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Biomedical subjects

H Mabuchi

Publications and source records attributed to H Mabuchi.

At least 235 records · Page 13Linked to original sources
PubMed1986

Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes.

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.

Animals↗
PubMed1985

Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.

Adult↗
PubMed1985

Normalization of low-density lipoprotein levels and disappearance of xanthomas during pregnancy in a woman with heterozygous familial hypercholesterolemia.

Serum lipids and lipoproteins were studied prior to conception, during pregnancy, and after delivery in a woman heterozygous for familial hypercholesterolemia. Prior to conception, serum and low-density lipoprotein (LDL) cholesterol levels were 613 and 528 mg/dL, respectively. At 37-week gestation, serum and LDL cholesterols decreased to the normal levels, 226 and 90 mg/dL, respectively. At two-week postpartum serum and LDL cholesterols returned to the preconception levels, 547 and 427 mg/dL, respectively. At delivery her cutaneous xanthomas almost disappeared. The patient was challenged by ethinyl estradiol of 120 micrograms/d for two months, as a result serum cholesterol decreased from 565 to 385 mg/dL, and LDL cholesterol fell from 460 to 208 mg/dL. During her second pregnancy, serum and LDL cholesterol decreased again significantly. Thus, this case, which showed dramatic reductions of serum and LDL cholesterol levels, may be considered a new variant of heterozygous familial hypercholesterolemia, and the reductions were probably brought about by the action of estrogens, which are known to increase LDL degradation through LDL receptors.

Adult↗
PubMed1984

Liver regeneration and tumor growth in the rat after partial hepatectomy.

Tumor growth of Yoshida sarcoma implanted in the remnant liver was studied in rats subjected to a hepatectomy. After 70 percent hepatectomy, the liver progressively regenerated and the total liver weight was reverted to by 10 days after the operation. Concomitantly with liver regeneration, tumor growth in the remnant liver was stimulated significantly, compared with that in the sham-operated liver. Incorporation of tritiated thymidine into tumor cells in the remnant liver was strikingly high and progressive, while that in the sham-operated liver was low and retained. Mitomycin C given to the hepatectomized rats was more effective against the tumor in the remnant liver than in the sham-operated liver. We conclude from this study that cancer cell proliferation in the remnant liver can be accelerated by the process of liver regeneration.

Animals↗
PubMed1984

ApoVLDL of the Watanabe Heritable Hyperlipidemic rabbit and the cholesterol-fed rabbit.

The Watanabe Heritable Hyperlipidemic rabbit (WHHL rabbit) and the cholesterol-fed rabbit have been reported to show elevations of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL), and a broad-beta band on agarose-gel electrophoresis. We have studied the lipid and lipoprotein composition of WHHL rabbits and cholesterol-fed rabbits using ultracentrifugal analysis and isoelectric focusing. The total cholesterol (TC)/triglyceride (TG) ratios of VLDL, IDL, and LDL in WHHL rabbits were slightly elevated, but almost normal compared with those of cholesterol-fed rabbits, whose TC/TG ratios were markedly elevated compared with normolipidemic rabbits. ApoVLDL of WHHL rabbits showed no compositional changes in apoE and apoC isoforms, and no marked changes in the apoE/apoC ratios. But apoVLDL of cholesterol-fed rabbits showed a significant decrease of apoC-III, a significant increase of apoC-V, and marked elevation of the apoE/apoC ratio. We conclude that serum lipoprotein compositions in the WHHL rabbit were normal, while the lipoprotein lipid and apolipoprotein composition in the WHHL rabbit are different from those in cholesterol-fed rabbits.

Animals↗
PubMed1983

Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine.

We studied the effects of the bile acid sequestrant cholestyramine, alone and in combination with the experimental agent compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum levels of lipoproteins in 10 heterozygous patients with familial hypercholesterolemia. After cholestyramine treatment alone for 2 to 16 months, serum total and low-density lipoprotein cholesterol decreased by 20 and 28 per cent, respectively. With the addition of compactin for 12 weeks there was a 39 per cent total decrease in serum cholesterol from the control value--from 356 +/- 14 to 217 +/- 10 mg per deciliter (9.27 +/- 0.36 to 5.64 +/- 0.26 mmol per liter [mean +/- S.E.M.]; P less than 0.001)--and a 53 per cent decrease in low-density lipoprotein cholesterol--from 263 +/- 13 to 125 +/- 10 mg per deciliter (6.84 +/- 0.34 to 3.25 +/- 0.26 mmol per liter; P less than 0.001). High-density lipoprotein cholesterol, which had increased during cholestyramine treatment, remained at its higher level. No adverse effects were observed. If long-term safety can be demonstrated, the compactin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia. prove useful in heterozygous familial hypercholesterolemia.

Adult↗
PubMed1983

A case of heterozygous familial hypercholesterolemia associated with hyperthyroidism: effects of triiodothyronine on low-density lipoprotein receptor and cholesterol synthesis.

A 58-year-old patient with heterozygous familial hypercholesterolemia (FH) showed normal levels of serum cholesterol (193 mg/dL) in coexistence with hyperthyroidism. After hyperthyroidism therapy with radioiodine and methimazole, the patient's lipid profile showed high concentrations of cholesterol (whole serum 318 mg/dL, VLDL 35 mg/dL, LDL 217 mg/dL, HDL 44 mg/dL). There was a significant inverse correlation between serum cholesterol levels and serum thyroxine levels (r = -0.815, p less than 0.01). Effects of triiodothyronine on LDL degradation and cholesterol synthesis from 14C-labeled acetate were studied in cultured skin fibroblasts. Triiodothyronine (T3) stimulated both LDL degradation and cholesterol synthesis in the cells from normal subjects and patients with heterozygous FH. The T3 increased cellular cholesterol synthesis markedly in the cells from patients with homozygous FH but did not increase LDL receptor activity. These results suggest that normal serum cholesterol levels in our case result in part from an enhancement of LDL receptors by thyroid hormone.

Cells, Cultured↗
PubMed1983

Medium-sized peptides in the blood of patients with uremia.

We have carried out high performance liquid chromatographic analysis of serum and ultrafiltrate of blood obtained from uremic patients and normal subjects to elucidate the presence of medium-sized peptides unique to uremia. Many fluorescamine-positive substances, excluding amino acids and guanidine compounds, were increased in uremic serum compared with normal serum. At the 0.5-1.0 pmol/ml serum level, several peaks were unique to uremia. The retention time, fluorescamine reactivity, molecular weight distribution and the result of enzymatic digestion revealed that these peaks are peptidic substances.

Chromatography, High Pressure Liquid↗
PubMed1983

Isolation and partial characterization of platelet aggregation inhibitors in the blood of dialyzed patients.

Platelet aggregation inhibitors were isolated from the blood of dialyzed patients by high-performance liquid chromatography. At least two inhibitors exist in the blood of dialyzed patients. These inhibitors not only inhibit platelet aggregation, but also suppress the chemiluminescence response of platelet. The chromatographic behaviors and the results of enzymatic digestion suggested that these inhibitors are relatively low molecular weight nonpeptidic substances.

Blood Platelets↗
PubMed1983

Serum and lipoprotein lipid levels in diabetic patients with familial hypercholesterolemia.

To examine the influence of glucose intolerance in familial hypercholesterolemia (FH) on coronary heart disease (CHD), we measured serum and lipoprotein lipid levels in heterozygous FH patients with and without glucose intolerance. The patients with FH were classified as having normal (N), borderline (B) and diabetic (D) glucose tolerance by 50 g OGTT according to the criteria of the Japan Diabetic Society. Fasting blood glucose levels (mean) were 78 mg/100 ml (N, n = 8), 97 (B, n = 10) and 199 (D, n = 9) in females and 85 (N, n = 12), 93 (B, n = 21) and 185 (D, n = 15) in males, respectively. Prevalence of CHD was 50% (N), 56 (B) and 89 (D) in females and 58 (N), 67 (B) and 50 (D) in males, respectively. Serum cholesterol (Chol) and triglyceride (TG) levels (mean) were 351 mg/100 ml and 112 mg/100 ml (N), 323 and 102 (B), and 342 and 187 (D) in females and 356 and 93 (N), 338 and 121 (B), and 305 and 161 (D) in males, respectively. Serum Chol in D was significantly lower than in N in males (p less than 0.02). Serum TG in D was significantly higher than in N (p less than 0.05) in both males and females. Chol and TG of VLDL in D (n = 15) were significantly higher than in B (n = 19) (p less than 0.02 and p less than 0.05) and in N (n = 15) (p less than 0.05 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Liquid-chromatographic profiling of endogenous fluorescent substances in sera and urine of uremic and normal subjects.

Endogenous fluorescent substances increase in serum during uremia. We have used "high-performance" liquid chromatography to profile these fluorescent substances in both uremic and normal body fluids. The fluorescence excitation and emission maxima we used were 322 and 415 nm, respectively. Of the numerous fluorescent substances found in uremic body fluids and in normal urine, some were also detectable in normal serum, but at relatively weak fluorescence intensities.

Chromatography, High Pressure Liquid↗
PubMed1982

Profiling of urinary medium-sized peptides in normal and uremic urine by high-performance liquid chromatography.

This report describes the profiling of medium-sized peptides in both normal and uremic urine by ion-pair reversed-phase high-performance liquid chromatography using an acetonitrile--heptafluorobutyric acid solvent system as eluent. Several medium-sized peptide peaks could be detected in both normal and uremic urine at low picomole level by using post-column fluorescence derivatization with fluorescamine. Contrary to expectation, uremic urine contained slightly larger amounts of medium-sized peptides compared with normal urine.

Chromatography, High Pressure Liquid↗