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Biomedical subjects

K Omoto

Publications and source records attributed to K Omoto.

At least 19 recordsLinked to original sources

[Prognosis for the cases after resection of pulmonary metastasis of osteosarcoma].

Osteosarcoma commonly metastasize to the lungs. Sixty-six cases with surgical treatment for pulmonary metastasis of osteosarcomas have been experienced for past 25 years in our hospital. Disease free interval (DFI) and the number of metastatic lesions were assessed in relation to their prognosis. As a result of our assessment, fewer metastasis (3 or less), and longer DFI (1 year or more) had relations to longer post-thoracotomy survival. And the relations between the number of metastatic lesions and DFI were found. Fewer metastasis were associated with longer DFI, and multiple metastasis were associated with short DFI. The cases with fewer metastasis (3 or less) and longer DFI (1 year or more) might have a survival advantage.

Adolescent↗

Triethylborane-induced bromine atom-transfer radical addition in aqueous media: study of the solvent effect on radical addition reactions.

A mixture of ethyl bromoacetate and 1-octene was treated with triethylborane in water at ambient temperature to provide ethyl 4-bromodecanoate in good yield. The bromine atom-transfer radical addition in benzene was not satisfactory. The addition proceeded smoothly in polar solvents such as DMF and DMSO, protic solvents such as 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol, and aqueous media. Ab initio calculations were conducted to reveal the origin of the solvent effect of water in the addition reaction. The polar effect of solvents, which is judged by the dielectric constant, on the transition states in the bromine atom-transfer and radical addition steps is moderately important. Calculations show that a polar solvent tends to lower the relative energies of the transition states. The coordination of a carbonyl group to a proton in a protic solvent, like a Lewis acid, would also increase the efficiency of the propagation.

Journal Article↗

Molecular phylogeny of butterflies Parnassius glacialis and P. stubbendorfii at various localities in East Asia.

The phylogeny of butterflies, Parnassius stubbendorfii and P. glacialis, collected at various localities in the Japan archipelago and the eastern part of the Asian continent was analyzed using mitochondrial DNA sequences coding for NADH dehydrogenase subunit 5 (805 bp). The molecular phylogenetic trees revealed that P. glacialis and P. stubbendorfii diverged from a common ancestor, and then the populations inhabiting the Japan archipelago and the Asian continent diverged in each species. The reliability of these divergences was supported by high bootstrap values. The divergences within the Japan archipelago and within the Asian continent in each species were unclear because of low bootstrap values. The genetic distance and a rough time-estimation in the UPGMA tree suggest that the both populations of P. glacialis and P. stubbendorfii may have been isolated in the Japan archipelago at the early time (about 1.7-2.0 Mya) of the glacial period in the Pleistocene. The genetic distance between the Japanese and the continental subspecies may be large enough that they can be classified as different species, in comparison with the genetic distances among some other parnassian species.

Animals↗

[Responses to a questionnaire on laboratory examinations performed by graduates of Jichi Medical School in rural practice].

Graduates from Jichi Medical School are obligated to work at rural clinics or hospitals, where most of them are the only medical doctor in the house. Our need to continuously improve medical education, including the learning that takes place in the clinical setting, requires us to understand how these graduates actually use laboratory examinations and what examinations they find most important in their practice. We designed a questionnaire to address these questions. Three hundred sixty-eight graduate physicians working at clinics or hospitals in both rural or urban areas were asked to complete the questionnaire, providing information on the size of their institution, the laboratory equipment and examinations that they have direct access to, and what examinations they find most important. Two hundred seventy-eight (75.5%) of the 368 recipients responded. More than seventy percent of the respondents reported that their institutions had electrocardiographs, abdominal and cardiac ultrasonographs, urinalysis test paper, and portable blood glucose meters; and more than half of them reported having used these instruments without assistance in emergency situations and outside of ordinary office hours. Moreover, a majority of the respondents said that they considered it important that a physician is able to use these instruments without the help of other staff members. These responses clearly show the importance and usefulness of covering examination techniques and the principles of laboratory medicine in medical education.

Attitude of Health Personnel↗

Theoretical study of activation of oxirane by bidentate acids

The reaction of oxirane with amines in the presence of some bidentate and monodentate Bronsted acids has been studied theoretically by taking some simplified reaction models. Acids have been shown to serve as temporary reservoirs of electronic charge during the reaction to strengthen the nucleophilicity of the substrate. The shift of electronic charges and enhancement of the nucleophilicity of oxirane have been represented by means of paired interaction orbitals and projected reactive orbitals. The reason the transition state appears at an earlier stage in the reaction catalyzed by 1,8-biphenylenediol relative to the reactions catalyzed by monodentate phenols and alcohols has been clarified.

Journal Article↗

Analysis of HLA genes and haplotypes in Ainu (from Hokkaido, northern Japan) supports the premise that they descent from Upper Paleolithic populations of East Asia.

The Ainu people are assumed to be the descendants of pre-agricultural native populations of northern Japan, while the majority of population of present-day Japan (Hondo-Japanese) is considered to have descended mainly from post-neolithic migrants. Sequence-level polymorphisms of the HLA-class I (HLA-A and HLA-B) genes were investigated in DNA samples of 50 Ainu living in Hidaka district, Hokkaido. HLA-A*2402, A*0201, A*0206, A*2601, A*3101, B*1501, B*5101, B*3901, and B*3501 were observed at frequencies of more than 10% and most of these have previously been found in populations of not only Asians but also North and South American Indians. A*68012, which has not so far been detected in Hondo-Japanese, was found in the Ainu (3%). On the other hand, several alleles common in Hondo-Japanese, including HLA-A*3303, A*1101, B*4403, B*5201, B*5401, B*4601, and B*0702 were infrequent in Ainu (0-1%). Correspondence and neighbor-joining analyses of various populations based on HLA-A, -B and -DRB1 gene frequencies enabled distinction between Asian, Native South American, European, and African populations. The Ainu, as well as Tlingit (Na-Dene), were placed midway between other East Asians, including Hondo Japanese, and Native South Americans (Amerindians) in the correspondence analysis. Furthermore, several HLA-A-B and HLA-B-DR-DQ haplotypes common in the Ainu, are shared with some Native American populations. These observations strongly suggest a unique place for the Ainu as descendants of some Upper Paleolithic populations of East Asia, from whom some Native Americans may have descended.

Alleles↗

Y chromosome markers and Trans-Bering Strait dispersals.

Five polymorphisms involving two paternally inherited loci were surveyed in 38 world populations (n = 1,631) to investigate the origins of Native Americans. One of the six Y chromosome combination haplotypes (1T) was found at relatively high frequencies (17.8-75.0%) in nine Native American populations (n = 206) representing the three major linguistic divisions in the New World. Overall, these data do not support the Greenberg et al. (1986) tripartite model for the early peopling of the Americas. The 1T haplotype was also discovered at a low frequency in Siberian Eskimos (3/22), Chukchi (1/6), and Evens (1/65) but was absent from 17 other Asian populations (n = 987). The perplexing presence of the 1T haplotype in northeastern Siberia may be due to back-migration from the New World to Asia.

Biological Evolution↗

Genetic origins of the Japanese: a partial support for the dual structure hypothesis.

Based on the morphological characteristics of the skull and teeth, Hanihara ([1991] Japan Review 2:1-33) proposed the "dual structure model" for the formation of modern Japanese populations. We examine this model by dividing it into two independent hypotheses: 1) the Upper Paleolithic population of Japan that gave rise to the Neolithic Jomon people was of southeast Asian origin, and 2) modern Ainu and Ryukyuan (Okinawa) populations are direct descendants of the Jomon people, while Hondo (Main Island)-Japanese are mainly derived from the migrants from the northeast Asian continent after the Aeneolithic Yayoi period. Our aim is to examine the extent to which the model is supported by genetic evidence from modern populations, particularly from Japan and other Asian areas. Based on genetic distance analyses using data from up to 25 "classic" genetic markers, we find first that the three Japanese populations including Ainu and Ryukyuan clearly belong to a northeast Asian cluster group. This negates the first hypothesis of the model. Then, we find that Ainu and Ryukyuans share a group contrasting with Hondo-Japanese and Korean, supporting the second hypothesis of the model. Based on these results, we propose a modified version of the dual structure model which may explain the genetic, morphological, and archaeological evidence concerning the formation of modern Japanese populations.

Asia↗

Regulatory T cells in maintenance and reversal of peripheral tolerance in vivo.

Whether regulatory T cells could suppress the immune responses to an unrelated Ag and could induce tolerance to that Ag was investigated. In female B6 (I-Ab) mice tolerized to MHC class II I-Abm12 (bm12) alloantigen by cyclophosphamide-induced system, regulatory T cells specific for bm12 Ag were induced. These regulatory T cells suppressed in vivo immune responses to an unrelated Ag (male Ag) that was co-expressed with bm12 Ag on the same graft. However, the immune responses to male Ag suppressed by regulatory T cells were reverted by immunization with male Ag alone, indicating regulatory T cells suppressed the induction of immune responses to the unrelated Ag co-expressed with suppressogenic determinant, but did not inactivate T cells specific for that third Ag, such as clonal anergy or deletion. These results provided that minor Ag adjacent to major Ag, even if they were expressed on the professional APC, could be suppressed in the periphery, and the responses to those minor Ag could be activated when the suppression mechanism was abrogated or ineffective.

Animals↗

Thymus ontogeny and the development of TCR alpha beta intestinal intraepithelial lymphocytes.

Murine T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (IEL), which express the CD8 molecule as a homodimer (CD8 alpha alpha), can be divided into two subsets: those which are CD4+ (CD4+CD8+alpha alpha) and those which are CD4- (CD4-CD8+alpha alpha). Here, we demonstrate that most TCR alpha beta CD4+CD8+alpha alpha IEL and TCR alpha beta CD4-CD8+alpha alpha IEL subsets appear to be of thymus origin, as neonatal thymectomy of BALB/c mice on Day 3 nearly eliminated both subsets. To further support this hypothesis, we demonstrate by grafting the thymus of CBF1 (BALB/c x C57BL/6) mice into nude mice that the thymus is capable of generating both TCR alpha beta CD4-CD8+alpha alpha IEL and TCR alpha beta CD4+CD8+alpha alpha IEL. However, which of the two TCR alpha beta IEL subsets is generated depends largely on the age of the thymus. The thymus from fetal up to 2 weeks of age generates predominantly TCR alpha beta CD4-CD8+alpha alpha IEL, but very scant amounts CD4+CD8+alpha alpha IEL. In contrast, the thymus after 2 weeks of age generates very little TCR alpha beta CD4-CD8+alpha alpha IEL, but generates an abundant amount of TCR alpha beta CD4+CD8+alpha alpha IEL. These results are consistent with the observation in euthymic mice that TCR alpha beta CD4-CD8+alpha alpha IEL precede the appearance of TCR alpha beta CD4+CD8+alpha alpha IEL by several weeks, thus further suggesting that the thymus is the major source of both TCR alpha beta IEL subsets.

Aging↗

Donor-specific prolongation of rat skin graft survival induced by rat-donor cells and cyclophosphamide under coadministration of monoclonal antibodies against T cell receptor alpha beta and natural killer cells in mice.

Because of the recent interest in human xenotransplantation, we investigated the possibility of inducing tolerance in a xenogeneic combination using cyclophosphamide (CP). Donor-specific prolongation of xenogeneic Fisher 344 (F344) rat skin graft survival for up to 60 days was induced in C57BL/6 (B6) mice by giving F344 bone marrow cells and spleen cells on day 0, CP on day 2, and monoclonal antibodies against murine TCR-alpha beta and NK1.1 on days--1 and 3. The inoculation of the xenogeneic cells brought accelerated repopulation of TCR-alpha beta+ T cells, even under the administration of anti-TCR-alpha beta mAb. The quick increase of the host TCR-alpha beta+ T cells caused by the xenogeneic cell injection was deeply suppressed by CP. Mixed lymphocyte reaction, CTL activity, and antibody production against donor F344 were profoundly suppressed for 50 days. Mixed xenogeneic chimerism was observed for 1 month after the inoculation of donor cells in the spleen and peripheral blood of the recipient B6 mice, but was never observed in the thymus. Moreover, when irradiated F344 cells were used in place of viable cells, chimerism was never detected and graft survival was only slightly prolonged. Clonal deletion of V beta 5- or V beta 11-bearing murine T cells was not observed on day 50 in the thymus or spleen of the recipient B6 mice. These results suggest that treatment with viable xenogeneic donor cells, CP, and mAbs against T and NK cells can induce a temporary peripheral mixed chimerism and donor-specific prolongation of xenogeneic skin graft survival. The destruction with CP of T and B cells that are xenoreactive and thus proliferating after antigen stimulation, followed by mechanism other than intrathymic clonal deletion, may be the mechanism of the hyporesponsiveness in the present system.

Animals↗

HLA class II alleles in Ainu living in Hidaka District, Hokkaido, northern Japan.

The Ainu people are considered to be the descendants of preagricultural native populations of northern Japan, while the majority of the population of contemporary Japan (Wajin) is descended mainly from postneolithic migrants. Polymorphisms of the HLA-DRB1, DRB3, and DQB1 alleles were investigated in DNA samples of 50 Ainu living in Hidaka district, Hokkaido. Unique features of the Ainu in this study were high incidences of DRB1*1401, DRB1*1406, and a newly described allele, DRB1*1106 (20%, 17%, and 5%, respectively). On the other hand, several common alleles in Wajin (DRB1*1502, 1302, 0803, and 1501) were found at relatively low frequencies (1-2%) in Ainu. Previously DRB1*1406 was described as a characteristic allele of some Native American or northeast Asian ethnic groups, and DRB1*1106 had been found in only two Singapore Chinese and one Korean. Principal component analysis of various populations based on HLA class II allele frequencies places the Ainu population midway between other east Asian populations, including Wajin, and Native Americans. These observations may support the hypothesis that the Ainu people are the descendants of some Upper Paleolithic populations of northeast Asia from which Native Americans are also descended.

Alleles↗

Anti-CD4 monoclonal antibody reduces the dose of cyclophosphamide required to induce tolerance to H-2 haplotype identical skin allografts in mice.

Cyclophosphamide (CP)-induced tolerance which consists of a single i.p. injection of 200 mg/kg CP 2 days after priming with 1 x 10(8) donor spleen cells (SC), leads to long-lasting donor-specific skin allograft tolerance in H-2 compatible, multiminor antigen incompatible, murine strain combinations. In this system, the optimal dose of CP has been suggested to be 200 mg/kg, however, such a dose of CP causes strong myelosuppression. In the present study, we therefore attempted to reduce the dose of CP by administering anti-CD4 monoclonal antibody (mAb) before donor cell priming in this tolerance-inducing system. When C3H/He (C3H; H-2k, Mls-1b) mice were injected i.p. with 200 micrograms anti-CD4 mAb on day -3, 1 x 10(8) AKR/J (AKR; H-2k, Mls-1a) SC plus 3 x 10(7) bone marrow cells (BMC) i.v. on day -2 and then 100 mg/kg CP i.p. on day 0, a long-lasting donor-specific skin allograft tolerance was established; furthermore, the decreases in the number of leukocytes and the concentration of hemoglobin (Hb) in the peripheral blood were all less in the C3H mice treated with this new combined protocol than in the C3H mice injected with 200 mg/kg CP following the previous protocol. In the periphery of these tolerant mice, the number of donor-reactive V beta 6+CD4+ T cells decreased and mixed chimerism was observed on both days 14 and 80. On the other hand, in the mice injected with AKR SC, BMC plus 100 mg/kg CP without anti-CD4 mAb, the number of V beta 6+CD4+ T cells decreased on day 14, and then recovered by day 80 when the mixed chimerism disappeared. These results therefore suggest that the combined use of anti-CD4 mAb with CP can reduce the dose of CP without affecting the efficiency of inducing donor-specific tolerance, probably due to the enhancement of the destruction effect of donor-reactive T cells by CP.

Anemia↗

Specific immunotherapy with tumour-draining lymph node cells cultured with both anti-CD3 and anti-CD28 monoclonal antibodies.

For providing costimulatory signals, we utilized anti-CD28 monoclonal antibody (mAb) for the in vitro culture of tumour-draining lymph node (LN) cells. The proliferation of B16 melanoma-draining LN cells in the culture with anti-CD3 mAb was remarkably enhanced by the addition of anti-CD28 mAb. In culture with both anti-CD3 and anti-CD28 mAb, the B16-draining LN cells produced a higher level of interferon-gamma, but not interleukin-4, than with anti-CD3 mAb alone. The B16-draining LN cells efficiently expanded in the culture with both anti-CD3 and anti-CD28 mAb and subsequently with a low dose of IL-2 (anti-CD3 plus anti-CD28/IL-2). The expanded cells consisted predominantly of CD8+ T cells and showed a specific cytolytic activity, in a major histocompatibility complex (MHC) class I-restricted manner, even without in vitro restimulation. In addition, the adoptive transfer of the B16-draining LN cells, expanded in the culture protocol of anti-CD3 plus anti-CD28/IL-2, showed a significant anti-tumour effect against metastatic B16 melanoma in combination with IL-2. The cured mice thus acquired a specific protective immunity. Moreover, this protocol was also moderately effective against poorly immunogenic 3LL carcinoma. Overall, our results suggest the potential for another immunotherapeutic strategy based on 'the costimulatory theory' other than vaccination with B7-transfected tumour cells.

Animals↗