tbuckley/cabot-search huggingface dataset:
Cytoprotection by the osmolytes betaine and taurine in ischemia- reoxygenation injury in the perfused rat liver
Authors: M Wettstein
Journal: Hepatology (1997)

Medium osmolarity sensitively regulates Kupffer cell functions like phagocytosis and prostaglandin (PG) and cytokine production. Betaine and taurine, recently identified as osmolytes in liver cells, interfere with these effects. Because Kupffer cell activation is an important pathogenic mechanism in ischemia-reoxygenation injury, the influence of osmolarity and osmolytes was investigated in a rat liver perfusion model of warm ischemia. Livers were perfused with different medium osmolarities for 60 to 90 minutes in the absence of oxygen, followed by another 90 minutes of reoxygenation. Lactate dehydrogenase (LDH) leakage into the effluent perfusate during the hypoxic and the reoxygenation period was eight- to 10-fold higher with a medium osmolarity of 385 mosmol/L than in normo-osmolarity, and further decreased with hypo-osmolar perfusion buffer. Betaine and taurine addition to the perfusate in near physiological concentrations decreased hypoxia-reoxygenation-induced LDH leakage, aspartate transaminase (AST) leakage, and perfusion pressure increase in hyperosmolar and normo-osmolar perfusions. Stimulation of PGD2, PGE2, thromboxane B2 (TXB2), and tumor necrosis factor alpha (TNF-alpha) release, as well as induction of carbon uptake by the liver during reoxygenation, were suppressed by betaine and taurine, pointing to an interference of these osmolytes with Kupffer cell function. In contrast, endothelial cell function as assessed by hyaluronic acid (HA) uptake was not influenced. It is concluded that warm ischemia- reoxygenation injury in rat liver is aggravated by hyperosmolarity and attenuated by hypo-osmolarity. The osmolytes betaine and taurine have a protective effect, presumably by inhibition of Kupffer cell activation. (Hepatology 1997 Dec;26(6):1560-6)
Why does exercise reduce falls in older people? Unrecognised contributions to motor control and cognition?
Authors: Catherine Sherrington, Nicholas Henschke
Journal: British Journal of Sports Medicine (2012)

<b>Background:</b> The relationship between cough receptor sensitivity and eosinophilic inflammation of the airway in patients with asthma remains unclear. <b>Methods:</b> Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled in a randomised parallel group study. Patients with asthma whose main symptom was cough were not enrolled in the study. Half the patients were randomly assigned to inhale saline and the other half to inhale HDM allergen. Cough receptor sensitivity to capsaicin, airway responsiveness to histamine, and sputum eosinophils analysed with hypertonic saline inhalation were investigated before and 24 hours after saline or HDM allergen bronchoprovocation. <b>Results:</b> Patients inhaling saline showed no significant changes in sputum eosinophils (from 7.87% (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18); p=0.97), airway responsiveness to histamine (from 726.68 μg/ml (95% CI 251.90 to 2096.36) to 773.01 μg/ml (95% CI 251.36 to 2377.23); p=0.96), or capsaicin sensitivity (from 7.23 μM (95% CI 2.45 to 21.31) to 7.24 μM (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all patients, and late asthmatic response was observed in six of nine patients inhaling HDM allergen. Although there were significant increases in sputum eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15); p&lt;0.01) and airway responsiveness to histamine (from 784.16 μg/ml (95% CI 318.24 to 1932.24) to 377.81 μg/ml (95% CI 118.43 to 1205.24); p&lt;0.05) 24 hours after HDM allergen inhalation compared with baseline levels, capsaicin sensitivity did not change significantly (from 5.75 μM (95% CI 1.91 to 17.30) to 6.20 μM (95% CI 2.21 to 17.38); p=0.77). <b>Conclusions:</b> These findings suggest that cough receptor sensitivity to capsaicin is not associated with eosinophilic inflammation of the airway in patients with allergic asthma whose main symptoms are wheezing and dyspnoea but not cough.
Acute hepatitis C: A 24-week course of pegylated interferon alpha-2b versus a 12-week course of pegylated interferon alpha-2b alone or with ribavirin
Authors: Teresa Santantonio, Massimo Fasano, Evangelista Sagnelli, Paolo Tundo, Sergio Babudieri, Paolo Fabris, Mario Toti, Giovanni Di Perri, Nicoletta Marino, Eligio Pizzigallo, Gioacchino Angarano
Journal: Hepatology (2014)

Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively ( P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. Conclusion : Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration. (Hepatology 2014;59:2101-2109)
Myosin Heavy Chain Expression in Contracting Myocytes Isolated During Embryonic Stem Cell Cardiogenesis
Authors: Joseph M. Metzger, Wan-In Lin, Ross A. Johnston, Margaret V. Westfall, Linda C. Samuelson
Journal: Circulation Research (1995)

Abstract Mouse embryonic stem (ES) cells are totipotent cells derived from the inner cell mass of the preimplantation blastocyst and are capable of differentiating in vitro into cardiac myocytes. Attached cultures of differentiating ES cells were established to document the timing of contractile development by microscopic observation and to permit the microdissection of cardiac myocytes from culture. The onset of spontaneous contraction varied markedly in differentiation culture, with contraction being maintained on average for 9 days (range, 1 to 75 days). Indirect immunofluorescence microscopy showed that myosin expression was localized to the contracting cardiac myocytes in culture. Myosin heavy chain (MHC) isoform expression in microdissected ES cell–derived cardiac myocytes was determined by means of sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The distribution of MHC isoform expression in isolated ES cell cardiac myocytes was as follows: 27% expressed the β-MHC isoform, 33% expressed both the α- and β-MHC isoforms, and 40% expressed the α-MHC isoform. MHC phenotype was correlated to the duration of continuous contractile activity of the myocytes. Myocytes that had just initiated spontaneous contractile activity predominantly expressed the β-MHC (average days of contraction before isolation, 2.5±0.7). The α-MHC isoform was detected after more prolonged contractile activity in vitro (1 to 5 weeks). A strong correlation was obtained between MHC phenotype and days of contraction of the cardiac myocyte preparations isolated from ES cell cultures ( r =.93). The apparent transition in MHC isoform expression during ES cell differentiation parallels the β- to α-MHC isoform transition characteristic of murine cardiac development in vivo. These findings are evidence that ES cell cardiac myocyte differentiation follows the normal developmental program of murine cardiogenesis.
Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey
Authors: Y. Belkacemi, O. Kaidar-Person, P. Poortmans, M. Ozsahin, M-C. Valli, N. Russell, I. Kunkler, J. Hermans, A. Kuten, G. van Tienhoven, H. Westenberg
Journal: Annals of Oncology (2014)
Relationships between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis
Authors: Nicolas Pottier, Cécile Chupin, Virginie Defamie, Bruno Cardinaud, Rachel Sutherland, Géraldine Rios, Francis Gauthier, Paul J. Wolters, Yves Berthiaume, Pascal Barbry, Bernard Mari
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Different sensitivities to profibrotic compounds such as bleomycin are observed among mouse strains.Objectives: To identify genetic factors contributing to the outcome of lung injury.Methods: Physiological comparison of C57BL/6 (sensitive) and BALB/c (resistant) mice challenged by intratracheal bleomycin instillation revealed several early differences: global gene expression profiles were thus established from lungs derived from the two strains, in the absence of any bleomycin administration.Measurements and Main Results: Expression of 25 genes differed between the two strains. Among them, two molecules, not previously associated with pulmonary fibrosis, were identified. The first corresponded to dipeptidyl-peptidase I (DPPI), a cysteine peptidase (also known as cathepsin C) essential for the activation of serine proteinases produced by immune/inflammatory cells. The second corresponded to tissue inhibitor of matrix metalloproteinase-3, which also inhibits members of the ADAM (a disintegrin and metalloproteinase) family, such as the tumor necrosis factor–converting enzyme. In functional studies performed in the bleomycin-induced lung fibrosis model, the level of expression of these two genes was closely correlated with specific early events associated with lung fibrosis, namely activation of polymorphonuclear neutrophil–derived serine proteases and tumor necrosis factor-α–dependent inflammatory syndrome. Surprisingly, genetic deletion of DPPI in the context of a C57BL/6 genetic background did not protect against bleomycin-mediated fibrosis, suggesting additional function(s) for this key enzyme.Conclusions: This study highlights the importance of the early inflammatory events that follow bleomycin instillation in the development of lung fibrosis, and describes for the first time the roles that DPPI and tissue inhibitor of matrix metalloproteinase-3 may play in this process.
Anti–IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis
Authors: Iris M. Otani, Arjun A. Anilkumar, Robert O. Newbury, Monica Bhagat, Lisa Y. Beppu, Ranjan Dohil, David H. Broide, Seema S. Aceves
Journal: Journal of Allergy and Clinical Immunology (2013)
Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis
Authors: Guillermo M. Ruiz-Palacios, Irene Pérez-Schael, F. Raúl Velázquez, Hector Abate, Thomas Breuer, SueAnn Costa Clemens, Brigitte Cheuvart, Felix Espinoza, Paul Gillard, Bruce L. Innis, Yolanda Cervantes, Alexandre C. Linhares, Pío López, Mercedes Macías-Parra, Eduardo Ortega-Barría, Vesta Richardson, Doris Maribel Rivera-Medina, Luis Rivera, Belén Salinas, Noris Pavía-Ruz, Jorge Salmerón, Ricardo Rüttimann, Juan Carlos Tinoco, Pilar Rubio, Ernesto Nuñez, M. Lourdes Guerrero, Juan Pablo Yarzábal, Silvia Damaso, Nadia Tornieporth, Xavier Sáez-Llorens, Rodrigo F. Vergara, Timo Vesikari, Alain Bouckenooghe, Ralf Clemens, Béatrice De Vos, Miguel O'Ryan
Journal: New England Journal of Medicine (2006)

The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)
Genetic basis of end‐stage hypertrophic cardiomyopathy
Authors: Pablo Garcia‐Pavia, Maria E. Vázquez, Javier Segovia, Clara Salas, Patricia Avellana, Manuel Gómez‐Bueno, Carlos Vilches, M. Esther Gallardo, Rafael Garesse, Jesús Molano, Belén Bornstein, Luis Alonso‐Pulpon
Journal: European Journal of Heart Failure (2011)
Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease
Authors: A Pesci, B Balbi, M Majori, G Cacciani, S Bertacco, P Alciato, CF Donner
Journal: European Respiratory Journal (1998)

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD). Although the precise sequence of events that leads a smoker to experience airway obstruction is not completely clear, airway inflammation is a relevant factor. To investigate airway inflammation, 12 nonatopic smoking COPD patients with a forced expiratory volume in one second (FEV1) < or = 75% predicted and 10 normal nonsmoking subjects (NS) were studied with bronchoscopy and bronchial lavage (BL). Serum immunoglobulin (Ig)E levels of COPD patients correlated with the smoking history (r=0.7, p=0.008). In BL of COPD patients there was an increase of neutrophils (median, range) (COPD 62.6x10(3), 1.2-323, NS 1.35, 0-19.2, p=0.001), eosinophils (COPD 1.6, 0-6.9, NS 0.15, 0-3.7, p=0.035), the levels of interleukin (IL)-8 (COPD 1079 pg x mL(-1), 121-2,500, NS 20.4, 7.2-59, p=0.001), myeloperoxidase (MPO) (COPD 752 microg x L(-1), 11-5,500, NS 22.1, 8-70, p=0.001) and eosinophil cationic protein (ECP) (COPD 21.5 microg x L(-1), 1.8-161, NS 2, 1.8-4.9, p=0.001). Significant correlations were found in BL of COPD patients between IL-8 and neutrophils (p=0.02), MPO and neutrophils (p=0.02), IL-8 and MPO (p=0.0001) and ECP and eosinophils (p=0.02). In addition, the ratios between the BL levels of MPO and the number of neutrophils and between ECP levels and eosinophils were higher in COPD patients than in NS (p=0.03 and 0.01, respectively). These data suggest that cigarette smoke is associated with increased amounts of airway interleukin-8, a chemotactic factor for neutrophils and eosinophils. Recruited neutrophils and eosinophils are activated and they release increased amounts of inflammatory mediators capable of damaging the bronchial tissue.
Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.
Authors: H N Hodis, W J Mack, S P Azen, P Alaupovic, J M Pogoda, L LaBree, L C Hemphill, D M Kramsch, D H Blankenhorn
Journal: Circulation (1994)

BACKGROUND The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions &lt; 50% diameter stenosis (%S) and coronary lesions &gt; or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride &lt; 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (&lt; 50% S) and severe (&gt; or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P &lt; .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.
2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial
Authors: Peter Gillgren, Krzysztof T Drzewiecki, Marianne Niin, Hans P Gullestad, Henrik Hellborg, Eva Månsson-Brahme, Christian Ingvar, Ulrik Ringborg
Journal: The Lancet (2011)
High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer
Authors: E. Pailler, N. Auger, C.R. Lindsay, P. Vielh, A. Islas-Morris-Hernandez, I. Borget, M. Ngo-Camus, D. Planchard, J.-C. Soria, B. Besse, F. Farace
Journal: Annals of Oncology (2015)

Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients.Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration.ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN.We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors.
BCX4161, an Oral Kallikrein Inhibitor, Showed Significant Benefits on Reducing Disease Burden and Improving Quality of Life in Subjects with Hereditary Angioedema in the Opus-1 Study
Authors: Markus Magerl, Emel Aygören-Pürsün, Jochen Graff, Inmaculada Martinez-Saguer, Wolfhart Kreuz, Hilary Longhurst, Iman Nasr, Murat Bas, Ulrich Straßen, Karsten Weller, Lei Fang, Melanie Cornpropst, Sylvia Dobo, Phil Collis, William Sheridan, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2015)
Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response.
Authors: D W Goldman, E J Goetzl
Journal: The Journal of Experimental Medicine (1984)

Human polymorphonuclear (PMN) leukocytes bound [3H]leukotriene B4 ([3H]-LTB4) specifically, as assessed by the displacement of 88% or more of the bound radioactivity by a 15,000-fold higher concentration of nonradioactive LTB4 or by micromolar concentrations of structural isomers of LTB4. The specific binding of [3H]LTB4 by PMN leukocytes was characterized by rapid association and dissociation, and was saturable at 800 nM LTB4. The results of computer analyses of the concentration dependence of binding of [3H]LTB4 were consistent with the expression of two classes of receptors having respective mean affinities of 3.9 X 10(-10) M and 6.1 X 10(-8) M and mean densities of 4.4 X 10(3) and 2.7 X 10(5) per PMN leukocyte. Structural isomers of LTB4 inhibited the binding of [3H]LTB4 to PMN leukocytes at concentrations similar to those required to elicit chemotaxis, while chemotactic peptides did not inhibit binding. PMN leukocytes that were deactivated by prior exposure to LTB4 lost high affinity binding sites selectively and concurrently with a reduction in the chemotactic response to LTB4. Chemotactic deactivation altered, but did not eliminate, the low affinity receptors for LTB4 and reduced only minimally the lysosomal degranulation elicited by LTB4. The high affinity receptors for LTB4 on normal human PMN leukocytes appear to transduce the chemotaxis evoked by LTB4 without substantially modifying lysosomal degranulation.
Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome
Authors: Marco Ladetto, Sonia Vallet, Andreas Trojan, Maria Dell'Aquila, Luigia Monitillo, Rosalba Rosato, Loredana Santo, Daniela Drandi, Alessandra Bertola, Patrizia Falco, Federica Cavallo, Irene Ricca, Federica De Marco, Barbara Mantoan, Beata Bode-Lesniewska, Gloria Pagliano, Roberto Francese, Alberto Rocci, Monica Astolfi, Mara Compagno, Sara Mariani, Laura Godio, Lydia Marino, Marina Ruggeri, Paola Omedè, Antonio Palumbo, Mario Boccadoro
Journal: Blood (2005)