tbuckley/cabot-search huggingface dataset:
Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group
Authors: Suzana Jordan, Jörg H W Distler, Britta Maurer, Dörte Huscher, Jacob M. Van Laar, Yannick Allanore, Oliver Distler, Tore K. Kvien, Paolo Airo, Juan José Alegre Sancho, Lidia Ananjeva, Codrina Michaela Ancuta, Martin Aringer, Alexandra Balbir-Gurman, Francesco Paolo Cantatore, Paola Caramaschi, Emmanuel Chatelus, Veronica Codullo, Dominique Farge-Bancel, Rosario Foti, Armando Gabrielli, Jörg Henes, Ilka Herrgott, Florenzo Iannone, Francesca Ingegnoli, Esthela Loyo, Marco Matucci-Cerinić, Walid Ahmed Abdel Atty Mohamed, Ulf Müller-Ladner, Øyvind Palm, Sergiu Popa, Gabriela Riemekasten, Simona Rednic, Edoardo Rosato, Marta Saracco, Agneta Scheja, Vanessa Smith, Carina Mihai, Gabriela Szucs, Matija Tomšić, Gabriele Valentini, Ulrich A. Walker, Rene Westhovens, Sule Kurhan Yavuz, Thierry Zenone
Journal: Annals of the Rheumatic Diseases (2014)

Objectives To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. Methods Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. Results 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; −24.0±5.2% vs −7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs −7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. Conclusions The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
Sinusoidal caliber in alcoholic and nonalcoholic liver disease: Diagnostic and pathogenic implications
Authors: Eva I. Vidins, Robert S. Britton, Alan Medline, Laurence M. Blendis, Yedy Israel, Hector Orrego
Journal: Hepatology (1985)

Portal hypertension in alcoholic liver disease has been attributed to an increased resistance to blood flow either of sinusoidal or of postsinusoidal origin. The former should be accompanied by sinusoidal compression while the latter is expected to result in an increased or a normal sinusoidal diameter. Patients with alcoholic liver disease showed a marked reduction (p less than 0.001) in relative sinusoidal area (995 +/- 135 micron 2; n = 19) when compared to nonalcoholic patients with normal liver histology (5,100 +/- 389 micron 2; n = 6), or to patients with nonalcoholic liver disease (6,242 +/- 467 micron 2; n = 19). Hepatocyte surface area was significantly increased in patients with alcoholic liver disease when compared to hepatocytes from normal biopsies (563 +/- 32 micron 2 vs. 301 +/- 26 micron 2; p less than 0.001). Patients with nonalcoholic liver disease had hepatocyte surface areas within the normal range (327 +/- 14 micron 2). There was a significant inverse correlation between hepatocyte size and sinusoidal area (r = -0.63; p less than 10(-6); n = 44), indicating that larger hepatocytes were associated with sinusoidal compression. In the alcoholic patients, portal pressure correlated inversely (r = -0.77; p less than 0.01) with sinusoidal area only after the sinusoidal area was markedly reduced to areas below 20% of normal. Such a threshold was not reached in patients with nonalcoholic liver disease, in whom no correlation between sinusoidal area and portal pressure was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats
Authors: M. McGuire, A. Bradford
Journal: European Respiratory Journal (2001)

Sleep-disordered breathing is associated with pulmonary hypertension and raised haematocrit. The multiple episodes of apnoea in this condition cause chronic intermittent hypoxia and hypercapnia but the effects of such blood gas changes on pulmonary pressure or haematocrit are unknown. The present investigation tests the hypothesis that chronic intermittent hypercapnic hypoxia causes increased pulmonary arterial pressure and erythropoiesis. Rats were treated with alternating periods of normoxia and hypercapnic hypoxia every 30 s for 8 h per day for 5 days per week for 5 weeks, as a model of the intermittent blood gas changes which occur in sleep-disordered breathing in humans. Haematocrit, red blood cell count and haemoglobin concentration were measured each week and systemic and pulmonary arterial blood pressure and heart weight were measured after 5 weeks. In relation to control, chronic intermittent hypercapnic hypoxia caused a significant increase in systemic (104.3+/-4.7 mmHg versus 121.0+/-10.4 mmHg) and pulmonary arterial pressure (20.7+/-6.8 mmHg versus 31.3+/-7.2 mmHg), right ventricular weight (expressed as ratios) and haematocrit (45.2+/-1.0% versus 51.5+/-1.5%). It is concluded that the pulmonary hypertension and elevated haematocrit associated with sleep-disordered breathing is caused by chronic intermittent hypercapnic hypoxia.
Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function
Authors: Ketul R. Chaudhary, Sri Nagarjun Batchu, Dipankar Das, Mavanur R. Suresh, John R. Falck, Joan P. Graves, Darryl C. Zeldin, John M. Seubert
Journal: Cardiovascular Research (2009)

AimsThis study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null).
Clinical outcome of S-1 monotherapy in patients with advanced non-small cell lung cancer after treatment of pemetrexed
Authors: Makoto Kawaishi, Hiroshi Wakui, Yutaka Yoshii, Kenji Kobayashi, Saburo Ito, Naoki Takasaka, Jun Kojima, Takeo Ishikawa, Kenichiro Shimizu, Takanori Numata, Hirromichi Hara, Keisuke Saito, Yumi Kaneko, Jun Araya, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2013)

Introduction: S-1 is an oral fluoropyrimidine anticancer drug that contains tegafur, gimeracil, and oteracil potassium. The target of S-1 is considered thymidylate synthase, which is known as that of pemetrexed (PEM). Recently, phIIIstudies have demonstrated that S-1 in combination with platinum agent has promising efficacy for patients with advanced non-small cell lung cancer as first-line treatment. However, clinical outcome of S-1 monotherapy after treatment of PEM has not been evaluated yet.  Aims: To evaluate the efficacy of single agent S-1 in patients with advanced non-squamous non-small cell lung cancer (NSCLC) after PEM treatment.  Methods: To assess the clinical outcome of S-1 monotherapy in patients with non-squamous NSCLC after PEM treatment, we reviewed the clinical records of patients treated with S-1 in Jikei University Hospital, from June 2009 to February 2013. Response rate (RR) and progression free survival (PFS) and toxity were evaluated.  Results: The 14 patients with lung adenocarcinoma were reviewed in this retrospective study. There were 8 males and 6 females with the median age of 69 years (range, 54-82 years). The subjects included 2 patients with PS 0, 5 with PS 1, and 7 with PS 2, and 1 patients in the stage of IIIA and 13 in IV.S-1 was used as third -line treatment for 2 patient, fourth-line treatment for 6, fifth-line treatment for 3, and sixth-line treatment for 3. As the results, the RR were 0 %, but 8 patients had SD and 3 patients had non-PR / non-PD. The median PFS were 5.1 months (range, 0.4-14.8 months).  Conclusions: Advanced non-squamous NSCLC patients receiving S-1 after treatment of PEM have not response but have better PFS.
A SEROLOGICAL DIFFERENTIATION OF SPECIFIC TYPES OF BOVINE HEMOLYTIC STREPTOCOCCI (GROUP B)
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1934)

Under uniform diet conditions the normal bile fistula dog will eliminate pretty constant amounts of cholesterol—about 0.5 to 1.0 mg. cholesterol per kilo per 24 hours. Diets rich in cholesterol (egg yolk) will raise the cholesterol output in the bile but compared to the diet intake (1.5 gm. cholesterol) the output increase in the bile is trivial (5–15 mg.). Calves' brains in the diet are inert. Bile salt alone will raise the cholesterol output in the bile as much and often more than a cholesterol rich diet. Bile salt plus egg yolk plus whole bile give maximal output figures for bile cholesterol—60 mg. per 24 hours. Liver injury (chloroform) decreases both bile salt and cholesterol elimination in the bile. Blood destruction (hydrazine) fails to increase the bile cholesterol output and this eliminates the red cell stroma as an important contributing factor. Certain cholagogues (isatin and decholin) will increase the bile flow but cause no change in cholesterol elimination. The ratio of cholesterol to bile salt in the bile normally is about 1 to 100 but the bile salts are more labile in their fluctuations. The ratio is about reversed in the circulating blood plasma where the cholesterol is high (150–300 mg. per cent) and the bile salt concentration very low. Cholesterol runs so closely parallel to bile salt in the bile that one may feel confident of a physical relationship. In addition there is a suspicion that the bile cholesterol is in some obscure fashion linked with the physiological activity of hepatic epithelium.
CIP2A Modulates Cell-Cycle Progression in Human Cancer Cells by Regulating the Stability and Activity of Plk1
Authors: Jae-Sung Kim, Eun Ju Kim, Jeong Su Oh, In-Chul Park, Sang-Gu Hwang
Journal: Cancer Research (2013)

Abstract Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1–dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development. Cancer Res; 73(22); 6667–78. ©2013 AACR.
Meta-Analysis of Nonpharmacological Interventions for Neuropsychiatric Symptoms of Dementia
Authors: Henry Brodaty, Caroline Arasaratnam
Journal: American Journal of Psychiatry (2012)

A meta-analysis showed that 9–12 sessions of supportive help delivered in the home to family caregivers for dementia patients had a salutary effect for the patients' behavioral symptoms, such as screaming and aggression, similar in size to the effect of pharmacological interventions. Psychosis was much less responsive. There was a smaller, but significant amelioration of caregiver reactions to the patient's behavioral symptoms.
[7] IN PTS WHO CLEAR HCVRNA AT WEEK 12, SVR IS HIGHER AFTER 72 THAN AFTER 48 WEEKS TX: RESULTS OF A RANDOMIZED CONTROLLED TRIAL (RCT)
Authors: A. Mangia, N. Minerva, D. Bacca, V. Carretta, N. Vuturo, G.L. Ricci, M. Romano, M. Cela, G. Scotto, G. Cristoforo, R. Cozzolongo, L. Mottola, A. Andriulli
Journal: Journal of Hepatology (2007)
Urinary 7α-hydroxy-3-oxochol-4-en-24-oic and 3-oxochola-4,6-dien-24-oic acids in infants with cholestasis
Authors: Akihiko Kimura, Mikako Suzuki, Tsuyoshi Murai, Takao Kurosawa, Masahiko Tohma, Michio Sata, Toshiro Inoue, Atsuo Hoshiyama, Eisuke Nakashima, Yasuhiro Yamashita, Takuji Fujisawa, Hirohisa Kato
Journal: Journal of Hepatology (1998)
Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?
Authors: M Drent, JA Jacobs, J de Vries, RJ Lamers, IH Liem, EF Wouters
Journal: European Respiratory Journal (1999)

The aim of this study was to assess whether the cellular bronchoalveolar lavage fluid (BALF) profile, particularly the number of polymorphonuclear neutrophils (PMNs), is associated with disease severity of sarcoidosis and its usefulness in determining remission. Twenty-six nonsmoking outpatients with sarcoidosis were included in this study. The patients were divided into two subgroups according to the absolute number of PMNs in BALF: &lt; or =0.2x10(4) cells x mL(-1) (group 1; n = 15) and &gt;0.2x10(4) cells x mL(-1) (group 2; n = 11). The radiographic stage, high-resolution computed tomography (HRCT) findings, 67Ga lung uptake as well as lung function tests differed significantly between group 1 and 2. Follow-up revealed that 14 (93.3%) patients of group 1 compared to four (36.4%) of group 2 recovered spontaneously without the help of corticosteroids. In contrast, no differences were found in the number of lymphocytes in BALF nor in the serum angiotensin converting enzyme (sACE) level between both groups. The number of PMNs, the transfer factor of the lungs for carbon monoxide (TL,CO), the forced expiratory volume in one second (FEV1) and one of the HRCT subscores discriminated between patients with different disease progression. Of these parameters the PMNs appeared to be the only one which differentiated patients who demonstrated remission and those who deteriorated. In conclusion, these results indicate that the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid distinguish between sarcoidosis patients who demonstrated remission and those having a more severe course of the disease. Whether polymorphonuclear neutrophils may be considered as markers of disease activity and/or prognosis in sarcoidosis needs further investigation.
Myeloid Differentiation Factor-88/Interleukin-1 Signaling Controls Cardiac Fibrosis and Heart Failure Progression in Inflammatory Dilated Cardiomyopathy
Authors: Przemyslaw Blyszczuk, Gabriela Kania, Thomas Dieterle, Rene R. Marty, Alan Valaperti, Corinne Berthonneche, Thierry Pedrazzini, Christoph T. Berger, Stephan Dirnhofer, Christian M. Matter, Josef M. Penninger, Thomas F. Lüscher, Urs Eriksson
Journal: Circulation Research (2009)

The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease.The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure.Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure.Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy.
163 Underestimated impact of alcohol consumption on the progression of fibrosis in patients transplanted for HCV related cirrhosis: A comparative study with patients transplanted for alcohol-related cirrhosis
Authors: R. Sobesky, C. Francoz, H. Boudjema, V. Paradis, F. Dondero, J. Belghiti, D. Valla, P. Marcellin, F. Durand
Journal: Journal of Hepatology (2006)
Thymic stromal lymphopoietin and interleukin-4 mediate the pathogenesis of halothane-induced liver injury in mice
Authors: William R. Proctor, Mala Chakraborty, Aaron M. Fullerton, Midhun C. Korrapati, Pauline M. Ryan, Kenrick Semple, Jeffrey C. Morrison, Julia D. Berkson, Lynette S. Chea, Qian Yang, Albert P. Li, Rosanne Spolski, Erin E. West, Yrina Rochman, Warren J. Leonard, Mohammed Bourdi, Lance R. Pohl
Journal: Hepatology (2014)

Liver eosinophilia has been associated with incidences of drug-induced liver injury (DILI) for more than 50 years, although its role in this disease has remained largely unknown. In this regard, it was recently shown that eosinophils played a pathogenic role in a mouse model of halothane-induced liver injury (HILI). However, the signaling events that drove hepatic expression of eosinophil-associated chemokines, eotaxins, eosinophil infiltration, and subsequent HILI were unclear. We now provide evidence implicating hepatic epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) and type 2 immunity, in particular, interleukin-4 (IL-4) production, in mediating hepatic eosinophilia and injury during HILI. TSLP was constitutively expressed by mouse hepatocytes and increased during HILI. Moreover, the severity of HILI was reduced in mice deficient in either the TSLP receptor (TSLPR) or IL-4 and was accompanied by decreases in serum levels of eotaxins and hepatic eosinophilia. Similarly, concanavalin A–induced liver injury, where type 2 cytokines and eosinophils play a significant role in its pathogenesis, was also reduced in TSLPR-deficient mice. Studies in vitro revealed that mouse and human hepatocytes produce TSLP and eotaxins in response to treatment with combinations of IL-4 and proinflammatory cytokines IL-1β and tumor necrosis factor alpha. Conclusion : This report provides the first evidence implicating roles for hepatic TSLP signaling, type 2 immunity, and eosinophilia in mediating liver injury caused by a drug. (Hepatology 2014;60:1741-1752)
Validation of a global self-assessment and peer-review quality programme dedicated to comprehensive cancer centres: A method to assess, improve and promote quality of integrated care, research, and education in cancer centers
Authors: M. Saghatchian, H. Hummel, R. Otter, D. de Valeriola, W. van Harten, A. Paradiso, J. Lovey, M. Kasler, P. Fumoleau, U. Ringborg, T. Tursz
Journal: Journal of Clinical Oncology (2009)

e17565 Background: Oncology is a specialty requiring a combination of multidisciplinary expertises, novel technology, integration of innovation into care and research efforts in order to improve the quality of life and survival of patients. Provision of high-quality care and improvement of disease outcome should be promoted in cancer centers. Methods: The Organization of European Cancer Institutes developed an Accreditation Programme combining: 1-a quantitative questionnaire assessing the human, technical and financial resources and activities in care, research and education dedicated to oncology; 2- a set of standards and criteria for high-quality cancer management integrated in an electronic tool with a scoring system of compliance; 3- a peer-review process for review of the self-assessment outcome and on-site visits; 4- a report and improvement plan allowing to designate comprehensive cancer centers complying with required criteria for high-quality comprehensive cancer patient management. All components of the Accreditation Programme were tested in 8 different voluntary cancer centers in Europe. The objectives were to assess the feasibility, reproducibility and acceptance of the Accreditation Programme; to improve the standards and criteria in terms of understanding and consensus; to validate the peer review methodology and establish a method for reporting and implementing an improvement plan; to provide with a preliminary system of designation of comprehensive cancer centers based on criteria of high-quality integrated research, care and education. Results: The 2 consecutive pilot tests allowed to validate 1- relevant items for the quantitative questionnaire; 2-criteria and standards for high-quality integrated multidisciplinary cancer patient's management. 3-The impact of the Accreditation Programme on improvement of patients management and professionals involvement. Conclusions: The OECI Accreditation Programme is ready for dissemination. Participation to the Programme allows development of improvement plans for innovative and integrated comprehensive cancer patients management in cancer centers. No significant financial relationships to disclose.
Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects
Authors: Frances M K Williams, Aruna T Bansal, Joyce B van Meurs, Jordana T Bell, Ingrid Meulenbelt, Pradeep Suri, Fernando Rivadeneira, Philip N Sambrook, Albert Hofman, Sita Bierma-Zeinstra, Cristina Menni, Margreet Kloppenburg, P Eline Slagboom, David J Hunter, Alex J MacGregor, Andre G Uitterlinden, Tim D Spector
Journal: Annals of the Rheumatic Diseases (2012)

Objective Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD. Methods We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2. Results This study of 4600 individuals identified four single nucleotide polymorphisms with p&lt;5×10 −8 , the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10 −8 ) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (β=8.74×10 −4 , p=0.006). Conclusions LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway.