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Biomedical subjects

M Takei

Publications and source records attributed to M Takei.

At least 73 records · Page 4Linked to original sources
PubMed1996

Interferon-gamma promotes the survival and Fc epsilon RI-mediated histamine release in cultured human mast cells.

We examined the effects of interferon-gamma (IFN-gamma) on 100% pure human mast cells generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of stem cell factor (SCF) and interleukin-6 (IL-6). When mast cells were suspended in serum-free medium without any cytokine after the withdrawal of SCF and IL-6, they died over a period of 5 days because of apoptosis. IFN-gamma in the cultures suppressed apoptosis and prolonged their survival in a dose-dependent manner. This survival-promoting effect of IFN-gamma was blocked by neutralizing antibodies to IFN-gamma or to IFN-gamma receptor (IFN-gamma R). When mast cells were incubated with IFN-gamma in serum-free medium for more than 4 hr during sensitization, immunoglobulin E (IgE)/anti-IgE antibody-induced histamine release was effectively enhanced. Polymerase chain reaction (PCR) amplification of the alpha-chain of IFN-gamma R (IFN-gamma R alpha) yielded products of the correct size predicted from the sequence of the receptor. In addition, flow cytometry using anti-IFN-gamma R monoclonal antibodies (mAbs) indicated that these mast cells bear IFN-gamma R on their surface. These findings suggested that IFN-gamma activates human mast cells via specific receptors in certain aspects of inflammatory reactions.

Antibodies↗
PubMed1996

Changes in tissue contents of zinc, copper and iron in rats and beagle dogs treated with polaprezinc.

Zinc, copper and iron levels of tissues in rats or beagle dogs were measured after a 13- or 52-week toxicity study of polaprezinc, which contains a zinc element. The zinc content in almost all rat tissues remarkably increased with a conspicuous decrease of copper and various changes of iron at doses of 600 mg/kg/day or more. Zinc and copper levels increased and decreased respectively, at 300 mg/kg/day. At a dose of 150 mg/kg/day, there was a slight increase of zinc in some tissues at 52-weeks, but no copper decrease. The results obtained from beagle dogs differed somewhat from that in rats. Dogs treated with polaprezinc at 50 mg/kg/day or more accumulated zinc in some tissues. A copper decrement was seen only in the liver and heart from the group given 300 mg/kg/day, whereas copper levels in the kidney of all treated groups were higher than that in the control, suggesting that canine polaprezinc toxicity is due to direct zinc toxic effects.

Animals↗
PubMed1996

Successful engraftment of allogeneic CD34-enriched marrow cell transplantation from HLA-mismatched parental donors.

The CD34 antigen is expressed on pluripotent stem cells and the CD34+ cell has been shown to be capable of hematopoietic reconstitution in animal and human autologous grafts. We asked if CD34+ cells could reconstitute hematopoiesis in human allogeneic transplantation from a HLA-mismatched donor. Three pediatric patients with advanced leukemia received allogeneic CD34-enriched marrow cell graft from HLA two (two patients) or three (one patient) loci-mismatched parental donors. CD34+ cell selection was performed with mouse anti-CD34 antibody 9C5 and magnetic beads coated sheep anti-mouse IgG1. 1.53 to 2.48 x 10(9) marrow cells were processed and 2.53 to 7.89 x 10(7) positively selected cells were recovered. The selected population showed 93.7 to 99.0% CD34+ cells and total recovery of CD34+ cells from the starting population was 54.6 to 62.3%. CD34+ cell selection resulted in more than 99.9% depletion of CD5+ cells from the bone marrow. The patients received 2.53 to 7.25 x 10(6) CD34-enriched cells/kg after myeloablative therapy. All patients achieved trilineage engraftment that was confirmed by various genetic markers. Acute graft-versus-host disease (GVHD) was grade 0 (two patients) or grade I (one patient), and hematological recovery was successfully achieved as follows; the days to reach granulocytes over 0.5 x 10(9)/I were 11 to 13 days, reticulocytes over 2% was 18 to 28 days, platelets over 50 x 10(9)/I was 33 to 58 days. One patient is surviving without relapse of leukemia and two patients died after either mixed hematopoietic chimerism or leukemia relapse was observed. These studies suggest that CD34+ marrow cells are capable of hematopoietic reconstitution from HLA two or three loci-mismatched donors even with the lowest dose of mature T cells.

Adult↗
PubMed1996

Promotion of differentiation and proliferation of peripheral blood CD34+ cells in vitro by G-CSF.

OBJECTIVE: To observe the effect of granulocyte-colony stimulating factor (G-CSF) on differentiation and proliferation of CD34+ cells from peripheral blood in presence of recombinant hematopoietic growth factor (HGF). METHODS: Peripheral blood mononuclear cells mobilized by G-CSF were obtained from patients suffering from carcinoma, preparing for autologous bone marrow transplantation. CD34+ cells were isolated by derivatized polystyrene tissue culture flask which had covalently immobilized soybean agglutinin lectin and was coated with anti-CD34 antibody; and this kind of cells were incubated in liquid culture medium for up to 28 days under the stimulation of combination of growth factors, i.e., stem cell factor (SCF) and interleukin-3 (IL-3) with or without G-CSF. The changes of nucleated cells, colony forming unit-granulocyte and monocyte (CFU-GM), burst forming unit-erythrocyte (BFU-E), colony forming unit-megakaryocyte (CFU-MK), and myeloid-associated markers were evaluated. RESULTS: An increase of nucleated cells (mean 640-fold increase) occurred during culture CFU-GM production is parallel to the nucleated cell production until the 11th day (mean 82-fold increase) in combination of 3 HGF, i.e., G-CSF, IL-3 and SCF. A large number of cells expressing late myeloid markers appeared on the 11th day in suspension culture of CD34+ cells. CONCLUSION: G-CSF was found to synergize with IL-3 and SCF in inducing rapid proliferation of purified CD34+ cells and differentiation to multiple myeloid lineages. The stroma-free, cytokine-driven culture system could achieve a degree of amplification of colony forming cells, suggesting the feasibility of culture of hematopoietic progenitor cells in vitro as an adjunct to hematopoietic stem cell transplantation.

Antigens, CD34↗
PubMed1995

Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by penasterol and penasterone.

Penasterol and penasterone, constituents of the Okinawan marine sponge Penares incrustans, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The concentrations of penasterol and penasterone required for 50% inhibition of anti-IgE-induced histamine release (IC50) were 0.5 and 1.5 microM, respectively. Both compounds dose-dependently inhibited phospholipase A2 (PLA2) activity. Moreover, they inhibited anti-IgE-induced [3H]arachidonic acid from rat mast cells. These results suggest that the mechanism of inhibition by these compounds of the histamine release induced by anti-IgE was through the inhibition of PLA2.

Animals↗
PubMed1995

[Effect of efonidipine hydrochloride, a calcium channel blocker, on the experimental cerebral ischemia/anoxia].

The anti-ischemic and anti-anoxic effects of efonidipine, a dihydropyridine calcium antagonist, were studied in several models for cerebral ischemia and anoxia in mice and rats, and the effects were compared with those of nicardipine and flunarizine. Both efonidipine and flunarizine showed protective effects in the models of KCN-induced anoxia and complete ischemia induced by decapitation in mice 6 hr after the treatment, while nicardipine did not show such a long-lasting effect. Efonidipine (1 mg/kg, i.p.), but not nicardipine and flunarizine, prolonged the tolerance times in the asphyxic anoxia model. In mice, efonidipine (4 mg/kg, i.p.) significantly reduced the cumulative mortality rate after bilateral carotid artery ligation. The survival rates at 20 hr after bilateral carotid artery ligation were 33% in the group treated with efonidipine, significantly higher than that in the control group, 0%. On the other hand, the treatment with nicardipine or flunarizine did not increase the rates at 20 hr after the ligation. Moreover, efonidipine attenuated the disturbance of cerebral energy metabolism induced by decapitation in rats. These effects of efonidipine observed in this study were on the whole superior to those of the reference drugs, strongly suggesting the improving effect of efonidipine on cerebral ischemia and anoxia.

Animals↗
PubMed1995

[Effect of efonidipine hydrochloride (NZ-105) on modification of low density lipoprotein induced by rat cultured endothelial cells].

We studied the effects of efonidipine hydrochloride [NZ-105: (+/-)-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2- yl)-4-(3-nitro-phenyl)-3-pyridinecarboxylate hydrochloride ethanol] and nisoldipine on endothelial cell-induced low density lipoprotein (LDL) modification. The modification of LDL by cultured rat endothelial cells was performed by incubating 3 micrograms protein/well LDL with 5 microM CuSO4 for 24 hr at 37 degrees C in the presence of confluent cells. The extent of modification was assayed by measuring the thiobarbituric acid-reactive substances (TBARS). Efonidipine hydrochloride reduced the TBARS level in a dose-dependent manner. At 3 x 10(-7) M, efonidipine hydrochloride showed a significant effect. On the other hand, the significant effect of nisoldipine was observed only at 10(-5) M. Thus the action of efonidipine hydrochloride on the inhibition of LDL-modification was much more potent than that of nisoldipine. As the modification of LDL was thought to play a key role in the initiation and progression of atherosclerosis, efonidipine hydrochloride may be useful against atherosclerosis.

Animals↗
PubMed1995

[A case of Sjögren's syndrome complicated with cryoglobulinemia, nephrogenic diabetes insipidus, and renal tubular acidosis].

A 68-year-old woman had been complained of xerostomia since she was 30 years old. Further symptoms of polyuria, polyposia and insomnia had been developed since she was 35 years old. The biopsy material from a minor salivary gland demonstrated the infiltration of lymphocytes into mesenchyme which was compatible with Sjögren's syndrome. She admitted to our hospital because of myalgia in bilateral gastrocnemius and petechiae in both lower extremities in addition to the complaints described above. Complete blood cell counts on admission revealed hemoglobin 9.7 g/dl, platelet count 12.5 x 10(4)/microliters, and white blood cell count 3,300/microliters. Marked polyuria, polyposia (more than 5,000 ml/day, respectively) and low urine gravity (1.005) were observed, although the serum creatinine level showed normal value. Serologic examination showed that the elevation of total serum protein concentration (9.5 g/dl) with marked elevation of serum IgG level (6,190 mg/dl). Her immunoglobulins contained cryoglobulin (cryocrit 20%), and immunoelectrophoresis demonstrated the existence of IgG-kappa monoclonal protein. A positive anti-nuclear antibody at 1:320 dilution, a positive rheumatoid factor and a positive antibody to SS-A (Ro) were also observed. The serial studies of blood gas analysis could not demonstrated the presence of metabolic acidosis. Together with the result of elevated plasma antidiuretic hormone level and results of vasopressin test, Fishberg's concentrating test and the tests of the overload of NH4Cl or bicarbonate, she was diagnosed Sjögren's syndrome with both diabetes insipidus and subclinical renal tubular acidosis. She was initially medicated with prednisolone (40 mg/day, orally), then she was given six courses of intravenous cyclophosphamide (750 mg/body/month).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗
PubMed1994

Potent inhibitors of histamine release: polyhydroxylated sterols from the Okinawan soft coral Sinularia abrupta.

A new polyhydroxylated steroid (24-methylene-1 alpha, 3 beta, 11 alpha-trihydroxycholest-5-ene-18-oic acid-3-acetate, 1) and known related compounds (2-4) from the soft coral Sinularia abrupta have potently inhibited histamine release from rat peritoneal mast cells induced by anti-immunoglobulin E. The inhibitory effect of 1 was approximately 6500 times stronger than that of disodium cromoglycate, a well-known antiallergic drug.

Animals↗
PubMed1994

Soluble CD4/CD8 molecules in rheumatic disorders.

The CD4 and CD8 glycoproteins which predominantly exist on T-helper and T-suppressor/cytotoxic cells are the physiological ligands for major histocompatibility complex class I or class II molecules on target cells such as B cells and antigen-presenting cells. These CD4 and CD8 molecules occur not only bound to membranes but also in soluble form in the serum. They may deliver regulatory signals to immunocompetent cells in vivo. The recent development of a solid-phase immunosorbent assay for soluble CD4 and CD8 molecules has enabled us to gain insight into the etiopathogenesis of autoimmune diseases on the basis of T-cell functional disability. This paper discusses the pathogenesis of autoimmune rheumatic diseases based on the findings for these molecules.

CD4 Antigens↗
PubMed1994

Inhibitory effects of calcium antagonists on mitochondrial swelling induced by lipid peroxidation or arachidonic acid in the rat brain in vitro.

Inhibitory effects of calcium antagonists, efonidipine (NZ-105), nicardipine, nifedipine, nimodipine and flunarizine, on mitochondrial swelling induced by lipid peroxidation or arachidonic acid in the rat brain in vitro were investigated. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid system showed a close and significant relationship. Mitochondrial swelling and lipid peroxidation induced by FeSO4 and ascorbic acid were inhibited by all of calcium antagonists tested. The order of inhibition was: flunarizine > nicardipine > efonidipine > nimodipine > nifedipine. This result suggests that calcium antagonists tested have anti-peroxidant activities resulting in protection of mitochondrial membrane damage and that each moiety of these structures would play an important role in appearance of anti-peroxidant activities. Furthermore, flunarizine and efonidipine inhibited mitochondrial swelling induced by arachidonic acid, which is not associated with lipid peroxidation. In contrast, nicardipine, nifedipine, and nimodipine did not inhibited this swelling. It is possible that flunarizine and efonidipine could directly interact with mitochondrial membrane. In conclusion, it is capable that calcium antagonists tested may protect from the membrane damage induced by lipid peroxidation and that flunarizine and efonidipine could stabilize the membrane, which is attributed to a direct interaction with the membrane.

Animals↗
PubMed1994

The anticonvulsant effect of citalopram on El mice, and the levels of tryptophan and tyrosine and their metabolites in the brain.

Serotonin(5-HT) plays an important role in the seizures of El mice since the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by oral administration of citalopram for 2 weeks. Citalopram increased tryptophan and tyrosine amounts, and decreased the 5-HT, 5-hydroxyindoleacetic acid, kynurenine, and dopamine amounts in the brain. These findings show that citalopram depresses monoaminergic metabolism. Given the known convulsant effect of kynurenine, it is suggested that its decrease by citalopram may involve attenuation of El mice seizures.

Animals↗
PubMed1994

Histamine release and calcium concentrations in rat mast cells are dependent on intracellular ATP: effects of prostaglandin D2.

When PGD2 (10 microM), was added to rat mast cells, it caused a rapid increase in adenosine 3',5'-cyclic monophosphate (cyclic AMP) and decrease in adenosine 5'-triphosphate (ATP), both of which recovered to their original levels within 2 min. The accumulation of cyclic AMP was maximal at 30 s after challenge with PGD2. The minimum level of ATP was observed at 30 s after addition of PGD2. The initial rise in [Ca2+]i and the histamine release induced by anti-IgE (200 micrograms/ml) were strongly inhibited at 30 s after incubation of the mast cells with PGD2. Removal of glucose from Tyrode-Hepes solution caused a rapid decrease on ATP level in mast cells, and showed strong inhibition on the rise in [Ca2+]i and histamine release induced by anti-IgE. Addition of glucose to the mast cells induced a time-dependent increase in ATP, and the rises in [Ca2+]i and histamine release were closely correlated with the recovery of ATP. These results suggested that the inhibitory mechanism of PGD2 on the initial rise in [Ca2+]i and histamine release induced by anti-IgE was due to the inhibition of ATP-dependent CA(2+)-release from the intracellular Ca(2+)-stores.

Adenosine Triphosphate↗
PubMed1994

Marchantin A trimethyl ether: its molecular structure and tubocurarine-like skeletal muscle relaxation activity.

Marchantin A is a novel macrocyclic bis(bibenzyl)ether isolated from the liverwort Marchantia species. An X-ray study of its derivative, marchantin A trimethyl ether, revealed that the molecule possesses convex and concave surfaces, with a central hole on the concave surface. The centroid-centroid separations of opposing benzene rings are 8.80 and 4.55 A. A pharmacological study showed that the skeletal muscle relaxation activity is about 3.5 times less potent than that of d-tubocurarine. A comparison of the X-ray structure of marchantin A trimethyl ether and that of O,O',N-trimethyltubocurarine reported by Sobell et al. revealed that the molecules share almost the same macrocyclic bis(bibenzyl)ether skeleton structure, portions of which may therefore be crucial for the skeletal muscle relaxation activity.

Animals↗
PubMed1994

Chronic administration of citalopram inhibited El mouse convulsions and decreased monoamine oxidase-A activity.

Serotonin (5-HT) is thought to play an important role in the seizures of El mice because the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by chronic administration of citalopram (80 mg/kg/day, p.o. for 2 weeks), but were not inhibited by acute administration of citalopram (80 mg/kg, i.p., 2 h after single injection). Both chronic and acute administration of citalopram decreased the concentration of 5-hydroxyindolacetic acid in the brain, whereas the concentration of 5-HT was not changed by treatment with citalopram. Tryptophan hydroxylase activity was not different between the citalopram and control groups, although the monoamine oxydase-A activity was lowered by chronic administration of citalopram. These findings suggest that both acute and chronic administration of citalopram depresses the 5-HT turnover rate, however chronic administration is necessary to inhibit El mouse convulsions.

Administration, Oral↗
PubMed1994

Isolation of human CD34+ peripheral blood stem cells using an immunomagnetic positive selection system: prior monocyte depletion using a nylon-wool column.

An immunomagnetic separation system has been used to collect CD34+ cells in mobilized blood after treatment with a nylon-wool column. Cell purities were increased from 2.6% preseparation to 94.6% postseparation, with a mean yield 45.2% (n = 4). Forty percent of CD34+ cells separated by the immunomagnetic procedure formed colonies in the presence of hematopoietic growth factors in a limiting dilution assay. Eleven percent of these clones proliferated to over 10(5) cells and contained megakaryocytes.

Antigens, CD↗