tbuckley/cabot-search huggingface dataset:
Abstract 17087: A Unique Calcium Channel Blocker Attenuates Myocardial Fibrosis and Prevents Human Cardiac Myofibroblast Activation Independent of Hemodynamics
Authors: Guoqi Teng, Henry J Duff, Darrell D Belke, Christopher H Meijndert, Edward O’Brien, Yangxiang Chen, Jeannine Turnbull, Paul W Fedak
Journal: Circulation (2014)

Introduction: Myocardial fibrosis is mediated by myofibroblasts that alter extracellular matrix (ECM). Tetrandrine (TTD) is a calcium channel blocker (CCB) with documented anti-fibrotic actions believed to be secondary to its effects on lowering blood pressure. In this study, for the first time, we identified that TTD can directly prevent in vitro human cardiac fibroblast activation and limit in vivo myocardial fibrosis independent of hemodynamic load. Methods and Results: IN VITRO: Cardiac fibroblasts from human atrial biopsies (N=10) were seeded in 3D collagen matrices. Cell-collagen constructs were exposed to TGF-β1 (10 ng/mL), with or without TTD (5μM) for 48 hours. Collagen gel contraction, myofibroblast activation (α-SMA expression), expression of pro-fibrotic mRNAs and rate of collagen protein synthesis was compared. TTD decreased collagen gel contraction (79.7±1.3 vs 60.1±8.9%, P< 0.01). Cell viability was similar between groups (annexin positive cells: 1.7% vs 1.4%). TTD decreased α-SMA expressio...
Afghanistan Aid Workers Struggle Through Threats
Authors: B Vastag
Journal: JAMA (2001)

WASHINGTON—Wearing a turban and carrying a fake passport, John McGill, MD, trekked hundreds of miles across rugged mountains, intent on delivering care to war-weary Afghanistan. He hid from a regime intent on killing him. He operated under the dull light of a spelunking helmet. He pulled shrapnel from the bodies of children. Saying good-bye to colleagues and abandoning her pediatric ward, Nicola Johnson, MD, trekked hundreds of miles across rugged mountains, barred from delivering care to war-weary Afghanistan. She fled a brutal regime and an anticipated attack. She holed up in a cramped office in Pakistan. Now she wonders which children, which friends, which colleagues will suffer the metallic sting of shrapnel. McGill’s adventure transpired in the mid-1980s, during the Soviet occupation of Afghanistan; Johnson’s occurred in September 2001. And despite the 15-year separation, both physicians, volunteers with Medecins sans Frontieres (MSF; Doctors Without Borders)—the international humanitarian aid group that won the 1999 Nobel Peace Prize—encountered similar risks. “The attacking superpower has changed but the feeling on the ground probably hasn’t,” McGill said in a telephone interview from Minneapolis, where he now works as an emergency physician. Press statements and interviews with aid workers from MSF, the International Committee of the Red Cross/ Red Crescent (ICRC), the United Nations’ World Food Program (WFP), UNICEF, and other groups reveal that the “feeling on the ground” in Central Asia includes large amounts of frustration, fear, and uncertainty. With conditions spiraling toward catastrophe, international relief experts hover outside Afghanistan, driven out by the dual threats of an angry populace and a daily pounding by US bombs. Several thousand of their Afghan colleagues still in the country do what they can to continue providing food, shelter, and medical aid to the estimated 500000 to 1 million internally displaced Afghans. Some have been killed by the bombs; others brutalized by the Taliban or other internal forces as civil order disintegrates. And though MSF has logged a 22year humanitarian track record in Afghanistan, surviving a decade of Soviet occupation, the rise of the obdurate Taliban, and the worst drought in 30 years, its relief programs are at risk. “It was very frustrating to abandon our work and it’s frustrating to just be waiting,” said Ridka Amsalu, MD, via phone from Islamabad, Pakistan, where she coordinates MSF activities in the region. After the war, she envisions an expanded slate of programs, as medical needs will be “much greater.”
CHD5 downregulation associated with poor prognosis in epithelial ovarian cancer in Hong Kong Chinese women
Authors: Raymond R. Wong, Loucia K.Y. Chan, Teresa B.T. Tsang, Coral W.S. Lee, T.H. Cheung, S.F. Yim, Nelson S.S. Siu, Sophia N.C. Lee, Stephen S.C. Chim, Y.F. Wong, Tony K.H. Chung
Journal: Clinical Cancer Research (2010)

Abstract Background: CHD5 gene located on 1p36, encodes a non-histone chromosomal protein, chromodomain helicase DNA binding protein 5. Recently, CHD5 has been shown to be a tumor suppressor gene candidate. This study was to investigate the involvement of CHD5 in epithelial ovarian cancer and its clinico-pathological significance. Methods: CHD5 expression in ovarian cancer and its normal counterpart was determined by quantitative RT-PCR. The methylation of CHD5 promoter was evaluated by methylation specific PCR. The correlation of CHD5 expression to patient age, tumor histological type and grade, clinical stage and status, recurrence and patient survival time was analyzed statistically. Results: CHD5 expression was down at least two-fold in 32 of 72 (41%) invasive epithelial ovarian carcinomas when compared to 12 normal controls in Hong Kong Chinese women. Hypermethylation in two promoter regions of CHD5 was not detected in any of the 20 tumor samples available to be analyzed. CHD5 down-regulation was correlated to clinical status (P&amp;lt;0.05), but not to patient age, tumor type and grade, recurrence and clinical stage (P&amp;gt;0.05). Kaplan-Meier survival analysis showed that patients with CHD5 down-regulation in their tumors were associated with shorter disease-free and total survival times compared to those without CHD5 down-regulation (P&amp;lt;0.05). Cox proportional hazard regression analysis indicated that down-regulation of CHD5 is an independent adverse prognostic factor in ovarian cancer. Conclusion: This preliminary study shows that CHD5 s down-regulated in a certain part of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival in Hong Kong Chinese women. If this role of CHD5 dysregulation can be confirmed in more prospective studies with a large number of patients, it is also worthwhile to further evaluate if CHD5 can be as an individualized molecular therapeutic target for epithelial ovarian cancer.
Use of Exercise Echocardiography for Prognostic Evaluation of Patients With Known or Suspected Coronary Artery Disease fn1fn1This study would not have been possible without the support of the sonographers, fellows and staff of the Echocardiography Laboratory of the Cleveland Clinic Foundation.
Authors: Thomas H. Marwick, Rajendra Mehta, Kristopher Arheart, Michael S. Lauer
Journal: Journal of the American College of Cardiology (1997)
Preserved DNA Damage Checkpoint Pathway Protects against Complications in Long-Standing Type 1 Diabetes
Authors: Shweta Bhatt, Manoj K. Gupta, Mogher Khamaisi, Rachael Martinez, Marina A. Gritsenko, Bridget K. Wagner, Patrick Guye, Volker Busskamp, Jun Shirakawa, Gongxiong Wu, Chong Wee Liew, Therese R. Clauss, Ivan Valdez, Abdelfattah El Ouaamari, Ercument Dirice, Tomozumi Takatani, Hillary A. Keenan, Richard D. Smith, George Church, Ron Weiss, Amy J. Wagers, Wei-Jun Qian, George L. King, Rohit N. Kulkarni
Journal: Cell Metabolism (2015)
Cord Blood Law Signed
Authors: Mike Mitka
Journal: JAMA (2006)

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
A memorable patient: "Now I can be remembered"
Authors: T. Reynolds
Journal: BMJ (1999)

During a visit to a psychiatric hospital in eastern Europe I was approached by a fluent English speaking patient and asked to take a photograph of another patient as a special favour. The hospital itself displays many of the problems of institutions in general and the more specific problems of neglected, ostracised, and stigmatised institutions in particular. Consequently, though it was mid-winter and viciously cold, many of the patients were clothed in nothing more than …
The new preventive detention: psychiatry's problematic responsibility for the control of violence
Authors: P S Appelbaum
Journal: American Journal of Psychiatry (1988)

The legal doctrine of the duty to protect potential victims of patients' violent acts has created problems beyond those usually discussed, which involve breach of patients' confidentiality. Fear of liability has led some psychiatrists to hospitalize, solely for the purpose of preventing violence, patients who do not otherwise require inpatient care. The result has been the creation of a de facto system of preventive detention that consumes psychiatric resources intended to serve therapeutic ends and compels psychiatrists to share the social control responsibilities of the criminal justice system. The author explores the costs and benefits of various means of removing the burden of preventive detention from psychiatry.
Abstract P1-07-17: Transcription factor Fra-1 modulates the adhesive properties of breast cancer cells contributing to a metastatic phenotype
Authors: Leticia Oliveira-Ferrer, Melanie Kürschner, Vera Labitzky, Daniel Wicklein, Volkmar Müller, Udo Schumacher, Karin Milde-Langosch, Christine Schröder
Journal: Cancer Research (2015)

Abstract Fra-1, a component of the transcription factor AP-1 family, has been found to be overexpressed in carcinomas with high metastatic potential such as in triple-negative breast cancer. The effect of Fra-1 on the morphology, motility and invasive potential of breast cancer cells has been previously described. Since tumor cell adhesion plays an essential role in the metastatic process, especially for extravasation from blood vessels, we investigated the influence of Fra-1 on breast cancer cell interactions with the endothelium. Using the human breast cancer cell lines MCF7 (weakly invasive, estrogen receptor (ER)-positive) and MDA MB 231 (strongly invasive, ER-negative) with stable Fra-1 overexpression, we performed dynamic cell-flow adhesion assays on surfaces coated with E-selectin or with human pulmonary microvascular endothelial cells (HPMEC). Our analyses revealed increased adhesion of Fra-1 overexpressing MCF7 cells to E-selectin but also to activated endothelial cells, whereas the per se highly invasive and Fra-1-positive MDA MB 231 cell line showed enhanced cell rolling and tethering on E-selectin and endothelium-coated surfaces, but no increased firm adhesion after Fra-1 overexpression. These different behaviors correspond to an up-regulation of various adhesion-related proteins such as CD44, Integrin α5 and CEACAM6 in Fra-1 overexpressing MCF7 cells measured by microarray analysis and flow cytometry in comparison to weaker differences in the expression of adhesion molecules found in the Fra-1 overexpressing MDA MB 231 cell line. In line with these results and based on cDNA microarray data of breast cancer patients (n=175) high Fra-1 expression significantly correlates with shorter overall survival and higher rate of lung metastasis in ER-positive breast cancer patients (n=130), but has no impact on the prognosis of patients with ER-negative tumors. Thus, in addition to its pro-invasive and pro-migratory effect, Fra-1 might influence the metastatic potential of breast cancer cells by changing the expression of adhesion molecules resulting in increased adherence to endothelial cells under flow conditions. Citation Format: Leticia Oliveira-Ferrer, Melanie Kürschner, Vera Labitzky, Daniel Wicklein, Volkmar Müller, Udo Schumacher, Karin Milde-Langosch, Christine Schröder. Transcription factor Fra-1 modulates the adhesive properties of breast cancer cells contributing to a metastatic phenotype [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-17.
Abstract 548: Non-Invasive Estimation of Left Ventricular Filling Pressures in Heart Failure Patients After Surgical Ventricular Restoration and Restrictive Mitral Annuloplasty
Authors: Ellen A ten Brinke, Matteo Bertini, Robert J Klautz, M. L Antoni, Eduard R Holman, Nico R van de Veire, Jeroen J Bax, Paul Steendijk
Journal: Circulation (2009)
A mouse model for hereditary thyroid dysgenesis and cleft palate
Authors: Mario De Felice, Catherine Ovitt, Elio Biffali, Alina Rodriguez-Mallon, Claudio Arra, Konstantinos Anastassiadis, Paolo Emidio Macchia, Marie-Genevieve Mattei, Angela Mariano, Hans Schöler, Vincenzo Macchia, Roberto Di Lauro
Journal: Nature Genetics (1998)
Dynamic hyperinflation in patients with severe COPD
Authors: Karin Klooster, Dirk-Jan Slebos
Journal: European Respiratory Journal (2011)

Introduction:  Dynamic hyperinflation (DH) is thought to be an important clinical feature in patients with COPD, but is difficult to measure.   Aim:  To investigate DH in patients with COPD referred for bronchoscopic lung volume reduction and to test the feasibility of using metronome paced hyperventilation (MPH).   Methods:  DH was measured by MPH using the breath-by-breath method (Oxycon Pro) in a 15-min protocol. After 3 baseline IC maneuvers, 3 MPH tests (40Hz for 60 sec; with 3 min. rest in-between) were performed. Each MPH test was directly followed by an IC maneuver. DH was defined as ΔIC/IC (decrease in IC/baseline IC) and calculated using the average of 3 IC9s.   Patients:  29 patients with severe emphysema, Gold-IV (n=15): FEV1 23%pred (±4.9), Gold-III (n=9): FEV1 37%pred (±4.7) and Gold-II (n=5): FEV1 51%pred (±1.3) were tested. For Gold-IV RV was 239% (±55), TLCbox 136%pred (±18), IC/TLC-He 25% (±3) and 6MWT 340m (±62). For Gold-II/III RV was 189%pred (±70), TLCbox 134%pred (±15), IC/TLC-He 36% (±11) and 6MWT 413m (±84).   Results:  All patients tolerated the MPH very well. IC variability was 4.6% (±3.0), and 8.6% (±4.4) after MPH. VE reached 28.8L/min (±12.6), calculated maximal VE (FEV1*37.5) was 34.5L/min (±15.5). MPH frequency was 39.7Hz (±1.4). For the Gold-IV patient group the IC of 1.83L (±0.47) decreased to 1.21L (±0.42) after MPH with a ΔIC/IC of 34% (±12). In Gold-II/III IC decreased from 2.39L (±0.93), to 1.79L (±0.63) with a ΔIC/IC of 23% (±12). In the overall group ΔIC/IC correlated with TLC-He (r=0.45, p=0.03) and FEV1 (r=-0.38, p=0.04).   Conclusion:  Measuring DH is feasible using MPH, and can be used in the routine clinical setting. DH is significantly present in patients with COPD and increases with disease severity.
Diltiazem and Raynaud's Syndrome
Authors: MATOBA TSUNETAKA
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 September 1982Diltiazem and Raynaud's SyndromeMATOBA TSUNETAKA, M.D., MASAHIKO OGATA, M.D., HIROSHI KUWAHARA, M.D.MATOBA TSUNETAKA, M.D.Search for more papers by this author, MASAHIKO OGATA, M.D.Search for more papers by this author, HIROSHI KUWAHARA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-3-455_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The therapeutic effect of calcium antagonists on Raynaud's phenomenon has been reported by Kahan and associates (1) and Vayssairat and associates (2). We conducted an open trial on the therapeutic effect of diltiazem, a calcium antagonist.Seventeen men with vibration disease, occupational Raynaud's syndrome were studied. The mean age was 54 years. No patient had cardiovascular disease. Primary and secondary cases of Raynaud's phenomenon were excluded.Diltiazem, 30 mg orally three time daily, was given to the patients for 6 weeks. Before and after this treatment period, we evaluated the subjected symptoms (30 items including Raynaud's phenomenon,...References1. KAHANWEBERAMORSAPORTAHODARADEGEORGES ASBLMM. Nifedipine and Raynaud's phenomenon [Letter]. Ann Intern Med. 1981;94:546 LinkGoogle Scholar2. VAYSSAIRATCAPRONFIESSINGERMATHIEUHOUSSET MLJJE. Calcium channel blockers and Raynaud's disease [Letter]. Ann Intern Med. 1981;95:243. LinkGoogle Scholar3. MATOBA T. The effect of physical therapy and balneotherapy on the patient with vibration disease. J Jpn Assoc Phys Med Balneol Climatol. 1978;42(1-2):39-41. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Yufuin Kosei Nenkin Hospital Ohita, Japan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRaynaud's phenomenon in the emergency departmentCalcium Channel BlockersNew Drug Therapy in Peripheral Vascular DiseaseCalcium Modulators: Future Agents, Future UsesThe Effect of the Calcium-entry Blocker Nifedipine on Cold-induced Digital VasospasmSome Extracardiac Effects of Diltiazem and Other Calcium Entry BlockersRaynaud's phenomenon: Pathophysiologic features and treatment with calcium-channel blockersA randomised double-blind trial of diltiazem in the treatment of Raynaud's phenomenon.Clinical effect of diltiazem acid (Herbesser tablet) for Raynaud phenomenon. A double blind trial comparing with placebo.Clinical applications of slow channel blocking compounds 1 September 1982Volume 97, Issue 3Page: 455-455KeywordsCalciumCalcium antagonist therapyCardiovascular diseasesRaynaud syndrome ePublished: 1 December 2008 Issue Published: 1 September 1982 PDF downloadLoading ...
Genetic variants at HbF‐modifier loci moderate anemia and leukocytosis in sickle cell disease in <scp>T</scp>anzania
Authors: Siana Nkya Mtatiro, Julie Makani, Bruno Mmbando, Swee Lay Thein, Stephan Menzel, Sharon E. Cox
Journal: American Journal of Hematology (2014)

Fetal hemoglobin (HbF) is a recognized modulator of sickle cell disease (SCD) severity. HbF levels are strongly influenced by genetic variants at three major genetic loci, Xmn1-HBG2, HMIP-2, and BCL11A, but the effect of these loci on the hematological phenotype in SCD, has so far not been investigated. In a cohort of individuals with SCD in Tanzania (HbSS and HbS/β° thalassemia, n = 726, aged 5 or older), HbF levels were positively correlated with hemoglobin, red blood cell (RBC) indices, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), and negatively with white blood cell (WBC) and platelet counts (all P < 0.0001). We subsequently assessed the contribution of the three HbF modifier loci and detected diverse effects, including a reduction in anemia, leukocytosis, and thrombocytosis associated with certain HbF-promoting alleles. The presence of the 'T' allele at Xmn1-HBG2 led to a significant increase in hemoglobin (P = 9.8 × 10(-3) ) but no changes in cellular hemoglobin content. Xmn1-HBG2 'T' also has a weak effect decreasing WBC (P = 0.06) and platelet (P = 0.06) counts. The BCL11A variant (rs11886868-'C') increases hemoglobin (P = 2 × 10(-3) ) and one of the HBS1L-MYB variants decreases WBC values selectively (P = 2.3 × 10(-4) ). The distinct pattern of effects of each variant suggests that both, disease alleviation through increased HbF production, and 'pleiotropic' effects on blood cells, are involved, affecting a variety of pathways.
Histone γ-H2AX as a pharmacodynamic biomarker for the indenoisoquinoline topoisomerase I inhibitors selected for preclinical development.
Authors: Smitha Antony, Keli A. Agama, Muthukaman Nagarajan, Mark Cushman, William M. Bonner, Yves Pommier
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5534 

Camptothecin derivatives are effective anticancer drugs, especially against solid tumors. Although they are known to selectively target DNA topoisomerase I (Top1) their action cannot be predicted based on Top1 levels. However, phosphorylated histone H2AX (γ-H2AX) formation can be detected by immunofluorescence microscopy following camptothecin treatment. Histone H2AX is rapidly phosphorylated in the chromatin flanking camptothecin-induced replication DNA double-strand break (DSB) (Furuta et al., J Biol Chem. 2003 May 30;278(22):20303-12). As camptothecins are chemically unstable and have clinical limitations, we have synthesized indenoisoquinolines as novel Top1 inhibitors. Of the 300 derivatives tested, based on potent Top1 inhibition, selectivity for Top1-overexpressing cells and potent antiproliferative activity, we presently report 4 novel indenoisoquinoline derivatives (NSC D-724998, NSC D-725776, NSC D-726972 and NSC D-727357) that are under consideration for therapeutic development. To help evaluate the efficacy of these drugs prior to clinical trials, our goal was to determine a biomarker that would validate the activity of the indenoisoquinolines in tumor samples. Dose and time dependent γ-H2AX foci formation was readily observed in cells treated with the indenoisoquinolines, indicative of DSBs formed as a consequence of a replication forks colliding with the drug-mediated Top1-DNA single-strand breaks. These γ-H2AX foci were detectable at pharmacologically relevant dose and thus could be used as biomarker for Top1 inhibitors. Work is in progress to evaluate if γ-H2AX foci can be detected in animal models.
WHAT IS AN INTERNIST?
Authors: O. H. Perry Pepper
Journal: Annals of Internal Medicine (1940)

Article1 April 1940WHAT IS AN INTERNIST?O. H. PERRY PEPPER, M.D., F.A.C.P.O. H. PERRY PEPPER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-10-1791 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPresidents annually come and, fortunately for you, Presidents annually go. Each performs his duties as well as he can; each meets certain problems which he solves if he can, and each year at the Convocation the President addresses you on the state of the College or on some phase of our College or professional activity. As one reads the Presidential Addresses of past years, one is impressed by the learning and wisdom of my predecessors in this office. They have settled all sorts of tremendous problems—political, ethical, medical, sociological—the discussion of which required the utmost bravery. On the other hand,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Presidential Address, delivered at the Convocation of the American College of Physicians, Twenty-fourth Annual Session, Cleveland, April 3, 1940. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1940Volume 13, Issue 10Page: 1791-1798 ePublished: 1 December 2008 Issue Published: 1 April 1940 Copyright & PermissionsCopyright, 1940, by The American College of PhysiciansPDF downloadLoading ...