tbuckley/cabot-search huggingface dataset:
Need for improved societal effort to keep inflammatory bowel disease patients in the labour market?
Authors: Tine Jess
Journal: Gut (2012)

The rate of work disability (WD) among patients with inflammatory bowel disease (IBD) varies from a few per cent in some studies to one-third of the IBD population in other studies.1–3 Differences in rates may to some extent depend on whether disability is self-reported or based on actual numbers of patients receiving disability pension (DP). However, even when focusing specifically on the number of patients receiving DP, rates vary markedly between study populations, potentially due to (1) differences in study designs, for example, selective assessment of patients from tertiary referral centres representing the more severely ill part of patients, which may be more likely to receive DP; (2) differences in length of follow-up of populations, if cumulative morbidity is seen as a predictor for DP; and (3) differences between regions or countries in societal acceptance of disease, in effort to help people back at work, or in accepted qualifications for DP.

Dr Hoivik and colleagues present the results of a 10-year follow-up study on WD and DP in a well-characterised, population-based and prospectively followed Norwegian IBSEN cohort.3 The IBSEN cohort represents all patients diagnosed with IBD during 1990–1993 (n=843) in a well-defined part of south-eastern Norway. Patients have been followed prospectively from diagnosis of IBD …
Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction
Authors: Masaru Hayashi, Takayoshi Tsutamoto, Atsuyuki Wada, Takashi Tsutsui, Chitose Ishii, Keijin Ohno, Masanori Fujii, Atsushi Taniguchi, Tomokazu Hamatani, Yoshitaka Nozato, Ken Kataoka, Naoki Morigami, Masato Ohnishi, Masahiko Kinoshita, Minoru Horie
Journal: Circulation (2003)

Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling.To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0+/-0.6% to 53.2+/-0.8% versus 46.5+/-0.8% to 51.0+/-0.8%, Pinteraction=0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5+/-1.0 to 90.6+/-2.4 versus 87.5+/-1.3 to 106.8+/-3.5 mL/m2, Pinteraction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (Pinteraction=0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (Pinteraction=0.002).These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.
Improving the Accuracy of Mammography: Volume and Outcome Relationships
Authors: Laura Esserman, Helen Cowley, Carey Eberle, Alastair Kirkpatrick, Sophia Chang, Kevin Berbaum, Alastair Gale
Journal: JNCI Journal of the National Cancer Institute (2002)

Countries with centralized, high-volume mammography screening programs, such as the U.K. and Sweden, emphasize high specificity (low percentage of false positives) and high sensitivity (high percentage of true positives). By contrast, the United States does not have centralized, high-volume screening programs, emphasizes high sensitivity, and has lower average specificity. We investigated whether high sensitivity can be achieved in the context of high specificity and whether the number of mammograms read per radiologist (reader volume) drives both sensitivity and specificity.The U.K.'s National Health Service Breast Screening Programme uses the PERFORMS 2 test as a teaching and assessment tool for radiologists. The same 60-film PERFORMS 2 test was given to 194 high-volume U.K. radiologists and to 60 U.S. radiologists, who were assigned to low-, medium-, or high-volume groups on the basis of the number of mammograms read per month. The standard binormal receiver-operating characteristic (ROC) model was fitted to the data of individual readers. Detection accuracy was measured by the sensitivity at specificity = 0.90, and differences among sensitivities were determined by analysis of variance.The average sensitivity at specificity = 0.90 was 0.785 for U.K. radiologists, 0.756 for high-volume U.S. radiologists, 0.702 for medium-volume U.S. radiologists, and 0.648 for low-volume U.S. radiologists. At this specificity, low-volume U.S. radiologists had statistically significantly lower sensitivity than either high-volume U.S. radiologists or U.K. radiologists, and medium-volume U.S. radiologists had statistically significantly lower sensitivity than U.K. radiologists (P<.001, for all comparisons).Reader volume is an important determinant of mammogram sensitivity and specificity. High sensitivity (high cancer detection rate) can be achieved with high specificity (low false-positive rate) in high-volume centers. This study suggests that there is great potential for optimizing mammography screening.
Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.
Authors: M Robinson, A L Hemming, J A Regnis, A G Wong, D L Bailey, G J Bautovich, M King, P T Bye
Journal: Thorax (1997)

Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline.Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl.There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1.Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.
Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure
Authors: Maciej Tomaszewski, James Eales, Matthew Denniff, Stephen Myers, Guat Siew Chew, Christopher P. Nelson, Paraskevi Christofidou, Aishwarya Desai, Cara Büsst, Lukasz Wojnar, Katarzyna Musialik, Jacek Jozwiak, Radoslaw Debiec, Anna F. Dominiczak, Gerjan Navis, Wiek H. van Gilst, Pim van der Harst, Nilesh J. Samani, Stephen Harrap, Pawel Bogdanski, Ewa Zukowska-Szczechowska, Fadi J. Charchar
Journal: Journal of the American Society of Nephrology (2015)

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P = 9.65 × 10(-5)) and diastolic BP (P = 7.61 × 10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0 × 10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples
Authors: S. Lundstrom, A. Reichenberg, H. Anckarsater, P. Lichtenstein, C. Gillberg
Journal: BMJ (2015)

<b>Objective</b> To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. <b>Design</b> Population based study. <b>Setting</b> Child and Adolescent Twin Study and national patient register, Sweden. <b>Participants</b> 19 993 twins (190 with autism spectrum disorder) and all children (n=1 078 975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. <b>Main outcome measures</b> Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. <b>Results</b> The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (P&lt;0.001 for linear trend). <b>Conclusions</b> The prevalence of the autism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder.
First evidence of oncologic neuropathic pain prevalence after screening 8615 cancer patients. Results of the On study
Authors: M.L. García de Paredes, F. del Moral González, P. Martínez del Prado, J.L. Martí Ciriquián, S. Enrech Francés, M. Cobo Dols, E. Esteban González, A.L. Ortega Granados, M. Majem Tarruella, J.D. Cumplido Burón, A. Gascó Hernández, E. López Miranda, J.P. Ciria Santos, F.J. de Castro Carpeño
Journal: Annals of Oncology (2010)
Inhibition of Histone Deacetylase Class I but not Class II Is Critical for the Sensitization of Leukemic Cells to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis
Authors: Satoshi Inoue, Antonello Mai, Martin J.S. Dyer, Gerald M. Cohen
Journal: Cancer Research (2006)

Abstract From work done largely on derived cell lines, it has been suggested that tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) might be a therapeutic target for many forms of malignancy. However, use of primary tumor cells, including chronic lymphocytic leukemic (CLL) cells, has shown inherent resistance to TRAIL. Although the molecular basis for this resistance remains unknown, treatment with histone deacetylase inhibitors (HDACi) often sensitizes resistant cells to TRAIL-induced apoptosis. We used structurally diverse HDACi to ascertain which HDAC needs to be inhibited for the sensitization. Inhibition of HDAC class I but not class II is required for sensitization to TRAIL-induced apoptosis of CLL cells and various cell lines. Using different HDACi together with small interfering RNA for HDAC1, HDAC2, HDAC3, and HDAC6, we report that inhibition of HDAC1 and HDAC2 but not HDAC3, HDAC6, and HDAC8 are primarily responsible for sensitization to TRAIL-induced apoptosis. Based on these data and our previous studies, we propose that a clinical trial in CLL is warranted using a combination of a selective HDACi that inhibits HDAC1 and/or HDAC2 together with a form of TRAIL that signals through TRAIL receptor 1. (Cancer Res 2006; 66(13): 6785-92)
Higher Levels of Urinary Albumin Excretion Within the Normal Range Predict Faster Decline in Glomerular Filtration Rate in Diabetic Patients
Authors: Tetsuya Babazono, Izumi Nyumura, Kiwako Toya, Toshihide Hayashi, Mari Ohta, Kumi Suzuki, Yuka Kiuchi, Yasuhiko Iwamoto
Journal: Diabetes Care (2009)

OBJECTIVE To assess the relationship between albuminuria, including elevation within the normal range, and decline in glomerular filtration rate (GFR) in diabetic patients. RESEARCH DESIGN AND METHODS A total of 5,449 Japanese diabetic patients were categorized according to sex and urinary albumin-to-creatinine ratio (ACR; <5, 5-9, 10-29, 30-99, 100-299, 300-999, 1,000-2,999, and > or =3,000 mg/g) and followed for at least 5 years. The rate of change in estimated GFR (eGFR) adjusted for age and baseline eGFR was compared among ACR categories. RESULTS A higher baseline ACR predicted a faster decline in eGFR for both sexes. Even within the normal range (<30 mg/g), ACR > or =10 mg/g in women and > or =5 mg/g in men was associated with a significantly greater rate of decline in eGFR relative to subjects with ACR <5 mg/g. CONCLUSIONS Elevated ACR, even within the normal range, is associated with a faster decline in eGFR in diabetic patients.
Alteration of the Soluble Guanylate Cyclase System in the Vascular Wall of Lead-Induced Hypertension in Rats
Authors: María Marques, Inmaculada Millás, Ana Jiménez, Elena García-Colis, Juan A. Rodriguez-Feo, Sandra Velasco, Alberto Barrientos, Santos Casado, Antonio López-Farré
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Low-level lead exposure is a known cause of hypertension that has been associated with increased reactive oxygen species activity and endothelial-dependent vasorelaxation impairment. The effect of lead exposure on the vascular nitric oxide (NO)/cyclic guanocine monophosphate (cGMP) system was analyzed. Wistar rats were exposed to 5 ppm lead acetate in the drinking water during 30 d. Mean arterial BP increased significantly in the lead-treated rats. Relaxation to both acetylcholine and sodium nitroprusside (SNP) was reduced in lead-treated rats; however, the vascular wall of lead-administered rats showed an increased expression of endothelial NO synthase. The expression of both subunits (α1 and β1) of soluble guanylate cyclase (sGC) and the cGMP accumulated in the vascular wall were decreased in lead-treated rats. Cotreatment of lead with vitamin C (3 mmol/L) prevented the increase on mean arterial BP, improved the relaxation to both acetylcholine and sodium nitroprusside, and restored the normal expression of endothelial NO synthase and sGC proteins in the vascular wall. In conclusion, lead exposure altered both the endothelium-dependent and -independent relaxing response and induced a reduced expression of sGC in the vascular wall. These effects were abrogated with the antioxidant vitamin C, which suggests the involvement of reactive oxygen species in the regulation of the NO/cGMP relaxing system in the vascular wall of lead-treated rats.
Granulocyte–Macrophage Colony-stimulating Factor to Reverse Sepsis-associated Immunosuppression
Authors: Christian Meisel, Joerg C Schefold, Rene Pschowski, Tycho Baumann, Katrin Hetzger, Jan Gregor, Steffen Weber-Carstens, Dietrich Hasper, Didier Keh, Heidrun Zuckermann, Petra Reinke, Hans-Dieter Volk
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Sustained sepsis-associated immunosuppression is associated with uncontrolled infection, multiple organ dysfunction, and death.In the first controlled biomarker-guided immunostimulatory trial in sepsis, we tested whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses monocyte deactivation, a hallmark of sepsis-associated immunosuppression (primary endpoint), and improves the immunological and clinical course of patients with sepsis.In a prospective, randomized, double-blind, placebo-controlled, multicenter trial, 38 patients (19/group) with severe sepsis or septic shock and sepsis-associated immunosuppression (monocytic HLA-DR [mHLA-DR] <8,000 monoclonal antibodies (mAb) per cell for 2 d) were treated with GM-CSF (4 microg/kg/d) or placebo for 8 days. The patients' clinical and immunological course was followed up for 28 days.Both groups showed comparable baseline mHLA-DR levels (5,609 +/- 3,628 vs. 5,659 +/- 3,332 mAb per cell), which significantly increased within 24 hours in the GM-CSF group. After GM-CSF treatment, mHLA-DR was normalized in 19/19 treated patients, whereas this occurred in 3/19 control subjects only (P < 0.001). GM-CSF also restored ex-vivo Toll-like receptor 2/4-induced proinflammatory monocytic cytokine production. In patients receiving GM-CSF, a shorter time of mechanical ventilation (148 +/- 103 vs. 207 +/- 58 h, P = 0.04), an improved Acute Physiology and Chronic Health Evaluation-II score (P = 0.02), and a shorter length of both intrahospital and intensive care unit stay was observed (59 +/- 33 vs. 69 +/- 46 and 41 +/- 26 vs. 52 +/- 39 d, respectively, both not significant). Side effects related to the intervention were not noted.Biomarker-guided GM-CSF therapy in sepsis is safe and effective for restoring monocytic immunocompetence. Use of GM-CSF may shorten the time of mechanical ventilation and hospital/intensive care unit stay. A multicenter trial powered for the improvement of clinical parameters and mortality as primary endpoints seems indicated. Clinical trial registered with www.clinicaltrials.gov (NCT00252915).
CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib
Authors: Roberto Piva, Bruce Ruggeri, Michael Williams, Giulia Costa, Ilaria Tamagno, Dario Ferrero, Valentina Giai, Marta Coscia, Silvia Peola, Massimo Massaia, Gabriella Pezzoni, Cecilia Allievi, Nicoletta Pescalli, Mara Cassin, Stefano di Giovine, Paola Nicoli, Paola de Feudis, Ivan Strepponi, Ilaria Roato, Riccardo Ferracini, Benedetta Bussolati, Giovanni Camussi, Susan Jones-Bolin, Kathryn Hunter, Hugh Zhao, Antonino Neri, Antonio Palumbo, Celia Berkers, Huib Ovaa, Alberto Bernareggi, Giorgio Inghirami
Journal: Blood (2007)
Targeting FSTL1 Prevents Tumor Bone Metastasis and Consequent Immune Dysfunction
Authors: Chie Kudo-Saito, Takafumi Fuwa, Kouichi Murakami, Yutaka Kawakami
Journal: Cancer Research (2013)

Bone metastasis greatly deteriorates the quality of life in patients with cancer. Although mechanisms have been widely investigated, the relationship between cancer bone metastasis and antitumor immunity in the host has been much less studied. Here, we report a novel mechanism of bone metastasis mediated by FSTL1, a follistatin-like glycoprotein secreted by Snail(+) tumor cells, which metastasize frequently to bone. We found that FSTL1 plays a dual role in bone metastasis-in one way by mediating tumor cell invasion and bone tropism but also in a second way by expanding a population of pluripotent mesenchymal stem-like CD45(-)ALCAM(+) cells derived from bone marrow. CD45(-)ALCAM(+) cells induced bone metastasis de novo, but they also generated CD8(low) T cells with weak CTL activity in the periphery, which also promoted bone metastasis in an indirect manner. RNA interference-mediated attenuation of FSTL1 in tumor cells prevented bone metastasis along with the parallel increase in ALCAM(+) cells and CD8(low) T cells. These effects were accompanied by heightened antitumor immune responses in vitro and in vivo. In clinical specimens of advanced breast cancer, ALCAM(+) cells increased with FSTL1 positivity in tumor tissues, but not in adjacent normal tissues, consistent with a causal connection between these molecules. Our findings define FSTL1 as an attractive candidate therapeutic target to prevent or treat bone metastasis, which remains a major challenge in patients with cancer.
SEROTYPES OF HFRS (HAEMORRHAGIC FEVER WITH RENAL SYNDROME) VIRUS IN EAST EUROPEAN AND FAR EASTERN U.S.S.R.
Authors: E.A. Tkachenko, M.A. Donets, G.V. Rezapkin, T.K. Dzagurova, A.P. Ivanov, E.V. Leshchinskaya, I. Reshetnikov, S.G. Drozdov, R.A. Slonova, G.P. Somov
Journal: The Lancet (1982)
Analysis of the receptor-ligand interactions in the natural killer–mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112)
Authors: Daniela Pende, Grazia Maria Spaggiari, Stefania Marcenaro, Stefania Martini, Paola Rivera, Andrea Capobianco, Michela Falco, Edoardo Lanino, Ivana Pierri, Renato Zambello, Andrea Bacigalupo, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Journal: Blood (2004)
Early B Cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue
Authors: Hui Gao, Niklas Mejhert, Jackie A. Fretz, Erik Arner, Silvia Lorente-Cebrián, Anna Ehrlund, Karin Dahlman-Wright, Xiaowei Gong, Staffan Strömblad, Iyadh Douagi, Jurga Laurencikiene, Ingrid Dahlman, Carsten O. Daub, Mikael Rydén, Mark C. Horowitz, Peter Arner
Journal: Cell Metabolism (2014)