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681.
The concentration of plasma Fn was determined in non-splenectomized and splenectomized patients with homozygous beta-thalassemia, before and 7-10 days after blood transfusion. The mean Fn concentration of non-splenectomized patients before transfusion did not differ from that of matched normal controls but appeared significantly decreased following blood transfusion. On the other hand, in splenectomized thalassemics, Fn levels were increased but were unrelated to transfusion. It is concluded that Fn plays some homeostatic function when RES activity of thalassemic patients is altered either as a result of splenectomy or blood transfusion. 相似文献
682.
Christina Piperi Elena Farmaki Fotis Vlastos Athanasios G. Papavassiliou Nadine Martinet 《Journal of biomolecular techniques》2008,19(5):281-284
Epigenetic changes, or heritable alterations in gene function that do not affect DNA sequence, are rapidly gaining acceptance as co-conspirators in carcinogenesis. Although DNA methylation signature analysis by methylation-specific polymerase chain reaction has been a breakthrough method in speed and sensitivity for gene methylation studies, several factors still limit its application as a routine diagnostic and prognostic test. 相似文献
683.
684.
Athanasios Kazantzis Michaela Waldner John W Taylor Aphrodite Kapurniotu 《European journal of biochemistry》2002,269(3):780-791
Calcitonin (Ct) is a 32-residue peptide hormone that is mainly known for its hypocalcemic effect and the inhibition of bone resorption. Our previous studies have led to potent, side-chain lactam-bridged human Ct (hCt) analogues [Kapurniotu, A. Kayed, R., Taylor, J.W. & Voelter W. (1999) Eur. J. Biochem. 265, 606-618; Kapurniotu, A. & Taylor, J.W. (1995) J. Med. Chem. 38, 836-847]. We have hypothesized that a possibly type I beta turn/beta sheet conformation in the region 17-21 may play an important role in hCt bioactivity. To investigate this hypothesis, analogues of the potent hCt agonist cyclo17,21-[Asp17,Lys21]hCt (1) bearing type I (and II') or II beta turn-promoting substituents at positions 18 and 19 were designed, synthesized and their solution conformations, human Ct receptor binding affinities and in vivo hypocalcemic potencies were assessed. The novel analogues include cyclo17,21-[Asp17,D-Phe19, Lys21]hCt (2), cyclo17,21-[Asp17,Aib18,Lys21]hCt (3), cyclo17,21-[Asp17,D-Lys18,Lys21]hCt (4), corresponding partial sequence peptides containing the lactam-bridged region 16-22, and nonbridged control peptides. Only 1 showed a higher Ct receptor binding affinity than hCt, whereas analogues 2-4 had similar receptor affinities to hCt. In the in vivo hypocalcemic assay, 3 and 4 were as potent as 1, whereas 2 completely lost the high potency of 1, suggesting that type I (and II') beta turn-promoting substituents are fully compatible with in vivo bioactivity. CD spectroscopy showed that analogues 1-4 were markedly beta sheet-stabilized compared to hCt and indicated the presence of distinct beta turn conformeric populations in each of the analogues. Unexpectedly, the D-amino acid- or Aib-containing cyclic analogues 2-4 but not 1 or hCt self-associated into SDS denaturation-stable dimers. Our results demonstrate a crucial role of the conformational and topological features of the residues in sequence 17-21 and in particular of residues 18 and 19 for human Ct receptor binding and in vivo bioactivity and also for the self association state of hCt. These results may assist to delineate the structure-function relationships of hCt and to design novel hCt agonists for the treatment of osteoporosis and other bone-disorder-related diseases. 相似文献