tbuckley/cabot-search huggingface dataset:
Involvement of Tissue Factor Pathway Inhibitor in the Coronary Circulation of Patients With Acute Coronary Syndromes
Authors: Paolo Golino, Amelia Ravera, Massimo Ragni, Plinio Cirillo, Orlando Piro, Massimo Chiariello
Journal: Circulation (2003)

Background— Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of the extrinsic coagulation pathway; however, its involvement during thrombus formation in patients with acute coronary syndromes (ACS) is still unknown. Methods and Results— Transcardiac (aorta/coronary sinus) free and total TFPI (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex levels, were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A plasma levels were measured. Samples were collected at baseline, after PTCA, and after stent deployment. In patients with ACS, both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study; conversely, a significant increase in TFPI/FXa complex plasma levels was observed in the coronary sinus as compared with the aorta. In contrast, in patients with stable angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in the coronary sinus as compared with the aorta. Conclusions— TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis.
Aspirin triggered lipid mediators: novel inhibitors of leucocyte trafficking
Authors: C. N Serhan
Journal: Thorax (2000)

Despite nearly 100 years of wide usage, complete knowledge of the therapeutic impact of aspirin is still evolving1-3and new beneficial effects are being uncovered in cardiovascular disease and cancer.4 5 The irreversible acetylation of cyclo-oxygenase (COX)-1 and its more recently discovered isoform COX-21 6 with inhibition of prostaglandins is well appreciated and explains some, but not all, of the pharmacological actions of aspirin.

Another series of bioactive lipid mediators on which aspirin has an impact are lipoxins (LX), and their C15 epimers (15R), denoted aspirin triggered lipoxins (ATL, fig 1), which are biosynthesised by separate routes involving transcellular circuits.7 Native LX in the nanomolar range inhibit the adhesion and transmigration of polymorphonuclear leucocytes (PMNs)8-10 and hence serve as counter-regulatory signals operative in the resolution of inflammatory sites.11 12 Not only do LX serve counter-regulatory roles, but specific enantiomerically modified LX (ATL) may also be actual effectors of well established anti-inflammatory therapeutic actions of aspirin. The impact of 5S,6R,15S-trihydroxy-7,9,13- trans -11- cis -eicosatetraenoic acid (LXA4) and ATL was investigated in tumour necrosis factor (TNFα) initiated PMN responses in vitro and in vivo using the metabolically more stable LX analogues 15R/S-methyl-LXA4and 15-epi-16-(parafluoro)-phenoxy-LXA4. These compounds represent subtle modifications to the native LXA4 and ATL structure that prevent rapid metabolic inactivation of the lipoxin and 15-epi-LX structures.13 14 These compounds are also potent novel inhibitors of TNFα driven PMN associated inflammatory events in vitro as well as in vivo, as shown in a murine model with end points relevant to pulmonary inflammation.



Figure 1 
Generation of aspirin triggered lipid mediators (ATLM): anti-inflammation signals. Arachidonic acid can be transformed via COX-1 or its inducible isoform COX-2 to produce prostaglandins and thromboxane. Acetylation by aspirin blocks this conversion.1 6 …
Melanoma Antigens: Immunological and Biological Characterization and Clinical Significance
Authors: M Herlyn, H Koprowski
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.
Authors: H C Stary, A B Chandler, S Glagov, J R Guyton, W Insull, M E Rosenfeld, S A Schaffer, C J Schwartz, W D Wagner, R W Wissler
Journal: Circulation (1994)

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). Type II lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. Type III (intermediate) lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.
Short term fluctuations in air pollution and hospital admissions of the elderly for respiratory disease.
Authors: J Schwartz
Journal: Thorax (1995)

BACKGROUND--Several recent studies have reported associations between short term changes in air pollution and respiratory hospital admissions. This relationship was examined in two cities with substantially different levels of sulphur dioxide (SO2) but similar levels of airborne particles in an attempt to separate the effects of the two pollutants. Significant differences in weather between the two cities allowed the evaluation of that potential confounder also. METHODS--Daily counts of admissions to all hospitals for respiratory disease (ICD 9 460-519) were constructed for persons aged 65 years and older in two cities - New Haven, Connecticut and Tacoma, Washington. Each city was analysed separately. Average daily concentrations of SO2, inhalable particles (PM10), and ozone were computed from all monitors in each city, and daily average temperature and humidity were obtained from the US weather service. Daily respiratory admission counts were regressed on temperature, humidity, day of the week indicators, and air pollution. A 19 day weighted moving regression filter was used to remove all seasonal and subseasonal patterns from the data. Possible U-shaped dependence of admissions on temperature was dealt with using indicator variables for eight categories each of temperature and humidity. Each pollutant was first examined individually and then multiple pollutant models were fitted. RESULTS--All three pollutants were associated with respiratory hospital admissions of the elderly. The PM10 associations were little changed by control for either ozone or SO2. The ozone association was likewise independent of the other pollutants. The SO2 association was substantially attenuated by control for ozone in both cities, and by control for PM10 in Tacoma. The magnitude of the effect was small (relative risk 1.06 in New Haven and 1.10 in Tacoma for a 50 micrograms/m3 increase in PM10, for example) but, given the ubiquitous exposure, this has some public health significance. CONCLUSIONS--Air pollution concentrations within current guidelines were associated with increased respiratory hospital admissions of the elderly. The strongest evidence for an independent association was for PM10, followed by ozone. These results are consistent with other studies and suggest that lowering air pollution concentrations would have some impact on public health.
Transformation-Associated Changes in Sphingolipid Metabolism Sensitize Cells to Lysosomal Cell Death Induced by Inhibitors of Acid Sphingomyelinase
Authors: Nikolaj H.T. Petersen, Ole D. Olsen, Line Groth-Pedersen, Anne-Marie Ellegaard, Mesut Bilgin, Susanne Redmer, Marie S. Ostenfeld, Danielle Ulanet, Tobias H. Dovmark, Andreas Lønborg, Signe D. Vindeløv, Douglas Hanahan, Christoph Arenz, Christer S. Ejsing, Thomas Kirkegaard, Mikkel Rohde, Jesper Nylandsted, Marja Jäättelä
Journal: Cancer Cell (2013)
A Nationwide Cohort Study of Oral and Depot Antipsychotics After First Hospitalization for Schizophrenia
Authors: Jari Tiihonen, Jari Haukka, Mark Taylor, Peter M. Haddad, Maxine X. Patel, Pasi Korhonen
Journal: American Journal of Psychiatry (2011)

Objective: Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited. The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finland. Method: The authors linked national databases of hospitalization, mortality, and antipsychotic prescriptions and computed hazard ratios, adjusting for the effects of sociodemographic and clinical variables, the temporal sequence of the antipsychotics used, and the choice of the initial antipsychotic for each patient. Results: Of 2,588 patients, 1,507 (58.2%) collected a prescription for an antipsychotic during the first 30 days after hospital discharge, and 1,182 (45.7%, 95% confidence interval [CI]=43.7–47.6) continued their initial treatment for 30 days or longer. In a pairwise comparison between depot injections and their equivalent oral formulations, the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications (adjusted hazard ratio=0.36, 95% CI=0.17–0.75). Compared with oral risperidone, clozapine (adjusted hazard ratio=0.48, 95% CI=0.31–0.76) and olanzapine (adjusted hazard ratio=0.54, 95% CI=0.40–0.73) were each associated with a significantly lower rehospitalization risk. Use of any antipsychotic compared with no antipsychotic was associated with lower mortality (adjusted hazard ratio=0.45, 95% CI=0.31–0.67). Conclusions: In Finland, only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia. Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds. Among oral antipsychotics, clozapine and olanzapine were associated with more favorable outcomes. Use of any antipsychotic was associated with lower mortality.
Progressive diffuse pulmonary Langerhans cell histiocytosis improved by cladribine chemotherapy
Authors: R Lazor, B Etienne-Mastroianni, C Khouatra, A Tazi, V Cottin, J-F Cordier
Journal: Thorax (2009)

recognise that the talc currently used in the UK and USA has serious side effects because of systemic dissemination of small particles.They omitted, however, an important experimental study which used larger talc particles (ie, the talc currently used in Europe for .70years) and clearly showed that this talc does not disseminate in organs, 2 unlike previous studies using American or Brazilian talc.This explains why many European respiratory physicians have used talc as a pleurodesing agent for .50years without experiencing serious side effects. 3 We thank the authors for referring to our European prospective study showing that talc poudrage under medical thoracoscopy is safe. 4 There is, however, some misunderstanding of our results.In our paper we reported that we did not find any significant difference in oxygen saturation after the procedure.Physicians had a free choice of patient follow-up after thoracoscopy.There was, indeed, an increase in supplemental oxygen saturation, but we should not forget that routine use of oxygen by nasal prongs is often performed after thoracoscopy, as is done after many interventional procedures such as bronchoscopy.We agree that 7/558 patients developed radiographic pulmonary infiltrates after talc poudrage.However, this does not prove that talc was responsible for this rare infiltrate, which might have been the result of lung re-expansion after pleurodesis.On the other hand, we are not sure that control of the calibre of talc particles will increase the cost of graded talc.The current graded talc used in Europe since 1930 is safe, but has a unique drawback.It is very cheap and does not interest pharmaceutical companies because of the lack of potential for financial benefit.We agree that more research needs to be done into the mechanism of pleurodesis.However, in the meantime, the talc debate should be clarified; many patients suffering from lasting and severe dyspnoea related to malignant pleural effusion are relieved by thoracoscopic talc poudrage performed without intubation, under local anaesthesia with moderate sedation.
Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: Correlation with induction of increased levels of intracellular interkukin-2 in peripheral blood lymphocytes
Authors: A Maraveyas, B Baban, D Kennard, G A Rook, M Westby, J M Grange, P Lydyard, J L Stanford, M Jones, P Selby, A G Dalgleish
Journal: Annals of Oncology (1999)
Ethnic and Sex Bias in Primary Care Screening Tests for Alcohol Use Disorders
Authors: Jeffrey R. Steinbauer
Journal: Annals of Internal Medicine (1998)

Background: The use of self-report screening tests for alcohol use disorders in the primary care setting has been advocated. Objective: To test for ethnic and sex bias in three self-report screening tests for alcohol use disorders in a primary care population. Design: Cross-sectional study with patients randomly selected from appointment lists. Setting: University-based family practice clinic. Patients: Probability sample of 1333 adult family practice patients stratified by sex and ethnicity. Measurements: Patients completed 1) a diagnostic interview to determine the presence of a current alcohol use disorder and 2) three screening tests: the CAGE questionnaire, the Self-Administered Alcoholism Screening Test (SAAST), and the Alcohol Use Disorders Identification Test (AUDIT). Results: The areas under the receiver-operating characteristic (ROC) curves for the CAGE questionnaire and the SAAST ranged from 0.61 to 0.88 and were particularly poor for African-American men and Mexican-American women. For the AUDIT, the area under the ROC curves was greater than 0.90 for each patient subgroup. The sensitivity of the CAGE questionnaire and the SAAST at standard cut-points was lowest for Mexican-American women (0.21 and 0.13, respectively). Positive likelihood ratios for the AUDIT were similar to or higher than those for the other screening tests, whereas negative likelihood ratios were lowest for the AUDIT (<0.33), indicating the superiority of this test in ruling out a disorder. Conclusions: A marked inconsistency in the accuracy of common self-report screening tests for alcohol use disorders was found when these tests were used in a single clinical site with male and female family practice patients of different ethnic backgrounds. The AUDIT does not seem to be affected by ethnic and sex bias.
CD4+CD28− T Lymphocytes Contribute to Early Atherosclerotic Damage in Rheumatoid Arthritis Patients
Authors: Roberto Gerli, Giuseppe Schillaci, Andrea Giordano, Elena Bartoloni Bocci, Onelia Bistoni, Gaetano Vaudo, Simona Marchesi, Matteo Pirro, Federica Ragni, Yehuda Shoenfeld, Elmo Mannarino
Journal: Circulation (2004)

Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated.The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-alpha led to a partial reappearance of the CD28 molecule on the CD4+ cell surface.Circulating CD4+CD28(null) lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-alpha blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.
Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction
Authors: P Cowburn
Journal: Cardiovascular Research (1998)

Objectives: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. Methods: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. Results: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100±3 [standard error of the mean]) to 107±3 mmHg; p<0.01) and systemic vascular resistance (1699±118 to 2033±135 dynes s/cm5; p<0.001) rose, while the cardiac index fell from 2.43±0.17 to 2.20±0.16 l/min/m2 (p<0.002). Mean pulmonary artery pressure (21±2 mmHg) and pulmonary vascular resistance (151±14 to 147±14 dynes s/cm5) did not change however. Conclusions: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.
Mechanical ventilation affects alveolar fibrinolysis in LPS-induced lung injury
Authors: P. Dahlem, A. P. Bos, J. J. Haitsma, M. J. Schultz, E. K. Wolthuis, J. C. M. Meijers, B. Lachmann
Journal: European Respiratory Journal (2006)

The aim of the present study was to determine the effects of mechanical ventilation on alveolar fibrin turnover in lipopolysaccharide (LPS)-induced lung injury. In a randomised controlled trial, Sprague-Dawley rats (n = 61) were allocated to three ventilation groups after intratracheal LPS (Salmonella enteritidis) instillations. Group I animals were subjected to 16 cmH(2)O positive inspiratory pressure (PIP) and 5 cmH(2)O positive end-expiratory pressure (PEEP); group II animals to 26 cmH(2)O PIP and 5 cmH(2)O PEEP; and group III animals to 35 cmH(2)O PIP and 5 cmH(2)O PEEP. Control rats (not mechanically ventilated) received LPS. Healthy rats served as a reference group. Levels of thrombin-antithrombin complex (TATc), D-dimer, plasminogen activator inhibitor (PAI) activity and PAI-1 antigen in bronchoalveolar lavage fluid were measured. LPS-induced lung injury increased TATc, D-dimer and PAI activity and PAI-1 antigen levels versus healthy animals. High pressure-amplitude ventilation increased TATc concentrations. D-dimer concentrations were not significantly raised. Instead, PAI activity increased with the amplitude of the pressure, from 0.7 U.mL(-1) in group I to 3.4 U.mL(-1) in group II and 5.0 U.mL(-1) in group III. There was no change in PAI-1 antigen levels. In conclusion, mechanical ventilation creates an alveolar/pulmonary anti-fibrinolytic milieu in endotoxin-induced lung injury which, at least in part, might be due to an increase in plasminogen activator inhibitor activity.
The Greeks have a word for it
Authors: A. Papagiannis
Journal: European Respiratory Journal (2009)

The Greeks have a word for itTo the Editors:The Greek noun ''penia'' (poverty) is used in medical terminology to signify absence, lack or deficiency of some body constituent, e.g.leucopenia, thrombocytopenia.As these terms often follow anaemia (spelled with the diphthong ''ae'', from ''haema'' for blood) in medical texts, they are occasionally (and wrongly) also spelled with ''ae''.However, penia has nothing to do with haema in linguistic terms: it only requires a plain ''e'' [1].Therefore, the noun ''sarcopenia'' (meaning ''lack of flesh'' in Greek) and the derived adjective ''sarcopenic'' in the paper by FRANSSEN et al. [2] should follow the same spelling rule.
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
Authors: Ryan M. O'Connell, Dinesh S. Rao, Aadel A. Chaudhuri, Mark P. Boldin, Konstantin D. Taganov, John Nicoll, Ronald L. Paquette, David Baltimore
Journal: The Journal of Experimental Medicine (2008)

Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155-induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
Progenitor Cells From the Explanted Heart Generate Immunocompatible Myocardium Within the Transplanted Donor Heart
Authors: David A. D'Alessandro, Jan Kajstura, Toru Hosoda, Alessandro Gatti, Ricardo Bello, Federico Mosna, Silvana Bardelli, Hanqiao Zheng, Domenico D'Amario, M. Elena Padin-Iruegas, Adriana Bastos Carvalho, Marcello Rota, Michael O. Zembala, David Stern, Ornella Rimoldi, Konrad Urbanek, Robert E. Michler, Annarosa Leri, Piero Anversa
Journal: Circulation Research (2009)

RETRACTION This article has been retracted: ( Circ Res . 2018;123:e00. DOI: 10.1161/RES.0000000000000245.)