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Biomedical subjects

T Okabayashi

Publications and source records attributed to T Okabayashi.

At least 55 records · Page 3Linked to original sources
PubMed1988

Characterization of [3H]U46619 binding in pig aorta smooth muscle membranes.

The binding characteristics of [3H]U46619, a tritiated thromboxane A2/prostaglandin H2 mimetic, were studied in pig aorta smooth muscle membranes. Binding was fast, saturable, selective and reversible. The KD values determined by kinetics, equilibrium binding and drug competition methods were 68, 42 and 53 nM, respectively. The Bmax was 87.8 fmol/mg protein. Specific binding was competitively displaced by thromboxane A2/prostaglandin H2 antagonists. Binding was also displaced by prostaglandins D2, E2 and F2 alpha with IC50 values of 8, 21 and 12 microM, respectively. U46619 contracted the rat and pig aorta smooth muscle, but the response of the latter was slower than that of the former. The antagonists prevented the U46619-induced contraction of rat aorta with the same rank order as that for the inhibition of ligand binding in pig aorta smooth muscle membranes. These results provide evidence that the putative thromboxane A2/prostaglandin H2 receptor in vascular smooth muscle membranes can be detected by a ligand binding technique.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Effects of latamoxef on in vitro and ex vivo thromboxane A2 generation in human platelets.

Although beta-lactam antibiotics cause similar platelet abnormalities in vitro and in vivo, it is still unclear whether the mechanism(s) leading to the defects in both conditions are the same. The present work compared in vitro and ex vivo effects of latamoxef (LMOX) on aggregation and thromboxane (TX)A2 generation, determined as TXB2 generation. In the in vitro systems, LMOX interfered with both responses induced with all agonists tested (ADP, collagen and thrombin). Furthermore, although LMOX did not suppress arachidonic acid (AA)-induced TXB2 generation, it significantly suppressed the aggregation. In ex vivo systems performed with four healthy subjects, LMOX administration clearly suppressed the ADP-induced responses, but not the responses induced with the other agonists or AA. These differences observed in vitro and ex vivo are discussed from the viewpoint of different action mechanisms of LMOX under the two conditions.

Adenosine Diphosphate↗
PubMed1987

Analysis of tissue lymphocytes by double fluorescent staining--gastric cancer tissue and regional lymph nodes.

An immunohistochemical study was performed on human lymphocytes in the tissue of gastric cancer, and also in the regional lymph nodes, by double fluorescent staining, using monoclonal antibodies. Leu3a+8+ cells (inducer T cells) which consist about 30 per cent of Leu 3a+ cells were seen in the tissue surrounding the gastric cancer. The other 70 per cent of Leu 3a+ cells were Leu3a+8- cells (helper T cells). In the lymph nodes they were noted in T cell areas in almost the same proportions, while in germinal centers, only Leu3a+8- cells were found. On the other hand, OKT8+Leu15- cells (cytotoxic T cells) were noted in a large number, while OKT8+Leu15+ cells (suppressor T cells) were few. Further, an increase of OKT8+Leu15- cells was seen around gastric cancer or metastatic cancer in lymph nodes. These immunohistochemical findings suggest that cytotoxic T cells are the main component in the tissue of gastric cancers and the regional lymph nodes. Increases in inducer T cells and helper T cells are probably required to induce cytotoxic T cells around the cancer tissue.

Antibodies, Monoclonal↗
PubMed1987

[An immunohistochemical study using a double staining method for regional lymph nodes in gastric cancer].

We have performed a double immunofluorescent staining of two monoclonal antibodies, obtained from gastric cancer patients, that were directed against lymphocyte surface antigens on the regional lymph nodes. Through this method we were able to identify the lymphoid cell subset in detail. As a result of our double staining, most OKT8+ lymphocytes were also found to be Leu 15- lymphocytes and these OKT8+ Leu 15- lymphocytes were regarded as being cytotoxic effector cells or precursors. A few OKT8+ Leu 15+ lymphocytes (suppressor T lymphocytes) were obtained. More Leu 3a+ Leu 8- lymphocytes (helper T lymphocytes) were observed than Leu 3a+ Leu 8- lymphocytes (suppressor inducer T lymphocytes). To investigate whether these T lymphocytes were activated, we used an OKT 9 monoclonal antibody directed against the transferrin receptor and an OKIa1 monoclonal antibody directed against the HLA-DR framework. Such double stained lymphocytes (activated T lymphocytes) were few.

Antibodies, Monoclonal↗
PubMed1987

[Immunohistochemical study of the regional lymph nodes in gastric cancer].

Immunohistochemical study with various monoclonal antibodies against the mononuclear cell surface antigen was performed on the regional lymph nodes of gastric cancer through Avidin-Biotin Complex (ABC) method. In the paracortical area (P.C.) of those lymph nodes without the metastasis of gastric cancer, T cells were dominant, and OKT3 positive (OKT3+) cells and OKT4+ cells were diffusely present, while OKT8+ cells were occasionally recognized. In the sinus, subsets of the above T cells, and OKT9+ cells and OKT10+ cells were observed. In the germinal center (G.C.), mantle zone (M.Z.) and primary follicle (P.F.), which were B cell regions, OKIa1+ cells and Leu12+ cells were diffusely present. OKB7+ cells, OKT9+ cells, OKT10+ cells and Leu7+ cells were also noted in G.C.. Leu8+ cells were observed in M.Z. and P.F.. OKIa1+ cells were occasionally noted in P.C. and sinus. In the lymph nodes with the metastasis, decrease of OKT4+ cells and increase of OKT8+ cells were noted in comparison to the lymph nodes without the metastasis. Using the tissue double fluorescence staining method, it was found that about half of the OKT4+ cells were helper T cells. The majority of OKT8+ cells were identified as cytotoxic T cells or their precursors. By preoperative endoscopic administration of OK-432 or PSK into the tumor, the IL-2 receptor+ cells, or OKM1+ cells and OKT4+ cells increased in the regional lymph nodes and the antitumor activity was intensified.

Antibodies, Monoclonal↗
PubMed1986

Suppression by beta-lactam antibiotics of thromboxane A2 generation and arachidonic acid release in rabbit platelets in vitro.

High concentrations of latamoxef and some other beta-lactam antibiotics suppressed thromboxane A2 generation as determined from the thromboxane B2 level in the in vitro aggregation of rabbit platelets in agonist-induced stimulations. In aggregation induced with a low concentration of collagen, the suppression of thromboxane B2 generation correlated well with the suppressions of aggregation and serotonin (5-HT) release; collagen produced thromboxane A2-dependent aggregation and 5-HT release as judged from the inhibitory action of indomethacin. Latamoxef also suppressed thromboxane B2 generation when platelet stimulation was induced by thrombin or platelet activating factor at concentrations at which it did not affect either aggregation or 5-HT release. However, latamoxef did not affect platelet responses including thromboxane B2 generation induced by exogenous arachidonic acid or calcium ionophore, A23187. Beta-lactam antibiotics also interfered with arachidonic acid release from the membrane phospholipids of platelets which had been prelabelled with [3H]arachidonic acid and aggregated with collagen. These results suggest that in the in vitro aggregation of platelets, beta-lactam antibiotics interfere with some of the receptor-stimulated processes which lead to arachidonic acid release from the membranes and this, in turn, suppresses thromboxane B2 generation.

Animals↗
PubMed1986

Bradykinin-induced cyclic AMP accumulation in mouse fibrosarcoma independent of prostaglandin E2 formation.

The relationship between bradykinin (BK)-induced prostaglandin E2 (PGE2) and cyclic AMP syntheses in mouse fibrosarcoma cells (HSDM1C1) was investigated. Maximal BK-induced increases in cyclic AMP preceded increases in PGE2 production. PGE2 synthesis reached maximum at a much lower concentration of BK than cyclic AMP synthesis. Indomethacin completely inhibited BK-induced PGE2 production, but did not influence the cyclic AMP levels. Arachidonic acid in the medium induced PGE2 production in large quantities, but increased cyclic AMP accumulation only slightly. A high PGE2 concentration increased cyclic AMP levels only slightly. Theophylline increased basal and BK-mediated cyclic AMP levels, but did not affect PGE2 production at all. These results indicate that BK-evoked PGE2 and cyclic AMP syntheses in HSDM1C1 are not dependent upon each other.

Animals↗
PubMed1985

Effects of caerulein-related peptides on cholecystokinin receptor bindings in brain and pancreas.

A number of caerulein (CLN)-related peptides were synthesized and compared in terms of their affinities for cholecystokinin (CCK) receptors. We have found that these peptides can be classified into three types according to their relative affinities for the brain and pancreatic receptors. The first group (type A) of peptides includes CLN and analogs retaining the Tyr(SO3H)4 residue and the COOH-terminal amide group. Type A peptides were as potent as CLN in inhibiting [125I]BH-CCK-8 binding and showed almost the same affinities for pancreatic and brain receptors. When the Tyr(SO3H)4 residue was either deleted or desulfated (type B), the affinities of the peptides decreased remarkably for the pancreatic receptors but much less for the brain receptors. The type C peptides were deamidated, oxidized, or shortened in the COOH-terminal region and exhibited greatly decreased affinities for both brain and pancreatic receptors but a much greater decrease for the brain receptor. These results indicate that, although the Tyr(SO3H)4 residue and the COOH-terminal structure are both essential for CLN to bind to the CCK receptors, the former is of critical importance for the binding to the pancreas and the latter is rather important for the binding to the brain.

Animals↗
PubMed1985

[Clinical and immunological study on the high incidence of malignant neoplasms in patients with chronic renal failure].

With the advancement of dialysis techniques, rehabilitation and high morbidity are becoming serious problems for patients with chronic renal failure. The authors, with the purpose of investigating the carcinogenic state of such patients, studied the incidence of malignant neoplasms and their immunity both clinically and fundamentally. Out of 499 patients with chronic renal failure, malignant neoplasms were found in 17 cases (3.40%), which is obviously a high rate with a statistically significant difference from that of the ordinary healthy population. In the fundamental immunity study, OKM1+ cells of the patients were significantly lower than those of healthy people, and a decrease in NK and K cells was inferred. Incidentally, the lymphocytes of patients strongly inhibited the mitogen response of healthy subjects. This decline in cellular immunity is considered to be closely related to the carcinogenicity of patients with chronic renal failure.

Adult↗
PubMed1985

[The immune defense system in gastric cancer tissue, regional lymph node and spleen--aspects from subsets and functions of lymphocytes].

Tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) were thought to play an important role in local immunity against cancer. But the natural cytotoxicity (NC) of TIL and LNL was very weak, and was not augmented by beta-IFN. This low cytotoxicity was augmented by IL-2, and especially LNL were activated to have higher lymphokine activated killer (LAK) activity than that of PBL. So it was proven that TIL and LNL had an potential of immunological defence system. In order to bring out these potential, immunomodulators (OK-432, PSK) were injected intralesionally under endoscopy one week prior to surgery. The cytotoxicity of TIL and LNL was augmented by the intralesional injection of OK-432 or PSK. There was no significant difference in LAK activity of LNL among the OK-432-, PSK-injected group, and the control. The 2-year survival rate of the OK-432-injected group was much longer than that of the control. From above results, intralesional injection of immunomodulators was thought to be a promising candidate for the immunotherapy of gastric cancer.

Humans↗
PubMed1984

Detection and determination of active metabolites of 1-(2-o-chlorobenzoyl-4-chlorophenyl)-5-glycyl-aminomethyl-3-dimethy l-carbamoyl-1H-1,2,4-triazole hydrochloride dihydrate, (450191-S), in rat tissues, using a radioreceptor assay for benzodiazepines.

1-(2-o-Chlorobenzoyl-4-chlorophenyl)-5-glycyl-aminomethyl-3- dimethylcarbamoyl -1H-1,2,4-triazole hydrochloride dihydrate, (450191-S), exhibits pronounced central nervous system (CNS) activities similar to those of benzodiazepines, but it has only low affinity for benzodiazepine receptors. However, when 450191-S was administered to rats at a dose of 10 mg/kg, brain extracts markedly inhibited [3H]diazepam binding to the receptors. Thin-layer chromatography (TLC), high performance liquid chromatography (HPLC), and radioreceptor assay (RRA) were used to isolate three metabolites that could inhibit [3H]diazepam binding prominently. These were identified by gas chromatography-mass spectrometry (GC/MS) as compounds having the triazolo-benzodiazepine skeleton. They showed high affinities for benzodiazepine receptors (Ki = 0.9 to 2.1 nM) and exerted potent pharmacological effects similar to those of 450191-S. In addition, their levels in the brain were sufficient to explain the pharmacological activity of 450191-S, which could not be detected in tissue extracts 15 min after administration. These results indicate that the pharmacological activity of 450191-S is largely due to the action of active metabolites, although some points remain to be elucidated to fully account for the large attenuation of the side effect (ataxia) compared with the major effects (anti-convulsant and hypnotic). We also determined the brain levels of metabolites following the administration of 450191-S and evaluated the extent to which each active metabolite contributes to the pharmacological activities of this drug.

Animals↗
PubMed1983

Influence of phospholipase treatments on ligand bindings to a benzodiazepine receptor-GABA receptor-chloride ionophore complex.

Treatment of rat cerebellar membranes with phospholipase A2 (PLA2) or phospholipase C (PLC) increased basal [3H]diazepam binding at 0 degrees C with concomitant disappearance of the stimulatory effect of Cl- ion on the binding. On the other hand, these treatments did not affect the stimulatory effect of GABA, nor the maximum enhancement obtained in the presence of both GABA and Cl- ion. These results suggest that PLA2 or PLC modified the phospholipids responsible for the interaction between the benzodiazepine receptor and the Cl- ionophore. This assumption was supported by the results of thermodynamic experiments which showed that the changes in thermodynamic parameters occurring after the addition of Cl- ion resembled those after PLA2 or PLC treatment. Since the effect of PLA2 was evident at very low concentrations, and a PLC concentration of at least one order of magnitude higher was required to induce a similar effect, the change of phospholipids especially to lysophospholipids seems to be of particular importance. Protein release from the membrane, which also occurs after PLA2 or PLC treatment, did not appear to be responsible for the present phenomenon.

Animals↗