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141.
EH Luque MM Mu?oz de Toro JG Ramos HA Rodriguez OD Sherwood 《Canadian Metallurgical Quarterly》1998,59(4):795-800
The modified fluorescence method was used to determine the accumulation of norfloxacin by Mycobacterium aurum A+ and Mycobacterium smegmatis mc(2)155. By using an exogenous norfloxacin concentration of 10 microg/ml, a steady-state concentration (SSC) of 160 to 180 ng of norfloxacin/mg of cells was obtained for M. aurum, and an SSC of 120 to 140 ng of norfloxacin/mg of cells obtained for M. smegmatis. For both species of mycobacteria, the SSC was achieved within 5 min. The silicon oil method was investigated and gave higher SSCs than the modified fluorescence method. Further studies on the mechanism of norfloxacin accumulation by M. aurum were performed. An increase in the pH of the wash buffer from 7.0 to 9.0 did not significantly affect the final SSC obtained. Accumulation was nonsaturated over a norfloxacin concentration range of 0 to 100 microg/ml, and the proton motive force inhibitor 2,4-dinitrophenol (1 and 2 mM), whether it was added before or after norfloxacin was added, had no effect on the final SSC obtained. 2,4-Dinitrophenol also had no effect on norfloxacin accumulation by M. smegmatis. Furthermore, norfloxacin accumulation by M. aurum was unaffected by the presence of either Tween 80 or subinhibitory concentrations of ethambutol in the growth medium. Therefore, it is proposed that norfloxacin accumulation by mycobacteria occurs by simple, energy-independent diffusion. 相似文献
142.
M Mack B Luckow PJ Nelson J Cihak G Simmons PR Clapham N Signoret M Marsh M Stangassinger F Borlat TN Wells D Schl?ndorff AE Proudfoot 《Canadian Metallurgical Quarterly》1998,187(8):1215-1224
CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal modification of the CCR5 ligand regulated on activation, normal T cell expressed and secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent inhibition of macrophage infection by HIV-1 under conditions where RANTES was barely effective. To investigate the mechanism of AOP-RANTES inhibition of HIV infectivity we examined the surface expression of CCR5 using a monoclonal anti-CCR5 antibody, MC-1. We demonstrate that AOP-RANTES rapidly caused >90% decrease in cell surface expression of CCR5 on lymphocytes, monocytes/ macrophages, and CCR5 transfected Chinese hamster ovary (CHO) cells. RANTES also caused a loss of cell surface CCR5, although its effect was less than with AOP-RANTES. Significantly, AOP-RANTES inhibited recycling of internalized CCR5 to the cell surface, whereas RANTES did not. When peripheral blood mononuclear cells are cultured for prolonged periods of time in the presence of RANTES, CCR5 expression is comparable to that seen on cells treated with control medium, whereas there is no CCR5 surface expression on cells cultured in the presence of AOP-RANTES. Immunofluorescence indicated that both AOP-RANTES and RANTES induced downmodulation of cell surface CCR5, and that the receptor was redistributed into endocytic organelles containing the transferrin receptor. When RANTES was removed, the internalized receptor was recycled to the cell surface; however, the receptor internalized in the presence of AOP-RANTES was retained in endosomes. Using human osteosarcoma (GHOST) 34/CCR5 cells, the potency of AOP-RANTES and RANTES to inhibit infection by the M-tropic HIV-1 strain, SF 162, correlated with the degree of downregulation of CCR5 induced by the two chemokines. These differences between AOP-RANTES and RANTES in their effect on receptor downregulation and recycling suggest a mechanism for the potent inhibition of HIV infection by AOP-RANTES. Moreover, these results support the notion that receptor internalization and inhibition of receptor recycling present new targets for therapeutic agents to prevent HIV infection. 相似文献
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144.
BR Moed BK Ahmad JG Craig GP Jacobson MJ Anders 《Canadian Metallurgical Quarterly》1998,80(4):537-546
Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon gamma. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease. 相似文献
145.
JM César AG Avello A Vecino C Cerveró JG Lara?a IF Fuertes J Villarrubia J López JP de Oteyza JL Velasco A Cantalapiedra P Herrera S Herrero JL Navarro 《Canadian Metallurgical Quarterly》1998,111(16):601-603
BACKGROUND: To describe the main characteristics and response to desmopressin infusion in 103 patients suffering from von Willebrand disease (vWD). PATIENTS AND METHODS: The criteria for diagnosis were (except for type 2N) the coexistence of von Willebrand factor ristocetin cofactor (vWF:RCo) activity < 50 U/dl with bleeding disease or one of the following data: von Willebrand factor antigen (vWF:Ag) activity < 50 U/dl, factor VIII (FVIII) activity < 50 U/dl or the existence of a increased bleeding time (BT). Multimeric studies of vWF were performed in 51 cases and ristocetin induced platelet aggregation (RIPA) was also performed. RESULTS: Spontaneous bleeding was found in 36 patients, while in 18 cases the diagnosis was done after surgical bleeding. Thirteen patients (6 presenting with mild bleeding) were studied for abnormalities in the routine preanestesic tests. Other 22 patients were diagnosed with vWD by familial studies. There were 3 patients with type 2B, 1 case with type 2N and other patient with type 3. BT was found increased in 26 out of 58 patients. The activities of vWF:CoR and vWF:Ag were 38.4 (9.4) U/dl and 45.8 (23.2) U/dl, respectively, while the activity of FVIII was 49.9 (20.8) U/dl. Prophylactic DDAVP (desmopressin) was infused in 32 patients. After 1 h, basal activities of vWF:CoR and vWF:Ag were increased by 3.1 (3.2) and 3.4 (3.1) times, respectively, and maintained for 3 h. FVIII activity increased 3.6 (2.3) times the basal levels decreasing after 3 h (2.9 [2.1]; p < 0.01). The BT was corrected in 8 out of ten patients. CONCLUSIONS: vWD is a major cause of surgical bleeding. Preanestesic anamnesis and coagulation tests can be useful to identify vWD. Many patients with vWD have normal BT. A failure in the response to desmopressin infusion is unusual. 相似文献
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147.
People viewed a security video and tried to identify the gunman from a photospread. The actual gunman was not in the photospread and all eyewitnesses made false identifications (n = 352). Following the identification, witnesses were given confirming feedback ("Good, you identified the actual suspect"), disconfirming feedback ("Actually, the suspect is number __" ), or no feedback. The manipulations produced strong effects on the witnesses' retrospective reports of (a) their certainty, (b) the quality of view they had, (c) the clarity of their memory, (d) the speed with which they identified the person, and (e) several other measures. Eyewitnesses who were asked about their certainty prior to the feedback manipulation (Experiment 2) were less influenced, but large effects still emerged on some measures. The magnitude of the effect was as strong for those who denied that the feedback influenced them as it was for those who admitted to the influence. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
148.
149.
150.
G Rock JG Kelton KH Shumak NA Buskard DM Sutton WB Benny 《Canadian Metallurgical Quarterly》1998,103(4):1031-1036
Thrombotic thrombocytopenic purpura is an uncommon disorder that requires prompt recognition and intervention to prevent death. To date, information regarding the classic laboratory abnormalities in the disease has been derived from small numbers of patients whose laboratory tests have been done at many different sites. We report the laboratory findings in 135 patients who presented with thrombotic thrombocytopenic purpura to 17 Canadian centres. 50 men and 85 women had a mean platelet count of 25.3+/-19.4x10(9)/l. The initial platelet count correlated with mortality; 32% of patients with a platelet count of 20x10(9)/l or less died compared with 18% of patients with a platelet count >20x10(9)/l (P=0.058). The platelet-associated IgG was elevated in 88% at presentation whereas the indirect platelet suspension immunofluorescence test was positive in only 18%, 93% of the sera showed reactivity against platelets following protein blotting. All sera tested also showed reactivity against endothelial cells. Immune complexes were seen in all patients, whereas the platelet aggregating factor was detected in 59%. Although the von Willebrand factor was elevated in the majority of patients at entry, the multimer pattern was variable and showed no predictive pattern. Renal dysfunction was common (18%). 相似文献