[Regulation of cation pump activity in nervous system].
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Animals↗
Biomedical subjects
N Inoue
Publications and source records attributed to N Inoue.
[Usefulness of particle size distribution analyzer for counting the number of sperm].
We tried to use particle size distribution analyzer to count the number of sperm. The epididymis was removed from male Syrian golden hamsters intratracheally instilled with indium arsenide, indium phosphide or phosphate buffer only, and the homogenate of the cauda epididymidis was used as the sperm sample. The number of sperm counted with particle size distribution analyzer correlated well with the number of sperm counted with hemocytometer (r = 0.96) and the coefficient of the regression line was almost 1. When the same sperm sample was counted repetitively (n = 4), there was no difference in the coefficient of variation between the sperm number counted with particle size distribution analyzer and the sperm number counted with hemocytometer (6.4 +/- 5.8% vs. 7.8 +/- 4.0%). From these results, particle size distribution analyzer was thought to be useful for counting the number of sperm.
Animals↗
The risk factors of death from the acetaminophen poisoning with antipyretic-analgesic drugs in Japan.
Since adverse effects rarely occur with the therapeutic doses of acetaminophen, it is commonly used as a mild antipyletic and analgesic. However, overdosage of acetaminophen causes fatal hepatic failure and acute renal failure. Therefore, we evaluated the risk factors for death among the reported cases of acetaminophen poisoning in Japan, which were obtained from Japan Science and Technology Corporation, Information Center for Science and Technology (JICST) on-line service in the Kyushu University Library. In a univariate analysis, the death rate of patients with hepatic failure (23.3% vs 0%, p = 0.04), disseminated intravascular coagulation syndrome (DIC) (38.1% vs 5.3%, p = 0.001) or plasma exchange treatment (33.3% vs 7.9%, p = 0.01) was significantly greater than those without it while a multivariate analysis revealed that DIC (with vs without; odds ratio = 23.04, 95% confidence interval = 2.80-189.75) and the treatment with plasma exchange (with vs without; odds ratio = 14.77, 95% confidence interval = 1.44-151.52) were independent risk factors. These results suggest that DIC and hepatic failure, especially requiring plasma exchange, were poor prognostic factors. In addition, about seventeen percent of the cases with less than 5 g of acetaminophen ingestion were death cases although the acute lethal adult dose is shown 13-25 g in western countries. This suggests that its acute lethal dose may be low in Japan, which may be partly due to the additional adverse effect of other drugs used in the mixed compounds while acetaminophen alone is used in western countries. An intensive treatment should be recommended for the acetaminophen poisoning patients regardless of the ingested dose.
Acetaminophen↗
Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.
The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.
Animals↗
Diltiazem inhibits naloxone-precipitated and spontaneous morphine withdrawal in rats.
The effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipitated and spontaneous morphine withdrawal were studied in male Sprague-Dawley rats. In naloxone-precipitated withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by diltiazem injected 4 or 2 and 4 h before naloxone, respectively. Three administrations of diltiazem (17, 11 and 5 h before naloxone) did not reduce the above withdrawal signs. Diarrhea was dose dependently inhibited by all schedule of diltiazem treatments. In spontaneous withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by two (6 and 12 h) or three (6, 12 and 18 h after the last morphine) treatments with diltiazem at 6-h intervals after the last morphine, but not by a single diltiazem injected 18 h after the last morphine.
Animals↗
PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.
Many eukaryotic cell surface proteins are bound to the membrane via a glycosylphosphatidylinositol (GPI) anchor. Assembly of the GPI anchor precursor is a sequential addition of components to phosphatidylinositol (PI) in the endoplasmic reticulum (ER). The first step is the transfer of N-acetylglucosamine (GlcNAc) to PI from UDP-GlcNAc to generate GlcNAc-PI. This simple step, however, is regulated by at least three genes because in both mammals and yeasts, there are three mutants of different complementation classes. To clarify this complexity, we analyzed the products of two cloned human genes, PIG-A and PIG-H. Here we demonstrate 1) that PIG-A is an ER transmembrane protein with a large cytoplasmic domain that has homology to a bacterial GlcNAc transferase and a small lumenal domain; 2) that PIG-H is a cytoplasmically oriented, ER-associated protein; and 3) that they form a protein complex. We also show that part of the small lumenal domain of PIG-A plays an essential functional role in targeting itself to the rough ER. Taken together with the cytoplasmic orientation of GlcNAc-PI, these results indicated that PIG-A and PIG-H are subunits of the GPI GlcNAc transferase that transfers GlcNAc to PI on the cytoplasmic side of the ER.
Animals↗
Rat C6 glioma cell growth is related to glucose transport and metabolism.
In order to establish whether growth of glioma cells is associated with glucose transport and metabolism, we investigated expression of the glucose transporter and hexokinase, as well as glucose transport and glucose phosphorylation in rat C6 glioma cells growing at different rates. Rat C6 glioma cells were subcloned to produce four different cell lines (CL1, CL2, CL3 and CL4) differing in growth, differentiation and morphology: CL1 cells were slow-growing with an astrocytic appearance whereas CL4 cells grew rapidly and were small and spindle-shaped. Immunocytochemical analysis using glial fibrillary acidic protein and galactocerebroside antibodies revealed that CL1 and CL4 cells differentiate to astrocytes and oligodendrocytes respectively. Both of these cell lines expressed GLUT1 mRNA predominantly, whereas little GLUT3 mRNA was evident by Northern-blot analysis. The GLUT1 mRNA level was much higher in CL4 than in CL1 cells, and the uptake of 2-deoxy-D-glucose and 3-O-methyl-D-glucose by CL4 cells was markedly higher than that by CL1 cells, indicating a correlation between the growth rate, glucose transporter (GLUT1) level and glucose-transport rate of C6 glioma cells. We then studied glucose metabolism by CL1 and CL4 cells by measuring their hexokinase activities and intracellular concentrations of glucose and ATP. The mitochondrial hexokinase activity of CL4 cells was about three times higher than that of CL1 cells, whereas the cytosolic hexokinase activity of CL4 cells was only about half that of CL1 cells. As the total amount of cellular hexokinase protein in CL4 cells was only slightly higher (about 20%) than that in CL1 cells, the hexokinase protein of CL4 cells was considered to have moved from the cytosol to the mitochondrial membranes. Consistent with the increased mitochondrial hexokinase activity of CL4 cells, the intracellular glucose concentration was undetectable, and the ATP concentration was higher than that of CL1 cells, suggesting that glucose transport is the rate-limiting factor for overall glucose metabolism is rapidly growing C6 cells. Therefore the present data demonstrate that glioma cell growth is related to glucose transport, which is closely associated with glucose metabolism.
Animals↗
PIG-C, one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2.
Glycosylphosphatidylinositol (GPI) protein anchors are ubiquitous in eukaryotic cells. GPI anchors are synthesized in the endoplasmic reticulum by actions of ten or more gene products. The first step of the biosynthesis, the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, is mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) and in yeast (GPI1, GPI2 and GPI3/SPT14/CWH6). PIG-A is homologous to GPI3/SPTI4/CWH6. However, PIG-H has no homology with GPI1 or GPI2. Here we cloned a human homologue of GPI2 and showed that it is PIG-C. PIG-C protein is a 297 amino-acid membrane protein in the endoplasmic reticulum that has 20% amino acid identity with GPI2. Since there are several human EST sequences that have homology to GPI1, our results suggest that four genes are involved in the first step of GPI anchor synthesis in mammalian cells.
Amino Acid Sequence↗
PIG-B, a membrane protein of the endoplasmic reticulum with a large lumenal domain, is involved in transferring the third mannose of the GPI anchor.
Many eukaryotic cell surface proteins are bound to the membrane via the glycosylphosphatidylinositol (GPI) anchor that is covalently linked to their carboxy-terminus. The GPI anchor precursor is synthesized in the endoplasmic reticulum (ER) and post-translationally linked to protein. We cloned a human gene termed PIG-B (phosphatidylinositol glycan of complementation class B) that is involved in transferring the third mannose. PIG-B encodes a 554 amino acid, ER transmembrane protein with an amino-terminal portion of approximately 60 amino acids on the cytoplasmic side and a large carboxy-terminal portion of 470 amino acids within the ER lumen. A mutant PIG-B lacking the cytoplasmic portion remains active, indicating that the functional site of PIG-B resides on the lumenal side of the ER membrane. The PIG-B gene was localized to chromosome 15 at q21-q22. This autosomal location would explain why PIG-B is not involved in the defective GPI anchor synthesis in paroxysmal nocturnal hemoglobinuria, which is always caused by a somatic mutation of the X-linked PIG-A gene.
Amino Acid Sequence↗
Possible Clustering of the Most Energetic Cosmic Rays within a Limited Space Angle Observed by the Akeno Giant Air Shower Array.
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Journal Article↗
A cardiotonic steroid bufalin-induced differentiation of THP-1 cells. Involvement of Na+, K(+)-ATPase inhibition in the early changes in proto-oncogene expression.
Human monocytic leukemia THP-1 cells were induced to differentiate into macrophage-like cells by treatment with cardiotonic steroid bufalin, which was previously shown to interact with the Na+, K+-ATPase with similar kinetics to ouabain, a specific inhibitor of the enzyme. This induction of differentiation was characterized by loss of proliferation, cell adherence, increased ability to reduce Nitro Blue tetrazolium (NBT), and increased expression of interleukin 1 beta (IL-1 beta). During this process, bufalin downregulated c-myb and c-myc expressions and induced c-fos and Egr-1 transcripts. Ouabain also caused similar changes in proto- oncogene expression and induced phenotypic markers of differentiated cells at concentrations comparable to bufalin. The 12-O-tetradecanoyl phorbol-13-acetate resistant THP-1 cell variant, which was unresponsive to this agent as to growth inhibition and proto-oncogene expression, responded to bufalin. The finding that protein kinase inhibitor H7 failed to bufalin-mediated c-fos induction further supports the theory that the signal transduction machinery caused by bufalin is separable from the phorbol ester. The cytotoxic effect of high doses of bufalin apparently disappeared in the medium where Na+ was replaced with choline ions. Furthermore, bufalin failed to induce c-fos expression and to downregulate c-myb transcripts in the low-Na+ medium. These findings indicate that an increased intracellular Na+ concentration resulting from the Na+, K(+)-ATPase inhibition possibly triggers the change in proto-oncogene expression evoked by bufalin.
Bufanolides↗
Masseter muscle activity in bottle feeding with the chewing type bottle teat: evidence from electromyographs.
It was reported that the activity of the masticatory muscles is reduced in bottle fed babies. The effects of chewing type bottle teats distributed in Japan on masticatory muscle activity were evaluated. Myoelectric activities of the masseter muscles of 12 babies bottle fed with chewing type bottle teats were recorded and analyzed by the same method as in the previous study. The electromyographic records of 12 breast fed babies and 12 babies bottle fed with regular sucking type bottle teats, which were reported in a previous study, were used as controls. The results show that the masseter muscle activity of babies bottle fed with chewing type bottle teats was similar to that of breast fed babies qualitatively as well as quantitatively. However, activity was visibly different from that of babies bottle fed with sucking type bottle teats, showing significant difference by ANOVA. These data suggest that babies who are ingesting milk from chewing type bottle teats do so with a chewing action similar to that of breast feeding, but very different from that of bottle feeding with sucking type bottle teats. The conclusion was that the chewing type bottle teat is useful for establishing masseter muscle activity.
Bottle Feeding↗
Cloning and characterization of the murine GPI anchor synthesis gene Pigf, a homologue of the human PIGF gene.
Many eukaryotic proteins are bound to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. Its core backbone, which is conserved in different organisms, is synthesized in the endoplasmic reticulum by the sequential addition of glycan components to phosphatidylinositol. One of the human GPI synthesis genes, PIGF (phosphatidylinositol glycan complementation class F), which is involved late in the synthesis pathway, has been cloned. In this study, we isolated complementary and genomic clones of Pigf, a murine counterpart of PIGF. Pigf encodes a 219 amino acid protein that complements a class F mutation. The Pigf gene consists of six exons spanning 30 kb and was mapped to chromosome 17 at 17E4-E5. These features are very similar to PIGF, thus demonstrating the interspecies conservation of structure, function, gene organization, and genetic locus between these GPI synthesis genes. The results also extend a region in murine distal chromosome 17 that is syntenic to human chromosome 2p16-p22.
Amino Acid Sequence↗
Simultaneous observation of families and accompanied air showers at Mt. Chacaltaya.
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Journal Article↗
Mechanisms by which the surface expression of the glycosyl-phosphatidylinositol-anchored complement regulatory proteins decay-accelerating factor (CD55) and CD59 is lost in human leukaemia cell lines.
We have investigated the mechanisms of defects in the glycosyl-phosphatidylinositol (GPI)-anchored complement regulatory proteins delay-accelerating factor (DAF) and/or CD59 in a panel of human leukaemia cell lines that lack surface expression of these proteins: U937 (DAF+/CD59-), CEM (DAF-/CD59+), TALL (DAF-/CD59-) and a substrain of Ramos [Ramos(-)] (DAF-/CD59-). Northern blotting and reverse transcription-PCR revealed that the main cause of the DAF and/or CD59 deficiency is the failure of mRNA expression in most of the cell lines, except in Ramos(-) in which sufficient mRNA for DAF and CD59 was produced. U937, CEM and TALL cells were not defective in GPI anchor formation as assessed by the detection of other GPI-anchored proteins. No gene abnormality corresponding to DAF or CD59 was detected by Southern blotting. Thus the cause of the defects of DAF and/or CD59 in these leukaemia cell lines except for Ramos(-) is virtually undetectable steady-state levels of the relevant mRNA, most likely attributable to lack of transcription in these cell lines. On the other hand, Ramos(-) cells failed to generate a GPI anchor, whereas they normally expressed DAF and CD59 transcripts. The transfection of phosphatidylinositol-glycan class A (PIG-A) cDNA into Ramos(-) cells restored DAF and CD59 expression, indicating that the defective mechanism in GPI anchor formation is similar to that in paroxysmal noctural haemoglobinuria (PNH) cells, i.e. a deficiency of the PIG-A gene product. Thus the mechanisms of the defects of DAF and/or CD59 in human leukaemia cell lines are not uniform, and in most cases are different from that proposed to cause PNH.
Antigens, CD↗
Analysis of PIG-A gene in a patient who developed reciprocal translocation of chromosome 12 and paroxysmal nocturnal hemoglobinuria during follow-up of aplastic anemia.
The relationships between paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia (AA), and myelodysplastic syndrome (MDS) are not clear. Here we describe a patient, J20, who developed a reciprocal translocation of chromosome 12 and PNH during follow-up of AA. All metaphases in CD59-deficient bone marrow mononuclear cells had the translocation, whereas none of the CD59-deficient cells had it, indicating that the PNH clone coincided with a cell population bearing the chromosomal aberration. We found a somatic single-base deletion mutation in the PIG-A gene of this patient's peripheral blood cells. This is the first patient with PNH with a PNH clone containing a chromosomal translocation.
Adult↗
Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation.
The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs.
Animals↗
Alterations of local cerebral blood flow, phorbol 12,13-dibutyrate binding activity, and histological damage during acute focal ischaemia in rat brain. A pathophysiology of acute focal ischaemia: Part 1.
The alterations of the local cerebral blood flow (LCBF), 3H-phorbol 12,13-dibutyrate (PDBu) binding activity were measured, and histological findings were also examined during the closed time course (0, 1, 3, 5, 7 hour) after middle cerebral artery occlusion (MCAO) in rat brain to assess the complex pathophysiology of acute focal ischaemia. From 1 to 3 hours after the start of MCAO, significant (p < 0.01) hyperreactivity of the second messenger system involving PDBu binding may be present, despite low perfusion of LCBF, and severe damage in the striatum whereas sparing almost completely the cortex on histological examination. At 5 hours, the PDBu binding activity increased slightly but not significantly but is reduced markedly at 7 hours after MCAO compared with the control group. The measurement of PDBu binding activity, additionally to measuring the LCBF and observation of the histological change might be a useful indicator in determining the threshold and duration of ischaemia which cause functionally irreversible cell damage in the brain.
Animals↗