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T Uede

Publications and source records attributed to T Uede.

At least 55 records · Page 3Linked to original sources
PubMed1999

Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.

Abatacept↗
PubMed1999

Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Successful treatment of cerebral aspergillosis with a high oral dose of itraconazole after excisional surgery.

We report a case of cerebral aspergillosis which originated from the sphenoid sinus, and involved a progressive decrease of visual acuity. The neurological signs indicated a cavernous sinus invasion. After extensive intracranial surgery we treated the residual aspergillosis with a high oral dose of itraconazole (800 mg/d for 4 months, followed by 400 mg/d for 5 months). The neurological impairments of the patient gradually subsided with the resolution of the fungal lesion shown on MRI. The successful therapy indicated that itraconazole has a significant role in the treatment of advanced cerebral aspergillosis if it is used in high doses (16 mg/kg/d for adults).

Administration, Oral↗
PubMed1999

Blockade of CD28/CTLA4-B7 pathway prevented autoantibody-related diseases but not lung disease in MRL/lpr mice.

We studied the role of CD28/CTLA4 costimulatory T-cell activation pathway on the pathogenesis of MRL/lpr mice. Administration of CTLA4IgG from day 0 significantly inhibited autoantibody production such as anti-double-stranded DNA antibody and rheumatoid factor. In addition, end-organ diseases in kidney, salivary gland, and liver were significantly improved. Improvement of pathologic findings coincided with a significant improvement in survival. At 350 days of age, 90% of mice treated with CTLA4IgG from day 0 were still alive, compared with none of mice treated with hIgG. As expected, activation of conventional T cells was significantly inhibited after CTLA4IgG treatment. However, lung disease that was characterized by perivascular accumulation and interstitial infiltration of lymphocytes and macrophages was not inhibited. Even after CTLA4IgG treatment from day 0, pathologic findings of lung disease were not improved. Additionally, the expression of activation markers such as B7-1, B7-2, CD71, ICAM1, and LFA1 on Mac1+ fraction in both spleen and lung and the concentration of TNFalpha in bronchoalveolar lavage fluid were not significantly suppressed. These results demonstrated that lung disease was independent of the CD28/CTLA4-B7 pathway. Thus, this study emphasizes the differential dependence of the CD28/CTLA4-B7 pathway in development of diseases in MRL/lpr mice.

Abatacept↗
PubMed1999

[Usefulness of galea suturing method for scalp closure].

A method for scalp closure to prevent alopecia along a suture line is described. Only the galea is sutured. By tacking a sufficient width of the galea on both sides with an absorbable suture material, the sutured wound forms a ridge. The outer layer is then closed with skin staples to keep the blood circulation undisturbed. This procedure contrasts with the traditional method in which the galea is sutured with the overlying subcutaneous tissue and consequently the hair follicles are strangled. By adopting the method of suturing the galea, development of alopecia along a suture line has been effectively prevented and scarring has become less conspicuous.

Alopecia↗
PubMed1998

Persistent and secondary adenovirus-mediated hepatic gene expression using adenovirus vector containing CTLA4IgG.

Adenovirus vectors can transfer recombinant genes efficiently into a wide variety of cells in vivo, but have serious limitations: gene expression is transient and secondary gene transfer is inefficient or impossible because of cellular and humoral immune responses against adenovirus-transduced cells. To solve these limitations, we have constructed an adenovirus vector, Adex1CACTLA4IgG, that expresses CTLA4IgG molecules. After in vivo administration of Adex1CACTLA4IgG (9.0 x 10(9) PFU), the peak level of serum CTLA4IgG was 29.8 mg/ml on day 4. The serum CTLA4IgG concentration gradually fell but was still 5.7 mg/ml on day 90. However, the serum concentration of CTLA4IgG was elevated after a second administration of Adex1CACTLA4IgG. The production of antibody against adenovirus was completely prevented after treatment with Adex1CACTLA4IgG. In addition, coadministration of Adex1CALacZ with Adex1CACTLA4IgG induced persistent hepatic expression of beta-Gal molecules, while administration of Adex1CALacZ alone induced transient expression of beta-Gal molecules. More importantly, on day 160 a secondary challenge with Adex1CALacZ was possible in mice treated with Adex1CALacZ plus Adex1CACTLA4IgG. Thus, we have demonstrated that (1) gene expression of a recombinant adenovirus, Adex1CACTLA4IgG, is persistent in liver and secondary administration of this adenovirus is possible, (2) coadministration of Adex1CACTLA4IgG virus with another adenovirus, AdexCALacZ, prolongs AdexCALacZ-mediated gene expression, and (3) Adex1CACTLA4IgG is useful for secondary challenge with Adex1CALacZ.

Abatacept↗
PubMed1998

Expression and co-stimulatory function of B7-2 on murine CD4+ T cells.

Co-stimulatory signals mediated by the interaction of B7-1/B7-2 with CD28 are important for the activation of CD4+ T cells stimulated with antigen on antigen-presenting cells. There are controversies about the expression and function of B7-1/B7-2 on CD4+ T cells. The aim of this study was to analyze the expression of B7-1/B7-2 on naive and memory CD4+ T cells and the co-stimulatory function in the activation of naive CD4+ T cells stimulated by TCR ligation. Present results indicate that memory CD4+ T cells express B7-2 molecules on their surface, whereas naive CD4+ T cells do not. Neither memory nor naive CD4+ T cells expressed B7-1 molecule on their surface, although B7-1 mRNA was faintly expressed in memory T cells. B7-2 molecules expressed on memory T cells co-stimulated CD4+ naive T cells stimulated with plate-coated anti-CD3 to produce IL-2. Naive CD4+ T cells were shown to express B7-2 after co-stimulation with B7-2 and TCR ligation, because the naive T cells stimulated with anti-CD3 and B7-2CHO expressed B7-2 on their surface, although it remained to be studied whether the co-stimulation with B7-2 directly induced B7-2 expression on naive T cells. Our present results indicate that memory CD4+ T cells play some role in the activation of naive CD4+ T cells through the co-stimulation with B7-2 molecules.

Animals↗
PubMed1998

Immunolocalization of extracellular matrix proteins and integrins in sarcoid lymph nodes.

To improve our understanding of the role of extracellular matrix (ECM) proteins and integrins during the processes of granuloma formation in sarcoidosis, we examined the distribution of ECM proteins and the expression of integrins in sarcoid lymph nodes by immunohistochemical methods. We also examined the expression of transforming growth factor-beta1 (TGF-beta1), which is one of major regulators for synthesis of ECM proteins. Most ECM proteins were detected in the periphery of the granulomas in a concentric pattern, and fibronectin was diffusely detected from an early to a regressive stage. Compared with normal lymph nodes, most beta1-integrin subfamilies (alpha1, alpha4, alpha5 and alpha6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the alpha5 molecule. Fibroblasts exhibited the expression of the alpha2 and alpha5 molecules surrounding ECM proteins. The alpha5beta1 molecule had a distribution similar to that of fibronectin. TGF-beta1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the alpha5beta1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-beta1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells.

Extracellular Matrix Proteins↗
PubMed1998

Intellectual functions and regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes in childhood moyamoya disease.

Most accepted operations for childhood moyamoya disease have attempted to increase cerebral blood flow (CBF) in the ischaemic cortical areas around the central fissure. Developed ischaemic brain damage in the prefrontal area may lead to poor intellectual outcome and restrict patients' daily lives. Thus, extensive cerebral revascularization in both the ischaemic anterior and middle cerebral artery territories is mandatory. We describe the long-term follow-up results for intellectual outcome and performance status and make an evaluation of regional cerebral haemodynamics after extensive omental transplantation spread over both frontal lobes performed as the initial management. In the past 10 years, 10 moyamoya patients less than 12 years of age consecutively underwent omental transplantation. The omental flap was spread over not only the symptomatic hemisphere but also the contralateral frontal lobe after a large craniotomy. Superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis was accomplished simultaneously. On the contralateral hemisphere, STA-MCA anastomosis combined with encephalomyosynangiosis was subsequently performed. The clinical observation period averaged 6.7 years (ranged 1.9 to 9.2 years). Apart from 2 patients in whom severe mental retardation had been disclosed pre-operatively, full-scale intelligence quotient scores have been maintained at over 90, that is, within the normal intellectual range. With respect to quality of life (QOL), these 8 patients have been leading normal daily lives since the operation. The focal decrease in CBF observed in the frontal lobe pre-operatively in 7 cases had disappeared after surgical treatment. In these patients, serial post-operative MR angiography revealed developed omental vessels and STAs. Deterioration of intellectual functions and QOL as well as cerebral ischaemic events in paediatric moyamoya patients can be prevented by extensive omental transplantation spread over both frontal lobes combined with STA-MCA anastomosis.

Cerebral Revascularization↗
PubMed1998

Vaccination with B7-1+ tumor and anti-adhesion therapy with RGD pseudo-peptide (FC-336) efficiently induce anti-metastatic effect.

We have previously shown that expression of costimulatory ligand B7-1 on MHC class I+ tumor cells (B16-BL6 melanoma) resulted in marked reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice and led to induction of immunity to the challenge by the parental B7-1 negative tumor. Here we investigated the effectiveness of irradiated B7-1 transfected tumor cells as a vaccine on established tumor metastasis and whether or not expression of B7-1 molecule on tumor cells in combination with administration of anti-adhesion peptide FC-336 can augment the antimetastatic efficacy. Immunization with X-irradiated B7-1 transfectants after i.v. injection of B7-1- parental B16-BL6 cells was effective in inhibiting lung metastasis. We also found that vaccination with irradiated B7-1 transfectants after excision of primary tumor on day 21 resulted in significant inhibition of spontaneous lung metastasis by intrafootpad injection of viable parental B16-BL6 melanoma, as compared with the untreated control. However, immunizing twice with mock transfectants did not affect inhibition of spontaneous lung metastasis of wild-type tumors. On the other hand, multiple administration of a pseudo-peptide of RGD sequence (FC-336) after tumor inoculation inhibited spontaneous lung metastasis through the interference of tumor invasion, migration and adhesion. Combined treatment of B7-1 transfected tumor vaccine and anti-adhesive therapy with FC-336 led to the augmentation of the antimetastatic effect in both experimental and spontaneous metastasis models, as compared with either treatment alone. B7-1- and FC-336-mediated inhibition of tumor metastasis may be mediated by different mechanisms at various steps of metastasis, based on the regulation (promotion or inhibition) of tumor interaction with host cells and components.

Animals↗
PubMed1998

Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.

Abatacept↗
PubMed1998

A novel monoclonal antibody against rodent common Thy-1.1 epitope.

Here we report a new anti-rat Thy-1 monoclonal antibody (MAb) 12C5 that recognized a novel epitope on a GPI-anchored Thy-1 antigen. In rat thymocytes, MAb 12C5 reacted with 25 kDa Thy-1 antigen purified with MAb OX7. In rats, MAb 12C5 was expressed on 94% of thymocytes, 46% of spleen cells, 31% of mesenteric lymphnode cells, 76% of bone marrow cells, and 24% of splenic T cells. Furthermore, MAb 12C5 reacted with the hematopoietic cells in Mongolian gerbils, hamsters, and AKR mice (Thy-1.1) as in rats. In AKR mice, almost all bone marrow cells reacted with MAb 12C5. Thus, MAb 12C5 recognized a novel epitope of Thy-1 that was widespread in hematopoietic cells of rats and mice, as well as other rodents.

Animals↗
PubMed1998

The mechanism by which proteolysis enhances the ligand-binding activity of guinea pig type II Fc receptor for IgG (FcgammaRIIB).

We have previously shown that the ligand-binding activity of type II Fc receptor for IgG (FcgammaRIIB) on guinea pig peripheral blood polymorphonuclear leukocytes is very low and dramatically increases after treatment of the cells with proteolytic enzymes. In the present study, we analyzed the mechanism of this augmentation. We found that the protease treatment failed to enhance the binding of monomeric IgG to FcgammaRIIB, increased the binding of small immune complexes (IC) prepared under antigen-excess conditions only modestly, but markedly enhanced the binding of large IC prepared under antibody-excess conditions. These results suggest that proteolysis increases the ligand-binding avidity but not the intrinsic affinity of FcgammaRIIB. Confocal laser scanning microscopy revealed that the mobility of FcgammaRIIB on the cell surface was increased after protease treatment. In addition, transfection experiments indicated that the effect of proteolysis on IC binding to CHO cells expressing guinea pig FcgammaRIIB was strongly dependent on the receptor density. Finally, we demonstrated that the transmembrane and cytoplasmic domains of FcgammaRIIB were not involved in the proteolysis-induced augmentation of IC binding. Together our results suggest that the mobility of FcgammaRIIB, which may be restricted due to the association of the ectodomain of the receptor with unknown membrane proteins, is enhanced by proteolysis, allowing the receptors to bind multivalent ligands more readily and hence with higher avidity.

Animals↗
PubMed1998

[Direct continuous observation of in situ thrombolysis in the cerebral embolic model of rabbits].

To investigate the occurrence of cerebral embolism, a rabbit embolic stroke model was used for the continuous monitoring of the change of the thrombus. Red thrombus was directly injected into the internal carotid artery via the catheter inserted into the external carotid artery. The migration of the thrombus into the middle cerebral artery was judged as the completion of an embolism. The change of the thrombus and its movement was observed for a period of two hours. The experimental group received recombinant tissue plasminogen activator (TPA) for the thrombolysis while the control group received a saline solution for 30 minutes. The thrombus in the middle cerebral artery was continuously observed for two and a half hours. 1. There was a spontaneous movement of the thrombus during the first two hours in six out of 18 cases. One case showed a spontaneous regression in size at the migration site. 2. White thrombus formation occurred around the thrombus in eight out of 18 cases. 3. In the TPA injected group, thrombolysis was observed in nine out of ten rabbits. The accompanied white thrombus was also found to be degraded. However, after the TPA injection, white thrombus was newly formed during the lysis of red thrombus. 4. In the saline solution injected control group, only partial recanalization occurred in three out of eight rabbits. There was no white thrombus formation in the control group. 5. There was no significant difference in the degree of Evans blue exudation between these two groups. Secondary activation of the platelet function easily occurred by the change of the blood flow during thrombus migration and also thrombolysis. In conclusion, thrombolysis therapy may be more effective when TPA is administered in conjunction with the suppression of platelet function.

Animals↗
PubMed1998

[Visual acuity outcome and recurrence in large or huge pituitary adenomas operated with transcranial approach: comparison between frontotemporal and interhemispheric approaches].

Pituitary macroadenomas which required transcranial removal were reviewed concerning visual acuity outcome as well as recurrence. We encountered 173 pituitary adenomas of which 27 (15.6%) were removed transcranially during the past 13 years. Eight cases were excluded due to inadequate information and improper utilization. Thus, a total of nineteen cases were reviewed in which the frontotemporal (FT) approach was utilized for seven cases and the interhemispheric (IH) approach for 12 cases. The mean size and volume of the tumors in the FT group were 3.0 x 3.7 x 3.1 cm and 18.2 cm3. The main reason for utilizing this approach was the fact that the tumors extended laterally involving the unilateral cavernous sinus or that unilateral preoperative visual acuity was obstructed. The visual acuity outcome was as follows: In six cases showing useful visual acuity on both sides before surgery, no apparent aggravation on either side was found in four cases, while in two cases there was complete obstruction on the operative side. The remaining case showed aggravation on both sides, though the approach side was decided upon because of the obstructed vision on that side. The mean size and volume of the tumors in the IH group were 4.6 x 4.8 x 4.9 cm and 71.1 cm3. This approach was used due to the extreme suprasellar extension because of the large size of the tumors. Although the tumors were relatively large and the visual acuity was assessed as fair prior to surgery, visual acuity showed no significant deterioration after the operation and was found to be satisfactory in 11 out of 12 cases. The complications in the FT group were oculomotor palsy in 3 cases, hemorrhage in one case, and frontal infarction in one case. On the other hand, three cases suffered hemorrhage in the tumor cavity of the IH group, though none needed surgical evacuation. Most of the cases in the IH group showed pituitary hypofunction following the surgical removal of the tumors as compared to the cases in the FT group. Recurrence had occurred, in some cases, several years after the operation. Furthermore, some of the tumors are still growing larger following only partial or subtotal removal. The prime aim of the treatment for huge pituitary adenomas which require the transcranial removal is to retain as much visual acuity as possible. In conclusion, the IH approach has been shown to be preferable in this situation. The FT approach was found to be more dangerous in terms of visual outcome than had been expected, even if the tumors were not particularly large.

Adenoma↗
PubMed1998

Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies.

Osteopontin (OPN) is an Arg-Gly-Asp-containing phosphoprotein that is secreted by activated T cells. The concentration of serum OPN protein is elevated in autoimmune-prone MRL-lpr mice as well as in patients with systemic lupus erythematosus. Previously, it was shown that OPN induces the polyclonal activation of B cells, resulting in the augmented production of immunoglobulin, indicating that OPN plays some role in the development of autoimmune disease. However, the link between OPN and development of autoimmune disease remains unclear. To analyze the role of OPN in immune system and autoimmune diseases, we have generated two kinds of transgenic mice: one carries the immunoglobulin (Ig) enhancer/SV40 promoter and the other carries the cytomegalovirus enhancer/chicken beta-actin (CAG) promoter. In both groups of transgenic mice, the B1 cell population in peritoneal cavity was markedly increased and titer of IgM and IgG3 antibodies in the serum was considerably higher than that in wild-type mice. Most important, the titer of the IgM class of anti-double-stranded DNA antibody was significantly elevated in transgenic mice. These results strongly suggest that OPN may have an important role in the propagation and differentiation of B1 cells and production of autoantibodies.

Animals↗