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M Ota

Publications and source records attributed to M Ota.

At least 109 records · Page 6Linked to original sources
PubMed1999

Feasibility in the inverse protein folding protocol.

Methods for protein structure (3D)-sequence (1D) compatibility evaluation (threading) have been developed during the past decade. The protocol in which a sequence can recognize its compatible structure in the structural library (i.e., the fold recognition or the forward-folding search) is available for the structure prediction of new proteins. However, the reverse protocol, in which a structure recognizes its homologous sequences among a sequence database, named the inverse-folding search, is a more difficult application. In this study, we have investigated the feasibility of the latter approach. A structural library, composed of about 400 well-resolved structures with mutually dissimilar sequences, was prepared, and 163 of them had remote homologs in the library. We examined whether they could correctly seek their homologs by both forward- and inverse-folding searches. The results showed that the inverse-folding protocol is more effective than the forward-folding protocol, once the reference states of the compatibility functions are appropriately adjusted. This adjustment only slightly affects the ability of the forward-folding search. We noticed that the scoring, in which a given sequence is re-mounted onto a structure according to the 3D-1D alignment determined by the dynamic programming method, is only effective in the forward-folding protocol and not in the inverse-folding protocol. Namely, the inverse-folding search works significantly better with the score given by the 3D-1D alignment per se, rather than that obtained by the re-mounting. The implications of these results are discussed.

Algorithms↗
PubMed1999

Allopurinol increases ear swelling and mortality in a dinitrofluorobenzene-induced contact hypersensitivity mouse model.

The immunomodulatory effects of allopurinol were investigated in a mouse contact hypersensitivity model. Allopurinol caused a time- and dose-dependent lethal effect in dinitrofluorobenzene (DNFB)-sensitized mice. Furthermore, allopurinol markedly increased ear swelling in the remaining mice. In contrast, TMX-67, a newly synthesized xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitor, had almost no effect on DNFB-sensitized mice. Allopurinol reduced both the spleen weight and white blood cell count in DNFB-sensitized mice without affecting the T cell subset of splenocytes. The production of interferon (IFN)-gamma, in the splenocytes of DNFB-sensitized mice was reduced by allopurinol administration. Death due to allopurinol was much lower in the non-sensitized mice than in the DNFB-sensitized mice. These findings indicate that allopurinol may interact with DNFB to enhance its toxicity and allopurinol might also modulate or enhance the inflammatory effect of DNFB. Also, DNFB may cause metabolic alterations via inflammation, leading to enhanced allopurinol toxicity.

Allopurinol↗
PubMed1999

Association of MICA gene and HLA-B*5101 with Behçet's disease in Greece.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.

Adult↗
PubMed1999

[Efficacy of adjuvant hepatic arterial infusion chemotherapy following resection of colorectal liver metastases].

PURPOSE: The aim of this study is to evaluate the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) following liver resection on the frequency of residual liver recurrence and overall survival. PATIENTS AND METHODS: During 1992 to 1997, 84 patients with liver metastasis from colorectal cancer resected curatively had undergone adjuvant HAIC. The regimen of the HAIC is 1,500 mg of 5-FU by 24-hr continuous infusion once a week for eight weeks. 37 cases in the HAIC group, including patients given more than 7 g of 5-FU, were compared with the control group. RESULT: The cumulative 5-year liver recurrence-free ratios were 72.6% in the HAIC group and 29.8% in the control group (p = 0.0005). The cumulative 5-year survival ratios were 61.4% in the HAIC group and 28.0% in the control group (p = 0.0069). Multivariate analysis revealed that more than 5 mm of surgical margin and adjuvant HAIC significantly decreased the risk of recurrences in residual liver. CONCLUSION: Adjuvant HAIC is an effective procedure to prevent recurrence in residual liver and improve the prognosis of patients with liver metastasis from colorectal cancer.

Adult↗
PubMed1999

Inhibition of retinoic acid-inducible transcription by COUP-TFI in human salivary gland adenocarcinoma cell line HSG.

Human salivary gland adenocarcinoma cells (HSG) express nuclear receptors, all-trans-retinoic acid (at-RA) receptors (RARs), and retinoid X/9-cis-retinoic acid (9-c-RA) receptors (RXRs). In order to investigate whether the endogenous RARs or RXRs of HSG cells can induce transcription activation, the thymidine kinase promoter (TK)-driven luciferase reporter gene containing the retinoic acid response element (RARE), of RARbeta, betaRARE2-TK-Luc, was transfected into HSG cells and ligand-dependent transcription activation was examined. Luciferase activity of cell lysate increased by the treatment with either at-RA or 9-c-RA. Co-transfection of RARalpha and (or) RXRalpha-expression plasmids with the reporter gene enhanced the luciferase activity, suggesting that endogenous RARs and RXRs work as ligand-dependent transfactors in HSG cells. Reverse transcriptase - polymerase chain reaction analysis revealed that HSG cells express chicken ovalbumin upstream promoter - transcription factor I (COUP-TFI). Co-transfection of COUP-TFI-expression plasmid suppressed the at-RA-induced transcription activation of the reporter gene. Similar results were shown using a chromatin-integrated reporter gene system, using a stably transfected beta-RARE2-TK-beta-galactosidase (beta-Gal) reporter gene. The at-RA-dependent increase in the beta-Gal expression was completely inhibited by COUP-TFI. The transfection of antisense oligonucleotide of COUP-TFI squelched the RA-dependent growth inhibition induced by RAR-RXR heterodimers. Conclusively, RARs and RXRs of HSG cells are functional and play roles as transactivators in at-RA-sensitive processes such as the proliferation or differentiation of cells. COUP-TFI very likely regulates these processes by repressing the functions of these transactivators.

Adenocarcinoma↗
PubMed1999

Nephrotoxic effects of allopurinol in dinitrofluorobenzene-sensitized mice: comparative studies on TEI-6720.

Allopurinol is widely used and generally well-tolerated. However, when used in patients with renal insufficiency it may have life-threatening toxic effects known as allopurinol hypersensitivity syndrome (AHS). We previously found that allopurinol increased ear swelling and mortality in a DNFB-induced contact hypersensitivity mouse model. In the present study, we investigated the toxic effect of allopurinol on DNFB-sensitized mice in order to clarify the mechanism responsible for the lethal effect of allopurinol. Allopurinol increased plasma GPT and GOT in DNFB-sensitized mice and markedly increased plasma creatinine and BUN. The increase in plasma GPT and GOT was moderate and declined time-dependently. In contrast, the increase in plasma creatinine and BUN was striking and continued until 18 hr after administration of allopurinol at 100 mg/kg/day. Although allopurinol increased GOT and GPT in DNFB-sensitized mice, no effect was observed in non-sensitized mice even at 100 mg/kg/day, indicating that allopurinol essentially has no toxic effect on the liver. A high dose of allopurinol induced renal impairment even in non-sensitized mice. These observations indicate that there is some biological interaction between allopurinol and DNFB, and suggest that allopurinol may modulate or enhance the inflammatory reactions induced by DNFB, and/or that DNFB may cause metabolic changes via inflammation, leading to the enhanced toxicity of allopurinol. In contrast, TEI-6720, a newly synthesized XOD/XDH inhibitor, had almost no effect on DNFB-sensitized mice. TEI-6720 at 1 mg/kg, in terms of hypouricemic effect, appeared to be more potent than allopurinol at 3 mg/kg. Therefore, the nephrotoxic effect of allopurinol observed in the present study may not be related to XOD/XDH inhibitory activity.

Acute Kidney Injury↗
PubMed1999

A comparative study on the hypouricemic activity and potency in renal xanthine calculus formation of two xanthine oxidase/xanthine dehydrogenase inhibitors: TEI-6720 and allopurinol in rats.

In this study, the hypouricemic efficacy of a novel xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, was compared with that of allopurinol in a hyperuricemic rat model established by feeding the animals oxonate, a uricase inhibitor. In addition, using normal rats, the changes in xanthine concentration in plasma and the concentrations and absolute quantities of uric acid, allantoin and xanthine in urine were analyzed during a 28-day period of repeated administration of TEI-6720 to determine the changes occurring during this period and the conditions required for the formation of xanthine crystals and calculi in comparison with allopurinol. TEI-6720 and allopurinol caused a significant dose-dependent decrease in plasma uric acid levels in the hyperuricemic rat model and the ED50 of TEI-6720 was lower than that of allopurinol, indicating that in terms of hypouricemic efficacy TEI-6720 is more potent than allopurinol. TEI-6720 also showed more potent activity than allopurinol in decreasing urinary uric acid and allantoin levels in normal rats. In addition, TEI-6720 and allopurinol showed similar dose-response curves for the decrease in uric acid or allantoin concentration, and the associated increase in xanthine concentration, indicating that TEI-6720 and allopurinol have similar pharmacological characteristics although the dosage required differs. The efficacy of TEI-6720 in increasing plasma and urinary xanthine levels in normal rats was approximately 10- to 30-fold greater than that of allopurinol. However, with respect to renal xanthine calculus formation, there was only about a 3-fold difference in dosage comparing TEI-6720 and allopurinol. This difference suggests that there may be another factor independent of xanthine, and dependent on the drug itself, involved in renal calculus formation caused by allopurinol. The daily excretion of purine metabolites per body weight was about 20-fold higher in rats than in humans. From these results, it is concluded that TEI-6720 has potent hypouricemic activity and that, compared to allopurinol, administration of TEI-6720 is not likely to result in a higher incidence of calculus formation.

Allantoin↗
PubMed1998

Genes from nine genomes are separated into their organisms in the dinucleotide composition space.

A set of 16 kinds of dinucleotide compositions was used to analyze the protein-encoding nucleotide sequences in nine complete genomes: Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Mycoplasma genitalium, Mycoplasma pneumoniae, Synechocystis sp., Methanococcus jannaschii, Archaeoglobus fulgidus, and Saccharomyces cerevisiae. The dinucleotide composition was significantly different between the organisms. The distribution of genes from an organism was clustered around its center in the dinucleotide composition space. The genes from closely related organisms such as Gram-negative bacteria, mycoplasma species and eukaryotes showed some overlap in the space. The genes from nine complete genomes together with those from human were discriminated into respective clusters with 80% accuracy using the dinucleotide composition alone. The composition data estimated from a whole genome was close to that obtained from genes, indicating that the characteristic feature of dinucleotides holds not only for protein coding regions but also noncoding regions. When a dendrogram was constructed from the disposition of the clusters in the dinucleotide space, it resembled the real phylogenetic tree. Thus, the distinct feature observed in the dinucleotide composition may reflect the phylogenetic relationship of organisms.

Amino Acids↗
PubMed1998

Association of high-altitude pulmonary edema with the major histocompatibility complex.

BACKGROUND: A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. METHODS AND RESULTS: The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6-positive subjects with HAPE was significantly higher than that of the HLA-DR6-negative subjects with HAPE. CONCLUSIONS: There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Adolescent↗
PubMed1998

Role of hydrophobic amino acids in gurmarin, a sweetness-suppressing polypeptide.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre consists of 35 amino acid residues and contains three intramolecular disulfide bonds. Nuclear magnetic resonance analysis showed that the hydrophobic side chains of Tyr-13, Tyr-14, Trp-28, and Trp-29 in gurmarin are oriented outwardly. Together with the hydrophobic side chains of Leu-9, Ile-11, and Pro-12, they form a hydrophobic cluster, and therefore these hydrophobic groups are assumed to act as the site for interaction with the receptor protein. To examine the roles of these hydrophobic amino acids, they were replaced by Gly. The resulting [Gly13,14,28,29] gurmarin and [Gly9,11,13,14,28,29]-gurmarin did not suppress the responses to sucrose, glucose, fructose, or Gly. This result strongly suggests that these hydrophobic amino acids are involved in the interaction with the receptor protein.

Amino Acid Sequence↗
PubMed1998

Synthesis, characterization, and sweetness-suppressing activities of gurmarin analogues missing one disulfide bond.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre consists of 35 amino acid residues and includes three intramolecular disulfide bonds. The roles of the three disulfide bonds were investigated by replacing each with two alanine residues by solid-phase synthesis. Nine analogues of [Ala3,18]gurmarin, [Ala10,23]gurmarin, and [Ala17,33]-gurmarin were obtained. Three analogues had native disulfide bonds, while the other six had non-native disulfide bonds. The three analogues with native disulfide bonds suppressed the response to sucrose, but not those to glucose, fructose, saccharin, or glycine in rats. In contrast, the six analogues with non-native disulfide bonds did not suppress the responses to any of these sweeteners. These results suggest that the native disulfide bonds of gurmarin are necessary for interaction with the receptor protein, and that the sucrose-specific receptor site is present in rats.

Amino Acid Sequence↗
PubMed1998

Subtyping and characterization of D1S80 alleles in a Japanese population using PCR-RFLP.

In a Japanese population study of the D1S80 locus 24 alleles ranging from allele 16 to allele43 were analysed using PCR-RFLP. As two repeat units were found to contain the restriction cleavage site (CCAGG) for EcoRII, we digested the alleles with EcoRII, separated the digested fragments on polyacrylamide gels and stained with ethidium bromide. Of the 24 alleles 11 band patterns were identified and tentatively labeled E1 to E11. A total of 42 subtypes were detected in a population group of 111 unrelated individuals. All samples of allele 18 were of the E3 type, while about 60% of the allele24 samples were of the E4 type and about 40% were of the E8 type. The third most frequent allele (allele30) contained four types, E4, E8, E5 and E6. No deviations from Hardy-Weinberg equilibrium were observed. Since this method could differentiate those samples which had the same length but different sequences, it is quite useful for paternity testing and individual identification.

Alleles↗
PubMed1998

The development of extrahepatic portal obstruction after undergoing multiple operations for a congenital dilatation of the bile duct: report of a case.

As a long-term complication after undergoing a cystenterostomy for a congenital dilatation of the bile duct, liver cirrhosis due to stenosis of the anastomosis or reflux cholangitis has been reported in conjunction with subsequent portal hypertension. We treated a 48-year-old Japanese woman who developed both portal hypertension and pancytopenia after undergoing multiple operations for a congenital dilatation of the bile duct. She underwent a Hassab's operation in July 1994, when an occlusion of the extrahepatic portal vein, which resulted in portal hypertension, was first noted; the liver was microscopically normal. The etiology of the extrahepatic portal obstruction in our patient was most likely due to either repeated inflammation or adhesion at the hepatic hilus. Based on these findings, the differential diagnosis of portal hypertension after an operation for a congenital dilatation of the bile duct should therefore include an extrahepatic portal obstruction in addition to liver cirrhosis.

Anastomosis, Surgical↗
PubMed1998

Association between MICA gene A4 allele and acute anterior uveitis in white patients with and without HLA-B27.

PURPOSE: Acute anterior uveitis is strongly associated with the HLA-B27 antigen and triggered by the involvement of some external factors. However, it is uncertain whether HLA-B27 itself or other gene(s) near the HLA-B region in a linkage disequilibrium with HLA-B27 predispose to this uveitis. We therefore investigated microsatellite polymorphism in the transmembrane region of the major histocompatibility complex class I chain-related gene A (MICA), located 47 kilobases (kb) on the centromeric side of the HLA-B gene on the short arm of chromosome 6 within 6p21.3. METHODS: We examined the following patients for MICA gene polymorphism by means of polymerase chain reaction and subsequent automated fragment detection by fluorescent-based technology: 64 (37 HLA-B27-positive and 27 HLA-B27-negative) whites with acute anterior uveitis, 74 (67 HLA-B27-negative and 7 HLA-B27-positive) ethnically matched random controls, and 36 HLA-B27-positive healthy controls. RESULTS: The microsatellite allele consisting of four repetitions of GCT/AGC (designated A4 allele) was present at the significantly higher phenotype frequency (71.9%) in the patient group than in the ethnically matched random control group (13.5%) (P < .0000001, corrected P < .0000001). The A4 allele was strongly linked to HLA-B27 in a white population. However, the A4 allele was also found at the significantly higher phenotype frequency (37.0%) even in the HLA-B27-negative patient group than in the ethnically matched HLA-B27-negative control group (4.5%) (P = .0086, corrected P = .043). CONCLUSIONS: These results suggest that the MICA gene itself or other nearby gene(s) linked to the MICA A4 allele may be involved in the development of acute anterior uveitis in a white population.

Acute Disease↗
PubMed1998

Effects of endothelin-induced nitric oxide on venous circulation and renal water-electrolyte handling.

To assess the interaction of endothelin (ET) with nitric oxide (NO) and the effects on venous circulation and handling of renal water and electrolytes, ET (1.0 ng/kg/min) or saline was administered with or without three doses (0.27, 2.7 and 27 ng/kg/min for 40 min) of N omega-nitro-L-arginine methyl ester (L-NAME), and NO synthase inhibitor, in anesthetized dogs. ET increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), urine flow (UF), and urinary K excretion (UKV), and decreased cardiac output (CO), urinary osmolality (Uosm), renal plasma flow (RPF), and glomerular filtration rate (GFR). L-NAME increased blood pressure (BP), TPR, PCWP, right atrial pressure (RAP), and mean circulatory filling pressure (MCFP), and decreased CO, RPF, and GFR, ET plus L-NAME markedly increased TPR, resistance to venous return, and plasma atrial natriuretic peptide (ANP), but not BP and MCFP, and curtailed the ET-induced responses in UF, UKV, and Uosm. Plasma aldosterone (ALD) was decreased in all groups, but plasma vasopressin (AVP) and renin activity (PRA) were not altered in any group. These results indicate that ET-induced NO formation might mitigate increases in venous as well as arterial vascular resistance and changes in renal handling of water and electrolytes, and might also play an inhibitory role in ANP release but not in PRA or AVP and ALD release.

Animals↗
PubMed1998

Twenty-six new polymorphic microsatellite markers around the HLA-B, -C and -E loci in the human MHC class I region.

The human major histocompatibility complex (MHC) class I region is believed to contain a large number of disease-related loci for diseases such as Behçet's disease and psoriasis vulgaris. Although many novel genes have recently been identified in this region, it still appears to be difficult to relate any of these new genes to MHC class I-associated diseases as causative genetic factors. During the course of large-scale genomic sequencing of the human MHC class I region, we identified 262 microsatellite sequences with dinucleotide to pentanucleotide repeats around the HLA-B, -C and HLA-E genes. Of these, 26 microsatellites were investigated for repeat polymorphism using 60 HLA homozygous B-cell lines and 60 healthy random individuals. The average number of alleles at these microsatellite loci was 9.6 with a PIC (polymorphism content value) of 0.69. These new polymorphic microsatellite markers will probably be very useful for precise mapping of disease-related genes within the HLA class I region in linkage analysis. Moreover, they will provide a powerful tool to study recombination events in this region, which contributes to haplotypic diversification.

Cell Line↗