tbuckley/cabot-search huggingface dataset:
Presentation of a T Cell Receptor Antagonist Peptide by Immunoglobulins Ablates Activation of T Cells by a Synthetic Peptide or Proteins Requiring Endocytic Processing
Authors: Kevin L. Legge, Booki Min, Nicholas T. Potter, Habib Zaghouani
Journal: The Journal of Experimental Medicine (1997)

T cell receptor (TCR) antagonism is being considered for inactivation of aggressive T cells and reversal of T cell–mediated autoimmune diseases. TCR antagonist peptides silence aggressive T cells and reverse experimental allergic encephalomyelitis induced with free peptides. However, it is not clear whether free antagonist peptides could reverse natural disease where the antigen is presumably available for endocytic processing and peptides gain access to newly synthesized class II MHC molecules. Using an efficient endocytic presentation system, we demonstrate that a proteolipid protein (PLP) TCR antagonist peptide (PLP-LR) presented on an Ig molecule (IgPLP-LR) abrogates the activation of T cells stimulated with free encephalitogenic PLP peptide (PLP1), native PLP, or an Ig containing PLP1 peptide (Ig-PLP1). Free PLP-LR abolishes T cell activation when the stimulator is free PLP1 peptide, but has no measurable effect when the stimulator is the native PLP or Ig-PLP1. In vivo, Ig-PLP1 induces a T cell response to PLP1 peptide. However, when coadministered with Ig-PLP-LR, the response to PLP1 peptide is markedly reduced whereas the response to PLP-LR is normal. Free PLP-LR coadministered with Ig-PLP1 has no effect on the T cell response to PLP1. These findings indicate that endocytic presentation of an antagonist peptide by Ig outcompete both external and endocytic agonist peptides whereas free antagonist hinders external but not endocytic agonist peptide. Direct contact with antagonist ligand and/or trans-regulation by PLP-LR–specific T cells may be the operative mechanism for Ig-PLP-LR–mediated downregulation of PLP1-specific T cells in vivo. Efficient endocytic presentation of antagonist peptides, which is the fundamental event for either mechanism, may be critical for reversal of spontaneous T cell–mediated autoimmune diseases where incessant endocytic antigen processing could be responsible for T cell aggressivity.
Primary chemotherapy followed by anterior craniofacial resection and radiotherapy for paranasal cancer
Authors: L. Licitra, L.D. Locati, R. Cavina, I. Garassino, F. Mattavelli, N. Pizzi, P. Quattrone, P. Valagussa, L. Gianni, G. Bonadonna, C.L. Solero, G. Cantu
Journal: Annals of Oncology (2003)
Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy
Authors: Bernard Brais, Jean-Pierre Bouchard, Ya-Gang Xie, Daniel L. Rochefort, Nathalie Chrétien, Fernando M.S. Tomé, Ronald G. Lafrentére, Johanna M. Rommens, Eichiro Uyama, Osamu Nohira, Segiu Blumen, Amos D. Korcyn, Peter Heutink, Jean Mathieu, André Duranceau, Francois Codère, Michel Fardeau, Guy A. Rouleau
Journal: Nature Genetics (1998)
Continuity of Care in Intensive Care Units
Authors: Naeem A. Ali, Karen M. Wolf, Jeffrey Hammersley, Stephen P. Hoffmann, James M. O'Brien, Gary S. Phillips, Mitchell Rashkin, Edward Warren, Allan Garland
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Little is known about the consequences of intensivists' work schedules, or intensivist continuity of care.Objectives: To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients.Methods: In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units.Measurements and Main Results: The primary patient outcome was ICU length of stay (LOS); we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17, P = 0.41). Intensivists experienced significantly higher burnout, work–home life imbalance, and job distress working under the continuous schedule.Conclusions: Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.Clinical trial registered with www.clinicaltrials.gov (NCT01145443).
Nitric oxide-donating statins: a new concept to boost the lipid-independent effects
Authors: S. H. Schirmer, C. M. Werner, U. Laufs, M. Bohm
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis’ by S. Momi et al ., doi:10.1093/cvr/cvs100. 

Statins decrease endogenous hepatic cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and augment systemic clearance of cholesterol-rich lipoproteins by the up-regulation of hepatic LDL receptors. Furthermore, this class of drug exerts a variety of so-called pleiotropic beneficial effects on the cardiovascular system. Atherosclerosis is initiated by impaired endothelial function characterized by a reduction in endothelial nitric oxide (NO) bioavailability. LDL-cholesterol (LDL-C) is an important negative regulator of endothelial NO synthase activity. In addition to their lipid-lowering effects, one central biological action of statins is their ability to ameliorate the impaired bioavailability of NO.1 Mechanistically, this occurs through increased expression (by inhibition of geranylgeranylation of small G-proteins)2 or enhanced activation (phosphorylation, activation of phosphatidylinositol 3-kinase and Akt) of endothelial NO synthase (eNOS).3 Consequently, statins improve vasodilation, exert antioxidative effects, and inhibit platelet aggregation, monocyte adhesion, and smooth muscle proliferation—all processes with disturbed regulation in atherosclerosis ( Figure 1 ). On top of—and through—enhancing NO bioavailability, statins have potent anti-inflammatory effects: they decrease inflammation in the vascular wall, in atherosclerotic plaques, and in circulating mononuclear cells and mobilize endothelial progenitor cells from the bone marrow.4 A complete review of vascular effects of statins can be found elsewhere.5 



Figure 1 
Both NO and HMG-CoA reductase inhibitors exert a variety of similar vasoprotective, anti-atherosclerotic functions. The eNOS is the predominant NO-producing enzyme in the vasculature. In the physiological ‘coupled’ state, eNOS forms dimers that are stabilized by the cofactor BH4 to generate more NO …
Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Trisha Suppes, Robert Silva, Josephine Cucchiaro, Yongcai Mao, Steven Targum, Caroline Streicher, Andrei Pikalov, Antony Loebel
Journal: American Journal of Psychiatry (2015)

Objective: Accumulating evidence indicates that manic symptoms below the threshold for hypomania (mixed features) are common in individuals with major depressive disorder. This form of depression is often severe and is associated with an increased risk for recurrence, suicide attempts, substance abuse, and functional disability. This study evaluated the efficacy and safety of lurasidone in major depressive disorder with mixed features. Methods: Patients meeting DSM-IV-TR criteria for major depressive disorder who presented with two or three protocol-defined manic symptoms were randomly assigned to 6 weeks of double-blind treatment with either lurasidone at 20–60 mg/day (N=109) or placebo (N=100). Changes from baseline in Montgomery-Åsberg Depression Rating Scale score (MADRS; primary outcome measure) and Clinical Global Impressions severity subscale score (CGI-S; key secondary outcome measure) were evaluated using a mixed model for repeated-measures analysis. Results: Lurasidone significantly improved depressive symptoms and overall illness severity, assessed by least squares mean change at week 6 in the MADRS and CGI-S scores: −20.5 compared with −13.0 (effect size, 0.80) and −1.8 compared with −1.2 (effect size, 0.60), respectively. Significant improvement in manic symptoms, assessed by the Young Mania Rating Scale, was also observed, in addition to other secondary efficacy endpoints. Rates of discontinuation due to adverse events were low. The most common adverse events were nausea (6.4% and 2.0% in the lurasidone and placebo groups, respectively) and somnolence (5.5% and 1.0%). Conclusions: Lurasidone was effective and well tolerated in this study involving patients with major depressive disorder associated with subthreshold hypomanic symptoms (mixed features).
Anti-CD20 (rituximab) therapy for anti–IFN-γ autoantibody–associated nontuberculous mycobacterial infection
Authors: Sarah K. Browne, Rifat Zaman, Elizabeth P. Sampaio, Kamonwan Jutivorakool, Lindsey B. Rosen, Li Ding, Minjal J. Pancholi, Lauren M. Yang, Debra Long Priel, Gulbu Uzel, Alexandra F. Freeman, Carlton E. Hayes, Roger Baxter, Stuart H. Cohen, Steven M. Holland
Journal: Blood (2012)
Efficacy of high-dose methotrexate, ifosfamide, etoposide and dexamethasone salvage therapy for recurrent or refractory childhood malignant lymphoma
Authors: J.T. Sandlund, C-H. Pui, H. Mahmoud, Y. Zhou, E. Lowe, S. Kaste, L.E. Kun, M.J. Krasin, M. Onciu, F.G. Behm, R.C. Ribeiro, B.I. Razzouk, S.C. Howard, M.L. Metzger, G.A. Hale, R. Rencher, K. Graham, M.M. Hudson
Journal: Annals of Oncology (2010)
Clinical Value of Fluorine-18 2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography in Bladder Cancer
Authors: Andrea B. Apolo, Jamie Riches, Heiko Schöder, Oguz Akin, Alisa Trout, Matthew I. Milowsky, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2010)

Fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been approved for imaging in many malignancies but not for bladder cancer. This study investigated the value of FDG-PET/CT imaging in the management of patients with advanced bladder cancer.Between May 2006 and February 2008, 57 patients with bladder cancer at our center underwent FDG-PET/CT after CT (n = 52) or magnetic resonance imaging (MRI; n = 5). The accuracy of FDG-PET/CT was assessed using both organ-based and patient-based analyses. FDG-PET/CT findings were validated by either biopsy or serial CT/MRI. Clinician questionnaires performed before and after FDG-PET/CT assessed whether those scan results affected management.One hundred thirty-five individual lesions were evaluable in 47 patients for the organ-based analysis. Overall sensitivity and specificity were 87% (95% CI, 76% to 94%) and 88% (95% CI, 78% to 95%), respectively. In the patient-based analysis, malignant disease was correctly diagnosed in 25 of 31 patients, resulting in a sensitivity of 81% (95% CI, 63% to 93%). FDG-PET/CT was negative in 15 of 16 patients without malignant lesions for a specificity of 94% (95% CI, 71% to 100%). Pre- and post-PET surveys revealed that FDG-PET/CT detected more malignant disease than conventional CT/MRI in 40% of patients. Post-PET surveys showed that clinicians changed their planned management in 68% of patients based on the FDG-PET/CT results.FDG-PET/CT has excellent sensitivity and specificity in the detection of metastatic bladder cancer and provides additional diagnostic information that enhances clinical management more than CT/MRI alone. FDG-PET/CT scans may provide better accuracy in clinical information for directing therapy.
Effects of tiaprofenic acid (Surgam) on cartilage proteoglycans in the rabbit joint immobilisation model.
Authors: I Meyer-Carrive, P Ghosh
Journal: Annals of the Rheumatic Diseases (1992)

A well established model of arthritis induced in rabbit knee joints by immobilisation in full extension for 30 days was used to evaluate the in vivo effects of 2.5, 5.0, and 10.0 mg/kg body weight of tiaprofenic acid on articular cartilage proteoglycans. The drug was given subcutaneously every 24 hours during the entire immobilisation period. Immobilised animals not treated with drugs and normal animals were used as controls. In the non-drug treated immobilised animals articular cartilage showed evidence of surface damage accompanied by synovial hypertrophy and effusion. Proteoglycan concentrations were reduced in cartilages of these joints and the incorporation of 35SO2-4 into macromolecular proteoglycans was higher than in cartilages of non-immobilised controls. Gel filtration chromatographic studies of both resident and 35S labelled proteoglycans isolated from immobilised joint cartilage showed reduced aggregation and the presence of degraded proteoglycan subunit species. Whereas the administration of 10.0 mg/kg tiaprofenic acid every 24 hours to immobilised animals exacerbated the degradation and loss of proteoglycans from joint cartilages, 5.0 mg/kg tiaprofenic acid provided some protection of these macromolecules, as shown by the concentrations and extractability of proteoglycans from cartilages, which were comparable with those from non-immobilised controls. A high incorporation of 35S into proteoglycans was demonstrated, together with reduced catabolism of proteoglycans, indicating preservation of chondrocyte anabolic activity. At a tiaprofenic acid dose of 2.5 mg/kg, however, no beneficial effects on cartilage proteoglycans could be shown.
Inhibition of maturation of human precursor lymphocytes by coformycin, and inhibitor of the enzyme adenosine deaminase
Authors: J Ballet, R Insel, E Merler, FS Rosen
Journal: The Journal of Experimental Medicine (1976)

High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes.
CD10 is expressed in dermal sheath cells of the hair follicles in human scalp
Authors: K-J. Lee, Y-L. Choi, W-S. Kim, J-H. Lee, J-M. Yang, E-S. Lee, D-Y. Lee, K-T. Jang
Journal: British Journal of Dermatology (2006)

Journal Article CD10 is expressed in dermal sheath cells of the hair follicles in human scalp Get access K‐J. Lee, K‐J. Lee Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Dong‐Youn Lee. E‐mail: dylee@smc.samsung.co.kr Search for other works by this author on: Oxford Academic Google Scholar Y‐L. Choi, Y‐L. Choi Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar W‐S. Kim, W‐S. Kim Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar J‐H. Lee, J‐H. Lee Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar J‐M. Yang, J‐M. Yang Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar E‐S. Lee, E‐S. Lee Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar D‐Y. Lee, D‐Y. Lee Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar K‐T. Jang K‐T. Jang Departments of Dermatology and Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon‐Dong, Gangnam‐Gu, Seoul 135‐710, Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 4, 1 October 2006, Pages 858–860, https://doi.org/10.1111/j.1365-2133.2006.07421.x Published: 01 October 2006
Significant similarity and dissimilarity in homologous proteins.
Authors: S Karlin, V Brendel, P Bucher
Journal: Molecular Biology and Evolution (1992)

Common practice emphasizes significant sequence similarities between different members of protein families. These similarities presumably reflect on evolutionary conservation of structurally and functionally essential residues. The nonconserved regions, on the other hand, may be either selectively neutral or differentiated. We propose several distributional sequence statistics (e.g., clustering of charged residues, compositional biases, and repetitive patterns) as indicators of differentiation events. These ideas are illustrated with various examples, including comparisons among G protein-coupled receptors, herpesvirus proteins, and GTPase-activating proteins.
Genetic Variation Predicting Cisplatin Cytotoxicity Associated with Overall Survival in Lung Cancer Patients Receiving Platinum-Based Chemotherapy
Authors: Xiang-Lin Tan, Ann M. Moyer, Brooke L. Fridley, Daniel J. Schaid, Nifang Niu, Anthony J. Batzler, Gregory D. Jenkins, Ryan P. Abo, Liang Li, Julie M. Cunningham, Zhifu Sun, Ping Yang, Liewei Wang
Journal: Clinical Cancer Research (2011)

Inherited variability in the prognosis of lung cancer patients treated with platinum-based chemotherapy has been widely investigated. However, the overall contribution of genetic variation to platinum response is not well established. To identify novel candidate single nucleotide polymorphisms (SNP)/genes, we carried out a genome-wide association study (GWAS) for cisplatin cytotoxicity by using lymphoblastoid cell lines (LCL), followed by an association study of selected SNPs from the GWAS with overall survival (OS) in lung cancer patients.A GWAS for cisplatin was conducted with 283 ethnically diverse LCLs. A total of 168 top SNPs were genotyped in 222 small cell lung cancer (SCLC) and 961 non-SCLC (NSCLC) patients treated with platinum-based therapy. Association of the SNPs with OS was determined by using the Cox regression model. Selected candidate genes were functionally validated by siRNA knockdown in human lung cancer cells.Among 157 successfully genotyped SNPs, 9 and 10 SNPs were top SNPs associated with OS for patients with NSCLC and SCLC, respectively, although they were not significant after adjusting for multiple testing. Fifteen genes, including 7 located within 200 kb up or downstream of the 4 top SNPs and 8 genes for which expression was correlated with 3 SNPs in LCLs were selected for siRNA screening. Knockdown of DAPK3 and METTL6, for which expression levels were correlated with the rs11169748 and rs2440915 SNPs, significantly decreased cisplatin sensitivity in lung cancer cells.This series of clinical and complementary laboratory-based functional studies identified several candidate genes/SNPs that might help predict treatment outcomes for platinum-based therapy of lung cancer.
Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease
Authors: Rosa Maria Rahmi, Augusto Hiroshi Uchida, Paulo Cury Rezende, Eduardo Gomes Lima, Cibele Larrosa Garzillo, Desiderio Favarato, Celia M.C. Strunz, Myrthes Takiuti, Priscyla Girardi, Whady Hueb, Roberto Kalil Filho, José A.F. Ramires
Journal: Diabetes Care (2012)

To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD).We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4).In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069).Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population.