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Biomedical subjects

M Sakuma

Publications and source records attributed to M Sakuma.

At least 181 records · Page 10Linked to original sources
PubMed1983

Abnormalities in plasma lipoprotein in familial partial lecithin:cholesterol acyltransferase deficiency.

Abnormalities in plasma lipoproteins from patients with familial partial lecithin:cholesterol acyltransferase deficiency were studied. In these patients the plasma cholesterol ester ratio was about 40% and plasma apolipoprotein B level remained within the normal range. The content of large-sized low-density-lipoproteins (LDL) was low. Apolipoprotein B-100 and B-48 were detected in very-low-density lipoproteins (VLDL) and LDL in patients' plasma. In patients' LDL, apolipoprotein B-48 was primarily present in large-sized particles. Apolipoprotein E and A-I were mainly detected in intermediate-sized LDL. High-density lipoproteins (HDL) were separated into three fractions by gel permeation chromatography. Large-sized HDL particles (150-200 A) including discoidal particles contained apolipoproteins, E, A-IV and A-I. The content of discoidal HDL was low and, on electron micrograph, rouleau-formed particles were rarely seen. Normal-sized HDL (80-100 A) contained apolipoproteins A-I and A-II and small-sized HDL (about 60 A) contained only apolipoprotein A-I. Although several lipoprotein abnormalities were similar to those in classical familial lecithin:cholesterol acyltransferase deficiency, remaining lecithin:cholesterol acyltransferase activity may, however, cause a lack of reduction of apolipoprotein B level, a low level of large-sized LDL and also a low level of discoidal HDL.

Adult↗
PubMed1982

Familial lecithin-cholesterol acyltransferase deficiency in a Japanese family: evidence for functionally defective enzyme in homozygotes and obligate heterozygotes.

Lecithin-cholesterol acyltransferase (LCAT) mass and activity were measured in a Japanese family with familial LCAT deficiency. The two LCAT-deficient subjects had LCAT mass approximately 40-46% of normal (2.65 and 2.31 micrograms/ml respectively, as compared with normal levels of 5.76 +/- 0.95 microgram/ml in 19 Japanese subjects) and enzyme activity less than 10% of normal (9.1 and 8.3 nmol/h/ml respectively, as compared with normal levels of 100 nmol/h/ml). All obligate heterozygotes examined, including the father of the two LCAT-deficient subjects, and all five children of the deficient subjects had LCAT mass approximately 72-80% of the normal LCAT mass (4.12, 4.38, 4.45, 4.48, 4.49, 4.61 micrograms/ml, respectively) and LCAT activity approximately half normal (51.9, 52.4, 54.2, 56.6, and 57.2 nmol/h/ml). We conclude that the two LCAT-deficient subjects of this family have functionally defective enzyme. Furthermore, the data suggest that the plasma of the obligate heterozygotes contain both normal and functionally defective enzymes.

Adolescent↗
PubMed1982

Familial plasma lecithin: cholesterol acyltransferase deficiency. A new family with partial LCAT activity.

A 43-year-old woman and her 47-year-old brother were studied because of corneal opacity. They showed a marked decrease in plasma high density lipoproteins (HDL) and a decrease in the ester ratio of plasma total cholesterol. Discoidal particles were found in the HDL2 fraction (d 1.063-1.125). A marked heterogeneity of low density lipoproteins was disclosed in both patients by electron microscopy. Apoprotein analysis revealed an increase in apo E and a decrease in apo A-I and A-II in both patients. These abnormalities were similar to the data reported in other cases with hereditary lecithin : cholesterol acyltransferase (LCAT) deficiency. However, several interesting dissimilarities have been disclosed as compared with the previously reported cases. Neither patient had proteinuria, and their kidney functions were within the normal limits. The ester ratios of plasma cholesterol of both patients were the highest among the cases reported thus far. Their plasma LCAT activities were 14.4 and 15% of the normal mean values determined by Glomset-Wright's common-substrate method. The enzyme activities determined by Stokke-Norum's self-substrate method were 40.2 and 29% respectively. These results may indicate that this inherited disorder is not characterized by absence of plasma LCAT or presence of inhibitory factors in plasma, but by the presence of partially inactive LCAT in patients' plasma.

Adolescent↗
PubMed1981

Effects of inducer of liver drug-metabolizing enzyme on blood level of active metabolites of cyclophosphamide in rats and in cancer patients.

It was already reported that a masked compound, cyclophosphamide (Endoxan, EX) undergoes the first step metabolism by a drug-metabolizing enzyme in liver microsomes, cytochrome P-450. By pretreatment with phenobarbital as an inducer of P-450, the maximum blood level of active metabolites of EX (normustard-like substances) in normal rats was 2.3 times higher than that in non-treated rats, in conformity with the increase in amount of liver P-450 and in alkylating activity of EX. In YS (Yoshida sarcoma)-bearing rats, the value of liver P-450 went down day by day to 1/2 on the 4th day after inoculation, but it remained normal when animals were pretreated with phenobarbital. In parallel with this, the blood level of normustard-like substances after EX administration was normal or showed a tendency toward increase. In 11 clinical cases pretreated with phenobarbital, the blood level of normustard-like substances 1 to 3 hr after EX administration, at the time when it reaches the peak was 1.5 times higher on an average than that in cases without pretreatment.

Adult↗
PubMed1981

Correlation between the level of urinary D-glucaric acid and the degree of activation of masked compound (FT-207) in cancer patients.

Phenobarbital stimulates the induction of liver microsomal drug-metabolizing enzyme, namely, cytochrome P-450, which enhances the rate of conversion of FT-207 to 5-FU, the active substance. When FT-207 is administered in combination with phenobarbital to cancer patients, the fluctuation in level of the drug-metabolizing enzyme, cytochrome P-450, should be taken into consideration. Therefore, it was investigated whether the urinary level of D-glucaric acid could be of value as an indicator for the evaluation of the activation of masked compounds, such as FT-207. The level of D-glucaric acid in urine was lower in cancer patients than in normal controls. The correlation between the level of urinary D-glucaric acid and that of 5-FU, which is an active metabolite of FT-207, in blood was statistically significant. The level of D-glucaric acid in urine was of use as an indicator for the evaluation of the activation of masked compounds, such as FT-207, in cancer chemotherapy.

Adult↗