tbuckley/cabot-search huggingface dataset:
Abstract 11685: Early Myocardial Gene Expression Profiling After Deep Hypothermic Circulatory Arrest Reveals Ontogenetic Adaptive Mechanisms Underlying Ischemia-Reperfusion Tolerance in the Swine
Authors: Miki Yamada, Amir Sheikh, Kevin Collins, James Frederiksen, George Quick, Andrew Lodge, Mihai Podgoreanu
Journal: Circulation (2014)

Previous studies suggest that immature hearts are more tolerant to ischemia than adult myocardium; whether differences exist during ontogenic development in severity of global myocardial ischemia/reperfusion (I/R) injury associated with cardiac surgery remains unknown. We employed swine models of deep hypothermic circulatory arrest (DHCA) to test the hypothesis that early differential regulation of cardioprotective genes is associated with increased tolerance of neonatal myocardium to surgical I/R. Male neonatal and adult pigs were randomized to DHCA or sham (N=5-14/group). DHCA animals underwent cardiopulmonary bypass (18°C), DHCA 60 min, and were recovered for 3h. Severity of perioperative myocardial injury was determined biochemically (Troponin I) and echocardiographically. Transcript levels were quantified in left ventricular myocardium using Affymetrix Porcine Genome arrays, followed by differential expression and pathway analysis. A 2-fold increase in severity of perioperative myocardial injury was found in adult pigs (Fig.A). Of 596 transcripts differentially expressed in neonates (≥1.5-fold change, DHCA vs. sham, FDR&lt;0.05), 53 were shared with adults (Fig.B). Among them, divergent expression patterns were found for oxysterol binding protein-like 6 (down-regulated in adults up-regulated in neonates) and bromodomain adjacent to zinc finger domain 2B (up-regulated in adults - down-regulated in neonates). Top transcripts uniquely upregulated in neonates but unchanged in adults were the apoptosis inhibitor baculoviral IAP repeat containing 2, and signal transducer and activator of transcription 3. mTOR signaling and p53 signaling were the top canonical pathways deregulated in adults and neonates, respectively. A high resistance to surgical I/R injury in neonatal vs adult swine heart is correlated with robust differences in early transcriptional programs, suggesting the involvement of fundamental adaptive ontogenetic processes.
The relationship of small airways disease to spirometry and emphysema in α-1 antitrypsin deficiency
Authors: Asem Ismail, James Stockley, Robert Stockley
Journal: European Respiratory Journal (2014)

Background   It has been suggested that small airways disease precedes the development of basal emphysema in α-1 antitrypsin deficiency (AATD)  1 . The present study assessed measures of small airway function, namely mean mid-expiratory flow between 25% and 75% of vital capacity (MMEF) in never smokers with AATD to determine the relationship to spirometry and CT densitometry.   Methods   We analysed percentage predicted values for MMEF and FEV 1  as well as the FEV 1 :FVC ratio from 198 never smokers with ZZ AATD. The relationship of MMEF to lung densitometry was also assessed using a cut off of -910 HU to separate normal from emphysematous lung   Results   Curvilinear relationships were observed between MMEF and FEV 1 , FEV 1 :FVC ratio (figure) and CT density. 20.2% of patients had a normal FEV 1  (>80% predicted) and reduced MMEF ( 1 :FVC (>70%) with reduced MMEF (Box-a). 10% of the patients had an abnormal MMEF when CT density was in the normal range.   Conclusion   The results demonstrate that a reduced MMEF is often present in subjects whose spirometry is in the normal range and before demonstrable emphysema is present on CT scan. This supports the concept that small airways disease precedes the development of emphysema and MMEF is more sensitive to the presence of early disease than traditional spirometric measurements.  1 Hogg JC  et al . NEJM 350.26 (2004): 2645-653.
Abstract 20622: Effect of Angiotensin Receptor Blockade on Carotid Artery Atherosclerosis
Authors: Ronnie Ramadan, Saurabh Dhawan, Ayman Alkhoder, Jose N Binongo, John Oshinski, Arshed A Quyyumi
Journal: Circulation (2014)

Background:  Angiotensin II plays a key role in the pathogenesis of atherosclerosis at least partly by promoting oxidative stress (OS) and inflammation.   Objectives:  We investigated the effects of Angiotensin II type-1 receptor (AT 1 R) blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis, OS, and inflammation.   Methods:  Subjects (n= 120, 60±9 years, 51% male) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan (n=80), titrated up to 320 mg daily, or placebo (n=40) for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging (MRI) was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area (VWA) and wall thickness (WT) were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent brachial artery vasodilation. Statistical comparisons between groups were performed using a linear mixed-effects model to account for multiple measurements within subject.   Results:  Over 2 years, the carotid bulb VWA decreased with valsartan (p=0.008) but not with placebo (p=0.28); p=0.01 between groups. Similarly, mean WT increased with placebo (p=0.0035) but remained unchanged with Valsartan (p=0.31); p=0.009 between groups. Importantly, plaque thickness decreased with Valsartan (p= 0.014) but was unchanged with placebo (p=0.16); p=0.01 between groups. These findings were independent of statin therapy and changes in blood pressure. Furthermore, there were significant improvements in the aminothiol cysteineglutathione disulfide and fibrinogen levels and in endothelium-independent vasodilation with Valsartan.   Conclusions:  AT 1 R blockade with Valsartan is associated with significant carotid arterial remodeling manifested as regression in carotid atherosclerosis, changes that may be secondary to improvement in OS, inflammation, and vascular function.
CORTISONE THERAPY IN PORPHYRIA HEPATICA, ACUTE INTERMITTENT TYPE: A REPORT OF UNFAVORABLE RESULTS
Authors: O C OLSON, M H STILES
Journal: Annals of Internal Medicine (1954)

Case Reports1 August 1954CORTISONE THERAPY IN PORPHYRIA HEPATICA, ACUTE INTERMITTENT TYPE: A REPORT OF UNFAVORABLE RESULTSO. CHARLES OLSON, M.D., F.A.C.P., MERRITT H. STILES, M.D., F.A.C.P.O. CHARLES OLSON, M.D., F.A.C.P.Search for more papers by this author, MERRITT H. STILES, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-2-357 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is not the purpose of this paper to review the clinical and pathologic features of porphyria, since they have been adequately covered in previous papers and these authors can add nothing further.We do believe it is worth while, however, to review briefly a tentative classification of porphyria which has been recently suggested by Dr. C. J. Watson.1 We believe that this classification will serve to clarify the clinical picture and to furnish a better understanding of the pathologic background of this disease.Gunther proposed the first classification of porphyria many years ago (1911), but his nomenclature is conflicting...Bibliography1. Watson CJ: A basic classification of porphyria: certain diagnostic and therapeutic considerations, Read before the American College of Physicians in Atlantic City, New Jersey, April 13, 1953. Google Scholar2. JanoffPoutaYoung LAJJD: Acute intermittent porphyria, prompt response to therapy with corticotropin, Arch. Int. Med. 91: 389, 1953. CrossrefGoogle Scholar3. GoldbergMacdonaldRimington AACC: Acute porphyria, experimental treatment with ACTH, Brit. M. J. 2: 1174, 1952. CrossrefMedlineGoogle Scholar4. OltmanFriedman JDS: Acute porphyria, report of a case showing ineffectiveness of ACTH, New England J. Med. 244: 173, 1951. CrossrefGoogle Scholar5. GilbertToupinBell JAHMRE: Acute porphyria, Canad. M. A. J. 65: 585, 1951. MedlineGoogle Scholar6. MellingerPearson GWCC: Acute porphyria: a case report, Ann. Int. Med. 38: 862, 1953. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Spokane, Washington*Received for publication September 2, 1953. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDas adrenocorticotrope Hormon (ACTH), die HormonederNebenniere(Cortison,Adrenalin) das Insulin, sowie die Hormone der Schilddrüse und NebenschilddrüseProgesterone-induced porphyria 1 August 1954Volume 41, Issue 2Page: 357-363KeywordsPorphyria ePublished: 1 December 2008 Issue Published: 1 August 1954 PDF downloadLoading ...
Maternal methylation imprints on human chromosome 15 are established during or after fertilization
Authors: Osman El-Maarri, Karin Buiting, Edwin G. Peery, Peter M. Kroisel, Basak Balaban, Klaus Wagner, Bulent Urman, Julia Heyd, Christina Lich, Camilynn I. Brannan, Jörn Walter, Bernhard Horsthemke
Journal: Nature Genetics (2001)
Response to acne, isotretinoin and suicide attempts: a critical appraisal
Authors: A. Sundström, L. Alfredsson, G. Sjölin-Forsberg, B. Gerdén, U. Bergman, J. Jokinen
Journal: British Journal of Dermatology (2011)

Journal Article Response to acne, isotretinoin and suicide attempts: a critical appraisal Get access A. Sundström, A. Sundström Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar L. Alfredsson, L. Alfredsson Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar G. Sjölin‐Forsberg, G. Sjölin‐Forsberg Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar B. Gerdén, B. Gerdén Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar U. Bergman, U. Bergman Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar J. Jokinen J. Jokinen Centre for Pharmacoepidemiology, Karolinska Institute, 171 76 Stockholm, Sweden E‐mail: anders.sundstrom@ki.se Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 6, 1 June 2011, Pages 1185–1186, https://doi.org/10.1111/j.1365-2133.2011.10370.x Published: 01 June 2011
An Essential Role of Caspase 1 in the Induction of Murine Lupus and Its Associated Vascular Damage
Authors: J. Michelle Kahlenberg, Srilakshmi Yalavarthi, Wenpu Zhao, Jeffrey B. Hodgin, Tamra J. Reed, Noriko M. Tsuji, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2013)

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome associated with organ damage and an elevated risk of cardiovascular disease resulting from activation of both innate and adaptive immune pathways. Recently, increased activation of the inflammasome machinery in SLE has been described. Using the mouse model of pristane-induced lupus, we undertook this study to explore whether caspase 1, the central enzyme of the inflammasome, plays a role in the development of SLE and its associated vascular dysfunction.Eight-week-old wild-type (WT) or caspase 1(-/-) mice were injected intraperitoneally with phosphate buffered saline or pristane. Six months after injection, mice were euthanized, and the development of a lupus phenotype and vascular dysfunction was assessed.While WT mice exposed to pristane developed autoantibodies and a strong type I interferon response, mice lacking caspase 1 were significantly protected against these features as well as against pristane-induced vascular dysfunction. Further, the development of immune complex glomerulonephritis, which was prominent after pristane exposure in WT mice, was significantly abrogated in caspase 1(-/-) mice.These results indicate that caspase 1 is an essential component in the development of lupus and its associated vascular dysfunction and that it may play an important role in the cross-talk between environmental exposures and autoimmunity development, thus identifying a novel pathway for therapeutic targeting.
Transferring genomics to the clinic: distinguishing Burkitt and diffuse large B cell lymphomas
Authors: Chulin Sha, Sharon Barrans, Matthew A. Care, David Cunningham, Reuben M. Tooze, Andrew Jack, David R. Westhead
Journal: Genome Medicine (2015)

Classifiers based on molecular criteria such as gene expression signatures have been developed to distinguish Burkitt lymphoma and diffuse large B cell lymphoma, which help to explore the intermediate cases where traditional diagnosis is difficult. Transfer of these research classifiers into a clinical setting is challenging because there are competing classifiers in the literature based on different methodology and gene sets with no clear best choice; classifiers based on one expression measurement platform may not transfer effectively to another; and, classifiers developed using fresh frozen samples may not work effectively with the commonly used and more convenient formalin fixed paraffin-embedded samples used in routine diagnosis.
Toxicology or The Effects of Poisons.
Authors: Frank P. Underhill
Journal: JAMA (1924)

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 12599: Visualizing Continuous Nocturnal Cardiac Output by Automatic Analysis of Circulation Time on Polysomnography in Patients With Heart Failure
Authors: Kazuya Hosokawa, Shin-ich Ando, Takeshi Tohyama, Yumi Tanaka, Hideki Otsubo, Ryo Nakamura, Toshiaki Kadokami, Takaya Fukuyama
Journal: Circulation (2014)

Background:  Although several types of non-invasive measurement of cardiac output have been developed, they are not fully satisfactory. Sleep disordered breathing (SDB) is observed in most heart failure (HF) patients. By utilizing oscillation in oxygen saturation accompanied with SDB of HF patients, we can determine lung to finger-tip circulation time (LFCT) by measuring the time delay between respiration and pulse oximetric saturation. By using the fact that LFCT is theoretically correlates to the reciprocal value of cardiac output, we developed an algorithm that automatically and continuously measure LFCT. The aim of this study is to verify whether LFCT determined by this algorithm correlates to actual cardiac output.   Method and Result:  In 31 patients with HF who were planned to undergo right-sided cardiac catheterization, we performed portable polysomnography. The pulse oximetric saturation monitor was equipped in the left finger-tip. We first developed an algorithm that automatically determines LFCT by a cross correlation analysis between respiratory air-flow and pulse oximetric saturation. The difference between automated algorithm derived LFCT vs. manually measured LFCT expressed by root mean squared error (RMSE) of was 2.3 ± 1.9 s. The overnight average LFCT also significantly correlated to the measured cardiac index (CI: p 2 =0.53, figure left). The relationship was approximated by the hyperbolic function given by CI(L/min/m 2 )={0.895(L/m 2 )х60(min/s)}/LFCT(s). The novel analysis visualizes nocturnal trend of cardiac output in HF patient with SDB (Figure right).   Conclusion:  Our novel analysis method of cardiac output using data of polysomnography would become an attractive tool for screening and managing HF patient.
Abstract 3692: Preclinical studies of a mutant p53 reactivating drug in pancreatic cancer
Authors: Xin Yu, Zhe Li, Oliver S. Eng, Ashley T. Tsang, Hongxia Lin, Murugesan Gounder, Darren R. Carpizo
Journal: Cancer Research (2014)

Abstract Pancreatic cancer therapy suffers from a lack of effective chemotherapy. TP53 is second only to Kras as the most commonly mutated gene in pancreatic cancer with point mutations occurring in 75% of patients. Recently, our laboratory identified NSC319726 (726) as an allele specific p53 mutant reactivating compound (Yu, et al. 2012, Cancer Cell). This compound selectively kills cancer cells that express the p53-R175H mutation by restoring wildtype structure and function to this mutant. It does not reactivate the DNA contact mutant, p53-R273H or p53-R248H. This established 726 as a lead compound for mutant p53 targeted drug development. We are currently investigating the potential of 726 as novel anti-cancer drug through pre-clinical studies in pancreatic cancer. We have investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of 726 in murine pancreatic cancer cell lines derived from the KPC mouse model expressing mutant KrasG12D and different alleles of TP53 (WT, null, p53R172H, p53R270H). Using LC/MS/MS we developed a sensitive assay for detection of 726 in mouse plasma. PK studies indicate a half-life of approximately 4 hours with an AUC of 199.78 ng/ml/h for a single 1mg/kg dose given Intravenously. Treatment of KPC cell lines with 726 indicates that the murine p53R172H protein is reactivated as indicated by loss of mutant conformation and induction of p53 target gene transcription. Cell growth inhibition assays reveal that the cell line KPCp53-R172H is sensitive to 726 while the KPCp53-R270H is not. We have developed a PD assay for 726 consisting of cleaved caspase-3 immunostaining and measurement of transcriptional levels of p53 targets PUMA, Noxa and p21. Using these assays we have tested several doses of 726 and found that we detect activity of 726 in KPCp53-R172H xenograft tumors while at the same time relatively no activity in KPCp53-R270H tumors. These same assays were also performed on KPC autochthanous tumors and again reveal activity of 726 in the KPCp53-R172H mice. Efficacy studies in the KPCp53-R172H xenografts reveal potent tumor growth inhibition at both IV (1mg/kg) and IP (5mg/kg) dosing while no evidence of growth inhibition in KPCp53-R270H. These studies confirm that 726 is an allele-specific p53 mutant reactivating compound and holds promise for future applications in pancreatic cancer. Citation Format: Xin Yu, Zhe Li, Oliver S. Eng, Ashley T. Tsang, Hongxia Lin, Murugesan Gounder, Darren R. Carpizo. Preclinical studies of a mutant p53 reactivating drug in pancreatic cancer. [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 3692. doi:10.1158/1538-7445.AM2014-3692
Hungarian parliament takes steps to privatise health service
Authors: Carl Kovac
Journal: BMJ (2000)

After a delay caused by political manoeuvring, the Hungarian parliament last week passed a bill during a special session providing an opportunity for the country's estimated 7000 family doctors, paediatricians, and dentists to privatise their practices.

The bill failed by one vote on 21 December in the absence of the junior coalition party, which was engaged in a dispute over other legislation with the …
The effect of Eudragit RL-100 on the mechanical and mucoadhesion properties of polycarbophil dosage forms1The results reported here form part of the dissertation projects of M.B. and T.N., completed in partial fulfilment of the requirements of their respective PhD and MSc degrees at the Hebrew University of Jerusalem. The study has been presented in part at the 22nd International Symposium on Controlled Release of Bioactive Materials, Seattle, WA, 1995.1
Authors: Boaz Tirosh, Muhammad Baluom, Taher Nassar, Michael Friedman, Abraham Rubinstein
Journal: Journal of Controlled Release (1997)
Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway
Authors: Nagesha Guthalu Kondegowda, Rafael Fenutria, Ilana R. Pollack, Michael Orthofer, Adolfo Garcia-Ocaña, Josef M. Penninger, Rupangi C. Vasavada
Journal: Cell Metabolism (2015)
Readmission and mortality after first hospital admission with acute hypercapnic respiratory failure (AHRF) requiring non-invasive ventilation (NIV)
Authors: Rebecca D'Cruz, Harman Saman, Olliver O'Sullivan, Norashikin Amran, Jumaa Bwika, Ben Beauchamp, Rahul Mukherjee
Journal: European Respiratory Journal (2013)

Introduction: Longer term data on mortality of patients requiring NIV due to AHRF have been reported (Thomas A et al. ERJ 2010; 36:54. 402s). We report 1-year mortality and readmission rates of a cohort of such patients admitted to a respiratory ward-based 11-bedded physiotherapy-led NIV unit in a hospital providing acute medical services to a population of about 450000.  Methods: An observational, single-centre, retrospective, follow-up study of all patients requiring NIV for AHRF (Arterial pH 7.35 and pCO2 6.0 kPa) for the first time between 01 Jan 2009 to 31 Dec 2009 was conducted.  Results: Of the 163 patients treated with NIV, data was complete on 149. Mean pH 7.21; mean FEV1 21% predicted.The most common cause for admission was exacerbation of COPD 76 (51%), followed by pneumonia 22 (14.7), Primary obese morbidity 13 (8.7%), left ventricular failure 6 (4.02%) and Multifactorial AHRF 32 (21.4%); Mortality at first admission was 38/149 (25.5%) and at 24 months was 86/149 (57.7%). Readmission for AHRF peaked at 1 year, with 32.9% of patients being readmitted at least once at 12 months after first presentation.  Discussion: Respiratory ward based NIV units in UK teaching hospitals tend to treat significantly more acidotic patients in real life than envisaged by the British Thoracic Society/Royal College of Physicians/Intensive Care Society 2008 guidelines. Allowing for that, short term (1-year) mortality and readmission rates remain similar to original studies on less severely acidotic AHRF patients, which probably indicates improved multidisciplinary team work and team learning.