tbuckley/cabot-search huggingface dataset:
Microparticles From Human Atherosclerotic Plaques Promote Endothelial ICAM-1–Dependent Monocyte Adhesion and Transendothelial Migration
Authors: Pierre-Emmanuel Rautou, Aurélie S. Leroyer, Bhama Ramkhelawon, Cécile Devue, Dominique Duflaut, Anne-Clémence Vion, Gilles Nalbone, Yves Castier, Guy Leseche, Stéphanie Lehoux, Alain Tedgui, Chantal M. Boulanger
Journal: Circulation Research (2010)

Membrane-shed submicron microparticles (MPs) released following cell activation or apoptosis accumulate in atherosclerotic plaques, where they stimulate endothelial proliferation and neovessel formation. The aim of the study was to assess whether or not MPs isolated from human atherosclerotic plaques contribute to increased endothelial adhesion molecules expression and monocyte recruitment.Human umbilical vein and coronary artery endothelial cells were exposed to MPs isolated from endarterectomy specimens (n=62) and characterized by externalized phosphatidylserine. Endothelial exposure to plaque, but not circulating, MPs increased ICAM-1 levels in a concentration-dependant manner (3.4-fold increase) without affecting ICAM-1 mRNA levels. Plaque MPs harbored ICAM-1 and transferred this adhesion molecule to endothelial cell membrane in a phosphatidylserine-dependent manner. MP-borne ICAM-1 was functionally integrated into cell membrane as demonstrated by the increased ERK1/2 phosphorylation following ICAM-1 ligation. Plaque MPs stimulated endothelial monocyte adhesion both in culture and in isolated perfused mouse carotid. This effect was also observed under flow condition and was prevented by anti-LFA-1 and anti-ICAM-1 neutralizing antibodies. MPs isolated from symptomatic plaques were more potent in stimulating monocyte adhesion than MPs from asymptomatic patients. Plaque MPs did not affect the release of interleukin-6, interleukin-8, or MCP-1, nor the expression of VCAM-1 and E-selectin.These results demonstrate that MPs isolated from human atherosclerotic plaques transfer ICAM-1 to endothelial cells to recruit inflammatory cells and suggest that plaque MPs promote atherosclerotic plaque progression.
Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice
Authors: Raphael P.H. Meier, Redouan Mahou, Philippe Morel, Jeremy Meyer, Elisa Montanari, Yannick D. Muller, Panayiotis Christofilopoulos, Christine Wandrey, Carmen Gonelle-Gispert, Leo H. Bühler
Journal: Journal of Hepatology (2014)

Mesenchymal stem cell (MSC) transplantation was shown to be effective for the treatment of liver fibrosis, but the mechanisms of action are not yet fully understood. We transplanted encapsulated human MSCs in two mouse models of liver fibrosis to determine the mechanisms behind the protective effect.Human bone marrow-derived MSCs were microencapsulated in novel alginate-polyethylene glycol microspheres. In vitro, we analyzed the effect of MSC-conditioned medium on the activation of hepatic stellate cells and the viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. The level of fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) was assessed after intraperitoneal transplantation of encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres.MSC-conditioned medium inhibited hepatic stellate cell activation and release of MSC secreted anti-apoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines. Viability, proliferation, and cytokine secretion of microencapsulated MSCs were similar to those of non-encapsulated MSCs. Within the microspheres, MSCs maintained their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. 23% (5/22) of the MSC clones were able to produce anti-inflammatory IL-1Ra in vitro. Microencapsulated MSCs significantly delayed the development of BDL- and CCl4-induced liver fibrosis. Fibroblasts had an intermediate effect against CCl4-induced fibrosis. Mice transplanted with encapsulated MSCs showed lower mRNA levels of collagen type I, whereas levels of matrix metalloproteinase 9 were significantly higher. Human IL-1Ra was detected in the serum of 36% (4/11) of the mice transplanted with microencapsulated MSCs.MSC-derived soluble molecules are responsible for an anti-fibrotic effect in experimental liver fibrosis.
Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function
Authors: Buddhadeb Dawn, Yiru Guo, Arash Rezazadeh, Yiming Huang, Adam B. Stein, Greg Hunt, Sumit Tiwari, Jai Varma, Yan Gu, Sumanth D. Prabhu, Jan Kajstura, Piero Anversa, Suzanne T. Ildstad, Roberto Bolli
Journal: Circulation Research (2006)

We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL– and G-CSF+SCF–treated but not in G-CSF–treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF–treated mice. G-CSF+FL therapy mobilized bone marrow–derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective .
Lung Volume Reduction Surgery and Airflow Limitation
Authors: HENRY E. FESSLER, SOLBERT PERMUTT
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Interest has recently been renewed in lung volume reduction surgery (LVRS) for end-stage emphysema. However, numerous questions about its role in the treatment of emphysema remain, including the clinical characteristics of optimal candidates and its mechanism of improvement in pulmonary function. In this report, we develop a mathematical analysis and graphic depiction of the mechanism of improvement in expiratory airflow and vital capacity. This analysis is based on consideration of the interaction between lung function and respiratory muscle function. We also reexamine previously published pulmonary mechanics in patients with alpha1-antitrypsin deficiency, chronic obstructive pulmonary disease, and asthma. We find a major determinant of airflow limitation common to these diseases is the ratio of residual volume to total lung capacity (RV/TLC). Moreover, RV/TLC is found to be the single most important determinant of the improvement in pulmonary function after LVRS. Regardless of the specific underlying lung disease, the impairment of airflow is due primarily to mismatch between the sizes of the lung and the chest wall, and the effects of LVRS are almost exclusively due to improvement of that match. This analysis can be used to develop testable hypotheses to guide patient selection for this procedure.
After the Tsunami — Facing the Public Health Challenges
Authors: Michael VanRooyen, Jennifer Leaning
Journal: New England Journal of Medicine (2005)

The humanitarian logistics supply chain can be described as a network of volunteer staff and that interact with a set of goods and services, this with the purpose of satisfying the demand of the population affected by a sudden flood.This work focuses on determining solutions to the problem of locating a point of distribution and multiple shelters whereas flood risk associated to the area, also to the problem of routing personnel, allowing to relieve the psychological and medical calamities among other present in the population affected in a post-disaster situation; This formulation is made by applying operations research as a solution tool.The aim of this article is to provide a functional model to strategically design network facilities, in addition to coordinating the provision of services required by the population in the shortest possible time.The flood that the town of Santa Lucia, Colombia suffered in 2010 is taken as a case study.
Characterization of Active Mitogen-Activated Protein Kinase in Ovarian Serous Carcinomas
Authors: Chih-Yi Hsu, Robert Bristow, Moon Seok Cha, Brant G. Wang, Chung-Liang Ho, Robert J. Kurman, Tian-Li Wang, Ie-Ming Shih
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal transduction. Activation of MAPK is regulated by upstream kinases including KRAS and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma. This study evaluates the expression of active MAPK in ovarian serous carcinomas, with response to treatment and survival. Experimental Design: Expression of active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous tumors. Immunoreactivity was correlated with tumor grade, mutational status of KRAS and BRAF, in vitro drug resistance, and clinical outcome. Result: There was a lower frequency of expression of active MAPK in high-grade ovarian serous carcinomas as compared with low-grade serous tumors, including borderline tumors and low-grade serous carcinoma (P &amp;lt; 0.001). Active MAPK was present in all of the 19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of 34 tumors with wild-type KRAS and BRAF in both low- and high-grade carcinomas. Expression of active MAPK alone served as a good survival indicator in the 2-year follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a combination of expression of active MAPK and in vitro sensitivity of paclitaxel significantly correlated with a better prognosis in 5-year survival rate (P = 0.048) in patients with advanced-stage high-grade serous carcinoma. Conclusions: Active MAPK is more frequently expressed in low-grade than in high-grade ovarian serous carcinoma. Active MAPK serves as a good prognostic marker in patients with high-grade serous carcinomas.
Phosphorylation of the Eukaryotic Translation Initiation Factor eIF4E Contributes to Its Transformation and mRNA Transport Activities
Authors: Ivan Topisirovic, Melisa Ruiz-Gutierrez, Katherine L. B. Borden
Journal: Cancer Research (2004)

Abstract The eukaryotic translation initiation factor eIF4E is dysregulated in a wide variety of human cancers. In the cytoplasm, eIF4E acts in the rate-limiting step of translation initiation whereas in the nucleus, eIF4E forms nuclear bodies and promotes the nucleo-cytoplasmic export of a subset of growth-promoting mRNAs including cyclin D1. The only known post-translational modification of eIF4E is its phosphorylation at S209. Many studies have examined the role of phosphorylation on cap-dependent translation. However, no studies to date have explored the role of phosphorylation on the ability of eIF4E to transform cells. Using mutagenesis and separately a small molecular inhibitor of eIF4E phosphorylation, we show that eIF4E phosphorylation enhances both its mRNA transport function and its transformation activity in cell culture. Thus, phosphorylation of nuclear eIF4E seems to be an important step in control of the mRNA transport and thus the transforming properties of eIF4E.
The Effects of Lithium Salts on Brain Activity in the Cat
Authors: ERNEST S. BARRATT, DANIEL L. CRESON, GLENN RUSSELL
Journal: American Journal of Psychiatry (1968)

Two sets of experiments were conducted to study the effects of lithium on the gross electrical activity of the cat brain. The first series, designed to study acute effects by means of recording evoked potentials using encephale isolé cats, suggests that the orbito-frontal cortex is a primary brain locus for the immediate effects of lithium. The second series of experiments, designed to study chronic effects, suggests that lithium produces widespread EEG slowing after it has been administered for seven days; marked behavioral changes were also observed in these cats following the seven-day course of lithium administration.
Changes in child exposure to environmental tobacco smoke (CHETS) study after implementation of smoke-free legislation in Scotland: national cross sectional survey
Authors: Patricia C Akhtar, Dorothy B Currie, Candace E Currie, Sally J Haw
Journal: BMJ (2007)

<b>Objective</b> To detect any change in exposure to secondhand smoke among primary schoolchildren after implementation of smoke-free legislation in Scotland in March 2006. <b>Design</b> Comparison of nationally representative, cross sectional, class based surveys carried out in the same schools before and after legislation. <b>Setting</b> Scotland. <b>Participants</b> 2559 primary schoolchildren (primary 7; mean age 11.4 years) surveyed in January 2006 (before smoke-free legislation) and 2424 in January 2007 (after legislation). <b>Outcome measures</b> Salivary cotinine concentrations, reports of parental smoking, and exposure to tobacco smoke in public and private places before and after legislation. <b>Results</b> The geometric mean salivary cotinine concentration in non-smoking children fell from 0.36 (95% confidence interval 0.32 to 0.40) ng/ml to 0.22 (0.19 to 0.25) ng/ml after the introduction of smoke-free legislation in Scotland—a 39% reduction. The extent of the fall in cotinine concentration varied according to the number of parent figures in the home who smoked but was statistically significant only among pupils living in households in which neither parent figure smoked (51% fall, from 0.14 (0.13 to 0.16) ng/ml to 0.07 (0.06 to 0.08) ng/ml) and among pupils living in households in which only the father figure smoked (44% fall, from 0.57 (0.47 to 0.70) ng/ml to 0.32 (0.25 to 0.42) ng/ml). Little change occurred in reported exposure to secondhand smoke in pupils9 own homes or in cars, but a small decrease in exposure in other people9s homes was reported. Pupils reported lower exposure in cafes and restaurants and in public transport after legislation. <b>Conclusions</b> The Scottish smoke-free legislation has reduced exposure to secondhand smoke among young people in Scotland, particularly among groups with lower exposure in the home. We found no evidence of increased secondhand smoke exposure in young people associated with displacement of parental smoking into the home. The Scottish smoke-free legislation has thus had a positive short term impact on young people9s health, but further efforts are needed to promote both smoke-free homes and smoking cessation.
Immunoregulatory Mechanisms in Nonspecific Inflammatory Bowel Disease
Authors: R G Strickland, D P Jewell
Journal: Annual Review of Medicine (1983)

Little is known of either the etiology or the pathogenesis of nonspecific inflammatory bowel disease (IBD). One hypothesis proposes the presence of a disorder of immune regulation as an initiating or perpetuating mechanism of continued bowel wall inflammation in these diseases. This chapter examines the basis for this proposal and reviews recent studies directed toward the demonstration of defective immunoregulatory mechanisms in IBD.
Effect of Coronary Blood Flow on Radioisotope Dilution Curves Measured by Precordial Scintillation Detection
Authors: ISMAEL MENA, ALBERT A. KATTUS, MOSES A. GREENFIELD, LESLIE R. BENNETT
Journal: Circulation Research (1961)

Two series of animal experiments are reported. In the first of these, the disappearance rates of intravenously injected radioactive boluses were monitored over the heart and from a peripheral artery. The disappearance rate over the heart was shown to be slower than in the artery. In a second series of experiments in which injection was made into the left ventricle or into a coronary artery while sampling from the right side of the heart, it was shown that the coronary transit time was several times longer than the left ventricular transit time. The prolonged presence of the radioactivity in the coronary vascular bed accounts for the difference in the heart and arterial disappearance slopes. A ratio of these two slopes may provide an index of coronary blood flow.
Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA.
Authors: R Evers, M Kool, L van Deemter, H Janssen, J Calafat, L C Oomen, C C Paulusma, R P Oude Elferink, F Baas, A H Schinkel, P Borst
Journal: Journal of Clinical Investigation (1998)

Apert syndrome, associated with fibroblast growth factor receptor (FGFR) 2 mutations, is characterized by premature fusion of cranial sutures. We analyzed proliferation and differentiation of calvaria cells derived from Apert infants and fetuses with FGFR-2 mutations. Histological analysis revealed premature ossification, increased extent of subperiosteal bone formation, and alkaline phosphatase- positive preosteoblastic cells in Apert fetal calvaria compared with age-matched controls. Preosteoblastic calvaria cells isolated from Apert infants and fetuses showed normal cell growth in basal conditions or in response to exogenous FGF-2. In contrast, the number of alkaline phosphatase- positive calvaria cells was fourfold higher than normal in mutant fetal calvaria cells with the most frequent Apert FGFR-2 mutation (Ser252Trp), suggesting increased maturation rate of cells in the osteoblastic lineage. Biochemical and Northern blot analyses also showed that the expression of alkaline phosphatase and type 1 collagen were 2-10-fold greater than normal in mutant fetal calvaria cells. The in vitro production of mineralized matrix formed by immortalized mutant fetal calvaria cells cultured in aggregates was also increased markedly compared with control immortalized fetal calvaria cells. The results show that Apert FGFR-2 mutations lead to an increase in the number of precursor cells that enter the osteogenic pathway, leading ultimately to increased subperiosteal bone matrix formation and premature calvaria ossification during fetal development, which establishes a connection between the altered genotype and cellular phenotype in Apert syndromic craniosynostosis.
The “bench-presser’s shoulder”: an overuse insertional tendinopathy of the pectoralis minor muscle
Authors: Deepak N Bhatia, Joe F de Beer, Karin S van Rooyen, Francis Lam, Donald F du Toit
Journal: British Journal of Sports Medicine (2006)

Tendinopathies of the rotator cuff muscles, biceps tendon and pectoralis major muscle are common causes of shoulder pain in athletes. Overuse insertional tendinopathy of pectoralis minor is a previously undescribed cause of shoulder pain in weightlifters/sportsmen.
T Cells in Crescentic Glomerulonephritis
Authors: Peter G. Tipping, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2006)

Crescent formation in glomerulonephritis (GN) is a manifestation of severe glomerular injury that usually results in a poor clinical outcome. In humans, crescentic GN is frequently associated with evidence of either systemic or organ-specific autoimmunity. T cells play a major role in initiation of adaptive immune responses that lead to crescentic injury. In experimental models of crescentic GN, Th1 predominant immune responses have been shown to promote crescent formation. Perturbation of regulatory T cell function may contribute to development of autoimmune crescentic GN. The presence of T cells and macrophages in crescentic glomeruli, frequently in the absence of humoral mediators of immunity, suggest a dominant effector role for T cells in crescentic GN. The association of cellular immune mediators with local fibrin deposition implicates cell-mediated "delayed-type hypersensitivity-like" mechanisms in crescent formation. Intrinsic renal cells also contribute to T cell-driven effector mechanisms in crescentic GN, via expression of MHC II and co-stimulatory molecules and by production of chemokines and cytokines that amplify leukocyte recruitment and injury.
Notes of an Autumn Holiday in America
Authors: T. S. Wells
Journal: BMJ (1868)

THE BRITISH MADICAL 7OURNAL uWS the stomach, are often engaged in this type of fever; to which, amongst other names, he gives that of gastro-enterite.Is it any wonder, I ask, with suclh a variety of morbid lesions, whether of the slightest on the one hand, or of the most profound and extensive on the other-is it any wonder that the symptonms during life should vary in a very marked way, or exhibit symptoms having the closest resemblance to gastric fever, or cven to typhus, as I myself have often seen?And have not the symptoms described as characteristic of ciiteric fever been too cir- cumscribed ?As examples, I may mention bleeding from the nose or bowels, both of whiclh, beyond all question, occsr in other types of fever besides the enteric, as I have proved in another place.Were it r.ecessary, it would be easy to pursue this part of my subject much far- ther; but I must hasten on.From the tenor of the preceding remarks, it will be xuderstood what my object has been.I wished to show that, while the types of fever may all usually be distinguished the one from the other, yet they
Contribution of Moxifloxacin or Levofloxacin in Second-Line Regimens with or without Continuation of Pyrazinamide in Murine Tuberculosis
Authors: Zahoor Ahmad, Sandeep Tyagi, Austin Minkowski, Charles A. Peloquin, Jacques H. Grosset, Eric L. Nuermberger
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: High-dose levofloxacin (L) (1,000 mg) was as active as moxifloxacin (M) (400 mg) in an early bactericidal activity trial, suggesting these fluoroquinolones could be used interchangeably. Whether pyrazinamide (Z) contributes sterilizing activity beyond the first 2 months in fluoroquinolone-containing second-line regimens remains unknown.Objectives: We compared the efficacy of M and high-dose L alone or in combination with ethionamide (Et), amikacin (A), and Z given for 2 or 7 months.Methods: A pharmacokinetic study was performed to determine the L dose equivalent to 1,000 mg in humans. Treatment started 2 weeks after aerosol infection with Mycobacterium tuberculosis H37Rv. Mice received M or L alone or in combination with 2 months of EtZA followed by 5 months of Et or EtZ.Measurements and Main Results: After 2 months of treatment, lung colony-forming unit (CFU) counts were similar in mice receiving either fluoroquinolone alone, but, after 4 and 5 months, CFU counts were 2 log10 lower in mice receiving M. Mice receiving 2MEtZA/3MEt and 2LEtZA/3LEt had 1.0 and 2.7 log10 lung CFUs, respectively. When Z was given throughout, both regimens rendered mice culture negative by 5 months, and most mice did not relapse after 7 months of treatment, with fewer relapses observed in the M group after 6 and 7 months of treatment.Conclusions: In murine tuberculosis, M had superior efficacy compared with L despite lower serum drug exposures and may remain the fluoroquinolone of choice for second-line regimens. Z contributed substantial sterilizing activity beyond 2 months in fluoroquinolone-containing second-line regimens, largely compensating for L's weaker activity.