Hyperlipidemias: Tada N

Hata Y, Mabuchi H, Saito Y, Itakura H, Egusa G, Ito H, Teramoto T, Tsushima M, Tada N, Oikawa S, Yamada N, Yamashita S, Sakuma N, Sasaki J, Anonymous00200. · No affiliation provided · J Atheroscler Thromb. · Pubmed #12238634 links to  free full text

Abstract: This paper described the Guideline for Diagnosis and Management of Hyperlipidemias for Prevention of Atherosclerosis proposed by The Japan Atherosclerosis Society (JAS) Guideline Investigating Committee (1,995-2,000) under the auspices of the JAS Board of Directors. 1) The guideline defines the diagnostic criteria for serum total cholesterol (Table 1), LDL-cholesterol (Table 1), triglycerides (Table 4) and HDL-cholesterol (Table 7). It also indicates the desirable range (Table 1), the initiation levels of management (Table 2) and the target levels of treatment (Table 2) for total and LDL-cholesterol. 2) Though both total and LDL-cholesterol are shown as atherogenic parameter in the guideline, the use of LDL-cholesterol, rather than total cholesterol, is encouraged in daily medical practice and lipid-related studies, because LDL-cholesterol is more closely related to atherosclerosis. 3) Elevated triglycerides and low HDL-cholesterol are included in the risk factors, since no sufficient data have been accumulated to formulate the guideline for these two lipid disorders. 4) Emphasis is laid on evaluation of risk factors of each subject before starting any kind of treatment (Table 2). 5) This guideline is applied solely for adults (age 20-64). Lipid abnormalities in children or the youth under age 19, and the elderly with an age over 65 have to be evaluated by their own standard. 6) This part of the guideline gives only the diagnostic aspects of hyperlipidemias. The part of management and treatment will follow in the second section of the guideline that will be published in future.

Yanai H, Tomono Y, Ito K, Furutani N, Yoshida H, Tada N. · Department of Internal Medicine, The Jikei University School of Medicine, Chiba, Japan. · Nutr J. · Pubmed #18072966 links to  free full text

Abstract: Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered.

Tada N. · Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, The Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #17824070 No free full text.

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Yoshida H, Shoda T, Yanai H, Tada N. · Department of Clinical Laboratory, The Jikei University Kashiwa Hospital. · Nippon Rinsho. · Pubmed #17824046 No free full text.

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Tada N. · Department of General Medicine, Kashiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347143 No free full text.

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Tada N. · Department of General Medicine, Kashiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347141 No free full text.

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Furutani N, Tada N. · Department of General Medicine, Kashiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347100 No free full text.

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Shoda T, Tada N. · Department of General Internal Medicine, Kasiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347091 No free full text.

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Tada N. · Department of General Medicine, Kashiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347044 No free full text.

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Tada N. · Department of General Medicine, Kashiwa Hospital, Jikei University School of Medicine. · Nippon Rinsho. · Pubmed #11347041 No free full text.

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Tada N. · Aoto Hospital, Department of Internal Medicine 4, Jikeikai University School of Medicine. · Nippon Rinsho. · Pubmed #10638214 No free full text.

Abstract: Remnant lipoproteins are intermediate metabolites of triglyceride-rich lipoproteins, such as chylomicron (CM) and very-low density lipoprotein (VLDL) in the circulation. Several lines of evidence have suggested that remnant lipoproteins are atherogenic. It is well known that some of the inherited dyslipidemias cause remnant hyperlipidemia and are accompanied with marked skin and tendon xanthomas, corneal arcus and premature or accelerated atherosclerosis. Among them, lipid abnormalities, clinical features and gene polymorphism of familial dyslipoproteinemia and hepatic lipase deficiency were reviewed. Even if one has affected alleles associated with these disorders, sometimes abnormal lipid profiles are difficult to reveal in the overnight fasting plasma. So, a tolerance test like a fat overloading may be required to elucidate such abnormalities.

Iwasaki M, Tada N. · Jikei Medical University, Internal Medicine 4(Aoto). · Nippon Rinsho. · Pubmed #10638209 No free full text.

Abstract: Primary Hyperchylomicronemia is known as a syndrome in which the accumulation of chylomicron occurs in the circulation. The main clinical symptoms of this disorder are the huge increase in plasma trigriceride and cholesterol, and the presence of xanthomatous eruption, lipemia retinalis, hepatosplenomegaly, and the complication of acute pancreatitis. With gene analysis, a deficiency of lipopreteinlipase (LPL) or apolipoprotein C-II is revealed as a main cause of primary chylomicronemia. Furthermore, in some cases, abnormalities of remnant receptors, the presence of antibody against LDL, apolipoprotein C-II, and LDL receptor are reported as causes of chylomicronemia syndrome. In the present paper, we summarized the major gene polymorphism and characteristics of clinical symptom of these disease.

Sumiyoshi K, Mokuno H, Iesaki T, Shimada K, Miyazaki T, Kume A, Kiyanagi T, Kuremoto K, Watanabe Y, Tada N, Daida H. · Department of Cardiology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. · Cardiovasc Res. · Pubmed #18694873 No free full text.

Abstract: AIMS: To clarify the role of Fc receptors (FcR) for immunoglobulin in endothelial dysfunction induced by hypercholesterolaemia, we evaluated the effect of deletion of the FcR gamma chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR gamma(-/-) mice compared with that in wild-type mice. METHODS AND RESULTS: Plasma cholesterol levels of those on the high-fat diet were significantly increased compared with those on the normal chow diet in both groups of mice. Endothelium-dependent relaxation of the aortic ring with acetylcholine in wild-type mice was significantly reduced by the high-fat diet (ED(50): 0.22 vs. 0.43 nM, P < 0.002), whereas the relaxation in FcR gamma(-/-) mice was not inhibited (ED(50): 0.22 vs. 0.23 nM, NS). Furthermore, superoxide detection by dihydroethidium-derived fluorescence and immunohistochemical staining of p22phox expression were significantly increased in wild-type mice fed on the high-fat diet, while these oxidative stresses in FcR gamma(-/-) mice were not enhanced by the high-fat diet. Oil Red O-staining showed no significant lipid accumulation at the aortic sinus in both groups of mice. CONCLUSION: This study demonstrates that the deletion of the FcR gamma chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR gamma(-/-) mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolaemia.

Yoshida H, Hirowatari Y, Kurosawa H, Tada N. · Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Chiba 277-856, Japan. · Clin Sci (Lond). · Pubmed #15907189 No free full text.

Abstract: The present study was performed to investigate the relevance of cholesterol levels of plasma lipoproteins [HDL (high-density lipoprotein), LDL (low-density lipoprotein), IDL (immediate-density lipoprotein), VLDL (very-LDL) and chylomicrons] determined by a novel HPLC method, with adiponectin, which is decreased in Type II diabetes and assumed to be involved in dysregulated metabolism and atherogenesis. Type II diabetic patients who were not treated with insulin, statins and fibrates were enrolled. Study subjects included Type II diabetic patients with normolipidaemia (DM-NL; n=15), type 4 hyperlipidaemia (DM-T4HL; n=13), Type IIa hyperlipidaemia (DM-T2aHL; n=15) and Type IIb hyperlipidaemia (DM-T2bHL; n=13). Fasting blood samples were collected. The serum adiponectin level was lower in DM-T2bHL than in any of the other groups. Cholesterol levels of each lipoprotein fraction, serum triacylglycerol (triglyceride), remnant-like particle-cholesterol, fasting plasma glucose, HbA1c (glycated haemoglobin), age, gender difference and BMI (body mass index) were incorporated into a stepwise regression analysis as independent variables. VLDL-cholesterol correlated inversely with adiponectin independently of age, BMI, gender difference and glycaemic control. Although the mechanisms remain to be explored, serum adiponectin was reduced particularly in Type II diabetics with type IIb hyperlipidaemia and correlated inversely with VLDL-cholesterol. Measuring VLDL-cholesterol may be helpful for understanding the pathological features of diabetic dyslipidaemia.

Tada N, Shoji K, Takeshita M, Watanabe H, Yoshida H, Hase T, Matsuo N, Tokimitsu I. · Department of Internal Medicine, Division of General Medicine, Kashiwa Hospital, The Jikei University School of Medicine, 163-1 Kashiwashita, Kashiwa, Chiba 277-8567, Japan. · Clin Chim Acta. · Pubmed #15698594 No free full text.

Abstract: BACKGROUND: We previously reported that diacylglycerol (DAG) as compared with triacylglycerol (TAG) suppressed increases in postprandial lipids in healthy volunteers. This study was to investigate the effects of DAG on postprandial lipids, particularly remnant lipoproteins in diabetics. METHODS: Emulsified DAG oil or TAG oil with a fatty acid composition similar to DAG oil was orally administered (30 g fat/m2 of body surface) to moderately controlled six diabetics, with hemoglobin A1c (HbA1c) below 8%, after fasting for at least 12 h in a randomized crossover manner. Serum cholesterol and TAG, lipids in remnant-like particles (RLP), and other lipid parameters including serum ketone bodies were measured prior to and 2, 4, and 6 h after fat loading. RESULTS: DAG loading significantly suppressed increases in postprandial serum TAG and lipids in RLP as compared with TAG loading. The incremental area under the curve (IAUC) for serum TAG and that for lipids in RLP with DAG loading were also significantly smaller than those with TAG loading. However, changes in serum levels of insulin, free fatty acids, and ketone bodies during fat loading were essentially the same for DAG and TAG. CONCLUSIONS: This pilot study suggests that substituting DAG intake for TAG may be beneficial to moderately controlled diabetics due to its effect in reducing postprandial hyperlipidemia.

Millar JS, Maugeais C, Ikewaki K, Kolansky DM, Barrett PH, Budreck EC, Boston RC, Tada N, Mochizuki S, Defesche JC, Wilson JM, Rader DJ. · Department of Medicine, University of Pennsylvania, 644 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #15637307 links to  free full text

Abstract: OBJECTIVE: We addressed the role of the low-density lipoprotein (LDL) receptor in determining clearance rates and production rate (PR) of apolipoprotein B (apoB) in humans. METHODS AND RESULTS: Kinetic studies using endogenous labeling of apoB with deuterated leucine were performed in 7 genetically defined patients with homozygous familial hypercholesterolemia (FH) and compared with 4 controls. The fractional catabolic rates (FCR) and PRs for apoB were determined by multicompartmental modeling. The FCRs of very-low-density lipoprotein 1 (VLDL1), VLDL2, intermediate-density lipoprotein (IDL), and LDL apoB were lower in FH than in controls, with the LDL apoB FCR being significantly lower (0.148+/-0.049 versus 0.499+/-0.099 pools x d(-1); P=0.008). Whereas receptor-defective FH patients had a total apoB PR similar to controls, receptor-null FH patients had a significantly greater total apoB PR than controls (35.97+/-10.51 versus 21.32+/-4.21 mg x kg(-1) x d(-1), respectively; P=0.02). CONCLUSIONS: This first study of apoB metabolism in homozygous FH using endogenous labeling with stable isotopes demonstrates that the LDL receptor contributes significantly to the clearance of LDL from plasma but plays a lesser role in the clearance of larger apoB-containing lipoproteins. Furthermore, these data also indicate that absence of a LDL receptor in humans substantially influences the apoB PR in vivo.

Hirowatari Y, Kurosawa H, Yoshida H, Doumitu KI, Tada N. · Scientific Instruments Division, TOSOH Corp., Kanagawa, Japan. · Anal Biochem. · Pubmed #12419348 No free full text.

Abstract: We have developed a new analysis method for lipoproteins in serum by high-performance liquid chromatography using a sulfopropyl-ligand column with eluents containing magnesium nitrate. The magnesium ion anchors lipoproteins to the ligands on the column gel. Lipoproteins are eluted from the column with a magnesium nitrate concentration gradient and detected by postcolumn reaction using a reagent containing cholesterol esterase and cholesterol oxidase. High-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein were eluted in order from the column. The within-assay and between-assay coefficients of variation for cholesterol concentration in lipoproteins were 1.1-3.7 and 1.3-5.8%, respectively. The correlation coefficients between the values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol obtained by the new method and those obtained by an enzymatic method using an automated chemical analyzer were 0.940, 0.979, and 0.909, respectively. The new method was successfully applied to the analysis of plasma lipoproteins of patients with hyperlipidemia.

Matsushima Y, Sakurai T, Ohoka A, Ohnuki T, Tada N, Asoh Y, Tachibana M. · Research Institute, Saitama Cancer Center, Ina, Japan. · J Atheroscler Thromb. · Pubmed #11866033 No free full text.

Abstract: Spontaneously hyperlipidemic (SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E (Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6, BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most severe in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions.

Okazaki M, Usui S, Tada N, Nakano T, Nakajima K. · Laboratory of Chemistry, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, 2-8-30, Kohnodai, Ichikawa-shi, Chiba, Japan. · Clin Chim Acta. · Pubmed #10807977 No free full text.

Abstract: Remnant-Like Particles (RLP) isolated by an immunoseparation method are heterogeneous in their physical and biochemical properties. The objective of this study was to examine the relation between RLP-triglyceride (RLP-TG) to RLP-cholesterol (RLP-C) ratio and particle size distribution in RLP-C profiles from patients with hyperlipoproteinemia by HPLC. RLP were isolated from serum samples from 147 subjects. RLP-C and RLP-TG were quantified by respective enzymatic methods. Particle sizes of the RLP were measured using HPLC with 4 connected TSKgel LipopropakXL columns. Based on HPLC profiles of RLP-C from individual subjects, three different types were classified: predominantly LDL, predominantly VLDL, and mostly VLDL types. All patients with type III hyperlipidemia were mostly VLDL type but with smaller particle size of VLDL (32 nm) than other subjects. Severe hypertriglyceridemic (TG>4.52 mmoll(-1)) subjects were mostly VLDL type with large particle size (41 nm). As for all subjects (n=105) without predominantly LDL type, a significant correlation between RLP particle size and RLP-TG to RLP-C ratio (r=0. 432, P<0.001) was obtained, but not in case of serum TG to RLP-C ratio (r=0.062). It suggests that RLP-TG to RLP-C ratio might be used for discrimination of atherogenic smaller-sized lipoprotein from larger-sized TG-rich lipoprotein remnants.

Yanai H, Tada N, Yoshida H, Tomono Y. · No affiliation provided · QJM. · Pubmed #17434913 links to  free full text

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