tbuckley/cabot-search huggingface dataset:
Lateral Zone of Cell-Cell Adhesion as the Major Fluid Shear Stress–Related Signal Transduction Site
Authors: Yumiko Kano, Kazuo Katoh, Keigi Fujiwara
Journal: Circulation Research (2000)

Abstract —It has been proposed previously that actin filaments and cell adhesion sites are involved in mechanosignal transduction. In this study, we present certain morphological evidence that supports this hypothesis. The 3D disposition of actin filaments and phosphotyrosine-containing proteins in endothelial cells in situ was analyzed by using confocal microscopy and image reconstruction techniques. Surgical coarctations were made in guinea pig aortas, and the same 3D studies were conducted on such areas 1 week later. Stress fibers (SFs) were present at both basal and apical regions of endothelial cells regardless of coarctation, and several phosphotyrosine-containing proteins were associated with SF ends. Apical SFs had one end attached to the apical cell membrane and the other attached to either the basal membrane or the lateral cell border. Within the coarctation area, the actin filament–containing and vinculin-containing structures became prominent, especially at the apical and the lateral regions. Substantially higher levels of anti-phosphotyrosine and anti-Src staining were detected in the constricted area, particularly at the cell-cell apposition, whereas the anti–focal adhesion kinase, anti–CT10-related kinase, anti–platelet endothelial cell adhesion molecule-l, anti-vinculin, and phalloidin staining intensities increased only slightly after coarctation. We propose that apical SFs directly transmit the mechanical force of flow from the cell apex to the lateral and/or basal SF anchoring sites and that the SF ends associated with signaling molecules are sites of signal transduction. Our results support the idea that the cell apposition area is the major fluid shear stress–dependent mechanosignal transduction site in endothelial cells.
Calcium Succinate Combined with Aspirin in the Treatment of Rheumatic Disease: II. Calcium Succinate with Aspirin as an Anti-Rheumatic Agent
Authors: D. C. Crain
Journal: Annals of the Rheumatic Diseases (1951)

CALCIUM SUCCINATE AND ASPIRIN IN RHEUMATIC DISEASE 121 manufacturer, and its effect compared with that of aspirin alone given by a similar course in similar doses.(3) Although " Dolcin " often gave relief from pain, the relief was symptomatic only, and the patient was no better than when aspirin was given alone.semejante y en dosis similares.(3) Aunque " Dolcin" frecuentemente calmo el dolor, el alivio fue meramente sintomatico y los enfermos no se sintieron mejor que cuando tomaron simplemente aspirina.
Is there any relationship between plasma antioxidant capacity and lung function in smokers and in patients with chronic obstructive pulmonary disease?
Authors: I. Rahman
Journal: Thorax (2000)

<h3>BACKGROUND</h3> It has been suggested that oxidative stress is an important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have shown that an oxidant/antioxidant imbalance occurs in the distal air spaces of smokers and in patients with COPD which is reflected systemically in the plasma. A study was undertaken to determine whether plasma antioxidant status correlated with lung function as assessed by forced expiratory volume in one second (FEV<sub>1</sub>) and forced vital capacity (FVC) in smokers and patients with COPD. <h3>METHODS</h3> Plasma antioxidant capacity, assessed by the Trolox equivalent antioxidant capacity (TEAC) as an index of overall systemic oxidative stress, and protein thiol levels were measured in 95 patients with stable COPD, in 82 healthy smokers, and in 37 healthy non-smokers. <h3>RESULTS</h3> Mean (SE) plasma TEAC levels were significantly decreased in patients with COPD (0.81 (0.03) mmol/l, p&lt;0.001) and in healthy smokers (0.87 (0.04) mmol/l, p&lt;0.001) compared with healthy non-smokers (1.31 (0.11) mmol/l). The mean differences in plasma antioxidant capacity (mM) were (0.81, 95% confidence interval (CI) 0.22 to 1.48), (0.87, 95% CI 0.2 to 1.46), and (1.31, 95% CI 1.09 to 1.58) in patients with COPD, healthy smokers, and healthy non-smokers, respectively. This reduction was associated with a 29% (95% CI 18 to 38) and a 30% (95% CI 19 to 40) decrease in plasma protein thiol levels in COPD patients and smokers, respectively. Current smoking was not the main contributor to the reduction in antioxidant capacity in patients with COPD as those patients who were still smokers had similar TEAC levels (mean (SE) 0.78 (0.05); n = 25) to those who had stopped smoking (0.84 (0.02); n = 70). No significant correlations were found between spirometric data measured as FEV<sub>1</sub> % predicted or FEV<sub>1</sub>/FVC % predicted and the plasma levels of TEAC in patients with COPD, healthy smokers, or healthy non-smokers. Similarly, there was no significant correlation between FEV<sub>1</sub> % predicted or FEV<sub>1</sub>/FVC % predicted and the levels of plasma protein thiols in the three groups. <h3>CONCLUSIONS</h3> These data confirm decreased antioxidant capacity in smokers and patients with COPD, indicating the presence of systemic oxidative stress. However, no relationship was found between protein thiols or TEAC levels and measurements of airflow limitation in either smokers or in patients with COPD.
A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo
Authors: Philip R. Taylor, Anna Carugati, Valerie A. Fadok, H. Terence Cook, Mark Andrews, Michael C. Carroll, John S. Savill, Peter M. Henson, Marina Botto, Mark J. Walport
Journal: The Journal of Experimental Medicine (2000)

The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.
Delayed preconditioning of the human myocardium: signal transduction and clinical implications
Authors: M Loubani
Journal: Cardiovascular Research (2003)

Ischemic preconditioning confers cardioprotection in early and delayed phases. We investigated the delayed window of pharmacological and ischemic preconditioning in human myocardium, and the involvement of mitoKATP, PKC and p38MAPK.These studies were carried out using human right atrial tissue in a cell necrosis model. The tissue was obtained from patients undergoing coronary artery surgery.The second window triggered by ischemia, phenylephrine or adenosine resulted in similar cardioprotection between 24 and 72 h following the intervention. Atrial tissue taken from patients with a single episode of angina between 24 and 72 h prior to surgery were already protected and preconditioning with ischemia, phenylephrine or adenosine did not add to the protection. The trigger of preconditioning with mitoKATP channel opener diazoxide, PKC activator PMA and p38MAPK activator anisomycin produced similar delayed protection to that of ischemia or phenylephrine. Cardioprotection was lost when mitoKATP channels were blocked by 5HD, PKC by chelerythrine and p38MAPK by SB203580 24 h after the trigger of preconditioning.Ischemic and pharmacological preconditioning induce similar delayed cardioprotection of the human heart. This second window of protection that is seen between 24 and 72 h occurs in vitro and in vivo and requires opening of mitoKATP channels and activation of PKC and p38MAPK.
P14. Cell-based gene delivery leverages conventional immunotherapy for cancer
Authors: C Günther, R Huss
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Current immunotherapies against cancer comprise of target specific antibodies, cellular therapies like activated immune cells (e.g. DCs or NK cells), vaccination strategies, the use of tumour-specific infectious agents like oncolytic viruses or a combination thereof including
Cardiac Allograft Vasculopathy
Authors: Daniel Schmauss, Michael Weis
Journal: Circulation (2008)

Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation. Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid- to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed.
The cognitive behavioural model of irritable bowel syndrome: a prospective investigation of patients with gastroenteritis
Authors: M. J Spence, R. Moss-Morris
Journal: Gut (2007)

<b>Aim:</b> To determine whether a combination of mood and personality factors together with illness beliefs and behaviours predict the onset of irritable bowel syndrome (IBS) post gastroenteritis, as suggested by the cognitive behavioural model of IBS. <b>Methods:</b> Primary care patients with a positive test for <i>Campylobacter</i> gastroenteritis, and no previous history of IBS or serious bowel conditions were recruited into this prospective study (n = 620). Participants completed a questionnaire at the time of infection, which included standardised measures of mood, perceived stress, perfectionism, negative illness beliefs and illness behaviours. Participants completed follow-up questionnaires designed to determine whether they met the Rome criteria for IBS 3 and 6 months after initial infection. <b>Results:</b> A total of 49 participants met the criteria for IBS at both follow-up points. Logistic regressions indicated that those who developed IBS had significantly higher levels of perceived stress (1.10, 95% CI 1.02 to–1.15), anxiety (1.14, 95% CI 1.05 to 1.23), somatisation (1.17, 95% CI 1.02 to 1.35) and negative illness beliefs (1.14, 95% CI 1.03 to 1.27) at the time of infection than those who did not develop IBS. Patients with IBS were also significantly more likely to remain active in the face of their acute symptoms until they felt forced to rest (all-or-nothing behaviour) (1.09, 95% CI 1.03 to 1.16), and significantly less likely to initially rest in response to their acute illness (0.93, 95% CI 0.88 to 0.97). Depression and perfectionism were not associated with the onset of IBS. <b>Conclusions:</b> Results suggest that patients with high stress and anxiety levels are more prone to develop IBS after a bout of gastroenteritis. Additional risk factors include a tendency to interpret illness in a pessimistic fashion and to respond to symptoms in an all-or-nothing manner.
Identification of cellular markers predicting relapses after immunoablation and autologous haematopoietic stem cell transplantation (ASCT) for refractory systemic lupus erythematosus
Authors: T Alexander, A Thiel, R Biesen, T Rose, A Sattler, H Radtke, G-R Burmester, A Radbruch, R Arnold, F Hiepe
Journal: Annals of the Rheumatic Diseases (2010)

We recently showed that clinical remissions in systemic lupus erythematosus (SLE) after immunoablation and autologous haematopoietic stem cell transplantation (ASCT) are associated with depletion of the autoreactive immunological memory and the de novo generation of a juvenile and tolerant immune system. Nevertheless, relapses of SLE may occur.

We further followed the clinical, serological and immunological data of our patients to identify predictive cellular markers for the development of lupus flares after ASCT.

Since 1998 …
Binding and cooperative interactions between two B cell-specific transcriptional coactivators.
Authors: J D Fontes, N Jabrane-Ferrat, C R Toth, B M Peterlin
Journal: The Journal of Experimental Medicine (1996)

The class II transactivator (CIITA) and B cell octamer-binding protein 1/octamer-binding factor 1/Oct coactivator from B cells (Bob1/OBF-1/OCA-B) represent two B cell-specific transcriptional coactivators. CIITA and Bob1 interact with proteins that bind to conserved upstream sequences in promoters of class II major histocompatibility genes and octamer-binding transcription factors Oct-1 and Oct-2, respectively. Both CIITA and Bob1 increase the expression from the DRA promoter, which is a prototypic class II promoter. Moreover, in the presence of CIITA, interactions between class II promoters and Bob1 are independent of the octamer-binding site. Using in vivo and in vitro binding assays, we confirm that Bob1 binds to CIITA. Thus, CIITA not only activates the expression of class II genes but recruits another B cell-specific coactivator to increase transcriptional activity of class II promoters in B cells.
Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38
Authors: David A. Morrow, Stephen D. Wiviott, Harvey D. White, Jose C. Nicolau, Ezio Bramucci, Sabina A. Murphy, Marc P. Bonaca, Christian T. Ruff, Benjamin M. Scirica, Carolyn H. McCabe, Elliott M. Antman, Eugene Braunwald
Journal: Circulation (2009)

Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI.We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P<0.0001). This benefit was present for procedure-related MIs (4.9% versus 6.4%; HR, 0.76; 95% CI, 0.66 to 0.88; P=0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P=0.0013) and consistently across MI size, including MIs with a biomarker peak > or =5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P=0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P=0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P=0.0069).Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy.
Relevance of Brain Natriuretic Peptide in Preload-Dependent Regulation of Cardiac Sarcoplasmic Reticulum Ca <sup>2+</sup> ATPase Expression
Authors: Harald Kögler, Peter Schott, Karl Toischer, Hendrik Milting, Phuc Nguyen Van, Michael Kohlhaas, Cornelia Grebe, Astrid Kassner, Erik Domeier, Nils Teucher, Tim Seidler, Ralph Knöll, Lars S. Maier, Aly El-Banayosy, Reiner Körfer, Gerd Hasenfuss
Journal: Circulation (2006)

In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis.We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8; P<0.001). Recombinant human BNP at a concentration typically found in end-stage HF patients (350 pg/mL) abolished SERCA upregulation by stretch (n=9; P<0.0001 versus BNP free). Inhibition of cyclic guanosine 3',5' monophosphate (cGMP)-phosphodiesterase-5 mimicked this effect, whereas inhibition of cGMP-dependent protein kinase restored preload-dependent SERCA upregulation in the presence of recombinant human BNP. Furthermore, in myocardium from human end-stage HF patients undergoing cardiac transplantation (n=15), BNP expression was inversely correlated with SERCA levels. Moreover, among 23 patients treated with left ventricular assist devices, significant SERCA2a recovery occurred in those downregulating BNP.Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF.
Sickle gene. Its origin and diffusion from West Africa.
Authors: J G Mears, H M Lachman, R Cabannes, K P Amegnizin, D Labie, R L Nagel
Journal: Journal of Clinical Investigation (1981)

Linked DNA polymorphisms can be used to study the evolution of structural gene mutations. Both the beta S-(beta 6Glu leads to Val) and beta C-(beta 6Glu leads to Lys) genes are common in West Africa. We have analyzed their linkage to a polymorphic Hpa 1 site appearing 3' to the beta-globin gene locus in selected populations from Wes Africa. A large reservoir of beta A-genes linked to 13-kilobase Hpa 1 fragments with a frequency of 17-18% has been identified. In addition, the beta S- and beta C-genes in Togo are found to be tightly linked to the 13-kilobase Hpa 1 fragment, whereas 72% of the beta S-genes in the Ivory Coast reside on the 7.6-kilobase Hpa 1 fragment. These studies are consistent with the selection and expansion of two different chromosomes bearing beta S-genes in at least two physically close, but ethnically separate regions of West Africa, with subsequent diffusion to North, Equatorial, and East Africa.
Early-Life Exposure to Traffic-related Air Pollution and Lung Function in Adolescence
Authors: Erica S. Schultz, Jenny Hallberg, Tom Bellander, Anna Bergström, Matteo Bottai, Flaminia Chiesa, Per M. Gustafsson, Olena Gruzieva, Per Thunqvist, Göran Pershagen, Erik Melén
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Exposure to air pollution during infancy has been related to lung function decrements in 8-year-old children, but whether the negative effects remain into adolescence is unknown.To investigate the relationship between long-term air pollution exposure and lung function up to age 16 years.A total of 2,278 children from the Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) performed spirometry at age 16 years. Levels of outdoor air pollution from local road traffic were estimated (nitrogen oxides [NOx] and particulate matter with an aerodynamic diameter of <10 μm [PM10]) for residential, daycare, and school addresses during the lifetime using dispersion modeling. Associations between exposure in different time windows and spirometry indexes were analyzed by linear regression and mixed effect models.Exposure to traffic-related air pollution during the first year of life was associated with FEV1 at age 16 years of -15.8 ml (95% confidence interval [CI], -33.6 to 2.0 for a 10 μg/m(3) difference in NOx), predominately in males (-30.4 ml; 95% CI, -59.1 to -1.7), and in subjects not exposed to maternal smoking during pregnancy or infancy. Later exposures appeared to have had an additional negative effect. High exposure during the first year of life was also associated with odds ratios for FEV1 and FVC less than the lower limit of normal (LLN) (defined as a z-score < -1.64 SD) of 3.8 (95% CI, 1.3-10.9) and of 4.3 (95% CI, 1.2-15.0), respectively. The results for PM10 were similar to those for NOx.Exposure to traffic-related air pollution in infancy is negatively associated with FEV1 at age 16 years, leading to increased risk of clinically important deficits.