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排序方式: 共有3045条查询结果,搜索用时 265 毫秒
921.
Wallén EA Christiaans JA Forsberg MM Venäläinen JI Männistö PT Gynther J 《Journal of medicinal chemistry》2002,45(20):4581-4584
New dicarboxylic acid bis(L-prolyl-pyrrolidine) amides were synthesized, and their inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. As compared with earlier described prolyl oligopeptidase inhibitors, these new compounds have in common an L-prolyl-pyrrolidine moiety, but the typical lipophilic acyl end group is replaced by another L-prolyl-pyrrolidine moiety connected symmetrically with a short dicarboxylic acid linker. These compounds are a new type of peptidomimetic prolyl oligopeptidase inhibitor. 相似文献
922.
Väisänen S Ryhänen S Saarela JT Peräkylä M Andersin T Mäenpää PH 《Molecular pharmacology》2002,62(4):788-794
The crystal structures of the ligand binding domain of human vitamin D receptor (VDR) complexed with its natural ligand or the superagonists MC1288 or KH1060 have recently been reported. The crystallized ligand binding domain (LBD) of VDR, however, differs from the full-length VDR with respect to deletion of 50 amino acids between its helices 2 and 3. In this study, we investigated structurally and functionally important amino acid interactions within the ligand binding pocket of the full-length VDR in the presence of several synthetic vitamin D(3) analogs. We used site-directed mutagenesis scanning combined with limited proteolytic digestion, electrophoretic mobility shift assay, and reporter gene assay and correlated the findings with the crystal structures of truncated VDR LBD. Our results suggest that structurally different agonists have distinct ligand-receptor interactions and that the amino acid residues H229, D232, E269, F279, and Y295 are critical for the agonistic conformation of the VDR. Our biological data, which were obtained with the full-length VDR, fit well with the crystal structure of the truncated VDR LBD and suggest that removal of the insertion domain between helices 2 and 3 of the receptor does not markedly influence the functionality of the VDR. 相似文献
923.
924.
Katja A. Puttonen rka Lehtonen Atso Raasmaja Pekka T. Mnnist 《Toxicology in vitro》2006,20(8):1446-1454
We studied the ability of prolyl oligopeptidase (POP) inhibitors, Z-Pro-Prolinal and JTP-4819, to prevent translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and formation of reactive oxygen species (ROS), in 6-hydroxydopamine (6-OHDA) and cytosine arabinoside (Ara-C) treated monkey fibroblast (CV1-P) and human neuroblastoma (SH-SY5Y) cells. The cells were pretreated with POP inhibitors (30 min) before addition of toxicants. GAPDH was analyzed by Western hybridization, ROS by fluorescent 2′7′-dichlorodihydro-fluorescein diacetate, and viability by the MTT method. Both toxicants induced GAPDH translocation to the particulate fraction (mitochondria and nuclei). Z-Pro-Prolinal was able to inhibit the translocation in 6-OHDA-exposed CV1-P cells. In SH-SY5Y cells and in JTP-4819 pretreated cells, no prevention of translocation was seen. However, the intensity of GAPDH in cytosolic fraction increased. Both inhibitors blocked 6-OHDA-induced ROS-production to the control level in CV1-P but, not in SH-SY5Y cells, without affecting their viability. In conclusion, POP inhibitors are able to prevent certain cell stress related factors such as ROS production or GAPDH translocation. 相似文献
925.
Eija Vesti MD Mika Harju MD Päivi Puska MD Ilkka Immonen MD 《Annals of Ophthalmology》2001,33(4):309-314
This study investigated whether retinal capillary circulation in the macula is affected in exfoliation glaucoma and whether
such changes can be detected in exfoliation syndrome without glaucoma. Blue-field entoptic simulation (measurement of macular
capillary leukocyte velocity and density) was performed in 2 groups: 10 subjects with unilateral exfoliation glaucoma and
11 subjects with unilateral normotensive exfoliation syndrome. Macular capillary leukocyte velocity was reduced in exfoliation
glaucoma but not in normotensive exfoliation syndrome. 相似文献
926.
Pharmacokinetics of finrozole (MPV-2213ad), a novel selective aromatase inhibitor, in healthy men
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Outi Ahokoski Kerttu Irjala Mikko Taalikka Pekka Manninen Kaija Halonen Lauri Kangas Eeva Salminen Risto Huupponen Harry Scheinin 《British journal of clinical pharmacology》2001,52(6):702-704
AIMS: To investigate the pharmacokinetics of finrozole (MPV-2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers. METHODS: The study was an open, partly randomized cross-over study including 23 volunteers receiving single doses of 3, 9 mg or 30 mg of finrozole as tablets or solution with 14 days between the administrations. The highest dose was given as tablets only. Serum concentrations of finrozole were determined using high performance liquid chromatography combined with mass spectrometry. RESULTS: The mean time to peak serum concentration ranged from 2.5 to 3.1, and 0.6-0.7 h after tablets and solution, respectively. The Cmax values increased as the dose increased. The calculated apparent mean elimination half-life (t(1/2,z)) was approximately 3 h after the solution, and approximately 8 h after the tablet. The AUC(0,infinity) after finrozole tablets increased proportionally from 3 mg to 9 mg and from 3 to 30 mg. The calculated relative mean bioavailabilities (AUC(0,infinity)-ratio) for the 3 mg and 9 mg doses of finrozole as tablets were 89% and 78%, respectively. CONCLUSIONS: The absorption of finrozole from the tablet formulation was relatively rapid, and the apparent elimination half-life was longer after the tablet than after the solution, probably reflecting overlap of the absorption with the elimination phase. 相似文献
927.
Mervi Hakanen Kari Luotola Jorma Salmi Pekka Laippala Katri Kaukinen Pekka Collin 《Digestive diseases and sciences》2001,46(12):2631-2635
Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance. 相似文献
928.
929.
CONCLUSIONS: In computer-assisted analysis of acinic cell cancer (ACC) morphological characteristics of CD34 immunoreactivity were detected. Bigger vessel size, vessel irregularity, and lower intensity of CD34-positive vessel staining may indicate unfavorable prognosis. OBJECTIVES: Salivary gland cancer (SGC) is a morphologically diverse group of malignancies, the most common histological types being mucoepidermoid, adenoid cystic and ACC, which has the most favorable prognosis of the three. The aim of this research was to study the applicability of automated image analysis as prognostic criteria in ACC. PATIENTS AND METHODS: In a nationwide study covering SGC patients in Finland during 1991-1996, 34 patients with ACC (15 males, 19 females, aged 19-95 years, mean 55 years) were included. Parameters were measured from CD34-stained samples. RESULTS: In all, 10 385 vessels were measured, of which 9873 were from specimens from patients who were alive 5 years after treatment (n=32, group I) and 512 were from patients who died of disease (n=2, group II). The following results were found in group II versus group I: mean vessel size 469 microm vs 272 microm (p=0.024); vessel irregularity 28.3 microm vs 22.3 microm (p<0.001); CD34 staining intensity 0.555 microm vs 0.584 microm (p=0.024). 相似文献
930.