tbuckley/cabot-search huggingface dataset:
Viral Double-Stranded RNA Aggravates Lupus Nephritis through Toll-Like Receptor 3 on Glomerular Mesangial Cells and Antigen-Presenting Cells
Authors: Prashant S. Patole, Hermann-Josef Gro[Combining Diaeresis]ne, Stephan Segerer, Raluca Ciubar, Emilia Belemezova, Anna Henger, Matthias Kretzler, Detlef Schlo[Combining Diaeresis]ndorff, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2005)

How viral infections trigger autoimmunity is poorly understood. A role for Toll-like receptor 3 (TLR3) was hypothesized in this context as viral double-stranded RNA (dsRNA) activates dendritic cells to secrete type I interferons and cytokines that are known to be associated with the disease activity in systemic lupus erythematosus (SLE). Immunostaining of nephritic kidney sections of autoimmune MRL(lpr/lpr) mice revealed TLR3 expression in infiltrating antigen-presenting cells as well as in glomerular mesangial cells. TLR3-positive cultured mesangial cells that were exposed to synthetic polyinosinic-cytidylic acid (pI:C) RNA in vitro produced CCL2 and IL-6. pI:C RNA activated macrophages and dendritic cells, both isolated from MRL(lpr/lpr) mice, to secrete multiple proinflammatory factors. In vivo, a single injection of pI:C RNA increased serum IL-12p70, IL-6, and IFN-alpha levels. A course of 50 microg of pI:C RNA given every other day from weeks 16 to 18 of age aggravated lupus nephritis in pI:C-treated MRL(lpr/lpr) mice. Serum DNA autoantibody levels were unaltered upon systemic exposure to pI:C RNA in MRL(lpr/lpr) mice, as pI:C RNA, in contrast to CpG-DNA, failed to induce B cell activation. It therefore was concluded that viral dsRNA triggers disease activity of lupus nephritis by mechanisms that are different from those of bacterial DNA. In contrast to CpG-DNA/TLR9 interaction, pI:C RNA/TLR3-mediated disease activity is B cell independent, but activated intrinsic renal cells, e.g., glomerular mesangial cells, to produce cytokines and chemokines, factors that can aggravate autoimmune tissue injury, e.g., lupus nephritis.
Efficacy and safety of steroid injections for shoulder and elbow tendonitis: a meta-analysis of randomised controlled trials
Authors: C Gaujoux-Viala, M Dougados, L Gossec
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To assess the efficacy and safety of steroid injections for patients with tendonitis of the shoulder or elbow. <h3>Methods:</h3> A systematic review of the literature using PubMed, EMBASE, the Cochrane library and manual searches was performed until April 2008. All randomised controlled trials (RCTs) reporting the efficacy on pain or functional disability, and/or the safety of steroid injections, versus placebo, non-steroidal anti-inflammatory drugs (NSAIDs) or physiotherapy in patients with tendonitis were selected. Pooled effect size (ES) was calculated by meta-analysis using the Mantel–Haenszel method. <h3>Results:</h3> In all, 20 RCTs were analysed (744 patients treated by injections and 987 patients treated by controls; 618 shoulders and 1113 elbows). The pooled analysis indicated only short-term effectiveness of steroids versus the pooled controls for pain and function (eg, pain at week 1–3 ES = 1.18 (95% CI 0.27 to 2.09), pain at week 4–8 ES = 1.30 (95% CI 0.55 to 2.04), pain at week 12–24 ES = −0.38 (95% CI −0.85 to 0.08) and pain at week 48 ES = 0.07 (95% CI −0.60 to 0.75)). Sensitivity analyses indicated similar results whatever the localisation, type of steroid and type of comparator except for NSAIDs: steroid injections were not significantly better than NSAIDs in the short-term. Steroid injections appeared more effective than pooled other treatments in acute or subacute tendonitis. The main side effects were transient pain after injection (10.7% of corticosteroid injections) and skin modification (4.0%). <h3>Conclusions:</h3> Steroid injections are well tolerated and more effective for tendonitis in the short-term than pooled other treatments, though similar to NSAIDs. No long-term benefit was shown.
Members of the miRNA-200 Family Regulate Olfactory Neurogenesis
Authors: Philip S. Choi, Lisa Zakhary, Wen-Yee Choi, Sophie Caron, Ezequiel Alvarez-Saavedra, Eric A. Miska, Mike McManus, Brian Harfe, Antonio J. Giraldez, Robert H. Horvitz, Alexander F. Schier, Catherine Dulac
Journal: Neuron (2008)

MicroRNAs (miRNAs) are highly expressed in vertebrate neural tissues, but the contribution of specific miRNAs to the development and function of different neuronal populations is still largely unknown. We report that miRNAs are required for terminal differentiation of olfactory precursors in both mouse and zebrafish but are dispensable for proper function of mature olfactory neurons. The repertoire of miRNAs expressed in olfactory tissues contains over 100 distinct miRNAs. A subset, including the miR-200 family, shows high olfactory enrichment and expression patterns consistent with a role during olfactory neurogenesis. Loss of function of the miR-200 family phenocopies the terminal differentiation defect observed in absence of all miRNA activity in olfactory progenitors. Our data support the notion that vertebrate tissue differentiation is controlled by conserved subsets of organ-specific miRNAs in both mouse and zebrafish and provide insights into control mechanisms underlying olfactory differentiation in vertebrates.
Incidence of Treatment for End-Stage Renal Disease Among Individuals With Diabetes in the U.S. Continues to Decline
Authors: Emmanuel Villar, Stephen Peter McDonald, Cécile Couchoud
Journal: Diabetes Care (2010)

We read with great interest the report from the U.S. Renal Data System (USRDS) by Burrows et al. (1) that described declining incidence rate of treated end-stage renal disease (ESRD) “related to diabetes” as primary renal disease among estimated U.S. population with diabetes. From 1996 to 2006 the overall incidence rate decreased at an average of 2.9% per year (1).

However, reported results raise the issue of the clinical relevance of this primary renal disease definition when a diabetic population is studied.

In ESRD patients, diabetes might be the cause of chronic kidney disease (diabetic nephropathy) or an associated disease not related to primary renal disease (diabetes as comorbidity). In type 2 diabetic patients …
Intrahepatic cholangiocarcinoma arising in Caroli's disease
Authors: Min Hye Jang, Yoon Jin Lee, Haeryoung Kim
Journal: Clinical and Molecular Hepatology (2014)

Caroli's disease (CD) is a rare congenital disorder characterized by non-obstructive segmental saccular dilatation of the large intrahepatic bile ducts.1 Two forms of CD have been described. The pure type is characterized by cystic dilatation of the intrahepatic bile ducts, while the complex type - also designated Caroli's syndrome - is associated with congenital hepatic fibrosis (CHF) and autosomal recessive polycystic kidney disease.2,3,4 CD usually affects the liver diffusely but some localized forms (monolobar CD) affect only a single lobe, predominantly the left lobe.5,6 Complications of Caroli's disease are frequently related to the stagnation of bile resulting from the saccular dilatation of bile ducts, and include intrahepatic lithiasis, recurrent cholangitis, abscess formation, septicemia and amyloidosis. Patients with CD have also been shown to be at risk for intrahepatic cholangiocarcinoma.7,8 A case of intrahepatic cholangiocarcinoma arising in a localized CD is described and the recent literature discussed.
Lipid lowering and the assessment of endothelial function
Authors: K Lee
Journal: Cardiovascular Research (2002)

We read with interest the report by Malik et al. [1] that both atorvastatin and fenofibrate equally improved endothelium-dependent arterial vasoreactivity in patients with combined hyperlipidaemia. Interestingly, a recent study by Sebestjen et al. [2] reported similar observations using cerivastatin and fenofibrate, although the effects seemed to be greater in the patients receiving the statin. Indeed, most of us now recognise that the beneficial effects of statins on the early cardiovascular events reduction in major clinical trials may involve mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation which may be unrelated, or indirectly related, to their lipid-lowering abilities [3].

Endothelial dysfunction has been regarded as an early event in atherogenesis, preceding the formation of atherosclerotic plaques. An important functional consequence of endothelial damage / dysfunction is a reduced vasodilatory responses to a variety of pharmacological and physiological stimuli …
Primary idiopathic osteolysis: description of a family.
Authors: A Naranjo, M A Muniain, J Martin, J Vazquez, J Nunez
Journal: Annals of the Rheumatic Diseases (1992)

A clinical, analytical, and radiological study was carried out on three members of the same family with multicentric idiopathic osteolysis. Transmission appeared to be via the dominant autosome present in the mother and two daughters. In the daughters osteolysis was seen in the carpal and tarsal bones, whereas in the mother radiology showed it to be in the phalanges of the hands and feet.
Transfer of suppressor of cytokine signaling 3 by an oncolytic adenovirus induces potential antitumor activities in hepatocellular carcinoma
Authors: Qiang Cui, Wei Jiang, Yingxin Wang, Chen Lv, Jingjing Luo, Wei Zhang, Fang Lin, Yuexiang Yin, Rong Cai, Ping Wei, Cheng Qian
Journal: Hepatology (2007)

The constitutive activation of signal transducer and activator of transcription 3 (STAT3) participates in carcinogenesis through up-regulation of genes encoding apoptosis inhibitors and cell cycle regulators, such as Bcl-xL, cyclins D1 and D2, and c-myc. Suppressor of cytokine signaling 3 (SOCS3) is one of the negative regulators of cytokine signaling and is frequently silenced in diverse cancers. In this study, we explored whether restoration of SOCS3 by oncolytic adenoviral vectors could inhibit the constitutive activation of the Janus kinase/STAT pathway and suppress tumor growth. Our data showed that SOCS3 was down-expressed in all liver tumor cell lines. The incorporation of SOCS3 or SOCS3 fused with cell-penetrating peptides (cpp-SOCS3) did not alter adenoviral replication selectively in liver tumor cells. The infection of cells with adenovirus CN305 (AdCN305)–SOCS3 and AdCN305-cpp-SOCS3 resulted in dramatic cytotoxicity in liver tumor cells. However, no cytotoxic effect was observed in normal cells infected with these vectors. Infection of liver tumor cells with AdCN305-SOCS3 and AdCN305-cpp-SOCS3 resulted in nearly complete inhibition of STAT3 phosphorylation and down-regulation of cyclin D1 and Bcl-xL. Treatment of the established tumor by AdCN305-SOCS3 and AdCN305-cpp-SOCS3 caused significant suppression of tumor growth. The suppression of tumor growth was due to the inhibition of STAT3 phosphorylation and induction of tumor cell death. Conclusion: This study suggests that transfer of SOCS3 by an oncolytic adenovirus represents a potent approach for cancer therapy. (Hepatology 2007.)
What Is the Best Predictor of Future Type 2 Diabetes?
Authors: Muhammad A. Abdul-Ghani, Ken Williams, Ralph A. DeFronzo, Michael Stern
Journal: Diabetes Care (2007)

OBJECTIVE—We sought to assess insulin secretion/insulin resistance index in predicting the risk for future type 2 diabetes RESEARCH DESIGN AND METHODS—A total of 1,551 nondiabetic subjects from the San Antonio Heart Study received an oral glucose tolerance test (OGTT) with measurement of plasma glucose and insulin concentrations at 0, 30, 60, and 120 min at baseline and after 7–8 years of follow-up. Insulin secretion/insulin resistance index was calculated as the product of Matsuda index and ΔI0–30/ΔG0–30 or ΔI0–120/ΔG0–120. The discriminatory power of various prediction models for development of type 2 diabetes was tested with the area under the receiver-operating characteristic (ROC) curve. RESULTS—Insulin secretion/insulin resistance index (0- to 30- and 0- to 120-min time periods) had the greatest areas under the ROC curve (0.85 and 0.86, respectively), which were significantly greater than the 2-h plasma glucose concentration during the OGTT or the San Antonio Diabetes Prediction Model (SADPM) (P &amp;lt; 0.001 and P &amp;lt; 0.0001, respectively). A model based on the combination of the SADPM and a modified version of the insulin secretion/insulin resistance index or 1-h plasma glucose concentration had equal power to predict the risk for future type 2 diabetes compared with the insulin secretion/insulin resistance index. CONCLUSIONS—The insulin secretion/insulin resistance index is useful as a predictor of future development of type 2 diabetes. A model based on the combination of the SADPM and either a modified version of the insulin secretion/insulin resistance index or 1-h plasma glucose concentration can equally predict future type 2 diabetes.
MEASURES OF MENTAL HEALTH FROM THE HUMM-WADSWORTH TEMPERAMENT SCALE
Authors: DONCASTER G. HUMM, KATHRYN A. HUMM
Journal: American Journal of Psychiatry (1950)

In undertaking to find a measure to give us a quantitative basis for the prediction of temperamental integration, we computed the difference between normal and each of the other components on the Humm-Wadsworth profile and, also, the sum of these differences. We did this first for a small number of subjects selected on the basis of known facts concerning their mental health; and then for 1,000 random permanent employees. We found that: (1) the integration index distinguished without exception between subjects known to be psychotic and subjects known to be well adjusted; (2) the component control measures significantly differentiated the means of the 2 groups; (3) distributions of the measures for 1,000 "permanent" employees provided data from which norms could be derived. From this we conclude that the measures of self-mastery provided an additional tool [See FIG. 3. in source pdf] for studying the temperaments of individuals and of groups.
Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment
Authors: G. Cartron, M. Ohresser, G. Salles, P. Solal-Céligny, P. Colombat, H. Watier
Journal: Annals of Oncology (2008)
Clinical and Molecular Evidence for c-kit Receptor as a Therapeutic Target in Neuroblastic Tumors
Authors: Stefania Uccini, Olga Mannarino, Heather P. McDowell, Ursula Pauser, Roberta Vitali, Pier Giorgio Natali, Pierluigi Altavista, Tiziana Andreano, Simona Coco, Renata Boldrini, Sandro Bosco, Anna Clerico, Denis Cozzi, Alberto Donfrancesco, Alessandro Inserra, George Kokai, Paul D. Losty, Maria R. Nicotra, Giuseppe Raschellà, Gian Paolo Tonini, Carlo Dominici
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Clinicobiological characteristics of neuroblastic tumor (NT) expressing c-kit tyrosine kinase receptor and/or its ligand, stem cell factor (SCF), are debated. This study aimed at investigating the clinicobiological features of primary NTs expressing c-kit and/or SCF in order to define the clinical relevance of selective therapeutic targeting. Experimental Design: c-Kit and SCF expression was studied in 168 NTs using immunohistochemistry and in 106 of 168 using Northern blot. Quantitative determination of c-kit expression in 54 additional NTs was also done using real-time reverse transcription-PCR. Correlations between c-kit and SCF expression and clinicobiological features were analyzed using χ2 test, univariate, and multivariate regression analyses. Results: c-Kit protein was detected in 21 of 168 NTs (13%) and its mRNA in 23 of 106 NTs (22%). SCF protein was shown in 30 of 106 NTs (28%) and its mRNA in 33 of 106 NTs (31%). No mutations in exon 11 of c-kit gene were identified. By univariate analysis, c-kit and SCF expression correlated with advanced stage, MYCN amplification, and 1p36 allelic loss. Cox simple regression analysis showed that overall survival probability was 17% in the c-kit–positive subset versus 68% in the negative (P &amp;lt; 0.001), 43% in the SCF-positive subset versus 78% in the negative (P &amp;lt; 0.001). When using real-time reverse transcription-PCR, significant levels of c-kit mRNA were found in 35 of 54 NTs (65%), but the correlations with clinicobiological features were no longer documented. Conclusions: c-Kit expression can be detected in the majority of primary NTs. High levels of expression are preferentially found in tumors with unfavorable clinicobiological variables. c-Kit may represent a useful therapeutic target in a subset of otherwise untreatable NTs.
<i>Ex vivo</i>micro-computed tomography analysis of bleomycin-induced lung fibrosis for preclinical drug evaluation
Authors: Chris J. Scotton, Brian Hayes, Robert Alexander, Arnab Datta, Ellen J. Forty, Paul F. Mercer, Andy Blanchard, Rachel C. Chambers
Journal: European Respiratory Journal (2013)

Research into the pathogenesis underlying the development of idiopathic pulmonary fibrosis is hampered by a repertoire of animal models that fail to recapitulate all the features of the human disease. Better use and understanding of what the animal models represent may improve clinical predictability. We interrogated ex vivo micro-computed tomography (CT) as a novel end-point measure in the mouse model of bleomycin-induced lung fibrosis (BILF), and to evaluate a therapeutic dosing regimen for preclinical drug evaluation. A detailed characterisation of BILF was performed using standard end-point measures (lung hydroxyproline and histology). High resolution micro-CT (∼13.7 μm voxel size) was evaluated for quantifying the extent and severity of lung fibrosis. The period from 14 to 28 days following bleomycin instillation represents progression of established fibrosis. A therapeutic dosing regimen during this period was validated using a transforming growth factor-β receptor-1 kinase inhibitor, and micro-CT provided a highly sensitive and quantitative measure of fibrosis. Moreover, fibrotic lesions did not completely resolve, but instead persisted for ≥6 months following a single insult with bleomycin. Ex vivo micro-CT analysis of BILF allows robust evaluation of therapeutic dosing once fibrosis is already well established, requiring fewer mice than conventional biochemical end-points.
THE INFLUENCE OF THE VAGUS NERVES ON THE FARADIZED AURICLES IN THE DOG'S HEART
Authors: G. Canby Robinson
Journal: The Journal of Experimental Medicine (1913)

An abnormal auricular activity is produced by faradization of the right auricle of the dog, which frequently becomes established and continues for varying periods of time after faradization is discontinued. This auricular activity consists of a rapid auricular tachycardia coexisting with true auricular fibrillation. In some dogs the auricles are thrown into this abnormal activity more readily by faradization after the vagi have been cut than before. Cutting the nerves has little or no effect on the abnormal auricular activity, but the ventricular rate may be much increased if the vagi are cut after the abnormal auricular activity has been established, apparently because of an improvement in the auriculoventricular conductivity. Stimulation of the right vagus nerve changes the character of the activity of the faradized auricles by inhibiting the auricular tachycardia while the fibrillation is uninfluenced. Stimulation of the left vagus nerve has little or no apparent inhibitory effect on the auricular tachycardia, but has possibly an inhibitory effect on the auricular fibrillation. Vagus stimulation increases the susceptibility of the auricles to faradization. The abnormal activity set up by faradization may be established in hearts otherwise refractory by vagus stimulation of short duration following the faradization. Vagus stimulation usually holds the auricles in the abnormal activity set up by faradization as long as it is continued in hearts in which, without vagus stimulation, the sequential beat always returns as soon as faradization is stopped. The right vagus is more effectual in this respect than the left. In some hearts vagus stimulation alone is capable of initiating the same abnormal auricular activity which is caused by auricular faradization. The normal sequential beat is often restored by vagus stimulation. It replaces the abnormal auricular activity not during, but a few seconds after, the termination of vagus stimulation. Left vagus stimulation is somewhat more effectual in producing this result than right vagus stimulation.
p53 Mutations in Benzo(a)Pyrene-Exposed Human p53 Knock-in Murine Fibroblasts Correlate with p53 Mutations in Human Lung Tumors
Authors: Zhipei Liu, Karl-Rudolf Muehlbauer, Heinz H. Schmeiser, Manfred Hergenhahn, Djeda Belharazem, Monica C. Hollstein
Journal: Cancer Research (2005)

Human p53 mutation spectra differ significantly from one cancer type to another. One possible reason is that carcinogenic risk factors differ, and these factors elicit distinct mutation patterns. There has been no mammalian assay, however, with which to generate mutation patterns in human p53 sequences experimentally, hampering interpretation of the human tumor spectra. We have designed a new mammalian cell assay using gene targeting technology that selects and scores human p53 gene sequence mutations in human-p53 knock-in (Hupki) murine embryonic fibroblasts (HUF) that have undergone immortalization. With the Hupki assay we examined here whether benzo(a)pyrene (BaP), a major tobacco smoke carcinogen could elicit p53 mutation patterns characterizing the human lung tumor p53 mutation spectrum. We found that, in contrast to unexposed HUFs or HUFs exposed to other carcinogenic agents, HUFs exposed to BaP acquire mutations that display major features of the human lung tumor p53 mutation spectrum: (a) predominance of G-to-T mutations, (b) unequivocal strand bias of the transversions, and (c) a mutation hotspot at codons 157 to 158. These data are consistent with the hypothesis that BaP has a direct role in causing smokers' lung tumor p53 mutations. The assay can be used to examine various hypotheses on the endogenous or exogenous factors responsible for the p53 mutations in human tumors arising in other tissues.
An immunodominant SSX-2–derived epitope recognized by CD4+ T cells in association with HLA-DR
Authors: Maha Ayyoub, Charles S. Hesdorffer, Monica Montes, Andrea Merlo, Daniel Speiser, Donata Rimoldi, Jean-Charles Cerottini, Gerd Ritter, Matthew Scanlan, Lloyd J. Old, Danila Valmori
Journal: Journal of Clinical Investigation (2004)

Ectopic gene expression in tumors versus normal somatic tissues provides opportunities for the specific immunotargeting of cancer cells. SSX gene products are expressed in tumors of different histological types and can be recognized by tumor-reactive CTLs from cancer patients. Here, we report the identification of an SSX-2–derived immunodominant T cell epitope recognized by CD4+ T cells from melanoma patients in association with HLA-DR. The epitope maps to the 37–58 region of the protein, encompassing the sequence of the previously defined HLA-A2–restricted immunodominant epitope SSX-241–49. SSX-237–58–specific CD4+ T cells were detected among circulating lymphocytes from the majority of melanoma patients analyzed and among tumor-infiltrating lymphocytes, but not in healthy donors. Together, our data suggest a dominant role of the 37–58 sequence in the induction of cellular CD4+ T cell responses against SSX antigens and will be instrumental for both the onset and the monitoring of upcoming cancer-vaccine trials using SSX-derived immunogens.