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S Aono

Publications and source records attributed to S Aono.

At least 55 records · Page 3Linked to original sources
PubMed1995

Synthesis of both the enantiomers of aseanostatin P5 (sarcinic acid), an inhibitor of myeloperoxidase release, and four diastereomers of aggreceride A, a platelet aggregation inhibitor.

Both the enantiomers of aseanostatin P5 (sarcinic acid), an inhibitor of myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN), with high optical purity were synthesized by starting from (S)-2-methylbutanol and methyl (S)-3-hydroxy-2-methylpropanoate. They were converted to four diastereomers of aggreceride A, a platelet aggregation inhibitor.

Fatty Acids↗
PubMed1995

Warfarin-induced eosinophilic pleurisy.

A 51-year-old man was admitted to our hospital because of dry cough and low grade fever with right-sided pleural fluid and blood eosinophilia. Warfarin had been prescribed following coronary artery bypass grafting. After the discontinuation of warfarin the clinical and chest X-ray findings improved; readministration of the drug caused recurrent blood eosinophilia and pleural effusion in the other lung. Since no other specific etiologies for eosinophilia and pleural effusion were determined by extensive evaluation, warfarin seemed to be associated with his illness. This is the first report of warfarin-induced eosinophilic pleurisy.

Anticoagulants↗
PubMed1994

Cloning and expression of the gene encoding the 7Fe type ferredoxin from a thermophilic hydrogen oxidizing bacterium, Bacillus schlegelii.

The structural gene (fdxA) coding for a 7Fe type ferredoxin of a thermophilic hydrogen oxidizing bacterium Bacillus schlegelii has been cloned and sequenced. The fdxA coding region is 231 nucleotides which codes for a 77 amino acids protein with the molecular weight of 8,744 except for iron-sulfur clusters. The fdxA gene has been expressed in E. coli to obtain the recombinant ferredoxin. The recombinant ferredoxin have shown the identical properties to the native one for absorption spectra, and SDS-PAGE.

Amino Acid Sequence↗
PubMed1994

Protective effects of D-penicillamine and a thiazole derivative, SM-8849, on pristane-induced arthritis in mice.

To evaluate the antiarthritic properties of a novel thiazole derivative, the drugs SM-8849, D-penicillamine and indomethacin were administered to pristane-injected DBA/1 mice. The mice were treated daily with the agents for 32 weeks, starting from the day of the pristane injection. Treatment with SM-8849 (50 mg/kg) resulted in an amelioration of arthritic disease, as assessed by clinical, radiographic, and histologic examinations. Similar results were obtained in mice treated with 50 mg/kg D-penicillamine, although this disease modifying antirheumatic drug was slightly less effective than the same dose of SM-8849. In contrast, indomethacin at the maximum tolerated dose of 2 mg/kg did not alter the course of the disease. SM-8849 and D-penicillamine were also shown to reduce serum levels of rheumatoid factors and the acute-phase reactant, serum amyloid P component. Indomethacin failed to affect either parameter. Flow cytometric analysis revealed an elevation in the T-cell population that expressed CD44, a marker of murine memory T-cells, in spleens from pristane-injected mice. SM-8849, but not D-penicillamine, prevented the increase in this cell population. These results led us to conclude that pristine-induced arthritis was a useful model for the evaluation of antirheumatic agents, in that using this model, we were able to distinguish disease modifying antirheumatic drugs from nonsteroidal anti-inflammatory drugs. Our findings also indicate that SM-8849 shows antiarthritic activity, with a unique mechanism of action, differing from that of D-penicillamine.

Adjuvants, Immunologic↗
PubMed1994

A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I.

Crigler-Najjar syndrome (CN) type I, which is characterized by the complete absence of bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT) activity, is inherited as an autosomal recessive trait associated with unconjugated hyperbilirubinemia. Phenobarbital has no effect on the bilirubin concentration in the serum of patients with CN type I. Recently, cDNA for two human liver bilirubin UGT (UGT1A and UGT1D) were isolated, and their genetic organization was determined. The UGT1A (UGT1*1) and UGT1D (UGT1*4) genes each have a unique exon 1, whereas exons 2-5 are common to both genes. It has been predicted that some defect in the exons common to both genes is responsible for the absence of UGT1A and UGT1D activities in CN type I, and five cases with such a mutation have been reported. We describe here a new type of defect in the gene for bilirubin UGT in a patient with CN type I, namely, an abnormality in the exon 1 that is characteristic of the UGT1A gene. This mutation is a single nucleotide substitution, that is, C is changed to A at base position 840 in UGT1A cDNA, and this change results in a stop codon. Our patient is homozygous for the defect, and his nonconsanguineous parents and elder brother, who are clinically normal, are heterozygous for the defective allele. No mutation was detected in any exons of the UGT1D gene. Our results suggest that a homozygous nonsense or deletion mutation is detected not only in the exons common to UGT1A and UGT1D genes but also in unique exon 1 of UGT1A in CN type I.

Amino Acid Sequence↗
PubMed1993

Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II.

Crigler-Najjar syndrome (CN) type II is characterized by severe chronic nonhemolytic unconjugated hyperbilirubinemia due to reduced hepatic bilirubin UDP-glucuronosyl-transferase (UGT) activity. Two bilirubin UGT isozymes, UGT1A and UGT1D, have been identified. We analyzed the DNA sequence of the bilirubin UGT genes in a 5-year-old Japanese male patient with CN type II, who had consanguineous parents. Point mutations were found on exons 1 of the UGT1A and UGT1D genes. The abnormalities were single nucleotide substitutions of G by A and of T by C at base position 211 of UGT1A cDNA and at base position 395 of the UGT1D, respectively. We found another single nucleotide substitution of T by G on exon 5 common to both genes at base position 1456 of the UGT1A cDNA or 1459 of the UGT1D cDNA. These three mutations result in changes of glycine to arginine and of tyrosine to aspartic acid at amino acid positions 71 and 486 of the UGT1A protein, and of leucine to proline and of tyrosine to aspartic acid at amino acid positions 132 and 487 of the UGT1D protein, respectively. Our patient was homozygous for all defects and his parents and elder brother were heterozygous for all defective alleles. The findings suggest that the CN Type II is inherited as an autosomal recessive trait.

Adult↗
PubMed1993

[Genetic defect of the hyperbilirubinemic Gunn rat, a model for Crigler-Najjar syndrome type I].

The hyperbilirubinemic Gunn rat lacks hepatic UDP-glucuronosyltransferase (UDPGT) activity toward bilirubin and has been used as an animal model for human Crigler-Najjar syndrome type I. Rat liver bilirubin UDPGT cDNA was isolated. The cDNA shared an identical 913-bp sequence (corresponding to the C-terminal 247 amino acid residues) with that for phenol UDPGT whose activity was also deficient in the Gunn rat. The bilirubin UDPGT gene was mapped at the position of 37 on mouse chromosome 1 by analyzing restriction endonuclease fragment length variations using the rat bilirubin UDPGT cDNA as a probe. The genetic defect of bilirubin UDPGT in the mutant rat was proved to be a -1 frameshift mutation. The mutation was found not only to be located in the region where the cDNA for bilirubin UDPGT shared the identical sequence with that for phenol UDPGT but also to occur in the same position in the two cDNAs from the mutant.

Amino Acid Sequence↗
PubMed1992

Purification and characterization of a 7Fe ferredoxin from a thermophilic hydrogen-oxidizing bacterium, Bacillus schlegelii.

A ferredoxin (Fd) was purified from a thermophilic hydrogen-oxidizing bacterium, Bacillus schlegelii. This ferredoxin was a monomer with apparent molecular weight of 13,000 and contained 7 mol Fe/mol ferredoxin. The oxidized ferredoxin showed the characteristic EPR spectrum for [3Fe-4S]1+ (1.2 spin/mol Fd). This signal disappeared upon reduction with dithionite and new signals due to [3Fe-4S]0 and [4Fe-4S]1+ (0.7 spin/mol Fd) appeared. The quantitation of EPR signals and the iron content reveal that B. schlegelii ferredoxin contains one [3Fe-4S]1+/0 and one [4Fe-4S]2+/1+ cluster. The ferredoxin has the characteristic distribution of cysteines (-Cys8-X7-Cys16-X3-Cys20-Pro-) for 7Fe ferredoxins in the N-terminus.

Amino Acid Sequence↗
PubMed1991

Determinants of protein hyperthermostability: purification and amino acid sequence of rubredoxin from the hyperthermophilic archaebacterium Pyrococcus furiosus and secondary structure of the zinc adduct by NMR.

The purification, amino acid sequence, and two-dimensional 1H NMR results are reported for the rubredoxin (Rd) from the hyperthermophilic archaebacterium Pyrococcus furiosus, an organism that grows optimally at 100 degrees C. The molecular mass (5397 Da), iron content (1.2 +/- 0.2 g-atom of Fe/mol), UV-vis spectrophotometric properties, and amino acid sequence (60% sequence identity with Clostridium pasteurianum Rd) are found to be typical of this class of redox protein. However, P. furiosus Rd is remarkably thermostable, being unaffected after incubation for 24 h at 95 degrees C. One- and two-dimensional 1H nuclear magnetic resonance spectra of the oxidized [Fe(III)Rd] and reduced [Fe(II)Rd] forms of P. furiosus Rd exhibited substantial paramagnetic line broadening, and this precluded detailed 3D structural studies. The apoprotein was not readily amenable to NMR studies due to apparent protein oxidation involving the free cysteine sulfhydryls. However, high-quality NMR spectra were obtained for the Zn-substituted protein, Zn(Rd), enabling detailed NMR signal assignment for all backbone amide and alpha and most side-chain protons. Secondary structural elements were determined from qualitative analysis of 2D Overhauser effect spectra. Residues A1-K6, Y10-E14, and F48-E51 form a three-strand antiparallel beta-sheet, which comprises ca. 30% of the primary sequence. Residues C5-Y10 and C38-A43 form types I and II amide-sulfur tight turns common to iron-sulfur proteins. These structural elements are similar to those observed by X-ray crystallography for native Rd from the mesophile C. pasteurianum. However, the beta-sheet domain in P. furiosus Rd is larger than that in C. pasteurianum Rd and appears to begin at the N-terminal residue. From analysis of the secondary structure, potentially stabilizing electrostatic interactions involving the charged groups of residues Ala(1), Glu(14), and Glu(52) are proposed. These interactions, which are not present in rubredoxins from mesophilic organisms, may prevent the beta-sheet from "unzipping" at elevated temperatures.

Amino Acid Sequence↗
PubMed1991

The extremely thermophilic eubacterium, Thermotoga maritima, contains a novel iron-hydrogenase whose cellular activity is dependent upon tungsten.

Thermotoga maritima is the most thermophilic eubacterium currently known and grows up to 90 degrees C by a fermentative metabolism in which H2, CO2, and organic acids are end products. It was shown that the production of H2 is catalyzed by a single hydrogenase located in the cytoplasm. The addition of tungsten to the growth medium was found to increase both the cellular concentration of the hydrogenase and its in vitro catalytic activity by up to 10-fold, but the purified enzyme did not contain tungsten. It is a homotetramer of Mr 280,000 and contains approximately 20 atoms of Fe and 18 atoms of acid-labile sulfide/monomer. Other transition metals, including nickel (and also selenium), were present in only trace amounts (less than 0.1 atoms/monomer). The hydrogenase was unstable at both 4 and 23 degrees C, even under anaerobic conditions, but no activity was lost in anaerobic buffer containing glycerol and dithiothreitol. Under these conditions the enzyme was also quite thermostable (t50% approximately 1 h at 90 degrees C) but extremely sensitive to irreversible inactivation by O2 (t50% approximately 10 s in air). The optimum pH ranges for H2 evolution and H2 oxidation were 8.6-9.5 and greater than or equal to 10.4, respectively, and the optimum temperature for catalytic activity was above 95 degrees C. In contrast to mesophilic Fe hydrogenases, the T. maritima enzyme had very low H2 evolution activity, did not use T. maritima ferredoxin as an electron donor for H2 evolution, was inhibited by acetylene but not by nitrite, and exhibited EPR signals typical of [2Fe-2S]1+ clusters. Moreover, the oxidized enzyme did not exhibit the rhombic EPR signal that is characteristic of the catalytic iron-sulfur cluster of mesophilic Fe hydrogenases. These data suggest that T. maritima hydrogenase has a different FeS site and/or mechanism for catalyzing H2 production. The potential role of tungsten in regulating the activity of this enzyme is discussed.

Amino Acids↗
PubMed1991

Genetic defect of bilirubin UDP-glucuronosyltransferase in the hyperbilirubinemic Gunn rat.

The genetic defect of bilirubin UDP-glucuronosyltransferase (UDPGT) in the hyperbilirubinemic Gunn rat was proved to be a -1 frameshift mutation. The mutation was found not only to be located in the region where bilirubin UDPGT cDNA shared an identical sequence with 3-methylcholanthrene (3M C)-inducible UDPGT cDNA but also to occur in the same position on the two cDNAs from the mutant rat. At the 5' end of the identical region there was a consensus sequence for splicing, of which position coincided with the boundary between the 2nd and 3rd exon of the testosterone UDPGT gene. These results strongly suggest that mRNAs for bilirubin and 3M C-inducible UDPGTs are produced from a single primary-transcript after an alternative splicing and the defects of bilirubin and 3M C-inducible UDPGTs in the mutant rat are caused by a point mutation on a common exon.

Animals↗
PubMed1991

Absence of erythrocyte arginase protein in Japanese patients with hyperargininemia.

In Japan, hyperargininemia has been reported in only 5 unrelated families and four patients are alive at present. In this study we examined arginase protein in erythrocytes of these Japanese patients using two analytical methods of immunoblotting and two-dimensional gel electrophoresis. Immunoblotting study with anti-E. coli-expressed human liver arginase rabbit IgG revealed lack of cross-reacting materials in the erythrocyte lysates from these patients. On two-dimensional gels, arginase protein was detected in any control subject, but it was completely absent in all the patients studied. These results suggest that either arginase protein in erythrocytes is not produced or it is structurally labile in these patients.

Adult↗
PubMed1990

Spectroscopic characterization of the novel iron-sulfur cluster in Pyrococcus furiosus ferredoxin.

Pyrococcus furiosus ferredoxin is the only known example of a ferredoxin containing a single [4Fe-4S] cluster that has non-cysteinyl ligation of one iron atom, as evidenced by the replacement of a ligating cysteine residue by an aspartic acid residue in the amino acid sequence. The properties of the iron-sulfur cluster in both the aerobically and anaerobically isolated ferredoxin have been characterized by EPR, magnetic circular dichroism, and resonance Raman spectroscopies. The anaerobically isolated ferrodoxin contains a [4Fe-4S]+,2+ cluster with anomalous properties in both the oxidized and reduced states which are attributed to aspartate and/or hydroxide coordination of a specific iron atom. In the reduced form, the cluster exists with a spin mixture of S = 1/2 (20%) and S = 3/2 (80%) ground states. The dominant S = 3/2 form has a unique EPR spectrum that can be rationalized by an S = 3/2 spin Hamiltonian with E/D = 0.22 and D = +3.3 +/- 0.2 cm-1. The oxidized cluster has an S = 0 ground state, and the resonance Raman spectrum is characteristic of a [4Fe-4S]2+ cluster except for the unusually high frequency for the totally symmetric breathing mode of the [4Fe-4S] core, 342 cm-1. Comparison with Raman spectra of other [4Fe-4S]2+ centers suggests that this behavior is diagnostic of anomalous coordination of a specific iron atom. The iron-sulfur cluster is shown to undergo facile and quantitative [4Fe-4S] in equilibrium [3Fe-4S] interconversion, and the oxidized and reduced forms of the [3Fe-4S] cluster have S = 1/2 and S = 2 ground states, respectively. In both redox states the [3Fe-4S]0,+ cluster exhibits spectroscopic properties analogous to those of similar clusters in other bacterial ferredoxins, suggesting non-cysteinyl coordination for the iron atom that is removed by ferricyanide oxidation. Aerobic isolation induces partial degradation of the [4Fe-4S] cluster to yield [3Fe-4S] and possibly [2Fe-2S] centers. Evidence is presented to show that only the [4Fe-4S] form of this ferredoxin exists in vivo.

Aerobiosis↗
PubMed1990

Heterogeneity of human islet cell antibodies in terms of cross-species reactivity.

There has been no consistent view about the cross-species reactivity of islet cell antibodies (ICA), and no report about their target antigens in the pancreatic islet cells of different species. Therefore, we examined the cross-reactivity of human ICA against rodent pancreatic islet cells, and found at least two types of ICA, one having a comparatively strong cross-reactivity and the other lacking it. Furthermore, using human as well as some rodent pancreatic tissues that had been modified chemically, we came to suspect that the target antigens of ICA were sialic acid residues of glycolipids. Therefore, we suggest that there are at least two types of ICA recognizing sialic acid residues of glycolipids, one reacting with antigen(s) commonly present in human and rat islets, and the other with antigen(s) only present in human islets.

Animals↗
PubMed1989

HLA-DQ antigens and DQ beta amino acid 57 of Japanese patients with insulin-dependent diabetes mellitus: detection of a DRw8DQw8 haplotype.

DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. Ala) at residue 57 of the DQ beta chain (non-Asp-57). Most Caucasoid IDDM patients are homozygous non-Asp-57. We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). Their DQB1 alleles and the aa encoded by their DQB1 codons 57 were identified, using 11 different sequence-specific oligonucleotide probes. Secondly, they were examined with DQw8 specific T lymphocyte clones and with anti-DQ monoclonal antibodies. The DQB1 genes on their DR4 and DRw9 haplotypes in all cases encoded Asp-57. Two patients were Asp-57 homozygous, the rest were Asp-57/non-Asp-57 heterozygous. The DR4 haplotypes all carried DQw4 (rather than DQw8), and the DRw9 haplotypes all carried DQw9. Furthermore, five of six DRw8 positive patients carried a previously undetected DRw8DQw8 haplotype, where both the DQA1 and DQB1 genes were similar to those usually found on the DR4DQw8 haplotype. Thus, the DR/DQ allele combinations and aa residue 57 of the DQ beta chain of Caucasoid and Japanese IDDM patients are largely different.

Antibodies, Monoclonal↗
PubMed1989

A novel and remarkably thermostable ferredoxin from the hyperthermophilic archaebacterium Pyrococcus furiosus.

The archaebacterium Pyrococcus furiosus is a strict anaerobe that grows optimally at 100 degrees C by a fermentative-type metabolism in which H2 and CO2 are the only detectable products. A ferredoxin, which functions as the electron donor to the hydrogenase of this organism was purified under anaerobic reducing conditions. It had a molecular weight of approximately 12,000 and contained 8 iron atoms and 8 cysteine residues/mol but lacked histidine or arginine residues. Reduction and oxidation of the ferredoxin each required 2 electrons/mol, which is consistent with the presence of two [4Fe-4S] clusters. The reduced protein gave rise to a broad rhombic electronic paramagnetic resonance spectrum, with gz = 2.10, gy = 1.86, gx = 1.80, and a midpoint potential of -345 mV (at pH 8). However, this spectrum represented a minor species, since it quantitated to only approximately 0.3 spins/mol. P. furiosus ferredoxin is therefore distinct from other ferredoxins in that the bulk of its iron is not present as iron-sulfur clusters with an S = 1/2 ground state. The apoferredoxin was reconstituted with iron and sulfide to give a protein that was indistinguishable from the native ferredoxin by its iron content and electron paramagnetic resonance properties, which showed that the novel iron-sulfur clusters were not artifacts of purification. The reduced ferredoxin also functioned as an electron donor for H2 evolution catalyzed by the hydrogenase of the mesophilic eubacterium Clostridium pasteurianum. P. furiosus ferredoxin was resistant to denaturation by sodium dodecyl sulfate (20%, wt/vol) and was remarkably thermostable. Its UV-visible absorption spectrum and electron carrier activity to P. furiosus hydrogenase were unaffected by a 12-h incubation of 95 degrees C.

Amino Acids↗
PubMed1989

Mode of bilirubin deposition in the cerebellum of developing jaundiced Gunn rats.

Bucolome is known as a potent displacer of bilirubin from the blood into tissues. The effects of the drug on newborn rats with congenital jaundice (Gunn rats) were examined on postnatal days 7, 11, 15 and 21. A single subcutaneous injection of bucolome resulted in a rapid fall of the total plasma bilirubin concentration and the lowered level persisted as long as 23 h. Concomitantly with the drop, the cerebellar bilirubin level increased within 1 h. Although cerebellar bilirubin returned to the initial level after 24 h in rats treated with bucolome on days 7 and 21, it remained almost constant or rather increased during the period of 1-24 h in rats treated on days 11 or 15. In 15-day-old rats, localized yellow staining in the cerebellum 24 h after treatment was most apparent in the granule cell layer of the ventral part of the pyramis and the dorsal part of the uvula under the dissecting microscope. These observations suggest that the period most susceptible to bilirubin deposition lies around day 15 in the cerebellum of jaundiced Gunn rats.

Aging↗