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Biomedical subjects

M Kurimoto

Publications and source records attributed to M Kurimoto.

At least 199 records · Page 11Linked to original sources

[Skull base aspergillosis granuloma originating from the sphenoid sinus: a case report].

A case of skull base Aspergillus granuloma originating from the sphenoid sinus was reported. This 64-year-old man complained of unilateral visual loss and serious facial pain, and was admitted to our department. He had been treated by transnasal sphenoidectomy because of sphenoid sinus aspergillosis. MRI showed a mass lesion located in the sphenoid sinus, cavernous sinus, ethmoid sinus and intraorbit. Angiography showed severe stenosis of the left internal carotid artery at the cavernous portion. As the symptoms gradually aggravated, we felt compelled to perform intracranial surgical treatment using the extradural approach to the skull base lesions. As the fibrous lesion was very hard and strongly adherent to the surrounding tissues, only partial removal of the lesion and resection of the trigeninal nerve were carried out. After surgery, the patient was released from severe facial pain and had an uneventful course. But, two months later, he died due to Aspergillus meningoencephalitis. Aspergillosis originating from the sphenoid sinus is rare, but it is known that some lesions show abrupt invasive extension to the skull base and the prognosis is bad. Early diagnosis and suitable treatment for the skull base or intracranial lesions is required.

Aspergillosis↗

In vitro hypoxia of cortical and hippocampal CA1 neurons: glutamate, nitric oxide, and platelet activating factor participate in the mechanism of selective neural death in CA1 neurons.

We prepared neuron-rich cultures from cortical and hippocampal CA1 regions of postnatal day 1 (P1) rats. Using these cultures, we investigated the sensitivity of neurons to hypoxic insults. The effects of MK-801, cycloheximide, NG-nitro-L-arginine (L-NNA), and anti-platelet-activating factor (anti-PAF) IgG on neuronal injury under hypoxic conditions also were examined. The percentage of astroglial cells was higher in CA1 than cortical cultures despite use of the same culture procedure. Despite this finding, the percentage of lactate dehydrogenase (LDH) released into the medium was greater in CA1 than cortical cultures under the conditions of 24-h hypoxia and 24-h incubation (P < 0.05). We then added MK-801 (500 nM), cycloheximide (3 microM), L-NNA (100 microM) and anti-PAF IgG (50 micrograms/ml) prior to inducing the hypoxia and measured LDH in the medium after 24-h hypoxia and 48-h incubation. Under the hypoxic condition, MK-801, L-NNA, and anti-PAF IgG significantly protected the CA1 neurons from hypoxic injury compared with cortical neurons, while cycloheximide protected both cultures equally. These results suggest that CA1 neurons are more sensitive to hypoxia than cerebral cortical neurons, and glutamate, nitric oxide, and PAF may participate in the mechanism of selective neural death in neurons of the CA1 region due to hypoxia.

Animals↗

Cloning and sequencing of a cluster of genes encoding novel enzymes of trehalose biosynthesis from thermophilic archaebacterium Sulfolobus acidocaldarius.

Trehalose biosynthesis genes, treZ, treX and treY, encoding maltooligosyltrehalose trehalohydrolase (TreZ), glycogen debranching enzyme (TreX), and maltooligosyltrehalose synthase (TreY) have been cloned from the thermophilic archaebacterium Sulfolobus acidocaldarius ATCC33909. The amino-acid sequences deduced from treZ, treX and treY are composed of 556, 713 and 720 amino-acid residues, respectively. TreZ and TreY are 33-40% homologous to the corresponding enzymes from Arthrobacter sp. Q36. We have proposed that the biosynthesis of trehalose in Sulfolobus occurs via the actions of the three enzymes encoded by treZXY.

Amino Acid Sequence↗

Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells.

Fas ligand (FasL), expressed on activated T cells, plays a central role in regulating the immune response by inducing apoptosis in activated lymphocytes through binding to its receptor, Fas. We report here that a newly discovered cytokine, interferon-gamma-inducing factor (IGIF) (H. Okamura et al., Nature 378, 88, 1995), selectively enhances the FasL-mediated cytotoxicity of cloned murine Th1 cells, but not Th0 or Th2 cells. Anti-IFN-gamma antibody (Ab) did not block the IGIF-induced cytotoxicity of Th1 cells, nor did IFN-alpha, IFN-gamma, or TNF-alpha augment the cytotoxic activity of Th1, thus indicating that this enhanced cytotoxicity of Th1 cells was mediated by IGIF. In addition, IL-12 was also found to enhance the FasL-mediated cytotoxicity of Th1 cells, suggesting that Th1 cells possesses receptors for both cytokines although these cytokines can act via different pathways. The results thus show that IGIF, recently proposed as IL-18, might play a potential role in immunoregulation or in inflammation by augmenting the functional activity of FasL on Th1 cells.

Animals↗

Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein.

We have recently reported that a novel molecule, murine IFN-gamma-inducing factor (IGIF) produced by mouse liver cells, possesses potent biologic activities, including the induction of IFN-gamma production by spleen cells and the enhancement of NK cell cytotoxicity. In this paper, we report on the isolation of human IGIF cDNA clones from normal human liver cDNA libraries using murine IGIF cDNA as a probe. The amino acid sequence deduced from the human cDNA clones indicated a 193-amino acid precursor peptide and revealed 65% homology with that of murine IGIF. The amino acid sequence of IGIF also included an IL-1 signature-like sequence. Subsequently, the cloned cDNA was expressed in Escherichia coli, and preliminary studies on the biologic activities of the recombinant protein were performed. The recombinant human IGIF induced IFN-gamma production by mitogen-stimulated PBMC and enhanced NK cell cytotoxicity, in a manner similar to murine IGIF. In addition, recombinant human IGIF also augmented granulocyte-macrophage-CSF production and decreased IL-10 production, but had no effect on IL-4 production by Con A-stimulated PBMC. Based on these pleiotropic effects of IGIF, we propose that this novel cytokine be designated as IL-18.

Adult↗

Cloning and sequencing of trehalose synthase gene from Pimelobacter sp. R48.

The gene encoding trehalose synthase (catalyzing the conversion of maltose into alpha, alpha-trehalose by intramolecular transglucosylation) was cloned from Pimelobacter sp. R48. Sequence analysis revealed a 1719-bp synthase gene and a 573-residue amino-acid sequence. The 220 N-terminal residues were homologous to those of maltases from Saccharomyces carlsbergensis and Aedes aegypti.

Amino Acid Sequence↗

Regulation of cytokine production by sugi allergen-pullulan conjugate.

Sugi basic protein (SBP), a major allergen of Japanese cedar (Cryptomeria japonica) pollen, conjugated to pullulan (alpha-1,4'-, alpha-1,6'-glucan) reportedly suppresses IgE anti-SBP antibody production and enhances IgG anti-SBP antibody production in mice. We analyzed cytokine production by SBP-specific T cells after stimulation with an SBP-pullulan conjugate (SBP-P), native SBP, or a mixture of SBP and pullulan. When SBP-specific T cell lines were stimulated with the SBP-P conjugate in the presence of antigen-presenting cells (APC), the production of IFN-gamma, IL-4, IL-5, and IL-10 decreased compared with the cytokine levels produced by SBP-stimulated T cells. However, when these T cells were repeatedly stimulated with the SBP-P conjugate, the production of IFN-gamma increased progressively, while that of IL-4, IL-5, and IL-10 remained decreased compared with the T cells that were repeatedly stimulated with native SBP. Stimulation of the T cells with the mixture of SBP and pullulan showed little difference in the cytokine production profile from that observed after stimulation with native SBP alone. Interestingly, when the T cell lines stimulated repeatedly with SBP-P were subsequently stimulated with native SBP, a further increase in IFN-gamma production was observed, while IL-10 production decreased. Inhibition of IL-4 production was also observed when SBP-specific Th2 clones were stimulated with SBP-P. These results indicate that stimulation of T cells with SBP-P up-regulates Th1 cytokine production, while down-regulating that of Th2. It is, therefore, conceivable that immunotherapeutic treatment with the SBP-P conjugate rather than with conventional SBP solutions is preferable for improving Japanese cedar pollen allergy.

Allergens↗

Cloning and sequencing of trehalose biosynthesis genes from Arthrobacter sp. Q36.

A 5.1-kbp genomic DNA fragment was cloned from trehalose-producing bacterium Arthrobacter sp. strain Q36. Sequence analysis of the DNA fragment revealed two open reading frames of 2325 and 1794 bp, encoding maltooligosyltrehalose synthase (TreY) and maltooligosyltrehalose trehalohydrolase (TreZ), respectively. The 3' end of treY overlaps with the 5' end of treZ by one nucleotide, and it is suggested that treYZ constitutes and operon. The deduced amino acid sequences of both enzymes have several regions common to amylolytic enzymes belonging to an 'alpha-amylase family'.

Amino Acid Sequence↗

O-glycosylated species of natural human tumor-necrosis factor-alpha.

Tumor-necrosis factor-alpha, produced by human B-cell lymphoblastoid cell line BALL-1, was expressed as four protein bands on SDS/PAGE analysis. It may have been glycosylated, based on the fact that the heavier two of the four bands disappeared after neuraminidase treatment. Sugar composition analyses revealed that the tumor necrosis factor-alpha contained galactose, N-acetylgalactosamine and N-acetylneuraminic acid as sugar components. To prepare sugar chains, tumor necrosis factor-alpha was treated with alkaline borodeuteride and the oligosaccharide-alditols liberated were fractionated by gel-filtration chromatography on a Bio-Gel P-4 column, followed by normal-phase HPLC. Three oligosaccharide-alditols were obtained, and the structures of two of them were identified by methylation analysis and exoglycosidase digestion. The structures of these oligosaccharide-alditols were Gal beta 1-3(NeuAc alpha 2-6)GalNAcol and Gal beta 1-3GalNAcol (GalNAcol, N-acetylgalactosaminitol). The structure of the remaining oligosaccharide-alditol was determined to be NeuAc alpha 2-3Gal1-3GalNAcol by composition and methylation analyses. About 20% of tumor necrosis factor-alpha was found to be 0-glycosylated, based on the results of the sugar composition and structure analyses. An amino acid sequence analysis of the glycosylated peptides was performed after Staphylococcus aureus V8 protease digestion of tumor necrosis factor-alpha had been completed, and it was proved that the 0-glycosylation site of tumor necrosis factor-alpha was Ser 4.

Amino Acid Sequence↗

Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production.

The novel cytokine interferon-gamma-inducing factor (IGIF) augments natural killer (NK) cell activity in cultures of human peripheral blood mononuclear cells (PBMC), similarly to the structurally unrelated cytokine interleukin (IL)-12. IGIF has been found to enhance the production of interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) while inhibiting the production of IL-10 in concanavalin A (Con A)-stimulated PBMC. In this study, when anti-CD3 monoclonal antibody (mAb)-stimulated human enriched T cells were exposed to IGIF, the cytokine dose-dependently enhanced the proliferation of the cells and this could be completely inhibited by a neutralizing antibody against IL-2 at lower concentrations of IGIF. Neutralizing antibody against IFN-gamma had only insignificant inhibitory effects on T cell proliferation at higher concentrations of IGIF. Enzyme-linked immunosorbent assays (ELISA) revealed that, like PBMC, T cells exposed to IGIF produced large amounts of IFN-gamma; however, changes in the production of IL-4 and IL-10 were minimal. IGIF, but not IL-12, significantly enhanced IL-2 and GM-CSF production in T cell cultures, as determined by CTLL-2 bioassay and ELISA, respectively; however, both IGIF and IL-12 enhanced IFN-gamma production by the T cells. When T cells were exposed to a combination of IGIF and IL-12, a synergistic effect was observed on the production of IFN-gamma, but not on production of IL-2 and GM-CSF. In conclusion, IGIF enhances T cell proliferation apparently through an IL-2-dependent pathway and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL-12 in terms of enhanced IFN-gamma production but not IL-2 and GM-CSF production. Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin-18.

Adult↗

Acute pathologic features with angiographic correlates of the nearly or completely occluded lesions of the cervical internal carotid artery.

BACKGROUND: The true pathologic process of nearly or completely occluded lesions of the cervical internal carotid artery (ICA) has not been studied sufficiently. This information is important in determining the critical indications for endarterectomy. METHODS: Acute pathologic features of these advanced occlusive lesions of the ICA were studied in 40 patients who underwent emergency carotid endarterectomy. Gross morphologic and histopathologic features of these occlusive lesions were examined, and the relationship between the clinical information and the pathologic characteristics was investigated. RESULTS: Thirty-seven lesions had histologic features of advanced atherosclerosis complicated by fresh intraplaque hemorrhages with or without transintimal extension. Thinwalled neovessels were thought to be an important etiologic factor in producing intraplaque hemorrhage. The remaining three lesions without these changes had strangulated embolic material at the occluded portion. A good correlation between these pathologic features and angiographic findings was found. CONCLUSION: The presented results clearly indicate that intraplaque hemorrhage is the most important factor in producing and determining the acute pathologic features of symptomatic and advanced atheromatous occlusive ICA lesions.

Acute Disease↗

Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage.

The use of cisternal drainage can lead to complications such as shunt-dependent hydrocephalus and meningitis. We assessed the indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The SAH scores by CT on admission and on the day after surgery were used to evaluate two parameters: the total amount of subarachnoid blood on admission and the clearance rate of subarachnoid blood by surgery. In patients whose parameters values belonged to the range where the total SAH score on admission exceeded 10 points and the surgical clearance rate was less than 50%, the possibility of cerebral infarction was significantly higher in patients without than in those with irrigation (p < 0.05). However, there was no difference between patients with and without irrigation for parameter values outside of the range. Therefore, this range may be useful in providing stricter indications for irrigation therapy with urokinase and thus avoiding the complications of cisternal drainage.

Adult↗

IFN-gamma in combination with IL-3 accelerates platelet recovery in mice with 5-fluorouracil-induced marrow aplasia.

The effects of interferon-gamma (IFN-gamma) on platelet recovery were examined in mice with marrow aplasia induced by i.p. injection of 250 mg/kg of 5-fluorouracil (5-FU). The cytokine was administrated by microosmotic pump, with an ability to deliver a consistent intact dose of cytokine for 7 consecutive days. Administration of 250 IU/kg/day of IFN-gamma in combination with 10(3) U/kg/day of IL-3, which alone had no effect on platelet counts, diminished the nadir for platelet count and shortened the duration of thrombocytopenia. The effect was comparable to that of higher doses of IL-3 (10(5) U/kg/day). The administration of 250 IU/kg/day of IFN-gamma in combination with 10(3) U/kg/day of IL-3 also induced megakaryocyte proliferation in bone marrow cell cultures. Single administration of either 250 IU/kg/day of IFN-gamma or 10(3) U/kg/day of IL-3 had no significant effects. The effect of this combination was also comparable to that of a higher dose of IL-3 (10(5) U/kg/day). We suggest that IFN-gamma accelerates megakaryocyte development, which leads to platelet production in chemotherapy-induced marrow aplasia. The administration of IFN-gamma in combination with IL-3 might be useful for the management of marrow aplasia.

Anemia, Aplastic↗

Interferon-gamma enhances megakaryocyte colony-stimulating activity in murine bone marrow cells.

We have demonstrated previously that interferon-gamma (IFN-gamma) accelerates platelet recovery in mice with 5-FU induced-marrow aplasia in vivo. However, the mechanism for the regulation of megakaryocyte development induced by IFN-gamma in bone marrow cells in vivo remains unknown. To further study the effects of IFN-gamma on megakaryocyte development, various steps during IFN-gamma-mediated accelerated differentiation of the megakaryocytes were investigated in serum-free cultures of murine bone marrow cells in vitro. IFN-gamma markedly induced acetylcholine esterase (AChE) activity, a marker of murine megakaryocytic cells, accompanied by increased colony formation of the megakaryocyte lineage. A prominent increase in megakaryocyte number was observed after IFN-gamma treatment. All of these effects were dependent on the presence of IL-3, and, therefore, these results suggest that IFN-gamma acts as a megakaryocyte potentiator (Meg-POT). However, IFN-gamma did not enhance megakaryocyte maturation with respect to increase in cell size. The effects of IFN-gamma on megakaryocyte maturation were similar to those observed after treatment with higher doses of IL-3 alone. Meg-POT is defined as a factor that induces megakaryocyte maturation. Since IFN-gamma enhanced IL-3-dependent megakaryocyte colony formation and proliferation rather than megakaryocyte maturation, the effects on megakaryocyte development, which were induced by IFN-gamma treatment, seem to be different from the effects of a Meg-POT. We, therefore, propose a new function for IFN-gamma as an enhancer of megakaryocyte colony-stimulating factor activity. The effect of IFN-gamma in vitro appears to correlate well with the acceleration of platelet recovery in vivo.

Acetylcholinesterase↗

Th1/Th2 response profiles to the major allergens Cry j 1 and Cry j 2 of Japanese cedar pollen.

Cry j 1 and Cry j 2 are known to be the major allergens of Japanese cedar pollen. A comparative study was carried out on the immune responses to stimulation with Cry j 1 and Cry j 2 in 24 symptomatic patients and six nonallergic subjects. In T-cell proliferation assays, mean stimulation indexes (SI) were 10.6 for Cry j 1 and 11.7 for Cry j 2 stimulation, respectively, in the allergic patients. Two of the nonallergic subjects showed strong T-cell proliferation to both allergens, while the remainder did not. All the allergic subjects (17/17) showed high titers of anti-Cry j 1 IgE antibody at a mean value of 165 U/ml, whereas only 64% responded to Cry j 2 with low titers at a mean value of 26 U/ml. Nonallergic subjects did not respond with IgE production. Allergic subjects were further examined for their cytokine production profiles. All allergic subjects tested (16/16) produced high levels of interferon-gamma (IFN-gamma) in response to Cry j 1 with a mean value of 918 pg/ml, while only five subjects showed significant elevation of IFN-gamma production in response to Cry j 2 with a mean value of 679 pg/ml. The remainder produced small amounts of IFN-gamma. Cry j 1 induced higher levels of interleukin (IL)-10 gene expression than did Cry j 2 stimulation, while both allergens induced IL-4 expression at a similar level. The IL-12 p35 gene was constitutively expressed, whereas the IL-12 p40 gene expression in Cry j 1-stimulated cells was elevated eightfold over that of nonstimulated cells. Increased expression of the IL-12 p40 gene was negligible in Cry j 2-stimulated cells. Thus, Cry j 1 stimulated mixed features of Th1 and Th2-like responses, while Cry j 2 played a minor role in inducing IgE production and cytokine (IFN-gamma, IL-10, and IL-12) production, except for IL-2 production and strong T-cell proliferative activity. Therefore, it was concluded that Cry j 1 is the more important allergen, and that T-cell proliferation assays do not necessarily reflect the level of allergenicity.

Allergens↗

Immunodominance of seven regions of a major allergen, Cry j 2, of Japanese cedar pollen for T-cell immunity.

The immunodominant regions of the Japanese cedar pollen allergen Cry j 2 for T-cell immunity were determined with whole peripheral blood lymphocytes (PBL) derived from seven allergic patients and three nonallergic subjects. Cry j 2-stimulated T-cell proliferation was inhibited by anti-HLA-DR, but not by anti-HLA-DQ antibody, indicating that the responding T cells recognized the allergen peptides associated with HLA-DR molecules. It was found that seven regions of Cry j 2, i.e., regions corresponding to amino acid numbers 1-26, 70-84, 151-167, 187-203, 252-279, 283-314, and 345-362, were immunodominant for T-cell proliferation. Thus, Cry j 2 bears a limited number of immunodominant regions despite polymorphic features of HLA-DR in the immune system. This suggests the possibility of molecularly designing Cry j 2 antagonists that could downregulate allergic reactions to Japanese cedar pollen.

Case-Control Studies↗

Isolation and identification of compounds from Brazilian propolis which enhance macrophage spreading and mobility.

Brazilian propolis is known to induce the activation of murine effector cells. We isolated and identified six compounds from a water-soluble extract of Brazilian propolis, all of which have enhancing effects on the spreading and mobility of murine macrophages. These compounds were identified as caffeoylquinic acid-derivatives, namely, 5-caffeoylquinic acid (1), chlorogenic acid (2), 4-caffeoylquinic acid (3), 4,5-dicaffeoylquinic acid (4), 3,5-dicaffeoylquinic acid (5) and 3,4-dicaffeoylquinic acid (6).

Animals↗

Purification and characterization of thermostable maltooligosyl trehalose synthase from the thermoacidophilic archaebacterium Sulfolobus acidocaldarius.

A thermostable maltooligosyl trehalose synthase was purified from a cell-free extract of the thermoacidophilic archaebacterium Sulfolobus acidocaldarius ATCC 33909 to an electrophoretically homogeneous state by successive column chromatography on Sepabeads FP-DA13, Butyl-Toyopearl 650M, DEAE-Toyopearl 650S, Ultrogel AcA44, and Mono Q. The enzyme had a molecular mass of 74,000 by SDS-polyacrylamide gel electrophoresis and a pI of 5.9 by gel isoelectrofocusing. The N-terminal amino acid of the enzyme was methionine. The enzyme showed the highest activity from pH 5.0 to 5.5 and at 75 degrees C, and was stable from pH 4.5 to 9.5 and up to 85 degrees C. The enzyme activity was inhibited by Hg2+ and Cu2+. The Kms of the enzyme for maltotetraose, maltopentaose, maltohexaose, maltoheptaose, and short chain amylose (DP 18) were 41.5 mM, 7.1 mM, 5.7 mM, 1.4 mM, and 0.6 mM, respectively.

Amino Acid Sequence↗