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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 325 records · Page 18Linked to original sources

Inhibition by drugs of passive cutaneous anaphylaxis-induced skin histamine decrease.

Passive cutaneous anaphylaxis (PCA) was produced in the rat with mouse IgE-rich antiserum. The effect of drugs on the PCA-induced skin histamine decrease and leakage of protein-bound dye was studied. Salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and cromoglycate (10 mg/kg i.v.) significantly inhibited the skin histamine decrease. A combination of salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c.) and aminophylline (25 mg/kg i.v. or 75 mg/kg s.c.) had an additive or greater than additive effect on the histamine decrease. Salbutamol (1.0 mg/kg s.c.) inhibited the dye leakage markedly, and aminophylline (75 mg/kg s.c.) slightly. These results indicate that the decrease in the skin histamine content is useful as an index of the in vivo inhibitory effect of antiallergic drugs on the antigen-induced histamine release.

Albuterol↗

Regional distribution of histamine and tele-methylhistamine in the rat, mouse and guinea-pig brain.

Regional histamine (HA) and tele-methylhistamine (t-MH) contents were determined in the rat, mouse and guinea-pig brain. The highest HA and t-MH levels were found in the hypothalamus of all species. Fairly high t-MH levels were observed in the amygdala of all species and in the guinea-pig hippocampus. The t-MH/HA ratio was higher in the regions of the telencephalon than in the diencephalon and brainstem. The cerebellum and spinal cord showed extremely low t-MH/HA ratios. These results suggest higher histaminergic neuronal activities in the hypothalamus and some regions of the telencephalon than in other parts of the brain.

Animals↗

Calcium requirement for the inhibition by theophylline of histamine release from mast cells.

When added to Ca2+-free Hanks' solution, Ca2+ (0.1-2.5 mM) had no significant effect on antigen-induced histamine release from rat mast cells, but Sr2+ (1.0-3.0 mM) dose-dependently increased the release. Ba2+ (1.0 and 2.0 mM) also enhanced the release. Ca2+ and Ba2+ inhibited compound 40/80-induced histamine release, in a dose-dependent manner. In ordinary Hanks' medium, theophylline and 3-isobutyl-1-methylxanthine (IBMX) dose-dependently inhibited the antigen-induced histamine release but these drugs were ineffective in Ca2+-free medium. Theophylline (1.0 mM) also inhibited compound 48/80-induced histamine release in the presence but not absence of Ca2+. There was an optimal Ca2+ concentration for the theophylline effect. Sr2+ but not Ba2+ could substitute for Ca2+ in supporting the theophylline effect. Theophylline (1.0 mM) and IBMX (1.0 mM) increased mast cell cyclic AMP levels both in the presence and absence of Ca2+. These results suggest that Ca2+ is required in the interaction of theophylline and specific sites on mast cells or in the mast cell response to theophylline which probably does not involve the cyclic AMP increase and is linked to the inhibition of histamine release.

1-Methyl-3-isobutylxanthine↗

Pharmacologic effects of metformin in relation to its disposition in alloxan diabetic rats.

The purpose of this investigation is to elucidate the relationship between the time course of pharmacologic effects and drug disposition after administration of metformin, an oral antidiabetic drug of biguanides. Alloxan diabetic rats and normal rats were used in the experiments. After administration of metformin, plasma glucose levels, blood pyruvate levels, blood lactate levels, plasma pancreatic glucagon immunoreactivity (pancreatic GI) and plasma gut glucagon like immunoreactivity (gut GLI) were determined as well as serum concentrations of metformin. In alloxan diabetic rats, gut GLI levels were significantly correlated to the logarithm of tissue metformin levels, calculated from serum metformin levels. The blood lactate, pyruvate and plasma glucose levels were also linearly related to gut GLI levels, after metformin administration. It was also clarified that metformin did not inhibit the intestinal absorption of glucose and that metformin presumably inhibited the hepatic gluconeogenesis. It is reasonable to consider that the effect of metformin on the gut GLI level is the primal effect, and that other pharmacologic effects such as plasma glucose lowering, blood lactate and pyruvate increasing effects are the consequences of the primal effect, at least in alloxan diabetic rats. While in normal rats, plasma gut GLI levels were not significantly related to metformin tissue levels, however, plasma glucose levels were considerably correlated with the logarithm of the plasma or tissue metformin levels. These results indicated that the effect of gut GLI was entirely masked by endogeneous insulin, which might be secreted by metformin administration.

Administration, Oral↗

Disodium cromoglycate inhibition of substance P-induced histamine secretion is calcium dependent.

Histamine secretion was induced by substance P, in a dose-dependent manner, from rat peritoneal mast cells, both in the presence and absence of Ca2+ in the medium, and disodium cromoglycate (DSCG) produced a dose-dependent inhibition of the histamine secretion in Ca2+-containing medium. However, in the absence of Ca2+, DSCG was ineffective or had a far weaker activity. Mg2+, Sr2+ and Ba2+ were ineffective in restoring the DSCG activity when added to medium devoid of divalent metal ions. Therefore, extracellular Ca2+ seems to be a specific requirement for the binding of DSCG to its "receptors" on the mast cell surface or some steps in the DSCG action.

Animals↗

Differential effects of adenosine on histamine secretion induced by antigen and chemical stimuli.

Adenosine had a dual effect on the IgE-mediated histamine secretion from rat peritoneal mast cells: an inhibition at relatively low concentrations and a potentiation at higher concentrations. An adenosine R-site analog, N6-methyladenosine, had a similar dual effect while adenosine P-site analogs, 9-beta-D-arabinofuranosyladenine and 2'-deoxyadenosine, had neither inhibitory nor potentiating effects. Both compound 48/80- and alpha-chymotrypsin-induced histamine secretion were dose-dependently inhibited by adenosine. Not only R- and P-site analogs of adenosine but also a wide variety of purine and pyrimidine derivatives such as adenine, AMP, cyclic AMP, ADP, guanosine, inosine and cytosine showed inhibitory activities on the compound 48/80-induced histamine secretion. Adenosine had no influence on substance P- and neurotensin-induced histamine secretion.

Adenosine↗

[Combination chemotherapy with mitomycin C, methotrexate, and vincristine (MMV) for metastatic breast cancer refractory to adriamycin].

Twenty-five patients with metastatic breast cancer who had failed with combination chemotherapies including adriamycin were treated with a combination of mitomycin C, methotrexate, and vincristine (MMV). MMC 5 mg/m2, methotrexate 18 mg/m2, vincristine 0.7 mg/m2 were given i.v. on days 1 and 8, and repeated every 21 days. Seven patients (28%) experienced a partial response: 7 maintained NC and 11 failed to respond (PD). Median duration of regression was 12 weeks. Median survival time in PR patients was one year and 3 months, contrary to 6 months in patients with NC or PD. This combination was well tolerated except thrombocytopenia in 5 patients.

Adult↗

[Evaluation of steroid hormone sensitivity of human breast cancer cells in culture (MCF-7) by a colony formation method].

The effects of steroid hormones on the colony forming activity of a human breast cancer cell line (MCF-7) were studied. Endrogeneous estrogens in the fetal calf sera used for culture were deprived using the dextran-coated charcoal, and only batches of E2-deprived serum were chosen with which there was a significant increase in the plating efficiency after E2 (estradiol-17 beta, 10(-8) M) treatment. Progesterone showed little effect on the growth of the cells. not being influenced by the addition of E2. The capacity of the cells to form colonies was stimulated by androgens (5 alpha-dihydrotestosterone, testosterone) only in the absence of E2. Dexamethasone had suppressive effects regardless presence of E2. Thus, MCF-7 cells showed variable responses to these steroid hormones, although the cells have specific receptors to the hormones. This colony formation method of MCF-7 cells may be a useful model system for the study of hormonal and non-hormonal anti-cancer agents.

Breast Neoplasms↗

Comparison between AP and SP parameters in trans- and extratympanic electrocochleography.

Results of the comparison of action potential (AP) and summating potential (SP) parameters in trans- (TT) and extratympanic (ET) methods in 2 normal-hearing ears and 20 hearing-impaired ears with various etiologies and audiogram shapes are reported. In normal and impaired ears the TT/ET ratio of N1 amplitude was intensity dependent and was greater at higher intensities than at lower intensities. N1 latency was identical in both methods. The AP waveform was almost identical in both methods in ears except in a noise-induced hearing loss: N1/N2 ratio was greater in the TT method than in the ET method. In the TT method +SP at high frequency tone bursts and -SP at low frequency tone burst were recorded in Menière's disease and progressive sensorineural hearing loss, while in the ET method only -SP was recorded at a tone burst of each frequency. Origins of N1 and N2 and a clinical value of -SP and +SP are discussed.

Acoustic Stimulation↗

Amylase secretion induced by histamine from guinea-pig parotid gland.

The mode of action of histamine and its analogues on the secretion of amylase from guinea-pig parotid gland was studied in vitro using chopped parotid tissue. Histamine, 4-methylhistamine and 2-(2-pyridyl)ethylamine dose-dependently stimulated the secretion of amylase in the presence of 3-isobutyl-1-methylxanthine. The effect of histamine was blocked by mepyramine but not by metiamide. Propranolol inhibited the effect of higher concentrations of histamine and 2-(2-pyridyl)ethylamine. A combination of mepyramine and propranolol markedly suppressed the effect of histamine and 2-(2-pyridyl)ethylamine. Atropine, phentolamine and tetrodotoxin had no influence on the histamine-induced secretion of amylase.

1-Methyl-3-isobutylxanthine↗

[Compound therapy including PSK for malignant head and neck cancer].

The effect of protein-bound polysaccharide preparation, PSK was studied in 44 cases with head and neck cancer. 1) Eight cases with laryngeal cancer received radiation therapy and PSK as immunotherapy, and eight cases as control received radiation alone. During radiation, the mean values of peripheral lymphocyte counts showed statistically significant difference (P less than 0.05) between the cases with immunotherapy and those without immunotherapy. 2) Twenty-eight cases received adjuvant immunochemotherapy with Carboquone and PSK. 22 out of 28 evaluable cases in the group received adjuvant immunochemotherapy were judged as effective. These studies suggest that PSK is one of the valid immunopotentiators.

Adjuvants, Immunologic↗