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Biomedical subjects

T Kasama

Publications and source records attributed to T Kasama.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effects of oral copper administration to pregnant heterozygous brindled mice on fetal viability and copper levels.

Copper (6 ppm) was administered to pregnant heterozygous brindled and normal mice from 13 to 18 days gestation. The copper and zinc concentrations in the cerebrum, cerebellum, liver, and kidneys of mothers and their fetuses were determined. The placental concentrations in fetuses of heterozygous mothers administered copper were also determined. The heterozygous mothers had smaller numbers of live fetuses than the normal mothers, but had the same number as normal mothers when copper was administered. The hepatic copper concentration in the heterozygous mothers was lower than that in the normal mothers and was not increased by the administration. The body and tissue wet weights of all fetuses were unaffected by the maternal genotype or drinking fluid. The cerebral copper concentrations in hemizygous and heterozygous fetuses were increased by the copper administration but did not reach normal levels. The hepatic and renal concentrations remained unchanged. The cerebral copper concentrations in normal fetuses of both heterozygous and normal mothers were increased by the copper administration. The copper administration increased the copper concentrations in liver of normal fetuses of heterozygous mothers and in kidneys of normal fetuses of normal mothers. The placental copper concentration in hemizygous fetuses was higher than those in heterozygous and normal fetuses. These results suggested that oral copper administration to pregnant females could improve an abnormal copper distribution in hemizygous and heterozygous fetuses without affecting fetal growth.

Animals↗
PubMed1988

Synthesis and structural identification of four dihydroxy acids and 11,12-leukotriene C4 derived from 11,12-leukotriene A4.

Using a partially purified 12-lipoxygenase from porcine leukocytes, (5Z,8Z,10E,14Z)-12-hydroperoxy-5,8,10,14-icosate traenoic acid was synthesized from arachidonic acid with a yield of over 35%. The absolute configuration of C-12 was determined as S by chiral-phase column chromatography. It was chemically converted to at least three epoxides with the conjugated triene structure. Two were identified by proton NMR and mass spectrometry to be (5Z,7E,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-ic osatetraenoic acid (11,12-leukotriene A4) and (5Z,7Z,9E,14Z)-(11S,12S)-11,12-oxido-5,7,9,14-ic osatetraenoic acid (7-cis-11,12-leukotriene A4). 11,12-Leukotriene A4 underwent acid hydrolysis to yield two diastereomers of (6E,8E,10E,14Z)-(12S)-5,12-dihydroxy-6,8,10,14-i cosatetraenoic acid and two isomers of (14Z)-(12S)-11,12-dihydroxy-5,7,9,14-icosatetraenoic acid. Upon incubation with rat liver glutathione S-transferase, 11,12-leukotriene A4 was converted to 11,12-leukotriene C4, a spasmogenic compound.

Animals↗
PubMed1988

Effect of CS-514 (pravastatin) on VLDL-triglyceride kinetics in rats.

The effect of CS-514 (pravastatin; Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, on triglyceride turnover, was studied in male Wistar rats. CS-514 (15 +/- 1 mg/day per rat) was administered as a 0.04% solution in drinking water for 14 days. Triglyceride and cholesterol in very low density lipoprotein (VLDL) and plasma triglyceride were reduced by treatment with CS-514. Plasma cholesterol level was not suppressed by CS-514. The CS-514 treated rats had a significantly suppressed triglyceride secretion rate (TgSR) during the fed state compared to control rats (0.85 +/- 0.1 vs. 1.07 +/- 0.3 mg/min, P less than 0.05). By contrast, CS-514 treatment did not suppress TgSR after an overnight fast. These data demonstrate that CS-514, an inhibitor of cholesterol biosynthesis can suppress VLDL-triglyceride secretion in rats and that this effect can be modified by dietary manipulation.

Animals↗
PubMed1988

Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects.

The effect of CS-514 (eptastatin, Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was investigated in 47 patients with hypercholesterolemia (WHO type IIa: 27, IIb: 20). Ten or 20 mg of CS-514 was administered daily for 3 months. In both types of patient, total cholesterol and phospholipid levels were significantly reduced by CS-514. The triglyceride, cholesterol and phospholipid content of low density lipoprotein (LDL) and the plasma levels of apolipoprotein B were also decreased in both groups. In contrast, total triglyceride, very low density lipoprotein (VLDL)-triglyceride and apolipoprotein C-II were decreased only in type IIb subjects. Also the levels of high density lipoprotein (HDL)-cholesterol and apolipoproteins A-I and A-II were increased by CS-514 in IIb but not in IIa patients. In both groups, no change occurred in either the cholesterol/triglyceride or phospholipid ratio in any lipoprotein fraction, nor in the ratio of HDL-cholesterol to apolipoprotein A-I or A-II, respectively. Therefore, CS-514 suppresses plasma levels of cholesterol in hypercholesterolemic patients without modifying lipoprotein composition. Moreover, this drug has different effects on the levels of plasma triglyceride and HDL-cholesterol of type IIa and IIb patients.

Adult↗
PubMed1988

The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns.

Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non-aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, while SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post-burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7th day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species.

Adult↗
PubMed1988

Follow-up study of lipid peroxides, superoxide dismutase and glutathione peroxidase in the synovial membrane, serum and liver of young and old mice with collagen-induced arthritis.

Because reactive oxygen species (ROS) are generally believed to play an important role in tissue injury in rheumatoid arthritis, we examined the levels of lipid peroxides, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the synovial membrane, serum and liver of young (8 wk) and old (12 mo) mice with collagen-induced arthritis. In the synovial membrane, serum and liver, lipid peroxide levels of both young and old mice were increased beginning on the 3rd day after the onset of arthritis. SOD activity, which scavenges O2- and inhibits lipid peroxidation, rose markedly in the synovial membrane of young mice in parallel with the increase in lipid peroxide levels, but not so markedly in old mice. Liver GSH-Px activity, which metabolizes already formed lipid peroxides, also rose in young arthritic mice to a greater degree than in old mice. This study suggests that in inflammatory synovial lesions, lipid peroxides are generated due to an increase in ROS concentration, with resultant cytotoxicity, and that younger animals or humans can prevent this unfavorable reaction more effectively than aged ones by enzyme induction. The hypothesis that lipid peroxides formed in the oxidative lesions of the primary organ are released into the serum, trapped by the liver and metabolized there is further supported by the present study.

Aging↗
PubMed1988

Effect of cholestanol feeding on sterol concentrations in the serum, liver, and cerebellum of mice.

In order to elucidate the mechanism of xanthoma formation in cerebrotendinous xanthomatosis, mice were fed for 32 weeks with a diet rich in 5 alpha-cholestan-3 beta-ol (cholestanol) (1%, w/w). The concentrations of sterols in the serum, liver, and cerebellum were determined using high performance liquid chromatography. In the cholestanol-fed mice, the cholestanol concentrations in the serum and liver reached maxima in the first 2 to 4 weeks; the levels were about 30- to 100-fold higher than in the control diet mice. The cholestanol concentrations declined thereafter, finally to 50-60% of the maxima. Cholesterol concentrations were slightly lower in the cholestanol-fed mice throughout the experiments than in the control diet mice. On the other hand, the levels of cholestanol in the cerebellum increased almost linearly in parallel to the feeding time, and no decline was observed. These results suggest that the capacity of the liver to remove or degrade cholestanol was increased by long-term intake of this compound, whereas the cerebellum had no such feed-back regulation. Histological examinations using an electron microscope revealed the enlargement of lysosomal granules in the liver of the cholestanol-fed mice.

Animals↗
PubMed1988

Identification of 10-methylsphinganine in cerebrosides of the guinea pig harderian gland.

A large amount of branched long chain bases was detected in the cerebrosides of guinea pig Harderian gland. The long chain bases of cerebrosides were analyzed by GLC as trimethylsilyl derivatives. The branched long chain bases were separated into four peaks (I, II, III, IV) according to the number of carbon atoms and the position of branching. In the present work, the structures of long chain bases in the four peaks were analyzed by GLC and GC-MS after conversion of them to aldehydes, alcohols, and fatty acids. Furthermore the main component of long chain bases (Peak II) was isolated by HPLC as N-acetyl derivatives and analyzed by NMR. The structures of branched long chain bases in Peaks I, II, III, and IV are as follows. Branched long chain bases of Peak I are 2-amino-10- (main component), 2-amino-9-, and 2-amino-8-methylhexadecane-1,3-diol. Branched long chain bases of Peak II also consist of a mixture of 2-amino-10-, 2-amino-9-, and 2-amino-8-methyl-heptadecane-1,3-diol. The branched long chain base of Peak III is 2-amino-10-methyl-octadecane-1,3-diol, while that of Peak IV is 2-amino-16-methyloctadecane-1,3-diol. Among these branched long chain bases, 10-methylsphinganines are dominant though the chain lengths are different. These branched long chain bases, in which the substituted positions exist in the middle part of aliphatic chain (10-, 9-, or 8-methylsphinganine) are novel long chain bases in mammals.

Animals↗
PubMed1988

Effects of copper administration on fetal and neonatal mice.

The effects of copper administration to neonatal male mice on the copper concentrations and activities of copper-containing enzymes in cerebrum, liver, and kidney were studied. Intraperitoneal copper injections at 7 and 10 days of age increased the activities of superoxide dismutase and cytochrome oxidase in cerebrum and liver, and also increased the copper concentrations in cerebrum, liver, and kidney at 13 days of age. Maternal copper administration during the late-gestational period (from 13 days gestation to delivery) decreased the activities of both enzymes and increased the copper concentration in cerebrum. This increased level of copper remained by 13 days of age after birth. Liver showed similar changes to those in cerebrum, but the renal responses were less remarkable. Maternal copper administration from the late-gestational through lactational periods affected neonatal growth, decreased the activity of cytochrome oxidase, and increased the copper concentrations in all tissues examined. It is known that the copper concentration and copper-containing enzyme activity are low in cerebrum of mottled mice as well as of patients with Menkes' disease. These results suggested that the cytochrome oxidase activity in cerebrum was decreased by not only copper deficiency but also excess. The combination of prenatal copper supplementation by means of maternal copper administration during the late-gestational period and intraperitoneal copper injections after birth, while being careful not to overdose, is expected to be efficient for the copper supplementation to mottled mice.

Animals↗
PubMed1988

Multiple cytokine activities and loss of interleukin 2 inhibitor in synovial fluids of patients with rheumatoid arthritis.

Attempts to detect immune mediators in rheumatoid arthritis synovial fluids (RA-SF) by bioassays have yielded conflicting results, and so we analyzed the immune reactions occurring within rheumatoid joints using monospecific immunoassays for cytokines such as interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and gamma interferon (gamma-IFN). Furthermore, we examined the IL-2 inhibitors to clarify the immunoregulatory mechanism in the lesion. SF from active RA contained a significant amount of IL-1 beta and IL-2 but not gamma-IFN. In contrast IL-2 inhibitor activity was depressed in RA-SF regardless of clinical disease activity. Our results suggest that cytokine overproduction and deficiency of inhibitory signals may result in the overactivity of cytokines and the overactivity may participate in the joint lesions of RA.

Antibodies, Monoclonal↗
PubMed1988

Activation of antioxidant activity in natural medicinal products by heating, brewing and lipophilization. A new drug delivery system.

On the basis of the authors' previous hypothesis (1) that treatment of natural plant products with heating and gastric juice results in liberation of low molecular weight compounds with antioxidant activity that exist in the native products as repeating subunits of high molecular weight polymers, they have developed specially treated natural health or medicinal products in which several identifiable low molecular weight compounds with antioxidant activity are liberated and activated. The principal features of the treatment protocol included heating at 80-95 degrees C with continuous manual stirring in an oriental pottery vessel over a Japanese traditional oven, subsequent brewing with Koji (Aspergillus oryzae), and final emulsification in sesame oil. These products were named AOA (antioxidant analogues) or B-H (Bio-harmony). AOA and B-H were markedly effective both in scavenging the reactive oxygen species (ROS) generated and in inhibiting lipid peroxidation; they also significantly reduced both adjuvant- and adriamycin-induced paw oedema in rats. These agents were strikingly effective in ameliorating a variety of inflammatory diseases in patients and caused a fall in their serum lipid peroxide levels. Significant levels of several low molecular weight antioxidant compounds such as flavoprotein and carotene were directly detected by analysis of the treated products. The authors conclude that the procedures are useful and effective for potentiating the bioavailability of pharmacologically active natural products.

Adult↗
PubMed1987

Quantitative analysis of sterols in serum by high-performance liquid chromatography. Application to the biochemical diagnosis of cerebrotendinous xanthomatosis.

A method for the simultaneous determination of 5 alpha-cholestan-3 beta-ol and cholesterol in serum by high-performance liquid chromatography was developed. After addition of internal standard (5 beta-cholestan-3 alpha-ol) and saponification with ethanolic potassium hydroxide, the sterols were converted into their benzoyl derivatives, which were subjected to reversed-phase liquid chromatography with ultraviolet detection at 228 nm. Only 0.1 ml of serum was needed to give a reproducible result. This method has been used for the biochemical diagnosis of cerebrotendinous xanthomatosis, a hereditary disorder of cholesterol metabolism.

Benzoates↗
PubMed1987

Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics.

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). In order to determine whether normocholesterolemic diabetics are at a higher risk of atherosclerosis, cholesterol concentrations in three subclasses of triglyceride-rich lipoprotein fraction (Sf 12-400) were examined. Their plasma triglyceride and cholesterol levels were limited to below 150 and 250 mg/dl, respectively. They were divided into 3 groups according to their treatment: insulin injection (group I), sulphonylurea (group S) and diet alone (group D). Age-matched healthy normolipidemic non-obese subjects served as controls (group C). Triglyceride-rich lipoproteins were separated by ultracentrifugation: very low density lipoprotein (VLDL), Sf 60-400; intermediate density lipoprotein (IDL1), Sf 20-60; IDL2; Sf 12-20. Cholesterol concentrations in total plasma, VLDL, IDL2 and high density lipoprotein (HDL) were all identical in every group. A significant increase in cholesterol concentration was found in IDL1 of groups S and D. Low density lipoprotein-cholesterol of group I was also increased. These findings indicate an increased risk factor in normolipidemic diabetics.

Adult↗