Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 163 records · Page 9Linked to original sources

PubMed1990

Histamine release induced by histone and related morphological changes in mast cells.

When isolated rat peritoneal mast cells were exposed to histone mixture, both histamine release and degranulation were evoked rapidly and dose-dependently at concentrations higher than 1 microgram/ml in a Ca-free medium. All of the histone subfractions (H1, H2A, H2B, H3 and H4) induced histamine release from mast cells in a Ca-free medium and, as in the case of histone mixture, the amount of histamine release was reduced by addition of Ca2+. By means of high-voltage electron microscopy, at least three types of degranulation were observed in mast cells exposed to histone mixture: (1) microfilament-associated degranulation, (2) extrusion of granules with the surrounding membrane, and (3) mass degranulation.

Animals↗

PubMed1990

Effects of histamine, granulocyte colony-stimulating factor and db-cAMP on the differentiation of HL-60 cells.

Histamine (10(-7) to 10(-3) M) dose-dependently decreased the incorporation of 3H-thymidine into HL-60 cells, starting from the third day of culture. Also, histamine 1 microM significantly induced the differentiation of HL-60 into cells having the morphological characteristics of mature neutrophils, as did db-cAMP and granulocyte colony-stimulating factor (G-CSF). Phosphorylation of proteins appeared at 60 kd and 120 kd was diminished. The phosphorylation profiles induced by G-CSF and db-cAMP were similar to that of histamine. In the case of db-cAMP, however, no phosphorylated band appeared at 120 kd.

Bucladesine↗

PubMed1990

Influence of certain H1-blockers on the step-through active avoidance response in rats.

The inhibitory effects of some newly developed H1-blockers on the step-through active avoidance response in rats were studied in comparison with those of classical H1-blockers. Single administration of diphenhydramine, pyrilamine, promethazine and chlorpheniramine caused dose-related depressant effects on the active avoidance response. Ketotifen and azelastine caused less potent inhibition than the classical H1-blockers, while the effects of astemizole and oxatomide were almost negligible in suppressing the response. Following chronic administration of pyrilamine and promethazine, the acquisition of active avoidance response was significantly retarded compared with the control group, whereas new H1-blockers caused a somewhat but not significantly slower acquisition than the control group. Chronic administration of astemizole and oxatomide caused only transient suppression of the response. However, classical H1-blockers such as pyrilamine and promethazine caused sustained inhibition for as long as drug administration was continued.

Administration, Oral↗

PubMed1990

Serum IgG from an autoimmune prone mouse C3H/HeJ-gld/gld supports the interleukin-3-dependent cell line through an autocrine mechanism.

C3H/HeJ-gld/gld(C3H/gld) mice have been shown to develop massive lymphadenopathy with autoimmunity. In this study, we tested whether C3H/gld-IgG supports the growth of the IL-3-dependent cell line, FDC-P2/185-4. Serum IgG from C3H/gld mice stimulated FDC-P2/185-4 cells to proliferate. On the other hand, IgG from C3H/HeJ-+/+ did not show such activity. This activity increased with age in both sexes of C3H/gld mice. It was suggested that a monomeric IgG component was responsible for the proliferative activity of C3H/gld mouse sera. The cell-induced growth required Fc gamma receptors on FDC-P2/185-4 cells. FDC-P2/185-4 cells stimulated with C3H/gld-IgG, secreted IL-3, and grew by themselves, indicating an autocrine mechanism. Thus, cytokines produced by serum IgG may play an important role in the development of disease in mice bearing the autosomal recessive mutation gld.

Age Factors↗

PubMed1990

Polyclonal and monoclonal IgGs from MRL/Mp-lpr/lpr mice induce an interleukin-3-dependent cell line to produce interleukin-3 through an Fc gamma-receptor-mediated mechanism.

Serum IgG from autoimmune MRL/MP-lpr/lpr(MRL/l) mice induced IL-3 mRNA, IL-3 synthesis, and cell proliferation in the IL-3-dependent cell line, FDC-P2/185-4. Cell growth, induced by MRL/l-IgG, was suppressed by anti-IL-3 antibody, suggesting an autocrine mechanism. We established hybridomas from the splenocytes of a nonimmunized MRL/l mouse. The mAbs, produced by these hybridomas, also stimulated IL-3 synthesis and cell growth in FDC-P2/185-4 cells. Both anti-IgG-Fc antibody and anti-Fc gamma RII mAb, 2.4G2 suppressed the cell growth induced by these mAbs. Our results suggest that some IgGs of MRL/l mice may induce IL-3 synthesis in cells by binding to Fc receptors.

Animals↗

PubMed1990

A mutant protein of human interleukin-1 beta with immunostimulatory but not pyrogenic potency.

Interleukin-1 (IL-1) mediates a variety of immune and inflammatory responses. In order to understand the mechanisms involved in multiple biological functions, it is important to define the active sites of IL-1. Using the technique for site-specific mutagenesis, we tested whether the arginine residue at the 4th position in human IL-1 beta is essential for multiple biological activities. In our experiments, the fourth position is replaced by a non-basic amino acid--either glycine or aspartic acid. The resulting mutant protein shows both immunostimulatory activity and the ability to induce hematopoietic growth factors similar to native IL-1 beta, but has a markedly reduced pyrogenic potency. Therefore, the mutant protein of IL-1 beta may represent a good candidate for use in vivo as an adjuvant for poor immunogenic vaccines.

Adjuvants, Immunologic↗

PubMed1990

Changes of bioactive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome.

The serum levels of bioactive luteinizing hormone (LH), immunoreactive LH, follicle-stimulating hormone, androstenedione (A), and testosterone (T) were determined in nine anovulatory women with polycystic ovarian syndrome (PCOS) before and after laparoscopic ovarian cautery. Eight ovulated spontaneously and three conceived after treatment. Before treatment, the mean (+/- SEM) levels of bioactive LH, immunoreactive LH, A, and T were 51.4 +/- 8.6 mIU/mL, 36.0 +/- 4.5 mIU/mL, 1.98 +/- 0.35 ng/mL, and 1.18 +/- 0.13 ng/mL, respectively, which were significantly higher than those of five control women (19.2 +/- 1.6 mIU/mL, 21.4 +/- 1.2 mIU/mL, 0.54 +/- 0.03 ng/mL, 0.28 +/- 0.03 ng/mL). After treatment, the mean levels of these hormones had significantly decreased. Decreases in the levels of these hormones by laparoscopic ovarian cautery in women with PCOS may result in both restoration of the ovulatory cycle and achievement of pregnancy.

Adult↗

PubMed1990

Electrocautery in polycystic ovary syndrome.

The serum levels of bioactive luteinizing hormone (LH), immunoreactive LH, follicle-stimulating hormone (FSH), and testosterone were determined in eleven anovulatory women with polycystic ovary syndrome (PCOS) before and after laparoscopic ovarian cautery. Before treatment, the mean +/- SEM levels of bioactive and immunoreactive LH and testosterone were 53.1 +/- 7.9 mIU/ml, 35.2 +/- 3.9 mIU/ml, and 1.14 +/- 0.13 ng/ml, respectively, which were significantly higher than those of five control women (19.2 +/- 1.6 mIU/ml, 21.4 +/- 1.2 mIU/ml, 0.28 +/- 0.03 ng/ml). After treatment, the mean levels of these hormones decreased significantly, ten women ovulated spontaneously and four conceived. The present results suggests that decreases in the levels of these hormones by laparoscopic ovarian cautery in women with PCOS may result in both restoration of the ovulatory cycle and the achievement of pregnancy.

Adult↗

PubMed1990

Regulation of in vivo expression of Fc receptors for IgE (Fc epsilon R) on murine lymphocytes. I. Detection of Fc epsilon R+ lymphocytes by flow cytometry.

Homologous monomeric IgE was employed in a flow cytometric assay for the detection of IgE Fc receptors (Fc epsilon R) on mouse lymphocytes. The expression of Fc epsilon R in normal BALB/c mice was detected on splenic and circulating lymphocytes, but not on bone marrow cells. The Fc epsilon R expression was observed in B cells with B220, surface IgM, and IgD, but not in T cells. Infection of mice with Nippostrongylus brasiliensis resulted in a marked increase in the expression of Fc epsilon R on splenic B cells. T cells, however, did not express Fc epsilon R even after N. brasiliensis infection. On the other hand, the Fc epsilon R expression on normal B cells decreased after a simple incubation at 37 degrees C for 24 h, while in the presence of IgE this decrease was inhibited. In contrast, B cells stimulated with interleukin 4 display Fc epsilon R with high densities. Interestingly, IgE enhanced the Fc epsilon R expression induced by interleukin 4, suggesting that both interleukin 4 and IgE may be responsible for an increase in the expression of Fc epsilon R on B cells of N. brasiliensis infected mice.

Animals↗

PubMed1990

Sequential analysis of histamine release and intracellular Ca2+ release from murine mast cells.

Stimulation of murine peritoneal mast cells with compound 48/80 at a concentration of 1 microgram/ml elicited rather slow histamine release; the onset of release was observed 5 s after stimulation, and it reached a plateau at about 60 s. Both inositol-1,4,5-trisphosphate (IP3) and inositol-1,4-bisphosphate (IP2) contents increased to their maximum 5 s after stimulation. The IP3 content decreased to the control level more rapidly than that of IP2. Changes in the intracellular Ca2+ concentration of the quin 2 loaded mast cells were determined using a video-intensified microscopy system. The fluorescence intensity due to Ca-quin 2 complex increased rapidly after 48/80 stimulation in a Ca-free medium and reached the maximum at about 6-7 s. It became clear that the increase in IP3 content and the resulting Ca2+ release from the intracellular Ca store precede histamine release from murine mast cells.

Animals↗

PubMed1990

Regulation of in vivo expression of Fc receptors for IgE (Fc epsilon R) on murine lymphocytes. II. Induction of Fc epsilon R and its inhibition in mice immunized with antigen.

The induction of Fc receptors for IgE (Fc epsilon R) and its regulation were studied in BALB/c, SJL/J, and nude mice by a flow cytometric assay with the use of homologous monomeric IgE. Immunization of BALB/c mice with alum-absorbed antigen induced a remarkable increase in the expression of Fc epsilon R on spleen cells, whereas no enhancement of the Fc epsilon R expression was observed in SJL/J and nude mice after immunization. This increase was correlated with the elevation of serum IgE levels. However, the IgG antibody response, which is inducible even in SJL/J mice, was not associated with the induction of Fc epsilon R. The enhanced expression of Fc epsilon R in BALB/c mice observed in the primary or secondary IgE antibody response was detected in B cells with B220, surface IgM, and IgD, but not in T cells. The induction of Fc epsilon R in immunized BALB/c mice was inhibited by suppressive factor of allergy isolated from ascites fluids of SJL/J mice inoculated with complete Freund's adjuvant. In addition, both cyclophosphamide and prednisolone had an inhibitory effect on the induction of Fc epsilon R. These results suggest that the Fc epsilon R induction is inhibited not only by suppressive factor of allergy, which is effective in inhibiting the IgE antibody response selectively, but also by some immunosuppressive agents which are capable of suppressing all isotypes.

Animals↗

PubMed1990

Effects of cholinergic drugs and cerebral metabolic activators on memory impairment in old rats.

Age-related changes in the acquisition and retention of memory based on the step-through active avoidance response were studied in rats and the effects of cholinergic drugs and cerebral metabolic activators on memory impairment in old rats were also tested. Six- and 12-month-old rats showed lower rates of acquisition of the active avoidance response than did 2-month-old rats. In addition, the retention of the active avoidance response in 6- and 12-month-old rats diminished rather rapidly compared with that observed in 2-month-old rats. Intraventricular injection of acetylcholine at doses of 20 and 50 ng caused a significant improvement of memory impairment in old rats. Physostigmine and arecoline also caused a significant ameliorating effect at doses of 0.02 and 0.05 mg/kg i.p. and 0.2 and 0.5 mg/kg i.p., respectively. Hopantenate calcium (100 mg/kg, p.o.), idebenone (20 and 50 mg/kg, i.p.), indeloxazine (50 mg/kg, p.o.) and DM-9384 (30 mg/kg, p.o.) also proved useful to improve memory impairment in old rats.

Acetylcholine↗

PubMed1990

[Mast cell].

It has been assumed that the histamine release from mast cells induced by various neuropeptides or basic protein plays some important roles in the development of the hyperreactivity of airways. In the present study, the mechanisms of the histamine release induced by neuropeptides and histone were investigated. Substance P, somatostatin, neurotensin or histone induced histamine release from isolated rat peritoneal mast cells even in the Ca free medium; Ca2+ release from intracellular Ca store was detected very significantly. In order to study the interaction between neuropeptides and phospholipid bilayer of cell membrane, model membrane systems were used. It was indicated that the interaction between basic amino acid residues of neuropeptides and acidic portion in the lipid bilayer caused the conformational changes of neuropeptides from the random coil in the water to the beta-form in the lipids. At the same time, hydrophobic amino acid residues may interact with the hydrophobic region in the lipid bilayer of cell membrane and induce the membrane perturbation, which may cause an increase of the permeability of the membrane. Subsequently, it became evident that after an increase in intracellular Ca2+ concentration, the cytoskeletons inside the mast cell were activated so as to extrude the granules out of the cell.

Animals↗

PubMed1990

Anti-platelet activating factor, anti-leukotriene D4 and some other antiallergic activities of mequitazine.

The bronchoconstrictions of guinea pigs elicited in vivo by leukotriene D4 (LTD4) and platelet activating factor (PAF) were inhibited by pretreatment with mequitazine (CAS 29216-28-2) (p.o.) in a dose-dependent manner at doses of 5-20 mg/kg. Mequitazine (0.5-50 nmol/l) also inhibited LTD4- and PAF- induced contractions of guinea pig tracheal chain. These results suggest that mequitazine possesses antagonistic activity for LTs and PAF; the effects of mequitazine against these two agonists were much more potent than those of ketotifen. The histamine release induced by either of compound 48/80, concanavalin A or A23187 was inhibited by mequitazine at concentrations ranging from 1 to 20 mumols/l. In the inhibition process, mequitazine may act not only to inhibit the Ca2+ release from intracellular Ca store of mast cells but also to stabilize the lipid bilayer of the cell membrane as shown in the order parameter and hypotonic hemolysis. From the present study, it was assumed that mequitazine may exert antiallergic activity by antagonizing LTs and PAF as well as by inhibiting histamine release from mast cells.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1990

Antiallergic effects of astemizole on immediate type hypersensitivity reactions.

Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.

Airway Resistance↗

PubMed1990

Histamine lipolysis I: changes in the free fatty acid levels of dog plasma after intravenous infusion of histamine.

The effects of histamine (Hi) and related compounds on free fatty acid (FFA) levels and % changes in FFA composition of dog plasma were studied after intravenous infusion. Hi at doses of 2-10 micrograms/kg while affecting no changes in the cardiovascular system elicited a dose-related increase in FFA levels in plasma, as did epinephrine. Though all of the FFA concentrations in plasma were increased by Hi infusion, % change of each FFA in the composition did not correspond to that of plasma concentration; % increases in palmitoleic acid, linolenic acid and linoleic acid were remarkable, while stearic acid (18:0) was lowest. The increase in arachidonic acid was not marked, but a dose-related increase was observed after Hi infusion. The H2-agonist 4-methylHi produced an increase in FFA levels, whereas the H1-agonist 2-methylHi was not effective. 4-MethylHi increased all of the plasma FFA levels and the relative changes were similar to those caused by Hi. The effect induced by Hi was blocked by the H2-antagonists cimetidine and ranitidine. Pretreatment with aminophylline potentiated the Hi effect, indicating that Hi lipolysis may be intimately related to cyclic AMP.

Aminophylline↗

PubMed1990

Central effect of the potent long-acting H1-antihistamine levocabastine.

The effects of levocabastine (R 50 547; CAS 79516-68-0) on the central nervous system were studied in comparison with those of diphenhydramine, ketotifen and azelastine. At high doses, levocabastine caused a decrease in locomotor activity, prolongation of thiopental-induced sleep, depression of acetic acid-induced writhing in mice and inhibition of active avoidance response in rats, but these adverse effects were much less potent than those seen in diphenhydramine, ketotifen and azelastine. Oxotremorine-induced tremor and salivation in mice were delayed after extremely high dosage of levocabastine; however, these were much less effective than those seen after diphenhydramine and ketotifen. Levocabastine did not affect the tonic extensor seizure induced by maximal electroshock in mice which is different from that of diphenhydramine. In EEG analysis, levocabastine at a dose of 20 mg/kg caused no significant changes in the EEG recorded from the frontal cortex, occipital cortex, hippocampus and amygdala in rats with chronic electrodes.

Acetates↗

PubMed1990

Histamine lipolysis II: effects of histamine and related compounds on membrane potentials of rat adipocytes.

The effects of histamine (Hi) and related compounds on rat mesenterial adipocytes were investigated using electrophysiological techniques. Hi caused a concentration-related depolarization and significant effect was observed at concentrations higher than 5 x 10(-6) M. Effective membrane resistance was also decreased by Hi. The H1-agonists 2-methylHi and 2-thiazolylethylamine caused no depolarization even at a concentration of 5 x 10(-4) M, but the H2-agonists, 4-methylHi and impromidine decreased resting membrane potentials. While 4-methylHi was less potent than Hi, impromidine was more potent. The H1-antagonists diphenhydramine and pyrilamine did not affect Hi-induced depolarization. However, H2-antagonists like cimetidine and ranitidine caused a significant inhibition even at a concentration of 10(-6) M. As in the case of isoproterenol, the decrease in resting membrane potentials induced by Hi was significantly potentiated by theophylline. Dibutyryl cyclic AMP treatment and intracellular application of cyclic AMP also caused a marked depolarization.

Adipose Tissue↗