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31.
Chronic murine paracoccidioidomycosis: effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response 总被引:2,自引:0,他引:2
In a murine model of chronic pulmonary and disseminated paracoccidioidomycosis, ketoconazole (100 mg kg-1 in 0.3% agar) given by gavage twice daily for 1 or 2 months enabled all mice to clear disseminated Paracoccidioides brasiliensis from the spleen. Clearance of P. brasiliensis from the lungs was more difficult, and was achieved in 60% of the mice treated for 2 months. Sera from agar-treated control mice at days 77 and 103 post-infection demonstrated precipitating antibodies to P. brasiliensis antigens, but sera from ketoconazole-treated mice were precipitin-negative, indicating a favorable prognosis. Delayed hypersensitivity reactions to P. brasiliensis antigens in ketoconazole-treated mice were not significantly greater than in controls; consequently this test correlated less well with response than levels of serum antibody. This is the first use of this animal model of paracoccidioidomycosis to study the effect of antifungal drug protocols on the resolution of the disease. It also demonstrates the utility of this model in addressing clinically relevant questions about this disease and its treatment. 相似文献
32.
Brummer T Schramek D Hayes VM Bennett HL Caldon CE Musgrove EA Daly RJ 《The Journal of biological chemistry》2006,281(1):626-637
The docking protein Gab2 is a proto-oncogene product that is overexpressed in primary breast cancers. To determine the functional consequences of Gab2 overexpression, we utilized the immortalized human mammary epithelial cell line MCF-10A. In monolayer culture, expression of Gab2 at levels comparable with those detected in human breast cancer cells accelerated epidermal growth factor (EGF)-induced cell cycle progression and was associated with increased basal Stat5 tyrosine phosphorylation and enhanced and/or more sustained EGF-induced Erk and Akt activation. Three-dimensional Matrigel culture of MCF-10A cells resulted in the formation of polarized, growth-arrested acini with hollow lumina. Under these conditions, Gab2 increased cell proliferation during morphogenesis, leading to significantly larger acini, an effect dependent on Gab2 binding to Grb2 and Shp2 and enhanced by recruitment of the p85 subunit of phosphatidylinositol 3-kinase. Pharmacological inhibition of MEK revealed that, in addition to direct activation of phosphatidylinositol 3-kinase, increased Erk signaling also contributed to Gab2-mediated enhancement of acinar size. In addition, Gab2 overcame the proliferative suppression that normally occurs in late stage cultures and conferred independence of the morphogenetic program from exogenous EGF. Finally, higher levels of Gab2 expression led to the formation of large disorganized structures with defective luminal clearance. These findings support a role for Gab2 in mammary tumorigenesis. 相似文献
33.
Nutridynamics--studying the dynamics of food components in products and in the consumer 总被引:1,自引:0,他引:1
The concentrations and biological effects of nutrients, antinutrients and bioactive compounds, including microbes and their constituents, are affected by production and processing steps, the food matrix in which they reside, the way they are digested and metabolized in the human body, and whether or not and in what form they subsequently reach their target site. A new scientific concept, denoted here as 'nutridynamics', aims to unravel the dynamics of these processes by using a systematic approach to study how a food component is affected by the food matrix itself and what it does in the body. This holistic concept has potential synergy with the areas of food technology and nutrigenomics, and provides a link between food production and the mechanistic effects of bioactive ingredients. 相似文献
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35.
Development of an RFLP map in diploid alfalfa 总被引:18,自引:3,他引:15
E. Charles Brummer Joseph H. Bouton Gary Kochert 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1993,86(2-3):329-332
Summary We have developed a restriction fragment length polymorphism (RFLP) linkage map in diploid alfalfa (Medicago sativa L.) to be used as a tool in alfalfa improvement programs. An F2 mapping population of 86 individuals was produced from a cross between a plant of the W2xiso population (M. sativa ssp. sativa) and a plant from USDA PI440501 (M. sativa ssp. coerulea). The current map contains 108 cDNA markers covering 467.5 centimorgans. The short length of the map is probably due to low recombination in this cross. Marker order may be maintained in other populations even though the distance between clones may change. About 50% of the mapped loci showed segregation distortion, mostly toward excess heterozygotes. This is circumstantial evidence supporting the maximum heterozygote theory which states that relative vigor is dependent on maximizing the number of loci with multiple alleles. The application of the map to tetraploid populations is discussed. 相似文献
36.
Influence of possible disinfectant transfer on Staphylococcus aureus plate counts after agar contact sampling. 总被引:1,自引:1,他引:0
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B Brummer 《Applied microbiology》1976,32(1):80-84
Asbestos-vinyl tile floor panels were mopped with three types of chemical disinfectant product, as well as after contact, with the untreated control panel were prepared according to the manufacturer's label instructions. Similar floor panels were inoculated artificially with Staphylococcus aureus. RODAC (replicate organism detection and counting) surface sampling plates were pressed to the disinfectant-treated panels or to the untreated control panel and then immediately pressed to sampling sites on the artificially inoculated floor panels. Plate counts were determined after contact with panels treated with each type of disinfectant, product, as well as after contact with the untreated control panel. Results indicate that disinfectant residues on environmental surfaces do not alter the average plate counts obtained by RODAC samplings. 相似文献
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38.
Herrera Abreu MT Hughes WE Mele K Lyons RJ Rickwood D Browne BC Bennett HL Vallotton P Brummer T Daly RJ 《Molecular biology of the cell》2011,22(1):105-116
The docking protein Gab2 is overexpressed in several human malignancies, including breast cancer, and is associated with increased metastatic potential. Here we report that Gab2 overexpression in MCF-10A mammary epithelial cells led to delayed cell spreading, a decrease in stress fibers and mature focal adhesions, and enhanced cell migration. Expression of a Gab2 mutant uncoupled from 14-3-3-mediated negative feedback (Gab2(2xA)) led to a more mesenchymal morphology and acquisition of invasive potential. Expression of either Gab2 or Gab2(2xA) led to decreased activation of RhoA, but only the latter increased levels of Rac-GTP. Expression of constitutively active RhoA in MCF-10A/Gab2 cells restored stress fibers and focal adhesions, indicating that Gab2 signals upstream of RhoA to suppress these structures. Mutation of the two Shp2-binding sites to phenylalanine (Gab2(ΔShp2)) markedly reduced the effects of Gab2 on cellular phenotype and RhoA activation. Expression of Gab2 or Gab2(2xA), but not Gab2(ΔShp2), promoted Vav2 phosphorylation and plasma membrane recruitment of p190A RhoGAP. Knockdown of p190A RhoGAP reversed Gab2-mediated effects on stress fibers and focal adhesions. The identification of a novel pathway downstream of Gab2 involving negative regulation of RhoA by p190A RhoGAP sheds new light on the role of Gab2 in cancer progression. 相似文献
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40.
Li X Wang X Wei Y Brummer EC 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(4):667-679
Segregation distortion (SD) is often observed in plant populations; its presence can affect mapping and breeding applications.
To investigate the prevalence of SD in diploid alfalfa (Medicago sativa L.), we developed two unrelated segregating F1 populations and one F2 population. We genotyped all populations with SSR markers and assessed SD at each locus in each population. The three maps
were syntenic and largely colinear with the Medicago truncatula genome sequence. We found genotypic SD for 24 and 34% of markers in the F1 populations and 68% of markers in the F2 population; distorted markers were identified on every linkage group. The smaller percentage of genotypic SD in the F1 populations could be because they were non-inbred and/or due to non-fully informative markers. For the F2 population, 60 of 90 mapped markers were distorted, and they clustered into eight segregation distortion regions (SDR). Most
SDR identified in the F1 populations were also identified in the F2 population. Genotypic SD was primarily due to zygotic rather than allelic distortion, suggesting zygotic not gametic selection
is the main cause of SD. On the F2 linkage map, distorted markers in all SDR except two showed heterozygote excess. The severe SD in the F2 population likely biased genetic distances among markers and possibly also marker ordering and could affect QTL mapping of
agronomic traits. To reduce the effects of SD and non-fully informative markers, we suggest constructing linkage maps and
conducting QTL mapping in advanced generation populations. 相似文献