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Biomedical subjects

K Sugiura

Publications and source records attributed to K Sugiura.

At least 19 recordsLinked to original sources
PubMed1999

Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously reported four quantitative trait loci (QTLs) responsible for NIDDM on Chromosomes (Chrs) 7, 14, 8, and 11 (Nidd1-4/of for Non-insulin-dependent diabetes1-4/oletf) by a whole-genome search in 160 F2 progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. Our present investigation was designed to identify and characterize novel QTLs affecting NIDDM by performing a genome-wide linkage analysis of genes for glucose levels and body weight and analysis for gene-to-gene and gene-to-body-weight interactions on an improved genetic map with a set of 382 informative markers in the 160 F2 progenies. We have identified seven novel QTLs on rat Chrs 1 (Nidd5 and 6/of), 5 (Nidd7/of), 9 (Nidd8/of), 12 (Nidd9/of), 14 (Nidd10/of) and 16 (Nidd11/of) which, together with the Nidd1-4/of, account for a total of approximately 60% and approximately 75% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F2. While the OLETF allele corresponds with increased glucose levels as expected for the novel QTLs except Nidd8 and 9/of, the Nidd8 and 9/of exhibit heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There are epistatic interactions between Nidd1 and 10/of and between Nidd2 and 8/of. Additionally, our results indicated that the Nidd6 and 11/of could also contribute to an increase of body weight, and that the other five QTLs could show no linkage with body weight, but Nidd8,9, and 10/of have an interaction with body weight.

Animals↗
PubMed1998

A strategy for organ allografts without using immunosuppressants or irradiation.

A strategy to achieve regular and long lasting organ and tissue allografts without using immunosuppressants and/or irradiation has been established for mice. One hundred percent of skin allografts can be induced to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be described as follows: (i) donor T cells from the spleen of the donor facilitate the acceptance of the allogeneic engraftment, (ii) donor-specific anergy is induced in the cytotoxic T-lymphocytes of the recipients, (iii) T helper type 2 cells become the dominant T cells in the recipients that are accepting the skin transplants, and (iv) a lasting chimerism (microchimerism) is established in these recipients. This strategy, perhaps with minor modifications, might permit one also to overcome major barriers to organ allografting in humans. If this were the case, it could represent production of long lasting immunologic tolerance without need for irradiation or cytotoxic chemo-preparative regimen and as such could greatly facilitate allotransplantation free of episodes of chronic or acute rejection or toxic and damaging preparatory regimens.

Adoptive Transfer↗
PubMed1998

Characterization of natural suppressor cells in human bone marrow.

Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In the present study, we characterize NS cells in human BM. NS activity was found in a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T cells, B cells, and monocytes. The NS activity was significantly decreased by the depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells. Hematopoietic progenitor cells committed to the myeloid lineage were also enriched in the CD34+CD33+ cells, which significantly correlated to the NS activity. From these findings, it is strongly suggested that NS activity in human BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell contact was not necessary for the action, NS cells seemed to secrete soluble mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor were, however, not the candidates, based on experiments using neutralizing antibodies.

Antigens, CD↗
PubMed1998

Effects of administration of monoclonal antibodies (anti-CD4 or anti-CD8) on the development of autoimmune diseases in (NZW x BXSB)F1 mice.

(NZW x BXSB)F1 (W/BF1) mice spontaneously develop autoimmune diseases, characterized by lymphadenopathy, lupus nephritis, and immune thrombocytopenia associated with various autoantibodies such as anti-DNA, anti-platelet and anti-cardiolipin antibodies (Abs). In the present study, we investigate the effects of administration of monoclonal Abs (anti-CD4 or anti-CD8 mAb) on the development of autoimmune diseases in W/BF1 mice. MAb was administered from the age of 7 weeks. Prolongation of survival rate and reduction of severity of autoimmune diseases were observed after treatment with anti-CD4 mAb. However, anti-CD8 mAb treatment accelerated the diseases. Serum levels of IFN-gamma and IL-10 in old W/BF1 mice were significantly high, whereas IL-4 levels were low in comparison with those of young W/BF1 mice; the expression of mRNA of IFN-gamma, IL-4 or IL-10 in CD4+ T cells of old W/BF1 mice was parallel to the serum levels of each cytokine. These observations suggest that CD4+ cells are involved in the development of autoimmune diseases in W/BF1 mice, and that CD8+ cells have a suppressive effect on the development of autoimmune diseases in W/BF1 mice.

Age Factors↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor expressed in T cells mediates immunity against herpes simplex virus type 1 encephalitis.

A model of herpes simplex virus type 1 (HSV-1) infection was developed in rats to study systemic immune responses elicited by intravitreous inoculation of the virus. HSV-1 inoculation led to distinct granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing memory T cells, which did not develop in rats inoculated with either HSV-1 intraperitoneally or inactivated HSV-1 intravitreously. On subsequent intraperitoneal viral boosting, systemic GM-CSF production was elicited as a secondary immune response that caused neutroeosinophilia. To examine the role of GM-CSF in anti-herpetic immunity, cytokine-producing and -nonproducing rats were intravitreously challenged with HSV-1, which causes lethal encephalitis. Only intravitreously primed rats were protected upon production of GM-CSF. Furthermore, pretreatment with recombinant GM-CSF protected unimmunized rats against the encephalitis. It is thus strongly suggested that the production of GM-CSF leads to anti-HSV-1 immunity against the transneuronal spread of challenged HSV-1 within the visual system.

Adoptive Transfer↗
PubMed1998

Effect of carbohydrate ingestion on sprint performance following continuous and intermittent exercise.

PURPOSE: This investigation was conducted to study the effects on sprint performance of glucose and fructose ingestion during a 15-min rest period half way through 90 min of continuous and intermittent exercise. On three occasions, eight subjects cycled at 76 +/- 2% VO2max for 90 min (continuous trials: CON trials) with a 15-min half-time break. METHODS: On another three occasions, they cycled for 90 min between moderate (65% VO2max) and high (100% VO2max) intensity (intermittent trials: INT trials) with the same half-time. In both trials, 90-min exercise was followed by a 40-s Wingate test to evaluate remaining sprint capacity. During half-time, they consumed either 20% glucose polymer (G), 20% fructose (F) or sweet placebo (P). Ingestion of G maintained plasma glucose levels, carbohydrate oxidation rate and lower value of ratings of perceived exertion (RPE) in both trials and indicated higher sprint performance compared with P (mean power of CON trials: 614.3 +/- 23.3 W vs 574.0 +/- 22.7 W, P < 0.001, INT trials: 629.5 +/- 27.6 W vs 596.3 +/- 25.5 W, P < 0.01). RESULTS: Ingestion of F showed similar effect in CON trials (603.8 +/- 26.1 W vs 574.0 +/- 22.7 W, P < 0.01) but had no positive effect in INT trials. Additionally, mean power of G was higher than F (629.5 +/- 27.6 W vs 598.4 +/- 34.2 W, P < 0.01) in INT trials. CONCLUSIONS: These results indicated that ingestion of G during half-time of 90-min exercise could maintain carbohydrate utilization and improve sprint performance in both CON and INT trials.

Adult↗
PubMed1998

Levodopa effective parkinsonism associated with aqueductal stenosis: a case report and review of the literature.

A case of aqueductal stenosis (AS) associated with marked parkinsonism is described. A ventriculoperitoneal (V-P) shunt was performed in an 18-year-old female because of hydrocephalus associated with non-neoplastic aqueductal stenosis. The patient developed acute parkinsonism with Parinaud's sign after the shunt revision. She had a marked response to levodopa and the parkinsonism improved. Subsequently, levodopa therapy was gradually discontinued without any manifestation of parkinsonism. The pathophysiology of this type of parkinsonism probably involved presynaptic dopaminergic dysfunction. However, the etiology of this complication has not been confirmed.

Adolescent↗
PubMed1997

Expression cloning and intracellular localization of a human ZF5 homologue.

We isolated a cDNA encoding a human homologue of ZF5 (hZF5), which has five Kruppel-like C2H2 type zinc fingers at carboxyl terminus and the BTB/POZ (poxvirus and zinc finger) at the amino terminus, using autoimmune sera from a patient with overlap syndrome (dermatomyositis and scleroderma). Sequencing of the entire cDNA revealed an open reading frame (ORF) of 1349 bp with a deduced protein sequence of 449 amino acid residues and a calculated molecular weight of 51.3 kDa. The deduced amino acid sequence of hZF5 is highly homologous to mouse ZF5 (99.3% identity). Immunofluorescence studies revealed that HA-tagged hZF5 transiently expressed in COS-7 cells showed the nuclear dot pattern in the BTB/POZ domain-dependent manner.

Adult↗
PubMed1997

Major histocompatibility complex restriction between hematopoietic stem cells and stromal cells in vivo.

Graft failure is a mortal complication in allogeneic bone marrow transplantation (BMT); T cells and natural killer cells are responsible for graft rejection. However, we have recently demonstrated that the recruitment of donor-derived stromal cells prevents graft failure in allogeneic BMT. This finding prompted us to examine whether a major histocompatibility complex (MHC) restriction exists between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone marrow cells (BMCs) and bones obtained from various mouse strains and analyzed the cells that accumulated in the engrafted bones. Statistically significant cell accumulation was found in the engrafted bone, which had the same H-2 phenotype as that of the BMCs, whereas only few cells were detected in the engrafted bones of the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the BMCs obtained from the MHC-compatible bone showed significant numbers of both colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings strongly suggest that an MHC restriction exists between HSCs and stromal cells.

Animals↗
PubMed1997

Intrathymically injected hemopoietic stem cells can differentiate into all lineage cells in the thymus: differences between c-kit+ cells and c-kit < low cells.

To investigate whether hemopoietic stem cells (HSCs) can differentiate into all lineage cells even in the thymus, we injected two types of HSCs (c-kit+ and c-kit < low cells) obtained from C57BL/6 Ly5.1 mice directly into the thymus of 7.5 Gy-irradiated C57BL/6 Ly5.2 mice. When c-kit < low cells (low density/lineage-/CD71-/major histocompatibility complex class I high/Sca-1+/Thy-1low/ c-kit < low) were injected, donor-derived (Ly5.1) cells were detected on day 8 after intrathymic (i.t.) injection, and the number reached a maximum on day 24 after injection. Granulocytes and macrophages were also detected on day 8 after injection. However, B220+ B cells were observed on day 13. Eighteen days after i.t. injection, the injected lobes showed red color due to the synchronous development of erythroid cells. Histological studies revealed the development not only of erythroid lineage cells but also of megakaryocytes in the thymus. In contrast, when c-kit+ cells were injected, a significant number of donor-derived cells were detected on day 5 after i.t. injection (three days earlier than in the case of c-kit < low cell injection). The differentiation into erythroid lineage cells was also observed six days earlier than when c-kit < low HSCs were injected. These findings suggest that c-kit < low HSCs are more primitive than c-kit+ HSCs, although both can differentiate into all lineage cells after i.t. injection.

Animals↗
PubMed1997

Requirement of major histocompatibility complex-compatible microenvironment for spleen colony formation (CFU-S on day 12 but not on day 8).

To clarify major histocompatibility complex (MHC) restriction between hematopoietic stem cells (HSCs) and microenvironments, T cell-depleted bone marrow cells (BMCs) were transplanted into MHC-compatible and MHC-incompatible recipients. A significantly larger number of spleen colony-forming units (CFU-S) on day 12 were noted in MHC-compatible recipients, while only a small number were observed in MHC-incompatible recipients. There was, however, no significant difference in CFU-S counts on day 8 between the two groups. A large number of CFU-S counts on day 12 were also observed in F1 hybrid recipients, as seen in syngeneic recipients. The decrease in CFU-S counts on day 12 in MHC-incompatible recipients was also observed even after in vivo abrogation of T and NK cells. The difference in CFU-S counts on day 12 became more prominent when HSC-enriched cells were transferred. These results suggest that an MHC restriction exists between pluripotent HSCs (P-HSCs) and spleen microenvironments. Furthermore, experiments using B10. A recombinant strains revealed that H-2D and S loci play a crucial role in the MHC restriction. The experiments of serial transplantation suggest that the differentiation and proliferation of P-HSCs are inhibited in MHC-incompatible microenvironments. It is therefore likely that the MHC-compatible microenvironment is essential to the differentiation and proliferation of P-HSCs.

Animals↗
PubMed1997

Low frequency of autoantibodies against Ki-67 antigen in Japanese patients with systemic autoimmune diseases.

The Ki-67 antigen, which is recognized by the monoclonal antibody Ki-67, is a marker of cell proliferation. During cDNA cloning using sera from a patient with systemic lupus erythematosus, we obtained a positive clone encoding part of Ki-67. We determined the frequency of autoantibodies against Ki-67 in patients with systemic autoimmune diseases. Serum samples from 252 patients with rheumatic diseases were examined by immunoblotting with HeLa nuclear extract and the recombinant N-terminus of the Ki-67 antigen. Autoantibodies against Ki-67 antigen were detected in two out of 76 patients with systemic lupus erythematosus and one out of 90 patients with scleroderma. While, in a previous report, anti-Ki-67 antibodies were frequently targeted by a certain strain of autoimmune mice, our results indicated that Ki-67 was a minor target of autoantibodies among Japanese patients with systemic autoimmune diseases.

Autoantigens↗
PubMed1997

An animal model of copulatory disorder induced by social stress in male mice: effects of apomorphine and L-dopa.

We investigated the possible role of dopamine receptors in the mediation of copulatory disorder induced by defeat experience in male mice, using L-dopa and apomorphine. To generate the copulatory disorder, male mice were attacked 20 times daily for 5 consecutive days, as intruders in confrontation with an aggressive resident. Following the repeated exposure to defeat, virtually all intruder males failed to display copulatory behavior towards estrous females. Acute injection of apomorphine (25, 50, 75 micrograms/kg, s.c.) significantly increased both the incidence and the frequency of copulatory elements (mounting and intromission) in a dose-dependent manner. The combination of L-dopa with carbidopa, a dopa decarboxylase inhibitor, also increased significantly copulatory behavior, revealing an inverted U-shaped dose-effect curve. In both cases, locomotion and digging frequencies were significantly decreased. This evidence suggests that dopaminergic mechanisms are involved in the mediation of social stress-induced copulatory disorder.

Aggression↗
PubMed1997

Induction of donor-specific T cell anergy by portal venous injection of allogeneic cells.

The mechanisms behind tolerance induction by portal venous (pv) injection of allogeneic cells are investigated. When a hematopoietic stem cell (HSC)-enriched population of BALB/c bone marrow was pv injected into C57BL/6 mice, the response of the T cells in the B6 mice to BALB/c alloantigens in mixed lymphocyte reaction (MLR) decreased until day 4 after the injection. Neither clonal deletion of V beta 11+ T cell nor donor-specific suppressor activity was observed. When recipient T cells were separated into CD4+ and CD8+ cells, only the CD8+ cell population showed donor-specific tolerance. The donor cells were trapped and retained in the host liver. MHC class I antigens were highly expressed on the trapped cells whereas class II antigens or B7 costimulatory molecules were not. The tolerance to BALB/c alloantigens in MLR was obtained also by the pv injection of Meth A, a BALB/c-derived sarcoma cell line. However, tolerance was not induced by the pv injection of B7-transfected Meth A cells. In addition to MLR, tolerance was also observed in DTH responses, and this was also due to the unresponsiveness of CD8+ cells to the donor alloantigens. However, the BALB/c-specific DTH responses were not suppressed after the pv injection of B7-transfected Meth A cells. These results strongly suggest that the tolerance induced by pv injection of allogeneic cells is due to clonal anergy generated by the absence of costimulatory signals in the interaction between donor-specific CD8+ T cells and donor hematopoietic cells trapped in the host liver.

Adoptive Transfer↗
PubMed1997

Cord blood IgE against milk and egg antigens.

The aim of the present study was to reevaluate the prenatal production of specific IgE for eggs and milk and, in those cases, to determine whether there is a relation to the amount of maternal egg and milk intake. Total and specific IgEs from 160 cord blood-samples were determined by immunoassays using a paramagnetic particle solid phase and an enzyme-mediated chemiluminescent reaction for signal detection. The levels of cord blood IgE for total, egg, and milk were 0.63 +/- (SD) 1.10 IU/ml, 0.020 +/- 0.055, and 0.036 +/- 0.053 IU/ml, respectively. IgE levels specific to egg and milk over 0.03 IU/ml were observed in 33 and 70 out of 160 cases, respectively. To address whether the maternal intake of eggs and milk affects the level of cord blood IgEs, all mothers except 9 were interviewed, and the amount of eggs and milk taken during pregnancy was recorded. No correlation was seen between egg and milk intakes and cord blood IgE levels. Our data demonstrate a high incidence of the prenatal production of specific IgE for eggs and milk which is independent of maternal egg and milk intakes.

Adult↗
PubMed1996

Liver NK1.1+ CD4+ alpha beta T cells activated by IL-12 as a major effector in inhibition of experimental tumor metastasis.

We demonstrate herein evidence that IL-12-activated alpha beta T cells with intermediate TCR (NK1+ TCRint cells) in the liver inhibit metastases in the lung as well as in the liver metastases of i-v. injected tumors. IL-12 administration enhanced NK1 expression of NK1+ TCRint cells (NK1high) and increased CD4 weakly positive (CD4low) TCRint cells, while both CD4+ TCRint cells and double-negative TCRint cells were proportionally diminished. Accordingly, the major parts of NK1high TCRint cells are CD4low cells, and most of these cells are V beta 8+ cells. The cytotoxic assays of IL-12-stimulated hepatic mononuclear cells after treatment with respective Abs and complement in vitro and after sorting revealed that CD4low NK1high TCRint cells are cytotoxic effectors. When IL-12-stimulated hepatic mononuclear cells (but not splenocytes) were transferred into tumor-preinjected mice, EL-4 cell metastases in the liver as well as 3LL cell metastases in the lung were inhibited. The antimetastasis of hepatic mononuclear cells transfer was abrogated by the depletion of NK1+ cells, CD3+ cells, or CD4+ cells but not CD8+ cells before transfer. Moreover, transfer of these cells of nude mice into tumor-preinjected mice also inhibited metastases in both organs. Although NK1+ TCRint cells are nearly absent in the hepatic vein blood, a significant proportion of NK1high TCRint cells appeared by IL-12 administration. These results demonstrate that IL-12-stimulated liver NK1high TCRint cells, including extrathymic ones, are major effectors against tumor metastasis and suggest that the cells migrate and inhibit lung metastases.

Animals↗