tbuckley/cabot-search huggingface dataset:
Talc pleurodesis in malignant pleural effusions: A 5-year experience
Authors: João Filipe Cruz, Daniela Alves, Cecília Pacheco, Manuel Vaz, Lourdes Iglésias, Adriana Magalhães
Journal: European Respiratory Journal (2012)

Introduction: Talc pleurodesis is an excellent therapeutic option in patients with malignant pleural effusions (MPE), however the best method to perform it remains a matter of debate.  Objectives: To compare two different methods of talc instillation in terms of clinical efficacy and safety in patients with MPE.  Methods: Retrospective study of patients with MPE submitted to talc pleurodesis between 2006 and 2010. Two different techniques were compared: thoracoscopic talc poudrage (TP) and talc slurry through the chest tube (TS).  Results: A total of 93 patients were evaluated (47 TP group, 46 TS group). Clinical demographics and primary malignancies were similar in both groups. The overall complication rate was 54,8%, without significant difference between the two groups. Most frequent complications were thoracic pain (32,3%), fever (24,7%), subcutaneous emphysema (7,5%) and prolonged drainage (5,4%). No serious complication or death was registered. The average length of hospital stay was 8 days in the TP group vs 19,7 days in the TS group (p=0,001). The average chest drain and suction duration was 5,6 days in the TP group vs 10 days in the TS group (p=0,001). Among patients alive at 30 days, efficacy in local control of MPE was 82,5% in the TP group (33/40) vs 72,1% in the TS group (31/43) (p=0,259). There was no difference in mortality between the two groups (p=0,336).  Conclusions: Talc pleurodesis was a safe and effective palliative treatment for patients with MPEs. Patients who underwent thoracoscopic talc poudrage had a significant shorter length of hospital stay and chest drainage duration. There was no difference regarding complications, efficacy and mortality.
Science of Emergency Medical Dispatch
Authors: Joseph P. Ornato
Journal: Circulation (2009)

O ut-of-hospital cardiac arrest (OOH-CA) claims the lives of almost 300 000 Americans each year, 1 a loss of life equivalent to that caused by a September 11 World Trade Center attack on the United States every 3 days!Despite advances in public education on recognition of cardiac arrest, early notification of emergency medical services (EMS) 9-1-1 centers, lay bystander cardiopulmonary resuscitation, automated external defibrillator use, and improvements in EMS service delivery, fewer than 8% of adult OOH-CA victims survive to hospital discharge.
PPARγ Regulates Resistance Vessel Tone Through a Mechanism Involving RGS5-Mediated Control of Protein Kinase C and BKCa Channel Activity
Authors: Pimonrat Ketsawatsomkron, Ramón A. Lorca, Henry L. Keen, Eric T. Weatherford, Xuebo Liu, Christopher J. Pelham, Justin L. Grobe, Frank M. Faraci, Sarah K. England, Curt D. Sigmund
Journal: Circulation Research (2012)

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) by thiazolidinediones lowers blood pressure, whereas PPARγ mutations cause hypertension. Previous studies suggest these effects may be mediated through the vasculature, but the underlying mechanisms remain unclear.To identify PPARγ mechanisms and transcriptional targets in vascular smooth muscle and their role in regulating resistance artery tone.We studied mesenteric artery (MA) from transgenic mice expressing dominant-negative (DN) mutant PPARγ driven by a smooth muscle cell-specific promoter. MA from transgenic mice exhibited a robust increase in myogenic tone. Patch clamp analysis revealed a reduced large conductance Ca(2+)-activated K(+) (BKCa) current in freshly dissociated smooth muscle cell from transgenic MA. Inhibition of protein kinase C corrected both enhanced myogenic constriction and impaired the large conductance Ca(2+)-activated K(+) channel function. Gene expression profiling revealed a marked loss of the regulator of G protein signaling 5 (RGS5) mRNA in transgenic MA, which was accompanied by a substantial increase in angiotensin II-induced constriction in MA. Small interfering RNA targeting RGS5 caused augmented myogenic tone in intact mesenteric arteries and increased activation of protein kinase C in smooth muscle cell cultures. PPARγ and PPARδ each bind to a PPAR response element close to the RGS5 promoter. RGS5 expression in nontransgenic MA was induced after activation of either PPARγ or PPARδ, an effect that was markedly blunted by DN PPARγ.We conclude that RGS5 in smooth muscle is a PPARγ and PPARδ target, which when activated blunts angiotensin II-mediated activation of protein kinase C, and preserves the large conductance Ca(2+)-activated K(+) channel activity, thus providing tight control of myogenic tone in the microcirculation.
Parathyroid hormone is a DPP-IV inhibitor and increases SDF-1-driven homing of CXCR4+ stem cells into the ischaemic heart
Authors: Bruno C. Huber, Stefan Brunner, Alexander Segeth, Petra Nathan, Rebekka Fischer, Marc M. Zaruba, Marcus Vallaster, Hans D. Theiss, Robert David, Armin Gerbitz, Wolfgang-Michael Franz
Journal: Cardiovascular Research (2011)

Parathyroid hormone (PTH) has been shown to promote stem cell mobilization into peripheral blood. Moreover, PTH treatment after myocardial infarction (MI) improved survival and myocardial function associated with enhanced homing of bone marrow-derived stem cells (BMCs). To unravel the molecular mechanisms of PTH-mediated stem cell trafficking, we analysed wild-type (wt) and green fluorescent protein (GFP)-transgenic mice after MI with respect to the pivotal stromal cell-derived factor-1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis. WT and GFP-transgenic mice (C57BL/6J) were infarcted by coronary artery ligation and PTH (80 μg/kg/day) was injected for 6 days afterwards. Number of BMCs was analysed by flow cytometry. SDF-1 protein levels and activity of dipeptidyl peptidase-IV (DPP-IV) were investigated by ELISA and activity assay. Functional analyses were performed at day 30 after MI. PTH-treated animals revealed an enhanced homing of CXCR4+ BMCs associated with an increased protein level of the corresponding homing factor SDF-1 in the ischaemic heart. In vitro and in vivo, PTH inhibited the activity of DPP-IV, which cleaves and inactivates SDF-1. Functionally, PTH significantly improved myocardial function after MI. Both stem cell homing as well as functional recovery were reversed by the CXCR4 antagonist AMD3100. In summary, PTH is a DPP-IV inhibitor leading to an increased cardiac SDF-1 level, which enhances recruitment of CXCR4+ BMCs into the ischaemic heart associated with attenuated ischaemic cardiomyopathy. Since PTH is already clinically used our findings may have direct impact on the initiation of studies in patients with ischaemic disorders.
Aortic Pathology Determines Midterm Outcome After Endovascular Repair of the Thoracic Aorta
Authors: Benjamin Patterson, Peter Holt, Chrisoph Nienaber, Richard Cambria, Ronald Fairman, Matt Thompson
Journal: Circulation (2013)

Endovascular repair of the thoracic aorta has become an increasingly utilized therapy. Although the short-term mortality advantage over open surgery is well documented, late mortality and the impact of presenting pathology on long-term outcomes remain poorly reported.A database was built from 5 prospective studies and a single institutional series. Rates of perioperative adverse events were calculated, as were midterm death and reintervention rates. Multivariate analysis was performed with the use of logistic regression modeling. Kaplan-Meier survival curves were drawn for midterm outcomes. The database contained 1010 patients: 670 patients with thoracic aortic aneurysm, 195 with chronic type B aortic dissection, and 114 with acute type B aortic dissection. Lower elective mortality was observed in patients with chronic dissections (3%) compared with patients with aneurysms (5%). Multivariate analysis identified age, mode of admission, American Society of Anesthesiologists grade, and pathology as independent predictors of 30-day death (P < 0.05). In the midterm, the all-cause mortality rate was 8, 4.9, and 3.2 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. The rates of aortic-related death were 0.6, 1.2, and 0.4 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively.This study indicated that the midterm outcomes of endovascular repair of the thoracic aorta are defined by presenting pathology, associated comorbidities, and mode of admission. Nonaortic mortality is high in the midterm for patients with thoracic aortic aneurysm, and managing modifiable risk factors appears vital. Endovascular repair of the thoracic aorta results in excellent midterm protection from aortic-related mortality, regardless of presenting pathology.
Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction
Authors: T Wang
Journal: Cardiovascular Research (1998)

Previous results from our laboratory have suggested that morphine can attenuate neutrophil activation in patients with acute myocardial infarction. To elucidate if morphine preconditioning (PC) has the same effects via activation of neutrophil endopeptidase 24.11 (NEP), we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), gp100MEL14 and NEP in adult Wistar rats subjected to ten different protocols (n=10 for each) at baseline, immediately after and 2 h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions (100 μg/kg) interspersed with 5-min drug-free periods before the prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. Pretreatment with morphine increased NEP activities (9.86±1.98 vs. 5.12±1.10 nmol/mg protein in control group; p<0.001). Naloxone (μ-opioid receptor antagonist) (4.82±1.02 nmol/mg protein) and phosphoramidon (NEP inhibitor) (4.66±1.00 nmol/mg protein) inhibited morphine-activated NEP, whereas glibenclamide (ATP-sensitive potassium channel antagonist) and chelerythrine (protein kinase C inhibitor) had no effects. The ICAM-1 and gp100MEL14 of the third sampling were lowest for those with morphine PC (280±30 ng/ml and 2.2±0.7 μg/ml; p<0.001), but naloxone (372±38 ng/ml and 3.8±0.9 μg/ml) and phosphoramidon (382±40 ng/ml and 4.2±1.1 μg/ml) abolished the above phenomenon. IS/AAR were definitely lowest for those with morphine PC (24±7%; p<0.05). Morphine preconditioning increases NEP activities to attenuate shedding of gp100MEL14 and to ICAM-1 and, thus, provides myocardial protection.
Concurrent Induction of Antitumor Immunity and Autoimmune Thyroiditis in CD4+CD25+ Regulatory T Cell–Depleted Mice
Authors: Wei-Zen Wei, Jennifer B. Jacob, John F. Zielinski, Jeffrey C. Flynn, K. David Shim, Ghazwan Alsharabi, Alvaro A. Giraldo, Yi-chi M. Kong
Journal: Cancer Research (2005)

Abstract When CD4+CD25+ regulatory T cells are depleted or inactivated for the purpose of enhancing antitumor immunity, the risk of autoimmune disease may be significantly elevated because these regulatory T cells control both antitumor immunity and autoimmunity. To evaluate the relative benefit and risk of modulating CD4+CD25+ regulatory T cells, we established a new test system to measure simultaneously the immune reactivity to a tumor-associated antigen, neu, and an unrelated self-antigen, thyroglobulin. BALB/c mice were inoculated with TUBO cells expressing an activated rat neu and treated with anti-CD25 monoclonal antibody to deplete CD25+ cells. The tumors grew, then regressed, and neu-specific antibodies and IFN-γ–secreting T cells were induced. The same mice were also exposed to mouse thyroglobulin by chronic i.v. injections. These mice produced thyroglobulin-specific antibody and IFN-γ–secreting T cells with inflammatory infiltration in the thyroids of some mice. The immune responses to neu or thyroglobulin were greater in mice undergoing TUBO tumor rejection and thyroglobulin injection than in those experiencing either alone. To the best of our knowledge, this is the first experimental system to assess the concurrent induction and possible synergy of immune reactivity to defined tumor and self-antigens following reduction of regulatory T cells. These results illustrate the importance of monitoring immune reactivity to self-antigens during cancer immunotherapy that involves immunomodulating agents, and the pressing need for novel strategies to induce antitumor immunity while minimizing autoimmunity.
Relationship Between Glycated Hemoglobin and Metabolic Syndrome of Type 1 and Type 2 Diabetes
Authors: Fernando M.A. Giuffrida, Celso F.C. Sallum, Monica A.L. Gabbay, Marilia B. Gomes, Antonio C. Pires, Sergio A. Dib
Journal: Diabetes Care (2010)

Glycated hemoglobin (GHb) is the best-characterized marker of glycemic control in patients with diabetes. Nevertheless, the relationship between GHb itself and aggregated cardiovascular risk factors, collectively denominated metabolic syndrome (MS), requires more studies in both type 1 and type 2 diabetes. Insulin resistance (IR) is notoriously associated with MS, but hyperglycemia, primarily resulting from insulin deficiency, might have as important a role as IR in MS of type 2 diabetes. MS is also observed in a minority of patients with type 1 diabetes, but its pathophysiology in such cases is poorly understood.

Factor analyses (FAs) have described from one to five factors underlying MS in type 2 diabetes, using only variables linked to IR (1⇓–3). Factors extraneous …
Thymic Stromal Lymphopoietin Directly Activates Eosinophil Degranulation
Authors: E.B. Cook, J.L. Stahl, E.A. Schwantes, C.J. Koziol-White, P.J. Bertics, F.M. Graziano, S.K. Mathur
Journal: Journal of Allergy and Clinical Immunology (2010)
Therapeutic Delivery of miR-200c Enhances Radiosensitivity in Lung Cancer
Authors: Maria Angelica Cortez, David Valdecanas, Xiaochun Zhang, Yanai Zhan, Vikas Bhardwaj, George A Calin, Ritsuko Komaki, Dipak K Giri, Caio C Quini, Tatiana Wolfe, Heidi J Peltier, Andreas G Bader, John V Heymach, Raymond E Meyn, James W Welsh
Journal: Molecular Therapy (2014)

The microRNA (miR)-200s and their negative regulator ZEB1 have been extensively studied in the context of the epithelial-mesenchymal transition. Loss of miR-200s has been shown to enhance cancer aggressiveness and metastasis, whereas replacement of miR-200 miRNAs has been shown to inhibit cell growth in several types of tumors, including lung cancer. Here, we reveal a novel function of miR-200c, a member of the miR-200 family, in regulating intracellular reactive oxygen species signaling and explore a potential application for its use in combination with therapies known to increase oxidative stress such as radiation. We found that miR-200c overexpression increased cellular radiosensitivity by direct regulation of the oxidative stress response genes PRDX2, GAPB/Nrf2, and SESN1 in ways that inhibits DNA double-strand breaks repair, increase levels of reactive oxygen species, and upregulate p21. We used a lung cancer xenograft model to further demonstrate the therapeutic potential of systemic delivery of miR-200c to enhance radiosensitivity in lung cancer. Our findings suggest that the antitumor effects of miR-200c result partially from its regulation of the oxidative stress response; they further suggest that miR-200c, in combination with radiation, could represent a therapeutic strategy in the future.
Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling
Authors: Bart Spee, Guido Carpino, Baukje A Schotanus, Azeam Katoonizadeh, Sara Vander Borght, Eugenio Gaudio, Tania Roskams
Journal: Gut (2009)

Background Hepatic progenitor cells (HPCs) hold a great potential for therapeutic intervention for currently untreatable liver diseases. However, in human diseases molecular mechanisms involved in proliferation and differentiation of HPCs are poorly understood. Methods and results In the present study activated HPCs and their microenvironment (niche) were investigated in acute and chronic human liver disease by gene-expression analysis and immunohistochemistry/immunofluorescence. Cryopreserved liver tissues were used from patients with parenchymal versus biliary diseases: acute necrotising hepatitis (AH), cirrhosis after hepatitis C infection, and primary biliary cirrhosis in order to study differentiation of HPCs towards hepatocytic versus biliary lineage. Keratin 7 positive HPCs/reactive ductules were captured by means of laser capture microdissection and gene-expression profiles were obtained by using a customised PCR array. Gene expression results were confirmed by immunohistochemistry and immunofluorescence double staining. In all disease groups, microdissected HPCs expressed progenitor cell markers such as KRT7 , KRT19 , NCAM , ABCG2 , LIF , KIT , OCT4 , CD44 and TERT . In AH, HPCs were most activated and showed a high expression of prominin-1 (CD133) and α -fetoprotein, and a strong activation of the Wnt pathway. In contrast to parenchymal diseases, HPCs in primary biliary cirrhosis (biliary differentiation) showed a high activation of Notch signalling. Conclusion A distinct pattern of HPC surface markers was found between acute and chronic liver diseases. Similar to what is known from animal experiments, strong evidence has been found signifying the role of Wnt signalling in proliferation of human HPCs whereas Notch signalling is involved in biliary differentiation. These pathways can be targeted in future therapies.
Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
Authors: Etienne Gagnon, David A. Schubert, Susana Gordo, H. Hamlet Chu, Kai W. Wucherpfennig
Journal: The Journal of Experimental Medicine (2012)

The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide–MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.
Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma
Authors: G P Currie
Journal: Thorax (2002)

<b>Background:</b> With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses. <b>Methods:</b> Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 μg/day followed by 1000 μg/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV<sub>1</sub>) of 20% or more (methacholine PD<sub>20</sub>) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC). <b>Results:</b> For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD<sub>20</sub> compared with baseline. The improvement was not significantly greater with 1000 μg/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p&lt;0.05) lower values at 1000 μg/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)). <b>Conclusion:</b> There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 μg/day. At 1000 μg/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.
Effect of angiotensin II and enalapril on transfer of low-density lipoprotein into aortic intima in rabbits.
Authors: L B Nielsen, S Stender, K Kjeldsen, B G Nordestgaard
Journal: Circulation Research (1994)

To assess the mechanism behind a possible atherosclerosis-promoting effect of angiotensin II, the influence of angiotensin II, noradrenaline, and enalapril on transfer of low-density lipoprotein (LDL) into the arterial wall was investigated in conscious rabbits. Intravascular infusion of angiotensin II (1.4 micrograms/kg per minute) initially increased the mean blood pressure from 70 to 80 mm Hg to 125 to 150 mm Hg; this effect was transient, and the blood pressure returned to baseline values within 2 hours, despite continuous infusion of angiotensin II. The normalized influx of LDL into the aortic intima, determined after in vivo exposure to 125I-LDL for 1 hour, was 88 +/- 17 (n = 6), 12 +/- 12 (n = 5), and 28 +/- 6 (n = 5) nL/cm2 per hour (mean +/- SEM) during angiotensin II infusion at high blood pressure, during angiotensin II infusion after the blood pressure had been normalized, and during continuous saline infusions, respectively (P &lt; .05 for high blood pressure versus low blood pressure and saline). When noradrenaline was used to increase blood pressure to a level similar to that induced by angiotensin II, the normalized influx of LDL in noradrenaline-treated rabbits was also increased markedly. Production of endogenous angiotensin II was inhibited with enalapril (2.9 mg/kg per day). Compared with placebo rabbits, enalapril-treated rabbits had a 92% lower plasma angiotensin-converting enzyme activity and a 23% lower blood pressure. The normalized influx of LDL, however, was similar in the two groups at 18 +/- 2 (n = 10) and 20 +/- 3 (n = 10) nL/cm2 per hour, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)