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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 577 records · Page 32Linked to original sources

[Surgical treatment of congenital atypical coarctation of the aorta and postoperative management for hypertension].

A 10-year-old boy was admitted to our hospital with severe hypertension due to unusual aortic coarctation at the level of the diaphragm without renal artery stenosis. We made left interior thoracotomy and left para-rectal incision through extraperitoneal approach, and extra-anatomic bypass was established with a 16 mm knitted Dacron graft from the descending aorta to the infrarenal abdominal aorta, under a circulatory assist. Postoperatively, he complained of abdominal pain with residual hypertension and required an intensive anti-hypertensive treatment to avoid intestinal necrosis. Pressure gradient between upper and lower extremities disappeared 3 weeks after repair. High level of plasma renin activity still continued 4.5 months after surgery in spite of oral administration of beta blockade and ACE inhibitor.

Administration, Oral↗

NGF stimulates differentiation of osteoblastic MC3T3-E1 cells.

The activities of NGF on induction of IL-6, ALP and collagen were studied in cultured osteoblastic cells, MC3T3-E1. Treatment of the cells with NGF induced IL-6 production in a dose dependent manner and enhanced ALP activity and collagen biosynthesis without affecting cell proliferation. Cyclo-oxygenase was activated in NGF-treated cells and prostaglandinE2 was detected as a major metabolite from arachidonic acid. Since prostaglandinE2 is an enhancer of ALP activity and collagen biosynthesis in MC3T3-E1 and was found to induce IL-6 production in this study, it is possible that NGF works on MC3T3-E1 cells through the mediation by endogenous prostaglandinE2.

3T3 Cells↗

The effect of perioperative portal venous injection of donor spleen cells on renal allograft survival in dogs.

Preoperative portal venous injection of donor lymphocytes has been shown to extend allograft survival in inbred animals. However, the effect of perioperative injection in a large animal model has not been carefully studied. We examined the effect of perioperative (day 0) donor spleen cell administration in a canine kidney transplant model using both a double-donor transplantation and a single-donor survival study. In the double-donor model, two kidneys from two separate donors were transplanted into a single recipient. Spleen cells obtained from only one of the donors were injected through the portal vein immediately after reperfusion of the allografts. Both allografted kidneys were resected 14 days after transplantation and studied. There was only a slight cellular infiltrate in the kidney derived from the donor from whom spleen cells had been obtained, whereas a much more extensive cellular infiltrate as well as edema and hemorrhage were present in the other kidney. In a survival study of single allografts, the injection of 2 x 10(9) spleen cells significantly prolonged the mean survival time (15.0 +/- 3.4 days) compared with untreated recipients (6.6 +/- 2.2 days). Addition of cyclosporine did not significantly prolong survival in the spleen cell inoculated animals. These findings suggest that perioperative protal venous injection of donor cells may be a specific immunosuppressive method useful in clinical organ transplantation.

Animals↗

Origin of thromboxane-mediated constriction due to neuropeptides in canine basilar artery.

Bradykinin, substance P and vasopressin induced a vasodilatation followed by a vasoconstriction in control perfused canine basilar arteries with endothelium. The dilatation was significantly reduced and the constriction was significantly enhanced by endothelial removal with saponin. The potentiated constriction was significantly blocked by sodium ozagrel, a thromboxane synthetase inhibitor. These results suggest that the dilatation due to these neuropeptides may depend on endothelium-derived relaxing factor, and that the augmented constriction after endothelial removal may be related to the thromboxane A2 production in cerebral arterial smooth muscles. This mechanism following the damage of endothelium might be implicated in cerebral vasospasm after subarachnoid haemorrhage.

Adenosine Triphosphate↗

Role of O-linked carbohydrate chains on leukocyte cell membranes in platelet-induced leukocyte activation.

We previously reported that activated platelets stimulated neutrophils and monocytes to produce superoxide anion (O2-) through the interaction between P-selectin and its carbohydrate ligand, sialyl Lewis X (sLeX) (Nagata, K., Tsuji, T., Todoroki, N., Katagiri, Y., Tanoue, K., Yamazaki, H., Hanai N., and Irimura, T. (1993) J. Immunol. 151, 3267-3273). In the present study, we investigated the role of cell surface carbohydrate chains of leukocytes in this process. Glycoconjugate-specific hydrolytic enzymes and inhibitors of glycosylation processing were applied. Granulocyte-like differentiated HL-60 (gHL-60) cells released an increased amount of O2- in response to activated platelets in a P-selectin-dependent manner. When HL-60 cells were differentiated in the presence of benzyl-alpha-N-acetylgalactosaminide (Bzl-alpha-GalNAc), an inhibitor of chain elongation of O-linked carbohydrates, the enhanced generation of O2- was abrogated in parallel with decrease in the expression of sLex structure and in the adhesion capacity to activated platelets. In contrast, treatment with swainsonine or 1-deoxymannojirimycin, inhibitors of processing of N-linked carbohydrate chains, did not show such effects. O-Sialoglycoprotease treatment of gHL-60 cells decreased the activated platelet-induced O2- production with concomitant reduction of cell surface sLex expression. Treatment of these cells with N-glycanase did not affect the O2- production. These results strongly suggested that serine/threonine-linked carbohydrate chains containing sLex played an essential role in the P-selectin-mediated leukocyte activation. By Western blotting analysis of gHL-60 cell lysates, we identified two glycoproteins which carried sLex structures and were sensitive to Bzl-alpha-GalNAc treatment.

Blood Platelets↗

Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin.

The humoral response in newborns is mainly restricted to IgM production, which may be attributable to the naive nature of both B and T cells at birth. In light of the current evidence that memory (CD45RO+) CD4+ T cells help B cell differentiation, the present study was undertaken to examine whether a specified population within memory CD4+ T cells could induce the maturation of neonatal naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG- and IgA-producing cells in addition to IgM production by neonatal B cells was significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells. Memory CD4+ T cells were further divided into two populations based on expression of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared to behave in different fashions concerning help for Ig production by naive (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig production by neonatal B cells as well as adult naive B cells, although less than that by mature B cells, was efficiently promoted by L-selectin-positive memory CD4+ T cells rather than L-selectin-negative ones. The results suggest that the capability of neonatal naive B cells to secrete IgG and IgA can be elicited by appropriate T-cell signals, especially from the L-selectin-positive population within memory CD4+ T cells, seemingly indicating its possible role for isotype switching in B cells.

Adult↗

Changes in the expression of sialyl-Lewisx, a hepatic necroinflammation-associated carbohydrate neoantigen, in human hepatocellular carcinomas.

BACKGROUND: Malignant transformation of cells is associated with the change in their carbohydrate antigens. Sialyl-Lewisx (SLEX) is a necroinflammation-associated carbohydrate antigen (NICA) of liver cells, because it is newly expressed in chronic inflammatory liver diseases. The authors addressed whether this type of carbohydrate antigen shows cancer-associated changes. METHODS: Expression of SLEX and its related structures was studied immunohistochemically using the well characterized monoclonal antibodies in 13 small and 6 advanced hepatocellular carcinomas (HCC). RESULTS: SLEX was negative in 7 small HCC, which were well differentiated histologically. Both negative and positive cells were observed in 6 other small HCC. When positive, SLEX was expressed membranously or cytoplasmically. The membrane positive HCC cells were well differentiated. Cytoplasmic expression was observed in the less differentiated cells. The SLEX-negative cells were associated with any degree of differentiation. In six advanced HCC, the expression of SLEX could also be correlated with their histologic differentiation. HCC expressed sialyl-type 2 chain N-acetyllactosamine (2-NAcLc), but not 2-NAcLc, Lewisx, and Lewisy. CONCLUSIONS: SLEX, a NICA, showed HCC-associated changes that were dependent on the levels of HCC cell differentiation. Suppression and reactivation of alpha 1-3fucosyl-transferase was a possible enzymatic basis for the observed changes.

Adult↗

TL antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells.

In contrast to broadly expressed classical class I antigens of the major histocompatibility complex, structurally closely related TL antigens are expressed in a highly restricted fashion. Unlike classical class I antigens, TL antigens are not known to be targets of cytotoxic T cells or to mediate graft rejection. Whereas classical class I antigens function as antigen-presenting molecules to T cell receptors (TCR), the role of TL is yet to be defined. To elucidate the function of TL, we have derived transgenic mice expressing TL in most tissues including skin by introducing a TL gene, T3b of C57BL/6 mouse origin, driven by the H-2Kb promoter. By grafting the skin of transgenic mice, we demonstrate that TL can serve as a transplantation antigen and mediate a TCR-alpha/beta+ CD8+ cytotoxic T cell response. This T cell recognition of TL does not require antigen presentation by H-2 molecules. Furthermore, we show that C57BL/6 F1 mice develop CD8+ T cells that are cytotoxic for C57BL/6 TL+ leukemia cells, providing further support for the concept that aberrantly expressed nonmutated proteins such as TL can be recognized as tumor antigens.

Animals↗

Hemocompatibility on graft copolymers composed of poly(2-methacryloyloxyethyl phosphorylcholine) side chain and poly(n-butyl methacrylate) backbone.

To improve the hemocompatibility on hydrophobic biomedical materials by a simple coating technique, graft copolymers composed of a hydrophilic side chain with phospholipid polar groups and a hydrophobic backbone were synthesized. The hydrophilic chain had phospholipid polar groups, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], and the hydrophobic backbone was poly[n-butyl methacrylate (BMA)]. Because the graft copolymers obtained could dissolve in ethanol, they could be used as a coating material. When the poly(MPC-graft-BMA) was coated onto a poly(BMA) membrane, the composition of the MPC units on the surface was maintained in the bulk graft copolymer even after immersion in water. Protein adsorption on the membrane coated with the graft copolymer from human plasma detected by a gold-colloid labeled immunoassay was drastically decreased compared with that on glass and the original membrane. Moreover, blood cell adhesion, activation, and aggregation on the membrane after contact with human citrated whole blood were suppressed by the coating of the graft copolymer. These results clearly show that the poly(MPC-graft-BMA) is a suitable material for improving hemocompatibility on the biomedical devices because of its protein adsorption and cell adhesion resistant properties.

Adsorption↗

Feasibility of agarose microbeads with xenogeneic islets as a bioartificial pancreas.

A bioartificial pancreas, that is, transplantation of islets of Langerhans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immuno-isolated from the host by the semipermeable membrane preventing rejection while maintaining control of glucose metabolism for an extended period. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a bioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combination of encapsulation of hamster islets in 5% agarose microbeads and in vitro culture of them prolonged xenograft survivals. Four of 6 recipients were still normoglycemic at 100 days after implantation. However, the same procedure was not effective in the recipients which were sensitized in advance by transplantation of free hamster islets and thus had high levels of anti-hamster antibodies. The average normoglycemic period was 32 days. Antibodies permeated through the microbeads and activated complement on the cell surfaces. The network of agarose microbeads was rendered dense by increasing the concentration of agarose to restrict the diffusion of antibodies. Graft survivals were prolonged with increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by the combination of the microbeads with a concentration of agarose higher than 7.5% and in vitro culture even in recipients having a high level of preformed antibodies.

Animals↗

Strategy for developing microbeads applicable to islet xenotransplantation into a spontaneous diabetic NOD mouse.

A bioartificial pancreas (BAP) created through the encapsulation of islets of Langerhans (islets) in a semipermeable membrane has been proposed as a promising approach to treating insulin-dependent diabetes patients. A nonobese diabetic (NOD) mouse, which shares many features of human insulin-dependent diabetes mellitus, is an ideal model for evaluating the function of BAP. However, the functions of BAPs that have been developed have been limited in NOD mice. We propose novel microbeads that can realize long-term BAP function in NOD mice. The novel microbeads were composed of agarose and poly(styrene sulfonic acid) (PSSa) mixed gel. A polyion complex layer between PSSa and polycationic polybrene was formed on and just inside the microbead, and the microbead surfaces were further covered by polyanions to produce anionic surface charges. The islets in the novel microbeads were intraperitoneally implanted. Graft-functioning periods were dependent on both PSSa concentration and the kinds of polyanion. Islets in the microbeads composed of 5% agarose and 5% PSSa, which had an outermost surface covered by carboxymethyl cellulose, produced normoglycemic periods of more than 60 days in all five recipients. Control mice receiving either transplants of unenclosed islets or islets in agarose microbeads showed normoglycemic periods of less than 12 days. We believe that agarose/PSSa microbeads are promising for producing semipermeable membranes that enable xenotransplantation of islets in spontaneous diabetes mellitus.

Animals↗