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Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 19 recordsLinked to original sources

Phosphorylation of smg p21B in rat peritoneal mast cells in association with histamine release inhibition by dibutyryl-cAMP.

IP3 formation and histamine release from rat peritoneal mast cells stimulated by compound 48/80 were dose-dependently inhibited by Bt2cAMP. These inhibitions were restored to the control level in the presence of H-8, a protein kinase A inhibitor. The 22 kDa protein in mast cells was revealed as a markedly phosphorylated protein by incubating with Bt2cAMP, and this phosphorylation was also diminished by H-8. The 22 kDa phosphoprotein of rat mast cells comigrated with phosphorylated smg p21B, purified from human platelets and phosphorylated by protein kinase A in cell-free system, in both one- and two-dimensional PAGE analysis. Moreover, 22 kDa protein in mast cells was identified as smg p21B by immunoblot analysis using an antibody against smg p21B. From the present study, it became clear that smg p21B is phosphorylated by means of protein kinase A system in rat peritoneal mast cells, and it was assumed that phosphorylated smg p21B plays some important role in the suppression of IP3 formation and histamine release from rat peritoneal mast cells.

Animals

Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A.

When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such as cimetidine, ranitidine and famotidine, but also by an inhibitor of protein kinase A (A kinase), KT-5720. Histamine increased the cAMP level and A kinase activity in HL-60 cells; both increases preceded the cell differentiation. Histamine also enhanced phosphorylation of a 160 kD protein in HL-60 cells, while H2 antagonists and KT-5720 inhibited this phosphorylation. The results of the present study indicate that an activation of A kinase via H2 receptor stimulation may cause the phosphorylation of a 160 kD protein and that this phosphorylation is probably involved in the process leading to differentiation of HL-60 cells.

Carbazoles

Cortisol secretion induced by substance P from bovine adrenocortical cells and its inhibition by calmodulin inhibitors.

When primary cultured bovine adrenocortical cells were treated with substance P (SP) at concentrations higher than 10 pM, cortisol output increased in a dose-dependent fashion. Although other neurokinins, such as neurokinin A (NKA) and neurokinin B (NKB), were also effective in secreting cortisol, SP was the most potent among the tested neurokinins, the potency order being SP greater than NKA much greater than NKB. This suggests that the NK-1 type receptor on adrenocortical cells may be the site of action of SP on cortisol secretion. The maximal response in SP-induced cortisol secretion was comparable to that elicited by adrenocorticotropic hormone (ACTH). SP-induced cortisol secretion was dependent upon extracellular Ca2+ concentrations, and 45Ca2+ uptake into adrenocortical cells treated with SP was long-lasting. While, in the case of ACTH, 45Ca2+ uptake proceeded transiently, the increase in intracellular cAMP content was much greater compared with that of SP. Although KT-5720, an inhibitor of protein kinase A, inhibited potently ACTH-induced cortisol secretion, SP-induced secretin was not affected by this inhibitor at all. On the other hand, calmodulin inhibitors, such as calmidazolium, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, were not more effective in inhibiting SP-induced cortisol secretion than secretion induced by ACTH. The present study indicates that SP may be one of the physiological stimulants of cortisol secretion and that an increase in intracellular Ca2+ concentration and the subsequent activation of calmodulin may precede SP-induced cortisol secretion.

Adrenal Cortex

Regulation of intracellular Mg2+ by superoxide in amnion cells.

Changes of intracellular free Mg2+ concentration ([Mg2+]i) in human amnion cells induced by superoxide anion were determined using a highly Mg(2+)-sensitive fluorescent dye Mg(2+)-fura2 or Mg(2+)-indol. Superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, induced decrease of [Mg2+]i. The decrease was significantly inhibited by an anion channel blocker, 4,4'diisothiocyano-2,2' disulfonic acid stilbene (DIDS). Superoxide dismutase (SOD), injected into cells by cell fusion, also inhibited the change of [Mg2+]i, but catalase did not. Superoxide anion induced prompt increase of intracellular pH (pHi) as well as decrease of [Mg2+]i and subsequently activated the increase of intracellular free Ca2+ ([Ca2+]i) and the release of arachidonate. In contrast to superoxide anion, NH4Cl which induces increase of pHi in amnion cells increased [Mg2+]i. The elevation of basal level of [Mg2+]i by Mg(2+)-ionophore inhibited the change of [Ca2+]i and the release of arachidonate induced by superoxide anion. These results suggest that superoxide anion, transported through anion channels into cells, decreases [Mg2+]i directly, not due to a pH-effect and that the decrease of [Mg2+]i may regulate biological functions of the cells via increase of [Ca2+]i.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Histamine-induced depolarization and the cyclic AMP--protein kinase A system in isolated guinea pig adipocytes.

The relationship between histamine (Hi)-induced depolarization and the cyclic AMP system in adipocytes was studied in guinea pigs, which seem to be more sensitive than rats to Hi. Hi caused a dose-dependent depolarization in guinea pig mesenterial and epididymal adipocytes with EC50 values of 1.69 x 10(-7) M and 1.19 x 10(-7) M, respectively. Guinea pig adipocytes were 280-750 times more sensitive than rat adipocytes to Hi. Isoproterenol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) also caused a depolarization, and the slopes of the concentration response lines for these drugs were almost the same as that for Hi. Furthermore, pretreatment with these drugs resulted in a potentiation of Hi-induced depolarization at lower concentrations which are not effective when each drug is used alone. In addition, Hi-induced depolarization was inhibited by pretreatment with prostaglandin E1 (PGE1) and insulin dose-dependently. The content of cyclic AMP in adipocytes was increased by Hi (10(-7) M) in association with a decrease in membrane potential. KT5720, a protein kinase A inhibitor, which provides no significant effect even at a concentration of 10(-6) M, showed an antagonistic effect on Hi-induced depolarization.

1-Methyl-3-isobutylxanthine

Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (II). Antagonistic effect of epinastine on chemical mediators, mainly antihistaminic and anti-PAF effects.

Anti-histamine and anti-PAF effects of epinastine were tested in rats, guinea pigs and rabbits. Epinastine showed a potent histamine H1-blocking effect, but the potency was slightly less than that of ketotifen in histamine-induced contraction of guinea pig ileum and histamine-induced cutaneous reactions in rats. In histamine-induced dye leakage into the nasal cavity tested in rats, the drug was slightly more potent than ketotifen and azelastine. Epinastine as well as ketotifen suppressed rabbit platelet aggregation induced by PAF at higher concentrations compared with WEB 2086, a specific PAF-antagonist. In the bronchospasm induced by PAF in guinea pigs, epinastine was more effective than ketotifen in inhibiting the bronchoconstriction, while it showed no remarkable effect on the hypotension induced by PAF. Epinastine caused a potent antagonistic effect on LTC4-induced contraction of isolated guinea pig trachea. In conclusion, the potent anti-histamine, anti-PAF and anti-LT effects of epinastine may significantly contribute to its antiallergic activity.

Animals

Histamine leukocytosis. I. Effect of histamine on peripheral leukocyte counts.

The effect of chronic administration of histamine on the number of cells in peripheral blood of dogs, rabbits and guinea pigs was tested by single and consecutive intramuscular injections of histamine in a beeswax-sesame oil mixture. Leukocytosis due to increased numbers of neutrophils occurred in all animals after single injections of histamine in beeswax, although erythrocytes and hematocrit values were unaffected in all species. When injection of histamine was repeated on consecutive days, the extent of leukocytosis subsided in some cases; however, the simultaneous administration of aminoguanidine restored leukocytosis. Single or daily injections of the beeswax-sesame oil mixture without histamine had none of these effects in any animals tested. Although simultaneous injections of histamine and H1 receptor antagonists did not alter histamine effects, the combined administrations of histamine and H2 receptor blocking agents suppressed histamine-induced leukocytosis.

Animals

Histamine leukocytosis. II. Source of histamine leukocytosis.

Leukocytes were labelled by intravenous injection of tritiated thymidine (3H-thymidine) in dogs to discover the source of the increased number of neutrophils in the circulating blood after injection of histamine in beeswax. Dogs with normal hemograms were given 1.0 mCi/kg of 3H-thymidine alone, and in different sequences, with histamine in beeswax. When 3H-thymidine was given during maintained histamine leukocytosis, labelled granulocytes appeared in and disappeared from the blood earlier than in control tests and the number of labelled cells was greater in the histamine-treated animals. Administration of histamine in beeswax 3 days after injection of 3H-thymidine also induced the premature appearance and disappearance of labelled neutrophils in the circulating blood. It was concluded that leukocytosis induced by the chronic action of histamine is due to 1) stimulated proliferation and differentiation of neutrophil precursor cells in the bone marrow and 2) the release of mature leukocytes from the bone marrow.

Animals

Characteristics of intraluminal pressure sensing balloons of different materials.

The physical properties of the balloons made of some polymeric substances were studied. The polyurethanes provided high frequency characteristics but air-leaking disqualified except ECD-651 which was most satisfactory: low permeability and ease of fabrication. Saran was proper but troublesome in making the balloon. Polypropylene and polyethylene, available in film, required heat sealing, which resulted in deformity and low frequency characteristics.

Intestines

Circulating immune complexes in the serum of diabetes mellitus in childhood by a modified 125I-C1q binding test.

The 125I-C1q binding test for the detection of soluble immune complexes in native unheated human serum was applied to the study of sera from 52 patients with diabetes mellitus in childhood. This radiolabeled C1q binding test is more sensitive and reproducible among the various methods proposed for the detection of immune complexes. The 125I-C1q binding activity in 52 sera from diabetes mellitus in childhood was 9.47 +/- 0.36% compared to 6.94 +/- 0.74% in normal controls. 125I-C1q binding values in diabetes mellitus in childhood were significantly higher than normal controls. Slight high values were seen in 3 patients with positive anti-DNA-antibodies in diabetes mellitus in childhood. 125I-C1q binding was not significantly increased in patients with positive antithyroid antibodies and insulin antibodies. There was no significant correlation between the duration of diabetes and 125I-C1q binding activity.

Adolescent

Characteristics of pressure sensing balloons made of various polymeric materials.

A variety of polymeric materials (polyurethane, polypropylene, polyethylene and polyvinylidine copolymer) have been evaluated for suitability in making of air-filled balloon to detect intraluminal pressure. The polyurethanes, in particular ECD, proved to be most suitable because of the ease of fabrication, low permeability to air and high frequency characteristics. Polyvinylidine copolymer was adequate but suffered from difficulties in fabrication. Polypropylene and polyethylene, available in film, were troublesome in making balloon and displayed low frequency characteristics.

Animals

Anti-allergic properties of a new histamine antagonist, 4-(p-chlorobenzyl)-2- [N-methyl-perhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride (azelastine).

Anti-allergic properties of 4-(p-chlorobenzyl)-2 [N-methyl-perhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride (azelastine, A-5610) were investigated focusing the most attention on its decongestive effect. Intravenous injection of azelastine into anesthetized dogs with doses more than 0.1 mg/kg prevented the changes in nasal impedance provoked by histamine sprayed into the nasal cavity. When azelastine was given orally, the minimum effective dose to abolish the impedance reduction due to histamine was 2 mg/kg, in the case of cleamastine the same dose was required. Histamine release from the rat mesentery pieces by the condensation product of N-methyl-homoanisylamine formaldehyde (compound 48/80) (0.005%) was inhibited almost completely by pretreatment with azelastine at the concentrations of 10(-4) to 10(-3) g/ml, and in those concentrations azelastine alone released histamine scarcely. When 5 mg/kg of azelastine was given i.v. to rabbits, the characteristic changes in EEG -- a high-voltage low-frequency pattern -- persisted more than 1 h, but not the least inhibition in arousal response was noted. With the dose of 0.5 mg/kg, diphenhydramine impaired arousal response and slow waves with high amplitude dominantly appeared in EEG.

Administration, Oral

Studies on rickettsia-like body in Kawasaki disease. Attempts of the isolation and characterization.

Rickettsia-like bodies were reportedly found in biopsies of the skin and lymph nodes from half the number of patients with Kawasaki's disease. In our present work, these microbodies were isolated from the peripheral whole blood of a patient with Kawasaki's disease (MLNS) through passage of guinea pigs and yolk sac culture. However, the isolated strains disappeared spontaneously during their stores at -80 degrees C for two weeks.

Animals

Function of phagocytosis and intracellular killing of peripheral neutrophils in Kawasaki disease.

NBT (Nitroblue Tetrazolium) test was performed in 17 patients with Kawasaki disease to examine the function of phagocytosis and intra-cellular killing of neutrophils. The value was high compared to other pediatric patients. Activation with Proteus OX-2 antigen before NBF test showed a significant higher level than other proteus antigens, which correspond in serum level. With previous electronmicroscopic observation of rickettsia-like body in biopsy specimen, these findings suggest the existence of an agent in Kawasaki disease which shares antigenicity with Proteus OX-2.

Antigens, Bacterial

Effects of n-decylamine and toluidine blue on the electric capacitance of isolated rat mast cells.

The electric capacitance of isolated rat mast cells and its change under the influence of either n-decylamine or toluidine blue was investigated. Since the electric circuit employed in the detection unit is the one merely sensitive for the capacitance changes, output signals pertain to the capacitance of the tested cell alone. N-decylamine released histamine without accompanying degranulation; and it caused a marked swelling of mast cells and a striking decrease of capacitance, although electric capacitance is usually proportional to the size of the cell. Morphological changes induced by toluidine blue are seemingly correlated with the changes in capacitance. At the concentrations (25-50 microgram/ml) in which the mast cell became enlarged, electric capacitances exceeded the control value. However, at the concentrations higher than 100 microgram/ml in which the cell became shrunken, the capacitance values were less than control value. Pretreatment with DNP (0.1 mM) or oxyphenbutazone (0.05-0.2 mM) was of little effect in inhibiting the histamine release, morphological alterations and capacitance changes due to n-decylamine, but pretreatment with either prevented all of those changes produced by toluidine blue. The mechanism of the capacitance changes in mast cells induced under influence of those compounds is discussed.

Amines

An experimental study on endoscopic papillotomy in monkeys.

Endoscopic papillotomy would appear to have distinct advantages in non-operative treatment of common bile duct stones. To investigate the effects of this procedure on the papilla and adjacent organs, diathermy papillotomy was performed at laparotomy in three monkeys. White-cell count and levels of liver function parameters temporarily increased during the follow-up period of twelve months, suggesting that diathermy papillotomy might have brought about some pathological changes in the hepatobiliary system of monkeys, whereas no definite evidence of cholestasis or pancreatitis were noticed, and an excellent condition of papillotomy orifice and adjacent ogans was revealed at autopsy about 1 year after diathermy papillotomy.

Ampulla of Vater