Taurine and kynureninase.
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Amino Acid Sequence↗
Biomedical subjects
F Takeuchi
Publications and source records attributed to F Takeuchi.
Ezrin, radixin and moesin are possible auto-immune antigens in rheumatoid arthritis.
In order to deduce which cellular molecules react with the sera from patients with rheumatoid arthritis (RA), human and mouse cellular extracts were fractionated stepwise, by ethanol precipitation and their reactivity analysed by Western blotting. It was found that three cytoplasmic molecules with molecular weights of 80,000, 81,000 and 77,000 were immunoreactive and they were identified as ezrin (E), radixin (R), and moesin (M), respectively, by partial amino acid sequencing. Using cDNA clones of these human molecules, recombinant proteins were produced in Escherichia coli and used to enable the antigens to detect the antibodies in the sera of patients with RA. Of 71 sera tested, 24 sera (33.8%) reacted with at least one of three recombinant antigens, although there was no significant correlation between the presence of the antibodies and clinical manifestations, such as disease duration or stage. There was also no discernible relationship to other auto-antibodies such as antinuclear antibodies (ANA) and rheumatoid factor. The results suggest that ERM proteins are possible novel auto-immune target antigens for RA.
Adult↗
A novel TAP 2 gene RFLP observed in a Japanese.
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
Association of complement alleles C4AQ0 and C4B5 with rheumatoid arthritis in Koreans.
OBJECTIVE: To investigate the association of complement C4 allotypes with rheumatoid arthritis in Koreans. METHODS: 65 rheumatoid arthritis patients and 255 controls were typed for C4 allotypes and HLA-A, B, C, DR, and DQ antigens. RESULTS: The frequencies of C4AQ0 (32.3% v 14.9%, P < 0.005) and C4B5 (29.2% v 12.2%, P < 0.005) were significantly increased in rheumatoid arthritis patients compared with healthy control subjects. Among rheumatoid patients, the frequency of C4AQ0 was significantly increased in both the rheumatoid factor (RF) positive (27.3%) and the RF negative (66.7%) subgroups. The frequencies of C4B5 and HLA-DR4 were significantly increased only in RF positive subgroup. C4B5 was strongly associated with HLA-DR4, whereas C4AQ0 did not show association with DR4. CONCLUSIONS: In Koreans, C4AQ0 and C4B5 are associated with susceptibility to rheumatoid arthritis, as in the Japanese. C4B5 is strongly associated with HLA-DR4. C4AQ0 is considered to be a DR4 independent risk factor, and a disease susceptibility allele in linkage disequilibrium with C4AQ0 is suggested in Korean patients with rheumatoid arthritis.
Adult↗
Polymorphisms of the TAP1 and TAP2 transporter genes in Japanese SLE.
OBJECTIVE: To determine how polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles contributed to the pathogenesis of systemic lupus erythematosus (SLE) in Japanese patients. METHODS: TAP1 and TAP2 typing was carried out in 52 Japanese patients with SLE and 95 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DR typing and HLA-DRB1*15 genotyping were carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method, respectively. RESULTS: No particular TAP 1 allele was associated with Japanese SLE or with immunological subgroup of SLE. TAP2H showed a tendency towards increased frequency in SLE (5.8% v 0% in control), but the corrected P value was not significant. No other particular association of TAP2 allele was observed. Furthermore, these was no evidence for linkage disequilibrium between any TAP1/TAP2 alleles and HLA-DRB1*1501--which is reported to be weakly but significantly association with Japanese SLE--in either the normal control or the SLE patient group. CONCLUSIONS: Neither the TAP1 nor the TAP2 gene appears to determine disease susceptibility to SLE in Japanese, and these results are in keeping with those reported in Caucasian SLE patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Association of specific amino acid sequence of HLA-DR with rheumatoid arthritis in Koreans and its diagnostic value.
OBJECTIVE: To analyze the association of susceptibility epitopes and alleles of HLA-DRB1 with rheumatoid arthritis (RA) in Koreans. METHODS: We performed HLA-DRB1 epitope typing in 61 patients and 82 controls using polymerase chain reaction (PCR) oligonucleotide hybridization, and HLA-DR4, DR1, and DR8 alleles were characterized by PCR single strand conformation polymorphism (SSCP). RESULTS: The frequency of HLA-DR4 was significantly increased in patients with RA compared with controls (61 vs 29%; RR = 3.7, p < 0.0001). Epitope analysis revealed that susceptibility sequences in Korean patients with RA were 70QRRA74A (52 vs 21%; RR = 4.2, p < 0.0001) and 70QKRA74A (10 vs 1%; RR = 8.8, p < 0.05). The frequency of patients carrying either QRRAA or QKRAA at the 70-74 position on the HLA-DR beta 1 molecule was significantly increased compared with controls (57 vs 22%; RR = 4.8, p < 0.0001). Genotypical analysis showed that DRB1*0405 and *0401 were the DR4 alleles associated with RA in Koreans (RR = 9.4, p < 0.00005; RR = 8.8, p < 0.05, respectively). No significant differences were noted for other alleles including DRB1*0404 and DRB1*0101. QRRAA epitope typing was considered to have some diagnostic value for early RA. CONCLUSION: Our observation indicates that a shared sequence 70QR(K)RA74A, especially in HLA-DR4 subtypes, is strongly associated with RA in the Korean population. Additionally, the importance of DRB1*0405 in the pathogenesis of RA in East Asian ethnic groups was confirmed. These data suggest that not only the specific amino acid sequences but also the whole structure of the HLA-DR beta 1 molecule are important with regard to susceptibility to RA.
Adult↗
Amino-acid sequence of rat liver kynureninase.
Amino-acid sequence of kynureninase purified from rat liver cytosol was determined by an amino-acid sequencer. The enzyme was degraded to small peptides with cyanogen bromide, TPCK-trypsin, endoproteinase Glu-C, lysyl endoprotease and alpha-chymotrypsin. The enzyme subunit consisted of 464 amino acids, and the molecular weight of subunit was determined to be 52,510. The coenzyme pyridoxal phosphate-binding residue was lysine of which position was 276, and the N-terminal residue was N-acetylmethionine. The homology search between this enzyme and the other pyridoxal phosphate-dependent enzymes showed that kynureninase was similar to mitochondrial aspartate aminotransferase, and also to cystathionine gamma-synthase and gamma-lyase to a lesser extent.
Amino Acid Sequence↗
Purification and phosphorylation of a M(r) 25,000 protein, an effective phosphate acceptor for casein kinase II and protein kinase C, detected in the cytosolic fraction of Xenopus laevis oocytes.
A common and effective phosphate acceptor protein for casein kinase II and Ca(2+)-phospholipid-dependent protein kinase (protein kinase C) was purified to near homogeneity from the cytosolic fraction of Xenopus laevis oocytes. Its molecular mass was estimated to be approximately 25,000 by SDS-polyacrylamide slab gel electrophoresis and gel filtration analyses. About 1 and 2 mol of phosphate were incorporated per mol of this protein with casein kinase II and protein kinase C, respectively, and the phosphorylated amino acid was identified as serine irrespective of the protein kinase employed. The Km values were calculated to be 1 and 0.5 microM for this M(r) 25,000 protein with casein kinase II and protein kinase C, respectively. However, this protein was a relatively poor substrate for casein kinase I and did not serve as one for cAMP-dependent protein kinase. The amino acid sequence of its amino-terminal region suggests that this protein is a newly identified substrate for these two protein serine/threonine kinases.
Amino Acid Sequence↗
[Genetical aspects of collagen disease].
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Arthritis, Rheumatoid↗
Event-related potentials in silent speech.
Event-related potentials (ERPs) in silent speech using the vowel /a/ were recorded from 12 scalp electrodes and three electrodes monitoring eye and throat movements in eight subjects cued by one of two randomly lit light-emitting diodes (LEDs). The average silent-speech potential minus nonsilent-speech potential showed two significant scalp potential distributions--a positive difference in the occipital scalp area at a 0.30-s latency from the LED onset and a negative difference in the frontal scalp area peaking at electrode Fz at a 0.42-s latency. The occipital scalp potential may include an endogenous component like P3. Possible sites of neural activities underlying the frontal negative difference are discussed in relation to the topography of the scalp potential and functions involved in silent speech.
Adolescent↗
Characteristics of the background fields in multichannel-recorded magnetic field responses.
We have studied the background fields in the auditory evoked magnetic field responses recorded with a 37-channel SQUID magnetometer. The background fields were found to have a main contribution from the spontaneous fields, which originate in the neural activities of the brain. The spontaneous fields had strong spatial correlation across the recording sites even after averaging over 100 epochs. The spatial distribution of the spontaneous fields consisted of 3 main components of single extremum pattern, dipolar pattern, and a dipolar pattern with some distortion. Computer simulations of the localization of a single dipole source of the evoked field response showed that the spontaneous background field could bring about large location errors in an unpredictable manner, as compared with the location errors caused by a spatially random Gaussian noise field.
Adult↗
Reduction of brain noise influence in evoked neuromagnetic source localization using noise spatial correlation.
In magnetoencephalographic measurements, magnetic fields caused by spontaneous brain activities not related to the neural activities under study are often referred to as brain noise. This is because the accuracy in neural source localization is considerably degraded by such spontaneous neuromagnetic fields. This paper reports the experimental results of applying the previously proposed noise covariance method to reducing the degradation caused by brain noise and to improving the accuracy in localizing auditory-evoked neural sources. Firstly we present the results of our experiments using measured brain noise and computer-generated signal fields. These results confirm that the covariance method can, in principle, improve the accuracy of evoked neural source localization. Next, the method was applied to source localization for actual neuromagnetic fields evoked by speech sounds. The results obtained strongly suggest that the method is effective in processing actual evoked neuromagnetic data.
Adult↗
Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans.
OBJECTIVE: To examine the association of complement C4 and HLA-DR to systemic lupus erythematosus (SLE) susceptibility in Korea. METHODS: Complement C4 protein typing was carried out by immunofixation and immunoblotting methods using EDTA-plasma from 60 patients with SLE and 72 healthy controls. Restriction fragment length polymorphism analysis of C4 genes was also carried out using TaqI or HindIII for restriction enzymes. HLA-DR was determined by polymerase chain reaction amplification with sequence specific primers using genomic DNA from 67 patients with SLE and 72 healthy controls. RESULTS: The frequency of the C4AQ0 allele was significantly higher in the patients with SLE than in controls (41.7 vs 25.0%, p < 0.05). The deletion of the C4A gene commonly found in Caucasian patients with SLE was not observed in any patients. For HLA-DR, a significant increase of the haplotype DRB1*1501 was observed in the patients (26.9 vs 12.5%, p < 0.05) and DR9 was also significantly increased (23.9 vs 11.1%, p < 0.05). An increase in each DR2 and DR9 was independent of an increase in C4AQ0. The frequencies of DR2 and DR9 were significantly decreased in patients with renal involvement and alopecia, respectively. CONCLUSION: Our data suggested that the presence of C4AQ0 allele, DRB1*1501-DRB5*0101 haplotype and DR9 contributed to susceptibility to SLE in Koreans and that Korean SLE is based on a different genetic background from Caucasian patients.
Adult↗
Association of HLA-DR with progressive systemic sclerosis in Japanese.
OBJECTIVE: To clarify the contribution of HLA-DR genes to the susceptibility to progressive systemic sclerosis (PSS). METHODS: HLA-DR typing was carried out in 36 Japanese patients with PSS, 42 with systemic lupus erythematosus and 104 healthy subjects by polymerase chain reaction (PCR) method using specific primers and by PCR-SSCP (single-standard DNA conformation polymorphism) method. RESULTS: A haplotype DRB1*1502-DRB5*0102 was significantly increased in PSS (50.0%, p < 0.00004, pc < 0.001), especially in antitopoisomerase I antibody (a-Scl-70) positive patients (62.5%, p < 0.00003, pc < 0.001) and PSS with diffuse scleroderma (75.0%, p < 0.00001, pc < 0.0001). In addition, DRB1*0802 was also increased in DRB1*1502 negative patients with a-Scl-70, (50.0%, p = 0.033, pc = not significant) and in DRB1*1502 negative patients with diffuse scleroderma (75.0%, p = 0.008, pc = not significant). Thus, 81.3% of a-Scl-70 positive patients, and 93.8% of patients with PSS with diffuse scleroderma showed either HLA-DRB1*1502 or 0802. CONCLUSIONS: Our observations show the extreme difference of genetic background of a-Scl-70 positive PSS, with regard to HLA-DR, between Japanese and other ethnic groups including Caucasian and American black persons. The increase in DRB1*1502-DRB5*0102 haplotype supported the hypothesis of Reveille, et al that uncharged polar amino acid residue at position 30 of HLA-DQB1 allele was important for a-Scl-70 positive PSS because close association of the haplotype with DQB1*0601 was well established in Japanese; listed as a hypothetical candidate of PSS susceptible DQB1 allele. DRB1*0802 were also associated with hypothetical candidates of DQ alleles. Furthermore, the sharing of the particular amino acid sequence: valine38 and phenylalanine67-lysine68-glutamic acid69-asparic acid70-arginine71, by DRB5*0102, DRB1*0802 and DR11 (associated with Caucasian PSS) also suggests a contribution of the sequence in HLA-DR molecules to the pathogenesis of PSS according to the shared epitope hypothesis.
Adult↗
[Recent advances in imaging diagnosis of pancreatic neoplasma with special reference to early diagnosis of the cancer].
Recent advance in various diagnostic imagings has enabled the early diagnosis of pancreatic tumors. In pancreatic cancer, the tumor-demonstrability by US, CT, and MRI has reached 80% in the recent 6 years, which is superior to the rate in the past decade from 1978 and 1987. However, the prognosis of pancreatic cancer is still poor even if the cancer can be resected. To improve the outcome of surgical intervention, early detection of small cancers (< or = 2 cm in diameter) and appropriate intervention based on preoperative diagnosis of the tumor extension are proposed. The tumor detectability of small pancreatic cancer by US, CT, MRI was 67%, 25%, 20%, respectively, and thus US was the most valuable tool. In the prediction of tumor extension of serosal invasion (S factor), retroperitoneal invasion (Rp factor) and vessel invasion (PV factor), both US and CT were efficacious with an accuracy of more than 70%. In conclusion, recently-advanced imaging seems to be useful for detecting a small pancreatic cancer and evaluating the tumor extension, but it remains difficult to diagnose a carcinoma in situ; a truly early cancer.
Adult↗
Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells.
Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down-regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C.
Amiloride↗
The lectin concanavalin A stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes.
We report that the activation of porcine peripheral blood lymphocytes (PBL) by lectin concanavalin A (Con A) led to the increase in tyrosine phosphorylation on 84-, 72-, 55-, 40-, and 33-kDa proteins. A non-receptor protein-tyrosine kinase (PTK), p72syk (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796), was detected in PBL around 0.1% of total protein and distributed in both particulate and cytosolic fractions. Furthermore, Con A induced a rapid activation of p72syk within 1 min in a manner similar to the time course of Con A-induced protein-tyrosine phosphorylation. These results suggest that p72syk plays a certain role in the activation of PBL and that p72syk may be one of the major non-receptor PTKs in T cells as well as in B cells.
Animals↗
Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin.
Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.
Acetylglucosamine↗