tbuckley/cabot-search huggingface dataset:
Abstract 5100: Expression of the insulin signaling related genes by infection of hepatitis C virus
Authors: Takuya Matsumura, Reiko Makino, Kazuo Ito, Michio Imawari, Takanobu Kato
Journal: Cancer Research (2010)

Abstract BACKGROUND: Hepatitis C virus (HCV) induces chronic liver diseases such as chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Either molecular or clinical studies support a correlation between HCV infection and insulin resistance. Patients with chronic HCV infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients. The HCV core protein is known to contribute to insulin resistance related steatosis, fibrosis, and carcinogenesis of the liver. Although several hypotheses have been demonstrated, a mechanism of insulin resistance by HCV infection is complex and still unclear. AIM: The aim of this study is to investigate the molecular mechanisms of liver injury by HCV through insulin signaling pathway. MATERIALS AND METHODS: HCV infected cultured cells and transgenic mice expressing HCV core gene were used for this study. A HCV strain JFH-1 replicates efficiently in cultured cells with production of infectious HCV. A transgenic mouse was established by introducing the core gene derived from the HCV genome of genotype 1b. Total RNA was extracted from the cells with and without HCV infection, and the livers of transgenic mice and their littermate wild type mice. The cDNA was synthesized from the RNA then applied to the real-time PCR. The relative amount of the mRNAs of 84 genes related to the insulin receptor and target genes for insulin signaling were compared between the cells or tissues with or without HCV. RESULTS and DISCUSSION: The expression of one of the insulin receptor substrate (IRS) family mRNA was increased in cells infecting HCV, compared to uninfected cells. On the other hand, the Akt mRNA expressed at higher level in the liver of transgenic mouse than that of normal littermate. The IRS family proteins are key mediators in insulin signaling and have been reported to associate with glucose metabolism. The Akt protein kinase is a critical regulator of human physiology that controls an impressive array of diverse cellular functions, including the modulation of growth, survival, proliferation and metabolism. The activation of Akt signaling may induce not only the insulin resistance but also the development of HCCs in the patients with HCV chronic infection. CONCLUSIONS: Our results indicates that the alteration of IRS family and Akt expression by HCV could be predictive for insulin resistance. Since the insulin resistance promotes inflammation and fibrogenesis in the liver, HCV infection leads to the development of liver cirrhosis and HCC by activation of insulin signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5100.
SP0039 Immunological and genetic basis of CRMO
Authors: C.M. Hedrich
Journal: Annals of the Rheumatic Diseases (2013)

Chronicnon-bacterial osteomyelitis (CNO) is an inflammatory bone disorder of yet unknown origin. The clinical spectrum ranges from relatively benign, self-limiting, mono-focal symptoms to destructive, multi-focal involvement (known as chronic recurrent multifocal osteomyelitis, CRMO). Secondary to the absence of high-titer autoantibodies and autoreactive T lymphocytes, CNO was classified as an autoinflammatory disorder. The diagnosis is based on the clinical picture, the exclusion of differential diagnoses (including infections and malignancies), and radiographic findings. Treatment options are empiric, including NSAIDs as first line therapy, and steroids, bisphosphonates, or biologicals in more treatment resistant cases. To date, the etiopathology of CNO remains to be elucidated. Linkage analyses point to a susceptibility locus on chromosome 18q. However, conclusive evidence is lacking. A rare syndromal form of CNO, referred to as Majeed syndrome, has been linked to mutations in the <i>LPIN2</i> gene on chromosome 18p. Further autoinflammatory syndromes, namely deficiency of IL-1 receptor antagonist (DIRA; mutations in <i>IL1RN</i>) and pyogenic arthritis, pyoderma gangrenosum and acne (PAPA; mutations in <i>CD2BP1</i> gene), share bone inflammation with CNO, however presenting with a more severe clinical picture. We will discuss 1) animal models, mimicking the phenotype of CRMO, 2) how genetic and immunological findings in related disorders may contribute to a better understanding of the pathophysiology of bone inflammation in CNO, and 3) most recent findings, indicating that monocytes from CNO patients fail to produce IL-10, resulting in a disrupted balance between pro- and anti-inflammatory cytokines. <h3>Disclosure of Interest</h3> None Declared
Autophagy Contributes to Release of IL-18 From Epithelial Cells in Alternaria Exposure
Authors: Hiroki Murai, Motoko Yasutomi, Hisako Hayashi, Akiko Kawakita, Koji Suzuki, Istvan Boldogh, Sanjiv Sur, Yusei Ohshima
Journal: Journal of Allergy and Clinical Immunology (2013)
P261 ROLE OF ANNEXIN A1 IN THE PROGRESSION OF NONALCOHOLIC STEATOHEPATITIS (NASH)
Authors: I. Locatelli, S. Sutti, A. Jindal, M. Vacchiano, C. Bozzola, C. Reutelingsperger, D. Kusters, S. Bena, M. Parola, C. Paternostro, E. Bugianesi, S. Mc Arthur, M. Perretti, E. Albano
Journal: Journal of Hepatology (2014)
Abstract 3459: Expression of oncogene-induced senescence markers in pilocytic astrocytomaIs associated with younger age and longer survival
Authors: Kah Suan Lim, Eli E. Bar, Eric H. Raabe, Deepali Jain, Charles G. Eberhart
Journal: Cancer Research (2011)

Abstract Pilocytic astrocytomas are the most common pediatric brain tumor. They are low grade neoplasms, and in some cases can spontaneously stop growing or regress. The recent discovery of constitutive BRAF activation in the majority of pilocytic astrocytomas, due either to gene duplication/fusion or point mutation, suggests a possible molecular basis for this relatively benign pathobiology. Oncogenic BRAF-induced senescence has previously been identified in benign melanocytic nevi and colonic polyps, but whether it also occurs in pilocytic astrocytomas is not clear. To investigate this, we examined the senescence marker acidic beta-galactosidase in low passage pilocytic astrocytoma cultures established from freshly resected tumors. Two of these cultures, tested at passages 2 to 3, were derived from tumors that contained KIAA1549:BRAF fusions, and both expressed the senescence marker in over half of the cells. Another culture tested at passage 3 was also strongly positive for acidic beta-galactosidase, but the genetic status of its parent tumor is not known. A final culture came from a pilocytic astrocytoma lacking the KIAA1549:BRAF fusion, or an activating V600E BRAF point mutation, and was negative for the senescence marker, but was tested at passage 10. To help confirm these effects in vivo, we immunostained a tissue microarray containing 78 pilocytic astrocytoma for p16 and p53, both of which have been implicated in oncogene-induced senescence in other tumor types. The majority of pilocytic astrocytoma expressed p16, but the 13% of tumors lacking this senescence marker were associated with significantly shorter overall survival (p = 0.0002). Patients whose pilocytic astrocytomas lacked p16 were also older (mean age 25 years) as compared to those with intermediate (mean age 12 years) or high expressing tumors (mean age 7 years). Immunohistochemical analysis of p53 revealed much weaker staining, and only 18 tumors were positive, but expression correlated positively with that of p16 (Spearman r = 0.45, p = 0.0001). Our data suggest that the low-grade phenotype of pilocytic astrocytomas may be due to oncogene-induced senescence driven by KIAA1549:BRAF fusions or BRAF V600E point mutations, and that expression of senescence markers in vivo is associated with younger age at presentation and better clinical outcomes. 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 3459. doi:10.1158/1538-7445.AM2011-3459
310 FGF INDUCIBLE PROTEIN 14 IS UPREGULATED IN NEOVESSELS DURING CHRONIC INFLAMMATORY LIVER DISEASE AND PROMOTES INTRAHEPATIC ENDOTHELIAL CELL ANGIOGENESIS IN VITRO FOLLOWING STIMULATION VIA TWEAK
Authors: M. Munir, E.H. Humphreys, A. Wilhelm, B.T.F. Stephenson, J. Caamano, D.H. Adams, L.C. Burkley, S.C. Afford
Journal: Journal of Hepatology (2013)
Abstract 1871: Honokiol, a natural plant product, inhibits ultraviolet radiation-induced skin tumorigenesis in mice through inhibition of inflammation and inflammatory mediators
Authors: Som D. Sharma, Mudit Vaid, Santosh K. Katiyar
Journal: Cancer Research (2010)

Abstract Chronic exposure of solar ultraviolet (UV) radiation is the major etiologic agent for over one million new cases of non-melanoma skin cancers in the US each year. These cutaneous malignancies thus have a tremendous impact on public health and healthcare expenditures. The use of natural plant products has received considerable interest to protect skin from adverse biological effects of UV radiation since the protective clothing and use of sunscreens are not adequate for skin photoprotection. The photoprotective effect of honokiol, a plant product from Magnolia species, therefore assessed using SKH-1 hairless mouse model. To determine the skin cancer chemopreventive effect and associated mechanism of honokiol, a hydrophilic cream based topical formulation was developed. Different groups of mice (n=20) treated with or without honokiol were subjected to photocarcinogenesis protocol. Mice were irradiated to UVB (180 mJ/cm2) three times a week. At the termination of the experiment at 24th week, we found that topical application of honokiol (1mg &amp; 3mg/mouse) inhibited UVB-induced skin tumor development in terms of tumor incidence (10-20%), tumor multiplicity (40-60%) and tumor size (50-75%). Since UV-induced inflammation plays a crucial role in the development of skin tumors, we examined the effect of honokiol on UVB-induced biomarkers of inflammation, such as the expression levels of cyclooxygenase-2 (COX-2), prostaglandins (PG), proliferating cell nuclear antigen (PCNA), infiltration of inflammatory leukocytes, development of edema and epidermal hyperplastic response using immunostaining, western blotting and RT-PCR. Our data revealed that topical application of honokiol before each exposure of UVB radiation resulted in a dose-dependent inhibition of UVB-induced expression of COX-2, PGE2, developments of edema and infiltration of leukocytes at the UVB-irradiated skin sites. Honokiol also inhibited the levels of PCNA (hyperplastic potential) in epidermal keratinocytes of UVB-exposed skin. The inhibitory effects of honokiol on inflammatory mediators were also found in skin tumor samples. The results of this study suggest that honokiol has the ability to inhibit UVB radiation-induced skin tumor development in mice and it is associated with the inhibition of UVB-induced inflammation and inflammatory mediators in mouse skin and skin tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1871.
Current Treatment of Infantile Hydrocephalus
Authors: Donald D. Matson
Journal: New England Journal of Medicine (1956)

PARENTS of an infant with internal hydrocephalus are interested, whether or not they are aware of it or admit it to themselves, not in survival of their child but in a chance for normal development. Although danger to the child's life itself may be the first problem such parents face, it soon becomes apparent that the possibility of sustaining a hopeless defective may be a much more devastating tragedy.From the surgeon's point of view, there is certainly little incentive to perform operations that permit life to go on but do not allow cerebral growth and development to proceed at . . .
EFFECT OF ECHOCARDIOGRAPHY-GUIDED LEFT VENTRICULAR LEAD PLACEMENT FOR CARDIAC RESYNCHRONIZATION THERAPY ON MORTALITY AND RISK OF DEFIBRILLATOR THERAPY FOR VENTRICULAR ARRHYTHMIAS: RESULTS FROM SPECKLE TRACKING ASSISTED RESYNCHRONIZATION THERAPY FOR ELECTRODE REGION (STARTER) TRIAL
Authors: Evan C. Adelstein, Mian Bilal Alam, David Schwartzman, Sandeep Jain, John Gorcsan, Samir Saba
Journal: Journal of the American College of Cardiology (2014)
Abstract 2364: Regulation of cofilin activity and tumor cell migration through protein kinase D
Authors: Samantha J. Spratley, Peter Storz
Journal: Cancer Research (2011)

Abstract During early metastatic events in cancer, reorganization of the actin cytoskeleton must occur to allow for cell invasion and migration. A key enzyme initiating actin remodeling at the leading edge is Cofilin, a small actin binding protein of the ADF/cofilin family with actin severing activities. Cofilin activity is tightly regulated by phosphorylation and dephosphorylation events that are mediated by LIM Kinase (LIMK) and the phosphatase Slingshot (SSH), respectively. Protein kinase D (PKD) is a serine/threonine kinase that has previously been shown to regulate actin driven directed cell migration through phosphorylation and thus inactivation of Slingshot. Here we show that PKD can also regulate cofilin activity via activation of LIMK. We further show that PKD-induced regulation of LIMK and the resulting diminished cofilin activity translates to altered cell motility. Our data suggest that PKD inactivates Cofilin through modulation of both of its regulatory pathways. Further elucidation of the mechanisms by which PKD regulates directed cell migration could enable development of a potential treatment strategy for invasive cancer. 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 2364. doi:10.1158/1538-7445.AM2011-2364
PMO-247 Mucosal cytokine expression in ulcerative colitis: elevated IL-8 but not TNF-α and reduced TGF-β in inflamed compared to non-inflamed mucosa
Authors: D S Pearl, K Shah, M Whittaker, H Nitch-Smith, J F Brown, J K Shute, T M Trebble
Journal: Gut (2012)

<h3>Introduction</h3> Ulcerative colitis (UC) is a chronic inflammatory condition of the colon of unconfirmed aetiology. Microscopic examination of inflamed biopsies is characterised by progressive neutrophil infiltration and tissue destruction. There is conflicting evidence from studies on the relative roles of TNFα, IL-8, TGFβ and other cytokines in UC; however, current therapy includes cytokine targeted interventions. We compared cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and age-sex matched controls. <h3>Methods</h3> Ethical approval was obtained. Patients were prospectively recruited from outpatients9 clinics. Mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age-sex matched controls undergoing FS. Severity of endoscopic (Sutherland) and histological (Gomes) inflammation were recorded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFN-γ were carried out using commercially available assays on tissue homogenates prepared with protease inhibitors, corrected for total protein. Statistical comparison was by Wilcoxon signed rank pair analysis and Spearman9s correlation. <h3>Results</h3> 69 active UC patients (54 paired normal/inflamed mucosa) and 69 controls were compared. Significant elevation in IL-8 (p&lt;0.001; p&lt;0.001) and reduction in TGFβ (p&lt;0.02; p&lt;0.0002) with significant positive correlation of IL-8 (r2=+0.46; p&lt;0.01) and negative correlation of TGFβ (r2=−0.46; p&lt;0.01) to severity of inflammation was detected in inflamed compared with non-inflamed mucosa from the same patient and compared to age-sex matched control mucosa; however, TNFα concentration was not significantly different. Comparisons of macroscopically inflamed mucosa compared with non-inflamed mucosa from the same patients also demonstrated significant reduction in concentration of IFNγ (p&lt;0.001), IL-4 (p&lt;0.005) and IL-17A (p&lt;0.002). No significant differences were noted between normal tissue from UC patients and external controls. <h3>Conclusion</h3> Our findings suggest that IL-8 (a neutrophil chemoattractant) is elevated and TGFβ (involved in cell repair) is reduced with no change demonstrated for TNFα. Significantly lower concentration of IFNγ, IL-4 and IL-17A suggests downregulation of Th1, Th2 and Th17 adaptive immune response. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing, with limited evidence for the role of TNFα in mild-moderate distal UC. <h3>Competing interests</h3> None declared.
CLINICAL FEATURES AND PREDICTORS OF PACING-INDUCED CARDIOMYOPATHY
Authors: Sung Woo Cho, Kwang Jin Chun, Kyoung-Min Park, Young Keun On, June Soo Kim, Suyeon Lee, Haseong Chang, Hyun Sung Joh, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2016)
Late Blood Pool Images After Tc-99m Tetrofosmin Injection in a Patient With Monoclonal Gammopathy of Uncertain Significance and Immunologic Disorders
Authors: LUCA CERIANI, LUCA GIOVANELLA, SILVANA GARANCINI
Journal: Clinical Nuclear Medicine (2000)

The authors report a case of abnormal biodistribution of Tc-99m tetrofosmin in a patient with immunologic disorders who underwent rest–stress myocardial perfusion scintigraphy to assess the operative risk for surgery of possible relapse of adenocarcinoma of the left maxillary sinus. The patient had monoclonal gammopathy of uncertain significance with a serum electrophoretic pattern of both monoclonal immunoglobulin A and free kappa light chain components and a mild form of idiopathic immunohemolytic anemia. Two different images at rest after injection of Tc-99m tetrofosmin showed a typical blood-pool pattern with absence of detectable myocardial uptake. Other patients injected with the same batch of radiopharmaceutical showed myocardial uptake. A change of the molecular characteristics of tetrofosmin after the injection could not be a factor, because the values of the main chemical and physical parameters of the blood were in the normal range. Accordingly, the authors propose the hypothesis that the monoclonal immunoglobulin A or the free kappa light chains of this patient accidentally recognized one or more epitopes of the tetrofosmin molecule, binding it with high affinity and causing an abnormal biodistribution, characterized by late blood-pool imaging. No similar experiences have been described in the scientific literature.
Biodiversity Treaty Still Unsigned by U.S.
Authors: Tom Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Biodiversity Treaty Still Unsigned by U.S. Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 15, 5 August 1992, Page 1148, https://doi.org/10.1093/jnci/84.15.1148 Published: 05 August 1992
On Cloning a Human Being
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1974)

IT is now theoretically possible to recreate an identical creature from any animal or plant, from the DNA contained in the nucleus of any somatic cell. A single plant root-tip cell can be teased and seduced into conceiving a perfect copy of the whole plant; a frog's intestinal epithelial cell possesses the complete instructions needed for a new, same frog. If the technology were further advanced, you could do this with a human being, and there are now startled predictions all over the place that this will in fact be done, some day, to provide a version of immortality for . . .
P42 Comparison of a 1- and 2-walk protocol for the endurance shuttle walk test when measuring change due to therapeutic intervention in COPD patients
Authors: S. Roberts, M. Stern, F. Schreuder, T. Watson
Journal: Thorax (2010)

<h3>Introduction</h3> The endurance shuttle walk test (ESWT) is an externally paced field endurance walking test. To perform the ESWT requires two incremental shuttle walk tests (ISWTs) to determine the walk speed for the ESWT, a practise ESWT (pESWT) and a repeat ESWT. The minimum important clinical difference (MCID) has been reported as 68%.1 Limits of agreement between ESWT carried out with and without a practise walk on the same day have been shown to be ±100 s2 and it is proposed the practise walk may not be needed. Completing the standard ESWT protocol presents a considerable burden to patients and clinicians alike; being able to drop the practise walk would be of benefit. This study investigated the need for a pESWT when measuring change after 8 weeks. <h3>Method</h3> A retrospective analysis of the data collected from ESWTs performed as part of another study was carried out. A 2-walk and a 1-walk protocol were defined. Both protocols required 2 ISWTs; the 2-walk protocol used 2 ESWTs, the longest taken as the outcome, the 1-walk protocol used the first walk as the outcome. Completion rates, floor and ceiling effects, same-day limits of agreement, and limits of agreement for change over 8 weeks were calculated for the protocols. <h3>Results</h3> 41 COPD patients (26 male) were recruited; mean (SD) age 68(11) years, FEV1% predicted 47(15.80)%. Results of comparison of protocols are given in Abstract P42 Table 1. At 80%, the limits of agreement for the protocols was less than the 92% change expected from pulmonary rehabilitation3 and less than that described2 as ‘somewhat better’ (113%) but greater than the MCID of 68%.2 The 1-walk protocol had superior completion but higher ceiling rates. <h3>Conclusion</h3> The data presented here suggests that, in clinical practice when measuring change related to an exercise intervention, only one ESWT is required. For research purposes, particularly for non-exercise interventions, the standard protocol should be retained as it is more likely to identify marginal difference and demonstrates less of a ceiling effect.