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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 541 records · Page 30Linked to original sources
PubMed1985

Release of histamine and arachidonate from mouse mast cells induced by glycosylation-enhancing factor and bradykinin.

Stimulation of normal rat splenic T cells with pertussigen (lymphocytosis-promoting factor from Bordetella pertussis) resulted in the release of a soluble factor that enhanced the assembly of N-linked oligosaccharides to IgE-binding factors during their biosynthesis. The glycosylation-enhancing factor (GEF) is a kallikrein-like enzyme and is purified by absorption to p-aminobenzamidine-Agarose followed by elution with benzamidine. Incubation of normal mouse mast cells with affinity-purified GEF or bradykinin, a product of cleavage of kininogen by kallikrein, resulted in the release of histamine and arachidonate from the cells. Passive sensitization of mast cells with mouse IgE antibody, followed by pretreatment of the cells with a suboptimal concentration of GEF, resulted in an enhancement of antigen-induced histamine release. It was found that GEF and bradykinin induced the same biochemical events in mast cells as those induced by bridging of IgE receptors. Both GEF and bradykinin induced phospholipid methylation and an increase in intracellular cyclic AMP (cAMP). Incorporation of 3H-methyl groups into phospholipids and intracellular cAMP levels both reached a maximum 30 sec after challenge with GEF or bradykinin, and then declined to base-line levels within 2 to 3 min. These biochemical events were followed by 45Ca influx and histamine release; 45Ca uptake reached a plateau value at 2 min, and histamine release reached a maximum at 5 to 8 min. The initial rise in cAMP induced by GEF (or bradykinin) was not inhibited by indomethacin, indicating that the activation of adenylate cyclase is not the result of prostaglandin synthesis. In both IgE-mediated and GEF-induced histamine release, inhibitors of methyltransferases, such as 3-deaza adenosine and L-homocysteine thiolactone, inhibited not only phospholipid methylation but also the cAMP rise and subsequent Ca2+ uptake and histamine release. The results indicate that GEF induces activation of methyltransferases and that phospholipid methylation is involved in the cAMP rise, Ca2+ uptake, and histamine release. The induction of the same biochemical events in the same sequence by bridging of IgE receptors and by GEF (bradykinin) supports the hypothesis that receptor bridging induces the activation of serine protease(s) and cleavage products of this enzyme in turn activate methyltransferases in mast cells.

Adenylate Cyclase Toxin↗
PubMed1985

Modulation of the biologic activities of IgE-binding factors. VII. Biochemical mechanisms by which glycosylation-enhancing factor activates phospholipase in lymphocytes.

Cells of the T cell hybridoma 23A4 produce IgE-binding factors lacking N-linked oligosaccharides (unglycosylated form) when they are incubated with IgE alone. In the presence of glycosylation-enhancing factor (GEF) or bradykinin, however, the same cells produce IgE-binding factors with N-linked oligosaccharides (glycosylated form). Switching the cells from the formation of unglycosylated IgE-binding factors to the formation of glycosylated factors was accompanied by the release of both glycosylation-inhibiting factor (GIF) in its phosphorylated form, i.e., phosphorylated lipomodulin, and arachidonate from the cells. Analysis of the biochemical processes for the release of GIF from 23A4 cells showed that affinity-purified GEF or bradykinin induced transient phospholipid methylation and diacylglycerol (DAG) formation, and enhanced 45Ca uptake into the cells. Inhibitors of methyltransferases, i.e., 3-deaza-adenosine plus L-homocysteine thiolactone, inhibited not only phospholipid methylation but also DAG formation and GIF release. Exogenously added 1-oleoyl-2-acetyl glycerol, i.e., a DAG that is permeable to the plasma membrane, induced the release of GIF from the cells. It was also found that 12-O-tetradecanoyl-phorbol 13-acetate (TPA) switched 23A4 cells and normal lymphocytes to the selective formation of N-glycosylated IgE-binding factor, and induced the release of GIF from the cells. 32PO4-labeled lipomodulin was detected in the extract of 23A4 cells 3 to 5 min after the addition of GEF, bradykinin, or TPA. These results indicate that GEF and bradykinin induced the activation of methyltransferases and phospholipase C for the formation of DAG, which in turn activated Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) for the phosphorylation of lipomodulin. Because lipomodulin loses phospholipase inhibitory activity after phosphorylation, increased phospholipase A2 activity would be expressed by this process.

Animals↗
PubMed1985

[Differential responses of tumor and normal skin tissue to low dose rate radiations].

HeLa S-3 cells in nude mice and the parabasal and basal cells of nude mouse skins were exposed to graded dose rates (37 or 55 rad/hour and 200 rad/minute) and doses of radiation and analyzed in terms of their cell cycle distribution using flow microfluorimetry. Standard procedures were HeLa cells, and the parabasal and basal cells were harvested from the skin using dispase and trypsin. In the case of the tumor cells, in vivo, 37 rad/hour proved to be the most effective in producing G2/M accumulation, which is the sensitive phase of the cell cycle. The same dose rate proved to be the most efficient in producing G2/M accumulation in the parabasal and basal cells of the skin, but sensitivity to this effect of radiation was far less than in the tumor. This differential sensitivity of normal and malignant cells to chronic radiation-induced accumulation in a radiosensitive phase of the cells might play an important role in increasing the therapeutic ratio.

Animals↗
PubMed1984

Unilateral palatal paralysis caused by lesion in the corticobulbar tract.

A patient with a cerebral infarct affecting the anterior limit of the superior segment of the corona radiata had unilateral paralysis of the palatal muscles without notable weakness of the extremities. The site of the lesion corresponded to the location of the corticofugal motor tract from the motor cortex to the genu of the internal capsule.

Aged↗
PubMed1984

Changes of n-hexane neurotoxicity and its urinary metabolites by long-term co-exposure with MEK or toluene.

It is well known that the neurotoxicity of n-hexane may be modified upon co-exposure with other organic solvents. In order to elucidate this mechanism further, rats were exposed to 500ppm n-hexane, 500ppm n-hexane plus 500ppm methyl ethyl ketone (MEK), 500ppm n-hexane plus 500ppm toluene, or air only for 8h per day for 33 weeks. The body weight, motor nerve conduction velocity (MCV) and distal latency (DL) were determined before exposure and after 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. From each group one rat was histologically examined after 33 weeks of exposure. To establish a relationship between the n-hexane neurotoxicity and changes in biotransformation, urinary metabolites (2-hexanol, methyl n-butyl ketone (MBK), 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone) were measured by gas chromatography on the first exposure day, and after 1, 2, 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. The total amounts of metabolites of n-hexane in the urine significantly decreased upon co-exposure of n-hexane, with MEK as well as with toluene, in comparison with those of animals exposed to n-hexane alone. 2,5-Hexanedione, which is considered the ultimate neurotoxic metabolite of n-hexane, also decreased. Electrophysiological and histological studies did not reveal statistically significant differences between any two groups among the four groups. It is considered that the present results might explain the combined effects of n-hexane and toluene which decrease n-hexane neurotoxicity, but do not explain those of n-hexane and MEK. Therefore, other mechanisms of the combined effects of n-hexane and MEK should be studied.

Animals↗
PubMed1984

Portal absorption of small peptides in rats under unrestrained conditions.

The intestinal absorption of small peptides was investigated in rats under unrestrained conditions. The peptide utilized in the experiment was hydrolysate of egg white protein with an average molecular weight of about 350 and containing less than 10% of free amino acids. We compared the intestinal absorption of these small peptides with that of an amino acid mixture with the same small peptide amino acid composition by determining the concentration of individual amino acids in portal blood after a single administration of a nitrogen source. The absorptive intensity of each amino acid was calculated from its rate of elevation in the portal blood; it was higher in the small peptides. The proportion of the amount of each amino acid absorbed in portal blood from small peptides was much more like the composition of the administered amino acids than like that from the amino acid mixture. Among the amino acids administered in the mixture, some amino acids such as L-tyrosine, L-threonine, L-serine and L-histidine increased more slowly in the blood than others. These results suggested that the small peptide formula was utilized more effectively than the amino acid mixture and had higher nutritive value.

Alanine↗
PubMed1984

[Chronic toxicity study of AC-1370 sodium, an antibiotics, intravenously administered in rats].

A study on chronic toxicity of AC-1370 sodium (AC) in addition to recovery from its toxicity, was carried out using the rat. AC was administered to the rat through the tail vein in doses of 30, 100, 300 and 1000 mg/kg body weight/day, with the periods for administration and recovery being 26 and 13 weeks, respectively. The results obtained from the present study were as follows. In each group, neither death case nor fatal damage was observed throughout the whole process. In the group of 1000 mg/kg, the below findings were observed in one or both sexes: suppression in increase of body weight, increases in drunk amount of water, urinary volume and urinary excretions of electrolytes, degeneration in renal tubules and several correlated changes, tendency of anemia, changes in serum biochemical tests, and changes in each organ weight. In the group of 300 mg/kg, the above findings were observed slightly in comparison to the group of 1000 mg/kg. In the groups of 100 and 30 mg/kg, any changes suggesting the damages were not observed. In the recovery test, the group of 1000 mg/kg was found to be incompletely restored from the damages, with the partially residual damages being shown. In contrast, the group of 300 mg/kg showed to be almost restored from the damages. These results denotes that the maximal non-toxic dose of AC in this study is 100 mg/kg/day in long-term administration.

Animals↗
PubMed1984

[Effects of intravenous administration of ranitidine hydrochloride on the fertility of the male and female rats].

The effects of ranitidine hydrochloride, a histamine H2-receptor antagonist, on the reproductivity of male and female rats of Crj:CD (SD) strain and the development of their fetuses were examined. Ranitidine hydrochloride was intravenously administered once daily at dose levels of 5, 15 and 40 mg/kg in base weight respectively, to males from 60 days before mating until the completion of mating, and to females from 14 days before mating up to day 7 of gestation. All pregnant females were killed on day 20 of gestation and their fetuses were examined morphologically. Tachypnea, prone position and transient tremor were observed for a short period of time directly after an intravenous administration of ranitidine in the dose of 40 mg/kg, which were probably induced by a rapid fall in blood pressure. There was a significant decrease in the weight of spleen in males of 15 and 40 mg/kg groups. Treatment with ranitidine hydrochloride did not have any influence on mating performances and pregnancy at all dose levels. In observation of the fetuses, there was no influence of ranitidine hydrochloride administration on fetal growth and development. A few external, skeletal and visceral malformations were seen sporadically in each group, and 19 cases of dwarf fetuses were observed in 2 dams of 40 mg/kg group, but these changes were not attributable to administration of the drug. These results indicated that ranitidine hydrochloride intravenously administered to males and females before mating and to pregnant females in early stages of gestation had no toxic effects on reproductivity in either sex at the dose of 40 mg/kg/day or less.

Abnormalities, Drug-Induced↗
PubMed1984

Neuropathological study of chorea-acanthocytosis.

Neuropathological studies of a woman with chorea-acanthocytosis were reported. The patient clinically showed generalized epileptic seizures, choreatic involuntary movements, hypotonia , areflexia, neurogenic muscular atrophy, tongue-biting and acanthocytosis of the peripheral blood and died from asphyxia at the age of 34. Autopsy revealed atrophy of the caudate nucleus but the cerebral cortex was well preserved. Histological examination showed severe neuronal loss associated with moderate fibrous gliosis of the caudate. The putamen was similarly but less markedly affected. The small striatal neurons were more severely depopulated than the large neurons, although the latter were not spared. Cytometrical study of the caudate head revealed that the remaining small neurons were significantly larger in size than the normal small neurons of the same area. The anatomical substratum of the choreatic involuntary movements in chorea-acanthocytosis is thought to be the degeneration of the striatum, especially the caudate nucleus. Neuropathological differentiation of chorea-acanthocytosis from Huntington's chorea which shows similar pathology was discussed.

Acanthocytes↗
PubMed1984

Studies on a new nucleoside antibiotic, dapiramicin. II. Isolation, physico-chemical and biological characterization.

New nucleoside antibiotics, dapiramicins A and B produced by a Micromonospora sp. SF-1917, have been isolated by column chromatography on Diaion HP-20 and silica gel. Physico-chemical properties suggested that they are disaccharide nucleosides. Dapiramicin A underwent epimerization, under acidic condition, into epidapiramicin A. Although dapiramicin A generally exhibits no in vitro activity, it is very effective against the sheath blight of rice plants caused by Rhizoctonia solani in a green house test.

Aminoglycosides↗
PubMed1984

Modulation of the biologic activities of IgE-binding factor. V. The role of glycosylation-enhancing factor and glycosylation-inhibiting factor in determining the nature of IgE-binding factors.

Glycosylation-enhancing factor (GEF) and IgE-potentiating factor were detected in culture supernatants of rat mesenteric lymph nodes (MLN) cells obtained 14 days after infection with Nippostrongylus brasiliensis (Nb), but not in supernatants of MLN cells of 8-day Nb-infected rats. Both factors were also released from T cells upon antigenic stimulation of KLH + alum-primed spleen cells. The GEF from the Nb-infected rats and KLH + alum-primed spleen cells had affinity for p-aminobenzamidine agarose and were inactivated by phenylmethylsulfonylfluoride, an inhibitor of serine proteases. These results indicate that the GEF obtained in the two systems is a serine protease and is identical to that obtained by stimulation of normal T cells with lymphocytosis-promoting factor (LPF) from Bordetella pertussis. The concomitant formation of IgE-potentiating factor and GEF by Nb infection, by antigenic simulation of KLH + alum-primed spleen cells, and by treatment of rats with Bordetella pertussis vaccine suggests that the serine protease is involved in a common pathway leading to the selective formation of IgE-potentiating factor. In contrast, glycosylation-inhibiting factor (GIF) is always found during the selective formation of IgE-suppressive factor. IgE-suppressive factor and GIF were formed by MLN cells of 8-day Nb-infected rats and KLH-CFA-primed spleen cells. GIF was detected in culture supernatants of T cell hybridomas 23A4 and 23B6, which form unglycosylated IgE-binding factors upon incubation with IgE. GIF obtained from all of these sources bound to monoclonal anti-lipomodulin. These findings indicate that GIF or lipomodulin is involved in all systems, which leads to the selective formation of IgE-suppressive factor. However, the formation of GIF was not restricted to those conditions in which IgE-suppressive factor was selectively formed. The culture supernatants of MLN cells of 14-day Nb-infected rats and antigen-stimulated KLH + alum-primed spleen cells contained a small amount of GIF, which could be detected after inactivation of GEF. It appears that T cells from these sources formed GEF and GIF, but that GEF overcame the effect of GIF on glycosylation of IgE-binding factors. The results indicate that the nature and biologic activities of IgE-binding factors are decided by the balance between GEF and GIF formed by T cells.

Animals↗
PubMed1984

Modulation of the biologic activities of IgE binding factor. VI. The activation of phospholipase by glycosylation enhancing factor.

Glycosylation enhancing factor (GEF) from rat T cells is a kallikrein-like enzyme and enhances the assembly of N-linked oligosaccharides to IgE binding factors during their biosynthesis, whereas another T cell factor, i.e., glycosylation inhibiting factor (GIF), is a fragment of phosphorylated lipomodulin (i.e., phospholipase inhibitor), which when dephosphorylated inhibits phospholipase and the glycosylation process. The two T cell factors compete with each other when they are added to normal mesenteric lymph node cells during the formation of IgE binding factors. The addition of GEF to T cell hybridoma 23A4 cell switches the cells from the formation of unglycosylated IgE binding factor to the formation of N-glycosylated IgE binding factor. However, GEF neither inactivated GIF nor inhibited the formation of GIF by the T cell hybridoma. Stimulation of the T cell hybridoma with either affinity-purified GEF or bradykinin resulted in the release of GIF from the cells. GIF released by GEF stimulation had a m.w. of approximately 15,000 and bound to monoclonal antibody against lipomodulin. GEF and bradykinin also induced normal mesenteric lymph node cells to release GIF. Incorporation of 14C-arachidonic acid into 23A4 cells, followed by stimulation of the cells with GEF, resulted in the release of 14C-arachidonate. The results suggest that lipomodulin, a phospholipase inhibitory protein, is present in lymphocytes, and indicate that GEF and bradykinin induce the activation of phospholipase by stimulating cells to release lipomodulin.

Animals↗
PubMed1984

[Assessment of the exposure of pest control operators to organophosphorus pesticides. Organophosphorus pesticides in blood and alkyl phosphate metabolites in urine].

Pest control operators usually spray pesticides in small areas such as a kitchen in a restaurant and are exposed to various pesticides, especially those of the organophosphorus (OP) type. In order to evaluate their occupational exposure to OP pesticides during the work, OP pesticides in blood and alkyl phosphate metabolites in urine of these operators were analyzed and the relationship between pesticide exposure and analytical results were studied. OP pesticides in blood were analyzed by gas chromatography with flame photometric detector (FPD-GC) after separation of phospholipid in blood with silicagel column chromatography. OP pesticides were not detected in any blood samples (the limit of detection was 1 ng/ml). Dimethylphosphate (DMP) and dimethylthiophosphate (DMTP), being urinary metabolites of OP pesticides, were analyzed by FPD-GC after benzyl derivatization. This method eliminated interfering peaks in gas chromatograms. The ratio of two isomeric derivatives of DMTP was found to be constant. Both DMP and DMTP of the exposed group were significantly higher than those of the non-exposed group, DMP being higher than DMTP. The ratio of DMP to DMTP in the fenitrothion-dichlorvos-exposed group was significantly higher than that in the fenitrothion-exposed group. It was considered that the ratio might reflect a result of pesticide exposure. The urinary metabolites of OP pesticides tended to become lower with the lapse of time since the last exposure. However, small amounts were detected in a few samples even 5 days after the last exposure.

Adult↗