PubMed Health⌕ Search

Biomedical subjects

M Takamatsu

Publications and source records attributed to M Takamatsu.

At least 19 recordsLinked to original sources
PubMed1992

Phosphorylation sites on tau by tau protein kinase I, a bovine derived kinase generating an epitope of paired helical filaments.

Tau protein kinase I (TPKI) isolated from bovine brain has been determined to phosphorylate tau at four distinct sites by detecting modified Ser and Thr residues with protein sequencer. Ser199, Thr231, Ser396 and Ser413 were all found to have been phosphorylated by TPKI (numbering of amino acids was done in relation to the longest human tau [Neuron, 3 (1989) 519-526]). These phosphorylations generate an epitope of PHF (paired helical filaments) and eliminate the recognition of tau by the monoclonal antibody, tau-1. These results suggested that TPKI might be responsible for at least some of the phosphorylation of tau to induce PHF formation.

Amino Acid Sequence↗
PubMed1992

Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments.

From bovine brain microtubules we purified tau protein kinase I (TPKI, Mr 45,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tau protein kinase II (TPKII) whose activity was attributed to a 30-kDa protein on SDS-PAGE by affinity-labeling using an ATP analog. Both kinases were activated by tubulin. TPKII, but not TPKI, phosphorylated tau fragment peptides previously used for detection of a Ser/ThrPro kinase activity. Therefore, TPKII was considered to be the Ser/ThrPro kinase. TPKI was more effective than TPKII for producing the decrease of tau-1 immunoreactivity and mobility shift of tau on SDS-PAGE. Moreover, TPKI, but not TPKII nor other well-known protein kinases, generated an epitope present on paired helical filaments. These findings suggested that tau phosphorylated by TPKI resembled A-68, a component of paired helical filaments.

Affinity Labels↗
PubMed1992

Platelet-activating factor acetylhydrolase activity in red blood cell-stroma from patients with cerebral thrombosis.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) is a bioactive phospholipid and inactivated by a specific enzyme, PAF acetylhydrolase (PAF-AH). We have measured PAF-AH activity in red blood cells (RBCs) from patients with a history of cerebral thrombosis and age-matched healthy controls. The activities in 34 patients and 34 controls were 1.29 +/- 0.28 and 1.64 +/- 0.26 nmol/10(9) RBCs/min (or, 30.0 +/- 5.8 and 35.1 +/- 4.7 nmol/g protein/min) (mean +/- SD), respectively, and the difference was significant (p less than 0.001). In patients, RBC PAF-AH activity correlated positively with RBC filterability, an index of RBC deformability (r = +0.501, p less than 0.05). The RBC activity may play a role in scavenging oxidation products of membrane phospholipids. Lower RBC PAF-AH activity may predispose to ischemic diseases by disturbing microcirculatory behavior of the RBCs.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1991

Platelet-activating factor (PAF) stimulates the production of PAF acetylhydrolase by the human hepatoma cell line, HepG2.

The human hepatoma cell line, HepG2, secreted an activity that degrades platelet-activating factor (PAF) by the hydrolysis of the sn-2 acetyl group. This activity was Ca++ independent, inhibited by diisopropylfluorophosphate but not by p-bromophenacyl bromide, and resistant to treatment with trypsin or pronase. Separation of HepG2-conditioned medium by gel filtration disclosed that the activity was associated with lipoproteins. An antiserum against PAF acetylhydrolase immunoprecipitated this activity. It was not recognized by an antibody against lecithin:cholesterol acyltransferase (LCAT), which also is secreted by HepG2 cells. Therefore the phospholipase A2 activity of LCAT was excluded as a source of the observed activity. PAF added to the culture medium stimulated the secretion of the PAF-degrading activity by HepG2 cells, while lyso-PAF was inactive. Maximal stimulation was observed with 5 ng/ml PAF, which induced a fivefold increase. The presence of 5 ng/ml PAF, enhanced the secretion of [35S]methionine-labeled PAF acetylhydrolase and cycloheximide inhibited both the basal and PAF-stimulated secretion of the labeled enzyme. We conclude that HepG2 cells produce PAF acetylhydrolase. The liver may be a major source of plasma PAF acetylhydrolase, and PAF may induce the production of its inactivating enzyme by the liver.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Mucoepidermoid carcinoma of the thyroid gland.

An extremely rare case of mucoepidermoid carcinoma of the thyroid in a 56-year-old woman is presented. The patient clinically having Hashimoto's thyroiditis was noted a nodule in her neck. The tumor was sited in the midportion of the left lobe of the thyroid, and histologically it showed both squamous features and mucin production. The squamous cells were arranged in solid sheets with horny pearls and the mucous cells tended to line dilated duct-like elements. Ultrastructurally, the epidermoid cells had aggregates of tonofilaments and well-developed desmosomal attachments, and the mucous cells contained numerous mucin granules in their cytoplasm. Immunohistochemical studies revealed that cytokeratin antibodies showed positivity for both the lining cells and squamous cells, whereas carcinoembryonic antigen positivity was found in the lining cells and intraluminal material. The tumor cells were negative for thyroglobulin, calcitonin, vimentin, chromogranin, and neuron-specific enolase. These unusual histologic and immunohistochemical features are suggestive of a tumor related to the so-called "solid cell nest" of the thyroid.

Carcinoembryonic Antigen↗
PubMed1990

Accumulation of gangliosides with N-acetylneuraminosyl(alpha 2-6)lactosamine structure in primary human hepatoma.

Gangliosides of hepatomas have been analyzed by using a monoclonal antibody directed to N-acetylneuraminosyl(alpha 2-6)lactoneotetraosylceramide (sialyl(alpha 2-6)paragloboside), which was prepared by injecting the monosialoganglioside fraction of human meconium into BALB/c mice. The monoclonal antibody, named MSG-15, was found to bind sialyl(alpha 2-6)paragloboside, but it failed to react with other gangliosides, including N-acetylneuraminosyl(alpha 2-3)lactoneotetraosylceramide (sialyl (alpha 2-3)paragloboside) and "Ii"-type gangliosides. MSG-15 was found to recognize NeuAc alpha 2-6Gal beta structure of the ganglioside. Gangliosides obtained from human hepatomas were analyzed by immunostaining on high-performance thin-layer chromatography plates using the monoclonal antibody MSG-15. All primary hepatoma samples used in this study (nine samples) were found to contain sialyl(alpha 2-6)paragloboside, which accounted for 13-31% of the monosialoganglioside fractions in the hepatomas. Furthermore, MSG-15 recognized several monosialogangliosides in addition to sialyl(alpha 2-6)paragloboside. These gangliosides apparently also contain a terminal NeuAc alpha 2-6Gal beta structure. Other ganglioside fractions obtained from hepatoma and meconium were immunostained on thin layer chromatography plates with MSG-15. Additionally, another monoclonal antibody (H-11), which recognizes terminal lactosamine structure, was used to immunostain these fractions after sialidase treatment. Bands stained with both monoclonal antibodies showed similar mobilities to each other in the di- and trisialoganglioside fractions as well as monosialoganglioside fraction. In control liver, GM3 ganglioside accounted for 92% of monosialoganglioside fraction, and sialyl(alpha 2-6)paragloboside accounted for less than 1% of the fraction. Immunohistochemical study by using MSG-15 in tissue sections from hepatocellular carcinoma and normal liver tissues demonstrated that only hepatocellular carcinoma cells gave a positive reaction. These results suggest that the biosynthetic pathway of gangliosides containing NeuAc alpha 2-6Gal beta 1-4GlcNAc beta structure is activated in hepatoma cells.

Animals↗
PubMed1990

Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from healthy habitual cigarette smokers.

The activity of platelet-activating factor acetylhydrolase, a specific metabolizing enzyme of platelet-activating factor (PAF), in plasma of 39 male subjects was determined radiochemically by the method of Stafforini et al., (1987) J Biol Chem 262: 4223-4230, to clarify to what extent PAF affects atherosclerotic disorders induced by habitual smoking. The subjects examined included 18 habitual smokers (mean age: 62 +/- 10.6 years) and 21 age-matched nonsmokers. Plasma PAF acetylhydrolase activity was higher in the smokers than in the nonsmokers. There was no difference between smokers and nonsmokers in platelet aggregability in response to PAF or ADP. A higher apoprotein B/apoprotein A-I ratio in smokers as compared to nonsmokers was the only manifestation of abnormal lipoprotein metabolism in the former group. In the smokers, plasma PAF acetylhydrolase activity was directly proportional to total cholesterol, LDL-cholesterol, triglyceride, apoprotein B, LDL-cholesterol/HDL-cholesterol or apoprotein B/apoprotein A-I, and inversely proportional to HDL-cholesterol or apoprotein A-I. The results obtained suggest that alterations in PAF acetylhydrolase levels result from a slightly abnormal lipoprotein metabolism. Determination of plasma PAF acetylhydrolase activity is useful to study the role of PAF in atherosclerotic changes induced by smoking.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

[A case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis].

We report a case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis. A 68-year-old woman succumbed to subarachnoid hemorrhage and acute myocardial infarction within a period of 3 days. Autopsy revealed white fibrotic lesions in the lateral wall of the left ventricle and interventricular septum of the heart in addition to acute myocardial infarction of the anterior wall. Histology showed fibrotic granulomatous lesions with infiltration of lymphocytes and epithelioid cells. Many multinucleated giant cells of Langhans and foreign body types were scattered among these lesions. There was no lesion in the bilateral hilar lymph nodes, but typical epithelioid granuloma was noticed in the lymph node of the carina, liver, and spleen. So we concluded that the heart lesion was a case of cardiac sarcoidosis. Striation could not be seen in the multinucleated giant cells of the cardiac sarcoid lesion, and, using light microscopy, it seemed to us that these cells had no relation to the cardiac muscles. However, by immunohistochemistry (PAP method) some giant cells tested positive for myoglobin, and others tested positive for lysozyme. The fact that giant cells are not always derived from the cardiac muscle can't be used, as a criterion for the diagnosis of cardiac sarcoidosis. Giant cells in the lung and lymph nodes tested positive only for lysozyme. Hence, using only cardiac histology, it is difficult to make a differential diagnosis between cardiac sarcoidosis and giant cell myocarditis, especially in cases where there is multiple organ involvement.

Aged↗
PubMed1989

Increased activity of the platelet-activating factor acetylhydrolase in plasma low density lipoprotein from patients with essential hypertension.

We have measured activity of platelet-activating factor (PAF) acetylhydrolase, an enzyme that specifically inactivates PAF, in plasma from patients with essential hypertension and healthy controls. The average activities in 34 patients and 22 controls were 113 +/- 60 and 79 +/- 32 nmol/ml/min, respectively, and the difference was significant (p less than 0.05). Approximately three fourths of the total plasma activity was recovered in LDL, with the remainder in HDL; and there was a significant difference in the activity associated with the LDL between patients and controls. The relative distribution of the activity among lipoproteins was almost equal in the two groups, and there was no difference in plasma lipids or apoproteins between them. In patients there was a tendency for plasma PAF acetylhydrolase activity to increase with the length of the history of hypertension. Further studies are needed to distinguish between a number of reasons for increased levels of plasma PAF acetylhydrolase in essential hypertension.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from patients with ischemic cerebrovascular disease.

Platelet-activating factor (PAF) is metabolized by a specific enzyme, PAF acetylhydrolase, which may play an important role in the manifestation of the biological activities of PAF in vivo. The activity of PAF acetylhydrolase in plasma of patients with ischemic stroke was higher than that in healthy controls. The incidence of irreversible platelet aggregation in response to PAF, as well as to ADP, was found to be higher in patients than in controls. The patients whose platelets responded with irreversible aggregation to PAF displayed a higher activity of plasma PAF acetylhydrolase than those with only reversible aggregation. In controls, PAF acetylhydrolase activity correlated positively, although weakly, with LDL-cholesterol, which may reflect the major role of LDL in carrying this enzyme. However, since there was no significant difference in plasma levels of lipids and apoproteins between patients and controls (except for apo B) and there was no significant relationship between the enzyme activity and the levels of other lipids and apoproteins, it is unlikely that increased plasma level of PAF acetylhydrolase activity in stroke patients is accounted for by an abnormality of lipoprotein metabolism. Platelet hyperfunction may be associated with augmented generation of PAF, which, in turn, may bring about the induction of the inactivating enzyme, PAF acetylhydrolase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1988

Glycolipids of metastatic tissue in liver from colon cancer: appearance of sialylated Le(x) and Le(x) lipids.

Glycolipids of metastatic tissue in liver from colon cancer were separated by HPLC and their structures were analyzed. Neutral glycolipid was composed of five major components. Four of them showed similar mobilities to GlcCer, LacCer, Gb3Cer, and nLc4Cer on TLC. The structure of the fifth major component was analyzed by exo-glycosidase treatments, 400 mHz proton NMR spectrometry, gas chromatography-mass spectrometry of the methylated sugars, and immunostaining on a TLC-plate, and concluded to be (Formula: see text). Ganglioside was composed of two major components. One of them was identical with GM3. The structure of the second ganglioside was analyzed by exo-glycosidase treatment, immunostaining on a TLC-plate, and gas chromatography-mass spectrometry of methylated sugars, and concluded to be (Formula: see text). These Le(x) and sialyl-Le(x) structure-containing lipids accounted for about 12% of the neutral glycolipid fraction and 42% of the ganglioside fraction, respectively. From these results, it appears that the biosynthetic pathway for Le(x) structure-containing lipids is activated in colon cancer.

Chromatography, High Pressure Liquid↗
PubMed1987

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones.

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.

Animals↗
PubMed1985

Surveys of workers occupationally exposed to PCBs and of yusho patients.

Surveys of workers occupationally exposed to polychlorinated biphenyls (PCBs) in the production of thread or of paint, and of yusho patients were carried out from 1973 to 1982. PCB concentrations in the plasma of the workers ranged from 2 to 521 ppb, and some showed higher PCB levels in the plasma than typical Japanese yusho patients. Gas chromatographic patterns of plasma PCBs of the workers with high PCB levels were shown to match the patterns of the PCBs to which they had been exposed in the workplace. Japanese yusho children showed remarkable decrease with time, but no such decrease was observed in the yusho adults and the workers. Polychlorinated quaterphenyls (PCQs) were detected in the blood of typical Japanese and Taiwanese yusho patients, but PCQ levels in the plasma of the workers were below the detection limit of 0.02 ppb. Clinical findings and subjective complaints of the workers were usually slight compared with typical yusho patients, though some of them had mild dermal manifestations and their PCB levels were suspected to be related to serum triglyceride values. On the basis of these results, we discussed the relationship between the health status of the subjects and their contamination with PCBs or related compounds.

Adult↗