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H Shimamura

Publications and source records attributed to H Shimamura.

52 records · Page 3Linked to original sources
PubMed1987

Relation between yawning behavior and central serotonergic neuronal system in rats.

Subcutaneously (s.c.) administered apomorphine (0.0125-0.4 mg/kg) or physostigmine (0.025-0.4 mg/kg) to rats elicited yawning. The dose-response curves were bell-shaped. The peak effects of apomorphine and physostigmine were observed with a dose of 0.1 mg/kg of each drug. Yawning elicited by apomorphine (0.1 mg/kg) or physostigmine (0.1 mg/kg) was reduced by intraperitoneally (i.p.) administered 5-hydroxytryptophan (5-HTP, 50-200 mg/kg, given 30 min before). Yawning elicited by apomorphine but not by physostigmine was enhanced by p-chlorophenylalanine (p-CPA, 25-400 mg/kg i.p., given 24 h before). Apomorphine elicited but not physostigmine-elicited yawning was enhanced by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 8 micrograms/rat, given 14 days before into the dorsal raphe). This treatment led to a 35% depletion of serotonin (5-HT) in the striatum. 5-HTP, p-CPA or 5,7-DHT given alone did not elicit yawning. Bilateral, intrastriatal microinjection of apomorphine (1.5-50 micrograms/site) but not physostigmine (5-50 micrograms/site) elicited yawning. The dose-response curve was also bell-shaped. These results indicate that central serotonergic pathways play an important role in modulating drug-elicited yawning in rats.

5,7-Dihydroxytryptamine↗
PubMed1986

Electrophysiological and behavioral assessments of dopamine autoreceptor activation to apomorphine in rats.

Single neuronal activity was recorded extracellularly in the substantia nigra pars compacta (SNC) in rats anesthetized with chloral hydrate. Haloperidol in a dose of 10 micrograms/kg had no significant effects on the SNC neurons. R(-)apomorphine (cumulative i.v. dose of 40 micrograms/kg, given as: 5, 5, 10 and 20 micrograms/kg) inhibited the firing rate of dopaminergic neurons, in a dose-dependent manner. Haloperidol (cumulative i.v. dose of 10 micrograms/kg, as: 2.5, 2.5 and 5 micrograms/kg) reversed the effect of apomorphine. Complete reversal of the firing rate to haloperidol was observed with a dose of 10 micrograms/kg. In rats pretreated with 10 micrograms/kg of haloperidol, there was a dramatic shift to the right of the apomorphine dose-response curve (cumulative i.v. dose of 800 micrograms/kg, as: 50, 50, 100, 200 and 400 micrograms/kg), and this inhibition was reversed by haloperidol (cumulative i.v. dose of 400 micrograms/kg, as: 50, 50, 100 and 200 micrograms/kg). Apomorphine in doses of 40 micrograms/kg and 800 micrograms/kg elicited yawning behavior and stereotypy, respectively. Apomorphine in a dose of 800 micrograms/kg elicited stereotypy in rats treated 3 min before with 10 micrograms/kg of haloperidol. Therefore, electrophysiological determinations of events in the SNC dopaminergic neurons are given support by the behavior observed in these rats.

Animals↗
PubMed1985

Effects of magnesium oxide on trichlormethiazide bioavailability.

The effect of an antacid, magnesium oxide (MgO), on the bioavailability of a thiazide diuretic, trichlormethiazide, was studied in 10 healthy subjects who fasted overnight. A single oral dose of 4 mg of 1 alone or in combination with 0.5 g of MgO was given in a two-way Latin-square crossover design. Urine concentrations of 1 during the 24 h after each dose were determined by an HPLC method. There were no significant differences for drug alone versus drug with MgO in the mean percentage recovery (60 versus 62%) and the cumulative amount excreted unchanged in urine over 24 h (2408 versus 2463 micrograms). However, coadministration of MgO increased the mean excretion rate of 1 at 0.75 h and 1.5 h (p less than 0.05), the cumulative amount excreted unchanged in urine over 2 h (p less than 0.05), and the absorption rate constant (p less than 0.05). Therefore, the extent of bioavailability was not influenced by MgO, but the rate of absorption was enhanced. The solubility of 1 increased remarkably by changing from pH 1.2 to 8.0 (141 to 1365 micrograms/mL). The dissolution rate of 4 mg of 1 in 500 mL of medium was not affected by an increase in pH. However, a 1.5-fold increase of the dissolution rate in 20 mL of medium was observed by changing from pH 1.2 to 7.3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Pyridazinones. 2. Synthesis and antisecretory and antiulcer activities of thiourea and 2-cyanoguanidine derivatives.

In an effort to develop new types of antiulcer agents, we synthesized a series of novel 2-[omega-(thioureido)alkyl]- and 2-[omega-(cyanoguanidino)alkyl]-3(2H)-pyridazinone derivatives. All target compounds were evaluated for gastric antisecretory activity in the pylorus-lygated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rats. Structure-activity relationships were established. Two series of the compounds had significant activity in antisecretory and/or antiulcer tests. The molecular features essential for the activities are a thiourea group or a 2-cyanoguanidine group, a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-carbon chain length between the 3(2H)-pyridazinone ring and the functional group, and a methyl group at the N-3 position of the functional group. Among them, the three thiourea derivatives (24, 26, and 38) and the six 2-cyanoguanidine derivatives (61, 62, 65, 75, 85, and 86) had the most potent antisecretory and/or antiulcer activities. These compounds are not histamine H2-receptor antagonists.

Acetylcholine↗
PubMed1983

Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives.

3(2H)-Pyridazinone derivatives having a 2-cyanoguanidine moiety, as well as a sulfur or an oxygen atom in the alkylene side chain, were synthesized and evaluated for gastric antisecretory and antiulcer activities. The key intermediates, free amines having a thioether linkage, were synthesized by the reaction of 2-(omega-chloroalkyl) derivatives with cysteamine, while other intermediates having an ether linkage were synthesized from 2-(omega-chloroalkyl)oxymethyl derivatives. These free amines were converted via the 3-cyano-2-methyl-1-isothiourea derivatives into the desired 2-cyano-3-substituted-1-guanidine derivatives. All compounds synthesized were evaluated for gastric antisecretory activity in the pylorus-ligated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rat. Structure-activity relationships are discussed. The molecular features for the best activities are a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-atom chain length between the 3(2H)-pyridazinone ring and the 2-cyanoguanidine moiety, and a thioether rather than an ether linkage. Among them, compound 14, 2-[[[2-(2-cyano-3-methyl-1-guanidino)ethyl]thio]methyl]-6-phenyl-3 (2H)-pyridazinone, had the most potent antisecretory and antiulcer activities. These compounds are neither histamine H2 receptor inhibitors nor anticholinergic agents.

Animals↗
PubMedDate not supplied

Irradiated pancreatic cancer cells undergo both apoptosis and necrosis, and could be phagocytized by dendritic cells.

The interaction of immature dendritic cells (DC) with irradiated pancreatic cancer cells was examined. Flow cytometric analysis using annexin V and propidium iodide revealed that ionizing radiation (25-35 Gy X-ray) induced both apoptosis and necrosis in pancreatic cancer cell lines. After irradiation, PK-1 and Panc-1 cells were likely to undergo necrosis, whereas MIAPaCa-2 cells underwent apoptosis. When DiO-stained immature DCs were co-incubated with DiI-stained irradiated MIAPaCa-2, it was observed under fluorescent microscopy that DCs phagocytized dead tumor cells as early as 4 h after co-incubation. The DCs' phagocytosis of irradiated tumor cells was also confirmed by flow cytometry. These results suggest that irradiated pancreatic cancer cells, which undergo both apoptosis and necrosis, could be a good source of tumor-associated antigens for cross-presentation by DCs.

Apoptosis↗
PubMedDate not supplied

Autologous serum deprivation restored IL-1 receptor antagonist production by peripheral blood mononuclear cells in patients with gastric cancer.

It has been established that cancer patients have immunosuppressive substances in their sera that depress cellular immunity. Although plasma exchanges have been attempted to remove these substances and to improve immunity to cancer, little is known about its mechanism from the viewpoint of cytokine pattern. The levels of the cytokines, tumour necrosis factor-alpha, interleukin 1beta, interleukin 6, interferon-gamma and interleukin-1 receptor antagonist (IL-1ra) by peripheral blood mononuclear cells (PBMC) were determined simultaneously by the whole-blood assay and the PBMC assay in 20 patients with gastric cancer and in 10 healthy volunteers. In both assays the cytokine levels were lower in patients with cancer compared with healthy controls, with the exception of IL-1ra. In the PBMC assay, the IL-1ra level in cancer patients was significantly higher than that in controls. No statistical correlation between the cytokine levels determined by the two assays was found. We suggest that autologous serum deprivation restored and enhanced IL-1ra production, and normalized the cytokine cascade in immune response, in patients with gastric cancer.

Adult↗
PubMedDate not supplied

Serum levels of circulating intercellular adhesion molecule 1 in hepatocellular carcinoma.

BACKGROUND/AIMS: This is a comparative study of the relationship between. MATERIAL AND METHODS: Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA assay in four patients with chronic hepatitis (CH), 16 with liver cirrhosis (LC), 38 with hepatocellular carcinoma (HCC), and in nine healthy controls. RESULTS: No significant difference in cICAM-1 levels was observed between LC and HCC. The cICAM-1 level in HCC did not correlate with tumor markers but correlated well with tumor size. cICAM-1 level in HCC Stage III + IV was significantly higher than that of Stage I, and was higher in HCC with liver metastasis as opposed to HCC without metastasis. Furthermore, the cICAM-1 level of HCC decreased significantly after hepatectomy. CONCLUSION: These findings showed a close relationship between cICAM-1 and the progress of intrahepatic metastasis of HCC, indicating a possibility for using cICAM-1 as a prognostic marker.

Biomarkers, Tumor↗