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Biomedical subjects

F Takeuchi

Publications and source records attributed to F Takeuchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients.

OBJECTIVES: To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among populations with different HLA susceptibility genes in SSc. METHODS: TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP. RESULTS: The frequency of TNFa13 was significantly increased in Japanese SSc (p=0. 011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1. 0 x 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I antibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3. 39, 800.76, and p<1.0 x 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and German controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR=3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especially in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequilibrium with HLA-DRB1*1502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls. CONCLUSION: TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.

Adult↗
PubMed2000

Modulation of neural activities during visual processing in the human extrastriate visual cortex.

Magnetoencephalographic responses to single letters (Japanese monosyllabic characters) presented in the left visual field were measured during visual cognition tasks, in which subjects judged matching of characters in two different processes based on phonological and graphical cues. Equivalent current dipoles, which represent focal neural activities, were localized in the extrastriate visual cortex of the occipital to occipitotemporal regions. The main activities were observed in the right lateral area when the subjects detected shape, and also in the medial and inferior areas of both hemispheres when they detected rhyme. These results suggest that the neural activities in the extrastriate cortex, which are related to early processing of familiar visual forms, can be modified by the top-down control.

Adult↗
PubMed1999

TNF-alpha and TNF-beta gene polymorphisms in systemic sclerosis.

Tumor necrosis factor (TNF)-alpha and TNF-beta, mediators of inflammatory responses, have been implicated in the pathogenesis of autoimmune diseases. The aim of this investigation was to determine whether two promoter region polymorphisms of the TNF-alpha gene (TNF-alpha -308 and TNF-alpha -238) and a determinant in the first intron of the TNF-beta gene (TNF-beta +252) affect susceptibility to systemic sclerosis (scleroderma) (SSc). Fifty patients and 60 healthy blood donors from Japan were genotyped for these markers by polymerase chain reaction-based methods. Fisher's exact test was used to test for significant associations. Because of very limited variation at the TNF-alpha -308 and TNF-alpha -238 loci in the Japanese people, statistical analyses with sufficient power could not be done for these genotypes. However, the two homozygous genotypes of the TNF-beta +252 locus were found to be significantly associated with SSc. Compared to controls, the frequency of the TNF-1 genotype was decreased, whereas that of TNF-2 was increased in SSc patients. The former implies an association with resistance, while the latter suggests an association with susceptibility to the disease. These results show that the TNF-beta +252 locus plays an important role in the etiopathogenesis of SSc.

Case-Control Studies↗
PubMed1999

Isolation and some properties of Thiobacillus ferrooxidans strains with differing levels of mercury resistance from natural environments.

Fifty iron-oxidizing bacteria isolated from natural environments were screened for resistance to mercuric ions (Hg2+). Thiobacillus ferrooxidans Funis 2-1, the strain found to show the greatest resistance to Hg2+ among the fifty isolates, gave a cell yield of 7.0 x 10(7) cells/ml after 8 d cultivation in an Fe2+-medium (pH 2.5) containing 0.7 microM Hg2+. Funis 2-1 volatilized 80% of the total mercury added to the medium over 8 d of cultivation. T. ferrooxidans AP19-3, more sensitive to Hg2+ than Funis 2-1, could not grow in an Fe2+-medium (pH 2.5) containing 0.7 microM Hg2+ even over a 28 d cultivation period. When resting cells of strains Funis 2-1 and AP19-3 were incubated for 3 h in a salt solution containing 0.7 microM Hg2+ (pH 3.0), 14.3% and 7.9% of the total mercury added to the reaction mixtures respectively, were volatilized. The activity of the mercuric reductase from Funis 2-1 was only 2.8 times higher than that of the enzyme from AP19-3. Since the markedly higher mercury resistance of Funis 2-1 compared with that of AP19-3 cannot be explained only by the level of the mercuric reductase activity, the levels of mercury resistance of iron oxidase and cytochrome c oxidase were studied. The 1 microM mercuric ions inhibited the 35% of iron-oxidizing activity from AP19-3. In contrast, the same concentration of Hg2+ did not inhibit the activity of iron oxidase from Funis 2-1. In the case of the cytochrome c oxidases purified from both strains, the 0.2 microM Hg2+ inhibited approximately 40% of cytochrome c oxidizing activity from AP19-3, on the contrary, the activity of the enzyme from Funis 2-1 was activated 1.8- and 1.2-fold, respectively, in the presence of 0.08 and 0.2 microM Hg2+. Since cytochrome c oxidase is one of the most important components of the iron-oxidizing system, these results indicate that both the existence of cytochrome c oxidase resistant to Hg2+ as well as that of mercuric reductase in the cells is responsible for the more rapid growth of Funis 2-1 than that of in an Fe2+-medium containing 0.7 microM Hg2+.

Journal Article↗
PubMed1999

[Clinical significance of urothelial dysplasia concomitant with superficial bladder cancer].

OBJECTIVE: Retrospective analysis was carried out to evaluate the prognostic value of urothelial dysplasia with superficial bladder cancer. PATIENTS AND METHODS: 62 patients with bladder cancer of pTa or pT1 who had been treated by transurethral resection (TUR-Bt), underwent random mucosal biopsies in the urinary bladder. The results of random biopsies were classified into 3 groups: negative group, dysplasia group and CIS group. The recurrence rate, progression rate and type of recurrences (true recurrence/new occurrence) were compared among the 3 groups. RESULTS: The results of random biopsies were as follows; negative group was found in 42 (68%), dysplasia group in 17 (27%) and CIS group in 3 (5%). There were no significant difference in the characteristics of the patients among the 3 groups. The recurrence rates at 1, 2 and 5 years after TUR-Bt were 3%, 12% and 21%, respectively, for negative group, and 37%, 51% and 67%, respectively, for dysplasia group (p < 0.01). For CIS group, 2 of 3 cases (67%) recurrenced within 1 year after TUR-Bt. Non of negative group progressed to muscle invasion, whereas 57% of dysplasia group invaded bladder muscle after 6 years post operatively (p < 0.001). No significant relationship was observed between the absence or presence of concomitant dysplasia and the rate of true recurrence. Dysplasia group revealed a higher rate (47.1%) of new occurrence than negative group (2.4%) (p = 0.0001). CONCLUSION: The presence or absence of concomitant dysplasia of superficial bladder cancer seems to be an important prognostic factor for future new ocurrence and progression after TUR-Bt.

Carcinoma in Situ↗
PubMed1998

Neural processing of words in the human extrastriate visual cortex.

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.

Adult↗
PubMed1998

Structural changes in the oligosaccharide moiety of human IgG with aging.

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.

Adolescent↗
PubMed1998

Detection of disease-specific augmentation of abnormal immunoglobulin G in sera of patients with rheumatoid arthritis.

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.

Arthritis, Rheumatoid↗
PubMed1998

Polymorphisms of DMA and DMB genes in Japanese systemic lupus erythematosus.

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.

Adult↗
PubMed1998

[Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors].

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.

Adenoma, Islet Cell↗
PubMed1997

Insulin degradation by Madin-Darby canine kidney cells expressing the insulin receptor.

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.

Animals↗
PubMed1997

Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis.

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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Association of DM genes in systemic sclerosis is secondary to the association with HLA genes.

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.

Adult↗
PubMed1996

Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation.

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.

Animals↗