tbuckley/cabot-search huggingface dataset:
Abstract 3910: Identification of lead organic compounds active against stem cell-like neuroblastoma cells by high throughput screening
Authors: Naohiko Ikegaki, Kiira Ratia, Ruth Hsiao, Mariko M. Limpar, Sarah Lomahan, Xao X. Tang
Journal: Cancer Research (2014)

Abstract Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics. We previously reported the establishment of induced neuroblastoma (NB) stem cells (iCSC), which were stable stem cell-like NB cells in sphere culture. These cells recapitulated the in vivo histological phenotypes of Large-Cell NB (LCN), the most aggressive and deadly subset of NB, including vesicular nuclei and two to three prominent nucleoli (PNAS Vol. 110: 6097-102 2013). In addition to the LCN phenotype, high-level expression MYC or MYCN is the consistent feature of the iCSC xenografts grown in immune-compromised mice. The goal of this study is to identify lead organic compounds active against NB iCSCs by high throughput screening. By using MTS assays, the SKNAS iCSC and the parental monolayer cells were used to screen the Prestwick Chemical Library®, containing 1200 FDA-approved small molecules. Growth suppressive compounds were defined as they exhibited cell survival reduction of greater than 80% compared to DMSO control. There were unexplored compounds with significant antineoplastic activity among existing antibacterial, antifungal, antiprotozoal, and anthelmintic compounds. Among the compounds screened, we identified a dozen of small molecules that were preferentially growth suppressive to the SKNAS iCSC over the monolayer cells. The secondary MTS assay confirmed so far that Chlorhexidine (antiseptic), Benzethonium (antiseptic) and Digoxin (cardiac glycoside) were potential anti-NB iCSC agents: they were more effective in suppressing growth of the SKNAS iCSC than the monolayer cells. In addition, these compounds exhibited MYC destabilizing activity in the SKNAS iCSC. Notably, JQ1, the recently identified MYC destabilizer, was less effective than Chlorhexidine, Benzethonium and Digoxin in suppressing growth of SKNAS iCSC. The above three compounds also showed the MYCN destabilizing effect in another pair of MYCN-amplified SKNBE(2)C iCSCs and SKNBE(2)C monolayer cells. We are currently completing characterization of the small molecules identified with focus on their anti- iCSC growth and anti-MYC/MYCN effects. This study would reveal specific pathways that regulate biological activities of the CSCs. In addition, it is a promising approach that could lead to development of safe and effective anti-cancer therapeutics not only for NB but also other cancer types. Citation Format: Naohiko Ikegaki, Kiira Ratia, Ruth Hsiao, Mariko M. Limpar, Sarah Lomahan, Xao X. Tang. Identification of lead organic compounds active against stem cell-like neuroblastoma cells by high throughput screening. [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 3910. doi:10.1158/1538-7445.AM2014-3910
Diagnosis of Blastomycosis
Authors: J P Areno, G D Campbell, R B George
Journal: New England Journal of Medicine (1986)

During the 100 years since Blastomyces dermatitidis was discovered as a cause of human disease, diagnostic tests, methods of collection of specimens, and laboratory techniques have improved significantly. Radiographic advances and the introduction of the fiberoptic bronchoscopy have allowed for more reliable clinical diagnoses. More sensitive serologic techniques and DNA probes have significantly improved the sensitivity of laboratory diagnosis. At present, the most reliable serologic tests are the sandwich enzyme immunoassay (sensitivity 88%, specificity 100%) and the 120-kd antigen radioimmunoassay (sensitivity 85%, specificity 100%). When positive and negative predictive values are applied, the sandwich enzyme immunoassay appears to be the most accurate. At the present time, a negative serologic test cannot be used to exclude blastomycosis. Further advances in refining the B dermatitidis antigen(s) for use in the newer, more sensitive, and specific assay techniques may allow for a definitive serologic diagnosis in the future, avoiding the necessity for invasive tests.
Biochemical Alterations in Blood in Obliterative Atherosclerosis
Authors: KORNEL GIBIŃSKI
Journal: Circulation (1959)

Biochemical alterations in blood due to pathologic changes in the legs are difficult to detect when the blood samples are taken from the cubital vein. In the reported investigations biochemical properties of this blood are compared with those of the venous blood flowing out from a leg affected by obliterative atherosclerosis.
ELECTROCONVULSIVE SHOCK THERAPY AND CARDIOVASCULAR DISEASE
Authors: Vernon L. Evans
Journal: Annals of Internal Medicine (1945)

Article1 May 1945ELECTROCONVULSIVE SHOCK THERAPY AND CARDIOVASCULAR DISEASEVERNON L. EVANS, M.D., F.A.C.P.VERNON L. EVANS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-5-692 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe deliberate induction of convulsions in the presence of known or suspected cardiovascular disease would seem to be a very hazardous undertaking. However, it has been possible to treat a considerable number of such patients for psychiatric disorders with very little trouble and a low mortality rate. When the convulsion is induced by the application of an electric current to the brain, there is no direct trauma to the cardiovascular system, and one would expect no more trouble than would follow one or two minutes of strenuous exercise. The results in this series of cases would seem to bear this... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Aurora, Illinois*Received for publication August 25, 1944. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byECT in the Treatment of Patients with Neurological and Somatic DiseaseElectroconvulsive Therapy in Psychiatric Patients With Severe Cardiovascular DiseaseBibliographyHjärt-kärlsjukdomar som kontraindikation mot elektrochockbehandlingErfarenheter vid elektrochockbehandling av åldringarElectroplectic Anæsthesia in Animals and Man 1 May 1945Volume 22, Issue 5Page: 692-695KeywordsBrainCardiovascular diseasesCardiovascular therapyConvulsionsDeath ratesShockStrenuous exercise ePublished: 1 December 2008 Issue Published: 1 May 1945 PDF downloadLoading ...
321. siFECT™: Optimised Formulation for the Delivery of siRNA at Minimum Doses and Maximum Specificity
Authors: Sebastien Spagnou, Michael Jorgensen, Andrew D. Miller, Michael Keller
Journal: Molecular Therapy (2004)

RNA interference (RNAi) has become a popular tool to down-regulate specific gene expression in many species including mammalian cells. Synthetic double stranded RNA sequences (siRNA) of 21–23 nucleotides were shown to have the potential to specifically silence gene function in cultured mammalian cells. This finding surged a great interest to apply siRNA in functional genomics programs to decipher specific gene function. However, literally no studies have been published in the literature on the impact of the lipid formulation on siRNA mediated gene silencing. For functional genomics studies to be valuable, specific gene down-regulation of one single target gene devoid of non-specific down-regulation of many cellular proteins has to be achieved.
Genotyping and antifungal susceptibility testing of Cryptococcus neoformans isolates from Cameroonian HIV-positive adult patients
Authors: S. Bertout, P. Drakulovski, C. Kouanfack, D. Krasteva, T. Ngouana, C. Dunyach-Rémy, J. Dongtsa, A. Aghokeng, E. Delaporte, S. Koulla-Shiro, J. Reynes, M. Mallié
Journal: Clinical Microbiology and Infection (2012)
PARKINSONISM AND RHEUMATOID ARTHRITIS
Authors: R O WALLERSTEIN
Journal: Annals of Internal Medicine (1951)

Article1 April 1951PARKINSONISM AND RHEUMATOID ARTHRITISRALPH O. WALLERSTEIN, M.D.RALPH O. WALLERSTEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-34-4-899 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEighty years ago Charcot first called attention to the possible relationship between Parkinsonism and rheumatoid arthritis. Since then several investigators have pointed out similarities between the two diseases. Chronic atrophic arthritis following encephalitis lethargica has been reported by Lichtwitz and Grimaldi. Describing certain clinical features common to both diseases, Sicard advanced the hypothesis of common central cerebral origin.In an effort to evaluate critically the relationship between the two diseases, 19 patients with frank clinical paralysis agitans, and 28 patients with far advanced, chronic atrophic arthritis were examined. All patients were inmates of the Laguna Honda Home for the aged...Bibliography1. Lichtwitz L: Hypophysäre Symptome und Hypophysenkrankheiten, Verhandl. d. deutsch. Gesellsch. f. inn. Med. Kong. 42: 35, 1930. Google Scholar2. Lichtwitz L: Functional pathology, 1941, Grune & Stratton, New York. Google Scholar3. Sicard JA: Parkinsonisme et rhumatisme chronique, Rev. neurol. 37: 682, 1921. Google Scholar4. BendaCobb CES: On pathogenesis of paralysis agitans (Parkinson's disease), Medicine 21: 95, 1942. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication September 17, 1949.From the University of California Service, San Francisco Hospital, Department of Public Health, J. C. Geiger, M.D., Director, and the Division of Medicine of the University of California Medical School, San Francisco. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEpidemiologie 1 April 1951Volume 34, Issue 4Page: 899-901KeywordsArthritisEncephalitisHospital medicineParkinson diseasePrevention, policy, and public healthRheumatoid arthritis ePublished: 1 December 2008 Issue Published: 1 April 1951 PDF downloadLoading ...
College says there is no place for “ageism” in care of elderly
Authors: Mark Silvert
Journal: BMJ (2000)

Better teamwork between groups of doctors is needed in order to improve the care of older patients, according to a new report from the Royal College of Physicians.

The large increase in the number of people over 85, together with the ever increasing expectations of patients, means that the need for fully coordinated services is becoming much more important for delivering high quality care to elderly …
Juvenile Pernicious Anemia
Authors: E H REISNER, J A WOLFF, R J McKAY, E F DOYLE
Journal: New England Journal of Medicine (1965)

Histories have been presented of two pairs of sibling children with recurrent macrocytic anemia with megaloblastic bone marrow responding specifically to liver extract and vitamin B12.  The clinical features and laboratory findings were similar to those of adult pernicious anemia in every respect except for the inconstant presence of histamine refractory achlorhydria. All the patients responded to vitamin B12 given parenterally, but in three to whom it was given by mouth no response was obtained. Two of these subsequently responded to oral B12 when it was accompanied by normal gastric juice. The other two developed histamine refractory achlorhydria while in hematologic remission. This is interpreted as proof that the anemia was due to deficient intrinsic factor in the gastric juice.  Three patients showed evidence of disease of the spinal cord, in two of whom the symptoms were severe. These symptoms were compatible with a diagnosis of dorsolateral sclerosis, and improved with antipernicious anemia therapy. In one of these patients, treated with folic acid, the neurologic lesions were aggravated severely.  Pernicious anemia due to the absence of gastric juice intrinsic factor occurs in children. The presence of free hydrochloric acid in the gastric contents does not preclude the possibility of the disease.
Amyloid β interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease
Authors: Alfredo Lorenzo, Menglan Yuan, Zhuohua Zhang, Paolo A. Paganetti, Christine Sturchler-Pierrat, Matthias Staufenbiel, Jorge Mautino, Francisco Sol Vigo, Bernd Sommer, Bruce A. Yankner
Journal: Nature Neuroscience (2000)
A pretargeted bispecific PAM4-based antibody system for nuclear imaging and therapy of pancreatic cancer
Authors: Habibe Karacay, Guy Newsome, Thomas M. Cardillo, William McBride, David M. Goldenberg, Robert M. Sharkey, David V. Gold
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6182 

Pancreatic cancer provides a major challenge, both in terms of diagnosing the disease and subsequent treatment options. With this in mind, we developed MAb, PAM4, reactive with a MUC1 epitope that is relatively restricted to pancreatic cancer. As a second-generation in vivo targeting agent, we examined the ability of a pretargeted, bispecific PAM4 (bsMAb) procedure to provide superior imaging and therapeutic outcome of pancreatic cancer, as compared to direct-radiolabeled whole IgG. Our initial studies (Clin Cancer Res, 10:3552, 2004) employed MAb-734, anti-In-DTPA Fab’, as the second arm of the bsMAb. In the present study, we have generated a new bsMAb employing MAb-679, reactive with the HSG hapten, as the second arm. MAb-679 provides a more universal system that can readily be adapted to several imaging technologies (SPECT, PET, US, etc.), and used to capture a wide range of therapeutic agents (radionuclides, drugs, biologicals, etc.) by incorporation of the HSG sequence into the imaging/therapeutic agent. BsPAM4 was produced by chemical conjugation of PAM4-Fab’-SH with o-PDM-modified 679-Fab’. After purification by size-exclusion and HSG-affinity chromatography, a single peak was identified on HPLC with a retention time consistent with a size of approximately 100Kd. Immunoreactive fraction was examined by use of an anti-PAM4 idiotype and HSG-peptide. By HPLC analyses, 93.4% of the bsMAb was reactive with the anti-PAM4 idiotype, and 97.8% of the bsMAb was reactive with the HSG-peptide. Non-tumor bearing mice were injected with 125I-labeled bsMAb, and individual groups of mice were necropsied at specific time-points. The highest concentration of radiolabeled antibody was within the blood at all time-points (20.97 ± 3.77, 2.42 ± 0.54, 0.89 ± 0.21, and 0.40 ± 0.14, %ID/g at 4, 24, 38, and 48 hrs post-injection, respectively). There was rapid clearance of the bsMAb from the blood with blood levels <0.5 %ID/g at 45 hrs. The bsMAb showed no evidence of accumulation in any normal tissues. A pretargeting study was then performed in mice by administration of 40 μg bsMAb, followed by administration of 111In-labeled HSG-peptide (24 μCi, 10:1 molar ratio, bsMAb:peptide) 44 hrs later, when blood levels of the bsMAb had fallen to <0.5%ID/g. At 3 hrs post-injection of radiolabeled peptide high tumor/non-tumor ratios [lowest value: 4.35 ± 1.48 (kidney)] were observed within mice bearing MUC1-producing tumors, whereas no evidence of tumor targeting was seen in mice bearing non-MUC1-producing tumors. These studies demonstrate the ability of this new bsMAb to specifically target pancreatic tumor with high signal-to-background ratios for use as imaging/therapy agents. (These studies were supported in part by NIH grant CA92723 and DE-FG02-95ER62028 from the DOE.)
The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice
Authors: Jan Bressler, Ting-Fen Tsai, Mei-Yi Wu, Shih-Feng Tsai, Maricela A. Ramirez, Dawna Armstrong, Arthur L. Beaudet
Journal: Nature Genetics (2001)
Abstract 143: Caveolae Regulate PI3K/Akt/RhoA-Mediated p38 MAPK Nuclear Translocation in Leptin-Induced Cardiomyocyte Hypertrophy
Authors: Asad Zeidan, Sabzali Javadov, Subrata Chakrabarti, Morris Karmazyn
Journal: Circulation (2007)

Background : Obesity is associated with increased leptin production which may contribute to cardiac hypertrophy. However, the mechanism of leptin-induced cardiac hypertrophy remains incompletely understood. Previous studies have shown that the RhoA/ROCK/cofilin pathway and p38 MAPK but not ERK1/2 activation are major contributors to leptin-induced cardiac hypertrophy. In this study we explored the roles of caveolae and the PI3K/Akt pathway in regulating RhoA and p38 MAPK activation during leptin-induced cardiomyocyte hypertrophy. Methods and Results : Neonatal rat ventricular myocytes were cultured with 3.1 nmol/L leptin for 24 hours. Caveolae number and expression of caveolin-3 were significantly increased after leptin treatment (2 and 3 fold, respectively; p&lt;0.01). These effects were associated with a 29% (p&lt;0.05) increase in cell surface area and a 40% (p&lt;0.05) increase in leucine incorporation, indicating cardiomyocyte hypertrophy. Disruption of cardiomyocyte caveolae with 5 mM methyl-beta-cyclodextrin (MβCD) significantly inhibited leptin-induced hypertrophy. RhoA was detected in caveolae fractions of a sucrose gradient after cardiomyocytes were treated with leptin for 5 min, demonstrating subcellular translocation of RhoA. Treatment with MβCD, 50 ng/ml C3 exoenzyme (a RhoA inhibitor) or 50 nM latrunculin B (actin filaments depolymerization agent) significantly attenuated leptin-induced RhoA translocation into caveolae fractions. Moreover, Western blot analysis showed that leptin-dependent activation of PI3K (116%; p&lt;0.05), Akt (115%; p&lt;0.05) and RhoA (330%; p&lt;0.05) were significantly inhibited by 50 μM LY294002, a specific PI3K inhibitor. In addition, LY294002 significantly attenuated leptin-induced increases in cell surface area and in leucine incorporation. Furthermore, we found that leptin-induced activation of p38 (189%; p&lt;0.05) and ERK1/2 (220%; p&lt;0.05) was associated with p38 MAPK but not ERK1/2 nuclear translocation. MβCD, C3 exoenzyme and LY294002 potently attenuated leptin-induced p38 MAPK nuclear translocation. Conclusions : Our results demonstrate that caveolae, the PI3K/Akt/RhoA pathway and p38 MAPK nuclear translocation play a pivotal role in leptin-induced cardiomyocyte hypertrophy.
Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy
Authors: Gennaro Cice, Luigi Ferrara, Antonello D’Andrea, Salvatore D’Isa, Attilio Di Benedetto, Antonio Cittadini, Pina Elvira Russo, Paolo Golino, Raffaele Calabrò
Journal: Journal of the American College of Cardiology (2003)
Immunoelectron-microscopic detection of globotriaosylceramide accumulated in the skin of patients with Fabry disease
Authors: T. Kanekura, T. Fukushige, A. Kanda, S. Tsuyama, F. Murata, H. Sakuraba, T. Kanzaki
Journal: British Journal of Dermatology (2005)

Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of alpha-galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL-3). To date, no direct detection of GL-3 by immunoelectron microscopy has been reported.To examine whether GL-3 is accumulated exclusively in lysosomes of cutaneous cells using an anti-GL-3 monoclonal antibody (mAb) and immunoelectron microscopy.Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electron microscopy using an anti-GL-3 mAb.By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti-GL-3 antibody. Electron microscopically, positive signals for GL-3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium.Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL-3 and the accumulated GL-3 was localized essentially to lysosomes.
163. Phenotypic Correction of a Hemophilia B Dog Following Systemic Administration of a Helper-Dependent Ad Vector Encoding Canine Coagulation Factor IX
Authors: Nicola Brunetti-Pierri, Donna Palmer, Timothy C. Nichols, Arthur L. Beaudet, Philip Ng
Journal: Molecular Therapy (2004)

Helper-dependent adenoviral vectors (HDAd) offer tremendous potential for liver-directed gene therapy because they can efficiently transduce hepatocytes following systemic delivery to direct high-level, long-term transgene expression with negligible chronic toxicity. In this study we have evaluated the potential of liver-directed, HDAd-mediated hemophilia B gene therapy in a large animal model. Two hemophilia B dogs were injected intravenously with 3x10e12 vp/kg of a HDAd encoding canine coagulation factor IX (FIX) under liver-restricted expression. In the first dog, the whole blood clotting time (WBCT) decreased from a baseline value of >60 min to the normal range of 8 to 12 min by 12 days post-injection and has persisted for 5 months, increasing slightly to 18 min for at least the next 3 months. Peak FIX activity of 34% was achieved at 12 d post-injection but declined to 14% 2 months post-injection. In the second dog, the WBCT normalized from >60 min pre-injection to 12 min 7 days post-injection and has remained normal for at least 3 months. Systemic vector administration was accompanied by mild and transient elevation of serum transaminases and thrombocytopenia. In conclusion our results show a sustained phenotypic correction in the absence of chronic toxicity thus supporting the potential for HDAd-mediated, liver-directed gene therapy of hemophilia B.
123. Efficient Gene Delivery To the Cone-Enriched Pig Retina By Dual AAV Vectors
Authors: Pasqualina Colella, Ivana Trapani, Giulia Cesi, Andrea Sommella, Anna Manfredi, Agostina Puppo, Carolina Iodice, Settimio Rossi, Massimo Giunti, Alberto Auricchio
Journal: Molecular Therapy (2014)