tbuckley/cabot-search huggingface dataset:
The relative prevalence of dermatomyositis and polymyositis in Europe exhibits a latitudinal gradient
Authors: G J D Hengstman
Journal: Annals of the Rheumatic Diseases (2000)

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic diseases that include the more familiar disease entities of dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM).1 The aetiology of IIM is unknown. DM and PM are commonly regarded as autoimmune diseases,1 while the immune response in IBM is thought to be secondary to degenerative changes in skeletal muscle tissue.2 The autoimmunity in DM and PM is most probably a result of the interaction of environmental and host factors.1 3 Environmental risk factors are suggested by the fact that several viruses (for example, picorna, influenza, paramyxo) have been associated directly or indirectly with IIM, by unconfirmed reports of coxsackie B virus antibodies in children with DM, and by …
Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone.
Authors: N R Schechter, C S Portlock, J Yahalom
Journal: Journal of Clinical Oncology (1998)

Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori infection. Many regard antibiotic therapy as the primary treatment of MLS, but in the absence of H pylori infection, or when salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have frequently been used. This study evaluates the efficacy of low-dose radiotherapy alone as an alternative to surgery.Seventeen patients with stage I to II(2) low-grade MLS without evidence of H pylori infection or with persistent lymphoma after antibiotic therapy of associated H pylori infection were included in this series. Median age was 69 years (range, 39 to 84). Median total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter.All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range, 11 to 68) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up.These results suggest that effective treatment of MLS with low-dose radiation therapy alone is feasible and safe, and allows stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H pylori-negative or antibiotic-resistant cases of MLS.
Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials
Authors: A. Le Cesne, M. Ouali, M.G. Leahy, A. Santoro, H.J. Hoekstra, P. Hohenberger, F. Van Coevorden, P. Rutkowski, R. Van Hoesel, J. Verweij, S. Bonvalot, W.P. Steward, A. Gronchi, P.C.W. Hogendoorn, S. Litiere, S. Marreaud, J.Y. Blay, W.T.A. Van Der Graaf
Journal: Annals of Oncology (2014)
Is activation of transversus abdominis and obliquus internus abdominis associated with long-term changes in chronic low back pain? A prospective study with 1-year follow-up
Authors: Monica Unsgaard-Tøndel, Tom Ivar Lund Nilsen, Jon Magnussen, Ottar Vasseljen
Journal: British Journal of Sports Medicine (2011)

Objective To investigate associations between deep abdominal muscle activation and long-term pain outcome in chronic non-specific low back pain (LBP). Methods Recruitment of transversus abdominis and obliquus internus abdominis during the abdominal drawing-in manoeuvre was recorded by B-mode ultrasound and anticipatory onset of deep abdominal muscle activity with M-mode ultrasound. Recordings were done before and after 8 weeks with guided exercises for 109 patients with chronic non-specific LBP. Pain was assessed with a numeric rating scale (0–10) before and 1 year after intervention. Associations between muscle activation and long-term pain were examined by multiple linear and logistic regression methods. Results Participants with a combination of low baseline lateral slide in transversus abdominis and increased slide after intervention had better odds for long-term clinically important pain reduction (≥2 points on the numeric rating scale) compared with participants with small baseline slide and no improvement in slide (OR 14.70, 95% CI 2.41 to 89.56). There were no associations between contraction thickness ratios in transversus abdominis or obliquus internus abdominis and pain at 1-year follow-up. Transversus abdominis lateral slide before intervention was marginally associated with a lower OR for clinically important improvement in pain at 1-year follow-up (OR 0.76, 95% CI 0.62 to 0.93). Delayed onset of the abdominal muscles after the intervention period was weakly associated with higher long-term pain. Conclusion Improved transversus abdominis lateral slide among participants with low baseline slide was associated with clinically important long-term pain reduction. High baseline slide and delayed onset of abdominal muscles after the intervention period were weakly associated with higher pain at 1-year follow-up. Clinical Trial Registration number The study was preregistered in ClinicalTrials.gov with identifier NCT00201513 .
Adjuvant Chemotherapy for Node-Positive Breast Cancer Patients: Which is the Reference Today?
Authors: Pierre Fumoleau, Jacques Bonneterre, Elisabeth Luporsi
Journal: Journal of Clinical Oncology (2003)

2, in the metastatic setting, demonstrated that epirubicin was as effective as, and less toxic than, doxorubicin when administered at equimolar doses (50 mg/m 2 ). The second trial (FASG-05), 3 comparing six cycles of FEC 50 (6 FEC 50) to 6 FEC 100 in poor prognosis N breast cancer patients, demonstrated a significant improvement in both 5-year disease-free survival (DFS) and overall survival (OS) with FEC 100 regimen. Lacking a direct comparison of the TAC regimen with our present standard treatment, we considered it important to evaluate the efficacy of FEC 100 regimen in comparison with TAC. Using the FASG-05 trial database, we analyzed DFS and OS using the Kaplan-Meier method, with a 33-month follow-up and an adjustment for the main patient and tumor criteria to be as comparable as possible with BCIRG 001 patients. With respect to patients’ characteristics, the populations in both studies were comparable for median age (49 years v 51 years), premenopausal status (51% v 50%), and hormone receptor positivity (69% v 67%). The surgical procedure was somewhat different, with 60% of overall patients having mastectomy in BCIRG-001 patients versus 53% in FASG-05 patients, and with tumor size more than 2 cm in 58% and 62% of BCIRG-001 and FASG-05 patients, respectively. The main difference was noted for number of positive nodes: In the BCIRG-001 trial, only 38% of 1,491 patients had more than three nodes, whereas 82% of the 565 patients included in the FASG-05 trial had more than three nodes. For this reason, our analysis of efficacy will focus on patients with more than three nodes. In the GFEA-05 trial 3 , only 98 patients (52 in 6 FEC 50 and 46 in 6 FEC 100) had one to three positive nodes; for this population, the protocol required a Scartt Bloom Richardson grade 2 to 3 and hormone receptor negativity. First, we compared the safety profile of both trials (Table 1). It is
Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis
Authors: Thomas Zimmermann, Andreas Gardemann, Georg Machnik, Rolf Dargel, Kurt Jungermann
Journal: Hepatology (1992)

Thioacetamide-induced rat cirrhosis was characterized by single-cell necroses, fibrosis, nodular parenchyma, decrease in parenchymal volume density and an increase in liver weight per body weight so that the total amount of parenchyma was not altered. The glycogen content was normal, and signs of decompensation were not found. Isolated livers were single-pass perfused by way of both the hepatic artery and the portal vein. In the normal livers stimulation of the nerve plexuses around the hepatic artery or portal vein (7.5 Hz; 2 msec) and infusions of noradrenaline (1 μmol/L) by way of either vessel and of acetylcholine (10 μmoI/L) by way of the artery only increased glucose output, reduced both portal and arterial flow and increased the intravascular pressures. Glucagon (0.5 nmol/L) augmented glucose release and had no hemodynamic effects. In chronically thioacetamide-injured livers all stimuli caused smaller metabolic alterations per gram of liver weight and decreased portal flow more and arterial flow less with stronger enhancements of intravascular pressures than in the controls. The lowered metabolic responsiveness per gram of cirrhotic liver was largely compensated by the increase in liver weight. Thus despite massive histological alterations and pronounced increases in stimulation-dependent resistances–predominantly in the portal system–cirrhotic rat livers responded in their glucose metabolism to nervous and hormonal stimuli in almost the same manner as normal livers. (Hepatology 1992;15:464–470).
DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions
Authors: Huseyin Saribasak, Robert W. Maul, Zheng Cao, William W. Yang, Dominik Schenten, Sven Kracker, Patricia J. Gearhart
Journal: The Journal of Experimental Medicine (2012)

Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although DNA polymerase (pol) η is the major low-fidelity polymerase, other DNA polymerases may also contribute. Existing data are contradictory as to whether pol ζ is involved. We reasoned that the presence of pol η may mask the contribution of pol ζ, and therefore we generated mice deficient for pol η and heterozygous for pol ζ. The frequency and spectra of hypermutation was unaltered between Polζ+/− Polη−/− and Polζ+/+ Polη−/− clones. However, there was a decrease in tandem double-base substitutions in Polζ+/− Polη−/− cells compared with Polζ+/+ Polη−/− cells, suggesting that pol ζ generates tandem mutations. Contiguous mutations are consistent with the biochemical property of pol ζ to extend a mismatch with a second mutation. The presence of this unique signature implies that pol ζ contributes to mutational synthesis in vivo. Additionally, data on tandem mutations from wild type, Polζ+/−, Polζ−/−, Ung−/−, Msh2−/−, Msh6−/−, and Ung−/− Msh2−/− clones suggest that pol ζ may function in the MSH2–MSH6 pathway.
A Single Recombinant Adenovirus Expressing p53 and p21-targeting Artificial microRNAs Efficiently Induces Apoptosis in Human Cancer Cells
Authors: Masashi Idogawa, Yasushi Sasaki, Hiromu Suzuki, Hiroaki Mita, Kohzoh Imai, Yasuhisa Shinomura, Takashi Tokino
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Gene transfer involving p53 is viewed as a potentially effective cancer therapy, but does not result in a good therapeutic response in all human cancers. The activation of p53 induces either cell cycle arrest or apoptosis. Cell cycle arrest in response to p53 activation is mediated primarily through the induction of the cyclin-dependent kinase inhibitor p21. Because p21 also has an inhibitory effect on p53-mediated apoptosis, the suppression of p53-induced p21 expression would be expected to result in the preferential induction of apoptosis. However, p21 also has tumor-suppressive properties. In this study, we developed an adenovirus vector that expresses p53 and suppresses p21 simultaneously to enhance p53-mediated apoptosis. Experimental Design: We constructed a replication-deficient recombinant adenovirus (Ad-p53/miR-p21) that enabled cocistronic expression of the p53 protein and artificial microRNAs that targeted p21, and examined the therapeutic effectiveness of this vector in vitro and in vivo. Results: The levels of p21 were significantly attenuated following infection with Ad-p53/miR-p21. In colorectal and hepatocellular carcinoma cells, infection with Ad-p53/miR-p21 augmented apoptosis as compared with an adenovirus that expressed p53 alone (Ad-p53/miR-control). Ad-p53/miR-p21 also significantly increased the chemosensitivity of cancer cells to adriamycin (doxorubicin). In a xenograft tumor model in nude mice, tumor volume was significantly decreased following the direct injection of Ad-p53/miR-p21 into the tumor, as compared with the injection of Ad-p53/miR-control. Conclusion: These results suggest that adenovirus-mediated transduction of p53 and p21-specific microRNAs may be useful for gene therapy of human cancers.
Interaction of <i>Muc2</i> and <i>Apc</i> on Wnt Signaling and in Intestinal Tumorigenesis: Potential Role of Chronic Inflammation
Authors: Kan Yang, Natalia V. Popova, Wan Cai Yang, Ioanna Lozonschi, Selam Tadesse, Scott Kent, Laura Bancroft, Ilze Matise, Robert T. Cormier, Stefan J. Scherer, Winfried Edelmann, Martin Lipkin, Leonard Augenlicht, Anna Velcich
Journal: Cancer Research (2008)

Abstract Somatic mutations of the adenomatous polyposis coli (APC) gene are initiating events in the majority of sporadic colon cancers. A common characteristic of such tumors is reduction in the number of goblet cells that produce the mucin MUC2, the principal component of intestinal mucus. Consistent with these observations, we showed that Muc2 deficiency results in the spontaneous development of tumors along the entire gastrointestinal tract, independently of deregulated Wnt signaling. To dissect the complex interaction between Muc2 and Apc in intestinal tumorigenesis and to elucidate the mechanisms of tumor formation in Muc2−/− mice, we crossed the Muc2−/− mouse with two mouse models, Apc1638N/+ and ApcMin/+, each of which carries an inactivated Apc allele. The introduction of mutant Muc2 into Apc1638N/+ and ApcMin/+ mice greatly increased transformation induced by the Apc mutation and significantly shifted tumor development toward the colon as a function of Muc2 gene dosage. Furthermore, we showed that in compound double mutant mice, deregulation of Wnt signaling was the dominant mechanism of tumor formation. The increased tumor burden in the distal colon of Muc2/Apc double mutant mice was similar to the phenotype observed in ApcMin/+ mice that are challenged to mount an inflammatory response, and consistent with this, gene expression profiles of epithelial cells from flat mucosa of Muc2-deficient mice suggested that Muc2 deficiency was associated with low levels of subclinical chronic inflammation. We hypothesize that Muc2−/− tumors develop through an inflammation-related pathway that is distinct from and can complement mechanisms of tumorigenesis in Apc+/− mice. [Cancer Res 2008;68(18):7313–22]
Developing and implementing an institute-wide data sharing policy
Authors: Stephanie OM Dyke, Tim JP Hubbard
Journal: Genome Medicine (2011)

The Wellcome Trust Sanger Institute has a strong reputation for prepublication data sharing as a result of its policy of rapid release of genome sequence data and particularly through its contribution to the Human Genome Project. The practicalities of broad data sharing remain largely uncharted, especially to cover the wide range of data types currently produced by genomic studies and to adequately address ethical issues. This paper describes the processes and challenges involved in implementing a data sharing policy on an institute-wide scale. This includes questions of governance, practical aspects of applying principles to diverse experimental contexts, building enabling systems and infrastructure, incentives and collaborative issues.
A Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Ian Flinn, Nancy L. Bartlett, Kristie A. Blum, Kirit M Ardeshna, Ann LaCasce, Christopher R. Flowers, Andrei R. Shustov, Kenneth Thress, Fred Zheng, Jeffery Skolnik, Jonathan W. Friedberg
Journal: Blood (2014)
Extraction of Foreign Bodies from the Ear
Authors: H. A. A. Nicholls
Journal: BMJ (1876)

et about a fourth of an ins i t' of fresh air, and do not keep the -piece quite close to the tace -ill the twitchings have nearly ceased.I lave never seen any harm result from the condition which causes tlese movements.If air were not given, they would increase, and then sbp; the respiration would become intermittent, and, some time after tlis, the heart would cease to beat.The fact that death may be pro- cuced, if signs of danger are disregarded, applies to all anesthetics.Nhenever the breathing becomes jerking, sobbing, or intermittent, the iace-piece should be removed, but applied directly the breatlhing loses that character, unless the pulse is much depressed.It is muclh less important to watch the pulse whilst giving gas and ether than in giving chloroform, but it is desirable; for, when it decidedly loses power, we may safely admit a little fresh air, and tlhus anticipate the need of re- moving the face-piece to a greater extent on account of muscular twitchmg or stertor.If the finger be talken from the pulse to do something else, I would give a little air, unless the patient had only just begun to inhale, or was evidently but slightly unider the anaesthetic.
Longitudinal changes of body mass index, spirometry and diffusion in a general population
Authors: M. Bottai, F. Pistelli, F. Di Pede, L. Carrozzi, S. Baldacci, G. Matteelli, A. Scognamiglio, G. Viegi
Journal: European Respiratory Journal (2002)

The aim of this study was to evaluate the effects of body mass index (BMI) changes over an 8-yr follow-up, on longitudinal changes of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and carbon monoxide diffusing capacity of the lung (DL,CO) indices in a general population sample of North Italy. To avoid including weight changes possibly related to physical growth, only the 1,426 adults (>24 yrs, 46% males) with complete follow-up were selected. Median linear regression models were applied to estimate the medians of change (computed as follow-up minus baseline values) of VC, FVC, FEV1 and DL,CO indices, as functions of changes of BMI over the follow-up period, separately by sex, after considering several potential confounders and effect modifiers. The extent of lung function loss tended to be higher among those who, at baseline, reported greater BMI values. Males experienced larger losses than females (20 and 16 mL FEV1 median reduction for a BMI unit increase in males and females, respectively). Conversely, longitudinal changes of BMI caused a slight and nonsignificant increase in DL,CO values in both sexes. Over an 8-yr follow-up, the detrimental effect of gaining weight might be reversible for many adults as most of those who reduced their body mass index values also increased their lung function. Overweight patients with ventilatory impairment should be routinely encouraged to lose weight for improving their lung function.
Interleukin 1: Regulation of hepatic carbohydrate metabolism by insulin or insulinomimesis
Authors: Oliver E. Owen
Journal: Hepatology (1987)

The purpose of this study was to investigate the effect of interleukin 1 (IL 1) on glucocorticoid-regulated hepatic metabolism. Steroid binding in liver cytosol, plasma glucose, plasma corticoster-one, and phosphenolpyruvate carboxykinase (PEPCK) activity were assayed in C3H/HeJ mice after IL 1 administration. Mice received 5 pyrogenic U (PU) of rabbit IL 1 i.p. and were sacrificed 4 hr later. In adrenal-intact mice, steroid binding and plasma glucose were significantly decreased (63 and 64% of control) and plasma corticosterone was significantly elevated threefold. In adrenalectomized mice, IL 1 (5 PU) treatment produced similar results in steroid binding (66% of control) and plasma glucose (71% of control). PEPCK was measured in intact mice fasted overnight and treated with 5 PU of IL 1. PEPCK was induced in fasted control animals (23.1 ± 1.4 U/mg) vs fed control animals (15.9 ± 0.7 U/mg). IL 1 treatment inhibited the induction of PEPCK in fasted animals (13.4 ± 2.0 U/mg) and caused a significant decrease in steroid binding (78% of fasted control) and plasma glucose (82% of fasted control). No difference in plasma corticosterone was seen in IL 1-treated mice and fasted control mice. These data indicate that IL 1 decreases intracellular steroid receptors, resulting in decreased induction of PEPCK and subsequent reduced gluconeogenesis and plasma glucose. We propose that IL 1 plays a regulatory role in glucocorticoid-regulated hepatic metabolism.
Cutaneous mercury deposits after henna dye application in the arm
Authors: G. Mouzopoulos, V. Tsouparopoulos, M. Stamatakos, I. Mihelarakis, D. Pasparakis, E. Agapitos
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Henna is used to prepare hair and body dyes. It is obtained from dried leaves which are powdered and mixed with oil or water.1 Application of temporary henna tattoos is popular in holiday resorts of the Mediterranean area among young people. However, this application may be accompanied by topical or systematic complications. Allergic contact dermatitis resulting from henna tattoo mixtures has been already reported, but there have been no reports concerning the effects of heavy metals, such as mercury, on granuloma formation and cutaneous abscess after henna tattoo application. Herein we describe a case of cutaneous mercury deposit after the application of henna dye containing red pigment and we discuss its diagnosis and proper management. A 13‐year‐old boy presented to us with a painful cutaneous granuloma and abscess on the lateral aspect of his swollen arm (Fig. 1). From history‐taking the parent revealed an incident of hot water burn in this particular region of the arm. Initial physical examination showed a second‐degree burn with signs of inflammation. He was given oral antibiotics and painkillers. Care of the wound was done with occlusive dressings. The patient was discharged after a single day of hospitalization, to be re‐examined in a week. Upon re‐examination we concluded that the signs of inflammation had subsided but the cutaneous granulomas were still present.