tbuckley/cabot-search huggingface dataset:
Farmer's lung - How much farming is required? A quantitative re-evaluation of eight cases of hypersensitivity pneumonitis attributed to indoor mould exposure
Authors: Henrik A. Kolstad, Zuzana Dornonville de la Cour, Simon Skov, Tine Halsen Malling, Elisabeth Bendstrup, Vivi Schlünssen
Journal: European Respiratory Journal (2012)

Background  Hypersensitivity pneumonitis is by definition caused by the inhalation of antigens, but limited quantitative data are available on exposure levels required to cause the disease.   Objective  To analyse exposure levels for mould spores in patients with clinical findings compatible with hypersensitivity pneumonitis and a history of indoor mould exposure.   Methods  We report eight consecutive patients diagnosed as hypersensitivity pneumonitis based on symptoms, high resolution computerized tomography, bronchoscopy, IgG findings, and self-reported mould exposure at home or work. Indoor and outdoor air samples from their dwellings or work sites were collected with slit to agar samplers, N6 Anderson samplers, and filter samplers used for quantification of moulds by the Camnea method. The concentration of fungi was calculated and expressed as colony forming units (CFU)/m 3  and total spores/m 3 .   Results  The indoor air concentration of viable fungi was comparable with the outdoor air concentration, while the total spore concentration was moderately increased indoors compared with outdoors but significantly lower than previously measured in documented cases of hypersensitivity pneumonitis among farmers.   Conclusion  We question if the lung diseases of these patients were caused by mould exposure in their indoor environments and document the need for quantitative exposure measurements when diagnosing hypersensitivity pneumonitis in patients living or working outside environments with well-documented high mould exposure levels.
Abstract 760: Suppression of ABCG2 mediated MDR <i>in vitro</i> and <i>in vivo</i> by a novel inhibitor of ABCG2 transport
Authors: Atish S. Patel
Journal: Cancer Research (2014)

Abstract Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR) that is its Achilles’ heel. Hence there is an immense demand for development of novel agents that can overcome the emergence of multidrug resistance (MDR) in cancer. A group of transmembrane proteins called ABC (ATP- binding cassette) transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR in various tumor types. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells both in vitro and in vivo. CCTA-1523 at concentrations upto 5 μM sensitized the cancer cells as well as transfected cells overexpressing ABCG2 to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the active efflux function of the transporter; also there was no change in the protein expression of the ABCG2 transporter in the presence of CCTA-1523 at reversing concentrations. Importantly the reversal effect produced by CCTA-1523 was reversible. Co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts without added toxicity. Taken together, our findings indicate that CCTA-1523 is a potent and reversible, modulator of ABCG2 export function that may offer therapeutic promise for multidrug- resistant malignancies. Citation Format: Atish S. Patel. Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 transport. [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 760. doi:10.1158/1538-7445.AM2014-760
Avoiding surgical errors by referencing anatomical landmarks
Authors: C. Pagliarello, A. Paradisi, C. Dianzani, M. Paradisi, P. Persichetti
Journal: British Journal of Dermatology (2012)

Journal Article Avoiding surgical errors by referencing anatomical landmarks Get access C. Pagliarello, C. Pagliarello Dermatology Unit, Campus Bio‐Medico Medical School, Via Alvaro del Portillo200, 00128 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Paradisi, A. Paradisi Department of Dermatology, Catholic University of Sacred Heart, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar C. Dianzani, C. Dianzani Dermatology Unit, Campus Bio‐Medico Medical School, Via Alvaro del Portillo200, 00128 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Paradisi, M. Paradisi Dermatology Unit, Campus Bio‐Medico Medical School, Via Alvaro del Portillo200, 00128 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar P. Persichetti P. Persichetti Plastic and Reconstructive Surgery Unit, Campus Bio‐Medico Medical School, Rome, Italy E‐mail: calogero.pagliarello@libero.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 4, 1 October 2012, Pages 951–952, https://doi.org/10.1111/j.1365-2133.2012.10981.x Published: 01 October 2012
Has primary tumour standardized maximum uptake value (SUV max) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) a prognostic value for survival in non-small cell lung cancer (NSCLC) ?: A systematic review and meta-analysis (MA)
Authors: Marianne Paesmans, Michelle Dusart, Thierry Berghmans, Claude Hossein-Foucher, Catherine Castaigne, Arnaud Scherpereel, Céline Mascaux, Michel Moreau, Martine Roelandts, Serge Alard, Anne-Pascale Meert, Jean-Jacques Lafitte, n. Patz, Jean-Paul Sculier
Journal: Journal of Thoracic Oncology (2007)
Analysis of MITF expression and its downstream genes in lung cancer
Authors: Sung-Liang Yu, Jeremy J.W. Chen, Su-Chin Chiu, Hsang-Yu Chen, Pan-Chyr Yang
Journal: Cancer Research (2004)

1723  Previously, we have established a series of lung adenocarcinoma cell lines with varying degrees of invasiveness. In this study, we used these model cell lines to identify invasion-assaociated genes using cDNA microarrays containing 31104 nonredundant expressed sequence tag clones. Among identified targets, microphthalamia-associated transcription factor (MITF) was noticed, whose expression was negatively correlated with cell line invasiveness. MITF encodes a transcription factor that is essential for normal melanocyte development and appears to regulate expression of several pigmentation genes. The mRNA expression analysis of MITF using quantitative real-time RTPCR demonstrated a tight correlation in its expression level in clinical lung cancer specimen. MITF was higher expressed in cancer tissues compared to the counterparts of normal tissues and its expression level also significantly corrected to the survival rates of cancer patients. In order to explore the downstream genes regulated by MITF, we constructed stable constitutive MITF-overexpressed transfectants in the highly invasive cell line CL1-5 and a cDNA microarray was used to profile alterations of gene expression after MITF overexpression. Quantitative real-time RTPCR and immunohistochemical staining confirmed the expressions of some targeted genes. The cDNA microarray data demonstrated that MITF regulated genes involving in angiogenesis, metastasis, cell proliferation and signal transduction. The present study is the first, to the best of our knowledge, that investigates the expression and the function of MITF in lung cancer (other than melanocytes and osteroclasts). MITF may potentially suppress tumorgenesis by regulation of a panel of genes.
Identification of novel mechanisms regulating histone methylation and epigenetics
Authors: Hui Zhang, Leigh Ann Higa, Min Wu
Journal: Clinical Cancer Research (2007)

C13  Histone methylation is a major regulatory mechanism of epigenetic control. While tri-methylation at histone H3 lysine 4 (H3K4) usually associates with active transcription, methylation at histone H3 lysine 9 and lysine 27 (H3K9 and H3K27) suppresses gene expression. Trimethylation at H3K4 is regulated by MLL methyltrasferase complexes that also contain essential WD40 repeat proteins WDR5 and RBBP5. Methylations at H3K9 and H3K27 are controlled by the polycomb repressive group 2 complex that containsEZH2, Suz12, and WD40 repeat protein EED. The dynamic regulation of H3K4 and H3K27 methylation is critical for the epigenetic control of the lineage-specific gene expression. However, the molecular mechanism by which histone methylation is regulated remains largely unknown. We have recently found that histone methylation at H3K4, K9, and K27 is regulated by ubiquitin E3 ligases containing CUL4 (cullin4) and its associated DDB1 (UV-damaged DNA Binding Protein 1). Specifically, we found that CUL4-DDB1 ubiquitin E3 ligases interact with WD-40 repeat proteins WDR5, RBBP5, and EED and use them as substrate-specific subunits to target proteins for ubiquitin-dependent proteolysis. We found CUL4-DDB1 ubiquitin E3 ligases also interact with methylated H3K4, K9, and K27. Inactivation of either CUL4 or DDB1 leads to the inhibition of histone methylation at H3K4, K9, and K27, similar to the inactivation of either WDR5 or EED. We are in the process to identify the substrates for these ubiquitin E3 ligases that regulate hitone methylation at these critical sites. Our study reveals novel mechanisms for the control of histone methylation and demonstrates that histone methylation is dynamically regulated by ubiquitin-dependent proteolysis.
Abstract 16658: Long-term Clinical Outcome following Successful Percutaneous Revascularization in Chronic Total Occlusions in the context of Multivessel Disease: The Milan Experience
Authors: Cosmo Godino, Fotios I. Economou, Giorgio Bassanelli, Kensuke Takagi, Alfonso Ielasi, Azeem Latib, Marco Mussardo, Alaide Chieffo, Matteo Montorfano, Mauro Carlino, Antonio Colombo
Journal: Circulation (2010)

Background: It is not yet clearly defined if successful percutaneous revascularization of chronic total occlusions (CTOs) in multivessel disease leads to long term survival improvement. Aim of the ...
Abstract 20699: GMP-Grade Cardiomyocyte Differentiation Media System for Pluripotent Stem Cells in Basic and Translational Research
Authors: Shayne Boucher, Stacy Jones, David Kuninger, Mohan Vemuri
Journal: Circulation (2014)

Objective: Current protocols for differentiating pluripotent stem cells (PSCs) have led to heterogeneous results, varying purity levels, and long lead times for generation of cardiomyocytes. We hypothesized that a simplified and rapid cardiomyocyte differentiation media system can be developed in a scalable workflow to enable generation of large numbers of consistent, spontaneously active cardiomyocytes that could be used in basic and translational research. Methods: High quality PSCs were maintained under xenofree, feeder-free culture conditions. At time of passaging, PSC were dissociated with 0.5 mM EDTA, seeded on 1:100 Geltrex © -coated surface as small clusters at ~0.5 to 1 x 10 5 /well of a 12-well plate and maintained for four days under serum-free condition. After reaching target confluence of ~60 to 80%, an induction media was added for two days followed by addition of a second induction media for two days. After the induction step, the media was replaced with maintenance media and re-fed every other day for up to five weeks. PSC-derived cardiomyocytes were analyzed by morphology, gene expression, flow cytometry, immunocytochemistry and multi-electrode array (MEA). Results: We observed individual beating cells by Day 7 and contracting syncytia by Day 10. An over 100 fold increase in cell number was noted from the time of plating to generation of contracting syncytia of cardiomyocytes. Quantitative flow cytometry detected populations of troponin T type 2 (TNNT2)-immunoreactive cells that reached as high as 96.6%. Number of TNNT2-positive cells dropped by 20% when induced at 90% versus 60% confluency. PCR studies confirmed expression of mesoderm (T, MIXL1, MESP1), cardiac mesoderm (ISL1, GATA4, MEF2C) and mature cardiomyocyte genes (NKX2.5, TNNT2, MYH6). Immunocytochemistry studies verified expression of cardiac markers NKX2.5,GATA4, MEF2C, TNNT2 and MYH6. Initial MEA studies corroborated the presence of electrically active cells. Conclusions: We conclude that a simplified complete differentiation media system could serve as a standardized culture system for generating large numbers of consistent, spontaneously active cardiomyocytes for basic and translational research studies.
Immunosuppressive effect of prolactin-induced protein: a new insight into its local and systemic role in chronic allergic contact dermatitis
Authors: S. Sugiura, M. Fujimiya, H. Ebise, Y. Miyahira, I. Kato, Y. Sugiura, T. Kimura, M. Uehara, H. Sato, H. Sugiura
Journal: British Journal of Dermatology (2010)

Prolactin-induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4-HLA-DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated.To define the role of PIP during the immunoresponse.Using a low-dose oxazolone-induced mouse chronic ACD model, expression of PIP was examined immunohistologically. Furthermore, effects of continued exposure to a peptide mimicking the major binding site of PIP (amino acids 106-132) for CD4 was examined in a mouse chronic ACD model.We clarified that keratinocytes, dermal infiltrating cells and spleen infiltrating mononuclear cells are positively stained with anti-PIP antibody. The PIP peptide significantly downregulated oxazolone-induced mouse ACD compared with controls. We also found that inflammation of the control ear, to which the PIP peptide had not been applied, was also suppressed in a synchronized manner in the late phase of ACD.These findings suggest that PIP might have a local and systemic immunosuppressive effect in mouse chronic ACD.
Abstract 17496: IL2 Soluble Receptor and Neopterin Levels in Peripartum Cardiomyopathy and Recent Onset Cardiomyopathy in Non-Peripartum Women and Men
Authors: Dennis M McNamara, Karen Hanley-Yanez, Leslie Cooper, Richard Sheppard, Daniel Pauly, Jagat Narula, Jessica Pisarcik, Charles McTiernan
Journal: Circulation (2011)

Introduction: IL2 soluble receptor (IL2Rs) and neopterin (NPT) are peripheral markers of T cell and monocyte activation investigated extensively in auto-immune disorders. We assessed these biomarkers in subjects with non ischemic cardiomyopathy of recent onset (ROCM) from the IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) registry. We compared the degree of cellular activation in peripartum cardiomyopathy (PPCM) with that evident in non-peripartum women and men with ROCM. Methods: 130 subjects were investigated: 96 subjects with ROCM including 37 women with PPCM (group 3), 27 non-peripartum women (group 2) and 32 men (group 1), and 34 controls without cardiac disease (CTL). All subjects with ROCM had serum obtained at entry and an assessment of LVEF by transthoracic echocardiography. LVEF was reassessed 6 months after enrollment. Results: The ROCM cohort (n=96, 64F/32M, mean age 30±6) had a mean LVEF at baseline of 0.24±0.08 which increased to 0.43±0.13 at 6 months. For controls (mean age 45±6, 24F/10M) the mean LVEF was 0.58±0.10. Both IL2Rs and NPT were markedly elevated in ROCM subjects compared to controls (IL2Rs: ROCM=1411±671, CTL=970±329 pg/ml, p&lt;0.001; NPT: ROCM=9.2±5.6, CTL=6.2±3.1 nmol/l, p=0.003). Increased NYHA class was associated with higher serum levels for both NPT (p=0.013) and IL2Rs (p=0.009). No differences were evident in subjects with PPCM versus men and women with ROCM for either IL2Rs (group 1/2/3 =1524±504/1531±904/1225±566 pg/ml, p=0.10) or NPT (group 1/2/3=9.4±6.5 /9.3±5.8 /8.9±4.7 nmol/l, p=0.92). IL2Rs levels were lower in black subjects: blacks (n=25) IL2Rs=1123±496; whites (n=71) 1513±698, p=0.012. Levels of IL2Rs and NPT did not predict the degree of recovery at 6 months, although there was a nonsignificant trend towards more recovery with lower IL2Rs levels. Conclusions: Marked elevation of IL2Rs and NPT, biomarkers of cellular immune activation, are evident in subjects with ROMC. The degree of activation in subjects with PPCM appears similar to that seen in men and non-peripartum women with ROCM, suggesting similar inflammatory pathogenesis for these syndromes of acute heart failure. The relationship of cellular activation to myocardial injury and recovery in ROCM should be further investigated.
Induction of arginase-I in murine prostate cancer following high-dose in vivo irradiation
Authors: Ji-Hong Hong, Chein-Sheng Tsai, Chun-Chieh Wang, Shih-Ming Jung, Chi-Rong Wu, Fang-Hsin Chen, Hsiang-Ling Huang, Chi-Shiun Chiang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4412 

The arginase and nitric oxide synththase (NOS) are two major enzymes that competitively catalyze the metabolism of arginine. The products from arginase pathway in tumors may suppress T-cell proliferation and function, and promote tumor growth. The aim of this study is to investigate the expression of arginase-I in the tumor following in vivo high-dose irradiation. TRAMP-C1 cell line which was derived from the Transgenic Adenocarcinoma of the Mouse Prostate and syngenic to C57BL/6J mouse was used as a tumor model. Tumors grew intramuscularly to the size of 4–5 mm, and were either continued to grow or irradiated with 25 Gy. Tumors were taken for analysis at various times since then. The tumor growth delay was 7 days by 25 Gy irradiation. The mRNA levels of arginase-I remained stable in un-irradiated tumors for 2 weeks, even tumors grew rapidly during this period. However, they were increased in the irradiated tumors from 8 hours to 3 weeks following irradiation. The immunohistochemistry (IHC) stain showed increased expression of arginase-I protein in the irradiated tumors, as compared with unirradiated tumors of the same size. Arginase-I mRNA levels were undetectable in vitro in the TRAMP-C1 cells and were not induced by high dose irradiation. To investigate the sources of arginase-I in the in vivo tumor, tumor suspension was fractionated into macrophage and non-macrophage populations by CD11b-conjugated magnetic beads. RPA and RT-PCR demonstrated that Arginase-I mRNA levels were mainly expressed in macrophages population, but barely detectable in non-macrophage population. These observations suggest arginase-I mRNA and protein levels were increased in the regrowing tumors following high-dose irradiation and the sources of production are tumor-associated macrophages. This suggests that Arg-I is a potential target for modulating tumor responses to irradiation. The combination of arginase inhibitor N -hydroxy-nor-L-arginine (nor-NOHA) with radiation therapy for murine prostate cancer is currently under investigation. (This study was supported by Grant NSC 93-2314-B-182-030 and CMRPG340251)
Comparative Efficacy of the Maze Procedure for Restoration of Atrial Contraction in Patients With and Without Giant Left Atrium Associated With Mitral Valve Disease 11This study was supported in part by Research Grant 8A-3 for Cardiovascular Diseases from the Ministry of Health and Welfare of Japan, Tokyo, Japan (1996 and 1997).
Authors: Satoshi Yuda, Satoshi Nakatani, Fumitaka Isobe, Yoshio Kosakai, Kunio Miyatake
Journal: Journal of the American College of Cardiology (1998)
Evidence for transcriptional activation of the MDR1 gene by CtBP1 in human multidrug resistant cancer cells
Authors: Wei Jin, William N. Hait, Jin-Ming Yang
Journal: Cancer Research (2006)

592  Drug resistance caused by overexpression of P-glycoprotein (P-gp), the MDR1 gene product, limits the therapeutic outcome in cancer patients. Although modulation of multidrug resistance (MDR) by pharmacological agents, antibodies, antisense oligonucleotides, siRNA, and inhibitors of signal transduction have been reported, clinical benefits have been disappointing. We and others have sought to understand the regulation of MDR1 gene expression as another approach to this problem. CtBP1 (C-terminal-binding protein 1) is a transcriptional co-regulator that plays an important role in oncogenesis. Recently, it was reported that CtBP1 could serve as both a co-activator and co-repressor of transcription. In this study, we determined the effect of CtBP1 on transcription of the MDR1 gene. Chromatin immunoprecipitation (ChIP) experiments demonstrated that CtBP1 bound to the promoter and coding regions of the MDR1 gene, but not to the non-coding regions. Knockdown of CtBP1 expression by siRNA repressed the expression of MDR1 gene, as evidenced by decreases in MDR1 mRNA (by RT-PCR) and P-gp expression (by Western blot) in the MDR human breast cancer cell line, MCF-7/AdrR, and the ovarian cancer cell line, A2780Dx. Knockdown of CtBP1 also enhanced the sensitivity of MDR cells to chemotherapeutic drugs including doxorubicin and vinblastine, as determined by MTT assay. To further probe the role of CtBP1 in MDR1 transcription, we co-transfected CtBP1 and MDR1 promoter/luciferase constructs into the human colon cancer cells SW620 and ovarian cancer cells A2780, and assayed promoter activity. Co-transfection of CtBP1 and MDR1 constructs resulted in a ∼3.5-fold increase in activity of the MDR1 promoter, confirming the effect of CtBP1 on transcriptional activation of MDR1 gene. Our results suggest that CtBP1 is an activator of MDR1 transcription, and therefore, inhibiting CtBP1 may represent a novel approach to overcoming drug resistance mediated by P-gp.