tbuckley/cabot-search huggingface dataset:
Concepts of functioning and health important to people with systemic sclerosis: a qualitative study in four European countries
Authors: Tanja A Stamm, Malin Mattsson, Carina Mihai, Juliane Stöcker, Alexa Binder, Bettina Bauernfeind, Georg Stummvoll, Gunvor Gard, Roger Hesselstrand, Gunnel Sandqvist, Oana Draghicescu, Ana Maria Gherghe, Malina Voicu, Klaus P Machold, Oliver Distler, Josef S Smolen, Carina Boström
Journal: Annals of the Rheumatic Diseases (2011)

Objective To describe the experiences of people with systemic sclerosis (SSc) in different European countries of functioning and health and to link these experiences to the WHO International Classification of Functioning, Disability and Health (ICF) to develop a common understanding from a bio-psycho-social perspective. Method A qualitative multicentre study with focus-group interviews was performed in four European countries: Austria, Romania, Sweden and Switzerland. The qualitative data analysis followed a modified form of ‘meaning condensation’ and the concepts that emerged in the analysis were linked to the ICF. Results 63 people with SSc participated in 13 focus groups. In total, 86 concepts were identified. 32 (37%) of these were linked to the ICF component body functions and structures, 21 (24%) to activities and participation, 26 (30%) to environmental factors, 6 (7%) to personal factors and 1 (1%) to the health condition itself. 19 concepts (22%) were identified in all four countries and included impaired hand function, household activities, paid work, drugs, climate and coldness, support from others and experiences with healthcare institutions, non-pharmacological treatment, social security and benefits. Conclusion Concepts identified in all four countries could be used for guiding clinical assessment, as well as interdisciplinary team care and rheumatological rehabilitation for patients with SSc. For a full understanding of the aspects of the disease that were most relevant to people with SSc, people with SSc from multiple countries needed to be involved.
The calcium-sensing receptor suppresses epithelial-to-mesenchymal transition and stem cell- like phenotype in the colon
Authors: Abhishek Aggarwal, Maximilian Prinz-Wohlgenannt, Charlotte Gröschel, Samawansha Tennakoon, Anastasia Meshcheryakova, Wenhan Chang, Edward M Brown, Diana Mechtcheriakova, Enikö Kállay
Journal: Molecular Cancer (2015)

The calcium sensing receptor (CaSR), a calcium-binding G protein-coupled receptor is expressed also in tissues not directly involved in calcium homeostasis like the colon. We have previously reported that CaSR expression is down-regulated in colorectal cancer (CRC) and that loss of CaSR provides growth advantage to transformed cells. However, detailed mechanisms underlying these processes are largely unknown. In a cohort of 111 CRC patients, we found significant inverse correlation between CaSR expression and markers of epithelial-to-mesenchymal transition (EMT), a process involved in tumor development in CRC. The colon of CaSR/PTH double-knockout, as well as the intestine-specific CaSR knockout mice showed significantly increased expression of markers involved in the EMT process. In vitro, stable expression of the CaSR (HT29CaSR) gave a more epithelial-like morphology to HT29 colon cancer cells with increased levels of E-Cadherin compared with control cells (HT29EMP). The HT29CaSR cells had reduced invasive potential, which was attributed to the inhibition of the Wnt/β-catenin pathway as measured by a decrease in nuclear translocation of β-catenin and transcriptional regulation of genes like GSK-3β and Cyclin D1. Expression of a spectrum of different mesenchymal markers was significantly down-regulated in HT29CaSR cells. The CaSR was able to block upregulation of mesenchymal markers even in an EMT-inducing environment. Moreover, overexpression of the CaSR led to down-regulation of stem cell-like phenotype. The results from this study demonstrate that the CaSR inhibits epithelial-to-mesenchymal transition and the acquisition of a stem cell-like phenotype in the colon of mice lacking the CaSR as well as colorectal cancer cells, identifying the CaSR as a key molecule in preventing tumor progression. Our results support the rationale to develop new strategies either preventing CaSR loss or reversing its silencing.
Diffuse Large B-Cell Lymphoma With Germinal Center B-Cell Phenotype Mimicking Primary Effusion Lymphoma
Authors: Yoojoo Lim, Tae-Yong Kim, In Sil Choi, Byung-Su Kim, Taek Sang Lee, Ji Eun Kim, Mee Soo Chang, Ki Hwan Kim
Journal: Journal of Clinical Oncology (2011)
New Approaches to CPR
Authors: Henry R. Halperin, Myron L. Weisfeldt
Journal: JAMA (1992)

A major stimulus to improve methods of cardiopulmonary resuscitation (CPR) has come from the realization that blood flow during conventional CPR is marginal, particularly the flow to the heart. To restart the heart, if initial defibrillation fails (or is not possible), coronary flow must be provided.<sup>1</sup>With well-performed CPR together with optimal use of epinephrine, brain blood flow probably reaches 30% to 60% of normal; however, myocardial blood flow is much more limited, in the range of 5% to 20% of normal. Repeated studies in animals and important confirmatory studies in man have shown a strong correlation between restarting the heart and higher levels of coronary blood flow.<sup>1-3</sup>In animals, coronary flow correlates strongly with the pressure gradient between the aorta and the right atrium. In man, restarting the heart has been shown to correlate with this pressure gradient. A pressure gradient between the aorta and right atrium,
Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts
Authors: J. H. M. van Esch, F. Gembardt, A. Sterner-Kock, S. Heringer-Walther, T. H. Le, D. Lassner, T. Stijnen, T. M. Coffman, H. P. Schultheiss, A. H. J. Danser, T. Walther
Journal: Cardiovascular Research (2010)

Our aim was to determine the contribution of the three angiotensin (Ang) II receptor subtypes (AT1a, AT1b, AT2) to coronary responsiveness, cardiac histopathology, and tissue Ang II levels using mice deficient for one, two, or all three Ang II receptors. Hearts of knockout mice and their wild-type controls were collected for histochemistry or perfused according to Langendorff, and kidneys were removed to measure tissue Ang II. Ang II dose-dependently decreased coronary flow (CF) and left ventricular systolic pressure (LVSP), and these effects were absent in all genotypes deficient for AT1a, independently of AT1b and AT2. The deletion of Ang II receptors had an effect neither on the morphology of medium-sized vessels in the heart nor on the development of fibrosis. However, the lack of both AT1 subtypes was associated with atrophic changes in the myocardium, a reduced CF and a reduced LVSP. AT1a deletion alone, independently of the presence or absence of AT1b and/or AT2, reduced renal Ang II by 50% despite a five-fold rise of plasma Ang II. AT1b deletion, on top of AT1a deletion (but not alone), further decreased tissue Ang II, while increasing plasma Ang II. In mice deficient for all three Ang II receptors, renal Ang II was located only extracellularly. The lack of both AT1 subtypes led to a baseline reduction of CF and LVSP, and the effects of Ang II on CF and LVSP were found to be exclusively mediated via AT1a. The lack of AT1a or AT1b does not influence the development or maintenance of normal cardiac morphology, whereas deficiency for both receptors led to atrophic changes in the heart. Renal Ang II levels largely depend on AT1 binding of extracellularly generated Ang II, and in the absence of all three Ang II receptors, renal Ang II is only located extracellularly.
Autoantibody profiles in the sera of European patients with myositis
Authors: R. Brouwer, G.J.D. Hengstman, W.T.M. Vree Egberts, H. Ehrfeld, B. Bozic, A. Ghirardello, G. Grondal, M. Hietarinta, D.A. Isenberg, J.R. Kalden, I. Lundberg, H.M. Moutsopoulos, P. Roux-Lombard, J. Vencovsky, A. Wikman, H.P. Seelig, B.G.M. van Engelen, W.J.W. van Venrooij
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To determine the prevalence of myositis <i>specific</i>autoantibodies (MSAs) and several myositis<i>associated</i> autoantibodies (MAAs) in a large group of patients with myositis. <h3>METHODS</h3> A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. <h3>RESULTS</h3> Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. <h3>CONCLUSIONS</h3> The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity.
An infant with pneumonia, failure to thrive and persistent radiographical changes
Authors: N. Thompson, S. Saglani, A. Bush
Journal: European Respiratory Journal (2007)

<h3>Abstract</h3> Pathogenic α-synuclein and tau are critical drivers of neurodegeneration and their mutations cause neuronal loss in patients. Whether the underlying preferential neuronal vulnerability is a cell-type intrinsic property or a consequence of increased expression levels is an open question. Here, we explore cell-type specific α-synuclein and tau expression in human brain datasets and use deep phenotyping as well as brain-wide single-cell RNA sequencing of &gt;200 live neuron types in fruit flies to ask which cellular environments react most to α-synuclein or tau toxicity. We detect phenotypic and transcriptomic evidence of differential neuronal vulnerability independent of α-synuclein or tau expression levels. Comparing vulnerable with resilient neurons enabled us to identify molecular signatures associated with these differential responses. We used these to verify, and then predict resilient and vulnerable neuron subtypes in human brains. This confirms <i>substantia nigra</i> dopaminergic neurons to be sensitive to α-synuclein, and we predict pathogenic tau vulnerable and protected cortical neuron subtypes. Our work indicates that cellular determinants confer selective vulnerability to specific types of amyloid toxicity, thus paving the way to leverage neuronal identity to uncover modifiers of neurodegeneration-associated toxic proteins.
Detection of HCV-RNA in saliva of patients with chronic hepatitis C.
Authors: P Couzigou, L Richard, F Dumas, L Schouler, H Fleury
Journal: Gut (1993)

Previous studies have provided conflicting results on the presence of hepatitis C virus-RNA in saliva. In this study, 23 (62%) of 37 patients tested positive for hepatitis C virus-RNA in saliva, using polymerase chain reaction analysis. A slightly greater proportion had a sporadic rather than a parenteral origin of chronic hepatitis C. These results provide a biological basis for saliva as a possible source of hepatitis C virus (HCV) infection, but do not necessarily imply transmission by this route.
Osteoarticular infection in intravenous drug abusers: influence of HIV infection and differences with non drug abusers.
Authors: S Munoz-Fernandez, M A Macia, L Pantoja, A Cardenal, J M Pena, E Martin Mola, A Balsa, F J Barbado, J J Vazquez, J Gijon Banos
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine (a) the influence of HIV in developing osteoarticular infections in intravenous drug abusers (IVDAs) and (b) the differences between the clinical features of osteoarticular infections in IVDAs and a control group of non-IVDAs. METHODS--A comparative study of the clinical features of osteoarticular infections in all HIV positive and HIV negative IVDAs admitted to the departments of rheumatology and internal medicine during a 10 year period was carried out. The joint infections of all IVDAs, irrespective of HIV status, were compared with those of a control group of non-IVDAs lacking risk factors for HIV infection. RESULTS--A total of 482 HIV positive and 85 HIV negative IVDAs was studied, in whom 25 (5%) and six (7%) osteoarticular infections were found respectively. There were no differences in age, sex, joints affected, and causative agents between these two groups. A comparison of the 31 (5.5%) osteoarticular infections in all IVDAs with 21 infections in 616 (3.4%) non-IVDAs showed significant differences in the mean age (27.5 v 54), the frequency of affection of the axial joints (hip, sacroiliac, and sternocostal joints) (64.5% v 16.6%), and in the incidence of Candida albicans (19% v 0%). CONCLUSIONS--(1) HIV may not predispose to osteoarticular infections in IVDAs. (2) The hip, sacroiliac, and sternocostal joints (axial joints) were most commonly affected in IVDAs. (3) In Spain, unlike other countries, Gram positive bacteria and C albicans seem to be predominant agents in osteoarticular infections in IVDAs, with a low incidence of Gram negative bacteria.
Is Insulin Sensitivity a Causal Intermediate in the Relationship Between Alcohol Consumption and Carotid Atherosclerosis?
Authors: Daniel E. Cooper, David C. Goff, Ronny A. Bell, Dan Zaccaro, Elizabeth J. Mayer-Davis, Andrew J. Karter
Journal: Diabetes Care (2002)

OBJECTIVE—A J-shaped association has been demonstrated between alcohol consumption and atherosclerosis. Insulin resistance, also a risk factor for atherosclerosis, has been shown to have a similar J-shaped association with alcohol intake. This raises the question of whether insulin sensitivity (SI) is a causal intermediate in the alcohol-atherosclerosis relationship. RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study was a multicenter cohort study designed to investigate relationships among SI, risk factors for cardiovascular disease, and carotid artery atherosclerosis. Using regression analysis, we tested whether adjustment for SI attenuated the alcohol-atherosclerosis relationship observed at baseline. RESULTS—A J-shaped association was observed between alcohol consumption and common carotid artery intimal medial thickness. The protective aspect of the alcohol-atherosclerosis relationship was attenuated by 25% after the adjustment for SI. However, an interaction was observed between alcohol consumption and glucose tolerance (GT) status. In comparison with never drinkers, all levels of alcohol consumption were associated with less atherosclerosis in participants with normal GT status. Participants with impaired GT status (but not diabetes) demonstrated a J-shaped alcohol-atherosclerosis association. All levels of alcohol consumption were associated with more atherosclerosis in participants with diabetes. CONCLUSIONS—SI may be a causal intermediate at protective levels of alcohol intake, but an alcohol-GT interaction precluded a definitive conclusion. Moderate alcohol consumption may increase the risk of atherosclerosis in people with diabetes. These findings contrast with previous reports and do not support current recommendations regarding moderate alcohol consumption in people with diabetes. More research is needed to clarify this issue.
Antigen Presented by Tumors<i>In vivo</i>Determines the Nature of CD8+ T-Cell Cytotoxicity
Authors: Anil Shanker, Alan D. Brooks, Kristen M. Jacobsen, John W. Wine, Robert H. Wiltrout, Hideo Yagita, Thomas J. Sayers
Journal: Cancer Research (2009)

The biological relevance of the perforin and Fas ligand (FasL) cytolytic pathways of CD8(+) T lymphocytes (CTL) for cancer immunotherapy is controversial. We investigated the importance of these pathways in a murine renal cell carcinoma expressing influenza viral hemagglutinin as a defined surrogate antigen (Renca-HA). Following Renca-HA injection, all FasL-dysfunctional FasL(gld/gld) mice (n = 54) died from Renca-HA tumors by day 62. By contrast, perforin(-/-) (51%; n = 45) and Fas(lpr/lpr) (55%; n = 51) mice remained tumor-free at day 360. Blocking FasL in vivo inhibited tumor rejection in these mice. Moreover, established Renca-HA tumors were cleared more efficiently by adoptively transferred HA(518-526)-specific T-cell receptor-transgenic CTL using FasL rather than perforin. Strikingly, a range of mouse tumor cells presenting low concentrations of immunogenic peptide were all preferentially lysed by the FasL but not the Pfp-mediated effector pathway of CTL, whereas at higher peptide concentrations, the preference in effector pathway usage by CTL was lost. Interestingly, a number of human renal cancer lines were also susceptible to FasL-mediated cytotoxicity. Therefore, the FasL cytolytic pathway may be particularly important for eradicating Fas-sensitive tumors presenting low levels of MHC class I-associated antigens following adoptive T-cell therapy.
Sarcoidosis patients with cardiac involvement in the National Tuberculosis & Lung Diseases Research Institute in Warsaw, Poland – 3 years experience
Authors: Magdalena Martusewicz-Boros, Anna Kempisty, Elzbieta Wiatr
Journal: European Respiratory Journal (2011)

Introduction: Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, however other organs can be involved, including heart, what is potentially life-threatening. The aim of this study was to evaluate the incidence of cardiac involvement in sarcoidosis patients diagnosed or followed up in 1st and 3rd Lung Diseases Departments of National TB & Lung Diseases Research Institute in Warsaw.  Method: Retrospective analysis of database discharged patients with the final diagnosis of sarcoidosis (D86). The analysis covered the period from January 2008 to October 2010. Diagnosis of cardiac sarcoidosis was verified according to Modified Guidelines for Diagnosis of Cardiac Sarcoidosis based on the Study Report on Diffuse Pulmonary Diseases: From the Japan Ministry of Health and Welfare, 1993 (9) and modifications 2006.  Results: 933 sarcoidosis patients were seen in two departments in the almost 3 years period. Multiorgan sarcoidosis (D86.8) was detected in 102 cases (10.9%). The cardiac involvement was found only in 30 patients of this group, which was 3.2% of the entire group. There were 19 males (63%) and 11 females (37%), 5 cases in stage I, 25 in stage II. The mean age was 45.5±12.6 years (range: 28 - 74). The time from the first diagnosis of sarcoidosis to detection of heart involvement was 10 months (median, CI 90% range 0 to 6.4 years).  Conclusion: Cardiac sarcoidosis in our own material was diagnosed in the similar percentage as in previously published data. According to post mortem diagnosis data from literature diagnosis of this form of the disease still remains a significant clinical problem.
Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage destruction in vitro
Authors: R L van Bezooijen
Journal: Annals of the Rheumatic Diseases (2002)

Interleukin 17 (IL17) is produced by activated T cells and has been implicated in the development of bone lesions and cartilage degradation in rheumatoid arthritis (RA).To determine whether IL17, alone or together with tumour necrosis factor alpha (TNFalpha), induces cartilage destruction in vitro.Fetal mouse metatarsals stripped of endogenous osteoclast precursors were used to study the effect of IL17 on cartilage degradation independently of osteoclastic resorption. Cartilage destruction was analysed histologically by Alcian blue staining.IL17 alone, up to 100 ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17 (>/=0.1 ng/ml), however, induced severe cartilage degradation when given together with TNFalpha (>/=1 ng/ml). The cytokine combination decreased Alcian blue staining, a marker of proteoglycans, throughout the metatarsals and induced loss of the proliferating and early hypertrophic chondrocyte zones. TNFalpha alone also decreased Alcian blue staining, but not as dramatically as the cytokine combination. In addition, it did not induce loss of chondrocyte zones. Treatment with inhibitors of matrix metalloproteinase (MMP) activity and nitric oxide synthesis showed that MMP activity played a part in cartilage degradation, whereas nitric oxide production did not.IL17, together with TNFalpha, induced cartilage degradation in fetal mouse metatarsals in vitro. IL17 may, therefore, participate in the development of cartilage destruction associated with RA by enhancing the effects of TNFalpha and may provide a potential therapeutic target.
Studies on the Chemotherapy of Experimental Brain Tumors: Evaluation of 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea, Vineristine and 5-Fluorouracil&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: William R. Shapiro
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Studies on the Chemotherapy of Experimental Brain Tumors: Evaluation of 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea, Vineristine and 5-Fluorouracil Get access William R. Shapiro, M.D. William R. Shapiro, M.D. Neuropsychiatric Service, Memorial Sloan-Kettering Cancer Center, and Department of Neurology, Cornell University Medical College, New York, New York 10021 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 2, February 1971, Pages 359–368, https://doi.org/10.1093/jnci/46.2.359 Published: 01 February 1971 Article history Received: 07 August 1970 Accepted: 21 October 1970 Published: 01 February 1971