tbuckley/cabot-search huggingface dataset:
Depressive Disorders and HLA: A Gene on Chromosome 6 That Can Affect Behavior
Authors: Lowell R. Weitkamp, Harvey C. Stancer, Emmanuel Persad, Christine Flood, Sally Guttormsen
Journal: New England Journal of Medicine (1981)

To determine whether HLA-linked genes on chromosome 6 influence susceptibility to depressive disorders, we tested hypotheses concerning the distribution of HLA haplotypes among specific constellations of affected and unaffected family members. HLA haplotype identity among pairs of affected siblings in families with two affected siblings and among pairs of older unaffected siblings in families with one or two affected siblings was increased over random expectation (P less than 0.005). There was no increase in HLA haplotype identity among affected siblings in sibships with more than two affected members. When parents had a relative difference in estimated load of genes for susceptibility, HLA haplotypes were randomly transmitted to unaffected or affected children from the affected, "high-load" parent, but not from the unaffected, "low-load" parent (P less than 0.001). These results locate a gene contributing to susceptibility to depressive illness on chromosome 6 and provide a second example of the value of the hypotheses in defining the genetic bases of nonmendelian, familial diseases.
Methylprednisolone plus Chlorambucil as Compared with Methylprednisolone Alone for the Treatment of Idiopathic Membranous Nephropathy
Authors: Claudio Ponticelli, Pietro Zucchelli, Patrizia Passerini, Bruno Cesana
Journal: New England Journal of Medicine (1992)

Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2).
Outcomes of triple negative breast cancer in African-Americans vs. Caucasians: a community-based study.
Authors: MM Shah, JK Patel, NA Fischbach
Journal: Cancer Research (2009)

Abstract Abstract #3043 Background: Breast cancers with a triple negative tumor (TNT) subtype are associated with inferior outcomes and more recently racial disparities in patients with TNT have been demonstrated with African American women experiencing worse outcomes compared to Caucasians. This study examines association of race (AA vs. Caucasians) and breast cancer outcomes in a large community hospital TNT population.&amp;#x2028; Methods: Breast cancers of the TNT subtype were reviewed from a hospital-based tumor registry. Cases diagnosed from 1999 to 2006 were included in the study. Multivariate regression analyses were conducted including socio-demographic, and treatment factors. Endpoints were local/systemic recurrence and death.&amp;#x2028; Results: Of 1827 newly diagnosed cases of breast cancer from 1999- 2006, 93 were of the TNT subtype. A higher number of AA (17.58%) had TNT compared to Caucasians (3.7%). In patients with TNT, AA presented at a younger age (mean age 51.78 years vs. 58.52 years, (&amp;lt;50 years) (p value=0.07), had more advanced disease at diagnosis (stage 3) (5.38% vs. 1.08%; p value 0.001) and had a poor insurance status (uninsured and Medicaid) (9.68% vs. 4.30%; p value 0.004). There was no difference in the histologic grade of the tumors. AA had a higher rate of local recurrence (4.30% vs. 2.15%; p value 0.029), systemic recurrence (19% vs. 10%; p value 0.02) [Figure 2] and death (17.20% vs. 13.98%; p value 0.005) [Figure 1] compared to Caucasians.&amp;#x2028; &amp;#x2028; &amp;#x2028; &amp;#x2028; Even after adjusting for insurance status and treatment modalities, AA had a higher mortality rate compared to Caucasians (p value 0.014).&amp;#x2028; Conclusions: The high prevalence of TNTs among AA women and poorer survival in spite of adjusting for insurance and treatment modalities, suggests an underlying biologic variation with respect to race/ ethnicity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3043.
The Bleeding Time as a Screening Test for Evaluation of Platelet Function
Authors: Laurence A. Harker, Sherrill J. Slichter
Journal: New England Journal of Medicine (1972)

The value of the standardized template bleeding time was studied in 100 normal subjects and 136 patients with various disorders. With normal platelets the bleeding time in this test is 4.5 ± 1.5 minutes (± 1 S.D.) when the circulating platelet concentration exceeds 100,000 per microliter, and is 30.5 – (platelet count per μl/3850) minutes at platelet counts between 100,000 and 10,000 per microliter. More prolonged bleeding times reflect impaired platelet function, as associated with acetylsalicylic acid ingestion, uremia, or von Willebrand's disease. In contrast, bleeding times shorter than predicted with normal platelets are due to increased hemostatic competence of young platelets, associated either with idiopathic thrombocytopenic purpura or with bone-marrow recovery after chemotherapy. The standardized bleeding time measures the overall hemostatic role of platelets in vivo, and is thus suitable for systematic screening.
AB0259 The high basal level antibodies to modified citrullinated vimentin (anti-MCV) – predictive factor of response to tocilizumab therapy in rheumatoid arthritis
Authors: A.S. Avdeeva, E.N. Alexandrova, A.A. Novikov, E.Y. Panasyuk, M.V. Cherkasova, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab (TCZ) is a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6 from binding to its receptor. To evaluate the activity of RA, along with DAS 28 is often used clinical disease activity index (CDAI) and simplified disease activity index (SDAI). Given the marked reduction in acute-phase reactants during therapy TCZ, CDAI is the best complex indicator for assessing the effectiveness of therapy than the DAS 28, as it only takes into account the clinical indicators of activity and does not include laboratory data <h3>Objectives</h3> To evaluate the frequency of DAS 28, SDAI and CDAI remission during therapy TCZ and identify predictive factors of good response to treatment <h3>Methods</h3> Data were obtained from the first Russian open-label, Phase IV, multicenter 24 week study of the efficacy and safety of TCZ in RA. 42 pts with RA (32 woman, mean age 50,5; 43,0-55,0 years, mean disease duration 56,5; 23,0-81,0 months, mean DAS 28 6,4; 5,8-7,05, SDAI 45,0; 36,2-57,0, CDAI 41,5; 32,0-53,0) received 6 intravenous TCZ infusions (8 mg/kg) every 4 weeks, in combination with DMARDs and glucocorticoids. Erythrocyte sedimentation rate – ESR (mm/hr) was determined by Westergren method; serum concentrations of CRP (mg/L) were measured by laser nephelometry; antibodies to modified citrullinated vimentin – anti-MCV (U/ml) were tested using ELISA <h3>Results</h3> On the 24-th week of therapy values [Me; interquartile range] DAS 28 were 2.11 (1.29-2.77), SDAI 4,4 (2,0-8,8), CDAI 3,6 (1,4-7, 6), the DAS 28 remission (&lt;2,6) was achieved at 30 patients (71%), SDAI (≤3,3) - in 13 (31%), CDAI (≤2,8) - in 14 (33%). Correlation was found with basal level of anti-MCV and DAS 28 (r =0,4 p=0,02), SDAI (r =0,35, p=0.04) and CDAI (r =0,4 p=0,02).In depend on the CDAI remission on the 24-th week of treatment, all patients were divided into two groups. RA patients (n=14) who achieved CDAI remission on the 24-th week of therapy TCZ revealed a higher basal level anti-MCV (2236,1; 979,7-2492,8 U/ml) than in the group of patients (n=28) who remained disease activity (502,9; 49,6-1107,7 U/ml p=0,02). Logistic regression analysis confirmed that patients with a positive determination in serum anti-MCV were more likely to reach CDAI remission at the 24-th week of therapy TCZ than anti-MCV - negative (OR: 18.4; p=0.03). Factors such as gender, age, disease duration, level CRP and ESR had no affect the incidence of remission <h3>Conclusions</h3> The high basal level anti-MCV in RA can be consider as a predictive factor of CDAI remission at the 24-th week of therapy TCZ <h3>Disclosure of Interest</h3> None Declared
Salmonella's iron armor for battling the host and its microbiota
Authors: Manuela Raffatellu, Andreas J. Bäumler
Journal: Gut Microbes (2010)

Most Salmonella enterica serotypes are associated with acute intestinal inflammation and diarrhea in humans. While the mechanisms triggering intestinal inflammation are well studied, relatively little is known about how the pathogen benefits from causing disease. Recent work has provided first insights into the genetic design that enables S. enterica to benefit from the host response by outgrowing the microbiota in the gut. The pathogen gained an edge over its competitors by acquiring genes conferring resistance against antimicrobials, such as lipocalin-2, that are encountered in the intestinal lumen only during inflammation. This strategy enables the pathogen to exploit host responses to gain a competitive advantage over other microbes during its growth in the inflamed gut.
Abstract 253: Identification of novel EWSR1-CREB3L1 fusion transcript in small cell osteosarcoma
Authors: Larisa V. Debelenko, Bangalore R. Shivakumar, Lisa McGregor, Howard D. Dorfman, Susana Raimondi
Journal: Cancer Research (2010)

Abstract Small cell osteosarcoma (SCOS) is an aggressive variant of osteogenic sarcoma that has some morphologic similarities to Ewing sarcoma. Little is known about the molecular biology of SCOS and no specific molecular abnormality has been reported in this tumor subtype to date. We performed a molecular biology study of a SCOS that was positive for the Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement by interphase fluorescent in situ hybridization and negative for EWSR1-FLI1, EWSR1-ERG and EWSR1-WT1 fusion transcripts by reverse transcriptase polymerase chain reaction. Rapid amplification of cDNA ends with the EWSR1 gene-specific forward primers revealed the exon 6 of the cAMP responsive element binding protein 3-like 1 gene (CREB3L1) fused in-frame to the EWSR1 exon 11, consistent with the EWSR1-CREB2L1 fusion transcript expressed in tumor tissue. The corresponding chimeric gene in the tumor DNA was confirmed by amplification and subsequent sequencing of the genetic breakpoint located in introns 11 and 5 of the EWSR1 and CREB3L1, respectively. No reciprocal fusion transcript or gene could be amplified in the tumor. An approximately 68 kDa product detected in tumor tissue lysate by immunoblotting with the CREB3L1 carboxyterminal antibody was consistent with a 656 aa predicted chimeric protein. This is the first report of a fusion transcript in osteosarcoma that demonstrates the relation of molecular mechanism of SCOS subtype to that of Ewing sarcoma. The 3'end fusion partner and the inferred structure of the new EWSR1-CREB3L1 chimera, however, are different from those underlying Ewing sarcoma, predicting different functions of the novel fusion product. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 253.
Abstract C26: Chromatin remodeling system and visualization of the “archaic” cancer attractors
Authors: Yue Zhang, Stuart K. Calderwood, Hisashi Moriguchi, Yinghua Li
Journal: Cancer Research (2011)

Abstract The cancer cell attractors theory provides a novel understanding of carcinogenesis. The mechanisms that the ectopic expression of some germline genes result in somatic tumors such as melanoma and brain tumors are emerging but not well understood. From mammals to model organisms like Caenorhabditis elegans and Drosophila melanogaster, the versatile Mi-2/Nucleosome remodeling and histone deacetylation (NuRD) complexes alongside their functionally related chromatin remodeling complexes (CRCs), i.e. the dREAM/Myb-MuvB(MMB)complex and polycomb group (PcG) complex are typical bottle-necked regulators of cell attractors. The trajectory that benign cells switch to cancerous could be the reverse (or close) of navigation of embryonic cells converging from a series of intermediate transcriptional states to a final adult state, which is supported by Gene Expression Dynamics Inspector (GEDI) assays and some cross-species genetic evidences. Hence Cancer could be triggered by cells undergoing abnormal cell attractor transitions, and may be reversible with “cyto-education”. In additon, we identified multidrug resistence genes and extracellular matrix (ECM) genes as conserved hub molecule fro Mi-2/NuRD. A complementary study will go to tumorigenicity and immunogenicity of induced pluripotent stem celles and the strategies of supppression. The understanding of involvement of CRCs in locking cancer attractors may forecast cancer “weather” and help find the recipes of perturbing genes to achieve successful reprogramming such that the reprogrammed cancer cell function in the same way as the normal cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C26.
Abstract 4391: OCTN1- and OCTN2-mediated uptake of oxaliplatin in rat dorsal root ganglion neurons and HEK293 cells over-expressing OCTN1 or OCTN2
Authors: Nancy N. Jong, Takeo Nakanishi, Johnson J. Liu, Ikumi Tamai, Mark J. McKeage
Journal: Cancer Research (2011)

Abstract Purpose: Organic cation transporters (OCTs) have been recently implicated in the uptake and toxicity of oxaliplatin. Peripheral neuropathy is the dose-limiting toxicity of oxaliplatin due to accumulation of platinum in the dorsal root ganglia (DRG) and damage to sensory neurons. This study sought to determine the role of OCTs in the DRG neuronal uptake of oxaliplatin. Experimental Design: [14C] Oxaliplatin uptake and cytotoxicity in HEK/rOctn1, HEK/rOctn2, HEK/hOCTN1, HEK/hOCTN2, and primary culture of DRG neurons was determined to evaluate the role of Octn1 and Octn2 in oxaliplatin transport and neurotoxicity. mRNA, protein and functional expression of organic cation transporters in rat lumbar DRG were characterised using RT-PCR, Western blotting and uptake of model OCT substrates [3H] MPP, [14C] TEA, [3H] ergothioneine and [3H] L-carnitine. Results: HEK293 cells over-expressing rOctn1, rOctn2, hOCTN1 and hOCTN2 showed increased uptake and cytotoxicity of oxaliplatin compared to Mock-transfected HEK293 controls, and Octn2-mediated uptake of oxaliplatin was significantly higher than Octn1 in both human and rat. Uptake of ergothioneine mediated by Octn1, and L-carnitine mediated by Octn2, was decreased during oxaliplatin exposure. Rat DRG showed high Octn1 and Octn2 mRNA levels, and uptake of ergothioneine and L-carnitine that was temperature- and sodium-dependent and significantly inhibited by model substrates of Octn1 and Octn2. In contrast, DRG had negligible functional activity and low or undetectable mRNA levels of Oct1, Oct2, and Oct3. [14C] Oxaliplatin uptake by DRG neurons was temperature- and sodium-dependent and inhibited by ergothioneine and L-carnitine. Ergothioneine and L-carnitine uptake by DRG neurons was inhibited in the presence of oxaliplatin. Conclusions: In conclusion, Octn1 and Octn2, but not Oct1, Oct2 or Oct3, are functionally expressed in rat DRG neurons. Oxaliplatin uptake by rat DRG neurons and HEK293 cells was mediated by Octn2 and to lesser extent by Octn1. Supported by Grant-in-Aid for Scientific Research (B) (I. T.), Research Activity Start-up (T. N.), Auckland Medical Research Foundation (Doctoral Scholarship) and Cancer Society of New Zealand (Research Grant). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4391. doi:10.1158/1538-7445.AM2011-4391
INDUCTION OF PERTURBED SHEAR STRESS LEADS TO FOCAL ADVANCED ATHEROSCLEROTIC PLAQUE FORMATION IN TRANSGENIC MINIPIGS WITH HYPERCHOLESTEROLEMIA
Authors: Christian Bo Poulsen, Ryan M. Pedrigi, Vikram V. Mehta, Anouk Post, Nilesh Pareek, Niels Ramsing Holm, Dogu Kilic, Mohammed El-Bahnasawi, Martin M. Bjørklund, Niels Peter Andersen, Anne K. Grøndal, Arun Nachiappan, Nicolas Foin, Justin E R Davies, Carlo Di Mario, Hans Erik Bøtker, Jacob F. Bentzon, Erling Falk, Rob Krams, Ranil de Silva
Journal: Journal of the American College of Cardiology (2015)
GENDER-RELATED DIFFERENCES IN LONG-TERM OUTCOMES OF HOSPITAL SURVIVORS WITH ACUTE TYPE A AORTIC DISSECTION
Authors: Eduardo Bossone, Hans-Henning Eckstein, Elizabeth Jackson, Sherene Shalhub, Marc Bonaca, Marek Ehrlich, Linda Pape, Rumi Faizer, Gabriel Loor, Toru Suzuki, G. Chad Hughes, Anil Bhan, Alessandro Della Corte, Daniel Montgomery, Eric Isselbacher, Kim Eagle, Christoph A. Nienaber
Journal: Journal of the American College of Cardiology (2016)
1230 CLINICAL AND LABORATORY FEATURES AND NATURAL HISTORY OF SERONEGATIVE HEPATITIS (SNH)
Authors: F. Barry, L. Donaghy, J.G. Hunter, W. Stapleforth, I.A. Murray, J. Palmer, R. Bendall, A.M. Elsharkawy, H.R. Dalton
Journal: Journal of Hepatology (2013)
SP0063 Novel Therapeutic Approaches for Still’s Disease
Authors: N. Ruperto
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Systemic juvenile idiopathic arthritis (JIA), also known as Still’s disease, is the most severe category within the group of chronic childhood arthritis which are grouped under the umbrella term of JIA. Systemic JIA has been considered a therapeutic orphan until few years ago when the disease was treated primarily with corticosteroids with the known side effect especially on child growth. More recently the availability of new treatment modalities with biologic agents such as anti IL 6 (tocilizumab) and anti IL1 (anakinra, rilonacept and canakinumab) therapies have greatly advanced the possibilities for these children to be adequately treated. Two trials have been recently completed one with tocilizumab and the other with canakinumab. In the first trial, 112 children with systemic JIA with or without fever were randomized to receive tocilizumab (8 mg/kg every 2 weeks for children over 30 kg of body weight and 12 mg/kg every 2 weeks for children below 30 kg intravenously) or placebo for 3 months followed by an open label extension. After 3 months there was a clear discrimination between tocilizumab and placebo and at the end of year 1 80% of the patients reached at least 70% JIA ACR improvement with 52% able to discontinue corticosteroids. Adverse event were mainly infections and laboratory abnormalities such as neutropenia and aminotransferase elevation. A total of 6 deaths occurred, (3 during the conduct of the study and 3 after). There were also two canakinumab trials administered at a dose of 4 mg/kg/monthly subcutaneously. The first was a single dose double blind placebo controlled trial for 84 patients with fever at enrollment showing that up to 61% of the patients reached at least a JIA ACR 70 response already at day 15. The second Phase III trial was a classic withdrawal study design in which, after 32 weeks of open-label treatment with canakinumab, 100/177 patients who had at least a JIA ACR 30 response and underwent corticosteroid tapering were randomly assigned to continued treatment with canakinumab or to placebo in a double blind fashion until flared occurred. In the withdrawal part the risk of flare was 26% of patients in the canakinumab group versus 75% in the placebo group with corticosteroids discontinuation in 42/128 patients (33%). There were 7 cases of MAS, and infections were more frequent with canakinumab than with placebo. A total of 4 deaths occurred (2 during the trial and 2 after canakinumab discontinuation). This lecture will describe the most recent evidence for the treatment of systemic JIA. <h3>Disclosure of Interest</h3> None Declared
SAT0505 Factors Associated with Destabilized Hypertension during the Treatment of Gouty Arthritis with Nsaids
Authors: E. Mikhnevich, N. Artichevskaja
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Hypertension (HTN) is a prevalent comorbidity in gout and occurs due to various combinations of factors (hyperuricemia, pain, renal function, severity of HTN). During gout attack, the development of unstable HTN can occur, with NSAIDs playing an important role in its development. <h3>Objectives</h3> to determine factors contributing to destabilized HTN in patients with gout arthritis (GA) regularly taking their antihypertensive treatment (AHT). <h3>Methods</h3> 405 patients enrolled with acute GA fulfilled ACR 1977 classification criteria for acute GA (1977, ACR). 87,9% of patients were males with the mean age of 56,6±9,5 years and average disease duration of 8,4±6,8 years. All patients were given a short-life NSAIDs. Destabilized HTN was defined as sitting blood pressure (BP) &gt;140/90mmHg, demanding correction of AHT. 74,1% (n=300) of patients had HTN and only 61,7% (n=185) of them regularly took their AHT. The latter were divided into 2 groups: group 1 (n=73) without elevated BP during the treatment period (group HTN-) and group 2 (n=112) with destabilized HTN (group HTN+). The groups were comparable in sex, age and duration of gout. Characteristics of gout, parameters of severity of HTN, doses of NSAIDs and duration of treatment, 60 parameters in total, were compared between the groups HTN+ and HTN-. We defined the factors of destabilized HTN in patients with acute GA and effective treatment of HTN. <h3>Results</h3> Comparing various features of the groups HTN+ and HTN- we found that the patients from group HTN+ had more frequent episodes of proteinuria including MAU (OR-2,67; 95%Cl, 1,72-2,69; p=0,027). In the same group, we observed statistically more patients with elevated levels of C-reactive protein (OR-2,12, 95%Cl, 1,68 – 2,66; p=0,016). Before the first registration of raised BP, the duration of acute GA treatment with NSAIDs was statistically different between the groups: the patients receiving NSAIDs for 20 days and more (AUC =0,63, p=0,016, S=90,4%, Sp-33,9%, OR-3,23, 95%Cl - 2,61-4,00) had higher risk of HTN destabilization. We found no differences between the groups in pain characteristics (VAS, number of affected and tender joints). <h3>Conclusions</h3> Destabilized HTN during gout flares treated with NSAIDs was observed in 60,5% of patients regularly receiving their AHT. Destabilized HTN in patients with GA despite regular and effective AHT before GA was associated with the presence of proteinuria and elevated level of C-reactive protein, as well as with the duration of NSAID treatment. In these cases, the AHT should be intensified during gout attacks treated with NSAIDs, more appropriate anti-inflammatory approach being required. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1464