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Biomedical subjects

T Mimura

Publications and source records attributed to T Mimura.

At least 253 records · Page 14Linked to original sources

Effect of mealing on plasma and brain amino acid, and brain monoamine in rats after oral aspartame.

Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food.

5-Hydroxytryptophan↗

Dietary aspartame with protein on plasma and brain amino acids, brain monoamines and behavior in rats.

Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester), was investigated for its ability to alter levels of the large neutral amino acids and monoamines in overnight fasted rats allowed to consume meals with or without protein for two hours. Additionally, the possible long term behavioral consequences of APM in 25% casein diets with or without 10% sucrose were determined. Acute APM ingestion increased both plasma and brain phenylalanine and tyrosine levels, but brain tryptophan levels were not altered regardless of dietary protein. Brain norepinephrine and dopamine levels were unaltered by any of the diet while serotonin levels were slightly increased when a protein-free diet was consumed. But APM and/or protein ingestion minimized this increase of brain serotonin levels as much as controls. Chronic APM ingestion failed to influence diurnal feeding patterns, meal size distributions, or diurnal patterns of spontaneous motor activity. The chronic ingestion of abuse doses of APM produced no significant chemical changes in brain capable of altering behavioral parameters believed to be controlled by monoamines in rats.

Amino Acids↗

Inconsistent reactivity of an anti-sperm monoclonal antibody and its relationship to sperm capacitation.

An anti-sperm monoclonal antibody was developed from female C57BL/6 mice immunized with epididymal sperm from a syngeneic male mouse. Immunofluorescence staining revealed that the antibody did not react to fresh epididymal sperm but attached to the capacitated sperm found in the peri-vitelline spaces of the ova. When the antibody was applied to sperm incubated in vitro, variously stained sperm were observed. It was presumed that the antigenic site detected by the antibody was hidden in the fresh epididymal sperm and was spread from the acrosomal cap region to the entire head during the capacitation process.

Animals↗

Factors predicting the course of diabetes mellitus in hyperthyroid patients.

The relationship between changes in glucose tolerance with treatment of hyperthyroidism and various factors that might be relevant to carbohydrate metabolism were investigated in 64 hyperthyroid patients with abnormal glucose tolerance, including 35 cases with fasting plasma glucose (FPG) levels of 140 mg/dl or more. All patients had diffuse toxic goiter. After correction of the hyperthyroidism, glucose intolerance improved in almost all cases, even in cases with fasting hyperglycemia, but diabetes mellitus in patients with FPG above 140 mg/dl and/or delta IRI/delta PG X 30' during a 50-g oral glucose tolerance test below 0.10, persisted. Patients who showed diabetic glucose tolerance even after remission from thyroid dysfunction had significantly lower delta IRI/delta PG X 30' values and a higher incidence of family histories of diabetes mellitus than those not showing diabetic glucose tolerance. There were no significant differences in serum T3 and T4 levels between these two groups of patients. The findings suggest that predisposition to diabetes may be an important factor in persistent glucose intolerance in the hyperthyroidism of Graves' disease. The FPG and delta IRI/delta PG X 30' values may be useful in predicting which patients with hyperthyroidism will have permanent diabetes.

Adolescent↗

Potent platelet antiaggregant action of an antiarrhythmic peptide (AAP).

A potent platelet antiaggregant action of an antiarrhythmic peptide (AAP) was demonstrated to be a cause of the antithrombotic effect. AAP (10, 20 or 40 mg/kg, i.v.) inhibited ex vivo platelet aggregation induced by collagen in a dose-dependent manner. AAP also inhibited the platelet aggregation of platelet-rich plasma (PRP) induced by collagen, Ca-ionophore A-23187, adenosine diphosphate (ADP), thrombin or arachidonic acid in vitro. The IC50 was 2.5 mM for collagen, 1.7 mM for A-23187, 5 mM for ADP, 0.4 mM for thrombin and 0.15 mM for arachidonic acid. The aggregation inhibitory activity of the peptide on washed platelet (WP), in a Ca2+-free medium, was stronger than on PRP. The IC50 was 1 mM for collagen and 20 microM for A-23187. No significant difference was found between antiaggregant activities of platelet-free plasma (PFP) from AAP-treated rats and PFP from normal rats supplemented with AAP. The direct action of AAP on platelets was also supported by the incorporation of AAP into platelet cytoplasma which caused a decrease of Ca2+-dependent 3':5'-cyclic nucleotide phosphodiesterase (Ca-PDE) activity. It was considered that AAP showed its platelet aggregation inhibitory activity by decreasing intracellular Ca2+ concentration through the inhibition of Ca-PDE activity.

3',5'-Cyclic-AMP Phosphodiesterases↗

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. IV. Induction of anti-inflammatory activity by chemical cleavage of interchain disulfide bonds in human immunoglobulin G and pharmacological activity of alkylated subfragments.

Commercially available human serum immunoglobulin G (IgG, native IgG) was separated into two fractions (Fr.I and II) using a diethylaminoethyl cellulose column. Heavy and light chains containing fractions were obtained from these two fractions after carboxamide-methylation. Thus, these fractions were subjected to an anti-inflammatory screening procedure and were shown to have a potent inhibitory activity against rat carrageenin induced paw edema, while no effect was observed in native IgG, Fr.I or II. The reduction and alkylation of the interchain disulfide bonds were essential to induce the anti-inflammatory activity. The anti-inflammatory activity of alkylated heavy and light chains of Fr.I (Fr.I-H and I-L) was also noted in subacute inflammation caused by the felt pellet and croton oil granuloma methods. Moreover, strong membrane stabilizing activities of Fr.I-H and I-L were demonstrated in vitro using rat red blood cell membrane and liver lysosomal membrane.

Alkylation↗

Studies on sperm capacitation using monoclonal anti-body--disappearance of an antigen from the anterior part of mouse sperm head.

C57BL/6 mice were immunized with cauda epididymal sperm from syngenic mice. A monoclonal antibody (TSC4) was obtained using a hybridization method with myeloma (P3U1) cells. The antibody was examined for its reactivity to sperm from different regions of the reproductive tract of male mice. The antigen was recognized only when the sperm reached the corpus epididymis. The area of antigen present on the sperm membrane was topographically restricted to the anterior part of sperm head. The antigen remained on the sperm after washing with phosphate buffered saline, disappearing, however, when sperm was capacitated.

Animals↗

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. V. Mechanism of anti-inflammatory action of carboxamide-methylated L-chain (Fr. I-L) and H-chain (Fr. I-H) from human serum IgG.

Using the xylene ear method in mice, it was demonstrated that the reduced and carboxamide-methylated fragments of human serum IgG (Fr. I-H and Fr. I-L) significantly suppressed capillary permeability. It was also shown that leucocyte emigration and protein leakage into and esterase activity of the pouch fluid, which was accumulated by carboxy-methyl cellulose injections, were suppressed by the administration of the fragments. Moreover, the lipid peroxide level was lowered by both Fr. I-H and Fr. I-L in the liver of either carrageenin-induced, paw edema-bearing or kaolin pouch inflammation in rats. The facts obtained in this study indicated the mechanisms of the anti-inflammatory effects of Fr. I-H and Fr. I-L were mainly caused by both the inhibitory effect on leucocyte emigration into the site of injury and stabilization of the membrane by inhibiting lipid peroxidation of the inflammatory tissue.

Acid Phosphatase↗

Response of immunoreactive antiarrhythmic peptide (IR-AAP) level associated with experimental arrhythmia in rats.

The change in endogenous antiarrhythmic peptide (AAP) levels in serum, heart and kidney from rats under several drug-induced arrhythmias was investigated using a sensitive and specific radioimmunoassay. The extracts from serum, heart and kidney were fractionated by Sephadex G-25 chromatography to obtain a fraction which was found at the same position as that of synthetic AAP. In serum, the immunoreactive (IR)-AAP level increased about threefold under CaCl2-, aconitine- and epinephrine-induced arrhythmias. In heart, the IR-AAP level was doubled by CaCl2, increased 1.4 times by aconitine and decreased by one third by epinephrine. The levels in serum and heart were slightly increased by ADP. The kidney IR-AAP level was not changed under these drug-induced arrhythmias. Considering the previous result that AAP could protect against CaCl2- and aconitine-induced arrhythmias but not against epinephrine-induced arrhythmia, the change in the IR-AAP level in heart coincided with the effect of AAP given to animals under arrhythmia. Quinidine, propranolol and verapamil had no effect on serum IR-AAP level. These results suggested that endogenous AAP in heart worked to suppress certain arrhythmia.

Aconitine↗

[Clinical studies on pulmonary metastases from differentiated thyroid carcinoma--characteristics of patients with pulmonary metastases which appear before thyroid operation or afterward].

At Ito Hospital we have experienced 70 primary cases of differentiated thyroid carcinoma with pulmonary metastasis during the last 32 years. These patients were divided into two groups; patients who presented with the metastasis before thyroid operation (M-1 cases) and afterward (M-O cases). Contrary to our expectation, the over-all survival rate was more favorable in M-1 cases. We therefore studied on the clinical characteristics of these patients to see if there may be any differences between the two groups. The over-all survival rate of M-1 and M-0 cases was 85.7% and 42.9%, respectively. This difference was statistically significant (p less than 0.001). In M-1 cases percentage of male patients was higher, mean age was lower, papillo-follicular carcinoma was more predominant, and the outcome of RI therapy was more favorable. There were no significant differences on the roentgenographical type of metastatic foci and on the intraoperative findings between the two groups. From these results it is suggested that differentiated thyroid carcinoma with pulmonary metastasis in younger patients may be pathogenetically different from those in the older, and that biological characteristics of the disease that shows pulmonary metastasis in early stage differ from that which shows later.

Adenocarcinoma↗

Isolation and characterization of calmodulin from a molluscan smooth muscle.

Calmodulin was purified from the anterior byssal retractor muscle (ABRM) of a mollusc Mytilus edulis. Ca2+-induced conformational changes in the ABRM calmodulin could be demonstrated by polyacrylamide gel electrophoresis, by u.v. absorption spectrum and by circular dichroic spectrum. The amino acid composition of the ABRM calmodulin closely resembled that of other invertebrate calmodulins. The ABRM calmodulin was less effective in activating rat brain phosphodiesterase than vertebrate calmodulins.

Amino Acids↗

Determination of immunoreactive antiarrhythmic peptide (AAP) in rats.

A sensitive and specific radioimmunoassay for antiarrhythmic peptide (AAP) has been developed, utilizing 3-(4-hydroxy, 5-[125I]iodophenyl)propionyl AAP and guinea pig anti-AAP serum. Synthetic AAP was used as a standard and the polyethylene glycol method was employed to separate free AAP from antibody-bound AAP. The minimum detectable dose of AAP was 0.2 pmol. In the assay system, immunoreactivity was shown not to be attributable to fragments derived from AAP, gelatin or collagen peptides, which sequences differ only by one amino acid from those of AAP. Immunoreactive (IR) AAP extracted from rat tissues and serum gave parallel dose-response curves to those of AAP. Thus, the AAP equivalents per g or ml of tissues measured in adult male rats were 203 pmol in heart, 166 pmol in kidney, 4 pmol in serum, and 2 to 6 pmol in the other tissues. IR-AAP was separated into two fractions by Sephadex G-25 chromatography. Fr. I was considered to have a larger molecular mass than AAP, while Fr. II appeared to have a molecular mass equal to AAP. Ratios of Fr. II in total IR-AAP were 50% in heart and 10% in kidney, while serum IR-AAP gave only Fr. II. The IR-AAP level in heart showed a positive correlation increase with age in rats.

Animals↗