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81.
82.
Christian Foged Christer Halldin Christian Loc’h Bernard Mazière Stefan Pauli Mariannick Maziére Holger C. Hansen Tetsuya Suhara Carl-Gunnar Swahn Per Karlsson Lars Farde 《European journal of nuclear medicine and molecular imaging》1997,24(10):1261-1267
NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand
for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241.
This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised
by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake
of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after
injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with
flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection.
The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands
for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.
Received 19 April and in revised form 10 June 1997 相似文献
83.
Roelf Valkema MD Berthe L. F. van Eck-Smit MD Ernst E. van der Wall MD 《Journal of nuclear cardiology》1994,1(6):546-560
Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable
tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients
with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty
acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals.
Alternatively,31P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet
clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses
combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static
and rapid dynamic studies. Currently, assessment of glucose metabolism with18F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile
function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement,
and therefore assessment of residual oxidative metabolism by11C-labeled acetate PET may prove to be more accurate than18F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized
only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional
improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the
myocyte are attractive for myocardial imaging. Examples are123I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-123I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography,
which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making
the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience
with31P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques,
insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid
changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of
myocardial metabolism. 相似文献
84.
浆细胞病患者IL-4产生细胞数减少的意义及机制探讨 总被引:2,自引:0,他引:2
本文运用APAAP法检测了16名浆细胞患者外周血细胞在PHA刺激下产生IL-4的能力。发现浆细胞病组阳性细胞比率明显低于正常对照组(P<0.001),且阳性细胞比率与患者血清中多克隆IgM、IgA水平呈正相关(r=0.806和r=0.703)。在正常人外周血中加入CRP50mg/L,经PHA刺激后IL-4产生细胞也明显减少。作者假设,由于IL-6增高引起CRP等急性期相蛋白大量分泌,使IL-4产生受到明显抑制,从而使B细胞激活发生障碍是浆细胞病中多克隆免疫球蛋白合成抑制的主要原因。 相似文献
85.
卵巢癌细胞多种细胞因子基因表达的研究 总被引:1,自引:0,他引:1
本文应用RT-PCR方法,检测5例刚分离的晚期上皮性卵巢癌患者肿瘤细胞和3例卵巢痛患者腹水中肿瘤细胞IL-2、IL-2R、TNF-a,IL-6、TGF-p、IL-10等细胞因子基因的表达,用免疫学方法检测卵巢癌细胞上清液中IL-6活性。结果发现:卵巢癌肿瘤细胞表达IL-6mRNA和抑制性细胞因子TGF-p、IL-10。腹水中存在较多量lL-6可能来自肿瘤细胞。 相似文献
86.
87.
L. M. TERAN M. G. CAMPOS B. T. BEGISHVILLI J.-M. SCHRÖDER R. DJUKANOVIC J. K. SHUTE M. K. CHURCH S. T. HOLGATE D. E. DAVIES† 《Clinical and experimental allergy》1997,27(4):396-405
Background Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. Objective To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. Method BAL fluid was obtained from 13 subjects (seven asthmatics and six normals). aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. Results NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutropbil chemotaxis. Conclusion This study demonstrates that bronchial asthmatic lavage fluid contains C5a/C5a des/Arg and iL-8, together with other as yet unidentified factors which may contribute to neutropbil recruitment in this disease. 相似文献
88.
BACKGROUND: We have previously demonstrated that the proteolytic activity of Der p 1 selectively cleaves human CD25, the 55 kDa alpha subunit of the IL-2 receptor. As a result of cleavage of surface CD25, peripheral blood T cells produce less IFN-gamma and more IL-4, thereby leading to progressive polarization of the T cells towards a Th2 cytokine profile. Therefore, these observations underline the potential role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis. OBJECTIVE: To study the effect of T cells that have been conditioned by the proteolytic activity of Der p 1 on IgE synthesis by B cells. METHODS: We have examined this concept in experiments whereby T cells that have been exposed to either proteolytically active or inactive Der p 1 were cocultured with autologous B cells and IgE antibody synthesis was monitored. RESULTS: Here we demonstrate for the first time that coculturing T cells that have been in contact with proteolytically active Der p 1 with autologous B cells leads to augmentation of IgE antibody responses. CONCLUSIONS: The proteolytic activity of Der p 1 conditions human T cells, which then become empowered to trigger enhanced IgE synthesis by B cells. 相似文献
89.
目的:观察中药肾康宁对家兔实验性肾炎黏附分子及细胞因子表达的影响,以及临床肾小球肾炎治疗前后尿蛋白的变化.方法:检测牛血清白蛋白所致急性实验性肾炎动物肾组织ICAM-1表达、血清IL-6水平的变化,以及临床肾小球肾炎肾康宁治疗前后血清IL-6水平、尿蛋白的变化.结果:肾康宁能明显降低实验动物血清IL-6含量,降低急性实验性肾炎模型中ICAM-1阳性细胞表达率,同时减轻肾小球基底膜(GBM)增厚及炎症细胞浸润,阻止毛细血管内微血栓的形成;在临床肾小球肾炎中,肾康宁能减少肾小球肾炎患者血清IL-6水平及24 h尿蛋白含量.结论:肾康宁通过降低细胞因子IL-6水平和黏附分子ICAM-1的表达,从而抑制免疫细胞的趋化、浸润、活化和增殖、减少免疫复合物的沉积,使肾小球炎症反应减轻,有效缓解家兔急性实验性和临床肾小球肾炎,使肾功能得以改善. 相似文献
90.
Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the immune system. Evidence suggests that UVB-induced immunosuppression is mediated in part by immunosuppressive and immunoregulatory cytokines. Our studies have utilized gene-targeted mutant mice to determine key molecular requirements essential for the development of UVB-induced immunosuppression. Preliminary results from our laboratory suggest that TNF-α plays a regulatory role in contact hypersensitivity, but is not a crucial factor for UVB-induced immunosuppression, and that multiple factors are involved in the induction of UVB mediated immunosuppression. 相似文献