Masaki Igarashi

The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. The treatment with the NAD(+) precursor nicotinamide riboside (NR) rejuvenates ISCs from aged mice and reverses an impaired ability to repair gut damage. The effect of NR is

NCEH1 is expressed in human atheromatous lesions, where it plays a critical role in the hydrolysis of CE in human macrophage foam cells, thereby contributing to the initial part of reverse cholesterol transport in human atherosclerosis.

Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD + ) upon the administration of nicotinamide mononucleotide (NMN), an NAD + precursor, can mitigate aging-related disorders; however, human data on this are limited. We investigated whether the chronic oral supplementation of NMN can elevate blood NAD + levels and alter physiological dysfunctions in healthy older participants. We administered 250 mg NMN per day to aged men for 6 or 12 weeks in a placebo

Neutral cholesterol ester hydrolase (NCEH) accounts for a large part of the nCEH activity in macrophage foam cells, a hallmark of atherosclerosis, but its subcellular localization and structure-function relationship are unknown. Here, we determined subcellular localization, glycosylation, and nCEH activity of a series of NCEH mutants expressed in macrophages. NCEH is a single-membrane-spanning type II membrane protein comprising three domains: N-terminal, catalytic, and lipid-binding domains. Th

Many previous studies have shown that many health benefits in calorie restriction (CR) are attributed to the down-regulation of the mammalian target of rapamycin complex 1 (mTORC1) and the up-regul...

Nifekalant (NF), a pure K(+) channel blocker developed in Japan, has been reported to be effective in the treatment of life-threatening ventricular arrhythmias. We studied its efficacy in 18 men and 4 women with out-of-hospital ventricular fibrillation (VF) admitted to our emergency department between August 2001 and March 2004. The number of DC shocks delivered for out-of-hospital VF, serum Na(+) and K(+), arterial blood pH, and base excess were compared in 8 patients treated with NF, 0.3 mg/kg

Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between

Intestinal SIRT1 in EECs modulates the EEPC cycle by regulating β-catenin activity and can control the number of EECs in HFD-fed mice, which is a previously unknown role.

紅茶葉抽出物 (JAT) の α-グルコシターゼ活性に及ぼす影響を検討した．JAT は酵母由来 α-グルコシターゼ活性を有意に，かつ濃度依存的に阻害し，その程度は食後過血糖改善薬，アカルボース (ACA) よりも強かった．また，2 型糖尿病モデル動物，db/db マウスに JAT (500 mg/kg) および ACA（同 100）を経口投与し，直ちにスクロースを負荷 (2 g/kg) した後，経時的に血糖値及びインスリン値を測定した．その結果，両群の血糖値は 30 分および 60 分後で有意に低下し，インスリン値は変化を示さなかった．JAT および ACA を経口投与し，スクロース負荷後に最も高い血糖値を示した 30 分後の摘出小腸スクラーゼ活性は，いずれも無処理群に対し有意に低下した．さらに，5 週間の JAT および ACA の混餌投与では，いずれも血糖値，インスリン値等に影響を及ぼさなかった．以上より，JAT はインスリン値に影響することなく，小腸 α-グルコシターゼ活性を阻害することにより食後高血糖を是正する有用な機能性食材と考えられた．

Numerous animal studies have shown that the decrease in the tissue Nicotinamide Adenine Dinucleotide (NAD+) levels during aging are closely related to age-related physiological decline and that the administration of NAD+ precursors restore NAD+ levels and promotes health and prolongs lifespan. Therefore, in order to demonstrate whether NAD+ supplementation by NAD+ precursors mitigate age-related physiological dysfunction including muscle weakness in older men. We conducted a placebo-controlled,

22才男性.昭和56年1月発熱,浮腫が出現,投薬により軽快したが, 1年半後再発.皮膚筋生検等より,筋症を合併したWeber-Christian病と診断. Steroid薬投与し症状の改善をみた.その後肝機能障害,糖尿病が出現,本疾患の再燃も考慮されたため, insulin治療および免疫抑制薬を投与し改善.本症では興味あることに筋症を合併し,さらに本症の活動性に一致してangiotensin-converting enzymeが上昇するという知見を得,示唆に富む1例と考えられる.

Abstract Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD+) levels on administration of an NAD+ precursor, nicotinamide mononucleotide (NMN), can mitigate aging-related disorders; however, human data are sparse. Therefore, we aimed to investigate whether the chronic oral supplementation of NMN can elevate blood NAD+ levels and alter physiological dysfunctions, including muscle weakness, in healthy elderly participants. We administered 250 mg NMN per

A 62-year-old man who had twice received laparotomies for abdominal pain of unknown origin was admitted to our hospital with acute abdominal pain. His family history of acute intermittent porphyria (AIP) suggested that it arose from acute porphyria. We treated the patient with 5% glucose solution by i.v. drip infusion and his abdominal pain improved rapidly. Diagnosis of AIP was established by the demonstration of reduced erythrocyte porphobilinogen deaminase (PBGD) activity and a point mutation