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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 145 records · Page 8Linked to original sources
PubMed2000

Specialized basement membrane of monkey maturation stage ameloblasts mediates firm ameloblast-enamel association by its partial calcification.

A basement membrane-like structure associated with the maturation stage ameloblasts of the monkey (Macaca fuscata) tooth germ was examined with high resolution electron microscopy. The tissue was prepared either with or without demineralization. This structure was composed of a lamina lucida-like (lamina lucida) and lamina densa-like (lamina densa) structure. The latter was made up of a fine "cord" network, the major constituent of the basement membrane. It was closely associated with the third layer of a 200 nm wide looser cord network. In specimens without demineralization the third layer and a part of the lamina densa were calcified, and it formed the edge of the enamel. This particular area had a higher electron density, and the size, shape, and arrangement of mineral crystals were different from those of the rest of the enamel. Also, mineralization appeared to be proceeding along the cords. These observations indicate that this dense layer is a highly specialized basement membrane which mediates the firm association of maturation stage ameloblasts with the enamel by means of the mineralization of a part of this basement membrane itself which becomes integrated as a part of the enamel. Also, this highly specialized manner of association is favorable with the reported control of the loss of organic substances in the maturing enamel by maturation stage ameloblasts.

Ameloblasts↗
PubMed2000

Profile of cytokine production during the inhibition of acute xenograft rejection.

Th2 cells have been shown to exert cell-mediated immune responses in vitro; therefore, the present study was conducted to investigate the cellular mechanisms of the long-term survival of cardiac xenografts by measuring cytokine production from recipient lymphocytes. Xenogeneic heart grafts from Lewis rats were transplanted into C57BL/6 mice, and the recipients were intravenously injected with H57-597 at the time of transplantation. The production of Th1 cytokines, namely, interleukin (IL)-2 and interferon (IFN)-gamma, and Th2 cytokines, namely, IL-4 and IL-10, from mixed lymphocyte culture cells was assayed by enzyme-linked immunosorbent assay. Splenocytes from the xenograft recipients treated with H57-597 produced significantly lower levels of IL-2, IFN-gamma, IL-4, and IL-10 than those from the untreated recipients, 100 days after transplantation. The findings of this study indicate that the long-term survival of cardiac xenografts induced by H57-597 is mediated by the inhibition of Th0, or both the Th1 and Th2 response.

Acute Disease↗
PubMed2000

Inhibition of L-leucine methyl ester mediated killing of THP-1, a human monocytic cell line, by a new anti-inflammatory drug, T614.

T614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne) is a member of the family of methanesulfonanilide non-steroidal anti-inflammatory drugs (mNSAIDs), most of which act as cyclooxygenase (COX)-2 inhibitors. L-leucine methyl ester (Leu-OME) is a reagent which has been shown to kill phagocytes following interaction with intracellular proteases. There are two pathways whereby Leu-OME becomes cytotoxic to phagocytes. Within lysosomes, Leu-OME is converted into free Leu, which causes disruption of the lysosomes and subsequent cell necrosis. The other is the conversion of Leu-OME into (Leu-Leu)(n)-OME, which is associated with the induction of apoptosis. In the present study, we examined the action of T614 on Leu-OME mediated killing of THP-1, a human monocytic cell line. We revealed that T614 and phenylmethyl sulfonyl fluoride (PMSF), a serine protease inhibitor, inhibited Leu-OME mediated killing of THP-1 cells. All the other mNSAIDs, including nimesulide (NIM-03), fluosulide (CGP28238), FK3311 and NS398, also rescued THP-1 from Leu-OME mediated killing, although to a lesser degree. Of the classical NSAIDs tested, a protective effect was observed with diclofenac at high concentration, but not with naproxen or indomethacin. Unlike conventional lysosomal inhibitors, such as chloroquine and ammonium chloride (NH(4)Cl), T614 and PMSF did not raise lysosomal pH, as measured by flow cytometry using fluorescein isothiocyanate dextran (FITC-dextran). Therefore, the mechanism whereby T614 and PMSF inhibit Leu-OME killing is distinct from that of chloroquine or NH(4)Cl. Based on the similarity of T614 and PMSF, we suggest that, besides their roles as COX-2 inhibitors, T614 and other mNSAIDs may act as lysosomal protease inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

The distributions of apoptotic cells in the medial preoptic areas of male and female neonatal rats.

The medial preoptic area (MPA) of the hypothalamus of the rat contains two sexually dimorphic nuclei, the periventricular preoptic nucleus (PVpo) and the medial preoptic nucleus (MPN). To examine the relationship between sexual dimorphism and neuronal death, we examined the number of apoptotic cells in the subdivisions of the MPA in neonatal rats of postnatal days 1 (P1), 4 (P4), 7 (P7) and 14 (P14). Apoptotic cells in these areas were classified according to their progression into three stages. P1 and P4 rats contained many apoptotic cells in the subfield along the third ventricle, including the PVpo, and their number was significantly larger in P1 males: in particular, the number of early-stage cells was larger in males than females. The number of apoptotic cells in the MPN was increased in P4 and P7 rats, although no significant sexual differences were seen in the total number or in the number of each progressive stage of apoptotic cells. In P14 rats, very few apoptotic cells were seen in the MPA. Our data revealed that the distribution of apoptotic cells in the MPA of developing rats depends on the sexuality, subdivision of the area and postnatal period.

Animals↗
PubMed2000

Spontaneous improvement in a case of C1q nephropathy.

A 17-year-old girl showed mild proteinuria accompanied by hematuria and mild hypocomplementemia. A light microscopic study of the first renal biopsy specimen showed diffuse mild to moderate mesangial proliferation and thickening of the glomerular basement membrane (GBM). An immunofluorescence study showed dominant positive staining (3+) of IgG and C1q in the glomerular mesangium and capillary loop. Staining for C3 and fibrinogen was weak or 1+. Staining for IgA and IgM was negative. Electron-dense deposits were present in the mesangial area and also in the subepithelial, subendothelial, and intramembranous space. Urinary findings improved after dipyridamole treatment. The second renal biopsy, which was performed 5 years later, showed histological improvements, and various pictures of washing-out of deposits were also noted in an electron microscopic study. However, dominant positive staining for IgG and C1q was persistent in an immunofluorescence study. The glomerulopathy of this case belongs in the criteria of neither membranoproliferative glomerulonephritis nor lupus nephritis but could be designated as C1q nephropathy. This is the first report of a histological improvement in C1q nephropathy.

Adolescent↗
PubMed2000

Putaminal necrosis presenting with hemidystonia.

A 7-year-old female presented with putaminal necrosis associated with hemidystonia. Cranial magnetic resonance imaging revealed bilateral putaminal lesions appearing as hypointense signals on T(1)-weighted images and hyperintense signals on T(2)-weighted images. After a differential diagnosis of basal ganglial degeneration was made, putaminal necrosis was diagnosed. Low doses of levodopa (0.5 mg/kg daily) were administered, but her clinical signs worsened. Positron emission tomography scanning with [(18)F]-6-fluoro-L-dopa revealed asymmetric uptake and right-sided dominant decreases of [(18)F]-6-fluoro-L-dopa uptake of the putamen. On the basis of these findings, standard doses of levodopa (10 mg/kg daily) were administered, and her clinical signs improved. These results suggest that hemidystonia is associated with a disturbance of the dopamine system.

Antiparkinson Agents↗
PubMed2000

A critical role for interleukin 4 in activating alloreactive CD4 T cells.

To generate antigen-specific responses, T cells and antigen presenting cells (APCs) must physically associate with each other and elaborate soluble factors that drive the full differentiation of each cell type. Immediately after T cell activation, CD4 T cells can produce both interferon gamma (IFN-gamma) and interleukin 4 (IL-4) before polarization into distinct T helper subsets. Inhibition of IL-4 during mixed allogeneic lymphocyte culture resulted in a defect in the ability of APCs to generate sufficient costimulatory signals for activation of alloreactive T cells. In vivo, a deficiency in IL-4 production inhibited the activation of alloreactive IL-2-, IL-4- and IFN-gamma-producing CD4 T cells in mice challenged with allogeneic skin grafts, resulting in prolonged skin graft survival. Thus, production of IL-4 by CD4T cells helps activate alloreactive T cells by affecting APC function.

Animals↗
PubMed2000

FK506-induced intractable leukoencephalopathy following allogeneic bone marrow transplantation.

FK506-related leukoencephalopathy has been reported to be reversible and readily treated by discontinuation or reduction of FK506. We describe two pediatric cases of FK506-related leukoencephalopathy following allogeneic bone marrow transplantation, which could not be readily controlled. These cases show that FK506-related leukoencephalopathy is not always reversible, and patients may develop epilepsy. Bone Marrow Transplantation (2000) 25, 331-334.

Acute Disease↗