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The synthesis of a series of azabicyclic indole esters is described and their potency reported as 5-HT4 receptor antagonists. Optimization of the most potent compound (19) by preparing the corresponding oxazino[3,2-a]indole ester afforded 34, which had a pIC50 of 9.5 in the guinea pig distal colon longitudinal muscle myenteric plexus preparation.  相似文献   
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Germ cell tumors are relatively rare tumors in childhood which often present with very large tumors in both gonadal and extragonadal locations. Extragonadal tumors are more common in neonates and infants, whereas gonadal sites predominate in childhood and adolescence. Management consists of surgical resection for localized disease, chemotherapy for residual or metastatic disease, and neoadjuvant chemotherapy and delayed surgical excision for unresectable lesions. The survival for children with germ cell tumors has improved significantly over the past 2 decades with the development of platinum-based chemotherapy. Mature and immature teratomas at any site, and completely resected (Stage I) malignant gonadal and extragonadal tumors, are treated with surgical excision and observation. Malignant lesions with microscopic residual, lymph node disease, or metastatic disease receive platinum-based chemotherapy. Current survival for low-stage (Stages I and II) gonadal sites approaches 100% and survival for higher stage (Stages III and IV) gonadal sites is approximately 95%. Survival for extragonadal lesions is approximately 90% for Stages I and II and 75% for Stages III and IV.  相似文献   
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The effects of OST-766, an inhibitor of vacuolar H+-ATPase activity, on adenylyl cyclase and phospholipase C activity were explored in the osteoblast cell line ROS 17/2.8. In fresh homogenates of ROS 17/2.8 cells, OST-766 inhibited adenylyl cyclase activity (ACA) in response to guanine nucleotide and forskolin but had no effect on basal ACA. OST-766 enhanced the basal generation of IP2, but not that formed in response to Ca2+ or guanine nucleotides. In marked contrast, incubation of intact ROS 17/2.8 cells with OST-766 for at least 48 hours resulted in an increase in basal ACA as well as in response to PTH, guanine nucleotides and forskolin. Under similar conditions, the compound also increased IP1, IP2 and IP3 generation in response to guanine nucleotides and Ca2+. Levels of the guanine nucleotide binding proteins Gs and Gi were also increased in OST-766-treated cells. The results suggest that the actions of this H+-ATPase inhibitor include effects on osteoblasts through PTH-sensitive signal transduction pathways.  相似文献   
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The prevalence and clinical significance of antibodies against beta2-glycoprotein I (anti-beta2GPI) and antibodies against oxidized low-density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti-beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.  相似文献   
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Organotin compounds including methyl- and butyltin species were determined in selected aquatic specimens (fish muscles, fish liver, mussels, algae) as well as in sediment and water from the mud flats of the German North Sea and the River Elbe. The concentration of tributyltin (TBT) ranged between 27-202 ng/g (fresh mass) in fish muscles, 54-223 ng/g (fresh mass) in fish liver, 10-25 ng/g (fresh mass) in common mussels and 42-97 ng/g (fresh mass) in bladderwrack. The concentration of total organotin compounds (mono-, di-, and trimethyltin + mono-, di-, and tributyltin) in water samples along the River Elbe up to the Elbe estuary ranged between 30-96 ng/l. Retrospective investigation of butylin compounds in mussel samples from the North Sea was performed by the analysis of cryogenically stored samples from 1985. A comparison of the results with that in muscles from 1993 shows that the total tin content and the TBT content decreased from 1985-1993 by a factor of 3.5 and 6.5, respectively. In addition estimated bioconcentration factors (BCF) for organotin compounds in samples from different trophic levels are presented.  相似文献   
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