tbuckley/cabot-search huggingface dataset:
Possible role of REG I protein in ulcerative colitis and colitic cancer
Authors: A Sekikawa
Journal: Gut (2005)

<b>Background and aims:</b> Although <i>regenerating gene</i> (REG) Iα protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the <i>REG Iα</i> gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for <i>REG Iα</i> gene expression and whether REG Iα protein has a trophic and/or an antiapoptotic effect on colon cancer cells. <b>Methods:</b> Expression of <i>REG Iα</i> mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on <i>REG Iα</i> promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Iα protein on growth and H<sub>2</sub>O<sub>2</sub> induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. <b>Results:</b> REG Iα protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of <i>REG Iα</i> mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. <i>REG Iα</i> promoter activity was enhanced by stimulation with interferon γ or interleukin 6. REG Iα protein promoted cell growth and conferred resistance to H<sub>2</sub>O<sub>2</sub> induced apoptosis in LoVo cells. REG Iα protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. <b>Conclusions:</b> The <i>REG Iα</i> gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.
Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice
Authors: Adam D. Judge, Marjorie Robbins, Iran Tavakoli, Jasna Levi, Lina Hu, Anna Fronda, Ellen Ambegia, Kevin McClintock, Ian MacLachlan
Journal: Journal of Clinical Investigation (2009)

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target's biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics.
Imatinib treatment duration is related to decreased estimated glomerular filtration rate in chronic myeloid leukemia patients
Authors: M.S. Marcolino, E. Boersma, N.C.D. Clementino, A.V. Macedo, A.D. Marx-Neto, M.H.C.R. Silva, T. van Gelder, K.M. Akkerhuis, A.L. Ribeiro
Journal: Annals of Oncology (2011)
Monoclonal antibodies specific for T cell-associated carbohydrate determinants react with human blood group antigens CAD and SDA.
Authors: A Conzelmann, L Lefrancois
Journal: The Journal of Experimental Medicine (1988)

The CT antigenic determinants have previously been shown to be present on the T200 glycoproteins and other proteins of murine cytotoxic T cell clones but not of T helper clones or nonactivated lymphocytes (1, 2). Two determinants recognized by mAbs CT1 and CT2 are also expressed on thymocytes in a developmentally regulated fashion during fetal thymus ontogeny and are found in a subset of Lyt-2+ intraepithelial lymphocytes in the intestinal mucosa (3-5). Previous studies of the biosynthesis of CT+ proteins suggested that these determinants were composed of carbohydrate (8). We now demonstrate that the anti-CT mAbs react with a carbohydrate determinant at the nonreducing terminus of O-linked oligosaccharides that has the configuration GalNAc beta 1,4[SA alpha 2,3]-galactose. The CT antibodies detected this determinant not only on CTL clones but also in the human blood group antigens Cad and Sda+. Variant CTL lines, non-Cad erythrocytes, and Sda- glycoproteins that lacked the GalNAc residue did not bind the CT mAb. Sialic acid was essential for CT antigen expression since neuraminidase or mild periodate treatment abrogated CT antibody binding. In addition, other carbohydrate structures with terminal GalNAc residues such as the A or Tn blood group antigens were not recognized. The CT antibodies thus define GalNAc and sialic acid containing carbohydrate antigens that are expressed on discrete subsets of T lymphocytes and may also be useful reagents for the detection of Cad and Sda+ blood group antigens.
Investigation of Schwann Cells at Neoplastic Cell Sites Before the Onset of Cancer Invasion
Authors: Ihsan Ekin Demir, Alexandra Boldis, Paulo L. Pfitzinger, Steffen Teller, Eva Brunner, Natascha Klose, Timo Kehl, Matthias Maak, Marina Lesina, Melanie Laschinger, Klaus-Peter Janssen, Hana Algül, Helmut Friess, Güralp O. Ceyhan
Journal: JNCI Journal of the National Cancer Institute (2014)

In neural invasion (NI), cancer cells are classically assumed to actively invade nerves and to cause local recurrence and pain. However, the opposite possibility, that nerves may reach cancer cells even in their preinvasive stage and thereby promote cancer spread, has not yet been genuinely considered. The present study analyzes the reaction of Schwann cells of peripheral nerves to carcinogenesis in pancreatic cancer and colon cancer.Two novel 3D migration and Schwann cell outgrowth assays were developed to monitor the timing and the specificity of Schwann cell migration and cancer invasion toward peripheral neurons through digital-time-lapse microscopy and after blockade of nerve growth factor (NGF) signalling via siRNA or a small-molecule inhibitor of the p75(NTR) receptor. The frequency and emergence of the Schwann cell markers Sox10, S100, ALDH1L1, and glial-fibrillary-acidic-protein (GFAP) around cancer precursor lesions were studied in human and conditional murine pancreatic and colon cancer specimens using multiple immunolabeling.Schwann cells migrated toward pancreatic and colon cancer cells, but not toward benign cells, before the onset of cancer migration toward peripheral neurons. This chemoattraction was inhibited after blockade of p75(NTR)-signaling on Schwann and pancreatic cancer cells. Schwann cells were specifically detected around murine and human pancreatic intraepithelial neoplasias (PanINs) (mean percent of murine PanINs surrounded by Schwann cells = 78.9%, 95% CI = 70.9 to 86.8%, and mean percent of human PanINs surrounded by Schwann cells = 52.5%, 95% CI = 14.7 to 90.4%; human: n = 44, murine: n = 14) and intestinal adenomas (mean percent of murine adenomas surrounded by Schwann cells = 64.2%, 95% CI = 28.6 to 99.8%, and mean percent of human adenomas surrounded by Schwann cells = 17.2%, 95% CI = -126.9 to 161.4; human: n = 36, murine: n = 12). The Schwann cell presence in this premalignant stage was associated with the frequency of NI in the malignant phase.Schwann cells have particular and specific affinity to cancer cells. Emergence of Schwann cells in the premalignant phase of pancreatic and colon cancer implies that, in contrast with the traditional assumption, nerves-and not cancer cells-migrate first during NI.
Immunoglobulin subclass distribution of specific antibodies in allergic patients
Authors: L. Hammarströ, C. I. E. Smith
Journal: Allergy (1987)

The IgG and IgA subclass distribution of specific antibodies against a variety of protein and polysaccharide antigens was determined in sera from individuals with high levels of IgE. No shift of the antibody pattern could be observed, suggesting that the aberrant regulation of responses against allergens noted in these patients is limited, encompassing selected antigens only. Antibodies against protein antigens are mainly of the IgG1 subclass. In addition, low levels of specific IgG3 or IgG4 antibodies may be formed. Our data suggest that a given antigen induces either IgG3 or IgG4 and that potential allergens, in addition to IgG1 and IgE, elicit a response restricted to IgG4.
Test-Retest Stability of the Repeatable Battery for the Assessment of Neuropsychological Status in Schizophrenia
Authors: Christopher M. Wilk, James M. Gold, John J. Bartko, Faith Dickerson, Wayne S. Fenton, Michael Knable, Christopher Randolph, Robert W. Buchanan
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was designed as a cognitive screening test, providing both a total scale score and five specific cognitive ability index scores. This study examined the test-retest stability of the RBANS in individual patients with schizophrenia relative to a healthy comparison group. METHOD: A total of 181 patients with schizophrenia or schizoaffective disorder were recruited from three clinical settings. Healthy comparison subjects were recruited as part of the RBANS standardization. Participants were administered one form of the RBANS on one occasion and another form at a later date, with intervals ranging from 1 to 134 days. RESULTS: Intraclass correlation coefficients for the RBANS total scale were 0.84 for the patients with schizophrenia and 0.77 for the healthy comparison subjects. Confidence intervals and percentile data for the total scale change scores were similar for both groups. CONCLUSIONS: The RBANS demonstrated reasonable intraclass correlation coefficient test-retest reliability for both schizophrenia patients and healthy comparison subjects. Confidence intervals are comparable to those previously published for the WAIS-R and Wechsler Memory Scale—Revised, suggesting that retest measurement error is not dramatically increased in the RBANS, despite the brevity of the test. These data may serve as an informative guide for using the RBANS to evaluate neuropsychological change on the level of the individual subject.
Gfi1b negatively regulates <i>Rag</i> expression directly and via the repression of <i>FoxO1</i>
Authors: Danae Schulz, Lothar Vassen, Kwan T. Chow, Sarah M. McWhirter, Rupesh H. Amin, Tarik Möröy, Mark S. Schlissel
Journal: The Journal of Experimental Medicine (2011)

Precise regulation of Rag (recombination-activating gene) expression is crucial to prevent genomic instability caused by the generation of Rag-mediated DNA breaks. Although mechanisms of Rag activation have been well characterized, the mechanism by which Rag expression is down-regulated in early B cell development has not been fully elucidated. Using a complementary DNA library screen, we identified the transcriptional repressor Gfi1b as negative regulator of the Rag locus. Expression of Gfi1b causes repression of Rag1 and Rag2 in cell lines and primary mouse cells. Conversely, Gfi1b-deficient cell lines exhibit increased Rag expression, double-strand breaks and recombination, and cell cycle defects. In primary cells, transcription of Gfi1b inversely correlates with Rag transcription, and simultaneous inactivation of Gfi1 and Gfi1b leads to an increase in Rag transcription early in B cell development. In addition, deletion of Gfi1 and Gfi1b in vivo results in a severe block in B cell development. Gfi1b orchestrates Rag repression via a dual mechanism. Direct binding of Gfi1b to a site 5′ of the B cell–specific Erag enhancer results in epigenetic changes in the Rag locus, whereas indirect inhibition is achieved through repression of the trans-activator Foxo1. Together, our experiments show that Gfi family members are essential for normal B cell development and play an important role in modulating expression of the V(D)J recombinase.
The Medical Research Council and clinical trial methodologies before the 1940s: the failure to develop a ‘scientific’ approach
Authors: Linda Bryder
Journal: Journal of the Royal Society of Medicine (2011)

In 1989 Joan Austoker and I set out our goal in Historical Perspectives of the Role of the MRC ‘to discuss the role of the Medical Research Council in shaping a national system of medical research in Britain’.1 We noted that the only general history of the Medical Research Council (MRC) at that time was authored by an MRC staff member, A Landsborough Thomson, who had produced two volumes in 1973 and 1975.2,3 Our book remains the only attempt apart from Landsborough Thomson's to construct a general overview of the work of the MRC, but over the past two decades, there has been considerable interest in the history of the MRC, particularly in relation to the lead-up to its world-famous streptomycin trial for pulmonary tuberculosis, which it reported in 1948.4 This commentary provides a review of the information that has accumulated since 1989 – which is scattered in monographs, articles and unpublished theses – relating to the pre-history of this important trial.
Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat
Authors: L. Brown, D. Nunez, C. Brookes, M. Wilkins
Journal: Cardiovascular Research (1995)

Objective: At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of the aortovenocaval (AV) fistula rat. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify cardiac mRNA expression of the endothelins and their receptors during the development of cardiac hypertrophy, while radioligand binding was employed to quantify the amount of [125I]-ET-1 binding to cardiac membranes. Tissue and plasma concentrations of ET-1 were measured by radioimmunoassay. Results: In control sham operated animals, ET-1 mRNA was ~fivefold greater in atria than in ventricles (P < 0.05), but there were no atrioventricular differences in ET-2 or ET-3 mRNA. In the AV fistula rats there was a prompt three- to fourfold increase in ET-1 mRNA in atria and a progressive five- to sevenfold rise in ventricles during cardiac hypertrophy. There were no changes in ET-2 or ET-3 transcript prevalences, except for a late rise (35 d) in ET-2 mRNA levels in left ventricle. Consistent with ET-1 mRNA measurements, immunoreactive endothelin levels were increased by 7 d in atria, but not in ventricles. In control rat hearts, ETAR mRNA levels were similar in atria and ventricles, but the prevalence of ETBR was ~sevenfold greater in the former. ETAR mRNA prevalence increased with hypertrophy in all chambers, while ETBR transcript levels were raised only in the right ventricle. There was no significant difference in [125I]-ET-1 binding between atrial samples from 35 d control and 35 d AV fistula rats, suggesting rapid turnover of endothelin receptors balanced by increased transcription from the ETAR gene. Conclusions: During cardiac hypertrophy in AV fistula rats there is increased activity of the endothelin system mediated principally by ET-1 and the ETAR subtype.
The importance of attitudes towards physical activity and its relationship with practice of physical activity
Authors: Adilson Marques, João Martins, Maria Martins, João Costa, Hugo Sarmento, Marcos Onofre, Francisco Carreiro da Costa
Journal: British Journal of Sports Medicine (2011)

The purpose of this study was to examine the importance given by children to physical activity (PA) and its relationship with the practice of formal PA as well as the perception of parents' participation. A total of 416 boys and 386 girls aged between 10 and 12 y, participated in the study. Data was collected using a questionnaire used on international research project on children's lifestyles. T-test was used to identify the difference of attitudes towards PA by gender and practice of PA. ANOVA was performed to analyse the attitude and parents participation. Significance level was p&lt;0.05. On a scale ranged from 1 to 10, most students showed a positive attitude towards PA (M=9.1). The difference between boys (M=9.2) and girls (M=8.9) was significant ( p =0.021). Pupils with higher attitude towards PA were more involved in formal PA than those with lower attitude (9.3 vs 8.8, p &lt;0.001), whether for boys (9.4 vs 8.9, p =0.001) or girls (9.3 vs 8.7, p &lt;0.001). The mean value for the attitude towards PA was not significant when we consider the difference among those who perceive that parents were active or inactive ( p =0.482). However, a trend was observed: those whose either parents or only the mother was active showed a higher attitude towards PA. PA seems to be something that most of kids like, but those who were involved with a formal PA in a club showed a higher attitude towards PA. The perception of parents' participation in PA seems to be associated with a favourable attitude toward PA.
Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype
Authors: Robert D. Loberg, Christopher J. Logothetis, Evan T. Keller, Kenneth J. Pienta
Journal: Journal of Clinical Oncology (2005)

Traditionally, prostate cancer treatment, as well as all cancer treatment, has been designed to target the tumor cell directly via various hormonal and chemotherapeutic agents. Recently, the realization that cancer cells exist in complex microenvironments that are essential for the tumorigenic and metastatic potential of the cancer cells is starting the redefine the paradigm for cancer therapy. The propensity of prostate cancer cells to metastasize to bone is leading to the design of novel therapies targeting both the cancer cell as well as the bone microenvironment. Tumor cells in the bone interact with the extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial cells to promote tumor-cell survival and proliferation leading to a lethal phenotype that includes increased morbidity and mortality for patients with advanced prostate cancer. Several strategies are being developed that target these complex tumor cell-microenvironment interactions and target the signal transduction pathways of other cells important to the development of metastases, including the osteoclasts, osteoblasts, and endothelial cells of the bone microenvironment. Current and new therapies in metastatic prostate cancer will comprise a multitargeted approach aimed at both the tumor cell and the tumor microenvironment. Here, we review the current therapeutic strategies for targeting the prostate cancer-bone microenvironment and several single- and multiagent targeted approaches to the treatment of advanced prostate cancer that are under development.
Traffic-related Air Pollution and the Right Ventricle. The Multi-ethnic Study of Atherosclerosis
Authors: Peter J. Leary, Joel D. Kaufman, R. Graham Barr, David A. Bluemke, Cynthia L. Curl, Catherine L. Hough, Joao A. Lima, Adam A. Szpiro, Victor C. Van Hee, Steven M. Kawut
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Right heart failure is a cause of morbidity and mortality in common and rare heart and lung diseases. Exposure to traffic-related air pollution is linked to left ventricular hypertrophy, heart failure, and death. Relationships between traffic-related air pollution and right ventricular (RV) structure and function have not been studied.To characterize the relationship between traffic-related air pollutants and RV structure and function.We included men and women with magnetic resonance imaging assessment of RV structure and function and estimated residential outdoor nitrogen dioxide (NO2) concentrations from the Multi-ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease at baseline. Multivariable linear regression estimated associations between NO2 exposure (averaged over the year prior to magnetic resonance imaging) and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus, and hypertension. Adjustment for corresponding left ventricular parameters, traffic-related noise, markers of inflammation, and lung disease were considered in separate models. Secondary analyses considered oxides of nitrogen (NOx) as the exposure.The study sample included 3,896 participants. In fully adjusted models, higher NO2 was associated with greater RV mass and larger RV end-diastolic volume with or without further adjustment for corresponding left ventricular parameters, traffic-related noise, inflammatory markers, or lung disease (all P < 0.05). There was no association between NO2 and RV ejection fraction. Relationships between NOx and RV morphology were similar.Higher levels of NO2 exposure were associated with greater RV mass and larger RV end-diastolic volume.
IgE-mediated chemotaxis of rat basophilic leukemia cells towards specific antigen.
Authors: N Orida, J D Feldman, D H Katz, F T Liu
Journal: The Journal of Experimental Medicine (1983)

We evaluated chemotactic properties of four sublines of rat basophilic leukemia cells using blindwell Boyden chamber assays. After sensitization with a mouse monoclonal IgE directed against dinitrophenyl (DNP), cells from sublines 2H3-C and 926a underwent chemotaxis toward DNP-bovine serum albumin (BSA) and sublines RBL-1 and 4A did not. Chemotactic responses required specific IgE and were determined by the IgE antigen specificity used for sensitization. The threshold for chemotaxis was on the order of 10(-10) M DNP-BSA. Release of incorporated [3H]-serotonin did not always parallel chemotactic responses, which suggests that chemotaxis and secretion may be two unlinked processes that occur during basophil activation. Our results predict a possible in vivo mechanism whereby specific chemotactic responses of basophils and other FcR epsilon-bearing cells are mediated via specific IgE bound to membrane FcR epsilon.
How Can We Use Our Knowledge of Alcohol-Tobacco Interactions to Reduce Alcohol Use?
Authors: Sherry A. McKee, Andrea H. Weinberger
Journal: Annual Review of Clinical Psychology (2012)

Currently, 8.5% of the US population meets criteria for alcohol use disorders, with a total cost to the US economy estimated at $234 billion per year. Alcohol and tobacco use share a high degree of comorbidity and interact across many levels of analysis. This review begins by highlighting alcohol and tobacco comorbidity and presenting evidence that tobacco increases the risk for alcohol misuse and likely has a causal role in this relationship. We then discuss how knowledge of alcohol and tobacco interactions can be used to reduce alcohol use, focusing on whether (a) smoking status can be used as a clinical indicator for alcohol misuse, (b) tobacco policies reduce alcohol use, and (c) nicotinic-based medications can be used to treat alcohol use disorders.