PubMed Health⌕ Search

Biomedical subjects

A Ochi

Publications and source records attributed to A Ochi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Activation of p21-CDC42/Rac-activated kinases by CD28 signaling: p21-activated kinase (PAK) and MEK kinase 1 (MEKK1) may mediate the interplay between CD3 and CD28 signals.

CD28, a T cell costimulatory receptor, provides a signal that induces both optimal proliferation and the production of IL-2 by TCR-activated T cells. We show that the stimulation of CD28 leads to the activation of p21-activated kinase and MEK kinase 1. The same pathway was also stimulated in T cells treated with the cell-permeable ceramide analogue, C2-ceramide. The combined stimulation of either CD3 and CD28 or CD3 concurrently with C2-ceramide largely enhanced the activity of p21-activated kinase and MEK kinase 1. Therefore the Rac1/CDC42-coupled pathway(s) is a candidate that transduces and facilitates cross-talk between the CD28 costimulatory signal and the TCR signal.

CD28 Antigens↗
PubMed1998

Stimulation of CD28 with B7-2 promotes focal adhesion-like cell contacts where Rho family small G proteins accumulate in T cells.

Unless a costimulatory signal is provided, TCR recognition of Ag bound to the MHC is insufficient to induce optimal T cell proliferation or the production of IL-2. Here we show that the stimulation of CD28, a T cell costimulatory receptor, by a specific Ab increases F-actin contents in T cells. The interaction between T cells and B7-2-transfected Chinese hamster ovary cells expressing the CD28 ligand leads to the rearrangement of the actin cytoskelton in the region of cell-cell contact. Within the Rho family of G proteins, Rac1, but not Rho, translocates to the sites of cell-cell contact where Tailin also accumulates. These results indicate that the interaction between B7-2 and CD28 establishes a focal adhesion-like cell contact between T cell and APCs. The results also suggest that CD28 signaling is primarily transduced by a cytoskeletal rearrangement/signaling pathway mediated by the Rho family G proteins.

Actin Cytoskeleton↗
PubMed1998

Inhibition of B-cell receptor-antigen complex internalization by FcgammaRIIB1 signals.

Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides loaded in class II MHC. Due to the specific nature of the BCR, the cognate interaction between T-cells expressing Ag-specific T-cell receptor and these Ag-presenting B-cells occur in a highly regulated and precise manner. Accordingly, efficient control of T-cell activation may be achieved through regulation of Ag presenting B-cells. A potent form of regulation of lymphocyte responses is mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent mechanisms. In this communication, the authors present data that an anti-idiotype (anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells. Inhibition by anti-Id Ab was dependent upon the presence of FcgammaRIIB1 on B-cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate Ca2+ responses in Ag-specific T-cells. The results suggest that co-crosslinking of FcgammaRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag-specific T-cell activation.

Animals↗
PubMed1998

Comparison of distortion product otoacoustic emissions with auditory brain-stem response for clinical use in neonatal intensive care unit.

OBJECTIVES: This study compares the clinical usefulness of distortion product otoacoustic emissions (DPOAEs) with the auditory brain-stem response (ABR) for neonates in the neonatal intensive care unit for the evaluation of hearing impairment. METHODS: Both DPOAEs and ABR were performed on 36 neonates (67 ears) on the same day. We defined neonates as having normal hearing when the thresholds of wave V of ABR were < or =45 dB hearing level. RESULTS: (1) We could not obtain DPOAEs at f2 = 977 Hz in neonates with normal hearing because of high noise floors. DPOAE recording time was 36 min shorter than that of ABR. (2) We defined as normal DPOAEs, the number of frequencies which showed the DPgram-noise floor > or =4 dB was > or =4 at 6 f2 frequencies, from 1416 Hz to 7959 Hz. (3) Normal thresholds of ABR and normal DPOAEs showed the same percentages, i.e. 68.7%, but the percentage of different results between ABR and DPOAEs was 6.0%. CONCLUSIONS: Our study indicates that DPOAEs represent a simple procedure, which can be easily performed in the NICU to obtain reliable results in high-risk neonates. Results obtained by DPOAEs were comparable to those obtained by the more complex procedure of ABR.

Acoustic Stimulation↗
PubMed1998

Infantile spasms associated with a histamine H1 antagonist.

Some anti-allergic agents act as histamine H1 antagonists and induce seizure discharges in epileptic patients. Of these agents, ketotifen has an especially potent effect. We have experienced 2 cases of 4-month-old boys who developed infantile spasms 8 to 10 days after ketotifen administration. They showed almost the same clinical course with regard to their age, the interval between ketotifen administration and the onset of seizures, their symptoms and EEG abnormalities. These cases suggest that the administration of ketotifen to young infants may be hazardous with regard to inducing infantile spasms.

Electroencephalography↗
PubMed1997

Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice.

Nonobese diabetic (NOD) mouse thymocytes are hyporesponsive to T cell antigen receptor (TCR)-mediated stimulation of proliferation, and this T cell hyporesponsiveness may be causal to the onset of autoimmune diabetes in NOD mice. We previously showed that TCR-induced NOD T cell hyporesponsiveness is associated with a block in Ras activation and defective signaling along the PKC/Ras/MAPK pathway. Here, we report that several sequential changes in TCR-proximal signaling events may mediate this block in Ras activation. We demonstrate that NOD T cell hyporesponsiveness is associated with the (a) enhanced TCR-beta-associated Fyn kinase activity and the differential activation of the Fyn-TCR-zeta-Cbl pathway, which may account for the impaired recruitment of ZAP70 to membrane-bound TCR-zeta; (b) relative inability of the murine son of sevenless (mSOS) Ras GDP releasing factor activity to translocate from the cytoplasm to the plasma membrane; and (c) exclusion of mSOS and PLC-gamma1 from the TCR-zeta-associated Grb2/pp36-38/ZAP70 signaling complex. Our data suggest that altered tyrosine phosphorylation and targeting of the Grb2/pp36-38/ZAP70 complex to the plasma membrane and cytoskeleton and the deficient association of mSOS with this Grb2-containing complex may block the downstream activation of Ras and Ras-mediated amplification of TCR/CD3-mediated signals in hyporesponsive NOD T cells. These findings implicate mSOS as an important mediator of downregulation of Ras signaling in hyporesponsive NOD T cells.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Defective TCR-mediated signaling in anergic T cells.

Extrathymic T cell tolerance to Ags can be achieved through clonal deletion by activation-induced programmed cell death as well as by functional unresponsiveness (anergy) of Ag reactive-T cells. Previous studies demonstrated that in vivo administration of staphylococcal enterotoxin B (SEB) induces SEB-specific T cell anergy. To investigate the molecular mechanisms of T cell anergy, we analyzed the TCR-mediated signal transduction in normal and anergic T cells. Anergic T cells exhibited impaired protein tyrosine phosphorylation on TCR-mediated stimulation. The altered tyrosine phosphorylation in anergic T cells may be caused by a defect in tyrosine phosphorylation of TCR zeta-chain and its subsequent association with ZAP-70 tyrosine kinase. Our data demonstrated that TCR zeta-chain phosphorylation and its sequential interaction with ZAP-70 are essential for the initiation of TCR-mediated signal transduction.

Animals↗
PubMed1995

Sphingomyelin-ceramide turnover in CD28 costimulatory signaling.

When the CD28 membrane glycoprotein of T cells binds to its ligand, a signal is transmitted that is required for T cell receptor-induced proliferation and cytokine secretion: T cells are not stimulated by the CD28 signal alone. Ligation of CD28 initiated sphingomyelin hydrolysis and generated ceramide. Treatment of T cells with either exogenous sphingomyelinase or a cell-permeable ceramide analogue. C6-ceramide, mimicked the CD28 signal by inducing T cell proliferation and interleukin-2 gene transcription. Stabilization of interleukin-2 mRNA was also observed in C6-ceramide-treated cells. Thus, the sphingomyelin-ceramide pathway is a candidate for mediating the costimulatory signal.

Animals↗
PubMed1994

Induction of clonal anergy by oral administration of staphylococcal enterotoxin B.

The staphylococcal enterotoxin is a major cause of food poisoning. The bacterial substance stimulates T cells expressing specific V beta T cell receptors (TcR) and is termed "the superantigen". We have previously demonstrated that intravenous injection of staphylococcal enterotoxin B (SEB) induces functional unresponsiveness (anergy) of reactive T cells as well as a partial deletion by activation-induced programmed cell death. In the present study, we examined the effect of oral administration of SEB in mice. Our results indicate that spleen T cells from SEB-primed mice are hyporesponsive to SEB stimulation in vitro, but the response to SEA was normal. V beta 8+ T cells purified from SEB-primed mice did not respond to stimulation of TcR. This SEB-specific unresponsiveness could not be reversed by exogenous interleukin-2, but was partially reversed by phorbol 12-myristate 13-acetate. Activation of mitogen-activated protein kinase during TcR-mediated stimulation was significantly inhibited in anergic T cells. Although the mechanisms of oral tolerance are not well understood, these results show that oral administration of SEB induce clonal anergy in peripheral T cells.

Administration, Oral↗
PubMed1994

Degradation of tri-n-butyltin in Ise Bay sediment.

The vertical distribution patterns of the transformation products of tri-n-butyltin (TBT) in sediment cores collected from 6 sites in Ise Bay, Japan indicated that TBT was transformed by two pathways: methylation and debutylation. Anaerobic incubation of sediment spiked with TBT showed that the methylation was mainly supported by sulfate reducing activity and debutylation was mainly supported by nitrate reducing activity. These results showed that contribution of the two transformation reactions of TBT varied according to the dominant microbial activities in the sediment. The two types of vertical distribution of butyltins observed in the sediment cores appear to be the result of different dominant microbial activity in the sediment.

Alkylation↗
PubMed1994

Variations in concentrations of bacterial metabolites, enzyme activities, moisture, pH and bacterial composition between and within individuals in faeces of seven healthy adults.

Variations between and within individuals, and correlations between concentrations of bacterial metabolites, including putrefactive products, ammonia and short chain fatty acids (SCFAs), enzyme activities, moisture and pH, as well as bacterial composition, were studied in faecal samples from seven healthy adults over a period of 7 months. Large variations, both between and within individuals, were observed in concentrations of putrefactive products. Although values for ammonia, SCFAs, enzyme activities, moisture and pH were generally variable, significant person-to-person differences were observed. While ranges of log viable counts of the predominant bacteria such as eubacteria, bifidobacteria and bacteroides in each subject remained between 0.2 and 1.3, those of enterobacteria, streptococci (including enterococci) and lecithinase-negative clostridia varied between 0.4 and 3.0. Levels of bifidobacteria, enterobacteria, streptococci and total aerobic bacteria showed inter-individual variations. Correlations were found among certain of the parameters: moisture correlated negatively with p-cresol (r = -0.707), pH (r = -0.671) and beta-glucosidase activity (GS) (r = -0.608), and positively with acetic acid (r = 0.621), while negative correlations were observed in pH with acetic and butyric acids (r = -0.690 and -0.623, respectively). No significant correlations were found between bacterial compositions, and other faecal factors such as pH, moisture, metabolic enzyme activities and concentrations of putrefactive products.

Adult↗
PubMed1993

Gamma delta T cells differentiate into a functional but nonproliferative state during a normal immune response.

To obtain a homogeneous population of gamma delta T cells to investigate their role in an immune response, we have made a scid mouse doubly transgenic for rearranged gamma and delta genes. The receptor (KN6) encoded by these genes is specific for the major histocompatibility complex class I protein encoded by the T22b gene. This mouse contains high levels of transgenic gamma delta T cells in the spleen and thymus and no other T lymphocytes. Immunization of these KN6-scid (H-2d, TLd) mice with 10(7) C57BL/6J (abbreviated B6) (H-2b, TLb) spleen cells resulted in proliferation and activation of the gamma delta T cells in spleen and clearing of the allogeneic B6 lymphocytes. Subsequently, the majority of activated cells died by apoptosis and the remaining cells were anergic with regard to proliferation. The anergic cells did not respond to restimulation by B6 spleen cells in vitro or in vivo, and addition of exogenous interleukin 2 failed to restore the response to B6 cells. Cytotoxicity, a property of KN6+ cells during a primary stimulation, was no longer detectable in the proliferatively anergic cells. However, B6 spleen cells injected into mice primed 12 days previously were cleared with a much greater efficiency than on primary challenge and in an antigen-specific manner. We conclude that after exposure to antigen, gamma delta T cells rapidly proliferate into blasts; the majority of the blasts rapidly die, with the nonproliferating cells remaining in a highly active state for several weeks and able to initiate elimination of lymphoid cells bearing the TLb epitope.

Animals↗
PubMed1993

In vivo tumor immunotherapy by a bacterial superantigen.

We have investigated the in vivo efficacy of Staphylococcus aureus enterotoxin B (SEB) coupled to tumor-specific anti-idiotypic antibody in redirecting T cell effector activity to the growth inhibition of B lymphoma 38C13. Incubation of 38C13 lymphoma cells with syngeneic C3H/He splenic cells and SEB-anti-Id conjugate was associated with between 80 and 100% growth inhibition of the tumor cells. V beta 8+ T cells were integral for the SEB-anti-Id-induced tumor cell growth inhibition. Administration of SEB-anti-Id i.v. to mice previously inoculated with 38C13 lymphoma cells led to greater than 40% survival at 100 days compared to a mean survival of 21 days in control animals. When we compared this reagent with other targeting constructs--the anti-CD3-anti-Id and anti-TCR V beta 8-anti-Id--these more or less effectively prevented tumor growth. However, anti-CD3-anti-Id impaired almost the entire T cell response, whereas the effects of SEB-anti-Id or anti-V beta 8-anti-Id had effects limited to V beta 8+ T cells. Previous studies showed that in vivo administration of SEB caused a small change in V beta 8+ T cell numbers in contrast to anti-V beta 8 antibody, which depleted the entire population. These results together suggest that SEB-anti-tumor antibody conjugates represent a potentially powerful approach for better tumor immunotherapy.

Animals↗
PubMed1993

The fate of anergic T cells in vivo.

The kinetics of Staphylococcal enterotoxin B-(SEB) induced peripheral tolerance has been investigated. Ten days after SEB injection, thymectomized BALB/cByJ mice showed suppressed spleen cell proliferative responses to SEB. After 2 mo the SEB-specific response was partly recovered. Four months later the response of spleen cells of SEB-primed mice was comparable to those of control mice. The proportion of CD4+, V beta 8+ T cells was diminished in the tolerized mice and was not restored even after the response was recovered. Purified CD4+, V beta 8+ T cells from SEB-primed mice after 4 mo responded similarly to SEB as control CD4+, V beta 8+ T cells. These expressed a similar profile of surface markers compared with that of unprimed control cells, except a homing receptor was slightly lower. An experiment that addressed the possibility that non-anergic T cells expand over time and are in fact responsible for the recovery of the proliferative response showed that such events unlikely occur in vivo. Therefore, the data indicate that T cell anergy is reversible in vivo. It is also suggested that the challenge with superantigen results in neither clonal expansion nor specific CD4+, V beta 8+ T cell memory.

Animals↗
PubMed1993

Not every superantigen induces tolerance in vivo.

We have distinguished TSST-1 from SEA and SEB with respect to its in vivo effect on T cells, that is, SEA and SEB induce tolerance in treated mice whereas injection of TSST-1 does not result in tolerance. Therefore, previous observations which relate superantigens to the suppression of reactive V beta TCR T cells seem difficult to generalize to all bacterial superantigens. Since the effects of superantigens are beginning to be exploited for immunotherapy, the differences between TSST-1 and SEB in terms of induction of tolerance suggest that all superantigens may not generally be useful in this respect. Each superantigen obviously should be studied in vivo in respect to T cell tolerance induction.

Animals↗
PubMed1993

T cell anergy is programmed early after exposure to bacterial superantigen in vivo.

We have investigated the effects of the protein synthesis inhibitor, cycloheximide (CHX), on the induction of post-thymic T cell tolerance in mice primed with the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB). A single injection of 1 mg CHX prevented protein synthesis in splenic cells for < 6 h in vivo. The concomitant administration of SEB and CHX prevented induction of SEB-specific anergy, but did not interfere with the deletion of SEB-specific V beta 8+ T cells by activation-induced, programmed cell death. When CHX was given > or = 24 h after SEB administration the expression of anergy was not affected. These findings suggest that anergy and deletion represent independent processes. Furthermore, these observations, together with the fact that SEB retains the potential to induce anergy in specific T cells 8 h after priming in vivo, imply that the determination of alternate fates (anergy or death) occurs at early time points after SEB injection.

Animals↗