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Biomedical subjects

N Yamauchi

Publications and source records attributed to N Yamauchi.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

Genomic organization and chromosomal localization of the human CTP synthetase gene (CTPS).

To elucidate the organization of the human genomic sequences encoding CTP synthetase (CTPS), fragments homologous to the cDNA were isolated from genomic lambda libraries. The fragments cloned were overlapping and cover over 40 kb. Cotransfection of the DNAs into CTPS-deficient, cytidine-requiring CHO mutants can transform them to cytidine-independent growth, indicating that the complete structural gene has been isolated. Direct sequencing and enzymatic amplification of the cloned genomic fragments revealed that the coding sequences are distributed to 19 exons covering about 35 kb. Multiple transcriptional start sites were detected by primer extension in a G + C-rich 5' flanking sequence that is separated from the translational start by an approximately 3-kb intron. A panel of human-rodent somatic cell hybrids and the CTPS cDNA were used to assign the structural gene to the short arm of human chromosome 1. This assignment was further refined through the use of somatic cell hybrids bearing fragments of the short arm of the chromosome, allowing localization to 1p36.11-p31, a region notable for its disruption in many types of tumors.

Animals↗
PubMed1991

Establishment and biochemical properties of cis-diamminedichloroplatinum(II)-resistant A549 lung cancer cells.

A 6.2-fold cis-diamminedichloroplatinum(II) (CDDP) resistant human lung cancer cell line (A549/CDDP5), which was capable of proliferating in the presence of 5 microM CDDP, was developed. Compared to the parent cell line, A549/CDDP5 subline had a significantly longer doubling time, increased population of S phase, enhanced sensitivity to 5-FU and elevated activities of dTMP synthase (EC 2.1.1.45) and thymidine kinase (EC 2.7.1.21) by 5.4- and 2.0-fold of the parent cells. These results suggest that the capacity of dTMP synthesis might have an important role in the acquisition of CDDP resistance of A549 cells.

Cell Division↗
PubMed1990

Suppressive effects of intracellular glutathione on hydroxyl radical production induced by tumor necrosis factor.

Protective effects of intracellular glutathione (GSH) against the cytotoxicity of human recombinant tumor necrosis factor (TNF) were investigated. Three tumor cell lines (L-M, B-16, HeLa) were used as target cells. Exposure of these cells to buthionine sulfoximine (BSO) or diethyl maleate (DEM) resulted in the depletion of intracellular GSH content to 5.2-43.0% of control values and enhancement of their susceptibility to TNF cytotoxicity. The hydroxyl radical production in L-M cells stimulated by TNF was increased by treatment with BSO or DEM. These results are consistent with the suggestion that intracellular GSH exerts its protective function against the cytocidal effect of TNF by inhibiting the hydroxyl radical production stimulated by TNF.

Animals↗
PubMed1990

Insulin-induced hypoglycemia, L-dopa and arginine stimulate GH secretion through different mechanisms in man.

We sought to clarify the mechanisms of growth hormone (GH) secretion induced by insulin hypoglycemia, L-dopa, and arginine in man. The secretion of GH as measured by increased plasma level, in response to oral administration of 500 mg L-dopa or 30 min-infusion of arginine, was not modified by prior intravenous administration of 200 micrograms GH-releasing hormone (GHRH). It was, however, completely blocked by preadministered 50 micrograms SMS201-995, a long-acting somatostatin (SRIH) analog. GH release with 200 micrograms GHRH was completely blocked by 100 micrograms SMS201-995. GH secretion caused by insulin-induced hypoglycemia was significantly reduced but still present after administration of 100 micrograms of the analog. These results suggest that a suppression of SRIH release may be partially involved in the stimulatory mechanism of GH secretion by L-dopa. Coadministration of GHRH accentuated the stimulatory effect of arginine on GH secretion. Arginine significantly raised plasma TSH levels. These findings suggest that arginine suppresses SRIH release from the hypothalamus to cause GH secretion because SRIH suppresses TSH secretion. It is also suggested that some factor (or factors) other than GHRH and SRIH are involved in the mechanism by which insulin-induced hypoglycemia stimulates GH secretion, because the effect of insulin was not fully blocked in the presence of SRIH analog. Thus all the tests for GH release appear to act via different mechanisms.

Adult↗
PubMed1990

Expression of endogenous tumor necrosis factor as a protective protein against the cytotoxicity of exogenous tumor necrosis factor.

Based on the finding that expression of endogenous tumor necrosis factor (TNF) which is not detected in TNF-susceptible cells was observed in TNF-resistant cells, the assumption was made that endogenous TNF may be a protective protein against the cytotoxic activity of TNF. In order to confirm this possibility, we investigated the relationship between expression of endogenous TNF and TNF susceptibility by using the gene transfection method. When L-M, TNF-highly sensitive murine fibrosarcoma cells were transfected with a human TNF gene, the stable transfectants expressed endogenous TNF and acquired resistance to TNF. Conversely, when endogenous TNF synthesis was inhibited by introducing an antisense TNF gene into HeLa, TNF-less sensitive human cervical cancer cells, the sensitivity was enhanced. These findings indicate that endogenous TNF is one of the protective factors against the cytotoxic activity of TNF.

Animals↗
PubMed1990

Identification of 17-hydroxyprogesterone and other steroid hormones in saliva from a normal child and patients with congenital adrenal hyperplasia by plasmaspray liquid chromatography/mass spectrometry.

A very sensitive, selective and simultaneous method for the analysis of salivary steroid hormones was examined by discharge-assisted thermospray liquid chromatography mass spectrometry (plasmaspray LC/MS). Plasmaspray LC/MS gave [M + H]+ or [MH - H2O]+ as a predominant ion in most of the steroids in this work and in some cases fragment ions were also observed. Eight salivary steroid hormones, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, aldosterone, and testosterone were identified within 10 minutes using the selected ion monitoring technique in conjunction with plasmaspray LC/MS. Progesterone, 17-hydroxyprogesterone, cortisol, aldosterone and testosterone were detected in 1 mL of saliva from a normal child and two patients with congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Molecular cloning of the human CTP synthetase gene by functional complementation with purified human metaphase chromosomes.

Successive rounds of chromosome-mediated gene transfer were used to complement a hamster cytidine auxotroph deficient in CTP synthetase activity and eventually to clone human genomic and cDNA fragments coding for the structural gene. Our approach was to isolate human Alu+ fragments from a tertiary transfectant and to utilize these fragments to screen a panel of primary transfectants. In this manner two DNA fragments, both mapping within the structural gene, were identified and used to clone a partial length cDNA. The remaining portion of the open reading frame was obtained through the RACE polymerase chain reaction technique. The open reading frame encodes 591 amino acids having a striking degree of similarity to the Escherichia coli structural gene (48% identical amino acids with 76% overall similarity including conservative substitutions) with the glutamine amide transfer domain being particularly conserved. As regulatory mutations of CTP synthetase confer both multi-drug resistance to agents widely used in cancer chemotherapy and a mutator phenotype, the cloning of the structural gene will be important in assessing the relevance of such phenotypes to the development of cellular drug resistance.

Amino Acid Sequence↗