tbuckley/cabot-search huggingface dataset:
Programmed Death Ligand 1 Is Expressed by Non–Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells
Authors: David J. Andorsky, Reiko E. Yamada, Jonathan Said, Geraldine S. Pinkus, David J. Betting, John M. Timmerman
Journal: Clinical Cancer Research (2011)

Programmed death ligand 1 (PD-L1) is expressed on antigen-presenting cells and inhibits activation of T cells through its receptor PD-1. PD-L1 is aberrantly expressed on some epithelial malignancies and Hodgkin lymphomas and may prevent effective host antitumor immunity. The role of PD-L1 in non-Hodgkin lymphomas (NHL) is not well characterized.PD-L1 expression was analyzed in cell lines and lymphoma specimens by using flow cytometry and immunohistochemistry. Functional activity of PD-L1 was studied by incubating irradiated lymphoma cells with allogeneic T cells with or without anti-PD-L1 blocking antibody; T-cell proliferation and IFN-γ secretion served as measures of T-cell activation. Similar experiments were conducted using cultures of primary lymphoma specimens containing host T cells.PD-L1 was expressed uniformly by anaplastic large cell lymphoma (ALCL) cell lines, but rarely in B-cell NHL, confined to a subset of diffuse large B-cell lymphomas (DLBCL) with activated B-cell features (3 of 28 cell lines and 24% of primary DLBCL). Anti-PD-L1 blocking antibody boosted proliferation and IFN-γ secretion by allogeneic T cells responding to ALCL and DLBCL cells. In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. In establishing cell lines from an aggressive PD-L1(+) mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions.PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy.
Intensive<i>versus</i>standard follow-up to improve continuous positive airway pressure compliance
Authors: Izolde Bouloukaki, Katerina Giannadaki, Charalampos Mermigkis, Nikolaos Tzanakis, Eleni Mauroudi, Violeta Moniaki, Stylianos Michelakis, Nikolaos M. Siafakas, Sophia E. Schiza
Journal: European Respiratory Journal (2014)

We aimed to compare the effect of intensive versus standard interventions on continuous positive airway pressure (CPAP) adherence 2 years after CPAP initiation, as well as on sleepiness, quality of life, depression, hospitalisation and death rate due to cardiovascular disease (CVD). 3100 patients with newly diagnosed sleep apnoea were randomised into the standard group, with usual follow-up care, or the intensive group, with additional visits, telephone calls and education. Subjective daytime sleepiness (Epworth Sleepiness Scale; ESS), quality of life (36-item Short Form Health Survey; SF-36) and the patient’s level of depression (Beck Depression Inventory; BDI) were recorded before and 2 years after CPAP initiation, together with CVD hospitalisations and death rate. 2 years after CPAP initiation, the intensive group used CPAP significantly more than the standard group (6.9 versus 5.2 h per night; p&lt;0.001). ESS, SF-36 and BDI scores were also significantly better in the intensive group. Furthermore, the standard group had significantly more deaths and hospitalisations due to CVD. CPAP usage can be improved by both intensive and standard patient support. However, the patients who received intensive CPAP support had significantly better ESS, BDI and SF-36 scores, and lower cardiovascular morbidity and mortality, suggesting that an intensive programme could be worthwhile.
AN ELECTRON MICROSCOPE STUDY OF SALIVARY GLAND CHROMOSOMES BY THE REPLICA METHOD
Authors: Sanford L. Palay, Albert Claude
Journal: The Journal of Experimental Medicine (1949)

A method for preparing replicas of salivary gland chromosomes for electron microscopy is described. Electron micrographs of these replicas show that the giant chromosomes are composed of a series of small granules of approximately equal size arranged transversely across the chromosome. In stretched preparations a linear network of filaments appears between the rows of granules. These fibers cannot be traced between corresponding granules of more than two consecutive rows. When the chromosomes are digested by desoxyribonuclease, these fibers disappear and only amorphous material remains between the bands. The characteristics of the strands suggest that they are artifacts produced when the chromosomes are stretched. The small granules are composed of desoxyribonucleic acid and at least one other component, probably a protein. The nucleic acid seems to lie at least in part on the surface of each granule.
Coverage and uptake of systematic postal screening for genital <i>Chlamydia trachomatis</i> and prevalence of infection in the United Kingdom general population: cross sectional study
Authors: John Macleod, Chris Salisbury, Nicola Low, Anne McCarthy, Jonathan A C Sterne, Aisha Holloway, Rita Patel, Emma Sanford, Andrea Morcom, Paddy Horner, George Davey Smith, Susan Skidmore, Alan Herring, Owen Caul, F D Richard Hobbs, Matthias Egger
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To measure the coverage and uptake of systematic postal screening for genital <i>Chlamydia trachomatis</i> and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures. <b>Design</b> Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home. <b>Setting</b> England. <b>Participants</b> 19 773 men and women aged 16-39 years invited to participate in screening. <b>Main outcome measures</b> Coverage and uptake of screening; prevalence of chlamydia. <b>Results</b> Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year. <b>Conclusions</b> Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.
High dose of interferonα (IFN) plus ribavirin (RIBA) for 6 or 12 months in non responder (NR) patients with chronic hepatitis C (CHC): Results of a randomized trial
Authors: P. Andreone, C. Cursaro, A. Gramenzi, M. Margotti, E. Ferri, S. Talarico, L. Di Giammarino, R. Carella, A. D'Errico, M. Spinosa, P. Spagnuolo, M. Bernardi
Journal: Journal of Hepatology (2000)
Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis.
Authors: R H Yolken, J A Peterson, S L Vonderfecht, E T Fouts, K Midthun, D S Newburg
Journal: Journal of Clinical Investigation (1992)

Acute gastrointestinal infections due to rotaviruses and other enteric pathogens are major causes of morbidity and mortality in infants and young children throughout the world. Breast-feeding can reduce the rate of serious gastroenteritis in infants; however, the degrees of protection offered against rotavirus infection vary in different populations. The mechanisms associated with milk-mediated protection against viral gastroenteritis have not been fully elucidated. We have isolated a macromolecular component of human milk that inhibits the replication of rotaviruses in tissue culture and prevents the development of gastroenteritis in an animal model system. Purification of the component indicates that the antiviral activity is associated with an acidic fraction (pI = 4.0-4.6), which is free of detectable immunoglobulins. Furthermore, high levels of antiviral activity are associated with an affinity-purified complex of human milk mucin. Deglycosylation of the mucin complex results in the loss of antiviral activity. Further purification indicated that rotavirus specifically binds to the milk mucin complex as well as to the 46-kD glycoprotein component of the complex. Binding to the 46-kD component was substantially reduced after chemical hydrolysis of sialic acid. We have documented that human milk mucin can bind to rotavirus and inhibit viral replication in vitro and in vivo. Variations in milk mucin glycoproteins may be associated with different levels of protection against infection with gastrointestinal pathogens.
IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas
Authors: N Gachard, M Parrens, I Soubeyran, B Petit, A Marfak, D Rizzo, M Devesa, M Delage-Corre, V Coste, M P Laforêt, A de Mascarel, J P Merlio, K Bouabdhalla, N Milpied, P Soubeyran, A Schmitt, D Bordessoule, M Cogné, J Feuillard
Journal: Leukemia (2012)
Metabolic Symbiosis and the Birth of the Plant Kingdom
Authors: P. Deschamps, C. Colleoni, Y. Nakamura, E. Suzuki, J.-L. Putaux, A. Buleon, S. Haebel, G. Ritte, M. Steup, L. I. Falcon, D. Moreira, W. Loffelhardt, J. N. Raj, C. Plancke, C. d'Hulst, D. Dauvillee, S. Ball
Journal: Molecular Biology and Evolution (2007)

Eukaryotic cells are composed of a variety of membrane-bound organelles that are thought to derive from symbiotic associations involving bacteria, archaea, or other eukaryotes.In addition to acquiring the plastid, all Archaeplastida and some of their endosymbiotic derivatives can be distinguished from other organisms by the fact that they accumulate starch, a semicrystalline-storage polysaccharide distantly related to glycogen and never found elsewhere.We now provide the first evidence for the existence of starch in a particular species of single-cell diazotrophic cyanobacterium.We provide evidence for the existence in the eukaryotic host cell at the time of primary endosymbiosis of an uridine diphosphoglucose (UDPglucose)-based pathway similar to that characterized in amoebas.Because of the monophyletic origin of plants, we can define the genetic makeup of the Archaeplastida ancestor with respect to storage polysaccharide metabolism.The most likely enzyme-partitioning scenario between the plastid's ancestor and its eukaryotic host immediately suggests the precise nature of the ancient metabolic symbiotic relationship.The latter consisted in the export of adenosine diphosphoglucose (ADP-glucose) from the cyanobiont in exchange for the import of reduced nitrogen from the host.We further speculate that the monophyletic origin of plastids may lie in an organism with close relatedness to present-day group V cyanobacteria.
Oesophageal cancer treatment in North East Thames region, 1981: medical audit using Hospital Activity Analysis data.
Authors: R Earlam
Journal: BMJ (1984)

Figures from the Hospital Activity Analysis in the North East Thames region in 1981 were used to perform a medical audit on oesophageal cancer treatment. Four hundred and forty four patients were admitted with this diagnosis; 80 had been intubated without a thoracotomy or laparotomy, and 73 had had surgery (two thirds radical and one third palliative) with an overall operative mortality of 33%. Fifty five patients had had radiotherapy and 179 patients had no recorded operation or investigation. One hundred and seventy seven different consultants had looked after all these inpatients, most being general surgeons. Only five consultants had looked after 10 or more patients each year. From a calculated estimate of a total 286 patients in the region, 28% had palliative intubation and 25% had surgery; 20% of all the patients had radiotherapy either as a radical or palliative treatment, the remainder having no recorded therapeutic procedure. One hundred and eighty seven patients (66% of the calculated total) died in hospital. Investigation and treatment do not seem to be limited by lack of money, but money is being wasted by admitting patients for terminal care into acute hospital beds. It would be more humane for these patients to die at home or in a hospice if they wished.
Efficient Identification of Mutated Cancer Antigens Recognized by T Cells Associated with Durable Tumor Regressions
Authors: Yong-Chen Lu, Xin Yao, Jessica S. Crystal, Yong F. Li, Mona El-Gamil, Colin Gross, Lindy Davis, Mark E. Dudley, James C. Yang, Yardena Samuels, Steven A. Rosenberg, Paul F. Robbins
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Cancer immunotherapy with adoptive transfer of tumor-infiltrating lymphocytes (TIL) represents an effective treatment for patients with metastatic melanoma, with the objective regressions in up to 72% of patients in three clinical trials. However, the antigen targets recognized by these effective TILs remain largely unclear. Experimental Design: Melanoma patients 2359 and 2591 both experienced durable complete regressions of metastases ongoing beyond five years following adoptive TIL transfer. Two conventional screening approaches were carried out to identify the antigens recognized by these clinically effective TILs. In addition, a novel approach was developed in this study to identify mutated T-cell antigens by screening a tandem minigene library, which comprised nonsynonymous mutation sequences identified by whole-exome sequencing of autologous tumors. Results: Screening of an autologous melanoma cDNA library using a conventional approach led to the identification of previously undescribed nonmutated targets recognized by TIL 2359 or TIL 2591. In contrast, screening of tandem minigene libraries encoding tumor-specific mutations resulted in the identification of mutated kinesin family member 2C (KIF2C) antigen as a target of TIL 2359, and mutated DNA polymerase alpha subunit B (POLA2) antigen as a target of TIL 2591. Both KIF2C and POLA2 have been found to play important roles in cell proliferation. Conclusions: These findings suggest that the minigene screening approach can facilitate the antigen repertoire analysis of tumor reactive T cells, and lead to the development of new adoptive cell therapies with purified T cells that recognize candidate-mutated antigens derived from genes essential for the carcinogenesis. Clin Cancer Res; 20(13); 3401–10. ©2014 AACR.
Alternate antigen processing in the presence of gamma interferon may misdirect the immune recognition of cancer
Authors: Katherine Woods, Ralf B Schittenhelm, Dani Heesterbeek, Ashley Knights, Matthew Anaka, Anthony W Purcell, Andreas Behren, Jonathan Cebon
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Degradation of cellular proteins by the proteasome is critical for the generation of MHC-associated peptides. The constitutive proteasome and the IFNγ-induced immunoproteasome (IP) differ in the use of three catalytic β subunits, which alters production of MHC class I epitopes.
Reasons for variations in the use of open access gastroscopy by general practitioners.
Authors: A P Hungin, M G Bramble, H O'Callaghan
Journal: Gut (1995)

This study aimed to investigate the wide variation between general practitioners (GPs) in their use of open access gastroscopy by assessing (i) their partnership share, workload, and the aggregated practice request rate; (ii) correlations with their professional and practice characteristics; and (iii) a comparison with referral rates to medicine, surgery, and all specialties. All 145 GPs and their practice managers were sent a questionnaire and hospital held data on all requests for open access gastroscopy over one year were reviewed. During the year, the 145 GPs made 1210 requests for open access gastroscopy, varying from one to 44 per GP. There were 987,880 practice consultations altogether, an average of 22,451 per practice or 7127 per whole time practitioner. Requests for open access gastroscopy formed 2.4% of all referrals, an average of one per 1000 consultations, or eight per GP. Of a total of 49,123 referrals to all specialties (371 per GP) 4218 (8.5%) were to medicine, and 6444 to surgery (13.1%). The following factors did not correlate with requests: vocational training, a concurrent hospital post, length of service, or receipt of the deprivation allowance by the practice. When the open access gastroscopy referral rate was aggregated for each practice the variation between practices was narrowed to essentially twofold. Requests for open access gastroscopy form a small proportion of all referrals (2.4%). Aggregated practice request rates are relatively uniform compared with the wide variation between individual GPs, suggesting a disproportionate gastroenterology workload between partners. The open access gastroscopy service does not seem to be subject to misuse from most GPs if a variation in practice usage is used as a measure.
AN INTEGRATIVE THEORY OF LOCUS COERULEUS-NOREPINEPHRINE FUNCTION: Adaptive Gain and Optimal Performance
Authors: Gary Aston-Jones, Jonathan D. Cohen
Journal: Annual Review of Neuroscience (2005)

Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
Predicting the 30-Year Risk of Cardiovascular Disease
Authors: Michael J. Pencina, Ralph B. D'Agostino, Martin G. Larson, Joseph M. Massaro, Ramachandran S. Vasan
Journal: Circulation (2009)

Background— Present cardiovascular disease (CVD) risk prediction algorithms were developed for a ≤10-year follow up period. Clustering of risk factors at younger ages and increasing life expectancy suggest the need for longer-term risk prediction tools. Methods and Results— We prospectively followed 4506 participants (2333 women) of the Framingham Offspring cohort aged 20 to 59 years and free of CVD and cancer at baseline examination in 1971–1974 for the development of “hard” CVD events (coronary death, myocardial infarction, stroke). We used a modified Cox model that allows adjustment for competing risk of noncardiovascular death to construct a prediction algorithm for 30-year risk of hard CVD. Cross-validated survival C statistic and calibration χ 2 were used to assess model performance. The 30-year hard CVD event rates adjusted for the competing risk of death were 7.6% for women and 18.3% for men. Standard risk factors (male sex, systolic blood pressure, antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking, and diabetes mellitus), measured at baseline, were significantly related to the incidence of hard CVD and remained significant when updated regularly on follow-up. Body mass index was associated positively with 30-year risk of hard CVD only in models that did not update risk factors. Model performance was excellent as indicated by cross-validated discrimination C=0.803 and calibration χ 2 =4.25 ( P =0.894). In contrast, 30-year risk predictions based on different applications of 10-year functions proved inadequate. Conclusions— Standard risk factors remain strong predictors of hard CVD over extended follow-up. Thirty-year risk prediction functions offer additional risk burden information that complements that of 10-year functions.
Genomic organization of the rat connexin40 gene: identical transcription start sites in heart and lung
Authors: W.Antoinette Groenewegen, Toon A.B van Veen, Huub M.W van der Velden, Habo J Jongsma
Journal: Cardiovascular Research (1998)

The gap junction protein connexin(Cx)40 is developmentally and tissue-specifically expressed. How Cx40 expression is regulated is unknown. We therefore set out to characterize the 5'-untranslated end of both the Cx40 gene and mRNA from different tissues and ages and to identify the Cx40 promoter region.The PCR method 5'-RACE was used to amplify the 5'-end of rat Cx40 mRNAs. Genomic rat Cx40 clones were isolated from a lambda EMBL3 library. The promoter sequence was isolated by long distance PCR. The transcription start site was identified by primer extension and RNase protection assays.Comparison of Cx40 genomic DNA and mRNA sequences revealed that the Cx40 gene contains a small untranslated exon, exon I, which is separated from the coding sequences by an intron of at least 5.5 Kb. The untranslated 5'-end of Cx40 mRNA sequences from adult rat lung, neonatal and adult rat heart and the rat aortic smooth muscle cell line A7r5 were identical. While the same transcription start site was found for the Cx40 mRNAs from different tissues and ages, and amount of Cx40 mRNA differed between tissues as follows: A7r5 cells > neonatal lung > adult lung > or = neonatal atrium > neonatal ventricle; Cx40 mRNA from adult atrium and ventricle was not readily detected by primer extension and RNase protection analyses. The genomic sequence upstream of the transcription start site contains multiple consensus binding sites for transcription factors putatively responsible for spatio-temporal control of Cx40 gene expression.Similar to other connexin genes, the Cx40 gene contains two exons. The same exon I sequence is present in all tissues and developmental stages examined and the relative amounts of Cx40 mRNA in these compare well with published data. Together our data suggest that tissue-specific and developmentally regulated expression of the Cx40 gene is controlled within the same promoter region by mechanisms that have yet to be detailed.