tbuckley/cabot-search huggingface dataset:
Statistics Notes: The use of transformation when comparing two means
Authors: J M. Bland, D. G Altman
Journal: BMJ (1996)

(1) Twenty-one synthetic compounds, all of them benzilic esters of alkamines, have been tested for mydriatic activity in the mouse; seven of them proved to be powerful mydriatics, comparable in intensity of action with atropine but shorter in duration. (2) Fifteen of them were tested in the cat for atropine-like action in the salivary gland and on the blood pressure. The powerful mydriatics were all more active than atropine in both respects, and several compounds weaker than atropine in mydriatic activity were more active than atropine in the salivary gland. (3) Several of the compounds were found to be atropine-like in smooth muscle and in the isolated cat9s heart. (4) Eight of the more active mydriatics were tested for toxicity; in mice all of them were more toxic than atropine on intraperitoneal or subcutaneous injection but two of the most promising compounds (E3 and P10) were less toxic than atropine on oral administration; the same two compounds produced much less severe symptoms on subcutaneous injection into cats than atropine did in equal doses. (5) Benzilic esters of quaternary alkamines were in general more active in all the tests used than those of corresponding tertiary alkamines. (6) The mydriatic activity of the quaternary metho-salts of atropine, l-hyoscyamine, l-hyoscine and eucatropine has been compared with that of their parent bases in the mouse pupil and after local application to the eye of the cat. In the mouse the metho-salts, except l-hyoscine methiodide, are more active than the tertiary bases; in the cat the tertiary bases are the more active mydriatics. (7) The relations between chemical structure and atropine-like action among the synthetic compounds and the belladonna alkaloids are discussed. (8) Among the synthetic benzilic esters benzilyloxyethyl dimethylethyl ammonium chloride (E3) appears to be the most promising substitute for atropine in ophthalmic practice; its action equals that of atropine in intensity but is shorter in duration and its toxicity compares favorably with that of atropine.
CD1d-lipid antigen recognition by the γδ TCR
Authors: Adam P Uldrich, Jérôme Le Nours, Daniel G Pellicci, Nicholas A Gherardin, Kirsty G McPherson, Ricky T Lim, Onisha Patel, Travis Beddoe, Stephanie Gras, Jamie Rossjohn, Dale I Godfrey
Journal: Nature Immunology (2013)
Abstract 1837: A HSP90 inhibitor, AUY922, is effective to overcome the MET- and AXL-mediated resistance to EGFR-TKI in lung cancer
Authors: Jin Kyung Rho, Yun Jung Choi, Seon Y. Kime, Gwang Sup So, Se Hoon Choi, Chang-Min Choi, Jae Cheol Lee
Journal: Cancer Research (2014)

Abstract Activation of bypass signals such as MET and AXL has been identified as one of possible resistant mechanisms to EGFR-TKI. Since various oncoproteins are dependent on HSP90 for its maturation and stability, we investigated the effect of AUY922, a newly developed HSP90 inhibitor of non-geldanamycin class, in lung cancer cells with MET- and AXL-mediated resistance. We established resistant cell lines with HCC827 harboring the deletion mutation on exon 19 of EGFR gene by long-term exposure to increasing concentrations of gefitnib and erlotinib (designated as HCC827/GR and HCC827/ER, respectively). The resistance of HCC827/GR was mediated by MET activation, whereas AXL activation caused resistance in HCC827/ER. AUY-922 treatment effectively suppressed the proliferation and induced cell death in both resistant cell lines. Accordingly, down-regulation of MET and AXL leading to decreased activation of Akt was noted. The inhibitory effect of AUY-922 on AXL and MET was also confirmed in AXL or MET-transfected LK-2 cells. In addition, AUY-922 led to reduced capability of invasion and migration of resistant cells. AUY-922 was effective to control the tumor growth in xenograft mouse models of HCC827/GR and HCC827/ER. Our study showed AUY-922 is one of promising therapeutic options for the MET- and AXL-mediated resistance to EGFR-TKI in lung cancer. Citation Format: Jin Kyung Rho, Yun Jung Choi, Seon Ye Kime, Gwang Sup So, Se Hoon Choi, Chang-Min Choi, Jae Cheol Lee. A HSP90 inhibitor, AUY922, is effective to overcome the MET- and AXL-mediated resistance to EGFR-TKI in lung cancer. [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 1837. doi:10.1158/1538-7445.AM2014-1837
JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia
Authors: Sandrine Degryse, Jan Cools
Journal: Journal of Hematology & Oncology (2015)

Recent studies of acute lymphoblastic leukemia have identified activating mutations in components of the interleukin-7 receptor complex (IL7R, JAK1, and JAK3). It will be of interest to investigate both JAK1 and JAK3 kinase inhibitors as targeted agents for these leukemias.
New Drug Delivery Technologies May Advance Personalized Cancer Therapy
Authors: Tracy Hampton
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MUCOID IMPACTION OF THE BRONCHI
Authors: A E GREER
Journal: Annals of Internal Medicine (1957)

Article1 March 1957MUCOID IMPACTION OF THE BRONCHIALLEN E. GREER, M.D.ALLEN E. GREER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-46-3-506 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe existence of dilated bronchi filled with inspissated mucus complicating asthma or obstructive bronchitis has recently been reported. Shaw1first described this condition as mucoid impaction of the bronchi. His original paper was presented before the American Association for Thoracic Surgery in 1951 and was published in theJournal of Thoracic Surgeryin August, 1951. The existence of such a condition associated with asthma or obstructive bronchitis was apparently not then noted by many interested in thoracic disease. Only one report since 1951 mentions the condition and summarizes Shaw's findings in a discussion of bronchiectasis.2Because of the lack of...Bibliography1. Shaw RR: Mucoid impaction of the bronchi, J. Thoracic Surg. 22: 149, 1951. CrossrefGoogle Scholar2. SchwartzKatz BH: Localized bronchiectasis simulating neoplasm, Ann. Int. Med. 43: 45, 1955. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oklahoma City, Oklahoma*Received for publication April 27, 1956.Presented at the Regional Meeting of The American College of Physicians, Hot Springs, Arkansas, December 3, 1955.Requests for reprints should be addressed to Allen E. Greer, M.D., Lister Medical Building, 430 Northwest Twelfth, Oklahoma City 3, Oklahoma. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byObstructive Pneumonia due to Unknown Eosinophilic Mucoid Impaction of Bronchi: a Case ReportMucoid Impactions: Finger-in-Glove Sign and Other CT and Radiographic FeaturesSigns in Thoracic ImagingAspectos radiológicos da atresia brônquica: relato de três casos e revisão da literaturaBronchial Casts in ChildrenCase 24-1982Röntgenologische Veränderungen bei chronischer Bronchitis, Bronchiektasie, Asthma und EmphysemCorrelation of Chest Roentgenology and Lung PhysiologyGutartige Primärtumoren der Bronchien und LungenMucoid impaction of the bronchi in relation to asthma and plastic bronchitisBronchial Asthma and Recurrent Pneumonia in Children: Clinical Evaluation of 14 ChildrenMucoid Impaction of the Bronchi Associated with AspergillusMucoid Impaction of the BronchiMucoid Impaction of the BronchiMUCOID IMPACTION OF THE BRONCHIPulmonary Atelectasis Complicating Bronchial AsthmaStudies with sputum 1 March 1957Volume 46, Issue 3Page: 506-522KeywordsAsthmaBronchiBronchiectasisBronchitisGranulomasLungsMucusPatientsPneumoniaThoracic surgery ePublished: 1 December 2008 Issue Published: 1 March 1957 PDF downloadLoading ...
Attempt to Detect a Mammary Tumor-Agent in Strain C Mice by X-Radiation
Authors: Howard B. Andervont, Thelma B. Dunn
Journal: JNCI Journal of the National Cancer Institute (1950)

Attempt to Detect a Mammary Tumor-Agent in Strain C Mice by X-Radiation Howard B. Andervont, Howard B. Andervont biologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Thelma B. Dunn Thelma B. Dunn pathologist National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 5, April 1950, Pages 1157–1189, https://doi.org/10.1093/jnci/10.5.1157 Published: 01 April 1950 Article history Received: 23 January 1950 Published: 01 April 1950
Dihydroceramide desaturases are differentially expressed in Fenretinide-resistant pediatric Acute Lymphoblastic Leukemia (ALL) cell lines
Authors: Jun Wu, Barry J. Maurer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1257 

Drug resistance to chemotherapy is a major obstacle to the treatment of primarily refractory and relapsed pediatric acute lymphoblastic leukemias (ALL). The leukemias of more than 25% of relapsed ALL patients exhibit altered p53 function and/or overexpression of various anti-apoptotic factors. It has been suggested that elevated intracellular level of ceramides or derivative sphingosine-based lipid second messengers may be involved in the apoptotic response to certain chemotherapy agents in other leukemia types. We have observed that fenretinide (4-HPR), a synthetic retinoid, is cytotoxic to a variety of human cancer cell lines in vitro in association with an increase of ceramides (saturated > unsaturated) via de novo synthesis. Dihydroceramides (dhCER, saturated) are converted to ceramides (CER)(unsaturated) by two distinct dihydroceramide desaturases, DES-1 and DES-2. The cytotoxic properties of long chain dhCERs are not known. We hypothesized that 4-HPR might increase dhCERs in ALL cell lines by decreasing DES activity. METHODS. DES-1 and DES-2 mRNA were quantitated by real-time PCR in 4-HPR (10 μM)-treated cells: established (MOLT-4) and newly established ALL cell lines (COG-LL-317 and 319, COG-LL-327), normal human peripheral blood mononuclear cells (PBMC), and normal human brain endothelial cells (EC). Sensitivity in vitro to 4-HPR of cell lines: COG-LL-317 (T-cell ALL cell line), LD99 = ∼6.57 μM; COG-LL-319 (pre-B cell line), LD99 = ∼125 μM and COG-LL-327 (T-cell ALL line), LD99 = 665 μM, respectively. MOLT-4, LD99 = ∼10 μM. RESULTS. Baseline expression of DES-1 in COG-LL-327 cells was 5 fold higher than in COG-LL-317, COG-LL-319, MOLT-4 cells, and in PBMC and EC. 4-HPR treatment decreased DES-1 mRNA levels by ∼30% in COG-LL-327 at +6 hrs, but did not affect DES-1 mRNA levels in COG-LL-317 and COG-LL-319. DES-1 levels were decreased in MOLT-4 cells at +2 hours by ∼70%, and down-regulation was maintained through +48 hours, at which time most cells were dead. Baseline expression of DES-2 in COG-LL-319 was ∼10 fold higher than in COG-LL-317, COG-LL-327, MOLT-4, PBMC and EC. In COG-LL-319 cells, DES-2 mRNA levels were decreased by ∼80% at +2 hrs, but with a slight recovery to ∼30% of baseline by +6 hrs. In contrast, in COG-LL-317 cells, DES-2 mRNA levels were decreased by ∼85% at +4 hrs, and barely detectable at +6 hrs. 4-HPR treatment decreased DES-2 mRNA levels in MOLT-4 by ∼95% by +2 hrs, and decreased DES-2 mRNA levels in COG-LL-327 cells by 75% at +4h. CONCLUSIONS. These results, in a limited cell line panel, suggest that high expression of either DES-1 or DES-2 may correlate with decreased sensitivity to 4-HPR in ALL cell lines, and imply that long chain dhCERs may contribute to 4-HPR cytotoxicity. Further investigations of 4-HPR on DES gene transcriptional regulation, and the role of long chain dhCERs in 4-HPR-induced cell death, are in progress.
Abstract 11849: Validating and Updating the Toronto In-Hospital Mortality Risk Score After Percutaneous Coronary Interventions in Brazil
Authors: Lucas Lodi-Junqueira, José Luiz P Silva, Lorena R Ferreira, Humberto L Oliveira, Guilherme R Athayde, Thalles O Gomes, Julio C Borges, Bruno R Nascimento, Enrico A Colosimo, Pedro A Lemos, Antonio L Ribeiro
Journal: Circulation (2014)

Background:  Estimating percutaneous coronary intervention (PCI) mortality risk by a clinical prediction model is imperative to help physicians, patients and family members make informed clinical decisions and optimize participation in the consent process, reducing anxiety and improving quality of care. At a healthcare system level, risk prediction scores are essential to measure and benchmark performance.   Hypothesis:  The Toronto PCI mortality risk score is accurate and precise in predicting death in a Brazilian population.   Methods:  Between 2009 and 2013, a cohort of 4,806 patients from the ICP-BR registry, treated with PCI in eight tertiary referral medical centers, was included in the analysis. This population was compared to 10,694 patients of the derivation dataset from the Toronto study. To assess predictive performance, an update of the model was performed by three different methods, which were compared by discrimination, calculating the area under the receiver operating characteristic curve (AUC), and by calibration, assessed through Hosmer-Lemeshow (H-L) test and graphical analysis. The score included the following predictors: age - 40-49 (1), 50-59 (2), 60-69 (3), 70-79 (4) and ≥80 (5); diabetes (2); renal failure (2), NYHA class IV heart failure symptoms (3); severe myocardial dysfunction (3); multivessel disease (1), left main disease (2); recent myocardial infarction (3); early PCI after thrombolysis (3); primary PCI (4); cardiogenic shock (6). After summing the score values we apply the equation: 1/(1+e^(- (-7.448 + risk score x 0.352))). We sought to re-divide the integer score according to the predictive risk in low ( 5% - score ≥13) risk groups.   Results:  Death occurred in 2.6% of patients in the ICP-BR registry and in 1.3% in the Toronto cohort. The median age was 64 and 63 years, 23.8 and 32.8% were female, 28.6 and 32.3% were diabetics, respectively. Through recalibration of intercept and slope (AUC= 0.8790; H-L p value= 0.3132), we achieved a well-calibrated and well-discriminative model.   Conclusions:  After updating to our dataset, we demonstrated that the Toronto PCI in-hospital mortality risk score has a good performance and discrimination in Brazilian hospitals.
Islands I Hardly Knew
Authors: B Chandra
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Quantitative analysis of Akt phosphorylation state in patient samples of glioblastoma using a nanofluidic capillary western platform
Authors: David H. Stokoe, Semanti Ganguly, John Gossett, David Voehringer, Roger O’Neill
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4462 

The role of PKB/Akt in cell cycle regulation and cell death contributes to its role as an indicator for tumor response to therapy in glioblastoma multiforme (GBM). Methods are currently lacking for accurate quantitative analysis of PKB/Akt (and other protein) phosphoforms in GBM extracts. Using a novel nanofluidic Western-blot-like analysis system (“Blotless Nano Western”), various phosphorylation states of PKB/Akt were identified using phosphorylation-site mutants of Akt. The identity of these different forms of PKB/Akt protein was confirmed by comparing analytical profiles of mutant proteins at Thr-308 and Ser-473 to those obtained from samples of wild-type protein. The Blotless Nano Western system utilized a charge-based separation enabling resolution and detection of phosphorylated and non-phosphorylated protein isoforms in a single analysis. Following separation, proteins were immobilized in the capillaries. Antibodies to total PKB/Akt, phospho-Thr308, and phospho-Ser473 were then flowed through the capillaries followed by secondary antibodies coupled with reporter molecules (as used in conventional Western blotting procedures). Antibody binding was detected by high sensitivity chemiluminescence detection. Peak identification of the various PKB/Akt mutants analyzed by the Blotless Nano Western system and confirmation by other detection methods enabled identification of individual phospho-PKB/Akt peaks identified in extracts of patient samples. From this information, patient survival time and response to molecular targeted therapies may in the future be correlated to the Akt phosphorylation levels measured in GBM samples.
Clinical presentation of leptospirosis: a retrospective study of 34 patients admitted to a single institution in metropolitan France
Authors: S. Jauréguiberry, M. Roussel, G. Brinchault-Rabin, A. Gacouin, A. Le Meur, C. Arvieux, C. Michelet, P. Tattevin
Journal: Clinical Microbiology and Infection (2005)
A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells
Authors: Naomi Mochizuki, Seiichi Shimizu, Toshiro Nagasawa, Hideo Tanaka, Masafumi Taniwaki, Jun Yokota, Kazuhiro Morishita
Journal: Blood (2000)
Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia [see comments]
Authors: E Thiel, BR Kranz, A Raghavachar, CR Bartram, H Loffler, D Messerer, A Ganser, WD Ludwig, T Buchner, D Hoelzer
Journal: Blood (1989)
Abstract 2689: Breast cancer inhibition by a novel and potent biguanide, N1-hexyl-N5-benzyl-biguanide
Authors: Zhijun Guo, Kathryn J. Chavez, Juan Alvarez, Xia Zhang, Beverly Norris, Michael Maher, Monique Morgan, Robert J. Schumacher, Rebecca Cuellar, Irina F. Sevrioukova, Thomas L. Poulos, Ilia Denisov, Stephen G. Sligar, Kalpna Gupta, Ian A. Blair, Jorge Capdevila, Ameeta Kelekar, Elizabeth Amin, Gunda Georg, David A. Potter
Journal: Cancer Research (2014)

Abstract Metformin is a widely used biguanide diabetes drug that is associated with decreased breast cancer risk and is currently being studied for treatment and prevention of breast cancer. While metformin and biguanides buformin and phenformin exhibit inhibitory activity against breast cancer in vitro and in vivo, they lack potency (IC50=5-20 mM) and their mechanisms of action remain unclear. More potent biguanides may provide insights into biguanide anti-cancer activity and we therefore studied the novel biguanide N1-hexyl-N5-benzyl-biguanide mesylate (HBB), which potently inhibits the MCF-7 and MDA-MB-231 breast cancer lines (IC50=20 uM for both lines). HBB induces AMPK phosphorylation in both lines at 10 uM concentration, whereas similarly dosed metformin, buformin or phenformin exhibits no activity. HBB also inhibits STAT3 phosphorylation at 10 uM concentration, whereas metformin dosed at 10 uM exhibits no activity. HBB reduced the mitochondrial membrane potential of both lines, but the effect was more prominent in the MDA-MB-231 line. HBB also induced ROS within 2.5 hours of exposure in the MCF-7 and MDA-MB-231 lines and caused rapid necrosis, but not apoptosis. N-acetylcysteine provides partial protection from HBB for MDA-231 line, but not the MCF-7 line. HBB provides proof of principle that highly potent biguanides can be synthesized with at least 250-fold greater potency than metformin, which can provide insights into the cancer inhibitory mechanisms of biguanide drugs. R01 CA113570, Randy Shaver Foundation, CTSI University of Minnesota Citation Format: Zhijun Guo, Kathryn J. Chavez, Juan Alvarez, Xia Zhang, Beverly Norris, Michael Maher, Monique Morgan, Robert J. Schumacher, Rebecca Cuellar, Irina F. Sevrioukova, Thomas L. Poulos, Ilia Denisov, Stephen G. Sligar, Kalpna Gupta, Ian A. Blair, Jorge Capdevila, Ameeta Kelekar, Elizabeth Amin, Gunda Georg, David A. Potter. Breast cancer inhibition by a novel and potent biguanide, N1-hexyl-N5-benzyl-biguanide. [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 2689. doi:10.1158/1538-7445.AM2014-2689