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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 973 records · Page 54Linked to original sources
PubMed1989

[A case of asbestosis complicated with double cancer of the stomach and colon].

A case of a double cancer, a stomach and a colon cancer, in a 84-year-old man is reported. The patient had an occupational history of asbestos exposure while working at two shipyards. His chest X-ray revealed typical, pleural plaque with calcification. Further, a significant number of asbestos bodies in his autopsied lung tissue was detected. In spite of failure to detect asbestos bodies in the stomach and the colon, our findings suggest that these two cancers may have been induced by asbestos exposure.

Adenocarcinoma↗
PubMed1988

Acute myelocytic leukemia after exposure to asbestos.

While the carcinogenicity of asbestos has been established in malignant mesotheliomas and lung cancers, and has recently been suspected in several other types of cancer, asbestos has not been implicated in the pathogenesis of acute leukemias. This article includes two cases of acute myelocytic leukemia in individuals with a long history of exposure to asbestos. Significant numbers of asbestos bodies were detected in specimens of their lungs and bone marrow. In addition, the kind of asbestos in both organs was crocidolite, which is implicated in carcinogenesis. No asbestos bodies were detected in the bone marrow specimens from a control group consisting of ten patients with lung cancer with similar occupational histories. The role of asbestos exposure in the development of leukemia requires further study.

Aged↗
PubMed1988

Functional significance of the central helix in calmodulin.

The 3-A crystal structure of calmodulin indicates that it has a polarized tertiary arrangement in which calcium binding domains I and II are separated from domains III and IV by a long central helix consisting of residues 65-92. To investigate the functional significance of the central helix, mutated calmodulins were engineered with alterations in this region. Using oligonucleotide-primed site-directed mutagenesis, Thr-79 was converted to Pro-79 to generate CaMPM. CaMPM was further mutated by insertion of Pro-Ser-Thr-Asp between Asp-78 and Pro-79 to yield CaMIM. Calmodulin, CaMPM, and CaMIM were indistinguishable in their ability to activate calcineurin and Ca2+-ATPase. All mutated calmodulins would also maximally activate cGMP-phosphodiesterase and myosin light chain kinase, however, the concentrations of CaMPM and CaMIM necessary for half-maximal activation (Kact) were 2- and 9-fold greater, respectively, than CaM23. Conversion of the 2 Pro residues in CaMIM to amino acids that predict retention of helical secondary structure did not restore normal calmodulin activity. To investigate the nature of the interaction between mutated calmodulins and target enzymes, synthetic peptides modeled after the calmodulin binding region of smooth and skeletal muscle myosin light chain kinase were prepared and used as inhibitors of calmodulin-dependent cGMP-phosphodiesterase. The data suggest that the different kinetics of activation of myosin light chain kinase by CaM23 and CaMIM are not due to differences in the ability of the activators to bind to the calmodulin binding site of this enzyme. These observations are consistent with a model in which the length but not composition of the central helix is more important for the activation of certain enzymes. The data also support the hypothesis that calmodulin contains multiple sites for protein-protein interaction that are differentially recognized by its multiple target proteins.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1988

Calcium/calmodulin-dependent protein kinase II. Characterization of distinct calmodulin binding and inhibitory domains.

Regulatory domains of the multifunctional Ca2+/calmodulin-dependent protein kinase II were investigated utilizing synthetic peptides. These peptides were derived from the sequence between positions 281 and 319 as translated from the cDNA sequence of the rat brain 50-kDa subunit (Lin, C. R., Kapiloff, M. S., Durgerian, S., Tatemoto, K., Russo, A. F., Hanson, P., Schulman, H., and Rosenfeld, M. G. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 5962-5966), which contain the putative calmodulin-binding region as well as potential autophosphorylation sites. Peptide 290 to 309 was found to be a potent calmodulin antagonist with an IC50 of 52 nM for inhibition of Ca2+/calmodulin-dependent protein kinase II. Neither truncation from the amino terminus (peptide 296-309) nor extension in the carboxyl-terminal direction (peptide 294-319) markedly affected calmodulin binding, whereas shortening the peptide from the carboxyl terminus (peptide 290-302) or from both ends (peptide 295-304) resulted in the elimination of this activity. Peptide 281-290 did not bind calmodulin, but was a good substrate for the enzyme, being phosphorylated at Thr-286. Several of the peptides inhibited the kinase in a partially competitive, substrate-directed manner, but were not themselves phosphorylated. These studies identify domains within Ca2+/calmodulin-dependent protein kinase II which may be involved in 1) inhibition of the kinase in the absence of calmodulin, 2) binding of calmodulin, and 3) the resulting activation. Additionally, it is suggested that phosphorylation of residues flanking these domains may be responsible for the known regulatory effects of autophosphorylation on the properties of the kinase.

Amino Acid Sequence↗
PubMed1988

A phospholipase A2 in the supernatant fraction of rat spleen. Its similarity to rat pancreatic phospholipase A2.

Rat spleen supernatant contained two forms of calcium-dependent cellular phospholipase A2 which could be separated from each other by TEAE-cellulose chromatography. The phospholipase A2, named PLA2 S-1, present in the major flow-through fraction was purified to homogeneity. The structural and catalytic properties of splenic PLA2 S-1 were systematically compared with those of rat pancreatic phospholipase A2. Structural evidence, including the sequence of the N-terminal 32 residues, peptide maps obtained on Achromobacter protease I digestion and cyanogen bromide cleavage, and the amino acid composition, showed the close similarity of the two enzymes. Their catalytic and immunochemical properties were also similar. These results demonstrated the existence of a pancreatic type phospholipase A2 in a non-pancreatic organ as a member of the cellular phospholipases A2 and suggest the potential functional involvement of pancreatic type phospholipase A2 in cellular phospholipid metabolism.

Amino Acid Sequence↗
PubMed1988

Purification and characterization of a membrane-associated phospholipase A2 from rat spleen. Its comparison with a cytosolic phospholipase A2 S-1.

A membrane-associated phospholipase A2 was purified from rat spleen. The phospholipase A2 was solubilized from the 108,000 x g pellet fraction with 0.3% lithium dodecyl sulfate and then purified to homogeneity by successive DEAE-Cellulofine AM, octyl-Sepharose, Cellulofine GCL 300-m, S-Sepharose, and Bio-Gel P-30 chromatographies in the presence of 0.5% 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate. The apparent Mr of the enzyme, estimated on sodium dodecyl sulfate polyacrylamide gel electrophoresis, was about 13,600. The purified enzyme had a pH optimum in the range of pH 8.0-9.5 and required the presence of Ca2+ (4 mM) for its maximal activity. The enzyme preferentially hydrolyzed the 2-acyl ester bonds of phosphatidylglycerol in the presence and absence of sodium cholate or sodium deoxycholate. Unlike the phospholipase A2 of rat spleen supernatant, no immunocross-reactivity was observed between the purified enzyme and anti-rat pancreatic phospholipase A2 antibody. The N-terminal amino acid sequence of the enzyme was determined and found to be homologous to that of viperid and crotalid venom phospholipases A2. The results in this and the preceding report (Tojo, H., Ono, T., Kuramitsu, S., Kagamiyama, H., and Okamoto, M. (1988) J. Biol. Chem. 263, 5724-5731) demonstrate that rat spleen contains two genetically distinct phospholipase A2 isoenzymes.

Amino Acid Sequence↗
PubMed1988

Adrenal medullary cells transmute into dopaminergic neurons in dopamine-depleted rat caudate and ameliorate motor disturbances.

Adrenal medullary cell suspensions, derived from newborn rats (postnatal day 1-6), were implanted into the head of the caudate nucleus in 35 rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopamine (DA) pathway. Behavioral recovery from Met-amphetamine induced circling, cell growth and morphological features (tyrosine hydroxylase positive cells), and release of adrenaline (Ad), noradrenaline (NA), DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated for 40 weeks after transplantation. Met-amphetamine induced circling decreased significantly in 43% (15/35) of the rats. The decrease was concurrent with transmutation of the tyrosine hydroxylase-like immunopositive (THLI) cells into mature neurons that had abundant elongated neurites with varicosities and synapses on neuronal elements in the host caudate. In the absence of behavioral recovery (57%, 20/35) THLI cells were very scant. DA, DOPAC and HVA were reduced more than 90% in perfusates collected by in vivo dialysis from the striata of the animals that were not improved by transplant. These levels recovered to 20-50% of controls in animals whose behavior recovered. Ad and NA were not detected in the perfusates of either recovered or non-recovered animals. The results suggest that some grafted adrenal medullary cells transform into dopaminergic neurons and the release of DA from these grafted cells functionally affects behavior improvement for at least 40 weeks.

Adrenal Medulla↗
PubMed1988

A pancreatic-type phospholipase A2 in rat gastric mucosa.

A phospholipase A2, which is immuno-crossreactive with the anti-rat pancreatic phospholipase A2 antibody, is present in rat gastric mucosa. The content of the enzyme in the gastric mucosa was comparable to that in the pancreas, but the specific activity in the gastric mucosa homogenate (60.7 +/- 19.5 nmol/min/mg) was higher than that in the pancreas homogenate (3.16 +/- 0.77 nmol/min/mg). A greater proportion of the enzyme was found in the particulate fraction. The gastric enzyme and its proenzyme were purified from the supernatant. The amino acid sequence of the N-terminal 15 residues of the gastric enzyme was determined and found to be identical with that of rat pancreatic phospholipase A2. Like the pancreatic proenzyme, the gastric proenzyme was activated on trypsin treatment.

Animals↗
PubMed1988

Habenular lesion attenuates methamphetamine-induced inhibition of dopamine neuronal activity in the substantia nigra pars compacta of rats.

The relation between the habenula and central dopaminergic system was investigated by examining the inhibitory effects of methamphetamine on the firing rate of dopamine neurons in the substantia nigra of habenular lesioned and unlesioned rats. Electrolytic lesions of the habenula attenuated the methamphetamine-induced inhibition of dopamine neurons in the substantia nigra. This, along with other findings, indicates possibly that the habenula is involved in a feedback pathway from the striatum to the substantia nigra and regulates the activity of dopamine neurons in the substantia nigra.

Action Potentials↗
PubMed1988

Immunocytochemical localization of hepatic fatty acid binding protein in the liver of fed and fasted rats.

The immunocytochemical localization of fatty acid binding protein (FABP) of liver type was studied at light and electron microscopic levels by the peroxidase-antiperoxidase (PAP) method using a specific polyclonal antibody against FABP in the liver of fed and fasted rats. In the liver of rats fed ad libitum, the intense immunoreactivity was confined to portions of the liver cell cytoplasm adjacent to the glycogen area. After 2-days' fasting, such a focal intracellular localization of the immunoreactivity was abolished, in association with the disappearance of the glycogen area, and was replaced by a diffuse distribution of the immunoreactivity throughout the cytoplasm, with higher intensity at the periphery of the cells. In liver cells exhibiting an overall hypertrophy of smooth endoplasmic reticulum (SER) induced by the treatment of fasted rats with phenobarbital, the peripheral localization of FABP immunoreactivity remained unchanged compared with that obtained in the case of fasting alone, and the immunoreactivity did not occur in association with the proliferated SER in the central cytoplasm. These results suggest that FABP, although cytosolic in nature, changes its localization within the liver cells in response to the general metabolic alterations caused by the starvation, inferring that FABP is intimately involved in the intracellular transport and metabolism of free fatty acids.

Animals↗
PubMed1988

Analysis of strongly acidic amino acids by the conventional amino acid analyzer: application to determination of protein-bound cysteine and glutathione.

A rapid analysis method of strongly acidic amino acids and related compounds by a simple modification of an existing amino acid analyzer is presented. In this method, an anion-exchanger column (2.6 X 150 mm) packed with Hitachi 3013-N resin was developed with 0.2 M citric acid. Complete separation of phosphothreonine, phosphoserine, phosphotyrosine, cysteic acid, homocysteic acid, and glutathionesulfonic acid was achieved within 35 min, with no regeneration of the column being required. Tyrosine-O-sulfate was analyzed by the same column using 2 M sodium acetate buffer, pH 5.5. Performic acid oxidation of a variety of proteins and direct analysis of the products by this system successfully detected cysteine, homocysteine, and/or glutathione bound to proteins through disulfide bonds. This suggest the potential use of the method for analysis of the states of protein thiol groups, especially those of clinically significant mutant proteins where mutation of arginine to cysteine is rather frequently recognized.

Animals↗
PubMed1988

A clinical study on frontal lobe epilepsy.

Of 30 patients whose epileptogenic focus was presumed to be located in the frontal lobe on the basis of a clinico-electrographic correlation, the principal seizure manifestation consisted of peculiar automatisms in about 40% of the cases. However, the nature of the automatisms was of a short duration lasting about one minute but in most cases it was accompanied by extremely violent movements, but this was not true in all cases. Of the 30 cases, only 5 cases showed marked improvement one year after being discharged from the hospital so that this type of seizure event is extremely intractable.

Adolescent↗
PubMed1988

Ontogeny of hepatic fatty acid-binding protein immunoreactivity in human liver and intestinal tract.

Liver and intestinal tissues of human fetuses at gestational ages between 6 and 30 weeks were immunostained with rabbit antibody against fatty acid-binding protein (FABP) isolated from rat liver, since the antibody crossreacted with human FABP of the hepatic type. FABP-immunoreactive hepatocytes were found in the liver as early as the 7th week of gestation, but not at the 6th week. The frequency of immunoreactive cells was about 80% throughout the gestational period examined. No immunoreactive cells other than hepatocytes were found in liver tissue. In the intestinal tract, ileal, colonic and vermiform appendicular FABP immunoreactivity was demonstrated at the 23rd week of gestation, and duodenal and jejunal immunoreactivity at the 26th week. Positive cells in the jejunum were very few at this stage, but numerous at the 30th week of gestation. The immunoreactive cells were primitive absorptive cells in intestinal villi, and no cryptic epithelial cells were positively immunostained. Thus, FABP immunoreactivity was considered to be a marker for hepatocytes at the early to late fetal stage, and for intestinal absorptive cells at mid- to late fetal stage.

Animals↗