Mortality from pneumonia and hip fractures in patients with advanced dementia.
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Dementia↗
Biomedical subjects
K Inoue
Publications and source records attributed to K Inoue.
Inhibition by diallyl trisulfide, a garlic component, of intracellular Ca(2+) mobilization without affecting inositol-1,4, 5-trisphosphate (IP(3)) formation in activated platelets.
Garlic has been used in herbal medicine for thousands of years. Some reports have shown that garlic has protective effects against atherosclerosis and inhibits platelet function. In this study, we investigated the mechanism by which diallyl trisulfide (DT), a component of garlic, inhibits platelet function. DT inhibited platelet aggregation and Ca(2+) mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. DT also had no inhibitory effects on thromboxane A(2) (TXA(2)) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca(2+) mobilization is regulated by phospholipase C-gamma2 (PLC-gamma2) activation. We evaluated the effect of DT on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP(3)). DT at concentrations that inhibited platelet aggregation and Ca(2+) mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP(3) induced by CRP. Similar results were obtained with thrombin-induced platelet activation. DT inhibited platelet aggregation and Ca(2+) mobilization induced by thrombin without affecting the production of IP(3.) We then evaluated the effect of DT on the binding of IP(3) to its receptor. DT at high concentrations partially blocked the binding of IP(3) to its receptor. Taken together, our findings suggest that the agent suppresses Ca(2+) mobilization at a step distal to IP(3) formation. DT may provide a good tool for investigating Ca(2+) mobilization.
Allyl Compounds↗
Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice.
Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein that specifically binds alpha-tocopherol, is known as a product of the causative gene in patients with ataxia that is associated with vitamin E deficiency. Targeted disruption of the alpha-TTP gene revealed that alpha-tocopherol concentration in the circulation was regulated by alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile; however, placentas of pregnant alpha-TTP(-/-) females were severely impaired with marked reduction of labyrinthine trophoblasts, and the embryos died at mid-gestation even when fertilized eggs of alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients. The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653) dietary supplement by alpha-TTP(-/-) females prevented placental failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals, alpha-TTP gene expression was observed in the uterus, and its level transiently increased after implantation (4.5 days postcoitum). Our results suggest that oxidative stress in the labyrinth region of the placenta is protected by vitamin E during development and that in addition to the hepatic alpha-TTP, which governs plasma alpha-tocopherol level, the uterine alpha-TTP may also play an important role in supplying this vitamin.
Animals↗
Determination of bisphenol A in human serum by high-performance liquid chromatography with multi-electrode electrochemical detection.
A simple and sensitive method using high-performance liquid chromatography with multi-electrode electrochemical detection (HPLC-ED) including a coulometric array of four electrochemical sensors has been developed for the determination of bisphenol A in water and human serum. For good separation and detection of bisphenol A, a CAPCELL PAK UG 120 C18 reversed-phase column and a mobile phase consisting of 0.3% phosphoric acid-acetonitrile (60:40) were used. The detection limit obtained by the HPLC-ED method was 0.01 ng/ml (0.5 pg), which was more than 3000-times higher than the detection limit obtained by the ultraviolet (UV) method, and more than 200-times higher than the detection limit obtained by the fluorescence (FL) method. Bisphenol A in water and serum samples was pretreated by solid-phase extraction (SPE) after removing possible contamination derived from a plastic SPE cartridges and water used for the pretreatment. A trace amount (ND approximately 0.013 ng/ml) of bisphenol A was detected from the parts of cartridges (filtration column, sorbent bed and frits) by extraction with methanol, and it was completely removed by washing with at least 15 ml of methanol in the operation process. The concentrations of bisphenol A in tap water and Milli-Q-purified water were found to be 0.01 and 0.02 ng/ml, respectively. For that reason, bisphenol A-free water was made to trap bisphenol A in water using an Empore disk. In every pretreatment, SPE methods using bisphenol A-free water and washing with 15 ml of methanol were done in water and serum samples. The yields obtained from the recovery tests using water to which 0.5 or 0.05 ng/ml of bisphenol A was added were 83.8 to 98.2%, and the RSDs were 3.4 to 6.1%, respectively. The yields obtained from the recovery tests by OASIS HLB using serum to which 1.0 ng/ml or 0.1 ng/ml of bisphenol A was added were 79.0% and 87.3%, and the RSDs were 5.1% and 13.5%, respectively. The limits of quantification in water and serum sample were 0.01 ng/ml and 0.05 ng/ml, respectively. The method was applied to the determination of bisphenol A in healthy human serum sample, and the obtained detection was 0.32 ng/ml. From these results, the HPLC-ED method should be the most useful in the determination of bisphenol A at low concentration levels in water and biological samples.
Benzhydryl Compounds↗
Troglitazone as an anti-inflammatory agent.
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Anti-Inflammatory Agents↗
Novel RING finger proteins, Air1p and Air2p, interact with Hmt1p and inhibit the arginine methylation of Npl3p.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in the mRNA processing and export and are post-translationally modified by methylation at arginine residues in their arginine-glycine-rich (RGG) domains. We screened the factors that can interact with the RGG domain of Npl3p only in the presence of Hmt1p with the two-hybrid system in Saccharomyces cerevisiae. An isolated clone, YIL079, encodes a novel RING finger protein that was not directly bound to Npl3p but associated with the N terminus of Hmt1p. Thus, we designated the gene product Air1p (arginine methyltransferase-interacting RING finger protein). Air1p inhibited the Hmt1p-mediated methylation of Npl3p in vitro. Overexpression of Air1p repressed the Hmt1p-dependent growth of cells. Since homology searches indicate that the YDL175 gene product has significant identity (45%) with Air1p, we designated the gene AIR2. Air2p also has a RING finger domain and was bound to Hmt1p. Although single disruption of either gene gave no effect on the cell growth, cells lacking Air1p and Air2p grew at an extremely slow rate with accumulated poly(A)(+) RNA in the nucleus. Thus, Air1p and Air2p may affect mRNA transport by regulating the arginine methylation state of heterogeneous nuclear ribonucleoproteins.
ATP-Binding Cassette Transporters↗
Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan.
Angiotensin-II (Ang-II) enhances the modification of LDL and the expression of its lectin-like receptor (LOX-1) by activating type 1 (AT(1)) receptors. This study was designed to determine the effect of hypercholesterolemia on LOX-1 expression in aorta and its modulation by the AT(1) receptor blocker losartan. Male New Zealand White rabbits were fed regular chow (Control group), chow with 1% cholesterol and 4% peanut oil (HC-diet group), or 1% cholesterol and 4% peanut oil diet plus losartan (25 mg/kg/day) (Losartan + HC-diet group) for 10 weeks. Animal body weight, serum cholesterol levels, and arterial blood pressure were measured. Aortic intimal thickening was quantitated in H&E-stained segments. LOX-1 expression in aortas was examined by immunohistochemistry and semi-quantitative RT-PCR. High-cholesterol diet did not affect body weight, but induced hypercholesterolemia and extensive intimal thickening. Aortas of rabbits in the control group showed a modest LOX-1 expression in the endothelium. Aortic intimal proliferation in HC-diet group was associated with a marked increase in LOX-1 expression (protein and mRNA) in the endothelium and neointima. Treatment with losartan attenuated aortic intimal proliferation and markedly decreased the enhanced LOX-1 expression. Thus high-cholesterol diet induces the upregulation of LOX-1 expression in neointima of aortas of rabbits. Treatment with losartan, an AT(1) blocker, markedly decreases this enhanced LOX-1 expression.
Angiotensin Receptor Antagonists↗
Stereocontrol in rare earth metal triflate-catalyzed 1,3-dipolar cycloaddition reaction of 2-benzopyrylium-4-olate with aldehydes
Exo-cycloadduct was obtained with high stereoselectivity by the addition of ytterbium triflate (Yb(OTf)(3)) (10 mol %) in the rhodium(II) acetate (Rh(2)(OAc)(4))-catalyzed decomposition of o-(methoxycarbonyl)-alpha-diazoacetophenone in the presence of benzaldehyde. In the reaction in the absence of Yb(OTf)(3), almost no selectivity was obtained. Stereoselectivity in the reactions with p-nitrobenzaldehyde, p-anisaldehyde, and benzyloxyacetaldehyde could be also controlled to high exo preference by the addition of Yb(OTf)(3).
Journal Article↗
Effect of self-etching primers containing N-acryloyl aspartic acid on dentin adhesion.
The purpose of this study was to evaluate the feasibility of aspartic acid derivative, N-acryloyl aspartic acid (N-AAsp) when used as a self-etching primer prior to the application of a commercial bonding agent containing 10-methacryloxydecyl dihydrogen phosphate. N-AAsp was synthesized by the reaction of DL-aspartic acid and acryloyl chloride. N-AAsp can be dissolved in water up to 25 wt % and can adequately remove the smear layer. When 20 wt % N-AAsp was applied as a self-etching primer, the tensile bonding strength of resin composite to dentin doubled to 16.0 MPa compared with that of the nonetching group or the 40 wt % H(3)PO(4) etching/water rinse group. Scanning electron microscopic observations revealed that the formation of the hybrid layer at the interface between the resin composite and dentin and the thickness of the hybrid layer increased with N-AAsp concentration. The hybrid layer in the specimens treated with 20 wt % N-AAsp aqueous solution presented a uniform structure, whereas those treated with 5 wt % N-AAsp solution showed a porous structure. We conclude that 20 wt % N-AAsp aqueous solution has good potential value as a self-etching primer.
Acid Etching, Dental↗
Effect of maternal separation on feeding behavior of rats in later life.
Effects of maternal separation on feeding behavior, particularly on rebound hyperphagia, in adult rats were examined. Time-restricted scheduled feeding (2 h per day for 6 days), was given at the age of 3, 6, 9 or 12 weeks in rats that were maternal separated from postnatal days (PD) 1-21 and control rats. Following the time-restricted scheduled feeding, rats were fed freely for 24 h (rebound hyperphagia). Body weight, daily normal food consumption and food consumption during time-restricted scheduled feeding and rebound hyperphagia were measured. Body weight of 3-week-old maternally separated rats were less than those of control rats. There was no significant difference in normal daily food consumption. Food consumption during rebound hyperphagia was significantly increased in 6- to 9-week-old female maternally separated rats, but there was no difference observed in males. Postnatal maternal separation enhanced rebound hyperphagia of female rats in later life. These results indicate that postnatal maternal separation made rats more vulnerable to the development of abnormal feeding behavior in response to food restriction in later life.
Aging↗
Combination therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation therapy for hepatocellular carcinoma.
BACKGROUND: A small number of microwave electrode insertions and microwave irradiations were used to obtain complete tumor necrosis in hepatocellular carcinomas (HCC) measuring > 2.0 cm but </= 3.0 cm in greatest dimension. The efficacy of combining transcatheter arterial chemoembolization (TACE) with subsequent percutaneous microwave coagulation therapy (PMCT) was assessed in this study. METHODS: Eighteen patients with cirrhosis and HCCs measuring > 2.0 cm but </= 3.0 cm in greatest dimension underwent TACE followed within 1-2 days by ultrasonographically guided PMCT. RESULTS: On dynamic computed tomography, 17 of the 18 patients showed complete necrosis of their tumor lesions and the treated tumor margins (>/= 5 mm). Necroses of tumors and noncancerous margins surrounding the tumors were obtained using 4 microwave irradiations (1 session) in 14 patients, 5 microwave irradiations (2 sessions) in 2 patients, and 6 microwave irradiations (2 sessions) in 1 patient. The follow-up period was short (12-31 mos), and all patients remained alive. No local recurrences in the treated areas were detected. No fatal complications were observed. Pleural effusion was observed in 1 patient only. CONCLUSIONS: This combined therapy of PMCT applied within 1-2 days of TACE effectively treated HCCs measuring > 2.0 cm but </= 3.0 cm in greatest dimension. A small number of microwave electrode insertions and microwave irradiations were used.
Aged↗
Involvement of the 5-HT(2) receptor in hyperthermia induced by p-chloroamphetamine, a serotonin-releasing drug in mice.
The effects of a serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine (PCA), on body temperature were investigated in mice. PCA induced hyperthermia in mice. PCA-induced hyperthermia was inhibited by the 5-HT(2A/2B/2C) receptor antagonist, 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 , 8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate (LY53857). The 5-HT(2A) receptor antagonist, ketanserin, reduced the PCA-induced hyperthermia, while the 5-HT(2B/2C) receptor antagonist, N-3-pyridinyl-3,5-dihydro-5-methyl-benzo[1,2-b:4, 5-b']dipyrrole-1(2H)-carboxamide (SB 206553), enhanced it. LY 53857, ketanserin and SB 206553 did not affect hyperactivity in mice treated with PCA. These results suggest that PCA-induced hyperthermia in mice is mediated by 5-HT(2A) receptors and is not related to changes in locomotor activity.
Animals↗
Molecular evidence for the early evolution of photosynthesis.
The origin and evolution of photosynthesis have long remained enigmatic due to a lack of sequence information of photosynthesis genes across the entire photosynthetic domain. To probe early evolutionary history of photosynthesis, we obtained new sequence information of a number of photosynthesis genes from the green sulfur bacterium Chlorobium tepidum and the green nonsulfur bacterium Chloroflexus aurantiacus. A total of 31 open reading frames that encode enzymes involved in bacteriochlorophyll/porphyrin biosynthesis, carotenoid biosynthesis, and photosynthetic electron transfer were identified in about 100 kilobase pairs of genomic sequence. Phylogenetic analyses of multiple magnesium-tetrapyrrole biosynthesis genes using a combination of distance, maximum parsimony, and maximum likelihood methods indicate that heliobacteria are closest to the last common ancestor of all oxygenic photosynthetic lineages and that green sulfur bacteria and green nonsulfur bacteria are each other's closest relatives. Parsimony and distance analyses further identify purple bacteria as the earliest emerging photosynthetic lineage. These results challenge previous conclusions based on 16S ribosomal RNA and Hsp60/Hsp70 analyses that green nonsulfur bacteria or heliobacteria are the earliest phototrophs. The overall consensus of our phylogenetic analysis, that bacteriochlorophyll biosynthesis evolved before chlorophyll biosynthesis, also argues against the long-held Granick hypothesis.
Bacteria↗
Platelet-activating factor (PAF)-dependent transacetylase and its relationship with PAF acetylhydrolases.
Platelet-activating factor (PAF)-dependent transacetylase (TA) is an enzyme that transfers an acetyl group from PAF to acceptor lipids such as lysophospholipids and sphingosine. This enzyme is distributed in membrane and cytosol of the cells. We previously revealed that TA purified from rat kidney membrane showed an amino acid sequence similarity to that of bovine PAF-acetylhydrolase (AH) (II). In the present study, we purified TA from the rat kidney cytosol and analyzed its amino acid sequence. The amino acid sequence of the cytosolic TA is similar to that of bovine PAF-AH (II) and membrane TA. To clarify the relationship between TA and PAF-AH (II), we isolated cDNA of rat PAF-AH (II). The predicted amino acid sequence of rat PAF-AH (II) from isolated cDNA included all the sequences found in TAs purified from the membrane and cytosolic TAs. In addition, monoclonal antibody to recombinant PAF-AH (II) cross-reacted with both cytosolic and membrane TAs. Consistent with sequence identity, recombinant PAF-AH (II) showed TA activity, whereas recombinant PAF-AH Ib, which is a different subtype of intracellular PAF-AHs, did not possess TA activity. Analysis of a series of site-directed mutant PAF-AH (II) proteins showed that TA activity was decreased, whereas PAF-AH activity was not affected in C120S and G2A mutant proteins. Thus, Cys(120) and Gly(2) are implicated in the catalysis of TA reaction in this enzyme. Furthermore, the transfer of acetate from PAF to endogenous acceptor lipids was significantly increased in a time-dependent manner in CHO-K1 cells transfected with PAF-AH (II) gene. These results demonstrate that PAF-AH (II) can function, as a TA in intact cells, and PAF-AH (II) and TA are the same enzyme.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Barnacle cement proteins. Importance of disulfide bonds in their insolubility.
Barnacles produce a cement that is a proteinaceous underwater adhesive for their secure attachment to the substratum. The biochemical properties of the cement have not previously been elucidated, because the insolubility of the cement proteins hampers their purification and characterization. We developed a non-hydrolytic method to render soluble most of the cement components, thereby allowing the proteins to be analyzed. Megabalanus rosa cement could be almost completely rendered soluble by its reduction with 0.5 m dithiothreitol at 60 degrees C in a 7 m guanidine hydrochloride solution, the high concentration of dithiothreitol being indispensable to achieve this. The effectiveness of this reduction treatment was confirmed by the detachment of the barnacle from the substratum. Three proteins comprising up to 94% of the whole cement were identified as the major cement components. The cDNA clone of one of these major proteins was isolated, and the site-specific expression of the gene in the basal portion of the adult barnacle, where the cement glands are located, was demonstrated. A sequence analysis revealed this cement component to be a novel protein of 993 amino acid residues, including a signal peptide. This is the first report of the major component of the barnacle cement protein complex.
Amino Acid Sequence↗
Polymerase chain reaction-single-strand conformation polymorphism based determination of two major genetic defects responsible for a phenotypic polymorphism of cytochrome P450 (CYP) 2C19 in the Japanese population.
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Alleles↗
Mutational analysis of RET/GDNF/NTN genes in children with total colonic aganglionosis with small bowel involvement.
Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the distal gut, resulting in bowel obstruction shortly after birth. Aganglionosis usually affects the distal colon, but may also extensively involve the entire colon and, rarely, the more proximal bowel. Recently, germline mutations of RET, GDNF, and NTN genes have been reported in HSCR. Here we describe the results of mutational analysis of these genes in 15 Japanese child patients with total colonic aganglionosis with small bowel involvement. DNA sequences of all the RET/GDNF/NTN coding regions were determined by the direct dyedeoxy terminator cycle method. Eight different RET mutations were identified in exons 1, 7, 10, 12, 15, and 17 in 10 of the 15 patients. Of these eight mutations, five were found in the tyrosine kinase domain. No GDNF or NTN mutation was found. Compared with typical HSCR, this patient group appeared to exhibit a higher percentage of RET mutations and accumulation of mutations in the tyrosine kinase domain. A homozygous (or hemizygous) RET mutation was found in a male baby with total intestinal aganglionosis, while the heterozygosity of the same mutation resulted in a less severe type of aganglionosis. In familial cases, all heterozygous for the same mutation, aganglionosis was more severe in male than in female siblings. These results also urge us to examine if the RET germline mutation may cause critical alteration of the GDNF/NTN-Ret signal transduction more severely in homo(hemi)zygosity and in male fetuses during organogenesis.
Child↗
Direct association of LIS1, the lissencephaly gene product, with a mammalian homologue of a fungal nuclear distribution protein, rNUDE.
LIS1 is a product of the causative gene for type I lissencephaly characterized by a smooth brain surface due to a defect in neuronal migration during brain development and a regulatory subunit of platelet-activating factor acetylhydrolase (PAF-AH). It is also a mammalian homologue of the fungal nuclear distribution (nud) gene, nudF, which controls the migration of fungal nuclei. Using the two-hybrid system, we identified a novel LIS1-interacting protein, rat NUDE (rNUDE), and found that it is a mammalian homologue of another fungal nud gene product, NUDE, and Xenopus mitotic phosphoprotein 43 which is phosphorylated in a cell cycle-dependent manner. rNUDE and the catalytic subunits of PAF-AH interact with the N- and C-termini of LIS1, respectively. However, these proteins, instead of simultaneously binding to LIS1, appeared to bind to LIS1 in a competitive manner. These results suggest that LIS1 functions in nuclear migration by interacting with multiple intracellular proteins in mammals.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗