tbuckley/cabot-search huggingface dataset:
Abstract LB-356: Micelle-encapsulated thiostrepton: an effective nanomedicine for inhibiting tumor growth
Authors: Ming Wang, Andrei Gartel
Journal: Cancer Research (2012)

Abstract The thiazole antiobiotic, thiostrepton, has been found to suppress the expression of FOXM1, the oncogenic forkhead transcription factor overexpressed in cancer cells. Thiostrepton has also been shown to induce cell death in cancer cells through a proteasome inhibitory mechanism. As thiostrepton is highly hydrophobic, encapsulation into nano-sized delivery vehicles not only aides its solubilization but also improves its targeting for tumors in vivo. This is achieved by encapsulating thiostrepton into the interior of an amphiphilic micelle, composed from an assembly of lipid-PEG (polyethylene glycol) conjugates. In this study, we examined the anti-tumor effects of micelle-thiostrepton in both subcutaneous xenograft models (HepG2 liver cancer, Capan-2 pancreatic cancer and MDA-MB-231 breast cancer) and endogenous liver tumor models (DEN/PB-induced adenocarcinomas). In the case of the xenograft tumor-bearing mice, biodistribution studies showed micelle-thiostrepton to accumulate into both the liver (30% of injected dose) and the xenograft tumors (60% of injected dose) from 4 hours post-administration. In the endogenous liver cancer models, micelle-thiostrepton accumulated into the liver only, allowing a high concentration of tumor-associated thiostrepton drug. Continuous administration of micelle-thiostrepton at doses of 40mg/kg, 3 times a week for 30 days retarded the growth rate of all subcutaneous tumors and reduced the occurrence of adenocarinomas in endogenous liver cancer models. Immunoblotting and immunohistochemical staining revealed that treatment with micelle-thiostrepton inhibited the expression of the oncogenic transcription factor FOXM1 in tumors, a reduction of which generally coincides with suppressed cell proliferation and increased cell death. Furthermore, it was found that the reduced tumor growth rate of thiostrepton-treated tumors was indeed related to increased apoptosis, as indicated by the elevated expression of cleaved caspase-3 in such tumors samples. Our data suggest that the thiazole antibiotic/proteasome inhibitor thiostrepton, when formulated into nanoparticles, may be highly suited as a nanomedicine for treating cancer, particularly that of liver cancer. 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 LB-356. doi:1538-7445.AM2012-LB-356
Unusual Haemoglobin Variant in a Gujerati Indian
Authors: A. B. Raper
Journal: BMJ (1957)

Acute Myeloblastic Leukaemia following Chloramphenicol TreatmentVarious blood dyscrasias, ranging from slight granulocytopenia to agranulocytosis and aplastic anaemia, following administration of chloramphenicol have been reported dur- ing the last few years, but no case of acute leukaemia has yet been published.A case has recently been seen where acute myeloblastic leukaemia was discovered following agranulocytosis and hypoplasia of bone marrow after a single course of chloramphenicol.CASE REPORT A man aged 63 was first seen in September, 1953, with a history of sudden attacks of amnesia over the last year.No very definite abnormality was found on physical exam- ination.; a peripheral blood film showed a normal picture with haemoglobin 94%.Wassermann reaction negative.He had no symptoms when seen in January, 1954, but was admitted to this hospital in August, 1954, with further attacks of amnesia, frontal headaches, and momentarv aphasia.Examination revealed slight nominal dysphasia, right homonymous hemianopia, slight papilloedema of right disk, and accentuated right-sided tendon jerks.A 'skull radiograph was normal, but the cerebrospinal fluid was xanthochromic, under enhanced pressure, and contained in- creased protein and excess globulin.Blood count on August 27: Hb 74%; R.B.C. 4.060,000 per c.mm.; C.I. 0.92; W.B.C. 6,800 per c.
Human Systemic-Pulmonary Arterial Collateral Circulation After Pulmonary Thrombo-Embolism
Authors: George T. Smith, John W. Hyland, Thomas Piemme, Roe E. Wells
Journal: JAMA (1964)

ALTHOUGH there is extensive literature on the experimental production of bronchial pulmonary arterial anastomoses in animals following pulmonary arterial ligation,<sup>1-5</sup>there remains a paucity of information concerning the collateral circulation in the human lung following pulmonary thromboembolism. There are three phases of response to pulmonary embolism: vascular occlusion, pulmonary infarction, and development of a collateral circulation.<sup>6</sup>The character and extent of the collateral circulation that develops following pulmonary embolization in man has not been fully defined. The present study was therefore undertaken to determine the distribution and localization of the pathological vascular alterations which occur in the development of this collateral circulation. Miller<sup>7</sup>clearly showed that the only communication between the bronchial and pulmonary arterial system in the normal lung of both man and dog was via capillaries. These anastomoses were shown to occur at two sites: (1) at the level of the respiratory bronchiole, where pulmonary arterial capillaries freely
CONGENITAL STRICTURES OF THE ESOPHAGUS
Authors: PORTER P. VINSON
Journal: JAMA (1923)

The literature concerning complete congenital strictures of the esophagus has been reviewed very fully by Plass,1Griffith and Lavenson,2Cautley3and Hirsch,4and I shall not endeavor to analyze the cases they have compiled. There have been numerous types of esophageal deformity, but the majority of them are represented by Figure 1a, in which the upper portion of the esophagus ends in a blind pouch and the lower portion enters the trachea, or a bronchus forming an esophagotracheal or esophagobronchial fistula. Another type of stricture (Fig. 1b) is represented by an upper and a lower culdesac connected by a strand of tissue. A third type is similar to this, with the exception that there is no connection between the two segments.  Again there may be an upper culdesac only, sometimes connected with the stomach by strands of tissue. These strands, however, are often absent.
Reversal of Traumatic Quadriplegia after Closed Reduction
Authors: John A Cowan, John E McGillicuddy
Journal: New England Journal of Medicine (2008)

A 39-year-old woman was struck by a truck traveling at high speed. Cervical computed tomography showed a dislocation between the C5 and C6 vertebrae (Panel A, sagittal reconstruction). Physical examination revealed less than antigravity strength in the bilateral deltoids with no other movement in the limbs. A C7 level with no sacral sensation was found. Gardner–Wells tongs were applied, and a closed reduction was performed within 4 hours after the initial injury. After reduction, the patient immediately regained antigravity strength in both arms and both legs. A posterior cervical fusion was performed in the operating room to stabilize normal alignment . . .
Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium
Authors: Everett J. Moding, Chang-Lung Lee, Katherine D. Castle, Patrick Oh, Lan Mao, Shan Zha, Hooney D. Min, Yan Ma, Shiva Das, David G. Kirsch
Journal: Journal of Clinical Investigation (2014)

Cells isolated from patients with ataxia telangiectasia are exquisitely sensitive to ionizing radiation. Kinase inhibitors of ATM, the gene mutated in ataxia telangiectasia, can sensitize tumor cells to radiation therapy, but concern that inhibiting ATM in normal tissues will also increase normal tissue toxicity from radiation has limited their clinical application. Endothelial cell damage can contribute to the development of long-term side effects after radiation therapy, but the role of endothelial cell death in tumor response to radiation therapy remains controversial. Here, we developed dual recombinase technology using both FlpO and Cre recombinases to generate primary sarcomas in mice with endothelial cell–specific deletion of Atm to determine whether loss of Atm in endothelial cells sensitizes tumors and normal tissues to radiation. Although deletion of Atm in proliferating tumor endothelial cells enhanced the response of sarcomas to radiation, Atm deletion in quiescent endothelial cells of the heart did not sensitize mice to radiation-induced myocardial necrosis. Blocking cell cycle progression reversed the effect of Atm loss on tumor endothelial cell radiosensitivity. These results indicate that endothelial cells must progress through the cell cycle in order to be radiosensitized by Atm deletion.
Fortnightly Review: Lessons from international experience in controlling pharmaceutical expenditure II: influencing doctors
Authors: K. Bloor, N. Freemantle
Journal: BMJ (1996)

remains a formidable, worldwide threat to health, particu- larly to children in poor populations.Clearly, this is an international problem requiring new approaches to com- bating an old foe, who once again is winning the battle.This review was in part funded by the COGENT Trust (trust or correction of genetic diseases by transplantation) and by the Westminster Hospitals Special Trustees.
Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization.
Authors: A Lenz, M Heine, G Schuler, N Romani
Journal: Journal of Clinical Investigation (1993)

Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid organs that are specialized to present antigens and to initiate primary T cell responses. The Langerhans cell of the epidermis is used as a prototype for studies of DC in the skin. We have characterized a population of DC in human dermis, one of the first examples of these cells in nonlymphoid organs other than epidermis. To identify their distinct functions and phenotype, we relied upon the preparation of enriched populations that emigrate from organ explants of dermis. The dermal cells have the following key features of mature DC: (a) sheet-like processes, or veils, that are constantly moving; (b) very high levels of surface MHC products; (c) absence of markers for macrophages, lymphocytes, and endothelium; (d) substantial expression of adhesion/costimulatory molecules such as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function for resting T cells. Dermal DC are fully comparable to epidermis-derived DC, except for the lack of Birbeck granules, lower levels of CD1a, and higher levels of CD36. DC were also detected in explants of mouse dermis. We conclude that cutaneous DC include both epidermal and dermal components, and suggest that other human nonlymphoid tissues may also serve as sources of typical immunostimulatory DC.
HEART TRANSPLANT RECIPIENTS WITH PRE-TRANSPLANT COAGULOPATHY HAVE AN INCREASED INDEPENDENT RISK OF IN-HOSPITAL MORTALITY: A PROPENSITY-MATCHED NATIONWIDE INPATIENT SAMPLE STUDY
Authors: Marjan Mujib, Wilbert Aronow, Gregg Lanier, Dhaval Kolte, Sahil Khera, Chandrasekar Palaniswamy, Sachin Sule, Gregg Fonarow, Ali Ahmed, William Frishman, Alan Gass, Sumanth Prabhu, Julio Panza
Journal: Journal of the American College of Cardiology (2014)
Efficacy of Helper-dependent Adenovirus Vector-mediated Gene Therapy in Murine Glycogen Storage Disease Type Ia
Authors: Dwight D Koeberl, B Sun, A Bird, YT Chen, K Oka, L Chan
Journal: Molecular Therapy (2007)

Genetic deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, also known as von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia and growth retardation. We tested whether helper-dependent adenovirus (HDAd)-mediated hepatic delivery of G6Pase would lead to prolonged survival and sustained correction of the metabolic abnormalities in G6Pase knockout (KO) mice, a model for a severe form of GSD-Ia. An HDAd vector encoding G6Pase was administered intravenously (2 or 5 x 10(12)vector particles/kg) to 2-week-old (w.o.) G6Pase-KO mice. Following HDAd vector administration survival was prolonged to a median of 7 months, in contrast to untreated affected mice that did not survive past 3 weeks of age. G6Pase levels increased more than tenfold between 3 days and 28 weeks after HDAd injection (P < 0.03). The weights of untreated 2 w.o. G6Pase-KO mice were approximately half those of their unaffected littermates, and treatment stimulated their growth to the size of wild-type mice. Severe hypoglycemia and hypercholesterolemia, which are hallmarks of GSD-Ia both in humans and in mice, were also restored to normalcy by the treatment. Glycogen accumulation in the liver was markedly reduced. The efficacy of HDAd-G6Pase treatment in reversing the physiological and biochemical abnormalities associated with GSD-Ia in affected G6Pase-KO mice justifies further preclinical evaluation in murine and canine models of GSD-Ia.
miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression
Authors: Rikako Sanuki, Akishi Onishi, Chieko Koike, Rieko Muramatsu, Satoshi Watanabe, Yuki Muranishi, Shoichi Irie, Shinji Uneo, Toshiyuki Koyasu, Ryosuke Matsui, Yoan Chérasse, Yoshihiro Urade, Dai Watanabe, Mineo Kondo, Toshihide Yamashita, Takahisa Furukawa
Journal: Nature Neuroscience (2011)
Ambulatory Pediatric Care
Authors: Orest Dubynsky
Journal: JAMA (1988)

Dr Dershewitz is joined by no fewer than 127 contributing authors in putting together this almost 900-page text. There are 23 chapters and a very practical appendix. Inherent in this type of publication is a significant difficulty with continuity of both advice and style. Since the authors must cover an enormous amount of material, the treatment of any subject tends to be rather superficial, but, then, this is certainly not intended as a definitive text. I did find this book to often have the weakness of providing a rather narrow range of advice that the physician might pass along to parents. There are many vexing, although perhaps not medically critical, problems (colic, toilet training, croup, etc) that lacked diversity of resolution. The chapter on croup was actually quite good, yet in the "ambulatory" setting, I like more in the way of practical suggestions (breathing cold air, for example, was mentioned).
O132 EFFECTIVE STRATIFICATION OF HEPATOCELLULAR CARCINOMA RISK IN PRIMARY BILIARY CIRRHOSIS: RESULTS OF A MULTI-CENTRE INTERNATIONAL STUDY
Authors: P.J. Trivedi, W.J. Lammers, H. van Buuren, H.L.A. Janssen, P. Invernizzi, P.M. Battezzati, A. Floreani, A. Pares, C.Y. Ponsien, C. Corpechot, R. Poupon, M.J. Mayo, J. Talwalkar, A.K. Burroughs, F. Nevens, A.L. Mason, T. Bruns, K.-K. Li, K. Kowdley, M. Leeman, T. Kumagi, A. Cheung, A. Lleo, N. Cazzagon, I. Franceschet, L. Cabelleria, K. Boonstra, E.M.G. de Vries, M. Imam, G. Pieri, P. Kanwar, K. Lindor, B. Hansen, G. Hirschfield
Journal: Journal of Hepatology (2014)
Human interleukin‐9 supports formation of a subpopulation of erythroid bursts that are responsive to interleukin‐3
Authors: Yoshiaki Sonoda, Taira Maekawa, Yuko Kuzuyama, Tatsuo Abe, Steven C. Clark
Journal: American Journal of Hematology (1992)

Abstract We have investigated the biological activities of recombinant human interleukin‐9 (IL‐9) on enriched hematopoietic progenitors, alone or in combination with other cytokines, including Epo, G‐CSF, IL‐3, and GM‐CSF, under serum‐containing and serum‐free cultures. IL‐9 alone did not support colony formation. However, IL‐9 plus Epo induced erythroid burst (BFU‐E) formation derived from peripheral blood (PB) progenitors. Delayed addition experiments demonstrated that a part of bone marrow (BM) derived BFU‐E, which seems to be immature, only responded to IL‐9 and formed erythroid bursts. The burst‐promoting activity (BPA) of IL‐9 was confirmed using neutralizing aIL‐3, aGM‐CSF, and aIL‐9 antisera and serum‐free culture. IL‐9 supported a part of BFU‐E population that respond to IL‐3, which was almost identical to the number of BFU‐E supported by GM‐CSF. IL‐9 had no additive effect on erythroid and mixed colony formation supported by IL‐3. In contrast, IL‐9 showed an additive effect on erythroid burst formation supported by GM‐CSF in serum‐free culture. These data suggest that IL‐9 and GM‐CSF act on distinct IL‐3‐responsive BFU‐E population. In addition, delayed addition experiment clearly demonstrated that IL‐9 supports survival and the early stage of proliferation of BFU‐E. These results led us to propose that IL‐9 possibly acts as a BPA and selectively supports a subpopulation of early class of BFU‐E that respond to IL‐3. © 1992 Wiley‐Liss, Inc.
War and Public Health
Authors: Arden S. Handler
Journal: Annals of Internal Medicine (1997)

Medical Writings15 September 1997War and Public HealthArden S. Handler, DrPHArden S. Handler, DrPHUniversity of Illinois School of Public Health, Chicago, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-6-199709150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail War and Public HealthLevy BS, Sidel VW; eds. 412 pages. New York: Oxford Univ Pr; 1997. $55.00. ISBN 0195108140. Order phone 800-451-7556.Field of medicine: Public health.Format: Hardcover book.Audience: Public health students, educators, practitioners, researchers, and other concerned health professionals.Purpose: To explicitly document the public health consequences of war, to describe the roles that public health professionals can play in preventing war and alleviating its impact, and to make the prevention of war an integral part of the global public health agenda.Content: This text is divided into seven sections. The first describes why war is ... Author, Article, and Disclosure InformationAffiliations: University of Illinois School of Public Health, Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1997Volume 127, Issue 6Page: 495-496KeywordsArmed forcesGlobal healthPopulation statisticsPrevention, policy, and public health Issue Published: 15 September 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent
Authors: Manuel Yepes, Maria Sandkvist, Timothy A. Coleman, Elizabeth Moore, Jiang-Young Wu, David Mitola, Thomas H. Bugge, Daniel A. Lawrence
Journal: Journal of Clinical Investigation (2002)

Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase expressed in the CNS during events that require neuronal plasticity. In this study we demonstrate that endogenous tPA mediates the progression of kainic acid-induced (KA-induced) seizures by promoting the synchronization of neuronal activity required for seizure spreading, and that, unlike KA-induced cell death, this activity is plasminogen-independent. Specifically, seizure induction by KA injection into the amygdala induces tPA activity and cell death in both hippocampi, and unilateral treatment of rats with neuroserpin, a natural inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi. Inhibition of tPA within the hippocampus by neuroserpin treatment does not prevent seizure onset but instead markedly delays the progression of seizure activity in both rats and wild-type mice. In tPA-deficient mice, seizure progression is significantly delayed, and neuroserpin treatment does not further delay seizure spreading. In contrast, plasminogen-deficient mice show a pattern of seizure spreading and a response to neuroserpin that is similar to that of wild-type animals. These findings indicate that tPA acts on a substrate other than plasminogen and that the effects of neuroserpin on seizure progression and neuronal cell survival are mediated through the inhibition of tPA.
Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group
Authors: D. T. Mangano
Journal: JAMA (1997)

To determine the effects of a purine nucleoside, acadesine, on the incidence of fatal and nonfatal cardiovascular and cerebrovascular complications following coronary artery bypass graft (CABG) surgery.Individual patient data from 5 randomized, placebo-controlled, double-blind clinical trials, including 81 international medical centers of the United States, Canada, and Europe.All patients from all clinical trials were included: a total of 4043 patients undergoing CABG surgery, evaluable for efficacy, and randomized to receive either placebo (n= 2031) or acadesine (0.1 mg x kg(-1) x min(-1); n=2012) by intravenous infusion for 7 continuous hours and via the cardioplegia solution.Individual patient data were collected prospectively using standardized forms and methods and double-data entry. A general parametric approach and analysis-by-patient meta-analysis were used, including both fixed effects and random effects models. Inclusion and exclusion criteria, general methodology, and outcome assessment techniques were similar for all trials.Acadesine decreased the incidence of the primary outcome, perioperative myocardial infarction (MI) by 27% (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.51-0.95; P=.02), decreased the incidence of cardiac death through postoperative day 4 by 50% (OR, 0.52; 95% Cl, 0.27-0.98; P=.04), and decreased the incidence of combined outcome (MI, stroke, or cardiac death) by 26% (OR, 0.73; 95% Cl, 0.57-0.93; P=.01). The random effects models for these outcomes also yielded significant results. The incidence of cerebrovascular accident was not significantly reduced by acadesine (OR, 0.69; 95% Cl, 0.44-1.08; P=.10). A secondary analysis of cardiac death following MI through postoperative day 4 demonstrated that acadesine decreased by 89% the number of deaths from 13.3% (13 deaths/98 MIs) in the placebo group to 1.4% (1 death/71 MIs) in acadesine-treated patients (P=.003). Acadesine also reduced the use of ventricular-assistance devices for severe postoperative heart failure by approximately one third (P=.05). Finally, regarding safety, the incidence of adverse events was similar in the acadesine vs placebo groups, with the exception of a transient increase in serum uric acid in the acadesine group.The results of this meta-analysis indicate that in patients undergoing CABG surgery, treatment with acadesine before and during surgery can reduce early cardiac death, MI, and combined adverse cardiovascular outcomes.