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Biomedical subjects

K Hori

Publications and source records attributed to K Hori.

At least 19 recordsLinked to original sources

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans

Enhanced monoamine release in the median preoptic area following reduced extracellular fluid volume in rats.

The role of monoaminergic neural inputs to fluid regulatory systems in the median preoptic nucleus (MnPO) was investigated by examination of monoamine metabolism during reduction of systemic extracellular fluid volume in freely moving rats. Extracellular fluid volume was decreased iso-osmotically by subcutaneous polyethylene glycol (PEG), and extracellular noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using intracerebral microdialysis techniques. PEG treatments significantly increased NA, DA and DOPAC release in the MnPO area. The results suggest that monoaminergic neural systems in the region of the MnPO are important in the control of extracellular fluid balance.

Animals

Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast.

AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM.

Antifungal Agents

Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats.

We evaluated changes in the cholinergic neuronal system and learning ability with aging. Choline acetyltransferase (ChAT) activity, a presynaptic index of the cholinergic system, was decreased in the cerebral cortex, hippocampus, striatum, and hypothalamus in the brain of aged rats compared with young adults. Muscarinic cholinergic binding sites (receptors, MCR), a postsynaptic index of the cholinergic system, were markedly decreased in all areas of the brain. However, intraperitoneal injection of 1 mg/kg of dihydroergotoxine (DHET) for 14 days normalized both ChAT and MCR in the cerebral cortex and hippocampus. In the striatum, ChAT was normalized, but MCR did not recover. Aged rats showed marked learning impairment in a 30-day operant type brightness discrimination learning test. Daily DHET administration restored the discrimination ability in the aged rats to nearly the young adult level. DHET had no effects on central cholinergic indices or learning test results in young adult rats. These findings suggest that learning is impaired in aged rats due to impairment in the central cholinergic neuronal system, and that DHET normalizes the decreased function in this system, restoring the learning ability.

Aging

Isolation and sequence of a developmentally regulated putative novel gene, priA, from the basidiomycete Lentinus edodes.

Screening for gene(s) homologous to v-Ha-ras (Harvey rat sarcoma viral ras gene) in the basidiomycete, Lentinus edodes, resulted in the isolation of a novel gene (designated priA), in addition to a ras gene homologue [Hori et al., Gene 105 (1991) 91-96]. The priA gene has a coding capacity of 258 amino acids (aa) interrupted by two short putative introns. The 5'-upstream region of priA contains GGGCGG box, CCAAT box, TATAAA box and CT sequence elements in 5'----3' order. One transcription start point (tsp) was located 10 nucleotides upstream from a TATAAA box and another tsp just in a CT sequence. The deduced PRIA protein (26.7 kDa), rich in Ser (42 residues), Pro (29 residues) and Thr (27 residues), contained different types of putative zinc-binding motifs. It initiated with a hydrophobic aa sequence and terminated with the unique sequence, Cys-Aaa-Aaa-Xaa (where Aaa is aliphatic aa and Xaa is any aa), implying an association with the inner membrane surface via acylation of the Cys residue. The priA gene expression was found to be developmentally regulated with primordia/immature fruiting bodies having much higher levels of priA transcript. Preprimordial mycelia and mature fruiting bodies, however, contain very low levels of priA transcript. The priA gene may play a role during the beginning of fruiting.

Amino Acid Sequence

Circadian variation of tumor blood flow in rat subcutaneous tumors and its alteration by angiotensin II-induced hypertension.

Circadian fluctuation in tumor blood flow of the rat subcutaneous tumor was investigated. Tumor tissue blood flows in the daytime zone (10 a.m. to 4 p.m.) and in the nighttime zone (10 p.m. to 4 a.m.) in both the first phase (doubling time of tumor volume = 1.7 days) and the second phase (doubling time of tumor volume = 5.7 days) of growth of the LY80 tumor in rats were measured using the hydrogen gas clearance technique. In the first phase of tumor growth, the tumor blood flow was 20.3 +/- 12.2 ml/min/100 g in the daytime zone (n = 22) and 46.6 +/- 19.3 ml/min/100 g in the nighttime zone (n = 22). In the second phase, tumor blood flow was 9.6 +/- 5.7 ml/min/100 g in the daytime zone (n = 45) and 19.4 +/- 8.2 ml/min/100 g in the nighttime zone (n = 38). Tumor blood flow in the nighttime zone was significantly higher than that in the daytime zone (first phase, P less than 0.001; second phase, P less than 0.001). However, there were no significant differences in the mean arterial blood pressure, tumor size, and body weight of rats between the daytime zone and the nighttime zone. There was also a marked difference in the effect of angiotensin II-induced hypertension on tumor blood flow between the daytime zone and the nighttime zone. These results suggest that circadian fluctuations in tumor blood flow should be carefully considered when developing strategies to maximize the effectiveness of cancer therapy in relation to the flow rate of circulating blood.

Angiotensin II

Progression of Takayasu's aortitis in a young Japanese woman: serial angiographic study.

Progression of Takayasu's aortitis was observed by serial angiography over 2 years. Acute aortic regurgitation due to marked dilatation of the proximal ascending aorta was followed by aneurysmal dilatation of the distal ascending aorta. Aneurysmal dilatation of the carotid arteries then developed, with subsequent obstruction of both the bilateral vessels by thrombosis.

Adult

In vivo study of flow pattern at human carotid bifurcation with regard to aneurysm development.

In order to investigate the developmental mechanism of cerebral aneurysms, the in vivo flow pattern around human cervical carotid bifurcations was studied by flow visualization using digital subtraction angiography with an isotonic contrast medium. The blood stream containing the medium impinged on the apex, then proceeded along the walls of the branches. After opacification of the whole lumen around the apex, most of the medium was carried away, while some remained for a few seconds at the carotid sinus. In the internal carotid artery, the blood struck the wall at an oblique angle near the tops of the arterial curvatures. In cases with atheromatous plaque or kinking of the branch, the blood passed through the stenosed segment and moved upstream, indicating turbulence. The study suggests that haemodynamic forces around the apex consist mainly of impingement on the apex and shear stress to the wall at and around the apex. In branches, high shear stress seems to exist. It might be possible that high shear stress causes degenerative changes in the endothelial layer, initiating the formation of saccular and fusiform cerebral aneurysms.

Adolescent

Deep negative T waves associated with reversible left ventricular dysfunction in acute adrenal crisis.

We report two cases of reversible left ventricular dysfunction associated with deep negative T waves during acute adrenal crisis due to isolated deficiency of adrenocorticotrophic hormone. There were no symptoms suggestive of heart disease in either case and left ventricular wall motion abnormalities, present mainly around the left ventricular apex, returned to normal in 1-2 weeks. Deep negative T waves normalized 4 weeks after corticosteroid administration. Acute adrenal crisis should be considered when deep negative T waves are associated with left ventricular dysfunction without cardiac symptoms.

Adrenal Insufficiency

Absorption of color additives and settling volume in water of blue-green alga, ishikurage (Nostoc commune).

The properties of ishikurage (Nostoc commune) and other algae were compared. Ishikurage and suizenji nori (Aphanothece sacrum) absorbed much more amaranth than others. They have a high settling volume (SV) in water. The high SV of ishikurage is attributable to its neutral detergent fiber (NDF). The acid detergent fiber (ADF) from the alga had a high amaranth absorption. However the absorption by the ADF did not explain the absorption by ishikurage. The results suggest that ishikurage may have a nutritional significance as a source of dietary fiber.

Absorption

Distribution of 5'-nucleotidase in muscle of some marine fishes.

A preliminary examination for the purification and characterization of 5'-nucleotidase of fish muscle was carried out and the following results were obtained. 1. The activities of 5'-nucleotidase in the muscles of marine vertebrates and invertebrates (total 11 species) were determined. The highest activity of 5'-nucleotidase was found in Blackrock fish Sebastes inermis, which was then used as a material for estimation of subcellular distribution and solubilization of the enzyme. 2. The 5'-nucleotidase of ordinary muscle of the fish Sebastes inermis was found in nuclear, microsomal and cytosolic fractions. About half of the total activity was found in the nuclear fraction, whereas the highest specific activity was observed in the microsomal fraction. 3. Complete solubilization of the enzyme was attained by using a high concentration of detergent such as Triton X-100, CHAPS, octylglucoside, octylthioglucoside and sodium deoxycholate, suggesting that the enzyme was tightly bound to the membrane. 4. Based on the results of solubility and stability tests, Triton X-100 seemed suitable for solubilizing 5'-nucleotidase from the membrane. 5. Microsomal 5'-nucleotidase was an Mg(2+)-activated enzyme, and no inactivation was observed up to 50 mM of Mg2+.

5'-Nucleotidase

Actin-actin contact: inhibition of actin-polymerization by subdomain 4 peptide fragments.

F-Actin was digested with alpha-chymotrypsin in 6 M urea, and two peptide fragments from subdomain 4 of actin molecule [Kabsch, W., Mannherz, H.G., Suck, D., Pai, E.F., & Holmes K.C. (1990) Nature 347, 37-44] were purified by reverse-phase HPLC and Sephadex G-50 gel filtration. The peptide fragments were identified as segments from Arg-177 to Tyr-198 (2.6-kDa peptide) and from Ser-199 to Tyr-279 (9.1-kDa peptide). Their effects on actin polymerization induced by 50 or 100 mM KCl were studied by measuring the increase in viscosity by the falling ball method. The 2.6-kDa peptide decreased the rate of actin polymerization and increased the critical concentration for the polymerization. Based on the atomic model of the actin filament [Holmes, K.C., Popp, D., Gebhard, W., & Kabsch, W. (1990) Nature 347, 44-49], the peptide is presumed to bind to the barbed end of the actin filament and inhibit the polymerization. By assuming that the peptide affected the rate of association of the actin monomer to the end of the actin filament, well-fitting curves for the polymerization kinetics were calculated. Computer-assisted results indicated that the dissociation constant of the 2.6-kDa peptide for F-actin is 200 to 260 microM. In contrast, the 9.1-kDa peptide only slightly inhibited actin polymerization. These results suggest that the actin-actin interface in the region between Arg-177 and Tyr-198 has a stronger interaction than those between Ser-199 and Tyr-279. The amino acid sequence L-T-D-Y-L present in the 2.6-kDa segment is homologous to a common sequence in the F-actin capping domain of various actin-binding proteins.

Actins

Inhibition of ionotropic neurotransmitter receptors by antagonists: strategy to estimate the association and the dissociation rate constant of antagonists with very strong affinity to the receptors.

Since binding of an agonist to an ionotropic neurotransmitter receptor causes not only channel opening, but also desensitization of the receptor, inhibition of the receptor by the antagonist sometimes becomes very complicated. The transient state kinetics of ligand association and dissociation, and desensitization of the receptor were considered on the basis of the minimal model proposed by Hess' group, and the following possibilities were proposed. 1) When an agonist is simultaneously applied to the receptor with an antagonist whose affinity to the receptor is extremely strong and different from that of the agonist, it is usually impossible to estimate the real inhibition constant exactly from the responses because desensitization of the receptor proceeds before the equilibrium of the ligand binding. Simultaneous addition of the antagonist with strong affinity to the receptor may apparently accelerate inactivation (desensitization) of the receptor. The association rate constant of the antagonist can be estimated by analyses of the rate of the inactivation in the presence and the absence of the antagonist. 2) A preincubated antagonist with a slow dissociation rate constant, i.e., a very effective inhibitor, may cause apparent noncompetitive inhibition of the receptor, since the receptor is desensitized by an agonist as soon as the antagonist dissociates from the receptor and the dissociation of the antagonist from the receptor becomes the rate-determining step. A nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus oocytes by injecting mRNA prepared from Electrophorus electricus electroplax and used for the experiments on inhibition by an antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Gene structure and multiple mRNA species of Drosophila melanogaster aldolase generating three isozymes with different enzymatic properties.

Genomic clones encoding the Drosophila aldolase gene were isolated and the organization of the gene was determined. The protein-coding region spanning nearly 3.5 kb consists of five coding exons (exon 2, 3, 4 alpha, 4 beta, and 4 gamma). The insect exon 2 corresponds to exons 2 to 7 of vertebrate aldolase genes and thus appears to have been formed by the fusion of these 6 exons into a single exon during evolution. The Drosophila aldolase gene is predicted to generate mRNAs for three isozymes (alpha-, beta-, and gamma-types) from the primary transcripts by alternative usage of the final three exons. The reverse transcriptase-PCR assay revealed the occurrence of mRNAs for the three isozymic forms at different developmental stages, and tissue-specific expression was also found to occur in adult flies. In addition to the usual type mRNA species for the alpha-, beta-, and gamma-isozymes, two novel forms of mRNAs, alpha beta- and beta gamma-type mRNAs, were detected tissue-specifically in adult flies, although their functions are unpredictable. The alpha beta-mRNA is an alpha-type mRNA in which exon 4 beta remains unspliced, while the beta gamma-mRNA is a beta-type mRNA with the exon 4 gamma remaining unspliced. Recombinant enzymes expressed in Escherichia coli were all active and exhibited different enzymatic properties.

Amino Acid Sequence

Studies on chimeric fusion proteins of human aldolase isozymes A and B.

Several kinds of fusion proteins between human aldolases A and B were prepared by recombinant DNA technology and their enzymic properties were examined. AB chimeras, which have aldolase A at the N-terminal region and aldolase B at the C-terminal region, were scarcely obtained, while BA chimeras were abundant (Kitajima et al., (1990), J. Biol. Chem., 265, 17493-17498). All the BAB chimeras, aldolase A fragments inserted in aldolase B, showed activity assignable to aldolase B type, which imply an essential role of Tyr residue at the C-terminus of aldolase A in the binding of fructose-1,6-bisphosphate (Fru-1,6-P2). BAB chimeras also showed reactivity to effectors such as fructose-2,6-bisphosphate (Fru-2,6-P2) and pyridoxal 5-phosphate (PLP), in a similar manner to aldolase B. BAB108 has a similarity to the BA108 chimera, but acts differently from other BAB chimeras, suggesting that its structure around active site looks like that of aldolase A.

Escherichia coli

Increased monoamine turnover in the subfornical organ area following body fluid depletion.

To clarify whether monoaminergic inputs to the subfornical organ (SFO) area participate in fluid regulatory systems, we examined the effects of body fluid depletion on monoamine turnover in the region of the SFO using microdialysis techniques in rats. An iso-osmotic reduction of fluid volume following subcutaneous treatment with polyethylene glycol (PEG) significantly increased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the SFO area. 5-hydroxytryptamine (5-HT) in the SFO area could be detected after the PEG treatment, while 5-HT was undetectable before the treatment. The data imply that both dopaminergic and serotonergic systems in the SFO area may be involved in controlling body fluid balance.

Animals