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Biomedical subjects

H Koshino

Publications and source records attributed to H Koshino.

At least 37 records · Page 2Linked to original sources

Adxanthromycins A and B, new inhibitors of ICAM-1/LFA-1 mediated cell adhesion molecule from Streptomyces sp. NA-148. II. Physico-chemical properties and structure elucidation.

Adxanthromycins A and B are new inhibitors of ICAM-1/LFA-1 mediated cell adhesion molecule isolated from the fermentation broth of Streptomyces sp. NA-148. The molecular formula of adxanthromycins A and B were determined as C42H40O17 and C48H50O22, respectively by FAB-MS and NMR spectral analyses, and the structures of both compounds were elucidated to be a dimeric anthrone peroxide skeleton containing alpha-D-galactose by various NMR spectral analyses and chemical degradation.

Anti-Bacterial Agents↗

Haematocin, a new antifungal diketopiperazine produced by Nectria haematococca Berk. et Br. (880701a-1) causing nectria blight disease on ornamental plants.

A new antifungal diketopiperazine named haematocin was isolated from the culture broth of Nectria haematococca Berk. et Br. (880701a-1) causing blight disease on ornamental plants, Phalaenopsis spp. and Doritanopsis spp. Its structure was established by spectroscopic methods. Haematocin inhibited the germ-tube elongation and spore-germination of Pyricularia oryzae at the ED50 values of 30 microg/ml and 160 microg/ml, respectively.

Anti-Bacterial Agents↗

[Henoch-Schönlein purpura nephritis (HSPN) in children: comparison of the incidence and severity between two 12-year groups].

From 1971 to 1982, we treated 286 patients of HSP in Kitasato University Hospital. In these 286 patients, 137 developed purpura nephritis (47.9%). During the second 12-year period (from 1985 to 1996), we treated 34 HSPN patients among 189 HSP patients (18.0%). The clinico-pathological evaluations and comparisons in 30 cases from 1971 to 1982 and in 11 cases from 1985 to 1996 were performed, using the ISKDC grading. The numbers of patients of HSP and the incidence of HSPN both decreased in the more recent 12-year group. Furthermore, the severity of the renal histopathological findings decreased in the more recent group as well.

Adolescent↗

Automatic and voluntary control of attention in young and older adults.

Young and older adults searched for a target character in a 3-item display. On each trial, both a symbolic cue (arrow at fixation) and a spatial cue (abrupt onset of one item) could indicate the target's position. Participants were told to use the central arrow cue on all trials because it had 75% validity. The onset cue also had 75% validity for half the participants and 25% validity for the other half. Both age groups showed about the same cost and benefit effects for the central arrow cues, but the abrupt onsets had much larger cuing effects for older adults. Young adults were able to suppress at least partially an automatic attentional response to an abrupt onset item when the arrow cue preceded the onset and had a higher validity than the onset cue. Older adults appeared to be less able to inhibit their responses to abrupt onsets and to disengage their attention from invalid onset cues than were the young adults.

Adult↗

Structural and immunochemical characterization of a Neisseria gonorrhoeae epitope defined by a monoclonal antibody 2C7; the antibody recognizes a conserved epitope on specific lipo-oligosaccharides in spite of the presence of human carbohydrate epitopes.

Lipo-oligosaccharides (LOS) produced by Neisseria gonorrhoeae are important antigenic and immunogenic components of the outer membrane complex. Previously, we showed that murine monoclonal antibody (mAb) 2C7 did not cross-react with human glycosphingolipids but identified the LOS epitope that is widely expressed in vivo and in vitro (Gulati, S., McQuillen, D. P., Mandrell, R. E., Jani, D. B., and Rice, P. A. (1996) J. Infect. Dis. 174, 1223-1237). In the present study, we analyzed the structure of gonococcal strain WG LOS containing the 2C7 epitope and investigated the structural requirements for expression of the epitope. We determined that the WG LOS components are Hep[1]-elongated forms of 15253 LOS that have a lactose on both Hep[1] and Hep[2] (Yamasaki, R., Kerwood, D. E., Schneider, H., Quinn, K. P., Griffiss, J. M., and Mandrell, R. E. (1994) J. Biol. Chem. 269, 30345-30351). In addition, we found that expression of the 2C7 epitope within the LOS is blocked when the Hep[2]-lactose is elongated. Based on the structural data of these LOS and the results obtained from immunochemical analyses, we conclude the following: 1) mAb 2C7 requires both the 15253 OS minimum structure and the N-linked fatty acids in the lipoidal moiety for expression of the epitope; 2) mAb 2C7 binds to the LOS that elongates the lactose on Hep[1] of the 15253 OS, but not the one on Hep[2]; and 3) the 2C7 epitope is expressed on gonococcal LOS despite the presence of human carbohydrate epitopes such as a lactosamine or its N-acetylgalactosaminylated (globo) form. Our study shows that the conserved epitope defined by mAb 2C7 could potentially be used as a safe site for the development of a vaccine candidate.

Antibodies, Bacterial↗

Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum.

Terpenoids, 1, 2 and 3, which selectively inhibit eukaryotic DNA polymerase activities, were isolated from the fruiting body of a basidiomycete, Ganoderma lucidum, and their structures were determined by spectroscopic analyses. New terpenes, lucidenic acid O (1) and lucidenic lactone (2), prevented not only the activities of calf DNA polymerase alpha and rat DNA polymerase beta, but also these of human immunodeficiency virus type 1 reverse transcriptase. Cerevisterol (3), which was reported to be a cytotoxic steroid, inhibited only the activity of DNA polymerase alpha. Although these compounds did not influence the activities of prokaryotic DNA polymerases and other DNA metabolic enzymes such as T7 RNA polymerase and deoxyribonuclease I.

Animals↗

Enantiomeric purity and odor characteristics of 2- and 3-acetoxy-1, 8-cineoles in the rhizomes of Alpinia galanga willd.

(S)-(+)-O-methylmandelate esters of trans- and cis-1,3, 3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-ols (2- and 3-hydroxy-1,8-cineoles) were prepared, and eight diastereomers were separated. The absolute configuration of the asymmetric carbons of the cineole moiety of each diastereomer was determined by (1)H NMR data according to the Mosher theory. Each mandelate was reduced with LiAlH(4) to obtain optically pure hydroxy-1,8-cineoles, this being followed by acetylation to afford optically pure acetoxy-1, 8-cineoles. These acetates were subjected to chiral GC, using a cyclodextrin column, and the enantiomeric purity of trans- and cis-1, 3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-yl acetates in the aroma concentrate from the rhizomes of Alpinia galanga was determined as 93.9 (5S), 19.4 (5R), 63.5 (6R), and 100 (6R) % ee, respectively. The aroma character of each enantiomer was also evaluated by GC-sniffing.

Aluminum Compounds↗

The cyanogenic glucoside, prunasin (D-mandelonitrile-beta-D-glucoside), is a novel inhibitor of DNA polymerase beta.

A DNA polymerase beta (pol. beta) inhibitor has been isolated independently from two organisms; a red perilla, Perilla frutescens, and a mugwort, Artemisia vulgaris. These molecules were determined by spectroscopic analyses to be the cyanogenic glucoside, D-mandelonitrile-beta-D-glucoside, prunasin. The compound inhibited the activity of rat pol. beta at 150 microM, but did not influence the activities of calf DNA polymerase alpha and plant DNA polymerases, human immunodefficiency virus type 1 reverse transcriptase, calf terminal deoxynucleotidyl transferase, or any prokaryotic DNA polymerases, or DNA and RNA metabolic enzymes examined. The compound dose-dependently inhibited pol. beta activity, the IC(50) value being 98 microM with poly dA/oligo dT(12-18) and dTTP as the DNA template and substrate, respectively. Inhibition of pol. beta by the compound was competitive with the substrate, dTTP. The inhibition was enhanced in the presence of fatty acid, and the IC(50) value decreased to approximately 40 microM. In the presence of C(10)-decanoic acid, the K(i) value for substrate dTTP decreased by 28-fold, suggesting that the fatty acid allowed easier access of the compound to the substrate-binding site.

Amygdalin↗

4-Hydroxy-17-methylincisterol, an inhibitor of DNA polymerase-alpha activity and the growth of human cancer cells in vitro.

An ergosterol derivative, 4-hydroxy-17-methylincisterol (HMI), was found to be an inhibitor of mammalian DNA polymerases in vitro. HMI inhibited the activity of calf thymus DNA polymerase alpha (pol. alpha). Among the polymerases tested, pol. alpha was the most sensitive to inhibition by HMI, and the inhibition was concentration dependent. The inhibitory effect of HMI on pol. alpha was almost the same as that shown by aphidicolin, a well-known potent pol. alpha inhibitor. HMI had relatively less effect on rat DNA pol. beta, human immunodeficiency virus type 1 reverse transcriptase (HIV-RT), and calf thymus terminal deoxynucleotidyl transferase (TdT) in vitro, and did not influence the activities of prokaryotic DNA polymerases such as Klenow Fragment of DNA polymerase I, or the DNA-metabolic enzyme DNase I. HMI was found to be able to prevent the growth of human cancer cell lines originating from patients with leukemia or various solid tumors; its IC50 values ranged from 7.5 to 12 microM. We also synthesized other ergosterol derivatives and tested them, and found that two compounds, 17-methylincisterol and 4-acetyl-17-methylincisterol, have similar inhibitory effects.

Animals↗

Trichothecene 3-O-acetyltransferase protects both the producing organism and transformed yeast from related mycotoxins. Cloning and characterization of Tri101.

Trichothecene mycotoxins such as deoxynivalenol, 4,15-diacetoxyscirpenol, and T-2 toxin, are potent protein synthesis inhibitors for eukaryotic organisms. The 3-O-acetyl derivatives of these toxins were shown to reduce their in vitro activity significantly as assessed by assays using a rabbit reticulocyte translation system. The results suggested that the introduction of an O-acetyl group at the C-3 position in the biosynthetic pathway works as a resistance mechanism for Fusarium species that produce t-type trichothecenes (trichothecenes synthesized via the precursor trichotriol). A gene responsible for the 3-O-acetylation reaction, Tri101, has been successfully cloned from a Fusarium graminearum cDNA library that was designed to be expressed in Schizosaccharomyces pombe. Fission yeast transformants were selected for their ability to grow in the presence of T-2 toxin, and this strategy allowed isolation of 25 resistant clones, all of which contained a cDNA for Tri101. This is the first drug-inactivating O-acetyltransferase gene derived from antibiotic-producing organisms. The open reading frame of Tri101 codes for a polypeptide of 451 amino acid residues, which shows no similarity to any other proteins reported so far. TRI101 from recombinant Escherichia coli catalyzes O-acetylation of the trichothecene ring specifically at the C-3 position in an acetyl-CoA-dependent manner. By using the Tri101 cDNA as a probe, two least overlapping cosmid clones that cover a region of 70 kilobase pairs have been isolated from the genome of F. graminearum. Other trichothecene biosynthetic genes, Tri4, Tri5, and Tri6, were not clustered in the region covered by these cosmid clones. These new cosmid clones are considered to be located in other parts of the large biosynthetic gene cluster and might be useful for the study of trichothecene biosynthesis.

Acetylation↗

A furanoid labdane diterpene from Potamogeton nodosus.

A new furanoid diterpene, 15,16-epoxy-12-oxo-8(17), 13(16), 14-labdatrien-20,19-olide (1) was isolated from an ethanolic extract of Potamogeton nodosus. Its structure was elucidated by the usual spectroscopic methods, including 2D NMR techniques. Compound 1 was found to exhibit moderate inhibitory activity against a number of both Gram-positive and Gram-negative bacteria.

Anti-Bacterial Agents↗

The relationship between occlusal support and physical exercise ability.

This study was conducted to elucidate the relationship between the presence of occlusal support in edentulous subjects and their ability for physical exercise. Ten complete denture wearers were selected and instructed to jump vertically while standing on a force plate with and without occlusal support (i.e. dentures). On the curve recorded by the force plate (1) reaction time (latency) (2) jump elevation time and (3) maximum kicking force were analysed. The reaction time, which is an index of physical quickness, was significantly prolonged when the subjects lost their occlusal support. This result suggests that reconstruction of occlusal support at a desirable mandibular position has significance not only for the restoration of masticatory function but also for the maintenance of physical exercise.

Dental Occlusion↗

An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta.

As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M., Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the activities of mammalian DNA polymerases. We found a natural product from a basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy-5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta). However, when EPO at 0.25 mM was present, 10 microM or less of LA almost completely inhibited the pol. beta activity, while almost complete inhibition by LA itself was achieved at 80 microM or higher. Interestingly, under the same conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of the EPO was discussed.

Animals↗

Tongue motor skills and masticatory performance in adult dentates, elderly dentates, and complete denture wearers.

STATEMENT OF PROBLEM: For complete denture wearers the tongue plays an important role in the retention and stability of dentures and has a great influence on masticatory function. PURPOSE OF STUDY: The purpose of this study was to elucidate the relationship between tongue motor behavior and masticatory function. MATERIAL AND METHODS: Thirty healthy, normal adult dentates, 10 normal elderly dentates, and 20 complete denture wearers whose dentures were constructed by the same methods and materials were selected. Tongue motor skills were examined by an ultrasound system and masticatory performance was evaluated by the sieving method. RESULTS: The tongue motor skills of elderly dentates and complete denture wearers were statistically lower compared with those of adult dentates (p < 0.05, Duncan test). Tongue motor skills of complete denture wearers were statistically correlated with age (p < 0.01). Masticatory performance was statistically lower in relation to age in complete denture wearers (p < 0.01). The correlation coefficient was 0.74 between tongue motor skill and masticatory performance in complete denture wearers, which was statistically significant (p < 0.01). CONCLUSION: Age-related decreases in tongue motor skills and masticatory performance were demonstrated by ultrasound observations and sieving methods.

Adult↗

New indole derivatives with free radical scavenging activity from Agrocybe cylindracea.

Two new indole derivatives were isolated as free radical scavengers from the MeOH extract of Agrocybe cylindracea. The structures of these compounds were determined to be 6-hydroxy-1H-indole-3-carboxaldehyde (1) and 6-hydroxy-1H-indole-3-acetamide (2) on the basis of spectroscopic studies. Compounds 1 and 2 inhibited lipid peroxidation in rat liver microsomes, with IC50 values of 4.1 and 3.9 micrograms/mL, respectively.

Animals↗