tbuckley/cabot-search huggingface dataset:
Abstract SY07-03: Gain-of-function activities of mutant p53
Authors: Guillermina Lozano
Journal: Cancer Research (2014)

Abstract Mutations in p53 in tumors vary from deletions and nonsense mutations that lead to the absence of p53 protein to missense mutations that disrupt the DNA binding function of p53 and that exhibit gain-of-function phenotypes. The p53R172H protein manifests one of its gain-of-function activities as a metastatic phenotype in vivo. To understand the contribution of mutant p53 to metastasis, expression arrays were used to compare primary osteosarcomas from p53R172H/+ mice with metastasis to osteosarcomas from p53+/- mice lacking metastasis. Of 213 gene differences, Pla2g16 was overexpressed in metastatic osteosarcomas and was of particular interest as it encodes a phospholipase that catalyzes phosphatidic acid into lysophosphatidic acid and free fatty acid (both implicated in metastasis). Functional analyses showed that Pla2g16 knockdown decreased migration and invasion in mutant p53 expressing cells, and vice versa, overexpression of Pla2g16 increased the invasion of p53-null cells. Mechanistically, various mutant p53 proteins bind the Pla2g16 promoter at ETS binding motifs and knockdown of ETS2 in particular suppressed mutant p53 induction of Pla2g16. Thus, our study identifies a phospholipase as a transcriptional target of mutant p53 that contributes to metastasis. Citation Format: Guillermina Lozano. Gain-of-function activities of mutant p53. [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 SY07-03. doi:10.1158/1538-7445.AM2014-SY07-03
Biochemical effects and zonal heterogeneity of peroxisome proliferation induced by perfluorocarboxylic acids in rat liver
Authors: Wilhelm W. Just, Karin Gorgas, Franz-Ulrich Hartl, Petra Heinemann, Manfred Salzer, Hans Schimassek
Journal: Hepatology (1989)

Rats were treated for 5 to 14 days with perfluoroacetate, perfluorobutyrate and perfluorooctanoate. Alterations in hepatic morphology with special reference to the peroxisomal compartment were investigated by light and electron microscopy following cytochemical staining of catalase activity with the alkaline 3,3'-diaminobenzidine medium. All three compounds induced hepatomegaly and peroxisome proliferation. Perfluorobutyrate and perfluorooctanoate were found to be more active than perfluoroacetate. Perfluorooctanoate-induced peroxisome proliferation was more prevalent in centrilobular than in periportal hepatocytes. Peroxisomes in centrilobular liver cells frequently were of round shape, exhibited diameters of up to 1.5 microns and were predominantly located within smooth endoplasmic reticulum-glycogen areas. In periportal cells, however, clusters of polymorphous peroxisomes ranging from 250 to 1,100 nm in diameter were observed at the periphery of smooth endoplasmic reticulum-glycogen regions. Peroxisome proliferation was accompanied by a change of peroxisomal and mitochondrial enzyme activities, in particular an increase in peroxisomal palmitoyl-CoA oxidation. Significant alterations in the concentration of peroxisomal matrix and membrane polypeptides were also noted. Within the first 2 days, perfluorooctanoate treatment exerted a strong hypolipidemic activity and both compounds perfluorooctanoate and perfluorobutyrate raised the level of hepatic free acid-soluble CoA nearly 10-fold as compared with control livers. The results suggest perfluorinated carboxylic acids to be model substances suitable to correlate biochemical and morphological parameters with the zonal heterogeneity of the peroxisomal compartment in rat liver. Due to the manifold hepatic effects, contact of humans with perfluorinated carboxylic acids or their metabolic precursors may represent a severe health risk.
Neonatal bronchopulmonary dysplasia predicts abnormal pulmonary HRCT scans in long-term survivors of extreme preterm birth
Authors: S M Aukland, K Rosendahl, C M Owens, K R Fosse, G E Eide, T Halvorsen
Journal: Thorax (2009)

There is an increasing understanding that extreme preterm birth carries a risk of long-term pulmonary sequelae. A study was undertaken to investigate if, and in what way, neonatal factors were associated with subsequent abnormalities on pulmonary high-resolution CT (HRCT) scanning and if pulmonary function was related to these abnormalities.HRCT scanning and pulmonary function tests were performed less than 2 weeks apart in 74/86 eligible subjects (86%) born at a gestational age of < or =28 weeks or with a birth weight of < or =1000 g within a defined area in Western Norway in 1982-5 (n = 42) or 1991-2 (n = 32). Mean age at examination was 18 and 10 years, respectively. HRCT scans were interpreted by a paediatric radiologist blinded to the clinical data using a structured system allowing scores from 0 to 50.Lung parenchymal abnormalities were found in 64 subjects (86%), the median (interquartile range) score being 3.0 (1.75-5.0) points. Prolonged neonatal requirement for oxygen treatment predicted poor outcome, and an increase of 100 days increased the average HRCT score by 3.8 points (p<0.001). There was also a positive association of the severity of pulmonary function abnormalities with the extent of HRCT abnormalities, exemplified by the relation between forced expiratory volume in 1 s and total HRCT score (beta = -0.090; p<0.001).In area-based cohorts of long-term survivors of extremely preterm birth, prolonged neonatal requirements for oxygen treatment predicted subsequent structural abnormalities on HRCT scans and in pulmonary function, and these two outcome measures were interrelated.
S4-7: Results of a Randomized, Double-Blind, Multicenter, Placebo-Controlled Study of Adjuvant Lapatinib in Women with Early-Stage ErbB2-Overexpressing Breast Cancer.
Authors: P Goss, I Smith, J O'Shaugnessy, B Ejlertsen, M Kaufmann, F Boyle, A Buzdar, P Fumoleau, W Gradishar, M Martin, B Moy, M Piccart-Gebhart, K Pritchard, G Aktan, E Rappold, L Williams, D Finkelstein
Journal: Cancer Research (2011)

Abstract Late-breaking — abstract will be available at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-7.
Patient Simulating Chest Pain
Authors: EDWIN B. KNIGHTS
Journal: Annals of Internal Medicine (1976)

Comments and Corrections1 February 1976Patient Simulating Chest PainEDWIN B. KNIGHTS, M.D.EDWIN B. KNIGHTS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-2-225_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Devereux and Miller (Ann Intern Med 80:283-284, 1974) reported the case of a young nurse who simulated pulmonary embolism. We have recently seen a patient who is probably the same person.A 27-year-old licensed practical nurse was admitted to the Osler service in September, complaining of severe crushingchest pain aggravated by breathing. She stated that she had two laminectomies in 1969 and developed calf vein thrombosis with pulmonary embolism after surgery. She claimed that she subsequently suffered at least 20 episodes of deep vein thrombosis and had 12 pulmonary emboli. Her previous surgical procedures included inferior vena... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: EDWIN B. KNIGHTS, M.D.Affiliations: Department of Medicine Johns Hopkins Hospital Baltimore, Maryland 21205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMunchausen’s syndrome: report of case 1 February 1976Volume 84, Issue 2 Page: 225-225 Keywords Breathing Deep vein thrombosis Ischemia Laminectomy Nurses Pain Pulmonary embolism Surgery Veins ePublished: 1 December 2008 Issue Published: 1 February 1976 PDF downloadLoading ...
Postgraduate Textbook of Clinical Orthopaedics
Authors: M. Mark Hoffer
Journal: JAMA (1984)

This is a 1,028-page comprehensive textbook designed for orthopedic surgeons in postgraduate training. It also can be used by the established orthopedic surgeon needing to refer to subjects not seen in his usual activities. I believe it is an appropriate textbook for both groups of people. There is no coverage of acute trauma in the text, nor are the operative techniques described in detail; the editor believes that these areas are adequately covered in other texts. The book contains 32 chapters under three sections ("Pediatric Orthopaedics," "General Orthopaedics," and "Special Topics"). There are more than 50 contributors of international reputation. A majority of the authors are orthopedic surgeons from the British Isles. However, basic scientists, rheumatologists, and pediatricians have also made contributions to this work. In addition, there are a number of well-respected American contributors. Most chapters are well written and the bibliography is generally complete. The chapter on metabolic
Granzyme B-Induced Apoptosis Requires Both Direct Caspase Activation and Relief of Caspase Inhibition
Authors: Ing Swie Goping, Michele Barry, Peter Liston, Tracy Sawchuk, Gabriela Constantinescu, Karolina M. Michalak, Irene Shostak, Darren L. Roberts, Allison M. Hunter, Robert Korneluk, R. Chris Bleackley
Journal: Immunity (2003)
Revelation of simple and complex liver acini after portal transplantation of pancreatic islets or thyroid follicles in rats
Authors: Frank Dombrowski, Matthias Evert
Journal: Hepatology (2007)

Abstract The microarchitecture of the liver is still not completely understood although various concepts of structural liver organization have been proposed. Among them, Rappaport's liver acinus stands out as one of the most accepted models. The correctness of this model, however, has also been doubted, and its applicability is hampered by the fact that the outlines of the liver acinus are disguised and nobody was ever able to give visual evidence by “unmasking” a simple liver acinus from the surrounding liver tissue. After intraportal transplantation of pancreatic islets or thyroid follicles into diabetic or thyroidectomized rats, respectively, the transplants engraft in small portal tracts and morphologically alter the downstream liver tissue due to excessive hormone secretion. Using a combined approach of perfusion fixation, stereomicroscopy, and light microscopy, we demonstrate in this study that these foci of altered liver tissue represent simple and complex liver acini, exactly as described by Rappaport. We present stereomicroscopical and histological examples of all important cut levels of altered simple and complex liver acini, including their topographical relation to the supplying and draining vessels and to the “central vein” liver lobule. Moreover, by computer-aided reconstruction of serial semi-thin sections, we were able to present the first 3-dimensional images of simple and complex liver acini. Conclusion: Our results prove the correctness of Rappaport's acinus model and confirm the simple liver acinus as the principal microcirculatory unit of the liver. (Hepatology 2007;45:705–715.)
State Aid for Private Medical Schools.
Authors: Emil Amberg
Journal: JAMA (1907)

Detroit, May 27, 1907. <h3>To the Editor:</h3> —The remarks on this subject inThe Journal, May 25, suggest to me that there exists another viewpoint besides that taken by the esteemed correspondent. The state, in my opinion, should not support any private medical school, because state support of private medical schools would be, I think, a most flagrant mistake from a national economic standpoint. Medical schools should be state institutions. It is to be regretted that the excellency of some private medical schools and the small number of state medical schools furnish a temporary excuse for the existence of the former. "It is not fair." says the correspondent, "that the owners of these schools should be taxed to support state schools." I think that it would be still less fair that the whole community should be taxed to support private medical schools. It would be taxation without due representation, so
REGIONAL ARTERIAL PRESSURE, BLOOD FLOW AND VASCULAR RESERVE IN HUMAN LOWER EXTREMITY PERIPHERAL ARTERY AT REST AND DURING PHARMACOLOGIC STRESS
Authors: Kojiro Miki, Kenichi Fujii, Daizo Kawasaki, Masashi Fukunaga, Hiroto Tamaru, Takahiro Imanaka, Masahiko Shibuya, Motomaru Masutani, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2013)
Further studies on the toxicology of the glycol ethers with emphasis on rapid screening and hazard assessment.
Authors: J E Doe
Journal: Environmental Health Perspectives (1984)

The discovery that ethylene glycol monomethyl ether (EGME) could affect the testis and the developing fetus in laboratory animals prompted further work to understand the effect of EGME and to examine additional glycol ethers to see if they showed EGME's reprotoxicity. Propylene glycol monomethyl ether (PGME) was shown not to cause testicular atrophy or to affect the development of rats at 600 ppm by inhalation, whereas EGME caused testicular atrophy at 300 ppm and showed teratogenic potential at 100 ppm. Diethylene glycol monomethyl ether (diEGME) was found to show no teratogenic potential when administered subcutaneously in rats at up to 1000 microL/kg, whereas EGME had effects at 40 microL/kg. EGME has been shown to cause effects on the testis in rats after a single exposure to 600 ppm or above for 4 hr. The effects can be seen as little as 24 hr after exposure. Ethylene glycol monoethyl ether (EGEE) also causes a reduction in testicular weight following a single exposure to saturated vapor for 3 hr (17 mg/l), but ethylene glycol monoisopropyl ether (EGPE) at 15 mg/l and ethylene glycol monobutyl ether (EGBE) at 4 mg/l showed no effect on the testis.
The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism.
Authors: M M Popovtzer, V L Subryan, A C Alfrey, E B Reeve, R W Schrier
Journal: Journal of Clinical Investigation (1975)

The acute effects of chlorothiazide (CTZ) on total (TSCA) and ionized (SCA-plus 2) serum calcium concentrations were studied in three groups of people: (a) eight subjects with normal parathyroid function; (b) six patients with hypoparathyroidism; and (c) two patients with hyperparathyroidism. Most subjects were studied on four occasions; at least 3 days intervened between studies on an individual subject. During each experiment the subject received an i.v. influsion of 5% dextrose in water at 1 ml/min from 8 a.m. to 4 p.m. Additions to the infusions were (a) none; (b) CTZ to deliver 3.33 mg/kg/h; (c) parathyroid extract to deliver 1 U/kg/h; or (d) both CTZ and parathyroid extract at the rates previously indicated. CTZ, when used, was added to the infusion at 10 a.m., parathyroid extract at 8 a.m. When CTZ was infused, the diuretic-induced losses of Na and water were replaced by i.v. infusion. In normal subjects 2 h after the start of CTZ infusion, there was a transient increase in SCA-plus 2 which coincided in time of day with a transient decrease in SCA-plus 2 in control experiments. At that time of day SCA-plus 2 was 4.18 plus or minus 0.12 mg/100 ml in control experiments and 4.56 plus or minus 0.08 in experiments with CTZ, P smaller than 0.025. The corresponding values for (TSCA) were 9.32 plus or minus 0.15 and 9.80 plus or minus 0.30, P smaller than 0.01. Such differences were not observed in the group with hypoparathyroidism. In the two patients with hyperparathyroidism, CTZ produced sustained increases in TSCA and SCA-plus 2. In normal subjects and those with hypoparathyroidism, CTZ plus parathyroid extract infusion resulted in sustained increases in both SCA-plus 2 and TSCA throughout the periods of observation when compared to experiments in which only parathyroid extract was infused, P smaller than 0.01 in all instances. The results suggest that the acute hypercalcemic action of CTZ requires the presence of circulating parathyroid hormone.
Antibacterial effect of microvesicles released from human neutrophilic granulocytes
Authors: Csaba I. Timár, Ákos M. Lőrincz, Roland Csépányi-Kömi, Anna Vályi-Nagy, György Nagy, Edit I. Buzás, Zsolt Iványi, Ágnes Kittel, David W. Powell, Kenneth R. McLeish, Erzsébet Ligeti
Journal: Blood (2012)
Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity
Authors: Kyle L. Hoehn, Nigel Turner, Michael M. Swarbrick, Donna Wilks, Elaine Preston, Yuwei Phua, Himani Joshi, Stuart M. Furler, Mark Larance, Bronwyn D. Hegarty, Simon J. Leslie, Russell Pickford, Andrew J. Hoy, Edward W. Kraegen, David E. James, Gregory J. Cooney
Journal: Cell Metabolism (2010)
Abstract LB-217: Long term safety observed with CEQ508: An oral RNAi drug targeting β-catenin of GI polyps
Authors: Alison D. Silva, Moreshwar B. Vaze, Alex Borrelli, Naimesh J. Kotadia, Lydia Lamriben, Barry Polisky
Journal: Cancer Research (2011)

Abstract Marina Biotech is developing a proprietary drug discovery and delivery platform called transkingdom RNAi (tkRNAi), to develop RNAi-based therapeutics in which non-pathogenic bacteria are engineered to: (1) express short hairpin RNA (shRNA), (2) invade via a specific cell surface receptor and (3) deliver shRNA to the cytoplasm of a targeted cell. CEQ508, an E. coli derivative delivered orally, is the first drug candidate utilizing this approach. CEQ508 expresses a shRNA directed against β-catenin, and has been shown in previous work to significantly reduce β-catenin mRNA levels in vitro and in vivo. In the colorectal cancer cell line, SW480, we observed 90% suppression of β-catenin mRNA. In the non-human primate distal ileum 65% knockdown of β-catenin mRNA was detected. β-catenin is a key oncogene implicated in Colorectal Cancer (CRC) and Familial Adenomatous Polyposis (FAP). FAP is a hereditary disease in which the formation of hundreds of polyps in the gastrointestinal tract ultimately leads to the development of colon cancer. CEQ508 will be tested in a Phase Ib/IIa clinical trial in FAP patients at Massachusetts General Hospital with first patient dosing expected in the first quarter of 2011. CEQ508 was recently granted orphan drug status for the intended treatment of FAP patients by the FDA's Office of Orphan Products Development. In preparation for later pivotal clinical trials, we recently completed a 9 month GLP non-human primate toxicology study assessing the safety of daily, oral chronic administration of CEQ508. In this study, 18 animals were dosed with either CEQ508 or two control articles. No CEQ508-related adverse responses were identified in the following study parameters analyzed: clinical observations, body weights and temperatures, serum chemistry, coagulation, hematology, urinalysis, cytokines and gross pathology. Preliminary conclusions identify the No Observed Adverse Effect Level (NOAEL) for long-term daily oral administration of CEQ508 as 1×1011 colony forming units (cfu)/day. In addition to presenting additional details of long term toxicology study, a clinical update on our Phase Ib/IIa trial will be provided. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-217. doi:10.1158/1538-7445.AM2011-LB-217
AUTONOMOUS THYROID NODULES
Authors: N. DAVID CHARKES
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 January 1968AUTONOMOUS THYROID NODULESN. DAVID CHARKES, M.D.N. DAVID CHARKES, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-1-254_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Silverstein, Burke, and Cogan have provided valuable information on the natural history of so-called "hot" thyroid nodules in their recent paper in the ANNALS(The natural history of the autonomous hyperfunctioning thyroid nodule.Ann. Intern. Med. 67: 539, 1967). One may take issue with their statement, however, that in Case 2 "the 50% decrease in131I uptake after1-triiodothyronine (1-T3) administration suggests that, initially, intranodular function was partially TSH-dependent." In a recent study of 25 patients with autonomous, hyperfunctioning thyroid nodules, my colleagues and I observed that although a marked fall in the 24-hr epithyroid count may...References References References1. CHARKESCANTORGOLUBOFF NDREB: A three day, double isotope, 1-triiodothyronine suppression test of thyroid autonomy. J. Nucl. Med. 8: 627, 1967. MedlineGoogle Scholar2. CANTORCHARKES REND: The effect of TSH on the solitary hyperfunctioning thyroid nodule. Ibid., p. 758. Google Scholar1. MILLERBLOCK JMMA: The autonomous functioning thyroid nodule. Therapeutic considerations. Arch. Surg. (Chicago). In press. Google Scholar2. MILLERHORNBLOCK JMRCMA: The autonomous functioning thyroid nodule in the evolution of nodular goiter. J. Clin. Endocr. 27: 1264, 1967. CrossrefGoogle Scholar3. CANTORCHARKES REND: Response of hot thyroid nodules to exogenous thyrotropin. J. Nucl. Med. 7: 370, 1966. Google Scholar1. CHARKESCANTORGOLUBOFF NDREB: A three day, double isotope, 1-triiodothyronine suppression test of thyroid autonomy. J. Nucl. Med. 8: 627, 1967. MedlineGoogle Scholar2. BURKE G: The triiodothyronine suppression test. Amer. J. Med. 42: 600, 1967. CrossrefMedlineGoogle Scholar3. CANTORCHARKES REND: The effect of TSH on the solitary hyperfunctioning thyroid nodule. J. Nucl. Med. 8: 758, 1967. MedlineGoogle Scholar4. MOLNARWILBERLEEWOOLNERKEATING GDRDRELBFR: On the hyperfunctioning solitary thyroid nodule. Mayo Clin. Proc. 40: 665, 1965. MedlineGoogle Scholar5. SILVERSTEINBURKECOGAN GEGR: The natural history of the autonomous hyperfunctioning thyroid nodule. Ann. Intern. Med. 67: 539, 1967. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: N. DAVID CHARKES, M.D.Affiliations: Division of Nuclear Medicine Temple University Hospital Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byScintigraphic evaluation of nodular goiterAUTONOMOUS THYROID NODULESN. DAVID CHARKES, M.D.Developments in Azo Colorants 1 January 1968Volume 68, Issue 1Page: 254-257KeywordsFallsThyroid ePublished: 1 December 2008 Issue Published: 1 January 1968 PDF downloadLoading ...
A faithful friend is the medicine of life.
Authors: J B Coltman, K M Coltman
Journal: Gut (1989)

A faithful friend is the medicine of life (Ecciesiaisticus 6. 16) The practice of mledicinic in the DCiles J B COLTMAN AND K M D COLTMAN In some of his articles Christopher Booth has refer- red to a particular practice in Wensleydale, covcrinig 12() square miles, in the confities of which his parents lived from 1939 onwards.At the time of his retire- mctit, it mnay he appropriate to consider some aspects of the Aysgarth practice which interested him.His famnily's cottage situated in Worton, lics three miles west of' Aysgarth and was bought by his mother in 1931 as a holiday homc for her family of five children, which included two sets of twins.After war broke out it bccamte their principle residence.Chris Booth went to Scdlbergh School which, at that time, was within the boundary of the o01 west riding of Yorkshire.There he was taught, among other things, to speak on July 12,