tbuckley/cabot-search huggingface dataset:
hprt mutant lymphocyte frequencies in workers at a 1,3-butadiene production plant.
Authors: J B Ward, M M Ammenheuser, W E Bechtold, E B Whorton, M S Legator
Journal: Environmental Health Perspectives (1994)

1,3-Butadiene is a major industrial chemical that has been shown to be a carcinogen at multiple sites in mice and rats at concentrations as low as 6.25 ppm. Occupational exposures have been reduced in response to these findings, but it may not be possible to determine by using traditional epidemiological methods, whether current exposure levels are adequate for protection of worker health. However, it is possible to evaluate the biological significance of exposure to genotoxic chemicals at the time of exposure by measuring levels of genetic damage in exposed populations. We have conducted a pilot study to evaluate the effects of butadiene exposure on the frequencies of lymphocytes containing mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in workers in a butadiene production plant. At the same time, urine specimens from the same individuals were collected and evaluated for the presence of butadiene-specific metabolites. Eight workers from areas of the plant where the highest exposures to butadiene occur were compared to five workers from plant areas where butadiene exposures were low. In addition, six subjects with no occupational exposure to butadiene were also studied as outside controls. All of the subjects were nonsmokers. An air sampling survey conducted for 6 months, and ending about 3 months before the study, indicated that average butadiene levels in the air of the high-exposure areas were about 3.5 +/- 7.5 ppm. They were 0.03 +/- 0.03 ppm in the low-exposure areas. Peripheral blood lymphocytes from the subjects were assayed using an autoradiographic test for hprt mutations.(ABSTRACT TRUNCATED AT 250 WORDS)
OP0155 A Novel Model of Systemic Sclerosis?: Loss of PTEN in Fibroblasts Results in Lung Fibrosis in A CCN2/CTGF-Dependent Fashion
Authors: S. Liu, A. Leask
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Scleroderma fibroblasts are characterized by elevated adhesive signaling. PTEN, a phosphatase that suppresses adhesive signaling, expression is reduced in scleroderma dermal fibroblasts. Previously, we showed that loss of PTEN expression in dermal mouse fibroblasts results in skin fibrosis associated with an elevated expression of the fibrotic marker CTGF/CCN2. . <h3>Objectives</h3> Our aim is to whether (a) loss of PTEN expression in fibroblasts also results in lung fibrosis ands (b) whether CCN2 mediates lung fibrosis caused by loss of PTEN. <h3>Methods</h3> A cre/lox system is used to delete PTEN and/or CCN2 in fibroblasts. Mice expressing a tamoxifen-dependent cre under the control of a fibroblast specific (COL1A2) promoter were generated that were homozygous for a loxP-PTEN allele and/or a loxP-CCN2 allele. Mice were injected with corn oil (to generate control mice) or tamoxifen (to delete PTEN and/or CCN2). Forty five days post-cessation of tamoxifen injection, lungs were harvested and subjected to histological and biochemical analyses to assess the effect of loss of PTEN and/or CCN2 on lung fibrogenesis (ie, Hematoxylin and eosin and trichrome stains, hydroxyproline/proline analysis, real time polymerase chain analysis, and immunohistological analyses with anti-type I collagen, anti-p-Akt, anti-CCN2, anti-phospho-Smad3 and anti-a-smooth muscle actin antibodies). Blood vessels were detected using anti-CD31 antibodies. Anti-NG2 antibodies were used to detect expansion of microvascular pericytes. <h3>Results</h3> Loss of PTEN expression resulted in lung fibrosis around the blood vessels. Loss of PTEN resulted in collagen and a-smooth muscle actin expression and deposition as visualized by immunohistochemical analysis (N=6, p&lt;0.05) and real time PCR analysis (N=3, p&lt;0.05), but not in PTEN/CCN2 double knockout animals. Smad3 and Akt phosphorylation were elevated in PTEN knockout mice; loss of CCN2 rescued elevated Smad3 but not Akt phosphorylation (N=6, p&lt;0.05). Double labeling analysis revealed that a-smooth muscle actin-postive cells were also NG2-positive, suggesting that these cells appeared to arise from a pericyte or pericyte-like population (N-6, p&lt;0.05). <h3>Conclusions</h3> Loss of PTEN in fibroblasts results in lung fibrosis, in a fashion dependent on CCN2. Thus mice deficient in PTEN may represent a novel model for certain features of scleroderma. These results moreover indicate that elevated adhesive signaling (due to loss of PTEN expression) is sufficient for fibrogenesis and that CCN2 may represent a common downstream mediator of fibrosis, possibly due to its ability to promote expansion of a pericyte or pericyte-like cell population. <h3>Disclosure of Interest</h3> None Declared
Morning Home Blood Pressure Is a Strong Predictor of Coronary Artery Disease
Authors: Kazuomi Kario, Ikuo Saito, Toshio Kushiro, Satoshi Teramukai, Yasuhiro Tomono, Yasuyuki Okuda, Kazuyuki Shimada
Journal: Journal of the American College of Cardiology (2016)

Few studies have evaluated out-of-office blood pressure (BP) measurements as predictors of coronary artery disease (CAD) events.The aim of this study was to determine morning home blood pressure (HBP) as a predictor of CAD events.Using data from the HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the relationship between morning HBP and incidence of stroke and CAD events.In 21,591 treated hypertensive patients (mean age 64.9 years; mean follow-up 2.02 years), 127 stroke events (2.92 per 1,000 patient-years), and 121 CAD events (2.78 per 1,000 patient-years) occurred. The incidence of stroke events was significantly higher in patients with morning home systolic blood pressure (HSBP) ≥145 mm Hg compared with <125 mm Hg, and in patients with clinic systolic blood pressure (CSBP) ≥150 mm Hg compared with <130 mm Hg. Hazard ratios (HRs) were 6.01 (95% confidence interval [CI]: 2.85 to 12.68) between patients with morning HSBP ≥155 mm Hg and those with morning HSBP <125 mm Hg and 5.82 (95% CI: 3.17 to 10.67) between patients with CSBP ≥160 mm Hg and those with CSBP <130 mm Hg; morning HSBP predicted stroke events similarly to CSBP. Incidence of CAD events was significantly higher in patients with morning HSBP ≥145 mm Hg compared with <125 mm Hg and in patients with CSBP ≥160 mm Hg compared with <130 mm Hg. The HR for morning HSBP ≥155 mm Hg was 6.24 (95% CI: 2.82 to 13.84) and for CSBP ≥160 mm Hg was 3.51 (95% CI: 1.71 to 7.20); therefore, compared with morning HSBP, CSBP may underestimate CAD risk. Goodness-of-fit analysis showed that morning HSBP predicted CAD events more strongly than CSBP.Morning HBP is a strong predictor of future CAD and stroke events, and may be superior to clinic BP in this regard. There does not appear to be a J-curve in the relationship between morning HBP and stroke or CAD events. (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure Study [HONEST]; UMIN000002567).
Is There a Role For PET/CT With Esophagogastric Junction Adenocarcinoma?
Authors: David Fuster, Maria Mayoral, Domenico Rubello, Estela Pineda, Gloria Fernández-Esparrach, Mario Pagès, Patrick M Colletti, Francesca Pons
Journal: Clinical Nuclear Medicine (2014)

The value of 18F-FDG PET/CT in the initial diagnosis and in the locoregional staging of esophagogastric junction adenocarcinoma is not fully established. However, 18F-FDG PET/CT is widely accepted as the best modality for identification of suspected metastases in staging of the disease. Results published in the literature suggest that 18F-FDG PET/CT may provide useful information for response assessment to neoadjuvancy and to differentiate responding and nonresponding tumors. We review the potential role of 18F-FDG PET/CT imaging in staging, restaging, and prognostic value after chemoradiation therapy in esophagogastric junction adenocarcinoma.
SP0203 Vertebral Fracture Assessment
Authors: C. Roux
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Vertebral fractures are the hallmark manifestation of osteoporosis, associated with back pain, increased morbidity and functional limitations. Prevalent vertebral fractures are associated with increased risk of hip fractures, and increased risk of mortality. Anti-osteoporotic treatments are effective in decreasing the risk of subsequent fractures in post-menopausal women with prevalent vertebral fractures. Thus, diagnosis of these fractures, even asymptomatic, is a key issue. Performing systematic X-ray is not feasible for radiation and costs concerns. Vertebral Fracture Assessment (VFA) is a new technology, through dual energy X-ray absorptiometry (DXA) devices. It delivers thus a low dose radiation and is considered now as a clinically useful alternative to standard spine X-rays. Cross sectional and prospective studies have shown good performance of VFA compared to X-rays for both prevalent and incident vertebral deformities. The main limitation of the technique is lack of visualisation of the upper thoracic spine (above T6) in some patients. VFA can be recommended when the results may influence clinical management, as concomitant glucocorticoid therapy. VFA is a reliable technique, which improves management of patients with primary or secondary osteoporosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6313
1205 PRELIMINARY EVALUATION OF A NEW AUTOPHAGY INHIBITOR ANTIVIRAL AGENT FOR HEPATITIS C VIRUS IN AN EX VIVO MODEL OF HUMAN LIVER SLICES CULTURE
Authors: S. Lagaye, H. Shen, J. Gaston, G. Rousseau, P.-P. Massault, A. Vallet-Pichard, P. Sogni, V. Mallet, J. Courcambeck, S. Brun, F. Bassisi, C. Camus, P. Halfon, S. Pol
Journal: Journal of Hepatology (2013)
Abstract 5234: Network interrogations on SNAIL inhibitor GN-25 induced perturbations in HMLE-SNAIL cell line models.
Authors: Asfar S. Azmi, Aliccia Bollig-Fisher, Bin Bao, Bum Joon-Park, SH Lee, Gyu-Yong Song, Ramzi M. Mohammad, Fazlul H. Sarkar
Journal: Cancer Research (2013)

Abstract HMLEs (HMLE-SNAIL and Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using pathway network analysis, we show that GN-25 induces the reversal of EMT to mesenchymal-to-epithelial transition (MET) in well recognized HMLE-SNAIL and Kras-HMLE-SNAIL models. GN-25 induced MET was found to be concurrent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. We performed systems and pathway network analysis on mRNA expression by microarrays from GN-25 treated Kras-HMLE-SNAIL cells that showed an orchestrated global re-organization of EMT network genes. The expression signatures were validated at the protein level using confocal microscopy, western blot analysis and time lapse videography, and we found down-regulation of mesenchymal markers such as TWIST1, TWIST2, ZEB-1 concurrently with up-regulation of epithelial marker E-Cadherin. Additionally, RNAi studies validated SNAIL dependent mechanism of action of the drug. Most importantly, GN-25 deregulated many major transcription factors (TFs) such as inhibition of oncogenic TFs Myc, TBX2, NR3C1 and enhancement in tumor suppressor TFs such as SMAD7, DD1T3, CEBPA, HOXA5, TFEB, IRF1, IRF7 and XBP1, resulting in MET as well as induction of cell death. Our systems and network investigations provide solid pre-clinical supportive evidence for clinical application of GN-25 for the reversal of EMT phenotype to MET in aggressive cancers. Citation Format: Asfar S. Azmi, Aliccia Bollig-Fisher, Bin Bao, Bum Joon-Park, SH Lee, Gyu-Yong Song, Ramzi M. Mohammad, Fazlul H. Sarkar. Network interrogations on SNAIL inhibitor GN-25 induced perturbations in HMLE-SNAIL cell line models. [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 5234. doi:10.1158/1538-7445.AM2013-5234
Evaluation of a Palpable Breast Mass
Authors: Jane F. Desforges, William L. Donegan
Journal: New England Journal of Medicine (1992)

CANCER of the breast is newly diagnosed in about 180,000 women per year in the United States.1 In the majority of these cases the cancer presents as a palpable mass, usually found by the patient. With intensive public education about breast cancer and the growing acceptance of routine self-examination of the breasts, particularly by young women, an increasing number of women can be expected to seek consultation for the evaluation of breast masses.A study by the Physician Insurers Association of America in 1990 found that failure to diagnose breast cancer was the second most frequent reason for claims brought . . .
Case 34-2010
Authors: David C. Ring, James H. Herndon, Gregg S. Meyer
Journal: New England Journal of Medicine (2010)

From the Departments of Orthopedics (D.C.R., J.H.H.) and Medicine (G.S.M.) and the Massachusetts General Physicians Organization (G.S.M.), Massachusetts General Hospital; and the Departments of Orthopaedic Surgery (D.C.R., J.H.H.) and Medicine (G.S.M.), Harvard Medical School — both in Boston.
Abstract 5597: Modulating therapeutic effects of c-Src inhibitor via estrogen receptor and HER2 in breast cancer cell lines
Authors: Ping Fan, Russell E. McDaniel, Helen R. Kim, V Craig Jordan
Journal: Cancer Research (2012)

Abstract Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are two successful therapeutic targets in breast cancer. c-Src functions as an important adapter protein with ER and HER2, which validates it as an attractive target for the treatment of breast cancer. However, a very recent phase II clinical trial shows that a c-Src inhibitor, dasatinib, had limited single-agent activity in patients with HER2+ and/or hormone receptor (HR)+ advanced breast cancer (Mayer E et al. Clin Cancer Res 2011, Epub ahead of print). Therefore, a specific c-Src inhibitor, PP2, was utilized to block c-Src activity to identify targeted vulnerabilities affected by ER and HER2 in a panel of breast cancer cell lines (i.e. MCF-7, T47D, ZR-75-1, BT474, MCF-7:5C, MCF-7:2A, MDA-MB-231, Sk-Br-3, MCF-7/F, and T47D:C42). The antiproliferative effect of PP2 correlated with blocking c-Src mediated ERK/MAPK and/or PI3K/Akt growth pathways. The signaling pathways of c-Src were modulated by ER and HER2 in breast cancer cells. Inhibition of c-Src tyrosine kinase predominantly blocked ER negative breast cancer cell growth, particularly the triple (i.e. ER, PR, and HER2) negative cells. In contrast, ER negative Sk-Br-3 cells with highest HER2 phosphorylation were resistant to PP2, in which over-activated HER2 directly regulated growth pathways but not through c-Src. However, blocking c-Src recovered ER expression which made Sk-Br-3 cells regain responses to 4-hydroxytamoxifen. The majority of ER positive breast cancer cells were not sensitive to PP2 regardless of wild-type or endocrine resistant cell lines. Overall, c-Src mediates the essential role of growth pathways in ER negative breast cancer cells without HER2 over-activation. ER expression and HER2 over-activation are two important predictive biomarkers for the resistance to a c-Src inhibitor. These data provided an important therapeutic rationale for patient selection in clinical trials with c-Src inhibitors in triple negative breast cancer. Acknowledgements This work (VCJ) is supported by the SU2C (AACR) Grant (SU2C-AACR-DT0409). 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 5597. doi:1538-7445.AM2012-5597
Early colon cancer presenting as intussusception and successfully treated using endoscopic submucosal dissection
Authors: Hideyuki Chiba, Akihiro Takahashi, Masahiko Inamori, Toru Goto, Ken Ohata, Nobuyuki Matsuhashi, Atsushi Nakajima
Journal: Endoscopy (2014)

Adult intussusception represents 5 % of all cases of intussusception, and accounts for 1 % of all cases of bowel obstruction [1]. Due to the significant risk of malignancy associated with this condition, with neoplasia found in approximately 65 % of cases [2], intussusception in adults is treated by surgery, and in most cases cancer is discovered intraoperatively [3]. Thus, in most cases adult intussusception requires treatment by definitive surgical resection [2]. We report the first case of adult intussusception caused by early sigmoid colorectal cancer, which was successfully resected endoscopically.
Do you see what I see? Towards standardized reporting of endoscopic findings in eosinophilic esophagitis
Authors: Evan Dellon
Journal: Endoscopy (2014)

The endoscopic findings in eosinophilic esophagitis are one of the hallmarks of the disease, a visible sign of an upper gastrointestinal process that has only been recognized over the past two decades [1]. The findings also contain important information. Features such as esophageal rings, linear furrows, decreased vascularity, or white plaques ([Fig. 1]) might prompt an endoscopist to obtain esophageal biopsies to assess for eosinophils if the diagnosis was unexpected, or might confirm a clinical suspicion or suggest that a prescribed therapy is not working. A diffusely narrowed esophagus or a focal esophageal stricture could indicate that the disease has been present and undiagnosed for many years [2] [3], leading to esophageal remodeling [4] and increasing the risk for food impactions [5]. However, these findings are in some way a conundrum. They are not a formal part of current diagnostic guidelines [1] [6], they are not pathognomonic for eosinophilic esophagitis [7], they may not uniformly respond to treatment [8], and reporting can be variable [7] [9] [10] [11].
AB0417 Frequency, Time Course and Outcomes of Infliximab-Induced Liver Injury in Rheumatic Diseases
Authors: F. Medina, D. Mulleman, N. El Gani, Y. Bacq, S. Mammou-Mraghni, P. Goupille, T. Bejan-Angoulvant
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Infliximab, a Tumour Necrosis Factor-alpha antagonist monoclonal antibody, is efficient in inflammatory diseases. Although some cases of liver injury have been reported, little information is available about liver injury in infliximab-treated patients. <h3>Objectives</h3> The aim of this study was to analyze the time course of ALT in a cohort of real-life infliximab-treated patients and to identify possible factors associated with ALT elevations. <h3>Methods</h3> We conducted a retrospective study in patients initiating infliximab between 2005 and 2012 in our department of rheumatology. Patients who presented during follow-up with alanine aminotransferase (ALT) &gt;75 UI/L and ≥100% increase from baseline value, defined as liver injury, were compared with the others. Those who presented with ALT &gt;150 UI/L and ≥100% of the baseline value were studied separately. <h3>Results</h3> One hundred and nighty six patients started infliximab during the study period. Liver injury occurred in 39 (20%), 85% during the first year of treatment. Eight patients (4%) discontinued infliximab due to liver injury, representing only 6.6% of all cause of treatment discontinuation. Demographics, disease activity, concomitant treatments and cardiovascular risk factors were not associated with occurrence of liver injury. An increase in ALT &gt;150 UI/L was observed in 8 patients, leading to discontinuation in four. A direct causality was probable in one case. <h3>Conclusions</h3> Liver injury occurred in one in five of infliximab-treated patients with inflammatory diseases in clinical practice but was rarely a cause for treatment discontinuation. <h3>Acknowledgements</h3> The authors thank Fadela Daoued and Alexis Lhommas for their cooperation for the collection of data. We are indebted to all the clinicians, Isabelle Griffoul, Virginie Martaillé, Emilie Ducourau, Chu Miow Lin, Francine Lauféron, Jean Camille-Méric, Guillaume Direz, Julien Melet, Florence Erny, for their help in collecting adverse events, to Françoise Gouais, Martine Creton, Marie-Françoise Coudray, Fabienne Chapacou, Dominique Guillon, Rodolphe Laurent, Patricia Pitault and Fabienne Georges for blood sampling and taking care for patients and to Alain Saraux and Jean-Marc Perrarnau for advice. <h3>Disclosure of Interest</h3> None declared
Marilyn Quayle Honors Cancer Information Service
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Marilyn Quayle Honors Cancer Information Service Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 24, 18 December 1991, Pages 1792–1793, https://doi.org/10.1093/jnci/83.24.1792 Published: 18 December 1991
Peripheral Entrapment Neuropathies of the Upper Extremity
Authors: W. A. L. Thompson, H. P. Kopell
Journal: New England Journal of Medicine (1959)

The concern with the cervical herniated disk and the popular whiplash injury as a source of pain in the upper extremity may exclude consideration of a more distal origin of such pain. It is the purpose of this presentation to demonstrate some of the syndromes that arise from more distal areas where nerves are subject to trauma because of some anatomic configuration. The nerve irritation at these anatomic locations, called entrapment points, may result in a neuropathy.The role of specific trauma in the origin of these neuropathies may not always be discerned. A single traumatic incident may set up . . .
Unusual cause of CA 19.9 elevation diagnosed by endoscopic ultrasound-guided fine needle aspiration: a retrorectal tailgut cyst
Authors: P. Pinto-Marques, J. Damião-Ferreira, E. Mendonça, A. Gaspar, M. Mafra, F. Mateus
Journal: Endoscopy (2012)

A 42-year-old woman underwent a magnetic resonance imaging (MRI) scan for CA 19.9 elevation, noted during a routine evaluation. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of a retrorectal cystic mass of unknown etiology was scheduled. A 5-cm multiseptated cystic lesion was noted ([Fig. 1]). Under antibiotic prophylaxis, FNA was performed (19-gauge needle; single pass); the aspirate was thick and yellowish. Cytological examination showed squamous epithelial cells but no atypia ([Fig. 2]). In-house MRI confirmed a multicystic lesion with a hyperintense signal on T1-weighted images ([Fig. 3]). The patient opted for a laparoscopic resection, which confirmed a tailgut cyst ([Fig. 4]), with later CA 19.9 normalization.