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Biomedical subjects

K Omoto

Publications and source records attributed to K Omoto.

At least 37 records · Page 2Linked to original sources
PubMed1996

Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation.

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-alpha beta mAb-treated ATX mice, as shown in the present study, most of TCR-alpha beta+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-alpha beta- Thy-1+ cells remained at that time. These TCR-alpha beta- Thy-1+ cells which have downmodulated their TCR-alpha beta expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-alpha beta on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-alpha beta mAb treatment are long-lived and re-express their TCR-alpha beta at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.

Animals↗
PubMed1996

mtDNA polymorphism in East Asian Populations, with special reference to the peopling of Japan.

Nucleotide sequences of the major noncoding (D-loop) region of human mtDNA from five East Asian populations including mainland Japanese, Ainu, Ryukyuans, Koreans, and Chinese were analyzed. On the basis of a comparison of 482-bp sequences in 293 East Asians, 207 different sequence types were observed. Of these, 189 were unique to their respective populations, whereas 18 were shared between two or three populations. Among the shared types, eight were found in common between the mainland Japanese and Koreans, which is the largest number in the comparison. The intergenic COII/tRNA(Lys) 9-bp deletion was observed in every East Asian population with varying frequencies. The D-loop sequence variation suggests that the deletion event occurred only once in the ancestry of East Asians. Phylogenetic analysis revealed that East Asian lineages were classified into at least 18 monophyletic clusters, though lineages from the five populations were completely intermingled in the phylogenetic tree. However, we assigned 14 of the 18 clusters for their specificity on the basis of the population from which the maximum number of individuals in each cluster was derived. Of note is the finding that 50% of the mainland Japanese had continental specificity in which Chinese or Koreans were dominant, while < 20% of either Ryukyuans or Ainu possessed continental specificity. Phylogenetic analysis of the entire human population revealed the closest genetic affinity between the mainland Japanese and Koreans. Thus, the results of this study are compatible with the hybridization model on the origin of modern Japanese. It is suggested that approximately 65% of the gene pool in mainland Japanese was derived from the continental gene flow after the Yayoi Age.

Asian People↗
PubMed1996

Genetic polymorphism of the 3' VNTR region of the human dopaminergic function gene DAT1 (human dopamine transporter gene) in the Mongolian population.

The hypervariable region of the dopamine transporter gene (DAT1) was amplified from samples in the Mongolian population. This region includes a variable number of tandem repeats of a 40-bp core unit in the 3' untranslated region of DAT1. Vandenbergh et al. (1992) reported variability in the number of repeats of this 3' flanking region ranging from 3 to 11 times in white and black populations. We examined polymorphism at the DAT1 locus in 78 native Mongolian subjects. We found alleles with 7 to 13 repeats, which is different from the findings of Vandenbergh et al. (1992). The allele distribution of the Mongolian population is similar to that in the Japanese population, reported previously by Nakatome et al. (1995). Chi-square analysis showed a significant lack of homogeneity between our findings in Mongolian subjects and those reported previously in white and black populations. The DAT1 locus was estimated to have a heterozygosity index of 14.1%, and the polymorphic information content was calculated to be 0.16.

Base Sequence↗
PubMed1995

Development of TCR-gamma delta CD4-CD8+ alpha alpha but not TCR-alpha beta CD4-CD8+ alpha alpha i-IEL is resistant to cyclosporin A.

Present evidence suggests that cyclosporin A (CSA) inhibits the development of both alpha beta and gamma delta T cells in the thymus. However, whether CSA can inhibit the development of murine intestinal intraepithelial lymphocytes (i-IEL) is unknown as most i-IEL are clearly derived from a different lineage than the conventional thymus-derived T cells found in the periphery. Using the adult thymectomized, lethally irradiated bone-marrow reconstituted chimera (ATXBM mice) as a model for the development of extrathymically derived i-IEL and the fetal thymus-grafted (FTG) nude mice as a model for the development of thymically derived i-IEL, we demonstrate that CSA nearly completely inhibited the development of extrathymically, and possibly thymically, derived TCR-alpha beta i-IEL. Most of the TCR-alpha beta i-IEL whose development was inhibited by CSA belonged to the CD4-CD8+ alpha alpha subset. In contrast, the development of extrathymically and thymically derived TCR-gamma delta i-IEL was completely resistant to CSA. The phenotype of CSA-resistant TCR-gamma delta i-IEL in these models was not different from those in control mice, and the TCR-gamma delta i-IEL in CSA-treated mice appear to be mature and activated as most were large, granular, and CD69+. Lastly, we demonstrate that CSA does not affect the extrathymic positive selection of V delta 4 i-IEL in C3H hosts. These results suggest that despite their similarity, the intracellular activation cascade involved after TCR stimulation between TCR-alpha beta CD4-CD8+ alpha alpha and TCR-gamma delta CD4-CD8+ alpha alpha i-IEL are markedly different.

Animals↗
PubMed1995

Priming with donor spleen cells and activated B cells can induce prolonged survival of class I-disparate skin allografts in cyclophosphamide-treated mice.

We have previously reported a method for inducing tolerance using cyclophosphamide (CP) in a murine model, in which 200 mg/kg of CP is administered intraperitoneally 2 days after intravenous priming with donor spleen cells. The CP-induced tolerance method, however, cannot induce long-lasting skin allograft survival in an MHC class I-disparate combination. In this study, we tried to explain this phenomenon based on a costimulatory theory. That is, allo-class I-reactive host CD8+ helper T cells may receive insufficient costimulatory signals from donor spleen cells and, therefore, they are resistant to subsequently administered CP. We demonstrated that activated donor B cells, which can deliver sufficient costimulatory signals, induce a more efficient proliferation of allo-class I-reactive host CD8+ helper T cells than naive B cells in vitro. In addition, we also demonstrated that our idea can also be applied to the CP-induced skin allograft tolerance in an MHC class I-disparate combination.

Animals↗
PubMed1995

Tolerance induction in a fully allogeneic combination using anti-T cell receptor-alpha beta monoclonal antibody, low dose irradiation, and donor bone marrow transfusion.

In a murine strain combination disparate in both H-2 antigens and minor histocompatibility antigens consisting of C57BL/6 (B6; H-2b, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, we reported that the administration of anti-TCR-alpha beta mAb nonspecifically suppresses the ability to reject allografts. However, such an effect was only temporary and all grafts were eventually rejected within 40 days in the anti-TCR-alpha beta mAb-treated mice. In this study, to induce donor-specific tolerance, the transfer of donor bone marrow cells was added to the administration of anti-TCR-alpha beta mAb but donor bone marrow cells were rejected and failed to cause donor-specific unresponsiveness. After donor bone marrow cell transfer in the anti-TCR-alpha beta mAb-treated mice, the B cells of the recipients were observed along with the production of antidonor antibody. To abolish the residual lymphocyte populations, low dose irradiation was also added. A long-lasting skin allograft tolerance can be achieved by the tolerance system, in which low dose irradiation was added to the combined treatment with anti-TCR-alpha beta mAb and transfer of donor bone marrow cells. Such a protocol also established central and peripheral chimerism, which suggests that hematopoietic chimerism is necessary to maintain the tolerance. B cells were completely abolished in recipients given this combined treatment and their antibody production against donor antigens after the transfer of donor bone marrow cells was also completely suppressed. A possible role of B cells in the rejection of donor bone marrow cells before the establishment of chimerism is discussed.

Animals↗
PubMed1995

Prevention of anti-T-cell receptor alpha beta monoclonal antibody-induced side-effects by treatment with cyclosporin A without interference of monoclonal antibody-induced immunosuppression in mice.

Anti-T-cell receptor (TCR)alpha beta monoclonal antibody (mAb; H57-597) injection in mice caused cytokine (tumour necrosis factor and interferon-gamma) release and clinical side-effects such as piloerection and body weight loss similar to anti-CD3 mAb (145-2C11) injection. Treatment with cyclosporin A (CsA) for 3 days, from day -2 to day 0, prior to anti-TCR alpha beta mAb injection almost completely abolished the mAb-induced cytokine release, and completely inhibited the mAb-induced body weight loss. Furthermore, treatment with CsA from day -2 to day 0 did not inhibit the mAb-induced in vivo immunosuppressive effects, i.e. prolongation of skin allograft and T-cell depletion in the periphery. These results indicate that CsA treatment prior to mAb treatment could effectively inhibit the mAb-induced side-effects without interference of the mAb-induced in vivo immunosuppression. From these results, we propose that CsA treatment prior to injection of anti-TCR alpha beta mAb may be recommended to reduce mAb-induced side-effects.

Animals↗
PubMed1995

Prolongation of kidney graft survival by cyclophosphamide-induced tolerance in rats.

In this study, we have extended a cyclophosphamide (CP)-induced tolerance system to kidney transplantation in rats to examine whether or not we can overcome fully allogeneic (major histocompatibility complex plus minor histocompatibility) antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT1(1)) rats that were primed intravenously with 4 x 10(8) spleen cells plus 2 x 10(8) bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney allografts, but not skin allografts, from BN was prolonged as compared with that in the untreated LEW rats. Some of the kidney allografts survived for more than 100 days without further immunosuppressants. The tolerant state induced was tolerogen specific, and the suppression of tissue damage of the grafted kidney in such tolerant rats was also confirmed by the histopathological findings of the grafted kidney. These results indicate that considerable levels of tolerance can be induced, at least in organ transplantation, across fully allogeneic antigen barriers in rats by a CP-induced tolerance system. We believe that the present study is the first step in applying our CP-induced tolerance system using skin grafting in the murine model to clinical organ transplantation.

Animals↗
PubMed1994

CD3-CD8+ intestinal intraepithelial lymphocytes (IEL) and the extrathymic development of IEL.

Present evidence suggests that a majority of murine CD3+ intraepithelial intestinal lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived IEL phenotypically express the CD8 homodimer (CD8 alpha alpha). Recently, CD3- IEL have been reported to express the recombination activating gene (RAG-1), suggesting that precursors to extrathymically derived CD3+CD8+ alpha alpha IEL exist on the intestinal epithelium. To study in detail whether these CD3-IEL can develop into CD3+CD8+ alpha alpha IEL, we analyzed the CD3-IEL subset and found that it can be separated into two subsets, namely CD3-CD8- and CD3-CD8+ IEL. We show that (1) CD3-CD8- IEL are mostly small, non-granular and phenotypically Pgp-1+ IL-2R+ B220-, while CD3-CD8+ IEL are mostly large, granular and phenotypically Pgp-1- IL-2R+ B220+, (2) CD(3-)-CD8+ IEL express the RAG-1 gene, and (3) CD3-CD8-, CD3-CD8+ and CD3+CD8+ alpha alpha IEL, respectively, appear sequentially in normal ontogeny and in bone marrow-reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+ alpha alpha IEL expressed the gamma delta T cell receptor (TCR), but not the alpha beta TCR. From this and what is presently known about T cell development, we propose that CD3-CD8+ IEL are an intermediate in extrathymic IEL development and that the development of extrathymically derived IEL occurs at the intestinal epithelium from CD3-CD8- to CD3-CD8+ to CD3+(gamma delta TCR)CD8+ alpha alpha.

Animals↗
PubMed1994

Lip closing pressure in disabled children: a comparison with normal children.

Lip functions play an important role in the oral stages of feeding. Lip closing is an important early motor act in food acquisition and is essential for controlling chewing and swallowing. To date, there have been few papers on the developmental aspects of lip closing strength when taking in food, especially with regard to disabled children. This investigation was designed to produce an ordinal scale of midline lip pressure measurements for a cross-sectional, age-grouped population of normal children. Developmental changes in lip pressure were then compared with those of two populations of disabled children. Pressure measurements were obtained with a strain gauge transducer that was embedded in a spoon during normal feeding. The study population consisted of 104 normal children ranging in age from 5 months to 5 years, 11 children who showed developmental delay (mean 4.5 years), and 10 children with cerebral palsy (mean 5.0 years). Lip pressure was found to increase steadily from 5 months to 3 years and to increase slightly from 3 to 5 years in the normal population. The developmentally delayed group and the cerebral palsied group produced lip pressures and coefficients of variation below those of the normal 1 to 2-year-old group.

Age Factors↗
PubMed1994

A Y-associated allele is shared among a few ethnic groups of Asia.

In our previous study, both of Y-associated alleles, Y1 and Y2, were detected in Japanese and Koreans, but only the Y1 allele was detected in each of other populations including Chinese in both Beijin and Guangzhou areas, Caucasians, Africans, and Jewish. In the present study, these observations were extended to other ethnic groups in East Asia. Evenks in central Siberia and Khalkhs in Mongolia had only the Y1 allele. On the other hand, two ethnic groups, Fo-lo and Hakka, in Taiwan had both of the Y1 and the Y2 alleles. Three of the eight Y2-positive men, 2 Fo-lo and a Hakka, shared family name Chen. Both Hakka people and ancestors of Chen families could be traced to the Province of Henan in northern China in early 4th century. They arrived in Fujian/Guangdong area in the south-east China via various routes and then some of them migrated to Taiwan in the 18th century. It is tempting to speculate that the Y2 allele may be originated from an ancestral population in Henan from which, Japanese, Koreans, and some of the Taiwanese diverged.

Alleles↗
PubMed1992

Five new alleles of plasma Zn-alpha 2-glycoprotein variants phenotyped by isoelectric focusing and immunoblotting in twelve populations.

Human Zn-alpha 2-glycoprotein (ZAG) in plasma samples from twelve populations was tested by immunoblotting after polyacrylamide gel isoelectric focusing. Eleven ZAG phenotypes produced by one common and nine rare alleles, including five new ones (ZAG*6-ZAG*10), were detected. Additionally, an application of separator IEF with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) was found to be useful for discriminating the rare ZAG 7 band.

Alleles↗
PubMed1992

[Studies on the erythrocyte membrane skeleton in a patient with chorea-acanthocytosis--theoretical speculation on the mechanism of neurological involvement].

Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthocytes↗
PubMed1992

Frequency of a 9-bp deletion in the mitochondrial DNA among Asian populations.

Individuals of the following Asian populations were surveyed for the presence of a 9-base-pair deletion of mitochondrial DNA (mtDNA): Ainu, Japanese, Korean, Negrito, and Vedda. Although the variation was detected in every population except the Vedda, the frequencies of the variation differed widely among the populations, suggesting a geographic cline.

Asian People↗
PubMed1991

Allele frequencies of human complement factor I in a sample from Iwate, northern Japan, with the description of geographical cline.

Serum samples from 270 healthy blood donors of Iwate prefecture, northern Japan, were examined for polymorphism of factor I (IF) by using polyacrylamide gel isoelectric focusing followed by semidry horizontal electroblotting with enzyme immunoassay. In 270 individuals four different patterns were observed, and these were controlled by two common alleles, IF*A and IF*B, and one rare allele, IF*A2. Allele frequencies were estimated to be 0.1019, 0.8963 and 0.0018 for IF*A, IF*B and IF*A2, respectively. The data of IF allele frequencies thus far reported in Japan excluding Okinawa Island were compared, and a statistically significant (p less than 0.01) geographical cline was detected for IF*A and IF*B alleles.

Alleles↗
PubMed1990

Evolutionary hypervariability in the hinge region of the immunoglobulin alpha gene.

The hinge region of the immunoglobulin molecule is responsible for antigen-binding and cross-linking reactions, varying the distance between the two antigen-binding sites. As the amino acid sequence of the hinge region is identical among immunoglobulin molecules of the same (sub)class, it has been regarded as a constant region. By comparison of the nucleotide sequences among primate C alpha genes, it is clear that there is a wide variety of length among the hinge regions of hominoid C alpha genes, which basically consist of tandem repeats of a 15 base-pair sequence. This reiterated structure probably facilitates rapid evolutionary changes in the length of the hinge region. The hinge region of the Old World monkey C alpha gene has a non-reiterated structure whose nucleotide sequence is quite different from those of the hominoid C alpha genes, although its surrounding region is conserved during evolution. This unusual hypervariability reveals that the hinge region has evolved as a semi-variable region in contrast to its constant character from an ontogenic viewpoint.

Amino Acid Sequence↗
PubMed1990

Direct sequencing of a HLA-DRB gene by polymerase chain reaction: sequence variation in DRw8 specificity.

The nucleotide sequence of a HLA-DRB gene with a predominant subtype of DRw8 specificity in Japanese (DR8.1) was determined with single-stranded DNA enzymatically amplified by polymerase chain reaction (PCR). The sequence differs at a single amino acid from both of the published DRw8/Dw8.1 and DRw8/Dw8.2 sequences: isoleucine67(AUC) instead of phenylalanine67(TTC) in DRw8/Dw8.1 and serine57(AGC) instead of aspartic acid57(GAT) in DRw8/Dw8.2. On the other hand the DR8.1 and DRw8/Dw8.3 have the same amino acid sequence although one silent nucleotide substitution has occurred between the two sequences. These results indicate that Japanese DR8.1 specificity corresponds to DRw8/Dw8.3. Furthermore, an oligonucleotide probe specific for this sequence was synthesized and hybridized with 33 HLA-typed controls. This probe clearly distinguished the particular subtype from other DRw8 subtypes and specificities.

Amino Acid Sequence↗