Biomarkers for ragwort poisoning in horses: identification of protein targets

BACKGROUND: Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasive in vitro model system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods. RESULTS: One dimensional gel electrophoresis revealed a significant alteration in the equine plasma protein profile following pyrrole exposure and the formation of a high molecular weight protein aggregate. Using mass spectrometry and confirmation by western blotting the major components of this aggregate were identified as fibrinogen, serum albumin and transferrin. CONCLUSION: These findings demonstrate that pyrrolic metabolites can modify equine plasma proteins. The high molecular weight aggregate may result from extensive inter- and intra-molecular cross-linking of fibrinogen with the pyrrole. This model has the potential to form the basis of a novel proteomic strategy aimed at identifying surrogate protein biomarkers of ragwort exposure in horses and other livestock

Platform Dependent Verification: On Engineering Verification Tools for 21st Century

The paper overviews recent developments in platform-dependent explicit-state LTL model checking.Comment: In Proceedings PDMC 2011, arXiv:1111.006

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort

Books

Human neurology The Human Central Nervous System: A Synopsis and Atlas. 3rd revised ed. Ed. by R. Nieuwenhuys, J. Voogd, C. H. R. van Huijzen. Pp. xii + 437. Illustrated. DM 85. Berlin: SpringerVerlag. 1988.Paediatric respiratory disorders Kendig's Disorders of the Respiratory Tract in Children. 5th ed. Ed. by Victor Chernick. Consulting ed. Edwin L. Kendig, jun. Pp. xxi + 1055. Philadelphia: WB Saunders. 1990.Maxillofacial imaging Maxillofacial Imaging. Ed. by A. M. Delbalso. pp. Vlll + 799. Illustrated. Kent: Harcourt Brace Jovanovich. 1990.Introduction to philosophy of medicine Philosophy of Medicine: An Introduction. Ed. by H. R. Wulff, S. A. Pedersen and R. Rosenberg. pp. xv + 222. £14,95. Oxford: Blackwell. 1990.Cataract management Management of Cataract in Primary Health Care Services. Pp. vi + 43. Illustrated. SFr. 15. Geneva: WHO. 1990.Family practice-management Family Practice Management. Ed. by G. J. and C. M. 1. Pistorius. Pp. 587. Illustrated. R99,50. Parow: Haurn/De Jager. J99O.Obstetrics and gynaecology Essential Obstetrics and Gynaecology. By E. Malcolm Symonds. pp. vi + 266. Illustrated. Edinburgh: Maskew Miller Longman.Surgical memoirs Surgical Roots and Branches. Ed. by R. Murley. Pp. x + 341. Illustrated. £18,50. Hamilton: Libriger Book Distribution. 1990.Survival in a hostile environment Staying Alive. Ed. by Ron Reid-Daly. Pp. ix + 259. Illustrated. R49,95. Rivonia: Ashami. 1990.Urolithiasis Urolithiasis: Medical and Surgical Reference. Ed. by M. 1. Resnick and C. Y. C. Pak. Pp. x + 375. Illustrated. R53,50. Kent: Harcoun Brace Jovanovich. 1990.Mental health in primary health care The Introduction of a Mental Health Component into Primary Health Care. pp. 1-59. SFr. 11,50. Geneva: WHO. 1990Tuberculosis in South Africa White Plague, Black Labor: Tuberculosis and the Political Economy of Health and Disease in South Africa. Ed. by Randall M. Packard. pp. xxii + 389. Illustrated. $40 (cloth) and$15,95 (paperback). California: University of California Press. 1989.Medical research Research in Medicine:"A Guide to Writing a Thesis in the Medical Sciences. Ed. by G. Murrell, C. Huang and H. Ellis. PP: xii + 105. Illustrated. £19,50 (hIb) £7,50 (Plb). Cambridge: Cambridge University Press. 1990

Identification of a Mutation Associated with Fatal Foal Immunodeficiency Syndrome in the Fell and Dales Pony

The Fell and Dales are rare native UK pony breeds at risk due to falling numbers, in-breeding, and inherited disease. Specifically, the lethal Mendelian recessive disease Foal Immunodeficiency Syndrome (FIS), which manifests as B-lymphocyte immunodeficiency and progressive anemia, is a substantial threat. A significant percentage (∼10%) of the Fell ponies born each year dies from FIS, compromising the long-term survival of this breed. Moreover, the likely spread of FIS into other breeds is of major concern. Indeed, FIS was identified in the Dales pony, a related breed, during the course of this work. Using a stepwise approach comprising linkage and homozygosity mapping followed by haplotype analysis, we mapped the mutation using 14 FIS–affected, 17 obligate carriers, and 10 adults of unknown carrier status to a ∼1 Mb region (29.8 – 30.8 Mb) on chromosome (ECA) 26. A subsequent genome-wide association study identified two SNPs on ECA26 that showed genome-wide significance after Bonferroni correction for multiple testing: BIEC2-692674 at 29.804 Mb and BIEC2-693138 at 32.19 Mb. The associated region spanned 2.6 Mb from ∼29.6 Mb to 32.2 Mb on ECA26. Re-sequencing of this region identified a mutation in the sodium/myo-inositol cotransporter gene (SLC5A3); this causes a P446L substitution in the protein. This gene plays a crucial role in the regulatory response to osmotic stress that is essential in many tissues including lymphoid tissues and during early embryonic development. We propose that the amino acid substitution we identify here alters the function of SLC5A3, leading to erythropoiesis failure and compromise of the immune system. FIS is of significant biological interest as it is unique and is caused by a gene not previously associated with a mammalian disease. Having identified the associated gene, we are now able to eradicate FIS from equine populations by informed selective breeding

Reactions of pulmonary emphysema patients before and after VRS - Forcusing on the rehabilitation, activity, surgery -

今まで内科的治療が主体であった肺気腫に対して,近年外科的治療(Volume Reduction Surgery 以後VRSと略す)が行われるようになった｡VRSを受ける患者の看護では,手術前後において, リハビリテーション(以後リハビリと略す)や機能回復に向けてのケアが必要不可欠とされる。そこで,本研究は肺気腫患者の適切な看護援助を検討するために,手術前後に示す肺気腫患者のリハビリや活動に対する反応を明らかにすることを目的とした｡対象者は当病棟に入院している肺気腫患者8名(VRS手術前8名,手術後はそのうちの6名である)で, リハビリ, 日常生活活動,呼吸,手術などについて,面接ならびに観察による調査を行った｡分析の結果,手術前においてリハビリでは≪義務感≫,頑張って行えば呼吸が楽になるという≪期待感≫,≪サポート≫,≪不安≫が,活動では≪活動の制限≫,手術では呼吸が楽になるのではという≪期待感≫,≪おまかせ≫,≪いちかばちかの賭け≫,≪不安≫,≪回復に向けての欲求の高まり≫が明らかになった｡手術後においてリハビリでは≪呼吸が楽になるための手段≫が, 日常生活活動では≪今の状態よりは良くなると いう期待感≫が,手術では≪達成感≫ と≪身体的苦痛≫が,将来については≪ささやかな欲求≫が明らかになった｡Pulmonary emphysema has been mainly treated with medicine, but recently VRS(volume reduction surgery) has been receiving much attention. In nursing care for VRS patients, it is important to help the patient improve his/her daily activities and recover physical function smoothly after surgery. The purpose of this study is to clarify the reactions of pulmonary emphysema patients before and after VRS for appropriate nursing. The subjects were eight pulmonary emphysema patients at a ward in Okayama University Hospital, but six of them completed both before and after VRS data collection. The data were collected by interview and observation, and from medical and nursing records. Contents of the interview included rehabilitation, daily activities, respiratory symptoms, operative stress, and so on. The results were as follows : , , , and on rehabilitation, on activity, , , , , and on surgery were extracted as pre-operative patients's reactions. on rehabilitation, on activity, and on surgery, on future were extracted as post-operative patients's reactions