tbuckley/cabot-search huggingface dataset:
Selectin Blockade Prevents Antigen-induced Late Bronchial Responses and Airway Hyperresponsiveness in Allergic Sheep
Authors: WILLIAM M. ABRAHAM, ASHFAQ AHMED, JUAN R. SABATER, ISABEL T. LAUREDO, YELENA BOTVINNIKOVA, ROBERT J. BJERCKE, X. HU, B. MITCH REVELLE, TIMOTHY P. KOGAN, IAN L. SCOTT, RICHARD A. F. DIXON, EDWARD T. H. YEH, PAMELA J. BECK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Antigen challenge can elicit an allergic inflammatory response in the airways that involves eosinophils, basophils, and neutrophils and that is expressed physiologically as a late airway response (LAR) and airway hyperresponsiveness (AHR). Although previous studies have suggested that E-selectin participates in these allergic airway responses, there is little information concerning the role of L-selectin. To address this question, we examined the effects of administering an L-selectin-specific monoclonal antibody, DU1-29, as well as three small molecule selectin binding inhibitors, on the development of early airway responses (EAR), LAR and AHR in allergic sheep undergoing airway challenge with Ascaris suum antigen. Sheep treated with aerosol DU1-29 before antigen challenge had a significantly reduced LAR and did not develop postchallenge AHR. No protective effect was seen when sheep were treated with a nonspecific control monoclonal antibody. Treatment with DU1-29 also reduced the severity of the EAR to antigen. Similar results were obtained with each of the three small molecule selectin inhibitors at doses that depended on their L-, but not necessarily E-selectin inhibitory capacity. The inhibition of the EAR with one of the inhibitors, TBC-1269, was associated with a reduction in histamine release. Likewise, treatment with TBC-1269 reduced the number of neutrophils recovered in bronchoalveolar lavage (BAL) during the time of LAR and AHR. TBC-1269, given 90 min after antigen challenge also blocked the LAR and the AHR, but this protection was lost if the treatment was withheld until 4 h after challenge, a result consistent with the proposed time course of L-selectin involvement in leukocyte trafficking. These are the first data indicating that L-selectin may have a unique cellular function that modulates allergen-induced pulmonary responses.
Statistical Methods and Applications of Bioassay
Authors: E M Laska, M J Meisner
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
Quality of life (QL) depending on psychological disorders (PD) of patients with chronic obstructive pulmonary disease (COPD)
Authors: Kiarina Cicirello-Konstantynovych, Yuriy Mostovoy, Tetyana Konstantynovych, Alina Dovgan
Journal: European Respiratory Journal (2014)

To estimate of QL-idexes at patients with COPD and set their dependence on PD of patients we observed 43COPD-patients (men 30 (69,7 %)), age (65,1±2,3) ys., duration COPD(10,6+3,2) ys. PD were studied by Wasserman, Spilberg-Hanin, Zung methods. To all patients conducted estimation of the QL-parameters by International questionnaire MOS SF-36. The inspection of PD of the COPD-patients showed that the concomitant clinically meaningful depressed disorders were observed at 23,2% patients, high level of reactive anxiety – in 20,3%, high level of the personal anxiety – in 75,8%, high level of neurotic reactions – in 41,5%. A basic group (1) was made by 17 (39,5%) COPD patients with the highest levels of PD, the control (2 group) was formed by 26 (60,5%) patients, having minimal level of PD. The common index of physical status (PhS) at COPD patients was (35,7+1,9) score, psychical status (PsS) - (37,2+1,9), general health (GH) - (30,3+1,4). At COPD patients with the highest levels of disorders of PS (group 1) the meaningful declines of all parameters of QL by comparison to the patients with the middle and minimal changes of PD at group 2 were determined statistically. The common index of PhS at the COPD patients of group 1 was (24,9+2,5) score (against (42,4+ 2,4) in group 2, p
Clinical Significance of Heparin-Binding Epidermal Growth Factor–Like Growth Factor and A Disintegrin and Metalloprotease 17 Expression in Human Ovarian Cancer
Authors: Yoshihiro Tanaka, Shingo Miyamoto, Satoshi O. Suzuki, Eiji Oki, Hiroshi Yagi, Kenzo Sonoda, Ayano Yamazaki, Hiroto Mizushima, Yoshihiko Maehara, Eisuke Mekada, Hitoo Nakano
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Lysophosphatidic acid, which is enriched in the peritoneal fluid of ovarian cancer patients, plays a key role in the progression of ovarian cancer. Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases. We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphatidic acid–induced pathogenesis of ovarian cancer. Experimental Design: We examined the expression of EGFR ligands and ADAM family members in 108 patients with normal ovaries or ovarian cancer, using real-time PCR, immunohistochemistry, and in situ hybridization, and analyzed the clinical roles of these molecules. Statistical analyses of these data were done using the Mann-Whitney test, Kaplan-Meier method, or Spearman's correlation analysis. Results: Large differences in expression were found for heparin-binding EGF-like growth factor (HB-EGF) and other EGFR ligands and for ADAM 17 and other ADAM family members. HB-EGF expression was significantly increased in advanced ovarian cancer compared with that in normal ovaries (P &amp;lt; 0.01). HB-EGF expression was significantly associated with the clinical outcome (P &amp;lt; 0.01). ADAM 17 expression was significantly enhanced in both early and advanced ovarian cancer compared with that in normal ovaries (both P &amp;lt; 0.01), although it had no clinical significance in the progression-free survival. HB-EGF expression was significantly correlated with ADAM 17 expression (γ = 0.437, P &amp;lt; 0.01). Conclusions: Our findings suggest that HB-EGF and ADAM 17 contribute to the progression of ovarian cancer and that HB-EGF plays a pivotal role in the aggressive behavior of a tumor in ovarian cancer.
Intrathoracic manifestations in non-Hodgkin's lymphoma.
Authors: A Manoharan, W R Pitney, M E Schonell, L V Bader
Journal: Thorax (1979)

A total of 16 of 86 patients (19%) with non-Hodgkin's lymphoma were found to have intrathoracic disease in this retrospective study. Paratracheal, mediastinal, and hilar lymphadenopathy was the commonest manifestation followed by pulmonary lesions and pleural effusion. The lymphoma was at an advanced clinical stage in all the patients with intrathoracic disease. About one-third of the intrathoracic lesions first developed at the time of relapse after successful initial therapy. There was a better response to therapy when intrathoracic disease was part of the initial presentation than when it was a manifestation of relapse. If it did not respond to therapy it was always indicative of a poor prognosis.
New Faculty of Sport and Exercise Medicine in Ireland
Authors: R Harland
Journal: British Journal of Sports Medicine (2003)

<i>BACKGROUND AND PURPOSE:</i> Cerebral hyperperfusion syndrome is a rare but serious complication of carotid endarterectomy (CEA). The aim of the present study was to determine whether intraoperative blood flow velocity (BFV) monitoring in the middle cerebral artery (MCA) by using transcranial Doppler ultrasonography (TCD) could be used as a reliable technique to detect cerebral hyperperfusion following CEA by comparing findings with those of brain single photon emission CT (SPECT). <i>METHODS:</i> Intraoperative BFV monitoring was attempted in 67 patients undergoing CEA for treatment of ipsilateral internal carotid artery (ICA) stenosis (≥70%). Cerebral blood flow (CBF) was also assessed using SPECT, which was performed before and immediately after CEA. <i>RESULTS:</i> Intraoperative BFV monitoring was achieved in 60 patients. Of the 60 patients, post-CEA hyperperfusion (CBF increase ≥100%, compared with preoperative values) was observed in six patients. The sensitivity, specificity, and positive predictive value of the BFV increases immediately after declamping of the ICA for detecting post-CEA hyperperfusion was 100%, 94% and 67%, respectively, with a cut-off point 2.0-fold that of preclamping BFV. The sensitivity and specificity of the BFV increases at the end of the procedure for detecting post-CEA hyperperfusion were 100% for both parameters, with cut-off points of 2.0- to 2.2-fold BFV of preclamping value. Hyperperfusion syndrome developed in two patients with post-CEA hyperperfusion, but intracerebral hemorrhage did not occur. In one of these two patients, BFV monitoring was not possible because of failure to obtain an adequate bone window. <i>CONCLUSION:</i> Intraoperative MCA BFV monitoring by using TCD is a less reliable method to detect cerebral hyperperfusion following CEA than postoperative MCA BFV monitoring, provided adequate monitoring can be achieved.
Using Global Initiative for Asthma guidelines to assess asthma severity in populations
Authors: R. Liard, B. Leynaert, M. Zureik, F-X Beguin, F Neukirch
Journal: European Respiratory Journal (2000)

The classification of asthmatics into severity categories is a crucial issue for assessing the asthma burden within a community, in which a proportion of patients is currently treated. There is no epidemiological method currently available. The Global Initiative for Asthma (GINA) was used to classify 4,362 patients aged 16-45 yrs (49% males, 42% taking inhaled corticosteroids), enrolled by 545 chest specialists in France with short standardized questionnaires including forced expiratory volume in one second (FEV1) measurements. Two independent GINA classifications were combined, one based only on symptoms and FEVI, and the other based only on current medication, to construct a final "symptom-FEV1 medication" classification. Almost 40% of the patients classed as step 1, 30% of those classed as step 2 and 13% of those classed as step 3 in the initial symptom-FEV1-classification, were allocated to categories of higher severity in the final classification. The approach was validated by showing that the proportions of: 1) patients considered by the physicians as having severe or moderately severe asthma; 2) patients with a history of hospital admission for asthma; and 3) patients with a history of emergency department visits for asthma, increased with severity steps in the final classification, for each step of the two initial independent classifications. The treatment manage plan in the Global Initiative for Asthma was not developed for assessing severity of asthma but rather to describe the recommended therapy for asthma with different severity. This is the first attempt to assess the severity of asthma in a large population of asthmatics mostly taking treatment, based on the Global Initiative for Asthma guidelines. The authors propose this simple and pragmatic procedure for a potential classification which should be put to the test in other studies.
Collateral flow and the acute phase treatment of myocardial infarction in diabetic patients
Authors: M D. LORGERIL, R FORRAT, L SEBBAG, S RENAUD
Journal: Cardiovascular Research (1993)

Collateral flow and the acute phase treatment of myocardial infarction in diabetic patients Get access M DE LORGERIL, M DE LORGERIL INSERM U63 and Hôpital Cardiologique, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar R FORRAT, R FORRAT INSERM U63 and Hôpital Cardiologique, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar L SEBBAG, L SEBBAG INSERM U63 and Hôpital Cardiologique, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar S RENAUD S RENAUD INSERM U63 and Hôpital Cardiologique, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 11, November 1993, Page 2079, https://doi.org/10.1093/cvr/27.11.2079 Published: 01 November 1993
Serotonin enhances platelet procoagulant properties and their activation induced during platelet tissue factor uptake
Authors: I. Lopez-Vilchez, M. Diaz-Ricart, J. G. White, G. Escolar, A. M. Galan
Journal: Cardiovascular Research (2009)

Circulating tissue factor (TF) has been linked to thrombus propagation. Our group demonstrated that platelets possess mechanisms to capture TF-rich microvesicles (TF-MVs). Serotonin facilitates the development of platelets with increased procoagulant activity. An enhanced platelet serotonin uptake has been identified with increased cardiovascular risk. We have investigated the involvement of serotonergic mechanisms facilitating the interaction of human platelets with TF-MVs. Inhibitory strategies aimed at blocking serotonin and coagulation mechanisms were also studied. Standard aggregometry, flow cytometry, electron microscopy, and thrombin generation assays were performed. TF-MVs induced platelet aggregation in heparinized platelet-rich plasma (PRP) samples; this aggregation was further accelerated by serotonin. In washed platelets, serotonin enhanced platelet aggregation to TF-MVs with a maximum peak of 55.9 ± 1.8 vs. 48.7 ± 2.1% (P < 0.05). Inhibitory strategies with a selective serotonin re-uptake inhibitor and with lepirudin decreased these aggregations. Ultrastructural analysis revealed that serotonin induced platelet pseudopodia formation, thus facilitating the engulfment of TF-MVs. In general, serotonin significantly enhanced (P < 0.05) thrombin generation and the expression of activation markers and procoagulant activity in platelets measured for TF-MVs alone. Serotonin enhances the interaction of platelets with TF-MVs, increases platelet activation, and potentiates their overall procoagulant activity. The present results could have significant implications in thrombus formation and in the thrombogenic profile of pathological situations with increased cardiovascular risk.
Mitochondrial dysfunction in heart failure: potential for therapeutic interventions?
Authors: W Stanley
Journal: Cardiovascular Research (2000)

See article by Jarreta et al. \[4\] (pages 860–865) in this issue. 

Cardiac work is supported by a high rate of ATP hydrolysis, matched by ATP production through mitochondrial oxidative phosphorylation (Fig. 1). Low ATP content in cardiac tissue was observed in patients with chronic heart failure despite the absence of myocardial ischaemia [1]. Mitochondrial function in cardiac tissue from the failing heart demonstrated that the capacity of the mitochondria for oxygen consumption and oxidative phosphorylation are significantly reduced compared to the normal heart [2]. Furthermore, morphological examination of the failing heart by electron microscopy revealed that the mitochondria are disrupted and damaged [3]. The paper by Jarreta et al. in this issue of Cardiovascular Research shows in both idiopathic dilated cardiomyopathy (IDC) and heart failure patients with a history of ischaemic coronary disease (IC) that the activity of complex III of the electron transport chain is reduced, without changes in the activities of complexes I, II or IV, or in the mitochondrial marker enzyme citrate synthase [4]. Evidence for a causal link between impaired mitochondrial metabolic function and cardiac failure was found in several cases of … 

* Corresponding author. Tel.: +1-216-368-5585; fax: +1-216-368-3952 wcs4{at}po.cwru.edu
The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism.
Authors: T K Keeton, W A Pettinger, W B Campbell
Journal: Circulation Research (1976)

Circulating angiotensin II is said to inhibit renin release by a direct, intrarenal action. This effect of angiotensin was studied indirectly using the selective angiotensin II antagonist saralasin (1Sar-8-Ala-angiotensin II) in conscious normal, sodium-depleted, and sodium-loaded rats. Saralasin caused a dose-related increase in plasma renin concentration (PRC) in normal and sodium-depleted rats, but had no effect on PRC in sodium-loaded animals. However, saralasin was 300 times more active in sodium-depleted rats than in normal rats. Saralasin caused hypotension and tachycardia in sodium-depleted rats, but not in normals. Propranolol inhibited saralasin-induced renin release by 99% in normal rats and by 75% in sodium-depleted rats but not alter the hypotensive effect of saralasin in the latter. Saralasin potentiated phentolamine-induced renin release, hypotension, and tachycardia in normal rats, and this potentiated renin release was blocked by propranolol. We conclude that a portion of saralasin-elicited renin release in sodium-depleted rats is mediated by hypotensive activation of the carotid baroreceptor reflex which increases sympathetic nervous activity in the kidney. However, in sodium-depleted rats saralasin induced a 42-fold increase in PRC, whereas an equipotent hypotensive dose of the vasodilator hydralazine caused only a 3.5-fold increase in PRC. Thus, we find that saralasin appears to have a selective effect on renin release over and above its hypotensive effect, which suggests an angiotensin-mediated, feedback mechanism inhibitory to renin release. Thus, we have come to the conclusion that for part of saralasin-induced renin release appears to be caused by disinhibition of angiotensin suppression of renin secretion. This "short-loop" feed-back mechanism is closely associated with intrarenal beta-adrenergic receptors, since propranolol impaired saralasin-induced renin release under all circumstances in our experiments.
Cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism: identification of predictive factors
Authors: F Michard, G Meyer, M Wysocki, JL Diehl, A Mercat, H Sors
Journal: European Respiratory Journal (1999)

The aim of this study was to evaluate the contribution of clinical, angiographic and haemodynamic findings in predicting the cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism. Haemodynamic measurements and pulmonary angiography were performed before (H0) and 12 h after (H12) initiating thrombolytic therapy in 23 patients with acute massive pulmonary embolism (Miller index &gt; or =20/34), and free of prior cardiopulmonary disease. Patients were divided into two groups according to the variation in oxygen delivery (deltaDO2) between H0 and H12: deltaDO2 &gt;20% (responders, n=10) and deltaDO2 &lt; or =20% (nonresponders, n=13). Before thrombolysis, clinical and angiographic findings were similar in both groups. Mean right atrial pressure (RAP) and total pulmonary (vascular) resistance (TPR) were higher, while cardiac index (CI), DO2 and mixed venous oxygen saturation (Sv,O2) were lower in responders. DO2 and Sv,O2 were more closely correlated with deltaDO2 than RAP, TPR and CI. Eight out of the 10 responders and two out of the 13 nonresponders had an Sv,O2 &lt;55%, while nine of the responders and two of the nonresponders had a DO2 &lt;350 mL x min(-1) x m(-2). In conclusion, the initial oxygen delivery and mixed venous oxygen saturation may predict the cardiorespiratory efficacy of thrombolytic therapy in acute massive pulmonary embolism. When pulmonary angiography is performed, measurement of mixed venous oxygen saturation may be a simple method by which to select patients for thrombolytic therapy.
Survival Signals and Targets for Therapy in Breast Implant–Associated ALK<sup>−</sup>Anaplastic Large Cell Lymphoma
Authors: Melissa G Lechner, Carolina Megiel, Connor H Church, Trevor E Angell, Sarah M Russell, Rikki B Sevell, Julie K Jang, Garry S Brody, Alan L Epstein
Journal: Clinical Cancer Research (2012)

Anaplastic lymphoma kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphoma (T-ALCL) in patients with textured saline and silicone breast implants is a recently recognized clinical entity for which the etiology and optimal treatment remain unknown.Using three newly established model cell lines from patient biopsy specimens, designated T-cell breast lymphoma (TLBR)-1 to -3, we characterized the phenotype and function of these tumors to identify mechanisms of cell survival and potential therapeutic targets.Cytogenetics revealed chromosomal atypia with partial or complete trisomy and absence of the NPM-ALK (2;5) translocation. Phenotypic characterization showed strong positivity for CD30, CD71, T-cell CD2/5/7, and antigen presentation (HLA-DR, CD80, CD86) markers, and interleukin (IL)-2 (CD25, CD122) and IL-6 receptors. Studies of these model cell lines showed strong activation of STAT3 signaling, likely related to autocrine production of IL-6 and decreased SHP-1. STAT3 inhibition, directly or by recovery of SHP-1, and cyclophosphamide-Adriamycin-vincristine-prednisone (CHOP) chemotherapy reagents, effectively kill cells of all three TLBR models in vitro and may be pursued as therapies for patients with breast implant-associated T-ALCLs.The TLBR cell lines closely resemble the primary breast implant-associated lymphomas from which they were derived and as such provide valuable preclinical models to study their unique biology.
Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq
Authors: Mehdi Motallebipour, Adam Ameur, Madhu Sudhan Reddy Bysani, Kalicharan Patra, Ola Wallerman, Jonathan Mangion, Melissa A Barker, Kevin J McKernan, Jan Komorowski, Claes Wadelius
Journal: Genome biology (2009)

The forkhead box/winged helix family members FOXA1, FOXA2, and FOXA3 are of high importance in development and specification of the hepatic linage and the continued expression of liver-specific genes.Here, we present a genome-wide location analysis of FOXA1 and FOXA3 binding sites in HepG2 cells through chromatin immunoprecipitation with detection by sequencing (ChIP-seq) studies and compare these with our previous results on FOXA2. We found that these factors often bind close to each other in different combinations and consecutive immunoprecipitation of chromatin for one and then a second factor (ChIP-reChIP) shows that this occurs in the same cell and on the same DNA molecule, suggestive of molecular interactions. Using co-immunoprecipitation, we further show that FOXA2 interacts with both FOXA1 and FOXA3 in vivo, while FOXA1 and FOXA3 do not appear to interact. Additionally, we detected diverse patterns of trimethylation of lysine 4 on histone H3 (H3K4me3) at transcriptional start sites and directionality of this modification at FOXA binding sites. Using the sequence reads at polymorphic positions, we were able to predict allele specific binding for FOXA1, FOXA3, and H3K4me3. Finally, several SNPs associated with diseases and quantitative traits were located in the enriched regions.We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation.