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41.
Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. 总被引:2,自引:1,他引:1 下载免费PDF全文
W M Bogers R K Stad D J Janssen N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,86(2):328-333
In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo. 相似文献
42.
Geraldo F. Busatto Lyn S. Pilowsky Durval C. Costa John Mertehs Dirk Terriere Peter J. Ell Rachel Mulligan Michael J. Travis Josée E. Leysen Dominic Lui Sveto Gacinovic Wendy Waddington Anne Lingford-Hughes Robert W. Kerwin 《European journal of nuclear medicine and molecular imaging》1997,24(2):119-124
The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands.
Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150 or123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary123I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately
2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice
multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free
from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately
100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100
min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic
data on the distribution of 5-HT2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET. 相似文献
43.
Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Normal excitation of glutamate receptors initiates the stimulation of phospholipases and lipases with the generation of second messengers that are necessary for normal cell function. The overstimulation of glutamate receptors can initiate a cascade of biochemical events including stimulation of membrane phospholipid turnover, excessive calcium entry, abnormal phosphorylation, and proteolysis. These events may be responsible for neuronal injury and degeneration found in Alzheimer disease, ischemia, spinal cord trauma, epilepsy, and Huntington disease. 相似文献
44.
用苔盼蓝及吖啶橙染色,DNA片段检定与DNA电泳等方法进行组织胺诱导胸腺细胞凋亡的研究,旨在探讨其可能机制及其在胸腺细胞负选择中的作用。结果表明,组织胺诱导使体外培养的胸腺细胞出现典型的细胞调亡。雷尼替丁可阻断上述作用,提示胸腺细胞存在H_2受体,活化该受体可能在胸腺细胞的负选择中起重要作用。 相似文献
45.
In this study, the behavioural response to dopamine D1-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D2-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive
shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and
direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on
the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC), SKF 77434 (0.1 mg/kg SC), quinpirole (0.1
and 0.25 mg/kg SC) or RU 24213 (0.3 mg/kg SC), when administered alone. In contrast, repeated ECS markedly increased locomotion
(activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration
of a D1-like agonist plus a D2-like agonist [SKF 38393 (7.5 mg/kg SC) plus quinpirole (0.25 mg/kg SC), SKF 81297 (0.2 mg/kg SC) plus quinpirole (0.1 mg/kg
SC), and SKF 77434 (0.1 mg/ kg SC) plus RU 24213 (0.3 mg/kg SC)]. This ECS-induced enhancement of dopamine-mediated behaviour
was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to
intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 μg/side, respectively). These results provide evidence that the enhancement
of dopamine function by repeated ECS requires concomitant stimulation of both D1-like and D2-like receptors, and that this effect is long-lasting.
Received: 24 January 1997 /Final version: 5 March 1997 相似文献
46.
Summary. Platelet membranes provide procoagulant surfaces for the assembly and expression of the factor X-activating complex and promote the proteolytic activation and assembly of the prothrombinase complex resulting in normal hemostasis. Recent studies from our laboratory and others indicate that platelets possess specific, high-affinity, saturable, receptors for factors XI, XIa, IX, IXa, X, VIII, VIIIa, V, Va and Xa, prothrombin, and thrombin. Studies described in this review support the hypothesis that the factor X-activating complex on the platelet surface consists of three receptors (for the enzyme, factor IXa; the substrate, factor X; and the cofactor, factor VIIIa), the colocalization of which results in a 24 million-fold acceleration of the rate of factor X activation. Whether the procoagulant surface of platelets is defined exclusively by procoagulant phospholipids, or whether specific protein receptors exist for the coagulant factors and proteases, is currently unresolved. The interaction between coagulation proteins and platelets is critical to the maintenance of normal hemostasis and is pathogenetically important in human disease. 相似文献
47.
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49.
Per Hartvig S.Å. Eckernäs Leif Lindström Bengt Ekblom Ulf Bondesson Hans Lundqvist Christer Halldin Kjell Någren Bengt Långström 《Psychopharmacology》1986,89(2):248-252
By means of positron emission tomography the uptake and kinetics of N-(methyl-11C)clozapine in different brain regions have been studied in Rhesus monkeys. 11C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of 11C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for 11C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug. 相似文献
50.
本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。 相似文献