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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 865 records · Page 48Linked to original sources
PubMed1988

Inhibitory effect of zinc-protoporphyrin on the induction of heme oxygenase and the associated decrease in cytochrome P-450 content in rats.

Pretreatment of rats with zinc-protoporphyrin, which has shown to be a potent competitive inhibitor of heme oxygenase, resulted in the inhibition of bromobenzene-mediated induction of heme oxygenase and decreases of the cytochrome P-450 content, aminopyrine demethylase and aniline hydroxylase activities. Such an inhibitory effect of zinc-protoporphyrin on the induction of heme oxygenase and concomitant decreases of drug-metabolizing enzymes occurred in a dose-dependent manner with complete inhibition of these effects at a dose of 40 mumol/kg. The effects of zinc-protoporphyrin were also observed in thioacetamide- and BCG-treated rats and ascitic tumor AH 66-bearing rats. Likewise, a decrease of cytochrome b5 content observed under these experimental conditions was also restored significantly by zinc-protoporphyrin. These results strongly suggest that the induction of heme oxygenase is a primarily important early event which consequently leads to the decrease in cytochrome P-450 content and associated enzyme activities.

Aminopyrine N-Demethylase↗
PubMed1988

Protection of isolated rat gastric cells by prostaglandins from damage caused by ethanol. Preliminary report.

The direct effects of exogenous and endogenous prostaglandins (PGs) on damage to isolated gastric cells caused by ethanol were assessed in rats. 16,16-Dimethyl-PGE2 (dmPGE2) significantly inhibited cellular damage caused by 15% ethanol in three fractions rich in surface epithelial cells, rich in parietal cells, and rich in chief cells at the concentration of 10(-6) M but it was less effective either at a lower concentration (10(-7) M) or a higher concentration (10(-5) M). The surface epithelial cells synthesized 6-keto-PGF1 alpha and thromboxane (TX) B2 predominantly, and less PGE2. Indomethacin completely inhibited synthesis of these prostanoids. This agent induced cellular damage in a dose-related way and this damage was inhibited by 10(-6) M dmPGE2. Indomethacin alone at the dose of 10(-4) M, at which synthesis of prostanoids was completely inhibited, did not affect the viability of the cells, but made the cells susceptible to damage caused by 15% ethanol. This effect of a minimum dose of indomethacin was inhibited by 10(-6) M dmPGE2. These results suggest that dmPGE2 has a direct protective effect on the isolated gastric cells in rats, and this effect is not limited to a specific cell type. That endogenous prostanoids have a possible role in the maintenance of cellular integrity is also postulated.

Animals↗
PubMed1988

Roles of endogenous leukotrienes in damage caused by ethanol in isolated rat gastric cells.

The activity of prostaglandin (PG) and leukotriene (LT) synthesis and the role of endogenous LT in cellular resistance were assessed in isolated parietal and nonparietal cells of rats. Rat gastric cells were isolated and the fractions rich (F1) and poor (F2) in parietal cells were obtained. In F1, more PGE2, PGI2 (measured as the stable metabolite 6-keto-PGF1 alpha), and sulfidopeptide (SP)-LTs and less thromboxane A2 (TXA2, measured as the stable metabolite TXB2) were synthesized than in F2. AA861, an inhibitor of 5-lipoxygenase, inhibited the synthesis of SP-LTs in both fractions in a dose-related way. AA861 alone at any concentrations used did not affect the viability of the cells, but prevented the cell damage caused by ethanol in both fractions, the effect of AA861 being inhibited by indomethacin. These results suggest that in rat stomach, PGs and LTs, except TX, are synthesized mainly in parietal cells rather than in nonparietal cells. Endogenous LT may play a crucial role in the development of cellular damage caused by ethanol independently of systemic and extracellular factors. The balance of PG and LT may be important for regulation of cellular resistance.

Animals↗
PubMed1988

Interleukin 2 stimulates the T-cells from patients with eosinophilia to produce CFU-Eo growth stimulating factor.

To explore the mechanism of eosinophilopoiesis in patients with reactive eosinophilia, we studied the effect of interleukin 2 (IL-2) on the production of CSFs, especially CFU-eosinophil growth stimulating factor (CFU-Eo GSF) from T-lymphocytes in patients with reactive eosinophilia. Conditioned media (CM) prepared from patients' E rosette forming cells (ERFC) with or without IL-2 was assayed for CFU-Eo, CFU-monocyte, macrophage (CFU-M) and CFU-neutrophil (CFU-N) GSF. The addition of IL-2 to the ERFC significantly stimulated the production of CFU-Eo and CFU-M GSF while only CFU-M GSF increased in normals. Serial testing of the CFU-Eo GSF in ERFC-CM demonstrated that the ability of ERFC to produce CFU-Eo GSF with IL-2 stimulation was retained even when the eosinophilia had disappeared. These results suggest that CFU-Eo GSF is produced from T-cells with IL-2 stimulation and that the T-cells from patients produce IL-2 stimulation and that the T-cells from patients produce CFU-Eo GSF with IL-2 stimulation after the disappearance of eosinophilia.

Colony-Forming Units Assay↗
PubMed1988

Gastric cytoprotection by tetraprenylacetone in human subjects.

We assessed the inhibition by tetraprenylacetone (TPA) of gastric mucosal damage caused by ethanol in human subjects. Seventeen healthy volunteers were given either TPA (a 50-mg capsule) or a placebo 3 times daily for 5 days. Then, 20 ml of 70% ethanol were sprayed onto the gastric antrum and 15 min later, visible mucosal lesions were evaluated with an endoscope, and biopsy specimens were taken from mucosa that looked normal but had been sprayed with ethanol. The specimens were observed by light microscopy and scanning electron microscopy. The gross mucosal damage was significantly less (p less than 0.05) in the subjects given TPA than in those given the placebo. Hyperemia and hemorrhage in the mucosa and surface epithelial damage were also significantly less (p less than 0.05) in the subjects given TPA. The results suggested that TPA protects the gastric mucosa from damage by ethanol as judged not only by the gross appearance of the mucosa but also by microscopic observation.

Adult↗
PubMed1988

Gastric mucosal resistance and prostanoid levels after cimetidine treatment in rats.

We studied the effects of cimetidine administered intraperitoneally to rats at a dose of 20 mg/kg twice daily for 7 days on gastric mucosal integrity and endogenous prostaglandins. Cimetidine significantly (p less than 0.05) reduced the mucosal concentration of prostaglandin E2 and 6-keto-prostaglandin F1 alpha both 30 min and 24 h after the last injection of this drug, and the level had returned to normal 5 days later. Cimetidine significantly (p less than 0.01) enhanced gastric mucosal lesions induced with 0.6 N HCl 24 h after the last injection; this increased vulnerability had disappeared 5 days later. Cimetidine did not affect the synthesis of these prostanoids in isolated gastric mucosa in vitro. Gastric secretion, which was significantly (p less than 0.05) inhibited 30 min after the last injection of cimetidine, returned to control level 24 h after the last injection. The increase in gastric mucosal vulnerability observed 24 h after the last cimetidine injection might be related to a decrease in the prostanoid content and recovery of acid secretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Protection of gastric surface epithelial cells of rats by 16,16-dimethyl prostaglandin E2 and sofalcone, a synthetic flavonoid derivative of sophoradin, against ethanol.

We studied the effects of 16,16-dimethyl prostaglandin E2 (dm-PGE2) and sofalcone, a new antiulcer agent developed in Japan, on ethanol damage to isolated surface epithelial cells (SEC) in vitro and gastric mucosa of rats in vivo. Rats were given 5 micrograms/kg dm-PGE2, 30, 100, or 300 mg/kg sofalcone, or the vehicle, intraperitoneally. In the in vitro study, damage of the SEC isolated from rats given dm-PGE2 or sofalcone was significantly less after exposure to 15% ethanol than for the SEC from the control rats. In the in vivo study, the 15% ethanol did not induce gross visible damage, but did cause surface epithelial damage in the control rats as judged by scanning electron microscopy. This damage was inhibited by dm-PGE2 or sofalcone. Damage from absolute ethanol was inhibited by both of the agents as judged by the gross appearance, but the surface epithelium was damaged in all rats. We concluded that dm-PGE2 and sofalcone protect gastric mucosa from gross damage caused by absolute ethanol, and protect SEC both in vivo and in vitro from being damaged by ethanol when the concentration of ethanol is 15%.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Antipeptide antibodies recognize c-erbA and a related protein in human A431 carcinoma cells.

Peptides corresponding to the deduced amino acid residues 15-29 of the amino-terminal region and 445-456 of the carboxyl-terminal region of the human placental c-erbA protein (hc-erbA-beta) were synthesized and used to produce site-specific rabbit polyclonal antipeptide sera. Antibodies to the carboxyl-terminal peptide (C-91) and the amino-terminal peptide (N-98) specifically immunoprecipitated the hc-erbA-beta proteins synthesized in vitro. Furthermore, 68% and 48% of the T3-binding activity of the hc-erbA-beta protein were immunoabsorbed by antibodies C-91 and N-98, respectively. These results indicate that C-91 and N-98 recognized hc-erbA-beta proteins. These antibodies were used to study the subcellular distribution of hc-erbA-beta protein in human cultured cells. Nuclear extracts were prepared from human A431 carcinoma cells; C-91 immunoabsorbed 50% of the specific T3-binding activity in these extracts. These results provide structural evidence to confirming that hc-erbA-beta is the T3 nuclear receptor. Cells were metabolically labeled with [35S]methionine, and the cytosolic extracts were immunoprecipitated by C-91 or N-98. A protein with a mol wt of 58,000 (Cp58) was specifically immunoprecipitated by N-98 or C-91. Peptide mapping by V8 digestion and cyanogen bromide cleavage showed that the Cp58 molecules immunoprecipitated by N-98 or C-91 was identical. Indirect immunofluorescence using N-98 or C-91 indicated that Cp58 is present exclusively in the cytoplasm. Other human cultured cells, HepG2, MCF-7, IM-9, and KB, were also evaluated, and similar results were found. These results raised the possibility that a precursor of hc-erbA-beta may be present in the cytosol. The functional significance of the hc-erbA-beta-related cytosolic Cp58 remains to be established.

Antibodies↗
PubMed1988

Natural killer and natural killer-like cell activity of peripheral blood and intrathyroidal mononuclear cells from patients with Graves' disease.

This study was undertaken to investigate the natural killer (NK) and natural killer-like (NK-like) cell cytotoxic activity toward autologous thyrocytes of peripheral blood mononuclear cells (PB-MNC) and thyroid gland mononuclear cells (TG-MNC) from previously hyperthyroid patients with Graves' disease, and the effects of recombinant interleukin-2 on such cytotoxic activity. The average cytotoxicities of PB-MNC from Graves' patients toward K562 cells (NK-sensitive cells), Raji cells (NK-resistant cells), and autologous thyrocytes were 23.9 +/- 10.8 (+/- SD) lytic units (LU), 7.4 +/- 3.8 LU, and 11.7 +/- 4.4 LU, respectively. There were no differences in the NK and NK-like cell activity of PB-MNC between Graves' disease patients and normal subjects. In contrast to PB-MNC from patients with Graves' disease, NK and NK-like cell activity was markedly decreased in TG-MNC (NK cell activity, 2.1 +/- 2.3 LU; NK-like cell activity, 1.5 +/- 1.5 LU). TG-MNC from Graves' patients had no cytotoxic activity against autologous thyrocytes. Using the monoclonal anti-Leu 7 and anti-CD16 antibodies and a two-color immunofluorescence method, the NK cell subsets were examined in PB-MNC and TG-MNC from Graves' patients. The percentage of CD16+ cells was significantly decreased in TG-MNC compared to PB-MNC, whereas there was no significant difference in the percentage of Leu 7+ cells between PB-MNC and TG-MNC. Incubation of TG-MNC with medium only did not increase the NK and NK-like cell activity of these cells. Furthermore, incubation of autologous PB-MNC with supernatants of minced thyroid tissues did not alter their NK and NK-like cell activity. The decreased NK and NK-like cell activity of TG-MNC was augmented when these cells were incubated with recombinant interleukin-2. These results suggest that the reduction of NK cell activity in TG-MNC may allow perpetuation of B-cell activation and lead to excessive production of autoantibody in thyroid tissue.

Adolescent↗
PubMed1988

[Studies on benexate.CD: effect of inclusion compound formation on the antiulcer activity of benexate, the effective ingredient of benexate.CD].

Benexate.CD, a new orally active antiulcer agent, is an inclusion compound of benexate and beta-cyclodextrin (beta-CD). The present report investigated the significance of complex formation on the antiulcer activity of benexate, the effective ingredient of benexate.CD. To evaluate the improvement of solubility, the dissolution properties of benexate from various pharmaceutical forms into the 1st fluid of the Pharmacopoeia of Japan, a model of gastric juice, were compared. Benexate itself was hardly soluble, but the physical mixture of benexate and beta-CD showed a solubility increase of benexate. On the other hand, benexate.CD showed a supersaturated dissolution curve and its peak concentration was 8 times higher than the solubility of the physical mixture. When benexate.CD was administered orally to pylorus ligated rats in the powder formulation, the similar supersaturated dissolution behavior was observed in the stomach, and the benexate level in gastric tissue was higher than that in benexate or the physical mixture administration. Benexate.CD extremely inhibited the ulcer formation caused by HCl-ethanol ingestion, but there was no significant inhibition after treatment with benexate or the physical mixture. These results indicated that it is necessary for benexate to form an inclusion compound in order to exert a strong antiulcer activity.

Administration, Oral↗
PubMed1988

The effects of cytokines, antithyroidal drugs and glucocorticoids on phagocytosis by thyroid cells.

The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-alpha, -beta, and -gamma (IFN-alpha, beta, and gamma), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37 degrees C for 20 h and were further incubated with fluoresceinated latex beads at 37 degrees C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-beta was consistently seen, little effect was detected with IFN-alpha and -gamma. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.

Antithyroid Agents↗
PubMed1988

Surface ultrastructure of larval Anisakidae (Nematoda: Ascaridoidea) and its identification by mensuration.

The surface ultrastructure of larval Anisakis type I, Anisakis type II, Raphidascaris, Contracaecum type A, Thynnascaris type A and Thynnascaris type B was examined by scanning electron microscopy. These species were identified clearly by the presence of a boring tooth, a mucron, and other morphological features. The means of the distances between transverse striations (DBTS) of larval Anisakis type I (5.45 +/- 0.125 micron), larval Raphidascaris (2.92 +/- 0.051 micron), and larval Contracaecum type A (1.68 +/- 0.056 micron) are significantly different (p less than 0.05). There was a correlation between the diameter of worm trunk (DOWT) and DBTS among these three larval types. In most cases a larva could be identified from the mean value of DBTS and DOWT even if obtained as a fragment from a patient.

Animals↗