Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.     

Dendritic reticulum cells in AIDS-related lymphadenopathy

Summary One of two cases of acquired immune deficiency syndrome-related persistent generalized lymphadenopathy revealed a profoundly altered pattern of dendritic reticulum cells as demonstrated by immunoreactive acid cysteine proteinase inhibitor. The alterations could be related to totally or partially destructed lymphoid secondary follicles.Acknowledgments. This work has been partially supported by the grant from the Sigrid Juselius Foundation, Finland.     

Flow microcalorimetry as a tool for an improved analysis of antibiotic activity: the different stages of chloramphenicol action

Flow microcalorimetry in combination with photometric mass determination of staphylococci in suspension was used to reveal alterations in the intensity, extent and efficiency of bacterial metabolism during inhibition of protein synthesis by chloramphenicol. It could be demonstrated that these three parameters of metabolic activity were distinctly affected by this drug, and that the method described promises to be a more reliable tool for assaying the degree and the mode of bacteriostatic inhibition than the conventional determination of the minimum inhibitory concentration.     

Chromosomal accumulation of3H-estradiol in dividing ovarial granulosa cells and ovarial squash preparations

Zusammenfassung ³H-Oestradiol wurde Mäusen injiziert und nachher autoradiographisch verfolgt, wobei Ag-Körnchen über den Chromosomen der Granulosazellen des Ovariums festgestellt werden konnten.     

Specificity in the hydrolysis of N-acyl-L-phenylalanine 4-nitroanilides by chymotrypsin

Summary The affinity of N-acyl-L-phenylalanine 4-nitroanilides for chymotrypsin is enhanced as the hydrophobicity of non-amino acid residues in the P₂-position of the substrates increases, whereas k_cat remains nearly constant. On the other hand, if alanine or leucine is in the P₂-position k_cat increases with decreasing K_M.