tbuckley/cabot-search huggingface dataset:
Abstract 2671: Structural analysis of the inhibitory mechanism of AP24534, a pan-BCR-ABL inhibitor overriding the T315I gatekeeper mutation
Authors: Xiaotian Zhu, Tianjun Zhou, William C. Shakespeare, Wei-Sheng Huang, Lois Commodore, Chester A. Metcalf, Yihan Wang, Mathew Thomas, Raji Sundaramoorthi, Dong Zou, Tomi K. Sawyer, Tim Clackson, David C. Dalgarno
Journal: Cancer Research (2010)

Abstract Although durable response in many chronic myeloid leukemia (CML) patients can be achieved by imatinib treatment, point mutations in the kinase domain of the BCR-ABL fusion protein can lead to drug resistance and relapse. Nilotinib and dasatinib, the two second generation Abl kinase inhibitors, are active against most imatinib resistant mutants with a few exceptions, particularly the T315I gatekeeper residue mutation. Using a structure-based approach we have identified AP24534, a molecule that potently inhibits the T315I mutant and all other mutants tested, thus acting as a pan-BCR-ABL inhibitor. To elucidate the basis for this unique profile of AP24534, we have used a combination of X-ray crystallographic and structure-activity relationship analysis on AP24534 and its analogs. The crystal structure of the T315I mutant Abl in complex with the inhibitor clearly demonstrates that AP24534 binds to Abl in a DFG-out binding mode with the ethynyl chemical moiety skirting the mutated gate-keeper residue avoiding steric clashes. The X-ray co-structures of both the wild type and the T315I mutant Abl, in conjunction with the SAR analysis, further reveal that AP24534 retains potency against the T315I and other imatinib-resistant ABL mutants through optimized multiple points of contact, balancing and distributing the overall binding affinity so that mutation-based disruption of one facet of the binding network results in only a slight reduction in binding affinity. Our structural analysis enables us to predict and rationalize the different degree of sensitivity of ABL point mutants to AP24534, and to understand how AP24534 can completely abrogate resistance in cell-based mutagenesis screens at relatively low concentrations. AP24534 is currently being investigated in a Phase I clinical trial in patients with refractory and resistant CML and other hematological malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2671.
Abstract 4605: CDIP-BAP31 complex bridges endoplasmic reticulum and mitochondria during ER-stress mediated apoptosis.
Authors: Takushi Namba, Fang Tian, Kiki Chu, So-Young Hwang, Sam W. Lee
Journal: Cancer Research (2013)

Abstract Resolved ER stress response is fundamentally essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. In addition, imbalances in homeostasis would result in improper cell functioning that may become an important pathogenic factor in a number of prevalent diseases, including neurodegenerative diseases, metabolic disorders, and cancers. However, the molecular mechanisms relating ER stress to apoptosis still remain largely unfamiliar. Here, we show that a proapoptotic p53 target, CDIP, acts as a key signal transducer of ER stress response. Applying a biochemical/proteomics approach, we characterize BAP31, B-cell receptor-associated protein 31 that is an integral protein of ER and known to crosstalk with mitochondrial proteins during the apoptosis process, as an interacting partner of CDIP. Upon ER stress, CDIP is induced and enhances an association with BAP31 at the ER membrane. We found that the CDIP-BAP31 complex formation is essential for ER stress-mediated apoptotic process. CDIP-/- or CDIP knock-down cells are strongly resistant to ER-stress-induced apoptosis. Moreover, we show that CDIP up-regulation and binding to BAP31 is required for BAP31 cleavage via caspase-8 activation in response to ER stress and also responsible for BAP31-Bcl-2 association, then resulting in Bcl-2 sequestration from BAX. The recruitment of Bcl-2 with BAP31-CDIP complex triggers BAX oligomerization/activation that causes its translocation to the mitochondria, followed by cyctochrome c release. Genetic knockout of CDIP in mice also leads to impaired response to ER-stress-mediated apoptosis, likely through reduced BAX activation. Together, our data demonstrate that the CDIP-BAP31→Bcl-2/BAX regulatory circuit represents a novel mechanism for establishing an ER-mitochondrial cross-talk for ER stress-mediated apoptosis signaling. Citation Format: Takushi Namba, Fang Tian, Kiki Chu, So-Young Hwang, Sam W. Lee. CDIP-BAP31 complex bridges endoplasmic reticulum and mitochondria during ER-stress mediated apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4605. doi:10.1158/1538-7445.AM2013-4605
Postexposure Treatment of People Exposed to the Human Immunodeficiency Virus through Sexual Contact or Injection-Drug Use
Authors: Mitchell H. Katz, Julie Louise Gerberding
Journal: New England Journal of Medicine (1997)

Among health care workers who have occupational exposures to the human immunodeficiency virus (HIV), a recent case–control study indicates that treatment with zidovudine after exposure decreases the odds of HIV infection by 79 percent.1 Although this observation has not been confirmed in a randomized, controlled trial, antiretroviral treatment is now the standard of care in the event of a parenteral occupational exposure to HIV.24 The probability of HIV infection due to puncture by a contaminated needle is similar to that estimated for a single episode of unprotected receptive anal or vaginal intercourse with an infected partner or for a . . .
Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study
Authors: L. MOLIN, T.P. CUTLER, I. HELANDER, B. NYFORS, N. DOWNES
Journal: British Journal of Dermatology (1997)

The efficacy, safety and tolerability of calcipotriol cream was compared with betamethasone 17‐valerate cream in the treatment of plaque‐type psoriasis in a multicentre double‐blind, parallel group study. Patients with stable mild‐to‐moderate chronic disease were randomized to treatment with either calcipotriol, 50 μg/g, in a cream formulation (210 patients) or betamethasone 17‐valerate cream, 1 mg/g (211 patients). After a wash‐out period of 2 weeks. the treatment was applied twice daily, without occlusion. for 8 weeks or to complete clearing. The severity of psoriasis was assessed using the PASI at baseline and after 4 and 8 weeks treatment. The mean percentage reduction of PASI from baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the betamethasone group. The reduction from baseline was highly significant in both groups. but the differecnce between the groups was not significant. There was a difference in the reduction in thickness of the lesions in favour of calcipotriol. The investigator's as well as the patient's overall assessment of treatment response at end of treatment showed no difference between the two treatment groups. Treatment‐related adverse events were more frequent with calcipotriol thanbetamethasone. Lesional/perilesional irritation was reported in 16% and 9% (P=0.03). and facial irritation in 10% and 0.5% (P<0.001), respectively. No change was found in serum levels of calcium. Calcipotriol in a cream formulation was effective, safe well‐tolerated. and equal in effect to betamethasone valerate cream.
POSTURAL TREATMENT OF TYMPANITES
Authors: William Snow
Journal: JAMA (1935)

The presence of gas in the small bowel of infants, observed in routine roentgen examination for various conditions, has been noted for some time. Its cause and significance have not been understood. The solution of this problem was found by placing infants in the semi-inclined position. In animals, in the all-four position, the entrance of the esophagus into the stomach is on a higher level than the exit through the pylorus. When they swallow gas with food it collects above the food and fluid secretions and can easily escape through the esophagus. Since infants lie on their backs for the most part, especially new-born infants in the hospital, the swallowed gas rises into the distal or pyloric end of the stomach, where it is trapped by fluids. It therefore cannot escape through the esophagus and must be forced through the pylorus into the small intestine.
Multicenter trial of one HLA-DR–matched or mismatched blood transfusion prior to cadaveric renal transplantation
Authors: Christian Hiesse, Marc Busson, Claude Buisson, Hossein Farahmand, Philippe Bierling, Marc Benbunan, Janine Bedrossian, Philippe Aubert, Denis Glotz, Chantal Loirat, Eric Rondeau, Béatrice Viron, Helène Bleux, Philippe Lang
Journal: Kidney International (2001)
Actinic prurigo deterioration due to degradation of DermaGard<sup>�</sup>window film
Authors: A.C. Kerr, J. Ferguson
Journal: British Journal of Dermatology (2007)

Journal Article Actinic prurigo deterioration due to degradation of DermaGard® window film Get access A.C. Kerr, A.C. Kerr Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: alikerr01@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar J. Ferguson J. Ferguson Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: alikerr01@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 3, 1 September 2007, Pages 619–620, https://doi.org/10.1111/j.1365-2133.2007.07977.x Published: 01 September 2007
Abstract C11: CD117 and Stro-1 identify osteosarcoma stem cells associated with metastasis and chemotherapy-drug resistance
Authors: Amit S. Adhikari, Neeraj Agarwal, Byron M. Wood, Constance Porretta, Bernardo Ruiz, Radhika Pochampally, Tomoo Iwakuma
Journal: Cancer Research (2009)

Abstract Osteosarcoma, the most common bone cancer, is the second highest cause of cancer-related death in children and adolescents. Approximately 90% of cases show micro-metastasis at diagnosis, making systematic chemotherapy the first choice of treatment. Despite intensive chemotherapy, the survival rate for high-grade osteosarcomas remains only 50-80%. The inadequacy of current treatments may result from the inability to effectively target cancer stem cells (CSCs) or tumor initiating cells (TI-Cs) of osteosarcoma. Thus, novel therapies targeting cancer stem cells (CSCs) in osteosarcoma is an urgent requirement for eradicating this dreadful disease. Here, we have identified mouse and human osteosarcoma CSCs using mesenchymal stem cell markers CD117 and Stro-1. These markers were preferentially expressed in spheres and doxorubicin-resistant cells. CD117+Stro-1+ cells efficiently formed serially transplantable tumors, whereas CD117-Stro-1-cells rarely initiated tumors. Upon orthotopic injections, CD117+Stro-1+-derived tumors metastasized at a high frequency. Further, CD117+Stro-1+ cells were capable of differentiating into adipogenic lineage, and were enriched for CXCR4 and ABCG2, respectively associated with metastasis and drug-resistance. Thus, CD117 and Stro-1 identify osteosarcoma CSCs with the most lethal characteristics of the disease—metastasis and drug-resistance—proposing these markers as potential candidates for CSC-targeted drug delivery towards eradication of osteosarcoma. Citation Information: Cancer Res 2009;69(23 Suppl):C11.
TCT-100 Effect of Intra cardiac echocardiography and yearly operator volume on Length of Stay and Cost of Care for Percutaneous Closure of Atrial Septal Defects and Patent Foramen Ovale: A Perspective of Last Decade
Authors: Shilpkumar Arora, Nileshkumar J. Patel, Ankit Chothani, Neeraj Shah, Kathan Mehta, Peeyush Grover, Vikas Singh, Abhishek J. Deshmukh, Ankit Rathod, Dhaval B. Khalpada, Ghanshyambhai T. Savani, Sidakpal S. Panaich, Narendrasinh G. Parmar, Vipulkumar Bhalara, Nilay Patel, Apurva Badheka, Mauricio G. Cohen, Eduardo de Marchena, William W. O'Neill
Journal: Journal of the American College of Cardiology (2013)
Immunotherapy for the Adjunctive Treatment of Sepsis: From Immunosuppression to Immunostimulation. Time for a Paradigm Change?
Authors: Jenneke Leentjens, Matthijs Kox, Johannes G. van der Hoeven, Mihai G. Netea, Peter Pickkers
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Sepsis is the leading cause of death in the intensive care unit and ranks in the top 10 causes of death in general worldwide. Proinflammatory mediators are related to symptoms observed early in patients with sepsis, such as fever and hemodynamic instability. However, in recent years it has become clear that most septic patients do not die from an overwhelming proinflammatory immune response but in an immunosuppressive state, which can last for days or even weeks, and that results in increased susceptibility to secondary (opportunistic) infections. Although infection control and supportive therapies will remain the cornerstone of treatment, especially in the early phase of sepsis, the identification of this so-called "immunoparalysis" is currently causing a paradigm shift in the adjunctive treatment of sepsis from therapies that suppress the immune system toward immunostimulation. In this Critical Care Perspective we give an overview of the pathophysiology of sepsis, with a focus on immunosuppressive mechanisms that play an important role in outcome. In addition, we present an appraisal of the recent advances in immunotherapy as an adjunctive treatment for sepsis.
Effect of Thermal Biofeedback-Assisted Relaxation Training on Blood Circulation in the Lower Extremities of a Population With Diabetes
Authors: Birgitta I Rice, Jay V Schindler
Journal: Diabetes Care (1992)

Investigate the effect of relaxation training/thermal biofeedback on blood circulation in the lower extremities of diabetic subjects.Diabetic subjects (n = 40) aged 17-73 yr were volunteers recruited through the University of Wisconsin-La Crosse, the local ADA Chapter, and a medical clinic. A within-subjects experimental design was used. During phase 1, all subjects used a self-selected relaxation method and recorded toe temperatures daily. During phase 2, subjects were taught a biofeedback-assisted relaxation technique designed to elicit sensations of warmth in the lower extremities and increase circulation and temperature. Subjects relaxed at home with the use of a designated relaxation tape. They measured and recorded toe temperatures. Each phase lasted 4 wk.Toe temperature and blood volume pulse (BVP) data were gathered at the beginning and end of phases 1 and 2. Paired t tests compared the means of temperature percent change scores between 1 and 2. Mean temperature change scores were 8.73% (phase 1) and 31.38% (phase 2) (t = -8.00, df = 39, P less than 0.001). Mean BVP change scores were 2.33% (phase 1) and 22.47% (phase 2) (t = -9.24, df = 35, P less than 0.001). Based on eta squared, 71% of the BVP increase in phase 2 was attributed to the relaxation technique. A multiple regression analysis indicated that none of the other examined variables affected by diabetes were significant predictors of BVP increase.Data indicate that diabetic patients show significant increases in peripheral blood circulation with this technique. This noninvasive method could serve as an adjunct treatment for limited blood flow in some complications of diabetes.
Quality of Care in Critical Access Hospitals—Reply
Authors: Martin S. Lipsky, Michael Glasser
Journal: JAMA (2011)

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 Hippo Pathway in Heart Development, Regeneration, and Diseases
Authors: Qi Zhou, Li Li, Bin Zhao, Kun-Liang Guan
Journal: Circulation Research (2015)

The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration.
Association between Tumor Epidermal Growth Factor Receptor Mutation and Pulmonary Tuberculosis in Patients with Adenocarcinoma of the Lungs
Authors: Yung-Hung Luo, Chieh-Hung Wu, Wen-Shuo Wu, Chu-Yun Huang, Wei-Juin Su, Chun-Ming Tsai, Yu-Chin Lee, Reury-Perng Perng, Yuh-Min Chen
Journal: Journal of Thoracic Oncology (2011)
The Significance of Atypical Mycobacteria in Human Disease.
Authors: Emanuel Wolinsky
Journal: Annals of Internal Medicine (1964)

s1 April 1964The Significance of Atypical Mycobacteria in Human Disease.Emanuel Wolinsky, M.D.Emanuel Wolinsky, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-734_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough recognized for a long time, it was not until recently that serious consideration was given to mycobacteria other than mammalian tubercle bacilli as agents of human disease. These so-called "atypical" mycobacteria now account for approximately 1 to 5% of newly recognized mycobacterial infections.Chronic pulmonary disease resembling ordinary tuberculosis is probably the most common. M. kansasii (slow growing, photochromogenic) is the usual pathogen except in the Southeastern states, where most of these infections are associated with the avian-like, nonpigmented "Battey bacilli." Orange-pigmented, smooth strains (scotochromogens), and rapidly growing strains like M. fortuitum have occasionally been implicated.Subacute lymphadenitis in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Emanuel Wolinsky, M.D.Affiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 734-735KeywordsMycobacteriaNontuberculous mycobacteriaPathogensPulmonary diseases ePublished: 1 December 2008 Issue Published: 1 April 1964 PDF downloadLoading ...
REGN727/SAR236553, A FULLY HUMAN PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 (PCSK9) MONOCLONAL ANTIBODY: EFFECTS ON SAFETY AND LIPID AND LIPOPROTEIN PROFILES WHEN ADMINISTERED SUBCUTANEOUSLY
Authors: Gary Swergold, Stephanie Biedermann, Rumiana Renard, Douglas Nadler, Richard Wu, Eleanor A. Lisbon, Maria J. Gutierrez, Scott Mellis
Journal: Journal of the American College of Cardiology (2011)
Succimer Chelation Improves Learning, Attention, and Arousal Regulation in Lead-Exposed Rats but Produces Lasting Cognitive Impairment in the Absence of Lead Exposure
Authors: Diane E. Stangle, Donald R. Smith, Stephane A. Beaudin, Myla S. Strawderman, David A. Levitsky, Barbara J. Strupp
Journal: Environmental Health Perspectives (2006)

There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure.
Long term treatment of depression with selective serotonin reuptake inhibitors and newer antidepressants
Authors: S. Reid, C. Barbui
Journal: BMJ (2010)

#### Summary points 

The introduction of fluoxetine in 1987 marked the arrival of the selective serotonin reuptake inhibitors (SSRIs) for the treatment for depression. In the United States antidepressant prescriptions accounted for 2.6% of primary care visits in 1989, rising to 7.1% in 2000.1 This pattern was reflected across Europe, where SSRIs are now the most commonly prescribed antidepressants. Newer antidepressants, such as the serotonin norepinephrine reuptake inhibitors, including venlafaxine and duloxetine, also contributed to the remarkable increase in antidepressant prescribing.2 

Several reasons were put forward for this trend: improved tolerability; reduced lethality in overdose; the aggressive marketing of newly patented drugs; the wider range of available antidepressants; and ease of prescription. An analysis of the UK general practice research database showed that prescriptions almost doubled from 1993 to 2005.3 However, the increase in antidepressant prescribing was not accounted for by new diagnoses but rather a rise in the number of prescriptions given for long term treatment: although the proportion of patients receiving short term treatment declined, the proportion of patients receiving continuing prescriptions for over five years increased. Another primary care study found that …