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31.
Hajime Kimata 《European journal of immunology》1994,24(11):2910-2913
The effects of gangliosides on human plasma cell responses were studied. Among the various gangliosides tested, only GM1 enhanced immunoglobulin (Ig) production and proliferation in the human plasma cell lines, IM-9 and AF-10, while other gangliosides (GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b) had no effect. Among the various cytokines tested, including interleukin (IL)-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, interferon (IFN)-α and IFN-γ, only IL-6 enhanced Ig production and proliferation in IM-9 and AF-10 cells. However, the enhancement of plasma cell responses by GM1 was specific and was not mediated by IL-6, since GM1 activity was blocked by anti-GM1 monoclonal antibody (mAb), but not by control IgM, anti-IL-6 Ab or the anti-IL-6 receptor mAb, PM1. Conversely, the enhancement by IL-6 was blocked by anti-IL-6 Ab and PM1, but not by anti-GM1 mAb. GM1, but not other gangliosides, also enhanced Ig production and proliferation in freshly separated plasma cells from patients with plasma cell leukemia and in plasma cells generated in vitro. These actions of GM1 were specifically blocked by anti-GM1 mAb, but not by anti-IL-6 Ab or PM1. These results indicate that GM1 may be an important regulator of plasma cell responses. 相似文献
32.
Swirski FK Gajewska BU Robbins CS D'Sa A Johnson JR Pouladi MA Inman MD Stämpfli MR 《European journal of immunology》2004,34(9):2375-2386
We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) breaks tolerance induction. The objective of this study was to determine whether GM-CSF breaks established inhalation tolerance. To induce tolerance, BALB/c mice were exposed to aerosolized ovalbumin (OVA) for 10 consecutive days. A control group was exposed to saline. Subsequently, tolerant and control animals were exposed to OVA in a GM-CSF-enriched airway microenvironment. Tolerant animals, unlike control animals, did not develop airway and peripheral blood eosinophilia, had diminished levels of OVA-specific IgE, and reduced airway hyper-responsiveness. While tolerant animals did not express IL-4, IL-5 and IL-13, levels of the regulatory cytokines IL-10, IFN-gamma and transfoming growth factor (TGF)-beta were similar between tolerant and non-tolerant animals. Lung CD4+ T cells were activated according to CD69, CD25 and T1/ST2 expression, but systemic responses characterized by splenocyte proliferation and Th2 effector function were dramatically reduced. Concurrent expression of GM-CSF and decorin, a natural inhibitor of TGF-beta, reversed eosinophilic unresponsiveness. Our study suggests that the breakdown of tolerance and, by extension, the emergence of eosinophilic inflammation, requires two signals: one that triggers sensitization and one that interferes with negative regulation. Moreover, our study shows that dysregulated expression of an extracellular matrix protein may break established tolerance and lead to eosinophilic airway inflammation. 相似文献
33.
Mounir Fouad F Mamer O Khayyal M Sauriol F Lesimple A Ruhenstroth-Bauer G 《Medical hypotheses》2004,63(6):1024-1034
We are elaborating on the kinetics and mechanisms of septic rabbit liver to de novo biosynthesize acute-phase response (APR) proteins under in vitro conditions of deepening ischemia in reference to their in vivo prevalence in serum and cerebrospinal fluids (CSF) collected at predetermined times. The significance of the data is interpreted as relevant to grafting cadaveric liver into end-stage liver diseased patients and APR-induced ischemic heart diseases (IHD). Hepatic APR was induced by CCl(4)-intubation, and the administration of cholera toxin (CT) or scorpion venom (SV), or both, to rabbits. Hepatic functional efficiency, in terms of biosynthesis of APR proteins in closed circuit perfusion of the isolated intoxicated liver with oxygenated saline or L-15 media paralleled the two-dimensional immunoelectrophoresis (2D-IEP) spectrum of APR serum proteins at time of liver isolation. We are suggesting: (a) in vitro biosynthesis of plasma proteins by isolated perfused liver is the result of in vivo decoded and retained APR inflammatory signals; and (b) decoded inflammatory signals are expressed not withstanding the perfusate's organic composition. Furthermore, 90 min of ischemic perfusion in saline or L-15 medium precipitated mitochondrial aberrations which resulted in further deterioration of de novo biosynthesis of APR plasma proteins. Regardless of the nature of the inflammatory stimuli, mitochondrial aberrations rendered the perfused organ a biologically inert tissue mass that was incapable of resuming biological function upon perfusion with oxygenated L-15 medium. This is most likely due to ischemia-induced irreversible hepatic necrosis. Thus, in vitro aberrations of mitochondrial function(s) critically limit the capability of the isolated liver to resume its organic function to sustain biosynthesis of de novo plasma proteins. Extrapolation of these results to the surgical management of end-stage liver diseases points to the importance of the status and the handling protocol(s) of the cadaver donor liver prior to successful grafting. We conclude that although histology of a cadaver liver may reveal well-preserved hepatic cellular organelles with at least minimal intra- and intercellular communication required for viable hepatic function, we deem it essential to further define acceptable minimal capabilities to de novo biosynthesize plasma proteins by a cadaver liver as a measure of its functional viability and suitability for transplantation. Ultimately, this measure may improve the success of liver transplants with minimal surgical and drug interventions. 相似文献
34.
On the search for the sources of the electroencephalogram 总被引:1,自引:0,他引:1
35.
神经节苷脂GM1对新生大鼠缺氧缺血性脑病的作用研究 总被引:1,自引:0,他引:1
目的 探讨单唾液酸四己糖神经节苷脂(GM1)对新生大鼠缺氧缺血性脑病(HIE)及其后的癫痫发作是否具有保护和预防作用以及可能作用机理,为临床应用GM1治疗HIE提供理论依据。方法 建立新生大鼠HIE模型。用组织化学方法和免疫组织化学方法观察缺氧缺血后脑损害的形态学改变,兴奋性氨基酸Glu阳性(Glu-IR)神经元和抑制性氨基酸GABA阳性(GABA-IR)神经元表达和GM1对上述变化的影响。结果 盐水处理组与GM1治疗组相比病变较重,Glu-IR神经元和GABA-IR神经元数目减少与GMI治疗组差异有显著性意义。结论 GM1能够在一定程度上减轻新生大鼠缺氧拭岂血后病损灶,保护Glu-IR神经元和GABA-IR神经元,尤其是对GABA-IR神经元的保护作用,提示GM1对新生大鼠缺氧缺血后的癫痫发作具有一定的预防作用。但尚需进一步探讨研究。 相似文献
36.
目的探讨中枢神经系统感染患儿血脑屏障(blood-brain barrier,BBB)与脑脊液(cerebrospinal-fluid,CSF)白蛋白指数的变化。方法采用溴甲酚绿法和免疫比浊法检测18例化脓性脑膜炎患儿急性期、恢复期及22例病毒性脑炎患儿急性期血清和CSF中白蛋白水平,并计算出CSF白蛋白指数。与正常对照组比较。结果化脓性脑膜炎、病毒性脑炎患儿急性期CSF白蛋白、CSF白蛋白指数显著高于正常对照组(P〈0.001),且化脑组显著高于病脑组(P〈0.001)。化脑组恢复期患儿CSF白蛋白、CSF白蛋白指数与对照组无明显差异(P〉0.05)。结论监测CSF白蛋白和CSF白蛋白指数的水平可作为化脓性脑膜炎和病毒性脑炎早期诊断、鉴别诊断,以及判断BBB损伤程度的参考指标。 相似文献
37.
Martin Griebe Michael Daffertshofer Mark Stroick Magdalena Syren Parviz Ahmad-Nejad Michael Neumaier Juergen Backhaus Michael G. Hennerici Marc Fatar 《Neuroscience letters》2007
Biological markers play an evolving role in the diagnosis of Alzheimer disease (AD). We compare conventional measurements of cerebrospinal fluid (CSF) tau and β-amyloid1–42 proteins to a novel approach – Fourier transformed infrared (FT-IR) spectroscopy – a simple technique derived from chemical and physical sciences that characterizes intramolecular bonds. For automatic diagnostic analysis, we developed an artificial neural network (ANN). We examined 71 patients with a clinical diagnosis of AD and 66 controls. β-Amyloid1–42 was decreased (sensitivity 80% and specificity 78%); tau was elevated (sensitivity 76% and specificity 88%) in CSF of AD patients. The combined tau/β-amyloid1–42 quotient was able to distinguish healthy from diseased subjects with 99% sensitivity and 86% specificity. The ANN could separate FT-IR spectroscopy data with 88.5% sensitivity and 80% specificity. FT-IR spectroscopy proved to be cost-effective and simple to perform. Diagnostic sensitivity and specificity is in the range of CSF tau and β-amyloid1–42 protein analysis. Larger sample numbers for ANN training and validation could increase diagnostic accuracy and thus prove to be a useful screening tool. 相似文献
38.
L. Hübner E.M. Kniep H. Laukel C. Sorg H. Fischer W.D. Gassel K. Havemann B. Kickhöfen M.-L. Lohmann-Matthes A. Schimpl E. Wecker 《Immunobiology》1980,157(2):169-178
Supernatants from Concanavalin A-stimulated murine spleen cells were subjected to hydrophobic interaction chromatography on phenyl-Sepharose. Macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF), T-helper cell-replacing factor (TRF) and colony-stimulating factor (CSF) were bound at high ionic strength and were released stepwise at low ionic strength. CSF thus could be separated from MCF, MIF and TRF and the bulk of other proteins. Chromatography of pools containing MCF, MIF and TRF on Sephadex did not lead to a separation of the three activities which were all found in a molecular weight range of 25.000-55.000. Isoelectric focusing of these pools in pH range from 4 to 9 gave two peaks for MCF at pH 8.2 and 7.2, whereas MIF activity focused from pH 4.5 to 5.5. TRF activity was found in a single sharp peak at pH 5.3. The results demonstrate that the four biological activities can be distinguished on a chemical basis and are accessible for purification and chemical characterization. 相似文献
39.
Gangliosides are glycosphingolipids found ubiquitously on thesurface of mammalian cells. They contain a ceramide tail thatis inserted into the membrane and exposed carbohydrate and sialicacid moleties. The non-toxic B subunit oligomer (EtxB) of Escherichiacoli heat-labile enterotoxin (Etx) is a potent immunogen invivo and has profound modulatory effects on EtxB-primed lymphocytesin vitro, properties which are dependent on its ability to bindto GM1 ganglioside receptors. Here, it is shown that cross-linkingGM1 by EtxB causes a differential effect on mature CD4+ andCD8+ T cells from lymph node cultures proliferating in responseto an unrelated antigen, ovalbumin. Addition of EtxB to suchcultures led to the complete depletion of CD8+ T cells comparedwith enhanced activation of CD4+ T cells [as measured by expressionof CD25 (IL-2R)]. By contrast, addition of a mutant EtxB, EtxB(G33D),which does not bind to GM1, failed to trigger CD8+ T cell depletion.When EtxB was added to isolated non-immune CD8+ lymphocytesrapid (12–18 h) alterations in nuclear morphology andthe appearance of sub-G0/G1 levels of DNA were induced; propertieswhich are characteristic of cells undergoing apoptosis. EtxB(G33D)failed to trigger apoptosis, indicating that the induction ofthe apoptotic signal was dependent on the binding of GM1. Thesefindings provide an insight into the potent immunogenicity andimmunomodulatory properties of E. coli enterotoxins as wellas heralding a novel method for the selective induction of apoptosisin mature CD8+ T lymphocytes. 相似文献
40.
Diagnostic challenges of using CSF assay of tau and beta-amyloid42 in atypical degenerative dementias of the Alzheimer type 总被引:1,自引:0,他引:1
Mark Wagner Gordon Teichner David L. Bachman 《Archives of clinical neuropsychology》2003,18(8):278-903
This report presents three cases of atypical degenerative dementias in order to illustrate challenges associated with the use of biologic markers of Alzheimer's disease (AD) for diagnosis and management. Clinical diagnostic methods followed the NINCDS-ADRDA criteria for AD. Additional diagnostic studies included serial neurocognitive testing, MRI, neuroSPECT, ApoE genotyping, and a CSF assay of tau and beta-amyloid(42). For patient 1, both the clinical and biologic markers were consistent with AD. The patient was diagnosed with AD with a high degree of confidence, even though the base rate of nonfamilial AD at this age group (<55 years) is exceedingly rare. This case argues favorably for the use of biologic markers to aid in confirming a diagnosis in an atypical dementia. Patient 2 met the NINCDS-ADRDA criteria for AD, although with less confidence. Neurocognitive data indicated a progressive right hemispheric syndrome, insight was preserved, and ApoE was 3/3, but tau concentrations and beta-amyloid(42) were highly consistent with cut-offs for AD; the differential fell on the Pick's disease/frontotemporal degeneration spectrum. Patient 3 had no clinical evidence of the disease, even when evaluated via extensive neurocognitive testing over a 2-year interval. However, ApoE was 4/4, and CSF assay of tau and beta-amyloid(42) were within the AD range. Therefore, while the CSF assay of tau and beta-amyloid(42) markers was confirmatory of AD, each case was highly atypical. Results illustrate the lack of normative data available when using biologic markers for highly atypical cases, calling into question their usefulness for such patients. These cases illustrate the interplay between neuropsychological and biological markers in establishing neurodegenerative diagnoses. 相似文献