tbuckley/cabot-search huggingface dataset:
Silencing of caspase-8 and caspase-3 by RNA interference prevents vascular endothelial cell injury in mice with endotoxic shock
Authors: N MATSUDA, Y TAKANO, S KAGEYAMA, N HATAKEYAMA, K SHAKUNAGA, I KITAJIMA, M YAMAZAKI, Y HATTORI
Journal: Cardiovascular Research (2007)

Objectives Septic shock and sequential multiple organ failure remain the cause of death in septic patients. Vascular endothelial cell apoptosis may play a role in the pathogenesis of the septic syndrome. Caspase-8 is presumed to be the apex of the death receptor-mediated apoptosis pathway, whereas caspase-3 belongs to the "effector" protease in the apoptosis cascade. Synthetic small interfering RNAs (siRNAs) specifically suppress gene expression by RNA interference. Therefore, we evaluated the therapeutic efficacy of caspase-8/caspase-3 siRNAs in a murine model of polymicrobial endotoxic shock. Methods Polymicrobial endotoxic shock was induced by cecal ligation and puncture (CLP) in BALB/c mice. In vivo delivery of siRNAs was performed by using a transfection reagent (Lipofectamine 2000) at 10 h after CLP. As a negative control, animals received non-sense (scrambled) siRNA. Results Marked increases in caspase-8 and caspase-3 protein expression in CLP aortic tissues were strongly suppressed by treatment with caspase-8/caspase-3 siRNAs. This siRNA treatment prevented DNA ladder formation and less phosphorylation of the pro-apoptotic protein Bad seen in CLP aortic tissues. Transferase-mediated dUTP nick end labeling (TUNEL) revealed that the appearance of apoptosis in aortic endothelium after CLP was eliminated by this siRNA treatment. Although all of the control animals subjected to CLP died within 2 days, administration of caspase-8/caspase-3 siRNAs indefinitely (>7 days) improved the survival of CLP mice. Conclusions Gene silencing of caspase-8 and caspase-3 with siRNAs provided profound protection against polymicrobial endotoxic shock. The prevention of vascular endothelial cell apoptosis appears to be, at least in part, responsible for their beneficial effects in endotoxic shock.
Graham Lancelot Hill
Authors: M. Keighley
Journal: BMJ (2013)

Graham Lancelot Hill was born in Dunedin, New Zealand. He was married to Bartha and together they had three sons—Andrew, Philip, and Douglas, who are all doctors practising in New Zealand (Andrew is a professor of surgery at the University of Auckland). Graham Lancelot Hill’s first surgical position was a missionary surgeon in Bandung, Indonesia. This was followed by a senior lectureship at Leeds University under J C Goligher, time as an attending surgeon in Houston with Stanley Dudrick, and a long tenure as professor and head of surgery at the University of Auckland.

He made many contributions to clinical surgery, including inflammatory bowel disease, pouch …
Malpractice and the Quality of Care
Authors: Robert H. Brook, Kathleen N. Williams
Journal: Annals of Internal Medicine (1978)

Editorials1 June 1978Malpractice and the Quality of CareROBERT H. BROOK, M.D., SC.D., KATHLEEN N. WILLIAMS, M.A.ROBERT H. BROOK, M.D., SC.D.Search for more papers by this author, KATHLEEN N. WILLIAMS, M.A.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-6-836 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPhysicians should be aware of the recent report on medical professional liability by the American Bar Association (ABA) Commission on Medical Professional Liability (1) (see review on p. 849), particularly for what it has to say with regard to relations between malpractice and quality assurance. Quality assurance, we sometimes need to remind ourselves, involves not only measuring the level of quality of care but, where necessary, taking steps to improve it.Two to three years ago, a malpractice crisis appeared to threaten serious disruption in the medical care system. Premiums for malpractice insurance were rising astronomically, especially for surgeons in...References1. : 1977 Report of the Commission on Medical Professional Liability. Chicago, American Bar Association, 1977 Google Scholar2. SOMERS H: The malpractice controversy and the quality of patient care. Milbank Mem Fund Q 55:193-232, 1977 CrossrefGoogle Scholar3. BROOKBRUTOCOWILLIAMS RRK: The relationship between medical malpractice and quality of care. Duke Law J 1975:1197-1231, 1976 CrossrefGoogle Scholar4. : Report on the Medical Insurance Feasibility Study. San Francisco, California Medical Association, 1977 Google Scholar5. : Vital Statistics of the United States, 1974. Volume II—Mortality, Part B. Rockville, Maryland, United States Government Printing Office, 1976 Google Scholar6. EVANSHEMELTOLSSON CMJ: A survey of professional liability incidence in Maryland, in Appendix of the Secretary's Commission on Medical Malpractice. DHEW No. (OS) 73-89. Washington, D.C., United States Government Printing Office, 1973 Google Scholar7. PABST W: Comments on the Maryland Professional Liabilities Survey, in Appendix of the Secretary's Commission on Medical Malpractice. DHEW NO. (OS) 73-89. Washington, D.C., United States Government Printing Office, 1973 Google Scholar8. PHELPS C: Experience Rating in Medical Malpractice Insurance. P-5877. Santa Monica, California, The Rand Corporation, 1977 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT H. BROOK, M.D., SC.D.; KATHLEEN N. WILLIAMS, M.A.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHandling of Complaints in Health Systems in the USA, Canada, England, and IsraelRisk Management and Nursing 1 June 1978Volume 88, Issue 6Page: 836-838KeywordsHealth care qualityHealth care quality assessmentSurgeons ePublished: 1 December 2008 Issue Published: 1 June 1978 PDF downloadLoading ...
Adverse reactions of low osmolality contrast media during cardiac angiography: A prospective randomized multicenter study
Authors: Edward W. Gertz, Judith A. Wisneski, Robert Miller, Merrill Knudtson, John Robb, Leonidas Dragatakis, Kevin F. Browne, George Vetrovec, Sidney C. Smith
Journal: Journal of the American College of Cardiology (1992)
Increased High-Molecular-Weight Thyrotropin with Impaired Biologic Activity in a Euthyroid Man
Authors: Irving M. Spitz, Derek Le Roith, Harry Hirsch, Pierre Carayon, Fredrika Pekonen, Yair Liel, Reuven Sobel, Zamir Chorer, Bruce Weintraub
Journal: New England Journal of Medicine (1981)

CIRCULATING high-molecular-weight forms of many polypeptide hormones have been described, but there have been few reports of their occurrence as the predominant forms of glycoprotein hormones.1 2 3 4 5 6 7 8 This paper describes the presence, in a healthy young man, of a high-molecular-weight species of immunoreactive thyrotropin (TSH), which bound normally to the TSH receptor but showed decreased stimulation of the adenylate cyclase of human thyroid membranes.Case ReportDuring studies of 30 to 40 normal medical-student volunteers, a healthy 29-year-old man was discovered to have an elevated serum TSH level in a double-antibody radioimmunoassay. His history was noncontributory, and there was no family . . .
Glucose-Lactate Inter-Relations in Man
Authors: Daniel Deykin, Christine Balko, Robert A. Kreisberg
Journal: New England Journal of Medicine (1972)

THE roles of carbohydrate, lipid and protein metabolism in the fuel economy of fed, fasting and exercising man1 2 3 have provided an intriguing saga in modern scientific investigation of intermediary metabolism. Lactate, a common intermediate or by-product of glycolysis that is produced in varying degrees by all tissues in the body, may exert a profound influence on the economy of glucose, since it is both an important precursor and an end product of glucose metabolism.4 Accelerated conversion of glucose to lactate, unless balanced by a commensurate increase in lactate conversion to glucose, could result in hypoglycemia. In certain cases tumor hypoglycemia . . .
Medical Research as Measured against the Needs of All
Authors: Thomas H. Weller
Journal: New England Journal of Medicine (1970)

An era of generous support for biomedical research in the United States is ending. A concerned citizenry focusing on domestic problems is more interested in the equitable utilization of available biomedical resources than in benefits that might derive from new knowledge. Recognition of domestic needs and a concurrent disenchantment with patterns of governmental activities overseas have fostered a national climate of isolationism. Economic and health-related assistance for the developing areas of the world has been curtailed. Yet the health problems of the underprivileged in the United States are essentially the same as those of three billion people living elsewhere in . . .
A novel role for IL-22R1 as a driver of inflammation
Authors: Ram Savan, Adelle P. McFarland, Della A. Reynolds, Lionel Feigenbaum, Karthika Ramakrishnan, Megan Karwan, Hidekazu Shirota, Dennis M. Klinman, Kieron Dunleavy, Stefania Pittaluga, Stephen K. Anderson, Raymond P. Donnelly, Wyndham H. Wilson, Howard A. Young
Journal: Blood (2010)
Management of a patient with HIV infection‐induced anemia and thrombocytopenia who presented with thrombotic thrombocytopenic purpura
Authors: Amy C. Gruszecki, Gay Wehrli, Brian D. Ragland, Vishnu V.B. Reddy, Lisle Nabell, Alejandro Garcia‐Hernandez, Marisa B. Marques
Journal: American Journal of Hematology (2002)

Abstract A 32‐year‐old male presented with fever, mental status changes, renal dysfunction, cytopenias and hemolysis. His platelet count was 14,000/μL, hemoglobin 5.7 g/dL and LDH 2,636 U/L. He was diagnosed with thrombotic thrombocytopenic purpura (TTP) and also found to be HIV positive on admission. TTP was confirmed by a low von Willebrand factor‐cleaving protease level, the gold standard test for TTP, which was 10–15%. No protease‐specific antibody was detected. Treatment of this patient consisted of 23 plasmapheresis procedures and trials of vincristine and dextran‐70. Despite therapy, the patient remained anemic and thrombocytopenic, though his mental status and renal abnormalities improved. Highly active anti‐retroviral therapy (HAART) consisting of efavirenz, 3TC, and d4T was started. Only after plasma exchanges were discontinued and HAART was instituted did the cytopenias resolve. He continued to improve following discharge, and platelet count was 206,000/μL and hemoglobin, 12.5 g/dL one month after the initiation of HAART. Am. J. Hematol. 69:228–231, 2002. © 2002 Wiley‐Liss, Inc.
A memorable journey into the past
Authors: J. Savin
Journal: BMJ (2001)

My grandfather worked as a medical missionary in Zhaotong, a small walled city in the Yunnan Province of China, from 1896 until his death there from typhus in 1918. My father spent his early childhood there too, returning to school in England when he was 12 years old. By then typhoid and chronic malaria had turned him into an animated human skeleton.

Later my father described in his unpublished memoirs how hard life had been in remote China in the early 1900s. He remembered seeing the decapitated heads of malefactors, stuck on spikes near the city gates. Rats scuttled around indoors; and the howls of wolves and jackals could be heard as they dug up the corpses of the Chinese poor from shallow graves just outside the city walls. Smallpox lurked in and around the city. …
Noninvasive Assessment of Blood Flow Based on Magnetic Resonance Global Coherent Free Precession
Authors: Igor Klem, Wolfgang G. Rehwald, John F. Heitner, Anja Wagner, Timothy Albert, Michele A. Parker, Enn-Ling Chen, Raymond J. Kim, Robert M. Judd
Journal: Circulation (2005)

Background— Magnetic resonance global coherent free precession (GCFP) is a new technique that produces cine projection angiograms directly analogous to those of x-ray angiography noninvasively and without a contrast agent. In this study, we compared GCFP blood flow with “gold standards” to determine the accuracy of noninvasive GCFP blood flow measurements. Methods and Results— The relationship between GCFP blood flow and true blood flow defined by invasive ultrasonic flow probe and by phase contrast velocity encoded MRI (VENC) was studied in anesthetized dogs (n=6). Blood flow was controlled by use of a hydraulic occluder around the left iliac artery. GCFP images were acquired by selectively exciting the abdominal aorta and visualizing temporal blood flow into the iliac arteries. GCFP flow was similar to ultrasonic blood flow at baseline (131.3±44.8 versus 114.8±34.2 mL/min), during occlusion (10.8±5.1 versus 6.5±7.2 mL/min), during reactive hyperemia (191.4±100.7 versus 260.3±138.7 mL/min), during the new resting state (135.5±52.4 versus 117.8±24.1 mL/min), and during partial occlusion (61.4±36.4 versus 49.3±13.1 mL/min, P =NS for all). Results comparing GCFP flow with VENC were similar. Statistical analysis revealed that GCFP flow was related to mean blood flow assessed by the flow probe ( P &lt;0.0001) and by VENC ( P &lt;0.0001). In the control right iliac artery, conversely, GCFP measurements were unaffected throughout all left iliac interventions ( P =NS). Conclusions— GCFP blood flow is linearly related to true blood flow for a straight, cylindrical blood vessel without branches. Although more complex geometries imply a qualitative rather than a quantitative relationship, the data nevertheless suggest that GCFP may serve as the basis for a new form of noninvasive stress testing.
How viewers get facts from fiction
Authors: U. Tayal
Journal: BMJ (2003)

We have long secretly suspected that medical students learn more from television dramas such as ER and Casualty than they do on the wards. But now a report claims that the general public may also have been learning more than we bargained for.

The report, Dramatic Licence: Fact or Fiction? , published by the UK Broadcasting Standards Commission and commissioned last month from market researchers NOP, looks at how accurately television drama series portray their featured professions

(www.bsc.org.uk/pdfs/research/dramatic.pdf). The research involved 14 group discussions—10 among the general public and four …
Urocortin-Induced Decrease in Ca <sup>2+</sup> Sensitivity of Contraction in Mouse Tail Arteries Is Attributable to cAMP-Dependent Dephosphorylation of MYPT1 and Activation of Myosin Light Chain Phosphatase
Authors: Lubomir T. Lubomirov, Katrin Reimann, Doris Metzler, Veronika Hasse, Robert Stehle, Masaaki Ito, David J. Hartshorne, Hristo Gagov, Gabriele Pfitzer, Rudolf Schubert
Journal: Circulation Research (2006)

Urocortin, a vasodilatory peptide related to corticotropin-releasing factor, may be an endogenous regulator of blood pressure. In vitro, rat tail arteries are relaxed by urocortin by a cAMP-mediated decrease in myofilament Ca2+ sensitivity through a still unclear mechanism. Here we show that contraction of intact mouse tail arteries induced with 42 mmol/L KCl or 0.5 micromol/L noradrenaline was associated with a approximately 2-fold increase in the phosphorylation of the regulatory subunit of myosin phosphatase (SMPP-1M), MYPT1, at Thr696, which was reversed in arteries relaxed with urocortin. Submaximally (pCa 6.1) contracted mouse tail arteries permeabilized with alpha-toxin were relaxed with urocortin by 39+/-3% at constant [Ca2+], which was associated with a decrease in myosin light chain (MLC20Ser19), MYPT1Thr696, and MYPT1Thr850 phosphorylation by 60%, 28%, and 52%, respectively. The Rho-associated kinase (ROK) inhibitor Y-27632 decreased MYPT1 phosphorylation by a similar extent. Inhibition of PP-2A with 3 nmol/L okadaic acid had no effect on MYPT1 phosphorylation, whereas inhibition of PP-1 with 3 micromol/L okadaic acid prevented dephosphorylation. Urocortin increased the rate of dephosphorylation of MLC20Ser19 approximately 2.2-fold but had no effect on the rate of contraction under conditions of, respectively, inhibited kinase and phosphatase activities. The effect of urocortin on MLC20Ser19 and MYPT1 phosphorylation was blocked by Rp-8-CPT-cAMPS and mimicked by Sp-5,6-DCl-cBIMPS. In summary, these results provide evidence that Ca(2+)-independent relaxation by urocortin can be attributed to a cAMP-mediated increased activity of SMPP-1M which at least in part is attributable to a decrease in the inhibitory phosphorylation of MYPT1.
Pulmonary complications following hematopoietic stem cell transplantation: Diagnostic approaches
Authors: Kasem Sirithanakul, Anan Salloum, Jared L. Klein, Ayman O. Soubani
Journal: American Journal of Hematology (2005)

Abstract Pulmonary complications are a significant cause of morbidity and mortality in hematopoietic stem cell transplant recipients. Pulmonary infiltrates in such patients pose a major challenge for clinicians because of the wide differential diagnosis of infectious and noninfectious conditions. It is rare for the diagnosis to be made by chest radiograph, and commonly these patients will need further invasive and noninvasive studies to confirm the etiology of the pulmonary infiltrates. This review describes the role of the different diagnostic tools available to reach a diagnosis in a timely manner in this patient population. Am. J. Hematol. 80:137–146, 2005. © 2005 Wiley‐Liss, Inc.
P0220 : JNK signaling activated by platelet-derived growth factor D (PDGF-D) stimulates secretion of vascular endothelial growth factor-C (VEGF-C) by cancer-associated fibroblasts to promote lymphangiogenesis and early metastasization in cholangiocarcinoma
Authors: M. Cadamuro, M. Vismara, S. Brivio, A. Furlanetto, M. Strazzabosco, L. Fabris
Journal: Journal of Hepatology (2015)
Abstract P2-06-03: The BRCA1 promoter methylation is one of the mechanisms of th BRCA1 dysfunction of triple-negative breast cancer
Authors: N Yamashita, E Tokunaga, K Tanaka, H Saeki, E Oki, H Kitao, M Morita, Y Maehara
Journal: Cancer Research (2013)

Abstract Background: Triple negative breast cancer (TNBC) is typically associated with aggressive tumor phenotype and poor prognosis. TNBC is also considered highly heterogeneous disease. A better understanding of molecular and histopathological features of TNBC is of great importance, in order to develop a new therapeutic strategy and to improve the prognosis of TNBC. TNBC has many similarities with basal-like breast cancer, and is also associated with BRCAness. The major role of BRCA1 is to respond to DNA damage by participating in cellular pathways for DNA repair, mRNA transcription, cell cycle regulation, and protein ubiquitination. BRCA1 function loss leads to impaired homologous recombination mediated DNA repair. A loss of BRCA1 may thus be a biomarker of responsiveness to DNA damaging agents such as PARP inhibitor and cis/carboplatin. Germline mutations in BRCA1, however, account for approximately 5% of breast cancer cases, somatic mutations in BRCA1 rarely occur. Instead, lower than normal expression of BRCA1 is reported to be an important contributing factor in sporadic tumors. The BRCA1 promoter methylation may thus play an important role in the BRCA1 function loss in sporadic breast cancer. Aim: To evaluate the clinical importance of BRCA1 promoter methylation in breast cancer. Materials and Methods: Specimens were obtained from 71 TNBC and 163 non-TNBC patients who underwent surgery without neoadjuvant therapy in our department between 1990 and 2011. BRCA1 promoter methylation was investigated by using combined bisulfate and restriction analysis (COBRA). The BRCA1 mRNA expression was evaluated by quantitive RT-PCR. The BRCA1 protein level was assessed by immnohistochemistry. Loss of heterozygosity(LOH) at the BRCA1 locus was analyzed with microsatellite markers (D17S855 and D17S579) using our microsatellite analysis system. Copy number variations(CNVs) were analysed by SNP-CGH array (Illumina, HumanOmni2.5-8). Results: We found 12 patients with BRCA1 promoter methylation and all of them were TNBC (p&amp;lt;0.0001). BRCA1 promoter methylation was associated with lymphovessel invasion (p = 0.009), high nuclear grade (p = 0.03), low BRCA1 mRNA expression (p = 0.002) and low BRCA1 protein expression (p&amp;lt;0.0001). CNVs were observed more frequently in TNBC(p = 0.012). High CNVs significantly correlated with BRCA1 LOH (p = 0.0025), but not with BRCA1 promoter methylation among TNBC patients. Conclusions: The BRCA1 promoter methylation is considered to be a specific feature of aggressive phenotype of TNBC and to be one of the mechanisms of BRCA1 dysfunction in breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-06-03.
Stable Human FIX Expression After 0.9G Intrauterine Gene Transfer of Self-complementary Adeno-associated Viral Vector 5 and 8 in Macaques
Authors: Citra NZ Mattar, Amit C Nathwani, Simon N Waddington, Niraja Dighe, Christine Kaeppel, Ali Nowrouzi, Jenny Mcintosh, Nuryanti B Johana, Bryan Ogden, Nicholas M Fisk, Andrew M Davidoff, Anna David, Donald Peebles, Marcus B Valentine, Jens-Uwe Appelt, Christof von Kalle, Manfred Schmidt, Arijit Biswas, Mahesh Choolani, Jerry KY Chan
Journal: Molecular Therapy (2011)

Intrauterine gene transfer (IUGT) offers ontological advantages including immune naiveté mediating tolerance to the vector and transgenic products, and effecting a cure before development of irreversible pathology. Despite proof-of-principle in rodent models, expression efficacy with a therapeutic transgene has yet to be demonstrated in a preclinical nonhuman primate (NHP) model. We aimed to determine the efficacy of human Factor IX (hFIX) expression after adeno-associated-viral (AAV)-mediated IUGT in NHP. We injected 1.0-1.95 × 10(13) vector genomes (vg)/kg of self-complementary (sc) AAV5 and 8 with a LP1-driven hFIX transgene intravenously in 0.9G late gestation NHP fetuses, leading to widespread transduction with liver tropism. Liver-specific hFIX expression was stably maintained between 8 and 112% of normal activity in injected offspring followed up for 2-22 months. AAV8 induced higher hFIX expression (P = 0.005) and milder immune response than AAV5. Random hepatocellular integration was found with no hotspots. Transplacental spread led to low-level maternal tissue transduction, without evidence of immunotoxicity or germline transduction in maternal oocytes. A single intravenous injection of scAAV-LP1-hFIXco to NHP fetuses in late-gestation produced sustained clinically-relevant levels of hFIX with liver-specific expression and a non-neutralizing immune response. These data are encouraging for conditions where gene transfer has the potential to avert perinatal death and long-term irreversible sequelae.
What’s new in invasive pulmonary aspergillosis in the critically ill
Authors: Despoina Koulenti, Dirk Vogelaers, Stijn Blot
Journal: Intensive Care Medicine (2014)

Epidemiology, risk factors, and outcomes Invasive pulmonary aspergillosis (IPA) has been increasingly recognized as an emerging and understudied opportunistic infection in critically ill patients without classic host factors reflecting profound immunosuppression as defined by the European Organization for the Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) [1, 2].Impaired immune response following critical illness and particular underlying conditions put patients at risk of IPA [1].Predisposing conditions frequently met in intensive care units (ICUs) include chronic obstructive pulmonary disease (COPD), corticosteroid (CS) use, decompensated liver disease, acute respiratory distress syndrome (ARDS), severe sepsis, post-sepsis immunoparalysis, and H1N1 virus infection (especially if CS prior to ICU admission) [1, 3-