tbuckley/cabot-search huggingface dataset:
AB0993 Indirect Assessment of Amyloid A Deposits in Different Structures of the Kidneys – A Postmortem Clinicopathologic Study of 161 Rheumatoid Arthritis Patients
Authors: Ά. Apáthy, M. Bély
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Amyloidosis is a progressive, cumulative process, involving in its early stage only a few structures in some organs, and increasingly more in the later stages of the disease [1]. <h3>Objectives</h3> The aim of this study was to study amyloid A deposits in the kidneys of rheumatoid arthritis (RA) patients at death. <h3>Methods</h3> A randomized autopsy population of 161 in-patients with RA was studied. AA amyloidosis (AAa) complicated RA in 34 (21.1%) cases. Tissue samples of both kidneys were available for histologic evaluation in 33 of these 34 patients. The existence of amyloid A deposits in various structures was determined histologically. The extent of amyloid A deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved blood vessels per light microscopic field (x40 objective of an Olympus BX51). <h3>Results</h3> Amyloid deposition is increasing simultaneously in all structures of kidney, but deposition in various structures does not begin at the same time. <h3>Conclusions</h3> In manifest amyloidosis the amount of deposited amyloid A protein increases simultaneously in blood vessels and in other renal structures, but deposition does not start at the same time in different structures. Amyloid A deposition starts in the most frequently involved structures of the most frequently involved organ (1). In the kidneys amyloid A starts depositing in the wall of arterioles and small arteries. Later interstitial collagen fibers, glomeruli, and peripelvic fat tissue are involved. The involvement of peripelvic nerves and cortical basement membranes of the convoluted tubules indicates advanced stages of amyloid deposition in the kidney. This chronology of amyloid A deposition allows an indirect assessment of the stage of amyloidosis. Based on the involved structures in renal biopsy specimens the pathologist may estimate the involvement of other structures. Involvement of arterioles alone (without involvement of small arteries) indicates an early stage of amyloidosis, whereas and vica versa amyloid A deposits in peripheral nerves suggests an advanced stage with massive involvement of numerous glomeruli. <h3>References</h3> Bély M, Apáthy Άgnes: Clinical Pathology of rheumatoid arthritis: Cause of death, lethal complications and associated diseases in rheumatoid arthritis. First English edition. Published by Akadémiai Kiadό, Member of Wolters Kluwer Group. Budapest 2012 http://www.akkrt.hu <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1230
Abstract 276: Role of AP1 elements and TCL1 protein in regulation of the gene encoding PTPROt (protein tyrosine phosphatase receptor-type O) in chronic lymphocytic leukemia
Authors: Tasneem Motiwala, Jharna Datta, Huban Kutay, Satavisha Roy, Allyn Checovich, Nicola Zanesi, Mohamed Kaou, Amy Johnson, John Hagan, John C. Byrd, Carlo M. Croce, Samson T. Jacob
Journal: Cancer Research (2011)

Abstract The gene for protein tyrosine phosphatase receptor-type O encodes two functional isoforms in a tissue-specific manner. The full-length form is expressed in epithelial cells, particularly in the brain and kidney, whereas the truncated form (PTPROt) is primarily expressed in hematopoietic cells. We have previously demonstrated that PTPROt is a bona fide tumor suppressor (J Biol Chem. 2009 Jan 2;284(1):455-64) and is down-regulated in primary CLL samples (Clin Cancer Res. 2007 Jun 1;13(11):3174-81). Further, studies from two laboratories including ours have shown that Syk and Lyn, two key protein tyrosine kinases involved in B-cell receptor signaling, are substrates of PTPROt, igniting interest in understanding deregulation of this tyrosine phosphatase in CLL. While the PTPRO promoter is methylated, the mechanism of its silencing in the pathogenesis of CLL is unexplored. Here, we utilized the Tcl1 transgenic (Tg) mouse model of CLL and a cell line with TPA-inducible expression of PTPROt to elucidate the mechanism of PTPROt silencing. This study demonstrates that PTPROt is transcriptionally silenced in CD19+ spleen B cells from Tcl1 transgenic (Tg) mouse when compared to wild type mice. As observed with primary human CLL, the methylation of PTPRO CGI (CpG island) is significantly higher in Tcl1 Tg CLL B-lymphocytes than in normal B lymphocytes. Significant suppression of PTPROt is also observed at very early time-point (∼7 wks) in CD19+ spleen B-cells from Tcl1 Tg mice compared to normal spleen B-lymphocytes from age-matched WT mice in the absence of detectable methylation at CGI. This data suggests that transcriptional silencing occurs prior to methylation. To understand further the potential transcriptional mechanism of PTPROt suppression in CLL, the role of AP1 in the expression of this gene was explored. We first demonstrate that AP-1 activation by TPA in U937 cells induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. PTPROt promoter is also responsive to over- and under-expression of AP-1 confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that Tcl1 can repress PTPROt promoter by altering c-fos expression and c-jun activation state. These findings further substantiate the importance of TCL1 in the pathogenesis of CLL. [Supported, in part, by grants CA101956 and CA086978]. 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 276. doi:10.1158/1538-7445.AM2011-276
Systemic Carnitine Deficiency — A Treatable Inherited Lipid-Storage Disease Presenting as Reye's Syndrome
Authors: Paul R. Chapoy, Corrado Angelini, W. Jann Brown, Jacqueline E. Stiff, Austin L. Shug, Stephen D. Cederbaum
Journal: New England Journal of Medicine (1980)

A 3 1/2-year-old boy presented at three months of age with an acute episode of lethargy, somnolence, hypoglycemia, hepatomegaly, and cardiomegaly, which responded poorly to restoration of the blood sugar level to normal. The absence of ketonuria during subsequent episodes of severe hypoglycemia prompted a search for a defect in fatty acid oxidation. Plasma carnitine (2.0 to 5.0 mumol per liter), muscle carnitine (0.01 to 0.02 mumol per gram, wet weight) and liver carnitine (0.021 to 0.065 mumol per gram, wet weight) were all less than 5 per cent of the normal mean. During a 36-hour fast, ketones were barely detectable. Prolonged treatment with oral carnitine over a six-month period resulted in increased muscle strength, a dramatic reduction in cardiac size, relief of cardiomyopathy, partial repletion of carnitine levels in plasma and muscle, and complete repletion in the liver. Systemic carnitine deficiency is an easily treatable cause of recurrent Reye's-like syndrome. Its diagnosis requires measurement of carnitine levels.
Risk Factors for Breast Cancer in Women with Proliferative Breast Disease
Authors: William D. Dupont, David L. Page
Journal: New England Journal of Medicine (1985)

To assess the importance of various risk factors for breast cancer in women with benign proliferative breast lesions, we reevaluated 10,366 consecutive breast biopsies performed in women who had presented at three Nashville hospitals. The median duration of follow-up was 17 years for 3303 women, 1925 of whom had proliferative disease. This sample contained 84.4 per cent of the patients originally selected for follow-up. Women having proliferative disease without atypical hyperplasia had a risk of cancer that was 1.9 times the risk in women with nonproliferative lesions (95 per cent confidence interval, 1.2 to 2.9). The risk in women with atypical hyperplasia (atypia) was 5.3 times that in women with nonproliferative lesions (95 per cent confidence interval, 3.1 to 8.8). A family history of breast cancer had little effect on the risk in women with nonproliferative lesions. However, the risk in women with atypia and a family history of breast cancer was 11 times that in women who had nonproliferative lesions without a family history (95 per cent confidence interval, 5.5 to 24). Calcification elevated the cancer risk in patients with proliferative disease. Although cysts alone did not substantially elevate the risk, women with both cysts and a family history of breast cancer had a risk 2.7 times higher than that for women without either of these risk factors (95 per cent confidence interval, 1.5 to 4.6). This study demonstrates that the majority of women (70 per cent) who undergo breast biopsy for benign disease are not at increased risk of cancer. However, patients with a clinically meaningful elevation in cancer risk can be identified on the basis of atypical hyperplasia and a family history of breast cancer. (N Engl J Med 1985; 312:146–51.)
AB0913 Influence of Gender on Disease Activity, Body Composition and Bone Mineral Density in Patients with Juvenile Idiopathic Arthritis
Authors: R. Lahlou, S. Rostom, A. Hari, S. Fanta, R. Bahiri, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate the association between gender, disease activity, body composition and bone mineral density in patients with juvenile idiopathic arthritis. <h3>Methods</h3> Our study was a cross-sectional study including Moroccan patients with juvenile idiopathic arthritis according to the International League of association of Rheumatology (ILAR) criteria, seen in rheumatology consultation or hospital. Sociodemographic and clinical data of the patients were collected. Bone mineral density of patients (BMD g/cm<sup>2</sup>) was measured by DXA X-ray Lunar Prodigy scanner. The disease activity was assessed by the number of painful joints (IA), swollen joint (SI), visual analogical scale measured by physician and patient vasP and VASp, biological markers of inflammation: the sedimentation rate (ESR) and C-reactive protein (CRP). BMD was measured in two sites: the lumbar spine (L1, L4) and the whole body. Lean and fat mass were measured by the same device in the whole body and expressed in grams. <h3>Results</h3> 33 patients were included, the mean of their age was 10±4.35 years old, with a male predominance (54.5%), the median of disease evolution was 2 (1 - 4.5) years. 24% had a systemic JIA, 27% had an oligoarticular JIA and 48% had a polyarticular JIA. The median of painful joints and synovial joint were respectively 3 (1-9) and 1 (0-3).The mean of DAS 28 was 5, 34±1.11 The mean of ESR was 37±18, with a median of CRP, VASP and VASp were respectively 20mg (10.5 to 40), 20 (10-50) and 20 (10-40). The median of BMD in the whole body, lumbar spine, lean mass and fat mass were respectively 0.720 g/cm<sup>2</sup> (0700-0900) 0.620 g/cm<sup>2</sup> (0530-0900), 20.49g (15.96-33.45) and 4.97g (3.63-15.09). We did not find a statistically significant association between gender and disease activity evaluated by the DAS28, articular index, synovial Index, VASP, VASp, ESR and CRP with p respectively at (p=0.79, p=0.068, p=0.75, p=0.75, p=0.71, p=0.80, p=0.73). There are also no statistically significant association between gender and lean body mass, fat mass, lumbar spineBMD or BMD of the whole body with p respectively at (p=0.39, p=0.99 p=0.29, p=0.65). <h3>Conclusions</h3> This study suggests that the gender of the patient does not influence the disease activity or body composition and BMD of patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5839
THE PSYCHIATRIC OPERATION, ARMY FORCES, FAR EAST, 1950-53
Authors: DONALD B. PETERSON
Journal: American Journal of Psychiatry (1955)

A statistical analysis of psychiatry in the Korean conflict has been presented with comment on the psychiatric operation. Purpose: to emphasize and reiterate "The Warning" that loss of awareness of military psychiatric principles may be already occurring, and that only frequent rereading of the experiences of the past, with understanding of their validity, will preserve this knowledge of concepts and techniques, for which, so far, there is no substitute.
Quantification de la concentration hépatique en fer (CHF) avec imagerie par résonance magnétique (IRM): les protocoles recommandés sont-ils suffisamment précis pour la pratique clinique?
Authors: A Castiella, E Zapata, JM Alustiza, J Emparanza, B Costero, MI Diez, P Otazua, J Fernandez, L Zubiaurre, A Aguirre, JA Arriola, E Elosegui, E Utrilla
Journal: Endoscopy (2012)

La quantification de la concentration hépatique en fer (LIC) avec IRM est une technique non invasive développée dans les années 1980. La recherche fondamentale pour le développement de la technique comprend celle menée par l'équipe de l'Université de Rennes, en France, dirigée par le Dr Y. Gandon. Objectif: Evaluer la quantification de la CHF par l'IRM selon l'algorithme diagnostique de l'Université de Rennes (URennes).
SHOULDER PAIN PROBLEMS IN YOUTH HANDBALL
Authors: M Møller, G Myklebust, J Attermann, N Wedderkopp, H Sørensen, M Lind
Journal: British Journal of Sports Medicine (2014)

Background Assessment of prevalence and consequences of shoulder pain problems in youth handball is an integral first step towards injury prevention, but the literature is scarce. Objective To evaluate prevalence and impact of shoulder pain problems among youth handball players. Design Pilot cohort study with 3 months of weekly SMS-based injury registrations based on the OSTRC Overuse Injury Questionnaire. Setting Danish youth handball. Participants Danish 109 male and 90 female aged 14–16 years (age group U16) and 16–18 years (age group U18) players recruited as a convenient sample from 5 handball schools in Denmark. Risk factor assessment Gender and age group differences in shoulder pain prevalence were assessed. Main outcome measurements Current and previous shoulder pain registered at baseline via the Fahlstrøm questionnaire. A weekly average severity score (0–100) for the 3-month period was calculated for those with current shoulder pain. Results At baseline, 14% and 33% players reported current and previous shoulder pain, respectively. Of all reported shoulder pain, 56% had gradual onset. There were no significant differences between gender (P=.783) and age groups (P=.187). For players with current or previous pain, 70% had changed their training habits and 30% had missed games. Seventy-eight percent suffered from shoulder pain in their throwing (dominant) arm. Of the players reporting present pain, 41%, 15%, 11%, and 15% had pain durations of &gt;0–4, &gt;4–12, &gt;12–26 and &gt;26–52 weeks, respectively, while 19% had pain duration of more than one year. Thirty percent of these players reported problems more than 8 weeks in the registration period with a median severity score of 48, which is defined as substantial problems. Conclusions Shoulder pain problems poses a significant burden to Danish youth handball players, with a negative impact on both training and game participation. Further studies to identify risk factors in this population are needed to develop injury prevention strategies.
Abstract P4-06-05: Silencing of Cyclin D1 Increases Breast Cancer Cell Migration through Increased Id1 Expression and Induction of Epithelial-Mesenchymal Transition
Authors: NP Tobin, K Lundgren, A Sims, G. Landberg
Journal: Cancer Research (2010)

Abstract Backround: The oncogene cyclin D1 is overexpressed in many breast cancers and despite proliferation activating properties, has been linked to a less malignant phenotype. We have previously shown that down-regulation of cyclin D1 in actively cycling breast cancer cells significantly increased their migratory capacity whilst also decreasing proliferation. Gene expression analysis and animal modeling have highlighted an increase in the inhibitor of differentiation-1 (Id1) gene following cyclin D1 gene (CCND1) silencing. Notably, increased Id1 is associated not only with enhanced migratory and invasive features of breast cancer cells but also with prevention of cell differentiation and induction of an epithelial-mesenchymal-like (EMT) phenotype. Here we sought to determine if the increase in cell motility following cyclin D1 silencing was through increased Id1 expression and induction of an EMT phenotype, and confirm our findings in a large patient cohort. Materials and Methods: Expression of cyclin D1, Id1 and SNAI2 was determined in MDA-MB-231 and ZR75 cells by qPCR and western blot, whilst cell migration was monitored by transwell assay. Gene expression of CCND1, ID1 and EMT markers was analysed from a pooled cohort of batch-mean centered publically available data sets, with data analysis performed in SPSS. Results: Silencing of cyclin D1 increased cell migration 1.38 and 1.72 fold in MDA-MB-231 (P&amp;lt;0.001), and ZR75 (P&amp;lt;0.001) cells respectively, an effect abolished by silencing of Id1. qPCR analysis confirmed an increase in Id1 (1.73) and SNAI2 (1.50) expression following siRNA treatment of cyclin D1, an effect reversed following siRNA treatment of Id1. CCND1 gene exression was negatively, while Id1 was positively, associated with the EMT markers Vimentin (P&amp;lt;0.001), SNAI2 (P&amp;lt;0.001) and TWIST1 (P&amp;lt;0.001) in 1,100 breast tumors. In ER+ patients CCND1 was negatively correlated to Id1 expression (0.050) and in CCND1 low patients increasing Id1 expression was predictive of worse cumulative survival (0.027). Conclusion: Decreased CCND1 expression enhances MDA-MB-231 and ZR75 cell migration through increased Id1 expression and induction of EMT. Moreover, both genes are correlated to EMT markers in breast cancer patients and in a subset of the cohort, confer a worse survival. These results may explain the conflicting data regarding cyclin D1 expression in breast carcinomas and solidifies the rationale of the protein as a clinical target. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-05.
A6.19 Non-canonical NF-κB signalling in endothelial cells promotes angiogenesis in a novel 3D model of rheumatoid arthritis synovial angiogenesis
Authors: CX Maracle, B Helder, AR Noort, C van der Horst, SW Tas
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Angiogenesis is a crucial mediator in rheumatoid arthritis (RA) pathogenesis. Current <i>in vitro</i>models of angiogenesis focus solely on endothelial cells (EC), however, RA fibroblast like synoviocytes (FLS) also contribute to this process. Therefore, a model including both EC and RA FLS would be more representative of synovial angiogenesis. Previous work demonstrates that the non-canonical NF-κB pathway with its main regulator NF-κB inducing kinase (NIK), induces angiogenesis in EC. Yet, this still remains to be studied in a co-culture model. <h3>Objective</h3> Generate a 3D model of RA synovial angiogenesis and study effects of non-canonical NF-κB signalling, RA synovial fluid (RASF) and inhibitors on angiogenesis. <h3>Methods</h3> We developed a 3D model in which HUVEC and RA FLS labelled with green or orange cell tracker dye, respectively, were incubated overnight to form spheroids. Subsequently, spheroids were harvested and plated in a collagen solution, and medium with or without lymphotoxinα1β2 (LT) or LIGHT (activators of non-canonical NF-κB signalling) or growth factors (bFGF/VEGF) was added. After 48 h, spheroids were fixed and imaged through confocal microscopy. Cumulative EC sprout length was quantified using Leica QWin Plus software. To demonstrate NIK dependency, EC were transfected with non-targeting or NIK-targeting siRNA before incorporation into the model. In addition, spheroids were incubated with RASF, with or without inhibitors, and subsequent changes in sprout formation were measured. <h3>Results</h3> Confocal analysis of the 3D model showed spheroids formed sprouts under all conditions. LT and LIGHT caused significant increases in cumulative sprout length (p &lt; 0.05). LTβR-induced sprout formation was significantly decreased by siRNA-mediated knockdown of NIK in EC as compared to the non-targeting controls. RASF induced sprout formation at all concentrations with a significant increase observed at 10%. This sprout formation was significantly decreased in the presence of different inhibitors of angiogenesis. <h3>Conclusion</h3> The 3D model is an effective tool for studying RA angiogenesis. This novel model incorporates two key cellular mediators of this process, EC and RA FLS, and true capillary-like structures are formed that can be easily quantified. Using this system, we have demonstrated that activation of the non-canonical NF-κB pathway induces angiogenesis in a NIK-dependent fashion. Therefore, targeting NIK may have therapeutic potential in reducing pathological angiogenesis and halting disease progression. Further studies testing the efficacy of NIK inhibitors are currently underway. Additionally, we have demonstrated that RASF is a potent inducer of angiogenesis in the 3D model and that this can be used to measure the effectiveness of pharmacological inhibitors of angiogenesis.
Case 5-2016
Authors: Anna R. Terry, Kristopher T. Kahle, Mykol Larvie, Jatin M. Vyas, Anat Stemmer-Rachamimov
Journal: New England Journal of Medicine (2016)

A 43-year-old man with a history of alcohol use presented with altered mental status. The initial blood pressure was 236/158 mm Hg; imaging studies of the head revealed ventriculomegaly and a mass at the foramen of Monro. A diagnostic procedure was performed.
1145 IMPACT OF PEGYLATED INTERFERON a2B PLUS RIBAVIRIN TREATMENT FOR CHRONIC HEPATITIS C PATIENTS WITH HISTORY OF HEPATOCELLULAR CARCINOMA
Authors: E. Ogawa, N. Furusyo, E. Kajiwara, K. Takahashi, H. Nomura, Y. Tanabe, T. Satoh, T. Maruyama, M. Nakamuta, K. Kotoh, K. Azuma, K. Dohmen, S. Shimoda, J. Hayashi
Journal: Journal of Hepatology (2012)
Interstitial pneumonia with autoimmune features: the new consensus-based definition for this cohort of patients should be broadened
Authors: Bridget Collins, Ganesh Raghu
Journal: European Respiratory Journal (2016)

We appreciate the research statement recently published by Fischer et al. [1] proposing new terminology: "interstitial pneumonia with autoimmune features" (IPAF) to characterise the heterogeneous group of patients with idiopathic interstitial pneumonia (IIP) who have a clinical flavour of underlying connective tissue disease (CTD) but do not meet the current American College of Rheumatology criteria for CTD. Indeed, a variety of terms and criteria have been used in studies to describe such patients, including "autoimmune featured interstitial lung disease", "undifferentiated connective tissue disease associated interstitial lung disease", and "lung-dominant connective tissue disease" [2–5]. Thus, the need for a consensus regarding the terminology and better characterisation of the clinical characteristics of this group of patients is evident. The proposed terminology, however, is not yet validated and does not include a provision for patients with clinical characteristics of CTD who do not meet American College of Rheumatology criteria for CTD or IPAF criteria, but are distinct from patients with IIP alone. To meet the proposed criteria for IPAF, a patient must have features of IIP on high-resolution computed tomography (HRCT) images and/or surgical lung biopsy. Alternative aetiologies of IIPs must be excluded by thorough clinical evaluation and the patient must fail to meet criteria for a specific CTD. The patient must then have at least one characteristic from at least two out of three domains: clinical, serological and morphological. We wish to share our concerns regarding the new IPAF classification. IPAF excludes patients with ILD associated with autoimmune features; IPAF morphological domain should be broadened <http://ow.ly/X6VSe>