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Biomedical subjects

I Aoki

Publications and source records attributed to I Aoki.

At least 127 records · Page 7Linked to original sources

Erythroid progenitors in tumor-bearing mice: erythroid inhibitory factors produced by adenocarcinoma-755.

Adenocarcinoma-755-bearing C57BL/6 mice developed anemia with the growth of the tumors. The numbers of granuloid and monocytoid progenitors (colony-forming unit in culture, CFU-C) of the bone marrow and spleen and the peripheral blood WBC counts increased in tumor-bearing mice. The erythroid progenitors (erythroid colony-forming units, CFU-E; erythroid burst-forming units, BFU-E) of the bone marrow showed a marked decrease, overcoming their increase in the spleen in tumor-bearing mice. Fractionation of conditioned medium of tumor cells led to the isolation of a protein of 80-kd molecular weight that stimulated murine CFU-C growth and inhibited the CFU-E and BFU-E growth in a dose-dependent manner. These results indicate that erythroid inhibitory factors produced by tumors exist in tumor-bearing mice. Erythroid inhibitory factors might also exist in non-hematological malignancies of humans, and they might be one of the mechanisms of anemia.

Adenocarcinoma↗

Effects of ubenimex on erythroid progenitors (CFU-E and BFU-E) in human bone marrow.

Ubenimex (UBX, bestatin) is known to be an immunomodulator and host-mediated antineoplastic agent. Effects of UBX on human bone marrow erythroid progenitors (erythroid colony-forming units, CFU-E; and erythroid burst-forming units, BFU-E) were investigated in vitro. UBX enhanced CFU-E and BFU-E growth in the nonseparated bone marrow mononuclear cell fraction at concentrations from 0.005 to 5 micrograms/ml. The enhancements of CFU-E and BFU-E were independent of the concentration of erythropoietin added to culture system. In the T-cell-depleted bone marrow fraction, UBX also increased CFU-E and BFU-E growth, but it failed to stimulate these cells in the nonphagocytic and nonadherent bone marrow fraction. These findings indicate that UBX may stimulate erythroid progenitors mediated through monocytes and macrophages.

Bone Marrow Cells↗

Effects of exercise and chills on entropy production in human body.

Entropy flows and changes of entropy content for naked subjects in the respiration calorimeter in exercise and chills are calculated from the energetic data given by Hardy et al. (1938, J. Nutr. 16, 477) and Du Bois (1939, Bull. N.Y. Acad. Med. 15, 143). By use of these values, entropy productions in the human body in exercise and chills are estimated. The entropy production in mild exercise is 1.5-2.4 times as great as that in basal conditions. The entropy production in violent exercise is six to eight times as great as that before exercise. The entropy production in chills in cold environments is about twice as large as that in basal conditions. The entropy production in a malarial chill is about four times of that in normal subjects. These increases in entropy production will be due to the increase in heat production within the body. It seems that there is a parallel between energy and entropy viewpoints for human physiology.

Cold Temperature↗

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in aplastic anemia and myelodysplastic syndrome.

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh-Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. In normals, the CFU-E numbers reached a plateau of increase at Ep doses of almost 2-5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU-E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU-E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU-E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU-E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU-E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB-T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh-Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.

Anemia, Aplastic↗

Effect of cyclosporin A on suppressor T cells.

The effect of cyclosporin A (CsA) on suppressor T cells (Ts) was evaluated by in vitro incubation with afferent-phase Ts (Ts-aff) and efferent-phase Ts (Ts-eff). 2,4-Dinitro-1-fluorobenzene (DNFB) and hen egg-white lysozyme (HEL) were used as antigens. Both Ts-aff and Ts-eff were resistant to high- and low-dose CsA treatments. However, T cells associated with delayed type hypersensitivity (DTH) [TDTH] to DNFB or HEL were sensitive to these CsA treatments. These results indicate that the effect of CsA treatment on contact sensitivity and DTH influences TDTH and not Ts.

Animals↗

Genetic control of nickel sulfate delayed-type hypersensitivity.

Genetic control of delayed-type hypersensitivity (DTH) to nickel sulfate antigen was studied using various strains on inbred mice. Mice with class II Ad,k,s haplotypes showed a high magnitude of response, whereas those with class II Ab,f were low responders. These results indicate that nickel sulfate DTH may be influenced by the I-A region of H-2. Transfer experiments revealed that these responses might be mediated by L3T4+, Lyt-2- T cells.

Animals↗

Genetic control by I-A subregion in H-2 complex of incidence of streptozocin-induced autoimmune diabetes in mice.

An experimental autoimmune diabetes in mice characterized by delayed-onset hyperglycemia with lymphocytic infiltrations of the pancreatic islets can be induced by multiple administrations of low doses of streptozocin (STZ). We report on the influence of the MHC (H-2 complex) on this autoimmune diabetes by comparing the susceptibilities of various congenic and recombinant strains with a B10 background. In congenic strains, C57BL/10 (H-2b) and B10.BR (H-2k) mice showed a high incidence of diabetes, whereas B10.D2 (H-2d) and B10.S (H-2s) mice showed a low incidence. Therefore, we suggest that the H-2 complex influences diabetes susceptibility and that both b and k are high-susceptibility alleles, whereas d and s are low-susceptibility alleles. In recombinant strains, those with the same haplotypes on the K, E, S, and D subregions of the H-2 complex showed undefined (high and low) susceptibilities, indicating that the diabetes-susceptibility genes are located outside these loci. Strains possessing I-Ab or I-Ak gene products (C57BL/10, B10.BR, B10.TL, B10.A, and B10.A(2R] showed high incidences, whereas strains possessing I-Ad or I-As (B10.D2, B10.S, B10.S(7R), B10.S(9R), and B10.GD) showed low incidences. In addition, administration of anti-I-A monoclonal antibody prevented the manifestation of diabetes in STZ-administered mice. Passive transfer of STZ-administered T lymphocytes to mice given minute doses of STZ induced significant hyperglycemia. This successful transfer was only observed in H-2-compatible mice. Thus, we conclude that one gene coding for susceptibility to this experimental diabetes was located in the I-A subregion within the H-2 complex.

Animals↗

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↗

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↗

Entropy flow and entropy production in the human body in basal conditions.

Entropy inflow and outflow for the naked human body in basal conditions in the respiration calorimeter due to infrared radiation, convection, evaporation of water and mass-flow are calculated by use of the energetic data obtained by Hardy & Du Bois. Also, the change of entropy content in the body is estimated. The entropy production in the human body is obtained as the change of entropy content minus the net entropy flow into the body. The entropy production thus calculated becomes positive. The magnitude of entropy production per effective radiating surface area does not show any significant variation with subjects. The entropy production is nearly constant at the calorimeter temperatures of 26-32 degrees C; the average in this temperature range is 0.172 J m-2 sec-1 K-1. The forced air currents around the human body and also clothing have almost no effect in changing the entropy production. Thus, the entropy production of the naked human body in basal conditions does not depend on its environmental factors.

Body Temperature Regulation↗

Determination of manidipine and its pyridine metabolite in human serum by high-performance liquid chromatography with ultraviolet detection and column switching.

A highly sensitive and selective high-performance liquid chromatographic method using column switching is described for the determination of the dihydropyridine calcium antagonist manidipine (I),2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl (+/- )-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5- pyridinedicarboxylate, and its pyridine metabolite (II), 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate, in human serum. The method is based on the combination of the column-switching technique and ion-pair chromatography. In the first ODS column, I and II are preseparated from endogenous substances in serum with a mobile phase containing sodium nonane sulphonate as an ion-pair reagent. After column switching, in the second ODS column, the heart-cut fraction containing I and II is further separated from the co-eluted substances through the first column with a mobile phase containing no ion-pair reagent. By using microbore columns with a diameter of 2.1 mm, the sensitivity is almost double that given by conventional bore columns with a diameter of 4.6 mm. The method offers high sensitivity and selectivity with short-wavelength ultraviolet detection at 230 nm. The detection limits of both I and II are 0.1 ng/ml using 1 ml of serum. The method is suitable for the pharmacokinetic study of I.2HCl after oral administration to man.

Administration, Oral↗

Interaction of the fluorescent dye 1-N-phenylnaphthylamine with Escherichia coli cells during heat stress and recovery from heat stress.

The fluorescent dye 1-N-phenylnaphthylamine permeated Escherichia coli cells after exposure to a heat stress at 55 degrees C in Tris/Mg2+ buffer, pH 8.0. The rate of dye permeation increased with time during heat treatment and decreased gradually during subsequent incubation at 37 degrees C in a minimal medium. The initial level of rapid adsorption of the dye also increased with heating time, although it remained roughly constant during post-heating incubation. The results obtained suggest that the permeability barrier to the dye in the outer membrane was damaged by heat stress and was repaired after sublethal heating. RNA, protein and lipid syntheses, as well as an energy-yielding process, appeared to be necessary for the repair of impermeability to the dye.

1-Naphthylamine↗

A case of temporal arteritis successfully treated with recombinant interleukin-2.

An 80-year-old Japanese woman with temporal arteritis was treated with systemic recombinant human interleukin-2 (IL-2) (1 x 10(6) unit/day for six weeks). The presenting symptoms of headache and skin necrosis and abnormal laboratory findings, such as an elevated erythrocyte sedimentation rate and CRP, promptly improved without any serious side effects. Although the pathogenesis of temporal arteritis and the mechanism(s) of the beneficial effect of IL-2 on it still remain unknown, this preliminary study highly encourages further investigations.

Aged↗

[In vitro effects of high titers of recombinant human erythropoietin on the bone marrow erythroid progenitors in patients with aplastic anemia].

To investigate the role of erythropoietin in aplastic anemia, the effects of high titers of recombinant human erythropoietin (rh-Ep) on CFU-E and BFU-E in patients with aplastic anemia were studied in vitro. Colony assays were performed by methylcellulose culture methods added with 1 to 500 units of rh-Ep. In normal bone marrow, the maximum CFU-E colony formation was observed at 2 to 5 units of rh-Ep, and BFU-E at 2 to 10 units. Colonies did not increase by addition of higher titer of rh-Ep to the cultures. In aplastic anemia, the numbers of CFU-E and BFU-E were low at 2 units of rh-Ep in culture system. In most patients with aplastic anemia studied, erythroid colonies were increased in accordance with the increase of rh-Ep added to cultures. These results suggest that the administration of high titers of rh-Ep in vivo may be useful for the improvement of anemia in aplastic anemia.

Adult↗