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Biomedical subjects

M Miyake

Publications and source records attributed to M Miyake.

At least 325 records · Page 18Linked to original sources

Protein carboxyl methylation in synaptic membrane of rat brain: the possible presence of adenosine-bound S-adenosyl-L-homocysteine hydrolase in the membrane.

The effects of some neurotransmitters, adenosine (Ad), and homocysteine (Hcys) on protein carboxyl methylation in synaptic plasma membranes from rat cerebral cortex were examined. Neither any of the neurotransmitters nor Ad had a detectable effect. Incubation of membrane with DL-Hcys alone (5 X 10(-5) M), the combination of both Ad (5 X 10(-5)) and DL-Hcys (5 X 10(-5)), or S-adenosyl-L-homocysteine (SAH) (1 X 10(-6)) strongly decreased the methyl ester formation. The inhibitory effect of the combination of both compounds may be interpreted in terms of the increased SAH concentration due to the presence of SAH hydrolase in the membrane. The inhibitory effect of Hcys alone was blocked by preincubation with Ad deaminase or Neplanocin A, a potent inhibitor of SAH hydrolase, suggesting the presence of Ad-bound SAH hydrolase in the synaptic membrane. Ad-bound SAH hydrolase activity estimated by the inhibition of methylation in the presence of Hcys was located in the membrane fractions including synaptosomes, myelin, and microsomes (about 70%), but the SAH hydrolase activity estimated on the basis of the inhibitory effect of the combination of both Ad and Hcys was localized exclusively in the soluble fraction (about 90%). The distribution of the latter activity is coincident with that of SAH hydrolase reported to date. Incubation of the synaptic membrane with Hcys markedly increased the SAH concentration. The stimulatory effect of Hcys alone was blocked by Ad deaminase.

Adenosylhomocysteinase↗

Purification and properties of calmodulin-lysine N-methyltransferase from rat brain cytosol.

A S-adenosylmethionine:protein-lysine N-methyltransferase (EC 2.1.1.43) has been purified from rat brain cytosol 7,080-fold with a yield of 8%, using octopus calmodulin as a substrate. It contains a lysine residue that is not fully methylated. The enzyme was purified by ammonium sulfate fractionation, Sephacryl S-200 gel filtration, and phosphocellulose and octopus calmodulin-Sepharose affinity chromatographies. Among protein substrates, it was highly specific toward octupus calmodulin. The Km values for octopus calmodulin and S-adenosyl-L-methionine were found to be 2.2 X 10(-8) M and 0.8 X 10(-6) M, respectively. The molecular weight was estimated to be 57,000 by gel filtration and the pH optimum was between 7.5 and 8.5. The enzyme was stimulated in the presence of 10(-7) M Mn2+ and 10(-4) M Ca2+. HPLC of the acid hydrolysate of methyl-3H-labeled calmodulin showed the formation of epsilon-N-mono, epsilon-N-di, and epsilon-N-trimethyllysine. Reverse-phase HPLC of tryptic peptides of the methyl-3H-labeled calmodulin demonstrated that the labeled N-methyllysine lies in the 107-126 peptide. These findings suggest that this enzyme methylated a specific lysine residue of octopus calmodulin.

Animals↗

[Malignant germ cell tumors in the mediastinum].

Mediastinal germ cell tumors are divided into seminomas and non-seminomatous germ cell tumors. The former is a radiosensitive tumor that can be successfully treated by surgery and radiation. The latter is much more malignant than the former, however, the therapy has been making remarkable progress owing to CDDP. Nevertheless, the median survival time of patients with mediastinal involvement is 14 months, much lower than that seen in patients with testicular involvement. From our 12 patients and a review of the literature, we drew the following conclusions. If malignant germ cell tumors are suspected among anterior mediastinal tumors affecting male patients of around 20 years old, tumor markers such as AFP and HCG must be investigated and then, tissue histology should be diagnosed from specimens obtained by mediastinoscopy or anterior mediastinotomy. In the case of NSGCT, or AFP and/or hCG producing seminoma, the first choice is the chemotherapy including CDDP. Seminomas, that do not produce either AFP or HCG, can be treated by surgery and radiation. If the patients have tumor markers such as AFP and/or HCG, these are very useful to evaluate the efficacy of the therapy. When the efficacy of chemotherapy reaches the maximum, adjuvant surgery may be indicated. Chemotherapy should be continued, when malignant tissues are present in the resected mass.

Adolescent↗

[Total femur replacement in osteogenic sarcoma of the femur].

A 14-year-old girl was admitted with a diagnosis of osteogenic sarcoma of the distal femur. Pre-operative chemotherapy was effective, and sclerosis of the lesion made clear the presence of a proximal femoral and pulmonary metastasis. Total femur and knee joint replacement with titanium alloy was made after a total resection of the femur. Her post-operative clinical course was excellent without local recurrence. Now, 14 months after the operation, she can walk without crutches. We wish to emphasize that the presence of a pulmonary metastasis is not absolutely a contraindication as long as the tumor appears surgically resectable and responsive to per-operative chemotherapy.

Adolescent↗

In vitro carboxymethylation of myelin basic protein.

During a study to find natural substrate proteins of carboxymethylation, myelin basic protein was found to be a good substrate. The two protein carboxymethylases were purified partially using myelin basic protein as a substrate. These two enzymes may be identical with protein carboxymethylase I and II, which have been found to methylate gamma-globulin. The Km of myelin basic protein (25 microM) was very small compared with other substrates. The activities of the two carboxymethylases were high in the rat brain in comparison to the other rat organs. The activity increased during the period of myelination in the rat brain. These findings suggest that carboxymethylation of myelin basic protein may play an important role in myelination.

Animals↗

Effects of bromocriptine on neuroleptic-induced amenorrhea, galactorrhea and impotence.

The effects of bromocriptine on neuroleptic-induced endocrinological disturbances (amenorrhea, galactorrhea and impotence) were investigated. Bromocriptine (5.0-7.5 mg/day) was administered to psychiatric patients receiving neuroleptics and developing hyperprolactinemia. The following results were obtained. Menses recurred in 7 of 10 patients with amenorrhea. A decrease in lactation appeared in 5 of 6 patients with galactorrhea. A significant increase in the serum levels of testosterone was observed after 8 weeks of the treatment in male patients. (N = 6). There was no remarkable deterioration in regard to the psychotic symptoms in schizophrenic patients. (N = 7). In non-schizophrenic patients (N = 9), a significant improvement was observed in regard to "somatic concern" (in Brief Psychiatric Rating Scale).

Adolescent↗

[General pharmacological action of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride). Influence on respiratory and cardiovascular systems, renal function, autonomic nervous system, isolated smooth muscle and digestive organs].

MCI-2016 at 3 mg/kg, i.v., caused slight changes in systemic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and ECG but at 10 mg/kg, i.v., it caused a significant increase in RR, decrease in SBP, increase or decrease in HR and a moderate change in ECG. Biphasic changes in SBP, HR and blood flow were sometimes observed after high doses. MCI-2016 also decreased SBP at 30 mg/kg, i.p., in SHR. MCI-2016 (50 mg/kg, p.o./day) showed little influence on SBP, HR and ECG in conscious beagle dogs. In isolated hearts, MCI-2016 decreased HR and contractility at the concentrations above 10(-5) g/ml, and 30 micrograms, i.a. MCI-2016 prolonged the AVCT at 10 mg/kg, i.v. MCI-2016 (i.v. or i.a.) moderately increased cerebral and femoral artery blood flows. MCI-2016 did not change CMRO2, but decreased MVO2. Coronary and renal artery flows were moderately increased by 10 mg/kg, i.v., of MCI-2016. Renal function was suppressed after 10 mg/kg, i.v., or 300 mg/kg, p.o., of MCI-2016. MCI-2016 potentiated the action of NE (increase in SBP, contractions of nictitating membrane and vas deferens), but showed little anti-cholinergic action. In contrast, MCI-2016 moderately increased gastrointestinal motility and salivatory response. As for the influence on isolated smooth muscles, MCI-2016 antagonized the contraction of blood vessels by high K+ at 10(-6) g/ml, or more, and it depressed the contractions by ACh, 5-HT, histamine and BaCl2 and also depressed spontaneous movements of uterus and ileum at 10(-5) M or more, in a nonspecific manner. MCI-2016 had no influence on liver damage and bile secretion, but inhibited stress ulcer and gastric acid secretion on the one hand, and caused gastric damage (125 mg/kg p.o., or more) on the other hand.

Animals↗

[General pharmacological action of tritoqualine (TRQ; (+/-)-(R*)-7-amino-4, 5, 6-triethoxy-3-[(R*)-5, 6, 7, 8-tetrahydro-4-methoxy-6-methyl-1, 3-dioxolo [4, 5-g] isoquinolin-5-yl] phthalide].

The general pharmacological action of TRQ was investigated, and the following results were obtained: With regard to its influence on the central nervous system, TRQ moderately potentiated the actions of hexobarbital (sleeping time) and methamphetamine (stereotyped behavior) at doses above 100 mg/kg, p.o. TRQ, however, had little influence on behavioral changes, EEG and motor function. TRQ only had slight influence on the respiratory and cardiovascular system at doses ranging from 0.1 to 3 mg/kg, i.v. Significant decrease in SBP and increases of HR, FAF and respiratory rate were observed after high doses (10-30 mg/kg, i.v.) of TRQ. TRQ also had little influence on contractility and pacemaker in isolated hearts, but moderately increased the coronary flow. The inhibitory effect of TRQ on the isolated smooth muscle was observed at high concentration and was non-specific. Furthermore, TRQ exhibited little influence on the autonomic nervous system. Among the effects of TRQ on the gastrointestinal system, it was shown that TRQ moderately increased the outflow of bile after doses above 1 mg/kg, i.v. TRQ also showed no remarkable actions on other aspects of the gastrointestinal system and blood coagulation system. Considering the present results, it may be suggested that there should be no serious problems in the application of TRQ as a hepatoprotective agent.

Animals↗

Age- and sex-related profiles of serum primary and total bile acids in infants, children and adults.

The relation of age and sex to serum primary (PBA) and total bile acid (TBA) concentrations was evaluated by an enzymatic fluorometric microassay in healthy infants, children and adults. TBA concentrations were the highest in the 6-day-old group and 1-month-old group and seemed to switch to almost normal adult levels by the age of 4-6 years, which persisted throughout life, while PBA concentrations were predominant over a period of 3 days to 3 months after birth. No sex-related differences were observed from neonates to very old persons for any of serum bile acids. These results show that the bile acid metabolism in the liver and the enterohepatic circulation of bile acids are usually matured in infancy and that aging and sex may insignificantly affect serum bile acid metabolic profiles.

Adolescent↗