tbuckley/cabot-search huggingface dataset:
Nuclear Accumulation of Truncated Atrophin-1 Fragments in a Transgenic Mouse Model of DRPLA
Authors: Gabriele Schilling, Jonathan D. Wood, Kui Duan, Hilda H. Slunt, Vicky Gonzales, Mitsunori Yamada, Jillian K. Cooper, Russell L. Margolis, Nancy A. Jenkins, Neal G. Copeland, Hitoshi Takahashi, Shoji Tsuji, Donald L. Price, David R. Borchelt, Christopher A. Ross
Journal: Neuron (1999)

Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of a family of progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, and premature death. These mice accumulate atrophin-1 immunoreactivity and inclusion bodies in the nuclei of multiple populations of neurons. Subcellular fractionation revealed 120 kDa nuclear fragments of mutant atrophin-1, whose abundance increased with age and phenotypic severity. Brains of DRPLA patients contained apparently identical 120 kDa nuclear fragments. By contrast, mice overexpressing atrophin-1 with 26 glutamines were phenotypically normal and did not accumulate the 120 kDa fragments. We conclude that the evolution of neuropathology in DRPLA involves proteolytic processing of mutant atrophin-1 and nuclear accumulation of truncated fragments.
Expression of vascular endothelial growth factor-b in human astrocytoma
Authors: Jean Christophe Gollmer, Annie Ladoux, Jeanine Gioanni, Philippe Paquis, Alain Dubreuil, Marcel Chatel, Christian Frelin
Journal: Neuro-Oncology (2000)

Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed.
Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case–control study
Authors: Vidya Navaratnam, Andrew W Fogarty, Tricia McKeever, Norma Thompson, Gisli Jenkins, Simon R Johnson, Gerard Dolan, Maruti Kumaran, Kate Pointon, Richard B Hubbard
Journal: Thorax (2013)

<h3>Background</h3> Laboratory studies suggest that the clotting cascade is activated in fibrotic lungs. Since humans vary in their tendency to clot due to a variety of inherited or acquired defects, we investigated whether a prothrombotic state increases the chance of developing idiopathic pulmonary fibrosis (IPF) and/or worsens the prognosis of IPF. <h3>Methods</h3> We recruited 211 incident cases of IPF and 256 age- and sex-matched general population controls and collected data on medical history, medication, smoking habit, blood samples as well as lung function and high-resolution CT scans done as part of routine clinical care. A prothrombotic state was defined as the presence of at least one inherited or acquired clotting defect or marker of fibrinolytic dysfunction. We used logistic regression to quantify the association between a prothrombotic state and IPF adjusted for age, sex, smoking habit and highly sensitive C reactive protein. Cox regression was used to determine the influence of a prothrombotic state on survival. <h3>Results</h3> Cases were more than four times more likely than controls to have a prothrombotic state (OR 4.78, 95% CI 2.93 to 7.80; p&lt;0.0001). Cases with a prothrombotic state were also likely to have more severe disease (forced vital capacity &lt;70% predicted) at presentation (OR 10.79, 95% CI 2.43 to 47.91) and had a threefold increased risk of death (HR 3.26, 95% CI 1.09 to 9.75). <h3>Conclusions</h3> People with IPF are more likely to have a prothrombotic state than general population controls and the presence of a prothrombotic state has an adverse impact on survival.
IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome
Authors: Andrew J. Murphy, Michael J. Kraakman, Helene L. Kammoun, Dragana Dragoljevic, Man K.S. Lee, Kate E. Lawlor, John M. Wentworth, Ajithkumar Vasanthakumar, Motti Gerlic, Lachlan W. Whitehead, Ladina DiRago, Louise Cengia, Rachael M. Lane, Donald Metcalf, James E. Vince, Leonard C. Harrison, Axel Kallies, Benjamin T. Kile, Ben A. Croker, Mark A. Febbraio, Seth L. Masters
Journal: Cell Metabolism (2015)
<i>Mig-6</i> Suppresses Endometrial Cancer Associated with <i>Pten</i> Deficiency and ERK Activation
Authors: Tae Hoon Kim, Jung-Yoon Yoo, Hong Im Kim, Jenifer Gilbert, Bon Jeong Ku, Jane Li, Gordon B. Mills, Russell R. Broaddus, John P. Lydon, Jeong Mook Lim, Ho-Geun Yoon, Jae-Wook Jeong
Journal: Cancer Research (2014)

PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate estrogen receptor α-dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice, where Mig-6 was overexpressed in progesterone receptor-expressing cells, exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PR(cre/+)Pten(f/f) mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer.
Characterization of Lymphoma-Derived Cell Lines: Comparison of Cell Lines Positive and Negative for Epstein-Barr Virus Nuclear Antigen. II. Surface Markers
Authors: Ian T. Magrath, Charles B. Freeman, Philip Pizzo, James Gadek, Elaine Jaffe, Maria Santaella, Carl Hammer, Michael Frank, Gregory Reaman, Ligita Novikovs
Journal: JNCI Journal of the National Cancer Institute (1980)

Fifteen of 16 lymphoma-derived cell lines and the Raji and P3HR1 cell lines were characterized with regard to certain surface markers, particularly immunoglobulins, complement receptors, Epstein-Barr virus (EBV) receptors, and Fc receptors. Ten lines positive for EBV nuclear antigen (EB-pos) were stained weakly or not at all by antihuman immunoglobulin fluorescein isothiocyanate conjugates, whereas EBV nuclear antigen negative (EB-neg) cell lines stained brightly. EB-pos lines frequently manifested Fc receptors, particularly for 7S antibody, whereas EB-neg lines did not. Receptors for the C3b component of complement and for EBV, which correlated significantly with each other, were expressed to a much lesser extent by EB-neg lines than by EB-pos lines. These findings are pertinent to an understanding of the infrequent association of this virus with American undifferentiated lymphomas of the Burkitt's and non-Burkitt's types.
Fatal Rocky Mountain Spotted Fever in Maryland—1901
Authors: J. Stephen Dumler
Journal: JAMA (1991)

Rocky Mountain spotted fever (RMSF), an infection caused by<i>Rickettsia rickettsii</i>, is transmitted via tick bite during spring through fall. Rocky Mountain spotted fever is a misonmer because most cases occur in the southeastern and south central United States.<sup>1</sup>The diagnosis is based on clinical suspicion, although the classic triad of fever, headache, and rash exists in only 3% of cases at presentation.<sup>2</sup>A risk for significant morbidity or mortality can occur either from delayed diagnosis or from late or inappropriate therapy. Although known in some western states in the 1870s, RMSF was first described in the eastern United States in 1931.<sup>3,4</sup>This report demonstrates a case of RMSF in the eastern United States in 1901. A search of the autopsy files at The Johns Hopkins Hospital, Baltimore, Md, yielded a single diagnosis coded as typhus fever. Hospital records indicated that an adult male patient was admitted
Increased Prevalence of Coronary Artery Aneurysms Among Cocaine Users
Authors: Aaron Satran, Bradley A. Bart, Christopher R. Henry, M. Bilal Murad, Sumaiya Talukdar, Daniel Satran, Timothy D. Henry
Journal: Circulation (2005)

Background— Cocaine abuse has been implicated in multiple cardiovascular complications. Coronary artery aneurysms (CAAs) and ectasia occur in 0.2% to 5.3% of patients referred for angiography and are associated with atherosclerosis, Kawasaki’s disease, and several rare disorders. After observing CAAs in multiple young cocaine users, we investigated the prevalence of CAAs among cocaine users undergoing coronary angiography. Methods and Results— Clinical and angiographic characteristics of 112 consecutive patients with a history of cocaine use and coronary angiography were compared with a control group of similar age and risk factors from an existing angiographic database over the same time period. Coronary angiograms were independently read by 3 reviewers blinded to cocaine use. Cocaine users were young (mean age, 44 years), predominantly male (80%), and cigarette smokers (95%). Control patients had higher rates of diabetes (33%) and more severe coronary artery disease ( P =0.01). Previous myocardial infarction was common in both groups (45% of cocaine users, 38% of control patients). Despite the frequent history of myocardial infarction among cocaine users, 48% had nonobstructive coronary artery disease. Among cocaine users, 34 of 112 (30.4%) had CAAs compared with 6 of 79 (7.6%) in the control group ( P &lt;0.001). Cocaine use was a strong predictor of CAA by univariate and multivariate analyses. Conclusions— This is the first description of an association between cocaine use and CAA. The prevalence of CAA among cocaine users was higher than expected (30.4%), given such a young cohort. Cocaine use may predispose to the formation of CAA, which may in turn be a contributing factor to myocardial infarction.
A case of HGV-related epigastric pain
Authors: C. A. Wadsworth, P. Ziprin, M. X. Pelling, L. R. Jiao, M. R. Thursz
Journal: Gut (2010)

Fraud in medical publications is an increasing concern. In particular, disciplines related to perioperative medicine—including anaesthesia and critical care—currently hold the highest rankings in terms of retracted papers for research misconduct. The dominance of this dubious achievement is attributable to a limited number of researchers who have repeatedly committed scientific fraud. In the last three decades, six researchers have authored 421 of the 475 papers retracted in perioperative medicine. This narrative review reports on six cases of fabricated publication in perioperative medicine that resulted in the paper’s retraction. The process that led to the unveiling of the fraud, the impact on clinical practice, and changes in regulatory mechanisms of scientific companies and governmental agencies’ policies are also presented. Fraud in medical publications is a growing concern that affects perioperative medicine requiring a substantial number of papers to be retracted. The continuous control elicited by readers, by local institutional review boards, scientific journal reviewers, scientific societies and government agencies can play an important role in preserving the ‘pact of trust’ between authors, professionals and ultimately the relationship between doctors and patients.
Role of cytochrome P-450 in reperfusion injury of the rabbit lung.
Authors: G K Bysani, T P Kennedy, N Ky, N V Rao, C A Blaze, J R Hoidal
Journal: Journal of Clinical Investigation (1990)

Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.
Tolerability, Pharmacodynamics, and Pharmacokinetics Studies of Depsipeptide (Romidepsin) in Patients with Acute Myelogenous Leukemia or Advanced Myelodysplastic Syndromes
Authors: Virginia M. Klimek, Sophia Fircanis, Peter Maslak, Ilhem Guernah, Michael Baum, Nian Wu, Katherine Panageas, John J. Wright, Pier Paolo Pandolfi, Stephen D. Nimer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Epigenetic modulation of gene expression plays an important role in cancer, including leukemia. Furthermore, histone deacetylase inhibitors may induce the reexpression or repression of genes critical for normal hematopoiesis. The purpose of this study was to evaluate the toxicity, pharmacokinetic profile, and selected pharmacodynamic properties of the histone deacetylase inhibitor depsipeptide in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML). Experimental Design: Depsipeptide was administered to MDS or AML patients at a (solid tumor) phase I dose of 18 mg/m2 i.v. on days 1 and 5 every 3 weeks. Toxicities and clinical activity were monitored and pharmacokinetic and pharmacodynamic studies were done. Results: Twelve patients (nine with AML, three with MDS) received one to five cycles of depsipeptide. The most common grade 3/4 toxicities were febrile neutropenia/infection (five patients), neutropenia/thrombocytopenia (nine patients), nausea (nine patients), and asymptomatic hypophosphatemia (three patients). No clinically significant cardiac toxicity was observed. The best response of 11 assessed patients was one complete remission in a patient with AML, stable disease in six patients, and progression of disease in four patients. Exploratory laboratory studies showed modest but rapid increases in apoptosis and changes in myeloid maturation marker expression. Histone H3 and H4 acetylation levels were evaluated in five patients; no consistent changes were observed. Conclusion: Depsipeptide therapy can be administered with acceptable short-term toxicity. However, gastrointestinal symptoms and fatigue seem to be treatment-limiting after multiple cycles. Depsipeptide monotherapy has limited clinical activity in unselected AML/MDS patients.
Capecitabine and Radiotherapy as Preoperative Treatment in Patients with Stage Ii-Iii Rectal Cancer
Authors: Julia Ruiz-Vozmediano, Encarnación González-Flores, Verónica Conde-Herrero, Beatriz González-Astorga, Aranzazu González-Vicente, Javier García-García, Isabel Linares, Juan Ramón lgado De Pérez, Lucia Castillo-Portellano, Cynthia González-Rivas
Journal: Annals of Oncology (2013)
Mobile phone use and glioma risk: comparison of epidemiological study results with incidence trends in the United States
Authors: M. P. Little, P. Rajaraman, R. E. Curtis, S. S. Devesa, P. D. Inskip, D. P. Check, M. S. Linet
Journal: BMJ (2012)

<b>Objective</b> In view of mobile phone exposure being classified as a possible human carcinogen by the International Agency for Research on Cancer (IARC), we determined the compatibility of two recent reports of glioma risk (forming the basis of the IARC's classification) with observed incidence trends in the United States. <b>Design</b> Comparison of observed rates with projected rates of glioma incidence for 1997-2008. We estimated projected rates by combining relative risks reported in the 2010 Interphone study and a 2011 Swedish study by Hardell and colleagues with rates adjusted for age, registry, and sex; data for mobile phone use; and various latency periods. <b>Setting</b> US population based data for glioma incidence in 1992-2008, from 12 registries in the Surveillance, Epidemiology, and End Results (SEER) programme (Atlanta, Detroit, Los Angeles, San Francisco, San Jose-Monterey, Seattle, rural Georgia, Connecticut, Hawaii, Iowa, New Mexico, and Utah). <b>Participants</b> Data for 24 813 non-Hispanic white people diagnosed with glioma at age 18 years or older. <b>Results</b> Age specific incidence rates of glioma remained generally constant in 1992-2008 (−0.02% change per year, 95% confidence interval −0.28% to 0.25%), a period coinciding with a substantial increase in mobile phone use from close to 0% to almost 100% of the US population. If phone use was associated with glioma risk, we expected glioma incidence rates to be higher than those observed, even with a latency period of 10 years and low relative risks (1.5). Based on relative risks of glioma by tumour latency and cumulative hours of phone use in the Swedish study, predicted rates should have been at least 40% higher than observed rates in 2008. However, predicted glioma rates based on the small proportion of highly exposed people in the Interphone study could be consistent with the observed data. Results remained valid if we used either non-regular users or low users of mobile phones as the baseline category, and if we constrained relative risks to be more than 1. <b>Conclusions</b> Raised risks of glioma with mobile phone use, as reported by one (Swedish) study forming the basis of the IARC's re-evaluation of mobile phone exposure, are not consistent with observed incidence trends in US population data, although the US data could be consistent with the modest excess risks in the Interphone study.
Acral lentiginous melanoma: Who benefits from sentinel lymph node biopsy?
Authors: Takamichi Ito, Maiko Wada, Konosuke Nagae, Misa Nakano-Nakamura, Takeshi Nakahara, Akihito Hagihara, Masutaka Furue, Hiroshi Uchi
Journal: Journal of the American Academy of Dermatology (2014)
UK government is likely to give more prominence to scientific advice before emergencies occur
Authors: A. O'Dowd
Journal: BMJ (2011)

The government is reviewing its system so that scientific advice plays more of a part in the planning process before emergency situations arise, such as the flu pandemic of 2009.

In a supplementary response to the parliamentary science and technology select committee report on scientific advice and evidence in emergencies published in March, the government says a review is underway.

MPs on the science and technology committee said in their earlier report that, although science was used effectively to aid the response to emergencies, they were concerned the government’s attitude to scientific advice was that it was “something to reach for once an emergency happens” rather than a key factor for consideration from the start of the …
PSORIASIS EARLY IMPAIRS CORONARY FLOW RESERVE: NEW INSIGHTS INTO INFLAMMATION AND CORONARY MICROVASCULAR DYSFUNCTION
Authors: Elena Osto, Stefano Piaserico, Anna Maddalozzo, Giulia Forchetti, Roberta Montisci, Andrea Peserico, Sabino Iliceto, Francesco Tona
Journal: Journal of the American College of Cardiology (2010)
Pemphigus-like syndrome induced by D-penicillamine
Authors: S.G. Tan, N.R. Rowell
Journal: British Journal of Dermatology (1976)

Journal Article Pemphigus‐like syndrome induced by D‐penicillamine Get access S.G. Tan, S.G. Tan Department of Dermatology, General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar N.R. Rowell N.R. Rowell Department of Dermatology, General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue 1, 1 July 1976, Pages 99–101, https://doi.org/10.1111/j.1365-2133.1976.tb15539.x Published: 01 July 1976
Application of Radiotherapeutic Strategies in the BCLC-defined Stages of Hepatocellular Carcinoma
Authors: Jihye Cha, Jinsil Seong
Journal: Liver Cancer (2012)

The Barcelona Clinic Liver Cancer (BCLC) staging system is the method currently used to stage hepatocellular carcinoma (HCC) and therefore plays an important role in deciding on an appropriate course of treatment. BCLC takes into consideration the extent of the disease as well as patient factors such as hepatic function and performance status. However, it does not propose solutions for all clinical situations. Although radiotherapy (RT) is not included in the BCLC guidelines, the potent local antitumor effect of RT should be considered seriously as a part of the treatment strategy. Novel RT technologies introduced during the last decade have made it possible to deliver higher doses of radiation to the tumor while avoiding damage to critical normal tissues adjacent to the tumor. Because of the growing interest in using RT for HCC patients unfit for or progressed beyond standard treatments, the role of RT for HCC patients needs to be specified within the BCLC staging system. Curative RT can be used for patients with either very early or early stage BCLC; focal high dose RTs, such as stereotactic body RT, are especially useful. Intermediate or advanced stage disease confined to the liver can be managed safely and effectively by localized RT in conjunction with other treatment modalities such as transarterial chemoembolization or concurrent or adjuvant chemotherapy. In this review, the efficacy of RT in each BCLC stage of HCC will be discussed.