tbuckley/cabot-search huggingface dataset:
Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells.
Authors: L G Baum, M Pang, N L Perillo, T Wu, A Delegeane, C H Uittenbogaart, M Fukuda, J J Seilhamer
Journal: The Journal of Experimental Medicine (1995)

Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T lymphoblastoid cells. Binding of T lymphoblastoid cells to thymic epithelial cells was inhibited by antibody to galectin-1 on the epithelial cells, and by two antibodies, T305 and 2B11, that recognize carbohydrate epitopes on the T cell surface glycoproteins CD43 and CD45, respectively. T lymphoblastoid cells and thymocytes bound recombinant galectin-1, as demonstrated by flow cytometric analysis, and lectin binding was completely inhibited in the presence of lactose. The degree of galectin-1 binding to thymocytes correlated with the maturation stage of the cells, as immature thymocytes bound more galectin-1 than did mature thymocytes. Preferential binding of galectin-1 to immature thymocytes may result from regulated expression of preferred oligosaccharide ligands on those cells, since we found that the epitope recognized by the T305 antibody, the core 2 O-glycan structure on CD43, was expressed on cortical, but not medullary cells. The level of expression of the UDP-GlcNAc:Gal beta 1,3GalNAc-R beta 1, 6GlcNAc transferase (core 2 beta 1, 6 GlcNAc transferase, or C2GnT), which creates the core 2 O-glycan structure, correlated with the glycosylation change between cortical and medullary cells. Expression of mRNA encoding the C2GnT was high in subcapsular and cortical thymocytes and low in medullary thymocytes, as demonstrated by in situ hybridization. These results suggest that galectin-1 participates in thymocyte-thymic epithelial cell interactions, and that this interaction may be regulated by expression of relevant oligosaccharide ligands on the thymocyte cell surface.
In situ identification of T6-positive cells in normal human dermis by immunoelectron microscopy*
Authors: G.F. MURPHY, A.K. BHAN, T.J. HARRIST, M.C. MIHM
Journal: British Journal of Dermatology (1983)

Journal Article In situ identification of T6‐positive cells in normal human dermis by immunoelectron microscopy Get access G.F. MURPHY, G.F. MURPHY Department of Pathology, Divisions of Dermatopathology and Immunopathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114Department of Pathology, Dermatopathology Unit, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, U.S.A. George F. Murphy, M.D., Assistant Professor of Pathology, Harvard Medical School and Department of Pathology, Dermatopathology Laboratory, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A.K. BHAN, A.K. BHAN Department of Pathology, Divisions of Dermatopathology and Immunopathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114Department of Pathology, Dermatopathology Unit, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T.J. HARRIST, T.J. HARRIST Department of Pathology, Divisions of Dermatopathology and Immunopathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114Department of Pathology, Dermatopathology Unit, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M.C. MIHM, JR M.C. MIHM, JR Department of Pathology, Divisions of Dermatopathology and Immunopathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114Department of Pathology, Dermatopathology Unit, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 4, 1 April 1983, Pages 423–431, https://doi.org/10.1111/j.1365-2133.1983.tb04594.x Published: 01 April 1983 Article history Accepted: 10 August 1982 Published: 01 April 1983
Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study
Authors: Joëlle Vermeulen, Katleen De Preter, Arlene Naranjo, Liesbeth Vercruysse, Nadine Van Roy, Jan Hellemans, Katrien Swerts, Sophie Bravo, Paola Scaruffi, Gian Paolo Tonini, Bruno De Bernardi, Rosa Noguera, Marta Piqueras, Adela Cañete, Victoria Castel, Isabelle Janoueix-Lerosey, Olivier Delattre, Gudrun Schleiermacher, Jean Michon, Valérie Combaret, Matthias Fischer, André Oberthuer, Peter F Ambros, Klaus Beiske, Jean Bénard, Bárbara Marques, Hervé Rubie, Janice Kohler, Ulrike Pötschger, Ruth Ladenstein, Michael D Hogarty, Patrick McGrady, Wendy B London, Geneviève Laureys, Frank Speleman, Jo Vandesompele
Journal: The Lancet Oncology (2009)
Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population
Authors: X.-j. Zhou, X.-l. Lu, J.-c. Lv, H.-z. Yang, L.-x. Qin, M.-h. Zhao, Y. Su, Z.-g. Li, H. Zhang
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Recent genome-wide association studies suggested the <i>PRDM1-ATG5</i> gene region as a systemic lupus erythematosus (SLE)-associated locus both in Caucasian and Chinese populations; however, the candidate gene was still obscure and the possible functional significance needed to be determined. <h3>Methods</h3> In this study, by a multistage integrative strategy, the authors first performed a case–control association study involving 1745 individuals in the Chinese population by genotyping nine single nucleotide polymorphisms within this region, and a meta-analysis was conducted. Correlation between associated genotypes and expression levels of messenger RNA in B-cell lines from 210 unrelated HapMap data was examined, and was validated in vitro. To determine the biological significance, a genetic association study was also checked in a pathway-based manner and the significant associations were validated in a second 844 Chinese cohort. <h3>Results</h3> A peak of association was found in the intergenic region (p=0.036–3.26×10<sup>−4</sup>). Meta-analysis consolidated the association between rs548234 and SLE (OR 1.254, p=1.28×10<sup>−16</sup>). Significant positive correlations with <i>ATG5</i> expression were identified, suggesting <i>ATG5</i> as a candidate gene in the region. Epstein–Barr virus B-cell-based downstream gene expression analysis supported a functional effect of rs548234 and rs6937876, and in-vitro experiments confirmed the regulatory effect of rs6937876 in B-cell populations. Finally, an autophagy pathway-based genetic association study identified <i>ATG7</i> (p=1.12×10<sup>−4</sup>) and <i>IRGM</i> (p=0.015) as novel candidate genes, and gene–gene interactions were observed between <i>ATG5</i>, <i>ATG7</i> and <i>IRGM</i>. <h3>Conclusion</h3> These data may demonstrate that autophagy is involved in the pathogenesis of SLE and imply a common biological pathway in autoimmunity.
Survival of Patients With Peripheral T-Cell Lymphoma After First Relapse or Progression: Spectrum of Disease and Rare Long-Term Survivors
Authors: Vivien Mak, Jeremey Hamm, Mukesh Chhanabhai, Tamara Shenkier, Richard Klasa, Laurie H. Sehn, Diego Villa, Randy D. Gascoyne, Joseph M. Connors, Kerry J. Savage
Journal: Journal of Clinical Oncology (2013)

A number of novel therapies are under investigation in relapsed or refractory peripheral T-cell lymphoma (PTCL); however, their relative impact on outcome is unknown. We examined the survival of patients with PTCL after relapse or progression in the absence of hematopoietic stem-cell transplantation and explored factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK] positive and ALK negative.After exclusions, 153 patients were analyzed (PTCL-NOS, n = 79 [52%]; AITL, n = 38 [25%]; ALK-positive ALCL, n = 11 [7%]; ALK-negative ALCL, n = 27 [16%; including ALK status unknown, n = 1]).Median time from initial diagnosis to relapse or progression after primary therapy was 6.7 months, and median age at relapse was 66 years (ALK-positive ALCL, 39 years). Median overall survival (OS) and median progression-free survival (PFS) after relapse or progression (second PFS) were 5.5 and 3.1 months, respectively, and were only marginally better in patients who received chemotherapy at relapse (n = 89 [58%]; 6.5 and 3.7 months, respectively). Patients with good performance status (PS) of 0 or 1 (n = 47) at relapse who received chemotherapy had a more favorable OS (P < .001; median OS, 13.7 months) and PFS (P = .006; median second PFS, 5.0 months), which remained significant in multivariate analysis (OS: hazard ratio [HR], 2.09; P = .002; second PFS: HR, 1.66; P = .030).Most patients with relapsed or refractory PTCL have poor outcomes with short survival. Select patients with good PS have more favorable outcomes with standard chemotherapy.
Impaired cation transport in thymocytes of rats with chronic uremia includes the Na+/H+ antiporter.
Authors: S Greiber, W C O'Neill, W E Mitch
Journal: Journal of the American Society of Nephrology (1995)

To examine how uremia changes sodium, potassium, and proton transport, thymocytes from chronic renal failure (CRF) rats were studied. If alterations in cation transport associated with chronic uremia (CRF) extend to intracellular pH regulation, the susceptibility to the catabolic effects of acidosis might be increased. To evaluate the influence of acidosis, cation transport in thymocytes from normal rats with NH4Cl-induced acidosis was also studied. Ouabain-sensitive 86Rb influx in thymocytes from acidotic CRF rats was 32% lower than in control cells (P < 0.05), but intracellular sodium concentration was unchanged. This may be related to a 47 +/- 22% reduction in 22Na influx. In thymocytes from nonuremic, acidotic rats, ouabain-sensitive 86Rb influx was decreased 39% (P < 0.025), similar to the change in CRF. In CRF thymocytes, Na(+)-H+ antiporter activity in response to cell acidification (7.13 +/- 0.8 versus 9.42 +/- 0.8 mmol of H+/L per min; CRF versus control), or to osmotic shrinkage (0.43 +/- 0.09 versus 0.82 +/- 0.11 mmol of H+/L per min; CRF versus control), was significantly (P < 0.01) reduced. Buffering capacity at resting and acidic intracellular pH was unchanged by uremia, but Na+/H+ antiporter activity in response to acid loading or osmotic shrinkage was unchanged in thymocytes of nonuremic rats with metabolic acidosis. Thus, CRF reduces both Na/K-ATPase and Na+/H+ antiporter activities in rat thymocytes. The former may be secondary to reduced sodium influx. Impaired Na+/H+ antiporter activity is not caused by metabolic acidosis alone, whereas reduced Na/K-ATPase activity is found in both acidosis and uremia.
Effect of Adenosine on Myocardial ‘Stunning’ in the Dog
Authors: Selim Sekili, Mohamed O. Jeroudi, Xian-Liang Tang, Marcel Zughaib, Jian-Zhong Sun, Roberto Bolli
Journal: Circulation Research (1995)

Abstract Recent evidence suggests a cardioprotective effect of adenosine in myocardial ischemia and reperfusion. The present study was undertaken to determine (1) whether adenosine attenuates myocardial stunning, (2) if so, whether the beneficial effect of adenosine takes place during ischemia or after reperfusion, and (3) whether adenosine preconditions against myocardial stunning. A total of 93 dogs were used. In phase A of the study, open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion received an intracoronary infusion of either saline (group I [control], n=14), 2 mg/min adenosine from 30 minutes before occlusion until 1 hour after reperfusion (group II, n=10), or 2 mg/min adenosine from 2 minutes before reperfusion until 1 hour after reperfusion (group III, n=11). Regional myocardial function (assessed as systolic wall thickening) was similar in the three groups at baseline and during ischemia. After reperfusion, dogs treated with adenosine before, during, and after ischemia (group II) demonstrated a significant improvement in the recovery of function that persisted throughout the 4 hours of reperfusion. In contrast, in dogs treated only during the reperfusion period (group III), the recovery of function was not statistically different from that in control dogs. The enhanced recovery effected by adenosine in group II could not be ascribed to differences in ischemic zone size, collateral flow during occlusion, coronary flow after reperfusion, arterial pressure, heart rate, or other hemodynamic variables. In phase B of the study, dogs received an intracoronary infusion of either saline (group IV [control], n=6) or adenosine (4 mg/min from 40 to 10 minutes before occlusion [group V, n=6]). Despite pretreatment with adenosine, the recovery of function in group V was indistinguishable from that in the control group. This study demonstrates that (1) continuous administration of adenosine before, during, and after ischemia results in a significant and sustained attenuation of myocardial stunning; (2) this improved recovery of function cannot be attributed to nonspecific variables, such as collateral flow during coronary occlusion, coronary flow after reperfusion, or other hemodynamic factors, and therefore reflects a direct cardioprotective action of adenosine; (3) the protection against stunning is lost or markedly diminished if adenosine is given only at reperfusion; and (4) administration of adenosine before ischemia does not precondition the myocardium against the stunning induced by a 15-minute occlusion. The failure of adenosine to produce a beneficial effect when given only at reperfusion indicates that in the 15-minute occlusion model, the nucleoside acts primarily by decreasing the severity of ischemic injury rather than by mitigating reperfusion injury.
A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
Authors: Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Inga Reynisdottir, Rafn Benediktsson, Thorbjorg Jonsdottir, G Bragi Walters, Unnur Styrkarsdottir, Solveig Gretarsdottir, Valur Emilsson, Shyamali Ghosh, Adam Baker, Steinunn Snorradottir, Hjordis Bjarnason, Maggie C Y Ng, Torben Hansen, Yu Bagger, Robert L Wilensky, Muredach P Reilly, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Vilmundur Gudnason, Guanjie Chen, Hanxia Huang, Kerrie Lashley, Ayo Doumatey, Wing-Yee So, Ronald C Y Ma, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Jana V van Vliet-Ostaptchouk, Marten H Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J Rader, Charles Rotimi, Mark Gurney, Juliana C N Chan, Oluf Pedersen, Gunnar Sigurdsson, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson
Journal: Nature Genetics (2007)
Carcinogen Hemoglobin Adducts, Urinary Mutagenicity, and Metabolic Phenotype in Active and Passive Cigarette Smokers
Authors: H. Bartsch, N. Caporaso, M. Coda, F. Kadlubar, C. Malaveille, P. Skipper, G. Talaska, S. R. Tannenbaum, P. Vineis
Journal: JNCI Journal of the National Cancer Institute (1990)

In 100 healthy volunteers, we have studied the relationship between the type (air- or flue-cured) and number of cigarettes smoked and different biomarkers relevant to the risk of bladder cancer, including the levels of 4-aminobiphenyl (ABP) hemoglobin adduct (a marker of internal dose), urinary mutagenicity in Salmonella typhimurium TA98, and the N-acetylation phenotype (a marker of susceptibility). ABP is a potent bladder carcinogen that is N-acetylated as an overall detoxification step. Levels of the ABP hemoglobin adduct were higher in smokers of black tobacco (air-cured) than in smokers of blond tobacco (flue-cured), confirming our earlier study. In addition, "slow" acetylators had higher levels of the ABP hemoglobin adduct for the same type and quantity of cigarettes smoked. Urinary mutagenicity was also associated with quantity of cigarettes but not with the acetylation phenotype. Convex dose-response relationships were found between the amount smoked and ABP hemoglobin adduct levels or urinary mutagenicity. In 15 nonsmokers who reported exposure to environmental tobacco smoke, ABP hemoglobin adduct levels, unlike urinary mutagenicity, were found to be an aspecific exposure indicator.
Trichloroethylene Exposure and Specific Somatic Mutations in Patients With Renal Cell Carcinoma
Authors: H Brauch, G Weirich, M A Hornauer, S Störkel, T Wöhl, T Brüning
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: The development of renal cell carcinoma (RCC) has been associated with both genetic and environmental factors—with mutations in the von Hippel-Lindau (VHL) tumor suppressor gene for clear-cell RCC specifically and with long-term exposure to high doses of trichloroethylene (TRI), an industrially important solvent, for RCC generally. We investigated whether TRI exposure produces RCC through a specific mutational effect on the VHL gene by analyzing VHL sequences in the RCCs of patients exposed to high, cumulative doses of TRI. METHODS: The level of exposure for each of 44 patients with RCC who had known industrial exposure to TRI was classified according to the duration, frequency, and mode of exposure. Samples of normal and cancerous tissues were microdissected from paraffin-embedded tissue. DNA was isolated from these samples, and somatic VHL mutations were identified by polymerase chain reaction analysis, single-strand conformation polymorphism analysis, DNA sequencing, and restriction enzyme digestion. Control samples included RCC DNA from 107 patients without known TRI exposure and lymphocyte DNA from 97 healthy subjects. RESULTS: RCCs of TRI-exposed patients showed somatic VHL mutations in 33 (75%) of 44 cases. The mutations were frequently multiple and accompanied by loss of heterozygosity, and there was an association between the number of mutations and the severity of TRI exposure. We observed a specific mutational hot spot at VHL nucleotide 454 in the RCCs of 13 (39%) of the patients, and this mutation was present in adjacent non-neoplastic kidney parenchyma in four of these patients. The nucleotide 454 mutation was neither detected in any of the RCCs from patients without TRI exposure nor in any of the healthy subjects. CONCLUSION: Our results suggest that RCC in patients with high, cumulative TRI exposure is associated with a unique mutation pattern in the VHL gene.
Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study
Authors: Christopher E Brightling, Eugene R Bleecker, Reynold A Panettieri, Mona Bafadhel, Dewei She, Christine K Ward, Xiao Xu, Claire Birrell, René van der Merwe
Journal: The Lancet Respiratory Medicine (2014)
MPs call on government to scrap 7bn NHS care records system
Authors: A. O'Dowd
Journal: BMJ (2011)

The government should consider dropping its £7bn (€8bn; $11.4bn) care records system for the NHS, still under development, as it is an “unworkable” and costly mistake, claims a report from an influential committee of MPs.

The Public Accounts Committee published a highly critical report on 3 August focusing on the care records system for the NHS in England—part of the £11.4bn national programme for IT in the NHS.

The programme was launched in 2002, and the Department of Health has spent £6.4bn on it so far.

For their inquiry the MPs on the committee focused on delivery of what is meant to be a fully integrated, electronic care records system under the programme and …
Risk related surveillance following colorectal polypectomy
Authors: G Nusko
Journal: Gut (2002)

<b>Background:</b> Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma and therefore need to be kept under surveillance. It is essential to avoid unnecessary examinations by tailoring the frequency of follow up examinations to individual risk. <b>Methods:</b> A total of 3134 patients undergoing endoscopic removal of colorectal adenomas were prospectively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996. A multivariate analysis of 1159 patients on long term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology—that is, adenomas &gt;10 mm or with high grade dysplasia or invasive carcinoma. <b>Results:</b> Univariate analysis revealed that sex, parental history of colorectal carcinoma, and characteristics of the initial findings—that is, size, multiplicity, and amount of villous structure—were significant predictors of metachronous adenomas of advanced pathology. On the basis of multivariate analysis, two risk groups were identified: (1) patients with no parental history of colorectal carcinoma with only small (≤10 mm) tubular adenomas at the initial clearing examination have a very low risk, and we estimated that 10% will develop advanced metachronous adenomas after 10 years; (2) the high risk group contained all other patients, 10% of whom will show metachronous adenomas of advanced pathology at follow up after only three years. <b>Conclusions:</b> The risk of developing metachronous adenomas with advanced pathology can be stratified for various patient and adenoma characteristics. Surveillance intervals can be scheduled for low risk (10 years) and high risk (three years) patients. Risk related follow up thus helps to avoid unnecessary examinations.
Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial
Authors: Pablo Aschner, Juliana Chan, David R Owens, Sylvie Picard, Edward Wang, Marie-Paule Dain, Valérie Pilorget, Akram Echtay, Vivian Fonseca
Journal: The Lancet (2012)