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Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 505 records · Page 28Linked to original sources

Stem cell factor-induced signal transduction in rat mast cells. Activation of phospholipase D but not phosphoinositide-specific phospholipase C in c-kit receptor stimulation.

Stem cell factor (SCF), a hematopoietic growth factor for primitive hematopoietic stem cells, is also known as mast cell growth factor. SCF induced serotonin release from rat peritoneal mast cells, connective tissue-type mast cells. The treatment of rat peritoneal mast cells with SCF failed to produce inositol 1,4,5-trisphosphate, indicating the absence of involvement of phosphoinositide-specific phospholipase C pathway. 1,2-Diacylglycerol (1,2-DG) and phosphatidic acid, however, were increased after stimulation by SCF. Phosphatidylethanol formation catalyzed by phospholipase D (PLD) was observed, together with the release of choline but not phosphocholine. Propranolol, an inhibitor of phosphatidate phosphohydrolase, blocked the production of 1,2-DG. These results indicate that the phosphatidylcholine-specific PLD pathway is the main pathway for the production of 1,2-DG in SCF-stimulated rat peritoneal mast cells. Furthermore, treatment of cells with protein tyrosine kinase inhibitor, genistein, inhibited 1,2-DG formation and serotonin release dose-dependently. Taken together, SCF induces the activation of PLD through the protein tyrosine kinase pathway without activation of phosphoinositide-specific phospholipase C.

Animals↗

Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines.

OBJECTIVE: To investigate the effects of hyaluronic acid (HA) on the release of proteoglycan by cultured rabbit chondrocytes. METHODS: Articular cartilage chondrocytes were isolated from the knee joints of New Zealand white rabbits. Proteoglycan synthesis after incubation with HA was determined by measuring 35S-sulfate incorporation. Cells incubated with HA were labeled with 3H-glucosamine and applied to a Sepharose CL-2B column. After incubation of confluent cells with 35S-sulfate and then with HA in various concentrations in the presence or absence of cytokines, proteoglycan release from the cell matrix layer was measured. RESULTS: HA (M(r) 3 x 10(5) to 19 x 10(5)), at 10 micrograms/ml to 1 mg/ml, had little effect on the incorporation of 35S-sulfate or 3H-glucosamine into cartilage matrix proteoglycans, or on the hydrodynamic size of proteoglycan monomers, in rabbit chondrocyte cultures. However, at 10-1,000 micrograms/ml, HA suppressed the release of 35S-proteoglycans from the cell matrix layer into the medium in the presence and absence of interleukin-1, tumor necrosis factor alpha, or basic fibroblast growth factor. CONCLUSION: These results suggest that HA is a potent inhibitor of the displacement of matrix proteoglycan into culture medium.

Animals↗

Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack.

In vitro models of pancreatic islet cell inflammation are the lysis of isolated islet cells by activated macrophages or by oxygen radicals released by the endothelial enzyme xanthine oxidase. Dihydrolipoic acid protected islet cells in both systems by different modes of action. Macrophage cytotoxicity towards islet cells, which is nitric-oxide-mediated, was suppressed by 2 h of preincubation of macrophages with lipoic acid. Similarly, 2 h of preincubation sufficed to protect islet cells against enzymatically produced oxygen radicals. Dihydrolipoic acid was found by chemiluminescence assay to scavenge directly such radicals. In macrophages dihydrolipoic acid suppressed the production of nitrite as a measure of nitric oxide release. These results suggest that dihydrolipoic acid is an anti-inflammatory agent which at the same time interferes with nitric oxide release from inflammatory macrophages and protects target cells from oxygen radical attack.

Animals↗

Gangliosides protect from TNF alpha-induced apoptosis.

The modulation of tumor necrosis factor alpha-mediated cytotoxicity by gangliosides was analyzed. When cells of the TNF alpha-sensitive fibrosarcoma cell line L929 were incubated for 16 h with recombinant TNF alpha (156 or 312 pg/ml), they were lysed to 65.2% or 78.0%, respectively. The presence of a bovine brain ganglioside mixture (BBG, Cronassial) inhibited the TNF alpha-mediated lysis in a dose-dependent manner (IC50 approximately 1 mg/ml). Maximum inhibition was achieved with 2 mg/ml BBG (82.6% inhibition for 156 pg/ml TNF alpha and 88.5% inhibition for 312 pg/ml TNF alpha). In situ nick translation revealed that BBG (2 mg/ml) significantly reduces the number of cells with TNF alpha-induced DNA-strand breaks from 71.2% to 6.6% (P < 0.0001), indicating a protection against TNF alpha-mediated apoptosis. We conclude that BBG prevents the cytotoxic action of TNF alpha on tumor cells. The inhibitory effect may be due to an interference of gangliosides with intracellular signal transduction pathways, resulting in an inhibition of the activation of DNA-cleaving endonucleases.

Animals↗

Branch growth and leaf gas exchange of Populus tremula exposed to low ozone concentrations throughout two growing seasons.

During two consecutive growing seasons, the same potted individuals of European aspen (Populus tremula), grown from root cuttings of one clone, were fumigated with either ambient air or ozone concentrations of 0 (control), 0.05 or 0.1 microlitre litre(-1). Structure and biomass of the annually formed branches were analysed after excision at the end of each season. Only at 0.1 microlitre litre(-1) was branch weight reduced, and crooked axes occurred in each season. During the second season, branch length and leaf sizes were strongly reduced, while many leaves displayed yellowish deficiency symptoms and lowered cation concentrations. Such leaves contrasted to those showing characteristic O3-bronzing. Although foliage density was enhanced due to reduced branch length, the area of attached foliage was limited by the small leaf sizes, necrotic leaves and premature leaf loss. During mid-summer of the second fumigation period, photosynthetic capacity, carboxylation efficiency and water-use efficiency (WUE) declined in (attached) yellowish and bronze leaves at 0.1 microlitre litre(-1), whereas green leaves at 0.05 microlitre litre(-1) displayed accelerated senescence in late summer while maintaining WUE. It is concluded that the differences in branch growth between the two growing seasons were caused in part by internal changes in those plant organs (root and basal stem), which had experienced both fumigation periods.

Journal Article↗

Fc gamma receptor-mediated biological activities of human leukemic cell lines and their modulation by transforming growth factor-beta 1 and interleukin 6.

Previously we reported that transforming growth factor-beta 1 (TGF-beta 1) remarkably enhanced the differentiation of human leukemic cell lines, HL-60 and THP-1, in the presence of 1 alpha,25-dihydroxyvitamin D3 (VD3) and also that it induced Fc receptor for immunoglobulin G (Fc gamma R), type IIIB, in the presence of retinoic acid (RA). The present study revealed that TGF-beta 1 enhanced the Fc gamma RI- and Fc gamma RII-mediated antibody-dependent cellular cytotoxicity (ADCC) of the cells differentiated in the presence of VD3 and RA. However, production of active oxygen molecules was suppressed by TGF-beta 1. On the other hand, IL-6 stimulated production of active oxygen molecules and ADCC of the cells treated with VD3 and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the levels of cell surface Fc gamma RI and Fc gamma RII were not clearly correlated with the ADCC. The TGF-beta 1/VD3-treated HL-60 cells were able to synthesize mRNAs for TGF-beta 1 and TNF-alpha, although TNF-alpha protein was not detectable. These results suggest that TGF-beta 1 has a bifunctional role, either stimulatory or inhibitory, in the modulation of macrophage activities through Fc gamma Rs and that IL-6 stimulates certain macrophage activities in mature cells.

Antibody-Dependent Cell Cytotoxicity↗

Short-term administration of anti-L3T4 MoAb prevents diabetes in NOD mice.

We treated 2-week-old and 8-week-old non-obese diabetic (NOD) mice with 1 mg of anti-L3T4 MoAb weekly for 4 weeks. This short-term treatment of anti-L3T4 MoAb prevented the development of overt diabetes in NOD mice, in both groups, even after cessation of the therapy. However, there were overt mononuclear cell infiltrations in the majority of islets, and no appreciable differences in the degree of insulitis between treated and control mice. There were also no significant differences in the percentage of L3T4+ T cells expressing V beta 5, V beta 8 and V beta 11 antigens between the treated and the control group. In contrast, most of the male NOD mice injected with 200 mg/kg of cyclophosphamide did not become diabetic when the spleen cells from the MoAb-treated female NOD mice were transferred to these animals 48 h before the cyclophosphamide injection. Thus, the tolerance induced by the short-term administration of anti-L3T4 MoAb to NOD mice may not be due to clonal deletion, but rather to newly generated suppressor cells in the animals.

Animals↗

Expression of anticardiolipin cofactor, human beta 2-glycoprotein I, by a recombinant baculovirus/insect cell system.

A full-length cDNA coding a human beta 2-glycoprotein I (beta 2-GPI) was introduced into the baculovirus genome to construct a recombinant baculovirus. Spodoptera frugiperda (Sf9) cells were infected with the recombinant baculovirus. A protein (mol. wt 43,000) reactive with anti-beta 2-GPI antisera was produced in the insect cells and secreted into the culture medium. The recombinant beta 2-GPI was purified from the culture supernatant by sequential cardiolipin (CL)-affinity column chromatography and gel filtration. The N-terminal amino acid sequence of the protein was identical to that of the native beta 2-GPI purified from human sera, and a putative signal peptide was cleaved from the secreted form of the recombinant protein. The purified recombinant protein had a cofactor activity which enhances CL binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients, as well as the native beta 2-GPI. Thus, the beta 2-GPI expressed in insect cells is an immunologically active cofactor.

Amino Acid Sequence↗

Anticardiolipin antibodies in Japanese patients with multiple sclerosis.

We evaluated circulating anticardiolipin antibodies (aCL) in 38 Japanese patients who fulfilled the criteria of clinically definite multiple sclerosis (MS), using a newly developed EIA system with aCL-cofactor. Two of 38 patients (5.3%) had a aCL-cofactor-dependent positive serology, and differences compared with findings in controls were statistically significant. The 2 aCL-positive patients had similar clinical features with acute transverse myelopathy (ATM), optic neuropathy (OPN), normal cranial MRI and negative oligoclonal IgG bands (OCBs) in the cerebrospinal fluid (CSF). Among the 38 patients, 3 had ATM, OPN, normal cranial MRI and negative OCBs, hence, in a significant number of the patients (2/3; 67%) with these distinctive features, serology for aCL was positive. Therefore, they may have another condition associated with aCL, masquerading as MS. Serological testing for aCL with aCL-cofactor is recommended for the patients with clinical diagnosis of MS, especially for those showing OPN and ATM during the clinical course, and in Asian peoples where the incidence of ATM and OPN is relatively high among the patients with diagnosis of MS.

Adolescent↗

Effects of interleukin-1 on syntheses of alkaline phosphatase, type X collagen, and 1,25-dihydroxyvitamin D3 receptor, and matrix calcification in rabbit chondrocyte cultures.

The effect of IL-1 on expression of the mineralization-related phenotype by chondrocytes was examined. In cultures of rabbit growth plate chondrocytes, IL-1 beta at 0.1 ng/ml caused 95% decreases in alkaline phosphatase activity, alkaline phosphatase mRNA levels, the incorporation of 45Ca into insoluble material, and the calcium content during the hypertrophic stage. These effects of IL-1 beta were dose-dependent and were observed in 24-48 h. Furthermore, IL-1 beta suppressed increase in cell size and the syntheses of 1,25-dihydroxyvitamin D3 receptor and type X collagen, other markers of hypertrophy, but had little effect on the synthesis of total protein including type II collagen. The inhibition of calcification was observed only when chondrocytes were exposed to IL-1 before the onset of calcification: IL-1 treatment from the mineralization stage had a marginal effect on 45Ca incorporation into insoluble material. These results suggest that IL-1 inhibits chondrocyte hypertrophy and the onset of calcification in ossifying cartilage.

Alkaline Phosphatase↗

Parkinson-like symptoms as a manifestation of systemic lupus erythematosus.

A 42-year-old Japanese woman with systemic lupus erythematosus (SLE) developed Parkinsonian-like movements. Steroid pulse therapy was most effective and additional anti-Parkinsonian drugs were not required. Although psychosis, seizures and meningitis are common central nervous system (CNS) manifestations in SLE patients, Parkinsonian-like symptoms are extremely rare. The putative genesis and treatment of CNS lupus are discussed.

Adult↗

Immunochemical detection of advanced glycation end products in renal cortex from STZ-induced diabetic rat.

To reassess the accumulation of advanced glycation end products in diabetic renal cortex, we used a newly developed enzyme-linked immunosorbent assay to measure AGEs in renal cortex from STZ-induced diabetic and age-matched control rats. Kidneys and aortas were obtained from rats after 5 and 20 wk of STZ injection. At 5 wk of diabetes, the mean AGE content in collagenase-digested materials of renal cortex was > 16-fold higher in diabetic animals compared with controls (1044.4 +/- 151.8 vs. 64.3 +/- 5.7 arbitrary units, P < 0.01). At 20 wk of diabetes, it was > 45-fold higher in diabetic compared with control animals (3841.0 +/- 1077.3 vs. 83.8 +/- 12.8 AUs, P < 0.01). These increases were surprisingly large compared with the < 1.5-fold increase in the fluorescence levels both after 5 and 20 wk of diabetes. In control animals, neither the AGE content nor the fluorescence level increased during this period. Moreover, at 20 wk of diabetes, the AGE content was 39-fold higher in renal cortex compared with aorta. This study provided the first immunochemical evidence that collagenase-digested materials of renal cortex, as well as aorta, contained AGE products and that these products were present in much higher levels in diabetic animals than in control animals. With duration of diabetes, the AGE contents increased significantly both in renal cortex and aorta. The excessive accumulation of AGEs was most apparent in the diabetic kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute myeloblastic leukemia.

A 58-year-old male was diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) with myelofibrosis in 1984. The administration of hydroxyurea and low dose splenic irradiation were initiated for abdominal distention due to splenomegaly in 1987. In May 1990 the patient developed smouldering acute myeloblastic leukemia (AML); and the blasts proliferated in response to G-CSF administered for refractory pneumonia. The patient died of pneumonia and pleural involvement of leukemia in September 1990. FACS analysis of the blasts using anti-decay accelerating factor (DAF) (CD55) and CD59 (membrane attack complex inhibition factor: MACIF) monoclonal antibodies demonstrated that 25.5% and/or 87.3% of the blasts were negative for DAF or CD59 respectively. There is the earlier evidence that about 90% leukemic myeloblasts from non-PNH AML patients are positive for DAF, and nearly 100% of non-PNH neutrophils have been shown to be positive for both DAF and CD59. Our data suggest that the leukemic blasts from this patient may have derived from the PNH clone.

Antigens, CD↗

[Biochemistry and biological activities of eosinophil granule proteins].

The biochemistry, the molecular biology and the biological activity of the eosinophil granule proteins, major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO) are reviewed. MBP is present in the core of the eosinophil granule and is toxic to parasite and host cells. ECP and EDN are proteins in the matrix of the granule and share sequence similarity and ribonuclease activity. These two proteins can provoke the Gordon phenomenon in rabbits and are toxic to parasites. EPO consists of two polypeptide and is a toxin for parasite and host cells with or without H2O2. The common characteristics of these proteins are their high isoelectric points and cytotoxic activities.

Amino Acid Sequence↗

Direct thrombolytic revascularization of the occluded basilar artery.

Successful direct revascularization in a 54-year-old man with embolism of the basilar artery following St Jude Medical valve replacement for mitral regurgitation 6 years earlier is reported. He arrived at the hospital in a deep coma. Computed tomography showed no new lesions, but subsequent angiography revealed occlusion of the basilar tip, bilateral posterior cerebral arteries and right superior cerebellar artery. Direct thrombolytic therapy was performed using 420,000 units urokinase through an infusion catheter placed in the basilar artery. The patient immediately regained consciousness, with only slight diplopia. Direct thrombolytic therapy is considered to be an effective treatment for thromboembolism following prosthetic valve replacement in certain selected cases.

Basilar Artery↗