Search for a light scalar top squark in e+e- reactions at Ec.m.=58 GeV.
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Journal Article↗
Biomedical subjects
M Higuchi
Publications and source records attributed to M Higuchi.
Expression of the alpha 2-macroglobulin-encoding gene in rat brain and cultured astrocytes.
The alpha 2-macroglobulin (alpha 2M), a protease inhibitor, is a major acute-phase protein in rats, and is produced in the liver during acute inflammation. Recently, it has been demonstrated that alpha 2M is also produced by cultured astrocytes from newborn rat brain and has neurite-promoting activity. Here, we found that the expression of the alpha 2M gene was significantly enhanced in the brain following intraperitoneal injection of the neurotoxicant, kainic acid (KA), suggesting that alpha 2M acts as an acute-phase protein in the brain, as in the case of the liver, and may be involved in neural repair processes. Expression of alpha 2M in cultured astrocytes was shown to be stimulated by interleukin-6 (IL-6) and/or leukemia inhibitory factor (LIF) in the presence of glucocorticoid. The amount of mRNAs for IL-6 and LIF increased in the brain of KA-injected rats prior to alpha 2M induction. These results strongly suggested that IL-6 and LIF are involved in alpha 2M induction in the brain, as in the case of the liver. Analysis of the cis-acting element(s) and the trans-acting factor(s) suggested that the regulatory mechanism for alpha 2M expression in astrocytes was similar to that in inflamed liver.
Animals↗
Differential roles of two types of the TNF receptor in TNF-induced cytotoxicity, DNA fragmentation, and differentiation.
Two different types of TNF receptors, the p60 receptor with a molecular mass of 60 kDa and the p80 receptor with a mass of 80 kDa, have been identified. TNF exhibits a wide variety of biologic actions, but which receptor is responsible for these biologic actions is not well characterized. In the present study, we examined the roles of the p60 and p80 receptors in three different TNF-induced biologic actions: 1) cytotoxicity; 2) DNA fragmentation; and 3) differentiation to macrophages. Analysis of TNF actions on various tumor cell lines revealed that TNF-induced cytotoxicity occurred in cells that expressed the p60 receptor, irrespective of expression of the p80 receptor. In contrast, DNA fragmentation and differentiation were observed only in cells that expressed both receptor types. Additionally, the specific Ab to each receptor were used to examine the roles of both receptors in the myelogenous leukemia cell line, ML-1a. Anti-p60 Ab alone showed cytotoxicity but little DNA fragmentation and differentiation, and anti-p80 Ab alone showed no effects. When these Abs were added in the presence of TNF, each independently, and almost completely, inhibited TNF-induced DNA fragmentation and differentiation. We also found that both Abs together synergistically induce differentiation and DNA fragmentation. These results indicate that signals through the p60 receptor are essential to induce cytotoxicity, but signals through both the p60 and p80 receptors are necessary, and act synergistically, for DNA fragmentation and differentiation.
Cell Differentiation↗
Staurosporine induces the cell surface expression of both forms of human tumor necrosis factor receptors on myeloid and epithelial cells and modulates ligand-induced cellular response.
Staurosporine, an inhibitor of protein kinase C, is commonly used to inhibit the growth factor-induced signal transduction pathway at the post-receptor level. In this report, we examined the effect of staurosporine on the constitutive expression of tumor necrosis factor (TNF) receptors in K562, a human erythroblastoid leukemic cell line. Exposure of these cells to staurosporine enhanced cell surface expression of TNF receptors by almost 7-fold in a dose- and time-dependent fashion. Maximum induction occurred at a concentration of 20 nM of the agent for 16 h at 37 degrees C. Induction of the TNF receptor was found to be temperature-dependent. No induction was observed at 22 or at 4 degrees C, suggesting the role of cell metabolism. Scatchard analysis indicated an increase in receptor number without any change in receptor affinity. TNF receptors were induced by staurosporine on a wide variety of human cells of both epithelial (primarily p60 receptors) and myeloid (mainly p80 receptor) origin. Receptor-specific antibodies showed that both TNF receptors were induced. The induction was abolished by inhibitors of protein synthesis, thus suggesting the de novo synthesis of the receptor. Furthermore, we found that staurosporine had no effect on the internalization or shedding of the receptor, but it induced the mRNA for both forms of the TNF receptor. Inhibitors of tyrosine kinases had no effect on the induction of TNF receptors. Modulation of the receptor number by staurosporine correlated with the enhancement of antiproliferative effects of TNF against different tumor cells. Thus, overall these results indicate that protein kinase C may be involved in the signal transduction of TNF not only at the postreceptor level but also at the receptor level.
Alkaloids↗
TNF induces internalization of the p60 receptor and shedding of the p80 receptor.
As is true for other peptide hormones, TNF causes the down-modulation of its own receptor. The process by which down-regulation occurs and the particular role of each of two recently identified receptors, however, are not understood. In this report we used Abs specific to p60 and p80 TNFR types to examine the ligand-induced down-regulation in histiocytic cell line U-937. These cells express both types of TNFRs, but the amount of p80 is two to three times greater than that of the p60 receptor. Treatment of U-937 cells with the ligand led to maximum down-modulation of TNFR within 30 min, and this decrease was found to be a result of receptor number and not affinity. When examined for the receptor type, approximately 90% of the p60 receptor and 35% of the p80 receptor was down-regulated by the cytokine. Rapid internalization of TNF in U-937 cells is mediated through p60, because this process was inhibited only by anti-p60 Ab and was also inhibited in cells (PMA-pretreated) that primarily express the p80 receptor. In contrast to p60, we observed that the ligand-induced shedding of the p80 receptor into the medium results in the down-regulation. Interestingly, however, the signal for shedding of the p80 receptor appears to be mediated through the p60 receptor, because anti-p60 Ab inhibited the shedding. Overall, our results provide evidence that ligand-induced down-modulation of TNFR is a result of the internalization of p60 and of the shedding of the p80 receptor and that the signaling for both is mediated through the p60 receptor.
Cell Line↗
Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes.
The gamma chain of the interleukin-2 (IL-2) receptor is shared with the functional IL-4 receptor and is causatively related to X-linked severe combined immunodeficiency (XSCID), which is ascribed to a profound T cell defect. Studies with monoclonal antibodies specific for the IL-2 receptor gamma chain showed that the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells. Participation of the gamma subunit in more than one receptor may enable the elucidation of the mechanisms of XSCID development and lymphocyte differentiation.
Animals↗
Suramin inhibits tumor cell cytotoxicity mediated through natural killer cells, lymphokine-activated killer cells, monocytes, and tumor necrosis factor.
Suramin, a polysulfonated naphthylurea, is an antitrypanosomal and antifilarial drug. Because of its anti-reverse transcriptase activity and antiproliferative activity, suramin is also used for the treatment of acquired immunodeficiency syndrome and cancer. In spite of these uses, very little is known about its effects on the immune system. In this report, we investigated the effects of suramin on peripheral blood mononuclear cells. We found that natural killer (NK) cell-mediated cytotoxicity against human erythroblastoid cell line K562 was completely inhibited by suramin in a dose-dependent manner. It also completely blocked lymphokine-activated killer (LAK) cell-mediated cytotoxicity against the human B lymphoblastoid cell lines Raji and Daudi. The cytotoxicity against the human melanoma tumor cell line A-375 mediated by unstimulated and stimulated monocytes was also suppressed by suramin. Maximum inhibition of monocyte-mediated cytotoxicity was observed when suramin was present during both the activation and the effector phases of cytotoxicity. Besides its effects on cell-mediated cytotoxicity, suramin also inhibited the cytotoxic effects of tumor necrosis factor (TNF) against different tumor cell lines. Furthermore, we found that suramin interferes with the binding of TNF with its receptor. Thus our results indicate that suramin overall downregulates the immune system by inhibiting cell-mediated and TNF-mediated cytotoxicity against different tumor cells.
Animals↗
Inhibitory effect of vapiprost on contractile responses of isolated dog renal arteries to thromboxane A2 analogue, U46619.
1. Cumulative administrations of U46619, a thromboxane A2 analogue, and prostaglandin (PG) F2 alpha produced concentration-dependent contractions of isolated dog renal arterial preparations, which were significantly and concentration-dependently inhibited by vapiprost. 2. A bolus administration of U46619 or PGF2 alpha produced sustained contracture of these preparations, which was concentration-dependently relaxed by cumulative vapiprost. 3. Results indicate that vapiprost inhibits U46619- and PGF2 alpha-induced dog renal arterial contractions through antagonism for so-called TP receptors.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene, second edition.
A large number of different mutations in the factor VIII (F8) gene have been identified as a cause of haemophilia A. This compilation lists known single base-pair substitutions, deletions and insertions in the F8 gene and reviews the status of the inversional events which account for a substantial proportion of mutations causing severe haemophilia A.
Base Sequence↗
Molecular cloning and sequence analysis of the gene encoding the H2O2-forming NADH oxidase from Streptococcus mutans.
Streptococcus mutans induces both H2O2-forming and H2O-forming NADH oxidases in the presence of O2 [M. Higuchi, J. Gen. Microbiol., 130, 1819-1826 (1984)]. In this paper, a nox-1 gene encoding H2O2-forming NADH oxidase (NOX-1) from Streptococcus mutans was cloned, and the nucleotides sequenced. The structural gene of nox-1 consisted of 1530 base pairs, which encode a polypeptide consisting of 510 amino acids with a predicted molecular mass of 55,196 Da. The deduced N-terminal amino acid sequence was consistent with that previously found for the purified NOX-1 protein. The nox-1 gene was expressed in Escherichia coli using its own promoter. Alignment of the amino acid sequence of NOX-1 with those of NADH oxidases from other microorganisms showed identities of 55.6%, 20.8%, 20.3%, and 7.3% for those of Amphibacillus xylanus Ep01, Streptococcus faecalis 10C1, Thermoanaerobium brockii Rt8.G4, and Thermus thermophilus HB8, respectively.
Amino Acid Sequence↗
Improved method for the analysis of ascorbic acid in plasma by high-performance liquid chromatography with electrochemical detection.
We improved the analytical method for the detection of ascorbic acid in plasma by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) to be more selective and rapid than the protocol previously used. Main improvements are as follows. Applied potential of ECD to obtain the maximal response for ascorbic acid was +450 mV versus Ag/AgCl, but it was reduced to +350 mV. In that condition, uric acid did not respond to ECD, and only ascorbic acid was detected. EDTA contained in sample extraction/stabilizing solution gave the peak after the ascorbic acid. The addition of EDTA (0.2 mM) to the mobile phase eliminated the EDTA peak. These two improvements gave the chromatogram in which the peak that appeared from the plasma sample was only ascorbic acid, and shorten the sample run time. Ascorbic acid in plasma was unstable even though the plasma was treated with methanol/EDTA: it decreased from 1.5 h at 4 degrees C. However, the treated sample, which was placed at -14 degrees C until the analysis was performed, gave the reliable ascorbic acid value at least up to 6 h. The data obtained from the HPLC-ECD method was consistent with those from the hydrazine method.
Ascorbic Acid↗
Effect of tumor necrosis factors, interferons, interleukins, and growth factors on the activation of NF-kappa B: evidence for lack of correlation with cell proliferation.
The nuclear transcription factor NF-kappa B has been identified as a critical component in signal transduction pathways. We used an electrophoretic gel mobility shift assay to examine the activation of NF-kappa B in human U-937 cells treated with tumor necrosis factor (TNF), lymphotoxin (LT), interferons (IFN)-alpha, IFN-beta, and IFN-gamma, interleukins (IL)-1 beta, IL-4, and IL-6, leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor-beta (TGF-beta). Only TNF, LT, and IL-1 activated NF-kappa B. Since interferons have been shown to induce TNF receptors and potentiate TNF-mediated cellular responses, we also measured the effect of interferons on TNF-induced activation of NF-kappa B. Under our conditions, all three IFNs potentiated the cytotoxic effects of TNF but had no effect on the TNF-dependent NF-kappa B activation. These results suggest overall that the activation of NF-kappa B is not a generalized mediator of signal transduction of most cytokines and also that NF-kappa B activation is not sufficient for antiproliferative effects mediated through certain cytokines.
Base Sequence↗
[Necessity of cerebral angiography in thunderclap headache patients who show no evidence of subarachnoid hemorrhage: investigation of 350 cases].
PURPOSE: The necessity of cerebral angiography was assessed in patients with thunderclap headache in whom subarachnoid hemorrhage had been ruled out on CT findings and the color of cerebrospinal fluid (CSF). SUBJECTS AND METHODS: The subjects of this study were 350 patients with thunderclap headache in whom subarachnoid hemorrhage was ruled out at our clinic based on CT findings and the color of CSF. The time span from the onset of thunderclap headache to the first visit to our clinic ranged from 1 to 9 days (mean: 2.5 days). The ages of the patients ranged from 22 to 64 years. 147 were male and 203 female. All patients underwent CT angiography. Percutaneous cerebral angiography was also performed in cases in which cerebral aneurysms were suspected on CT angiography or the CSF cell count was elevated (over 10/3mm3 on white blood cells). RESULTS: (1) Of the 350 patients, 162 were suspected to have cerebral aneurysms when examined by CT angiography. When these 162 patients were examined by percutaneous cerebral angiography, cerebral aneurysms were found in 34 patients (9.7%). (2) Four patients had an elevated CSF cell count. Cerebral aneurysms were found in all these patients. (3) Of the 34 patients with cerebral aneurysms, 31 consented to and underwent direct surgery. Localized subarachnoid hemorrhage around their aneurysms was found in seven (22.6%) of these 31 patients intraoperatively. Elevation in CSF cell count was shown in three of these patients. CONCLUSION: Even when CT and CSF studies reveal no abnormalities in the early stage after the onset of thunderclap headache, subarachnoid hemorrhage can not be ruled out. Therefore, cerebral angiography is recommended in patients with thunderclap headache.
Adult↗
[A case of pulmonary alveolar proteinosis with increased IgE and CEA].
We report here a case of pulmonary alveolar proteinosis with significantly increased IgE and CEA values, in both serum and bronchoalveolar lavage fluid. A 35-year-old man presented with exertional dyspnea, diffuse abnormal shadows on radiological examination of the chest and physiologic evidence of a restrictive lung disease. Bronchoalveolar lavage and transbronchial lung biopsy proved that the patient was suffering from pulmonary alveolar proteinosis. He had worked as a landscape gardener for the past 2 years, and had been exposed to insecticides. IgE and CEA levels were significantly elevated in both serum and bronchoalveolar lavage fluid. After whole lung lavage, general status improved remarkably and serum CEA fell to the normal range. The serum IgE level was, however, reduced by only half. Proliferating type II epithelial cells in pulmonary alveolar proteinosis have been suggested to produce CEA. However, the cause of the increased IgE level remains unknown. This case report suggests that some abnormal immunological events, leading to hyperproduction of IgE, could play a role in the onset of pulmonary alveolar proteinosis.
Adult↗
RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency.
A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B is controlled by RNA editing that operates in the nucleus, since in brain and clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in the Q/R site CAG codon and, additionally, in intronic adenosines. Transfection of GluR-B gene constructs into PC12 cells revealed that the proximal part of the intron downstream of the unedited exonic site is required for Q/R site editing. This intron portion contains an imperfect inverted repeat preceding a 10 nt sequence with exact complementarity to the exon centered on the unedited codon. Single nucleotide substitutions in this short intronic sequence or its exonic complement curtailed Q/R site editing, which was recovered by restoring complementarity in the respective partner strand. Base conversion in the channel-coding region of GluR-B directed by base paired sequences may be executed by a ubiquitous nuclear adenosine deaminase specific for double-stranded RNA.
Adenosine Deaminase↗
Ex vivo effect of insulin on normal and diabetic rat hearts hypoperfused with norepinephrine.
The effect of ex vivo insulin on contractile and energy metabolism dysfunctions was examined during hypoperfusion (0.6 ml/min per g heart weight) with 10(-6) M norepinephrine in isolated non-diabetic and streptozotocin-diabetic rats hearts. Insulin (2 mU/min per g heart weight) was infused for 15 min before as well as during 60-min hypoperfusion. Insulin significantly reduced the elevated diastolic tension in diabetic hearts (from 3.8 to 0.7 delta g), but not in non-diabetic hearts (from 1.4 to 1.2 delta g). Insulin partly improved the ATP decrease in the subendocardium of the left ventricle of the diabetic hearts (from 3.5 to 10.2 mumol/g dry weight) but did not affect non-diabetic hearts (from 6.9 to 6.8 mumol/g dry weight). Insulin also partly improved the creatine phosphate decrease and the inorganic phosphate increase in diabetic hearts only. Lactate accumulation was greater in non-diabetic than in diabetic hearts, even in the presence of insulin (77 vs. 45 mumol/g dry weight). The results indicate that acute intracoronary application of insulin in diabetic hearts improves hypoperfusion with norepinephrine injury to a level above that of non-diabetic hearts, but does not improve a less severe injury in non-diabetic hearts.
Animals↗
P80 form of the human tumor necrosis factor receptor is involved in DNA fragmentation.
Two different types of TNF receptors with molecular masses of 60 kDa (p60) and 80 kDa (p80) have been identified. TNF is known to cause DNA fragmentation in certain tumor cell lines but the role of p60 and p80 in this action is not understood. In the present study, we examined the role of these receptors in TNF-induced DNA fragmentation. Treatment of U-937 cells with phorbol ester caused downregulation of both types of TNF receptors and this was accompanied by disappearance of the TNF-induced DNA fragmentation. The removal of phorbol ester led to two time-dependent events: (1) the rapid regeneration of the p80 form but not the p60 form of the TNF receptor; and (2) the reappearance of TNF-induced DNA fragmentation. These results suggest that the p80 receptor could mediate the TNF-induced DNA fragmentation.
Cells, Cultured↗
Particle spectrum in gluon jets produced in e+e- annihilations at sqrt s around 58 GeV.
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Journal Article↗