tbuckley/cabot-search huggingface dataset:
Role of adenosine as mediator of bradyarrhythmias during hypoxia in isolated guinea pig hearts
Authors: R. C WESLEY, M. T BOYKIN, L. BELARDINELLI
Journal: Cardiovascular Research (1986)

Tissue concentrations of adenosine, an endogenous metabolite with negative chronotropic and dromotropic actions, are known to increase when myocardial oxygen supply is reduced. In this study the concentrations of endogenous adenosine released during a period of hypoxic perfusion were measured to determine whether they are sufficient to account for the effect of hypoxia on atrioventricular conduction in isolated perfused guinea pig hearts. In addition, the efficacy of competitive adenosine antagonism in reversing the effect of hypoxia on atrioventricular conduction and atrial automaticity were compared. Effluent samples for adenosine were collected at the onset of spontaneous and atrial pacing induced second degree atrioventricular block during hypoxic perfusion (Po2 3.07 kPa) and during the combined infusion of adenosine plus the nucleoside transport blocker, dipyridamole (Po2 71.1 kPa). The mean (SEM) atrial cycle lengths associated with the onset of atrioventricular block were 333(10) and 297(2) ms respectively. Effluent concentrations of adenosine associated with atrioventricular block during hypoxia (2342(160) pmol·min−1·g−1 heart weight) were approximately equal to those obtained during the infusion of adenosine plus dipyridamole (2538(256) pmol·min−1·g−1 heart weight) (no statistically significant difference). During hypoxic perfusion, among hearts showing spontaneous atrioventricular block and those in which atrial slowing prevented the onset of spontaneous block, the competitive adenosine antagonist aminophylline (60 μmol·litre−1) reversed either spontaneous or atrial pacing induced block without any effect on spontaneous atrial cycle length. In conclusion, the production and release of endogenous adenosine are sufficient to account for the effects (negative chronotropic and dromotropic) of hypoxia. Moreover, the effect of endogenously released adenosine during hypoxia is greater on atrioventricular conduction than on atrial automaticity. There may be an important role for adenosine antagonists in the treatment of atrioventricular block.
rhG-CSF resistant neutropenia in SLE
Authors: M. FROSCH, J. ROTH, E. HARMS
Journal: Annals of the Rheumatic Diseases (1997)

Pain in the rheumatic diseasesWe were very interested to read Professor Croft's article 1 about pain in the rheumatic diseases because we are interested in studying the relation between patients' perception of disease and objective signs. 2 In the daily management of a cohort of approximately 600 patients with inflammatory arthritis at Poole Hospital we noticed a dissociation between reported pain and objective measures of disease activity in a number of patients.To further study this phenomenon we randomly selected a sample of 100 patients with rheumatoid arthritis (mean (SD) age = 63 (12) years, 73% rheumatoid factor positive).We looked at the pattern of change of reported pain (10 cm visual analog scale (VAS)), number of swollen joints (EULAR 28 articular index), and serum C reactive protein (CRP, normal <10 mg/l) in the previous two years.We identified a close linear relation in 72 patients.In 18 patients pain was repeatedly reported at not less than 20 mms VAS despite no evidence of disease activity (CRP <10 mg/l and swollen joint count = 0) at any point during their follow up.In 10 patients pain was repeatedly scored as absent despite disease activity markers reflecting joint inflammation (CRP >15 mg/l, with or without >2 swollen joints).Fifteen of 18 patients showing pain but no disease activity were rheumatoid factor positive and there was no obvious diVerence in the degree of joint deformity clinically although detailed assessment of joint damage radiologically was not made.These preliminary data support our contention that, in about one third of patients followed up in a district general hospital, there is a dissociation between reported pain and objective signs of joint inflammation.These diVerences may be related to joint damage in the patients with pain but no disease activity but cannot be so explained in those patients with disease activity but no pain.A more detailed analysis of these patients may reveal the reasons for this dissociation.In the meantime we suggest that rheumatologists might consider managing pain separately from disease activity in some of their patients.We also urge caution in interpreting summated disease activity indices that include pain and joint tenderness as major parts of their score.
Hemophilia and the Acquired Immunodeficiency Syndrome
Authors: Oscar D. Ratnoff, Michael M. Lederman, Carl Krill, Lawrence M. Pass, Charles E. Ross
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 March 1985Hemophilia and the Acquired Immunodeficiency SyndromeOSCAR D. RATNOFF, M.D., MICHAEL M. LEDERMAN, M.D., CARL KRILL JR., M.D., LAWRENCE M. PASS, M.D., CHARLES E. ROSS, M.D.OSCAR D. RATNOFF, M.D.Search for more papers by this author, MICHAEL M. LEDERMAN, M.D.Search for more papers by this author, CARL KRILL JR., M.D.Search for more papers by this author, LAWRENCE M. PASS, M.D.Search for more papers by this author, CHARLES E. ROSS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-3-412_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Approximately 2 years have elapsed since the first description of the acquired immunodeficiency syndrome in patients with classic hemophilia (factor VIII deficiency) (1). An update of the frequency of problems related to this syndrome in Northeast Ohio may provide some insight into the magnitude of the problem in this population. As of 1 January 1982, 91 patients with classic hemophilia were enrolled in home therapy programs using lyophilized preparations of antihemophilic factor (factor VIII). Since that date, 7 patients have died, 3 of processes apparently unrelated to the syndrome, including 2 who died of chronic active hepatitis...References1. . P-neumocystis carinii pneumonia among patients with hemophilia A. MMWR. 1982;31:365-7. MedlineGoogle Scholar2. ELLIOTTHOPPESPLATTTHOMASPATELGANSAR JWMJIA. The acquired immunodeficiency syndrome and Mycobacterium avium-intracellular bacteremia in a patient with hemophilia. Ann Intern Med. 1983;98:290-3. LinkGoogle Scholar3. GORDONBERKOWITZSTRANDJORDKURCZYNSKIGOLDBERGCOCCIA ERSEJP. Burkitt lymphoma in a patient with classic hemophilia receiving factor VIII concentrates. J Pediatrics. 1983;103:75-7. CrossrefMedlineGoogle Scholar4. RATNOFFMENITOVEASTERLEDERMAN OJRM. Coincident classic hemophilia and "idiopathic" thrombocytopenic purpura in patients under treatment with concentrates of antihemophilic factor (factor VIII). N Engl J Med. 1983;308:239-42. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByA Full-Blown Epidemic 1 March 1985Volume 102, Issue 3Page: 412-412KeywordsAIDSChronic hepatitisHemophiliaHemophilia A Issue Published: 1 March 1985 PDF DownloadLoading ...
Granulocyte-macrophage colony-stimulating factor. Sensitive and receptor-mediated regulation by 1,25-dihydroxyvitamin D3 in normal human peripheral blood lymphocytes.
Authors: A Tobler, J Gasson, H Reichel, A W Norman, H P Koeffler
Journal: Journal of Clinical Investigation (1987)

We show that 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), the most hormonally active metabolite of vitamin D3, modulates sensitively and specifically both the protein and messenger RNA accumulation of the multilineage growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). The regulation of GM-CSF expression is seen in both normal human mitogen-activated T lymphocytes and T lymphocytes from a line (S-LB1) transformed with human T cell lymphotropic virus 1 (HTLV-1). In contrast, cells from a HTLV-1 transformed T lymphocyte line (Ab-VDR) established from a patient with vitamin D-resistant rickets type II with undetectable 1,25(OH)2D3 cellular receptors are resistant to the action of 1,25(OH)2D3. Inhibition of GM-CSF expression by 1,25(OH)2D3 can occur independently of interleukin 2 regulation and is probably mediated through cellular 1,25(OH)2D3 receptors. We conclude that 1,25(OH)2D3 may be important in the physiology of hematopoiesis.
Abstract 1716: Mechanisms of resistance in carboplatin, docetaxel and dual drug resistant ovarian cancer cell lines
Authors: Carita Lannér, Stephen Armstrong, Irina Kalatskaya, Baoqing Guo, Amadeo Parissenti
Journal: Cancer Research (2011)

Abstract Carboplatin and docetaxel are two standard chemotherapeutics used to treat ovarian cancer. Patients often exhibit resistance to single agent therapy, and dual agent therapy was developed to overcome this resistance. However, resistance still commonly occurs in dual agent therapy. It is known that specific changes in gene expression occur in single agent resistance, but it is not known whether resistance to combined chemotherapy involves novel gene expression changes or if resistance is only the sum of changes seen in single agent resistant cells. Using the chemotherapy-naïve A2780 ovarian cancer cell line, we have generated three resistant cell lines including carboplatin and docetaxel single agent resistant lines (A2780CBN, and A2780DXL respectively), and a carboplatin/docetaxel dual resistant line (A2780CBNDXL) by exposing A2780 cells to increasing concentrations of drug until a dose is reached where resistance could no longer be developed. The concentration of drug at which 50% of cells die (IC50) was measured for reach resistant cell line using a clonogenic assay. The IC50 of A2780CBN is 8×10−5 M, 13-fold more resistant than the parent line. The IC50 of A2780DXL is 3×10−7 M, 5000-fold more resistant than the parent line. The IC50 of A2780CBNDXL is 8×10−6 M for carboplatin and 8×10−9 M for docetaxel. Changes in gene expression associated with the development of resistance in each cell line were identified by microarray analysis on Agilent 4×44k total human genome arrays. In the A2780CBN line there were a total of 1209 significant changes in gene expression, in the A2780DXL line there were 955 changes, and in the A2780CBNDXL line there were 1336 changes. The majority of changes in each cell line (70%) were unique, indicating that novel changes in gene expression occur in the dual line. A Functional Interaction Network-based analysis was conducted on the microarray data identify important gene clusters acting in the drug resistant A2780 ovarian cancer cell lines. Ten major clusters were found in the A2780CBN line, 8 clusters in the A2780DXL line and 10 clusters in the A2780CBNDXL line. Although similar clusters occurred among the lines, the genes in them were different and several unique clusters occurred in the dual line. Functional enrichment analysis will be done for every cluster and the most significant pathways will be taken into further consideration for validation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1716. doi:10.1158/1538-7445.AM2011-1716
CARDIOVASCULAR PROGNOSIS OF COMBINED PATTERNS OF RESISTANT HYPERTENSION AND SMOKING STATUS: A 3.6 YEAR FOLLOW-UP STUDY
Authors: Konstantinos P. Tsioufis, Alexandros Kasiakogias, Athanasios Kordalis, Kyriakos Dimitriadis, Ioannis Liatakis, Konstantinos Kintis, Lefki Nikolopoulou, Evaggelia Koutra, Theodoros Kalos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Immunohistochemically Defined T1N0 Breast Cancer Subgroups Have Different Clinical Outcomes. A Retrospective Turkish Oncology Group Study.
Authors: G. Basaran, S. Okkan, H. Caglar, M. Benekli, M. Gumus, A. Haydaroglu, Y. Eralp, H. Abali, F. Yildiz, N. Bese, B. Gursel, N. Guney, D. Derin
Journal: Cancer Research (2009)

Abstract Introduction: T1N0 breast cancer (BC) has a very favorable outcome therefore the need of adjuvant systemic therapy is controversial. Molecular profiling studies identified BC subtypes with distinct clinical outcomes. We planned to determine whether immunohistochemically (IHC) defined subgroups of T1N0 BC patients have different clinical outcomes. Methods: Medical records of pts with T1N0 BC and known ER, PR and Her-2 status who have been treated between 1998-2008 were reviewed. Patients with bilateral disease, who had adjuvant trastuzumab therapy were excluded. Clinical/pathological, treatment characteristics were recorded and patients were subdivided into four BC subtypes: triple negative (ER, PR, HER2 negative), HER2 (ER and PR-negative, HER2-positive), luminal B (ER-positive and/or PR-positive, HER2-positive), and luminal A (ER and/or PR-positive and HER2-negative). Her-2 positivity was defined as IHC 3+ or FISH positive IHC2 2+. Survival outcome of the IHC defined subgroups were analyzed the Kaplan-Meier method and compared with the log-rank test. Results: A total of 1035 pts have been identified from 17 Medical/Radiation Oncology centers in Turkey. Median age was 51 and median follow up was 39 months. Forty-four % of patients were premenopausal, 55% had left breast involved, 73% had breast conserving surgery, 81% had invasive ductal carcinoma. T1a,b,c tumors were 7%, 30%, 63% ; grade 1,2,3 tumors were 20%, 53%, 27% respectively. HER2 was 2 + in 59 (6%) and 3 + in 111 (11%) tumors. Twelve % tumors were triple negative. Thirty-seven % patients had adjuvant chemotherapy; 80 % had adjuvant endocrine therapy 73% had adjuvant radiotherapy. Five-yr DFS and OS of the whole group were 92% and 99% respectively. So far, 19 pts had local and 24 pts had distant metastases, 4 pts had secondary cancers, 6 patients contralateral BC and 11 patients died (7/11 pts died from breast cancer). Classification based on ER, PR and Her-2 status had significant impact on 5-yr DFS (p:0.00) and OS (p:0.00). The 5-yr DFS and OS were 84%;74%;%;94% and 96%;83%;100%;99% respectively for triple negative, HER2, luminal B, and luminal A subgroups respectively. Hormone receptor and triple negative status were the two other parameters affecting survival outcome significantly (p:0.00, p: 0.007) in the univariate analyses. Conclusion: Most patients with T1N0 disease have generally a favorable clinical outcome, however even within this very early stage of BC there are subgroups with diverse clinical outcomes. Despite our short follow up with low number of events, we found that Her-2 positive and triple negative T1N0 BC have poor clinical outcomes compared to luminal T1N0 subgroups and therefore they might need special concern with respect to adjuvant systemic therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3167.
Dapsone to delay symptoms in Creutzfeldt-Jakob disease
Authors: Laura Manuelidis, William Fritch, Igor Zaitsev
Journal: The Lancet (1998)

There is a need for effective drug treatments in patients with Creutzfeldt-Jakob disease (CJD). The importance of host inflammatory responses to the infectious agents that cause spongiform encephalopathies have been dismissed 1 Prusiner S The prion diseases. Sci Am. 1995; 272: 30-37 Crossref Scopus (122) Google Scholar although bone-marrow-derived cells and macrophages carry the infectious agent. 2 Manuelidis L Fritch W Xi YG Evolution of a strain of CJD that induces BSE-like plaques. Science. 1997; 277: 94-98 Crossref PubMed Scopus (124) Google Scholar Recent experiments with a rat-adapted CJD agent have shown that brain microglia (antigen-presenting cells of myeloid lineage) and astroglia are activated as early as 150 days after infection while function is comprised only after more than 300 days. 2 Manuelidis L Fritch W Xi YG Evolution of a strain of CJD that induces BSE-like plaques. Science. 1997; 277: 94-98 Crossref PubMed Scopus (124) Google Scholar Vaccination effects in CJD also implicate inflammatory cells in processing the infective agent and suppression of more virulent strains. 3 Manuelidis L Vaccination with an attenuated CJD strain prevents expression of a virulent agent. Proc Natl Acad Sci USA. 1998; 95: 2520-2525 Crossref PubMed Scopus (69) Google Scholar Radiation and cyclophosphamide, which affect rapidly dividing B and T cells but not long-lived macrophages, microglia, or astrocytes, have had no effect on scrapie incubation, although compounds which target macrophages can prolong or even abolish peripheral infections. 2 Manuelidis L Fritch W Xi YG Evolution of a strain of CJD that induces BSE-like plaques. Science. 1997; 277: 94-98 Crossref PubMed Scopus (124) Google Scholar We tested the effects of indometacin and dapsone, anti-inflammatory drugs which enter the brain after being taken by mouth. Indometacin, an inhibitor of prostaglandin synthesis, can reduce HIV-1 replication in cultured T cells, 4 Bourinbaiar A Lee-Huang S The non-steroidal anti-inflammatory drug, indomethacin as an inhibitor of HIV replication. FEBS Lett. 1995; 360: 85-88 Summary Full Text PDF PubMed Scopus (32) Google Scholar and dapsone has been used to subdue organisms that hide in macrophages. Dapsone may also decrease amyloid formation. 5 Namba Y Kawatsu K Izumi S Ueki A Ikeda K Neurofibrillary tangeles and senile plaques in brain of elderly leprosy patients. Lancet. 1992; 340: 978 Abstract PubMed Scopus (57) Google Scholar
Platelet-Activating Factor Acetylhydrolase Activity Indicates Angiographic Coronary Artery Disease Independently of Systemic Inflammation and Other Risk Factors
Authors: Karl Winkler, Bernhard R. Winkelmann, Hubert Scharnagl, Michael M. Hoffmann, Andrea Busse Grawitz, Markus Nauck, Bernhard O. Böhm, Winfried März
Journal: Circulation (2005)

Platelet-activating factor acetylhydrolase (PAF-AH), also denoted as lipoprotein-associated phospholipase A2, is a lipoprotein-bound enzyme that is possibly involved in inflammation and atherosclerosis. This study investigates the relationship of PAF-AH activity to angiographic coronary artery disease (CAD), the use of cardiovascular drugs, and other established risk factors.PAF-AH activity, lipoproteins, sensitive C-reactive protein (sCRP), fibrinogen, serum amyloid A, and white blood cell count were determined in 2454 subjects with angiographically confirmed CAD and in 694 control subjects. PAF-AH activity was highly correlated with LDL cholesterol (r=0.517), apolipoprotein B (r=0.644), and non-HDL cholesterol (r=0.648) but not with sCRP or fibrinogen. PAF-AH activity was lower in women than in men and was affected by the intake of lipid-lowering drugs (-12%; P<0.001), aspirin (-6%; P<0.001), beta-blockers (-6%; P<0.001), and digitalis (+7%; P<0.001). Unlike sCRP, fibrinogen, and serum amyloid A, PAF-AH activity was not elevated in unstable angina, non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction. When nonusers of lipid-lowering drugs were examined, PAF-AH activity was associated with the severity of CAD and the number of coronary vessels with significant stenoses. In individuals not taking lipid-lowering drugs and after adjustment for use of aspirin, beta-blocker, and digitalis, the odds ratio for CAD associated with increasing PAF-AH activity was 1.39 (95% CI 1.26 to 1.54, P<0.001), a finding that was robust against further adjustments.PAF-AH activity is not an indicator of the systemic inflammation that accompanies acute coronary syndromes. PAF-AH activity is affected by a number of cardiovascular drugs; however, after such medication use was accounted for, PAF-AH activity was associated with angiographic CAD, complementary to sCRP and independently of established risk factors such as LDL cholesterol.
BASOPHIL ADENOMA OF THE PITUITARY GLAND WITH RENAL CHANGES
Authors: H. G. Close
Journal: BMJ (1935)

Priming of human NK cells with IL-2 is necessary to render them functionally competent upon NKG2D engagement. We examined the underlying mechanisms that control NKG2D responsiveness in NK cells and found that IL-2 upregulates expression of the amino acid transporters SLC1A5 and CD98. Using specific inhibitors to block SLC1A5 and CD98 function, we found that production of IFN-γ and degranulation by CD56<sup>bright</sup> and CD56<sup>dim</sup> NK cells following NKG2D stimulation were dependent on both transporters. IL-2 priming increased the activity of mTORC1, and inhibition of mTORC1 abrogated the ability of the IL-2–primed NK cells to produce IFN-γ in response to NKG2D-mediated stimulation. This study identifies a series of IL-2–induced cellular changes that regulates the NKG2D responsiveness in human NK cells.
Physics in Medicine and Biology Encyclopedia: Medical Physics, Bioengineering and Biophysics
Authors: Paul A. Bottomley
Journal: JAMA (1987)

There exists a field of endeavor at the edge of medicine whose challenge is to introduce new technologies and maintain the old. Commonly called<i>medical physics or biomedical engineering</i>, depending on the origins of its contributors, it has achieved many and marvelous successes throughout the history of medicine—from x-rays to hearing aids and heart valves to magnetic resonance imaging—that bear testimony to what may be accomplished when physicians, physicists, chemists, engineers, and mathematicians collaborate with common goals. Yet, the diversity of medical technology and the interdisciplinary nature of the collaboration often leave the medical physicist's role ill defined and the subject relegated to the periphery of mainstream conferences and journals devoted to the recognized disciplines. Moreover, questions like "What is a medical physicist?" often receive nebulous responses or are left completely unanswered, even by those employed as such. At least in this sense, the<i>Physics in Medicine and Biology Encyclopedia</i>
Symptomatic esophageal stricture and buried metaplasia after radiofrequency ablation of Barrett’s esophagus
Authors: F. Janssens, A. Rougemont, J. Deviere, P. Fockens, J. Dumonceau
Journal: Endoscopy (2009)

A 64-year-old woman with high-grade dysplasia (HGD) arising in Barrett’s esophagus was referred for treatment. Endoscopy with narrow band imaging confirmed the presence of Barrett’s esophagus (Prague C13M14) and no irregularity was detected at this level. Radiofrequency ablation (RFA) was the only treatment given, using the HALO system (BÂRRX Medical Inc., Sunnyvale, California, USA) in a standard manner, by an endoscopist highly experienced in this technique [1] [2]. After measuring the inner esophageal diameter, two consecutive circumferential ablations (12 J/cm2, 40 W/cm2) were carried out using a 31-mm in-diameter balloon, with removal of tissue debris between ablations using a cap-fitted endoscope. The procedure was uneventful and esomeprazole (40 mg twice daily) was prescribed. Ten weeks later the patient (still taking esomeprazole) presented with dysphagia. An upper endoscopy disclosed a stricture and neosquamous mucosa with salmon-colored islands ([Fig. 1]). Four-quadrant biopsies (every 2 cm) from the original Barrett’s esophagus segment disclosed no residual dysplasia, but buried glands were detected in one specimen sampled above the stricture ([Fig. 2]). The stricture was dilated twice with a balloon (up to a diameter of 18 mm), and 12 months after the RFA, the patient is doing well with neither residual dysphagia nor dysplasia. However, the buried glands are more widespread (detected in biopsies at four out of seven sampled levels). No more RFA has been attempted and the patient remains under close endoscopic surveillance.