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Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 325 records · Page 18Linked to original sources

Non-requirement of calcium on protamine phosphorylation by calcium-activated, phospholipid-dependent protein kinase.

Phosphorylation of clupeine sulfate by purified rat brain calcium-activated, phospholipid-dependent protein kinase (protein kinase C) was studied. In the absence of Ca2+, phosphatidylserine and diolein markedly stimulated its phosphorylation. However Ca2+ did not stimulate but inhibit this phosphorylation about 30% in the presence of phospholipids. Random polymer (Arg, Ser) 3:1 and (Lys, Ser) 3:1 could be phosphorylated by protein kinase C. In the presence of phospholipids Ca2+ is not needed for the phosphorylation of polymer (Arg, Ser) 3:1, while Ca2+ is necessary for polymer (Lys, Ser) 3:1. Non-requirement of Ca2+ on clupeine phosphorylation by protein kinase C is briefly discussed.

Calcium↗

Is there a relation between bone strength and percolation?

The thermal contraction temperature of collagen in partially demineralized bone was measured as a function of the volume fraction of the mineral phi m. Initially, the contraction temperature gradually increased with an increase in phi m and then rapidly increased in the vicinity of phi m = 0.17. The resisting force against the contraction stress caused by collagen, which corresponds to the compressive strength, was estimated from the thermal contraction temperature of partially demineralized bone. The phi m-dependence of the resisting force of partially demineralized bone was roughly explained in terms of the percolation theory which gives a good description of a sol-gel transition. This suggests that bone can be approximately regarded as a percolated structure of the mineral on a collagen matrix.

Animals↗

Activation of phosphorylase kinase through autophosphorylation by membrane component phospholipids.

Phosphatidic acid (PtdOH) has been shown not only to stimulate autophosphorylation and autoactivation of phosphorylase kinase of rabbit skeletal muscle but also to decrease the apparent Ka for Ca2+ on autophosphorylation sharply [Negami et al. (1985) Biochem. Biophys. Res. Commun. 131, 712-719]. In this study we investigated the interaction between PtdOH and other phospholipids on autophosphorylation and autoactivation of this enzyme. Acidic phospholipids, such as phosphatidylserine (PtdSer), phosphatidylinositol (PtdIns) and PtdOH, stimulated this reaction about 2-4-fold, and the approximate Ka values of this reaction were 10 micrograms/ml, 6.3 micrograms/ml and 30 micrograms/ml respectively. The molar ratio of PtdIns and PtdSer with maximal effect on autophosphorylation was about 1:1. Under these conditions PtdOH stimulated the initial velocity of autophosphorylation about 5.2-fold. When fully autophosphorylated, about 12-13 mol phosphate per tetramer (alpha beta gamma delta) were incorporated in the presence of mixed acidic phospholipids (PtdOH:PtdIns:PtdSer = 2:1:1), which was about twice as much as values observed without effectors. In the presence of mixed acidic phospholipids there was a concomitant enhancement of kinase activity, about 30-40-fold at pH 6.8 and 2.5-3-fold at pH 8.2. Mixed acidic phospholipids sharply decreased an apparent Ka for Ca2+ from 4 X 10(-5) M to 8 X 10(-7) M. With mixed acidic phospholipids as effectors this autophosphorylation occurred through an intramolecular mechanism. Based on these results, autophosphorylation and autoactivation of phosphorylase kinase in the presence of acidic phospholipids may account for an important regulatory mechanism of glycogenolysis in muscle contraction.

Adenosine Triphosphate↗

Pure red cell aplasia in association with malignant histiocytosis.

The authors report a case of malignant histiocytosis complicated with pure red cell aplasia. Erythrophagocytic histiocytes were found only rarely and no histiocyte ingested erythroblasts. Neither serum immunoglobulin G nor peripheral blood T-cells have any inhibitory activity to erythroid colony growth from allogeneic bone marrow. Pure red cell aplasia is an unusual complication in malignant histiocytosis.

Anemia, Aplastic↗

Value of ultrasonographic examination combined with measurement of serum tumor markers in the diagnosis of pancreatic cancer of less than 3 cm in diameter.

Ultrasonographic examinations and measurements of CA 19-9 and elastase 1 were done simultaneously in 14 patients with resectable pancreatic cancer of less than 3.0 cm in longest diameter and 48 patients with pancreatitis. Although a pancreatic mass was detected ultrasonically in only six (42.9%) of the patients with tumors of less than 3.0 cm in diameter, one or more of the abnormal ultrasonic findings (a pancreatic mass and dilatation of the pancreatic and/or bile duct) was significantly more frequent in patients with pancreatic cancer than in those with pancreatitis. An abnormally high level of CA 19-9 and/or elastase 1 also was significantly more frequent in patients with pancreatic cancer than in those with pancreatitis. The rates of detection of pancreatic cancer by ultrasonography only and by measurement of tumor markers only were 92.9% and 100%, respectively, but the specificities and predictive values of positive results by each of these tests alone were low. Thirteen (92.9%) of 14 pancreatic cancers were found in patients giving positive results by both ultrasonography and measurement of tumor markers, whereas no tumors were found in patients giving negative results in both of these examinations. A combination of these two examinations raised the specificity and predictive value of positive results to 87.5% and 68.4%, respectively, but had little or no influence on the sensitivity or predictive value of negative results. Therefore, patients in whom ultrasonographic findings are abnormal and in whom the serum levels of tumor markers also are abnormally high should be examined more extensively. This combination of examinations indicates the possibility of earlier detection of pancreatic cancer.

Adult↗

Effect of ionic strength on production of cAMP- and Ca2+-independent protein kinase from rat liver plasma membrane.

Production of cAMP- and Ca2+-independent protein kinase was stimulated when rat liver plasma membrane was incubated with increasing concentrations of NaCl. This protein kinase release was diminished by addition of protease inhibitor. The molecular mass of this enzyme was approx. 50 kDa and a high concentration of Mg2+ was required for whole histone phosphorylation. These properties are similar to those of the protease-activated form of protein kinase C. The NaCl effect could be replaced by other salts such as LiCl and NaHCO3. These results suggest that membrane-bound protein kinase C is activated by limited proteolysis corresponding to an increase in ionic strength.

Animals↗

Values of carcinoembryonic antigen, elastase 1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas.

The levels of carcinoembryonic antigen (CEA), elastase 1, and carbohydrate antigen determinant (CA 19-9) in the pancreatic cystic fluid and the serum from five patients with cystadenocarcinoma of the pancreas, one patient with retention cyst due to pancreatic carcinoma, three patients with cystadenoma, and eight patients with benign pseudocyst accompanying or following pancreatitis, were determined by immunoassay technique. Fluid from pancreatic cysts was obtained by ultrasonically-guided percutaneous fine-needle aspiration biopsy. The specimens were centrifuged and the supernatant was used for the measurement of CEA, elastase 1, and CA 19-9, while the cell pellet was examined cytologically. The levels of CEA in the aspirated fluid were significantly higher in patients with malignant cysts of the pancreas than in those with benign cystadenomas and pseudocysts. In contrast, the levels of elastase 1 were significantly lower in patients with malignant cysts than in those with benign pancreatic cysts. Although the levels of CA 19-9 were significantly higher in patients with malignant cysts than in those with pseudocysts, the overlap between the values of patients with malignant and benign pancreatic cysts is too great. The serum CA 19-9 was most useful, however, to distinguish an individual patient with malignant cysts of the pancreas from those with benign pancreatic cyst, since there were no significant differences between the levels of serum CEA and elastase 1 in patients with malignant and benign pancreatic cysts. Correct diagnoses were made cytologically in 4 (66.7%) of 6 patients with malignant cysts. In two patients with malignant cyst, in whom no cancer cells were detectable in the aspirated materials, levels of CEA were abnormally high, but high levels of elastase 1 did not occur. Therefore, the combined measurement of CEA and elastase 1 in the aspirated cystic fluid of the pancreas could be used as an aid in diagnosis of malignant cysts of the pancreas.

Antigens, Neoplasm↗

Value of serum alpha-fetoprotein and ferritin in the diagnosis of hepatocellular carcinoma.

Alpha-fetoprotein (AFP) and ferritin in the serum were determined by radioimmunoassay and enzyme immunoassay, respectively, in 224 healthy subjects, 55 patients with benign hepatic disease and 44 patients with hepatocellular carcinoma (HCC). The AFP levels in the serum were significantly higher in patients with HCC than in healthy subjects and in patients with benign hepatic disease, but this level was not a satisfactory indicator of small HCC since it was elevated in only 75.0% of the patients with a tumor of less than 3.0 cm in its greatest diameter. Although serum ferritin was elevated in only 56.8% of the patients with HCC, the combination of these two tests raised the diagnostic rate of HCC from 65.9% by serum AFP measurement alone to 88.6% with no appreciable decrease in the specificity for HCC. In particular, it raised the diagnostic rates of lesions of less than 3.0 cm in the greatest diameter from 75.0% by measuring AFP alone to 100%. Thus the combination of AFP and ferritin measurement in the serum is useful for the early detection of HCC.

Adult↗

Inhibitory effects of tetragastrin and histamine on carcinogenesis in the small intestines of W rats by N-methyl-N'-nitro-N-nitrosoguanidine.

The effects of tetragastrin and histamine on the incidence and histology of tumors induced in the small intestine by N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] were investigated in male W rats. Animals were given MNNG at 150 micrograms/ml in their drinking water for 25 weeks and then 300 micrograms tetragastrin or 4 mg histamine dihydrochloride sc per day in depot form. Administration of tetragastrin or histamine after MNNG treatment resulted in a significant increase in gastric acid secretion and a significant reduction in the incidence of tumors in the duodenum; however, only histamine decreased the incidence of tumors in the jejunum. Histologically, the tumors induced in the small intestine were mostly adenocarcinomas, and their histologic type was not affected by either tetragastrin or histamine.

Adenocarcinoma↗

Two activated forms of protease-sensitive protein kinase isolated from rat liver plasma membrane.

Rat liver plasma membrane contains a protease-activated kinase which corresponds to protein kinase C. When the solubilized enzyme was digested with trypsin in the absence of NaCl, a partially activated form with an approximate molecular weight of 8 X 10(4) was produced. However, another active form of molecular weight of 5 X 10(4) was obtained when the enzyme was digested in the presence of NaCl. The larger molecular weight form was converted to the smaller form by tryptic digestion in the presence of NaCl. These results suggest the existence of two protease-activated forms of protein kinase C.

Animals↗

Effect of tetragastrin on the colonic mucosa of rats during intrarectal administration of N-methyl-N'-nitro-N-nitrosoguanidine.

The effects of the C-terminal tetrapeptide of gastrin, tetragastrin, on the colonic mucosa on Days 15 and 25 during intrarectal administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and its effects on the incidences of colonic tumors in experimental Wk 20 and 35 were investigated in Wistar rats. Administration of tetragastrin in depot form during instillation of MNNG resulted in significant decreases in the incidences of mucosal erosions, ulcerations, and atypical regenerative glandular hyperplasias in the colonic mucosa, most of these lesions being greater in the distal half of the colon. Administration of tetragastrin also significantly decreased the incidences and/or numbers of colonic tumors in Wk 20 and 35. The distribution of colonic tumors induced in Wk 20 and 35 corresponded well to those of erosions, ulcerations, and atypical regenerative glandular hyperplasias induced during the administration of MNNG. These findings suggest that the effect of tetragastrin in decreasing the incidences of erosions, ulcerations, and atypical regenerative glandular hyperplasias in the colonic mucosa during instillation of MNNG is related to its effect in reducing the development of colonic tumors.

Animals↗

Values of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic material in the diagnosis of malignant pancreatic tumor.

The diagnostic accuracy of the measurement of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic fluid in the diagnosis of pancreatic tumors was assessed in 32 patients with malignant pancreatic tumors and 19 patients with pancreatitis. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation with a duodenofiberscope after intravenous administration of secretin. Pancreatic material was obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance. Abnormally high CA 19-9 levels in the serum were significantly more frequent in patients with malignant pancreatic tumors than in those with pancreatitis: they were elevated in 71.9% of the patients with pancreatic tumors. High CA 19-9 levels were found primarily in patients with a tumor of the head of the pancreas, in those with a tumor greater than 3 cm in its greatest diameter, and in those with an unresectable cancer. Only 57.1% of seven patients with a tumor of less than 3 cm in its greatest diameter showed an increase in CA 19-9 level. The CA 19-9 levels in pure pancreatic juice were significantly higher in patients with pancreatic tumors than in patients with pancreatitis without pancreatic stone. However, it was not useful for differentiating pancreatic tumors from pancreatitis with pancreatolithiasis. The CA 19-9 level in pancreatic materials obtained by aspiration biopsy was significantly higher in patients with malignant pancreatic tumors than in those with pancreatitis. Eight patients (80%) with pancreatic tumors had values above 1000 U/ml, whereas all five patients with pancreatitis had values of less than 30 U/ml. Although CA 19-9 levels in pancreatic materials was useful only when cytologic examination did not provide any evidence of malignancy, the combination of the CA 19-9 assay and the cytologic study of specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Adult↗

Proteolytic activation of protein kinase C by membrane-bound protease in rat liver plasma membrane.

Incubation of rat liver plasma membrane produced histone phosphorylating activity at 75 mM Mg2+ in the soluble fraction. The release of the kinase activity was inhibited by leupeptin and bovine pancreatic trypsin inhibitor, suggesting the involvement of membrane-bound protease. When partially purified protein kinase C from rat liver cytosol was treated with the trypsin-like protease purified from rat liver plasma membrane, histone phosphorylating kinase which was independent of Ca2+ and phospholipids, produced with a molecular weight of about 5 X 10(4). These results suggest that membrane-bound, trypsin-like protease activates protein kinase C in plasma membrane and the activated kinase is released from the membrane to the soluble fraction.

Animals↗

Stimulating effect of phosphatidic acid on autophosphorylation of phosphorylase kinase.

Autophosphorylation of phosphorylase kinase from rabbit skeletal muscle was stimulated by acidic phospholipids such as phosphatidic acid (PA), phosphatidylinositol, and phosphatidyl-serine. PA stimulated an initial velocity of autophosphorylation 3.8-fold. When fully autophosphorylated, about 11 mol of phosphate per tetramer (alpha beta gamma delta) were incorporated in the presence of PA and about 6.5 mol in the absence of PA. In the presence of PA (100 micrograms/ml), there was a concomitant enhancement of its kinase activity about 25-fold at pH 6.8. PA (100 micrograms/ml) sharply decreased an apparent Ka for Ca2+ on autophosphorylation from 4.0 X 10(-5) M to 1.0 X 10(-6) M. Available evidence indicates that the Ca2+-activated, PA-dependent autophosphorylation of phosphorylase kinase shows an ability to stimulate glycogen breakdown.

Animals↗

Protease-activated protein kinase in rat liver plasma membrane.

Upon limited proteolysis with trypsin, a cAMP and Ca2+-independent protein kinase was produced from rat liver plasma membrane. This enzyme showed a multifunctional capacity and phosphorylated calf thymus histone and rat liver ribosomal proteins. The molecular weight was estimated to be 5.0 X 10(4). When plasma membrane was treated with a buffer containing Triton X-100, a proenzyme with a molecular weight of 8.4 X 10(4) was extracted. By tryptic digestion, the proenzyme was converted to an active protein kinase which was similar to the enzyme obtained by the direct digestion of membrane. However, this proenzyme phosphorylated H1 histone in the presence of Ca2+ and phospholipid without proteolytic digestion. These results indicate the existence of a protease-activated protein kinase in rat liver plasma membrane and the proenzyme seems to be same as protein kinase C.

Animals↗