tbuckley/cabot-search huggingface dataset:
Integrated regional genetic services: current and future provision Commentary: The future development of regional genetic services will rely on partnerships
Authors: D. Donnai
Journal: BMJ (2001)

# Integrated regional genetic services: current and future provision {#article-title-2} This is an important time in the history of genetics. Now that we have the sequence of the human genome in “working draft” form commentators predict a huge increase in activity in genetic medicine. Here we describe how the benefits of this rapidly expanding knowledge are being brought to the UK population as genetic services, and how they may develop in the future. Few doubt that medicine will be increasingly founded on the understanding of genetics and underpinned by testing. The biggest uncertainty concerns the large scale genetic screening of healthy people for susceptibility to common diseases: how widely this will happen, how soon, and how it might be organised. #### Summary points UK genetic services are based on a network of geographical centres offering specialist services to families at high risk of serious genetic disorders Regional genetic centres provide diagnosis, risk estimation, counselling, surveillance, and support Links with secondary and tertiary specialists are established, and links with primary care are being developed Genetic counsellors have a key role in the delivery of integrated services Genetic testing is already helping many families at high risk and in the future will play a central part in the clinical management and prescribing practice for all specialties The role of testing for genetic variants predisposing to common diseases has yet to be established Our information derives from the experience of the regional genetic centres in 12 UK health regions and international comparisons reported in recent scientific and official publications. Our vision for the development of integrated genetic services draws on these sources, recent initiatives to commission genetic services, and the literature on the impact of the new genetics in medicine. #### Genetic centres Special skills Correspondence to: D Ravine
Aberrant methylation in lung cancer identified by EBUS-TBNA as a marker of advanced staging
Authors: Laura Millares, Laia Setó, José Sanz, Mariona Llatjos, Felipe Andreo, Eva Castellà, Eduard Monsó
Journal: European Respiratory Journal (2012)

Introduction   Aberrant methylation of DNA results in gene silencing and is frequently observed in tumours from lung cancer patients. Methylation aberrancies can also be detected in lymph nodes,but it is unknown if the assessment of the nodal methylation status may identify more advanced stages of the disease   Objective    To determine the relationship between the methylation status of 5 genes in metastatic lymph node and tumours samples obtained by EBUS-TBNA and the presence of an advanced stage of lung cancer   Methods   Nodal and tumour samples positive for lung cancer were obtained with EBUS-TBNA. The methylation status of DAPK, p16, RASSF1, APC and CDH13 genes was determined by methylation-sensitive high resolution melting   Results   23 samples were analysed, 15 samples (12 mediastinal nodes, 1 lobar node and 2 tumour) were early cases of lung cancer (T1/T2) and 8 (4 mediastinal nodes, 3 lobar nodes and 1 tumour) more advanced lung cancer (T3/T4).Percentages of methylated samples for each gene according to T staging are shown in the figure.The samples from patients with a more advanced stage of lung cancer had significantly more genes methylated (p= 0.043) than the samples from patients with early lung cancer.   Conclusion   The level of methylation in tumour cells obtained from lymph nodes and/or tumours accessible to EBUS-TBNA is higher in patients with more advanced stages of lung cancer, identified by a higher T staging  Funded FIS09/01612.
Küçük Hücreli Dışı Akciğer Kanserinde Neoadjuvan Kemoterapinin Sağkalım Yararı
Authors: Wei-An Song, † Nai-Kang Zhou, Wei Wang, † Xiang-Yang Chu, Chao-Yang Liang, Xiao-Dong Tian, Jun-Tang Guo, Xi Liu, Yang Liu, Wei-Min Dai
Journal: Journal of Thoracic Oncology (2010)
Long-term Cardiovascular Consequences of Diuretics vs Calcium Channel Blockers vs Angiotensin-Converting Enzyme Inhibitors
Authors: Jan Laws Houghton
Journal: JAMA (2003)

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 18483: Therapeutic Administration of IL-2/ Anti-IL-2 Monoclonal Antibody Complexes Enhances Healing After Experimental Myocardial Infarction in Mice
Authors: Johannes Weirather, Ulrich Hofmann, Niklas Beyersdorf, Thomas Kerkau, Stefan Frantz
Journal: Circulation (2014)

Background: The role of innate immunity in healing and remodeling after myocardial infarction (MI) has been studied in great detail. Recently, we demonstrated that Foxp3+CD4+ regulatory T cells (Treg cells) facilitate wound healing post-MI. We therefore pursued a strategy to activate Treg cells in a therapeutic fashion by employing a treatment modality with clinical potential, i.e. by administration of interleukin (IL)-2/ anti-IL-2 monoclonal antibody (IL-2 mAB) complexes. Methods and results: Mice were subjected to experimental MI and treated with IL-2/ IL-2 mAB complexes beginning on day 1 after infarction. IL-2 and anti-IL-2 mAB (clone JES5-1) were mixed at a molar ratio of 1:2 and each mouse was treated on three consecutive days receiving a dose of 6 μg IL-2/ IL-2 mAB complexes per injection corresponding to approximately 5000 IU IL-2 per day. Mice were monitored for up to 7 days. IL-2/ IL-2 mAB complex treatment attenuated left-ventricular remodeling by trend and preserved cardiac function compared t...
Peptide‐mediated targeted drug delivery
Authors: Sumit Majumdar, Teruna J. Siahaan
Journal: Medicinal Research Reviews (2010)

Abstract Targeted drug delivery to specific group of cells offers an attractive strategy to minimize the undesirable side effects and achieve the therapeutic effect with a lower dose. Both linear and cyclic peptides have been explored as trafficking moiety due to ease of synthesis, structural simplicity, and low probability of undesirable immunogenicity. Peptides derived from sequence of cell surface proteins, such as intercellular adhesion molecule‐1 (ICAM‐1), LHRH, Bombesin, and LFA‐1, have shown potent binding affinity to the target cell surface receptors. Moreover, peptides derived from ICAM‐1 receptor can be internalized by the leukemic T‐cells along with the conjugated moiety offering the promise to selectively treat cancers and autoimmune diseases. Systematic analyses have revealed that physicochemical properties of the drug–peptide conjugates and their mechanism of receptor‐mediated cellular internalization are important controlling factors for developing a successful targeting system. This review is focused on understanding the factors involved in the development of an effective drug–peptide conjugate with an emphasis on the chemistry and biology of the conjugates. Reported results on several promising drug–peptide conjugates have been critically evaluated. The approaches and results presented here will serve as a guide to systematically approach targeted delivery of cytotoxic drug molecules using peptides for treatment of several diseases. © 2010 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 637‐658, 2012
TOXIC REACTION TO ALPHA-DINITRO-ORTHO-CRESOL
Authors: Murray B. Gordon, Mark J. Wallfield
Journal: Annals of Internal Medicine (1935)

Case Reports1 August 1935TOXIC REACTION TO ALPHA-DINITRO-ORTHO-CRESOLMURRAY B. GORDON, M.D., F.A.C.P., MARK J. WALLFIELD, M.D.MURRAY B. GORDON, M.D., F.A.C.P.Search for more papers by this author, MARK J. WALLFIELD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-2-198 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe use of the nitrophenol group as a metabolic stimulant has brought to light many reports of toxic reactions1, 2, 3, 4and even fatalities.5Cutting, Mehrtens and Tainter2have sounded a sombre note of warning that the drug is still too new in usage and the various manifestations of toxicity are not known. More recently, Dodds and Pope6have reported better results in the treatment of obesity with the use of dinitro-ortho-cresol instead of dinitrophenol. The clinical application of the drug by Dodds and Robertson7has shown it to be from three to five times as strong as dinitrophenol,...Bibliography1. JACKSONDUVALL HAI: Dinitrophenol poisoning, Jr. Am. Med. Assoc., 1934, cii, 1844-1845. CrossrefGoogle Scholar2. CUTTINGMEHRTENSTAINTER WCHGML: Actions and uses of dinitrophenol, Jr. Am. Med. Assoc., 1933, ci, 193-195. CrossrefGoogle Scholar3. CUTTINGTAINTER WCML: Metabolic actions of dinitrophenol, 1933, ci, 2099-2102. Google Scholar4. ANDERSONREEDEMERSON HHACGA: Toxicity of alpha-dinitrophenol, Jr. Am. Med. Assoc., 1933, ci, 1053-1055. CrossrefGoogle Scholar5. GEIGER JC: Death from alpha-dinitrophenol poisoning, Jr. Am. Med. Assoc., 1933, ci, 1333. CrossrefGoogle Scholar6. DODDSPOPE ECWJ: Dinitro-o-cresol as stimulator of metabolism, Lancet, 1933, ii, 352-353. CrossrefGoogle Scholar7. DODDSROBERTSON ECJD: Clinical applications of dinitro-o-cresol, Lancet, 1933, ii, 1137-1139. CrossrefGoogle Scholar8. TAINTERSTOCKTONCUTTING MLABWC: Use of dinitrophenol in obesity and related conditions, Jr. Am. Med. Assoc., 1933, ci, 1472-1475. CrossrefGoogle Scholar9. ISAACS BL: Dinitrophenol poisoning, Jr. Am. Med. Assoc., 1934, cii, 2218. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York*Received for publication September 14, 1934.From the Endocrine Clinic, Israel-Zion Hospital, Brooklyn, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySome Observations on the Effects of Environment on Mice Dosed with Dinitro-Ortho-Cresol 1 August 1935Volume 9, Issue 2Page: 198-200KeywordsAdverse reactionsDrugsHospitalsObesityToxicity ePublished: 1 December 2008 Issue Published: 1 August 1935 PDF downloadLoading ...
Strain-Encoded Cardiac Magnetic Resonance During High-Dose Dobutamine Stress Testing for the Estimation of Cardiac Outcomes
Authors: Grigorios Korosoglou, Gitsios Gitsioudis, Andreas Voss, Stephanie Lehrke, Nina Riedle, Sebastian J. Buss, Christian Zugck, Evangelos Giannitsis, Nael F. Osman, Hugo A. Katus
Journal: Journal of the American College of Cardiology (2011)
Abstract 3501: Aspirin modulates oncogene expression in hct 116 colon cancer cells
Authors: Rakesh Dachineni, Goqiang Ai, Jayarama B. Gunaje
Journal: Cancer Research (2014)

Abstract Aspirin is a 100 year old Non-steroidal anti-inflammatory drug (NSAID). Beside its use a cardio-protective agent, it is also used for treatment of headache, fever, and inflammation. Many studies have shown that regular intake of aspirin for 5 years or more reduces the risk of colon, breast, prostate, lung and skin cancers. However, mechanism for such actions is not very well understood. Since transformation of a normal cell to cancer cell often involves mutation and activation of proto-oncogene, we initiated this research to understand if aspirin modulates the level of oncogene products. In this study we focused on three different oncogenes; c-FOS, c-JUN and c-RAF. c-FOS and c-JUN are transcription factors, they form a heterodimer called Activator protein (AP-1) transcription factor and regulate the expression of other genes. We observed that, in serum starved HCT-116 colon cancer cells Aspirin and Salicylic acid inhibited serum induced c-FOS protein expression, however, levels of c-JUN protein were not inhibited. In fact Aspirin and Salicylic acid increased c-JUN levels marginally over the serum induced levels at all time points examined. Exposure of cells to Aspirin and Salicylic acid inhibited c-RAF levels in a concentration dependent fashion. Inhibition was observed at physiologically achieved concentration of 250 -500 micro molar Salicylic acid suggesting that Aspirin may mediate its effects through the formation of Salicylic acid. We are currently investigating how inhibition of c-RAF levels by Aspirin and Salicylic acid affects downstream signaling molecules such as p42/p44 MAP kinases. Modulation of proto oncogenes by Aspirin may represent an important pathway by which Aspirin may mediate its anti-cancer effects. Citation Format: Rakesh Dachineni, Goqiang Ai, Jayarama B. Gunaje. Aspirin modulates oncogene expression in hct 116 colon cancer cells. [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 3501. doi:10.1158/1538-7445.AM2014-3501
Control of HIF-1α Expression by eIF2α Phosphorylation–Mediated Translational Repression
Authors: Keyi Zhu, WaiKin Chan, John Heymach, Miles Wilkinson, David J. McConkey
Journal: Cancer Research (2009)

Hypoxia inducible factor 1alpha (HIF-1alpha) plays a central role in regulating tumor angiogenesis via its effects on vascular endothelial growth factor (VEGF) transcription, and its expression is regulated through proteasome-mediated degradation. Paradoxically, previous studies have shown that proteasome inhibitors (PI) block tumor angiogensis by reducing VEGF expression, but the mechanisms have not been identified. Here, we report that PIs down-regulated HIF-1alpha protein levels and blocked HIF-1alpha transcriptional activity in human prostate cancer cells. PIs induced phosphorylation of the translation initiation factor 2alpha (eIF2alpha), which caused general translational repression to inhibit HIF-1alpha expression. Furthermore, PIs induced HIF-1alpha accumulation in LNCaP-Pro5 cells depleted of eIF2alpha via siRNA transfection and in MEFs expressing a phosphorylation-deficient mutant form of eIF2alpha. Finally, PIs failed to induce eIF2alpha phosphorylation or translational attenuation in DU145 or 253JB-V cells, and, in these cells, PIs promoted HIF-1alpha accumulation. Our data established that PIs down-regulated HIF-1alpha expression in cells that display activation of the unfolded protein response by stimulating phosphorylation of eIF2alpha and inhibiting HIF-1alpha translation.
Public Health Targets Teens' Private ActsNew Paradigms Sought to Explain Occupational and Environmental DiseasePioneers in Providing a Competency InventoryEbbing Epidemic: Youth Homicide Rate at a 14-Year LowMiscellanea MedicaPublic Health Targets Teens' Private ActsNew Paradigms Sought to Explain Occupational and Environmental DiseasePioneers in Providing a Competency InventoryEbbing Epidemic: Youth Homicide Rate at a 14-Year LowMiscellanea Medica
Authors: M Mitka
Journal: JAMA (1999)

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 Journals 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 2024 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 P161: Drug-Eluting Stent Utilization and Post-Coronary Revascularization Procedure Mortality: Do Racial Disparities Matter?
Authors: Alexander V Sergeev
Journal: Circulation (2014)

Background: Besides being a major risk factor for coronary artery disease (CAD), diabetes mellitus (DM) also worsens CAD patients’ prognosis. Percutaneous coronary intervention (PCI) with stenting is an effective treatment procedure for certain categories of CAD patients with DM (CAD-DM). Newer drug-eluting stents (DES) were developed to minimize the occurrence of restenosis known to hinder PCI with older non-drug-eluting stents (non-DES). We hypothesized that disparities in DES utilization and post-procedure mortality would exist in CAD-DM patients. Methods: We conducted a retrospective cohort study of in-hospital mortality in 132,934 CAD-DM patients [mean+SD age: 65.3+11.4 years; 62.7% (83,409 of 132,934) males] after PCI with DES and non-DES in the years 2007,2009. Patient race was classified as white, black, or other Asian, Pacific Islander, Native American). Due to short length of stay, in-hospital death was defined as a binary variable (discharged alive vs. deceased). Multivariable logistic regression was used to obtain adjusted odds ratios (ORs) for in-hospital death after DES and non-DES PCI in relation to patients’ race, adjusting for confounders: age, gender, comorbidities, number of stents inserted, number of vessels treated, socio-economic status, emergency department (ED) admission, rural/urban area status. Results: Blacks were less likely to receive newer DES stent than any other racial group: 75.7% blacks, 76.9% whites, 79.0% other (p&lt;0.04). Blacks were more likely to undergo an emergency rather than planned procedure: 45.7% blacks, 39.8% whites, and 42.7% other were ED-admitted (p&lt;0.01). In adjusted multivariable analysis, controlling for the type of stent and confounding factors, post-PCI mortality in blacks was similar to whites (adjusted OR 0.824, 95% CI: 0.672-1.010, p=0.06), but in other was higher than in whites (adjusted OR 1.284, 95% CI: 1.151-1.434, p&lt;0.001). Conclusions: Racial disparities exist in DES utilization by CAD-DM patients and in post-PCI in-hospital mortality: blacks are least likely to receive DES, but patients of other racial groups are more likely to die after PCI. Further studies investigating the mechanisms responsible for these disparities are warranted.
Beta-blockers in asthma.
Authors: Luke Bereznicki, Bonnie Bereznicki
Journal: BMJ (1981)

Australia has one of the highest prevalence rates for asthma in the world, affecting around 15% of the population. Short-acting beta 2  agonists (SABAs) have a longstanding role as the main treatment option for the acute relief of symptoms, while more recently long-acting beta 2  agonists (LABAs) have been recommended for use as add-on therapy to inhaled corticosteroids for the prevention of symptoms.
Changes in epidemiology, clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season
Authors: D. Viasus, E. Cordero, J. Rodríguez-Baño, J.A. Oteo, A. Fernández-Navarro, L. Ortega, I. Gracia-Ahufinger, M.C. Fariñas, E. García-Almodovar, A. Payeras, J.R. Paño-Pardo, E. Muñez-Rubio, J. Carratalà
Journal: Clinical Microbiology and Infection (2011)
CONGENITAL MALFORMATIONS OF THE PULMONIC AND AORTIC VALVES
Authors: Donald W. Ingham
Journal: Annals of Internal Medicine (1938)

Article1 November 1938CONGENITAL MALFORMATIONS OF THE PULMONIC AND AORTIC VALVESDONALD W. INGHAM, M.D.DONALD W. INGHAM, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-5-609 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCongenital malformations of the semilunar valves are relatively infrequent and usually consist of a variation in the number of cusps. Acquired malformations are seldom found, but must be carefully distinguished from the congenital form.Simonds, in 1923, collected 209 records of cases of alteration in the number of cusps. In his paper on this subject, he reported his series together with those of three other investigators, a total of 43 cases discovered in the course of 15,666 postmortem examinations. Abbott, in 1932, in her tabulation of 1000 cases, reported 43 instances in which the defects were unaccompanied by other lesions...References1. ABBOTT ME: Congenital heart disease. In: Nelson New Loose-Leaf Medicine, New York, Thomas Nelson and Sons, Part 2, Chapter 1, vol. 4, 1932, pp. 207-321. Google Scholar2. BISHOPTRUBEK LFM: Bicuspid aortic valve; a differential study between inflammatory and congenital origin, Jr. Tech. Methods, 1936, xv, 111-131. Google Scholar3. OSLER W: The bicuspid condition of the aortic valves, Trans. Assoc. Am. Phys., 1886, i, 185-192. Google Scholar4. SIMONDS JP: Congenital malformations of the aortic and pulmonary valves, Am. Jr. Med. Sci., 1923, clxvi, 584-595. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Submitted for publication October 19, 1937.Extract from thesis submitted to the Faculty of the Graduate School of the University of Minnesota in partial fulfillment of the requirements for the degree of M.S. in Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOutcomes after repair or replacement of dysfunctional quadricuspid aortic valveQuadricuspid semilunar valveAbsence of the pulmonary valve associated with ventricular septal defect∗DYNAMIC PULMONARY REGURGITATION ASSOCIATED WITH A BICUSPID VALVE*JANET DICKENS, M.D., GEORGE T. RABER, B.S., HARRY GOLDBERG, M.D., F.A.C.P.Isolated congenital bicuspid pulmonary valve 1 November 1938Volume 12, Issue 5Page: 609-613KeywordsAortic valveAutopsyGraduate medical educationLesions Issue Published: 1 November 1938 PDF downloadLoading ...