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R Hirano

Publications and source records attributed to R Hirano.

At least 19 recordsLinked to original sources
PubMed2001

Regulation by long-chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells.

Cholesteryl ester transfer protein (CETP) is an important determinant of lipoprotein function, especially high density lipoprotein (HDL) metabolism, and contributes to the regulation of plasma HDL levels. Since saturated and polyunsaturated fatty acids (FA) appear to influence the CETP activity differently, we decided to investigate the effects of FA on the expression of CETP mRNA in HepG2 cells using an RNA blot hybridization analysis. Long-chain FA (>18 carbons) at a 0.5 mM concentration were added to the medium and incubated with cells for 48 h at 37 degrees C under 5% CO2. After treatment with 0.5 mM arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA), the levels of CETP mRNA were less than 50% of the control levels (AA, P = 0.0005; EPA, P < 0.01; DHA, P < 0.0001), with a corresponding significant decrease in the CETP mass. These results suggest that FA regulate the gene expression of CETP in HepG2 and this effect is dependent upon the degree of unsaturation of the acyl carbon chain in FA.

Arachidonic Acid↗
PubMed2001

Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection.

OBJECTIVES: This study was done to elucidate the effects of interleukin (IL)-1 gene polymorphisms on coronary artery disease (CAD) associated with Chlamydia pneumoniae (CP) infection. BACKGROUND: It was suggested that CP was associated with CAD. However, genetic factors involved in CAD associated with CP infection are unknown. METHODS: We evaluated CP immunoglobulin G (IgG) seropositivity and IL-1 beta (a C/T transition at -511) and IL-1 receptor antagonist (IL-1Ra) (a variable-number repeat in intron 2) gene polymorphisms in 292 patients undergoing coronary angiography. RESULTS: Seropositivity for CP was present in 61% of patients with CAD versus 51% without CAD (p = NS). The percentage of patients having IL-1 beta (-511) C/C genotype and/or IL-1Ra (intron 2) 2- or 3-repeat allele was higher in patients with CAD than without CAD (29 vs. 16%, p < 0.025). To clarify the effects of these CAD-associated variants (IL-1 beta C/C and/or IL-1Ra 2- or 3-repeat), patients were divided into four groups. A stepwise increase in CAD prevalence was observed depending on CP seropositivity and the variants. Odds ratios (ORs) for CAD were 1.4 in the group with seropositivity alone, 1.7 with the variants alone and 3.8 with seropositivity and the variants. Such variants were associated with CAD in both patients with and without seropositivity. Interestingly, high prevalence of myocardial infarction (MI) was confined to the group with seropositivity and the variants (OR, 2.8). The variants were associated with MI only in patients with CP seropositivity. CONCLUSIONS: The IL-1 gene polymorphisms were found to play a role in the development of CAD, especially MI, in patients with CP infection.

Aged↗
PubMed2001

[Effects of aging on oxidisability of low density lipoprotein].

Oxidised LDL is taken up by macrophages via scavenger receptors, leading to foam cell formation and is thus considered to contribute to atherogenesis. Aging results in the increase of lipids and the decrease of antioxidant enzyme activity in serum. In this study, we investigated the effects of aging on LDL oxidisability. We measured LDL oxidation lag time, plasma lipids, albumin and uric acid were examined in 306 Japanese (169 men, 137 women). The mean +/- SE of LDL oxidation-lag time in subjects was 58.9 +/- 1.0 min. The lag time (80.3 +/- 4.8 min) was longest in subjects in their 20 s and shortest in those in their 40 s (58.9 +/- 1.0 min). The longest lag time was in second-decade men (88.9 +/- 6.2 min) and shortest in fourth-decade women (50.7 +/- 2.2 min), and these results were similar even excluding subjects with abnormal biochemical data (total cholesterol, triglyceride, GOT, GPT, gamma GTP, creatinine and glucose). We analyzed the effects of various factors on lag time using multiple linear regression. Aging, uric acid and LDL-cholesterol significantly influenced lag time. Our results suggest that LDL oxidisability might been regulated by aging, changes in LDL-cholesterol with aging and variations in physical antioxidant function.

Adult↗
PubMed2001

Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation.

Flavonoids, a group of polyphenolic compounds, exist naturally and serve as antioxidants in vegetables, fruits, and so on. The inhibition of low density lipoprotein (LDL) oxidation may be an effective way to prevent or delay the progression of atherosclerosis. In the present study, we analyzed the radical scavenging capacity of 10 flavonoids (catechin, epicatechin [EC], epigallocatechin [EGC], epicatechin gallate [ECg], epigallocatechin gallate [EGCg], myricetin, quercetin, apigenin, kaempferol, and luteolin) toward 1,1-diphenyl-2-picryl-hydrazyl [DPPH]. After 20 min of incubation, EGCg was the most effective DPPH radical scavenger, luteolin being the least active of this flavonoid group. The mutual antioxidant effect of flavonoids with alpha-tocopherol (alpha-toc) on LDL oxidizability was investigated by using the lipophilic azo radical initiator 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) [AMVN-CH3O]. An inhibitory effect of flavonoids on LDL oxidation was observed in the order of luteolin>ECg>EC>quercetin>catechin>EGCg>EGC>myricetin>kaempferol> apigenin. The shortened lag time induced by higher doses of alpha-toc (6 mg/100 mL) was restored by flavonoids. These results suggest that 1) radical trapping effects of flavonoids differ according to their structure, and 2) flavonoids act as hydrogen donors to alpha-toc radical; furthermore, by interaction with alpha-toc, they have a greater potential to delay the oxidation of LDL.

Antioxidants↗
PubMed2000

Identification of a two-component signal transduction system involved in fimbriation of Porphyromonas gingivalis.

Porphyromonas gingivalis, a periodontopathogen, is an oral anaerobic gram-negative bacterium with numerous fimbriae on the cell surface. Fimbriae have been considered to be an important virulence factor in this organism. We analyzed the genomic DNA of transposon-induced, fimbria-deficient mutants derived from ATCC 33277 and found that seven independent mutants had transposon insertions within the same restriction fragment. Cloning and sequencing of the disrupted region from one of the mutants revealed two adjacent open reading frames (ORFs) which seemed to encode a two-component signal transduction system. We also found that six of the mutants had insertions in a gene, fimS, a homologue of the genes encoding sensor kinase, and that the insertion in the remaining one disrupted the gene immediately downstream, fimR, a homologue of the response regulator genes in other bacteria. These findings suggest that this two-component regulatory system is involved in fimbriation of P. gingivalis.

Amino Acid Sequence↗
PubMed2000

Acute myocardial infarction in a patient with anomalous left coronary artery origin and primary antiphospholipid syndrome.

Anomalous left main coronary artery (LMCA) originating from the right coronary sinus and running between the aorta and pulmonary trunk is a rare congenital condition. Although this disease is known to be associated with myocardial infarction and sudden death, the precise mechanism is uncertain. A 14-year-old male with this anomaly developed myocardial infarction during exercise complicated by primary antiphospholipid syndrome. He was admitted to hospital with persistent chest pain and sudden cardiac collapse that occurred while he was running. Cardiac catheterization demonstrated a narrowed segment in the LMCA and impaired blood flow, prompting a diagnosis of extensive anterior myocardial infarction. Emergency bypass surgery was performed using a single saphenous vein graft to the left anterior descending artery. Postoperative angiography showed the presence of an anomalous LMCA arising from the right sinus of Valsalva and running between the great vessels. The aortic samples were pathologically normal. He was discovered to also have primary antiphospholipid syndrome and was discharged without symptoms after warfarin therapy. Complicated primary antiphospholipid syndrome may trigger myocardial infarction in asymptomatic patients with this type of coronary anomaly.

Acute Disease↗
PubMed2000

Antioxidant effects of polyphenols in chocolate on low-density lipoprotein both in vitro and ex vivo.

Cacao is rich in polyphenols such as (-)-epicatechin, and a colored component of cacao (cacao-red) is polyphenol, which is an antioxidant. These properties stimulated an investigation of the effects of cacao liquor polyphenols (CLP) on low-density lipoprotein (LDL) oxidation. The 2.2 '-azobis(4-methoxy-2,4-dimethylvaleronitrile) (AMVN-CH2O)-induced oxidizability of LDL was assessed by monitoring the absorbance at 234 nm. In vitro. 0.1-0.5 mg/dL CLP prolonged the oxidation lag time of LDL in a dose-dependent manner. Compared with the controls, it was prolonged 1.7-fold in the presence of 0.1 mg/dL CLP, 2.9-fold at 0.2 mg/dL, 3.8-fold at 0.3 mg/dL, 5.4-fold at 0.4 mg/dL, and 6.4-fold at 0.5 mg/dL. Furthermore, we enlisted 13 male volunteers to consume 35 g delipidated cocoa. Venous blood samples were taken before and at 2 h and 4 h after consuming the cocoa. The oxidation lag time of LDL before cocoa ingestion was 59.0 +/- 6.3 min, but it was prolonged at 2 h after cocoa (68.3 +/- 6.0 min); before returning to the initial lag time (61.7 +/- 5.7 min) before consumption. Thus we have shown that cocoa inhibited LDL oxidation both in vitro and ex vivo.

Adult↗
PubMed2000

Effects of cacao liquor polyphenols on the susceptibility of low-density lipoprotein to oxidation in hypercholesterolemic rabbits.

The effects of cacao liquor polyphenols (CLP) on the susceptibility of low-density lipoprotein (LDL) to oxidation in hypercholesterolemic rabbits were examined. Six Japanese white rabbits which had been fed a high cholesterol diet (HCD) for 3 weeks were fed HCD containing 1% CLP for the following 10 days. The susceptibility of LDL to oxidation induced by 2-2'-azobis(4-methoxy-2, 4-dimethylvaleronitrile) (V-70) was evaluated by measuring the production of conjugated dienes and thiobarbituric acid reactive substances (TBARS). The lag time was significantly prolonged from 37.7 min before intake of CLP to 42.9, 44.2 and 45.8 min after 4, 7 and 10 days of CLP intake. TBARS production after intake of CLP was also markedly reduced compared with the level before intake. There was no difference in plasma lipid concentrations comparing the levels before and after CLP intake. In conclusion, in hypercholesterolemic rabbits, orally administered CLP was absorbed and distributed to the blood, and the resistance of LDL to oxidation was thereby increased.

Animals↗
PubMed2000

Inhibition of low-density lipoprotein oxidation by astaxanthin.

Marine animals produce astaxanthin which is a carotenoid and antioxidant. In this study we determined the in vitro and ex vivo effects of astaxanthin on LDL oxidation. The oxidation of LDL was measured in a 1 ml reaction system consisting of increasing concentrations of astaxanthin (12.5, 25.0, 50.0 microg/ml), 400 microM V-70 (2, 2'-azobis(4-methoxy-2, 4-dimethylvaleronitrile)), and LDL (70 microg/ml protein). Astaxanthin dose, dependently significantly prolonged the oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min). For the ex vivo study 24 volunteers (mean age 28.2 [SD 7.8] years) consumed astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg per day for 14 days. No other changes were made in the diet. Fasting venous blood samples were taken at days 0, +14. LDL lag time was longer (5.0, 26.2, 42.3 and 30.7% respectively) compared with day 0 after consuming astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg for 14 days compared with day 0, but there was no difference in oxidation of LDL between day 0 (lag time 59.9+/-7.2 min) and day 14 (57.2+/-6.0 min) in the control group. Our results provide evidence that consumption of marine animals producing astaxanthin inhibits LDL oxidation and possibly therefore contributes to the prevention of atherosclerosis.

Adult↗
PubMed1999

The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.

Citrullinaemia (CTLN) is an autosomal recessive disease caused by deficiency of argininosuccinate synthetase (ASS). Adult-onset type II citrullinaemia (CTLN2) is characterized by a liver-specific ASS deficiency with no abnormalities in hepatic ASS mRNA or the gene ASS (refs 1-17). CTLN2 patients (1/100,000 in Japan) suffer from a disturbance of consciousness and coma, and most die with cerebral edema within a few years of onset. CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21). We collected 118 CTLN2 families, and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. Using positional cloning we identified a novel gene, SLC25A13, and found five different DNA sequence alterations that account for mutations in all consanguineous patients examined. SLC25A13 encodes a 3.4-kb transcript expressed most abundantly in liver. The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function.

Adult↗
PubMed1997

Efficient transfer of synthetic ribozymes into cells using hemagglutinating virus of Japan (HVJ)-cationic liposomes. Application for ribozymes that target human t-cell leukemia virus type I tax/rex mRNA.

We investigated the usefulness of ribozymes in inhibiting the expression of human T-cell leukemia virus type I (HTLV-I) gene. Two hammerhead ribozymes that were against HTLV-I rex (RR) and tax (TR) mRNA were synthesized. Both ribozymes were sequence-specific in the in vitro cleavage analysis of run-off transcripts from tax/rex cDNA. Intracellular activities of the ribozymes were studied in HTLV-I tax cDNA-transfected rat embryonic fibroblasts (Rat/Tax cells), which expressed the Tax but not Rex. Ribozymes were delivered into cells using anionic or cationic liposomes fused with hemagglutinating virus of Japan (HVJ). Cellular uptake of ribozymes complexed with HVJ-cationic liposomes was 15-20 times higher cellular uptake than naked ribozymes, and 4-5 times higher than that of ribozymes complexed with HVJ-anionic liposomes. HVJ-cationic liposomes promoted accumulation of ribozymes in cytoplasm and accelerated transport to the nucleus. Tax protein levels were decreased about 95% and were five times lower when the same amount of TR was introduced into the cells using HVJ-cationic, rather than HVJ-anionic liposomes. Inactive ribozyme and tax antisense oligodeoxynucleotides reduced Tax expression by about 20%, whereas RR and tax sense oligodeoxynucleotides had no effect. These results suggest that the ribozymes' effect against tax mRNA was sequence-specific, and HVJ-cationic liposomes can be useful for intracellular introduction of ribozymes.

Animals↗
PubMed1997

Effects of antioxidants on the oxidative susceptibility of low-density lipoprotein.

An important event in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low-density lipoprotein (LDL) initiated by a free radical-driven lipid peroxidation process. Vitamin E acts as a lipophilic chain-breaking antioxidant, while water-soluble chain-breaking antioxidants such as vitamin C or uric acid suppress the oxidation of LDL initiated by aqueous radicals. In this study, we established a new method of measuring the lag time of inhibited lipid peroxidation using the lipophilic azo radical initiator V-70:2-2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) and investigated in vitro the susceptibility of LDL to oxidation using this method when lipid- and water-soluble antioxidants were added. When the lipid-soluble antioxidant, vitamin E, was added to LDL, the lag time was extended whereas a higher dose of vitamin E led to a shortened lag time of V-70-induced lipid peroxidation in LDL. These results suggest that vitamin E radicals (tocopheroxyl radicals) act as prooxidants during the autoxidation of LDL. It was also shown that the shortened lag time induced by higher doses of vitamin E was restored when lipid- and water-soluble antioxidants were added simultaneously, which suggests that vitamin E radicals derived from vitamin E are subsequently reduced by vitamin C to regenerate vitamin E. Thus, the interaction between lipid- and water-soluble antioxidants provides an important function in maintaining LDL resistance to oxidation.

Adult↗
PubMed1997

Factors affecting longevity.

In view of the fact that hypercholesterolemia occurs in 31.4%, hypertension in 16.7% and the smoking rate is 58.8% in males (Table 8), risk factors are not low. Despite this, we Japanese preserve a leading position regarding longevity. I hope that I have provided some evidence supporting the proposal that apparently not only a low fat intake but other factors including genetic make up and a relatively high antioxidant intake contribute to our longevity.

Antioxidants↗
PubMed1994

Clinical experience with Nikkiso centrifugal pumps for extracorporeal circulation.

A comparative study of a newly developed impeller-type centrifugal pump, Nikkiso HMS-15, was made to assess the effects on hemolysis, platelet function, and renal function for extracorporeal circulation (ECC) during open heart surgery. The Bio-pump (cone-type, Medtronic) and the roller pump were used as controls. The increase of serum hemoglobin level in the Nikkiso pump was significantly lower than that in the other pumps. The decrease of platelet counts was recognized after the initiation of ECC in the three pumps whereas the levels of platelet factor 4 and beta-thromboglobulin in the Nikkiso pump group increased by far less than in the other two groups. Moreover, renal function was better maintained in the Nikkiso pump group; in particular, a significantly higher urine output was recorded during ECC and for 1 h after the termination of ECC. The results of our clinical studies suggest that the Nikkiso centrifugal pump is suitable for ECC during open heart surgery.

Extracorporeal Circulation↗
PubMed1975

[Red tide].

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Dinoflagellida↗