tbuckley/cabot-search huggingface dataset:
Topoisomerase IIβ–Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane
Authors: Yi Lisa Lyu, John E. Kerrigan, Chao-Po Lin, Anna M. Azarova, Yuan-Chin Tsai, Yi Ban, Leroy F. Liu
Journal: Cancer Research (2007)

Abstract Doxorubicin is among the most effective and widely used anticancer drugs in the clinic. However, cardiotoxicity is one of the life-threatening side effects of doxorubicin-based therapy. Dexrazoxane (Zinecard, also known as ICRF-187) has been used in the clinic as a cardioprotectant against doxorubicin cardiotoxicity. The molecular basis for doxorubicin cardiotoxicity and the cardioprotective effect of dexrazoxane, however, is not fully understood. In the present study, we showed that dexrazoxane specifically abolished the DNA damage signal γ-H2AX induced by doxorubicin, but not camptothecin or hydrogen peroxide, in H9C2 cardiomyocytes. Doxorubicin-induced DNA damage was also specifically abolished by the proteasome inhibitors bortezomib and MG132 and much reduced in top2β−/− mouse embryonic fibroblasts (MEF) compared with TOP2β+/+ MEFs, suggesting the involvement of proteasome and DNA topoisomerase IIβ (Top2β). Furthermore, in addition to antagonizing Top2 cleavage complex formation, dexrazoxane also induced rapid degradation of Top2β, which paralleled the reduction of doxorubicin-induced DNA damage. Together, our results suggest that dexrazoxane antagonizes doxorubicin-induced DNA damage through its interference with Top2β, which could implicate Top2β in doxorubicin cardiotoxicity. The specific involvement of proteasome and Top2β in doxorubicin-induced DNA damage is consistent with a model in which proteasomal processing of doxorubicin-induced Top2β-DNA covalent complexes exposes the Top2β-concealed DNA double-strand breaks. [Cancer Res 2007;67(18):8839–46]
A coding-independent function of an alternative Ube3a transcript during neuronal development
Authors: Jeremy Valluy, Silvia Bicker, Ayla Aksoy-Aksel, Martin Lackinger, Simon Sumer, Roberto Fiore, Tatjana Wüst, Dominik Seffer, Franziska Metge, Christoph Dieterich, Markus Wöhr, Rainer Schwarting, Gerhard Schratt
Journal: Nature Neuroscience (2015)
Myeloma cells suppress osteoblasts through sclerostin secretion
Authors: S Colucci, G Brunetti, A Oranger, G Mori, F Sardone, G Specchia, E Rinaldi, P Curci, V Liso, G Passeri, A Zallone, R Rizzi, M Grano
Journal: Blood Cancer Journal (2011)

Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.
AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATT
Authors: NEUTON S. STERN
Journal: Annals of Internal Medicine (1937)

Article1 September 1937AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATTPAROXYSMAL VENTRICULAR TACHYCARDIA: REPORT OF THREE CASES; MECHOLYL USED AND INEFFECTIVE IN TWO*NEUTON S. STERN, M.D., F.A.C.P.NEUTON S. STERN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-3-519 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe comparative rarity of paroxysmal ventricular tachycardia, and the opportunity to report upon the ineffective use of mecholyl in proved cases suggested the presentation of these cases.CASE REPORTSCase 1. S. B. C., female, single, aged 75, seen in consultation with Dr. Otis S. Warr. She was admitted to the Baptist Memorial Hospital December 25, 1936, for pain in her chest, cough and expectoration. Diagnosis was made of bronchopneumonia and hypertension, the blood pressure being 155 systolic and 110 diastolic on admission. Three days later she became semicomatose, cyanotic, with shallow breathing of the Cheyne-Stokes type. Blood pressure 135... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Memphis, Tennessee*Received for publication June 18, 1937. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByVentricular tachycardia in children without heart diseaseSimultaneous tachycardiasParoxysmal ventricular tachycardia of prolonged durationMeasures Used in the Prevention and Treatment of Cardiac ArrhythmiasLes effets de l'injection intraveineuse d'acetylcholine chez lhommePAROXYSMAL VENTRICULAR TACHYCARDIAThe effect of acetylcholine on the mammalian heart 1 September 1937Volume 11, Issue 3Page: 519-526KeywordsBlood pressureBreathingHypertensionPneumoniaSystolic pressureThoraxVentricular tachycardia Issue Published: 1 September 1937 PDF DownloadLoading ...
Adjuvant early and late cardioprotective therapy: access to the heart
Authors: Rabea Hinkel, Peter Boekstegers, Christian Kupatt
Journal: Cardiovascular Research (2012)

Coronary heart disease is still the leading cause of death in industrialized nations, occurring either as acute coronary occlusion and myocardial infarction or as chronic ischaemic cardiomyopathy caused by continuous obstruction of one or more coronary arteries. Even after successful reperfusion, an additional loss of otherwise vital cardiomyocytes may occur in the primary ischaemic area, called lethal reperfusion injury. In experimental settings, delivery of therapeutic agents targeting the reperfusion injury reduces the infarct size by 30%. In addition to the choice of therapeutic agent and time point, the mode of application may be crucial for the therapeutic success. Therefore, this review focuses on the current and future administration techniques for early and late post-myocardial infarction therapies.
Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease
Authors: Mahmut I. Yilmaz, Dimitrie Siriopol, Mutlu Saglam, Yasemin G. Kurt, Hilmi U. Unal, Tayfun Eyileten, Mahmut Gok, Hakki Cetinkaya, Yusuf Oguz, Sebahattin Sari, Abdulgaffar Vural, Irina Mititiuc, Adrian Covic, Mehmet Kanbay
Journal: Kidney International (2014)
Lymphatic vessels and tertiary lymphoid organs
Authors: Nancy H. Ruddle
Journal: Journal of Clinical Investigation (2014)

Tertiary lymphoid organs (TLOs) are accumulations of lymphoid cells in chronic inflammation that resemble LNs in their cellular content and organization, high endothelial venules, and lymphatic vessels (LVs). Although acute inflammation can result in defective LVs, TLO LVs appear to function normally in that they drain fluid and transport cells that respond to chemokines and sphingosine-1-phosphate (S1P) gradients. Molecular regulation of TLO LVs differs from lymphangiogenesis in ontogeny with a dependence on cytokines and hematopoietic cells. Ongoing work to elucidate the function and molecular regulation of LVs in TLOs is providing insight into therapies for conditions as diverse as lymphedema, autoimmunity, and cancer.
A death in the family: a lay view.
Authors: S Hancock
Journal: BMJ (1973)

Royal College of Physicians on 29 November 1972.Surgeon Rear-Adral J. M. Hogford took the chair in the absence of Sir George Godber.Below we print versions of the papers presented at the Symposium.These have been preparedfrom the speakers' original scripts or abstracts of their papers prepared from the transcript of the proceedings.The Secretary of State, SirKeith Joseph, welcomed memers of the audience, and expressed the hope that, with so many different organizations represented, a useful and valuable exchange of ideas might improve stdds of care of the dying.
ED-22 * CONCURRENCE OF GLIOMAS IN PATIENTS WITH MULTIPLE SCLEROSIS: CASE REPORT AND LITERATURE REVIEW
Authors: E. Neil, N. Majd, J. Morris, N. Karim, J. Molano, P. Colapietro, R. Curry
Journal: Neuro-Oncology (2014)

The concurrence of multiple sclerosis (MS) and gliomas is rare. Even though new symptoms in MS patients are likely due to disease progression, here we report a case demonstrating the importance of thorough clinical and radiologic evaluation and maintaining an open differential when investigating these new complaints. CASE REPORT: 79 year old man with MS diagnosed in 1980 managed on interferon-beta prior to 2009 complained of rapidly progressive cognitive decline in 12/2013 that began 3 months prior. Neurologic examination in 04/2014 revealed significant deterioration in memory and attention, worsened generalized weakness and ataxia, and the presence of aphasia, acalculia, and a left homonymous hemianopsia. A subsequent MRI brain with contrast showed a new extensive, infiltrative mass extending from the right parietoccipital region across a markedly expanded corpus callosum. CSF analysis demonstrated elevated protein, normal cell count, and negative EBV/ JC virus PCR and cytology. Pathology from a stereotactic biopsy confirmed the diagnosis of anaplastic glioma. The family declined further intervention and the patient died five days later in hospice. DISCUSSION: While MS complaints are broad and progressive, attributing all new, especially rapidly progressive, symptoms to MS should be cautioned. This case demonstrates the rare concurrence of MS and glioma. Limited data and epidemiology studies suggest that MS patients are not predisposed to primary brain tumors and coexistence of these entities does not influence the evolution of either disease. Data of long-term effects of immunomodulators used in the management of MS suggests no increased cancer risk. The most common brain tumors reported in MS patients include; oligodendroglioma, astrocytoma, glioblastoma, and gliomatosis cerebri. It is postulated that chronic inflammation in MS plaques induces neoplastic transformation of glial cells. However, contiguity between tumor and potentially neoplastic astrocytes within plaques is not always present. Additional research may determine the presence of any causal relationships.
Cardiac protein phosphorylation: functional and pathophysiological correlates
Authors: Stephen T Rapundalo
Journal: Cardiovascular Research (1998)

Protein phosphorylation acts a pivotal mechanism in regulating the contractile state of the heart by modulating particular levels of autonomic control on cardiac force/length relationships. Early studies of changes in cardiac protein phosphorylation focused on key components of the excitation-coupling process, namely phospholamban of the sarcoplasmic reticulum and myofibrillar troponin I. In more recent years the emphasis has shifted towards the identification of other phosphoproteins, and more importantly, the delineation of the mechanistic and signaling pathways regulating the various known phosphoproteins. In addition to cAMP- and Ca2+-calmodulin-dependent kinase processes, these have included regulation by protein kinase C and the ever-emerging family of growth factor-related kinases such as the tyrosine-, mitogen- and stress-activated protein kinases. Similarly, the role of protein dephosphorylation by protein phosphatases has been recognized as integral in modulating normal cardiac cellular function. Recent studies involving a variety of cardiovascular pathologies have demonstrated that changes in the phosphorylation states of key cardiac regulatory proteins may underlie cardiac dysfunction in disease states. The emphasis of this comprehensive review will be on discussing the role of cardiac phosphoproteins in regulating myocardial function and pathophysiology based not only on in vitro data, but more importantly, from ex vivo experiments with corroborative physiological and biochemical evidence.
Identification of a CD36-related Thrombospondin 1–binding Domain in HIV-1 Envelope Glycoprotein gp120: Relationship to HIV-1–specific Inhibitory Factors in Human Saliva
Authors: René Crombie, Roy L. Silverstein, Clarinda MacLow, S. Frieda A. Pearce, Ralph L. Nachman, Jeffrey Laurence
Journal: The Journal of Experimental Medicine (1998)

Human and non-human primate salivas retard the infectivity of HIV-1 in vitro and in vivo. Because thrombospondin 1 (TSP1), a high molecular weight trimeric glycoprotein, is concentrated in saliva and can inhibit the infectivity of diverse pathogens in vitro, we sought to determine the role of TSP1 in suppression of HIV infectivity. Sequence analysis revealed a TSP1 recognition motif, previously defined for the CD36 gene family of cell adhesion receptors, in conserved regions flanking the disulfide-linked cysteine residues of the V3 loop of HIV envelope glycoprotein gp120, important for HIV binding to its high affinity cellular receptor CD4. Using solid-phase in vitro binding assays, we demonstrate direct binding of radiolabeled TSP1 to immobilized recombinant gp120. Based on peptide blocking experiments, the TSP1-gp120 interaction involves CSVTCG sequences in the type 1 properdin-like repeats of TSP1, the known binding site for CD36. TSP1 and fusion proteins derived from CD36-related TSP1-binding domains were able to compete with radiolabeled soluble CD4 binding to immobilized gp120. In parallel, purified TSP1 inhibited HIV-1 infection of peripheral blood mononuclear cells and transformed T and promonocytic cell lines. Levels of TSP1 required for both viral aggregation and direct blockade of HIV-1 infection were physiologic, and affinity depletion of salivary TSP1 abrogated >70% of the inhibitory effect of whole saliva on HIV infectivity. Characterization of TSP1-gp120 binding specificity suggests a mechanism for direct blockade of HIV infectivity that might be exploited to retard HIV transmission that occurs via mucosal routes.
Phase II Study of the Mammalian Target of Rapamycin Inhibitor Ridaforolimus in Patients With Advanced Bone and Soft Tissue Sarcomas
Authors: Sant P. Chawla, Arthur P. Staddon, Laurence H. Baker, Scott M. Schuetze, Anthony W. Tolcher, Gina Z. D'Amato, Jean-Yves Blay, Monica M. Mita, Kamalesh K. Sankhala, Lori Berk, Victor M. Rivera, Tim Clackson, John W. Loewy, Frank G. Haluska, George D. Demetri
Journal: Journal of Clinical Oncology (2011)

Purpose Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. Patients and Methods Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease ≥ 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. Results A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. Conclusion Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas.
Experts Say Projected Surgeon Shortage a “Looming Crisis” for Patient Care
Authors: Rebecca Voelker
Journal: JAMA (2009)

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
Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome
Authors: Sébastien Malinge, Meghan Bliss-Moreau, Gina Kirsammer, Lauren Diebold, Timothy Chlon, Sandeep Gurbuxani, John D. Crispino
Journal: Journal of Clinical Investigation (2012)

Individuals with Down syndrome (DS; also known as trisomy 21) have a markedly increased risk of leukemia in childhood but a decreased risk of solid tumors in adulthood. Acquired mutations in the transcription factor–encoding GATA1 gene are observed in nearly all individuals with DS who are born with transient myeloproliferative disorder (TMD), a clonal preleukemia, and/or who develop acute megakaryoblastic leukemia (AMKL). Individuals who do not have DS but bear germline GATA1 mutations analogous to those detected in individuals with TMD and DS-AMKL are not predisposed to leukemia. To better understand the functional contribution of trisomy 21 to leukemogenesis, we used mouse and human cell models of DS to reproduce the multistep pathogenesis of DS-AMKL and to identify chromosome 21 genes that promote megakaryoblastic leukemia in children with DS. Our results revealed that trisomy for only 33 orthologs of human chromosome 21 (Hsa21) genes was sufficient to cooperate with GATA1 mutations to initiate megakaryoblastic leukemia in vivo. Furthermore, through a functional screening of the trisomic genes, we demonstrated that DYRK1A, which encodes dual-specificity tyrosine-(Y)-phosphorylation–regulated kinase 1A, was a potent megakaryoblastic tumor–promoting gene that contributed to leukemogenesis through dysregulation of nuclear factor of activated T cells (NFAT) activation. Given that calcineurin/NFAT pathway inhibition has been implicated in the decreased tumor incidence in adults with DS, our results show that the same pathway can be both proleukemic in children and antitumorigenic in adults.
Gly482Ser polymorphism in the peroxisome proliferator–activated receptor γ coactivator–1α gene is associated with oxidative stress and abdominal obesity
Authors: Shao-Wen Weng, Tsu-Kung Lin, Pei-Wen Wang, I-Ya Chen, Hsin-Chen Lee, Shang-Der Chen, Yao-Chung Chuang, Chia-Wei Liou
Journal: Metabolism (2009)
A CASE OF BUTYN DERMATITIS
Authors: Arthur M. Greenwood
Journal: JAMA (1924)

The occurrence of dermatitis venenata in susceptible persons caused by synthetic local anesthetics, such as stovain, apothesin and procain, has been frequently noted and reported. We have found no references in the literature to such a condition caused by butyn, one of the newest of this group of substances. <h3>REPORT OF CASE</h3> A genito-urinary specialist, aged 42, whose family history was negative, had had rheumatic endocarditis at 14, which was followed by aortic and mitral regurgitation. About Aug. 12, 1923, there appeared a vesicular eruption on the hands and arms. Severe itching and burning accompanied it. As there had been a possible exposure to poison ivy, the eruption was considered to be due to this. It was treated with a zinc oxid and calamine lotion, and subsided in two days. August 16, there was a recurrence of the eruption, plus marked swelling and itching of the penis and scrotum. August
Avoiding premature death in epilepsy
Authors: L. Ridsdale
Journal: BMJ (2015)

General practice is the place to start, and much can be done

An estimated 1.16 per 1000 people with epilepsy die suddenly each year.1 In 2013 there were 680 deaths from epilepsy among people aged under 75 (973 deaths at all ages) in England and Wales.2 Sudden death in epilepsy peaks in young adults, particularly men, so a 20 year old with epilepsy has a greater than 1% risk of dying before he reaches 30, before adding other known risks for sudden death. Comparing years of potential life lost from neurological disease, epilepsy is second only to stroke.1 Research on this topic has focused on cohort studies1 and whether risk should be explained to patients.3 However, equally important and currently unanswered questions are: can group and individual risks for death be identified, perhaps using patients’ routine electronic records? Are some identified risks amenable to better medical management? And will cash strapped governments pay for it?

Some deaths are unavoidable, but improved care might result in fewer unnecessary, untimely deaths. General practitioners routinely identify risks of heart disease and stroke in the UK using electronic records and discuss them with patients. National strategy also supports risk identification for cancer in primary care.4 

With others, I conducted a …
UTILITY OF DOPPLER MYOCARDIAL IMAGING, CARDIAC BIOMARKERS AND CLONAL IMMUNOGLOBULIN GENES TO ASSESS LEFT VENTRICULAR PERFORMANCE AND STRATIFY RISK FOLLOWING PERIPHERAL BLOOD STEM CELL TRANSPLANTATION IN PATIENTS WITH SYSTEMIC LIGHT CHAIN AMYLOIDOSIS (AL).
Authors: Diego Bellavia, Roshini S. Abraham, Patricia A. Pellikka, Angela Dispenzieri, John C. Burnett, Ghormallah B. Al-Zahrani, Morie A. Gertz, Fletcher A. Miller, Theodore P. Abraham
Journal: Journal of the American College of Cardiology (2010)