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ASP2397: a novel antifungal agent produced by Acremonium persicinum MF-347833

Nakamura I, Yoshimura S, Masaki T, Takase S, Ohsumi K, Hashimoto M, et al.

J Antibiot (Tokyo), 2017 Jan;70(1):45-51.
PMID: 27599768 DOI: 10.1038/ja.2016.107

The novel antifungal agent ASP2397 (Vical's compound ID VL-2397) is produced by the fungal strain MF-347833 that was isolated from Malaysian leaf litter and is identified here as an Acremonium species based on its morphology, physiological properties and 28S ribosomal DNA sequence. Because of its potential importance for producing novel antifungal agents, we determined the taxonomic and biologic properties of MF-347833. We show here that ASP2397 is a cyclic hexapeptide that chelates aluminum ion and is therefore similar to ferrichrome, a hydroxamate siderophore. However, ASP2397 differs structurally from licensed antifungal agents such as amphotericin B, triazoles and echinocandins. To understand the relationship between chemical structure and biological function, we isolated certain ASP2397 derivatives from the culture broth, and we further chemically converted the metal-free form to other derivatives.
Intrahepatic cholangiocarcinoma and portal hypertension developing in a patient with multicystic biliary microhamartomas

Sugawara T, Shindoh J, Hoshi D, Hashimoto M

Malays J Pathol, 2018 Dec;40(3):331-335.
PMID: 30580365

INTRODUCTION: We report a case of intrahepatic cholangiocarcinoma and portal hypertension developing in a liver with biliary microhamartomas (von Meyenburg's complex).
CASE REPORT: The patient was a 55-year-old man who had a past medical history of diffuse multiple liver abscesses. During follow-up examination, a hypovascular nodule measuring 2.1 cm in diameter was incidentally found in segment 8 of the liver. Surgical resection was performed based on a suspected diagnosis of hepatocellular carcinoma. A gastrofiberscopy examination detected characteristic findings of portal hypertensive gastropathy. During the laparotomy, multiple tiny cystic lesions were observed in a diffuse pattern across the liver surface. The liver parenchyma was slightly fibrotic and haemorrhagic. A histopathological examination revealed intrahepatic cholangiocarcinoma with vascular invasions in von Meyenburg's complex. Multiple biliary adenomas were also observed among the biliary microhamartomas adjacent to the main tumour, suggesting that the malignant transformation of the biliary adenomas might have been responsible for the development of the intrahepatic cholangiocarcinoma. The histopathologic examination also revealed sinusoidal dilation and abnormal spacing of the portal tracts and central veins as evidence of portal hypertension.
Fulltext Population Genetics in Malaysia and Japanese Populations Using Power Plex Y23 System

Nakamura Y, Samejima M, Minaguchi K, Nambiar P, Hashimoto M

Bull. Tokyo Dent. Coll., 2020 Jul 04;61(2):83-94.
PMID: 32522936 DOI: 10.2209/tdcpublication.2019-0023

Population flow between Southeast Asian countries and Japan continues to gather pace. Accordingly, the number of foreigners involved in incidents in Japan has markedly increased, which means that forensic dentistry is now increasingly being faced with the need to analyze DNA from persons of non-Japanese extraction. The DNA test currently used for personal identification mainly utilizes short tandem repeats (STRs) on autosomal chromosomes and the Y-chromosome. This test was developed for use in personal identification, not for distinguishing among races; nonetheless, the standard method for personal identification is often used because the procedure has been established. To determine the degree to which racial differences can be distinguished by standard DNA analysis, 23 STRs located on the Y chromosome were investigated in 218 Malay and 426 Japanese males. The frequencies of each STR were calculated in the two populations. The difference in the power of discrimination between the Malay and Japanese populations ranged from a minimum of 0.01 to a maximum of 0.27; the difference in polymorphic information content ranged from 0.01 (minimum) to 0.23 (maximum). No major differences were noted in the polymorphisms in these two Mongoloid populations, but the distributions of the 17 STRs differed significantly. Short tandem repeat types demonstrating a likelihood of racial differences were identified in 14 of the STRs. Race-specific STR types were identified in 10 STRs. These results suggest that the likelihood of Malay or Japanese genetic background can be judged based on Y-chromosome STR test results.
Fulltext Effects of Oxidation of Human Serum Albumin on the Binding of Aripiprazole

Sakurama K, Nishi K, Chuang VTG, Hashimoto M, Yamasaki K, Otagiri M

Biol Pharm Bull, 2020;43(6):1023-1026.
PMID: 32475912 DOI: 10.1248/bpb.b20-00205

Aripiprazole (ARP) is one of antipsychotics and binds to human serum albumin (HSA) with a high affinity. In this study, we investigated the binding characteristics of ARP to oxidized HSA as observed in chronic disease conditions. Oxidized HSAs were prepared using chloramine-T (CT-HSA) or metal-catalyzed oxidation system (MCO-HSA) in vitro, respectively. An increase in the carbonyl content was confirmed in oxidized HSAs. From the results of circular dichroism (CD) and tryptophan fluorescence spectra, no significant structural change of oxidized HSAs was observed. These results indicate that prepared HSAs are mildly oxidized and well reflects the status of HSA during chronic diseases. However, oxidized HSAs were observed to have a significant decrease in binding to ARP. The results of the induced CD spectrum suggested that ARP bound to oxidized HSAs with a similar orientation. These results suggest that oxidation of HSA during chronic disease state significantly affected the microenvironment of the binding site for ARP and binding capacity of HSA to ARP.
Fulltext Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al.

Nat Genet, 2022 Nov;54(11):1640-1651.
PMID: 36333501 DOI: 10.1038/s41588-022-01213-w

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P
Fulltext Characterization of Bovine Lactoferrin Nanoparticle Prepared by Desolvation Technique

Taguchi K, Chuang VTG, Hashimoto M, Nakayama M, Sakuragi M, Enoki Y, et al.

Chem Pharm Bull (Tokyo), 2020;68(8):766-772.
PMID: 32741918 DOI: 10.1248/cpb.c20-00222

Lactoferrin (Lf) nanoparticles have been developed as a carrier of drugs and gene. Two main methods, desolvation technique and emulsification method, for preparation of protein nanoparticles have been reported so far, but most of the previous reports of Lf nanoparticles preparation are limited to emulsification method. In this study, we investigated the optimal conditions by desolvation technique for the preparation of glutaraldehyde-crosslinked bovine Lf (bLf) nanoparticles within the size range of 100-200 nm, and evaluated their properties as a carrier for oral and intravenous drug delivery. The experimental results of dynamic light scattering and Transmission Electron Microscope suggested that glutaraldehyde-crosslinked bLf nanoparticles with 150 nm in size could be produced by addition of 2-propanol as the desolvating solvent into the bLf solution adjusted to pH 6, followed by crosslinking with glutaraldehyde. These cross-linked bLf nanoparticles were found to be compatible to blood components and resistant against rapid degradation by pepsin. Thus, cross-linked bLf nanoparticles prepared by desolvation technique can be applied as a drug carrier for intravenous administration and oral delivery.