tbuckley/cabot-search huggingface dataset:
Protease activated prodrugs as anti-cancer agents
Authors: Edwin L. Madison, Ofir Moreno, John Brekken, David Duncan, Scott Kemp, Davina Heller, Crystal Nakamoto
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4587 

Synthetic conjugation of cytotoxic agents to recognition sequences designed for activation by membrane associated tumor proteases is a strategy to enhance selective delivery of the therapeutic agent to tumor cells, resulting in improved efficacy and decreased cytotoxic side effects to non-tumor tissues. Urokinase plasminogen activator (u-PA) is a (chymo)trypsin-like serine protease that binds to the u-PA receptor expressed by a wide variety of human tumors, and high tumor u-PA activity correlates with poor patient survival and decreased disease free intervals for several human cancers. We have synthesized a novel doxorubicin (dox) prodrug that is efficiently activated by u-PA both in vitro and in vivo. Administration of CVS-10290 using a variety of dosing schedules, including once weekly, produced greater efficacy and lower toxicity than doxorubicin in multiple animal models of prostate and breast cancer. CVS-10290 may therefore represent a promising new class of anti-cancer prodrug that offers both greater efficacy and safety than conventional chemotherapy.
Percutaneous Aortic Valve Replacement for Severe Aortic Stenosis in High-Risk Patients Using the Second- and Current Third-Generation Self-Expanding CoreValve Prosthesis
Authors: Eberhard Grube, Gerhard Schuler, Lutz Buellesfeld, Ulrich Gerckens, Axel Linke, Peter Wenaweser, Barthel Sauren, Friedrich-Wilhelm Mohr, Thomas Walther, Bernfried Zickmann, Stein Iversen, Thomas Felderhoff, Raymond Cartier, Raoul Bonan
Journal: Journal of the American College of Cardiology (2007)
A cascade of arabinosyltransferases controls shoot meristem size in tomato
Authors: Cao Xu, Katie L Liberatore, Cora A MacAlister, Zejun Huang, Yi-Hsuan Chu, Ke Jiang, Christopher Brooks, Mari Ogawa-Ohnishi, Guangyan Xiong, Markus Pauly, Joyce Van Eck, Yoshikatsu Matsubayashi, Esther van der Knaap, Zachary B Lippman
Journal: Nature Genetics (2015)
Abstract 16564: Analysis of the Mechanisms of Intravenous Immunoglobulin-Resistant Kawasaki Disease Using iPS Cell Technology
Authors: Kazuyuki Ikeda, Tomonaga Ameku, Yui Nomiya, Masahiro Nakamura, Satoshi Matsui, Tomoyo Yahata, Akiko Okamoto-Hamaoka, Chinatsu Suzuki, Yuki Kuchitsu, Akira Watanabe, Kenji Osafune, Kenji Hamaoka
Journal: Circulation (2014)

Introduction: Kawasaki disease (KD) is a systemic vasculitis of unknown origin. Although the treatment of intravenous immunoglobulin (IVIG) significantly resolves inflammation, 10-20% of KD patients have persistent or recurrent fever after the administration of IVIG, and IVIG-resistant patients have a particularly high risk of developing coronary artery abnormalities. Hypothesis: The mechanisms of IVIG-resistant KD have been analyzed using the patients’ leukocyte samples. However, vascular endothelial cells (ECs), closely related to the vasculitis of KD, have not been examined in the previous reports. We propose a hypothesis that ECs are mainly involved in the etiology of IVIG-resistance. Methods: The purpose of this study is to establish new in vitro disease models of vasculitis using induced pluripotent stem cell (iPSC) technology, and clarify the mechanisms of IVIG-resistance in KD. Dermal fibroblasts or T cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by episomal vectors encoding Oct3/4, Sox2, Klf4, L-Myc, LIN28, and p53 shRNA. The iPSC lines were then differentiated into ECs by using a previously-reported differentiation method, and the EC samples were subjected to the microarray analyses. Results: The KD patient-derived iPSCs could be differentiated into ECs. The gene expression profiles were compared between iPS-derived ECs (iPS-ECs) generated from IVIG-resistant and IVIG-responsive KD patients. We found that 107 genes were at least two fold up-regulated and 101 genes were at least two fold down-regulated in iPS-ECs from IVIG-resistant KD patients compared with those from IVIG-responsive patients. The Principle Component Analysis (PCA) was performed, but the gene expression levels showed no significant differences between the groups. The Gene Set Enrichment Analysis (GSEA) revealed that the gene sets related to IL-6, NRAS (a member of the RAS oncogene family) and breast cancer were up-regulated in iPS-ECs from IVIG-resistant KD patients. Conclusions: Taking into account that the concentration of IL-6 has been reported to be elevated in acute phase of IVIG-resistant KD, our results suggest that the up-regulation of IL-6 related genes in ECs might be involved in the pathogenesis of IVIG-resistant KD.
Fluoxetine in the treatment of borderline and schizotypal personality disorders
Authors: P J Markovitz, J R Calabrese, S C Schulz, H Y Meltzer
Journal: American Journal of Psychiatry (1991)

Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful.
Past clinical studies and future directions.
Authors: J. Robert Stewart
Journal: Cancer Research (1984)

The biological rationale for hyperthermia and radiation is strong, initial results in superficial tumor sites have established efficacy in human cancer, and deep tumor sites are beginning to yield to our efforts at deep regional heating. Major thrusts of new clinical research should go toward improved equipment and defining techniques with existing devices, which can lead us into definitive Phase III trials to assess the role of regional hyperthermia in primary multimodality management of cancer. Detailed thermometry is an absolute requirement for all future clinical studies. Invasive techniques to achieve deep hyperthermia are under investigation and may prove to be useful. Whole-body hyperthermia with radiation and/or chemotherapy has been less well studied in the laboratory than has local hyperthermia, and studies to show clinical efficacy in humans are lacking.
Urinary neopterin levels discriminate active from latent mycobacterium tuberculosis infection
Authors: Michael Eisenhut, Dougal Hargreaves, Anne Scott, David Housley, Andrew Walters, Rohinton Mulla, Parthipan Kanthapillai, James Ramsay, Oliver Eikenberg, Ralf Edelmann
Journal: European Respiratory Journal (2011)

Background: A biomarker to discriminate active from latent mycobacterium (m.) tuberculosis infection could help in exclusion of occult tuberculosis and avoid under treatment of those patients. Neopterin is released by macrophages in response to stimulation by interferon gamma.

Objective: To assess whether urinary levels of neopterin can discriminate between latent and active mycobacterium tuberculosis infection.

Methods: Urinary neopterin/creatinine ratio's were determined in patients with active and latent m. tuberculosis infection and controls without m. tuberculosis infection. Latent m. tuberculosis infection was defined as reactive interferon gamma release assay for m. tuberculosis in the absence of active disease.

Results: Seven patients with active tuberculosis, 27 patients with latent m. tuberculosis infection and seven controls were recruited. There was no difference in age or gender between groups. Urinary neopterin/creatinine ratio was higher in patients with active tuberculosis (412.8 micromol/mol, 95% CI 89.7 to 735.8) than patients with latent m tuberculosis infection (147.5 micromol/mol, 95% CI 114.0 to 180.8) and controls (122.2 micromol/mol, 95% CI 71.2 to 173.1) (p<.01). ROC curve analysis revealed an area under the curve of 0.81 (95% CI 0.62 to 0.99). A cut-off of 349 micromol/mol showed 100% diagnostic specificity in detection of active tuberculosis in people with m. tuberculosis infection.

Conclusions: Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent m. tuberculosis infection. These findings suggest that neopterin appears to be a suitable marker to reflect tuberculosis disease activity.
Reforming the Continuing Medical Education System
Authors: Steven E. Nissen
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
The Pentothal Test in the Management of Orthopaedic Patients with Hysterical Illness
Authors: M S Cornell, T Ahktar, R N S Slater, C J Walker
Journal: Journal of the Royal Society of Medicine (1996)

Hysterical illness may be defined as symptoms normally associated with disease without pathological basis. Orthopaedics attracts more of these patients than most specialties. They are intensively and expensively investigated, yet clinicians remain anxious they are missing genuine pathology. We use examination under pentothal, without analgesia, to help distinguish real from imagined symptoms. The results of a review of patients evaluated under pentothal over the past two years are presented.
Abstract P331: Associations Of Coronary Heart Disease With Common Carotid Artery Near And Far-wall Intima-Media Thickness (IMT): The Multi-Ethnic Study Of Atherosclerosis.
Authors: Joseph F Polak, Moyses Szklo, Daniel H O'Leary
Journal: Circulation (2014)

Background: Intima-media thickness (IMT) as measured on ultrasound images of the common carotid artery (CCA) is associated with cardiovascular events and used to measure the effects of lipid lowering interventions. Far wall CCA IMT is favored over near wall IMT based on the physics of ultrasound. Materials and Methods: We studied 6606 members of the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study (mean age 62.1 years; 52.7% female) who had near wall and far wall CCA IMT measurements. Multivariable linear regression models were used to estimate model goodness-of-fit of near wall IMT, far wall IMT, and mean IMT with Framingham risk factors (FRF). Multivariable Cox proportional hazards models were used to estimate hazard ratios for incident coronary heart disease (CHD) events for each IMT variable. Change in Harrell’s C-statistic was used to compare the incremental value of each IMT variable when added to FRF. Results: Mean IMT had the strongest association with risk factors (R2 = 0.31), followed by the near wall (R2 = 0.26) and far wall IMT (R2 = 0.22). Far wall IMT improved the prediction of coronary artery disease events (change in C statistic: 0.009; 95% Confidence Intervals: 0.004, 0.015; p= 0.001) as did mean IMT (p=0.033) but near wall IMT did not. Conclusion: Far wall CCA IMT had the strongest association with incident CHD whereas combined near wall and far wall IMT had the strongest association with risk factors. Selected IMT variables may give different results in intervention trials than in outcome studies.
COBRA VENOM INEFFECTIVE IN TWO CASES
Authors: Wingate M. Johnson
Journal: Annals of Internal Medicine (1940)

Case Reports1 August 1940COBRA VENOM INEFFECTIVE IN TWO CASESWINGATE M. JOHNSON, M.D., F.A.C.P.WINGATE M. JOHNSON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-2-325 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the Annals of Internal Medicine for April 1938, Dr. David I. Macht presented an intriguing article on the use of cobra venom for the relief of persistent pain. The impression was left with this reader, at least, that cobra venom was usually so effective in relieving persistent pain that it could be substituted for opium derivatives, and that in doses at intervals of two to four days it would keep a patient as comfortable as would several doses a day of morphine.Since the only way properly to evaluate a new, or newly discovered, drug clinically is for enough... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Winston-Salem, North Carolina*Received for publication December 9, 1938. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1940Volume 14, Issue 2Page: 325-325KeywordsDrugsMorphineOpiumVenoms ePublished: 1 December 2008 Issue Published: 1 August 1940 PDF downloadLoading ...
A foodborne outbreak due to Cryptosporidium parvum in Helsinki, November 2008
Authors: A Pönka, H Kotilainen, R Rimhanen-Finne, P Hokkanen, M L Hänninen, A Kaarna, T Meri, M Kuusi
Journal: Eurosurveillance (2009)

We report the first foodborne outbreak caused by Cryptosporidium parvum in Finland. The outbreak occurred among personnel of the Public Works Department in Helsinki, who had eaten in the same canteen. 72 persons fell ill with diarrhoea, none was hospitalised. Four faecal samples obtained from 12 ill persons were positive for Cryptosporidium by an antigen identification assay and microscopy. The vehicle of infection could not be identified with certainty but a salad mixture was suspected.
Abstract 9: Early, Single-Dose Post-Burn Estrogen Significantly Decreases Lung Inflammation and Improves Lung Function 7 Days Following Severe Bum Injury
Authors: Jane G Wigginton, Joshua W Gatson, David L Maass, James W Simpkins, Robert Barber, Qun Zang, Ryan Huebinger, Sue Yi, Katharine G Wigginton, Paul E Pepe, Joseph P Minei, Ahamed H Idris
Journal: Circulation (2010)

Objective: In patients with severe burn injury, the most common cause of morbidity and mortality is pulmonary dysfunction. We tested estrogen, an anti-oxidant, anti-apoptotic, and anti-inflammatory...
Cirmtuzumab Vedotin (UC-961ADC3), An Anti-ROR1-Monomethyl Auristatin E Antibody-Drug Conjugate, Is a Potential Treatment For ROR1-Positive Leukemia and Solid Tumors
Authors: Bing Cui, George F. Widhopf, Charles E. Prussak, Christina C.N. Wu, Anil Sadarangani, Suping Zhang, Fitzgerald Lao, Catriona HM Jamieson, Dennis A. Carson, Thomas J. Kipps
Journal: Blood (2013)
Abstract 9248: GATA-4 Gene Transfer Increases Mesenchymal Stem Cell Mediated Myocardial Salvage Through Regulating Expression of miRNAs
Authors: Bin Yu, Zeeshan Pasha, Yigang Wang, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2011)

Recent studies have provided increasing evidence that microRNAs (miR) play an important role in ischemic heart repair. We have previously reported that GATA-4 gene transfection increases mesenchymal stem cells (MSC) mediated cardioprotection. In this study, we investigated whether the cardioprotective effect of MSC overexpressing GATA-4 was associated with regulation of miR. Methods and Results: MSC were transduced with GATA-4 (MSC GATA-4 ) using the murine stem cell virus (pMSCV) retroviral expression system, control cells were transduced with empty vector (MSC Null ). The expression of miR in MSC was assessed by miR microarray and quantitative real-time PCR. Primary cultured cardiomyocytes (CM) were obtained from neonatal rat ventricles. Hypoxic treatment was used to mimic ischemic injury. The cardioprotection in vitro of MSC GATA-4 was examined through measurements of Lactate dehydrogenase release, MTT intake, and Annexin-V staining. To further determine the effect of MSC GATA-4 on ischemic myocardium, MSC were injected into the peri-infarct region in myocardial infarction model in SD rats developed by ligation of the left anterior descending coronary artery (LAD). Overexpression of GATA-4 regulated several miR expression in MSC, especially, downregulation of miR-15b, miR-16, and miR-195 which belong to miR-15 family, and upregulation of miR-221/222. MSC GATA-4 markedly protected CM against ischemic injury. Quantitative fluorescence in situ hybridization and immunostaining results showed that miR-221 as well as Bcl-w and VEGF, two proteins of target genes of miR-15 family, were transferred from MSC to CM. Gap junctions were observed between CM and MSC in a co-culture system. MSC GATA-4 treated animals showed significantly improved cardiac function by echocardiography. Furthermore, histological studies revealed reduced infarction size. Conclusions: Overexpression of GATA-4 regulates miR expression in MSC, which plays an important role in protection of myocytes from ischemia.
Minimize interobserver differences.
Authors: D H Spodick
Journal: Circulation (1976)

In an otherwise interesting article on the value of aprindine in the treatment of ouabain-induced ventricular rhythms in dogs, the authors discuss the results of treatment by aprindine.1Aprindine was injected at a rate of 0.36 mg/kg every 2 minutes up to a total amount of 2.9 mg/kg.The authors used that scheme because it was "clinically recommended" and they found aprindine to be the most effective drug in suppressing ouabain-induced ven- tricular rhythms.As the first investigator and clinician to use aprindine in human subjects and to demonstrate its effectiveness as an antiarrhythmic drug, I established that a repetitive injection of about 20 mg (0.3 mg/kg) every 2 minutes in human subjects up to a total dosage of about 150 (2 mg/kg) is an effective and safe way to administer aprindine intravenously.'I Moreover, in the very first and subse- quent publications concerning the clinical use of the drug, it has been both mentioned and demonstrated that aprindine is effective in suppressing ventricular and supraventricular arrhythmias due to digitalis intoxication.2'These findings were not acknowledged by the authors.Aprindine HC is now widely used in Europe and can be con- sidered as a very valuable addition to the existing list of anti- arrhythmic drugs.
Abstract 3265: Influence of a Lipid Lowering Therapy on Calcified and Non-Calcified Coronary Plaques Monitored by Multi-Slice Detector Computed Tomography: Results of the New Age-II-Study
Authors: Christof Burgstahler, Torsten Beck, Anja Reimann, Axel Kuettner, Harald Brodoefel, Martin Heuschmid, Andreas F Kopp, Stephen Schroeder
Journal: Circulation (2006)
Sirt1 mediates the effect of the heme oxygenase inducer, cobalt protoporphyrin, on ameliorating liver metabolic damage caused by a high-fat diet
Authors: Xiaojun Liu, Yong Gao, Meixia Li, Chao Geng, Haifeng Xu, Yaoguo Yang, Yongjun Guo, Tao Jiao, Fude Fang, Yongsheng Chang
Journal: Journal of Hepatology (2015)
Extended-spectrum and CMY-type b-lactamase-producing Escherichia coli in clinical samples and retail meat from Pittsburgh, USA and Seville, Spain
Authors: Y. Doi, D.L. Paterson, P. Egea, A. Pascual, L. López-Cerero, M.D. Navarro, J.M. Adams-Haduch, Z.A. Qureshi, H.E. Sidjabat, J. Rodríguez-Baño
Journal: Clinical Microbiology and Infection (2009)
Relationship between London chest daily living activity scale and i-BODE index in COPD
Authors: Ezgi Simsek Utku, Dicle Yilmaz Kaymaz, Pinar Ergun, Pervin Demir, Nilgun Mendil Alptekinoglu, Ipek Candemir, Nese Demir
Journal: European Respiratory Journal (2013)

INTRODUCTION-AIM: Positive effects of the increase of exercise capacity on daily living activity is one of the biggest targets for COPD patients going on Pulmonary Rehabilitation(PR) programmes. In this study, it was aimed to evaluate the relationship between i-BODE index, a multi-scoring system evaluating exercise capacity by Incremental Shuttle Walk Test(ISWT), and London Chest Activity of Daily Living(LCADL) scale which is used for evaluating daily living activities.  MATERIALS-METHODS: 38 patients directed for PR programme with COPD diagnosis were evaluated before PR by methods below: Body composition by bioelectrical impedance system,obstruction grading by lung function tests, dyspnea perception by Modfied Medical Research Council(MMRC), exercise capacity by Incremental Shuttle Walk Test(ISWT), daily living activity by London Chest Activity of Daily Living (LCADL) scale.  RESULTS: Mean age of the cases were 61.61±6.08 years and 34 were male. Median value for LCADL was found 18.5, ISWT 220 meters(interquartile range: 205 m.), FEV1 %33(interquartile range: %21) and i-BODE index 5. The relationship between total score of daily living activity and MRC, ISWT, FEV1 and i-BODE index was found statistically significant(in order r=0.441 p=0.006, r=-0.557 p  DISCUSSION: This study showed that during configuring personal PR programmes in COPD, daily living activities must take part in the initial evaluation with the other compounds.
<i>FTO</i> Obesity Variant Circuitry and Adipocyte Browning in Humans
Authors: Melina Claussnitzer, Simon N. Dankel, Kyoung-Han Kim, Gerald Quon, Wouter Meuleman, Christine Haugen, Viktoria Glunk, Isabel S. Sousa, Jacqueline L. Beaudry, Vijitha Puviindran, Nezar A. Abdennur, Jannel Liu, Per-Arne Svensson, Yi-Hsiang Hsu, Daniel J. Drucker, Gunnar Mellgren, Chi-Chung Hui, Hans Hauner, Manolis Kellis
Journal: New England Journal of Medicine (2015)

Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive.