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Biomedical subjects

E Maeda

Publications and source records attributed to E Maeda.

At least 37 records · Page 2Linked to original sources
PubMed1995

[The measurement of blood lactate concentration and its age change in days on healthy infant].

We measured the lactate concentration in whole blood of healthy infant with use of the recently developed assay system consisting of an enzyme-coated electrode and a small meter. The mean values of blood lactate concentration at each age in days were not showed the significant difference between male and female infants. The trace of lactate concentration change in days showed the peak at the age in 1 days and then, gradually decreased to the almost constant level at the age in 6 days after. At the age in 6-7 days, the concentration mean values of infants, born in 38-40 gestational weeks were lower than that of 37 and 41 weeks one. It was assumed by mathematically that these equilibrium constant level of the lactate concentration in early neonatal period was arrived at 6.20 days and the equilibrium level was estimated to 1.29 mmol/l. As the results, the normal ranges were calculated to the value of 0.49-3.95 mmol/l as initial (age in 0-3 days) and that of 0.29-2.92 mmol/l as final (age in 6-7 days) period, by the truncation method, respectively.

Aging↗
PubMed1995

Two novel point mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in LCAT deficiency: LCAT (G873 deletion) and LCAT (Gly344-->Ser).

We investigated the genetic defects in two patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. Their clinical manifestations including corneal opacities, anemia, proteinuria, and hypoalphalipoproteinemia were identical for familial LCAT deficiency. Their LCAT activities and the cholesterol esterification rate (CER) were nearly zero, and their LCAT masses were below 10% of normal control values. Sequence analysis of the amplified DNA of case 1 revealed one base deletion of G at base 873 (first position of Val264) in exon 6, leading to a premature termination by frameshift. Sequence analysis of amplified DNA of case 2 revealed a single G to A converting Gly (GGT) to Ser (AGT) substitution at residue 344. When COS-1 cells were transfected with these mutants, LCAT activity in the medium was nearly zero, and the LCAT mass was undetectable (< 0.01 microgram/ml). In contrast, LCAT activity in the medium of COS-1 cells, transfected with wild-type LCAT, was 1.7 nmol/h per ml and the LCAT mass was 0.09 micrograms/ml. The LCAT mass in the cell lysates of the mutants was less than 12% of control for case 1 and 18% of control for case 2. Northern blot analysis of the mRNA of COS-1 cells transfected with the mutants showed the same amounts of LCAT mRNA as compared with wild-type LCAT. Biosynthesis of mutant LCATs was analyzed by pulse-chase and immunocytochemistry in transfected baby hamster kidney cells. SDS-PAGE/fluorography demonstrated that wild-type LCAT was synthesized as a high-mannose type of 56 kDa, which was very slowly converted to a mature form of 67 kDa and was secreted into the media. In contrast to the wild-type LCAT, the mutant precursors were not processed into the mature form but slowly degraded along with chase times. On steady and continuous labeling in the case of wild-type LCAT, the mature 67 kDa form was observed in both the cell lysate and media, whereas no mature form was detected in the cell lysates and media which were transfected mutant LCATs. These data suggest that the mutant LCATs are actually synthesized in an amount comparable to that of wild-type, but they are slowly degraded without being processed into the mature form. The immunocytochemistry revealed that mutant LCATs were mainly retained in the endoplasmic reticulum. These data suggest that these two mutations may disrupt the mutant LCATs' transport from the endoplasmic reticulum into Golgi apparatus, resulting in LCAT deficiency.

Adult↗
PubMed1994

Effect of long-term administration of probucol on triglyceride turnover in rats.

BACKGROUND: Our previous observation revealed that probucol, a well known cholesterol-lowering drug, can improve impaired catabolism of plasma triglyceride in streptozotocin-diabetic rats without reducing plasma glucose. The present study was conducted using Triton WR1339 and endogenously radiolabeled lipoproteins in order to examine the mechanisms whereby the drug can stimulate triglyceride removal from the circulation in rats independent of glucose metabolism. METHODS: The short- and long-term effects of probucol on triglyceride turnover were examined in rats. Male Wistar rats received a diet containing probucol (1%) for 2 weeks and 4 months. Triglyceride turnover was estimated in rats using Triton WR1339. RESULTS: After 2 weeks of probucol administration, triglyceride and cholesterol concentrations in plasma and in the very-low-density lipoprotein (VLDL) fraction were suppressed slightly but significantly in the probucol-administered rats compared with standard chow-fed control rats. However, triglyceride secretion rates were similar in the two groups. Probucol-administered rats showed markedly suppressed triglyceride concentration in plasma and the VLDL fraction compared with chow-fed control rats after 4 months of administration. However, triglyceride secretion rate was significantly increased in rats given probucol. The radioisotope experiment revealed that probucol-administered rats can remove VLDLs (lipoproteins either from probucol-administered or control rats) from their system faster than normal rats and that probucol-containing VLDL can be removed from the circulation of both groups of rats more rapidly than normal VLDL. Therefore, probucol-administered rats as well as probucol-containing VLDL (lipoprotein from probucol-administered rats) are responsible for accelerated catabolism of VLDL-triglyceride. CONCLUSION: No significant differences in the lipid composition of newly-secreted VLDL particles between control rats and those given probucol were noted after Triton injection. The precise mechanism behind increased triglyceride secretion rate in rats after long-term administration of probucol is not known. However, we concluded from the present data that long-term administration of probucol results in markedly accelerated VLDL-triglyceride turnover without affecting lipid composition of newly secreted VLDL particles in normal rats.

Animals↗
PubMed1994

Hepatitis C virus RNA and anti-N14 antibody levels during interferon alpha therapy for chronic hepatitis C.

To investigate the markers useful for evaluating the long-term efficacy of interferon (IFN) therapy, the quantity of hepatitis C virus (HCV) RNA and two anti-HCV antibody titers (anti-N14 and anti-C-100-3 antibody) in 21 chronic hepatitis C patients were determined. In all complete responders, a sustained clearance of the virus and reductions in the anti-HCV antibody titers were observed during and after therapy. In most of the temporary responders, reductions in the HCV RNA levels and in both anti-HCV antibody titers were observed temporarily during the therapy, and relapse followed. In nonresponders, although the HCV RNA levels and anti-N14 antibody titer tended to remain unchanged or increased during and after therapy, the anti-C-100-3 antibody titers showed no tendency. These results demonstrate that the monitoring of the HCV RNA level and anti-N14 antibody titer is clinically useful for following the patient's response to IFN therapy for chronic hepatitis C.

Antigens, Viral↗
PubMed1994

Japanese family with a deficiency of lecithin:cholesterol acyltransferase (LCAT).

We present findings in the ninth known Japanese family with lecithin:cholesterol acyltransferase (LCAT) deficiency. A 54-year-old man (proband) and his 58-year-old brother presented with corneal opacity. Both subjects showed a marked decrease in serum high density lipoprotein (HDL)-cholesterol and in the cholesteryl ester ratio. Although apo A-I and A-II were low, apo E tended to be high. Serum LCAT activity and mass were not detectable. Urinary examination showed microhematuria or proteinuria. Renal function was normal and no anemia was demonstrated, but blood smears showed poikilocytosis with target cells. The serum LCAT activity of the proband's three sons, obligate heterozygotes of LCAT deficiency, was about one-half the normal level, and HDL-cholesterol and apo A-I levels were low normal.

Adult↗
PubMed1993

Development of a specific enzyme-linked immunosorbent assay for the hepatitis C virus antibody using clone 14.

The authors isolated a specific cDNA clone (clone 14) for non-A, non-B hepatitis virus infection. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) using a synthetic oligopeptide encoded by clone 14 and examined its usefulness for detecting hepatitis C virus (HCV) antibody in 181 patients with chronic NANB hepatitis, 88 with cirrhosis and 24 with hepatocellular carcinoma associated with NANB hepatitis virus. Anti-clone 14 antibody was detected in 75% of patients with chronic NANB hepatitis, 57% of cirrhotic patients and 58% hepatocellular carcinoma patients. Anticlone 14 and anti-C-100 antibody assayed using a commercial kit were found in serum from 199 (69%) and 205 (70%) of these 294 patients, respectively. Approximately 85% of the patients showed the presence of anticlone 14 and/or anti-C-100 antibodies. We compared the presence of these antibodies and the second generation anti-HCV antibody using ELISA and HCV RNA by the polymerase chain reaction assay, in the same blood samples from 49 patients with chronic liver disease who had anti-clone 14 and/or anti-C-100 antibody. HCV RNA was detected in 38 of 40 (95%) plasma samples containing anti-clone 14 antibody, the prevalence of which was similar to that for anti-C-100 antibody (41/42, 98%) and the second generation anti-HCV antibody (46/47, 98%). Furthermore, 6 of 7 plasma samples containing anti-clone 14 antibody and lacking anti-C-100 antibody were positive for the second generation anti-HCV antibody and HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Effect of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on triglyceride kinetics in chronically streptozotocin-diabetic rats.

The effect of simvastatin (MK-733, Banyu, Tokyo, Japan), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on triglyceride kinetics, was studied in chronically streptozocin-diabetic rats. Diabetic rats, in whom diabetes was induced by a single intravenous injection of streptozotocin (40 mg/kg body weight) 2 months before the experiment, had significantly higher plasma glucose, triglyceride, and cholesterol levels compared with nondiabetic control rats, but triglyceride secretion rate was not increased. Both triglyceride secretion rate and plasma triglyceride level were significantly suppressed under nonfasting conditions in diabetic rats fed a (0.1%) simvastatin-containing diet for 10 days. After an overnight fast, their triglyceride secretion rate was not suppressed by this diet. However, their plasma triglyceride level was significantly (50%) suppressed, suggesting improved triglyceride removal from the circulation. In diabetic rats, the newly secreted triglyceride-rich lipoprotein particles were significantly cholesterol-enriched, but simvastatin had no effect on their lipid composition. These results suggest that the hypertriglyceridemia seen in chronically diabetic rats is mainly due to a triglyceride-removal defect, and that simvastatin reduces plasma triglyceride levels in these rats both by stimulating triglyceride removal and by reducing its entry into the circulation.

Animals↗
PubMed1993

Hypertriglyceridemia in nephrotic rats is due to a clearance defect of plasma triglyceride: overproduction of triglyceride-rich lipoprotein is not an obligatory factor.

This study was conducted to determine whether overproduction of triglyceride-rich lipoprotein is an obligatory factor for experimental hypertriglyceridemia in nephrotic rats. Nephrosis was induced in male Wistar rats by administration of 150 mg/kg puromycin aminonucleoside. Nephrotic rats had slightly increased triglyceride secretion rate (TGSR) estimated using Triton WR1339 (0.53 +/- 0.05 vs. 0.45 +/- 0.04 mg/min, P < 0.05 vs. control rats) and marked hypertriglyceridemia (330.4 +/- 78.6 mg/dl). Rats made diabetic by 40 mg/kg streptozotocin were normotriglyceridemic (66.3 +/- 12.1 mg/dl) but had suppressed TGSR (0.33 +/- 0.09 mg/min). Experimental nephrosis was induced in diabetic rats. Their TGSR remained suppressed (0.35 +/- 0.06 mg/min) but they had marked hypertriglyceridemia (296.6 +/- 72.4 mg/dl) suggesting further impairment of triglyceride removal from the circulation in diabetic rats caused by nephrosis. Endogenously radiolabeled very low density lipoprotein (VLDL)-triglyceride from donor rats was reinjected into normal recipient rats. [3H]VLDL from the experimental groups (the rats with nephrosis, diabetes with nephrosis, and diabetes alone) were more slowly cleared by normal rats than VLDL from normal rats. These results suggest that circulating insulin is essential for increased triglyceride secretion in experimental nephrosis and that nephrotic hypertriglyceridemia can be induced only by a triglyceride removal defect. Therefore, hypersecretion of triglyceride-rich lipoprotein is not an obligatory factor for nephrotic hypertriglyceridemia.

Animals↗
PubMed1993

[Diabetes mellitus as a risk factor for arteriosclerosis].

Diabetes mellitus is an important risk factor for coronary heart disease and cerebral vascular disease. Moreover, diabetic patients are frequently hyperlipidemic (our recent study has revealed that approximately 70% of diabetic patients are dyslipidemic) and are at a higher risk when complicated with hyperlipidemia. In addition, abnormalities in lipoprotein metabolism, which may promote arteriosclerosis, are seen even in normolipidemic diabetics. One such alteration is an increased cholesterol level in intermediated-density lipoproteins from normolipidemic diabetic patients. Recently, abnormal particles in low-density lipoprotein (LDL) fraction, glycated-LDL and small, dense LDL, are regarded as atherogenic lipoproteins. Several factors promoting arteriosclerosis in diabetics, such as abnormal lipoprotein metabolism, increase of lipoprotein (a), hyperinsulinemia, enhancement of polyol pathway, dysfunction of platelet, are described here.

Arteriosclerosis↗
PubMed1992

Effect of long-term insulin deficiency and insulin treatment on the composition of triglyceride-rich lipoproteins and triglyceride turnover in rats.

The effect of long-term (4 months) insulin deficiency on triglyceride turnover was examined using Triton WR1339 in rats. Triglyceride secretion rate was estimated in rats 2 weeks and 4 months after induction of diabetes with 40 mg/kg of streptozotocin. By the second week diabetic rats showed prominent hyperglycemia and the plasma insulin level was very low. In spite of a lower triglyceride secretion rate compared to non-diabetic control rats, diabetic rats showed normotriglyceridemia. Thus, the estimated fractional catabolic rate for plasma triglyceride was decreased in the diabetic rats of 2 weeks duration. By the fourth month diabetic rats still showed a suppressed triglyceride secretion rate but plasma triglyceride was markedly higher than in the non-diabetic control rats. Therefore, their estimated fractional catabolic rate for plasma triglyceride was severely suppressed. They also showed hyperglycemia and hypercholesterolemia. The triglyceride-rich lipoprotein particles obtained after Triton injection in long-term diabetic rats were significantly cholesterol-enriched and triglyceride-depleted compared to control rats. These changes were already present in 2-week diabetic rats but the magnitude was significantly smaller that those in long-term diabetic rats. All of these abnormalities (including triglyceride turnover and the particle composition) were almost normalized by 2 weeks of insulin treatment (6 units/day). Thus, it was concluded from the present data that duration of insulin deficiency is an important determinant of triglyceride removal rate from the circulation in rats. Further modification of lipid composition of triglyceride-rich lipoprotein particles by long-term insulin-deficiency could be one of the reasons for this removal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of mild diabetes and dietary fructose on very-low-density lipoprotein triglyceride turnover in rats.

Very-low-density lipoprotein (VLDL) triglyceride turnover was examined in mildly streptozotocin (25 mg/kg)-diabetic rats, using Triton WR1339. Diabetic rats fed standard rat chow showed mild hyperglycemia and suppressed levels of plasma insulin. Their triglyceride secretion was significantly suppressed despite an elevated level of plasma free fatty acids. However, the plasma triglyceride level of these diabetic rats was significantly elevated compared with nondiabetic controls. This suggested that the removal of triglyceride from the circulation, as well as its entry into the circulation, was impaired in mildly insulin-deficient rats. Glucose or fructose supplementation (10% in drinking water for 14 days) significantly increased the triglyceride secretion rate of diabetic rats. Especially, fructose supplementation increased plasma insulin to normal levels, but resulted in markedly elevated plasma triglyceride levels (three times higher than glucose-supplemented or chow-fed diabetic rats) despite similar triglyceride secretion rates between the two types of sugar-supplemented diabetic rat groups. This suggested an impairment of triglyceride removal by dietary fructose. The result obtained from chow-fed diabetic rats indicates that mild but significant insulin deficiency resulted in mild hypertriglyceridemia, linked to impaired triglyceride removal rather than to an overproduction of VLDL-triglyceride, despite elevated levels of plasma free fatty acids. Furthermore, fructose feeding induced prominent hypertriglyceridemia not only by stimulating triglyceride secretion, but also by suppressing triglyceride removal from the circulation of mildly diabetic rats.

Animals↗
PubMed1992

Effect of probucol on recovery from streptozotocin diabetes in rats.

The present study was conducted to see the effect of probucol on streptozotocin diabetes in rats. After 2 weeks of a 1% probucol diet, 35 or 50 mg/kg of streptozotocin were intravenously injected into male Wistar rats. All the rats became diabetic 2 days after treatment. Thereafter, in order to see the effect of probucol on spontaneous recovery from streptozotocin diabetes, 25 mg/kg of streptozotocin was injected into rats after two weeks of probucol diet and the diet was continued for additional two weeks. All the rats with a standard diet (group CS, n = 13) and 12 of 13 rats with probucol diet (group PS) became diabetic 2 days after streptozotocin injection. One rate from group PS did not develop diabetes. Two weeks after injection, only 4 of 13 rats in groups CS showed recovery, while 11 of 12 rats in group PS showed recovery from streptozotocin diabetes (p less than 0.05). The average blood glucose levels in group PS were significantly lower than group CS (10.5 +/- 4.6 vs 18.5 +/- 0.6 mM, p less than 0.05). In addition, the pancreatic insulin content of group PS was 8 times greater than that of group CS (0.75 +/- 0.24 vs 0.09 +/- 0.03 mmol/pancreas, p less than 0.01). Thus, the in vivo diabetogenic action of streptozotocin could not be reduced by pretreatment with probucol. However, recovery from streptozotocin diabetes was induced by subsequent treatment with probucol. The precise mechanisms for this phenomenon were not known; but the present findings suggest the protective effect of probucol on beta-cell damage induced by small dose of streptozotocin.

Animals↗
PubMed1991

Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene.

The plasma enzyme, human lecithin-cholesterol acyltransferase (LCAT) is responsible for the majority of cholesterol ester formation in human plasma and is a key enzyme of the reverse transport of cholesterol from peripheral tissue to the liver. We sequenced genomic DNA of the LCAT gene from a Japanese male patient who was clinically and biochemically diagnosed as a familial LCAT deficiency. Analysis of all exons and exon-intron boundaries revealed only a single G to A transition within the sixth exon of both allele of the gene, leading to the substitution of methionine for isoleucinle at residue 293 of the mature enzyme. This mutation creates a new hexanucleotide recognition site for the restriction endonuclease Ndel. Familial study of Ndel digestion of the genomic DNA and determination of plasma LCAT activity established that the patient and his sister whose plasma LCAT activity were extremely reduced were homozygous and his children whose plasma LCAT activity were about half of normal controls were heterozygous for this mutation.

Base Sequence↗
PubMed1991

Effect of probucol on triglyceride turnover in streptozotocin-diabetic rats.

The long-term effect of probucol on triglyceride turnover was examined in streptozotocin (40 mg/kg) diabetic rats. Two diabetic groups were prepared: one group received a probucol-containing (1%) diet (probucol-treated diabetic) and the other standard diet (diabetic control). After 4 months of probucol diet, triglyceride turnover was estimated using Triton WR1339. In diabetic control rats, glucose, triglyceride and cholesterol concentrations in plasma and in the very low density lipoprotein (VLDL) fraction were markedly elevated and plasma insulin was suppressed compared to non-diabetic control rats. There was no significant difference in body weight, plasma glucose and insulin between the 2 diabetic groups. However, the probucol-treated diabetic group showed significantly suppressed levels of triglyceride and cholesterol in total plasma and in the VLDL fraction compared to each corresponding diabetic control value. On the other hand, there were no significant differences in triglyceride secretion rate between the 2 diabetic groups. Newly secreted VLDL particles after Triton injection from diabetic control rats were significantly cholesterol-enriched and triglyceride-depleted compared to those from non-diabetic control rats. However, the composition of those from probucol-treated diabetic rats was similar to that of non-diabetic control group. Prominent hypertriglyceridemia without increase in triglyceride secretion rate in diabetic control group indicates triglyceride removal defect in diabetic rats. Significant suppression of plasma triglyceride level without changes in the triglyceride secretion rate in the probucol-treated diabetic group suggests that probucol stimulated triglyceride removal in diabetic rats. Thus, probucol might normalize VLDL composition, thereby contributing to accelerated triglyceride removal from the circulation of streptozotocin diabetic rats without affecting glucose metabolism.

Animals↗
PubMed1991

[The anti-pyretic mechanism of alminoprofen].

The anti-pyretic activity of alminoprofen (AP), a non-steroidal anti-inflammatory agent, and its mode of action were investigated in conscious febrile rabbits. A fever was evoked by i.v. injection of lipopolysaccharide (LPS), intracisternal (i.c.) injection of leukocytic pyrogen (LP) or i.c. injection of arachidonic acid (AA). The amount of PGE2 or AP in the cerebrospinal fluid (CSF) after i.v. LPS was estimated using an RIA or HPLC method. AP (3-30 mg/kg, p.o.) dose-dependently inhibited the LPS (0.5 micrograms/kg, i.v.)-induced fever; AP, ibuprofen, indomethacin and pranoprofen had ED50 values of 9.64, 26.45, 4.41 and 11.91 mg/kg, p.o., respectively. PGE2 in the CSF was markedly increased during the elevation of body temperature after i.v. LPS (0.5 microgram/kg). AP (30 mg/kg, p.o.) markedly inhibited the increase in PGE2 that was observed in the CSF during fever developed in response to i.v. LPS (0.5 micrograms/kg). The AP concentration in the CSF 2 hr after AP (30 mg/kg, p.o.) was 2.86 x 10(-6) (1.15-4.57 x 10(-6) M, a concentration too low to inhibit PG synthesis. A dose-dependent fever was observed after i.c. LP (1-8 unit) or AA (10-100 micrograms). AP (30 mg/kg, p.o.) shifted the dose-response curves for the i.c. LP-induced fever to the right, but did not have any effect on the i.c. AA-induced fever. These results suggest that AP has a relatively potent anti-pyretic activity, and its mechanism of action involves competition with LP at a site in the CNS, but does not involve an inhibition of cyclooxygenase at a central site, which has been considered as an anti-pyretic mechanism of nonsteroidal anti-inflammatory drugs.

Animals↗
PubMed1991

[Effects of alminoprofen on sodium urate crystal-induced inflammation].

Effects of alminoprofen (AP), a non-steroidal anti-inflammatory agent, were investigated using several experimental gouty models. AP (3-30 mg/kg, p.o.) dose-dependently inhibited urate crystal-induced rat paw edema. AP (3-30 mg/kg, p.o.) inhibited the accumulation of exudate and decreased the total counts of leukocytes and the amount of PGE2 in a dose-dependent manner in sodium urate crystal-induced pleuritic rats. AP (0.3-10 mg/kg, p.o.) showed a dose-related analgesic activity on the pain response in sodium urate crystal-induced arthritic rats. AP (10(-5)-10(-3)M) inhibited the sodium urate crystal-induced beta-glucuronidase release from guinea pig neutrophils at more than 10(-4) M. AP (10(-5)-10(-3)M) did not inhibit the sodium urate crystal-induced production of O2- from guinea-pig neutrophils. AP (10(-6)-10(-4) M) inhibited dose-dependently the chemotaxis of leukocytes induced by chemotactic factors from guinea pig neutrophils stimulated with sodium urate crystals. AP (10(-6)-10(-4) M) inhibited the sodium urate crystal-induced production of PGE2 from rat peritoneal leukocytes in a dose-related manner. These results suggest that AP has a potent anti-inflammatory and analgesic activity in sodium urate crystal-induced inflammations, and these effects are exerted through its combined inhibitions of PGE2 synthesis, leukocyte chemotaxis and lysosomal enzyme release.

Animals↗