Hepatic protein kinase C: translocation stimulated by prolactin and partial hepatectomy

Prolactin stimulates a hepatotrophic response similar to that caused by phorbol esters or partial hepatectomy in rats. Since phorbol esters, which activate protein kinase C, mimic prolactin action in liver, the relationship between prolactin administration and subsequent hepatic protein kinase C translocation was assessed. Prolactin administration rapidly stimulated a 4-fold elevation of membrane protein kinase C activity. The effect of prolactin on hepatic protein kinase C was specific for lactogenic hormones but could be duplicated by phorbol esters. Further, an increase in serum prolactin was demonstrated subsequent to partial hepatectomy and preceding hepatic protein kinase C translocation. Therefore, translocation of hepatic protein kinase C appears important for hepatic proliferation in response to prolactin administration and to partial hepatectomy.     

MAGI: Methylation analysis using genome information

By incorporating annotation information into the analysis of next-generation sequencing DNA methylation data, we provide an improvement in performance over current testing procedures. Methylation analysis using genome information (MAGI) is applicable for both unreplicated and replicated data, and provides an effective analysis for studies with low sequencing depth. When compared with current tests, the annotation-informed tests provide an increase in statistical power and offer a significance-based interpretation of differential methylation.     

SURGICAL TREATMENT OF INFANTILE HYDROCEPHALUS

The operation of endoscopic coagulation of the choroid plexuses for the relief of infantile hydrocephalus is now 18 years old. Nearly a hundred cases have been reported and the indications and procedure are well standardized. Several patients have grown up apparently normally from the earliest series of operations.In a recent series of 20 operations performed on ten patients in the past ten years, there have been no deaths attributable to the procedure. The operation has substantially decreased the pressure in all cases, and has brought it within normal limits in all cases in which it was performed before the head became grossly enlarged.The mentality has improved following relief of pressure in all cases. When the operation was performed before deterioration began, the results were uniformly excellent.     

Neutrophil myeloperoxidase is a potent and selective inhibitor of mast cell tryptase.

Myeloperoxidase (MPO) is an important component of the neutrophil response to microbial infection. In this paper we report an additional activity of MPO, the potent and selective inhibition of human mast cell tryptase. MPO inhibits human mast cell tryptase in a time-dependent manner with an IC50 of 16 nM at 1 h. In contrast, MPO does not inhibit trypsin, thrombin, plasmin, factor Xa, elastase, or cathepsin G. It is the native protein conformation of MPO and not its enzyme activity that is responsible for tryptase inhibition. Heparin, at high concentrations, can prevent the inhibition of tryptase by MPO. We have shown by size-exclusion chromatography that MPO promotes the dissociation of active tryptase tetramer to inactive monomer. These data suggest that MPO inhibits tryptase by interfering with the heparin stabilization of tryptase tetramer. We have previously shown that lactoferrin (another neutrophil-associated protein) also inhibits tryptase activity by a similar mechanism. The finding that MPO is a potent inhibitor of tryptase lends further support to the hypothesis that neutrophil proteins, such as MPO and lactoferrin, may play a regulatory role as endogenous suppressers of tryptase enzyme activity.