tbuckley/cabot-search huggingface dataset:
Vaccination against<i>Clostridium difficile</i>using toxin fragments
Authors: Janice Spencer, Rosanna Leuzzi, Anthony Buckley, June Irvine, Denise Candlish, Maria Scarselli, Gillian R Douce
Journal: Gut Microbes (2014)

Clostridium difficile is a major cause of antibiotic associated diarrhea. Recently, we have shown that effective protection can be mediated in hamsters through the inclusion of specific recombinant fragments from toxin A and B in a systemically delivered vaccine. Interestingly while neutralizing antibodies to the binding domains of both toxin A and B are moderately protective, enhanced survival is observed when fragments from the glucosyltransferase region of toxin B replace those from the binding domain of this toxin. In this addendum, we discuss additional information that has been derived from such vaccination studies. This includes observations on efficacy and cross-protection against different ribotypes mediated by these vaccines and the challenges that remain for a vaccine which prevents clinical symptoms but not colonization. The use and value of vaccination both in the prevention of infection and for treatment of disease relapse will be discussed.
Identification of a Nondeletion Defect in α-Thalassemia
Authors: Yuet Wai Kan, Andree M. Dozy, Richard Trecartin, David Todd
Journal: New England Journal of Medicine (1977)

The molecular defect that has been demonstrated in alpha-thalassemia is the deletion of the alpha-globin structural genes. Since thalassemias are composed of heterogeneous groups of disorders, other types of defects could also result in alpha-thalassemia. We studied a Chinese family in which analysis of the mode of inheritance of alpha-thalassemia-1 and hemoglobin-H disease suggests a lesion that is not due to structural-gene deletion. Molecular hybridization studies with synthetic radioactive DNA's complementary to alpha-globin mRNA sequences show that in addition to the usual deletion defect, a nondeletion defect produces the phenotype of alpha-thalassemia-1. The combination of the deletion and non-deletion defects results in hemoglobin-H disease and not homozygous alpha-thalassemia associated with hydrops fetalis.
CORONARY ARTERY CALCIUM DISTRIBUTION IS AN INDEPENDENT PREDICTOR OF INCIDENT MAJOR CORONARY HEART DISEASE EVENTS: RESULTS FROM THE FRAMINGHAM HEART STUDY
Authors: Maros Ferencik, Karol M. Pencina, Ting Liu, Joseph Massaro, Ralph D’Agostino, Christopher O’Donnell, Udo Hoffmann
Journal: Journal of the American College of Cardiology (2015)
Cellular Reactivity to<i>Candida albicans</i>Antigen
Authors: Daniel C. Shannon, Gordon Johnson, Fred S. Rosen, K. Frank Austen
Journal: New England Journal of Medicine (1966)

THE assessment of the integrity of delayed hypersensitivity reactions is frequently useful in certain clinical entities. An antigen that evokes a universally positive response in a normal population would consequently be most reliable for the detection of delayed skin unreactivity in patients with certain pathologic entities. Although Lewis and his associates1 described a 46 per cent incidence of delayed hypersensitivity to oidiomycin (Candida albicans antigen) in 192 healthy subjects, and Good et al.2 reported a 57 per cent incidence of delayed skin reactivity to C. albicans antigen in 208 hospitalized patients, we have found reactivity to this antigen to . . .
Abstract 2931: Inherited variation at chromosome 12p13.33 including <i>RAD52</i> influences squamous cell lung carcinoma risk
Authors: Jianxin Shi, Nilanjan Chatterjee, Melissa Rotunno, Yufei Wang, Angela C. Pesatori, Dario Consonni, Peng Li, Peter Broderick, Marc Henrion, Timothy Eisen, Zhaoming Wang, Wei Chen, Qiong Dong, Demetrius Albanes, Michael Thun, Margaret Spitz, Pier Alberto Bertazzi, Neil Caporaso, Stephen Chanock, Christopher Amos, Richard Houlston, Maria Teresa Landi
Journal: Cancer Research (2012)

Abstract While lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies (GWAS) in Europeans have robustly demonstrated only three polymorphic variations influencing lung cancer risk. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a GWAS of 5,355 European smoking lung cancer cases and 4,344 smoking controls, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 SNPs mapping to 917 genes in the HuGE-defined “inflammation” pathway. We identified a susceptibility locus for squamous cell lung carcinoma (SQ) at 12p13.33 (RAD52, rs6489769), and validated it in three independent samples totaling 3,359 SQ cases and 9,100 controls (odds ratio=1.20, Pcombined=2.3×10−8). The combination of pathway-based approaches and information on disease specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2931. doi:1538-7445.AM2012-2931
SAT0265 Distilling Key Elements of Existing Questionnaires to Create a New Screening Tool for Psoriatic Arthritis
Authors: L. C. Coates, J. A. Walsh, M. Haroon, O. FitzGerald, P. S. Helliwell
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Many screening questionnaires have been developed to identify PsA amongst patients with psoriasis but their performance in head to head studies has been diappointing. <h3>Objectives</h3> To combine most discriminatory questions from established PsA screening questionnaires to create a more sensitive and specific screening test for PsA. <h3>Methods</h3> Data from the CONTEST study, a head-to-head study of the PEST, PASE and ToPAS screening questionnaires in secondary care dermatology clinics, were used to establish which questions from any of the three questionnaires had a Youden's index of &gt;0.1 using CASPAR criteria for PsA as the gold standard. Optional weighting was included based on logistic regression of individual questions. The number of painful joint areas on the PEST mannequin predictive of PsA was identified using ROC analysis. CART analysis was used to identify other questions that showed good differentiation. Data from comparative head-to-head studies based in Dublin and Utah were used to independently validate the new proposed questionnaires. <h3>Results</h3> In this individual analysis, only 2 of 25 questions showed significant differentiation of PsA cases using Fishers exact test: ToPAS 2A "Have you ever noticed any of these changes in your fingernails – pits in the nails?" and PEST 4 "Have you had pain in your heel?". These were the only questions identified using logistic regression with an OR of 5 and 2 respectively. A further 10 questions had a Youden score of ≥0.1 and these were considered for inclusion into the first candidate questionnaire. Where overlapping questions about similar symptoms (eg nail psoriasis) were identified, the most discriminatory question was chosen. One question (ToPAS 7A) was excluded as many patients did not complete that question. This resulted in the CONTEST questionnaire of 8 yes/no questions. The weighted CONTEST questionnaire used the OR identified above and weighted all other questions as 1 giving a score of 0-13. CONTEST-joint included the presence of joint areas on the PEST mannequin with a cut off of ≥6 areas being positive. CART analysis identified a further 5 questions for inclusion giving a total of 13 questions for CONTEST-tree. In the original CONTEST data the AUC for the CONTEST, CONTEST-weighted, CONTEST-joint and CONTEST-tree were 0.69, 0.74, 0.70, 0.59 respectively with p&lt;0.01 for all except CONTEST-tree which was not analysed further. The remaining candidates were tested in the validation cohorts and the results are shown in table 1. <h3>Conclusions</h3> The CONTEST questionnaires provide a new tool which could improve sensitivity and specificity of identifying PsA compared to existing questionnaires. Further research in independent populations is required to identify the optimal cut point for referral. <h3>Disclosure of Interest</h3> None Declared
Molecular correlates of anemia in primary myelofibrosis: a significant and independent association with U2AF1 mutations
Authors: D Barraco, Y C Elala, T L Lasho, K H Begna, N Gangat, C Finke, C A Hanson, R P Ketterling, A Pardanani, A Tefferi
Journal: Blood Cancer Journal (2016)

Anemia is a cardinal manifestation of primary myelofibrosis (PMF) and constitutes a negative prognostic factor, being an independent risk factor for survival both in the international prognostic score system (IPSS) 1 and dynamic IPSS (DIPSS)-plus. 2Anemia in myelofibrosis is also inversely correlated with patient-reported quality of life.Between 35 and 54% of patients with PMF are anemic at diagnosis with a hemoglobin level of o10 g/dl 1 with the proportion increasing to 47-64% after about 1 year from the time of diagnosis. 3][5] Current drugs, including JAK inhibitors, are suboptimal in the treatment of PMF-associated anemia and better information on its pathogenesis is critical for the development of more effective drugs.In the current study of JAK2/CALR/MPL-annotated patients with PMF, we examined the correlation between anemia with both driver and non-driver mutations, 6,7 as well as cytogenetic abnormalities, in order to gain better insight into its pathogenesis.
DETERMINATION OF FUNCTIONAL P-GLYCOPROTEIN IN PATIENTS WITH OSTEOSARCOMA BY TECHNETIUM-99M SESTAMIBI SCINTIGRAPHY
Authors: D. A. Erb, H. A. Nabi, B. E. McGrath
Journal: Clinical Nuclear Medicine (1998)

Department of Nuclear Medicine, Department of Orthopaedics, State University of New York at Buffalo, Buffalo, New York.
Abstract 4316: Villin expression is frequently lost in colon cancers with microsatellite instability.
Authors: Diego Arango, Sheren Al-Obaidi, David S. Williams, Jose Dopeso, Rocco Mazzolini, Georgia A. Corner, Do-Sun Byun, Carmel Murone, Lars Togel, Nikolajs Zeps, Lauri A. Aaltonen, Barry Iacopetta, John Martin Mariadason
Journal: Cancer Research (2012)

Abstract Colorectal cancers are classified as having chromosomal instability (CIN) or microsatellite instability (MSI). MSI colon cancers frequently display poorly differentiated histology the molecular basis of which is not well understood. Gene expression profiling of CIN and MSI colon cancer cell lines and tumours revealed significant downregulation of the intestinal-specific cytoskeletal protein villin, in MSI tumours, with complete absence observed in 62% and 17% of MSI cell lines and primary tumours, respectively. Investigation of 577 colon cancers demonstrated loss of villin expression was linked to poorly differentiated histology in MSI and MSS (microsatellite stable) tumours. Furthermore, mislocalization of villin away from the membrane was prognostic for poorer outcome in MSS patients. Loss of villin expression was not due to coding sequence mutations, epigenetic inactivation, or promoter mutation. Conversely, villin promoter activity reflected endogenous villin expression, suggesting villin loss is transcriptionally mediated. A screen of gut-specific transcription factors revealed a significant correlation between expression of villin and the homeobox transcription factor, Cdx-1. Cdx-1 overexpression induced villin promoter activity, Cdx-1 knockdown downregulated endogenous villin expression, and deletion of a key Cdx binding site within the villin promoter attenuated promoter activity. Loss of Cdx-1 expression was associated with Cdx-1 promoter methylation. These findings demonstrate that loss of villin expression as a result of Cdx-1-dependent transcriptional deregulation is a feature of poorly differentiated colon cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4316. doi:1538-7445.AM2012-4316
P05.03 * EFFECT OF COMBINED THERAPY WITH BEVACIZUMAB AND TEMOZOLOMIDE (TMZ) IN PEDIATRIC MALIGNANT GLIOMAS (MG)
Authors: O. G. Geludkova, I. D. Borodina, A. G. Melikian, Y. V. Kushel, L. V. Shishkina, M. V. Rizhova, S. V. Gorbatih, V. E. Popov, E. V. Pavlova, O. I. Scherbenko
Journal: Neuro-Oncology (2014)

METHOD: There were 19 pts with MG, who enrolled in the study from May 2010 till March 2014 (10 boys and 9 girls), median age 9 yrs (range, 3-17 yrs). 15 pts (79%) were with glioblastoma (GB), 4 (21%) - anaplastic astrocytoma (AA). In 16 pts the tumor was localized supratentorial (84.21%), in 3 - infratentorial (15.79%). All pts received resection of the tumor (total resection was detected in 3 pts (15.79%), subtotal in 13 pts (68.43%), partial in 2 pts (10.52%), biopsy 1 pts (5.26%)), local radiation therapy (RT) 55 Gy with parallel chemotherapy (CT): TMZ 75 mg/m2 p.o. everyday + Bevacizumab 5 mg/kg i.v. every 2 weeks (twice), followed by 6 cycles of combined CT: TMZ 150-200 mg/m2 (1-5 days) + Bevacizumab 5 mg/kg every 2 weeks, followed by maintain therapy for two years with Bevacizumab 15 mg/kg every 3 weeks. In 3 patients due to residual tumor after CT and 2 patients due to residual tumor after maintain therapy the stereotactic radiosurgery (gamma knife) was performed. RESULTS: For the analyzed moment 13 pts are still alive (68.42%), 6 pts with PD died (31.58%). 4-years PFS/OS in all pts is 0,58 ± 0.11/0,68 ± 0.11. Median of observing time - 39 months (range, 12-53). After RT the objective response observed in all 19 pts: CR 5 (26.32%), PR 11 (57.89%), SD 3 (15.79%). All 19 pts received combined therapy TMZ + Bevacizumab (18 pts - 6 cycles and 1pt - only 4 cycles). The objective response after combined CT was: CR 7 (36.85%), PR 2 (10.52%), SD 4 (21.05%), PD 6 (31.58%). 13 pts received maintain therapy with Bevacizumab. Median of number of cycles for 1 pt was 22 (range 4-22). The objective response after combined CT was: CR 9 (69.42%), SD 2 (15.38%), PD 2 (15.38%). 4-years PFS was better in pts older 5 years vs under 5 years - 0.62 and 0.33, respectively (p = 0.50), in boys vs girls - 0.67 and 0.37, respectively (p = 0.50), in pts with supratentorial localization vs infratentorial - 0.60 and 0.33, respectively (p = 0.58), in pts with total resection vs subtotal - 0.67 and 0.56, respectively (p = 0.88), in pts with AA vs GB - 0,75 and 0.53, respectively (p = 0.53). CONCLUSION: The combined therapy with Bevacizumab and TMZ after resection tumor is an effective strategy in children with AA and GB.
Systemic-Portal Shunt in Unilateral Iliac Vein Stenosis
Authors: SEIGO KINUYA, JUNICHI TAKI, MASAHIKO FUJIOKA, TAKATOSHI MICHIGISHI, NORIHISA TONAMI
Journal: Clinical Nuclear Medicine (1997)

Systemic-portal shunt was shown as a "hot spot" in the liver on Tc-99m MAA radionuclide venography. This finding is well known in the inferior vena cava syndrome. Scintigraphy in this case showed the patent inferior vena cava and the unilateral common iliac vein stenosis. The"hot spot" in this situation has not been previously reported.
Abstract 5733: Detection of M1dG and 6-oxo-M1dG from biological samples in rats
Authors: Sarah C. Shuck, Philip J. Kingsley, Dapo Akingbade, Lawrence J. Marnett
Journal: Cancer Research (2012)

Abstract Reactive oxygen species (ROS) produced from cellular metabolism and exposure to environmental agents pose a significant threat to genomic stability. Direct DNA oxidation by ROS or indirect modification by products of lipid peroxidation results in the formation of mutagenic DNA adducts that are implicated in carcinogenesis. Following oxidation of phospholipid and/or DNA, several reactive aldehydes are formed including base propenal and malondialdehyde (MDA), both of which can react with DNA to form oxopropenyl-adducted bases. The most abundant DNA adduct produced, M1dG, is the product of reaction with deoxyguanosine. This adduct has been extensively characterized and shown to be mutagenic in both mammalian and bacterial systems and repaired by the nucleotide excision repair (NER) pathway. M1dG has also been detected in the genomic DNA of both healthy and disease-bearing individuals, indicating its presence and significance in cellular metabolism. Previous work has demonstrated that M1dG is oxidized in rats to a single metabolite, 6-oxo-M1dG, which can be detected in both urine and feces and has the potential to be used as a biomarker for oxidative stress and disease. We have developed antibodies against M1dG and 6-oxo-M1dG, which are being utilized in a novel assay for the analysis of M1dG and 6-oxo-M1dG in biological samples. Using solid phase extraction and mass spectrometry, we have developed a reliable assay for the analysis of 6-oxo-M1dG in urine and feces from male Sprague-Dawley rats. We have determined the level of excreted 6-oxo-M1dG to be 0.19 pmol/kg/day in urine and 0.92 pmol/kg/day in feces. We are currently expanding our studies to analyze samples from animals with increased oxidative stress in order to determine how excretion and metabolism of M1dG is altered under these conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5733. doi:1538-7445.AM2012-5733
Abstract 1076: Reversible effect of all-<i>trans</i>-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression
Authors: Lynea Murphy, Tanya Moore, Stephen Nesnow
Journal: Cancer Research (2010)

Abstract The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive properties of atRA which functions to regulate levels of cell cycle proteins essential for the G1/S transition and progression through S phase. Using AML12 cells, a non-transformed immortalized mouse hepatocyte cell line, the goals of this study were to first determine if changes in AML12 cell proliferation could be observed in response to atRA treatment and establish whether this was a suitable system to investigate molecular mechanisms altered by hepatocarcinogens. Cells were treated with 1µM and 5 µM atRA for 2 to 10 days. At various time points, control (DMSO) and treated cells were enumerated to determine the effect of atRA on AML12 cell proliferation. At 5 days of atRA treatment, there was a 56% decrease in the number of atRA treated cells when compared to control cells. This effect was reversible as an increase in cell number was observed two days after removal of atRA from the treatment media. Cell cycle analysis by flow cytometry using propidium iodide stained AML12 cells showed a significant reduction (p&amp;lt;0.05) in S phase cells and a significant increase (p&amp;lt;0.05) in G1 phase cells with 48 hours of atRA treatment when compared to control cells indicating a block at the G1/S checkpoint. Western analysis of control and treated whole cell lysates revealed a decrease in phosphorylated (Serine807/Serine811) retinoblastoma protein (pRb). Taken together, these results indicate that proliferation in AML12 hepatocytes can be reversibly modified by atRA by regulating these cells at the G1/S checkpoint with a reduction in pRb. Previous studies of liver tissues collected from mice exposed to the hepatocarcinogenic fungicide, propiconazole, have revealed an increase in cellular proliferation, increases in atRA metabolism as well as decreases in the levels of hepatic atRA. Based on the results of the present experiments, AML12 hepatocytes provide an optimal in vitro system to elucidate the molecular mechanism by which propiconazole induces hepatotumorigenesis. This work was reviewed by EPA and approved for publication but does not necessarily reflect official Agency policy. 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 1076.
ASSOCIATION OF THE INTENSITY AND DURATION OF CIGARETTE SMOKING EXPOSURE WITH CARDIAC STRUCTURE AND FUNCTION IN SMOKERS: THE ECHOCARDIOGRAPHIC STUDY OF HISPANIC/LATINOS (ECHO-SOL)
Authors: John Leigh, Robert Kaplan, Katrina Swett, Pelbreton Balfour, Mayank Kansal, Gregory Talavera, Krista Perreira, Michael Blaha, Emelia Benjamin, Rose Marie Robertson, Aruni Bhatnagar, Carlos Rodriguez
Journal: Journal of the American College of Cardiology (2016)
Biologicals Studied Increasingly as Treatments for Childhood Cancer
Authors: L. Anderson
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Biologicals Studied Increasingly as Treatments for Childhood Cancer Get access Linda Anderson Linda Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 6, 15 March 1989, Pages 394–396, https://doi.org/10.1093/jnci/81.6.394 Published: 15 March 1989
S114 Lymphatic vessel distribution in fibrotic lung diseases
Authors: E. A. Renzoni, E. Weber, F. Sozio, A. Rossi, A. U. Wells
Journal: Thorax (2011)

<h3></h3> Relatively little is known on lymphatic vessel remodelling in lung fibrosis, and whether differences in lymphatic distribution underlie the worse survival seen in idiopathic pulmonary fibrosis, compared to the other fibrotic interstitial pneumonias. Lymphatic vessel remodelling and a deficit in lymphatic clearance could lead to prolonged exposure to pathogenic antigens and/or pro-inflammatory/pro-fibrotic mediators in the alveolar-interstitial space. In this study, we compared lymphatic and blood vessel morphology in lung biopsies of six patients with idiopathic pulmonary fibrosis (with usual interstitial pneumonia pattern-UIP), six patients with fibrotic non-specific interstitial pneumonia associated with scleroderma (NSIP) five patients with fibrotic organising pneumonia (FOP) and five controls (normal lung peripheral to resected cancer). Consecutive sections were stained with Movat9s pentachrome and with double immunostaining for von Willebrand factor (blood vessels) and for podoplanin (lymphatic specific marker D2-40) (see Abstract S114 figure 1). Area, perimeter and position were recorded for all lymphatic vessels and for blood vessels with a diameter &gt;15 μm, to be sure to exclude capillaries. In the three disease groups, blood vessels were significantly smaller (mean diameter: FOP 18±2, NSIP 13±1, UIP 13±1 μm) compared to controls (23±2 μm). Density of lymphatic vessels was significantly reduced in NSIP and UIP (21±2 mm<sup>−2</sup>), compared to controls (35±4 mm<sup>−2</sup>) and their size was significantly greater (mean diameter: NSIP 111±10 μm, UIP 121±5 μm, controls: 74±9 μm). In controls, 85±6% of the parenchymal lymphatics were close (&lt;100 μm) to a blood vessel, and only 5±4% were in proximity of bronchoalveolar spaces, while in all three disease groups they were less frequently perivascular (FOP 47±6%, NSIP 55±3%, UIP 56±2%) and more frequently associated with the bronchoalveolar lumen (FOP 52±11%, NSIP 85±3%, UIP 69±2%). Lymphatic vessels were rarely seen inside Masson bodies and never inside fibroblastic foci (Abstract S114 figure 1). These data are consistent with a substantial remodelling of lymphatic vessels in fibrotic lung disease, with a shift of lymphatics away from blood vessels.