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1.
Surface antigens of Actinomyces viscosus T14V were released from cell walls by digestion with lysozyme. These were separated by ion-exchange and gel filtration chromatography into fractions rich in carbohydrate or protein. The former contained a polysaccharide high in 6-deoxytalose, along with a peptide fragment from the cell wall. In the protein-rich fractions, material of high molecular weight was present, which contained some carbohydrate and up to 14.3% nitrogen. Aspartic acid, threonine, glutamic acid, lysine, alanine, and glycine were detected in these fractions, along with smaller amounts of 10 other amino acids. Most of the alanine was present as the L isomer and thus was not from peptidoglycan. Electron microscopy of the high-molecular-weight material revealed long fibrils, 3.5 to 4.5 nm in diameter, which resembled those seen on bacterial cells. V-specific antiserum, prepared by absorbing anti-A. viscosus T14V serum with cell walls of the avirulent strain (A. viscosus T14AV), did not react with the 6-deoxytalose polysaccharide but reacted well with isolated fibrils, and this was not inhibited by 6-deoxytalose. 相似文献
2.
Oxygen radical scavengers protect alveolar macrophages from hyperoxic injury in vitro 总被引:3,自引:0,他引:3
Damage to alveolar macrophages (AM) from hyperoxia (95% O2) is associated with release of factors that recruit and activate neutrophils, but the mechanisms underlying injury to AM from hyperoxia are unknown. We hypothesized that damage to AM from hyperoxia involves generation of highly reactive toxic oxygen derivatives, and we tested this premise by exposing cultured rabbit AM to hyperoxia in the presence of scavengers that inactivate various reactive oxygen species. We found that either dimethyl thiourea, a scavenger of hydroxyl radical, or catalase, a scavenger of H2O2, protected cultured rabbit AM against hyperoxic damage, which suggests that H2O2 or an H2O2-derived product, such as hydroxyl radical, contribute to damage to AM from hyperoxia. 相似文献
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W.?VetterEmail author M.?E.?Hahn G.?Tomy S.?Ruppe S.?Vatter N.?Chahbane D.?Lenoir K.-W.?Schramm G.?Scherer 《Archives of environmental contamination and toxicology》2004,48(1):1-9
Physicochemical parameters (vapor pressure, water solubility, Henrys law constant) and biological activities of two halogenated natural products frequently detected in marine samples and food were determined. Synthetic 2,3,3,4,4,5,5-heptachloro-1-methyl-1,2-bipyrrole (Q1) and 2,4,6-tribromoanisole (TBA) were available in pure form. The physicochemical parameters were in the range of anthropogenic chlorinated compounds of concern. The aqueous solubilities at 25°C (Sw,25) of Q1 and TBA were 4.6 g/L and 12,200 g/L, respectively, whereas subcooled liquid vapor pressures were 0.00168 Pa (Q1) and 0.06562 Pa (TBA) as measured by the gas chromatographic–retention time technique. Q1 was negative by established test systems for the determination of ethoxyresorufin-O-deethylase (EROD) induction and by sulforhodamine B assay. EROD induction potency was at least 10–7 times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). At a relatively high concentration (20 M), Q1 inhibited specific binding of 2 nM [3H]TCDD to the in vitro-expressed human aryl hydrocarbon receptor (AHR) by 18%; lower concentrations showed no effect. Molecular modeling showed that Q1 is nonplanar, consistent with its relatively modest affinity as an AHR ligand. When tested for cell-growth inhibitory/cytocidal activity in human tumor cells, Q1 was only marginally, if at all, active with an IC50 value >50 M compared with five to ten times lower IC50 values for potent cytotoxins tested in the test system used. Furthermore, standard pesticide tests on insecticidal, herbicidal, and fungicidal activity did not provide any significant activity at highest concentrations. For TBA, the results in all tests were comparable with Q1. The SRB assay was also applied to the halogenated natural product 4,6-dibromo-2-(2,4-dibromo)phenoxyanisole, but no toxic response was found. Although it was apparent that Q1 and TBA had been proven to have relatively low biological activity in all tests performed, further research is necessary to clarify whether metabolites of the compounds eventually may possess a risk to humans or other living organisms. Nevertheless, the role of Q1 in nature remains uncertain. 相似文献
5.
Reversal of tissue hypoxia by a single intraventricular dose of sodium nitroprusside in a patient with severe medically refractory cerebral vasospasm after subarachnoid haemorrhage
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A Raabe H Vatter M Zimmermann V Seifert 《Journal of neurology, neurosurgery, and psychiatry》2002,72(1):123-124
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Increasing numbers of experimental investigations and recently also of clinical trials strongly suggest an integral involvement of the endothelin (ET)‐system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system. Ambrisentan (LU 208075), a selective ETA‐receptor antagonist, is an orally active diphenyl propionic acid derivative. It has been shown to have a very promising efficacy to safety ratio in the initial clinical trials. Phase II and Phase III trials with ambrisentan in pulmonary arterial hypertension have been performed. The pharmacological properties and data from the experimental investigations suggest additional possible uses of ambrisentan in the prevention of reperfusion injury after organ transplantation and in restenosis following coronary artery dilatation. Furthermore, the pharmacological profile of ambrisentan indicates that this drug may also be suitable in the treatment of cerebrovascular disorders. In the present article basic investigations, animal studies and clinical trials with ambrisentan are reviewed. This review may help to define pathophysiological conditions, in which ambrisentan could be indicated and further evaluated in appropriate preclinical and clinical trials. 相似文献
8.
Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells 总被引:13,自引:0,他引:13
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Nam S Buettner R Turkson J Kim D Cheng JQ Muehlbeyer S Hippe F Vatter S Merz KH Eisenbrand G Jove R 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(17):5998-6003
Stat3 protein has an important role in oncogenesis and is a promising anticancer target. Indirubin, the active component of a traditional Chinese herbal medicine, has been shown previously to inhibit cyclin-dependent kinases, resulting in cell cycle arrest. Here, we show that the indirubin derivatives E564, E728, and E804 potently block constitutive Stat3 signaling in human breast and prostate cancer cells. In addition, E804 directly inhibits Src kinase activity (IC(50) = 0.43 microM) in an in vitro kinase assay. Levels of tyrosyl phosphorylation of c-Src are also reduced in cultured cells 30 min after E804 treatment. Tyrosyl phosphorylation of Stat3, which is known to be phosphorylated by c-Src, was decreased, and constitutive Stat3 DNA binding-activity was suppressed in cells 30 min after E804 treatment. The antiapoptotic proteins Mcl-1 and Survivin, which are encoded in target genes of Stat3, were down-regulated by indirubin derivatives, followed by induction of apoptosis. These results demonstrate that E804 directly blocks the Src-Stat3 signaling pathway, suggesting that the antitumor activity of indirubin compounds is at least partially due to inhibition of this pathway. 相似文献
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Concomitant with glucose-induced insulin release, there occurred an increase of ATP from 4.40 plus or minus 0.21 to 23.16 plus or minus 0.52 pmol/100 islets/min (P less than 0.001) in the effluent from perifused rat islets. There is a linear relationship between circulating ATP and insulin levels both in the stimulated and basal state (r = 0.689, P less than 0.01). Islets incubated with labeled adenine for a short period of time (37.5 min) showed no release of radioactivity upon subsequent glucose-induced insulin release. Islets incubated for a prolonged interval with labeled adenine (150 min) showed an increase in acid soluble radioactivity in the effluent during glucose-induced insulin release. Following incubation of the islets with labeled adenine for 150 min, approximately 5% of the homogenate radioactivity was found in the secretory granules. Using column chromatography to separate the adenine nucleotides, the distribution of radioactivity among the various nucleotides in the secretory granule fraction was found to be: AMP 54.42 plus or minus 4.96%, ADP 14.20 plus or minus 1.63%, ATP 15.39 plus or minus 3.84%, and cAMP 16.07 plus or minus 2.11%. The distribution of radioactivity in the effluent adenine nucleotides after glucose-induced insulin release was: AMP 32.83 plus or minus 4.62%, ADP 24.52 plus or minus 2.77%, ATP 28.13 plus or minus 5.45%, and cAMP 26.01 plus or minus 3.34%. The absolute levels of adenine nucleotides in the secretory granules were ATP 4.19 plus or minus 0.88, ATP madp 7.94 plus or minus 2.20 and cAMP 4.46 plus or minus 1.74 pmol/ug prot. The levels in the islet effluent were ATP, 15.30 plus or minus 2.70, ATP qDP, 29.43 plus or minus 3.49 and cAMP 7.66 plus or minus 1.93 pmol/100 islets/min for the first ten min of glucose-stimulated insulin release. Thereafter there was a rapid decline in effluent cAMP while ATP and ADP remained in essentially equivalent amounts. The distribution of radioactivity and absolute levels of the adenine nucleotides in the effluent reflects that found in the secretory granules, confirming previous observations that insulin release is occurring by exocytosis. 相似文献