tbuckley/cabot-search huggingface dataset:
A1.31 The type I IFN signature in sorted leukocyte subsets from peripheral blood of rheumatoid arthritis patients; a major contribution by granulocytes
Authors: TD de Jong, J Lübbers, S Turk, S Vosslamber, E Mantel, HJ Bontkes, CJ van der Laken, JW Bijlsma, D van Schaardenburg, CL Verweij
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> A subgroup of rheumatoid arthritis (RA) patients displays elevated type I IFN response gene (IRG) expression in peripheral blood, which has shown clinical relevance in relation to disease onset and therapy response. Identification of the cell type(s) contributing to this IFN signature could provide insight into its functional consequences and pathologic role in RA. This study aimed to investigate the contribution of the major peripheral leukocyte subsets to the IFN signature in RA. <h3>Methods</h3> Blood was collected from 26 early RA patients and lysed directly or separated into mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). Using flow cytometry, PBMCs were sorted into CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, CD19<sup>+</sup> B cells and CD14<sup>+</sup> monocytes. mRNA expression levels of three IRGs (RSAD2, IFI44L and MX1), as well as type I IFN receptors IFNAR1 and IFNAR2, were determined in blood and cell subsets by qPCR. IRG expression was averaged to calculate an IFN score for each sample. <h3>Results</h3> Patients were designated "IFN<sup>high</sup>" (n = 8) and "IFN<sup>low</sup>" (n = 18) based on the IFN score cutoff in peripheral blood from healthy controls. As expected, IFN scores were significantly higher in all cell subsets from IFN<sup>high</sup> patients compared to IFN<sup>low</sup> patients. This difference was remarkably large for the PMN fraction (mean 25-fold, p &lt; 0.0001) compared to the other subsets (mean 6–9-fold, p ≤ 0.0009). Moreover, the relative contribution of the PMN fraction was significantly higher than expected from its relative abundance in blood alone (3-fold, p = 0.008), whereas this was 3–7-fold lower for the other subsets (p ≤ 0.063). Both IFNAR1 and IFNAR2 expression was highest in the PMN fraction compared to the other subsets, suggesting increased sensitivity of PMNs to type I IFNs. Concordantly, we observed IFNAR1 and IFNAR2 upregulation compared to healthy controls selectively in RA PMNs (p ≤ 0.0077) but not in the PBMCs. <h3>Conclusions</h3> PMNs are the main contributors to the whole blood type I IFN signature in RA patients, which seems due to increased sensitivity to type I IFN signalling. Considering the well-established role of neutrophils in the pathology of RA, this further supports a pathologic role of type I IFN activity in the disease.
Abstract 1223: Fibronectin induced lung cancer cell proliferation is dependent on induction of ILK through integrin B1-mediated activation of p38 MAPK and PI3-K
Authors: XiaoJuan Sun, Jeffrey D. Ritzenthaler, XiaoRong Zhong, Jesse Roman, Shouwei Han
Journal: Cancer Research (2010)

Abstract Fibronectin is a multi-functional matrix glycoprotein protein that has been linked to tumor progression. We previously demonstrated that cellular fibronectin (cFN) increased non-small cell lung carcinoma (NSCLC) cell growth through signals mediated by the integrin α5β1. Here, we explore the role of integrin-linked kinase (ILK), an integrin β1 subunit cytoplasmic domain interactor in cFN induced cell growth. We found that cFN increases ILK expression and kinase activity, promotes protein-protein interactions between ILK and integrin β1. Silencing of ILK attenuated the effect of cFN on cell proliferation. Knockdown of the integrin β1 subunit, but not the integrin α5, blocked the effect of cFN on ILK expression. In addition, the inhibitor of p38MAPK, SB239063, and the inhibitor of PI3-K, wortmannin, abrogated the effect of cFN on ILK expression, whereas the inhibitor of ERK, PD98059, had no effect. Taken together, our results demonstrate that fibronectin induces the expression of ILK through integrin β1-mediated signals that include p38 MAPK and PI3-K. This in turn, promotes lung carcinoma cell proliferation. 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 1223.
Abstract 1353: KIR copy-number variation and cutaneous melanoma risk.
Authors: Heather H. Nelson, Karin Vineretsky, DeAnn Lazovich
Journal: Cancer Research (2013)

Abstract Prevention of cutaneous malignant melanoma requires the identification and clearance of abnormal, pre-cancerous cells by the immune system. Central to this immune surveillance is the interplay between KIR receptors present on natural killer cells and their HLA ligands expressed on target cells. Like HLA, the KIR genes are highly polymorphic. They encode both activating receptors (that trigger NK-cell mediated killing), and inhibitory receptors (important in NK cell education and self-tolerance). Many of the KIR genes occur as copy number variants, and we hypothesize that inter- individual variability in KIR copy number is associated with melanoma risk. A random sample of cases and controls within the large, population-based Minnesota Skin Health Study were selected for examination (84 cases and 87 controls). Using Luminex technology and genomic DNA isolated from subject buccal cells we tested for the presence or absence of specific KIR genes (KIR3DL1, KIR2DS1, KIR2DL2, KIR2DL3, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4 {truncating allele}, KIR2DS5, KIR2DS1). In addition to investigating each gene as a melanoma risk factor, we created an integrated locus score for 2DL2/DL3 and 3DL1/DS1, reflecting the typical mutual exclusivity of these genes at their respective loci. Results: Homozygous deletion of the activating KIR gene 2DS1 was associated with both an increasing number of nevi (p&amp;lt;0.04), and increased melanoma risk (OR 2.2, 95% CI 1.2 - 4.3). Similarly, at the shared 3DL1/3DS1 locus, absence of the activating KIR3DS1 gene was significantly associated with increased melanoma risk (OR 2.0, 95% CI 1.0 - 3.3), and a borderline significant increase in the number of nevi (p&amp;lt;0.07). In contrast, at the KIR2DL2/2DL3 locus, which encodes two inhibitory KIR alleles, our data suggest that a lack of diversity at this locus may be more important than the presence or absence of either gene; individuals homozygous for either 2DL2 or 2DL3 were at increased risk for both nevi (p&amp;lt;0.03), and melanoma (OR 1.8, 95% CI 1.0 - 3.4) relative to those who had both 2DL2 and 2DL3. These novel analyses at the complex KIR locus indicate that absence of certain activating KIR receptors, and balance in diversity of KIR inhibitory receptors are important determinants of cutaneous melanoma risk. Citation Format: Heather H. Nelson, Karin Vineretsky, DeAnn Lazovich. KIR copy-number variation and cutaneous melanoma risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1353. doi:10.1158/1538-7445.AM2013-1353
FRI0464-HPR Reliability of the fox-walk test in patients with rheumatoid arthritis
Authors: C.A. Verberkt, C. Fridén, W.J.A. Grooten, C.H. Opava
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Health-enhancing physical activity increasingly takes place outside the health care system and calls for self-monitored feedback tests to retain motivation. The Fox-walk test is a new method used to estimate aerobic capacity outside a clinical environment, which may be useful in the implementation of daily health-enhancing physical activity. Its measurement properties have been established in different populations, but not yet among people with rheumatoid arthritis (RA). <h3>Objectives</h3> The purpose of this study was to determine the test-retest reliability of the Fox-walk test in patients with RA and to study potential influence on reliability of disease-related factors. <h3>Methods</h3> Fifteen participants (14 women, mean age 63 years, mean time since first clinical visit 3.5 years) with RA according to ACR 1987 criteria performed the Fox-walk test three times with weekly intervals. A sample size calculation (α =0.05, β =0.80) indicated that 10 subjects would be enough to demonstrate a reliability of &gt;0.8 when repeating the measurements three times. The intraclass correlation coefficient (ICC), the standard error of measurement (SEM) and the smallest detectable change (SDC) were used to estimate the reliability. General health perception, lower limb pain and fatigue were measured to determine their potential influence on the reliability. <h3>Results</h3> There were no systematic differences between the three test occasions (p=0.190) and the reliability was almost perfect (ICC =0.982). None of the covariates influenced the reliability. The SEM was 0.999 ml/kg/min or 3.4% and the SDC was 2.769 ml/kg/min or 9.4%. <h3>Conclusions</h3> Our findings demonstrate that the Fox-walk test is reliable in people with RA and enables differentiation between people with RA aas well as monitoring progress. The validity of the test among people with RA is however still to be determined. <h3>Disclosure of Interest</h3> None Declared
Enhanced Expression and HIV-1 Inhibition of Chimeric tRNALys3-Ribozymes under Dual U6 snRNA and tRNA Promoters
Authors: Zongli Chang, Shawn Westaway, Shirley Li, John A. Zaia, John J. Rossi, Lisa J. Scherer
Journal: Molecular Therapy (2002)

We previously demonstrated that chimeric tRNA(Lys3)-ribozymes targeting the primer binding site of HIV produced virions with reduced infectivity. To further enhance the anti-HIV efficiency of these ribozymes by increasing their level of transcription, we designed several tRNA(Lys3) promoter variants and compared their expression levels from the internal tRNA(Lys3) promoters and also from an exogenous human U6 snRNA promoter. The dual U6/tRNA promoter constructs gave rise to much higher levels of expression than constructs that used only an internal tRNA promoter. The most abundant expression is produced when a U6 promoter drives a chimeric tRNA(Lys3)-ribozyme containing a mutation in the tRNA B box. As detected by fluorescent in situ hybridization, transcripts from a construct with the tRNA promoter alone localized strictly to the cytoplasm, whereas transcripts from dual U6/tRNA promoter were present in both the cytoplasm and the nucleus. Inhibition of HIV-1 correlates well with expression levels of the chimeric constructs. The results presented demonstrate that U6 and tRNA promoters can be placed in tandem for high-level expression of small RNA therapeutic transcripts.
Abstract P4-02-06: Beyond CYP2D6 Genotyping: Personalized Dosing of Tamoxifen (Tam) Based on Low Serum Endoxifen Levels
Authors: MF Barginear, M Jaremko, C Yu, I Peter, Y Kasai, M Kemeny, K Adelson, R Desnick, G. Raptis
Journal: Cancer Research (2010)

Abstract Background: The efficacy of Tam varies widely. Tam is biotransformed to endoxifen and 4-OH-Tam by the cytochrome P450 2D6 enzymes. Studies on 2D6 variants as a predictor of Tam's efficacy show conflicting results. Compared to Tam, endoxifen and 4-OH-Tam have a 100-fold greater affinity for the estrogen receptor (ER) and in suppressing estrogen-dependent cell proliferation. However, endoxifen is present at concentrations up to 20-fold higher and is pharmacologically distinct from 4-OH-Tam. Endoxifen's effect on ERα-degredation and transcription is concentration dependent; serum endoxifen levels ≥40nM block ERα-mediated transcriptional activation and inhibit estrogen-induced breast cancer cell proliferation. Methods: Pts taking Tam 20 mg/day, for any reason, were potentially eligible. Serum Tam, Tam metabolites and nineteen 2D6 alleles were analyzed. 2D6 genotyping was performed by PCR-based procedures and metabolites were assessed on Liquid Chromatography/Tandem Mass Spectrometry. Pts were stratified by 2D6 function into 3 groups: extensive metabolizers (EM) who had normal enzyme activity; intermediate metabolizers (IM) who had reduced enzyme activity; and poor metabolizers (PM) who had no enzyme activity. Tam was increased to 30 mg/day if serum endoxifen &amp;lt; 40nMol. Serum Tam and Tam metabolites were measured every 2 weeks for 90 days. Results: 121 patients have enrolled to date. Age, ethnicity, BMI, concomitant medications, and adherence were recorded. 25/117 (21%) pts had low serum endoxifen; all of these pts were increased to Tam 30 mg/day. Of this cohort, 36% were PMs (PM/PM and PM/IM), 32% were IMs (EM/PM and IM/IM) and 32% were EMs (EM/EM and EM/IM). All patients’ serum endoxifen increased to &amp;gt;40nMol by day 30 (Diagram below). Conclusions: 1) Sub-therapeutic serum endoxifen can be found in any 2D6 phenotype. 2) It is possible to achieve therapeutic serum endoxifen/Tam metabolite levels by optimizing the dose of Tam. 3) Subsequently, it is likely that other gene variants are involved in Tam metabolism hence why 2D6 testing may lead to conflicting results. 4). Further investigation is warranted as personalizing the dose of Tam is feasible and may potentially improve the outcome of pts taking Tam regardless of 2D6 genotype. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-06.
PTH-048 Benchmarking in Upper Endoscopy - Best Practice Markers
Authors: R J Mead, N Hawkes
Journal: Gut (2013)

<h3>Introduction</h3> UK practise in diagnostic oesophago-gastric-duodenoscopy (OGD) has changed little over the last 10–20 years. Currently the only quality measure relates to ability to reach the second part of the duodenum. Evidence-based quality indicators in colonoscopy pertain to the quality of views, the amount of time spent examining the mucosa and expected levels of lesion detection, in addition to completion rates. Their adoption, in combination with robust clinical governance has undoubtedly improved the detection of colorectal diseases, patient safety and patient experience. The equivalent evidence base for diagnostic OGD does not exist and this has limited development. Benchmarking is a process measuring the practise of one organisation against its peers and may provide a basis for developing quality standards for upper GI practise. This study measures routine OGD practise in the UK and practise in a Japanese centre of excellence for endoscopy and oesophago-gastric cancers. <h3>Methods</h3> Two experienced endoscopists recorded OGD practise in the National Cancer Centre Hospital in Tokyo. The following were recorded: net procedural time spent screening the oesophagus, stomach, and duodenum; lens cleaning, mucosa cleaning, presence of residual food; use of dye spray and narrow band imaging; picture numbers and biopsies; patient age and sex. One experienced endoscopist recorded OGD practise during routine diagnostic lists at 3 hospitals. <h3>Results</h3> 134 procedures were recorded, 67 in each country. The average age in the UK was 58.5 yrs (60% male) and 68.2 yrs in Japan (57% male). The average screening time in Japan was 6:51 mins, and 5:49 mins in the UK. The Japanese use advanced imaging techniques 73% of the time. They were never used in routine UK practise. Japanese endoscopists met weekly reviewing all pathology detected and discussing therapeutic cases. All images were reviewed closely and were an essential part of decision making and education in the unit. <h3>Conclusion</h3> Comparison of the ‘cultures of practise’ are interesting, revealing significant differences of approach in UGI examination. In the Japanese cohort a 48% higher yield of pathological findings was achieved despite the average screening time being only one minute longer per case. Although there are differing disease prevalence’s in the background populations, it seems likely that better cleaning of the upper GI tract, use of mucosal enhancement techniques, care in image capture, and better awareness of upper GI pathology will have significantly contributed to increased detection. Further investigation is needed into which factors can be used as independent measures of quality in UGI examination, including time taken to examine the upper GI tract and measures of endoscopists’ lesion recognition skills (not currently assessed as part of endoscopy training). <h3>Disclosure of Interest</h3> None Declared.
Abstract B11: Development and validation of HPV-16 chimeric VLPs and peptide as vaccine candidates against cervical cancer
Authors: Neeta Singh
Journal: Cancer Research (2011)

Abstract Background: High-risk HPVs such as HPV-16 have been implicated in the pathogenesis of cervical cancer and its premalignant lesions. Prophylactic vaccines derived from the noninfectious protein coat of HPV 16 and 18 are available commercially. However, therapeutic vaccines capable of eliminating HPV-infected cells and clearing HPV-associated tumors are not available. CTLs specific for E6 and E7 act as desirable immune effectors in recognizing and destroying HPV-infected cells and therefore HPV 16, E6, and E7 proteins pose as logical targets for immunotherapy against cervical cancer. Objective: To develop vaccine strategies which would have both prophylactic and therapeutic potential against HPV16. Methods: Software predicted synthetic CTL epitope dominant peptide from HPV-16, L1, L2, E6, and E7 region was synthesized (48mer) and its therapeutic vaccine potential evaluated using different adjuvants. For chimeric VLPs, DNA was isolated from HPV-16-positive cervical cancer, cloning of L1 and E7 was done in appropriate vector, recombinant protein expressed and purified. In vitro assembly of chimeric virus-like particles (CVLPs) done. Immune response to peptide and CVLPs was measured by T cell proliferation assay, cytokine ELISA, cytotoxicity measured using LDH assay, and in vivo tumor induction (using TC-1 cells) and regression analysis done in C57BL/6J mice. Results: Subcutaneous injection with peptide along with different adjuvants (mycobacterium Mw, alum, PLGA microspheres) enchanced serum IgG levels, showed lymphocyte proliferation, generated peptide-specific CTL-mediated cytotoxic secretion of different cytokines. Regression of tumors on in vivo challenge to TC-1 cells in C57BL6 mice was observed. Among adjuvants, peptide encapsulated in PLGA microspheres showed the best response. CVLPs showed lymphoproliferative response and CTL generation in vitro against E7 protein and essentially showed Th-1 response. Antitumor efficacy to TC-1 cells induced tumors in C57BL/6 mice was also seen. Seroreactivity of young women with persistent HPV16 infection showed that CVLPs detected neutralizing antibodies against L1 capsid protein. Antibodies against L1 capsid protein were able to inhibit hemaglutination. Conclusion: The above study has provided a basis for rational design of peptide-based vaccine and protein-based chimeric vaccine for controlling HPV-16 infection and its associated tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B11.
Improving the Quality of Care
Authors: Mark R. Chassin
Journal: New England Journal of Medicine (1996)

Quality of care is making a comeback. After more than two decades of preoccupation with the costs of health care, more attention is being devoted to quality. But much of the attention is coming from unlikely sources — organizations more often associated with efforts to reduce costs. Employers are talking about the quality of health care.1,2 Managed-care companies and insurers talk about it.3,4 Data touted as measures of quality are increasingly appearing in newspaper and magazine articles.57 The Health Care Financing Administration and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) have called for a more . . .
Skull Clamps Are Slipping
Authors: Rebecca Voelker
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Activation of the Properdin Pathway of Complement in Patients with Gram-Negative Bacteremia
Authors: Douglas T. Fearon, Shaun Ruddy, Peter H. Schur, William R. McCabe
Journal: New England Journal of Medicine (1975)

To determine the pathway used for activation of complement component C3, serum levels of components C1, C4, C2, C3, C5, C6, and C9 and two properdin factors, properdin and factor B, were measured in 42 patients with gram-negative bacteremia, in 19 of whom shock subsequently developed. Mean levels of the classical components C1, C4, and C2 in bacteremic patients in whom shock subsequently developed did not differ significantly (p greater than 0.05) from those of patients with uncomplicated bacteremia. Levels of properdin, factor B and C3, C5, C6, and C9 were significantly (p less than 0.05) decreased in patients with shock in comparison with those with uncomplicated bacteremia. Taken together, these findings are consistent with activation of C3 and the terminal complement sequence, C5-C9, occurring primarily by the properdin pathway, in patients with gram-negative bacteremia eventuating in shock. Biologically active products released during activation of C3-C9 may contribute to the development of shock.
IMPORTANCIA DE AL ECOENDOSCOPIA EN LA SELECCION DE CANDIDATOS A TRATAMIENTO NEOADYUVANTE EN PACIENTES CON ADENOCARCINOMA GASTRICO
Authors: A Vilella, A Brotons, J Di Giorgio, C Dolz
Journal: Endoscopy (2010)

Introducción: Con las nuevas pautas de neoadjuvancia en el tratamiento del adenocarcinoma gástrico en estadios localmente avanzados es imprescindible disponer de un estadiaje preciso para poder decidir el enfoque terapéutico de estos pacientes.