tbuckley/cabot-search huggingface dataset:
Absorption of iron instilled into the stomach, duodenum, and jejunum.
Authors: J Rhodes, D Beton, D A Brown
Journal: Gut (1968)

The CD28 ligands CD80 and CD86 are expressed on APC, and both provide costimulatory function. However, the reason for the expression of two separate CD28 ligands remains unclear. We have previously shown that blockade of CD80 costimulation by Y100F-Ig, a CTL-associated Ag-4 (CTLA4)-Ig mutant that does not bind CD86, inhibits the development of lung inflammatory immune responses, but does not affect blood eosinophilia or Ab production. Each of those responses was inhibited by treatment with CTLA4-Ig, which binds both CD80 and CD86. To clarify the mechanism underlying these observations we have developed a model of lung inflammation using adoptively transferred CD4<sup>+</sup> T cells expressing a Vα11<sup>+</sup>Vβ3<sup>+</sup> transgenic TCR specific for I-E<sup>k</sup> and moth cytochrome <i>c</i>. Treatment with Y100F-Ig inhibited the induction of lung eosinophilia in adoptively transferred mice. However, Y100F-Ig did not detectably affect the accumulation of Ag-specific T cells at the site of peptide deposit or in the draining lymphoid tissues. Acquisition of an activated phenotype and expression of adhesion molecules required for migration into the lung were modestly affected. Importantly, treatment with Y100F-Ig diminished the ability of T cells to produce the cytokines IL-4 and IL-5 following intranasal challenge with Ag. All the responses examined were severely inhibited by treatment with CTLA4-Ig. We conclude that T cells require CD80 costimulation for the optimal production of IL-5 following intranasal administration of Ag. Decreased IL-5 production is the most likely explanation for the diminished airway eosinophilia observed.
EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees
Authors: M Dougados
Journal: Annals of the Rheumatic Diseases (2004)

EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees I t is the objective of the EULAR executive committee to promote actions and/or projects aimed at improving the knowledge and/or the recognition of musculoskeletal disorders.The chief aim is to contribute to the improvement of outcome of patients with rheumatic disorders.Apart from the projects devoted to education and research, projects aimed at facilitating the conduct of clinical studies or at improving the management of musculoskeletal disorders are welcome.Such studies can be categorised in four sections:N Studies dedicated to a proposal for classification and/or diagnostic criteria N Recommendations for designing and/or conducting clin- ical trials in specific musculoskeletal disorders N Recommendations for monitoring and/or management and/or treatment of specific musculoskeletal disorders N Standardisation of (laboratory and other) procedures. I RATIONALE OF STANDARDISED OPERATING PROCEDURESIt is the objective of the EULAR executive committee to maintain and to homogenise a high level of intrinsic quality and comparability of such studies.To achieve such an objective it appeared that the definition and publication of standardised procedures for the elaboration, evaluation, dissemination, and implementation of recommendations might be a relevant and useful starting point.Obviously these standardised operating procedures should not be a barrier to acceptance of a project if not all points are satisfied but might be important to consider before starting a project.These recommendations are not mandatory in themselves but can be used flexibly.
Pulmonary radioaerosol mucociliary clearance in primary ciliary dyskinesia
Authors: Woolf T. Walker, Aneurin Young, Michael Bennett, Matthew Guy, Mary Carroll, John Fleming, Joy Conway, Jane S. Lucas
Journal: European Respiratory Journal (2014)

Chronic Obstructive Pulmonary Disease (COPD) has a high mortality. Many indices have been developed to classify disease severity including the 2007 and 2011 GOLD classification and BODE index. However, no study has compared the prediction of mortality by those indices.

This is an observational study of 96 patients with COPD and followed prospectively for a median of 60 months. We performed at baseline pulmonary function tests, 6-minute walking test, dyspnea scale mMRC, anthropometric and questionnaire measures of exacerbations. BODE index and GOLD 2007 and GOLD 2011 classification was calculated. The capacity of all indices to predict mortality was compared using Cox proportional hazard analysis and Kaplan Meier survival cruves. A total of 55 men and 41 women were studied, of whom 50% died during a follow-up time mean of 69 +/- 37 months. The mean FEV1 was 27% +/- 5%. Statistically significant associations were observed between mortality and BODE index (p = 0.024) and male sex (p = 0.021). Cox regression analysisshowed that the only statistically significant association was with BODE (p=0,037; IC: 95% 1,024-2,17). The Kaplan-Meier curves for BODE, 2007 GOLD and GOLD ABCD were calculated and are The BODE index predicts all cause mortality better than the old GOLD classification based on FEV1 and the new ABCD grading . We also observed that patients classified as GOLD B has higher mortality than those classified as GOLD C.
THE EFFECT OF 10-WEEK TAE-BO INTERVENTION PROGRAMME ON PHYSICAL FITNESS AND HEALTH RELATED RISK FACTORS IN OVERWEIGHT/OBESE FEMALES
Authors: ML Mathunjwa, SJ Semple, C du Preez
Journal: British Journal of Sports Medicine (2013)

The prevalence of obesity, sedentary lifestyle and associated cardiometabolic disease (CMD) is increasing among black African women and requires urgent attention in the form of preventative strategies. To date, there is limited scientific evidence highlighting the efficacy of Tae-bo as an intervention for reducing weight and CMD risk factors. The aim therefore was to establish the efficacy of Tae-bo as an intervention for increasing physical fitness components and reducing CMD risk factors. At the University of Zululand, South Africa, 60 previously sedentary participants [25±5 y] who were overweight (BMI&gt;25–29.9 kg.m −2 ) or obese (BMI≥30–39.9 kg.m −2 ) were recruited for the study. Participants performed a 10-week aerobic (Tae-bo) programme 60 min/day for three days a week at moderate intensity for the first 5 weeks and high intensity for the last 5 weeks. Anthropometric parameters (height, weight, waist and hip circumference and sum of skinfolds), blood pressure, fasting glucose, lipoproteins and physical fitness components (sit and reach, step test, hand grip strength, push ups, Nelson hand test, ruler drop, stork stand test, horizontal jump, 20-m shuttle run) were measured at baseline, after six weeks and 24 hours after completion of the 10-week programme. Data was analysed using repeated measures ANOVA and a Tukey Post hoc test . The prevalence of metabolic syndrome was 26.7% pre-intervention and decreased to 16.3% post intervention. There was an improvement (p≤0.05) in weight, BMI, waist and hip circumference, glucose, triglycerides, total cholesterol, LDL-C, HDL-C, resting heart rate and resting systolic and diastolic blood pressures following the intervention. A 10-week 30 session Tae-bo exercise programme was effective in reducing traditional risk factors associated with cardiometabolic disease in overweight/obese university students.
Cathepsin B contributes to TNF-α–mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c
Authors: M. Eugenia Guicciardi, Jan Deussing, Hideyuki Miyoshi, Steven F. Bronk, Phyllis A. Svingen, Christoph Peters, Scott H. Kaufmann, Gregory J. Gores
Journal: Journal of Clinical Investigation (2000)

TNF-α–induced apoptosis is thought to involve mediators from acidic vesicles. Cathepsin B (cat B), a lysosomal cysteine protease, has recently been implicated in apoptosis. To determine whether cat B contributes to TNF-α–induced apoptosis, we exposed mouse hepatocytes to the cytokine in vitro and in vivo. Isolated hepatocytes treated with TNF-α in the presence of the transcription inhibitor actinomycin D (AcD) accumulated cat B in their cytosol. Further experiments using cell-free systems indicated that caspase-8 caused release of active cat B from purified lysosomes and that cat B, in turn, increased cytosol-induced release of cytochrome c from mitochondria. Consistent with these observations, the ability of TNF-α/AcD to induce mitochondrial release of cytochrome c, caspase activation, and apoptosis of isolated hepatocytes was markedly diminished in cells from CatB–/– mice. Deletion of the CatB gene resulted in diminished liver injury and enhanced survival after treatment in vivo with TNF-α and an adenovirus construct expressing the IκB superrepressor. Collectively, these observations suggest that caspase-mediated release of cat B from lysosomes enhances mitochondrial release of cytochrome c and subsequent caspase activation in TNF-α–treated hepatocytes.
Clinical Correlations of Chromosome Change in Human Solid Tumors: The Tip of the Iceberg?
Authors: J. M. Trent
Journal: JNCI Journal of the National Cancer Institute (1989)

It is now clearly recognized that a large variety of human cancers (including many solid tumors) display recurring chromosome abnormalities. However, what is the biologic significance of these findings? How do these chromosomal changes relate to changes in expression of important growth regulatory genes, e.g., cellular oncogenes? What clinical significance, if any, do specific cytogenetic abnormalities have, particularly for solid tumors, in which they are often found against a background of other genetic alterations? These and other related questions have received a significant amount of attention over the past 5 years. In general, it appears that recurring sites of chromosome change may indeed represent the byproduct of molecular events, which themselves may participate in the generation or progression of human cancers. Our recognition and ultimately our molecular understanding of chromosome abnormalities will unquestionably provide further insights into neoplasms generally and solid tumors particularly. The diversity of structural chromosome alterations across the spectrum of human cancers is enormous and increasing rapidly. Information on cancer-associated chromosome alterations is currently accumulating at a rate in excess of 2,000 new cases per year, with well over 15,000 cases of chromosome abnormalities in cancers now reported in the literature (7,2). Recent attempts of a special committee (2) to summarize this immense amount of technical information has resulted in the identification of 149 nonrandom chromosome changes involving 43 types of neoplastic disorders, including now many benign proliferations (2). These changes include a plethora of genomic alterations including deletions, translocations, isochromosomes, insertions, inversions, etc. Taken together, every human chromosome except the Y can now be included in some form of neoplasia-associated alteration. With the explosion in our knowledge base of human chro
Serum Levels of the Adipokine FGF21 Depend on Renal Function
Authors: Sebastian Stein, Anette Bachmann, Ulrike Lössner, Jürgen Kratzsch, Matthias Blüher, Michael Stumvoll, Mathias Fasshauer
Journal: Diabetes Care (2008)

To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) >50 ml/min.FGF21 was determined by enzyme-linked immunosorbent assay in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.Median serum FGF21 levels were >15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR >50 ml/min (201.9 ng/l) (P < 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P < 0.05).FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects.
Best Practices in Robot-assisted Radical Cystectomy and Urinary Reconstruction: Recommendations of the Pasadena Consensus Panel
Authors: Timothy G. Wilson, Khurshid Guru, Raymond C. Rosen, Peter Wiklund, Magnus Annerstedt, Bernard H. Bochner, Kevin G. Chan, Francesco Montorsi, Alexandre Mottrie, Declan Murphy, Giacomo Novara, James O. Peabody, Joan Palou Redorta, Eila C. Skinner, George Thalmann, Arnulf Stenzl, Bertram Yuh, James Catto
Journal: European Urology (2015)
The diagnosis of primary lung cancer with special reference to sputum cytology
Authors: N. C. Oswald, K. F. W. Hinson, G. Canti, A. B. Miller
Journal: Thorax (1971)

Of 2,545 in-patients with primary lung cancer, pathological proof of the diagnosis was obtained by sputum cytology in 48%, by bronchoscopy in 32%, by biopsy from miscellaneous sites in 12%, and at thoracotomy or necropsy only in 19%. The diagnosis was made solely on clinical and radiological evidence in 8%. One or more satisfactory specimens of sputum from 2,035 patients gave a positivity rate of 59%. When three specimens of sputum were tested the positivity rate was 69% and when four or more were tested, 85%. The maximum false positivity rate was 0·7%. Agreement between the types of malignant cells found in the sputum and in resected or necropsy specimens occurred in 84%. The pathological diagnosis was based solely on sputum cytology in 40% of the patients in whom malignant cells were found in the sputum. The total work of the sputum laboratories was analysed for one year (1967); sputum was examined from 1,598 patients, of whom 266 (17%) had positive results. Of 1,518 patients who had a bronchoscopy, the positivity rate was 53%, and of 524 patients with biopsies from miscellaneous sites the rate was 64%. Sputum cytology, as practised at present, is a very valuable method of diagnosis, but its demands on time and expertise make it unsuitable for general application outside large medical centres.
FDG–PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin's lymphoma has a high negative predictive value
Authors: J. Markova, C. Kobe, M. Skopalova, K. Klaskova, K. Dedeckova, A. Plütschow, H.T. Eich, M. Dietlein, A. Engert, T. Kozak
Journal: Annals of Oncology (2009)
Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial
Authors: Tom W J Huizinga, Roy M Fleischmann, Martine Jasson, Allen R Radin, Janet van Adelsberg, Stefano Fiore, Xiaohong Huang, George D Yancopoulos, Neil Stahl, Mark C Genovese
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA). <h3>Methods</h3> In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed. <h3>Results</h3> The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors. <h3>Conclusions</h3> Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.
Cellular Pathways of Hereditary Spastic Paraplegia
Authors: Craig Blackstone
Journal: Annual Review of Neuroscience (2012)

Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticulum, as well as intracellular membrane trafficking and distribution as primary defects underlying the HSPs, with clear relevance for other long axonopathies affecting peripheral nerves and lower motor neurons.
Revalidation of the retired
Authors: J. Rawlins
Journal: Journal of the Royal Society of Medicine (2002)

I wrote to the British Medical Association and the General Medical Council to say that the simplest and most important form of revalidation would be to have a 3-5-yearly exam of the pharmacology and therapeutics of the drugs that a practitioner normally uses. Clearly there would be no objection to retired doctors' reinstating their entitlement.
Lipid lowering for primary prevention of stroke in older adults?
Authors: G. J. Hankey
Journal: BMJ (2015)

Not yet, but new findings justify trials in this age group

Vascular events of the heart (myocardial infarction) and brain (stroke) are the world’s leading cause of death and disability. Most events occur in older people without previous symptomatic vascular disease. Although this group has a lower relative risk of vascular events than people with a previous history, they are substantially more prevalent and so account for a greater absolute number of events.1

Strategies to reduce the burden of vascular events include lipid lowering with statins. Every 1.0 mmol/L reduction in low density lipoprotein cholesterol reduces major vascular events by one fifth in populations of mean age 63 years, among whom many (60%) have previous vascular disease.2 The absolute benefit of statins is also proportional to the absolute risk of vascular events,2 so guidelines recommend adding statins to lifestyle changes if the 10 year risk exceeds 7.5-10%.3 4 Nevertheless, guidelines do not generally recommend statins for adults aged over 75 years without vascular disease because robust evidence is limited.5 6 7

In a linked paper (doi:10.1136/bmj.h2335), Alperovitch and colleagues report that use of statins or fibrates to lower serum cholesterol was associated with a one third lower risk of stroke …
Disseminated Tumor Cells in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease Predicts Biochemical Recurrence
Authors: Todd M. Morgan, Paul H. Lange, Michael P. Porter, Daniel W. Lin, William J. Ellis, Ian S. Gallaher, Robert L. Vessella
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Men with apparently localized prostate cancer often relapse years after radical prostatectomy. We sought to determine if epithelial-like cells identified from bone marrow in patients after radical prostatectomy, commonly called disseminated tumor cells (DTC), were associated with biochemical recurrence. Experimental Design: We obtained bone marrow aspirates from 569 men prior to radical prostatectomy and from 34 healthy men with prostate-specific antigens &amp;lt;2.5 ng/mL to establish a comparison group. Additionally, an analytic cohort consisting of 98 patients with no evidence of disease (NED) after radical prostatectomy was established to evaluate the relationship between DTC and biochemical recurrence. Epithelial cells in the bone marrow were detected by magnetic bead enrichment with antibodies to CD45 and CD61 (negative selection) followed by antibodies to human epithelial antigen (positive selection) and confirmation with FITC-labeled anti-BerEP4 antibody. Results: DTC were present in 72% (408 of 569) of patients prior to radical prostatectomy. There was no correlation with pathologic stage, Gleason grade, or preoperative prostate-specific antigens. Three of 34 controls (8.8%) had DTC present. In patients with NED after radical prostatectomy, DTC were present in 56 of 98 (57%). DTC were detected in 12 of 14 (86%) NED patients after radical prostatectomy who subsequently suffered biochemical recurrence. The presence of DTC in NED patients was an independent predictor of recurrence (hazard ratio 6.9; 95% confidence interval, 1.03-45.9). Conclusions: Approximately 70% of men undergoing radical prostatectomy had DTC detected in their bone marrow prior to surgery, suggesting that these cells escape early in the disease. Although preoperative DTC status does not correlate with pathologic risk factors, persistence of DTC after radical prostatectomy in NED patients was an independent predictor of recurrence.
G-CSF receptor truncations found in SCN/AML relieve SOCS3-controlled inhibition of STAT5 but leave suppression of STAT3 intact
Authors: Gert-Jan M. van de Geijn, Judith Gits, Lambertus H. J. Aarts, Claudia Heijmans-Antonissen, Ivo P. Touw
Journal: Blood (2004)
For debate Time to put "cot death" to bed? Not time to put cot death to bed
Authors: M A Green, S. Limerick
Journal: BMJ (1999)

# For debate {#article-title-2}

The increased awareness of deliberate harm to infants by parents and carers has prompted debate on the terminology used for “cot deaths.” These two papers give historical context of the debate and consider whether the use of “sudden infant death syndrome” should be abandoned.

# Time to put “cot death” to bed? {#article-title-3}

In a recent editorial in the Journal of Clinical Pathology I argued that pathologists should approach sudden and unexpected death in the first year of life with greater caution than may have been applied in recent years.1 In consequence of the increased awareness of deliberate harm by parents and carers reported by Meadow and so graphically captured on video recordings by Southall and Banks,2–4 I said that the term “not ascertained” should be used much more widely than it is at present. I am fully aware of the distress that such an approach may cause to recently bereaved and totally innocent parents. I am also old enough to recall the “bad old days” of the 1960s, when deaths were wrongly attributed to unsuitable bedding or inappropriate care, leading to unnecessary inquests and pillorying of the parents in the local press. At the other end of the spectrum we used to invent meaningless diagnoses such as “acute interstitial pneumonitis” and “viral bronchiolitis.”

Until late 1971 the registrar general would not accept the sudden infant death syndrome or any of its synonyms as a cause of death. This refusal had two undesirable consequences. Firstly, we had no idea of the true incidence of such deaths in the United Kingdom (or any other society) until reports such as that of Banks gave an indication of the size of the problem.5 Secondly, we focused our attention on an ever enlarging battery of laboratory investigations, rather than closely scrutinising the child's and the parents' histories, especially …