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Biomedical subjects

M Takei

Publications and source records attributed to M Takei.

At least 91 records · Page 5Linked to original sources

Induction of lupus-associated autoantibodies by immunization with native and recombinant Ig polypeptides expressing a cross-reactive idiotype 4B4.

A human mAb designated 4B4 with anti-Sm activity was derived from a patient with systemic lupus erythematosus. This antibody expressed a lupus-associated cross-reactive Id, partially related to the monoclonal murine anti-Sm (Y2) from MRL/lpr mice. Studies were performed to investigate the ability of 4B4 to induce lupus in nonautoimmune-prone mice. BALB/c mice immunized with 4B4 produced antibodies to dsDNA, ssDNA, Sm ribonucleoprotein, and mouse Fc fragment. There was no antibody activity against SSA/Ro, SSB/La, and hen egg lysozyme. Ag inhibition studies show that the autoantibodies were not polyreactive. Mice were also immunized with r4B4 polypeptides representing the H/L heterodimer, H chain and L chain. Autoantibodies were induced in mice immunized against the H/L and H polypeptides. No autoantibodies were induced in mice immunized with recombinant L chain. Furthermore, from 20 to 68% of antibody activity to Sm or dsDNA could be inhibited with anti-Id antiserum (either anti-4B4 or Y2). The autoantibody was initially IgM and then underwent an isotype switch to IgG. These results show that lupus-associated autoantibodies can be induced by immunization with 4B4 and that the 4B4 VH region is important in this induction process. The finding of murine IgG autoantibody expressing a cross-reactive Id similar to the immunizing 4B4 suggests a role for anti-idiotypic Th cells in this autoimmune response.

Animals↗

Mast cell activation by pedicellarial toxin of sea urchin, Toxopneustes pileolus.

Pedicellarial toxin, partially purified from the sea urchin Toxopneustes pileolus, dose-dependently and time-dependently caused histamine release from rat peritoneal mast cells. Pedicellarial toxin induced a rapid initial rise in [Ca2+]i within several seconds which was followed by a further slower increase of [Ca2+]i (second rise). The toxin induced a dose-dependent formation of inositol 1,4,5-triphosphate (IP3) as well as the histamine release in mast cells. Furthermore, the toxin stimulated phosphoinositide-specific phospholipase C (PI-PLC) activity in mast cell membranes. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), a PLC inhibitor, inhibited the activation of PI-PCL induced by pedicellarial toxin. Cholera toxin inhibited pedicellarial toxin-induced histamine release, whereas pretreatment of pertussis toxin failed to inhibit it. These results suggest that pedicellarial toxin from T. pileolus activates PI-PCL and the stimulation of PI turnover may lead to the release of IP3 into the cytoplasm, resulting in histamine release from rat mast cells.

Animals↗

Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine sponge Xestospongia bergquistia.

Histamine release from rat peritoneal mast cells induced by anti-IgE was essentially complete within 4-5 min. Xestobergsterol A and B, which are constituents of the Okinawan marine sponge Xestospongia bergquistia Fromont, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The IC50 values of xestobergsterol A and B for histamine release in mast cells activated by anti-IgE were 0.07 and 0.11 microM, respectively. Anti-IgE stimulated PI-PLC activity in a mast cell membrane preparation. Xestobergsterol A dose-dependently inhibited the generation of IP3 and membrane-bound PI-PLC activity. Moreover, xestobergsterol A inhibited Ca(2+)-mobilization from intracellular Ca(2+)-stores as well as histamine release in mast cells activated by anti-IgE. On the other hand, xestobergsterol B did not inhibit the membrane-bound and cytosolic PI-PLC activity, IP3 generation or the initial rise in [Ca2+]i in mast cells activated by anti-IgE. These results suggest that the mechanism of inhibition by xestobergsterol A of the initial rise in [Ca2+]i, of the generation of IP3, and of histamine release induced by anti-IgE, was through the inhibition of PI-PLC activity.

Animals↗

Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand.

Both human and mouse c-kit ligand induced differentiation of human mast cells in a long-term culture of the mononuclear cells of umbilical cord blood. Growth factor activity for human mast cells present in conditioned medium of BALB/3T3 fibroblasts was due to mouse c-kit ligand. Recombinant c-kit ligand induced differentiation and proliferation of mast cell progenitors in early stages of culture. However, apparent selective growth of mast cells by c-kit ligand in cord blood cell cultures is mainly due to the effect of the cytokine to selectively maintain survival of immature mast cells. Electron microscopic analysis indicated that human mast cells developed by c-kit ligand were similar to human mast cells in the lung and gut mucosa, while those developed in coculture of cord blood cells with Swiss albino/3T3 fibroblasts were similar to skin mast cells. This conclusion was supported by the fact that the majority of mast cells developed by c-kit ligand contained only tryptase in their granules, whereas those developed in the cocultures contained both tryptase and chymase. It was also found that mast cells developed by c-kit ligand were immature even after culture for 14 weeks. Nevertheless, these cells express Fc epsilon RI, and could be sensitized with human IgE for anti-IgE-induced release of histamine, prostaglandin D2, and leukotriene C4.

Animals↗

Immunologic significance of increased soluble CD8/CD4 molecules in patients with active systemic lupus erythematosus.

This study attempted to estimate soluble CD4(sCD4)/CD8(sCD8) molecules in active systemic lupus erythematosus (SLE) patients. Measurements were made by solid-phase enzyme-linked immunosorbent assay. sCD8 or sCD4 molecules were significantly increased in the patients as compared to control subjects. sCD8 correlated with the erythrocyte sedimentation rate. sCD4 correlated with the anti DNA antibody titer, the IgG concentration, and negatively with the complement titer. An association of these molecules with immunologic abnormalities and disease activity exists in SLE patients.

CD4 Antigens↗

Histamine release from rat mast cells induced by the inhibition of adenosinetriphosphatase for Na and K channels.

6-Tridecylresorcylic acid (TRA) caused histamine release from rat peritoneal mast cells in a dose-dependent manner. The release of histamine by TRA was also time dependent. On the other hand, high K+ (150 mM) strongly inhibited TRA-induced histamine release from rat mast cells. These results suggest that histamine release from mast cells might be associated with K+ channel activity.

Actomyosin↗

Effect of a potent selective protein kinase C inhibitor on histamine release from rat mast cells.

3,10-Dihydroxy-10-[(dimethylamino)methyl]-2,3,9,10,11,12-hexahydro-9- methyl-9,12-epoxy-1H-diindolo[1,2,3-fg-3',2',1'-k1]pyrrolo[3,4- l][1,6]benzodiazocin-1-one (UCN-01) strongly and dose-dependently inhibited histamine release from rat peritoneal mast cells that was induced by anti-immunoglobulin E (anti-IgE), calcimycin (A 23187), and 1,2-o-tetradecanoyl-13-acetate (TPA). The concentrations of UCN-01 required for 50% inhibition of histamine release induced by anti-IgE, A23187, and TPA were 1.5, 2.7, and 1.4 nM, respectively; these values are similar to those for 50% inhibition of protein kinase C. These results suggest possible participation cells induced by various secretagogues.

Alkaloids↗

Characterization of a cross-reactive idiotype on two human autoantibodies associated with systemic autoimmune disease.

A human-human hybridoma was derived from a patient with primary Sjogren's Syndrome. The monoclonal antibody from this hybridoma, P36, was found to be polyreactive. P36 shared idiotypic cross-reactivity with a lupus-associated monoclonal antibody called 4B4. There was a strong correlation between P36 and 4B4 idiotype levels in systemic lupus erythematosus sera. Western blot studies showed that this shared idiotype was found on the heavy chain of both antibodies. This study shows that the heavy chain is important in the expression of this idiotype and provides another immunologic link between these two rheumatic diseases.

Antibodies, Monoclonal↗

Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus.

We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

Adolescent↗

Effect of okadaic acid on histamine release from rat peritoneal mast cells activated by anti-IgE.

The effect of okadaic acid, a potent inhibitor of protein phosphatase 1 and 2A, on histamine release from mast cells has been investigated. Okadaic acid strongly and dose-dependently inhibited histamine release from mast cells induced by anti-IgE. The IC50 value of okadaic acid on histamine release induced by anti-IgE was 3.2 nM. However, okadaic acid failed to inhibit histamine release induced by A23187 and compound 48/80. Moreover, okadaic acid showed no effect on the initial rise in intracellular Ca2+, Ca(2+)-mobilization from intracellular Ca(2+)-stores and the generation of inositol trisphosphate. These results suggest a possible involvement of protein phosphatase 2A in the histamine release from mast cells induced by anti-IgE.

Animals↗

The time course of phosphate metabolites and intracellular pH using 31P NMR compared to recovery heat in rat soleus muscle.

1. The recovery time course of changes in phosphate metabolites and pH, after tetanic contractions of 6 and 9 s were studied using 31P NMR with 4 and 16 s resolution, in rat soleus muscles at 20 degrees C. Muscles were at a sarcomere length of 3.15 microns (active), being greater than optimum for force which was 2.88 microns (active). 2. The post-contraction recovery of chemical changes was compared with the heat production in parallel experiments. Initial and recovery heat production were measured in tetanically stimulated muscles. 3. During recovery from tetanic contractions the changes in phosphocreatine (PCr) matched the changes in inorganic phosphate (Pi). The change in intracellular pH (pHi) was biphasic. The pHi first became more alkaline after contraction and then decreased until it reached a point below the baseline value. There was then a final recovery. 4. The initial heat and recovery heat production were greater than that expected from the PCr hydrolysis estimated during the tetanus and the PCr resynthesis that follows. 5. These data support the presence of 'unexplained heat' during a contraction and its related recovery processes in rat soleus muscle.

Animals↗

Activation of multiple protein kinases including a MAP kinase upon Fc epsilon RI cross-linking.

Previous studies have shown that protein-serine/threonine kinases and protein-tyrosine kinase(s) are activated by cross-linking of the high-affinity receptor for IgE, Fc epsilon RI, on mast cells and basophils. In vitro kinase assays (ISDR kinase assays) on cellular proteins immobilized on polyvinylidene difluoride membrane after denaturation and renaturation were employed to estimate the complexity of protein kinases expressed in mouse mast cells. The results demonstrated that a large number (more than 60) of both serine/threonine- and tyrosine-specific kinases are present in a mouse mast cell line, PT-18. Cross-linking of Fc epsilon RI-induced activation of a subset of both serine/threonine kinases and tyrosine kinases in PT-18 as well as bone marrow-derived mouse mast cells, as revealed by the ISDR kinase assay. Among them, MAP kinase (or ERK2) was shown to be tyrosine phosphorylated and activated transiently upon Fc epsilon RI cross-linking, suggesting its potential role in mast cell signal transduction.

Animals↗

[Effects of NC-1100, a calcium channel blocker, on experimental cerebral ischemia/anoxia in rodents].

The anti-ischemic and anoxic effects of NC-1100, a piperazine type calcium channel blocker, were investigated in various cerebral ischemia and anoxia models in mice, gerbils and guinea pigs. Minimal effective doses of NC-1100 were 8 mg/kg, i.p. and 30 mg/kg, p.o. for KCN-induced anoxia; 16 mg/kg, i.p. for decapitation-induced gasping; 30 mg/kg, i.p. for cerebral ischemia induced by occlusion of bilateral carotid arteries in gerbils; and 10 microM for the in vitro ischemic model in hippocampal slices. Moreover, NC-1100 attenuated the disturbance of cerebral energy metabolism induced by decapitation in mice. These results suggest that NC-1100 has a cerebral protective effect, and that attributable to its ability to improve the cerebral energy metabolism disturbance.

Animals↗

[Long-term clinical course of sequelae in patients with neonatal anoxic encephalopathy resulting in profound mental retardation and motor disturbance].

A long-term observation has been made in 58 patients (30 males and 28 females) with severe sequelae of neonatal anoxic encephalopathy. They aged from 8 months to 65 years. All of them had motor disturbances and profound mental retardation. Motor function was improved in 4 patients with aging. In contrast, motor activity deteriorated in 11 cases, of which 4 showed a mental regression. Among them, patients who had originally better motor ability than sitting were likely to deteriorate by uncontrollable epilepsy and/or excessive administration of anticonvulsants. Regression of the patients with worse motor ability like bedridden appeared to attributable hypertonia of muscles and bodily deformation. Fifteen cases showed an exacerbation of general condition which originated predominantly to respiratory distress. Twelve patients died including 6 exacerbated cases. Exacerbation or death may have occurred frequently in specific periods of infancy, adolescence and youth with the patients who showed very low motor function such as bedridden and no locomotion.

Adolescent↗

Distribution of pacinian corpuscles in the cat forefoot.

The distribution of pacinian corpuscles in the cat forefoot was investigated using celloidin sections stained with haematoxylin and eosin. The corpuscles were oval or elliptical, their longitudinal and transverse diameters being 590.0 +/- 207.6 microns and 320.0 +/- 119.6 microns. There were 667 corpuscles (mean value for 4 feet) in each forefoot, 80% of which were in the toe region and the remainder in the palmar region. The number of corpuscles was similar in both forefeet. There was no difference in light microscopic structure. Corpuscles were located (1) in the dermis and subcutaneous tissue of the skin folds covering the claw, (2) between the flexor digitorum tendon and middle phalanx, (3) in the subcutaneous adipose tissue of the metacarpal pad and (4) in short digital muscle of the carpal pad. Scattered corpuscles were found in contact with the periosteum of distal and middle phalanges and with flexor tendon sheath, and in the dermis of the palm. Corpuscles were observed to be clustered in the skin folds of the toes. Skin folds, made of dorsal hairy skin, covered the claw on both sides, with most corpuscles in contact with hair follicles and others scattered between hair follicles. Forefoot corpuscles were often in proximity with blood vessels. Corpuscles in the palmar region were seen to be arranged along the superficial palmar metacarpal nerve.

Adipose Tissue↗