Where do perception and recognition of words take place in the brain? A neuromagnetic approach.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Takeuchi.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Measurements of neuromagnetic fields were made for the responses to visually presented words comprised of Japanese characters (phonograms), and for comparison of responses to single characters and character symbols, while subjects performed, respectively, semantic category matching, rhyming, and character matching tasks. The magnetic field responses recorded from the occipital and occipitotemporal regions consisted of 2-3 major peak components, occurring between 150 and 300 ms after the onset of the visual forms. The localization of equivalent current dipole sources of these components within the brain structure of individual subjects indicated that the main regions of the neural activity occurring at 150-250 ms were located in the extrastriate visual cortices. They included the lateral area mostly at the occipital gyrus, medial area consisting of parieto-occipital and calcarine sulci and lingual gyrus, and ventral area which is continuous from the lingual gyrus (LG) to fusiform gyrus (FG). In the ventral LG/FG area the left side was activated primarily by words, while the right side was responsive in more or less equally to words, characters, and symbols. It is suggested that the left occipitotemporal LG/FG mediates the neural function that subserves the specific visual word processing and/or general analysis of complex graphical features of visual forms.
In order to elucidate the relationship between glycosylation of IgG and aging, oligosaccharide structures of human IgG purified from sera of men and women aged 18 to 73 years were investigated. Oligosaccharides were liberated quantitatively from IgG by hydrazinolysis followed by N-acetylation and were tagged with p-aminobenzoic acid ethyl ester. The oligosaccharide structures were then analyzed by HPLC in conjunction with sequential exoglycosidase digestion. All IgG samples were shown to contain a series of biantennary complex type oligosaccharides which consisted of +/-Galbeta1-4GlcNAcbeta1-2Manalpha1-6(+/-GlcNAcbeta 1-4)(+/-Galbeta1-4GlcNAcbeta1-2Man(alpha)1-3)Man(beta)1-+ ++4GlcNAcbeta1-4(+/- Fucalpha1-6)GlcNAc and their mono- and disialo glycoforms in different ratios. In female IgG samples only, the incidence of non-galactosylated oligosaccharides with non-reducing terminal GlcNAc residues increased with aging (r>0.8), whereas that of digalactosylated oligosaccharides decreased (r<-0.8). A weaker correlation was observed between aging and the incidence of neutral and monosialo oligosaccharides in female IgG (r=0.461 and r= -0.538, respectively) and between aging and the incidence of oligosaccharides with a bisecting GlcNAc in both male and female IgG samples (r=0.566 and r=0.440, respectively). In addition, a significant change with aging in the galactosylation of IgG oligosaccharides was observed in females in their thirties, fifties, and sixties (p<0.02, p<0.01, and p<0.04, respectively). These findings may contribute to our understanding of autoimmune diseases such as rheumatoid arthritis in which glycosylation is involved.
Galactose-free immunoglobulin G (IgG), which is known to be higher in the sera of patients with rheumatoid arthritis, was prepared from IgG of healthy volunteers using enzymes. Its reactivity to lectins was analyzed. The galactose-free IgG showed no reactivity to Ricinus communis agglutinin 120 but displayed greater reactivity to concanavalin A and Lens culinaris lectin than did intact human IgG. Then, IgG in serum samples was bound to protein A immobilized on a nitrocellulose membrane, and its reactivity to biotinylated concanavalin A was measured with streptavidin-conjugated horseradish peroxidase. When the reactivity to concanavalin A of IgG in sera from healthy individuals and patients with rheumatoid arthritis (RA), osteoarthritis, systemic lupus erythematosus, or hepatic disease was compared, higher levels were shown in patients with RA, notably in 60% of the seronegative patients and 80% of the early phase patients. Therefore, it was suggested that augmentation of the abnormal IgG in sera was highly specific to patients with RA and that this novel serum test could be very useful for an accurate diagnosis of this disease.
Associations between polymorphisms of DMA and DMB alleles and systemic lupus erythematosus (SLE) were studied in 51 Japanese SLE patients and 77 normal subjects by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Phenotype frequencies of DMB*0101 tended to increase in SLE, but the difference was not significant (76.5% vs 70.1% in controls). The phenotype frequency of DMB*0103 was decreased in the SLE group, but the difference was not significant (49.0% vs 53.2%). Furthermore, there was no evidence of any association of either DMA or DMB alleles with HLA-DRB1*1501. The phenotype frequency of DMB*0101 was higher in the SLE group with anti-double-stranded DNA antibody (a-dsDNA) than in the SLE group without a-dsDNA, but the difference was not significant (P = 0.045, corrected P not significant). No other DMA or DMB alleles showed any associations in various immunological subgroups of SLE. These data suggest that neither the DMA nor the DMB gene determines susceptibility to SLE in Japanese.
Explore the source record for details and available documents.
In this report, we showed the efficacy of a new contrast agent (SH/TA-508, Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular invasion by cancer became to be easily evaluated. On the other hand, hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were increased in color Doppler signals of vessels by SH/TA-508. We concluded that SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as well as vascularity of hypervascular mass and solid component of cystic neoplasma.
Prior studies have shown that Madin-Darby canine kidney cells (MDCK) overexpressing the human insulin receptor bind and respond normally to insulin (T.C. Yeh, R.A. Roth, Diabetes 43 (1994) 1297-1303). Moreover, the insulin receptor preferentially localizes to the basolateral membrane of these cells. In the present studies, insulin was added to either the apical or the basolateral side of these cells and the extent of degradation of the insulin was assessed. Radioactive insulin added to either side was bound to its receptor and the radioactivity which reached the other side of the cell was to a large extent degraded fragments. Insulin added to the apical side was degraded to a larger extent (83%) than when added to the basolateral side (49%) although the basolateral side has much more insulin receptors than the apical side. This degradation process was not inhibitors of either lysosomal enzymes, the proteasome complex or cathepsins. The degradation process could however, be potently inhibited by the sulfhydryl alkylating agent N-ethylmaleimide. Further, cell surface biotinylation study showed that the insulin degrading enzyme was preferentially localized on the apical membranes. These results suggest that insulin added on the apical side of MDCK cells are more closely linked to the degradation process than that added on the basolateral side.
Contribution of polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles to pathogenesis of Japanese rheumatoid arthritis (RA) was studied in 92 RA patients by PCR-RFLP. The allele frequency of TAP2A was slightly low (38.0%) and the frequencies of TAP2B and TAP2C were slightly high (39.7% and 17.9%) in RA, but these differences were not significant. These increases and decrease were due to the positive or negative associations with HLA-DRB1*0405. It was very likely that slight differences in TAP2A, TAP2B and TA2C in RA were secondary phenomenon reflecting an increase in HLA-DRB1*0405. The prevalence of TAP2E allele was low (3.3%, P < 0.01, Pc = not significant) and not correlated with HLA-DRB1*0405.
The contribution of polymorphism of DMA and DMB alleles to the pathogenesis of Japanese Systemic Sclerosis (SSc) was studied in 55 Japanese SSc patients and 77 normal Japanese subjects using the PCR-RFLP (restriction fragment length polymorphism) method. The allele frequencies of DMB*0101 allele were increased in SSc with diffuse scleroderma (70.0% vs 49.4%, p < 0.05, pc = not significant (NS)) and in SSc with antitopoisomerase I antibody (a-Scl-70), (68.2%, p < 0.05, pc = NS). The phenotype frequencies of DMB*0101 in these subgroups of SSc were increased significantly (95.0%, p = 0.014, pc < 0.05; 95.5%, p = 0.0088, pc < 0.05, respectively). In contrast, DMB*0102 and DMB*0103 alleles tended to decrease in diffuse scleroderma and SSc with a-Scl-70, but the decreases were not significant. Association analysis among DMA, DMB, and DRB1*1502 in Japanese SSc with diffuse scleroderma and SSc with a-Scl-70 indicated that the increase in DMA*0101 was not primary, but reflected an increase in HLA DRB1*1502.
Akt is a serine/threonine kinase that is stimulated by receptor tyrosine kinases and contains a pleckstrin homology domain. One model proposed to explain this activation suggests that receptor tyrosine kinases stimulate a phosphatidylinositol 3-kinase whose lipid products directly activate Akt kinase by interacting with its pleckstrin homology domain. In the present study, we show, in three cell types, that Akt does not require its pleckstrin homology domain to respond to either insulin or platelet-derived growth factor. Moreover, attachment of the src myristoylation signal to target Akt, without its pleckstrin homology domain, to the membrane constitutively activates Akt by causing an increase in its basal level of phosphorylation. This constitutively active form of Akt can also activate p70(S6K), indicating that the pleckstrin homology domain is not necessary for downstream interactions. Fusion of the inter src homology 2 domain from the p85 regulatory subunit of the phosphatidylinositol 3-kinase to Akt also constitutively activated Akt and induced an association with the lipid kinase. Phosphorylation of this fusion protein still critically contributes toward its increased activity. The sum of these results indicates that the primary mechanism of Akt activation is via protein phosphorylation.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
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.
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.