Design, synthesis, and evaluation of beta-galactosylceramide mimics promoting beta-glucocerebrosidase activity in keratinocytes.

We have established an efficient synthesis of mimics of beta-galactosylceramide (beta-GalCer) increasing a beta-glucocerebrosidase (beta-GlcCer'ase) activity that associates with the skin barrier function. Among the synthetic beta-GalCer analogues (6a-6e) described herein, compound 6e exhibited a potent effect on the activation of beta-GlcCer'ase function in vitro and reduced the transepidermal water loss (TEWL) level in a UVB-induced barrier disrupted mice model. These findings indicated that compound 6e could be useful for cosmetics and medicines to improve skin barrier function.

Relevance network between chemosensitivity and transcriptome in human hepatoma cells.

Generally, hepatoma is not a chemosensitive tumor, and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively evaluate the relationship between chemosensitivity and gene expression profile in human hepatoma cells, by using microarray analysis, and analyze the data by constructing relevance networks. In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2), the baseline expression levels of 2300 genes were measured by cDNA microarray.

Detection of genes with tissue-specific expression patterns using Akaike's information criterion procedure.

We applied a method based on Akaike's information criterion (AIC) to detect genes whose expression profile is considerably different in some tissue(s) than in others. Such observations are detected as outliers, and the method we used was originally developed to detect outliers. The main advantage of the method is that objective decisions are possible because the procedure is independent of a significance level.

Structure determination and conformational change induced by tyrosine phosphorylation of the N-terminal domain of the alpha-chain of pig gastric H+/K+-ATPase.

It has been well established that phosphorylation is an important reaction for the regulation of protein functions. In the N-terminal domain of the alpha-chain of pig gastric H(+)/K(+)-ATPase, reversible sequential phosphorylation occurs at Tyr 10 and Tyr 7. In this study, we determined the structure of the peptide involving the residues from Gly 2 to Gly 34 of pig gastric H(+)/K(+)-ATPase and investigated the tyrosine phosphorylation-induced conformational change using CD and NMR experiments.

Inhibition of adhesion of type 1 fimbriated Escherichia coli to highly mannosylated ligands.

The inhibitory potencies of a number of mannosides, di- and trivalent mannosides, a set of mannose-terminating dendrimers, and five types of mannose-bearing neoglycoproteins were determined by using a binding assay that measures the binding of (125)I-labeled, highly mannosylated neoglycoprotein to a type 1 fimbriated Escherichia coli (K12) strain in suspension. The IC(50) values (the concentration of inhibitor that causes 50 % reduction in the bound (125)I-ligand to E. coli) obtained by this method were much lower than the equivalent values obtained by hemagglutination or in assays that involve microplate immobilization.

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.

Cell-wall engineering of living bacteria.

The cell walls of living bacteria were chemically modified by adding cell-wall precursors. As the precursors to be incorporated into the cell wall, UDP-MurNAc pentapeptide, lipid I, and lipid II derivatives were synthesized. The aimed compounds were attached to the amine residue of lysine at the pentapeptide moiety.

Erythrocyte-like liposomes prepared by means of amphiphilic cyclodextrin sulfates.

A novel class of sulfated glycolipids with excellent self-assembling capacity to form stable monolayers at an air-water interface and specific erythrocyte-like liposomes was synthesised from alpha, beta, and gamma-cyclodextrins as starting materials.

High-dose chemotherapy in children with metastatic hepatoblastoma.

Background: Despite the advent of effective chemotherapy,a poor prognosis has been reported for patients with metastatic hepatoblastoma. To improve this prognosis, we conducted high-dose chemotherapy with autologous bone marrow rescue in patients with metastatic hepatoblastoma.

Methods And Results: Three patients were treated with high-dose chemotherapy.

Low plasma levels of hemostatic proteins during the induction phase in children with acute lymphoblastic leukemia: A retrospective study by the JACLS. Japan Association of Childhood Leukemia Study.

Background: Thromboembolic and bleeding events are serious complications associated with the administration of L-asparaginase (ASP) during the induction phase in children with acute lymphoblastic leukemia (ALL). Prophylactic supplementation of plasma-derived coagulation products remains controversial. The purposes of this study were to examine the plasma levels of hemostatic proteins during the induction phase and the efficacy of prophylactic replacement of plasma-derived products.

Encounter with unexpected collagenase-1 selective inhibitor: switchover of inhibitor binding pocket induced by fluorine atom.

Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly selective inhibition against MMP-1. A possible mechanism of the selectivity of MMP-1 inhibitors through the switchover of the binding pocket was speculated by computational calculations. As a consequence of the unexpected selectivity, the specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket of MMP-1 conducted a low binding energy.

Germ cell survival through carbohydrate-mediated interaction with Sertoli cells.

Spermatogenesis is a precisely regulated process in which the germ cells closely interact with Sertoli cells. The molecular basis of this cell-cell adhesion is unknown. Here, we demonstrate that targeted disruption of Man2a2, a gene encoding alpha-mannosidase IIx (MX), an enzyme that forms intermediate asparagine-linked carbohydrates (N-glycans), results in Man2a2 null males that are largely infertile.