tbuckley/cabot-search huggingface dataset:
Neuroprotection by Hsp104 and Hsp27 in Lentiviral-based Rat Models of Huntington's Disease
Authors: Valérie Perrin, Etienne Régulier, Toufik Abbas-Terki, Raymonde Hassig, Emmanuel Brouillet, Patrick Aebischer, Ruth Luthi-Carter, Nicole Déglon
Journal: Molecular Therapy (2007)

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of glutamine repeats in the huntingtin (htt) protein. Abnormal protein folding and the accumulation of mutated htt are hallmarks of HD neuropathology. Heat-shock proteins (hsps), which refold denatured proteins, might therefore mitigate HD. We show here that hsp104 and hsp27 rescue striatal dysfunction in primary neuronal cultures and HD rat models based on lentiviral-mediated overexpression of a mutated htt fragment. In primary rat striatal cultures, production of hsp104 or hsp27 with htt171-82Q restored neuronal nuclei (NeuN)–positive cell density to that measured after infection with vector expressing the wild-type htt fragment (htt171-19Q). In vivo, both chaperones significantly reduced mutated-htt-related loss of DARPP-32 expression. Furthermore, hsps affected the distribution and size of htt inclusions, with the density of neuritic aggregates being remarkably increased in striatal neurons overexpressing hsps. We also found that htt171-82Q induced the up-regulation of endogenous hsp70 that was co-localized with htt inclusions, and that the overexpression of hsp104 and hsp27 modified the subcellular localization of hsp70 that became cytoplasmic. Finally, hsp104 induced the production of endogenous hsp27. These data demonstrate the protective effects of chaperones in mammalian models of HD. Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of glutamine repeats in the huntingtin (htt) protein. Abnormal protein folding and the accumulation of mutated htt are hallmarks of HD neuropathology. Heat-shock proteins (hsps), which refold denatured proteins, might therefore mitigate HD. We show here that hsp104 and hsp27 rescue striatal dysfunction in primary neuronal cultures and HD rat models based on lentiviral-mediated overexpression of a mutated htt fragment. In primary rat striatal cultures, production of hsp104 or hsp27 with htt171-82Q restored neuronal nuclei (NeuN)–positive cell density to that measured after infection with vector expressing the wild-type htt fragment (htt171-19Q). In vivo, both chaperones significantly reduced mutated-htt-related loss of DARPP-32 expression. Furthermore, hsps affected the distribution and size of htt inclusions, with the density of neuritic aggregates being remarkably increased in striatal neurons overexpressing hsps. We also found that htt171-82Q induced the up-regulation of endogenous hsp70 that was co-localized with htt inclusions, and that the overexpression of hsp104 and hsp27 modified the subcellular localization of hsp70 that became cytoplasmic. Finally, hsp104 induced the production of endogenous hsp27. These data demonstrate the protective effects of chaperones in mammalian models of HD.
BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis
Authors: Hidetaka Ohnuki, Hirofumi Inoue, Nobuaki Takemori, Hironao Nakayama, Tomohisa Sakaue, Shinji Fukuda, Daisuke Miwa, Eiji Nishiwaki, Masahiko Hatano, Takeshi Tokuhisa, Yaeta Endo, Masato Nose, Shigeki Higashiyama
Journal: Blood (2012)
ESSENTIAL CHARACTERISTICS OF A MALIGNANT CELL
Authors: ALEXIS CARREL
Journal: JAMA (1925)

The best method of ascertaining the properties that characterize a malignant tissue would be to transform in vitro a strain of cells of a known type into cells capable of producing sarcoma or carcinoma, and to study the changes undergone by the strain. The comparison of the normal and the malignant strains would show what characteristics are specific of the state of malignancy. As we possess pure cultures of normal cells of several types, and as the contaminating agent of Rous sarcoma renders feasible the transformation in vivo of a normal cell into a malignant one, an attempt could be made to change in vitro normal cells into sarcoma cells. The first experiments consisted in determining the nature of the cells that are susceptible to the agent of Rous sarcoma. It was obvious that the strain selected for the attempt at contamination must be of the same type as the
Primary pulmonary extranodal natural killer/T-cell lymphoma: nasal type with multiple nodules
Authors: Kengo Oshima, Yoshinori Tanino, Suguru Sato, Yayoi Inokoshi, Junpei Saito, Takashi Ishida, Takeaki Fukuda, Kazuo Watanabe, Mitsuru Munakata
Journal: European Respiratory Journal (2012)

To the Editors:

Primary pulmonary lymphoma (PPL) is an uncommon disease representing only 3–4% of extranodal non-Hodgkin’s lymphoma (NHL), and <1% of NHL [1]. The true incidence of PPL other than NHL is unknown, while primary pulmonary T-cell lymphoma is extremely rare. Natural killer (NK)/T-cell lymphoma usually shows an extranodal presentation. Nasal NK/T-cell lymphomas occur in the nose and the upper aerodigestive tract. Extranasal NK/T-cell lymphomas represent the counterpart of nasal NK/T-cell lymphomas and can involve every other part of the body. Primary sites of involvement are mainly the skin, soft tissue, gastrointestinal tract and testis [2]. Although some cases of primary pulmonary T-cell lymphoma have been reported, there are only two reports written in English to date [3, 4]. Here, we describe a case of primary pulmonary NK/T-cell lymphoma with multiple nodules in both lung fields.

The patient was a 50-yr-old Japanese male with an abnormal shadow on chest radiography in a health examination (fig. 1a). He was an office worker with no history of dust inhalation or asbestos exposure and was a current smoker (50 pack-yrs). He had a history of hypertension and gallstones. He had a high fever of over 39°C for 10 days before the health examination, and had appetite loss and general fatigue. A chest computed tomography (CT) on admission revealed multiple nodules, measuring a maximum of 40 mm in size, were in both lung fields (fig. 1b–d). Administration of broad-spectrum antibiotics did not resolve his symptoms. Bronchoscopic examination and CT-guided needle biopsy did not give a definite diagnosis. Laboratory data showed elevation of lactate dehydrogenase, transaminases, hepatobiliary enzymes and an inflammatory reaction without cytopenia. Two sets of blood …
Synthesis of aberrant decay-accelerating factor proteins by affected paroxysmal nocturnal hemoglobinuria leukocytes.
Authors: D J Carothers, S V Hazra, S W Andreson, M E Medof
Journal: Journal of Clinical Investigation (1990)

Paroxysmal nocturnal hemoglobinuria (PNH) leukocytes fail to express decay-accelerating factor (DAF) but contain DAF mRNA transcripts resembling those in normal cells. To further investigate the nature of the DAF defect in affected cells, patients' polymorphonuclear and mononuclear leukocytes (PMN and MNC) were biosynthetically labeled and newly synthesized DAF proteins examined. Analyses of greater than 98% surface DAF-negative PMN and MNC from a patient with PNH III erythrocytes showed precursor DAF protein approximately 3 kD smaller in each cell type than in normal cells. The proportion of precursor to mature (O-glycosylated) DAF protein was increased and soluble DAF protein was detected in the medium. Studies of 70-80% surface DAF-negative PMN and MNC from four patients with type II erythrocytes showed mixtures of the 3 kD smaller and normal DAF precursors. Partitioning with Triton X-114 detergent and biosynthetic labeling with the anchor precursor [3H]ethanolamine indicated that the abnormal peptides lacked glycosyl-inositolphospholipid membrane-anchoring structures. Thus, in PNH cells nascent DAF polypeptides are synthesized. Some of the abnormal pro-DAF molecules are processed in the Golgi and some are released extracellularly.
Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic Implications and Regulation by Vascular Endothelial Growth Factors-A, -C, and -D
Authors: Yasuyoshi Miyata, Shigeru Kanda, Kojiro Ohba, Koichiro Nomata, Yasushi Hayashida, Jiro Eguchi, Tomayoshi Hayashi, Hiroshi Kanetake
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF)-A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A, VEGF-C, and VEGF-D in human bladder cancer. Experimental Design: We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models. Results: LVD was associated with tumor grade but not with pT stage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD, VEGF-D was associated only with LVD. VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor. Conclusions: Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.
Cromolyn Sodium Trial in Perennial Asthmatics.
Authors: David A. Mathison
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Cromolyn Sodium Trial in Perennial Asthmatics.David A. Mathison, M.D., John J. Condemi, M.D., F.A.C.P., Frank W. Lovejoy Jr., M.D., John H. Vaughan, M.D., F.A.C.P.David A. Mathison, M.D.Search for more papers by this author, John J. Condemi, M.D., F.A.C.P.Search for more papers by this author, Frank W. Lovejoy Jr., M.D.Search for more papers by this author, John H. Vaughan, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-810_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCromolyn sodium (disodium cromoglycate), an inhibitor of antigen-antibody-induced mediator release, has been shown to prevent acute asthma in allergic subjects when inhaled prior to challenge with inhalant allergens. It has been available for general physician use in Great Britain since 1968 and is undergoing clinical trials in several U. S. centers.Cromolyn sodium has been administered (20 mg powder inhalation, four or more times daily) in open trial to 29 adults with perennial asthma who had been corticoid-dependent and who completed a 14-week double blind, double crossover trial comparing cromolyn sodium and placebo. Patients kept daily record of symptoms and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: David A. Mathison, M.D.; John J. Condemi, M.D., F.A.C.P.; Frank W. LovejoyJr., M.D.; John H. Vaughan, M.D., F.A.C.P.Affiliations: Rochester, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5 Page: 810-811 Keywords Allergens Antigens Asthma Clinical trials Inhalation Sodium ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Transplacental transfer of environmental genotoxins--polycyclic aromatic hydrocarbon-albumin in nonsmoking women.
Authors: H Autrup, A B Vestergaard
Journal: Environmental Health Perspectives (1996)

Transplacental transfer of genotoxic material has been determined by measuring the polycyclic aromatic hydrocarbon-albumin adduct level in serum isolated from the mother and the umbilical cord blood using a competitive enzyme-linked immunoadsorbent assay (ELISA) and the antibody (8E11( against benzo[a]pyrene (B[a]P) tetrols. Smoking women (median = 5.54 fmol B[a]P eq/micrograms albumin; n = 21 cases) and nonsmoking women living in rural areas (median = 4.99; n = 30) had higher adduct levels than nonsmoking women living in suburbia (median = 4.09; n = 37), whereas nonsmoking women living in the city of Aarhus had an intermediate level (median = 4.82; n = 40). The median adduct level in umbilical cord blood was significantly lower than in maternal blood, the maternal/fetal ratio being approximately 1.3. A positive association between the adduct levels in the mother and umbilical cord blood was observed. This study indicates that the competitive ELISA to detect B[a]P bound to serum albumin is sensitive enough to detect differences in the burden of genotoxic compounds in nonoccupationally exposed individuals. The lower adduct level in people living in suburbia suggests that local production of incomplete combustion products, like vehicle exhaust or heat generation, is a contributing factor to genotoxic compounds in the general environment.
MAPHY and the Two Arms of HAPPHY
Authors: Ingar Holme
Journal: JAMA (1989)

<h3>To the Editor.—</h3> <i>JAMA</i>recently published comments on the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) Study, together with a response from the authors.<sup>1</sup>I have some additional remarks. Although the Heart Attack Primary Prevention in Hypertension (HAPPHY) and MAPHY trials are judged as different by the Steering Committee of the HAPPHY trial, the MAPHY trial cannot be interpreted independently of the HAPPHY trial findings because all patients in the MAPHY Study are in the HAPPHY trial. Therefore, the meta-analysis presented by Staessen et al cannot be used for comparison of the MAPHY Study with previous trials.<sup>1</sup>The only valid way the comparison could be done would be to make a meta-analysis of the Medical Research Council trial and the International Prospective Primary Prevention Study in Hypertension and the atenolol part of the HAPPHY trial. The Steering Committee of the HAPPHY trial, therefore, should publish the results in the
Tumor-Initiating Cells in Childhood Neuroblastoma—Response
Authors: Loen M. Hansford, David R. Kaplan
Journal: Cancer Research (2012)

We agree that the lines in question were contaminated by Epstein Barr Virus (EBV) and immediately withdrawn from circulation. In contrast to the note of caution expressed by Pahlman about using these 3 neuroblastoma tumor-initiating lines (NB12, NB88R2, and NB122R), we have recommended to the
Hospital episode statistics <i>v</i> central cardiac audit database
Authors: Paul Aylin, Alex Bottle, Paul Elliott, Brian Jarman
Journal: BMJ (2007)

We published the follow-up of the Bristol Royal Infirmary analysis to which Westaby et al refer1 2 and have some comments on their paper.

The online version suggests that the clinical teams did not verify the data. We wrote to the clinical team at Oxford over a year before our paper was published. After some months and a reminder letter sent to them, we received a response from the medical director of the trust …
Combination of BAY 60-4552 and Vardenafil Exerts Proerectile Facilitator Effects in Rats With Cavernous Nerve Injury: A Proof of Concept Study for the Treatment of Phosphodiesterase Type 5 Inhibitor Failure
Authors: Alexandra Oudot, Delphine Behr-Roussel, Sarah Poirier, Peter Sandner, Jacques Bernabé, Laurent Alexandre, François Giuliano
Journal: European Urology (2011)
LOWER EXTREMITY PERIPHERAL ARTERY DISEASE IS ASSOCIATED WITH GREATER LONG-TERM MORTALITY RISK THAN HISTORY OF CORONARY ARTERY DISEASE: A NATIONWIDE STUDY
Authors: Emil L. Fosbol, Sumeet Subherwal, Manesh Patel, Lars Kober, Eric Peterson, William Jones, Gunnar Gislason, Christian Torp-Pedersen
Journal: Journal of the American College of Cardiology (2012)
Assessment and Treatment of Dementia in Medical Patients
Authors: Julia M. Foy, John M. Starr
Journal: Psychotherapy and Psychosomatics (2000)

The incidence of dementia rises rapidly with age. Elderly people commonly have significant medical conditions that impact on cognition and functional ability. The diagnosis of dementia requires both a decline in cognition and loss of functional ability. Assessment of dementia in medical patients requires a holistic approach that encompasses the spectrum of disease from measuring impairment of specific mental abilities to evaluating handicap in the patient’s normal social setting. Similarly, treatment can be aimed at any point in this spectrum. Recent licensing of new cholinesterase inhibitors for the treatment of Alzheimer’s disease has introduced specific problems in the treatment of medical patients with dementia. This review provides a framework for clinicians to assess and treat dementia in medical patients and describes a practical approach to the prescribing of cholinesterase inhibitors in patients with concomitant medical conditions.
IVUS PREDICTORS FOR DRUG ELUTING BALLOON FAILURE IN THE TREATMENT OF IN–STENT RESTENOSIS
Authors: Sung Yun Lee, Sang–Wook Kim, Jin Bae Lee, Eun–Seok Shin, Joon Hyung Doh, Hyunmin Choi, Young Joon Hong
Journal: Journal of the American College of Cardiology (2013)
Hepatitis B virus vaccines: Some cryptic issues
Authors: Subhash C. Arya
Journal: Hepatology (1998)

Some Cryptic IssuesTo the Editor: Hepatitis B virus (HBV) is an infection with highest prevalences in Asia and sub-Saharan regions of the world where temperatures may vary widely, and where cold storage is not readily available.These are also regions where universal vaccination against HBV infection is essential to break the long-standing cycle of mother-to-infant transmission of this virus.HBV vaccine is a heat-labile product that must be stored between 2°C to 8°C in single-or multidose vials.Any potential deterioration in its potency during exposure to adverse conditions has been tested by prolonged exposure to high temperatures.The recombinant yeast-derived HBV vaccine, Engerix-B, was exposed to temperatures of 45°C for 1 week or to temperatures of 37°C for 1 month.One hundred thirty-eight volunteers were immunized with these exposed lots, and high rates of protective immunity achieved, without adverse reactions, 1 indicated that the immunogenicity of the vaccine would be preserved even in suboptimal environmental conditions.Such reports of the stability of HBV vaccine in potentially adverse environments are misleading.They underestimate the ground realities of environmental hazards that are encountered in the field.Moreover, assessment of adequate immunogenicity may be inaccurate, because vaccine failures are often not apparent until many years after immunization.HBV infection in infants and preschool-aged children are typically subclinical without clinical manifestations of an episode of acute viral hepatitis. 2Thus, vaccine failures would not be evident either at the time of initial vaccination or even at the completion of several vaccine doses.Many decades would need to elapse before inadvertent failure would become clinically apparent with symptoms of chronic hepatitis, cirrhosis, or primary hepatocellular carcinoma.Quantification of the potency lots of HBV vaccine is a complex procedure.Unlike live measles or poliomyelitis vaccines that are quantified by inoculations of cell cultures in vitro, validation of HBV vaccine lots requires inoculation in human volunteers or experimental animals in vivo.The lack of an in vitro assay greatly limits our ability to measure the potency of a large number of HBV vaccine lots that have been exposed to ''field conditions.''Frequent assessment of potency will not be practical until simple in vitro assays are routinely available.To optimize immunogenicity, vaccine manufacturers should be aware of variations in temperature, humidity, air velocity,
Report of B.M.A. Film Committee
Authors: P. Hansell
Journal: BMJ (1947)

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that modulate physiological and pathological processes by post-transcriptional inhibition of gene expression. They were first recognised as regulators of development in worms and fruitflies. In recent years extensive research has explored their pivotal role in the pathogenesis of human diseases. Over 1,000 human miRNAs have been discovered to date; however, the biological function and protein targets for the majority remain to be uncovered. Within the respiratory system, miRNAs are important in normal pulmonary development and maintaining lung homeostasis. Recent studies have also begun to reveal that altered miRNA expression profiles may be associated with pathological processes within the lung and lead to the development of various pulmonary diseases, ranging from inflammatory diseases to lung cancers. Advancing our understanding of the role of miRNAs in the respiratory system will help provide new perspectives on disease mechanisms and reveal intriguing therapeutic targets and diagnostic markers for respiratory disorders.
Dr. Jacobi's Address and "Sectionalism."
Authors: A. Jacobi
Journal: JAMA (1900)

New York City, Sept. 10, 1900. <h3>To the Editor:</h3> —As a reply to the criticisms on some remarks delivered by me before the Thirteenth International Medical Congress, August 6, permit me to say to Dr. J. Wilkinson Jervey<sup>1</sup>that nothing is further from me than to harbor or try to create any sectional feelings. I deplore to have given him any such impression. The Doctor says himself that, "It is not the actual expression to which the Doctor gave tongue that is objectionable, but the inferential and insinuating quality of his remarks addressed to those good people across the water who know us not, save as existing, and who quite naturally accept the imputations and inferences." In this fear, Mr. Editor, I am happy to say, the Doctor is mistaken, and I feel sure he will be pleased to learn, in spite of his objections to some—shall I say