Publications by authors named "Naohiko Sakai"

Article Synopsis
  • Postprandial hyperlipidemia involves the buildup of chylomicrons and their remnants after eating, which may be linked to cardiovascular diseases, though research is ongoing.
  • A study enrolled 189 patients undergoing coronary angiography to investigate the relationship between chylomicron remnants and coronary artery disease (CAD), focusing on biochemical markers of lipid metabolism.
  • Results showed that fasting serum apo B-48 levels were significantly higher in CAD patients compared to non-CAD subjects, indicating that elevated apo B-48, especially when combined with other risk factors, is associated with a higher prevalence of CAD.
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  • The study investigates postprandial hyperlipidemia (PH), focusing on how impaired metabolism of triglyceride-rich lipoproteins impacts lipid levels after high-fat or standard meals, aiming to find simpler markers for PH without using time-consuming tests.* -
  • Ten healthy male subjects were given high-fat and standard meals, and their lipid and apolipoprotein levels were measured, revealing significantly higher triglyceride and apo B-48 levels after the high-fat meal compared to the standard meal.* -
  • The findings suggest that the postprandial triglyceride increase is primarily linked to chylomicrons and their remnants, with fasting apo B-48 levels strongly predicting this increase, indicating it could serve as an easy marker for
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Nestin is an intermediate filament protein, and serves as a hair follicle stem cell and neural stem cell marker. Recent studies have suggested that nestin expression is also important for tumorigenesis. Previous reports from our laboratory have revealed that nestin is a marker of HMB-45-negative melanoma cells in dermal invasive lesions of nodular malignant melanoma.

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  • A study was conducted on 205 Japanese individuals with familial hypercholesterolemia (FH) to analyze mutations in the LDLR gene and identify common variants in the population.
  • The researchers found 53 small mutations and 10 large deletions, with eight mutations occurring more frequently, accounting for 32% of the FH cases.
  • Notably, the L547V mutation showed a milder clinical effect, linked to higher receptor activity, and appeared more frequently in the general population than initially thought, suggesting it might be a predominant mutation in this demographic.*
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Homeobox genes encode a set of transcription factors of fundamental importance for body patterning during embryogenesis. Hoxa9-a13 and Hoxd9-d13 play an especially important part in vertebrate limb development. Synpolydactyly (SPD) is characterized by various malformations of the limbs.

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Article Synopsis
  • A low level of high-density lipoprotein (HDL) is linked to metabolic syndrome and increased risk of cardiovascular issues, but its regulatory mechanisms are not fully understood.* -
  • Research focused on angiopoietin-like protein 3 (ANGPTL3), which affects HDL metabolism; mice lacking ANGPTL3 had lower HDL levels, whereas supplementation restored them, indicating ANGPTL3's role in HDL regulation.* -
  • ANGPTL3 inhibits endothelial lipase (EL), an enzyme that lowers HDL levels; findings suggest a correlation between ANGPTL3 levels and HDL in humans, pointing to ANGPTL3's potential importance in managing HDL cholesterol.*
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  • Researchers studied lipoprotein lipase (LPL) X447 homozygotes to see if they have better clearance of apoB48, a protein involved in lipid metabolism.
  • The study involved five X447 homozygotes and five S447 homozygotes, finding that X447 individuals had significantly higher levels of apoB48 and a greater rate of its breakdown and production.
  • The results indicate that the LPL S447X variant enhances metabolism for both apoB48 and apoB100, suggesting a potential impact on lipid processing in the body.
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  • Oxidized low-density lipoprotein (Ox-LDL) is linked to the development of atherosclerosis and is mainly taken up by macrophages through the CD36 receptor, which is found on various cell types including platelets and heart tissues.
  • Research identified specific mutations in the CD36 gene in patients with CD36 deficiency, leading to reduced binding of Ox-LDL by macrophages, suggesting CD36's key role in this process.
  • CD36 deficiency was associated with clinical issues such as hyperlipidemia, insulin resistance, and a higher prevalence of coronary heart disease, highlighting its potential importance in cardiovascular health.
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  • RECS1 is a gene that responds to mechanical stress, and its knockout (KO) leads to older mice developing cystic medial degeneration (CMD) and potential aortic dilation.
  • In tests, KO mice showed higher levels of gelatinases (proteins that break down the matrix) like MMP-2 and MMP-9 compared to wild-type mice, especially with age, which correlates with CMD and aortic dilation in older KO mice.
  • The study concludes that RECS1 plays a protective role in vascular health by regulating MMP-9 production, suggesting that understanding this regulation could help in preventing or treating conditions like aneurysms.
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Article Synopsis
  • RECS1 is a new gene that reacts to shear stress and encodes a protein with seven potential transmembrane domains, found in most mouse tissues except the thymus, spleen, and testis.
  • The mRECS1 protein has unique sequences rich in proline and glycine, and variations in protein size were observed in different tissues due to likely posttranslational modifications.
  • Knockout studies in mice showed that the absence of RECS1 leads to vascular issues, indicating its protective role in maintaining blood vessel health.
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The frequent lipoprotein lipase S447X variant (LPLS447X) is firmly associated with a lower incidence of cardiovascular disease, the mechanisms for which remain to be established. To further unravel these beneficial effects, we studied the consequences of LPLS447X heterozygosity on LPL mass and activity, as well as on the postprandial lipoprotein profile. Fifteen male heterozygous LPLS447X carriers and 15 matched control subjects received an oral fat load (30 g/m(2)).

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HDL and its major component, apolipoprotein A-I (apoA-I), play a central role in reverse cholesterol transport. We recently reported the involvement of a glycosylphosphatidylinositol anchor (GPI anchor) in the binding of HDL and apoA-I on human macrophages, and purified an 80 kDa HDL/apoA-I binding protein. In the present study, we characterized the GPI-anchored HDL/apoA-I binding protein from macrophages.

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  • A family was identified with a unique form of tendon xanthomatosis, where multiple members developed massive Achilles tendon growths starting around the age of 30.
  • The proband, a 58-year-old man, showed normal low-density lipoprotein receptor activity and had only mild cholesterol elevation, suggesting an unusual disease mechanism.
  • Investigations into the macrophages of the proband revealed reduced cholesterol efflux related to high-density lipoprotein 3, indicating that this might contribute to the development of their condition.
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Article Synopsis
  • * The research measured the kinetics of different types of lipoproteins (VLDL, IDL, LDL) in 53 men, using stable isotopes to estimate their production and breakdown rates.
  • * Results showed that higher levels of apoB-48 and RLP-cholesterol were linked to lower breakdown rates of VLDL and IDL, while non-HDL cholesterol was positively associated with VLDL production and inversely associated with LDL breakdown.
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The reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which high-density lipoprotein (HDL) removes cholesterol from lipid-laden cells and delivers it to the liver. Scavenger receptor class B type I (SR-BI) is a HDL receptor in the liver and adrenal glands and is involved in the selective uptake of cholesteryl ester from HDL, which has been extensively, analyzed using rodent models. However, the expression and regulation of the human homologue of this receptor are not known yet.

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Werner syndrome (WS) is characterized by the early onset of senescent phenotypes including premature atherosclerotic cardiovascular diseases, although the underlying molecular mechanism for atherosclerosis has not been fully understood yet. Cholesterol efflux from the cells is the initial step of reverse cholesterol transport, a major protective system against atherosclerosis. The aim of the present study was to determine whether this crucial step may be altered in WS.

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Background: Adipocytokines are bioactive peptides that may play an important role in the regulation of glucose and lipid metabolism. In this study, we investigated the association of plasma adipocytokine concentrations with markers of triglyceride-rich lipoprotein (TRL) metabolism in men.

Methods: Fasting adiponectin, leptin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), apolipoprotein (apo) B-48, apo C-III, and remnant-like particle (RLP)-cholesterol concentrations were measured by immunoassays and insulin resistance by homeostasis assessment (HOMA) score in 41 nondiabetic men with a body mass index of 22-35 kg/m2.

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  • The study investigates the relationship between visceral fat accumulation and serum lipoprotein subclasses in 62 male participants with visceral fat syndrome or obesity.
  • Findings show a significant positive correlation between visceral fat and levels of VLDL and LDL subclasses, while large HDL subclasses had a negative correlation with visceral fat.
  • The research suggests that high-performance liquid chromatography is a useful method for detecting and evaluating abnormal distributions of lipoprotein subclasses related to visceral fat.
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Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport (RCT), a protective system against atherosclerosis. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with marked hyperalphalipoproteinemia (HALP).

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  • Takayasu arteritis (TA) is a chronic condition affecting large arteries, requiring careful monitoring of disease activity, as it may worsen despite treatment.
  • Current markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) lack specificity for accurately tracking TA’s activity.
  • This study found that matrix metalloproteinases (MMP-3 and MMP-9) are reliable indicators of disease activity in TA, as their levels correlate with disease status, while MMP-2 is useful for diagnosis.
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