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191.
Promotion of Salmonella typhimurium adherence and membrane ruffling in MDCK epithelia by staurosporine 总被引:1,自引:0,他引:1
Katharine A. Reed Trevor A. Booth Barry H. Hirst Mark A. Jepson 《FEMS microbiology letters》1996,145(2):233-238
Abstract Infection of Madin-Darby canine kidney epithelial cell monolayers with Salmonella typhimurium SL1344 for 60 min results in widespread bacterial invasion which is associated with remodelling of the apical cell membrane to form 'membrane ruffles'. Treatment of Madin-Darby canine kidney cell monolayers with the protein kinase inhibitor staurosporine resulted in a 12-fold increase in the number of adhered bacteria without significantly affecting bacterial invasion. Staurosporine treatment also significantly increased both the number and size of membrane ruffles. As S. typhimurium adhere preferentially to these areas of membrane lacking microvilli, the increased extent of membrane ruffling may explain the increased bacterial adherence. These data provide evidence that the propagation of membrane ruffles during S. typhimurium infection is modulated by changes in the phosphorylation state of host proteins. 相似文献
192.
Paul D. Jepson Robert Deaville Karina Acevedo-Whitehouse James Barnett Andrew Brownlow Robert L. Brownell Jr. Frances C. Clare Nick Davison Robin J. Law Jan Loveridge Shaheed K. Macgregor Steven Morris Sinéad Murphy Rod Penrose Matthew W. Perkins Eunice Pinn Henrike Seibel Ursula Siebert Eva Sierra Victor Simpson Mark L. Tasker Nick Tregenza Andrew A. Cunningham Antonio Fernández 《PloS one》2013,8(4)
On 9 June 2008, the UK''s largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3–4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. 相似文献
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Jürg Hüsler PD Dr. 《Biometrical journal. Biometrische Zeitschrift》1987,29(4):423-428
The binomial test is applied for the problem of testing a hypothesis based on a sample of independent, but non-identically distributed random variables. The used basic idea is that each random variable indicates the presence of the hypothesis. Hence each random variable is transformed such that the binomial test can be used as a simple procedure. 相似文献
196.
Ewart M. Jepson F. Clifford Rose Richard D. Tonkin 《BMJ (Clinical research ed.)》1958,1(5078):1025-1027
197.
All hematological malignancies are characterized by considerable clinical heterogeneity. The diverse entities can be subdivided into a variety of prognosis-defining subtypes on the basis of cytogenetic aberrations and molecular mutations. To adapt the intensity of treatment to the patient’s individual risk profile, an exact classification of the subtypes on the basis of genetic markers is essential. Diverse fluorescent in situ hybridization (FISH) techniques thereby play a central role in interaction with classic chromosome banding analyses for clarifying findings of chromosome analyses, such as in the acute leukemias, or for classifying the diverse subtypes, as in the non-Hodgkin’s lymphomas. Depending on the disease, the clinical impact of FISH varies. It is used as the method of choice for genetic characterization (e.g., in multiple myeloma) or is used in combination with chromosome banding analysis. Furthermore, interphase FISH is essential when rapid confirmation of the diagnosis is needed, as in acute promyelocytic leukemia with the t(15;17)/PML-RARA rearrangement, for which therapy with all-trans retinoic acid (ATRA) should be immediately started. 相似文献
198.
Modern noninvasive methods of prenatal medicine, in particular first-trimester-screening, enable early risk evaluation of the most common forms of aneuploidy. With over 4000 certified gynecologists in Germany, this method nowadays represents the standard in prenatal risk evaluation. The importance of classic genetic sonography during the second trimester by detection of soft markers for aneuploidy has declined. However, detailed sonography during the second trimester remains the gold standard for the detection of congenital anomalies. Therefore, the specialist in prenatal medicine must be able to recognize soft markers during this examination in order to re-evaluate the maternal risk for aneuploidy. 相似文献
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200.
Jepson S Vought B Gross CH Gan L Austen D Frantz JD Zwahlen J Lowe D Markland W Krauss R 《The Journal of biological chemistry》2012,287(26):22184-22195
Overcoming remyelination failure is a major goal of new therapies for demyelinating diseases like multiple sclerosis. LINGO-1, a key negative regulator of myelination, is a transmembrane signaling protein expressed in both neurons and oligodendrocytes. In neurons, LINGO-1 is an integral component of the Nogo receptor complex, which inhibits axonal growth via RhoA. Because the only ligand-binding subunit of this complex, the Nogo receptor, is absent in oligodendrocytes, the extracellular signals that inhibit myelination through a LINGO-1-mediated mechanism are unknown. Here we show that LINGO-1 inhibits oligodendrocyte terminal differentiation through intercellular interactions and is capable of a self-association in trans. Consistent with previous reports, overexpression of full-length LINGO-1 inhibited differentiation of oligodendrocyte precursor cells (OPCs). Unexpectedly, treatment with a soluble recombinant LINGO-1 ectodomain also had an inhibitory effect on OPCs and decreased myelinated axonal segments in cocultures with neurons from dorsal root ganglia. We demonstrated LINGO-1-mediated inhibition of OPCs through intercellular signaling by using a surface-bound LINGO-1 construct expressed ectopically in astrocytes. Further investigation showed that the soluble LINGO-1 ectodomain can interact with itself in trans by binding to CHO cells expressing full-length LINGO-1. Finally, we observed that soluble LINGO-1 could activate RhoA in OPCs. We propose that LINGO-1 acts as both a ligand and a receptor and that the mechanism by which it negatively regulates OPC differentiation and myelination is mediated by a homophilic intercellular interaction. Disruption of this protein-protein interaction could lead to a decrease of LINGO-1 inhibition and an increase in myelination. 相似文献