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71.
The relationships between Listeria monocytogenes (LM) pathogenesis, based on bacterial load, and serum levels of IL-6, IFNgamma, and corticosterone (CORT) were quantified. Serum IFNgamma levels increased along with the LM burden; however, with LM burdens > or =3 x 10(6) CFU per spleen, the serum IFNgamma level decreased along with a decrease in splenic weight. Serum IL-6 levels exponentially increased with increases of LM, and the CORT level positively correlated with the increase in IL-6 and LM. The serum level of IFNgamma appeared to be a good biomarker of the host's ability to combat the infection only when the LM burden did not exceed a critical level (>3 x 10(6) CFU per spleen). Interestingly, the LM load at which the IFNgamma level began to decline was near the dose at which the IL-6 concentration exponentially increased, suggesting a transition point shift from stress (assessed as CORT level) being immunoenhancing to becoming immunosuppressive. The IL-6:IFNgamma ratio may be a good indicator of disease severity and/or the ability to cope with an infection. 相似文献
72.
Li JS Yager E Reilly M Freeman C Reddy GR Reilly AA Chu FK Winslow GM 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):1855-1862
Previous studies of Ehrlichia chaffeensis infection in the mouse have demonstrated that passive transfer of polyclonal Abs from resistant immunocompetent mice to susceptible SCID mice ameliorated infection and disease, even when Abs were administered during established infection. To identify particular Abs that could mediate bacterial clearance in vivo, E. chaffeensis-specific mAbs were generated and administered to infected SCID mice. Bacterial infection in the livers was significantly lowered after administration of either of two Abs of different isotypes (IgG2a and IgG3). Moreover, repeated administration of one Ab (Ec56.5; IgG2a) rescued mice from an otherwise lethal infection for at least 5 wk. Both protective Abs recognized the E. chaffeensis major outer membrane protein (OMP)-1g. Further studies revealed that both Abs recognized closely related epitopes within the amino terminus of the first hypervariable region of OMP-1g. Analyses of human sera showed that E. chaffeensis-infected patients also generated serological responses to OMP-1g hypervariable region 1, indicating that humans and mice recognize identical or closely related epitopes. These studies demonstrate that OMP-specific mAbs can mediate bacterial elimination in SCID mice, and indicate that Abs, in the absence of cell-mediated immunity, can play a significant role in host defense during infection by this obligate intracellular bacterium. 相似文献
73.
Since initial studies with the steroids norethindrone and ethynylestradiol, reported by White and Muller-Eberhard in 1977 (Biochem. J. 166, 57-64), there has been continuing interest in xenobiotics that bear terminal or sub-terminal acetylenic groups which can cause catalysis-dependent inhibition of CYP monooxygenases associated either with loss of prosthetic group heme or protein adduct formation. Mifepristone is a synthetic steroid bearing a propyne substitution on carbon 17 and this suggested to us that it may act as a mechanism-based inhibitor of the CYP isoforms responsible for its metabolism. In human and rat liver, CYP3A isoforms have been implicated in mifepristone clearance and mifepristone administration to rats has also been shown to induce CYP3A enzymes and the associated diazepam C3-hydroxylase activity (Cheesman, Mason and Reilly, J. Steroid Biochem. Mol. Biol., 58, 1996, 447-454). With microsomes prepared from the livers of untreated female rats and others in which diazepam C3-hydroxylase has been induced, we show here that mifepristone can cause catalysis-dependent inhibition of this monooxygenase. In addition, incubation of microsomes with mifepristone in the presence, but not in the absence, of NADPH caused loss of spectrally detectable cytochrome P450. These results suggest that heme adduct formation may result from mifepristone metabolism by CYP3A monooxygenases which undergo self-catalysed irreversible inactivation with this drug as substrate. Since mifepristone administration in vivo is able also to cause induction of the synthesis of hepatic CYP3A apoprotein, mifepristone may have the potential in human medicine for complex interactions with other co-administered drugs which are also substrates for CYP3A monooxygenases. 相似文献
74.
The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model 总被引:4,自引:0,他引:4
McKenzie SE Taylor SM Malladi P Yuhan H Cassel DL Chien P Schwartz E Schreiber AD Surrey S Reilly MP 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(7):4311-4318
In humans, the Fc receptor for IgG, FcgammaRIIA, is expressed on macrophages and platelets and may play an important role in the pathophysiology of immune-mediated thrombocytopenia. Mice lack the genetic equivalent of human FcgammaRIIA. To better understand the role of FcgammaRIIA in vivo, FcgammaRIIA transgenic mice were generated and characterized. One transgenic mouse line expressed FcgammaRIIA on platelets and macrophages at levels equivalent to human cells, and cross-linking FcgammaRIIA on these platelets induced platelet aggregation. Immune-mediated thrombocytopenia in this transgenic line was studied using i.v. and i.p. administration of anti-mouse platelet Ab. In comparison with matched wild-type littermates that are negative for the FcgammaRIIA transgene, Ab-mediated thrombocytopenia was significantly more severe in the FcgammaRIIA transgenic mice. In contrast, FcR gamma-chain knockout mice that lack functional expression of the Fc receptors FcgammaRI and FcgammaRIII on splenic macrophages did not demonstrate Ab-mediated thrombocytopenia. We generated FcgammaRIIA transgenic x FcR gamma-chain knockout mice to examine the role of FcgammaRIIA in immune clearance in the absence of functional FcgammaRI and FcgammaRIII. In FcgammaRIIA transgenic x FcR gamma-chain knockout mice, severe immune thrombocytopenia mediated by FcgammaRIIA was observed. These results demonstrate that FcgammaRIIA does not require the FcR gamma-chain for expression or function in vivo. Furthermore, taken together, the data suggest that the human Fc receptor FcgammaRIIA plays a significant role in the immune clearance of platelets in vivo. 相似文献
75.
This study investigates whether endotoxin-induced contractile dysfunction is associated with a defect in the modulation of calcium homeostasis and the potential mechanisms involved. Treatment of rats in vivo with endotoxin significantly decreased the magnitude of contractile transients in electrically stimulated left ventricular papillary muscle isolated after an equilibration period of 6 hours. Although no significant difference was found in the peak intracellular calcium concentration ([Ca2+]i) between the endotoxin-treated and control groups, resting [Ca2+]i) was significantly elevated in the endotoxin-treated group, producing a smaller Ca2+ transient (basal-peak difference) in this group. Pretreatment of rats with dexamethasone prevented the endotoxin-induced decrease in peak tension and inhibited the elevation in resting [Ca2+]i, with a resultant maintenance of Ca2+ transient magnitude. Similar observations were made during stimulation of the muscles by the beta-adrenoceptor agonist, isoprenaline. These results show that endotoxin-induced reduction of cardiac contractile performance is mediated, at least in part, by elevating resting [Ca2+]i, and a glucocorticoid protected from these negative effects. While endotoxin reduces the magnitude of the Ca2+ transient it does not alter peak [Ca2+]i availability. Further investigation is required to determine whether endotoxin decreases contractile performance by reducing the sensitivity of cardiac myofilaments to calcium. 相似文献
76.
Haemophilus influenzae is an important respiratory tract pathogen. Toward understanding the progression of H. influenzae from commensal to pathogen, we need to understand the steps of colonization and infection, processes which must involve overcoming the normal host mucociliary clearance mechanism. A reliable method for the screening and quantitation of mucin-H. influenzae binding to allow for the assessment of the physiological variables significant to H. influenzae-mucin interactions in the normal and diseased conditions, will provide insight on how to intervene to prevent, inhibit, or treat infection. The current methods for enumeration of mucin-bound H. influenzae are labor intensive and rely on viable organisms. In this report, we present a new detection method, which reduces the number of variables, processing steps, and time involved, providing an economical, rapid, and reliable means to screen for and quantitate mucin-bound H. influenzae. Organisms are applied to mucin-coated microtiter wells for a set time; nonadherent organisms are removed with gentle rinses; wells are incubated with the phosphomonoesterase substrate p-nitrophenyl phosphate; and the absorbance, reflecting phosphatase activity of the mucin-bound organisms, is read at 410 nm in a microtiter plate reader against enzymatic activity calibration curves. All nonencapsulated and encapsulated H. influenzae tested exhibited significant acid phosphate activity within 20 min, which provided linear relationships with the numbers of organisms present. H. influenzae mucin binding characteristics obtained by this method were generally comparable to published data, and ranged from 10(3) to 10(6) organisms per well, depending on both strain of organism and type of mucin employed. This convenient, rapid and economical mucin adherence assay, will enable more extensive and comprehensive studies of the interactions of H. influenzae adhesins and specific ligands on mucin macromolecules, as well as the nonspecific means by which mucins function in preventing bacterial infection. 相似文献
77.
Diurnal variation in muscle performance has been well documented in the past few years, but almost exclusively in the male population. The possible effects of the menstrual cycle on human circadian rhythms have remained equivocal, particularly in the context of muscle strength. The purpose of the study was to analyze the isolated and combined effects of circamensal variation and diurnal changes on muscle strength. Eight eumenorrheic females (age 30 +/- 5 yrs, height 1.63 +/- 0.06m and body mass 66.26 +/- 4.6kg: mean +/- SD) participated in this investigation. Isokinetic peak torque of knee extensors and flexors of the dominant leg were measured at 1.05, 3.14rad.s(-1) (through 90 degrees ROM) at two times-of-day (06:00, 18:00 h) and five time points of the menstrual cycle (menses, mid-follicular, ovulation, mid-luteal, late luteal). In addition, maximum voluntary isometric contraction of knee extensors and flexors and electrically stimulated isometric contraction of the knee extensors were measured at 60 degrees of knee flexion. Rectal temperature was measured during 30min before the tests. There was a significant time-of-day effect on peak torque values for isometric contraction of knee extensors under electrical stimulation (P< 0.05). At 18:00 h, muscle force was 2.6% greater than at 06:00 h. The time-of-day effect was not significant when the tests were performed voluntarily without stimulation: effect size calculations indicated small differences between morning and evening for maximal voluntary isometric contraction and peak torque (at 1.05rad.s(-1) for the knee extensors. A circamensal variation was observed for peak torque of knee flexors at 1.05rad.s(-1), extensors at 3.14rad.s(-1), and also isometric contraction of knee flexors, values being greatest at the ovulation phase. Interaction effects between time-of-day and menstrual cycle phase were not observed in any of the indices of muscle strength studied. The phase of the menstrual cycle seemed to have a greater effect than did the time-of-day on female muscle strength in this group of subjects. The present results suggest that peripheral rather than central mechanisms (e.g., motivation) are implicated in the diurnal variation of maximal isometric strength of women. 相似文献
78.
In recent years, monoclonal antibodies have emerged as an increasingly important class of human therapeutics. A variety of forms of antibodies, including fragments such as Fabs, Fab'2s and single-chain Fvs, are also being evaluated for a range of different purposes. A variety of expression systems and improvements within these systems have been developed to address these growing and diverse needs. 相似文献
79.
Reilly K Gómez-Vásquez R Buschmann H Tohme J Beeching JR 《Plant molecular biology》2004,56(4):625-641
A major constraint to the development of cassava (Manihot esculenta Crantz) as a crop to both farmers and processors is its starchy storage roots’ rapid post-harvest deterioration, which can render it unpalatable and unmarketable within 24–72 h. An oxidative burst occurs within 15 min of the root being injured, that is followed by the altered regulation of genes, notably for catalase and peroxidase, related to the modulation of reactive oxygen species, and the accumulation of secondary metabolites, some of which show antioxidant properties. The interactions between these enzymes and compounds, in particular peroxidase and the coumarin, scopoletin, are largely confined to the vascular tissues where the visible symptoms of deterioration are observed. These, together with other data, are used to develop a tentative model of some of the principal events involved in the deterioration process. 相似文献
80.
Zhou YP Marlen K Palma JF Schweitzer A Reilly L Gregoire FM Xu GG Blume JE Johnson JD 《The Journal of biological chemistry》2003,278(51):51316-51323