tbuckley/cabot-search huggingface dataset:
Molecular Determinants of the Cytotoxicity of Platinum Compounds
Authors: Antoine Vekris, Delphine Meynard, Marie-Christine Haaz, Martine Bayssas, Jacques Bonnet, Jacques Robert
Journal: Cancer Research (2004)

Gene expression profiling of tumors allows the establishment of relationships between gene expression profiles and sensitivity to anticancer drugs. In an attempt to study the molecular determinants of the activity of platinum compounds, we explored the publicly available databases of the National Cancer Institute (NCI; http://dtp.nci.nih.gov), which allow access to the gene expression profiles of the 60 cell lines for which drug cytotoxicity patterns already existed. Using this database, we have conducted an in silico research to identify the genes the expression of which was positively or negatively correlated to the sensitivity to four platinum compounds (cisplatin, carboplatin, oxaliplatin and tetraplatin). Important similarities were noticed between cisplatin and carboplatin on one hand, and tetraplatin and oxaliplatin on the other hand. In the restricted panel of 1416 genes and molecular markers, we identified 204 markers, among which 120 corresponded to identified genes, that significantly correlated (P < 0.001) with the cytotoxicity of at least one platinum compound. For example, the functionality of the p53-activated pathway appeared positively correlated with the cytotoxicity of all platinum compounds. More specific are the positive correlations between RAS gene mutations and MYC expression and the cellular sensitivity to oxaliplatin. Among the parameters already known as related to the sensitivity to platinum compounds, we identified, in the complete set of 9400 genes, numerous significant relationships, such as the negative correlations between ERB-B2 and BCL-X(L) expressions and the cytotoxicity of the platinum compounds. Public databases mining, therefore, appears to be a valuable tool for the identification of determinants of anticancer drug activity in tumors.
Circulating pemphigus IgG in families of patients with pemphigus: Comparison of indirect immunofluorescence, direct immunofluorescence, and immunoblotting
Authors: Renate Brandsen, Marina Frusic-Zlotkin, Helena Lyubimov, Flory Yunes, Beno Michel, Anat Tamir, Yoram Milner, Sarah Brenner
Journal: Journal of the American Academy of Dermatology (1997)
Reverse Interferon Signature Is Characteristic of Antigen‐Presenting Cells in Human and Rat Spondyloarthritis
Authors: Ingrid Fert, Nicolas Cagnard, Simon Glatigny, Franck Letourneur, Sébastien Jacques, Judith A. Smith, Robert A. Colbert, Joel D. Taurog, Gilles Chiocchia, Luiza M. Araujo, Maxime Breban
Journal: Arthritis & Rheumatology (2013)

Objective In HLA–B27–transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. Methods Transcriptome analysis of ex vivo–purified splenic CD103+CD4+ DCs from B27‐transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase–polymerase chain reaction. A meta‐analysis of our rat data and published data on gene expression in macrophages from ankylosing spondylitis (AS) patients was further performed. Results Interferon (IFN) signaling was the most significantly affected pathway in DCs from B27‐transgenic rats; the majority of genes connected to IFN were underexpressed in B27‐transgenic rats as compared to controls. This pattern was already present at disease onset, persisted over time, and was conserved in 2 disease‐prone B27‐transgenic rat lines. In DCs from B27‐transgenic rats, we further found an up‐regulation of suppressor of cytokine signaling 3 (which may account for reverse IFN signaling) and a down‐regulation of interleukin‐27 (a cytokine that opposes Th17 differentiation and promotes Treg cells). The meta‐analysis of data on conventional DCs from rats and data on monocyte‐derived macrophages from humans revealed 7 IFN‐regulated genes that were negatively regulated in both human and rat SpA (i.e., IRF1, STAT1, CXCL9, CXCL10, IFIT3, DDX60 , and EPSTI1) . Conclusion Our results suggest that expression of HLA–B27 leads to a defect in IFNγ signaling in antigen‐presenting cells in both B27‐transgenic rats and SpA patients, which may result in Th17 expansion and Treg cell alteration (as shown in B27‐transgenic rats) and contribute to disease pathogenesis.
High-Resolution Genomic Profiling Reveals Association of Chromosomal Aberrations on 1q and 16p with Histologic and Genetic Subgroups of Invasive Breast Cancer
Authors: Daniel E. Stange, Bernhard Radlwimmer, Falk Schubert, Frank Traub, Andreas Pich, Grischa Toedt, Frank Mendrzyk, Ulrich Lehmann, Roland Eils, Hans Kreipe, Peter Lichter
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Invasive ductal carcinoma and invasive lobular carcinoma (ILC) represent the major histologic subtypes of invasive breast cancer. They differ with regard to presentation, metastatic spread, and epidemiologic features. To elucidate the genetic basis of these differences, we analyzed copy number imbalances that differentiate the histologic subtypes. Experimental Design: High-resolution genomic profiling of 40 invasive breast cancers using matrix-comparative genomic hybridization with an average resolution of 0.5 Mb was conducted on bacterial artificial chromosome microarrays. The data were subjected to classification and unsupervised hierarchical cluster analyses. Expression of candidate genes was analyzed in tumor samples. Results: The highest discriminating power was achieved when combining the aberration patterns of chromosome arms 1q and 16p, which were significantly more often gained in ILC. These regions were further narrowed down to subregions 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. Located within the candidate gains on 1q are two genes, FMO2 and PTGS2, known to be overexpressed in ILC relative to invasive ductal carcinoma. Assessment of four candidate genes on 16p11.2 by real-time quantitative PCR revealed significant overexpression of FUS and ITGAX in ILC with 16p copy number gain. Unsupervised hierarchical cluster analysis identified three molecular subgroups that are characterized by different aberration patterns, in particular concerning gain of MYC (8q24) and the identified candidate regions on 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. These genetic subgroups differed with regard to histology, tumor grading, frequency of alterations, and estrogen receptor expression. Conclusions: Molecular profiling using bacterial artificial chromosome arrays identified DNA copy number imbalances on 1q and 16p as significant classifiers of histologic and molecular subgroups.
The Quality of Laboratory Staff and the Accuracy of Results
Authors: K. Michael Peddecord
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The report by Lunz et al<sup>1</sup>entitled "The Impact of the Quality of Laboratory Staff on the Accuracy of Laboratory Results" has serious problems. This report, like others published during the past 20 years,<sup>2</sup>draws attention to the difficulties in assessing the quality of laboratory performance and its relationship to laboratory personnel. The title misleads by using the term<i>laboratory staff</i>when the report deals only with technologists. Other essential staff members, such as supervisors, technicians, and medical directors, are excluded. "Impact" implies causality, which cannot be established from a cross-sectional study. The exact nature of the study sample is unclear. In addition to the number of technologists employed, the types of hospital laboratories, directors, and supervisors are essential data in understanding this sample. The statement that "the findings can be appropriately generalized to laboratories in other states" has no basis in the data presented.
Shear Stress Downregulation of Platelet-Derived Growth Factor Receptor-β and Matrix Metalloprotease-2 Is Associated With Inhibition of Smooth Muscle Cell Invasion and Migration
Authors: Roberta Palumbo, Carlo Gaetano, Guido Melillo, Elena Toschi, Andrea Remuzzi, Maurizio C. Capogrossi
Journal: Circulation (2000)

After endovascular injury, smooth muscle cells (SMCs) may be exposed to hemodynamic shear stress (SS), and these forces modulate neointima accumulation. The effect of SS on SMC migration and invasion is unknown, and it was examined in the present study.Bovine aortic SMCs were exposed to laminar SS of 12 dyne/cm(2) for 3 (SS3) or 15 (SS15) hours; control (C3 and C15) SMCs were kept under static conditions. Platelet-derived growth factor (PDGF)-BB-directed SMC migration and invasion were evaluated by a modified Boyden chamber assay with filters coated with either gelatin or reconstituted basement membrane proteins (Matrigel), respectively. SS15 inhibited both SMC migration and invasion (P<0.0001). There was no significant difference between SS3 and C3 cells. Media conditioned with SS15 cells exhibited a reduction in matrix metalloprotease-2 (MMP-2) by zymography and Western analysis. Northern blot analysis revealed no effect of SS15 on MMP-2 mRNA. In contrast, SS15 decreased MMP-2 activator and membrane-type MMP (MT-MMP or MMP-14) mRNA and protein. Furthermore, SS15 decreased PDGF receptor-beta (PDGF-Rbeta) mRNA and protein (P<0.05), and the SS-dependent decrease in PDGF-BB-directed cell migration was rescued by overexpressing PDGF-Rbeta.SS inhibits SMC migration and invasion via diminished PDGF-Rbeta expression. This effect of SS is associated with decreased MMP-2 secretion and MT-MMP downregulation.
Allergic Response to Hyaluronidase
Authors: P. H. Kendall
Journal: BMJ (1957)

<h3>Background</h3> Revalidation is the UK process forthe review of doctors to ensure they are fit to practise. Revalidation will include patient feedback. <h3>Aim</h3> To investigate the role of patient feedback on GPs9 consultations in revalidation. <h3>Design and setting</h3> Cross-sectional survey of patients consulting 171 GPs. <h3>Method</h3> A total of 6433 patients aged 16 years or over completed the consultation satisfaction questionnaire (CSQ). Generalisability analysis was undertaken, scale scores calculated, and outliers identified using two and three standard deviations from the mean as control limits. Comments made by patients were categorised into positive, neutral, or negative. <h3>Results</h3> After averaging each scale for each doctor, mean scores (standard deviation), out of a possible score of 100, were: general satisfaction 78.1 (7.2); professional care 82.1 (6.1); relationship 71.2 (7.1); perceived time 65.7 (7.6). A D-study (which enables estimation of the reliability from 0-1 of the CSQ scores for different numbers of responders for each doctor), indicated that ratings by 19 patients would achieve a generalisability coefficient of 0.80 for the combined score. Fifteen GPs had one or more scale scores below two standard deviations of the mean. Comments were more often negative for GPs with scores below two standard deviations of the mean. <h3>Conclusion</h3> Most patients of most GPs are satisfied with their experience of consultations, and ways to make patient feedback formative for these doctors is required. For a few GPs, most patients report some dissatisfaction. Patient feedback may identify doctors who need educational support and possibly remediation, but agreed questionnaire score thresholds are required, and agreement is needed on the weight to be attached to patient experience in comparison with other aspects of performance.
Thirty-one-year survival following chemotherapy and autologous bone marrow in malignant lymphoma
Authors: Farid I. Haurani
Journal: American Journal of Hematology (1997)

A 21-year-old woman with malignant lymphoma received a large dose of nitrogen mustard followed by autologous bone marrow. She achieved a complete remission that lasted 21 years. This was followed in a span of 10 years by two relapses that responded to chemotherapy and splenectomy. Death resulted from sepsis. At autopsy, there was minimal evidence of malignant lymphoma, but evidence for side effects of chemotherapy was present.
The p68 autoantigen characteristic of rheumatoid arthritis is reactive with carbohydrate epitope specific autoantibodies
Authors: C. Meier, H W Vohr, M Schwochau, C. Specker, G R Burmester
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> The autoantigen p68 is a target of autoantibodies as well as autoreactive T cells with a high specificity in rheumatoid arthritis (RA). The binding characteristics of the autoantibodies to their antigen were now analysed biochemically and cytologically. <h3>METHODS</h3> Deglycosylation techniques as well as lectin and sugar competition experiments were performed to p68 to discover if the antibodies detected a glycoepitope. Its antigenicity was investigated applying anti-p68 antibodies derived from RA patients in comparison with polyclonal rabbit anti-p68 antibodies. <h3>RESULTS</h3> p68 specific antibodies from RA patients did not to bind to p68 that had been deglycosylated by alkaline β-elimination, <i>O</i>-glycosidase or periodate treatment. In contrast, binding of p68 specific antibodies raised in rabbit was unaffected by either deglycosylation protocol. Furthermore, lectins specific for the carbohydrate <i>N</i>-acetylglucosamine competed with p68 specific antibodies from RA patients for antigen binding.<i>N</i>-acetylglucosamine by itself also competed with patient derived anti-p68 antibodies for p68 binding. Again, rabbit anti-p68 antibodies did not elicit these competitive effects. Applying cytoimmunofluorescence, p68 was present in the cytoplasm or endoplasmic reticulum and also in low abundance on the cell surface. Under heatshock conditions, p68 was detectable in the nucleus. <h3>CONCLUSIONS</h3> Autoimmunity to p68 during RA is carried by anti-carbohydrate autoantibodies. The carbohydrate modification of p68 appears to be <i>N</i>-acetylglucosamine, which may reflect the regulation of intracellular localisation of the antigen. It is hypothesised that a shift in glycosylation pattern accompanied by an unphysiological localisation of the antigen could trigger antigenicity of p68 during the pathogenesis of RA.
Ovarian Cancer Incidence Trends in Relation to Changing Patterns of Menopausal Hormone Therapy Use in the United States
Authors: Hannah P. Yang, William F. Anderson, Philip S. Rosenberg, Britton Trabert, Gretchen L. Gierach, Nicolas Wentzensen, Kathleen A. Cronin, Mark E. Sherman
Journal: Journal of Clinical Oncology (2013)

Purpose After a report from the Women's Health Initiative (WHI) in 2002, a precipitous decline in menopausal hormonal therapy (MHT) use in the United States was linked to a decline in breast cancer incidence rates. Given that MHT use is also associated with increased ovarian cancer risk, we tested whether ovarian cancer incidence rates changed after 2002. Methods Using the North American Association of Central Cancer Registries database (1995 to 2008; N = 171,142 incident ovarian cancers), we applied standard analytic approaches and age-period-cohort (APC) models to estimate ovarian cancer incidence rate changes before (1995 to 2002) and after (2003 to 2008) the WHI report. Results Among women age ≥ 50 years, age-standardized ovarian cancer incidence declined by 0.8% per year (95% CI, −1.8% to −0.5% per year) before the WHI announcement; after the WHI report, the rate declined by 2.4% per year (95% CI, −2.5% to −2.2% per year). APC models confirmed an accelerated decline in ovarian cancer incidence after the WHI report, adjusted for age and birth cohort effects. This sudden change was notable among women most likely to have used MHT (ie, women age 50 to 69 years, white women, and residents of regions with highest MHT prescription frequency). The largest changes were found for the endometrioid histologic subtype. Conclusion After a marked reduction in MHT use around 2002, ovarian cancer incidence rates demonstrated an accelerated decline, with the largest changes for endometrioid carcinomas. This strong temporal association, although not proving a causal role of hormones in ovarian carcinogenesis, suggests that future analytic research supporting cancer control efforts should clarify the role of hormonal exposures on the development and behavior of subtypes of ovarian cancer.
What can naturally occurring mutations tell us about the pathogenesis of COPD?
Authors: S J Marciniak, D A Lomas
Journal: Thorax (2009)

The airway and emphysema phenotypes of chronic obstructive pulmonary disease (COPD) cluster in susceptible families. Some of this clustering is likely to be the result of shared genetic factors. There are a number of relatively rare syndromes that predispose to COPD, and a growing number of association and linkage studies that have assessed the genetic factors that predispose smokers to airflow obstruction. A review of the literature was performed to determine what has been learnt about the factors and pathways that predispose some individuals to progressive airflow obstruction while others are relatively resistant. There is very strong evidence that the integrity of the extracellular matrix, and in particular the elastin fibres, are important in the pathogenesis of COPD. There is also support for the role of proteinase-antiproteinase imbalance and probably oxidative stress. However, many of the genetic studies have focused on pathways that have already been implicated in disease. It is now essential that future studies take advantage of multiple large cohorts that have been phenotyped for both airways disease and emphysema, and use modern technology to perform unbiased genome-wide analyses of genetic variation in COPD. Only then will we have new insights into the pathways that underlie this common condition.
Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis
Authors: A. C. Tricco, H. M. Ashoor, J. Antony, J. Beyene, A. A. Veroniki, W. Isaranuwatchai, A. Harrington, C. Wilson, S. Tsouros, C. Soobiah, C. H. Yu, B. Hutton, J. S. Hoch, B. R. Hemmelgarn, D. Moher, S. R. Majumdar, S. E. Straus
Journal: BMJ (2014)

<b>Objective</b> To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. <b>Design</b> Systematic review and network meta-analysis. <b>Data sources</b> Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. <b>Study selection</b> Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. <b>Results</b> 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A<sub>1c</sub> compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses. <b>Conclusions</b> Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A<sub>1c</sub>. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility. <b>Systematic review registration</b> PROSPERO CRD42013003610.
Chromogranin A is an autoantigen in type 1 diabetes
Authors: Brian D Stadinski, Thomas Delong, Nichole Reisdorph, Richard Reisdorph, Roger L Powell, Michael Armstrong, Jon D Piganelli, Gene Barbour, Brenda Bradley, Frances Crawford, Philippa Marrack, Sushil K Mahata, John W Kappler, Kathryn Haskins
Journal: Nature Immunology (2010)
Heberden's Nodes in a Girl of Fifteen Years of Age
Authors: J. B. Burt
Journal: Annals of the Rheumatic Diseases (1939)

to the Devonshire Hospital complaining of pains in the feet, hands, shoulders and spine.There was a history of pain in the hands for two years and in the elbows for some time longer.Two years previously she had been in bed for two months for some vague spinal trouble.Previous Disea8es.-Variouschildren's ailments not specified.Tonsillectomy had been performed the previous year.Family History.-Oneaunt suffered from phthisis; no history of gout or rheumatism.Condition on Admission.-Childwas fat, well nourished, and of good colour.There was some thickening of all the joints of her fingers and Heberden's nodes on all the fingers of both hands.There was some tenderness over the dorsal vertebrae, but no sign of deficiency of movement or spondylitic changes.There was definite panniculitis over the inner side of both knees, and the 52 copyright.
Does adding the presence of MRI detected bone marrow oedema improve the accuracy of the 2010 EULAR/ACR criteria for rheumatoid arthritis?: Table 1
Authors: Wouter P Nieuwenhuis, Monique Reijnierse, Annette Hm van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2014)

Does adding the presence of MRI detected bone marrow oedema improve
Release of a stable cardiodepressant mediator after myocardial ischaemia during reperfusion
Authors: Stephan B Felix, Verena Stangl, Thomas M Frank, Claudia Harms, Thomas Berndt, Reinhard Kästner, Gert Baumann
Journal: Cardiovascular Research (1997)

Objective: The aim of this study was to investigate whether cardiodepressant mediators are released after myocardial ischaemia during reperfusion. Methods: Using a double heart model, the effect of the reoxygenated coronary effluent of an isolated guinea pig heart on a sequentially perfused second heart was studied under control conditions and after 10 min ischaemia of the first heart. Investigation of the modulating role of known autacoids took place by using free radical scavengers, an NO synthase inhibitor and adenosine receptor antagonists. In order to identify the chemical nature of cardiac metabolites, the coronary effluent was also subjected to different chemical treatment modes. Results: No haemodynamic changes were observed during sequential perfusion under control conditions. After 10 min of global ischaemia in heart I, a marked decrease in LVP (−22%), LVdP/dtmax (−43%), LVdP/dtmin (−41%) and coronary perfusion pressure (−25%) was measured in heart II during sequential perfusion. The negative inotropic effect was rapid in onset and reversible within 5 min; free radicals, nitric oxide and adenosine were not involved. Storage of the coronary effluent of the first heart up to 24 h, heating, or protease treatment did not modify its cardiodepressant effects on the second sequentially perfused heart. Conclusions: These results suggest the release—from an isolated heart after ischaemia during reperfusion—of a cardiodepressant mediator which induces a potent reversible negative inotropic effect on a sequentially perfused heart. The mediator is stable and in all probability not a protein.