20 research outputs found

    Barbicidal overdose

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    Acute severe methemoglobinaemia is an uncommon but life-threatening condition caused by a variety of oxidizing agents commonly used in both health care and industrial settings. Thus, recognition is important as it is readily treatable. The oxygen transport is compromised as a result of abnormal levels of oxidized haemoglobin, and this leads to skin discolouration and a variety of symptoms. Diagnostic confusion occurs as the oxygen saturations (SpO2) on the pulse oximeter are unreliable (Sharma V, Haber A. Acquired methaemoglobinaemia: a case report of benzocaine-induced methaemoglobinaemia and a review of the literature. Clin Pul Med. 2002;9(1):53–8). A case of severe methaemoglobinaemia due to self poisoning with barbicide is presented with a brief discussion of the patho-physiology and an overview of the treatment. A barbicidal overdose has never been reported before

    Modification of the L1-CAM carboxy-terminus in pancreatic adenocarcinoma cells

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    The neural cell adhesion molecule L1 has recently been shown to be expressed in pancreatic adenocarcinoma (PDAC) cells. In this report, we demonstrate that L1 is expressed by moderately- to poorly-differentiated PDAC cells in situ, and that L1 expression is a predictor of poor patient survival. In vitro, reduced reactivity of an anti-L1 carboxy-terminus-specific antibody was observed in the more poorly differentiated fast-growing (FG) variant of the COLO357 population, versus its well-differentiated slow-growing (SG) counterpart, even though they express equivalent total L1. The carboxy-terminus of L1 mediates binding to the MAP kinase-regulating protein RanBPM and mutation of T1247/S1248 within this region attenuates the expression of malignancy associated proteins and L1-induced tumorigenicity in mice. Therefore, we reasoned that the differential epitope exposure observed might be indicative of modifications responsible for regulating these events. However, epitope mapping demonstrated that the major determinant of binding was actually N1251; mutation of T1247 and S1248, alone or together, had little effect on C20 binding. Moreover, cluster assays using CD25 ectodomain/L1 cytoplasmic domain chimeras demonstrated the N1251-dependent, RanBPM-independent stimulation of erk phosphorylation in these cells. Reactivity of this antibody also reflects the differential exposure of extracellular epitopes in these COLO357 sublines, consistent with the previous demonstration of L1 ectodomain conformation modulation by intracellular modifications. These data further support a central role for L1 in PDAC, and define a specific role for carboxy-terminal residues including N1251 in the regulation of L1 activity in PDAC cells

    Cholera- and Anthrax-Like Toxins Are among Several New ADP-Ribosyltransferases

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    Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences – including a primary sequence pattern – to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data – and we need high-throughput validation – our approach provides insight into the newest toxin ADP-ribosyltransferases

    Excess Thermodynamic Properties for Binary Mixtures of Ionic Liquid 1-Ethyl-3-methylimidazolium Ethyl Sulfate and 2-Methoxyethanol from T = (298.15 to 328.15) K at Atmospheric Pressure

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    The density (rho), speed of sound (u) and refractive index (n (D)) for pure [Emim][EtSO4], 2-methoxyethanol and their binary mixtures were measured using an Anton Paar vibrating tube density and sound velocity meter (DSA 5000 M) and automatic refractometer over the whole composition range as a function of temperature between 298.15 and 328.15 K in steps of 10 K at atmospheric pressure. Experimental values were used to calculate the excess values of molar volumes (), partial molar volumes (), partial molar volumes at infinite dilution (), isentropic compressibility (), acoustic impedance (Z (E)), free length (), speeds of sound (), internal pressure (), free volume () and deviations in refractive index ( ) for the binary mixtures. These properties were fitted to a Redlich-Kister type equation to obtain the binary coefficients and the standard deviations. The negative values of , , ,, and and positive values for Z (E), ,, and indicate the existence of strong interactions between the components. This was further supported by IR spectroscopy analysis
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