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Biomedical subjects

A Inoue

Publications and source records attributed to A Inoue.

At least 307 records · Page 17Linked to original sources

Risk factors for hepatocellular carcinoma among patients with chronic liver disease.

BACKGROUND AND METHODS: To detect potentially curable cases of hepatocellular carcinoma, outpatients with chronic hepatitis or compensated liver cirrhosis who were seen at the Center for Adult Diseases (Osaka, Japan) were examined periodically by means of ultrasonography and measurement of serum alpha-fetoprotein. Risk factors for hepatocellular carcinoma were identified with a Cox proportional-hazards model. RESULTS: A total of 917 patients, 40 to 69 years old, were registered from May 1987 to March 1991. By the end of September 1991, liver cancer had developed in 54. The three-year cumulative risk of liver cancer was 12.5 percent for 240 patients with liver cirrhosis at enrollment and 3.8 percent for 677 patients with chronic hepatitis. Cox regression analysis showed that the risk of liver cancer was increased almost sevenfold in patients with hepatitis B surface antigen (rate ratio, 6.92; 95 percent confidence interval, 2.92 to 16.39) and fourfold in patients with hepatitis C antibody (rate ratio, 4.09; 95 percent confidence interval, 1.30 to 12.85). A high alpha-fetoprotein value at enrollment was also a risk marker for liver cancer. CONCLUSIONS: Patients with hepatitis C virus infection have a greatly increased risk of liver cancer. Further studies are required to clarify the roles of other risk factors, including drinking and smoking habits.

Adult↗

Fatty acyl-CoA binding activity of the nuclear thyroid hormone receptor.

Long-chain fatty acids and their acyl-CoA esters are potent inhibitors of nuclear thyroid hormone (T3) receptor in vitro. In the present study, we obtained evidence for acyl-CoA binding activity in the nuclear extract from rat liver. The activity sedimented at a position (3.5 S) identical with that of the T3 receptor, and the two activities sedimented together. Similarly, they coeluted on DEAE-Sephadex. After partial purification of the receptor, it was again inhibited strongly by acyl-CoAs. Heat stability and a partial trypsin digestion of the receptor both suggested that the action site of oleoyl-CoA overlapped the T3-binding domain of the receptor. In addition, thyroid hormone receptor beta 1, synthesized in vitro, bound oleoyl-CoA specifically and its T3-binding activity was inhibited. The dissociation constant for oleoyl-CoA binding to the partially purified receptor was 1.2 x 10(-7) M. This value as well as its molecular size distinguished the nuclear binding sites from the cytoplasmic fatty acid/acyl-CoA binding proteins. Oleoyl-CoA had no effect on the glucocorticoid receptor, another member of the nuclear hormone-receptor superfamily. From these results, we propose that thyroid hormone receptor is a specific acyl-CoA binding protein of the cell nucleus.

Acyl Coenzyme A↗

Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by human rheumatoid synovial fibroblasts.

The effects of linoleic acid hydroperoxide on the production of matrix metalloproteinases (MMPs) including MMP-1 (tissue collagenase), -2 ("type IV collagenase"), and -3 (stromelysin) and of tissue inhibitor of metalloproteinase 1 (TIMP-1), as well as DNA synthesis were investigated in rheumatoid synovial fibroblasts. Our results demonstrated that the levels of proMMP-1 and -3 and TIMP-1 were extremely elevated when 0.5-2.0 nmole/ml of linoleic acid hydroperoxide was added to cultures of rheumatoid synovial fibroblasts. DNA synthesis, however, was inhibited by linoleic acid hydroperoxide. These results indicate that lipid peroxide causes the disruption of extracellular matrix macromolecules and the inhibition of cell repair in synovial tissue. Therefore, they also suggest that an elevated level of oxygen free radical and/or lipid peroxides in synovial fluid may play an important role in the process of rheumatoid arthritis, resulting in the disruption of the joint.

Arthritis, Rheumatoid↗

Hookwire localizer as an aid for ultrasonic detection of small liver nodules.

We applied a V-shaped localizer and evaluated its clinical usefulness in nine patients with small hepatic nodules less than 2 cm in diameter. A small hepatic nodule was punctured with a 21-gauge localization needle under ultrasonic guidance, and the V-shaped localizer was pushed into the nodule with a wire. The localizer could be observed as a strong echo line by ultrasonography and as a high-density bar by computed tomography (CT). By this method, it was possible to precisely localize the nodule. Intraoperative ultrasonography became less time-consuming, and resection of the nodules could be confirmed with low-kilovoltage radiography.

Aged↗

Cementation in the treatment of giant cell tumor of bone.

This study was designed to review the clinical experience of cementation in the treatment of giant cell tumor of bone and to clarify its biologic basis. Eleven patients treated by this technique had results rated excellent. No recurrences of the tumor were found. Serious complications, including infection, late fracture, or secondary osteoarthrosis, did not occur. The possibility of immediate fixation and stabilization of large defects is the most valuable point of this method. Local recurrence seems to be easily detectable by magnetic resonance imaging. A cell line of mononuclear cells from giant cell tumor of bone was examined for its response to hyperthermic exposure. Hyperthermic treatment was carried out at temperature of 60 degrees for 10 min and in other conditions. The numbers of cells surviving after heat treatment were counted, and flow cytometry was used to analyze the positive rate of surface antigens of the cells and the pattern of DNA distribution at the different temperatures. The heat treatment caused a fair number of the cells to fall into S-phase, and the tetraploid value was very low. The higher the temperature and the longer the time, the fewer cells survived and the less the expression of the monocytic phenotype. No cells survived after heating at 60 degrees for 10 min. Cementation seemed to have a hyperthermic effect to the cells of giant cell tumor of bone.

Adult↗

Immunoelectron microscopic localization of the HPC-1 antigen in rat cerebellum.

HPC-1 antigen is a neuron-specific 34 kDa protein, identical to p35A (syntaxin), and is thought to play important roles in docking or fusion of synaptic vesicles to presynaptic active zones. In the present study we analyze the distribution of HPC-1 antigen in rat cerebellum by a cryoimmunogold technique using an antibody against the fusion protein of beta-galactosidase and the HPC-1 antigen. HPC-1 antigen was detected at high density on the plasma membranes and synaptic vesicles of presynaptic boutons which formed synapses with dendrites of Purkinje cells, and on the plasma membranes of parallel fibres in the cerebellar molecular layer. In the granule cell layer, gold particles were also detected on the endoplasmic reticulum, nuclear membranes and the plasma membranes of granule cells. Presynaptic membranes and synaptic vesicles in glomeruli were also labelled by gold particles. To determine the topology of HPC-1 antigen on the membranes, the synaptosome fraction prepared from rat cerebellum was embedded in agarose, and processed for the pre-embedding protein A-gold technique. Intact synaptosomes were not labelled by gold particles. However, when fixed in hypotonic fixative to rupture plasma membranes, or when ruptured after fixation in normotonic fixative, the cytoplasmic surfaces of presynaptic membranes and synaptic vesicles were labelled by gold particles. These results suggest that most of the epitopes of HPC-1 antigen are located on the cytoplasmic surface of plasma membranes and synaptic vesicle membranes.

Animals↗

Neuron specific expression of a membrane protein, HPC-1: tissue distribution, and cellular and subcellular localization of immunoreactivity and mRNA.

The monoclonal antibody HPC-1 recognizes a protein antigen in the hippocampus, and its specific reactivity to the plasma membrane of the amacrine cell somas and the inner plexiform layer in rat retina has been reported. Sequencing the cDNA indicated in our previous study that the HPC-1 antigen was a membrane protein. By means of immunoblotting, an antiserum against the fusion protein of Escherichia coli beta-galactosidase and the HPC-1 antigen detected several proteins of about 35 kDa in the nervous tissues including retina, cerebral cortex, hippocampus, cerebellum and spinal cord, but no signal was obtained in the non-neuronal tissues. Immunofluorescent histochemistry of the various rat tissues revealed that the HPC-1 antigen was confined to the nervous system, including the matrices of the cerebral cortex and hippocampus, the molecular layer, membranes of granular cell somas and glomeruli in the cerebellum and gray matter of spinal cord. However, little staining was seen in the white matter of the central nervous tissues. Thus, the HPC-1 antigen was accumulated in the synapse-rich regions of neuronal cells. In situ hybridization revealed that the HPC-1 mRNA was present in most, if not all, neurons in the central and peripheral nervous systems except for the retina. In the retina, mRNA signals were detected in amacrine and ganglion cells in which HPC-1 immunoreactivity was absent in their soma, suggesting polarized localization of the HPC-1 mRNA on the ganglion cell axon terminal.

Animals↗

Effects of detergents on binding of 5-hydroxytryptamine3 receptor antagonist [3H]GR65630 to rat cortical membranes.

In the absence of detergent, specific binding of [3H]GR65630, a 5-hydroxytryptamine3 (5-HT3) antagonist, determined in the presence of 5-HT3 receptor antagonist ICS205-930, was at most 30% of the total binding. To decrease the level of nonspecific binding, the effects of detergents on [3H]GR65630 binding to rat cortical membranes were investigated. The use of a detergent (0.1% Lubrol PX or Triton X-100) decreased nonspecific binding, increasing the proportion of specific binding to 70% of total binding. In the presence of 0.1% Triton X-100, binding of [3H]GR65630 was rapid, reversible and saturable at 25 degrees C. The rank order of 5-HT3 receptor active drugs in inhibiting [3H]GR65630 binding was quipazine > ICS205-930 > 2-methyl-5-HT = 5-HT > metoclopramide, which confirmed that [3H]GR65630 efficiently labeled 5-HT3 receptors in the presence of Triton X-100. Triton X-100 improved 5-HT3 receptor binding with rat brain membranes.

Animals↗

[A case of infective endocarditis with subaortic-valve aneurysm].

We report a 64-year-old female patient with a subaortic-valve aneurysm due to infective endocarditis, in whom the aneurysm and its perforation was detected by Doppler color flow imaging. She had severe aortic and mitral valve regurgitation, and underwent aortic valve replacement with plication of the aneurysm. Transthoracic echocardiography doesn't have enough usefulness to clarify periaortic-annular changes, but combination with Doppler color flow imaging is supposed to be informative for subaortic-valve changes same as transesophageal echocardiography especially in the cases with abnormal flow.

Aortic Aneurysm↗

Simple bone cyst. Treatment by trepanation and studies on bone resorptive factors in cyst fluid with a theory of its pathogenesis.

Simple bone cysts were treated by trepanation. The technique consists of drainage of cyst fluid, lavage of the cystic cavity with saline, and the making of multiple drilling holes through the cortical and the medullary bone of the cyst wall. Injection of corticosteroid was omitted. In 11 cases treated by this method, the clinical outcome was good. Biochemical analyses of the cyst fluid showed bone-resorptive factors, i.e., prostaglandins, interleukin 1, proteolytic enzymes. Electrophoretic analysis of proteolytic enzymes in polyacrylamide gel containing sodium dodecyl sulfate and polymerized gelatin showed proteins with molecular weights of about 130,000, 92,000, 72,000, and lower than 50,000. Increase in such bone-resorbing activities seems to be one of the causative factors in simple bone cysts. The technique was effective in decompressing the internal pressure of the cysts, improving the blood flow through the medullary bone of the cyst wall, stimulating the periosteum to induce bone formation, and eliminating bone destruction.

Adolescent↗

Neuron-specific antigen HPC-1 from bovine brain reveals strong homology to epimorphin, an essential factor involved in epithelial morphogenesis: identification of a novel protein family.

We have already cloned the cDNA for the HPC-1 antigen, a neuron-specific protein antigen from the rat brain. Here we report the molecular cloning of the bovine HPC-1 antigen homologue, and much strong sequence conservation between rat and bovine. By searching the recent protein data base, it was found that the HPC-1 antigen revealed unusual similarity to epimorphin which was mesenchymal factor related to the morphogenesis of primitive epidermal tissues in embryonic stages. We also found that the HPC-1 antigen was identical to p35A (syntaxin) which bound both to a synaptic vesicle protein and to N-type calcium channel. Although the relationship of the physiological functions, structures and topologies along cellular membrane between the HPC-1 antigen and epimorphin have not been consistent yet, these two proteins belong to a novel protein family.

Amino Acid Sequence↗

Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1.

A monoclonal antibody (mAb), HPC-1, labels the plasma membrane of the amacrine cell soma and inner plexiform layer in rat retina and other central neurons. HPC-1 antigen recognizes several proteins of about 35 kDa. In this study, an HPC-1 positive cDNA, HPC-113, was isolated from a lambda gt11 cDNA library of the rat hippocampus. HPC-113 had the 894-base pair nucleotide sequence in an open reading frame and the calculated molecular mass of the deduced amino acid sequence (298 residues) was 33,989 Da, implying that HPC-113 contains almost the full-length coding region of HPC-1 antigen is an integrated membrane protein revealing the characteristic alpha-helical structure with periodical heptad repeats usually seen in proteins with coiled-coil structures. Although the entire amino acid sequence did not show significant homology to any proteins so far known, a few local sequences in the possible extracellular domain of the HPC-1 antigen molecule had notable homology to some partial sequences in the laminin B1 chain. These sequences of laminin are included in the portion which has neurite outgrowth and/or survival promoting activity. The HPC-1 gene was transcribed in nerve tissues much more predominantly than in non-neuronal tissues. Thus, HPC-1 antigen(s) was confined to be a newly identified neuronal cell membrane protein(s) localized in a subpopulation of neurons.

Amino Acid Sequence↗

A novel regulatory effect of myosin light chain kinase from smooth muscle on the ATP-dependent interaction between actin and myosin.

The actin-binding activity of myosin light chain kinase (MLCK) from smooth muscle was studied with special reference to the ATP-dependent interaction between actin and myosin. MLCK in the presence of calmodulin endowed sensitivity to Ca2+ on the movement of actin filaments on phosphorylated myosin from smooth muscle that was fixed on a coverslip. This regulatory effect was not attributable to the kinase activity of MLCK but could be explained by its actin-binding activity. The importance of the actin-binding activity was further substantiated by results of an experiment with Nitellopsis actin-cables in which MLCK regulated the interaction under conditions where MLCK was exclusively associated with the actin-cables.

Actins↗

Differential tissue expression of multiple genes for chicken smooth muscle/nonmuscle myosin regulatory light chains.

The cDNA clones for two distinct mRNAs encoding one of the two known isoforms of chicken smooth muscle/nonmuscle myosin regulatory light chain were isolated. The nucleotide sequences of these cDNAs were very similar to each other (99% nucleotide identities) in the 516 bp translated regions and in the first 33 bp of the 3' noncoding regions, whereas the rest of the 3' noncoding regions and the 5' noncoding regions had no significant similarity. Genomic Southern blot analysis showed that these two mRNAs were encoded in two individual genes. Whereas these two genes encoded almost identical polypeptides with only one conservative substitution of amino acid residues, expression of the mRNAs was differentially regulated both at the transcriptional and translational levels in various tissues of the chicken.

Animals↗

Loss of thyroid hormone receptor activity in primary cultured rat hepatocytes is reversed by 2-mercaptoethanol.

In primary cultures of rat hepatocytes, specific thyroid-hormone-binding activity diminished with time and was hardly detectable at 24 h. In accordance with the loss of 3,5,3'-tri-iodothyronine (T3) binding, responses to the hormone disappeared, as indicated by low induction of the thyroid-hormone-responsive gene S14. In contrast, thyroid hormone receptor proteins were present, as determined by immunostaining with a specific antibody against the receptor. Thus the loss of T3 binding was due to receptor inactivation. After various attempts to restore the T3-binding activity, we found that 2-mercaptoethanol, a reducing agent, when added to the culture medium restored the hormone binding activity in a dose- and time-dependent manner. The observed kinetics and experiments using cycloheximide suggested that mercaptoethanol prevented inactivation of the newly synthesized receptors. Oxidoreductive conditions within cells may have a role in determining the level of activity of thyroid hormone receptors.

Animals↗