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11.
T van der Poll C C Braxton S M Coyle M A Boermeester J C Wang P M Jansen W J Montegut S E Calvano C E Hack S F Lowry 《Infection and immunity》1995,63(9):3396-3400
Triglyceride-rich lipoproteins can inhibit endotoxin activity in vitro and in rodents. We sought to determine whether Intralipid, a triglyceride-rich fat emulsion which in contact with plasma functions similarly to endogenous lipoproteins, can alter the human response to endotoxin. Intralipid inhibited endotoxin-induced cytokine production in human whole blood in vitro in a dose-dependent manner, with maximal inhibition (up to 70%) being achieved at a concentration of 10 g/liter. In healthy men, a bolus intravenous injection of endotoxin (lot EC-5; 20 U/kg of body weight) was given midway through a 4-h infusion (125 ml/h) of either 5% glucose (n = 5) or 20% Intralipid (n = 5). The infusion of Intralipid led to an increase in triglyceride levels in serum from 95 +/- 16 to 818 +/- 135 mg/dl prior to endotoxin administration, i.e., levels that importantly reduced cytokine production in endotoxin-stimulated whole blood. However, in vivo hypertriglyceridemia did not influence inflammatory responses to endotoxin (fever, release of tumor necrosis factor and soluble tumor necrosis factor receptors, and leukocytosis) or even potentiated endotoxin responses (release of interleukins 6 and 8 and neutrophil degranulation). Hypertriglyceridemia does not inhibit the in vivo responses to endotoxin in humans. 相似文献
12.
Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections 总被引:4,自引:0,他引:4
Mairuhu AT Peri G Setiati TE Hack CE Koraka P Soemantri A Osterhaus AD Brandjes DP van der Meer JW Mantovani A van Gorp EC 《Journal of medical virology》2005,76(4):547-552
C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment. 相似文献
13.
Inactivation of C-1 inhibitor by proteases: demonstration by a monoclonal antibody of a neodeterminant on inactivated, non-complexed C-1 inhibitor. 总被引:4,自引:0,他引:4
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Monoclonal antibodies were raised against kallikrein-C-1 inhibitor and factor XIIa-C-1 inhibitor complexes. One of the monoclonal antibodies (KII) appeared to react predominantly with C-1 inhibitor complexes in an ELISA. However, the apparent binding of KII to C-1 inhibitor complexes was probably due to the presence of proteolytically inactivated C-1 inhibitor in the complex mixture used for the coating:KII did not bind either kallikrein-C-1 inhibitor or factor XIIa-C-1 inhibitor complexes generated in plasma by dextran sulphate. SDS-PAGE analysis of C-1 inhibitor incubated with proteases revealed that KII-reactive C-1 inhibitor has a lower molecular weight than native C-1 inhibitor. We propose that the determinant that reacts with KII is exposed after cleavage of C-1 inhibitor in its reactive site. The monoclonal antibody KII will enable us to study the inactivation of C-1 inhibitor in human inflammatory disease. 相似文献
14.
The CD8+ granzyme B+ T-cell subset in peripheral blood from healthy individuals contains activated and apoptosis-prone cells.
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P C Wever H J Van Der Vliet L H Spaeny A M Wolbink F N Van Diepen C J Froelich C E Hack I J ten Berge 《Immunology》1998,93(3):383-389
Granzyme B (GrB) has been implicated in induction of apoptosis in target cells. The presence of GrB in peripheral blood CD8+ T cells from healthy individuals was analysed in immunocytochemical and flow cytometric studies. Furthermore, CD8+ GrB- T cells and CD8+ GrB+ T cells were compared regarding phenotypical characteristics and susceptibility to both spontaneous and Fasmediated apoptosis. GrB was expressed by approximately one-fifth of CD8+ T cells. Compared with the CD8+ GrB- T-cell subset, the CD8+ GrB+ T-cell subset contained cells that were relatively more activated and more prone to spontaneous apoptosis. Culturing of cells with immunoglobulin M (IgM) anti-Fas monoclonal antibody had no additional effect on the number of CD8+ GrB+ T cells undergoing apoptosis. We suggest that the presence of CD8+ GrB+ T cells in peripheral blood from healthy individuals results from immune surveillance or contact with infectious agents, and that spontaneous apoptosis of these cells might serve as a mechanism for their eventual clearance. 相似文献
15.
The IgG detected in the C1q solid-phase immune-complex assay is not always of immune-complex nature 总被引:3,自引:0,他引:3
The properties of the solid-phase C1q immune-complex assay as well as the nature of the IgG detected by this assay in patients' sera were investigated. Aggregated IgG was used as a model for immune complexes. Aggregated IgG bound to solid-phase C1q was detected by 125I-anti-IgG. Fluid-phase C1q (either in normal human serum or purified) neither inhibited the binding of aggregated IgG to solid-phase C1q nor dissociated bound aggregated IgG from the solid-phase C1q. Therefore, we concluded that the solid-phase C1q has a higher affinity for aggregated IgG than the fluid-phase C1q, probably because of the polymerization of the solid-phase C1q. To get more insight into the nature of the IgG detected by the C1q solid-phase assay in patients' sera, we investigated whether C4 and/or C3 were present on it. With the use of 125I-anti-C4 and 125I-anti-C3 instead of 125I-anti-IgG, C4 and C3, respectively, were easily detected on the aggregated IgG that had bound to the solid-phase C1q. The lower limit of detection of these assays was 30 micrograms aggregated IgG/ml of normal human serum. Sera of patients suffering from rheumatoid arthritis and systemic lupus erythematosus were tested with these assays and, despite positive results with 125I-anti-IgG, no positive results were obtained with either 125I-anti-C4 or 125I-anti-C3. So, on the IgG detected by the C1q solid-phase assay in patients' sera, neither C4 nor C3 are present. Furthermore, in five of the six sera tested, this IgG sedimented as monomeric IgG. Therefore, it seems unjustified to refer to this IgG as circulating immune complexes. 相似文献
16.
15 different monoclonal antibodies (mcAbs) have been raised against the cleaved (inactive) form of the serpin alpha 1-antitrypsin (AT). In initial experiments these mcAbs were analysed for their ability to bind the native and the cleaved form of this inhibitor: eight of the 15 mcAbs appeared to react predominantly with cleaved AT. Additional experiments with mixtures of purified native AT, AT complexed to neutrophilic elastase and inactivated AT revealed that all mAbs that preferentially reacted with inactivated AT also bound to complexed AT. Using two of the mcAbs against inactivated AT a quantitative and sensitive sandwich-type radioimmunoassay was developed to determine levels of proteolytically inactivated AT in biological fluids. With this assay increased levels of inactivated AT were found in synovial fluid from patients with rheumatoid arthritis corresponding to about 2.4% (range 0.3-11%) of total AT. Approximately 10% of this inactivated AT appeared to consist of AT complexed to neutrophil elastase. The mcAbs described here further illustrate the structural resemblance between the complexed and cleaved forms of AT. In addition, these mcAbs appear to be useful tools for the study of AT in human disease. 相似文献
17.
The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% N(2)/5% CO(2) for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by [(3)H]O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxiain vitro. 相似文献
18.
The effect of the root ofCoptis japonica (COPT), both the dichloromethane soluble (CH2Cl2) and insoluble (H2O) fractions, on catecholamine contents and tyrosine hydroxylase (TH) activity in PC12 cells was investigated. CH2Cl2 and H2O fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a concentration of 40 μg/ml in medium: the H2O fraction provided a greater inhibitory effect. The TH activity was reduced by the treatment of COPT (H2O fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells. 相似文献
19.
Veerhuis R Janssen I De Groot CJ Van Muiswinkel FL Hack CE Eikelenboom P 《Experimental neurology》1999,160(1):289-299
Complement activation products C1q, C4c/d, and C3c/d in amyloid plaques in Alzheimer's disease probably result from direct binding and activation of C1 by amyloid beta peptides. RT-PCR and in situ hybridization studies have shown that several complement factors are produced in the brain parenchyma. In the present study, cytokines that can be detected in amyloid plaques (i.e., interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha) were found to differentially stimulate the expression of C1 subcomponents, C1-Inhibitor (C1-Inh), C4, and C3, by astrocyte and microglial cell cultures derived from postmortem adult, human brain specimens and by neuroblastoma cell lines in culture. C1r and C1s were secreted at low levels by astrocytes and neuroblastoma cell lines. Exposure of cells to IL-1 alpha, IL-1 beta, TNF-alpha and to a far lesser extent IL-6, markedly upregulated C1r, C1s, and C3 production. C4 synthesis increased in response to interferon (IFN)-gamma and IL-6, whereas that of C1-Inh could be stimulated only by IFN-gamma. Thus, C1-Inh production is refractory to stimulation by plaque-associated cytokines, whereas these cytokines do stimulate C1r, C1s, and also C4 and C3 secretion by astrocytes and neuronal cells in culture. In contrast to the amyloid plaque associated cytokines IL-1 beta, IL-1 alpha, and TNF-alpha, the amyloid peptide A beta 1-42 itself did not stimulate C1r and C1s synthesis by astrocytes, microglial cells, or neuroblastoma cell lines. Microglial cells were the only cell type that constitutively expressed C1q. The ability of C1q to reassociate with newly formed C1r and C1s upon activation of C1 and subsequent inactivation by C1-Inh, may enable ongoing complement activation at sites of amyloid deposition, especially when C1-Inh is consumed and not replaced. 相似文献
20.
L-Thyroxine (T4) is commonly prescribed medication for hypothyroidism in humans and animals. Overdose has generally resulted in limited symptomatology managed with sedatives and beta-adrenergic receptor antagonists. We describe the largest acute T4 ingestion ever reported, which resulted in a profound thyrotoxicosis, resistant to treatment. A 34-y-old man ingested 900 (0.8 mg) tablets of veterinary T4 (720 mg) and was given 60 g of activated charcoal. He became lethargic on post-ingestion days 2 and 3; had vomiting, diaphoresis and insomnia on day 4; on day 5 he "looked like he had too much coffee", began "using a lot of words" and became agitated, assaultive and stopped speaking intelligibly; and on day 6 returned to the hospital combative and confused. He was diaphoretic, mydriatic, hyperreflexic, tremulous, with clear lungs and active bowel sounds, and received activated charcoal, haloperidol, diazepam, and phenobarbital, and was tracheally intubated. During hospitalization he was rehydrated, treated with propranolol and diazepam, but remained continuously tachycardic. On day 12 he became afebrile and his tachycardia resolved. Free T4 levels ranged from > 13 mcg/dL on day 6 to 1.2 mcg/dL on day 12. By discharge (day 15) he had lost 20 kilograms of body weight, but was clinically euthyroid 2 w later. This case suggests that large intentional T4 ingestions should be managed differently than current T4 overdose protocol. 相似文献