tbuckley/cabot-search huggingface dataset:
Atrophic Remodeling of the Heart In Vivo Simultaneously Activates Pathways of Protein Synthesis and Degradation
Authors: Peter Razeghi, Saumya Sharma, Jun Ying, Yi-Ping Li, Stanislaw Stepkowski, Michael B. Reid, Heinrich Taegtmeyer
Journal: Circulation (2003)

Background— Mechanical unloading of the heart results in atrophic remodeling. In skeletal muscle, atrophy is associated with inactivation of the mammalian target of rapamycin (mTOR) pathway and upregulation of critical components of the ubiquitin proteosome proteolytic (UPP) pathway. The hypothesis is that mechanical unloading of the mammalian heart has differential effects on pathways of protein synthesis and degradation. Methods and Results— In a model of atrophic remodeling induced by heterotopic transplantation of the rat heart, we measured gene transcription, protein expression, polyubiquitin content, and regulators of the mTOR pathway at 2, 4, 7, and 28 days. In atrophic hearts, there was an increase in polyubiquitin content that peaked at 7 days and decreased by 28 days. Furthermore, gene and protein expression of UbcH2, a ubiquitin conjugating enzyme, was also increased early in the course of unloading. Transcript levels of TNF-α, a known regulator of UbcH2-dependent ubiquitin conjugating activity, were upregulated early and transiently in the atrophying rat heart. Unexpectedly, p70S6K and 4EBP1, downstream components of mTOR, were activated in atrophic rat heart. This activation was independent of Akt, a known upstream regulator of mTOR. Rapamycin treatment of the unloaded rat hearts inhibited the activation of p70S6K and 4EBP1 and subsequently augmented atrophy in these hearts compared with vehicle-treated, unloaded hearts. Conclusions— Atrophy of the heart, secondary to mechanical unloading, is associated with early activation of the UPP. The simultaneous activation of the mTOR pathway suggests active remodeling, involving both protein synthesis and degradation.
TCT-656 Two-year Clinical and Angiographic Outcomes Compared Between Biolimus- and Everolimus-eluting Stent Implantations in Real-world Practice
Authors: Masanobu Ohya, Kazushige Kadota, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2014)
Time to rethink asthma management
Authors: R. E Ruffin
Journal: Thorax (2009)

From around the world we have had evidence that the “guideline-driven” attainment of good asthma control is not being achieved.1 2 3 Surveys over the past decade have provided the evidence and concluded that “physicians and patients should raise their expectations of the level of asthma control that can be achieved”,2 and “the critical need for improved asthma care, including a more global evaluation of asthma control, implementation of asthma treatment plans and addressing co-morbid conditions”.3 In this issue of Thorax the article by Kandane-Rathnayake et al 4 describes the loss of lung function in middle-aged patients not using inhaled corticosteroids for their asthma ( see page 1025 ). This study adds to the survey evidence1 2 3 by providing lung function data in a population that has been part of an asthma cohort study for several decades. It is a timely wake-up call that, in spite of having doctor-agreed guidelines for asthma management available for two decades,5 predominantly in …
The Dynamics of Health and Return Migration
Authors: Anita A. Davies, Rosilyne M. Borland, Carolyn Blake, Haley E. West
Journal: PLoS Medicine (2011)

The increasing importance and complexity of migration globally also implies a global increase in return migration, and thus an increased interest in the health of returning migrants. The health of returning migrants is impacted by the cumulative exposure to social determinants and risk factors of health during the migration process, during the return movement, and following return. Circular migration often occurs among the diaspora, which can result in the transfer of knowledge and skills that contribute to development, including health system strengthening. Migrants with dual nationality often return to countries with better health services than their country of origin when they are sick and can not get care at home. To maintain and improve the health of returning migrants, multi-sectoral policies at global and national levels should facilitate access to appropriate and equitable health services, social services, and continuity of care across and within borders.
Symposium on Coronary Dilator Drugs
Authors: LLOYD L. HEFNER, BEN FRIEDMAN, T. JOSEPH REEVES, E. E. EDDLEMAN, TINSLEY R. HARRISON
Journal: Circulation (1957)

This conference on coronary vasodilator drugs is best begun by presentation of a patient, a 59-year old white male semi-retired lumber dealer.He was first admitted to the University Hospital oIn September 28, 1955, complaining of chest pain.He had been entirely well until 3 months prior to admission, when after carrying a heavy suit- case about 23 yards, he noted an aching pain in the left side of the neck and a sensation of pressure ill the substernal area.Movement of the arms, thorax, or neck had no influence onl the pain.There was no associated feeling of dyspnea, faintness, weakness, palpitation, or
Maximal oxygen intake and independence in old age
Authors: R J Shephard
Journal: British Journal of Sports Medicine (2008)

This brief review examines the likelihood that a deterioration of aerobic fitness will lead to a loss of independence in old age. The rate of deterioration of maximal aerobic power observed in middle-aged adults continues unabated during the retirement years. Loss of independence seems likely if maximal oxygen intake falls below a threshold of 18 ml/[kg.min] in men and 15 ml/[kg.min] in women, reached at 80–85 years. A regular programme of aerobic exercise can slow or reverse the functional deterioration, reducing the individual’s biological age by 10 or more years, and potentially prolonging independence by a similar amount. There remains a need to clarify the importance of decreasing aerobic fitness relative to other potential causes of dependency but, from the practical viewpoint, regular aerobic activity should be commended to elderly people since it can address many of the issues of both functional loss and chronic disease.
T1 Aspirin reduces pulmonary inflammation in an inhaled lipopolysaccharide model of acute respiratory distress syndrome (ARDS) in healthy volunteers and in a human ex vivo lung perfusion model of ARDS
Authors: U. I. Hamid, J. Conlon, S. Spence, A. Boyle, M. Fitzgerald, M. Shyamsundar, A. Krasnodembskaya, A. Kissenpfennig, R. Verghis, C. Scott, D. McAuley, C. O'Kane
Journal: Thorax (2014)

<h3>Introduction</h3> Platelet activation may play a role in the pathogenesis of ARDS.<sup>1</sup> Animal studies have shown that aspirin therapy reduces pulmonary oedema and development of lung injury.<sup>2</sup> Our recent observational study has shown patients with ARDS on aspirin had a reduced risk of death.<sup>3</sup> <h3>Objective</h3> To test the hypothesis that aspirin reduces pulmonary inflammation in clinically relevant models of ARDS induced by inhaled lipopolysaccharide (LPS). <h3>Methods</h3> Healthy subjects were enrolled in a double-blind, placebo-controlled, allocation concealed study and were randomised to receive aspirin 75 mg or aspirin 1200 mg or placebo (1:1:1) for seven days prior to LPS inhalation. Measurements were performed in bronchoalveolar lavage (BAL) fluid obtained at 6 h after inhaling 50 micrograms of LPS. Parallel experiments were run in an <i>ex vivo</i> lung perfusion model (EVLP) using human lungs to determine the effects of aspirin on inflammatory cytokine production and BAL neutrophils in response to intra-bronchial administration of LPS (6 mg). <h3>Results</h3> 33 healthy volunteers were enrolled. There was no significant difference between aspirin 75 mg and aspirin 1200 mg. Data for both aspirin groups were combined as per the <i>a priori</i> analysis plan. Aspirin pre-treatment reduced LPS-induced BAL neutrophilia (Figure 1a), MMP-9 (33 ng/ml vs 48 ng/ml, p = 0.03), the neutrophil-specific protease MMP-8 (3 ng/ml vs 6 ng/ml, p = 0.03) and the pro-inflammatory cytokine TNF-α (80 pg/ml vs 106 pg/ml, p = 0.02). There was also a non-significant trend towards reduction in a range of inflammatory cytokines (IL-1 β, IL-8 and IL-6). Pre-treatment with aspirin in the EVLP model also showed a similar reduction in BAL neutrophilia (Figure 1b), along with a trend towards reduction in pro-inflammatory cytokines (IL-8, IL-6, TNF-α, MCP-1). <h3>Conclusion</h3> This is the first data to find that aspirin can reduce neutrophilic inflammation in both these models of ARDS. Further clinical studies are planned to assess the role of aspirin in ARDS. <h3>References</h3> Kuebler WM. <i>J Clin Invest</i>. 2006 Dec;116(12):3106–8 Looney MR <i>et al</i>.<i> J Clin Invest</i>. 2009;119(11): 3450–61 Boyle A <i>et al</i>. <i>Thorax</i> 2013;68:Suppl 3 A142–A143
THE SMALL SUBUNIT OF HL-A ANTIGENS IS ß2-MICROGLOBULIN
Authors: Howard M. Grey, Ralph T. Kubo, Sonia M. Colon, M. D. Poulik, Peter Cresswell, Timothy Springer, Mervyn Turner, Jack L. Strominger
Journal: The Journal of Experimental Medicine (1973)

ItL-A antigens prepared from human lymphoid cells by treatment of either intact cells or membranes with papain or nonionic detergents have been shown to contain two polypeptide chains.The antigen prepared by treatment of cells or cell membranes with papain contains polypeptide chains with a mol wt of about 34,000 and 11,000 (1), whereas the detergent-solubilized antigen has polypeptides of tool wt about 43,000 and 11,000 (2).Another membrane-bound protein found on human lymphocytes is ~2-microglobulin, an 11,700 mol wt polypeptide which was first isolated from the urine of patients with renal tubular disease (3) and which has subsequently been sequenced and shown to possess a moderate degree of sequence homology to constant region domains of immunoglobulin polypeptide chains (4, 5).The purpose of the present work was to determine if any relationship existed between the 11,000 dalton peptide chain found in HL-A antigens and/32-microglobulin.The data obtained indicate that these two peptides are in fact identical as assessed by immunologic techniques.
Early radiographic features in patients with anterior cruciate ligament rupture
Authors: J C Buckland-Wright
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To determine, in a preliminary cross sectional study of patients with anterior cruciate ligament (ACL) ruptured knees, which of the radiographic features—subchondral cortical plate thickness, trabecular sclerosis, and osteophytosis—appears before or in association with changes in joint space width (JSW) as a surrogate for articular cartilage thickness in patients with ruptured knees. <h3>METHODS</h3> 19 patients (14 men), mean (95% CI) age 28.7 (23.6 to 33.8) years, had ACL rupture in one knee only, confirmed by arthroscopy. Anterior draw, Lachman9s test, and pivot shift tests were performed and ×5 posteroanterior macroradiographs of both knees in a standing semiflexed view were taken at a mean (95% CI) time from injury of 34.3 (26.9 to 41.7) months. In each radiograph, computerised methods were used to measure minimum JSW and fractal signature analysis (FSA) to quantify the vertical and horizontal trabecular organisation, osteophyte area, and the subchondral cortical plate thickness, in the medial and lateral tibial compartments of all knees. <h3>RESULTS</h3> Physical examination confirmed the presence of joint laxity in the injured knees. No statistical difference in either medial or lateral JSW and subchondral cortical plate thickness was detected between ACL ruptured and uninjured knees. FSA showed a significant decrease in fractal dimension for the horizontal trabeculae (size 0.42 mm) in the medial compartment of the ACL ruptured knees compared with the uninjured knees (p&lt;0.01, multivariate analysis of variance). There was an inverse correlation (R −0.74) between the time since knee injury and the difference in FSA values for ACL ruptured and uninjured knees in medial compartment horizontal trabeculae (size 0.4 mm). No significant changes were detected in the lateral compartment. Osteophytes were detected in the medial compartment of nine ACL injured knees. <h3>CONCLUSION</h3> Compared with the uninjured knee, ACL rupture leads to thickening of subchondral horizontal trabeculae (decreased FSA) in the medial tibial compartment of all knees, reaching significance at about four years after injury. Osteophytes were present in the same compartment in 9/19 knees. No changes in JSW and subchondral cortical plate thickness were detected. Whether the bony changes detected in these ACL ruptured knees presage those of early osteoarthritis requires further study.
Airway and Tissue Resistance in Wheezy Infants
Authors: ANDREW C. JACKSON, WERNER TENNHOFF, RICHARD KRAEMER, URS FREY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We partitioned total respiratory system resistance into airway (Raw) and tissue (Rti) resistance in 16 sedated infants (age 15 to 88 wk) with a history of wheezing disorders before and after inhalation of albuterol. Using systems identification methods, airway (Raw-z) and tissue resistance (Rti-z) were extracted from measurements of respiratory system transfer impedance (Ztr[omega]) over a wide frequency range (typically, 4 < f < 140 Hz). Baseline Raw-z (80.6 +/- 31.5 cm H(2)O/L/s) was significantly (p < 0.01) reduced after albuterol inhalation (60.6 +/- 22.2 cm H(2)O/L/s) but pre- and postalbuterol Rti-z were not significantly different (2.3 +/- 1.7 and 2.7 +/- 2.4 cm H(2)O/L/s, respectively). Raw-z was compared with airway resistance measured with whole-body plethysmography (Raw-p) in 10 of the 16 infants. Raw-z and Raw-p were significantly different in baseline as well as postalbuterol conditions (86.4 +/- 36.9 versus 19.0 +/- 7.0, and 60.6 +/- 22.0 versus 22.5 +/- 14.7, respectively) and they were not correlated. There was no significant difference between Raw-p under baseline and postalbuterol conditions. We conclude that airway resistance estimated from Ztr measurements comprises the major portion of total resistance (approximately 97%) in infants with wheezing disorders in baseline as well as post-beta agonist inhalation, and it is significantly reduced by albuterol inhalation.
DDT/DDE and infant exposure.
Authors: K Mariën
Journal: Environmental Health Perspectives (1997)

DDT/DDE and Infant ExposureThe article by L6pez-Carrillo et al. (1), which discusses the public health implica- tions of using DDT in Mexico, is a wel- come contribution to the literature.DDT is a public health concern not only in the countries still using the chemical but also in those countries that have restricted, phased out, or banned use of the chemical.Presently, it is difficult to conclude if DDT contributes to breast cancer incidence, and the lack of complete confidence in our understanding of the relationship between this xenoestrogen and breast cancer should not prevent us from finding alternatives to DDT that have less public health impact.L6pez-Carrillo et al. (1) base their concern for DDT primarily on the possible increase of breast cancer with exposure.Although this endpoint is of concern, toxicological endpoints that deserve equal attention pertain to infant exposure.Teratology studies by Eriksson et al.
Haemolysis in chronic renal failure.
Authors: A. B. Shaw
Journal: BMJ (1967)

BRITISH 213was advised to seek her pleasure in some less hygienically orientated milieu. SummaryNine cases are reported in which vaccination or inoculation apparently provoked the onset or exacerbation of multiple sclerosis, and the implications of these observations are discussed in relation to the aetiology and pathogenesis of the disease.We wish to thank Dr. E. J. Field for helpful criticism and suggestions
Obesity surgery data show success in tackling life threatening illnesses
Authors: A. O'Dowd
Journal: BMJ (2011)

Clinicians are calling for greater investment in bariatric surgery after a new report shows that such surgery has significant and varied health benefits for patients in the United Kingdom.

The report claims to show for the first time on a nationwide scale the positive effects of bariatric surgery in treating a range of life threatening diseases, including an 85% reduction in the number of patients with type 2 diabetes two years after surgery.

The first report by the UK national bariatric surgery registry—a consortium of the Association of Laparoscopic Surgeons, the Association of Upper Gastrointestinal Surgeons, and the British Obesity and Metabolic Surgical Society—was published on 13 April jointly with the company Dendrite Clinical Systems.

Bariatric Surgery Report 2010 includes …
Occlusion of Small Intracranial Arteries as a Cause of Stroke
Authors: B. Albert Ring
Journal: JAMA (1968)

A patient with an acute stroke had Gerstmann's syndrome. Cerebral angiography disclosed occlusion of the posterior parietal branch of the middle cerebral artery. The patient has remained physically well over a three-year period with only slight residual impairment in the intellectual spheres. Intracranial occlusions of smaller arterial branches can be diagnosed by cerebral angiography and occlusions of isolated branches give rise to characteristic clinical findings.
Dysregulation of Claudin-5 in HIV-induced Interstitial Pneumonitis and Lung Vascular Injury. Protective Role of Peroxisome Proliferator–activated Receptor-γ
Authors: Hong Li, Sangya Singh, Raghava Potula, Yuri Persidsky, Georgette D. Kanmogne
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

HIV-1-induced interstitial pneumonitis (IP) is a serious complication of HIV-1 infection, characterized by inflammation and cellular infiltration in lungs, often leading to respiratory failure and death. The barrier function of the pulmonary endothelium is caused in part by tight junction (TJ) proteins, such as claudin-5. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in lung tissues and regulates inflammation. We hypothesize that HIV-1 induces vascular lung injury, and HIV-1-mediated damage of the pulmonary endothelium and IP is associated with dysregulation of PPAR-γ.Investigate the effects of HIV-1 infection on the pulmonary microvasculature and the modulatory effects of the PPAR-γ ligands.Using human lung tissues, we demonstrated down-regulation of claudin-5 (marker of pulmonary barrier integrity), down-regulation of PPAR-γ transcription, and expression in lung tissues of HIV-1-infected humans with IP.Human lung microvascular endothelial cells expressed the TJ proteins claudin-5, ZO-1, and ZO-2; HIV-1 decreased TJ proteins expression and induced nuclear factor-κB promoter activity, which was reversed by PPAR-γ agonist. Using two murine HIV/AIDS models, we demonstrated decreased claudin-5 expression and increased macrophage infiltration in the lungs of HIV-1-infected animals. Activation of PPAR-γ prevented HIV-1-induced claudin-5 down-regulation and significantly reduced viremia and pulmonary macrophage infiltration.HIV-induced IP is associated with injury to the lung vascular endothelium, with decreased TJ and PPAR-γ expression, and increased pulmonary macrophage infiltration. PPAR-γ ligands abrogated these effects. Thus, regulation of PPAR-γ can be a therapeutic approach against HIV-1-induced vascular damage and IP in infected humans. Removal of Expression of Concern: Issues leading to the previous expression of concern for this article have been resolved after further revisions and editorial review. No further concerns exist.
Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial
Authors: Martin Bornhäuser, Joachim Kienast, Rudolf Trenschel, Andreas Burchert, Ute Hegenbart, Michael Stadler, Herrad Baurmann, Kerstin Schäfer-Eckart, Ernst Holler, Nicolaus Kröger, Christoph Schmid, Herrmann Einsele, Michael G Kiehl, Wolfgang Hiddemann, Rainer Schwerdtfeger, Stefanie Buchholz, Peter Dreger, Andreas Neubauer, Wolfgang E Berdel, Gerhard Ehninger, Dietrich W Beelen, Johannes Schetelig, Matthias Stelljes
Journal: The Lancet Oncology (2012)
Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience
Authors: Franziska Anne Stressmann, Geraint B Rogers, Christopher J van der Gast, Peter Marsh, Louic S Vermeer, Mary P Carroll, Lucas Hoffman, Thomas W V Daniels, Nilesh Patel, Benjamin Forbes, Kenneth Deans Bruce
Journal: Thorax (2012)

<h3>Background</h3> Culture-independent analysis of the respiratory secretions of people with cystic fibrosis (CF) has identified many bacterial species not previously detected using culture in this context. However, little is known about their clinical significance or persistence in CF airways. <h3>Methods</h3> The authors characterised the viable bacterial communities in the sputum collected from 14 patients at monthly intervals over 1 year using a molecular community profiling technique—terminal restriction fragment length polymorphism. Clinical characteristics were also collected, including lung function and medications. Ecological community measures were determined for each sample. Microbial community change over time within subjects was defined using ecological analytical tools, and these measures were compared between subjects and to clinical features. <h3>Results</h3> Bacterial communities were stable within subjects over time but varied between subjects, despite similarities in clinical course. Antibiotic therapy temporarily perturbed these communities which generally returned to pretreatment configurations within 1 month. Species usually considered CF pathogens and those not previously regarded as such exhibited similar patterns of persistence. Less diverse sputum bacterial communities were correlated to lung disease severity and relative abundance of <i>Pseudomonas aeruginosa</i>. <h3>Conclusion</h3> Whilst not true in all cases, the microbial communities that chronically infect the airways of patients with CF can vary little over a year despite antibiotic perturbation. The species present tended to vary more between than within subjects, suggesting that each CF airway infection is unique, with relatively stable and resilient bacterial communities. The inverse relationship between community richness and disease severity is similar to findings reported in other mucosal infections.
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy
Authors: Takeharu Hayashi, Takuro Arimura, Manatsu Itoh-Satoh, Kazuo Ueda, Shigeru Hohda, Natsuko Inagaki, Megumi Takahashi, Hisae Hori, Michio Yasunami, Hirofumi Nishi, Yoshinori Koga, Hiroshi Nakamura, Masunori Matsuzaki, Bo Yoon Choi, Sung Won Bae, Cheol Woon You, Kyung Hoon Han, Jeong Euy Park, Ralph Knöll, Masahiko Hoshijima, Kenneth R. Chien, Akinori Kimura
Journal: Journal of the American College of Cardiology (2004)
Bleeding Angiodysplasia in the Duodenum
Authors: Kuang-I Fu, Takahiro Fujimori
Journal: New England Journal of Medicine (2006)

An 86-year-old woman with cirrhosis and esophageal varices due to chronic hepatitis C infection was referred for evaluation of anemia and fatigue. Esophagogastroduodenoscopy revealed active bleeding in the third part of the duodenum (Panel A). After the area was washed with water, angiodysplasia with a bleeding vessel was revealed (Panel B, arrow). Before argon plasma coagulation was performed, submucosal saline solution was injected to minimize the thermal injury and prevent perforation (Panel C, arrow). The bleeding was successfully controlled (Panel D). At one year of follow-up, the patient has had no recurrence of bleeding or anemia.