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Y Kondo

Publications and source records attributed to Y Kondo.

At least 379 records · Page 21Linked to original sources
PubMed1996

[Study on a predictive marker for evaluating the effectiveness of steroid therapy in IgA nephropathy-significance of extracapillary changes].

In order to obtain a useful index that can predict the effectiveness of steroid therapy in IgA nephropathy, we investigated the relationship between steroid therapy and extracapillary change. We analysed 51 cases consisting of a group of 24 cases in which steroid was administered (initial dose: prednisolone 20-60 mg/day orally, or pulse therapy), and a group of 27 cases in which steroid was not administered. First of all, we compared these two groups in terms of a clinical improvement rate over 3, 12 and 60-month-periods after the therapy, respectively. It was found that steroid therapy led to a higher improvement rate (p < 0.01-0.05), indicating that steroid is effective for IgA nephropathy. Among the group undergoing steroid therapy, the frequency of cellular crescents (C) was significantly higher (p < 0.05-0.01) in the cases in whom steroid was effective and that of fibrous crescents or adhesion (F) was significantly lower (p < 0.05-0.01). We then assessed C/F in each case of the steroid-administered group, and studied its relationship with the improvement rate. As a result, the improvement rate was below 50% in the group of C/F < 0.25, over 50% of the group of 0.25 < or = C/F < 0.75, and 100% of the group of 0.75 < or = C/F. Accordingly, we concluded that C/F could be used a parameter for predicting the effectiveness of steroid therapy in IgA nephropathy and for determining indications for steroid therapy.

Adolescent↗
PubMed1996

Contribution of the glycolytic pathway to enzymatic metmyoglobin reduction in myocytes.

The metmyoglobin (oxidized form of myoglobin) reducing enzyme system was examined in rat myocytes. An inhibitor of the glycolytic pathway (2-deoxy-D-glucose) inhibited the reduction of metmyoglobin in myocytes. An inhibitor of the citric acid cycle (malonic acid), did not inhibit this reaction. From the results of this study along with those of our previous work, we proposed that the glycolytic pathway may have a significant role in the enzymatic metmyoglobin reduction, presumably by its supply of cytoplasmic NADH for the NADH-cytochrome b5 reductase system, in muscle.

Animals↗
PubMed1995

Age-related changes in composition of transcription factor, AP-1 complex in the rat brain.

We examined age-related changes in composition of transcription factor, activator protein-1 (AP-1) which binds to TPA responsive element (TRE) in the non-stimulated rat brain, using electrophoretic mobility-shift assay with immunodepletion/supershift assay. The total TRE-binding activity in the frontal cortex and the hippocampus of the aged rats markedly decreased to 66% and 43%, respectively, and TRE-bindings of AP-1 in both regions also decreased to 82% and 66%, respectively, with aging. Jun-Jun dimers accounted for approximately half of the total TRE-bindings and 80-90% of the AP-1 bindings, while there were fewer Fos-Jun dimers, in both examined regions of the non-stimulated adult. The proportion of active Fos-Jun heterodimers in the frontal cortex increased to up to half of the AP-1 bindings in the aged rats, indicating that cortical AP-1-related transcription may increase with aging even under the non-stimulated condition. In the hippocampus, inactive Jun-Jun homodimers became predominant in AP-1 with aging. This regional diversity of age-related changes in the composition of AP-1 in the brain may be related to changes or dysfunction in neuronal signal transduction in the aged.

Aging↗
PubMed1995

Pertussis toxin inhibits phospholipase C activation and Ca2+ mobilization by sphingosylphosphorylcholine and galactosylsphingosine in HL60 leukemia cells. Implications of GTP-binding protein-coupled receptors for lysosphingolipids.

Extracellular sphingosylphosphorylcholine (SPC) and galactosylsphingosine (psychosine) induced Ca2+ mobilization in a dose-dependent manner in HL60 leukemia cells. The rapid and transient increase in intracellular Ca2+ concentration ([Ca2+]i) elicited by SPC and psychosine at concentrations lower than 30 microM was inhibited by treatment of the cells with pertussis toxin (PTX) and U73122, a phospholipase C inhibitor, as was the case for UTP, a P2-purinergic agonist. The increase in [Ca2+]i induced by these lysosphingolipids was associated with inositol phosphate production, which was also sensitive to PTX and U73122. The inositol phosphate response is not secondary to the increase in [Ca2+]i as evidenced by the observation that thapsigargin and ionomycin, Ca2+ mobilizing agents, never induced inositol phosphate production and, unlike lysosphingolipids, the [Ca2+]i rise by these agents was totally insensitive to PTX and U73122. When HL60 cells were differentiated into neutrophil-like cells by dibutyryl cyclic AMP, inositol phosphate and Ca2+ responses to AlF4- were enhanced, probably reflecting an increase in the amount of Gi2 and Gi3 compared with undifferentiated cells. In the neutrophil-like cells, however, the responses to SPC and psychosine were markedly attenuated. This may exclude the possibility that the lysosphingolipids activate rather directly PTX-sensitive GTP-binding proteins or the phospholipase C itself. Other lysosphingolipids including glucosylsphingosine (glucopsychosine) and sphingosylgalactosyl sulfate (lysosulfatides) at 30 microM or lower concentrations also showed PTX- and U73122-sensitive Ca2+ mobilization and inositol phosphate response in a way similar to SPC and psychosine. However, platelet-activating factor and lysoglycerophospholipids such as lysophosphatidylcholine and lysophosphatidic acid were less effective than these lysosphingolipids in the induction of Ca2+ mobilization. Taken together, the results indicate that a group of lysosphingolipids at appropriate doses induces Ca2+ mobilization through inositol phosphate production by phospholipase C activation. The lysosphingolipids-induced enzyme activation may be mediated by PTX-sensitive GTP-binding protein-coupled receptors, which may be different from previously identified platelet-activating factor receptor or lysophosphatidic acid receptor.

Calcium↗
PubMed1995

Involvement of prostaglandin E2 synthesis in the intestinal secretory action of Escherichia coli heat-stable enterotoxin II.

The prostaglandin response of mouse intestinal epithelial cells after exposure to Escherichia coli heat-stable enterotoxin II was examined. The quantity of prostaglandin E2 produced by the intestinal cells was directly related to the dose of heat-stable enterotoxin II. The change in the amount of prostaglandin E2 over time correlated to that of the volume of fluid released into the intestinal lumen. We then demonstrated that administration of heat-stable enterotoxin II into the intestinal loops of mice induced elevation of arachidonic acid and phosphatidic acid levels in intestinal epithelial cells. These results show that heat-stable enterotoxin II stimulates arachidonic acid metabolism in intestinal epithelial cells and that the synthesized prostaglandin E2 functions as a mediator of fluid secretion induced by this enterotoxin.

Animals↗
PubMed1995

Metallothionein null cells have increased sensitivity to anticancer drugs.

Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anticancer agents, and reactive oxygen species. We have examined the effect of the loss of MT expression on the cytotoxicity of anticancer agents and mutagens using embryonic fibroblast cells from transgenic mice with targeted disruptions of MT I and II genes (MT -/-). MT -/- cells expressed no detectable MT. Compared to wild type cells, MT -/- cells showed enhanced sensitivity to a 2-h exposure to cisplatin, melphalan, bleomycin, cytarabine, or N-methyl-N'-nitro-N-nitrosoguanidine but were equally sensitive to doxorubicin and neocarzinostatin. Basal expression of the DNA damage-response genes, gadd 45 and gadd 153, were elevated in MT -/- cells compared to MT +/+ cells. Anticancer drug treatment, however, did not produce a greater increase in gadd 45 or gadd 153 expression in MT null cells compared to MT +/+ cells. These results support the hypothesis that endogenous MT levels affect the sensitivity of mammalian cells to mutagens and clinically important anticancer drugs.

Animals↗
PubMed1995

Intracellular cross-talk between thyrotropin receptor and A1 adenosine receptor in regulation of phospholipase C and adenylate cyclase in COS-7 cells transfected with their receptor genes.

COS-7 cells were transiently transfected with human thyrotropin receptor (TSHR) and dog A1 adenosine receptor (A1R) cDNA. TSH stimulated both inositol phosphate production and cyclic AMP (cAMP) accumulation in the cells. An A1 agonist, N6-(L-2-phenylisopropyl)adenosine (PIA), which is ineffective alone, significantly enhanced TSH-induced inositol phosphate production, but insignificantly inhibited TSH-induced cAMP accumulation was revealed by short-term treatment with the protein kinase C inhibitors, staurosporine and K252a, or long-term treatment with 12-myristate 13-acetate, suggesting that endogenous protein kinase C inhibits the A1R-mediated inhibition of the TSHR-adenylate cyclase system. In staurosporine-treated cells, the stimulatory and inhibitory permissive actions of PIA on TSH-induced phospholipase C and adenylate cyclase activation respectively were completely reversed by pretreatment with pertussis toxin whereas intrinsic TSH-induced effects were hardly affected by the toxin. The cross-talk between the signalling pathway for TSHR and that for A1R was not detected in a mixture of cells expressing either TSHR or A1R. We conclude that a single species of A1R, via pertussis-toxin-sensitive GTP-binding proteins, not only inhibits adenylate cyclase but also stimulates phospholipase C in collaboration with an activated TSHR within a single cell expressing both types of receptor.

Adenylate Cyclase Toxin↗
PubMed1995

Enhanced sensitivity to oxidative stress in cultured embryonic cells from transgenic mice deficient in metallothionein I and II genes.

Embryonic cells from transgenic mice with targeted disruption of metallothionein I and II genes expressed no detectable metallothionein either constitutively or after treatment with cadmium, in contrast to cultured cells that were wild type or heterozygous for the loss of the metallothionein genes. Metallothionein null cells were most sensitive to the cytotoxic effects of cadmium, the membrane permeant oxidant tert-butylhydroperoxide, and the redox cycling toxin paraquat. No marked differences were seen among the wild type, heterozygous, or metallothionein null cells in glutathione levels or in the activity of CuZn-superoxide dismutase, glutathione peroxidase, or catalase. Nevertheless, metallothionein null cells were more sensitive to tert-butylhydroperoxide-induced oxidation as ascertained by confocal microscopic imaging of dichlorofluoroscein fluorescence. These results indicate basal metallothionein levels can function to regulate intracellular redox status in mammalian cells.

Animals↗
PubMed1995

An enzymatic formation of 13-oxo-trideca-9,11-dienoic acid from 13-hydroperoxylinolenic acid by a homolytic hydroperoxide lyase in elicitor-treated soybean cotyledons.

An activity of homolytic hydroperoxide lyase (HPLS) catalyzing the specific cleavage of 13-hydroperoxylinolenic acid to form a volatile compound and 13-oxo acid was found in the enzyme extract from soybean cotyledons. 2-Penten-1-ol was characterized as a volatile metabolite by gas chromatography-mass spectrometry analysis. The methyl ester derivatives of reaction products were separated and isolated by a normal-phase high-performance liquid chromatography, and identified to be 13-oxo-trideca-9(Z),11(E)-dienoic acid methyl ester and its geometric isomer possessed 9(E),11(E) moiety by the analyses of high resolution mass spectrometry and nuclear magnetic resonance spectrometry. An activity of homolytic HPLS found in soybean cotyledons was evidently enhanced by elicitation. The products of 13-oxo-tridecadienoic acid with alpha, beta, gamma, delta-unsaturation were shown to be antifungal substances by a chromatographic bioassay. The metabolites via lipoxygenase and HPLS pathways may have physiological roles in the resistant action of host plants.

Aldehyde-Lyases↗
PubMed1995

Metallothionein localization and cisplatin resistance in human hormone-independent prostatic tumor cell lines.

Metallothioneins (MT) are major cysteine-rich proteins with poorly characterized functions. We have examined the MT amount, isotype expression, and subcellular distribution in 4 human hormone-independent prostatic carcinoma cell lines. Both PC-3 and DU-145 cells were thiol-rich cells with similar MT and glutathione levels, while HPC36M and PC-3 MA2 were thiol-poor cells with lower MT and glutathione levels. All 4 prostatic cell lines expressed the MTIIA isoform at a basal level; DU-145 cells also constitutively expressed MTIE mRNA. Using antibodies for both total MT and MTIIA, we defined MT to cytoplasmic and nuclear domains in PC-3 cells, to perinuclear and nuclear domains in HPC36M cells, and to prominent nonnucleolar nuclear domains in DU-145 and PC-3 MA2 cells. These results indicate that the subcellular distribution is cell type specific and not reflective of the total MT content or MT isoform. Resistance to cadmium in all 4 cell lines was correlated with total MT levels, while resistance to the anticancer agent cisplatin correlated best with nuclear MT content. We suggest that the subcellular localization of MT is functionally important in cellular protection against the anticancer agent cisplatin in human prostatic cancer cells.

Blotting, Northern↗
PubMed1995

Limited development capacity of the earliest embryonic murine thymus.

Previous studies have demonstrated that murine thymus separates from the pharynx during 11.5-12 days of gestation, and that the proliferation of thymic cells starts at this age. We characterized embryonic day 12 thymus in terms of the surface phenotype of the thymus cells, the function of the lobe in supporting T cell development in organ culture, and the precursor activity of the thymus cells in a mixed culture with deoxyguanosine-treated lobes. The phenotype of the major population of embryonic day 12 thymus cells was HSA+, CD44+, c-kit+, Thy-1-, CD25-, CD4-, CD8-, TcR-, and Sca-1-. In organ culture of embryonic day 12 thymus lobes, most of the lobes did not develop well and failed to generate CD4+CD8+, CD4+CD8-, or CD4-CD8+ cells, even when embryonic day 14 thymus cells were added. However, thymus cells on embryonic day 12 contained T cell precursors that developed into mature T cells in co-culture with deoxyguanosine-treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine-treated embryonic day 14 thymus lobes expressed the surface molecules I-A and H-2D, whereas these cells in embryonic day 12 thymus lobes were negative for these surface molecules. Thus, our findings suggest that the embryonic day 12 thymus lobe contains T cell precursors, but that the undeveloped thymic stromal cells are insufficient to support full T cell development.

Animals↗
PubMed1995

Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain.

To investigate the relationship between the immune system and convulsions in an animal model, we examined the effects of repeated administration with the immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions and the changes in the mRNA expression of its binding protein cyclophilin in the rat brain. The consecutive administration of cyclosporin A (5 mg/kg, s.c., 14 days) significantly aggravated the severity of convulsions induced with PTZ 75 mg/kg, i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in several brain regions and inhibited the PTZ-induced increase of hippocampal cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group treated with chronic vehicle administration after the PTZ-preinjection, chronic cyclosporin A administration after the initial injection of PTZ apparently aggravated convulsions after the second PTZ injection. Interestingly, the increase in hippocampal cyclophilin mRNA observed after a single PTZ injection was not found after the second PTZ injection in the group with PTZ pretreatment. Therefore, these findings suggest that cyclosporin A administered peripherally can affect the central nervous system, and that an immune response associated with the first convulsive episode plays a key role in severity during subsequent attacks.

Amino Acid Isomerases↗
PubMed1995

Inhibitory effect of tyrphostin on the replication of herpes simplex virus type 1.

Tyrphostins 9 and 47, inhibitors of protein-tyrosine kinase, inhibited the replication of herpes simplex virus type 1 (HSV-1), whereas tyrophostin 1, which does not inhibit protein-tyrosine kinase, did not affect the replication of HSV-1. The inhibitory effect of tyrphostin 9 was more potent than that of tyrphostin 47, and the IC50 of tyrphostin 9 was 40 nM. Sodium orthovanadate, an inhibitor of protein phosphotyrosine phosphatase, increased HSV-1 plaque formation and its effect was partly reversed by tyrphostin 9. The phosphorylation of viral phosphoproteins was decreased by tyrphostin 9 in a dose-dependent manner, but the tyrphostin 9-induced reduction of protein synthesis was not dose-dependent. At the late stage of infection, tyrosine phosphorylation was demonstrated in HSV-1 phosphoproteins. These results indicate that protein-tyrosine kinase is involved in the replication of HSV-1 and that tyrphostin can inhibit the synthesis and post-translational phosphorylation of the viral proteins.

Animals↗
PubMed1995

Functional association between the medial amygdala and the medial preoptic area in regulation of mating behavior in the male rat.

We examined the effects of combined lesions of the medial preoptic area and the medial amygdala on male copulatory behavior to understand a functional relation between these two structures in regulation of the behavior in the rat. Young adult male rats were castrated and received Silastic implants containing testosterone. After baseline copulatory tests, a unilateral medial preoptic lesion (uPOL) was made. Males with uPOL showed less intromission behavior than sham-operated males did, but none of them showed elimination of the behavior. Following the observations after the uPOL, these males were subjected to a unilateral medial amygdala lesion (uMAL) ipsilateral or contralateral to the previous uPOL. The ipsilateral uMAL did not affect copulatory behavior compared to that of sham-operated uPOL males. However, the copulatory behavior in the animals with uPOL was severely disrupted by the contralateral uMAL. These results suggest that the medial preoptic area is closely related to the medial amygdala in regulation of male rat copulatory behavior, and these areas may play a critical role in the behavior as an unitary system.

Amygdala↗
PubMed1995

Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining.

We analyzed the p53 expression immunohistochemically in 50 specimens of hepatocellular carcinoma (HCC) using two monoclonal antibodies (DO7 and PAb1801) and one polyclonal antibody (CM1), which recognize both wild and mutant type p53 proteins and can be used for paraffin-embedded sections. Fifteen of the 50 HCC specimens (30%) showed p53 expression localized at tumor nuclei, and this expression was significantly more frequent in HCCs with histologically lower differentiation. Except for serum titers of alpha-fetoprotein, the p53 expression had no statistically significant correlation with clinicopathological parameters, including hepatitis virus infection, tumor size, and background liver diseases. Conversely, the cell proliferative activities of tumor cells as assessed by mitotic index and immunostaining for MIB-1 were well correlated with the grade of histological differentiation. Moreover, MIB-1 immunostaining was shown to be useful in distinguishing well differentiated HCC from hepatocytes in chronic liver diseases. It also was shown that p53 expression was strongly associated with cell proliferative activity. Our results indicate that p53 expression takes place in the late stage of tumor progression and is related to the high malignant potential of HCCs.

Antibodies, Monoclonal↗
PubMed1995

Comparative morphometric studies of benign and malignant intraductal proliferative lesions of the breast by computerized image analysis.

Using computerized image analysis, we newly devised a method for automatic quantitative evaluation of nuclear arrangements in variable proliferative intraductal (cribriform) lesions of the breast, by calculating angles of longest nuclear diameter to a horizon (LNDA). Internuclear correlation in the cribriform lesions was thus examined, comparing 22 benign and 62 malignant cases. In the malignant lesions, nuclear arrangements tended to be multidirectional, probably because of vertical nuclear arrangements toward acinar lumens as reflected by the wide distribution of LNDAs. Conversely, in the benign lesions, groups of nuclei tended to arrange toward one certain direction, forming a complex streaming pattern with the distribution of LNDAs usually producing a distinctive peak. Other conventional nuclear features, such as nuclear area, nuclear perimeter, shortest nuclear diameter (SND), and leading variables were also quantitatively assessed for multivariate analysis. It was noted that nuclear arrangements could represent a favorable discriminator. Linear discriminant function could classify 66 of the total 84 cases (78.6%) as being consistent with the diagnosis of pathologists. We conclude that internuclear arrangement could be a useful discriminating variable in benign and malignant breast lesions for the further development of an automatic analytic system.

Adenocarcinoma↗