| Project/Area Number |
61440050
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
SHIGETA Yukio Shiga Univ. of Med Sci., Dep. of Med., Professor, 医学部, 教授 (60028321)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Tamio Osaka Univ., Dep of Nutrition, Assistant Prof., 医学部, 講師 (70135721)
KOSUGI Keisuke Shiga Univ. of Med. Sci., Dep. of Med., Instructor, 医学部, 助手 (00153544)
HIDAKA Hideki Shiga Univ. of Med. Sci., Dep. of Med., Instructor, 医学部, 助手 (80156603)
KASHIWAGI Atsunori Shiga Univ. of Med. Sci., Dep. of Med. Assistant Prof., 医学部, 講師 (20127210)
HARANO Yutaka Nat. Cardiovas. Center, Dep. of Med., Chief, Div. of Metab., 部長 (10028615)
|
|---|
| Project Period (FY) |
1986 – 1989
|
| Keywords | Atherosclerosis / Diabetes mellitus / Low density lipoproteins(LDL) / Denatured LDL / Apolipoprotein B / Hypobetalipoproteinemia / Gene analysis / Sitosterolemia |
|---|
| Research Abstract |
Apolipoprotein B contents in low-density-lipoproteins(LDL) in atherosclerotic diseases were increased relative to cholesterol determined by a newly developed enzyme immunoassay for apolipoprotein B, and similar phenomenon was observed in poorly control led diabetic subjects, suggesting that the abnormality may account for the higher prevalence of atherosclerotic diseases in DN. Metabolic characteristics of LDL have been also analyzed in cultured human fibroblasts and macrophage cell line; J774.1. In diabetic states, including experimentally diabetic monkey, LDL contains more triglycerides(TG) relative to cholesterol and the LDL has less affinity to LDL receptor. Glycated LDL, one of the abnormal LDL, is metabolized by neither LDL pathway nor savenger pathway inmacrophage, but by (an)other pathway(s) in cultured hepatocytes. Lipoprotein abnormalities in diabetic patients were reproduced in experimentally diabetic monkey, and can be improved by insulin therapy, indicating that the abnorm
… More
alities are secondary to metabolic derangements induced by insulin deficiency. After long duration of diabetes in monkey, microvascular complications as well as atherosclerotic lesions were observed.
A family study of hypobetalipoproteinemia indicated that the disease is inherited as an autosomal dominant trait. In homozygous patients, apolipoprotein B-100 as well as B-48 can be detected by a newly developed HPLC method for the determination of apo B isoform, even though LDL concentrations in plasma were trace in these patients. Southern analysis of patients' DNA could not reveal abnormalities by this point. Metabolic characteristics of the patients LOL were normal in cultured fibroblasts. These data suggest that this familial hypobetalipoproteinemia may be due to the abnormality of the regulation of apolipoprotein B synthesis.
A patient of sitosterolemia who presented with paraplegia due to spinal compression by multiple xanthomas was reported. This is the first report that sitosterolemia can show neurological symptoms. We also found that heterozygotes with sitosterolemia have increased plant sterol levels in this family. A case of hypercholesterolemia and xanthomatosis with anti-LDL antibody was reported. Less
|
