Abstract. Cryptdin mRNA codes for the apparent precursor to a corticostatin/defensin-related peptide that accumulates to high levels in mouse intestinal crypt epithelium during postnatal development. The primary structure, intestinal cell distribution, and developmental appearance of cryptdin mRNA have been determined. Cryptdin mRNA is 450-480 nucleotides long. Translation of the partial cryptdin cDNA sequence reveals a 70-amino acid open reading frame that includes 32 carboxy-terminal residues that align with those in the consensus sequence,

A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-Å resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads. Inhibitors of PKC1 are currently being used in clinical trials for various types of cancer, and a PKC␤ inhibitor is being used in clinical trials for diabetes-related retinopathy (1).PKC and PKB/AKT kinase domains are related by sequence homology; however, there are key structural differences in the regulatory domains and second messenger cofactor requirements. PKB/AKT contains an N-terminal pleckstrin homology domain regulated by phosphoinositide second messengers, a central catalytic kinase domain, and a C-terminal regulatory region facilitating key protein-protein interactions with signal-

Summary:Purpose: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy.Methods: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sexand age-matched healthy children.Results: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism.Conclusions: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage. Key Words: Bone metabolism-CarbamazepineEpilepsy patients-Vitamin D-Pubertal stage.In recent years, many reports of altered calcium, vitamin D, and bone metabolism associated with anticonvulsant therapy have been published (1-5), but the results of these studies are conflicting. Recently some biochemical markers have been proposed to provide information about the dynamics of bone turnover. In particular, the markers of bone formation are osteocalcin (OC) or bone ␥-carboxyglutamic acid protein, noncollagenous protein of the bone matrix secreted by osteoblasts; circulating peptides of type I collagen, like the carboxy-terminal propeptide of type I procollagen (PICP) (6); and aminoterminal propeptide of type III procollagen (PIIINP), which reflects the rate of collagen type III synthesis (7). Among the markers of bone resorption, there are the serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX), which are the degraded products from osteoclastic activity (8). The aims of the study were to evaluate, prospectively, whether and to what extent differences exist in bone metabolism in prepubertal, pubertal, and postpubertal patients receiving CBZ in comparison to healthy controls and to determine the possible relations between these parameters and CBZ dosage and its serum concentration. MATERIALS AND METHODSWe studied 60 children with new onset of idiopathic partial seizures; their age ranged from 6.5 to 19.0 years. These patients were subdivided in three groups according to their pubertal stage: 20 (10 boys and 10 girls) prepubertal children (Ph1G1 and Ph1B1, respectively), 20 (10 boys and 10 girls) pubertal children (Ph2G2-Ph4G4 and Ph2B2-Ph4B4, respectively), and 20 (10 boys and 10 girls) postpubertal children (Ph4G4-Ph5G5 and Ph4B4-Ph5B5, respectively).The stage of sexual development was evaluated according to Tanner classification (9).Patients were recruited from the

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