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Biomedical subjects

M Maruyama

Publications and source records attributed to M Maruyama.

At least 37 records · Page 2Linked to original sources
PubMed2003

Resting T cells negatively regulate osteoclast generation from peripheral blood monocytes.

There is accumulating evidence that T cells may be involved in osteoclastogenesis in a variety of murine systems. However, the precise role of human T cells in the regulation of osteoclast generation is still unclear. To address this issue, we investigated the effect of resting peripheral T cells on receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast generation from human peripheral monocytes. Although osteoclasts were not generated in the culture of human peripheral blood mononuclear cells (PBMC) in the presence of RANKL and macrophage colony-stimulating factor (M-CSF), the addition of cyclosporine A (CsA), a potent inhibitor of T-cell function, resulted in the formation of an increasing number of lacunae resorption on dentine, suggesting T cells may inhibit osteoclast formation. In a coculture of T cells and monocytes, which were isolated from PBMC, T cells inhibited the osteoclast generation from monocytes, as determined by tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine. This inhibition of osteoclast generation by T cells was also observed in a culture of the parathyroid hormone-stimulated SaOS4/3 osteoblast cell line and monocytes. The culture in Transwell plates revealed that the cell-to-cell interaction was not required for the inhibition, suggesting that T-cell cytokines may be responsible for the inhibition. Among inhibitory T-cell cytokines on osteoclastogenesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) were actively produced by CD4 T cells but not CD8 T cells in the coculture of T cells with monocytes, and the neutralizing antibodies to these cytokines partially rescued the T-cell-induced inhibition of osteoclast formation. Although CsA did not affect RANKL-induced osteoclast generation in the culture of monocytes alone, it completely rescued the T-cell-induced inhibition of osteoclast formation and strongly inhibited the production of GM-CSF and IFN-gamma. Thus, we demonstrate that resting T cells negatively regulate the osteoclast generation via production of GM-CSF and IFN-gamma by CD4 T cells and that CsA stimulates the osteoclast generation through the inhibition of the production of these cytokines. These findings provide new insight into therapeutic strategies for immunosuppression-induced bone loss in transplant and other diseases.

Bone Remodeling↗
PubMed2002

A histopathological and lectin-histochemical study of the lining epithelium in postoperative maxillary cysts.

OBJECTIVE: Histopathological and lectin-histochemical characteristics were studied in the lining epithelium of postoperative maxillary cysts (POMC). MATERIALS AND METHODS: Histological (HE, PAS, AB), immunohistochemical (CD3 and L26) and lectin (wheat germ agglutinin, WGA; Ulex europaeus agglutinin I, UEA-I; concanavalin A, ConA) stainings were performed in the 360 POMC specimens. The number of goblet cells and inflammatory cells was counted and statistically analyzed. RESULTS: The lining epithelium was classified into three types based on histopathological characteristics; pseudostratified ciliated epithelium (pSCE), transitional epithelium (TE) and stratified squamous epithelium (SSE). Local infiltration of inflammatory cells into the cyst wall was associated with an increased number of goblet cells in the lining epithelium. The observed association between the infiltration of inflammatory cells and an increase in the number of goblet cells was statistically significant in groups with lining pSCE and TE. Glycoconjugate histochemical analysis revealed that the surfaces of the lining epithelium with squamous metaplasia showed an increased degree of staining reactivity with UEA-I, whereas the staining reactivity with ConA was reduced. Goblet cells were able to be stained with WGA and UEA-I, but showed extremely low reactivity with ConA. CONCLUSION: Changes in the glycoconjugate expression of the metaplastic lining epithelium and goblet cell development play an important role in the local defense mechanisms against inflammatory factors in POMC.

Adult↗
PubMed2002

Up-regulation of the urokinase-type plasminogen activator receptor by monocyte chemotactic proteins.

The urokinase-type plasminogen activator receptor (uPAR) is a multifunctional molecule involved in migration and adhesion of leukocytes to sites of inflammation. Based on our hypothesis that a chemoattractant can stimulate uPAR expression by its target cell, thereby promoting cell migration, we employed three chemokines [monocyte chemotactic protein (MCP)-1, MCP-2 and MCP-3] as chemoattractants, and examined their effect on uPAR expression in a human monocyte-like cell line, U937. Northern blot analysis demonstrated that all three chemokines tested increased the level of uPAR mRNA in time-dependent and dose-dependent manners. Among them, MCP-3 exhibited the most potent effect. Scatchard analysis showed that incubation with MCP-3 (1 x 10(-8) mol/l) for 16 h resulted in a significant increase in the number of uPAR from (6.8 +/- 0.3) x 10(3) to (10.3 +/- 1.6) x 10(3)/cell, and in a slight increase in the equilibrium dissociation constant, K(d). The effect of anti-uPAR antibodies on MCP-3-induced U937 cell migration across an endothelial cell monolayer and a type I collagen layer was assessed by means of the modified Boyden chamber assay. Although MCP-3 caused a three-fold increase in migration, incubation with an antibody to uPAR markedly abrogated the induced cell migration. These results support our hypothesis and suggest that up-regulation of uPAR in target cells might be an important and common feature of chemoattractants.

Antibodies, Monoclonal↗
PubMed2001

Total synthesis of ciguatoxin CTX3C.

More than 20,000 people suffer annually from ciguatera seafood poisoning in subtropical and tropical regions. The extremely low content of the causative neurotoxins, designated as ciguatoxins, in fish has hampered the isolation, detailed biological studies, and preparation of anti-ciguatoxin antibodies for detecting these toxins. The large (3 nanometers long) and complicated molecular structure of ciguatoxins has impeded chemists from completing their total synthesis. Our highly convergent strategic approach featuring the chemoselective ring-closing metathesis reaction as a key tactic has enabled the total synthesis of ciguatoxin CTX3C, which will provide a practical supply for further studies.

Animals↗
PubMed2001

alpha-Synuclein affects the MAPK pathway and accelerates cell death.

Insoluble alpha-synuclein accumulates in Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy. However, the relationship between its accumulation and pathogenesis is still unclear. Recently, we reported that overexpression of alpha-synuclein affects Elk-1 phosphorylation in cultured cells, which is mainly performed by mitogen-activated protein kinases (MAPKs). We further examined the relationship between MAPK signaling and the effects of alpha-synuclein expression on ecdysone-inducible neuro2a cell lines and found that cells expressing alpha-synuclein had less phosphorylated MAPKs. Moreover, they showed significant cell death when the concentration of serum in the culture medium was reduced. Under normal serum conditions, the addition of the MAPK inhibitor U0126 also caused cell death in alpha-synuclein-expressing cells. Transfection of constitutively active MEK-1 resulted in MAPK phosphorylation in alpha-synuclein-expressing cells and improved cell viability even under reduced serum conditions. Thus, we conclude that alpha-synuclein regulates the MAPK pathway by reducing the amount of available active MAPK. Our findings suggest a mechanism for pathogenesis and thus offer therapeutic insight into synucleinopathies.

14-3-3 Proteins↗
PubMed2001

Identification of a caspase-9 substrate and detection of its cleavage in programmed cell death during mouse development.

The caspase family of proteases represents the main machinery by which apoptosis occurs. In vitro studies have revealed that upstream caspases are activated in response to apoptotic stimuli, and the active caspases in turn process downstream effector caspases that are involved in the destruction of cellular structure. Caspase-9 is an upstream caspase that can become active in response to cellular damage, including deprivation of growth factors and exposure to oxidative stress in vitro. Little is known, however, about how activation of caspase-9 is temporally and spatially regulated in vivo, e.g. during development. We have identified vimentin as the first example of a caspase-9 substrate that is not a downstream procaspase. Immunohistochemical analysis, using a specific antibody against the vimentin fragments generated by caspase-9, showed that caspase-9 cleaves vimentin in apoptotic cells in the embryonic nervous system and the interdigital regions. This result is consistent with observations that gene knockouts of caspase-9 and its activator, Apaf-1, result in developmental defects in these tissues. Our results show that the specific antibody is useful for in situ detection of caspase-9 activation in programmed cell death.

Animals↗
PubMed2001

Identification and molecular cloning of a novel brain-specific receptor protein that binds to brain injury-derived neurotrophic peptide. Possible role for neuronal survival.

Brain injury-derived neurotrophic peptide (BINP) is a synthetic 13-mer peptide that supports neuronal survival and protects hippocampal neurons in primary cultures from cell death caused by glutamate. We have developed a monoclonal antibody named mAb 6A22 against the 40-kDa BINP-binding protein, p40BBP. mAb 6A22 inhibits binding between BINP and rat brain synaptosomes and abolishes the protective effect of BINP. The antigen of mAb 6A22 should be the BINP-binding protein that mediates the neuroprotective action of BINP. Using an expression cloning approach with mAb 6A22, we isolated a cDNA encoding a novel receptor protein that shows binding activity of BINP. COS7 cells transfected with the cloned cDNA show binding of BINP and cell surfaces that are stained by 6A22. The mRNA for p40BBP is specific for the rat brain and is increased after birth. From immunohistochemical studies using mAb 6A22, p40BBP increased after kainic acid treatment in rat hippocampal neurons.

Amino Acid Sequence↗
PubMed2001

Leukaemia inhibitory factor and interleukin 6 inhibit secretion of prolactin and growth hormone by rat pituitary MtT/SM cells.

The rat pituitary cell line, MtT/SM, has the characteristics of somatomammotrophs. The cells secrete both prolactin (PRL) and growth hormone (GH). We examined the effects of cytokines such as leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), oncostatin M and interleukin 11 on the secretion of these hormones by the cells. These cytokines stimulate proliferation of the cells and inhibit the secretion of PRL by 70-80% and that of GH by 50%. They induce tyrosine phosphorylation of STAT3 in the cells. The cells containing PRL or GH decreased at 48 h after treatment of the cells with LIF or IL-6. These results suggest that the LIF/IL-6 family of cytokines inhibits the functions of mammotrophs and somatotrophs in the pituitary gland.

Animals↗
PubMed2001

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer.

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05). It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.

Adult↗