A novel stop-gain variant in neurofibromatosis type 1 and bilateral optic atrophy without optic gliomas.

Background: Neurofibromatosis type 1 (NF1) is a multisystem disorder that primarily affects the skin and peripheral nervous system and is caused by chromosomal abnormalities and mostly truncating variants in the gene. Ocular complications such as Lisch nodules and optic pathway gliomas (OPGs) can occur in NF1 patients. Herein, we report a novel variant in an NF1 patient with bilateral optic atrophy.

Association of pulse pressure with all-cause mortality in older Japanese patients with type 2 diabetes mellitus: A observational cohort study.

Aim: Although systolic and diastolic blood pressures as well as blood glucose are monitored when nurses care for patients with type 2 diabetes, the same is not true for pulse pressure. We aimed to determine the association between pulse pressure and all-cause mortality.

Methods: We conducted a longitudinal study of outpatients with type 2 diabetes aged 65 years and older at diabetes-specialized hospitals in Japan from September 2004 to December 2016.

Characterization of the hepatic cellular uptake of α(1) -acid glycoprotein (AGP), part 1: a peptide moiety of human AGP is recognized by the hemoglobin β-chain on mouse liver parenchymal cells.

Human α(1) -acid glycoprotein (AGP), a serum glycoprotein, is known to have anti-inflammatory activity. We recently reported that AGP was mainly incorporated into the liver in mice via a receptor-mediated pathway, although the mechanism for this was largely unknown. The objective of this study was to identify the specific cellular surface protein that recognizes the peptide moiety of AGP.

Structural insights into differences in drug-binding selectivity between two forms of human alpha1-acid glycoprotein genetic variants, the A and F1*S forms.

Human α(1)-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type.

Construction of an expression system for human alpha(1)-acid glycoprotein in E. coli: The roles of oligosaccharide moieties in structural and functional properties.

Unglycosylated recombinant human alpha(1)-acid glycoprotein (hAGP) variants (rF1(*)S and rA) were prepared in an E. coli expression system using the Origami B strain and pET-3c vector. Thioredoxin was co-expressed to promote the appropriate folding of hAGP.

Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes.

Voriconazole metabolism is mostly mediated via the cytochrome P450 (CYP) 2C19 isozyme. The non-wild (mutant) type of CYP2C19 is generally found in 60-70% of Asian populations. Because the voriconazole trough plasma concentration has been reported to correlate with hepatotoxicity, this study investigated the effect of CYP2C19 polymorphism on the relationship between voriconazole trough concentrations and liver function abnormalities in 29 Japanese patients with fungal infections (CYP2C19 wild-type, n=10; non-wild-type, n=19).

A site-directed mutagenesis study of drug-binding selectivity in genetic variants of human alpha(1)-acid glycoprotein.

Human alpha(1)-acid glycoprotein (AGP), a major carrier of many basic drugs in circulation, consists of at least two genetic variants, namely A and F1*S variant. Interestingly, the variants of AGP have different drug-binding properties. The purpose of this study was to identify the amino acid residues that are responsible for the selectivity of drug binding to genetic variants of AGP using site-directed mutagenesis.

Involvement of disulfide bonds and histidine 172 in a unique beta-sheet to alpha-helix transition of alpha 1-acid glycoprotein at the biomembrane interface.

Human alpha(1)-acid glycoprotein (AGP), which is comprised of 183 amino acid residues and 5 carbohydrate chains, is a major plasma protein that binds to basic and neutral drugs as well as to steroid hormones. It has a beta-sheet-rich structure in aqueous solution. Our previous findings suggest that AGP forms an alpha-helix structure through an interaction with biomembranes.

Construction of expression system for human alpha 1-acid glycoprotein in Pichia pastoris and evaluation of its drug-binding properties.

Human alpha1-acid glycoprotein (hAGP) is a plasma glycoprotein that functions as a major carrier of basic ligands. This is the first report of the recombinant hAGP (rhAGP). In this study, rhAGP was expressed in the methylotropic yeast Pichia pastoris (GS115) using the expression vector, pPIC9, and then purified by anionic exchange, hydrophobic interaction, and gel filtration chromatography.