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61.
Aparici CM Narula J Puig M Camprecios M Martín JC Tembl A Flotats A Estorch M Catafau AM Bernà L Ballester M Carrió I 《European journal of nuclear medicine》2000,27(12):1754-1759
The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4,745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the following week. These preliminary results indicate the feasibility of targeting activated lymphocytes with somatostatin receptor imaging in the detection of cardiac allograft rejection. Somatostatin receptor imaging may predict impending rejection at least 1 week before the endomyocardial biopsy becomes positive. The late appearance of diagnostic endomyocardial biopsy probably reflects a lag-time between lymphocytic activation and induction of myocyte damage. Furthermore, somatostatin receptor imaging at 4 h may in any case allow earlier intervention in the event of rejection, given the time required for histological processing of endomyocardial biopsy. 相似文献
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Randall B. Murphy Richard Einstein David I. Schuster A. P. S. Narula Laurence R. Meyerson 《Drug development research》1988,15(4):381-387
The binding of the putative affinity ligand α-flupenthixyl chloride (FPT-Cl), a derivative of the neuroleptic α-flupenthixol (FPT), to rat striatal dopamine, α1-adrenergic, and muscarinic cholinergic recognition sites, as well as to serotonin (5-HT) receptors and to the presynaptic 5-HT transport complex, was examined in vitro. FPT and FPT-Cl were relatively potent at inhibiting the binding of [3H]-flupenthixol and [3H]-spiroperidol in striatal tissue preparations as well as [3H]/spiroperidol and [3H]-WB-4101 in cortex with Ki values in the 10–20 nM range. With the exception of the muscarinic cholinergic sites (3H-quinuclidinyl-benzilate [3H-QNB]), where FPT-Cl was more potent than FPT, the Ki values for FPT-Cl were, in general, slightly greater than those for FPT for other neuro-receptors tested. FPT-Cl was found to be essentially inactive at 5-HT binding sites labeled with [3H]-LSD and at the 5-HT transport complex labeled with [3H]-imipramine, with lC50 values for both exceeding 5μM. It is concluded that the transformation of FPT to FPT-Cl is not severely detrimental to its dopamine receptor binding characteristics, suggesting that in the presence of appropriate antagonists for masking other receptors, FPT-Cl may represent a useful affinity ligand to label dopamine receptors. 相似文献
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Inhibition of the development of collagen-induced arthritis in rhesus monkeys by a small molecular weight antagonist of CCR5 总被引:2,自引:0,他引:2
Vierboom MP Zavodny PJ Chou CC Tagat JR Pugliese-Sivo C Strizki J Steensma RW McCombie SW Celebi-Paul L Remarque E Jonker M Narula SK Hart B 《Arthritis and rheumatism》2005,52(2):627-636
OBJECTIVE: Collagen-induced arthritis (CIA) in the rhesus monkey is a nonhuman primate model of rheumatoid arthritis (RA). The close phylogenetic relationship between humans and the rhesus monkey makes this model useful for the preclinical safety and efficacy testing of new therapies that are inactive in animals more distinctly related to humans. In this study, we tested the therapeutic potential of a novel, small molecular weight antagonist of CCR5, SCH-X, in this model. METHODS: CIA was induced in 10 rhesus monkeys. The animals were allocated to receive SCH-X or saline as the control (n = 5 in each group). Treatment was initiated on the day of CIA induction and continued for 45 days. Monkeys were monitored before and 63 days after CIA induction for macroscopic signs of clinical arthritis, such as soft-tissue swelling and body weight. Furthermore, markers of inflammation and joint degradation were monitored to follow the disease course. RESULTS: Only 2 of 5 animals in the SCH-X-treated group displayed prominent soft-tissue swelling, compared with all 5 saline-treated monkeys. In addition to the suppression of joint inflammation, treatment with SCH-X resulted in a reduction in joint destruction, as demonstrated by lower rates of urinary excretion of collagen crosslinks, with confirmation by histology. Whereas in all saline-treated monkeys, marked erosion of joint cartilage was observed, this was absent in 4 of the 5 SCH-X-treated monkeys. CONCLUSION: The systemic effects of treatment with SCH-X were a suppressed acute-phase reaction (reduction in C-reactive protein level) in the 3 treated monkeys with CIA that remained asymptomatic, and an altered antibody response toward type II collagen. The results suggest that the CCR5 antagonist SCH-X might have a strong clinical potential for treatment during periods of active inflammation, as seen in RA. 相似文献
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