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Biomedical subjects

H Matsuda

Publications and source records attributed to H Matsuda.

At least 271 records · Page 15Linked to original sources

Quick selection of representative protein chain sets based on customizable requirements.

MOTIVATION: Protein structure classification has been recognized as one of the most important research issues in protein structure analysis. A substantial number of methods for the classification have been proposed, and several databases have been constructed using these methods. Since some proteins with very similar sequences may exhibit structural diversities, we have proposed PDB-REPRDB: a database of representative protein chains from the Protein Data Bank (PDB), which strategy of selection is based not only on sequence similarity but also on structural similarity. Forty-eight representative sets whose similarity criteria were predetermined were made available over the World Wide Web (WWW). However, the sets were insufficient in number to satisfy users researching protein structures by various methods. RESULT: We have improved the system for PDB-REPRDB so that the user may obtain a quick selection of representative chains from PDB. The selection of representative chains can be dynamically configured according to the user's requirement. The WWW interface provides a large degree of freedom in setting parameters, such as cut-off scores of sequence and structural similarity. This paper describes the method we use to classify chains and select the representatives in the system. We also describe the interface used to set the parameters.

Databases, Factual↗

Abnormal regional cerebral blood flow in childhood autism.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Adolescent↗

Reduction of the major xenoantigen on glycosphingolipids of swine endothelial cells by various glycosyltransferases.

The effect of the various glycosyltransferases on glycosphingolipids was examined, using transfected swine endothelial cell (SEC) lines. The reactivity of parental SEC to normal human serum (NHS) and Griffonia simplicifolia IB(4) (GSIB4) lectin, which binds to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (alpha-galactosyl epitope), was reduced by approximately 20% by the treatment with D-PDMP (D-threo-1-phenyl-2-decan- oylamino-3-morpholino-1-propanol), suggesting that glycosphingolipids contained by SEC have a considerable amount of the alpha-galactosyl epitope. The overexpression of two different types of glycosyltransferase, N-acetylglucosaminyl transferase III (GnT-III), as well as alpha2, 6-sialyltransferase (ST6Gal I), alpha2,3-sialyltransferase (ST3Gal III), and alpha1,2-fucosyltransferase (alpha1,2FT), suppresses the total antigenicity of SEC significantly. However, the reduction in reactivities toward NHS and GSIB4 lectin in the case of GnT-III transfectants was milder than those in other transfectants. Western blot analysis indicated that the glycoproteins in all transfectants had diminished reactivity to NHS and GSIB4 lectin to approximately the same extent. Therefore, the neutral glycosphingolipids of these transfectants were separated by thin layer chromatography, followed by immunostaining with NHS and GSIB4 lectin. The levels of the alpha-galactosyl epitope in glycosphingolipids were not decreased in the GnT-III transfectants but were in the ST6Gal I, ST3Gal III, and alpha1,2FT transfectants. These data indicate that ST6Gal I, ST3Gal III, and alpha1,2FT reduced the alpha-galactosyl epitope in both glycoproteins and glycosphingolipids, while GnT-III reduced them only in glycoproteins.

Animals↗

IL-12 is produced by antigen-presenting cells stimulated with soluble alphabeta TCR and restores impaired T(h)1 responses.

Contact sensitivity (CS) is a cutaneous T(h)1 response that is induced by skin painting with reactive hapten. In prior in vivo studies of CS, we showed that recombinant soluble alphabetaTCR (sTCR) acted non-specifically to protect CS-effector T cells from suppression, but no molecular mechanism was determined. In the current study, we employed an in vitro system to investigate the mechanism of how sTCR protect CS-effector T cells from suppression. Immune CS-effector cells and appropriate hapten-conjugated antigen-presenting cells (APC) were incubated together with down-regulatory culture supernatant produced by suppressive spleen cells from mice tolerized i.v. with specific hapten, which produced strong inhibition of IFN-gamma production by the CS-effector cells. Importantly, addition of two different sTCR, of unrelated specificity, reversed this down-regulation and thus restored IFN-gamma production. We found that the APC, and not the CS-effector T cells, were the locus of the sTCR-mediated protection and showed direct binding of sTCR to APC by flow cytometry. Further, addition of anti-IL-12 showed that sTCR protection was due to IL-12 induced by sTCR and released by the APC, and was confirmed by ELISA measurement of IL-12 induced in APC supernatants by sTCR incubation. These results indicated a possible new regulatory loop in which suppression was reversed by IL-12 derived from APC, following direct surface binding of sTCR, and enhanced by IFN-gamma production from the T(h)1 CS-effector cells.

Animals↗

Class switch recombination of the chicken IgH chain genes: implications for the primordial switch region repeats.

In mammals and the amphibian, Xenopus, isotypes of antibodies have been shown to be changed through class switch recombination within the IgH chain gene locus. Here, we identified switch (S) repetitive sequences in the 5' introns of the Ig C(mu) and C(gamma) genes of the chicken. The S(mu) region is composed of two homologous regions, S(mu)1 and S(mu)2. The S(mu)1 region is an upstream 3.7 kb sequence composed of 37 repeats of a consensus sequence containing tandem repeats of the decamer ACCAGTATGG. The S(mu)2 region is a downstream 1.4 kb sequence consisting of simple tandem repeats of a decamer CCCAGTACAG. The S(gamma) region contains repeats of the decamer TATGGGGCAG. Analysis of chicken IgG-producing hybridomas revealed that the C(mu) gene was deleted from the chromosome by the recombination occurring between the S(mu) and S(gamma) regions. Recombination breakpoints at the C(mu) gene of splenocytes from an immunized chicken were scattered around the S(mu) region and two such breakpoints, the precise position of which were determined, were located within possible hairpin loop structures at the palindromic sequence of S(mu)1. A primordial palindromic sequence from which the prevalent switch repeat motifs of mammals, chickens and amphibians may have diverged is presented.

Animals↗

Physical nature of higher-order mutual information: intrinsic correlations and frustration

This paper studies some properties and implications of higher-order mutual information functions, which should serve for the analysis of general complex systems. We note that the higher-order mutual information can either be positive or negative depending on the correlation among ensembles. Two opposite types of correlations are discussed in connection with the concept of frustration. Simple examples are presented to demonstrate that our concepts are especially helpful in understanding the nature of correlations in frustrated systems. The higher-order mutual information provides an appropriate measure of the frustration effect.

Journal Article↗

High-dose corticosteroid administration induces increase of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada's disease.

To investigate the influence of corticosteroid administration on the serum level of macrophage migration inhibitory factor (MIF), sera obtained from 9 patients with Vogt-Koyanagi-Harada's disease who had been treated with high-dose corticosteroid were analyzed. The serum MIF levels of most patients were prominently increased on day 7 and/or day 14 after corticosteroid treatment. No TNF-alpha was detected in the sera. The average serum MIF level of nine patients at the highest stages after corticosteroid administration was significantly higher than that before the corticosteroid treatment. It seems that MIF is a unique cytokine and acts together with corticosteroid to regulate inflammation and immunity.

Administration, Oral↗

Malaria infection induces rapid elevation of the soluble Fas ligand level in serum and subsequent T lymphocytopenia: possible factors responsible for the differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection.

The intraerythrocytic stage of the simian malaria parasite Plasmodium coatneyi (CDC strain) was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, including four Japanese macaques (Macaca fuscata) and three cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria and eventually became moribund, while the infected cynomolgus macaques, natural hosts of the parasite, exhibited no severe manifestation of disease except anemia and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4(+) and CD8(+) T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible at least in part for the T lymphocytopenia. Furthermore, soluble Fas ligand levels in sera of the infected Japanese macaques increased gradually to a markedly high level of 28. 83 +/- 10.56 pg/ml (n = 4) when the animals became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or elevated soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.

Animals↗

Phenotypes of fission yeast defective in ubiquinone production due to disruption of the gene for p-hydroxybenzoate polyprenyl diphosphate transferase.

Ubiquinone is an essential component of the electron transfer system in both prokaryotes and eukaryotes and is synthesized from chorismate and polyprenyl diphosphate by eight steps. p-Hydroxybenzoate (PHB) polyprenyl diphosphate transferase catalyzes the condensation of PHB and polyprenyl diphosphate in ubiquinone biosynthesis. We isolated the gene (designated ppt1) encoding PHB polyprenyl diphosphate transferase from Schizosaccharomyces pombe and constructed a strain with a disrupted ppt1 gene. This strain could not grow on minimal medium supplemented with glucose. Expression of COQ2 from Saccharomyces cerevisiae in the defective S. pombe strain restored growth and enabled the cells to produce ubiquinone-10, indicating that COQ2 and ppt1 are functional homologs. The ppt1-deficient strain required supplementation with antioxidants, such as cysteine, glutathione, and alpha-tocopherol, to grow on minimal medium. This suggests that ubiquinone can act as an antioxidant, a premise supported by our observation that the ppt1-deficient strain is sensitive to H(2)O(2) and Cu(2+). Interestingly, we also found that the ppt1-deficient strain produced a significant amount of H(2)S, which suggests that oxidation of sulfide by ubiquinone may be an important pathway for sulfur metabolism in S. pombe. Ppt1-green fluorescent protein fusion proteins localized to the mitochondria, indicating that ubiquinone biosynthesis occurs in the mitochondria in S. pombe. Thus, analysis of the phenotypes of S. pombe strains deficient in ubiquinone production clearly demonstrates that ubiquinone has multiple functions in the cell apart from being an integral component of the electron transfer system.

Alkyl and Aryl Transferases↗

Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis.

AIMS: To determine whether macrophage migration inhibitory factor (MIF) levels were increased in sera of the patients with iridocyclitis. METHODS: Sera were obtained from 41 patients with acute iridocyclitis, 13 patients with chronic iridocyclitis, and 44 healthy control subjects. MIF levels were determined by a human MIF ELISA. RESULTS: The average levels of MIF in the sera of patients with both acute and chronic iridocyclitis were significantly higher than that of healthy subjects. CONCLUSION: Uveitis induces the elevation of serum MIF, which may affect various inflammatory symptoms in uveitis.

Acute Disease↗

Vagus nerve is involved in lack of blood reflow into sinusoids after rat hepatic ischemia.

Although recovery of microcirculation is an important determinant for ischemia-reperfusion injury, little information is available about hepatic blood flow after ischemia. To examine regulatory mechanisms of postischemic hepatic microcirculation, we studied the sinusoidal blood flow after portal triad clamping of rat livers for 5, 15, or 30 min. Hepatic tissue blood flow and erythrocyte blood flow in sinusoids were measured using a laser-Doppler flowmeter and an intravital microspectroscope, respectively. There was a time of no blood flow (lag time) in sinusoids after declamping, dependent on the ischemic time. Cholinergic blockade agents eliminated the lag time, whereas nerve stimulation at the hiatus esophagus or on the hepatoduodenal ligament during reperfusion prolonged it. Chemical denervation with 10% phenol or surgical denervation on the hepatoduodenal ligament eliminated the lag time. The prolongation of lag time by nerve stimulation was completely abrogated by truncal vagotomy. These results suggest that the cholinergic vagus nerve is involved in causing the lag time of sinusoidal blood flow in hepatic ischemia-reperfusion.

Animals↗

Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF.

Using a rat model of ischemia/reperfusion injury, we demonstrate here that HGF is cardioprotective due to its antiapoptotic effect on cardiomyocytes. Following transient myocardial ischemia and reperfusion, c-Met/HGF receptor expression rapidly increased in the ischemic myocardium, an event accompanied by a dramatic increase in plasma HGF levels in the infarcted rats. When endogenous HGF was neutralized with a specific antibody, the number of myocyte cell deaths increased markedly, the infarct area expanded, and the mortality increased to 50%, as compared with a control group in which there was no mortality. Plasma from the myocardial infarcted rats had cardioprotective effects on primary cultured cardiomyocytes, but these effects were significantly diminished by neutralizing HGF. In contrast, recombinant HGF administration reduced the size of infarct area and improved cardiac function by suppressing apoptosis in cardiomyocytes. HGF rapidly augmented Bcl-xL expression in injured cardiomyocytes both in vitro and in vivo. As apoptosis of cardiomyocytes is one of the major contributors to the pathogenesis in subjects with ischemia/reperfusion injury, prevention of apoptosis may prove to be a reasonable therapeutic strategy. Supplements of HGF, an endogenous cardioprotective factor, may be found clinically suitable in treating subjects with myocardial infarction.

Animals↗

Medicinal foodstuffs. XVIII. Phytoestrogens from the aerial part of Petroselinum crispum MIll. (Parsley) and structures of 6"-acetylapiin and a new monoterpene glycoside, petroside.

In the course of our screening for natural estrogenic compounds from Occidental medicinal herbs, the extracts of several herbs were found to show proliferative activity in MCF-7 (an estrogen-sensitive breast cancer cell line). Among these active herbs, the methanolic extract from the aerial parts of Petroselinum crispum (parsley) showed potent estrogenic activity, which was equal to that of isoflavone glycosides from soybean. Through bioassay-guided separation, we isolated several flavone glycosides and a new flavone glycoside, 6"-acetylapiin, with estrogenic activity together with a new monoterpene glucoside, petroside. The structures of 6"-acetylapiin and petroside were characterized by the chemical and physicochemical evidence. Estrogenic activities of these flavone glycosides were found to be enhanced by removal of their glycoside moieties. The EC50 values (concentration needed to enhance the MCF-7 proliferation 50% compared to non-estrogen treated cell) of their aglycones are as follows, apigenin (1.0 microM), diosmetin (2.9 microM), and kaempferol (0.56 microM). The estrogenic activities of these flavones are nearly equal to those of the isoflavones, daidzein (0.61 microM) and genistein (0.60 microM). The methanolic extract of parsley, apiin, and apigenin restored the uterus weight in ovariectomized mice when orally administered for consecutive 7 days.

Animals↗

Bioactive saponins and glycosides. XVI. Nortriterpene oligoglycosides with gastroprotective activity from the fresh leaves of Euptelea polyandra Sieb. et Zucc. (1): structures of Eupteleasaponins I, II, III, IV, V, and V acetate.

The saponin fraction from the fresh leaves of Euiptelea polyandra Sieb. et Zucc. was found to exhibit potent gastroprotective activity. Fourteen new nortriterpene saponins called eupteleasaponins were isolated from the saponin fraction with gastroprotective activity. The structures of eupteleasaponins I, I1, III, IV, V, and V acetate were determined on the basis of chemical and physicochemical evidence as 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1 -->3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1 -->4)-beta-D-glucopyranosyl(1-->3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D- D-glucopyranosyl(1-->3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-rhamnopyranosyl(1 -->4)-beta-D-glucopyranosyl(1-->3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl(1 -->2)-[alpha-L-arabinopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-- >4)]-beta-D- glucopyranosyl(1-->3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosvl(1-->2)-[alpha-L-arabinopyranosyl (1 -->4)-beta-L-rhamnopyranosyl(1 -->4)]-beta-D-glucopyranosyl(1 -->3)-beta-D-xylopyranosylakebonoic acid, 3-O-alpha-L-rhamnopyranosyl(1 -->2)-beta-D-glucopyranosvl(1-->3)-beta-D-xylopyranosyleupteleo genin, and 3-O-alpha-L-rhamnopyranosyl(1-->2)-6"-O-acetyl-gamma-D-glucopyranosyl(1 -->3)-beta-D-xylopyranosyleupteleogenin.

Animals↗

Bioactive constituents of Chinese natural medicines. V. Radical scavenging effect of Moutan Cortex. (1): Absolute stereostructures of two monoterpenes, paeonisuffrone and paeonisuffral.

The methanolic extract and the ethyl acetate-soluble and methanol-eluted fractions from Chinese Moutan Cortex, the roots of Paeonia suffruticosa ANDREWS, were found to exhibit scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anion radical generated by the xanthine-xanthine oxidase system. Two monoterpenes called paeonisuffrone and paeonisuffral were isolated from the ethyl acetate-soluble fraction. Their absolute stereostructures were elucidated on the basis of chemical and physiochemical evidence, which included the application of a modified Mosher's method and lipase catalyzed debenzoylation reaction.

Bepridil↗

Medicinal foodstuffs. XX. Vasorelaxant active constituents from the roots of Angelica furcijuga Kitagawa: structures of hyuganins A, B, C, and D.

From the methanolic extract with vasorelaxant activity obtained from Angelica furcijuga Kitagawa, four new khellactone-type coumarins, hyuganins A, B, C, and D, were isolated together with twelve known coumarins, two known acetylenic compounds, and a known lignan. The structures of hyuganins A, B, C, and D were determined on the basis of chemical and physicochemical evidence. Nine principal coumarins (hyuganin A, anomalin, pteryxin, isopteryxin, isoepoxypteryxin, praerosides II and IV, apiosylskimmin, (R)-peucedanol 7-O-beta-D-glucopyranoside), two acetylenic compounds [(-)-falcarinol and falcarindioll, and related compounds were examined for inhibitory activities on high concentration of K+ (High K+)- and dl-norepinephrine (NE)-induced contractions. The results indicate that the 3'- and 4'-acyl groups of khellactone-type coumarins are essential for the inhibitory activity on the contractions by High K+. Hyuganin A and anomalin showed inhibitory effects on High K+-induced contraction, but not on NE-induced contraction. Other active coumarins (pteryxin, isopteryxin, isoepoxypteryxin) and an acetylenic compound (falcarindiol) non-selectively inhibited both contractions by High K+ and NE.

Animals↗

Medicinal foodstuffs. XIX. Absolute stereostructures of canavalioside, a new Ent-kaurane-type diterpene glycoside, and gladiatosides A1, A2, A3, B1, B2, B3, C1, and C2, new acylated flavonol glycosides, from sword bean, the seeds of Canavalia gladiata.

A new ent-kaurane-type glycoside, canavalioside, and eight new acylated flavonol glycosides, gladiatosides A1, A2, A3, B1, B2, B3, C1, and C2, were isolated from the seed of Canavalia gladiata together with robinin, kaempferol 3-O-beta-D-galactopyranosyl-7-O-alpha-L-rhamnopyranoside, and kaikasaponin III. The absolute stereostructures of canavalioside and gladiatosides A1, A2, B1, B2, B3, C1, and C2 were elucidated on the basis of chemical and physicochemical evidence.

Chemical Phenomena↗