tbuckley/cabot-search huggingface dataset:
Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h
Authors: Keith A. Daniels, Gene Devora, Wayne C. Lai, Carey L. O'Donnell, Michael Bennett, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (2001)

Antiviral roles of natural killer (NK) cell subsets were examined in C57BL/6 mice infected with murine cytomegalovirus (MCMV) and other viruses, including lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and mouse hepatitis virus (MHV). Each virus vigorously induced an NK cell infiltrate into the peritoneal cavity and liver, causing some redistributions of NK cell subsets defined by monoclonal antibody (mAb) directed against Ly49A, C/I, D, and G2. Striking results were seen with a mAb (1F8) reactive with the positively signaling molecule Ly49H, present in MCMV-resistant C57BL/6 mice. mAb 1F8 also stains Ly49 C and I, but exclusion of those reactivities with mAb 5E6, which recognizes Ly49 C and I, indicated that Ly49H+ cells infiltrated the peritoneal cavity and liver and were particularly effective at synthesizing interferon γ. Depletion of 1F8+ but not 5E6+ cells in vivo by mAb injections enhanced MCMV titers by 20-1,000-fold in the spleen and approximately fivefold in the liver. Titers of LCMV or VV were not enhanced. These anti-MCMV effects were attributed to prototypical NK1.1+CD3− NK cells and not to NK1.1+CD3+ “NK/T” cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset.
Oral Small Peptides Render HDL Antiinflammatory in Mice and Monkeys and Reduce Atherosclerosis in ApoE Null Mice
Authors: Mohamad Navab, G.M. Anantharamaiah, Srinivasa T. Reddy, Susan Hama, Greg Hough, Joy S. Frank, Victor R. Grijalva, Vannakambadi K. Ganesh, Vinod K. Mishra, Mayakonda N. Palgunachari, Alan M. Fogelman
Journal: Circulation Research (2005)

A peptide containing only 4 amino acid residues (KRES) that is too small to form an amphipathic helix, reduced lipoprotein lipid hydroperoxides (LOOH), increased paraoxonase activity, increased plasma HDL-cholesterol levels, rendered HDL antiinflammatory, and reduced atherosclerosis in apoE null mice. KRES was orally effective when synthesized from either L or D-amino acids suggesting that peptide-protein interactions were not required. Remarkably, changing the order of 2 amino acids (from KRES to KERS) resulted in the loss of all biologic activity. Solubility in ethyl acetate and interaction with lipids, as determined by differential scanning calorimetry, indicated significant differences between KRES and KERS. Negative stain electron microscopy showed that KRES formed organized peptide-lipid structures whereas KERS did not. Another tetrapeptide FREL shared many of the physical-chemical properties of KRES and was biologically active in mice and monkeys when synthesized from either L- or D-amino acids. After oral administration KRES and FREL were found associated with HDL whereas KERS was not. We conclude that the ability of peptides to interact with lipids, remove LOOH and activate antioxidant enzymes associated with HDL determines their antiinflammatory and antiatherogenic properties regardless of their ability to form amphipathic helixes.
Gastrin-Induced Cyclooxygenase-2 Expression in Barrett’s Carcinogenesis
Authors: Salem I. Abdalla, Pierre Lao-Sirieix, Marco R. Novelli, Laurence B. Lovat, Ian R. Sanderson, Rebecca C. Fitzgerald
Journal: Clinical Cancer Research (2004)

Cyclooxygenase (COX)-2 has been causally implicated in carcinogenesis. The evidence for increased COX-2 in the malignant progression of Barrett's esophagus is contradictory. We hypothesize that COX-2 expression may be causally affected by the gastrin status via the cholecystokinin 2 (CCK(2)) receptor.COX-2 and prostaglandin E(2) expression were evaluated by Western blotting and enzyme-linked immune assay in samples of squamous esophagus, Barrett's esophagus with varying degrees of dysplasia to adenocarcinoma, and normal duodenum. Differentiation status was evaluated by histopathology and villin expression. A longitudinal case-control study compared COX-2 in patients who progressed to adenocarcinoma with nonprogressors matched for age and length of follow-up. Messenger RNA levels of gastrin and CCK(2) receptor in biopsies and cell lines were evaluated by reverse transcription-PCR, and in vitro gastrin stimulation was conducted with and without inhibitors for CCK(2) (YM022) and COX-2 (NS-398). Cell proliferation was evaluated using minichromosome maintenance protein 2 (Mcm2) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays.COX-2 expression is significantly increased in Barrett's esophagus before dysplasia development. Expression is highly variable within Barrett's dysplasia and adenocarcinoma samples independent of differentiation status. In a longitudinal case-control study, the expression levels within patients increased over time, regardless of the degree of malignant progression. Biopsies from nondysplastic Barrett's esophagus expressed increased gastrin mRNA levels compared with other biopsies. Gastrin significantly induced COX-2, prostaglandin E(2), and cell proliferation in biopsies and cell lines. Gastrin-induced proliferation can be inhibited by YM022 and NS-398.COX-2 is up-regulated early in the Barrett's metaplasia sequence. During carcinogenesis, gastrin is a significant determinant of COX-2 activity levels via the CCK(2) receptor.
Anti-idiotypic antibodies to the Coombs antibody in NZB F1 mice.
Authors: P L Cohen, R A Eisenberg
Journal: The Journal of Experimental Medicine (1982)

The F1 hybrids of NZB and several normal mouse strains are known to produce less anti-erythrocyte (Coombs) autoantibody and develop a milder hemolytic anemia than their NZB parents. We have found that serum from some (NZB x CBA)F1 mice agglutinated erythrocytes from certain Coombs-positive NZB mice, often in extremely high titer, whereas other (CBA x NZB)F1 sera agglutinated erythrocytes from different individual NZB mice. The agglutination was due to antibody, but was not due to rheumatoid factor activity. Because F(ab')2 fragments of the F1 sera agglutinated erythrocytes coated with F(ab')2 fragments of the appropriate NZB sera, the observed reactivity was probably caused by idiotype-anti-idiotype interactions. In addition, because F1 sera could not agglutinate mouse erythrocytes coated with monovalent NZB Fab' fragments, the recognized idiotype probably involved the antigen-binding site. Anti-idiotypic antibodies against anti-erythrocyte autoantibodies may play an important role in the regulation of autoantibody formation.
Long-term Holter ECG monitoring of volleyball players
Authors: J C de la Cruz-Campos, J C de la Cruz-Márquez, B Cueto-Martín, A de la Cruz-Campos
Journal: British Journal of Sports Medicine (2011)

Background The resting ECG can detect many cardiac abnormalities, but high levels of training to which athletes are subjected can trigger episodes of abnormal heart function, which should be evaluated by means of long-term records. Objective The purpose of the study was to detect the frequency and nature of rhythmic alterations in volleyball players during the late recovery period following a match. Design Retrospective study. Setting and participants 12 volleyball players, volunteers, from 18–32 years old (mean: 24.5±1.2 years), members of a First National Division team. All were declared fit for volleyball and had no ECG abnormalities. The subjects underwent Holter ECG recording before and immediately after a match. The Holter used was NORAV DXP-1000 model. Interventions Both the day before and after a match, the players did not train but did all work or academic activities normally. They were instructed to record their times of sleep and activity. Dependent variables: pertaining to heart rate, rhythm and ST space. Independent variable: physical exercise (match). Results The average pre/post-match heart rates were 68.3±8.9 bpm when awake; 64.1±5.6 (p&lt;0.01) and 62.8±7.7; 61.2±8.5 (p&lt;0.01) when sleeping. Both before and after the match, 11 players (91%) had a mild or pronounced respiratory sinus arrhythmia. Isolated atrial or ventricular premature contractions were observed in 1 (8.3%), first-degree intermittent A-V blocks and second-degree A-V blocks with Wenckebach periods were observed in 1, high T-waves were found in 5 (41.6%), and high take-off of ST segments were found in 6 (50%). Conclusions After the match, there are fewer pulsations recorded, there are more bradycardic rhythms and there are fewer arrhythmic events.
Effect of prolonged exercise in a hypoxic environment on cardiac function and cardiac troponin T
Authors: R E Shave, E Dawson, G Whyte, K George, D Gaze, P Collinson
Journal: British Journal of Sports Medicine (2004)

Background: Exercise induced cardiac fatigue has recently been observed after prolonged exercise. A moderate to high altitude has been suggested as a possible stimulus in the genesis of such cardiac fatigue. Objective: To investigate if exercise induced cardiac fatigue and or cardiac damage occurs after prolonged exercise in a hypoxic environment. Methods: Eight trained male triathletes volunteered for the study. Each completed two 50 mile cycle trials, randomly assigned from normobaric normoxia and normobaric hypoxia (15% F io 2 ). Echocardiographic assessment and whole blood collection was completed before, immediately after, and 24 hours after exercise. Left ventricular systolic and diastolic functional variables were calculated, and serum was analysed for cardiac troponin T. Results were analysed using a two way repeated measures analysis of variance, with α set at 0.05. Results: No significant differences were observed in either systolic or diastolic function across time or between trials. Cardiac troponin T was detected in one subject immediately after exercise in the normobaric hypoxic trial. Conclusions: A 50 mile cycle trial in either normobaric normoxia or normobaric hypoxia does not induce exercise induced cardiac fatigue. Some people, however, may exhibit minimal cardiac damage after exercise in normobaric hypoxia. The clinical significance of this is yet to be elucidated.
Effect of dynamic humeral centring (DHC) treatment on painful active elevation of the arm in subacromial impingement syndrome. Secondary analysis of data from an RCT
Authors: Johann Beaudreuil, Sandra Lasbleiz, Mounir Aout, Eric Vicaut, Alain Yelnik, Thomas Bardin, Philippe Orcel
Journal: British Journal of Sports Medicine (2013)

Background The physiotherapy dynamic humeral centring (DHC) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm. The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome. Methods This is a secondary analysis of results of a randomised controlled trial of the effectiveness of DHC. Sixty-nine patients with subacromial impingement syndrome were prospectively included. Patients and the assessor were blinded to the study hypothesis and treatment, respectively. Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises. Outcomes were pain-free range of motion and presence of painful arc of the shoulder, both in active flexion and abduction of the arm at 3 months. Results At 3 months, pain-free range of motion, both flexion and abduction, was greater in the DHC group than in the mobilisation group. The number of patients with painful arc during flexion was decreased in the DHC group. Conclusions DHC improves painful active elevation of the arm. We suggest that DHC may act via a specific effect on subacromial impingement mechanism.
Potent Immunomodulatory Effects of the Trifunctional Antibody Catumaxomab
Authors: Diane Goéré, Caroline Flament, Sylvie Rusakiewicz, Vichnou Poirier-Colame, Oliver Kepp, Isabelle Martins, Julien Pesquet, Alexander Eggermont, Dominique Elias, Nathalie Chaput, Laurence Zitvogel
Journal: Cancer Research (2013)

Abstract Catumaxomab (CatmAb), a trifunctional bispecific antibody directed against the epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3, is approved as intraperitoneal therapy for the treatment of malignant ascites in patients with EpCAM-positive carcinomas. The immunomonitoring results of a phase II/III study using CatmAb revealed a tumoricidal effect associated with reduced VEGF levels, CD69-expressing T cells, and the release of T-helper cell (TH)-1 cytokines. We comprehensively dissected the immunomodulatory effects of the CatmAb on the major subsets of malignant ascites-infiltrating leukocytes and the molecular fingerprint of tumor cell death. Herein we show that in the presence of EpCAM-positive tumor targets, CatmAb markedly enhanced T-cell activation [CD69, CD107A (LAMP1), HLA-DR and PD-1(PDCD1) expression] and stimulated inflammatory CD4+ TH1 and CD8+ TH1 to release IFN-γ but failed to trigger TH17 cells. Engagement of CD16-expressing cells caused upregulation of TRAIL (TNFSF10) and costimulatory CD40 and CD80 molecules. CatmAb promoted tumor cell death associated with ATP release and strongly synergized with oxaliplatin for the exposure of the three hallmarks of immunogenic cell death (calreticulin, HMGB1, and ATP). These findings warrant validation as potential biomarkers of efficacy of CatmAb. Cancer Res; 73(15); 4663–73. ©2013 AACR.
Receptor Activity-Modifying Proteins (RAMPs): New Insights and Roles
Authors: Debbie L. Hay, Augen A. Pioszak
Journal: The Annual Review of Pharmacology and Toxicology (2015)

It is now recognized that G protein-coupled receptors (GPCRs), once considered largely independent functional units, have a far more diverse molecular architecture. Receptor activity-modifying proteins (RAMPs) provide an important example of proteins that interact with GPCRs to modify their function. RAMPs are able to act as pharmacological switches and chaperones, and they can regulate signaling and/or trafficking in a receptor-dependent manner. This review covers recent discoveries in the RAMP field and summarizes the known GPCR partners and functions of RAMPs. We also discuss the first peptide-bound structures of RAMP-GPCR complexes, which give insight into the molecular mechanisms that enable RAMPs to alter the pharmacology and signaling of GPCRs.
The impact of psoriasis on health care costs and patient work loss
Authors: Joseph F. Fowler, Mei Sheng Duh, Ludmila Rovba, Sharon Buteau, Lisa Pinheiro, Francis Lobo, Jennifer Sung, Joseph J. Doyle, Andrine Swensen, David A. Mallett, George Kosicki
Journal: Journal of the American Academy of Dermatology (2008)
ET<sub>A</sub> and ET<sub>B</sub> Receptors Modulate the Proliferation of Human Pulmonary Artery Smooth Muscle Cells
Authors: NEIL DAVIE, STEPHEN J. HALEEN, PAUL D. UPTON, JULIA M. POLAK, MAGDI H. YACOUB, NICHOLAS W. MORRELL, JOHN WHARTON
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We determined the distribution of ET(A) and ET(B) receptors in pulmonary arteries from pulmonary hypertensive patients and control subjects, using in vitro autoradiography, and investigated their role in mediating the proliferative effects of endothelin-1 (ET-1) on distal human pulmonary artery smooth muscle cells (PASMCs). Distal arteries possessed more medial [(125)I]-ET-1 binding sites (105 +/- 10 versus 45 +/- 6 amol/mm(2); p < 0.001) and a greater proportion of ET(B) receptors than proximal arteries (36 +/- 3% versus 3 +/- 1%; p < 0.001). Receptor density in distal arteries and lung parenchyma was twofold greater (p < 0.05) in pulmonary hypertensive patients than in control subjects. ET-1 (10(-9)-10(-7) mol/L) stimulated DNA synthesis (147 +/- 10% of control subjects; p < 0.05) and attenuated the antiproliferative action of cicaprost and forskolin on PASMCs, these effects being mediated via ET(A) and ET(B) receptors. Serum-stimulated proliferation was attenuated by inhibiting either endogenous ET-1 release with phosphoramidon (10(-5) mol/L) or its action with PD145065 (10(-5) mol/L). Cicaprost (10(-10)-10(-7) mol/L) inhibited ET-1 release from PASMCs (49 +/- 16% of control after 24 h; p < 0.001) and increased intracellular cAMP levels, whereas ET(B) receptor stimulation selectively reduced cAMP levels. In conclusion, ET(A) and ET(B) receptors are differentially distributed in human pulmonary arteries. Both receptors promote the proliferation of PASMCs in vitro and may contribute to vascular remodeling in pulmonary hypertension.
Asia Pacific consensus recommendations for colorectal cancer screening
Authors: J J Y Sung, J Y W Lau, G P Young, Y Sano, H M Chiu, J S Byeon, K G Yeoh, K L Goh, J Sollano, R Rerknimitr, T Matsuda, K C Wu, S Ng, S Y Leung, G Makharia, V H Chong, K Y Ho, D Brooks, D A Lieberman, F K L Chan
Journal: Gut (2008)

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5–9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.
Mortality Differences by Dialysis Modality among Incident ESRD Patients with and without Coronary Artery Disease
Authors: Santhi K. Ganesh, Tempie Hulbert-Shearon, Friedrich K. Port, Kim Eagle, Austin G. Stack
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. It is unclear whether peritoneal dialysis (PD) compared with hemodialysis (HD) confers a survival advantage in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). This hypothesis was tested in a national cohort of 107,922 patients starting dialysis therapy between May 1, 1995, and July 31, 1997. Data on patient characteristics were obtained from the Center for Medicare and Medicaid Services Medical Evidence Form (CMS) and linked to mortality data from the United States Renal Data System (USRDS). Patients were classified on the basis of CAD presence and followed until death or the end of 2 yr. Nonproportional Cox regression models estimated the relative risk (RR) of death for patients with and without CAD by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetic patients (DM) and nondiabetic patients (non-DM) were analyzed separately. Among DM, patients with CAD treated with PD had a 23% higher RR (95% CI, 1.12 to 1.34) compared with similar HD patients, whereas patients without CAD receiving PD had a 17% higher RR (CI, 1.08 to 1.26) compared with HD. Among non-DM, patients with CAD treated with PD had a 20% higher RR (CI. 1.10 to 1.32) compared with HD patients, whereas patients without CAD had similar survival on PD or HD (RR = 0.99; CI, 0.93 to 1.05). The mortality risk for new ESRD patients with CAD differed by treatment modality. In both DM and non-DM, patients with CAD treated with PD had significantly poorer survival compared with HD. Whether differences in solute clearance and/or cardiac risk profiles between PD and HD may explain these findings deserves further investigation. E-mail: [email protected]
Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline.
Authors: S Javaheri, L Guerra
Journal: Thorax (1990)

A rapid proinflammatory response after peripheral nerve injury is required for clearance of tissue debris (Wallerian degeneration) and effective regeneration. Unlike the CNS, this response is rapidly terminated in peripheral nerves starting between 2 and 3 weeks after crush injury. We examined the expression and role of the anti-inflammatory cytokine IL-10 in the resolution of inflammation and regeneration after sciatic nerve crush injury in mice. IL-10 mRNA increased over the first 7 d after injury, whereas at the protein level, immunofluorescence labeling showed IL-10<sup>+</sup> cells increased almost 3-fold in the first 3 weeks, with macrophages being the major cell type expressing IL-10. The role of IL-10 in nerve injury was assessed using IL-10-null mice. Increased numbers of macrophages were found in the distal segment of IL-10-null mice at early (3 d) and late (14 and 21 d) time points, suggesting that IL-10 may play a role in controlling the early influx and the later efflux of macrophages out of the nerve. A chemokine/cytokine PCR array of the nerve 24 h after crush showed a 2- to 4-fold increase in the expression of 10 proinflammatory mediators in <i>IL-10</i><sup>−/−</sup> mice. In addition, myelin phagocytosis <i>in vitro</i> by LPS stimulated bone-marrow-derived macrophages from IL-10-null mice failed to downregulate expression of proinflammatory chemokines/cytokines, suggesting that IL-10 is required for the myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory/pro-repair phenotype. The failure to switch off inflammation in IL-10-null mice was accompanied by impaired axon regeneration and poor recovery of motor and sensory function. <b>SIGNIFICANCE STATEMENT</b> An appropriately regulated inflammatory response after peripheral nerve injury is essential for axon regeneration and recovery. The aim of this study was to investigate the expression and role of the anti-inflammatory cytokine IL-10 in terminating inflammation after sciatic nerve crush injury and promoting regeneration. IL-10 is rapidly expressed by macrophages after crush injury. Its role was assessed using IL-10-null mice, which showed that IL-10 plays a role in controlling the early influx and the later efflux of macrophages out of the injured nerve, reduces the expression of proinflammatory chemokines and cytokines, and is required for myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory. Furthermore, lack of IL-10 leads to impaired axon regeneration and poor recovery of motor and sensory function.