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31.
Mechanism of inhibition of a poxvirus topoisomerase by the marine natural product sansalvamide A. 总被引:1,自引:0,他引:1
Y Hwang D Rowley D Rhodes J Gertsch W Fenical F Bushman 《Molecular pharmacology》1999,55(6):1049-1053
At present no antiviral agents are available for treatment of infection by the pathogenic poxvirus molluscum contagiosum virus (MCV). Here we report the identification and characterization of an inhibitor active against the virus-encoded type-1 topoisomerase, an enzyme likely to be required for MCV replication. We screened a library of marine extracts and natural products from microorganisms using MCV topoisomerase assays in vitro. The cyclic depsipeptide sansalvamide A was found to inhibit topoisomerase-catalyzed DNA relaxation. Sansalvamide A was inactive against two other DNA-modifying enzymes tested as a counterscreen. Assays of discrete steps in the topoisomerase reaction cycle revealed that sansalvamide A inhibited DNA binding and thereby covalent complex formation, but not resealing of a DNA nick in a preformed covalent complex. Sansalvamide A also inhibits DNA binding by the isolated catalytic domain, thereby specifying the part of the protein sensitive to sansalvamide A. These data specify the mechanism by which sansalvamide A inhibits MCV topoisomerase. Cyclic depsipeptides related to sansalvamide A represent a potentially promising chemical family for development of anti-MCV agents. 相似文献
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33.
3,5-二溴水杨醛Schiff碱的Cu(Ⅱ)螯合物研究 总被引:2,自引:0,他引:2
目的:寻找新型的抑菌药物。方法:以3,5-二溴水杨醛Schiff碱为配体合成了3种Cu(Ⅱ)新螯合物,并进行了初步抑菌活性实验。结果:合成的螯合物经元素分析,红外光谱确证其结构组成。结论:初步抑菌实验表明,合成螯合物对多种菌株有明显的抑菌活性。 相似文献
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FAGAN EA; DAVISON FD; TROWBRIDGE R; CARMAN WF; SMITH HM; TEDDER R; WILLIAMS R 《QJM : monthly journal of the Association of Physicians》1991,78(2):123-134
Excluding studies from Brechot and co-workers, little supporthas been found for a role of the hepatitis B virus in the pathogenesisof HBsAg seronegative patients with predominantly chronic liverdiseases, including primary liver cancer. In this study liverDNA from 59 predominantly British patients (four cases withpaired biopsies, 612 months apart) with different, mostlychronic, liver diseases was analysed by molecular hybridization.All were seronegative for HBsAg and serum hepatitis B virusDNA (dot blot hybridization) and their liver diseases were believedto be unrelated to hepatitis B virus infection. Hepatitis Bvirus DNA was detected in liver of 11 (18.6 per cent) patients;nine had episomal(3.2 Kb) DNA and eight had higher molecularweight bands suggesting integrated forms. Six patients werealso seronegative for anti-HBc. Patients of UK and non-UK originwere equally represented. Hepatitis B virus DNA was detectedin serum of six of nine patients tested using the polymerasechain reaction. The detection of hepatitis B virus DNA in liverand in serum by this assay in a significant proportion of patientswith chronic liver disease, hitherto unsuspected of being hepatitisB virus-related, suggests a possible role for this virus inlow- as well as high-prevalence countries. 相似文献
37.
Cyclosporin nephrotoxicity in heart and lung transplant patients 总被引:1,自引:0,他引:1
Griffiths MH; Crowe AV; Papadaki L; Banner NR; Yacoub MH; Thompson FD; Neild GH 《QJM : monthly journal of the Association of Physicians》1996,89(10):751-763
Twenty-two patients with heart, lung or heart and lung transplants
maintained on cyclosporin for periods ranging from 3 months to 10 years
developed renal insufficiency which was investigated by renal biopsy. The
histopathological changes were: (i) severe vascular and glomerular damage
due to thrombotic microangiopathy (TM); (ii) a form of focal segmental
glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being
separate entities, these changes appeared to represent a spectrum of
pathology, some biopsies showing all three forms of glomerular injury. In
all cases the glomerular changes were accompanied by arteriolar and
arterial pathology, and we identified novel ultrastructural changes in the
arteriolar endothelial basal lamina. Tubular atrophy was a consistent
feature, the severity of which reflected the severity of the glomerular
sclerosis, and which appeared to be a consequence of glomerular loss. Our
findings are consistent with the nephrotoxic effects of cyclosporin being
mediated chiefly via damage to preglomerular vessels and glomerular
capillary endothelium. From an analysis of the clinical aspects of these
cases, the effects of cyclosporin appear to be to some extent
idiosyncratic, and therefore not entirely preventable, but strict
monitoring of blood cyclosporin levels is essential to minimize the risk of
permanent renal damage. Monitoring urinary protein in addition to plasma
creatinine may detect the onset of FSGS, as proteinuria precedes creatinine
elevation.
相似文献
38.
Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults 总被引:1,自引:0,他引:1
Anderson PL Zheng JH King T Bushman LR Predhomme J Meditz A Gerber J Fletcher CV 《AIDS (London, England)》2007,21(14):1849-1854
INTRODUCTION: Concentrations of zidovudine (ZDV)- and lamivudine (3TC)-triphosphates (TP) have been quantified in unfractionated peripheral blood mononuclear cells (PBMC) from HIV+ patients. The objective of this study was to determine whether concentrations of ZDV-TP and 3TC-TP in PBMC reflect the concentrations within CD4 T cells in HIV-seronegative adults. METHODS: Volunteers had taken 300 mg of ZDV plus 150 mg of 3TC twice daily for > or = 7 days. Blood (60 mL) was collected 2 or 5 h post observed dose. PBMC were processed into three cell fractions using CD4 magnetic immunobeads: CD4-purified cells; unfractionated PBMC; and CD4-depleted PBMC. TP were determined in each cell fraction with liquid chromatography-mass spectrometry and compared across cell types by non-parametric analyses. RESULTS: Six males and two females participated. The median (range) percentage of CD4 T cells (CD4%) in each fraction were: CD4-purified, 99%; unfractionated, 63% (range, 53-70); and CD4-depleted, 14% (range, 4-29). Corresponding median (range) ZDV-TP concentrations were 8.0 (5.3-10.3), 26.5 (12.9-42.2), and 34.2 (16.4-52.2) fmol/1 x 10 cells (Friedman P = 0.0008). The 3TC-TP values were 4.6 (2.3-6.7), 4.8 (3.5-8.8), and 6.8 (4.0-13.1) pmol//1 x 10 cells (Friedman P = 0.01). In mixed model analyses: ZDV-TP (fmol/1 x 10 cells) = 42-0.32 (CD4%); P < 0.001 and 3TC-TP (pmol/1 x 10 cells) = 7.3-0.03(CD4%); P = 0.003. CONCLUSIONS: In HIV-seronegative volunteers, 3TC-TP concentrations in PBMC reflected the concentrations within CD4 T cells, but ZDV-TP concentrations were more than 70% lower in CD4 T cells than in PBMC. Thus, TP concentrations differ according to cell type in vivo with corresponding efficacy and toxicity implications for cells with low or high triphosphates. 相似文献
39.
Atazanavir-containing renal calculi in an HIV-infected patient 总被引:1,自引:0,他引:1
Anderson PL Lichtenstein KA Gerig NE Kiser JJ Bushman LR 《AIDS (London, England)》2007,21(8):1060-1062
40.
AM Holmes JA Rudd FD Tattersall Q Aziz PLR Andrews 《British journal of pharmacology》2009,157(6):865-880
Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms. 相似文献