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T Uede

Publications and source records attributed to T Uede.

At least 73 records · Page 4Linked to original sources
PubMed1997

Selective antigen presenting activity of cortical thymic epithelial cells against CD4+ T cells associated with both lack of costimulatory molecules and inefficient presentation of MHC-peptide ligands.

Selective activation among several effector functions of a T cell clone, DB14, specific for pigeon cytochrome c 43-58 (p43-58) and restricted to I-Ab/d was induced by antigen (Ag) presentation with nonprofessional Ag-presenting cells (APC), cortical thymic epithelial cells (c-TEC) (B7-1- CD40-), whereas full activation of the DB14 was induced with another nonprofessional APC, I-Ab L cell (B7-1+ CD40+). In the present study, to elucidate the mechanism underlying the selective activation of DB14 cells by c-TEC, we established c-TEC transfected with human CD40 alone (huCD40-c-TEC) or both human CD40 and murine B7-1 (huCD40/mB7-1-c-TEC), and compared the APC functions with those of the original c-TEC and I-Ab L cell. IFN-gamma production but not the proliferative response of DB14 was elevated by Ag presentation with huCD40-c-TEC as compared with unmanipulated c-TEC. On the other hand, upon stimulation with Ag plus huCD40/mB7-1-c-TEC both a significant proliferative response and IFN-gamma production were induced in DB14. However, the level of these responses did not reach that induced in the presence of I-Ab L cell. A similar pattern of APC functions was demonstrated with the other B7-independent T cell clone, PAB3, or T cell hybridomas (DBhy22 and BD7-5) which are basically independent of costimulation for the activation. The present finding along with our previous report that several structural differences of I-Ab molecules are present between c-TEC and I-Ab L cell suggests that the distinct APC activity of c-TEC is attributable not only to a lack of B7-1 and CD40 but also to inefficient presentation of MHC-peptide complex on the c-TEC.

Animals↗
PubMed1997

B7-1-transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rats bearing highly metastatic osteosarcoma cells.

To investigate the therapeutic efficacy of B7-1-expressing tumor vaccine on metastatic osteosarcoma, we introduced mouse B7-1 cDNA into a rat osteosarcoma cell line, MSK-8G. Flow cytometric analysis confirmed that the transfectants designated as B7-1-8G 10-1 and B7-1-8G 15-5 stably expressed B7-1 molecules on the cell surface. B7-1 transfectants were not only rejected by immunocompetent F344 rats but also conferred systemic immunity that protected against challenge with B7-negative parental osteosarcoma cells. In contrast, T-cell-deficient nude rats failed to reject B7-1 transfectants, indicating that T cells play a major role in the development of systemic immunity. We then conducted experimental therapies using irradiated B7-1-transfected tumor vaccine and methotrexate in an orthotopic implantation model. B7-1-transfected tumor vaccine significantly reduced the number of pulmonary metastatic nodules. Moreover, the combination of methotrexate and tumor vaccine further decreased the number of pulmonary metastatic nodules. Most important, the combined therapy with methotrexate and tumor vaccine resulted in a tumor-free condition as judged by the histopathological absence of tumors and survival of rats for more than 180 days. Furthermore, B7-1-transfected tumor vaccine could counteract the immunosuppressive effect of methotrexate. These findings strongly suggest that the B7-1-transfected tumor vaccine may be of clinical value for patients with metastatic osteosarcoma who exhibit immunosuppression due to chemotherapy.

Animals↗
PubMed1997

Involvement of a common 10-amino-acid segment in the cytoplasmic region of CD40 but different MAP kinases in different CD40-mediated responses.

CD40-mediated signals can induce cell aggregation, proliferation and rescue from apoptosis in WEHI231. To define which segment of cytoplasmic domain of CD40 and how signals are involved in those events, we generated mutant CD40 transfectants. We demonstrated the same 10 amino acid segment that could bind to tumor necrosis factor receptor associated factor-2 and -3 mediated all those responses. However, activation pattern of mitogen activated protein kinases was different. Immunoglobulin M-mediated apoptosis was inhibited by CD40-mediated signal that activated c-Jun aminoterminal kinase synergistically. While, CD40 stimulus through the 10 amino acid segment alone that induced cell aggregation and proliferation resulted in activation of extracellular signal-regulated protein kinase 2.

Amino Acid Sequence↗
PubMed1997

Costimulatory effect of IL-12 on the activation of naive, memory CD4+ T cells, and Th1 clone.

In the present experiments, costimulatory effects of interleukin 12 (IL-12) and B7-2 on interleukin 2 receptor alpha chain (IL-2R alpha) expression and IL-2-dependent proliferation of naive and memory CD4+ T cells were studied in comparison with the effect of these molecules on Th1 clones. The naive and memory T cells were negatively sorted on the basis of the expression of CD44 and CD45RB, respectively, to diminish the effect of these antibodies on the activation of these cells. When these three T cell populations were stimulated with allogeneic B cells, the addition of IL-12 elicited IL-2R alpha expression and proliferation of all these T cell populations. With anti-B7-2 being included in culture, these responses of naive T cells were abrogated, whereas those of memory T cells and Th1 clones were affected only marginally. When they were stimulated with immobilized anti-CD3, the inclusion of either IL-12 or Chinese hamster ovary cells expressing B7-2 (B7-2CHO) induced IL-2R alpha expression and enhanced IL-2-dependent proliferation of memory T cells, whereas these responses of naive T cells were induced by the inclusion of B7-2CHO and enhanced by the addition of IL-12, although the addition of IL-12 alone did not affect the responses. The responses of Th1 clones were markedly enhanced by IL-12, but not by B7-2CHO, and the enhancement of the proliferation was augmented further by the addition of both IL-12 and B7-2CHO. In IFN-gamma production B7-2 costimulation was required for the enhancing effect of IL-12 on the responses of naive T cells. IL-2 production of all T cell populations was not affected by IL-12 even in the presence of B7-2CHO. These results indicate that IL-12 provides the costimulation for IL-2R alpha expression and IL-2-dependent proliferation of memory T cells and Th1 clones stimulated with TCR ligation, whereas naive T cells require B7-2 costimulation for their response to IL-12. Possible mechanisms of B7-2 costimulation in the response of T cells to IL-12 is discussed.

Animals↗
PubMed1997

Limb allografts in rats treated with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

This study examined whether administration of anti-ICAM-1 mAb (monoclonal antibody) and anti-LFA-1 mAb were effective for inhibition of the acute rejection reaction in a rat-limb allograft model. The grafts were carried out using major histocompatibility complex mismatch pairs of rats: ACI rats as the donors and Lewis rats as the recipients. The subjects were of species with completely different major histocompatibility complexes. The average length of survival in this combination was 4.7 +/- 0.6 days. When anti-ICAM-1, anti-LFA-1 mAb, or a combination of both were administered intraperitoneally at 1 mg/kg body weight daily for 7 days after the graft, the mean survival times were 4.3 +/- 0.6, 4.7 +/- 0.6, or 4.7 +/- 0.6 days, respectively. The agents were found to exercise no beneficial effects for transplants. Transplants were then carried out with a single intramuscular administration of FK506 at 3mg/kg body weight on the day of the operation to observe the effect of this adjunct therapy. The mean survival time averaged 16.0 +/- 5.5 days with FK506 alone. Administration of anti-ICAM-1, anti-LFA-1, and both antibodies together with FK506 resulted in mean survival times of 15.4 +/- 3.0, 25.0 +/- 5.8 and 13.2 +/- 5.8 days, respectively. Thus, a significant prolongation of survival time was observed when the combination of anti-LFA-1 mAb and FK506 was used. In contrast, anti-ICAM-1 mAb and FK506 or both mAb and FK506 showed no beneficial effects.

Animals↗
PubMed1997

Thoracic dumbbell-shaped neurinoma treated by unilateral hemilaminectomy with partial costotransversectomy--case report.

A 56-year-old male was admitted in January 1994, with back pain persisting for 2 months. Magnetic resonance imaging disclosed a homogeneously enhanced mass occupying the spinal canal at the T-8 level and extending into the retropleural space through the left intervertebral foramen between T-8 and T-9. The diagnosis was a thoracic dumbbell-shaped neurinoma. The tumor was successfully removed through a posterolateral approach using hemilaminectomy and partial costotransversectomy with preservation of ipsilateral joint facets. Histological examination indicated neurinoma. This approach allows excellent visualization of anterior paraspinal components of the tumor, preserves important anatomic structures, and requires minimal compression of the cord for removal of the lesion.

Humans↗
PubMed1997

[Factors influencing the long-term function of the facial nerve following removal of acoustic neurinomas].

Thirty-five cases with removal of acoustic neurinomas were reviewed to demonstrate the factors which influenced the postoperative long term function of the facial nerve. All cases were operated on via a suboccipital route. The group consisted of 7 cases with the tumor confined to the internal auditory meatus, 4 cases with a neurinoma of 20 mm or less in diameter, 13 cases with a neurinoma of 30 mm or less, and 11 cases with a neurinoma over 30 mm. The consistency of the tumors was solid in 27 cases, and cystic in 8 cases. Dislocation of the facial nerve was observed during the operation except in 7 intrameatal cases. The dislocation is summarized as follows: dislocated in the cranial direction in 2 cases, ventrocranial in 7, ventral in 5, ventrocaudal in 10, dorsocaudal in one, and caudal in 3 cases. No case showed dislocation of the facial nerve in the dorsocranial or dorsal direction. Careful observation of the facial nerve at the entrance of the internal auditory meatus showed a severe kinking in 2 cases, moderate kinking in 2, but no kinking at all in the remaining 31 cases. The facial nerve was preserved anatomically in all cases. Long term function of the facial nerve can be summarized as excellent in 18 cases, good in 8 cases, and poor in 9 cases. Three cases showed an almost complete paresis of the facial nerve immediately after the operation and recovery was never observed. Neurinoma facial score was defined in 28 cases, except intrameatal cases, according to the degree of preoperative facial nerve function, tumor size, presence of the cystic component within the tumor, direction of the facial nerve dislocation, and the presence of kinking of the facial nerve. The correlation between the long-term facial nerve function and the neurinoma facial score was statistically examined and was found to be significant (Sperman's correlation coefficient by ranks; rs = 0.38596 > 0.375; P = 0.05). In conclusion, neurinoma cases that show the least facial nerve function are: cases in which facial function had deteriorated, cases in which the tumor was large or when the tumor had no cyst, when dislocation of the facial nerve was in the cranial direction, and in cases where there was kinking of the facial nerve at the internal auditory meatus. In such cases, the removal should be carried out intracapsularly so as to preserve facial nerve bundle which may spread and become flattened like a tumor capsule. This might minimize the postoperative deterioration of the facial nerve function.

Adult↗
PubMed1997

[Direct surgical management of giant and large intracerebral aneurysms, associated with intraluminal thrombus and/or atherosclerotic thickening of aneurysmal neck].

Direct surgical management of giant or large cerebral aneurysms remains one of the most challenging topics in the neurosurgical field. Surgical results have remained unsatisfactory. We review 22 cases of large or giant aneurysms with intraluminal thrombus and/or atherosclerotic thickening of the aneurysmal neck that have received direct surgical management in our department during the period from 1984 to 1996. As initial symptoms, ten patients presented with mass effect, five with ischemic attack, and three with subarachnoid hemorrhage. Sixteen aneurysms were supratentorial and six were in the posterior fossa. Direct neck clipping was attempted in sixteen cases. Two giant basilar aneurysms among them were clipped under deep hypothermia with cardiac arrest. Simple trapping of the parent artery was performed in three aneurysms and trapping with bypass graft was also carried out in three aneurysms. Ten patients made an excellent clinical recovery. Eleven patients suffered mild to severe disability. One death resulted from brain stem infarction, not directly related with surgical management. Appropriate preoperative assessment and intraoperative management of the associated thrombus and atherosclerotic change of the aneurysmal neck are essential for obtaining acceptable surgical results of large or giant cerebral aneurysms.

Adult↗
PubMed1996

Identification and characterization of an alternative cytotoxic T lymphocyte-associated protein 4 binding molecule on B cells.

To determine whether alternative cytotoxic T lymphocyte-associated protein 4 (CTLA4) binding proteins exist on B cells, we constructed (i) mCTLA4hIgG consisting of the extracellular region of a mouse CTLA4 molecule and the Fc portion of a human IgG1 molecule and (ii) PYAAhIgG, a mutant mCTLA4hIgG, having two amino acid substitutions on the conserved MYPPPY motif in the complementarity-determining region 3-like region and lacking detectable binding to both B7-1 and B7-2 molecules. Using these fusion proteins (mCTLA4hIgG and PYAAhIgG), we demonstrated that a mouse immature B-cell line, WEHI231 cells, expressed alternative CTLA4 binding molecules (ACBMs) that were distinct from both B7-1 and B7-2. ACBMs were 130-kDa disulfide-linked proteins. More importantly, ACBMs were able to provide costimulatory signal for T-cell proliferation in the presence of anti-CD3 monoclonal antibodies. In addition, we demonstrated that more than 20% of B220+ cells obtained from normal mouse spleen expressed ACBMs.

Amino Acid Sequence↗
PubMed1996

The role of the B7-1a molecule, an alternatively spliced form of murine B7-1 (CD80), on T cell activation.

B7 molecules (CD80 (B7-1) and CD86 (B7-2/B70)) on APCs provide costimulatory signals for T cell proliferation. We previously described the presence of an alternatively spliced form of murine CD80 (previously termed MB7-2 and renamed as B7-1a) that completely lacks the second Ig-like domain coded by exon 3 in activated murine B cells. in this study, we first examined whether B7-1a mRNA can be detected in vivo by RNase protection assay. The expression of B7-1a mRNA was only detected in lymphoid organs although the level of expression was lesser than that of CD80 mRNA. However, we demonstrated that the expression of B7-1a mRNA like CD80 mRNA was considerably augmented in spleen cells treated with either LPS in vitro or OVA/CFA conjugate in vivo. We next determined the functional activity of B7-1a using Chinese hamster ovary (CHO) cells transfected by B7 genes. When resting T cells were cocultured with CHO cells expressing B7-1a molecules in the presence of PMA/ionomycin, T cell proliferation was not detected, while CHO cells either expressing CD80 or CD86 could promote the proliferation of resting T cells. in contrast to resting T cells, CHO cells expressing B7-1a could support the proliferation of activated T cells. Thus, costimulatory activity of B7-1a molecules was dependent upon the activation stage of T cells. Therefore the IgV-like region of CD80 contains a critical region for functional interaction with its ligands and can transduce a costimulatory signal for T cell proliferation.

Alternative Splicing↗
PubMed1996

Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice.

The present study demonstrates that the transfection of B7-1 or its variant MB7-2 genes into MHC class I+ tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice. However, i.v. injection of the transfectants into T cell-deficient nude mice did not affect reduction of lung tumor colonies as compared with parental wild-type tumors, suggesting that such an inhibitory effect was closely associated with T cell-mediated responses. The reduced metastasis of B7+ tumor cells consequently led to the significant prolongation of survival. Expression of B7 on tumor cells did not influence the tumorigenicity in vivo and tumor cell invasion into basement membrane Matrigel in vitro. We also found that immunization of X-irradiated B7 transfectants was effective as a tumor vaccine for preventing lung metastasis caused by i.v. injection of B7- parental B16-BL6 cells but not against other syngeneic 3LL tumors. Thus, the B7-mediated anti-metastatic effect was tumor-specific. Vaccinations of irradiated B7+ tumor cells before and after surgical excision of the s.c. inoculated primary B7- tumors on day 21 achieved effectively the prevention of spontaneous lung metastasis. Our report that vaccination of irradiated B7+ tumor cells led to a therapeutic effect in an established tumor metastasis model clearly expands and confirms previous related observations.

Animals↗
PubMed1996

Non-RGD domains of osteopontin promote cell adhesion without involving alpha v integrins.

Osteopontin (OPN) is an integrin-binding secreted protein that contains an Arg-Gly-Asp (RGD) amino acid sequence and binds to various cell types via RGD-mediated interaction with the alpha v beta 3 integrin. We have identified a cell line whose binding to OPN does not require RGD or alpha v interactions. We compared the ability of two murine cell lines, L929 fibroblastic cells and B16-BL6 melanoma cells, to interact with OPN (from human milk, and recombinant human and mouse OPN) as well as recombinant OPN prepared to include either the N-terminal or C-terminal halves but lacking the RGD sequence. Both cell lines adhered to GRGDS peptides coupled to BSA, and these interactions were inhibited by addition of GRGDS (but not GRGES) peptides or a monoclonal antibody specific to the alpha v integrin subunit. Adhesion of L929 cells to OPN was also dependent on the RGD sequence and the alpha v integrin subunit. However, the binding of B16-BL6 cells was not inhibited by either GRGDS peptides or the anti-alpha v antibody. B16-BL6 (but not L929) cells were also able to adhere to and spread on both N-terminal and C-terminal OPN proteins that lack the RGD sequence, and these interactions were not inhibited by either GRGDS peptides or anti-alpha v antibody. Together these results indicate that B16-BL6 cells can adhere to OPN by interactions that are independent of either the RGD sequence or the alpha v integrin subunit, and suggest that some cells can interact with additional, non-RGD binding sites in OPN.

Amino Acid Sequence↗
PubMed1996

Application of interleukin 12 to antitumor cytokine and gene therapy.

In vivo administration of interleukin 12 (IL-12) at 2000 U/mouse induced IL-12-activated killer (IL-12AK) cells in parallel with an elevation in serum interferon-gamma (IFN-gamma) activity. Although NK1.1+CD3- natural killer cells are the major precursor of IL-12AK cells, asialoGM1+CD8+ T-cells were also demonstrated to be novel precursors. Such anomalous killer cells may play an important role in the early stages of the host defense mechanisms against tumors. It was also shown that IL-12 is effective in inducing tumor-specific cytotoxic T-lymphocytes. Consistent with these data, IL-12 had marked activity against various kinds of established tumors when given systemically. Mice cured of tumors by IL-12 treatment acquired tumor-specific T-cell immunity. Moreover, we initially demonstrated that IL-12 was effective in preventing and inhibiting the growth of primary tumors induced by the chemical carcinogen methylnitrosourea using c-Ha-ras transgeneic mice. Finally, we investigated the application of IL-12 to antitumor gene therapy. Transfer of the IL-12 gene into A20 B-lymphoma cells resulted in the continuous production of IL-12 and caused abrogation of in vivo tumorigenicity. Tumor cells transfected with the IL-12 gene are potentially a good tool as a tumor vaccine, as they effectively induced IL-12AK cells, IFN-gamma production, and tumor-specific protective immunity. Although B16-BL-6 melanoma cells, which are a highly metastatic subclone of B16 melanoma cells, showed resistance to IL-12 gene therapy, combination therapy with the B7-1 gene and systemic IL-12 administration almost completely inhibited tumor metastasis. Similar results were obtained using B16-BL-6 melanoma cells transfected with both B7-1 and IL-12 genes. These results suggest that IL-12 is a promising cytokine for antitumor cytokine and gene therapy.

Animals↗
PubMed1996

Pathogenesis of hyponatremia following subarachnoid hemorrhage due to ruptured cerebral aneurysm.

BACKGROUND: Hyponatremia following subarachnoid hemorrhage (SAH) occurs due to the inappropriate secretion of antidiuretic hormone (SIADH). However, this condition is also sometimes associated with certain dehydration states. METHODS: To clarify the pathogenesis, daily values of urine volume, water balance, and sodium balance (Na Bal) were correlated with plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), and plasma renin activity (PRA) in 31 cases of SAH. RESULTS: Na Bal was markedly negative on days 2 and 3. Cumulative Na Bal showed continuous negative values until day 10 following SAH. ANP values showed a consistent elevation, while ADH showed only an initial surge. PRA, as the gross indicator of circulatory volume, showed a lack of suppression, indicating no increase in the circulatory volume. CONCLUSION: Hyponatremia following SAH therefore appears to be the result of increased natriuresis, due to the inappropriate elevation of ANP rather than SIADH. In this situation, water restriction should not be recommended, since the circulatory volume is decreased.

Adult↗
PubMed1996

CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimulate the proliferation of B6 anti-bm12 CD4+ T cells. While stimulation in vitro to B6 splenic T cells with bm12 antigen-presenting cells (APC) induced IL-2 mRNA expression and IL-2 production, T cells stimulated with bm12 B cells expressed much less IL-2 mRNA and secreted very low but detectable levels of IL-2. Moreover, the T cells stimulated with the bm12 B cells did not proliferate and this was not corrected by the addition of rIL-2 responsiveness. Further, whereas IL-2 receptor (IL-2R) alpha chain expression was significantly induced on B6 T cells stimulated with bm12 APC; stimulation with bm12 B cells did not induce IL-2R expression over background levels. However, virgin T cells stimulated with both bm12 B cells and anti-CD28 mAb proliferated and displayed a dramatic increase in IL-2 production as well as IL-2R expression to levels commensurate with those resulting from bm12 B cells plus anti-CD28 mAb even in the presence of sufficient amounts of anti-IL-2 mAb for neutralizing produced IL-2; while levels of IL-2R were significantly lower compared to those induced in the absence of anti-IL-2 mAb, increased frequencies of IL-2R+ cells were comparable. Conversely, IL-2R was not induced by bm12 B cell stimulation in the presence of IL-2. Moreover, IL-2R expression and proliferation induced by stimulation with bm12 APC was inhibited by CTLA-4-Ig, a soluble recombinant fusion protein capable of blocking the CD28 co-stimulatory signals not only stimulate IL-2 production but also induce IL-2R expression by an IL-2-independent mechanism.

Abatacept↗