tbuckley/cabot-search huggingface dataset:
Tasidotin HCl (formerly ILX651), a tubulin-binding dolastatin-15 analog, demostrates a wide spectrum of In Vivo antitumor activity
Authors: Larry Arthaud, Katherine Martinez, Stephanie Roth, Roy Krumbholz, Murray Stackhouse, Steve Weitman
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5876 

Tasidotin HCl is a synthetic pentapeptide derivative of dolastatin-15 with a unique mechanism of action that potentially differs from that of microtubulin stabilizers (taxanes and epothilones) and tubulin inhibitors (vinca alkaloids). Tasidotin HCl at low concentrations inhibits microtubule nucleation or elongation which is likely to disrupt mitotic spindle formation and mitosis. The objective of the present investigation was to evaluate the in vivo activity of Tasidotin HCl against a wide variety of human cancer cell lines, including Hep-3B hepatic, Caki-1 renal, A-673 rhabdomyosarcoma, H-Meso-1 mesothelioma, RL lymphoma, and RPMI-8226 multiple myeloma. Treatment was initiated when median SC tumor size was approximately 150-200 mm3. Tasidotin HCl was administered IP daily times 5 for 2 weeks dosing regimen at 125, 62.5, and 31.25 mg/kg/day for all of the tumor lines, except for RL and RPMI-8226 (only high dosage administered). Tasidotin HCl was well tolerated (≤20% body weight loss or toxic deaths) at the 125 mg/kg/day dosage for the Caki-1 tumor cell line, and at the 62.5 and 31.25 mg/kg/day dosages for the remaining tumor lines. Tasidotin HCl was very effective against the A-673 rhabdomyosarcoma and H-Meso-1 mesothelioma xenografts producing median tumor growth delays (T-C) of >76.5 and >20.4 days, respectively, at the 62.5 mg/kg/day dosage level. In the A-673 rhabdomyosarcoma study, there were ten complete regressions in animals that remained tumor free at the conclusion of the study. Tasidotin HCl was moderately effective against Caki-1 renal cell carcinoma and Hep-3B hepatocellular xenografts producing median tumor growth delays of 10.5 and 9.5 days, respectively, at the 62.5 mg/kg/day dosage level. Tasidotin HCl at a dosage of 125 mg/kg/day was very active against RL and RPMI-8226 tumor xenografts with tumor growth delays of 49.4 and 30.8 days and 6/10 and 4/10 complete responses in surviving mice, respectively. Due to numerous toxic deaths, the RL and RPMI-8226 studies are currently being repeated at lower dosage levels. These data indicate that Tasidotin HCl has good antitumor activity in vivo against a variety of different types of tumor cell lines.
Embryonal Carcinoma P19 Cells Produce Erythropoietin Constitutively But Express Lactate Dehydrogenase in an Oxygen-Dependent Manner
Authors: Taiho Kambe, Junko Tada, Mariko Chikuma, Seiji Masuda, Masaya Nagao, Terumasa Tsuchiya, Peter J. Ratcliffe, Ryuzo Sasaki
Journal: Blood (1998)

Abstract Embryonic stem cells and embryonal carcinoma P19 cells produce erythropoietin (Epo) in an oxygen-independent manner, although lactate dehydrogenase A (LDHA) is hypoxia-inducible. To explore this paradox, we studied the operation of cis-acting sequences from these genes in P19 and Hep3B cells. The Epo gene promoter and 3′ enhancer from P19 cells conveyed hypoxia-inducible responses in Hep3B cells but not in P19 cells. Together with DNA sequencing and the normal transcription start site of P19 Epo gene, this excluded the possibility that the noninducibility of Epo gene in P19 cells was due to mutation in these sequences or unusual initiation of transcription. In contrast, reporter constructs containing LDHA enhancer and promoter were hypoxia inducible in P19 and Hep3B cells, and mutation of a hypoxia- inducible factor 1 (HIF-1) binding site abolished the hypoxic inducibility in both cells, indicating that HIF-1 activation operates normally in P19 cells. Neither forced expression of hepatocyte nuclear factor 4 in P19 cells nor deletion of its binding site from the Epo enhancer was effective in restoring Epo enhancer function. P19 cells may lack an unidentified regulator(s) required for interaction of the Epo enhancer with Epo and LDHA promoters.
Prevention of Contrast-Induced Nephropathy With Sodium Bicarbonate
Authors: Robert E Siegel
Journal: JAMA (2004)

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
Prophets, Cults and Madness
Authors: Trevor Turner
Journal: BMJ (2001)

Anthony Stevens, John Price 

Duckworth, £18, pp 256

ISBN 0 7156 2940 9

Rating: ![Graphic][1] ![Graphic][2]    ![][3] 

Schizophrenia is puzzling. The strong influence of genetics in its aetiology is not a sufficient and full explanation of why some people become hallucinated, deluded, disordered in thinking, and socially excluded. Its lifetime prevalence, just under 1% worldwide, is also unusual. The question of whether there might be some evolutionary advantage from the condition has therefore led to an increasingly influential evolutionary psychiatry. Stevens and Price are admirably qualified in this respect, and they have chosen cult leaders as the focus …

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Level of Exercise and Risk of Cardiovascular Disease
Authors: Lorraine L. Tosiello, Nallu Reddy
Journal: JAMA (2004)

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
Abstract 77: Regional Variation in the Incidence of OHCA and Bystander CPR
Authors: Lahn Straney, Janet Bray, Judith Finn, Karen Smith
Journal: Circulation (2014)

Background:  Bystander CPR is a significant predictor of survival among people who have an out of hospital cardiac arrest (OHCA). We aimed to identify areas with a high incidence of OHCA and low rates of bystander CPR, across a population of 5.7 million in the State of Victoria (Australia).   Methods:  We extracted adult data for presumed cardiac OHCAs from the Victorian Ambulance Cardiac Arrest Registry for 2008 to 2011. We calculated the incidence of OHCA in Victorian Local Government Areas (LGAs) using yearly population data from the Australian Bureau of Statistics, and bystander CPR rates for each LGA.  For the incidence rate (log-transformed) and the bystander CPR rate we calculated the standard score (Z-score) using the mean and standard deviation among all LGAs, and standardized by dividing the standard deviation by the square root of the population in each LGA.   Results:  Over the study period there were 22,990 OHCA attended. The mean annual incidence rate of OHCA among LGAs was 91.9 cases per 100,000 population (IQR: 71.5-106.5). The rate of CPR for bystander witnessed OHCAs was 59.6%, the median value among LGAs was 58.6% (IQR: 51.3%-70.6%).  The figure shows significant variation in the rate of bystander CPR across regions. The bubble size indicates the relative volume of cases. The LGA highlighted in green represents Melbourne Central Business District, where arrests are more likely to occur in public places. The box outlined in the lower right indicates those LGAs with low bystander CPR and high incidence of OHCA. This LGA highlighted in yellow was ranked first in the state in an index of socio-economic disadvantage for 2011.   Conclusions:  Our data supports reports of regional variation in OHCA incidence and bystander CPR rates -which in our case occured even across a large metropolitan city and among bystander witnessed OHCAs. Visualising bystander CPR rates in the context of OHCA incidence and volume identifies those regions where there is the greatest capacity to improve survival.
Do <i>GST</i> Polymorphisms Modulate the Frequency of Chromosomal Aberrations in Healthy Subjects?
Authors: Pavel Vodicka, Alessio Naccarati, Ludmila Vodickova, Veronika Polakova, Maria Dusinska, Ludovit Musak, Erika Halasova, Simona Susova, Pavel Soucek, Kari Hemminki
Journal: Environmental Health Perspectives (2009)
ABC of antithrombotic therapy: Antithrombotic therapy in acute coronary syndromes
Authors: R. D S Watson
Journal: BMJ (2002)

The use of antithrombotic therapy in acute coronary syndromes has reduced the incidence of death and Q wave myocardial infarction dramatically in recent years. Antithrombotic drugs in routine use include antiplatelet drugs (aspirin, clopidogrel, and glycoprotein IIb/IIIa receptor antagonists) and anticoagulants (unfractionated and low molecular weight heparin, warfarin, and direct thrombin inhibitors).



Thrombosis in relation to acute coronary syndromes



Thrombosis is the basic pathophysiological process underlying the acute coronary syndromes. Thus, antithrombotic therapy is the cornerstone of management, and the appropriate choice of antithrombotic drugs to reduce platelet aggregation or interfere with the clotting process can be critical.

Rupture of the fibrous cap of an atheromatous plaque exposes the lipid core, which is highly thrombogenic and contains an abundance of procoagulant tissue factor. Plaque rupture (exposing surface binding glycoproteins) allows platelets to adhere to the plaque, become activated, and release thromboxane A2, which causes further platelet aggregation and vasoconstriction. As the platelets aggregate around the ruptured plaque, membrane glycoprotein IIb/IIIa receptors undergo a configuration change to bind fibrinogen and form a complex platelet linkage. Further incorporation of fibrin and red blood cells within this platelet-rich thrombus results in a partial or total occlusion of the coronary artery. Alternatively, thrombus may break off from a ruptured plaque and occlude a downstream vessel. Occlusion may also follow from trapping of circulating thrombi formed elsewhere in the circulation.



Thrombus within right coronary artery (arrow) in a patient with unstable angina





Reduction of adverse events in patients treated with aspirin, heparin, or both compared with neither drug



### Antiplatelet drugs

#### Aspirin 

Aspirin has been in use for more than 150 years and is cheap and effective. It has been shown to reduce the risk of fatal and non-fatal myocardial infarction by at least 50% in patients with unstable angina. Aspirin blocks cyclo-oxygenase and formation of thromboxane A2, thus …
Lesson of the week: Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate * Commentary: Exogenous glucocorticoids influence adrenal function, but assessment can be difficult
Authors: A J Drake
Journal: BMJ (2002)

Children taking high dose fluticasone propionate may present with hypoglycaemia secondary to iatrogenic adrenal suppression
Website of the week: Privacy and confidentiality
Authors: D. Carnall
Journal: BMJ (1999)

The criticism by the Association of Community Health Councils of England and Wales (ACHCEW) of the GMC's latest pronouncements on patient confidentiality are reported elsewhere in the BMJ (p 336). ACHCEW does have a single web page at www.nhsconfed.net/achcew/, which does not seem to be undated often, but a minimalist web presence is still worth having: …
OLD AGE IN THE BIBLE AND POETRY
Authors: L A M KRAUSE
Journal: Annals of Internal Medicine (1952)

Article1 January 1952OLD AGE IN THE BIBLE AND POETRYLOUIS A. M. KRAUSE, M.D., F.A.C.P.LOUIS A. M. KRAUSE, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-1-152 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe finest description of old age, describing its organic changes in classical prose, is found in the Book of Ecclesiastes, written about 400 years more or less before the days of Christ. Let us consider each verse separately, looking at it through medical eyes."Remember now thy creator in the days of thy youth While the evil days come not nor the years draw nigh when thou shalt say I have no pleasure in them."Here obviously the speaker is talking to young people, saying "remember thy creator in the days of thy youth." This we must always emphasize... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LOUIS A. M. KRAUSE, M.D., F.A.C.P.Affiliations: Baltimore, Maryland*Delivered under the title, "A Biblical Introduction to Geriatric Medicine," at the Thirty-second Annual Session of the American College of Physicians, St. Louis, Mo., April 13, 1951. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1952Volume 36, Issue 1Page: 152-156KeywordsAdolescentsGeriatrics ePublished: 1 December 2008 Issue Published: 1 January 1952 PDF downloadLoading ...
Communicating with Medical Patients
Authors: Moira Stewart, Debra Roter
Journal: Annals of Internal Medicine (1990)

INTRODUCTION - Moira Stewart and Debra Roter The Need for a Transformed Clinical Method - Ian McWhinney PART ONE: TRANSFORMING THE PHYSICIAN Doctors Learning Communication Skills - W Wayne Weston and Mack Lipkin Jr Developmental Issues Balint Groups in Clinical Training - Jacques Frenette and Fernand Blondeau Physician Self-Awareness - Mark F Longhurst The Neglected Insight PART TWO: APPLYING THE NEW CLINICAL METHOD The Importance of Patient's Beliefs - W Wayne Weston and Judith Belle Brown Evaluating the Patient's Primary Problem(s) - Richard Frankel and Howard Beckman Eliciting Patients' Feelings - Antony Cox Patient-Centered Clinical Interviewing - Joseph H Levenstein et al PART THREE: TEACHING AND EVALUATION Consultation Skills of Young Doctors - Benefits of Undergraduate Feedback Training in Interviewing - Peter Maguire, Susan Fairbairn and Charles Fletcher A Model for Teaching Doctor-Patient Communication during Residency - Theo Schofield and Paul Arntson Curriculum Structuring to Enhance Communication Skill Development - Suzanne Kurtz Evaluating Undergraduate Training - A Checklist for Medical Interviewing Skills - Herro Kraan et al PART FOUR: RESEARCH ISSUES A. ASSESSING AND SYNTHESIZING THE LITERATURE Which Facets of Communication have Strong Effects on Outcome - A Meta Analysis - Debra Roter Design Issues in Research on Doctor-Patient Communication - Thomas S Inui and William B Carter Analysis of Verbal and Non-Verbal Behavior in Doctor-Patient Encounters - William B Stiles and Samuel M Putnam B. FUTURE DIRECTIONS Outcome Based Research on Doctor-Patient Communication - Howard Beckman, Sherrie H Kaplan and Richard Frankel A Review The Impact of the Doctor-Patient Relationship on Outcomes of Chronic Disease - Sherrie H Kaplan, Sheldon Greenfield and John E Ware Jr The Past and the Future of Research in Doctor-Patient Relations - Barbara M Korsch
Abstract 17798: “The Left Main Coronary Artery - A Potential Hazard During Ablation of Left Atrial and Outflow Tract Arrhythmias”
Authors: Katie A Walsh, Gerard J Fahy
Journal: Circulation (2014)

Introduction: Left main coronary artery (LMCA) damage is an uncommon but catastrophic complication of cardiac ablation procedures. Tissue necrosis can occur within 5 mm of radiofrequency (RF) energy application, with highest risk within 2mm. Hypothesis: We tested the hypothesis that the LMCA may be exposed to risk of injury in RF ablation procedures for left atrial and outflow tract arrhythmias. The anatomic relationship of the LMCA to these adjacent structures was assessed using analysis of computed tomographic coronary angiograms (CTCA). Methods: We studied 100 patients (55 males, age 51±10 years) who were investigated for chest pain with CTCA acquired using General Electric Discovery CT 750 HD (GE Healthcare, GE Medical Systems, Milwaukee, WI) with slice thickness of 0.625mm. Measurements were made of the LMCA and adjacent structures, and the relationships between them were described by analysis of 2D images and 3D reconstructions using OsiriX open-source DICOM viewer (OsiriX; Pixmeo, Geneva, Switzerla...
Clinics, Hospitals and Health Centers.
Authors: Michael Marks Davis
Journal: JAMA (1928)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Percutaneous Mitral Valve Repair Using the Edge-to-Edge Technique
Authors: Ted Feldman, Hal S. Wasserman, Howard C. Herrmann, William Gray, Peter C. Block, Patrick Whitlow, Fred St. Goar, Leonardo Rodriguez, Frank Silvestry, Allan Schwartz, Timothy A. Sanborn, Jose A. Condado, Elyse Foster
Journal: Journal of the American College of Cardiology (2005)
Abstract 4544: Induction of KLF4 by LOR-253 as an innovative therapeutic approach to induce apoptosis in acute myeloid leukemia
Authors: Ronnie Lum, Mojib Javadi, Tiffany Cheng, Robert Peralta, Howard Cukier, Jeff Lightfoot, Yoon Lee, Aiping Young, William G. Rice
Journal: Cancer Research (2014)

Abstract LOR-253, a small molecule anticancer agent that acts through induction of the tumor suppressor Krüppel-like factor 4 (KLF4), has demonstrated antitumor activity as a single agent in a Phase I study in patients with advanced or metastatic solid tumors. Recently, the vast majority of patients with acute myeloid leukemia (AML) were shown to inappropriately express the embryonic CDX2 gene in bone marrow stem and progenitor cells, resulting in down-regulation of KLF4 expression as the leukemogenic event. Consequently, we examined the antitumor activity and mechanism of action for LOR-253 in AML cells and cells representing other hematological malignancies. Indeed, LOR-253 was found to inhibit proliferation of various human leukemia and lymphoma cell lines in vitro with low nM IC50 values. Further LOR-253 induced high levels of KLF4 mRNA expression in AML cells and a resultant significant increase in expression of p21, a cyclin-dependent kinase inhibitor that is transcriptionally regulated by KLF4. Consistent with these findings, in AML cells we found that LOR-253 induced G1/S cell cycle arrest and apoptosis, based on positive Annexin V staining, activated caspase-3, and increased BAX mRNA expression. Studies are underway to further characterize the pathway that mediates KLF4 induction by LOR-253, to characterize the effects of LOR-253 in combination with approved chemotherapies for AML, and to assess the efficacy of LOR-253 in animal models of AML. Induction of KLF4 represents a novel approach to the treatment of AML and other hematologic malignancies, and LOR-253 is the only clinical stage agent to act through this mechanism of action. Citation Format: Ronnie Lum, Mojib Javadi, Tiffany Cheng, Robert Peralta, Howard Cukier, Jeff Lightfoot, Yoon Lee, Aiping Young, William G. Rice. Induction of KLF4 by LOR-253 as an innovative therapeutic approach to induce apoptosis in acute myeloid leukemia. [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 4544. doi:10.1158/1538-7445.AM2014-4544