Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 253 records · Page 14Linked to original sources

PubMed1998

Metallothionein deficiency promotes mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.

To investigate a possible involvement of metallothionein (MT) in chemical carcinogenesis, MT-I and MT-II gene-deficient [MT (-/-)] transgenic mice and wild-type [MT (+/+)] control mice were topically applied at a single dose of 100, 250, 500, or 1000 microg of 7,12-dimethylbenz[a]anthracene (DMBA) on the dorsal skin and thereafter compared. After 14 weeks of DMBA treatment, the skin tumor occurred in MT (-/-) mice only and in a dose-dependent manner, whereas no change was observed in MT (+/+) mouse skin given the same DMBA treatment. The tumor cells showed proliferative activity, as shown by proliferative cell nuclear antigen staining. These results demonstrate that MT acts as an endogenous defensive factor against DMBA-induced skin tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus.

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.

Animals↗

PubMed1998

Cancer-associated expression of glycolipid sulfotransferase gene in human renal cell carcinoma cells.

Human renal cell carcinoma (RCC) tissue and a cell line derived therefrom, SMKT-R3, showed markedly increased glycolipid sulfotransferase [cerebroside sulfotransferase (CST); EC 2.8.2.11] activity and accumulated sulfoglycolipids. Recently, we cloned a human CST cDNA from a SMKT-R3 cDNA library (K. Honke et al., J. Biol. Chem., 272: 4864-4868, 1997). In this study, we investigated the expression of the CST gene in seven human RCC lines (SMKT-R1, SMKT-R2, SMKT-R3, SMKT-R4, TOS-1, TOS-2, and ACHN) and their normal counterpart, human renal proximal tubular cells. On Northern blot analysis, a marked increase of CST mRNA was observed in every RCC line, except for ACHN, as compared with normal cells. ACHN cells showed a slightly increased level of CST mRNA. CST activity was correlated with the amount of mRNA. Sulfoglycolipid analysis revealed that expression of lactosylceramide sulfate was correlated with the CST level. Furthermore, we examined the effects of epidermal growth factor (EGF), tetradecanoylphorbol-13-acetate, and genistein, which are known to regulate CST activity in SMKT-R3 cells, on CST-gene expression in various RCC cells. On treatment with EGF, CST mRNA time-dependently increased in accord with its activity in SMKT-R3 cells. Yet, augmentation by EGF was only observed in SMKT-R3. In contrast, a reduction of CST mRNA and activity by tetradecanoylphorbol-13-acetate and genistein was observed in all of the lines examined. Taken together, these findings indicate that in human RCC cells, the CST gene is generally overexpressed via a signaling pathway involving protein kinase-C and tyrosine kinases.

Carcinoma, Renal Cell↗

PubMed1998

Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a).

We studied the effect of beta-casomorphin-5 (mu-acting opioid peptides derived from milk protein beta-casein) on neurite outgrowth of mouse neuroblastoma cell line, Neuro-2a. Beta-casomorphin-5 stimulated neurite outgrowth of Neuro-2a cells in a naloxone-reversible manner. The stimulating effect of beta-casomorphin-5 was observed even at picomolar concentrations. The selective mu-agonist, (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) exhibited the similar stimulating effect only at micromolar concentrations. On the other hand, (D-Pen(2,5))-enkephalin (DPDPE) (a delta-agonist), U-50,488 (a kappa-agonist), and endogenous opioid peptides, such as enkephalins and dynorphin A (1-13), showed no such stimulating effect. These results suggest that the neurite outgrowth-stimulating action of beta-casomorphin-5 may be mediated via a receptor which has mu-like characteristics and high sensitivity to beta-casomorphin-5, and that beta-casomorphins may play a role as a neurite elongation factor during the suckling period.

Animals↗

PubMed1998

Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells.

The expression of the mRNAs for stromal cell-derived factor-1alpha and -1beta (SDF-1alpha and -1beta) and their receptor CXCR4 in cultured rat glial and neuronal cells was examined. SDF-1alpha mRNA was expressed intensely in astrocytes and weakly in neurons, but not in microglia. SDF-1beta mRNA was expressed weakly in these three types of cells. The expressions of SDF-1alpha and -1beta mRNAs in astrocytes were decreased by treatment with LPS (100 ng/ml) for 1-6 h but markedly increased by that for 24-72 h, whereas the expression of SDF-1beta mRNA in microglia was hardly changed by the treatment for 0.5-6 h, and was decreased by that for 24-48 h. The expression of CXCR4 mRNA was observed in astrocytes, microglia and neurons, and was not altered by LPS treatment.

Animals↗

PubMed1998

Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia?

Localization of the mRNAs for fractalkine, a CX3C chemokine, and for its receptor CX3CR1 was investigated in the rat brain. In situ hybridization study revealed that fractalkine mRNA was dominantly expressed in neuronal cells particularly in the olfactory bulb, cerebral cortex, hippocampus, caudate putamen and nucleus accumbens. In vitro study using enriched neuronal or glial culture supported the dominant expression of fractalkine mRNA in neurons. On the other hand, CX3CR1 mRNA was dominantly expressed in glial cells throughout the whole brain. The in vitro study suggested the cells expressing CX3CR1 mRNA are microglia, not astrocytes or neurons. Fractalkine appears to function as a signal molecule from neuron to microglia.

Amino Acid Sequence↗

PubMed1998

DAMGO recognizes four residues in the third extracellular loop to discriminate between mu- and kappa-opioid receptors.

Previously, we reported that replacement of the region from the fifth transmembrane domain to the C-terminus of kappa-opioid receptor with the corresponding region of mu-opioid receptor gives high affinity for [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), a mu-opioid receptor-selective ligand, to the resultant chimeric receptor, suggesting that the difference in the amino acid sequence within this region is critical for the discrimination between mu- and kappa-opioid receptors by DAMGO. In the present study, we constructed further six mu/kappa-chimeric receptors and revealed that at least two separate regions around the third extracellular loop are critical for the discrimination between mu- and kappa-opioid receptors by DAMGO. Furthermore, we constructed several mutant receptors by a site-directed mutagenesis technique and found that the difference between Glu297 of kappa-opioid receptor and Lys303 of mu-opioid receptor in one region, and the difference between Ser310, Tyr312 and Tyr313 of kappa-opioid receptor and Val316, Trp318 and His319 of mu-opioid receptor in the other region, are critical for the discrimination between these receptors by DAMGO. The mutant receptor, kappa (E297K + Y313H + Y312W + S310V), in which the Glu297, Ser310, Tyr312 and Tyr313 of kappa-opioid receptor were changed to Lys, Val, Trp and His, respectively, bound to DAMGO with high affinity (Kd = 8.7 +/- 1.2 nM) and efficiently mediated the inhibitory effect of DAMGO on intracellular cAMP accumulation. The present results showed that these four amino acid residues act as determinants for the discrimination between mu- and kappa-opioid receptors by DAMGO.

Adenylyl Cyclases↗

PubMed1998

Intracellular Ca2+ store-operated influx of Ca2+ through TRP-R, a rat homolog of TRP, expressed in Xenopus oocytes.

To elucidate whether rat transient receptor potential (TRP-R), a rat TRP4 homolog, functions as a store-operated Ca2+ channel (SOC), we have measured the Ca2+ entry after thapsigargin treatment in Xenopus oocytes injected with mRNA for TRP-R. While non-injected oocytes elicited an SOC response, significantly larger responses were observed in the oocytes expressing TRP-R. The oocyte-native SOC response was inhibited by injection of antisense oligodeoxyribonucleotide for mammalian TRP1. When Ca2+ concentration-SOC response curve was examined, the EC50 value was much smaller in oocytes expressing TRP-R than that of non-injected oocytes. These results suggest that TRP-R functions as SOC having higher sensitivity to external Ca2+ than amphibian TRP1 channel.

Animals↗

PubMed1998

FK960, a novel potential anti-dementia drug, augments long-term potentiation in mossy fiber-CA3 pathway of guinea-pig hippocampal slices.

Our previous studies have demonstrated that FK960 (FR59960; N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate), a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various animal models of amnesia in rats [M. Yamazaki, N. Matsuoka, N. Maeda, Y. Ohkubo, I. Yamaguchi, FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action, J. Pharmacol. Exp. Ther., 279 (1996) 1157-1173.] and in rhesus monkeys [N. Matsuoka, T.G. Aigner, FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine, J. Pharmacol. Exp. Ther., 280 (1997) 1201-1209]. To clarify the synaptic mechanisms of its antiamnesic action, FK960 was investigated for its effects on the development of long-term potentiation (LTP) in guinea-pig hippocampal slices. The magnitude of LTP of population spike recorded in CA3 pyramidal neurons was significantly augmented by perfusing FK960 (10-9-10-6 M) for 25 min before and during tetanic stimulation of the mossy fibers, whereas the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10-7 M. Scopolamine (10-6 M) per se had little effect on the magnitude of LTP in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FK960 (10-7 M). In hippocampal slices from animals treated with cysteamine (200 mg/kg, s.c.), which was shown to deplete the hippocampal somatostatin, FK960 (10-7 M) hardly affected the LTP. These results suggest that FK960 enhances the magnitude of LTP in the mossy fiber-CA3 pathway through an activation of the cholinergic-somatostatinergic link in the hippocampal formation. Furthermore, it can be postulated that the drug regulates the cognitive function by modulating directly synaptic plasticity in the hippocampal neuronal network.

Analysis of Variance↗

PubMed1998

Regional differences in alpha1-adrenoceptor subtypes and mechanisms in rabbit arteries.

Contractility mediated through alpha1-adrenoceptor subtypes and the maximum binding site (Bmax value) and the dissociation constant (Kd value) for [125I]HEAT ([125I]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca2+-free physiological saline solution (Ca2+-free PSS), the pA2 values for 5-methylurapidil were also similar except for the renal artery, in which there were no stable contractions. In normal PSS, the concentration-response curves for norepinephrine with chloroethylclonidine-pretreatment were shifted to the right (pD2 values of 5.58, 5.70, 5.74, 5.98 and 6.38 for thoracic and abdominal aorta, mesenteric, renal and iliac arteries, respectively). In the [125I]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the Bmax values (33.2-105.2 fmol/mg protein) for [125I]HEAT varied considerably among arteries, while the Kd values (0.20-0.26 nM) were identical. The logarithm of Bmax values is proportional to the pD2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (pD2 value) of the alpha1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha1-adrenoceptor subtypes in rabbit arteries.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1998

Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina.

This study was performed to examine the roles of body temperature, NMDA receptors and nitric oxide (NO) synthase in post-ischemic retinal injury in rats. Cell loss in the ganglion cell layer and thinning of the inner plexiform layer were observed 7 days after ischemia. Cell loss in the ganglion cell layer but not thinning of the inner plexiform layer was reduced by hypothermia during ischemia. Intravenous injection of dizocilpine (MK-801) or Nomega-nitro-L-arginine methyl ester (L-NAME) prior to ischemia ameliorated retinal injury. These results suggest that activation of NO synthase following NMDA receptor stimulation is involved in ischemia-induced retinal injury.

Animals↗

PubMed1998

Metallothionein-mediated resistance to multiple drugs can be induced by several anticancer drugs in mice.

We examined the role of metallothionein in the chemosensitivity of transplanted tumors in mice. The antitumor activities of cisplatin, adriamycin, bleomycin, peplomycin, cyclophosphamide, and melphalan were significantly suppressed when the concentration of metallothionein in the tumor was increased to only twice the control level. On the other hand, the antitumor activities of mitomycin C, 5-fluorouracil, and vinblastine were hardly affected by increases in the concentration of metallothionein in the tumors in mice. Moreover, all the antitumor drugs examined increased the concentration of metallothionein in transplanted tumors to a level that was high enough to suppress the antitumor activity of these drugs. These observations suggest that treatment of patients with certain antitumor drugs might result in the resistance of their tumors to multiple drugs.

Animals↗

PubMed1998

Involvement of NK1+ T cells and their IFN-gamma production in the generalized Shwartzman reaction.

IL-12 (or LPS) priming and subsequent challenge by LPS produces the generalized Shwartzman reaction. IFN-gamma induced by IL-12 is a crucial cytokine in the priming phase. In vivo depletion of both NK cells and NK1+ alphabeta T cells of mice by anti-NK1.1 Ab greatly reduced the elevation of serum IFN-gamma induced by IL-12 and significantly reduced mortality after subsequent injection of LPS, whereas depletion of NK cells alone by anti-asialo GM1 Ab only partially decreased serum IFN-gamma, and lethality was not changed. Cell sorting and culture experiments confirmed that liver NK1+ alphabeta T cells of IL-12-injected mice produced greater amounts of IFN-gamma than did liver NK cells. MHC class I-deficient mice of C57BL/6 background, which lack a majority of NK1+ alphabeta T cells, produced low amounts of IFN-gamma by IL-12; no mortality was observed after the LPS challenge. However, production of TNF-alpha in the second phase (after LPS challenge) was not inhibited by depletion of NK cells alone or both subsets. IL-12 and subsequent LPS challenge activated NK1+ alphabeta T cells in the liver and induced strong cytotoxicity of these cells not only against tumor cells (including Fas-negative tumors) but also against a syngeneic hepatocyte cell line. Our findings show that IFN-gamma produced by NK1+ alphabeta T cells is essential for the IL-12 priming of the Shwartzman reaction, and the autoreactivity of NK1+ alphabeta T cells in the liver is involved in the hepatic disorders that are sometimes caused by IL-12, LPS, or the generalized Shwartzman reaction.

Adjuvants, Immunologic↗

PubMed1998

Involvement of dendritic adhesion molecule telencephalin in hippocampal long-term potentiation.

Telencephalin (TLCN) is a cell adhesion molecule belonging to the immunoglobulin superfamily whose expression is restricted to neurons within the most highly developed brain segment, telencephalon. Immunoelectronmicroscopic study revealed that in the hippocampal CA1 region, TLCN was localized at the surface membrane of postsynaptic spines of pyramidal cell dendrites but not at that of axonal terminals. Blocking of TLCN function using anti-TLCN antibody or recombinant soluble TLCN protein caused a striking suppression of the long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses. The suppression was observed even when the blocking was initiated immediately after the tetanic stimuli. These observations suggest a role for TLCN-mediated cell-cell interactions as a key step in the development of LTP.

Animals↗

PubMed1998

Generation of a monoclonal antibody that induces apoptosis of hematopoietic cells.

Here, we developed anti-murine myeloid cell (NFS-60 cell) monoclonal antibodies in order to characterize the further mechanism of cell-to-cell interaction between the stromal cells and the hematopoietic progenitor cells. The established antibody, designated mAb UNF, inhibited proliferation of NFS-60 cells and induced apoptosis. Incubation of NFS-60 cells with mAb UNF initiated the cell aggregation within 3 hours. This phenomena did not require newly synthesized proteins, since the pretreatment of 1 mM cycloheximide failed to prevent the agglutination. Fifty-eight percent of mouse hematopoietic stem cells, Lin-, c-Kit+, Sca-1+ bone marrow cells, were shown to express UNF antigen. The glycolipid prepared from NFS-60 cells was specifically immunostained by mAb UNF.

Animals↗

PubMed1998

Radiotherapy for Kimura's disease: the optimum dosage.

PURPOSE: To evaluate retrospectively the optimum dosage of irradiation for Kimura's disease. METHODS AND MATERIALS: Twenty patients with Kimura's disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS: At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS: Radiotherapy is an effective treatment for Kimura's disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

Adolescent↗

PubMed1998

A comparative analysis of the proteins between the fibroblasts from Werner's syndrome patients and age-matched normal individuals using two-dimensional gel electrophoresis.

Werner's syndrome (WS) is an autosomal recessive disorder causing symptoms of premature aging. The fibroblasts of WS patients have a shorter life-span than normal fibroblasts. We analyzed the fibroblast proteins from three WS patients and from three age-matched normal individuals using two-dimensional gel electrophoresis and image processing. The expressions of 12 proteins were shown to be augmented or suppressed in WS fibroblasts compared with normal fibroblasts: 11 of 12 spots on the electrophoresis gel of WS fibroblasts were denser than the corresponding spots of normal individual fibroblasts, while the remaining one spot was fainter in WS fibroblasts than in normal fibroblasts. The abundance of these proteins were compared to those of the corresponding proteins from normal fibroblasts at various cell passages in vitro reported in the TMIG-2DPAGE database. The result shows that the change in the protein patterns in in vitro aging did not necessarily correspond to the change in WS fibroblasts, except for three proteins abundant in WS fibroblasts, which increased their abundance during in vitro aging. These results suggest that the premature aging process of WS fibroblasts shares only part of the in vitro aging process of normal fibroblasts.

Adult↗

PubMed1998

Catheterization of the pulmonary artery using a 3 French catheter in patients with congenital heart disease.

A 3 French (3F) coaxial polyurethane catheter was utilized for catheterization of the pulmonary artery in patients with complex congenital heart disease with concomitant stenosis or atresia of the pulmonary valve, with or without Blalock-Taussig shunts. Mean aortic and atrial pressures measured with the 3F catheter were compared with those measured with 5-6F conventional catheters. The values measured with the 3F catheter were identical to those measured with 5-6F catheters. Mean pulmonary arterial pressure measured using the 3F catheter was significantly higher than that measured using the 5-6F catheters, but it was not significantly different from mean pulmonary venous wedge pressure. Of 43 patients, 5-6F conventional catheters could be inserted into the branch pulmonary artery in 22 patients, but the 3F catheter could be inserted into the pulmonary artery in all patients. These data suggest that the 3F catheter is useful for catheterization in patients with complex congenital heart disease associated with pulmonary atresia or severe pulmonary stenosis.

Adolescent↗