tbuckley/cabot-search huggingface dataset:
Abstract 1897: Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices for diagnosis of pancreatic neoplasms
Authors: Suguru Yonezawa, Seiya Yokoyama, Michiyo Higashi
Journal: Cancer Research (2014)

Abstract Mucins play crucial roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. In our clinicopathological investigation for mucin expression in human pancreatic ductal adenocarcinomas (PDACs) and intraductal papillary mucinous neoplasms (IPMNs), we had reported that MUC1 (pan-epithelial membrane mucin) or MUC4 (tracheobronchial mambrane mucin) expression is related with the aggressive behavior and a poor outcome of the patients, whereas MUC2 (intestinal secretory mucin) expression tends to be related with the indolent behavior and a favorable outcome of the patients. We investigated the mechanism of mucin genes expression from the DNA methylation standpoint in human cancer cell lines using the mapping of methylated cytosines by the quantitative MassARRAY analysis, followed by the confirmation with MSP analysis and a novel DNA methylation analysis method ‘methylation specific electrophoresis (MSE, international patent open: WO 2011/132798)’, and compared the results with expression levels of mucin core protein and mRNA in the cancer cells. The results obtained showed that MUC1, MUC2 and MUC4 expression is regulated by DNA methylation at their proximal 5′ flanking regions in the cancer cells. The MSE method greatly decreases the amount of input DNA, although conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. The lower detection limit for distinguishing different methylation status is under 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We applied the MSE method to human pancreatic juices from 45 patients with various pancreatic lesions. The analyses for DNA methylation status of MUC1, MUC2 and MUC4 combined with image data were useful for differential diagnosis of various human pancreatic neoplasms. The examination of 45 samples of human pancreatic juices by the MSE method combined with the image examination showed the following specificity and sensitivity by quadratic discrimination analysis: PDAC, 87% and 80%; gastric-type IPMN (safe type), 88% and 77%; intestinal-type IPMN (dangerous type), 100% and 88%; respectively. The MSE analysis of human pancreatic juices may give us very useful informations for the selection of the treatment methods for pancreatic neoplasms. Citation Format: Suguru Yonezawa, Seiya Yokoyama, Michiyo Higashi. Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices for diagnosis of pancreatic neoplasms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1897. doi:10.1158/1538-7445.AM2014-1897
Why don't you die when I sneeze? Biochemical analysis of hypermutational targeting by wild type and mutant AID
Authors: Myron F. Goodman
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY35-3 

The synthesis of high affinity antibodies requires activation-induced cytidine deaminase (AID) to initiate somatic hypermutation (SHM), targeting the variable region of immunoglobulin genes, and class-switch recombination (CSR). We have investigated AID-catlyzed deamination of C → U on single-stranded DNA and actively transcribed closed double-stranded DNA. Mutations are initially favored at canonical WRC (W = A or T, R = A or G) SHM hotspot motifs, but over time mutations at neighboring non-hotspot sites increase creating random clusters of mutated regions, in a seemingly processive manner. N-terminal AID mutants and appear less processive and have altered mutational specificity compared to wild type AID. In contrast, a C-terminal deletion mutant defective in CSR in vivo , but normal for SHM, closely resembles wild type AID. A mutational spectrum generated during transcription of closed circular double-stranded DNA indicates that AID retains its specificity for WRC hotspot motifs within the confines of a moving transcription bubble while introducing clusters of multiple deaminations predominantly on the non-transcribed strand. A model involving the discrete action of dimeric AID subunits is proposed to account for the accumulation of random clusters of mutations.
Abstract 17543: DMPK E Disrupts Sarcomere Structure by Inhibition of SRF Transcriptional Activity
Authors: Ies Elzenaar, Amin Damanafshan, Inge van der Made, Yigal M Pinto, Ralph J van Oort
Journal: Circulation (2014)

Background: Heart failure is associated with elongation of cardiomyocytes and loss of sarcomeres. Although the transcription factor myocyte enhancer factor-2 (MEF2) has an important role in this adverse remodeling, the mechanism underlying the structural changes of cardiomyocytes remains to be elucidated. In a screen for MEF2 target genes, we have recently identified myotonic dystrophy protein kinase (DMPK) as a potential mediator of adverse cardiomyocyte remodeling. However, it remains to be determined whether DMPK levels are increased in failing hearts and if DMPK is sufficient to induce structural remodeling of cardiomyocytes. Methods and Results: Since the DMPK gene is subject to extensive alternative splicing, we performed RT-PCR and QPCR analysis of known DMPK splice variants in hearts from mice subjected to transverse aortic constriction (TAC) or sham surgery. This demonstrated a 1.6 fold increase in the DMPK E isoform in failing mouse hearts compared to controls (P&lt;0.05). To test the role of this specific splice isoform, we generated adenoviruses expressing DMPK E or a kinase dead mutant DMPK E. Overexpression of wildtype DMPK E, but not of the kinase dead mutant, in cardiomyocytes resulted in severe loss of sarcomeric structure. Moreover, QPCR analysis showed a decrease in mRNA levels for several sarcomeric genes after overexpression of DMPK E. Since these genes are known targets of the transcription factor serum response factor (SRF) and DMPK is known to phosphorylate SRF, we tested the effect of DMPK E on SRF activity. Luciferase experiments demonstrated that DMPK E is an inhibitor of SRF transcriptional activity. Finally, immunostaining revealed a translocation of SRF from the nucleus to the cytosol upon DMPK E overexpression. Conclusion: Our data indicate that the expression of DMPK E is increased in heart failure. Moreover, increased expression of this DMPK splice variant results in a decrease in sarcomeric gene expression by translocation and inhibition of SRF. Together, these results assign a novel function to DMPK in adverse cardiomyocyte remodeling during heart failure development.
The 0.8% ultraviolet B content of an ultraviolet A sunlamp induces 75% of cyclobutane pyrimidine dimers in human keratinocytes<i>in vitro</i>
Authors: None Woollons, None Kipp, None Young, None Petit-Frère, None Arlett, None Green, None Clingen
Journal: British Journal of Dermatology (1999)

Tanning lamps, emitting predominantly ultraviolet (UV) A, are used widely throughout the U.K. and other countries, but little is known about the long-term risks associated with their use, especially with respect to skin cancer. We have exposed normal human epidermal keratinocytes to a commercial tanning lamp and used the comet assay in association with DNA repair enzymes T4 endonuclease V and endonuclease III to investigate the relative yields of directly formed cyclobutane pyrimidine dimers (CPDs) and indirectly formed types of oxidative DNA damage. To put the risk of using tanning lamps into perspective, the sunbed used in this study (five Philips Performance 80W-R UVA tubes at a distance of 35 cm) was found to be approximately 0.7 times as potent at inducing CPDs as U.K. natural sunlight around noon on a fine summer day. This compares with a relative risk for CPD induction and erythema of 0.8 and 0.7 times, respectively, calculated from the relevant action spectra of tanning lamps and British noontime sunlight. To determine the relative contribution of UVB and UVA to the induction of CPDs and oxidative DNA damage, we modified the spectral output of the tanning lamps with a series of Schott WG UVB filters. The induction of CPDs was more dependent on the UVB component of the sunbed than oxidative types of damage. Schott WG UVB filters with 50% transmission at 305 nm reduced the yield of T4 endonuclease V sites by 42% while there was only a 17% decrease in the yield of endonuclease III sites. CPD induction was not completely abolished after irradiation through WG335 and WG345 nm filters despite there being no detectable UVB. From these data, it was estimated that, although the tanning lamps emitted only 0.8% of their total output in the UVB range, these wavelengths were responsible for the induction of over 75% of CPDs and 50% of the oxidative damage to DNA.
Anastrozole-induced subacute cutaneous lupus erythematosus
Authors: M. Trancart, A. Cavailhes, B. Balme, F. Skowron
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, We describe a 73‐year‐old woman who was referred to our department for an intense cutaneous eruption. She had recently had breast cancer, which had been treated with surgery 7 months previously, then with radiotherapy, followed by anastrozole. She also had a high arterial blood pressure, treated for many years with an angiotensin‐converting enzyme (ACE) inhibitor. The cutaneous eruption had begun 1 month after the beginning of anastrozole treatment. This treatment was discontinued and the ACE inhibitor was stopped and replaced with atenolol. The eruption improved slightly. Five weeks later, anastrozole was reintroduced and the eruption reappeared with greater intensity. This eruption affected the upper trunk, neck, face, and extensor surfaces of the upper arms (Fig. 1). Lesions were annular, polycyclic and erythematosquamous, with a desquamative collarette. The patient had an intense burning sensation and pruritus. Clinical examination was otherwise normal; in particular, there was no oral ulceration.
Second-generation deinstitutionalization, I: The impact of Brewster v. Dukakis on state hospital case mix
Authors: J L Geller, W H Fisher, J L Wirth-Cauchon, L J Simon
Journal: American Journal of Psychiatry (1990)

A 1978 consent decree affecting one region of Massachusetts mandated a drastic reduction of census at its state hospital, where considerable deinstitutionalization had already occurred over the prior two decades. The transfer of patients from hospital to community was to be accomplished through the unprecedented expansion of community resources. This second-generation deinstitutionalization effort achieved substantial census reduction but less than was envisioned. It was most effective in discharging geriatric and mentally retarded patients but far less effective with longterm and new chronic patients, many of whom continue to require repeated hospitalizations despite the availability of a comprehensive array of community-based services.
Skin Cancer Diagnosis With Reflectance Confocal Microscopy
Authors: Francesca Farnetani, Alon Scope, Ralph P. Braun, Salvador Gonzalez, Pascale Guitera, Josep Malvehy, Marco Manfredini, Ashfaq A. Marghoob, Elvira Moscarella, Margaret Oliviero, Susana Puig, Harold S. Rabinovitz, Ignazio Stanganelli, Caterina Longo, Carlotta Malagoli, Marco Vinceti, Giovanni Pellacani
Journal: JAMA Dermatology (2015)

Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested.To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis.Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors.The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users.Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%).The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.
Biological pathways discriminating susceptible from resistant mouse strains to radiation induced lung damage
Authors: Latha Ramdas, Min Du, Xinhui Zhou, John Allard, Gary Peltz, Elizabeth L. Travis
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4399 

A limiting factor in the treatment of cancers of the thorax, particularly lung cancer and esophageal cancer is radiation induced alveolitis and pulmonary fibrosis both of which are multi-faceted pathologic processes leading to loss of lung function, morbidity and death. Current therapies aimed at treating alveolitis have had limited success in the clinic and there are no effective therapies to treat pulmonary fibrosis. The purpose of our study was to identify biological pathways and susceptibility genes underlying radiation-induced lung injury. The whole thorax of fibro sis prone C57BL/6 mice and fibrosis resistant but alveolitis prone C3H mice was irradiated with 16Gy single dose and sacrificed one month after irradiation for lung RNA isolation and hybridized to Affymetrix mouse arrays. We compared gene expression in irradiated vs. age-matched non-irradiated mice of each strain. Genes with at least 66% concordance among all possible pairwise comparisons and at least one two-fold change were used for pathway and network analysis. The data was imported into a web-delivered Ingenuity Pathway Analysis program to systematically analyze the data in the context of biological pathways to establish functional relationships amongst genes. Global functional analysis identified cellular movement, hematological system development and function, and immune response as the top level functions for the genes significantly altered in C3H after radiation. For C57BL/6, the top three functions that were significant were identified as cancer, cell cycle, and cell death. The signaling pathways identified in C3H after irradiation, include integrin signaling, p38 MAPK signaling, PI3K/AKT signaling, and IL-6 signaling, while in C57BL/6 this includes folate biosynthesis, p38 MAPK signaling, Wnt/β-catenin signaling, and T cell receptor signaling. In conclusion, we identified biological functions and pathways that may be associated with specific radiation-induced lung injury. Supported by NIH NCI grants RO1 CA64193 and P30 CA16672.
Abstract 19515: Statin Use is Associated with Reduced All-Cause Mortality Following Bioprosthetic Heart Valve Implantation
Authors: Mazen S Albaghdadi, Adin-Christian Andrei, Zhi Li, Jane Kruse, Eileen McDonald, Robert Bonow, Patrick McCarthy
Journal: Circulation (2014)

Objective: This study examined the impact of statin use on clinical outcomes in patients undergoing bioprosthetic heart valve (BHV) implantation. Background: The medical management of patients undergoing BHV implantation is primarily directed at the management of co-morbid conditions. The anti-atherogenic and anti-inflammatory effects of statin use may contribute to improved clinical outcomes following BHV implantation. Methods: A retrospective analysis of patients (n=1957) undergoing aortic (n=1609) and mitral (n=436) BHV replacement with available data on statin use from 2004 to 2013 was performed. All-cause mortality was assessed using the Social Security Death Index. Association of baseline characteristics and statin use during follow-up with the incidence of events was assessed using a time-dependent covariate Cox regression model. Results: Follow-up was complete in 100% of patients. Total follow-up time was 3.9 ± 2.4 years during which death occurred in 10% of patients. Pre-discharge statin use was not significantly associated with mortality at 30 days or medium-term follow-up. After adjustment for covariates, post-BHV implantation use of statins was associated with a significant reduction in the risk of all-cause mortality in the entire cohort: HR=0.55, 95% CI: 0.40-0.74, P&lt;0.001. In addition, post-BHV statin use was associated with a decreased risk of all-cause mortality in the aortic valve replacement subgroup: HR=0.59, 95% CI: 0.42-0.84, P=0.003, and mitral valve replacement subgroup: HR=0.30, 95% CI: 0.17-0.54, P&lt;0.001. After exclusion of patients with known CAD (43% of the cohort), post-BHV use of statin therapy remained associated with a lower risk of death: HR=0.51, 95% CI: 0.33-0.80, P=0.004. Conclusion: Statin treatment is associated with a significant reduction in medium-term all-cause mortality in patients with and without CAD undergoing aortic and mitral BHV implantation.
Abstract 12298: Inducible Nitric Oxide Synthase Expression in Mesenchymal Stromal Cells Induces Immunomodulation but Enhances Tumorigenic Conversion in Allogenic Cell Sheet Transplantation for Rat Myocardial Infarction
Authors: Yukiko Imanishi, Esko Kankuri, Antti Siltanen, Shigeru Miyagawa, Satsuki Fukushima, Yoshiki Sawa, Ari Harjula
Journal: Circulation (2014)

Background:  Mesenchymal stromal cell (MSC) reportedly induce immune tolerance against allogenic antigens via inflammation-related expression of inducible nitric oxide synthase (iNOS). Combination of MSC may be promising therapeutic option in treating allogenic cell for cell therapy. However, tumorigenic conversion of MSCs is a major concern. Here, we hypothesized that immunomodulation property induced by iNOS in MSC impacts their tumorigenic conversion. We evaluated tumor formation following combined transplantation of iNOS-expressing MSCs with allogenic skeletal myoblasts in a rat model of myocardial infarction.   Methods and Results:  Fischer rat-derived MSCs were prepared as a cell sheet for transplantation on the surface of the infarcted or normal myocardium of Wistar rats. Seven days after transplantation, iNOS expression of the cell sheet which was transplanted on the infarcted myocardium was greater than that transplanted on the normal myocardium. Next, iNOS expression in the MSC was enhanced by interferon-γ and lipopolysaccharide (IL) treatment before creating cell sheet. Survivals of luciferase-expressing L6 skeletal myoblasts following subcutaneous cell-sheet transplantation were evaluated by in vivo imaging. Addition of the MSCs to the L6 sheet prolonged the survival of the L6 cells, which was further extended by IL treatment of MSCs prior to the cell sheet preparation. Then, we transplanted cell sheets over the infarcted myocardium of Wistar rats. Tumor growth was not observed in the rats that received allogenic skeletal myoblast sheets at 28 days. While, mixed cell sheets transplanted over the infarcted myocardium showed formation of MSC-derived tumors (2 / 10), and tumor formation elevated by the IL pre-treatment in MSCs (8 / 10).   Conclusion:  Inflammatory stimulation, such as transplantation to the infarcted myocardium or IL treatment in vitro enhanced iNOS expression in MSCs, prolonging the survival of transplanted allogenic myoblast cell sheets. However, iNOS expression in the MSCs was also associated with tumorigenic conversion, indicating that iNOS expression in MSCs should be considered when optimizing the concomitant transplantation therapy of MSCs and allogenic cells for treatment of heart failure.
The Clinical Practice of Emergency Medicine
Authors: edited by Ann L. Harwood-Nuss
Journal: Annals of Internal Medicine (1991)

Recommended in the Brandon/Hill selected list of print books and journals for the small medical library - April 2003 Formatted for easy use while on the move, The Clinical Practice of Emergency Medicine, Third Edition is a comprehensive reference that offers quick access to clinically relevant material. Each chapter covers clinical presentation, diagnosis, evaluation, management and disposition. With emphasis on both medical and managerial essentials, this book covers everything from geriatrics to sociocultural violence, MRIs to pain management
PR39, a peptide regulator of angiogenesis
Authors: Jian Li, Mark Post, Rudiger Volk, Youhe Gao, Min Li, Caroline Metais, Kaori Sato, Jo Tsai, William Aird, Robert D. Rosenberg, Thomas G. Hampton, Jianyi Li, Frank Sellke, Peter Carmeliet, Michael Simons
Journal: Nature Medicine (2000)
Aluminium‐induced granulomas after inaccurate intradermal hyposensitization injections of aluminium‐adsorbed depot preparations
Authors: M. Vogelbruch, B. Nuss, M. Körner, A. Kapp, P. Kiehl, W. Bohm
Journal: Allergy (2000)

Background: The development of persistent subcutaneous nodules at the injection sites of aluminium‐adsorbed hyposensitization solutions is rare. These nodules have been interpreted as a delayed, granulomatous hypersensitivity reaction to aluminium. We report for the first time a case of persistent intradermal granulomas that developed at the sites of inaccurate intradermal, instead of subcutaneous, hyposensitization injections. Methods: An intradermal nodule was excised and processed for histopathology, scanning electron microscopy, and X‐ray microanalysis. Intradermal and patch tests with aluminium hydroxide were performed. Results: Histologically, the nodule presented a pattern of granulomatous inflammatory reaction surrounding foci of necrotic tissue. Scanning electron microscopy and X‐ray microanalysis revealed deposits of aluminium within the granulomas. Patch tests with aluminium hydroxide were negative, and intradermal tests caused persistent intradermal granulomas. Subsequent hyposensitization therapy in our department with the usual subcutaneous injections of aluminium‐adsorbed allergen extracts was well tolerated by the patient. Conclusions: Local toxic effects of aluminium may be crucial in the development of persistent intradermal injection‐site granulomas. Such intradermal nodules may develop even if the subcutaneous route is well tolerated. We conclude that inaccurate intradermal injections of aluminium‐containing solutions have to be strictly avoided.