Gifu University of Medical Science

About: Gifu University of Medical Science is a education organization based out in Gifu City, Japan. It is known for research contribution in the topics: Imaging phantom & Motion sickness. The organization has 89 authors who have published 202 publications receiving 1350 citations.

Mechanism of reactive oxygen species generation and oxidative DNA damage induced by acrylohydroxamic acid, a putative metabolite of acrylamide

Abstract: Acrylamide is formed during the heating of food and is also found in cigarette smoke. It is classified by the International Agency for Research on Cancer as a probable human carcinogen (Group 2A). Glycidamide, an epoxide metabolite of acrylamide, is implicated in the mechanism of acrylamide carcinogenicity. Acrylamide causes oxidative DNA damage in target organs. We sought to clarify the mechanism of acrylamide-induced oxidative DNA damage by investigating site-specific DNA damage and reactive oxygen species (ROS) generation by a putative metabolite of acrylamide, acrylohydroxamic acid (AA). Our results, using 32P-5’-end-labeled DNA fragments, indicated that, although AA alone did not damage DNA, AA treated with amidase induced DNA damage in the presence of Cu(II). DNA cleavage occurred preferentially at T and C, and particularly at T in 5’-TG-3’ sequences, and the DNA cleavage pattern was similar to that of hydroxylamine. The DNA damage was inhibited by methional, catalase, and Cu(I)-chelator bathocuproine, suggesting that H2O2 and Cu(I) are involved in the mechanism of DNA damage induced by AA treated with amidase. In addition, amidase-treated AA increased 8-oxo-7,8-dihydro-2’-deoxyguanosine formation in calf thymus DNA, an indicator of oxidative DNA damage, in a dose-dependent manner. In conclusion, hydroxylamine, possibly produced from AA treated with amidase, was autoxidized via the Cu(II)/Cu(I) redox cycle and H2O2 generation, suggesting that oxidative DNA damage induced by ROS plays an important role in acrylamide-related carcinogenesis.

Compression stocking length effects on arterial blood pressure and heart rate following head-up tilt in healthy volunteers.

Abstract: Background: Change in posture from supine to standing induces a footward fluid shift. This shift might decrease arterial pressure (AP) and induce orthostatic hypotension. To prevent decrease in AP, compression stockings are recommended, but the effects of various lengths have not been compared. Objective: The aim was to compare AP and heart rate (HR) by compression stocking length during head-up tilt (HUT). Methods: The effects of elastic compression stockings of three lengths on AP and HR were examined at the onset of HUT. The stockings were knee-high, compressing the foot and calf; thigh-high, compressing the toe to the thigh; and waist-high, compressing the toe to the waist. Results: AP did not significantly change at the onset of HUT without stockings or with any length of stockings compared with the AP in the supine position. HR was significantly higher at the onset of HUT without stockings and with the knee-high and thigh-high stockings than that during supine position. No significant difference in HR was observed among the three conditions. However, the HR increase was significantly depressed with the waist-high stockings. Discussion: These results suggest that the use of waist-high stockings that afford abdominal compression is needed to affect cardiovascular dynamics at the onset of HUT and may prevent orthostatic hypotension.

NT5DC2 affects the phosphorylation of tyrosine hydroxylase regulating its catalytic activity.

Abstract: 5'-Nucleotidase domain-containing protein 2 (NT5DC2) has been revealed by genome-wide association studies (GWAS) as a gene implicated in neuropsychiatric disorders related to the abnormality of dopamine (DA) activity in the brain. Based on its amino acid sequence, NT5DC2 is assumed to be a member of the family of haloacid dehalogenase-type phosphatases; although there is no information about its function and structural conformation. We recently reported that NT5DC2 binds to tyrosine hydroxylase (TH) and that the down-regulation of NT5DC2 tended to increase DA synthesis. In this study, we investigated whether NT5DC2 could regulate the catalytic activity of TH, which converts tyrosine to DOPA, because the phosphorylation level of TH, controlled by protein kinases and phosphatases, is well known to regulate its catalytic activity. The down-regulation of NT5DC2 by siRNA increased mainly DOPA synthesis by TH in PC12D cells, although this down-regulation tended to increase the conversion of DOPA to DA by aromatic L-amino acid decarboxylase. The increased DOPA synthesis should be attributed to the catalytic activity of TH controlled by its phosphorylation, because Western blot analysis revealed that the down-regulation of NT5DC2 tended to increase the level of TH phosphorylated at its Ser residues, but not that of the TH protein. Moreover, the induction of kinase activity by forskolin markedly potentiated the phosphorylation of TH at its Ser40 in PC12D cells having down-regulated NT5DC2. Immunocytochemical analysis of PC12D cells demonstrated that NT5DC2, TH protein, and TH phosphorylated at its Ser40 were predominantly localized in the cytoplasm and that the localization of NT5DC2 and TH proteins partially overlapped. Collectively, our results indicate that NT5DC2 could work to inhibit the DOPA synthesis by decreasing the phosphorylation of TH at its Ser40. We propose that NT5DC2 might decrease this phosphorylation of TH by promoting dephosphorylation or by inhibiting kinase activity.

Renin-angiotensin System Blockade Therapy for Early Renal Involvement in MYH9-related Disease with an E1841K Mutation.

Abstract: MYH9-related disease is a rare genetic disorder characterized by macrothrombocytopenia, with frequent proteinuric nephropathy, hearing loss, and cataract. Although proteinuric nephropathy usually progresses to renal failure, there is no established treatment for the nephropathy. We herein describe the case of a 19-year-old man carrying an E1841K MYH9 mutation, who developed persistent proteinuria. The patient was diagnosed with early-stage MYH9-related nephropathy based on the histological examination of a kidney biopsy specimen. The patient was treated with enalapril, which significantly reduced the proteinuria with no decline in his renal function. The early administration of renin-angiotensin system blockade therapy may have beneficial effects on MYH9-related nephropathy in patients with E1841K mutations. We also briefly summarize previously published cases of MYH9-related nephropathy treated with renin-angiotensin system (RAS) blockade therapy.