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T Uede

Publications and source records attributed to T Uede.

At least 37 records · Page 2Linked to original sources
PubMed2000

Abortive alloantigen presentation by donor dendritic cells leads to donor-specific tolerance: a study with a preoperative CTLA4lg inoculation.

Donor dendritic cells (DCs) within allografts initiate the induction of an allospecific T cell response, while an abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. We thus investigated the tolerogenic effect of donor DCs that were made incompetent in alloantigen presentation by treatment of CTLA4Ig. When we treated rats with donor DCs (2 x 10(6)/rat i.v.) on the preoperative day, nine rejected allografts in an accelerated manner (5.0 +/- 2.2 vs. 8.2 +/- 1.6 days in the control group). Preoperative inoculation of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked an accelerated rejection (5.6 +/- 1.7 days). When DCs and CTLA4Ig (500 microg/rat i.p. on days -9, -7 and -5) were concomitantly inoculated, allograft survival was significantly prolonged (>38.7 +/- 40.0 days); a preoperative CTLA4Ig inoculation alone failed to do so (7.5 +/- 1.2 days). Long-term graft survivors tolerated skin grafts from the donor but not from those from a third party. These results indicate that abortive alloantigen presentation by donor DCs, upon which an accessory signal pathway is suppressed by CTLA4Ig, leads to prolonged graft survival and donor-specific tolerance.

Abatacept↗
PubMed2000

Increased expression of osteopontin in activated Kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver.

Osteopontin is an extracellular matrix component that can act as a chemokine to induce macrophage migration. The significance of osteopontin in macrophage infiltration into the liver was examined in rats given heat-killed Propionibacterium acnes. In normal rats, osteopontin mRNA expression in the liver was minimal, determined by quantitative-competitive reverse transcription-polymerase chain reaction (RT-PCR) assay. Northern blot analysis revealed that osteopontin mRNA was not expressed in Kupffer cells isolated from normal rats. When rats received heat-killed P. acnes intravenously, marked macrophage accumulation, forming granulomas, developed in the liver later than 3 days after the injection and its extent became maximal between 5 and 7 days. In these rats, osteopontin mRNA expression was increased in the liver later than 1 day (with its peak at 3 days after the injection), and the mRNA expression was increased markedly in Kupffer cells and hepatic macrophages isolated at 7 days. The mRNA expression of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), chemokines for monocytes and macrophages, was also increased in the liver of P. acnes-treated rats, with peak expression at 3 days. We conclude that osteopontin derived from Kupffer cells and hepatic macrophages may contribute to the infiltration of monocytes and macrophages into the liver cooperatively with the actions of MCP-1 and MIP-1alpha in P. acnes-treated rats.

Animals↗
PubMed2000

CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice.

MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.

Abatacept↗
PubMed2000

The role of osteopontin in the development of granulomatous lesions in lung.

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression may be a common factor involved in formation of granulomas of various origin.

Adenoviridae↗
PubMed2000

Enhanced expression of osteopontin in human diabetic artery and analysis of its functional role in accelerated atherogenesis.

We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C-dependent pathways as well as hexosamine pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the staining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smooth muscle cells. OPN and PDGF synergistically activated focal adhesion kinase as well as extracellular signal-regulated kinase; this finding seems to explain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken together, our present results raise a possibility that OPN plays a role in the development of diabetic vascular complications.

Adult↗
PubMed2000

Involvement of CD28/CTLA4-B7 costimulatory pathway in the development of lymphadenopathy and splenomegaly in MRL/lpr mice.

MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3+ CD4- CD8- B220+ (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules, CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.

Abatacept↗
PubMed2000

Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms.

We have generated synthetic peptides corresponding to various portions of human osteopontin (OPN) and have immunized rabbits and mice with these peptides to generate polyclonal and monoclonal antibodies specific to human OPN. We then generated six distinct sandwich enzyme-linked immunoabsorbent assay (ELISA) systems by using different pairs of polyclonal and monoclonal antibodies against human OPN. These systems allowed us to detect not only various isoforms and truncated forms of recombinant OPN, but also the glycosylated form of native urinary OPN. Most importantly, tumor-derived OPN was differentially detected by the six ELISA systems. The ELISA systems that we have developed will be useful for clarifying the functional roles for OPN in vivo in various physiologic and pathologic conditions.

Adult↗
PubMed2000

Janus kinase 2 is associated with a box 1-like motif and phosphorylates a critical tyrosine residue in the cytoplasmic region of cytotoxic T lymphocyte associated molecule-4.

It is a consensus that a cytotoxic T lymphocyte associated molecule-4 (CTLA-4) transduces inhibitory signal for T cell activation under physiological condition, indicating that this molecule is an important regulator of T cell homeostasis in vivo. It has been reported that phosphorylation and dephosphorylation of tyrosine residue Y-165 in the cytoplasmic region of CTLA-4 play an important role in its negative signaling and cell surface expression. Some signaling molecules such as Src homology 2 protein tyrosine phosphatase 2 (SHP-2) and the p85 subunit of phosphatidylinositol 3 kinase (PI3 kinase) associate with phosphorylated tyrosine residue Y-165, through Src homology 2 (SH2) domains. On the other hand, the adapter complex proteins, AP-2 and AP-50 interact with the same tyrosine residue when unphosphorylated, resulting in clathrin-mediated endocytosis of CTLA-4 molecules. The objective of this study is to identify a tyrosine kinase that can directly bind and phosphorylate the critical tyrosine residue, Y-165 in the cytoplasmic domain of CTLA-4. Here, we demonstrated that 1) Janus Kinase 2 (Jak2) was directly associated with a box 1-like motif in the cytoplasmic tail of CTLA-4 molecule, 2) Jak2 phosphorylated Y-165 residue in the cytoplasmic region of CTLA-4 molecule, and 3) Jak2 was associated with CTLA-4 in HUT 78 T cell lines.

Abatacept↗
PubMed2000

Vascular endothelial growth factor and osteopontin in tumor biology.

Tumor growth and metastasis are angiogenesis-dependent and tumor angiogenesis is a result of complex interplay of positive and negative regulators. Vascular endothelial growth factor (VEGF) occupies a particular place among the positive regulators of angiogenesis due to its potency and specificity for endothelial cells. VEGF upregulates several molecules such as growth factors, adhesion molecules, proteases, and protease receptors and it actually induces microvascular hyperpermeability, resulting in activation of thrombin from prothrombin. Osteopontin (OPN) is a secreted arginine-glycine-asparic acid (RGD)-containing phosphoprotein and it contains a predicted thrombin cleavage site. OPN binds to several integrins and CD44 variants. OPN has diverse functions such as cell adhesion, chemoattraction, and immunomodulation, and it induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. OPN expression is upregulated in human carcinomas. This review documents the functional roles of VEGF and OPN in angiogenesis and their clinical significance in tumor biology.

Animals↗
PubMed2000

[A case of tentorial meningioma presented with pure word deafness].

It has been known that an isolation of Wernicke's area from auditory input results in pure word deafness. In this report, a 73-year-old female case with tentorial meningioma suffering from pure word deafness is reported. The patient initially presented with hydrocephalus, and was treated with a ventriculo-peritoneal(V-P) shunt. A year after the V-P shunt, she suffered from a symptom of deafness. On admission, her repetition and auditory comprehension were severely impaired, while reading and visual comprehension were almost normal. Auditory brain stem response(ABR) revealed normal latency between wave I and V, while wave VI and VII was disappeared. Middle latency response(MLR) showed no wave peak. On MRI, tentorial meningioma compressed bilateral medial geniculate bodies, but not auditory radiation or temporal lobe. 99mTc-HMPAO single photon emission computed tomography(SPECT) showed hypoperfusion in the left temporal lobe, considered as a diaschisis resulting from the isolation of left temporal lobe from auditory input via bilateral medial geniculate bodies.

Aged↗
PubMed1999

Detection of various epitopes of murine osteopontin by monoclonal antibodies.

We immunized rats with recombinant murine osteopontin protein and obtained four monoclonal antibodies recognizing distinct epitopes of murine osteopontin. OPN1.2 recognized the amino-terminal half of OPN, while OPN2.2, OPN2.3, and OPN3.1 recognized the carboxy-terminal half of OPN. The epitope recognized by OPN2.2 was destroyed by further cleavage of the carboxy half of OPN. The epitope recognized by OPN2.3 was located in the amino-terminal end of the carboxy half of OPN, whereas that recognized by OPN3.1 was located in the carboxy-terminal end of the carboxy half of OPN. OPN1.2 and OPN2.2 recognized thrombin-cleaved osteopontin, whereas thrombin-cleaved osteopontin was not recognized by OPN2.3 and OPN3.1. Thus, these monoclonal antibodies will be useful in structure/function studies of the role of osteopontin in murine models of disease.

Animals↗
PubMed1999

Expression of osteopontin in Kupffer cells and hepatic macrophages and Stellate cells in rat liver after carbon tetrachloride intoxication: a possible factor for macrophage migration into hepatic necrotic areas.

Activated Kupffer cells and macrophages accumulate in necrotic areas in the liver. Osteopontin, an extracellular matrix with RGD sequence, has been shown to act as a chemokine that can induce monocyte migration. The possibility that osteopontin can play a role in infiltration of both cells into hepatic necrotic areas was investigated in rats. Northern blot analysis revealed that osteopontin mRNA expression was minimal in Kupffer cells and hepatocytes immediately after isolation from normal rats, but slight in hepatic stellate cells assumed nearly quiescent in function after 3 days of culture on plastic dishes. When rat received carbon tetrachloride, liver necrosis developed between 1 and 3 days following the intoxication. In these rats, osteopontin mRNA expression assessed by quantitative competitive RT-PCR was increased in the liver later than 1 day with its peak at 2 days following the intoxication. Kupffer cells and hepatic macrophages and hepatic stellate cells isolated from such liver showed marked expression of osteopontin mRNA on Northern blotting. Immunohistochemical examination disclosed that osteopontin was stained in macrophages including Kupffer cells and stellate cells in the necrotic areas. On electron microscopy, osteopontin stains were present in the Golgi apparatus in these cells. Recombinant human osteopontin promoted migration of Kupffer cells isolated from normal rats and cultured in a Transwell cell culture chamber in a dose-related manner. We conclude that activated Kupffer cells and hepatic macrophages and stellate cells express osteopontin. These cells might contribute to the infiltration of Kupffer cells and macrophages into hepatic necrotic areas by expressing osteopontin.

Animals↗
PubMed1999

CTLA4IgG treatment induces long-term acceptance of rat small bowel allografts.

BACKGROUND: CTLA4 immunoglobulin (Ig)G that binds to B7 effectively inhibits the signaling of CD28/CTLA4-B7 pathway and induces antigen specific T cell unresponsiveness in vitro and in vivo. Using CTLA4IgG, we examined induction of long-term graft survival and the mechanism of maintenance of tolerance in rat allogeneic small bowel transplantation. METHODS: Small bowels of Brown-Norway rats (RT1n) were heterotopically transplanted into Lewis rats (RT1l). Recipients were treated with an i.p. injection of either CTLA4IgG or control IgG for 7 days. RESULTS: Long-term survival was observed in rats treated with CTLA4IgG, whereas control rats died within 16 days after transplantation. To examine whether a tolerant state was established in long-term survival rats, secondary transplantation was performed using small bowels of Brown-Norway rats or ACI (RT1b) rats. It was demonstrated that small bowels of Brown-Norway rats were accepted; however, those of ACI rats were rejected within 10 days. Serum concentrations of interleukin (IL)-4 were maintained at >50 microg/ml for 7 days after transplantation in rats treated with CTLA4IgG but <15 microg/ml in control rats. IL-2 concentration was reduced to half in CTLA4IgG-treated rats compared with that in control recipients. Serum IFN-gamma in CTLA4IgG-treated recipients increased after transplantation and was not distinguishable from that of control recipients during the first 7 days after transplantation. Conclusion. We demonstrated that CTLA4IgG treatment alone for 7 days induced a long-term donor specific tolerance in rat allogeneic small bowel transplantation. The induction of long-term acceptance of small bowel allografts by CTLA4IgG is not caused by simply the shift of anti-alloimmune responses from Thl to Th2 cytokine production.

Abatacept↗
PubMed1999

CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis.

The expression of osteopontin (OPN), CD44 variants, and integrins has been correlated with tumorigenesis and metastasis. Here we show that these proteins cooperate to enhance cell motility. First, we demonstrate that several different CD44 variants bind to OPN in an arginine-glycineaspartic acid-independent manner, but that the standard form of CD44 does not. These CD44 variants bind to both the amino- and COOH-terminal portions of OPN independently of the arginine-glycine-aspartic acid sequence, suggesting that multiple domains on OPN can be bound by the CD44 variants. Antibodies directed against the integrin beta1 subunit are able to inhibit this binding. The binding of CD44 variants to OPN is significantly augmented by both anti-CD44s and anti-CD44v antibodies. This augmentation by anti-CD44 antibodies is OPN specific and, again, can be blocked by anti-beta1 antibodies. Finally, we show that OPN binding by CD44 variants/beta1-containing integrins promotes cell spreading, motility, and chemotactic behavior.

Animals↗
PubMed1999

Quantification of osteopontin in the urine of healthy and stone-forming men.

Osteopontin (OPN) is one of the most important components in calcium stone matrix, but its role in stone formation is not clear. Since quantitative data regarding the excretion of OPN are necessary to assess its role, we have developed a quantitative enzyme-linked immunosorbent assay (ELISA) for OPN, and measured the urinary OPN concentrations in urolithiasis patients. Forty-seven men with urinary stones composed chiefly of calcium oxalate participated in the study. The controls were 13 normal healthy male volunteers. Urine samples were collected early in the morning and analyzed by a quantitative ELISA employing purified polyclonal antibodies to synthesized OPN aminopolypeptides. The urinary ratio of the concentrations of OPN and creatinine (OPN/Cre) in the urolithiasis patients (0.039 +/- 0.029) was significantly lower than that in the control subjects (0.062 +/- 0.030) (P<0.05). Single stone formers (n = 26; 0.050 +/- 0.020) had significantly higher OPN/Cre ratios compared with recurrent stone formers (n = 21; 0.031 +/- 0.021) (P<0. 05). The results show that OPN excretion in urolithiasis patients was lowered, presumably because of the incorporation of OPN by kidney stones.

Adult↗
PubMed1999

Suppressive effects of CTLA4-Ig on nasal allergic reactions in presensitized murine model.

Ag-specific T cell activation requires the engagement of T cell receptor (TCR) with antigen in the context of MHC, and the engagement of appropriate costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory pathway plays an important role in the induction of T helper (Th) cells in T-cell dependent immune reactions. In this study, we evaluated the effects of blocking the costimulatory pathway by systemic administration of CTLA4-Ig during repeated nasal antigen challenges in systemically presensitized mouse. The antigen-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the treatment. In relation to cytokine levels in the tissue extracts of the nasal mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels of IL-5 and IFN-gamma were not affected by the treatment. These results suggest that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2-related allergic reactions in the nose.

Abatacept↗
PubMed1999

Operative approach to mediosuperior cerebellar tumors: occipital interhemispheric transtentorial approach.

BACKGROUND: The transtentorial approach is well known as an approach to the pineal region. We have modified this approach for mediosuperior cerebellar tumors. METHODS: We describe six cases of tumor excision in this region using an occipital interhemispheric transtentorial approach. RESULTS: The lesions were easily accessible and the tumor was totally removed by this modified approach in all cases. Transient visual field disturbance with spontaneous recovery occurred in two patients. The lateral margin of the tumor was accessed easily up to 35 mm from the midline on the operative side and up to 17 mm from the midline on the contralateral side. CONCLUSION: This approach proved to be very useful for mediosuperior lesions of the cerebellum, without causing any neural structural damage, and allowed for a wider operative field.

Aged↗