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N Yamauchi

Publications and source records attributed to N Yamauchi.

At least 19 recordsLinked to original sources
PubMed1995

Physiological concentrations of retinoic acid suppress the osteoblastic differentiation of fetal rat calvaria cells in vitro.

The effects of retinoic acid (RA) on osteoblastic differentiation and activity were studied in fetal rat calvaria cells cultured for up to 24 days. Fetal bovine serum used for the experiments was treated with an anion-exchange resin to remove endogenous RA. The depletion of RA in the treated serum was confirmed by high-performance liquid chromatography and tritiated RA tracing. Under the culture conditions employed, the continuous presence of RA for 14 days at 10(-9) mol/l or higher decreased both alkaline phosphatase (ALP) activity on day 12 and the number of bone nodules on day 14 in a dose-dependent manner. Short-term (24 h) exposure to RA at 10(-8) mol/l, which is a physiological concentration, decreased and increased the levels of ALP and osteopontin mRNA on day 6, respectively. Retinoic acid at 10(-8) mol/l also increased the level of osteocalcin mRNA on day 12. However, these effects were not obvious at later stages (days 18 and 24). At a high concentration (10(-6) mol/l), RA increased the level of osteopontin mRNA on day 6 and decreased the levels of ALP and osteocalcin mRNA irrespective of culture period. These results suggest that, at physiological concentrations, RA suppresses the differentiation of osteoprogenitor cells and regulates osteoblastic functions.

Alkaline Phosphatase↗
PubMed1994

Beta 1-adrenergic mechanism is involved in stress-induced increase in arousal.

It has been shown that 1 h restraint shortens pentobarbital (PbNa)-induced sleeping time and that brain corticotropin-releasing hormone (CRH) is involved in the mechanism by which restraint shortens. PbNa-induced sleeping time. The present study was designed to further examine the mechanism of the antagonistic effect of 1 h restraint on PbNa in rats. Intracerebroventricular (i.c.v.) administration of propranolol and metoprolol, but not butoxamine reversed the shortening of PbNa-induced sleeping time by 1 h restraint. The i.c.v. administration of phentolamine blocked the shortening of PbNa-induced sleeping time by restraint, while the same dose of phentolamine prolonged the sleeping time in unrestrained rats. Atropine did not affect the PbNa-induced sleeping time in restrained rats. These results suggest that in addition to CRH, the brain beta 1-adrenergic system is involved in the restraint stress-induced increase in arousal.

Animals↗
PubMed1992

Endogenous tumor necrosis factor functions as a resistant factor against hyperthermic cytotoxicity.

One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF by scavenging the reactive oxygen molecules. The intracellular hydroxyl radical production is also known to be involved in the heat-induced cytotoxicity. In the present study, we therefore examined the possibility that enTNF may act as a protective protein against the heat-induced cytotoxicity in a manner similar to that of exogenous TNF. Heat-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with a human TNF expression vector to produce enTNF. The stable transfectants showed apparent resistance to heat treatment. Conversely, when HeLa (human uterine cervical cancer) cells, originally producing an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced. Furthermore, L-M cells which were transfected with nonsecretory human TNF expression vector also acquired resistance to heat treatment. In these cells, heat resistance correlated well with expression of enTNF and intracellular levels of manganous superoxide dismutase. These results indicate that enTNF exerts its intracellular protective effect against the heat-induced cytotoxicity by scavenging reactive oxygen with induced manganous superoxide dismutase in a manner similar to that found in cells treated with exogenous TNF.

Animals↗
PubMed1992

Endogenous tumor necrosis factor exerts its protective function intracellularly against the cytotoxicity of exogenous tumor necrosis factor.

Based on the findings that expression of endogenous tumor necrosis factor (enTNF), which is not present in TNF-susceptible cells, was generally observed in TNF-resistant cells and that TNF gene transfection gives rise to TNF resistance, the assumption was made that enTNF may be a protective protein against the cytotoxicity of exogenous TNF. However, it remains unknown whether the protection by enTNF is exerted in an intracellular or extracellular (autocrine) manner. We therefore transfected a nonsecretory human TNF gene (pTNF delta pro) into highly TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) and investigated their TNF susceptibility. The transfectants expressed enTNF which was not secreted into the medium and acquired an appreciable degree of resistance to exogenous TNF. A significant increase in the manganous superoxide dismutase level was also noted in the transfectants. These findings suggest that enTNF exerts its protective function intracellularly by inducing manganous superoxide dismutase production.

Animals↗
PubMed1992

Induction of synthesis of manganous superoxide dismutase in L-M(pNTnF) cells carrying an inducible TNF gene.

Based on findings that the cytotoxic effects of tumor necrosis factor (TNF) are closely related to levels of intracellular oxygen radicals, and on the results of TNF gene transfection studies, the hypothesis was made that endogenous TNF (enTNF) acts as a protective factor against exogenous TNF by inducing inhibitors or scavengers of oxygen radicals. In order to test this hypothesis, we investigated the intracellular levels of manganous superoxide dismutase (MnSOD) and glutathione (GSH) in L-M(pNTnF) cells carrying a TNF gene induced by dexamethasone (DM). When L-M(pNTnF) cells were treated with DM they expressed enTNF, and acquired resistance to exogenous TNF. There was no change in the GSH concentration after enTNF induction, but a 1.9- to 3.9-fold increase in MnSOD levels was noted. Our findings suggest that enTNF exerts its protective function against the cytocidal effect of exogenous TNF by inducing MnSOD production.

Animals↗
PubMed1992

The role of 5'-methylthioadenosine on rat calvaria cell differentiation.

The role of 5'-methylthioadenosine (MTA), formed during the process of polyamine biosynthesis, on differentiation of osteoprogenitor cells was assessed by its effects on alkaline phosphatase (ALP) activity, bone nodule formation and osteopontin contents of cultured rat calvaria (RC) cells. These three markers were stimulated by exogenous MTA and were depressed by 5'-difluoromethylthioadenosine (DFMTA), a synthetic inhibitor of MTA phosphorylase, which cleaves MTA to adenine and 5-methylthioribose-1-phosphate. 5-Methylthioribose and 2-keto-4-methylthiobutyrate, metabolites of 5-methylthioribose-1-phosphate, had no effects on ALP activity and bone nodule formation in the presence or absence of DFMTA. On the other hand, adenine enhanced ALP activity, bone nodule formation and osteopontin contents in mineralized nodules and also partially reversed DFMTA-induced inhibition of these three markers. MTA, its metabolites and DFMTA did not affect the growth of RC cells under these culture conditions. These results suggest that adenine formed from MTA is important in the differentiation of RC cells.

Adenine↗
PubMed1992

Enhancement of lysosomal enzyme activity by recombinant human tumor necrosis factor and its role in tumor cell killing in vitro.

We investigated the effect of recombinant human tumor necrosis factor (TNF) on the lysosomal enzyme activity of various established cell lines in vitro. Incubation of 1 x 10(6) TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) in the presence of TNF (100 U/ml) for 48 h increased the total (the sum of the enzyme activities in the lysosomes and the cytoplasm) acid phosphatase and beta-glucuronidase activities by 3.7- and 4.2-fold, respectively. The same increase was observed even when 1 U/ml of TNF was added to some cultures and no further augmentation occurred at 10 or 100 U/ml. Measurement of total and free enzyme activities showed that TNF stimulation not only enhanced the total intracellular enzyme activity but also accelerated the conversion into free (cytoplasmic) enzyme activity. Addition of a lysosomotropic agent (methylamine) suppressed both the enhancement of lysosomal enzyme activity and the cytotoxicity of TNF. A similar enhancement of lysosomal enzyme activities was also detected in various TNF-sensitive tumor cell lines, and a strong correlation (acid phosphatase: r = 0.836, beta-glucuronidase: r = 0.910) was observed between the enhancement of enzyme activity and sensitivity to TNF. No such increase was detected in TNF-resistant human diploid cells. These results show that TNF induces the activation and release of lysosomal enzymes in TNF-sensitive cells, and suggest that such events may play an important role in TNF-mediated cytotoxicity.

Acid Phosphatase↗
PubMed1992

Mechanism of synergistic cytotoxic effect between tumor necrosis factor and hyperthermia.

We previously reported that recombinant human tumor necrosis factor (rhTNF) and hyperthermia had a synergistic effect against tumors, in vitro and in vivo. We have now investigated the mechanism of this synergy by measuring the lysosomal enzyme activity and hydroxyl radical production of L-M cells treated with rhTNF and/or hyperthermia. A synergistic activation of lysosomal enzyme and the induction of hydroxyl radical production in L-M cells treated with both rhTNF and hyperthermia was observed. A synergistic cytotoxic effect was observed when rhTNF and hyperthermia were combined, and was inhibited by the addition of a reactive oxygen scavenger, dimethyl sulfoxide or bipyridine. The results show that the augmenting effect of hyperthermia on lysosomal enzyme activation and induction of hydroxyl radical production by rhTNF plays an important role in the synergistic cytotoxic effect.

Acid Phosphatase↗
PubMed1992

Serum tumor necrosis factor activity in inflammatory bowel disease.

Serum tumor necrosis factor (TNF) levels in 33 patients with inflammatory bowel disease (IBD) were measured by using a sensitive enzyme immunoassay. Four of five Crohn's diseases (CD) and nine of twenty eight ulcerative colitis (UC) had elevated levels of serum TNF. In active CD or UC, a greater fraction of patients studied had significantly increased serum TNF levels (3/3 for CD and 8/11 for UC). Production of TNF by peripheral blood monocytes when stimulated by lipopolysaccharide was also increased in these patients and correlated with their serum TNF levels. These results suggest that TNF may have some pathoetiological meaning in IBD.

Adult↗
PubMed1992

Biochemical studies on 2-deoxy-scyllo-inosose, an early intermediate in the biosynthesis of 2-deoxystreptamine. I. Chemical synthesis of 2-deoxy-scyllo-inosose and [2,2-2H2]-2-deoxy-scyllo-inosose.

A practical preparative method for 2-deoxy-scyllo-inosose, the earliest key intermediate leading to 2-deoxystreptamine, was devised as a prerequisite to more detailed biochemical studies on the biosynthesis of 2-deoxystreptamine. [2,2-2H2]-2-Deoxy-scyllo-inosose was also synthesized through a modified Ferrier reaction.

Anti-Bacterial Agents↗
PubMed1992

Biochemical studies on 2-deoxy-scyllo-inosose, an early intermediate in the biosynthesis of 2-deoxystreptamine. II. Quantitative analysis of 2-deoxy-scyllo-inosose.

A practical quantitative analysis of 2-deoxy-scyllo-inosose by means of GC-MS selected-ion monitoring (SIM) was exploited in order to assay the enzymatic 2-deoxy-scyllo-inosose formation, the first stage of the 2-deoxystreptamine biosynthesis. Mass spectral fragmentations of 2-deoxy-scyllo-inosose tetra-O-trimethylsilyl (TMS) ether was also investigated by the use of [2,2-2H2]-2-deoxy-scyllo-inosose.

Anti-Bacterial Agents↗
PubMed1992

[Use of the newly designed long-handled forceps for respiratory surgery].

We report on use of the newly designed long-handled forceps for respiratory surgery. The forceps have a curved-end in the same plane as its handles. This contributes to the easier clamping of vessels running horizontally in the deep fields. It is very useful not only in thoracic surgery, such as respiratory and esophageal surgery, but also in pelvic surgery.

Equipment Design↗
PubMed1991

Brain corticotropin-releasing hormone increases arousal in stress.

The effect of restraint stress on pentobarbital-induced sleeping time was examined in rats. Restraint for 60 and 75 min significantly shortened pentobarbital-induced sleeping time. The shortening of sleeping time by restraint was completely reversed by intracerebroventricular (i.c.v.) administration of alpha-helical CRH(9-41), a corticotropin-releasing hormone (CRH) receptor antagonist. In conjunction with our previous finding that i.c.v. administration of CRH shortens pentobarbital-induced sleeping time, the results suggest that restraint stress increases arousal through brain CRH.

Animals↗
PubMed1991

In vitro release of growth hormone-releasing factor (GRF) from the hypothalamus: somatostatin inhibits GRF release.

The manner of release of growth hormone-releasing factor (GRF) from the rat hypothalamus was studied in a perifusion system using a highly sensitive radioimmunoassay for rat GRF. The recovery of GRF in this system was 50-60%. The release of GRF from the rat hypothalamic blocks was almost stable for 20-240 min after the start of the perifusion and was stimulated by depolarization induced by high K+ concentration. The release of GRF was inhibited by somatostatin at concentrations of 10(-11) to 10(-8) M with maximum inhibition to 52.5% of the basal release at a concentration of 10(-9) M. These results suggest that this system is useful in studying the regulatory mechanism of GRF release and that, in addition to its action on the pituitary, somatostatin appears to act at the level of the hypothalamus in inhibiting GRF release in the regulation of GH secretion.

Animals↗
PubMed1991

Successful treatment of a case of hepatocellular carcinoma with tumor necrosis factor and local hyperthermia.

A case of unresectable hepatocellular carcinoma which responded favorably to combined therapy with tumor necrosis factor (TNF) and local hyperthermia is reported. A 58-year-old man was admitted to our hospital in June 1988 for treatment of hepatocellular carcinoma affecting S4 and S8. After three sessions of transcatheter arterial embolization (TAE) therapy, the serum alpha 1-fetoprotein level decreased, and a reduction in the size of the lesions was also noted. Thereafter, the patient received local hyperthermia once a week (60 minutes of irradiation from a Thermotron-RF8 at 1,100W), but the alpha 1-fetoprotein level increased again in February 1989. On examination, enlargement of the S8 lesion and a new nodule in S7 were recognized. Since TAE was contraindicated due to liver dysfunction, human recombinant TNF (1 x 10(6)U) was given by intravenous infusion together with local hyperthermia once a week. Eight sessions of the combined therapy reduced the serum alpha 1-fetoprotein level markedly (7,512.0 to 2,782.0 pg/ml) and after eighteen sessions, 58.1% regression of tumor size (partial response) on computed tomography scans was observed. This anecdotal case supports previous experimental evidence suggesting that TNF plus hyperthermia may be effective for treating unresectable hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1991

The effects of chronic central administration of corticotropin-releasing factor on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones.

The effects of chronic central administration of corticotropin-releasing factor (CRF) on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones were investigated in rats. The infusion of ovine CRF at doses of 0.3 and 1.0 microgram/h continuously induced decrease in food intake and a suppression of body-weight gain for 7 days. The inhibition of body weight gain induced by CRF could not be accounted for solely by a decreased food intake since the suppression of body-weight gain in CRF-infused rats was significantly greater than that observed in rats which received the same amount of food as the CRF-infused rats. The content of proopiomelanocortin (POMC) -derived peptides in the anterior lobe of the pituitary as well as the plasma levels of ACTH and corticosterone (B) were significantly elevated in CRF-treated rats, and the CRF content in the hypothalamus was significantly decreased. These results suggest that chronic intracerebroventricular (icv) administration of CRF stimulates the synthesis and secretion of POMC-related peptides in the pituitary and suppresses food intake accompanied by inhibition of body weight gain. The results are similar to clinical and laboratory findings observed in patients with stress-induced anorexia.

Adrenocorticotropic Hormone↗
PubMed1991

Interleukin-1 inhibits stress-induced gastric erosion in rats.

The effect of interleukin (IL)-1 on the occurrence of stress-induced gastric erosions was examined in rats. The intracerebroventricular (icv) administration of IL-1 beta significantly inhibited the occurrence of water-immersion restraint stress-induced gastric erosion at doses of 200 ng, 500 ng and 1 microgram, whereas the intravenous (iv) administration of IL-1 beta altered the occurrence of gastric erosion only at a dose of 1 microgram. The inhibitory effect of IL-1 alpha icv administered on the occurrence of gastric erosion was found only at a dose of 1 microgram. The inhibitory effect of IL-1 beta icv administered on the occurrence of stress-induced gastric erosion was not influenced by icv administration of alpha-helical CRF(9-41), a corticotropin-releasing factor (CRF) receptor antagonist. Indomethacin completely blocked the inhibitory action of IL-1 beta icv administered on stress-induced gastric erosion. It is concluded from these results that IL-1 acts mainly in the central nervous system to inhibit the occurrence of stress-induced gastric erosion and that the IL-1 beta-induced inhibition of gastric erosion is mediated by prostaglandin in a manner that is independent of brain CRF.

Animals↗