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Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 343 records · Page 19Linked to original sources

Two separate tyrosine protein kinases in human platelets.

Tyrosine protein kinase activities were detected in the cytosolic fraction (PC-TPK) and the particulate fraction (PM-TPK) in human platelets using the synthetic peptide, E11G1 (Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly) as a substrate. PC-TPK and PM-TPK were different in substrate specificities, divalent cation requirements and apparent Mr values. These results strongly suggest that in platelets there exist at least two separate tyrosine protein kinases; one is present in cytosol and the other might be associated with membranes.

Blood Platelets↗

Purification of protein phosphatase from hen oviduct.

Two protein phosphatases of 103 and 29 kDa as determined by gel filtration, were purified from hen oviducts. The 103 -kDa phosphatase was purified 7300-fold to near homogeneity and dissociated into two polypeptides in the presence of SDS. Molecular masses of these polypeptides were estimated to be 60 and 38 kDa by SDS-polyacrylamide slab gel electrophoresis using the buffer system of Laemmli, but 68 and 35 kDa using the buffer system of Weber and Osborn. The stoichiometry of these polypeptides was approx 1:1 according to the densitometric analysis of gels at 550 nm. The 29 -kDa phosphatase was purified 2900-fold. Both phosphatases dephosphorylated the alpha-subunit of phosphorylase kinase more rapidly than the beta-subunit.

Animals↗

Calcium- and calmodulin-dependent phosphorylase kinase activity in porcine uterine smooth muscle.

Porcine uterine smooth muscle phosphorylase kinase has been partially purified. The enzyme was activated about 1.5-2.0-fold by exogenous calmodulin. Half maximal stimulation was observed at about 100 nM calmodulin. The activation was dependent on calcium and was maximum at pH 7.5 in the range of pH from 6 to 9. This activation was completely abolished by 100 microM trifluoperazine. The result suggested that unlike slow and cardiac muscles, phosphorylase kinase of uterine smooth muscle showed similar response to calmodulin with that of fast muscle. The physiological role of the calcium and calmodulin-dependent activation of myometrium phosphorylase kinase is briefly discussed.

Animals↗

Gastrin has no promoting effect on chemically induced colonic tumors in Wistar rats.

The effects of prolonged administration of tetragastrin from the beginning of intrarectal instillation of 1 ml of 0.25% N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and after MNNG-treatment on the incidence and histology of colonic tumors were compared in inbred Wistar rats. In week 35 prolonged administration of testragastrin in depot form from the beginning of MNNG-treatment resulted in a significant reduction in the incidence of colonic tumors and a significant increase in the incidence of mucinous adenocarcinoma, unlike the well-differentiated adenocarcinoma produced in controls without gastrin. In contrast, prolonged administration of tetragastrin after MNNG-treatment had little or no influence on the incidence, size or histology of colonic tumors. Thus tetragastrin had no promoting effect on colonic tumors.

Adenocarcinoma↗

Comparison of enzyme activities on glycogen metabolism in rabbit slow and fast muscles.

Activities of glycogen synthase (total) and branching enzyme in slow (soleus) muscle are higher than those in fast (vastus lateralis) muscle, while those of phosphorylase kinase (total), phosphorylase (total) and debranching enzyme are reversed. The active form ratio of glycogen synthase is higher in fast muscle, while those of phosphorylase kinase and phosphorylase are higher in slow muscle. Activities of cAMP-dependent protein kinase and protein phosphatase in slow muscle are higher than those in fast muscle. These results suggest that glycogen metabolizing enzymes in slow muscle, distinct from those in fast muscle, are regulated more strongly by cAMP-dependent protein kinase rather than by protein phosphatase.

Animals↗

Glycogen storage disease confined to the heart with deficient activity of cardiac phosphorylase kinase: a new type of glycogen storage disease.

The case of a male infant with marked deposition of glycogen, confined to the heart, is presented. Clinically, prominent cardiomegaly had been evident from immediately after birth until the infant's death due to heart failure. There were no significant clinical manifestations in other organs, including liver and skeletal muscle, during the clinical course. Autopsy revealed abnormal deposition of normally structured glycogen in the heart, but no deposition in the liver, skeletal muscle, or other systemic organs. This unusual pattern of glycogen deposition was also confirmed by measurement of the glycogen content of each organ. This is the first report of glycogen storage disease confined to the heart. Enzymatic analysis revealed no decrease in the activities of acid maltase, amylo-1,6-glucosidase, and phosphorylase in the heart or in the liver or skeletal muscle. However, phosphorylase kinase activity was not detectable in the heart, although high activity levels were observed in the liver and skeletal muscle. In this case the inborn error of metabolism responsible for the isolated deposition of glycogen in heart muscle may have been due to a deficiency of cardiac phosphorylase kinase.

Cardiomyopathies↗

Effect of a chemically defined diet in liquid form on colon carcinogenesis in rats.

The effects of ad libitum feeding of a chemically defined diet in liquid form on the incidence and histology of colon cancer induced by 10 weekly sc injections of 7.4 mg/kg of azoxymethane [(AOM) CAS: 25843-45-2] were investigated in W-rats. The chemically defined diet was adjusted once every 24 hours from 4 weeks before injection of the carcinogen to the end of the experiment at week 40. Oral administration of the defined diet resulted in significant increase in the incidence of colon cancer at week 40. Histologic examination showed that unlike adenocarcinomas with high mucin-producing activity, which were common in rats on pellet diet, most of the adenocarcinomas that developed in rats fed on defined diet were highly or well differentiated, with a typical glandular pattern. Administration of the chemically defined diet also resulted in marked colon mucosal hypoplasia and reduced gastrin levels in the serum at weeks 4 and 40.

Adenocarcinoma↗

Stimulation of autophosphorylation of rabbit skeletal muscle phosphorylase kinase by glycogen synthase on glycogen particles.

Glycogen synthase stimulated the autophosphorylation and autoactivation of phosphorylase kinase from rabbit skeletal muscle. This stimulation was additive to that by glycogen and the reaction was dependent on Ca2+. The effect by glycogen synthase was maximum within the activity ratio (the activity of enzyme without glucose-6-P divided by the activity with 10 mM glucose-6-P) of 0.3 and over 0.3 it was rather inhibitory. The results suggest that autophosphorylation of phosphorylase kinase in the presence of glycogen synthase on glycogen particles may be an important regulatory mechanism of glycogen metabolism in skeletal muscle.

Animals↗

Promotion by vagotomy of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of truncal vagotomy after administration of N-methyl-N'-nitro-N-nitrosoguanidine on the incidence and number of gastric carcinomas and gastric acid secretion, gastrin secretion, antral pH, and duodenal reflux were investigated in inbred Wistar rats. Rats were subjected to truncal vagotomy after N-methyl-N'-nitro-N-nitrosoguanidine treatment. Vagotomy significantly increased the incidence and number of adenocarcinomas of the glandular stomach. It also resulted in significantly more atypical glandular hyperplasias, which are precursors of gastric cancer. Furthermore, it caused a decrease in gastric secretion and an increase in mucosal pH in the antrum but did not increase duodenal reflux. These findings indicate that vagotomy has a promoting effect on the development of gastric cancers. The reduced gastric acid secretion, but not duodenal reflux, may be related to this increased incidence of gastric cancer.

Animals↗

Effect of glucagon on gastric motility examined by the acetaminophen absorption method and the endoscopic procedure.

The effects of glucagon and butropium bromide on gastric motility were compared by the acetaminophen absorption method and the endoscopic procedure. Intramuscular administration of 1 USP unit of glucagon and 4 mg of butropium bromide caused a significant decrease in the serum acetaminophen level 30 min after digestion of a test meal. Results indicated that glucagon significantly delayed gastric emptying, and that its inhibitory effect was similar to that of butropium bromide. Moreover, endoscopic examinations showed that glucagon and butropium bromide had similar inhibitory effects on gastric peristalsis. However, butropium bromide caused side effects more frequently than glucagon. Therefore, premedication with glucagon is superior to that with butropium bromide for upper gastrointestinal endoscopy.

Acetaminophen↗

Mg2+ counteracts the inhibitory effect of spermine on liver phosphorylase kinase.

When the effect of polyamines on pig liver phosphorylase kinase was examined, spermine was found to be the most inhibitory. Although putrescine stimulated the reaction slightly, the spermidine effect was dependent on the phosphorylase b concentration. The inhibitory effect of spermine was counteracted by increasing the Mg2+ concentration. At 0.3 mM Mg2+, the apparent Km for phosphorylase b was increased 9-fold by the addition of 5 mM spermine. However, increasing Mg2+ to 3 mM decreased the value to the initial level obtained at 0.3 mM Mg2+ alone. These results suggest that a possible role of Mg2+ in the regulation of liver phosphorylase kinase is to protect the enzyme from the inhibitory action of a polyamine such as spermine.

Animals↗

High tyrosine protein kinase activities in soluble and particulate fractions in bone marrow cells.

High tyrosine protein kinase activities were detected in soluble and particulate forms from bone marrow cells using synthetic peptide (Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly) as a substrate. Total activity of tyrosine protein kinase was 2.4 times higher in the soluble fraction but the specific activity was slightly higher in the particulate one. Mg2+ or Mn2+ requirements of these two enzymes for maximal activity were quite different from each other. Physiological significance of these two forms of enzymes is briefly discussed.

Animals↗

Phosphorylation of myelin basic protein by glycogen phosphorylase kinase.

The ability of homogeneous glycogen phosphorylase kinase (Phk) from rabbit skeletal muscle to phosphorylate bovine brain myelin basic protein (MBP) was investigated. Phk could incorporate a maximum of 1.9 mol phosphate/mol MBP. The apparent Km and Vmax for Phk phosphorylation of MBP were 27 microM and 90 nmol/min per mg enzyme, respectively. Properties of MBP phosphorylation by Phk are similar to those of phosphorylase as a substrate. Only serine residues of MBP are phosphorylated by Phk. Phosphorylation sites of MBP by Phk are not identical to those by cAMP-dependent protein kinases.

Animals↗

A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase.

A five-month-old Japanese boy was found to have marked glycogen accumulation only in the heart. A survey of enzymes revealed normal activities of phosphorylase, cyclic AMP-dependent protein kinase, acid maltase and amylo-1,6-glucosidase. However, the heart had capacity of activating neither rabbit muscle phosphorylase b nor endogenous phosphorylase b, which was converted to active form only when supplemented rabbit muscle phosphorylase kinase. In contrast to the heart, activities of phosphorylase kinase were found within normal levels in other organ tissues so far tested. These findings indicate that the present case of the cardiac glycogenosis is caused by deficiency of cardiac phosphorylase kinase.

Animals↗

Two diverse effects of poly(L-lysine) on rabbit skeletal muscle phosphorylase kinase: stimulation of autophosphorylation and inhibition of its activity.

Polylysine greatly stimulated the autophosphorylation of phosphorylase kinase from rabbit skeletal muscle. When fully autophosphorylated, about 14 mol of phosphate per tetramer (alpha beta gamma delta) were incorporated in the presence of polylysine, which was twice as much as those observed without polylysine. In contrast to this stimulatory effect of polylysine on the autophosphorylation, polylysine strongly inhibited the conversion reaction of phosphorylase b to a. The inhibition is competitive with a Ki of 2.3 micrograms/ml. No effects of polylysine were observed on the activities of phosphorylase and cAMP-dependent protein kinase.

Animals↗