[Show abstract][Hide abstract] ABSTRACT: The Chiba Lipid Intervention Program (CLIP) Study was designed to clarify the prognosis of Japanese hypercholesterolemic patients taking pravastatin for 5 years. Hypercholesterolemic patients (n = 2,529) with a total cholesterol level > or = 220 mg/dl and without histories of ischemic coronary heart disease and/or cerebral infarction were administered pravastatin (10-20 mg/day). Among them, 2,131 took pravastatin fully (Pravastatin-continued group), and 398 discontinued the treatment (Discontinued group). The baseline total cholesterol level was 264.3 +/- 34.7 mg/dl (mean +/- standard deviation). The mean reduction rates of total cholesterol and low-density lipoprotein (LDL) cholesterol were 18.0% and 27.2%, respectively. Mild and moderate adverse events occurred in 86 cases (3.6%). Serious adverse events were not observed. Death rates of the pravastatin-continued group and of the discontinued group were 2.6 and 16.0/1,000 persons/year, respectively. Cardiac events (fatal and nonfatal myocardial infarction, cardiac death, angina pectoris) in all, occurred in 35 patients (incidence rate = 2.77/1,000 persons/year). In the pravastatin continued group, 9 causes of fatal and nonfatal myocardial infarction occurred (0.84/1,000 persons/year), whereas in the discontinued group, 4 cases occurred (2.06/1,000 persons/ year). The risk ratio for cardiac events was correlated with the number of risks. In the low-risk group (< or = 1 risk), decreased rates of LDL-cholesterol were less in the cardiac event group than the non-cardiac event group (LDL-cholesterol; 16% vs 25%, p = 0.04). These results suggested the following; 1) Pravastatin maintained a cholesterol lowering effect long-term without serious complications. 2) Pravastatin administration might reduce the mortality rate and myocardial infarction. 3) The combination of multiple risks is a strong factor for a cardiac event in addition to hypercholesterolemia.
No preview · Article · Jan 2002 · Journal of atherosclerosis and thrombosis
[Show abstract][Hide abstract] ABSTRACT: To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LP mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was . The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were and , respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 μmol FFA released/h/μg LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than −2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than −2 S.D. despite the fact that LPL masses were not less than −2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.
[Show abstract][Hide abstract] ABSTRACT: Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate sectreted into the medium by Werner's fibroblasts was 2–3 times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibloblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain lenght of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in thematrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain.
No preview · Article · Jul 1992 · Biochimica et Biophysica Acta
[Show abstract][Hide abstract] ABSTRACT: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide “C” insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
No preview · Article · Dec 1991 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: We measured the serum apolipoprotein (Apo) levels in various hyperlipidemias and determined their correlations with the serum cholinesterase and albumin levels. The objective was to elucidate which apolipoprotein(s) commonly reflects the liver function, as shown by the albumin and cholinesterase levels, in various hyperlipidemias.The subjects consisted of 53 normal controls and 86 type IIa, 38 type IIb, 28 type IV, and 9 type V hyperlipidemias. Each apolipoprotein level generally reflected the characteristic changes of lipoproteins for each hyperlipidemia.As for the correlation of apolipoproteins with cholinesterase and albumin, Apo A-II showed a positive correlation with cholinesterase in the normal controls and in all types of hyperlipidemia, though it was not significant in types IIb and V. And Apo A-II also showed a significantly positive correlation with albumin in all types of hyperlipidemia except type V.Considering that cholinesterase and albumin are known to reflect the liver function, these results are consistent with the idea that among the various apolipoproteins, Apo A-II may best reflect the liver function in all types of hyperlipidemia.
No preview · Article · Jan 1991 · Journal of Clinical Biochemistry and Nutrition
[Show abstract][Hide abstract] ABSTRACT: Pulse wave velocity (PWV) is known to reflect the stiffness of the aorta [2,7], one of the major features of atherosclerosis. To clarify the severity and progression mechanism of atherosclerosis in hemodialysis patients and the preventive effect of nifedipine, PWV was annually measured for 2 years, and the change of PWV and contributory factors were analyzed. PWV in hemodialysis patients was faster than in age-matched normal controls. PWV was correlated with the duration of hemodialysis. PWV, which is obtained from the difference in PWV over 1 year, was positively correlated with age, high blood pressure, and serum cholesterol levels and was negatively correlated with HDL levels. The CaPi value was also positively correlated with PWV. Nifedipine was administered to 47 patients for 2 years, and the change of PWV was compared with age-matched control hemodialysis patients. The PWV of the control group was gradually increased by 10%. The PWV of the group given nifedipine decreased by 2%. These results suggested that administration of nifedipine may prevent the progression of PWV in hemodialysis patients and may decrease the progression of atherosclerosis.
No preview · Article · Aug 1990 · Cardiovascular Drugs and Therapy
[Show abstract][Hide abstract] ABSTRACT: Palmitate oxidation activity and the activities of several enzymes involved in long-chain fatty acid metabolism were examined in the liver of young adult (2-month-old) and senescent (32-month-old) female rats. Palmitate oxidation activity in rat liver mitochondria showed age-related decrease, as judged by the rates of both 14CO2 production and formation of radioactive acid-soluble products from [1-14C]palmitate. In addition, long-chain acyl-coenzyme A synthetase activity was found to be decreased in liver mitochondria and increased in liver microsomes in senescent rats. These results suggest that, in the rat liver, preferential channeling of long-chain fatty acids through the triacylglycerol synthetic pathway may increase with age, and as a result, energy production by their oxidation may decrease.
No preview · Article · Aug 1988 · Mechanisms of Ageing and Development