tbuckley/cabot-search huggingface dataset:
Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees.
Authors: T van der Poll, J Jansen, M Levi, H ten Cate, J W ten Cate, S J van Deventer
Journal: The Journal of Experimental Medicine (1994)

Interleukin 10 (IL-10) has been shown to inhibit endotoxin-induced tumor necrosis factor (TNF) production. To assess the role of TNF in the induction of IL-10 in endotoxemia, four healthy men were studied after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). In addition, 13 healthy chimpanzees were investigated after a bolus intravenous injection of Escherichia coli endotoxin (4 ng/kg), 6 animals received endotoxin only, 4 animals received a simultaneous intravenous injection of a monoclonal anti-TNF antibody, whereas 3 chimpanzees were treated with an anti-TNF F(ab')2 fragment 30 min after the administration of endotoxin. TNF induced a modest rise in IL-10 concentrations peaking after 45 min (47 +/- 32 pg/ml; p < 0.05). IL-10 peaked 2 h after injection of endotoxin (202 +/- 61 pg/ml; p < 0.005). In both anti-TNF-treated groups, the early endotoxin-induced TNF activity was completely neutralized. Simultaneous anti-TNF treatment attenuated endotoxin-induced IL-10 release (73 +/- 13 pg/ml; p < 0.01 versus endotoxin alone), whereas postponed anti-TNF treatment did not significantly affect this response (p = 0.21). These results indicate that TNF, in part, mediates the induction of IL-10 in endotoxemia, resulting in an autoregulatory feedback loop.
Natural killer cell recognition and killing of activated hepatic stellate cells
Authors: Joan Clària
Journal: Gut (2012)

Liver fibrosis is a major cause of morbidity and mortality worldwide as a result of chronic liver injury. Liver fibrosis is a scarring process, eventually leading to liver cirrhosis and cancer, and represents the final common pathway for most chronic liver diseases including viral hepatitis, alcoholic hepatitis and, more recently, fatty liver disease associated with obesity.1 Fibrosis is characterised by both quantitative and qualitative changes in the composition of the connective tissue, which results from the imbalance between the production and degradation of extracellular matrix components. Fibrosis is part of the liver's wound-healing response and is preceded by an inflammatory response, which is the driving force for the progressive accumulation of extracellular matrix components in the liver.1

Hepatic stellate cells (HSC) play a pivotal role in the initiation and progression of hepatic fibrosis.2 HSC are resident vitamin A-storing cells located in the space of Disse between the fenestrated sinusoidal endothelium and the layer of hepatocytes. Scattered within the sinusoidal lining and in direct contact with the blood are the Kupffer cells, the professional resident macrophages involved in detoxification processes. This complex architecture of the hepatic sinusoid ensures full hepatic functionality by providing a unique environment where each single hepatocyte is in close contact with these sinusoidal cells as well as with other hepatocytes. The paradigm in liver injury is initiated when Kupffer cells are activated by lipid peroxidation products derived from damaged hepatocytes or in response to increased …
Malignant Tumour of Thymus
Authors: R. G. P. Evans
Journal: BMJ (1938)

white cells 15,200 per c.mm.; haemoglobin 90 per cent., colour index 1.0.Average diameter of red cells, 7.1 ,I.April 23: Pleulral Fluid-The fluid contained a large amount of blood.Films showed blood cells, polymorphs, and Iympho-
Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2)
Authors: Frank Buttgereit, Daksha Mehta, John Kirwan, Jacek Szechinski, Maarten Boers, Rieke E Alten, Jerzy Supronik, Istvan Szombati, Ulrike Romer, Stephan Witte, Kenneth G Saag
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA). <h3>Methods</h3> In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed. <h3>Results</h3> MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p&lt;0.001) and ACR50 (22% vs 10%, p&lt;0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p&lt;0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28) (p&lt;0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p&lt;0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%). <h3>Conclusion</h3> Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms. <h3>ClinicalTrials.gov, number</h3> NCT00650078
1013-114 Improvement of endothelial function in patients with myocardial inflammation by angiotensin-converting enzyme inhibition with quinapril: A randomized double-blind, placebo controlled study
Authors: Katja B Vallbracht, Uwe Kuehl, Peter L Schwimmbeck, Bettina Seeberg, Heinz-Peter Schultheiss
Journal: Journal of the American College of Cardiology (2004)
CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells
Authors: Wen Min Lau, Eileen Teng, Hui Shan Chong, Kirsten Anne Pagaduan Lopez, Amy Yuh Ling Tay, Manuel Salto-Tellez, Asim Shabbir, Jimmy Bok Yan So, Shing Leng Chan
Journal: Cancer Research (2014)

The surface marker CD44 has been identified as one of several markers associated with cancer stem cells (CSC) in solid tumors, but its ubiquitous expression in many cell types, including hematopoietic cells, has hindered its use in targeting CSCs. In this study, 28 paired primary tumor and adjacent nontumor gastric tissue samples were analyzed for cell surface protein expression. Cells that expressed pan-CD44 were found to occur at significantly higher frequency in gastric tumor tissues. We identified CD44v8-10 as the predominant CD44 variant expressed in gastric cancer cells and verified its role as a gastric CSC marker by limiting dilution and serial transplantation assays. Parallel experiments using CD133 failed to enrich for gastric CSCs. Analyses of another 26 primary samples showed significant CD44v8-10 upregulation in gastric tumor sites. Exogenous expression of CD44v8-10 but not CD44 standard (CD44s) increased the frequency of tumor initiation in immunocompromised mice. Reciprocal silencing of total CD44 resulted in reduced tumor-initiating potential of gastric cancer cells that could be rescued by CD44v8-10 but not CD44s expression. Our findings provide important functional evidence that CD44v8-10 marks human gastric CSCs and contributes to tumor initiation, possibly through enhancing oxidative stress defense. In addition, we showed that CD44v8-10 expression is low in normal tissues. Because CD44 also marks CSCs of numerous human cancers, many of which may also overexpress CD44v8-10, CD44v8-10 may provide an avenue to target CSCs in other human cancers.
Regional differences in sympathetic reinnervation after human orthotopic cardiac transplantation.
Authors: R F Wilson, D D Laxson, B V Christensen, A L McGinn, S H Kubo
Journal: Circulation (1993)

In the majority of humans > or = 1 year after cardiac transplantation, cardiac norepinephrine (NE) stores reappear, suggesting late sympathetic reinnervation.To determine whether there are regional differences in reinnervation, we measured markers of sympathetic reinnervation of the sinus node (SN) and left ventricle (LV) in five early transplant recipients (< or = 4 months after cardiac transplantation), 45 late transplant recipients (> or = 1 year after cardiac transplantation), and seven normally innervated control patients. SN reinnervation was defined as an increase in heart rate by more than five beats per minute after injection of tyramine into the artery supplying the SN. LV reinnervation was defined as a measurable LV NE release after left main coronary injection of 8 micrograms/kg tyramine. In 13 patients with previously known LV reinnervation, regional LV reinnervation was assessed by NE release after subselective injection of tyramine (4 micrograms/kg) into the proximal left anterior descending and circumflex arteries. Five of five patients < or = 4 months after cardiac transplantation had no change in heart rate and no LV NE release, confirming early, total denervation. In contrast, > or = 1 year after cardiac transplantation, tyramine caused a heart rate increase (eight to 49 beats per minute) in 32 of 45 patients and LV NE release in 33 of 45. Although LV NE release was correlated with the change in heart rate in late cardiac transplantation recipients (r = .61), eight of 45 had only heart rate response, nine had only LV NE release, and four had neither. In late cardiac transplantation recipients with LV reinnervation, tyramine caused NE release from both the anterior descending and circumflex perfusion fields in 10 of 14, but one of 14 patients released NE only after circumflex tyramine and three of 14 only after left anterior descending tyramine stimulation. Tyramine caused a marked heart rate increase and LV NE release in all control patients.Sympathetic reinnervation after cardiac transplantation is regionally heterogeneous. SN reinnervation is not associated necessarily with LV reinnervation, and LV reinnervation can involve the anterior and posterior walls together or separately.
Prospective, Randomized Study of Single Compared With Double Autologous Stem-Cell Transplantation for Multiple Myeloma: Bologna 96 Clinical Study
Authors: Michele Cavo, Patrizia Tosi, Elena Zamagni, Claudia Cellini, Paola Tacchetti, Francesca Patriarca, Francesco Di Raimondo, Ettore Volpe, Sonia Ronconi, Delia Cangini, Franco Narni, Affra Carubelli, Luciano Masini, Lucio Catalano, Mauro Fiacchini, Antonio de Vivo, Alessandro Gozzetti, Antonio Lazzaro, Sante Tura, Michele Baccarani
Journal: Journal of Clinical Oncology (2007)

We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Differential Expression Patterns of Claudins, Tight Junction Membrane Proteins, in Mouse Nephron Segments
Authors: Yumiko Kiuchi-Saishin, Shimpei Gotoh, Mikio Furuse, Akiko Takasuga, Yasuo Tano, Shoichiro Tsukita
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. As the first step in understanding the physiologic functions of claudins (tight junction integral membrane proteins) in nephrons, the expression of claudin-1 to -16 in mouse kidneys was examined by Northern blotting. Among these claudins, only claudin-6, -9, -13, and -14 were not detectable. Claudin-5 and -15 were detected only in endothelial cells. Polyclonal antibodies specific for claudin-7 and -12 were not available. Therefore, the distributions of claudin-1, -2, -3, -4, -8, -10, -11, and -16 in nephron segments were examined with immunofluorescence microscopy. For identification of individual segments, antibodies specific for segment markers were used. Immunofluorescence microscopic analyses of serial frozen sections of mouse kidneys with polyclonal antibodies for claudins and segment markers revealed that claudins demonstrated very complicated, segment-specific, expression patterns in nephrons, i.e., claudin-1 and -2 in Bowman's capsule, claudin-2, -10, and -11 in the proximal tubule, claudin-2 in the thin descending limb of Henle, claudin-3, -4, and -8 in the thin ascending limb of Henle, claudin-3, -10, -11, and -16 in the thick ascending limb of Henle, claudin-3 and -8 in the distal tubule, and claudin-3, -4, and -8 in the collecting duct. These segment-specific expression patterns of claudins are discussed, with special reference to the physiologic functions of tight junctions in nephrons.
Role of stenotrophomonas maltophilia infection in CF pulmonary exacerbations
Authors: Ana-Maria Vasile, Iustina Violeta Stan, Mihai Craiu, Valentina Daniela Comanici
Journal: European Respiratory Journal (2013)

Background and aim: Recently a new group of Gram-negative bacilli emerged among well documented germs involved in CF exacerbations. Stenotrophomonas maltophilia (SM), an aerobic Gram-negative opportunistic bacillus generates treatment issues due to high antimicrobial resistance. SM infection produces pulmonary function decline mostly in high-risk patients. The aim of our study was to describe the impact of SM infection in a pediatric regional center.

Material and methods: Two years retrospective study was conducted for evaluating impact of SM pulmonary infection. We analyzed clinical data, cough-swab or sputum cultures, dynamic of pulmonary function tests and x-ray aspects. SM severe exacerbations were hospitalized and treated according to CF guides.

Results: We evaluated a cohort of 50 patients during 322 visits, aged between 3 months and 33 years, with male predominance (62%). 5 of them (10%) were SM positive : 3 patients with acute exacerbation and 2 with chronic infection (>3 distinct episodes of positive cultures). Age range of patients was 8 months to 30 years. Sensitivity-guided treatment had favorable outcome in 4(80%) patients. An adult with a severe pulmonary impairment, chronic infection with Pseudomonas Aeruginosa [PA] and severe malnutrition, had a modest decline in FEV1 after cure. Lung-functional impairment of SM was significantly lower than in PA infection.

Conclusion: 

1. SM exacerbations can be documented in ∼10% of CF patients in the era of anti-pseudomonal prophylaxis.

2. Prognostic features of SM episodes are better than those of PA infection.

3. SM infection has a poor prognostic when associated with other risk factors (low BMI, baseline low-FEV1, co-infections).
TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group
Authors: Andy Trotti, Thomas F Pajak, Clement K Gwede, Rebecca Paulus, Jay Cooper, Arlene Forastiere, John A Ridge, Deborah Watkins-Bruner, Adam S Garden, K Kian Ang, Wally Curran
Journal: The Lancet Oncology (2007)
THE MITOGENIC EFFECT OF LIPOPOLYSACCHARIDE ON BONE MARROW-DERIVED MOUSE LYMPHOCYTES
Authors: Jan Andersson, Fritz Melchers, Chris Galanos, Otto Lüderitz
Journal: The Journal of Experimental Medicine (1973)

Lipopolysaccharides with different structure, isolated from different mutant strains of Escherichia coli and Salmonella bacteria, and chemical degradation products of these lipopolysaccharides have been employed to investigate which part of the lipopolysaccharide molecule exerts mitogenic effects on bone marrow-derived mouse lymphocytes. Within the structure of lipopolysaccharide consisting of lipid A, a core polysaccharide, and the O-polysaccharide antigen, lipid A was found to be the mitogenic part. The mitogenic effect of lipid A, consisting of phosphorylated glucosamine disaccharide units with ester- and amide-linked fatty acids, was lost after alkali treatment, which removes ester-linked fatty acids. Insertion of the lipid A portion of lipopolysaccharides into the lipid bilayer of the plasma membranes of bone marrow-derived lymphocytes is discussed as the initial mitogenic action.
Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis.
Authors: R P Gladue, L A Carroll, A J Milici, D N Scampoli, H A Stukenbrok, E R Pettipher, E D Salter, L Contillo, H J Showell
Journal: The Journal of Experimental Medicine (1996)

Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on cell infiltration and paralysis. Injection of encephalogenic T cells into naive animals induced paralysis and weight loss that was completely inhibited by treatment with the selective LTB4 receptor antagonist CP-105,696 (ED50= 8.6 mg/kg orally). Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase. These results demonstrate that eosinophil recruitment in EAE is dependent on LTB4 receptor ligation and further reveal a previously unrecognized role for eosinophils in the pathogenesis of this disease.
Tissue metabolism during endotoxin shock after pretreatment with monophosphoryl lipid A
Authors: S Klaus
Journal: Cardiovascular Research (2003)

Preconditioning pigs with low doses of monophosphoryl lipid A (MPL), a non toxic derivate of lipid A, has been shown to induce endotoxin hyporesponsiveness and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, the mechanism is presently unclear. This study was designed to elucidate the effects of pretreatment with MPL on tissue metabolism in different organs by in vivo microdialysis of interstitial fluid.In a controlled animal study at the university research laboratory, seven female mixed-breed pigs were exposed to an endotoxin infusion (1 microg/kg b.w. per h) after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. Seven animals receiving a saline pretreatment served as a control group. Hemodynamic variables and blood gas analyses including blood lactate were determined every 30 min until the animals died. Interstitial lactate and glycerol levels were measured in muscle, subcutaneous tissue and liver using in vivo microdialysis.Survival time was significantly prolonged after MPL preconditioning (8.95 (7.5-9.1) h vs. 5.35 (5.0-5.6) h, P<0.05). Hemodynamic parameters were not significantly different between the treatment and control groups, while mixed venous saturation (81% (70-93%) vs. 30% (22-48%)) and arterial blood pH (7.39 (7.33-7.44) vs. 7.21 (7.1-7.25)) and pO(2) were significantly higher in the preconditioned group (P<0.05). The interstitial concentrations of lactate and glycerol in all investigated tissues were significantly higher in control animals than the those who had been pretreated with MPL (P<0.05).Preconditioning with low doses of monosphosphoryl lipid A attenuates the negative effects of endotoxemia on tissue metabolism, probably by reducing O(2)-consumption. These changes may be subtle and, hence, only fully detectable by monitoring tissue metabolism.
ENDEMIC GOITRE IN CENTRAL CHINA CAUSED BY EXCESSIVE IODINE INTAKE
Authors: Li Mu, Qu Chengyi, Qian Qidong, Jia Qingzhen, CreswellJ. Eastman, JohnK. Collins, Liu Derun, Zhang Peiying, Zhang Chunde, Wang Huaixing, StevenC. Boyages, JamesJ. Jupp, GlenF. Maberly
Journal: The Lancet (1987)
Risperidone Nonadherence and Return of Positive Symptoms in the Early Course of Schizophrenia
Authors: Kenneth L. Subotnik, Keith H. Nuechterlein, Joseph Ventura, Michael J. Gitlin, Stephen Marder, Jim Mintz, Gerhard S. Hellemann, Leslie A. Thornton, Indira R. Singh
Journal: American Journal of Psychiatry (2011)

This study examined the effect of medication nonadherence on the return of positive symptoms among recent-onset schizophrenia patients.Three sets of operational criteria for medication nonadherence with differing levels of severity were compared for their ability to predict relapse. Explicit operational criteria are provided with the hope that they will be adopted by others. Psychotic symptoms were prospectively rated on a frequent basis, and systematic criteria were applied using a computer scoring program to identify periods of psychotic symptom return. In addition, a specialized statistical survival analysis method, optimal for examining risk periods and outcomes that can recur during the follow-up assessment, was used.As hypothesized, medication nonadherence robustly predicted a return of psychotic symptoms during the early phase of schizophrenia (hazard ratios=3.7-28.5, depending on the severity of nonadherence).Even brief periods of partial nonadherence lead to greater risk of relapse than what is commonly assumed. Patients in the early phase of schizophrenia should be cautioned about the possible consequences of partial or relatively brief periods of antipsychotic medication nonadherence.