion in senescent cells, whereas this effect was reduced in cells transfected with hTERT. Prior exposure to fluid flow significantly reduced subsequent monocyte adhesion in all groups. These studies demonstrate that replicative aging results in decreased endothelial expression of eNOS accompanied by enhanced monocyte binding. Stable expression of hTERT results in endothelial cells with a younger phenotype with greater amount of eNOS and NO activity. Thus, telomerase transfection may have important functional consequences on endothelial cells.
Respiratory Disability in Coal Miners
Authors: W. Keith C. Morgan
Journal: JAMA (1980)

It has been suggested that the assessment of ventilatory capacity alone is inadequate for the determination of disabling occupational respiratory impairment in coal miners. The Department of Labor has accepted this view and now routinely requests blood gas analyses in those claimants not meeting the ventilatory criteria. We tested the validity of this contention by selecting two groups of coal miners claiming total disability. The first consisted of 150 claimants who were referred for spirometry, while the second consisted of 50 claimants who had been referred for blood gas studies. Of those in group 1, eight met the extent criteria for disability, while only two of those in group 2 satisfied the criteria, and, in both, cardiac disease was responsible. We conclude that blood gas analyses are unnecessary in the determination of pulmonary disability in coal miners.
Healthcare service utilisation costs are reduced when rheumatoid arthritis patients achieve sustained remission
Authors: Cheryl Barnabe, Nguyen Xuan Thanh, Arto Ohinmaa, Joanne Homik, Susan G Barr, Liam Martin, Walter P Maksymowych
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Determine healthcare service utilisation costs among patients using biological therapies for rheumatoid arthritis (RA), considering the magnitude and duration of patient response achieved. <h3>Methods</h3> Clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm) was linked with provincial physician billing claims, outpatient visits and hospitalisations. The annual mean healthcare service utilisation costs (total, RA-attributable, non-RA attributable) were estimated for patients during the best disease activity level reached during treatment. <h3>Results</h3> Of 1086 patients: 16% achieved DAS28 remission &gt;1 year, 37% had a DAS28 remission period &lt;1 year, 13% had a low disease activity (LDA) period &lt;1 year and 31% had persistent moderate or high disease activity. Mean annual healthcare service utilisation cost savings for those in sustained remission was $2391 (95% CI 1437 to 3909, p&lt;0.001) and $2104 (95% CI 838 to 3512, p&lt;0.001) for those with non-sustained LDA, relative to the persistent disease activity group. Savings were also observed for those in sustained remission compared to non-sustained remission (annual savings $1422, 95% CI 564 to 2796, p&lt;0.001). RA-related costs were consistent across disease activity and cost categories; the majority of costs were attributable to non-RA related hospitalisations. <h3>Conclusions</h3> We provide evidence of economic benefits to the healthcare system when RA patients achieve persistent good disease control. Benefits from brief periods of remission and LDA are also observed. Coupled with an expected increase in productivity from improved disease control, there is societal benefit to the utilisation of biologics in RA management to achieve treatment goals.
Cardiomyopathy in Murine Models of Systemic Sclerosis
Authors: Paulius Venalis, Gábor Kumánovics, Hendrik Schulze‐Koops, Alfiya Distler, Clara Dees, Pawel Zerr, Katrin Palumbo‐Zerr, László Czirják, Zygmunt Mackevic, Ingrid E. Lundberg, Oliver Distler, Georg Schett, Jörg H. W. Distler
Journal: Arthritis & Rheumatology (2014)

Objective Cardiomyopathy has emerged as a leading cause of death in patients with systemic sclerosis (SSc). However, the pathogenesis of SSc‐related cardiomyopathy is poorly understood, and new therapies as well as platforms for testing are needed. The aim of this study was to characterize the histopathologic features of cardiomyopathy in patients with SSc and in common mouse models of SSc. Methods The histopathologic features of myocardial tissue specimens obtained at autopsy from 5 subjects with SSc and 5 control subjects matched for sex, age, and cardiovascular risk factors were evaluated and compared with those of myocardial tissue specimens obtained from 3 common mouse models of SSc with systemic manifestations: Fra‐2–transgenic mice, mice with sclerodermatous chronic graft‐versus‐host disease (GVHD), and TSK‐1 mice. Results Myocardial tissue from autopsy subjects with SSc and no clinically manifest cardiac involvement showed endothelial cell apoptosis with reduced capillary density, perivascular inflammation, myofibroblast differentiation, and accumulation of collagen. Only selected features of SSc‐related cardiomyopathy were observed in the mice with chronic GVHD and TSK‐1 mice. However, the myocardial tissue of Fra‐2–transgenic mice mimicked all features of SSc‐related cardiomyopathy and also demonstrated comparable vascular, inflammatory, and fibrotic manifestations. Of note, the expression of Fra‐2 was also increased in the myocardium of autopsy subjects with SSc. Conclusion We demonstrate that all typical manifestations of SSc‐related cardiomyopathy are mimicked in Fra‐2–transgenic mice. Moreover, overexpression of Fra‐2 in the myocardium of autopsy subjects with SSc may suggest similar underlying pathogenic mechanisms. Thus, Fra‐2–transgenic mice might be a suitable preclinical model with which to study the mechanisms of and therapeutic approaches to myocardial involvement in SSc.