tbuckley/cabot-search huggingface dataset:
Genetic variants of lipase activity in chronic pancreatitis: Table 1
Authors: Holger Kirsten, Markus Scholz, Peter Kovacs, Harald Grallert, Annette Peters, Konstantin Strauch, Josef Frank, Marcella Rietschel, Markus M Nöthen, Heiko Witt, Jonas Rosendahl
Journal: Gut (2015)

Genetic variants of lipase activity in chronic pancreatitisWe read with great interest the article by Weiss et al 1 reporting genetic associations of rs632111 (fucosyltransferase 2; FUT2), rs8176693 (ABO) and rs889512 (chymotrypsinogen B2; CTRB2) with lipase levels.Weiss et al also claimed that the variants at the FUT2 and ABO loci were associated with chronic pancreatitis (CP).No association with CP was observed for the CTRB2 locus.Elevated lipase levels are a diagnostic criterion for acute pancreatitis and might mirror subclinical pancreatic injury in patients without severe complaints.Hence, variants associated with elevated serum lipase levels might also be associated with CP risk.In a recent genome-wide association study, genetic variants of CP risk were identified in PRSS1 and CLDN2-MORC4. 2 A large European replication study refined these associations to alcohol-related CP. 3 However, no associations were revealed at FUT2 and ABO in the former genome-wide association study. 2 Given the relatively moderate association of genetic variants with CP in the paper by Weiss et al, we analysed the above-mentioned FUT2 and ABO single nucleotide polymorphism (SNPs) regarding association with CP in a German cohort of 1458 cases (non-alcohol-related CP n=584; alcohol-related CP n=874) and 5133 controls derived from the KORA study and patients with alcohol dependence (GESGA (-) consortium) according to DSM-IV criteria to replicate the finding.Controls included 1488 individuals with alcohol consumption of >60 g/day and 1915 individuals with alcohol consumption of <20 g/day.All individuals were genotyped using Illumina SNP-chip technology.Briefly, data was filtered using Plink 1.9 at an individual-and SNP-wise call-rate >0.99 for relatedness ( pi-hat <0.185), minor allele frequency >0.01 and Hardy-Weinberg disequilibrium with p value >10 -6 .Imputation at 1000 Genomes reference panel ( phase 1, release 3, software SHAPEIT V.2+IMPUTE2.3.0) was performed with 279 188 high-quality SNPs available in all cohorts.Analyses were conducted with R applying logistic regression with the first three principal components of the SNP data included as covariates to account for possible population stratification.We analysed additive, recessive and dominant models of inheritance and subgroup and interaction analysis regarding alcohol consumption status.Our analyses revealed no significance for rs632111 and rs8176693 in statistical models reported previously (table 1). 1 For rs632111, the same (non-significant) direction of effect was observed, while for rs8176693, the effect direction was reverse.Interaction and subgroup analysis revealed significant interaction effects of rs632111 with alcohol consumption ( p value 0.04, OR 0.82, 95% CI 0.68 to 0.99) and for rs8176693 for the subgroup of alcohol-dependent individuals ( p value 0.04, OR 0.78, 95% CI 0.62 to 0.98);
Joint and soft tissue injections in the community: questionnaire survey of general practitioners' experiences and attitudes
Authors: G J Gormley
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objectives:</b> To investigate the numbers and types of joint and soft tissue injections performed by general practitioners (GPs) and to explore attitudes to training in joint and soft tissue injection and perceived barriers to performing injections. <b>Methods:</b> A self administered questionnaire was mailed to a random sample of 410 (30%) of 1367 GPs in Northern Ireland. Two mailings were used to increase the response rate. Questions explored the GPs' demographic characteristics, types and numbers of injections performed, previous training experience, attitudes towards training, and perceived barriers. <b>Results:</b> The overall response rate was 75%. Practitioners who were men, worked in a "rural" or "mixed" locality, and had had a previous post in rheumatology, orthopaedics, or sports medicine were more likely to perform joint and soft tissue injections. Forty six per cent of GPs did not currently perform any injections; 5% of GPs performed most of the injections in the community. Injections into the shoulder, knee, and lateral epicondylitis were found to be the most commonly performed injections. The GPs preferred to train on "real patients" rather than "mannequin models". Those GPs who had trained on "real patients" were more likely to perform injections. The main perceived barrier to performing joint and soft tissue injections in the community was the "inability to maintain injection skills". <b>Conclusion:</b> Postgraduate training, methods of training, and the ability to maintain injection skills seemed to be determinants affecting GP confidence and the amount of joint and soft tissue injections that they performed. Most injections were performed by a few GPs in the community. These findings may have implications for the developing role of GP specialists in primary care trusts.
Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice
Authors: Angus M. Tester, Mark Waltham, Se-Jeong Oh, Seog-Nyeon Bae, Margaret M. Bills, Emma C. Walker, Francis G. Kern, William G. Stetler-Stevenson, Marc E. Lippman, Erik W. Thompson
Journal: Cancer Research (2004)

Abstract The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents.
Clustering Gene Expression Data Based on Predicted Differential Effects of <i>GV</i> Interaction
Authors: Hai-Yan Pan, Jun Zhu, Dan-Fu Han
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract Microarray has become a popular biotechnology in biological and medical research. However, systematic and stochastic variabilities in microarray data are expected and unavoidable, resulting in the problem that the raw measurements have inherent “noise” within microarray experiments. Currently, logarithmic ratios are usually analyzed by various clustering methods directly, which may introduce bias interpretation in identifying groups of genes or samples. In this paper, a statistical method based on mixed model approaches was proposed for microarray data cluster analysis. The underlying rationale of this method is to partition the observed total gene expression level into various variations caused by different factors using an ANOVA model, and to predict the differential effects of GV (gene by variety) interaction using the adjusted unbiased prediction (AUP) method. The predicted GV interaction effects can then be used as the inputs of cluster analysis. We illustrated the application of our method with a gene expression dataset and elucidated the utility of our approach using an external validation.
Inhibition of Renal Rho Kinase Attenuates Ischemia/Reperfusion-Induced Injury
Authors: Jai Prakash, Martin H. de Borst, Marie Lacombe, Frank Opdam, Pieter A. Klok, Harry van Goor, Dirk K.F. Meijer, Frits Moolenaar, Klaas Poelstra, Robbert J. Kok
Journal: Journal of the American Society of Nephrology (2008)

The Rho kinase pathway plays an important role in dedifferentiation of epithelial cells and infiltration of inflammatory cells. For testing of the hypothesis that blockade of this cascade within the kidneys might be beneficial in the treatment of renal injury the Rho kinase inhibitor, Y27632 was coupled to lysozyme, a low molecular weight protein that is filtered through the glomerulus and is reabsorbed in proximal tubular cells. Pharmacokinetic studies with Y27632-lysozyme confirmed that the conjugate rapidly and extensively accumulated in the kidney. Treatment with Y27632-lysozyme substantially inhibited ischemia/reperfusion-induced tubular damage, indicated by reduced staining of the dedifferentiation markers kidney injury molecule 1 and vimentin, and increased E-cadherin relative to controls. Rho kinase activation was inhibited by Y27632-lysozyme within tubular cells and the interstitium. Y27632-lysozyme also inhibited inflammation and fibrogenesis, indicated by a reduction in gene expression of monocyte chemoattractant protein 1, procollagen Iα1, TGF-β1, tissue inhibitor of metalloproteinase 1, and α-smooth muscle actin. Immunohistochemistry revealed reduced macrophage infiltration and decreased expression of α-smooth muscle actin, collagen I, collagen III, and fibronectin. In contrast, unconjugated Y27632 did not have these beneficial effects but instead caused systemic adverse effects, such as leukopenia. Neither treatment improved renal function in the bilateral ischemia/reperfusion model. In conclusion, the renally targeted Y27632-lysozyme conjugate strongly inhibits tubular damage, inflammation, and fibrogenesis induced by ischemia/reperfusion injury.
Genetic Associations of 115 Polymorphisms with Cancers of the Upper Aerodigestive Tract across 10 European Countries: The ARCAGE Project
Authors: Cristina Canova, Mia Hashibe, Lorenzo Simonato, Mari Nelis, Andres Metspalu, Pagona Lagiou, Dimitrios Trichopoulos, Wolfgang Ahrens, Iris Pigeot, Franco Merletti, Lorenzo Richiardi, Renato Talamini, Luigi Barzan, Gary J. Macfarlane, Tatiana V. Macfarlane, Ivana Holcátová, Vladimir Bencko, Simone Benhamou, Christine Bouchardy, Kristina Kjaerheim, Ray Lowry, Antonio Agudo, Xavier Castellsagué, David I. Conway, Patricia A. McKinney, Ariana Znaor, Bernard E. McCartan, Claire M. Healy, Manuela Marron, Paul Brennan
Journal: Cancer Research (2009)

Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.
The Compleat Forensic Psychiatrist
Authors: AMES ROBEY, WILLIAM J. BOGARD
Journal: American Journal of Psychiatry (1969)

The compleat forensic psychiatrist, as described by the authors, must not only have competence in many areas—pre-trial evaluation, post-trial treatment and follow-up, training, and research—but must be able to communicate his ideas to lay people as well as professionals. To help attract able persons into this field a clear identity and role for the forensic psychiatrist is suggested; eventually an American Academy of Forensic Psychiatrists and Board certification in this subspecialty should be considered.
Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours
Authors: G B Turner, B T Johnston, D R McCance, A McGinty, R G P Watson, C C Patterson, J E S Ardill
Journal: Gut (2006)

Midgut carcinoid tumours are uncommon tumours with an unpredictable clinical behaviour and few useful prognostic markers. Somatostatin analogues are widely used in treatment but a survival advantage has not been proven. We analysed features associated with poor prognosis and assessed the clinical implications of the biochemical response to therapy.Clinical and biochemical data were collected for patients with midgut carcinoid tumours attending a tertiary referral neuroendocrine clinic from 1978 to 2000. Using death as the end point, univariate and multivariate survival analyses were performed to identify prognostic indicators. The significance of altering biomarkers with therapy was also studied by including repeated measurements of the most prognostic biochemical parameter in a time dependent covariate survival analysis.We identified 139 patients with sufficient data for our analyses. Factors associated with a poor outcome on univariate analysis included: plasma neurokinin A (NKA), urinary 5-hydroxyindolacetic acid output, age, and >/=5 liver metastases. Plasma NKA was the strongest and only independent predictor of outcome on multivariate analysis. Patients in whom NKA continued to rise despite somatostatin analogues had a significantly worse survival than those in whom NKA stabilised or fell (one year survival rate 40% v 87%). Time dependent covariate analysis concluded that survival was better predicted by the most recent plasma NKA value rather than by the initial value.Plasma NKA is an accurate marker of prognosis for midgut carcinoid tumours. This is the first paper to support a survival advantage in patients in whom plasma NKA is altered by somatostatin analogues.
Symptomatic intravertebral disc herniation (Schmorl's node) in the cervical spine.
Authors: S J Lipson, D A Fox, J L Sosman
Journal: Annals of the Rheumatic Diseases (1985)

A case of a Schmorl's node in the cervical vertebra causing neck pain is reported. An inflammatory focus was found on histological examination of Schmorl's node indicating a possible mechanism of pain production.
Opening the<i>Chamber of secrets</i>: our response to “The end of the beginning”
Authors: S H Till, M E Batt
Journal: British Journal of Sports Medicine (2006)

The importance of exercise medicine and its impact on public health has been recognised by sports medicine physicians in Britain

This is a formal response to the editorial, “The end of the beginning”, published by the editor of this journal in January of this year.1

The year 2006 heralds a new dawn for those in Britain working in sport and exercise medicine (SEM). We now have a combined single professional organisation, we are looking forward to six years of planning the 2012 London Olympics, and, perhaps most importantly, we have now been recognised as the newest medical specialty by the Department of Health. The excitement of these developments was palpable at BASEM’s 2005 congress in Edinburgh. Imagine therefore our surprise that the first BJSM editorial of 2006 talks in such negative tones about the state of philosophical readiness of those of us engaged …
Genome-Wide Screening of Genomic Alterations and Their Clinicopathologic Implications in Non–Small Cell Lung Cancers
Authors: Tae-Min Kim, Seon-Hee Yim, Jung-Sook Lee, Mi-Seon Kwon, Jae-Wook Ryu, Hyun-Mi Kang, Heike Fiegler, Nigel P. Carter, Yeun-Jun Chung
Journal: Clinical Cancer Research (2005)

Although many genomic alterations have been observed in lung cancer, their clinicopathologic significance has not been thoroughly investigated. This study screened the genomic aberrations across the whole genome of non-small cell lung cancer cells with high-resolution and investigated their clinicopathologic implications.One-megabase resolution array comparative genomic hybridization was applied to 29 squamous cell carcinomas and 21 adenocarcinomas of the lung. Tumor and normal tissues were microdissected and the extracted DNA was used directly for hybridization without genomic amplification. The recurrent genomic alterations were analyzed for their association with the clinicopathologic features of lung cancer.Overall, 36 amplicons, 3 homozygous deletions, and 17 minimally altered regions common to many lung cancers were identified. Among them, genomic changes on 13q21, 1p32, Xq, and Yp were found to be significantly associated with clinical features such as age, stage, and disease recurrence. Kaplan-Meier survival analysis revealed that genomic changes on 10p, 16q, 9p, 13q, 6p21, and 19q13 were associated with poor survival. Multivariate analysis showed that alterations on 6p21, 7p, 9q, and 9p remained as independent predictors of poor outcome. In addition, significant correlations were observed for three pairs of minimally altered regions (19q13 and 6p21, 19p13 and 19q13, and 8p12 and 8q11), which indicated their possible collaborative roles.These results show that our approach is robust for high-resolution mapping of genomic alterations. The novel genomic alterations identified in this study, along with their clinicopathologic implications, would be useful to elucidate the molecular mechanisms of lung cancer and to identify reliable biomarkers for clinical application.
Hepatitis C Virus Infection as a Risk Factor for Hepatocellular Carcinoma in Patients with Cirrhosis
Authors: R G Simonetti, C Cammà, F Fiorello, M Cottone, M Rapicetta, L Marino, G Fiorentino, A Craxì, A Ciccaglione, R Giuseppetti
Journal: Annals of Internal Medicine (1992)

Objective: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. Design: Two pair-matched case-control studies. Setting: A referral-based hospital. Patients: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. Measurements: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history. Main Results: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma. Conclusions: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender.
A Novel Function for the nm23-H1 Gene: Overexpression in Human Breast Carcinoma Cells Leads to the Formation of Basement Membrane and Growth Arrest
Authors: A. R. Howlett, O. W. Petersen, M. J. Bissell, P. S. Steeg
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article A Novel Function for the nm23-H1 Gene: Overexpression in Human Breast Carcinoma Cells Leads to the Formation of Basement Membrane and Growth Arrest Get access Anthony R. Howlett, Anthony R. Howlett *Division of Life Sciences, Lawrence Berkeley Laboratory, University of CaliforniaBerkeley Search for other works by this author on: Oxford Academic PubMed Google Scholar Ole W. Petersen, Ole W. Petersen Structural Cell Biology Unit, Department of Medical Anatomy A, The Panum Institute, University of CopenhagenCopenhagen N, DenmarkDepartment of Tumor Endocrinology, Division for Cancer Biology, The Danish Cancer Society, Copenhagen Ø; and Division of Life Sciences, Lawrence Berkeley Laboratory, University of California. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mina J. Bissell, Mina J. Bissell *Division of Life Sciences, Lawrence Berkeley Laboratory, University of CaliforniaBerkeley Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia S. Steeg Patricia S. Steeg Women's Cancers Section, Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 24, 21 December 1994, Pages 1838–1844, https://doi.org/10.1093/jnci/86.24.1838 Published: 21 December 1994 Article history Received: 01 January 1994 Revision received: 25 July 1994 Accepted: 13 September 1994 Published: 21 December 1994