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Biomedical subjects

S Motohashi

Publications and source records attributed to S Motohashi.

At least 19 recordsLinked to original sources

[Differences in postoperative course by preoperative left ventricular volume after closure of ventricular septal defect during early infancy].

A total of 38 early infants with ventricular septal defect (VSD) were divided into 2 groups by preoperative LVEDV. The group A (n=14, LVEDV>250% N) showed significantly longer period of intubation, cathecholamine drip, and hospitalization compared with the group B (n=28, LVEDV<250% N). At dischage, both groups showed significant lowered right ventricular (RV) pressure, but LVSF in the group A was significantly lower than that in the group B. The patients with larger left ventricular (LV) volume preoperatively were thought to be potential high-risk groups in cardiac and pulmonary function and their postoperative course was prolonged and recovery of LV function was worse. In such patients, special care is mandatory to do postoperative management and to decide timing of operation.

Cardiac Volume↗

Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14 NKT cells.

A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments. Valpha14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated anti-tumor activity.

Adoptive Transfer↗

Stereoselective reactions. XXXIV. Enantioselective deprotonation of prochiral 4-substituted cyclohexanones using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon.

Using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon, enantioselective deprotonation of prochiral 4-substituted cyclohexanones in the presence of excess trimethylsilyl chloride was examined in THF in the absence and in the presence of HMPA. It is shown that enantioselectivity of the reactions decreases as the substituent on the chiral carbon of the chiral lithium amides and the substituent at the 4-position of cyclohexanones become reasonably bulky. An eight-membered cyclic transition state model is proposed for this deprotonation reaction.

Cyclohexanones↗

15-Deoxy-Delta(12,14)-prostaglandin J(2) facilitates thyroglobulin production by cultured human thyrocytes.

A cyclopentenone-type prostaglandin, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15-d-PGJ(2)), has been shown to induce the cellular stress response and to be a ligand for the peroxisome proliferator-activated receptor (PPAR)-gamma. We studied its effect on the basal and thyrotropin (TSH)-induced production of thyroglobulin (TG) by human thyrocytes cultured in the presence of 10% FBS. In 15-d-PGJ(2)-treated cells in which the agent itself did not stimulate cAMP production, both the basal production of TG and the response to TSH were facilitated, including the production of TG and cAMP, whereas such production was decreased in untreated cells according to duration of culture. PGD(2) and PGJ(2), which are precursors to 15-d-PGJ(2), exhibited an effect similar to 15-d-PGJ(2). However, the antidiabetic thiazolidinediones known to be specific ligands for PPAR-gamma, and WY-14643, a specific PPAR-alpha ligand, lacked this effect. 15-d-PGJ(2) and its precursors, but not the thiazolidinediones, induced gene expression for heme oxygenase-1 (HO-1), a stress-related protein, and strongly inhibited interleukin-1 (IL-1)-induced nitric oxide (NO) production. Cyclopentenone-type PGs have been recently shown to inhibit nuclear factor-kappaB (NF-kappaB) activation via a direct and PPAR-independent inhibition of inhibitor-kappaB kinase, suggesting that, in human thyrocytes, such PGs may inhibit IL-1-induced NO production, possibly via an inhibition of NF-kappaB activation. On the other hand, sodium arsenite, a known activator of the stress response pathway, induced HO-1 mRNA expression but lacked a promoting effect on TG production. Thus 15-d-PGJ(2) and its precursors appear to facilitate TG production via a PPAR-independent mechanism and through a different pathway from the cellular stress response that is available to cyclopentenone-type PGs. Our findings reveal a novel role of these PGs associated with thyrocyte differentiation.

Anticholesteremic Agents↗

6S,8R-Stereochemistry of the C27- and C29-alkane-6,8-diols isolated from three compositae flowers.

The Deltadelta (deltaS-deltaR) values for the C-1 methyl 1H signals in the 1H-NMR spectroscopy of the bis-MTPA esters of four synthetic stereoisomers of alkane-6,8-diols, viz., bis-MTPA esters of (6S,8R)-C27- (1a) and C29- (3a) (Deltadelta = -0.05 ppm), (6R,8S)-C27- (2a) and C29- (4a) (Deltadelta = +0.05 ppm), (6S,8S)-C27- (5a) (Deltadelta = -0.01 ppm), and (6R,8R)-C27- (6a) (Deltadelta = +0.01 ppm) alkane-6,8-diols, made it possible to differentiate unequivocally among the four stereoisomers. This allowed the determination of the (6S,8R)-stereochemistry (Deltadelta = -0.05 ppm for the bis-MTPA esters) for the natural C27- and C29-alkane-6,8-diols isolated from the flowers of three Compositae plants, Carthamus tinctorius, Cynara cardanclus, and Taraxacum platycarpum.

Alkanes↗

Intracranial lipomas: demonstration by computed tomography and magnetic resonance imaging.

We present two cases of a very rare tumor, intracranial lipoma, diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). In one case, the lipoma was in the superior cerebellar cistern, the other was in the periphery of the corpus callosum. In the case in which MRI was used, identification of the lipoma using a routine MRI examination was difficult. These cases are reported now because the incidental diagnosis of intracranial lipoma is likely to increase due to advanced neuroradiological techniques such as CT and MRI.

Brain Neoplasms↗

Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells.

Human V alpha24 NKT cells bearing an invariant V alpha24J alphaQ antigen receptor, the counterpart of the murine V alpha14 NKT cells, are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the alpha-GalCer-activated V alpha24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that V alpha24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of alpha-GalCer-activated V alpha24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.

Adult↗

Interleukin-6 and transforming growth factor-beta regulate the expression of monocyte chemoattractant protein-1 and colony-stimulating factors in human thyroid follicular cells.

Monocytes and T-lymphocytes, both of which play a pivotal role in immune/inflammatory responses, can be attracted from the circulation into tissues by monocyte chemoattractant protein-1 (MCP-1), and monocytes can be further activated by colony-stimulating factors (CSFs), granulocyte/macrophage CSF (GM-CSF) or macrophage CSF (M-CSF). We examined whether either interleukin-6 (IL-6) or transforming growth factor-beta (TGF-beta), both of which are produced by thyroid follicular cells (TFC), can regulate the production of MCP-1 or CSF(s) in human TFC. IL-6, being effective only in the presence of soluble IL-6 receptor (sIL-6R), stimulated the expression of both MCP-1 and M-CSF, but was inhibitory on GM-CSF expression. On the other hand, TGF-beta stimulated the expression of both MCP-I and GM-CSF, but suppressed M-CSF expression. These results suggest a possible role of IL-6 or TGF-beta on the initiation and/or modulation of thyroid immune/inflammatory responses via MCP-1 production and differential production of GM-CSF or M-CSF by TFC.

Cells, Cultured↗

Smoking before surgery predicts poor long-term survival in patients with stage I non-small-cell lung carcinomas.

PURPOSE: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known. However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I-NSCLC. RESULTS: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease. Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. CONCLUSION: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC.

Aged↗

Elevated levels of circulating plasma matrix metalloproteinase 9 in non-small cell lung cancer patients.

Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have been implicated as playing important roles in tumor invasion and metastasis in various tissues. We investigated the relationship between circulating plasma MMP-9, its expression in tumor samples, and other clinical features in patients with non-small cell lung cancer (NSCLC). A series of 73 patients (45 men and 28 women) who underwent surgery for NSCLC was used in this study. Preoperative plasma concentrations of MMP-9 were examined using a one-step sandwich enzyme immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0 +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers (P < 0.0001). MMP-9 concentrations were elevated in 33 of 73 cases (45.2%), compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There were statistically significant differences in MMP-9 concentration in adenocarcinoma versus squamous cell carcinoma (P = 0.014) and adenocarcinoma versus large cell carcinoma (P = 0.014). Five of 24 patients (20.8%) had positive immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to correlate with MMP-9 production by cancer and stromal cells. We concluded that the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

Aged↗

Production of granulocyte/macrophage and macrophage colony-stimulating factors by human thyrocytes in culture.

Monocytes/macrophages can be activated by the colony-stimulating factors (CSFs), granulocyte/macrophage CSF and macrophage CSF, and play a pivotal role in immune and inflammatory responses. We examined whether human thyrocytes can produce these CSFs. Interleukin-1 (IL-1) strongly up-regulated the gene and protein expression of the two CSFs. Interferon-gamma stimulated M-CSF expression but inversely suppressed GM-CSF expression in either basal or IL-1-stimulated condition. Thyrocytes prepared from Graves' thyroid tissues produced relatively larger amounts of GM-CSF in response to IL-1 and M-CSF in both basal and IL-1-stimulated conditions when compared to those obtained from normal and adenomatous goiter thyroid tissues. Thyrotropin attenuated M-CSF, but not GM-CSF, production. The present finding indicates that human thyrocytes themselves produce both GM-CSF and M-CSF, and thus may participate in immune and inflammatory responses through these CSFs production.

Cells, Cultured↗

Co-induction of nitric oxide and tetrahydrobiopterin synthesis in the myocardium in vivo.

Induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) in the myocardium is implicated as a mechanism in the development of cardiac depression in immune activated states associated with an enhanced release of cytokines, such as septic shock. We evaluated the in vivo synthesis of NO and tetrahydrobiopterin (BH4), a cofactor of NOS, in the heart tissue using a model of LPS injection in rats (LPS: 10 mg/kg, i.v.). In control rats, iNOS activity or iNOS mRNA in the heart was negligible. Three hours after LPS administration, a marked induction of iNOS mRNA and activity was observed in the heart. A significant increase in BH4 content and GTP cyclohydrolase mRNA abundance was also observed in the heart from LPS-treated rats. Our results demonstrate induction of NO synthesis and parallel increase in BH4 concentration in the heart of rats after LPS treatment in vivo and may provide molecular evidence responsible for the increased production of BH4 which may up-regulate iNOS activity in the heart in vivo.

Animals↗

Induction of tetrahydrobiopterin synthesis in rat cardiac myocytes: impact on cytokine-induced NO generation.

Because tetra-hydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) formation, we investigated whether BH4 synthesis is required for cytokine-induced NO production in cultured rat cardiac myocytes. The total biopterin content of untreated cardiac myocytes was below our limit of detection. However, treatment with interleukin-1 alpha (IL-1 alpha) + interferon-gamma (IFN-gamma) caused a significant rise in biopterin levels and induced NO synthesis. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTP cyclohydrolase I (the rate-limiting enzyme for de novo BH4 synthesis), completely abolished the elevation in biopterin levels induced by IL-1 alpha + IFN-gamma. DAHP also caused a concentration-dependent inhibition of (IL-1 alpha + IFN-gamma)-induced NO synthesis. Similarly, N-acetylserotonin, an inhibitor of the BH4 synthetic enzyme sepiapterin reductase, blocked increases in biopterin levels as well as NO synthesis induced by IL-1 alpha + IFN-gamma. Sepiapterin, substrate for BH4 synthesis via the pterin salvage pathway, prevented this inhibition by DAHP or N-acetylserotonin, and this effect was blocked by methotrexate. Sepiapterin and, to a lesser extent, BH4 dose dependently enhanced (IL-1 alpha + IFN-gamma)-induced NO synthesis, suggesting that the concentration of BH4 limits the rate of NO production. Inducible NO synthase mRNA and GTP cyclohydrolase I mRNA were induced by IL-1 alpha + IFN-gamma in parallel. We thus demonstrate that BH4 synthesis is an absolute requirement for induction of NO synthesis by cytokines in cardiac myocytes.

Animals↗

Expression of monocyte chemoattractant protein-1 mRNA and protein in cultured human thyrocytes.

Monocytes as well as lymphocytes infiltrate in the stroma of thyroid tissue in autoimmune and destructive thyroiditis. Monocyte chemoattractant protein-1 (MCP-1) is a cytokine that attracts T-lymphocytes as well as monocytes. Using human thyrocytes in primary cultures, we show that expression of MCP-1 mRNA and protein is remarkably stimulated by both interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), and also that interferon-gamma (IFN-gamma) by itself is a weak stimulant but has a synergistic activity with either IL-1 or TNF-alpha. The finding indicates that MCP-1 can be produced by thyrocytes themselves, suggesting a possible role of thyrocytes on accumulation of monocytes and T-lymphocytes to the tissue from the blood in autoimmune and destructive thyroiditis.

Cells, Cultured↗

Nitric oxide inhibits cell growth in cultured human thyrocytes.

Effect of NO induced by interleukin-1 (IL-1) or IL-1/interferon- gamma (IL-1/IFN-gamma) was investigated on cell growth using primary cultures of human thyrocytes. Cytokine-induced NO production was associated not only with an increase in cyclic GMP (cGMP) formation but also with an inhibition of cell growth determined by bromo-deoxyuridine (Br-dU) incorporation into DNA. When NO synthesis was blocked by NG-monomethyl-L-arginine (L-MMA), cGMP formation was prevented in parallel with NO production and inversely a restoration of cell growth was evident. S-nitroso-N-acetyl-penicillamine, a NO donor, but not a cell permeable cGMP analog, 8-bromo-cGMP, inhibited cell growth in a dose-dependent manner. The present findings strongly indicate that endogenous NO produced by the cytokine treatment as well as exogenous NO, has a cGMP-independent inhibitory action on human thyrocyte growth.

Cell Division↗