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Biomedical subjects

N Yamauchi

Publications and source records attributed to N Yamauchi.

At least 109 records · Page 6Linked to original sources
PubMed1990

Brain corticotropin-releasing factor acts as inhibitor of stress-induced gastric erosion in rats.

Gastric lesions are known to be caused by stress. Corticotropin-releasing factor (CRF) is a key peptide initiating various stress response. This study was designed to investigate how brain CRF is involved in the occurrence of stress-induced gastric erosion in rats. Intracerebroventricular (icv) administration of CRF suppressed the occurrence of gastric erosion induced by water-immersion restraint stress, and its suppressive effect was blocked by coadministration of a CRF receptor antagonist in rats. The peripheral administration of CRF had no influence on the occurrence of erosion. The icv administration of a CRF receptor antagonist or anti-rat CRF gamma-globulin increased gastric erosion induced by the stress. Ganglionic blockade with chlorisondamine, muscarinic blockade with atropine, or bilateral adrenalectomy by itself significantly inhibited the occurrence of stress-induced gastric erosion, and no additional effect of CRF on these treatments-induced inhibition of erosion was found. These results, therefore, suggest that the occurrence of stress-induced gastric erosion is mediated by the autonomic nervous system- and adrenal-dependent pathway, and that brain CRF reduces the occurrence of stress-induced gastric lesions by acting on its specific receptor within the central nervous system, probably through the autonomic nervous system- and adrenal-dependent mechanism.

Animals↗
PubMed1990

[Prediction of the need for postoperative mechanical ventilation in myasthenia gravis patients].

The prediction of the need for postoperative mechanical ventilation in 23 myasthenia gravis patients, who had undergone thymectomy from January 1983 to December 1989, was evaluated. Five patients who had needed postoperative mechanical ventilation over 24 hours were compared with the patients in whom the tracheal tubes had been uneventfully extubated within 24 hours postoperatively. In this study, 47.8%, 78.3%, 91.3% of the patients were correctly predicted using the scoring systems proposed by Leventhal et al., Makii et al. and Kimura et al., respectively. The product of %VC by FEV1.0% was proposed in this study for the prediction of the need of postoperative mechanical ventilation in patients with myasthenia gravis. If the product is less than 8,300, the patient is expected to need postoperative mechanical ventilation. Nineteen patients out of 23 cases (82.6%) were predicted correctly by this value. Only one patient, who had been predicted to be in no need, was actually ventilated for 3 days. In conclusion, the product of %VC by FEV1.0% is a simple and practical method of predicting whether a patient with myasthenia gravis undergoing thymectomy requires postoperative mechanical ventilation or not.

Adolescent↗
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of U-937 cells.

Exposure of U-937 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine metabolism. Within 24 h after treatment with 1.62 x 10(-9) M TPA, the reciprocal alteration in the activities of opposing enzymes of thymidine metabolism observed during normal cell culture growth was reversed. In TPA-treated cells, the activities of anabolic enzymes thymidine kinase (EC 2.7.1.75)and thymidylate synthase (EC 2.1.1.45) declined with time linearly to 20 and 16% of those of untreated cells by 72 h. Incorporation of [3H]thymidine and [3H]deoxyuridine into acid-insoluble fractions also decreased in parallel with the decline in enzyme activities. In contrast, the activities of catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrothymine dehydrogenase (EC 1.3.1.2) increased. The rise in thymidine phosphorylase activity peaked at 48 h with 406% elevation over the control. The activity of dihydrothymine dehydrogenase was not altered for the first 24 h, but it increased up to 338% by 96 h. Immunotitration of dihydrothymine dehydrogenase with monoclonal antibody against this enzyme showed that the rise in activity in the differentiated cells was due to the increase in the amount of enzyme protein. No significant difference was observed in the Km values for the substrate of each enzyme between untreated and TPA-treated cells. These metabolic alterations during induced differentiation were in line with the changes in cell morphology and accompanied by an accumulation of the cells in G1 at the expense of S phase. These observations indicate that induced differentiation of U-937 cells results in a reversal of the enzymic phenotype of thymidine metabolism and suggest that emergence of thymidine metabolic imbalance may serve as an early marker of differentiation of these cells.

Cell Cycle↗
PubMed1989

Effects of the combination of acivicin and cis-diamminedichloroplatinum(II) on thymidylate synthesis of A549 lung cancer cells.

Compared to either compound alone, the combination of acivicin and cis-diamminedichloroplatinum(II) markedly enhanced the inhibition of the activities of thymidylate synthase and thymidine kinase, the enzymes involved in the final steps of the de novo and salvage pathways in pyrimidine metabolism in A549 lung cancer cells. The enhancement of enzymic inhibition paralleled that of cell growth inhibition. These results indicate that the combination of these drugs can inhibit the capacities of the pyrimidine pathways, resulting in an efficient reduction of DNA synthesis.

Antimetabolites↗
PubMed1989

Intracellular hydroxyl radical production induced by recombinant human tumor necrosis factor and its implication in the killing of tumor cells in vitro.

This study investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells (2 X 10(7) cells) in the presence of rhTNF (100 U), hydroxyl radical production as detected by the evolution of methane gas from dimethyl sulfoxide increased gradually, at 18 h reaching 1.8 times that in the absence of rhTNF. This increase was dependent on the concentration of rhTNF and was effectively prevented by the simultaneous addition of anti-rhTNF monoclonal antibody III 2F3, which inhibited both the binding of rhTNF to its receptor and the cytotoxic activity of rhTNF. The addition of iron chelator 2,2'-bipyridine, which inhibits iron-catalized Fenton reaction and so inhibits hydroxyl radical generation, suppressed both the increase of hydroxyl radical production and the cytotoxicity induced by rhTNF. A similar increase in hydroxyl radical production in the presence of rhTNF was also detected with TNF-sensitive human myosarcoma-derived KYM cells, but no such increase was detected with TNF insensitive human embryonic lung fibroblast HEL cells. The results show that rhTNF induces increased hydroxyl radical production in TNF-sensitive cells, and suggest that this plays an important role in the mechanism of tumor cell killing by rhTNF.

2,2'-Dipyridyl↗
PubMed1989

Signalling pathway of tumor necrosis factor in normal and tumor cells.

Several aspects of the activity and effects of tumor necrosis factor (TNF) were investigated to gain further insight into its cytotoxic mechanism. The relation between number of TNF receptors and TNF susceptibility of both tumor cells and normal cells was studied, utilizing a specific binding assay. Among the tumor cells, a fairly close correlation (r = 0.855) was observed between receptor number and sensitivity to TNF. No cytotoxic effect by TNF was observed on any of the normal cells tested, even though TNF receptors were shown to be present, and cell proliferation was apparently stimulated by TNF in some cases. TNF internalization and intracellular distribution were studied by pulse-labelling and Percoll density gradient centrifugation. In L-M (murine tumorigenic fibroblasts, highly sensitive to TNF cytotoxicity) cells and HEL (human embryonic lung cells, non-sensitive to TNF cytotoxicity) cells, receptor-bound 125I-labelled recombinant human TNF was rapidly internalized and delivered to lysosomes within 15-30 min, and this was followed by degradation and release into the culture medium. The presence of either a cytoskeletal disrupting agent or a lysosomotropic agent was observed to inhibit the cytotoxic effect of TNF, thus also indicating that TNF internalization, followed by delivery to lysosomes, is essential in the cytolytic mechanism of TNF. As observed by [3H]uridine incorporation, TNF did not affect RNA synthesis in L-R cells (TNF-resistant cell lines derived from L-M cells) and HEL cells, but markedly stimulated (by 3.5 times) RNA synthesis in L-M cells.

Animals↗
PubMed1989

Effects of ingestion of glucose on GH and TSH secretion: evidence for stimulation of somatostatin release from the hypothalamus by acute hyperglycemia in normal man and its impairment in acromegalic patients.

Ingestion of glucose is known to induce suppression of GH secretion in normal subjects and this phenomenon is often absent in acromegalic patients. To clarify the mechanism of GH suppression in acute hyperglycemia in normal subjects and disturbed GH response in acromegalic patients, the effects of acute hyperglycemia on plasma GH and TSH levels were examined in normal subjects and acromegalic patients. Plasma GH levels were significantly lowered 45-60 min after ingestion of 75 g glucose and elevated at 210 and 240 min in nine normal subjects. Plasma TSH levels were also significantly lowered between 45 and 120 min after ingestion; levels then gradually rose. Subcutaneous administration of 50 micrograms SMS 201-995, a long acting somatostatin analog, lowered plasma TSH levels in both normal subjects and acromegalic patients, and there was no significant difference in the degree of decrease in plasma TSH levels between the normal subjects and patients. These results, taken together with several reports that somatostatin suppresses TSH secretion as well as GH secretion, suggest that acute hyperglycemia stimulates somatostatin release from the hypothalamus, thus causing inhibition of GH and TSH secretion. However, in ten acromegalic patients, only two showed suppression of plasma GH levels to below 50% of basal level and the degree of suppression of TSH secretion was significantly less than in normal subjects in the glucose tolerance test. It is, therefore, suggested that somatostatin release in response to acute hyperglycemia is impaired in most acromegalic patients and that this abnormality may be one of causes for the absence of the normal GH response to acute hyperglycemia in this disorder.

Acromegaly↗
PubMed1989

Reversal of enzymic phenotype of thymidine metabolism in induced differentiation of HL-60 cells.

Exposure of HL-60 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in specific alterations in thymidine (TdR) metabolism. Within 12 h after treatment with 1.62 nM TPA, the reciprocal alteration in the activities of opposing pathways of TdR metabolism observed during normal culture cell growth was reversed. In TPA-treated cells, the activities of anabolic enzymes, TdR kinase (TK; EC 2.7.1.21) and thymidylate synthase (TS; EC 2.1.1.45), declined to 15% and 18% of those of untreated cells by 96 h. Incorporation of 3H-TdR and 3H-deoxyuridine also decreased in parallel with decline in enzyme activities. In contrast, the activities of catabolic enzymes, TdR phosphorylase (TP; EC 2.4.2.4) and dihydrothymine dehydrogenase (DHT DH; EC 1.3.1.2), increased to 399% and 318% by 96 h. Immunotitration of DHT DH with monoclonal antibody showed that the rise in activity in the differentiated cells was due to the increase in protein amount. Kinetic properties of the enzymes were not altered during differentiation. These metabolic alterations were accompanied by an accumulation of the cells in G1 at the expense of S-phase. Present data indicate that induced differentiation of HL-60 cells results in a reversal of enzymic phenotype of TdR metabolism due to a consequence of decreased proliferation and suggest that emergence of TdR metabolic imbalance may serve as early markers of differentiation of these cells.

Cell Cycle↗
PubMed1989

[Isoflurane anesthesia for a child with myotonic dystrophy].

A 5 year-old boy with myotonic dystrophy was anesthetized with isoflurane for bilateral orchiopexy. Intubation was easily done without muscle relaxants, following slow induction using isoflurane, nitrous oxide and oxygen. Myotonia was not observed perioperatively and postoperative course was uneventful. It is concluded that isoflurane is an anesthetic of choice for a patient with myotonic dystrophy.

Anesthesia, Inhalation↗
PubMed1989

[A possible circadian rhythm of susceptibility to thiamylal].

A circadian rhythm of the susceptibility to thiamylal was evaluated in 30 patients. They were divided into two groups; 15 patients were induced around 9 AM (Morning-group) and the rest were in the early afternoon (Afternoon-group). The induction was performed by intravenous administration of thiamylal sodium. Parameters measured were the time and doses of thiamylal sodium to obtain the loss of consciousness and the loss of eyelash reflex. The results were as follows; the doses of thiamylal sodium to obtain the loss of consciousness were 3.5 +/- 0.6 mg.kg-1 (mean +/- SD) in Morning-group, and 4.1 +/- 0.4 mg.kg-1 in Afternoon-group, respectively. Thus, larger doses of thiamylal were necessary to obtain the loss of consciousness in Afternoon-group than in Morning-group (P less than 0.01). The doses of thiamylal sodium to obtain the loss of eyelash reflex were 4.4 +/- 0.8 mg.kg-1 in Morning-group and 5.0 +/- 0.6 mg.kg-1 in Afternoon-group, respectively. Also, larger doses of thiamylal were necessary to obtain the loss of eyelash reflex in Afternoon-group than in Morning-group (P less than 0.05). This study suggests that a circadian rhythm of the susceptibility to thiamylal exists in humans.

Adult↗
PubMed1988

Induction of synthesis of tumor necrosis factor in human and murine cell lines by exogenous recombinant human tumor necrosis factor.

Treatment of sensitive human myosarcoma cells (KYM-S) with exogenous tumor necrosis factor (r-TNF) resulted in the production of TNF by the cells. The newly synthesized cellular TNF was identified immunologically on Western blots and as a single 1.8-kilobase band on Northern blots. TNF synthesis began within 2 h of administration of the exogenous TNF in a dose-dependent manner. r-TNF also induced TNF synthesis in mouse tumorigenic fibroblasts (L-M). Resistant sublines of these cells as well as TNF nonsensitive human diploid fibroblasts possessed TNF mRNA without pretreatment, indicating an inverse correlation between levels of TNF expressed and sensitivity to the cytotoxic effects of exogenous TNF. It is conceivable that the newly synthesized cellular TNF functions in some protective manner to block cytolytic effects of exogenous TNF.

Animals↗
PubMed1988

Continuous internalization of tumor necrosis factor receptors in a human myosarcoma cell line.

The cell dynamics of the receptor for tumor necrosis factor (TNF) were examined in TNF-sensitive KYM cells derived from human myosarcoma. With receptor synthesis inhibited by cycloheximide, the half-life of the surface TNF receptor was 2 h in the absence of TNF and 30 min in its presence, suggesting that the TNF receptor is non-recycling and that its internalization is accelerated by TNF. During cell incubation with TNF receptor degradation suppressed by chloroquine, the number of surface TNF receptors remained approximately constant, but the total number of surface and internal TNF receptors increased gradually, at 3 h reaching 1.5 times the initial number, thus suggesting continuous synthesis, externalization, internalization, and degradation of the TNF receptor in the absence of cycloheximide. On cell incubation with 125I-TNF, the intracellular quantity of the pulse-labeled TNF-receptor complex promptly increased, reaching a maximum at 20 min, and then gradually declined, thus confirming that the TNF receptor is internalized as a TNF-receptor complex in the presence of TNF. During incubations with protein synthesis suppressed by cycloheximide following surface TNF receptor digestion by trypsin, TNF receptors reappeared on the cell surface, increasing in number to a peak at 60 min and gradually decreasing, and cells previously exposed to cycloheximide with or without TNF showed no recurrence of surface TNF receptors, suggesting that the TNF receptor is non-recycling. The results of the study thus suggest that the TNF receptor is continuously internalized and degraded intracellularly by lysosomes without being recycled regardless of the presence or absence of TNF and, further, that its internalization is accelerated when it is part of the TNF-receptor complex.

Cell Line↗
PubMed1988

Toxic effect of tumor necrosis factor on tumor vasculature in mice.

Stereoscopic observation via an implanted sight glass in mice bearing transplanted methylcholanthrene-induced A-cells showed tumorivascular hemorrhage at 1-2 h after tumor necrosis factor (TNF) administration, congestion at 4-6 h, and hemorrhage, congestion, and blood circulation blockage at 24 h. Histological examination after TNF administration to mice bearing similar methylcholanthrene-induced A-cell transplants showed thrombus formation in the tumor vasculature at 4 h and thereafter. Suppression of this thrombus formation with heparin had no apparent influence on the necrotic response, tumor growth inhibition or complete cure rate following TNF administration to mice bearing the methylcholanthrene-induced A-cell tumors. The results suggest that direct toxicity of TNF on tumor vasculature is a factor in the overall antitumor mechanism of TNF.

Animals↗
PubMed1988

Synergistic effects of recombinant human tumor necrosis factor and hyperthermia on in vitro cytotoxicity and artificial metastasis.

Synergy in cytotoxic effect between recombinant human tumor necrosis factor and hyperthermia (incubation at 38.5 degrees C or 40 degrees C) was observed to occur against L-M (mouse tumorigenic fibroblast) cells and shown to be related to an accelerated turnover rate of recombinant human tumor necrosis factor-receptor complex under elevated temperatures rather than to changes in number of cell receptors or binding strength. However, no synergy in cytotoxic effect was observed to occur against human embryonic lung (HEL) cells. A clearly synergistic inhibition of metastatic tumor growth by combined administration of recombinant human tumor necrosis factor (300 units) and whole-body hyperthermia (40 degrees C, 30 min) was also observed in BALB/c mice previously given injections of 1 x 10(6) Meth-A (MH) cells/mouse via tail vein, neither of which alone resulted in significant inhibition.

Animals↗
PubMed1988

Synergistic cytotoxic and antitumor effects of recombinant human tumor necrosis factor and hyperthermia.

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of rH-TNF against L-M cells in incubation for 12 h at 38.5 and 40 degrees C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37 degrees C. As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i.v. administration of rH-TNF at 1000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40 degrees C), whereas rH-TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i.v. administration of rH-TNF three times at 100 or 300 units/mouse together with hyperthermia (40 degrees C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth. The results suggest that combination therapy including rH-TNF and hyperthermia may be of value in the treatment of malignancy in human patients.

Animals↗
PubMed1988

Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat.

The mechanism by which restraint stress induces suppression of food intake and the influence of intracerebroventricular (icv) administration of somatostatin on the anorexia induced by restraint stress were examined in the rat. Ninety minutes of restraint stress reduced food intake of rats to approximately 60% that of control. Anorexia induced by 90 min restraint stress was partially reversed by icv administration of alpha-helical CRF (9-41), a corticotropin-releasing factor (CRF) antagonist, and completely reversed by anti-CRF gamma-globulin. These results provide further evidence in support of the theory that CRF is involved in the inhibitory mechanism of food intake in restraint stress. ICV administration of somatostatin 14 and SMS 201-995, an analog of somatostatin, also reversed restraint stress-induced anorexia. It is, therefore, suggested that somatostatin may counteract the suppressive action of CRF on food intake in stress.

Animals↗
PubMed1988

Effect of sodium ion on atrial natriuretic factor release from rat hypothalamic fragments.

The effects of Na ion and choline chloride on the release of atrial natriuretic factor (ANF) and growth hormone-releasing factor (GHRF) from rat hypothalamic fragments including the organum vasculosum of the lamina terminalis (OVLT) were examined in vitro. Although the release of ANF was stimulated by Na ion, choline chloride, and glucose in concentration-dependent manners, the release was more sensitive to a change in concentration of Na ion than to those of choline chloride and glucose. On the other hand, the change in Na ion concentration did not affect the release of GHRF. It can be therefore proposed that Na ion is the first candidate controlling ANF release from the brain tissue and that ANF in the hypothalamus and/or OVLT may play some role in the regulation of the Na ion and water balance in the central nervous system.

Animals↗