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101.
In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: Review of the literature 总被引:15,自引:0,他引:15
Voriconazole (Vfend™) is a new triazole that currently is undergoing phase III clinical trials. This review summarizes the
published data obtained by NCCLS methods on the in vitro antifungal activity of voriconazole in comparison to itraconazole,
amphotericin B, fluconazole, ketoconazole and flucytosine. Voriconazole had fungistatic activity against most yeasts and yeastlike
species (minimum inhibitory concentrations [MICs] <2 μg/ml) that was similar or superior to those of fluconazole, amphotericin
B, and itraconazole. Against Candida glabrata and C. krusei, voriconazole MIC ranges were 0.03 to 8 and 0.01 to >4 μg/ml, respectively. For four of the six Aspergillus spp. evaluated, voriconazole MICs (< 0.03 to 2 μg/ml) were lower than amphotericin B (0.25 to 4 μg/ml) and similar to itraconazole
MICs. Voriconazole fungistatic activity against Fusarium spp. has been variable. Against F. oxysporum and solani, most studies showed MICs ranging from 0.25 to 8 μg/ml. Voriconazole had excellent fungistatic activity against five of the
six species of dimorphic fungi evaluated (MIC90s < 1.0 μg/ml). The exception was Sporothrix schenckii (MIC90s and geometric mean MICs ≥ 8 μg/ml). Only amphotericin B had good fungistatic activity against the Zygomycetes species (voriconazole
MICs ranged from 2 to >32 μg/ml). Voriconazole showed excellent in vitro activity (MICs < 0.03 to 1.0 μg/ml) against most
of the 50 species of dematiaceous fungi tested, but the activity of all the agents was poor against most isolates of Scedosporium prolificans and Phaeoacremonium parasiticum (Phialophora parasitica). Voriconazole had fungicidal activity against most Aspergillus spp., B. dermatitidis, and some dematiaceous fungi. In vitro/in vivo correlations should aid in the interpretation of these results.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
102.
MacDonell LE Skinner FK Ward PE Glen AI Glen AC Macdonald DJ Boyle RM Horrobin DF 《Prostaglandins, leukotrienes, and essential fatty acids》2000,63(1-2):37-39
Research findings are increasingly reporting evidence of physiological abnormalities in dyslexia and sites for dyslexia have been identified on three chromosomes. It has been suggested that genetic inheritance may cause phospholipid abnormalities in dyslexia somewhat similar to those found in schizophrenia. A key enzyme in phospholipid metabolism, Type IV, or cytosolic, phospholipase A2 (cPLA2), releases arachidonic acid (AA), a 20-carbon fatty acid, which is the major source of production of prostaglandins and leukotrienes. An entirely new assay, which for the first time has enabled determination of the amount of the enzyme rather than its activity, was used to measure cPLA2 in dyslexic-type adults and controls and the two groups were found to differ significantly, the dyslexic-types having more of the enzyme. A report elsewhere of schizophrenics having even greater amounts of the enzyme suggests that dyslexia may be on a continuum with schizophrenia, as may be other neurodevelopmental disorders - which have also been described as phospholipid spectrum disorders. 相似文献
103.
D'Costa SS Romer TG Boyle MD 《Biochemical and biophysical research communications》2000,278(3):826-832
The normally cytosolic glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, (GAPDH) has been reported to be expressed on the surface of Streptococcus pyogenes, group A, where it can act as a plasmin binding protein (Plr), and potentially a signaling molecule. In studies of wild-type and isogenic mutants, an association between surface expression of antigenic GAPDH/Plr and M and M-related fibrinogen-binding proteins was identified. Inactivation of the mga gene, whose product controls expression of M and M-related proteins also influenced expression of surface GAPDH/Plr. Revertants or pseudorevertants of mga mutants led to concomitant re-expression of surface GAPDH/Plr and M and M-related proteins. Using surface enhanced laser desorption ionization (SELDI) mass spectroscopy, a physical association between GAPDH/Plr and streptococcal fibrinogen-binding proteins was demonstrated. These studies support the hypothesis that surface M and M-related proteins are involved in anchoring GAPDH/Plr on the surface of group A streptococci. 相似文献
104.
Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function 总被引:1,自引:0,他引:1
Inclusions containing actin-depolymerizing factor (ADF) and cofilin, abundant proteins in adult human brain, are prominent in hippocampal and cortical neurites of the post-mortem brains of Alzheimer's patients, especially in neurites contacting amyloid deposits. The origin and role of these inclusions in neurodegeneration are, however, unknown. Here we show that mediators of neurodegeneration induce the rapid formation of transient or persistent rod-like inclusions containing ADF/cofilin and actin in axons and dendrites of cultured hippocampal neurons. Rods form spontaneously within neurons overexpressing active ADF/cofilin, suggesting that the activation (by dephosphorylation) of ADF/cofilin that occurs in response to neurodegenerative stimuli is sufficient to induce rod formation. Persistent rods that span the diameter of the neurite disrupt microtubules and cause degeneration of the distal neurite without killing the neuron. These findings suggest a common pathway that can lead to loss of synapses. 相似文献
105.
106.
107.
Boyle GM Roucou X Nagley P Devenish RJ Prescott M 《Journal of bioenergetics and biomembranes》2000,32(6):595-607
We have sought to elucidate how the oligomycin sensitivity-conferring protein (OSCP) of the mitochondrial F1F0-ATP synthase (mtATPase) can influence proton channel function. Variants of OSCP, from the yeast Saccharomyces cerevisiae, having amino acid substitutions at a strictly conserved residue (Gly166) were expressed in place of normal OSCP. Cells expressing the OSCP variants were able to grow on nonfermentable substrates, albeit with some increase in generation time. Moreover, these strains exhibited increased sensitivity to oligomycin, suggestive of modification in functional interactions between the F1 and F0 sectors mediated by OSCP. Bioenergetic analysis of mitochondria from cells expressing OSCP variants indicated an increased respiratory rate under conditions of no net ATP synthesis. Using specific inhibitors of mtATPase, in conjunction with measurement of changes in mitochondrial transmembrane potential, it was revealed that this increased respiratory rate was a result of increased proton flux through the F0 sector. This proton conductance, which is not coupled to phosphorylation, is exquisitely sensitive to inhibition by oligomycin. Nevertheless, the oxidative phosphorylation capacity of these mitochondria from cells expressing OSCP variants was no different to that of the control. These results suggest that the incorporation of OSCP variants into functional ATP synthase complexes can display effects in the control of proton flux through the F0 sector, most likely mediated through altered protein—protein contacts within the enzyme complex. This conclusion is supported by data indicating impaired stability of solubilized mtATPase complexes that is not, however, reflected in the assembly of functional enzyme complexes in vivo. Given a location for OSCP atop the F1-33 hexamer that is distant from the proton channel, then the modulation of proton flux by OSCP must occur at a distance. We consider how subtle conformational changes in OSCP may be transmitted to F0. 相似文献
108.
The intracellular pathogenesis-related proteins have been identified in a broad range of flowering plants. Some display quite different patterns of expression, in many cases unrelated to the pathogenic response. Nevertheless, these proteins are all very similar and in most cases share more than 35% sequence identity. In this report we investigate the significance of a rather weak similarity between the intracellular pathogenesis-related (IPR or PR-10) proteins and a group of proteins identified in the latex of opium poppy and in Arabidopsis, among others. A sequence analysis held together with the recently published three-dimensional structure of Bet v 1, an IPR protein from birch pollen, strongly suggests sequential and structural homology between the two protein families. 相似文献
109.
FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure
110.
Michelle J. Boyle Prasanna Jagannathan Lila A. Farrington Ijeoma Eccles-James Samuel Wamala Tara I McIntyre Hilary M. Vance Katherine Bowen Felistas Nankya Ann Auma Mayimuna Nalubega Esther Sikyomu Kate Naluwu John Rek Agaba Katureebe Victor Bigira James Kapisi Jordan Tappero Mary K Muhindo Bryan Greenhouse Emmanuel Arinaitwe Grant Dorsey Moses R. Kamya Margaret E. Feeney 《PLoS pathogens》2015,11(7)
FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations. 相似文献