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Biomedical subjects

Hiroyuki Arai

Publications and source records attributed to Hiroyuki Arai.

At least 37 records · Page 2Linked to original sources
PubMed2006

Dietary intakes and plasma 8-iso-prostaglandin F2alpha concentrations in community-dwelling elderly Japanese: the Tsurugaya project.

We examined the association between dietary intakes and oxidative stress status in elderly Japanese. We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment conducted in 2002. The subjects included 961 Japanese subjects aged 70 years or older who were non-daily antioxidant supplements users. We measured plasma total 8-iso-prostaglandin (PG)F(2alpha) concentrations, a measurable lipid peroxidation biomarker, using a specific enzyme immunoassay kit. Dietary intakes were assessed through a food frequency questionnaire. Subjects were divided into three groups according to their dietary intake frequencies. Logistic regression was applied to calculate the odds ratios (ORs) for being in the highest tertile of plasma 8-iso-PGF(2alpha) concentration. Frequent intake of orange or other citrus fruits, or persimmon, strawberry, or kiwi fruit was associated with lower plasma 8-iso-PGF(2alpha) concentrations, respectively. After adjustment for potential confounders, the ORs and 95% confidence intervals (CIs) for orange or other citrus fruits were 1.00 (reference), 0.66 (0.47, 0.92), and 0.58 (0.39, 0.87) (p for trend, 0.009). Intake of persimmon, strawberry, or kiwi fruit showed similar results. These associations were partly explained by vitamin C intake. Other dietary intakes had no association. Intake of fruits may have a beneficial effect against oxidative stress in elderly Japanese.

Age Factors↗
PubMed2006

Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.

Aged↗
PubMed2006

A novel sulfotransferase abundantly expressed in the dauer larvae of Caenorhabditis elegans.

We have isolated a gene (clone Y113G7A.11) from Caenorhabditis elegans (C. elegans), that we have designated as ceST1, and which is the only member of the cytosolic sulfotransferase (SULT) gene family present in the genome of this organism. We identified the SULT motifs of ceST1 based upon their deduced amino acid sequence, and subsequently expressed the ceST1 cDNA in Escherichia coli and characterized its enzymatic properties. The recombinant protein showed sulfation activity for 4-nitrophenol and 2-naphthol substrates, but did not catalyze the sulfation of either monoamines or hydroxysteroids. Another compound sulfated by ceST1 is bisphenol A, which is known to stimulate germ cell proliferation in C. elegans. SULT activity was not detected in the cytosol of C. elegans, probably due to heat labile inhibitors. The ceST1 protein was detectable in the cytosol of C. elegans using anti-sera raised against recombinant ceST1, and transcripts could also be detected throughout the developmental stages. Moreover, high levels of ceST1 expression were evident at both the embryonic and adult stages and were augmented in dauer larva. These findings suggest that this sulfotransferase either forms part of a defence system against xenobiotics or regulates germ cell proliferation in C. elegans.

Amino Acid Sequence↗
PubMed2006

Analysis of PPAR alpha function in human kidney cell line using siRNA.

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPARalpha is mainly expressed in the liver, kidney, heart and muscle. PPARalpha activates fatty acid catabolism, stimulates gluconeogenesis and ketone body synthesis and is involved in the control of lipoprotein assembly. Although PPARalpha is well characterized in the liver, its physiological function is unknown in the kidney. To investigate the intimate function of PPARalpha in the kidney, we analyzed the target gene expression in human metastatic renal cell carcinoma cell line, Caki-1, using small interfering RNA (siRNA) against PPARalpha and real-time RT-PCR methods. We found that some selected genes (long-chain fatty-acid-CoA ligase (FACL1), carnitine palmitoyltransferase 1A (CPT1A), adipose differentiation-related protein (ADRP) and aquaporin 3 (AQP3)) were down-regulated by PPARalpha siRNA. These results suggest that PPARalpha regulates fatty acid metabolism and body water homeostasis in this cell line.

Body Water↗
PubMed2006

Effects of menthol on the triggering of the swallowing reflex in elderly patients with dysphagia.

AIMS: To investigate the effect of menthol on swallowing reflex sensitivity in elderly patients with dysphagia. METHODS AND RESULTS: The swallowing reflex sensitivity of institutionalized elderly patients was evaluated as a latent time of swallowing reflex (LTSR), induced by the injection of 1 ml solution into the pharynx. LTSR was significantly shortened in a concentration-dependent manner, from 13.8 s [95% confidence interval (CI) 11.1, 16.5] by distilled water to 9.4 s (95% CI 7.1. 11.8) by 10(-2)m menthol. CONCLUSION: Using menthol with elderly patients with dysphagia may improve the sensitivity of their swallowing reflex, resulting in prevention of aspiration pneumonia.

Aged, 80 and over↗
PubMed2006

Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels.

Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of neutropenia in hematologic disorders. The neuroprotective effects of G-CSF were reported in neurological disease models. In the present study, we examined whether G-CSF can protect dopaminergic neurons against MPTP-induced cell death in a mouse model of Parkinson's disease. Mice of one group were injected intraperitoneally with MPTP for five consecutive days, those of another group with MPTP and intraperitoneal G-CSF at 2 days and 1 day before the first MPTP injection, and 30 min before each MPTP injection, while control mice received saline injections. Immunohistochemistry, western blotting analysis, and HPLC were performed to evaluate damage of substantia nigra dopaminergic neurons and expression of Bcl-2 and Bax protein. MPTP induced dopaminergic cell death in the substantia nigra. G-CSF significantly prevented MPTP-induced loss of tyrosine hydroxylase-positive neurons (p < 0.05), increased Bcl-2 protein and decreased Bax protein expression. Our findings indicate that G-CSF provides neuroprotection against MPTP-induced cell death and this effect is mediated by increasing Bcl-2 expression levels and decreasing Bax expression levels in C57BL/6 mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction.

OBJECTIVES: To determine the effect of olfactory stimulation with volatile black pepper oil (BPO) on risk factors for pneumonia. DESIGN: A 1-month randomized, controlled study. SETTING: Nursing homes in Japan that serve as long-term care facilities for older residents who are physically handicapped, mainly because of cerebrovascular disease. PARTICIPANTS: One hundred five poststroke residents. MEASUREMENTS: Latency of the swallowing reflex (LTSR), the number of swallowing movements, serum substance P (SP), and regional cerebral blood flow (rCBF). RESULTS: Nasal inhalation of BPO for 1 minute shortened LTSR, compared with that of lavender oil and distilled water (P < .03). Compared with the period before the study, the 1-month intervention using BPO improved LTSR with an increase of serum SP (P < .01). The number of swallowing movements for 1 minute during the nasal inhalation of BPO increased (P < .001). Multiple comparisons showed a poststudy increase in rCBF within the insular cortex (P < .001). Compared with the prestudy rCBF, BPO intervention increased rCBF in the right orbitofrontal and left insular cortex (P < .001). CONCLUSION: Inhalation of BPO, which can activate the insular or orbitofrontal cortex, resulting in improvement of the reflexive swallowing movement, might benefit older poststroke patients with dysphagia regardless of their level of consciousness or physical and mental status.

Aged↗
PubMed2006

Role of two 2-oxoglutarate:ferredoxin oxidoreductases in Hydrogenobacter thermophilus under aerobic and anaerobic conditions.

Hydrogenobacter thermophilus TK-6 is a thermophilic, hydrogen-oxidizing bacterium that fixes carbon dioxide as a sole carbon source via the reductive tricarboxylic acid cycle. 2-Oxoglutarate:ferredoxin oxidoreductase (OGOR) is one of the key enzymes in the pathway. Strain TK-6 has at least two isozymes of OGOR, namely For and Kor. These OGORs showed different expression patterns under aerobic conditions than under anaerobic conditions. In this work, we developed a homologous recombination method for Hydrogenobacter, and constructed a For mutant and a Kor mutant. Observation of phenotypes of the mutant strains showed that Kor was essential for anaerobic growth and that For activity supported robust aerobic growth of the organism.

Aerobiosis↗
PubMed2006

Purification, characterization, and gene cloning of thermophilic cytochrome cd1 nitrite reductase from Hydrogenobacter thermophilus TK-6.

A thermophilic, chemolithoautotrophic hydrogen-oxidizing bacterium, Hydrogenobacter thermophilus TK-6 can grow autotrophically under anaerobic conditions by denitrification. One of the denitrification enzymes, cytochrome cd(1) nitrite reductase, was isolated and its gene was cloned from strain TK-6. The subunit molecular mass of the purified enzyme was 61.5 kDa and the isoelectric point was determined to be 9.3. The optimum temperature and pH for the enzymatic reaction were 70-75 degrees C and 6.5-7.0, respectively. The structural gene for the enzyme, nirS, is probably transcribed as a hexacistronic operon with the following genes encoding a putative diheme cytochrome c and the proteins required for biosynthesis of heme d(1). The NirS sequence was phylogenetically distinct from those of proteobacteria. The consensus -35 and -10 sequences were found in the putative nirS promoter region, but the consensus sequences for the DNR/NnrR-type or the NorR/FhpR-type nitric oxide sensing regulators were not found in this region.

Amino Acid Sequence↗
PubMed2006

Purification and properties of glutamine synthetase from Hydrogenobacter thermophilus TK-6.

Hydrogenobacter thermophilus TK-6, a thermophilic and obligately chemoautotrophic bacterium, assimilates ammonium using glutamine synthetase (GS). GS was purified using three chromatography steps. The purified GS was found to belong to GS type I on the basis of its subunit composition and molecular weight. The Mg2+ -dependent activity of this GS significantly increased after incubation with phosphodiesterase, indicating that GS is subject to adenylyl/deadenylyl regulation, a posttranslational modification system reported mainly among enterobacteria. The degree of this posttranslational modification changed depending on growth phase, confirming that adenylyl/deadenylyl regulation functions in vivo. Interestingly, the Km for glutamate of H. thermophilus GS was significantly higher than those of other organisms, suggesting that GS activity is affected by intracellular glutamate concentration.

Bacterial Proteins↗
PubMed2006

Gene structure and expression profile of cytochrome bc nitric oxide reductase from Hydrogenobacter thermophilus TK-6.

The genes for a nitric oxide reductase-like cytochrome bc complex were cloned from a thermophilic, chemolithoautotrophic hydrogen-oxidizing bacterium, Hydrogenobacter thermophilus TK-6. The structural genes norC and norB, which encode cytochrome c and cytochrome b subunits of the complex respectively, are probably transcribed as a tricistronic operon with a following gene encoding a putative membrane protein. NorC has, unusually, two hydrophobic transmembrane spans in its N-terminus. Immunoblot analysis showed that expression of NorC was induced by nitrate, nitrite, or sodium nitropurusside, suggesting that the norCB gene product is a denitrification enzyme, nitric oxide reductase. The consensus sequences for the DNR/NnrR-type or the NorR/FhpR-type nitric oxide-sensing regulators of proteobacteria were not found in the norC promoter region, but consensus -35 and -10 sequences were found in this region. These results indicate that strain TK-6 has a nitrogen oxide-sensing regulatory system that differs from proteobacterial systems.

Bacteria↗
PubMed2006

Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis.

Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and the His-Gly dipeptide motif, has provided a previously unannotated gene that is induced during 3T3-L1 adipocytic differentiation. Because of its remarkable structural resemblance to triacylglycerol hydrolase (TGH) with 70.4% identity, we have tentatively designated this enzyme as TGH-2 and the original TGH as TGH-1. TGH-2 is also similar to TGH-1 in terms of tissue distribution, subcellular localization, substrate specificity, and regulation. Both enzymes are predominantly expressed in liver, adipose tissue, and kidney. In adipocytes, they are localized in microsome and fatcake. Both enzymes hydrolyzed p-nitophenyl butyrate, triolein, and monoolein but not diolein, cholesteryl oleate, or phospholipids; hydrolysis of short-chain fatty acid ester was 30,000-fold more efficient than that of long-chain fatty acid triacylglycerol. Fasting increased the expression of both genes in white adipose tissue, whereas refeeding suppressed their expression. RNA silencing of TGH-2 reduced isoproterenol-stimulated glycerol release by 10% in 3T3-L1 adipocytes, while its overexpression increased the glycerol release by 20%. Thus, TGH-2 may make a contribution to adipocyte lipolysis during period of increased energy demand.

3T3 Cells↗
PubMed2006

Activation of mitogen-activated protein kinases by lysophosphatidylcholine-induced mitochondrial reactive oxygen species generation in endothelial cells.

Lysophosphatidylcholine (lysoPC) evokes diverse biological responses in vascular cells including Ca(2+) mobilization, production of reactive oxygen species, and activation of the mitogen-activated protein kinases, but the mechanisms linking these events remain unclear. Here, we provide evidence that the response of mitochondria to the lysoPC-dependent increase in cytosolic Ca(2+) leads to activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase through a redox signaling mechanism in human umbilical vein endothelial cells. ERK activation was attenuated by inhibitors of the electron transport chain proton pumps (rotenone and antimycin A) and an uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), suggesting that mitochondrial inner membrane potential plays a key role in the signaling pathway. ERK activation was also selectively attenuated by chain-breaking antioxidants and by vitamin E targeted to mitochondria, suggesting that transduction of the mitochondrial hydrogen peroxide signal is mediated by a lipid peroxidation product. Inhibition of ERK activation with MEK inhibitors (PD98059 or U0126) diminished induction of the antioxidant enzyme heme oxygenase-1. Taken together, these data suggest a role for mitochondrially generated reactive oxygen species and Ca(2+) in the redox cell signaling path-ways, leading to ERK activation and adaptation of the pathological stress mediated by oxidized lipids such as lysoPC.

Calcium↗
PubMed2006

[Role of certified geriatric medical doctors in university hospitals in Japan].

The role of certified specialists in geriatric medicine in Japanese University Hospitals is discussed in this section. First, they should act as geriatric general physicians to provide a comprehensive medical care for elderly patients against a background complicatedly divided medical departments in university hospitals. Second, they should create attractive undergraduate programs for geriatric education in medical schools and training programs in geriatric medicine for doctors to develop certified specialists in geriatric medicine in the future. Finally, they should perform clinical research to provide an evidence to construct better social policies to keep older people healthy.

Aged↗
PubMed2006

[Importance of vascular aspects in Alzheimer's disease].

Elevated plasma homocysteine levels are associated with an increased risk of developing atherosclerotic vascular disorders such as stroke, but have also been implicated for neurodegenerative diseases including Alzheimer's disease (AD). Other studies have reported that hyperhomocysteinemia is associated with developing silent brain infarctions and white matter lesions in community-dwelling elderly people. It is not uncommon for such ischemic cerebrovascular lesions to be found in otherwise typical AD patients on magnetic resonance imaging. Such co-existing cerebrovascular diseases in AD must be important in developing aspiration pneumonia and falls. Previous studies demonstrated that basal ganglia infarcts, either silent or symptomatic, impaired swallowing function and these lesions were associated with an increased risk of developing aspiration pneumonia in AD patients, particularly in later stages. Further, periventricular white matter lesions are associated with an increased risk of falls irrespective of clinical stages of AD.

Accidental Falls↗