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K Aoyagi

Publications and source records attributed to K Aoyagi.

16 recordsLinked to original sources

Concurrent measurement of serotonin metabolism and single neuron activity changes in the lateral hypothalamus of freely behaving rat.

To further investigate the activity of serotonin neurons in relation to feeding behavior, the metabolic activity of the serotonergic system and single neuron activity changes in the lateral hypothalamic area (LHA) were investigated concurrently in freely behaving rats. The extracellular concentration of 5-hydroxyindoleacetic acid (5-HIAA), a metabolic product of serotonin in the LHA, began to increase concomitantly with the early stage of nocturnal eating. The increased 5-HIAA returned to the basal level within 3 or 4 h. In conjunction with the increase in serotonin metabolism, activity of 12 out of 30 LHA neurons (40%) increased, whereas it decreased in 7 (23%), and in 11 (37%) it showed no change. An intracerebroventricular injection of lisuride suppressed the increased activity in 7 of the 12 neurons, but had no effect on the others. These results suggest that the concurrent increase in serotonin metabolism and neuron activity changes in the LHA may occur in the early portion of the nocturnal eating period, and may be important in controlling feeding behavior.

Animals

Role of Mg2+ in activation of NADPH oxidase of human neutrophils: evidence that Mg2+ acts through G-protein.

The membrane fraction and three cytosolic proteins of neutrophils, p47-phox, p67-phox and a G-protein, are involved in the cell-free activation of the O2(-)-generating NADPH oxidase in the presence of SDS, though it has been controversial whether the G-protein is required or just enhancing the activity. We have used the three cytosolic factors, the solubilized membrane fraction, GTP gamma S and SDS, and found that both G-protein and GTP gamma S are essential for the activation of the NADPH oxidase. The effect of GTP gamma S is modified by Mg2+: the cations enhance the O2- generation at low concentrations of GTP gamma S, whereas they attenuate the activity at higher concentrations of GTP gamma S. In presence of 10 microM GTP gamma S, the maximal activity is observed at 0.1 microM Mg2+, which is several-fold higher than that at 1 mM Mg2+. The omission of Mg2+ followed by the chelation with EDTA results in loss of the activation, which is completely restored by the addition of Mg2+. Thus, Mg2+ seems to modulate the activation of the NADPH oxidase at the level of the G-protein.

Antibodies, Monoclonal

Enhancement of host resistance to opportunistic infections by ubenimex (bestatin).

Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections.

Animals

Biosynthesis of methylguanidine in the hepatic microsomal fraction.

We have investigated various synthetic mechanisms for the production of methylguanidine, a potent uremic toxin, and reported a role for active oxygen in its biosynthesis from creatinine in studies using isolated hepatocytes. In this study, we turn our attention to the hepatic microsomes. Liver homogenates were made from rats, and various organelles were obtained by centrifugation and incubated with creatinine. The results show that methylguanidine synthesis occurs only in the microsomal fraction in the presence of nicotinamide adenine dinucleotide phosphate, reduced form. The microsomal activity is inhibited by the addition of methimazole, metyrapone, superoxide dismutase, catalase or dimethylsulfoxide. These results suggest that methylguanidine is synthesized from creatinine by microsomes, and at least 2 enzymes are involved, an FAD-containing monooxygenase and a P-450-dependent oxidase based on the inhibitory effect of methimazole and metyrapone, respectively. Moreover, the inhibition by various scavengers of active oxygen suggests that active oxygen plays a role in the intermediate steps of the enzymatic reaction.

Animals

A retrospective study of resected gastric cancers.

From 1976 to 1989, a total of 1303 patients with gastric cancers underwent gastrectomies in the First Department of Surgery, Kurume University Hospital. Of these, 358 (27.5%) were total gastrectomies, 84 (6.4%) were proximal gastrectomies and 825 (63.1%) were distal gastrectomies. The 5-year survival rate was 44.8% after the total gastrectomies, 38.9% after the proximal and 72.4% after the distal gastrectomies. The 5-year survival rate was 86.2% with the absolute curative resection, 36.3% with the relative curative resection, 29.3% with the relative non-curative resection and 9.4% with the absolute non-curative resection. Macroscopically, the 5-year survival rate was 95.1% for type 0 (early cancers), 61.3% for Borrmann type 1, 58.8% for Borrmann type 2, 37.5% for Borrmann type 3 and 16.5% for Borrmann type 4. According to the pathological cancer stage, the 5-year survival rate was 94.8% for stage I, 79.3% for stage II, 49.2% for stage III and only 11.3% for stage IV.

Gastrectomy

Gastric cancer surgery in the elderly.

Although there is a decreasing number of gastric cancer patients in Japan, the number of patients over 80 years of age is increasing. Forty patients over 80 years of age (from 80 to 88 years) with gastric cancer (Group 1) during the 10 years from 1980 to 1989 were retrospectively investigated and compared with those 70-79 years of age (Group 2). The resectability rate was 80% in Group 1 and 89% in Group 2. Early gastric cancer was observed at a rate of only 25% in Group 1 and 39% in Group 2. Pathologically, the differentiated type occurred in 78% of those in Group 1 and 68% of Group 2. Total gastrectomy was performed in only 6% of the resected cases in Group 1 and in 25% of Group 2. A combined resection including such operations as pancreatico-splenectomy or splenectomy (PS) was employed in none of the total gastrectomy cases in Group 1 and in 30% of Group 2. R3 gastrectomy was performed in none of the patients in Group 1 and in 21% of those in Group 2. Postoperative complications occurred in 25% of Group 1 patients and in 12% of Group 2 patients. Anastomotic leakage occurred in 3% of those in Group 1 and in 4% of those in Group 2. The 5-year survival rate was 47% for all the resected cases in Group 1 and 68% for Group 2. The 5-year survival rate was 61% for those who underwent a curative (radical) gastrectomy in Group 1, and 84% for those in Group 2.

Aged

Enhancement by ubenimex (bestatin) of host resistance to Candida albicans infection.

Ubenimex is a low molecular weight microbial metabolite which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the protective effect of ubenimex on Candida albicans infection was investigated in normal and immunosuppressed mice. In normal mice, treatment with ubenimex at 0.5, 5 and 25 mg/kg for 5 days prior to infection prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, ubenimex treatment at 5 mg/kg for 5 days significantly increased the number of survivors. Ubenimex-treated mice had a significant increase in number of peritoneal exudate cells with neutrophils as well as enhanced functions, including phagocytosis and active oxygen production. These results suggest the potential usefulness of ubenimex as a prophylactic agent for the management of patients with opportunistic fungal infections.

Animals

[Changes in retinal blood flow volume in experimental retinal vein compression].

The authors quantitated the retinal blood flow volume during and immediately after experimental compression of the temporal retinal vein in 5 Macaca fuscata monkey eyes. The hydrogen clearance method was used to quantitate the retinal blood flow volume. After placing a microelectrode on the retinal surface, we measured the blood flow volume 4 times at a 15-minute interval. This value served as a baseline for the experiments. Next we compressed the temporal retinal vein near the disc with a 25-gauge needle with a rounded tip under guidance by an indirect ophthalmoscope. We measured the blood flow volume during compression. The compression was maintained for 3 minutes. Further blood flow determination was performed 7 minutes after release of compression and was repeated 4 times at a 15-minute interval. During compression of the temporal retinal vein, the retinal blood flow volume in the area served by the vein decreased by an average of 35%. The flow volume recovered rapidly and remained stable after release of compression. There was no reactive hyperemia. This model appears useful to elucidate the retinal circulation of branch retinal vein occlusion.

Animals

Resonance Raman study on intact pea phytochrome and its model compounds: evidence for proton migration during the phototransformation.

Resonance Raman (RR) scattering from intact pea phytochrome was observed in resonance with the blue band at ambient temperature. The relative populations of the red-light-absorbing form (Pr) and far-red-light-absorbing form (Pfr) under laser illumination were estimated from the absorption spectra. The most prominent RR band of Pr obtained by 364-nm excitation under 740-nm pumping exhibited a frequency shift between H2O and D2O solutions, but that of Pfr obtained by 407-nm excitation under 633-nm pumping did not, indicating a distinct difference in a protonation state of their chromophores. Since the protonation level of a whole molecule of intact phytochrome remains unchanged between Pr and Pfr, this observation indicates migration of a proton from the chromophore of Pr to the protein moiety of Pfr. As model compounds, octaethylbiliverdin (OEBV-h3), its deuterated and 15N derivatives, and their protonated forms were also studied with both RR and 1H and 15N NMR spectroscopies. The RR spectrum of the protonated form, for which the protonation site was determined to be C-ring pyrrole nitrogen by NMR, displayed a deuteration shift corresponding to that of Pr, suggesting a similar protonated structure for the pyrrolic rings of Pr. The RR spectral difference between OEBV-h3 and OEBV-d3 and that between H2O and D2O solutions of Pfr suggested that the N-H protons of the A-, B-, and D-rings of intact phytochrome are replaced with deuterons in D2O. A role of the 7-kDa segment of phytochrome is discussed on the basis of RR spectral differences between the intact and large phytochromes.

Biliverdine

Effects of iodothyronines on chemotactic peptide-receptor binding and superoxide production of human neutrophils.

We studied the action of iodinated thyronines on the superoxide (O2-) production of human neutrophils stimulated with a chemotactic peptide N-formylmethionylleucylphenylalanine (FMLP) in vitro. L-Thyroxine and L-triiodothyronine elicited dose dependently a potent inhibitory action on the FMLP-induced O2- production with IC50 values of about 10(-6) M and 7.10(-6) M, respectively, but L-diiodothyronine did not. No difference in the inhibition was observed between the L-form and the D-form of the compounds. Inhibition of the O2- production by L-thyroxine was restored by the washing of the cells. L-Thyroxine did not affect the O2- production stimulated with either the fifth component of the complement (C5a) or phorbol 12-myristate 13-acetate. L-Thyroxine and L-triiodothyronine were found to block [3H]FMLP binding to its own receptor with IC50 values similar to those for the inhibition of the O2- production by changing the affinity for the peptide but not the number of the receptors. These results suggest that thyroxine and triiodothyronine interfere with the binding of FMLP to the receptors, leading to the inhibition of neutrophil functions, such as O2- production, and that the inhibitory effects result from extranuclear actions rather than nuclear receptor-mediated ones.

Chemoreceptor Cells

[Active oxygen].

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Animals

Inhibition of urea synthesis by pent-4-enoate associated with decrease in N-acetyl-L-glutamate concentration in isolated rat hepatocytes.

Pent-4-enoate at 0.1 to 1.0 mM strongly inhibited urea synthesis in isolated rat hepatocytes. Pent-4-enoate at the same concentrations markedly decreased concentrations of N-acetyl-L-glutamate, an essential activator of carbamoyl-phosphate synthase-I (EC 2.7.2.5), and the decrease was well in parallel with the inhibition of urea synthesis by pent-4-enoate. This compound also lowered cellular concentrations of acetyl-CoA, a substrate of acetylglutamate synthase (EC 2.3.1.1). Pent-4-enoate in a dose of 1 mM did not significantly affect cellular concentrations of ATP, and had no direct effect on acetylglutamate synthase activity. These results suggest that the inhibition of urea synthesis by pent-4-enoate is due to decrease in N-acetyl-L-glutamate concentration and that the decrease is probably brought about by decreased rate of its synthesis due to the lowered concentration of cellular acetyl-CoA.

Acetyl Coenzyme A