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Biomedical subjects

M Kohyama

Publications and source records attributed to M Kohyama.

At least 19 recordsLinked to original sources
PubMed2005

Ocular blood flow changes after dynamic exercise in humans.

PURPOSE: To investigate control mechanisms for ocular blood flow changes after dynamic exercise using two different methods. METHODS: Changes over time in the tissue blood flow in the retina and choroid-retina of healthy volunteers were determined after dynamic exercise (Master's double two-step test), using scanning laser Doppler flowmetry (SLDF) and laser speckle flowgraphy (LSFG). Changes in intraocular pressure (IOP), blood pressure, plasma CO(2) gas concentration (pCO(2)), and levels of nitric oxide (NO) metabolites were examined. RESULTS: Retinal blood flow measured by SLDF increased significantly only at 15 min after exercise. In contrast, normalized blur (NB) values in the choroid-retina, obtained by LSFG, increased significantly up to 60 min after exercise. Ocular perfusion pressure (OPP), calculated from IOP and blood pressure, increased significantly immediately and 15 min after exercise. The plasma NO metabolite levels increased significantly, although pCO(2) levels were unchanged. CONCLUSIONS: Dynamic exercise changes OPP and produces increased tissue blood flow in the retina in the immediate postexercise period, while blood flow increases more persistently in the choroid-retina. Difference in control of blood flow in these two regions may be related to stronger autoregulatory mechanism of blood flow in the retina. Nitric oxide may play a role in the regulation of blood flow.

Adult↗
PubMed2001

IL-4-mediated development of TGF-beta1-producing cells from naïve CD4(+) T cells through a STAT6-independent mechanism.

Transforming growth factor-beta1 (TGF-beta1) is an inhibitory cytokine increasingly recognized as a key factor for immuno-regulation. The function of IL-4 in the regulation of TGF-beta1 production from T cells has been reported previously; however, the precise molecular mechanism still remains to be elucidated. For a better understanding of the mechanism involved in regulation, we have investigated a relationship between the STAT6-dependent pathway and TGF-beta1 production from naïve T cells. TCR crosslinking initiates TGF-beta1 production in CD4(+) T cells, and IL-4-mediated signaling enhances the TGF-beta1 production from naïve CD4(+) T cells. The IL-4-mediated up-regulation of TGF-beta1 production from naïve CD4(+) T cells is elicited in STAT6-deficient (STAT6 KO) mice, but not in IL-4 receptor-deficient (IL-4R KO) mice. These results clearly demonstrate that a STAT6-independent pathway is working in IL-4-mediated enhancement of TGF-beta1 production from naïve CD4(+) T cells. Moreover, the addition of IL-4 showed no additive effect on TGF-beta1 promoter-mediated transcription stimulated by TCR. Therefore, we hypothesize that the IL-4-mediated signaling does not work directly on the transcription of the TGF-beta1 gene, but rather regulates the expansion of TGF-beta1-secreting T cells.

Animals↗
PubMed2000

Tumor formation suppressed in gammadeltaT knock-out mice.

Tumor formation was examined in mice in which the beta-chain gene of alphabetaT was knocked out (alphabetaT-KO mice) or the delta-chain gene of gammadeltaT was knocked out (gammadeltaT-KO mice). Development of Hepa 1-6 cell hepatoma was observed in six of six alphabetaT-KO mice, in four of six wild-type mice, and in only one of six gammadeltaT-KO mice. These results imply that gammadeltaT cells play a role in suppression of killer cell activity in tumor-bearing mice.

Animals↗
PubMed1999

Cytolytic and IFN-gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are T cell receptor-beta-chain dependent.

We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2- to 3-month-old mutant mice rendered deficient in different gene(s) in which the number of IEL expressing either T cell receptor (TCR)-alpha beta (alpha beta-IEL) or TCR-gamma delta (gamma delta-IEL) were absent or markedly diminished. When compared with wild-type littermates, cytolytic activity of gamma delta-IEL was sharply attenuated in TCR-beta mutant mice but remained unaltered in TCR-alpha mutant mice in which a minor population of dull TCR-beta+ (betadim)-IEL was also present. Cytolytic activity of gamma delta-IEL was maintained in mice doubly homozygous for beta2-microglobulin and transporter associated with antigen processing 1 gene mutations in which a conspicuous decrease was noted in absolute numbers of alpha beta-IEL. In contrast, both TCR-delta and IL-7 receptor-alpha gene mutations that lead to lack of gamma delta-IEL generation did not affect the development or cytolytic activity of the remaining alpha beta-IEL. The anti-CD3 and anti-TCR-gamma delta mAb-induced IFN-gamma production of gamma delta-IEL showed the same TCR-alpha and TCR-beta mutation-dependent variability. These results indicate that cytolytic and IFN-gamma-producing activities of gamma delta T cells in mouse intestinal epithelium are TCR-beta-chain-dependent.

Animals↗
PubMed1999

Transport kinetics of leucine enkephalin across Caco-2 monolayers: quantitative analysis for contribution of enzymatic and transport barrier.

In this study, we determined the activities of four aminopeptidases such as aminopeptidase B (APB), M (APM), N (APN) and dipeptidylpeptidase IV (DPP IV) in Caco-2 cells and compared with those in the rat intestinal mucosae. The activities of APB, APM and APN appeared to be highest in rat small intestinal mucosa, while DPP IV activity was much higher in Caco-2 cells than that in the rat intestinal mucosa. Next the inhibitory effects of various protease inhibitors were examined in Caco-2 homogenate. Three tested inhibitors, bacitracin, amastatin and puromycin, effectively inhibited the activities of APM, APN and DPP IV except for APB. Further, we quantitatively evaluated the permeation and degradation properties of leucine enkephalin (Leu-Enk) in the presence or absence of inhibitors in Caco-2 monolayer system. Leu-Enk had a high degradation clearance (CLd) and a low permeation clearance (CLp) in Caco-2 monolayers. This finding indicates that the very rapid degradation of Leu-Enk on the apical side of Caco-2 monolayers was due to aminopeptidases. However, these protease inhibitors besides sodium glycocholate were able to reduce the CLd values markedly, thereby increasing the permeation amount of Leu-Enk across Caco-2 monolayers. In particular, amastatin significantly decreased the CLd value and increased the CLp value. This enhanced CLp value was further increased by the coadministration with an absorption enhancer, EDTA or laurylmaltoside. These findings are relevant to the oral administration of peptide drugs and to developing an efficient oral delivery system.

Aminopeptidases↗
PubMed1998

Selective induction of CD8+ T cell functions by single substituted analogs of an antigenic peptide: distinct signals for IL-10 production.

The CD8+ T cell clone 5F1 produces interleukin 10 (IL-10) and interferon gamma(IFN-gamma) in response to stimulation with a peptide corresponding to region 142-149 of bovine alpha(s1)-casein (p142-149). Ninety analog peptides derived from p142-149 with single amino acid substitutions of putative T cell receptor contact residues were prepared to examine whether production of IL-10 and IFN-gamma by 5F1 can be altered by stimulation with these peptides. We found that some peptides triggered only IL-10 production whereas others induced production of IFN-gamma alone or both of these cytokines. Peptides inducing IFN-gamma production triggered both cytotoxicity and a proliferative response, whereas peptides inducing production of IL-10 but not IFN-gamma triggered neither of these responses. Our results clearly demonstrate that the signaling pathway required for IL-10 production in CD8+ T cells differs from that required for IFN-gamma production. The distinct cellular signals for IL-10 production appear to be independent of those for cytotoxicity and the proliferative response of CD8+ T cells.

Animals↗
PubMed1998

Enhancement of antigen-specific IFN-gamma production from CD8(+) T cells by a single amino acid-substituted peptide derived from bovine alphas1-casein.

Modulation of CD8(+) T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8(+) T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142-149 (p142-149; LAYFYPEL) of alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8(+) T cells which recognize the parent peptide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production.

Amino Acid Sequence↗
PubMed1998

Direct activation of human CD8+ cytotoxic T lymphocytes by interleukin-18.

Direct activation of human cytotoxic T lymphocytes (CTL) by interleukin (IL)-18 was observed in a system in which CTL effective against autologous tumor cells were generated. Peripheral blood mononuclear cells (PBMC) from tumor-bearing patients, after removal of natural killer (NK) cells, were cultured in a medium containing IL-1, -2, -4, and -6, with or without IL-18, and stimulated with autologous tumor cells. IL-18 increased the activity of the CTL and the proportion of autologous CD8+ T cells present after 28 days in the induction culture. When purified CD8+ T cells were cultured in the presence of IL-18 and IL-2 for 7 days, the CTL showed enhanced cytotoxic activity against autologous tumor cells. Moreover, a purified CD8+ T cell population, which did not exhibit any apparent cytotoxic activity against autologous tumor cells, displayed cytotoxic activity after 7-day incubation with IL-18. These results suggest that IL-18 may be useful to generate autologous CTL in humans and may thereby contribute to adoptive immunotherapy for tumors.

Adenocarcinoma↗
PubMed1997

Analysis of cytokine producing activity of intestinal intraepithelial T cells from TCR beta-chain and delta-chain mutant mice.

Intestinal intraepithelial T cells (IELs) expressing either gammadelta TCR or alphabeta TCR have been proposed to play an important role in the regulation of intestinal epithelia by producing cytokines that directly influence the adjoining intestinal epithelial cell (IEC) functions. To illuminate this issue, we utilized TCR mutant mice to obtain gammadelta IELs, alphabeta IELs and mixed gammadelta and alphabeta IELs from corresponding alphabeta T-cell-deficient (beta-/-), gammadelta T-cell-deficient (delta-/-) and wild-type (WT) littermate mice. The production of IFN-gamma by these IELs as well as the mRNA for IFN-gamma, TGF-alpha, TGF-beta1, TNF-alpha and TNF-beta in these IELs, in conjunction with the effect of produced cytokines on the expression of class II MHC molecules by the in vitro cell line IEC-6, were investigated. IFN-gamma and TNF-alpha [corrected] specific mRNA were detectable in all freshly isolated gammadelta, alphabeta and WT IELs. In addition to the IFN-gamma and TNF-alpha [corrected] mRNA, alphabeta and WT IELs that had been activated in culture plates coated with anti-CD3 mAb contained mRNA for TGF-beta1 and TNF-beta proteins. In the cultured gammadelta IELs, however, the signals for IFN-gamma and TNF-alpha [corrected] transcripts were weak, and mRNA for the latter two cytokines was almost undetectable. Supernatants from in vitro culturing of alphabeta and WT IELs but not gammadelta IELs induced class II MHC gene expression in IEC-6, whereas, in the presence of anti-IFN-gamma mAb, the same culture supernatants failed to do so. In fact, the concentration of IFN-gamma in supernatants from alphabeta and WT IEL cultures was ten- to twentyfold higher than that in the supernatant from the gammadelta IEL culture. Finally, TGF-alpha specific mRNA was not detectable in the gammadelta and alphabeta IELs even after in vitro activation. These results indicate that alphabeta IELs are superior to gammadelta IELs in the ability to produce IFN-gamma, TGF-beta1, TNF-alpha [corrected] and TNF-beta through TCR crosslinking primary in vitro stimulation.

Animals↗
PubMed1997

Enhancing effect of interleukin-4 on the secretion of interferon-gamma by alpha s1-casein-specific CD8+ T cells.

alpha s1-Casein-specific CD8+ T cell clones expressed the interleukin (IL)-4 receptor, although they did not secrete detectable IL-4. We found that IL-4 significantly enhanced the secretion of interferon (IFN)-gamma by these CD8+ T cell clones. IL-4 also enhanced the secretion of IFN-gamma induced by stimulating the immobilized anti-CD3 antibodies of polyclonal CD8+ T cells which had been isolated from lymph nodes and were stimulated in vitro with the immobilized anti-CD3 antibody and IL-2. In addition, IL-4 added at the time of this first in vitro stimulation induced strong IFN-gamma productivity, as well as IL-4 and IL-10 productivity, which were detectable upon restimulation of these cells. Results are discussed in relation to the inhibitory effects of IFN-gamma production on IL-4-producing cells.

Animals↗
PubMed1997

[Simultaneous operation of emergency coronary artery bypass grafting and gastrotomy with suturing ulcer].

A 62-year-old man with complaints of severe chest pain came to our hospital. An emergency coronary angiography was performed and he was diagnosed as having acute myocardial infarction. Due to severe triple vessels disease he was referred to the department of Cardiovascular Surgery to undergo emergency coronary artery bypass grafting. In the coronary care unit, sudden hematoemesis due to hemorrhagic gastric ulcer occurred, however, just when he was going to be transferred to the operation room. Because the gastric bleeding was thought to be serious under extracorporeal circulation, which was indispensable for coronary artery bypass grafting, gastrotomy with suturing ulcer was performed prior to median sternotomy with use of intraaortic balloon pumping. Severe infection was not complicated. His postoperative course was uneventful.

Coronary Artery Bypass↗
PubMed1997

[A case of left atrial thrombi following mitral valvuloplasty for mitral regurgitation associated with idiopathic thrombocytopenic purpura].

A 58-year-old man, who had been submitted to an indication of mitral valvuloplasty (MVP) because of severe mitral regurgitation, was diagnosed as idiopathic thrombocytopenic purpura (ITP). In order to diminish the peri-operative blood loss, splenectomy and high-dose bolus administration of gamma-globulin (400 mg/kg/day) were performed at the time of two weeks and during last five days respectively, prior to MVP surgery. In early post-operative stage, anticoagulant therapy was held down considering ITP, and we were not troubled with bleeding throughout the peri-operative period. On the fourteenth post-operative day, however, mural thrombi in the left atrium were pointed out by transesophageal echocardiography (TEE). Then anticoagulant therapy was reinforced by increasing the warfarin dose. When TEE was restudied on 36th, post-operative day, mural thrombi had almost disappeared. Although it is commonly known that mitral valvuloplasty has low risk of thrombosis and less necessity of anticoagulation, hyper coagulability may be feasible in the early post-operative period of our case whose ITP is meticulously treated prior to surgery. Suitable anticoagulation should have been performed regardless of ITP immediately after MVP.

Heart Atria↗
PubMed1997

[Short-term results of leaving elephant trunk in type A aortic dissection].

Elephant trunk prosthesis was devised for treatment of multiple aortic aneurysm. But it has applied to type A aortic dissection. Because residual false lumen often dilates gradually and come to have the risk of rupture. Two patients who were diagnosed as type A aortic dissection were performed total aortic arch replacement with Elephant trunk prosthesis on distal anastmosis. Postoperative diagnostic images showed that residual false lumen of proximal descending aorta were thrombosed. Now it is not necessary to perform next extensive aortic replacement. Complication which is threatened in using Elephant trunk prosthesis, paraplegia, thromboembolism, kinking of prosthesis could have been avoided by setting suitable length and diameter of the prosthesis.

Aortic Dissection↗
PubMed1996

Difference in signal transduction for IL-10 and IFN-gamma production in a CD8+ T cell clone.

CD8+ T cell clones produced both interleukin 10 (IL-10) and interferon-gamma (IFN-gamma) when these cells were stimulated with a T-cell-specific mitogen, concanavalin A (Con A). One of these CD8+ T cell clones, 13G2, secreted IFN-gamma at similar levels with calcium ionophore, A23187, as well as by Con A, but IL-10 production by A23187 was less than by Con A. On the other hand, N6,O2-dibutyryl cAMP enhanced the production of IL-10 but not IFN-gamma when the low doses of Con A or A23187 coexisted. In a T cell clone, the production of these two cytokines required different signal transductions. These results indicate that a T cell clone can produce diverse cytokines depending on the surrounding condition.

Animals↗
PubMed1995

CD8+ T cells specific to the exogenous antigen. Mode of antigen recognition and possible implication in immunosuppression.

This study demonstrates and characterizes CD8+ T cells specific to the exogenous Ag, bovine alpha s1-casein. Purified CD8+ T cells from alpha s1-casein-primed lymph node cells proliferated well in response to an alpha s1-casein derivative, trypsin-digested alpha s1-casein. CD8+ T cell repertoire for the exogenous Ag was directly demonstrated in the primary culture condition. The intact alpha s1-casein primed the responding CD8+ T cells in vivo more efficiently than the tryptic alpha s1-casein; however, the in vitro proliferative response by the intact alpha s1-casein was weaker than that of the tryptic alpha s1-casein. CD8+ T cells recognized the exogenous Ag in association with MHC class I molecules as revealed by an Ab-blocking study. The major immunodominant region for the CD8+ T cells was mapped to region 136-151 of alpha s1-casein, and peptide 136-151 primed the responding CD8+ T cells but not any CD4+ T cells. Peptide 136-151 is the CD8+ T cell-specific determinant. Upon antigenic stimulation, the exogenous Ag-specific CD8+ T cells produced a significant level of IFN-gamma, which has immune suppressive activity for IgE synthesis. Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression.

Age Factors↗