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Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 379 records · Page 21Linked to original sources
PubMed1998

STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition.

The signal transducer and activator of transcription molecules (STATs) play key roles in cytokine-induced signal transduction. However, their role in cell growth has not been clear. In the present study, we show that STAT3 plays a key role in the G1 to S phase cell-cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D2, D3 and A, and cdc25A, and the concomitant downregulation of p21 and p27. Furthermore, unexpectedly, we found that gp130 could induce the expression of p21 when STAT3 activation was suppressed. Such contradictory signals regulating cell-cycle progression could be simultaneously delivered from distinct cytoplasmic regions of gp130. We propose an 'orchestrating model' for cytokine and growth factor action in which contradictory signals are orchestrated to produce a specific effect in a target cell.

Cell Line↗
PubMed1998

A gene cluster for 6-deoxy-L-talan synthesis in Actinobacillus actinomycetemcomitans.

The serotype c antigen of Actinobacillus actinomycetemcomitans consists of 6-deoxy-l-talose. A gene cluster involved in the synthesis of serotype-specific polysaccharide antigen was cloned from the chromosomal DNA of A. actinomycetemcomitans NCTC 9710 (serotype c). This cluster consisted of 17 open reading frames. Escherichia coli produced the polysaccharide that reacts with the serotype c-specific antibody when transformed with a plasmid containing the cluster. Comparing the structure of the gene cluster with a similar cluster from A. actinomycetemcomitans Y4 (serotype b), which produces a polysaccharide consisting of l-rhamnose and d-fucose, revealed that a 5.7 kb region containing seven genes in the cluster from strain Y4 was replaced by a 3.8 kb region containing three genes in strain NCTC 9710. The results suggest that these region, as well as dTDP-6-deoxy-l-talose-forming dTDP-4-keto-l-rhamnose reductase, is essential to the production of extracellular polysaccharide specific to serotype c.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

Relation between evolutionary distance and enzymatic properties among the members of the CYP52A subfamily of Candida maltosa.

The CYP52A subfamily of the alkane-assimilating yeast Candida maltosa consists of six structurally related isoforms. Four of them (CYP52A3, 4, 5, and 9) are strongly induced by alkanes and play an important role for the conversion of various alkanes and fatty acids. Taking advantage of a homologous overexpression system, we found in the present study that both of the two other CYP52A forms, CYP52A10 and CYP52A11, represent specialists for the hydroxylation of lauric acid suggesting their preference for short-chain fatty acids. At the same time, they hydroxylated palmitic acid only moderately and failed to convert hexadecane. Based on the now completed knowledge about the principal substrate specificities of all members of the CYP52A subfamily of C. maltosa, it became apparent that evolutionarily more distantly related P450 forms developed either to alkane or to fatty acid hydroxylases, whereas P450 forms which retained the ability to convert both types of substrates were also found to be evolutionarily related to both alkane and fatty acid hydroxylases.

Candida↗
PubMed1998

Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to glioma cells: implications for gene therapy.

Astrocytic tumors frequently express Fas/APO-1 (Fas), in sharp contrast to surrounding normal brain cells, providing a potential window through which selective killing of tumor cells could be pursued. To assess this possibility, we transduced Fas into U251, a glioma cell line resistant to anti-Fas antibody-mediated apoptosis, and obtained transfectants with high levels of Fas expression. Anti-Fas antibody showed significantly enhanced cytotoxicity for the transfectants, suggesting that U251 cells maintained an intercellular cascade of Fas-mediated apoptosis. When U251 transfectants with high-level Fas expression were transduced with Fas ligand-encoding gene via retrovirus, they were unaffected by exposure to anti-Fas antibody or Fas ligand adenovirus (Adeno-FL). Thus, retroviral induction of Fas ligand into the glioma cells with high levels of Fas led to the selection of cells that were resistant to Fas-dependent apoptosis. These resistant U251 transfectants were susceptible to FADD adenovirus (Adeno-FADD)-induced apoptosis, indicating that a cascade of death signals was blocked at the steps between Fas ligand and FADD. As for adenoviral transduction of Fas ligand into gliomas, gliomas with a relatively high level of expression of Fas were remarkably sensitive to Adeno-FL-induced apoptosis. Besides, Adeno-FADD induced pronounced apoptosis in all glioma cells. Our data suggest the possibility of using adenovirus-mediated transduction of Fas ligand and FADD genes as a therapeutic approach to target gliomas.

Adenoviridae↗
PubMed1998

Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK.

The function and the outside-in signaling pathways of alphaIIbbeta3 were examined in relation to cell adhesion using a megakaryoblastic leukemia cell line, CMK. After 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, the cells adhered to the culture plate and underwent megakaryocytic differentiation with expression of alphaIIbbeta3. Binding of soluble fibrinogen to the cells via alphaIIbbeta3 was dependent on cell adhesion. Cell detaching reduced the affinity of this integrin for soluble fibrinogen, although its surface expression was almost unchanged. In contrast, detached cells became tightly adherent to the fibrinogen-coated plate (solid-phase fibrinogen). The same ligand, fibrinogen, present either in soluble or solid-phase form, triggered differential signaling pathways mediated by alphaIIbbeta3. By the stimulation with soluble fibrinogen, Syk was tyrosine-phosphorylated but FAK was dephosphorylated, whereas solid-phase fibrinogen promptly caused tyrosine phosphorylation of FAK followed by delayed phosphorylation of Syk. In addition, the binding of soluble fibrinogen to the cells adherent to fibrinogen-coated plate resulted in tyrosine phosphorylation of integrin beta3 and a complex formation of integrin beta3 with Syk. This implies the cooperation of both soluble and solid-phase fibrinogen-mediated signaling pathways.

Cell Adhesion↗
PubMed1998

Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity.

The synthesis and in vitro optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives discovered by a random screening process, are described. FR180102 (7f), having a 3-acetamido-2,6-dichlorobenzyl moiety, was found to have extremely potent activity against H. pylori and no effect against a series of common Gram-positive and Gram-negative bacteria.

Acetamides↗
PubMed1998

Aspirin induces short-chain free fatty acid accumulation in rats.

Aspirin is used for the prophylaxis of infarction. A low dose of aspirin is effective for the prophylaxis of myocardial infarction, whereas a higher dose is necessary for that of stroke. Salicylic acid, the in vivo metabolite of aspirin, inhibits the beta-oxidation of short-chain fatty acids. Accordingly, drinking water containing 400, 800, or 1200 mg/l aspirin was given to each of eight rats for 30 days to determine the serum short-chain fatty acid levels. Analysis of variance and a post-hoc Fisher's protected least significant differences test revealed significantly increased levels (P < 0.05) of monocarboxylic acids, n-hexanoate, n-octanoate, n-decanoate, n-dodecanoate, and dicarboxylic acids, adipate (C6,) and suberate (C8): 78.7 +/- 36.2, 61.1 +/- 30.6, 215 +/- 151, 47.5 +/- 24.0, 3.64 +/- 2.09 and 1.71 +/- 1.45 micromol/l in the 800 mg/l aspirin group compared to 23.8 +/- 12.3, 20.1 +/- 9.0, 24.3 +/- 12.1, 6.3 +/- 5.6, 0.56 +/- 0.50 and 0.44 +/- 0.25 micromol/l in the control group, respectively. These levels were also increased in the 400 or 1200 mg/l aspirin groups but less so. These findings may help us to understand the aspirin toxicity in Reye's syndrome.

Analgesics, Non-Narcotic↗
PubMed1998

Large-scale preparation of human thrombin: polyethylene glycol potentiates the factor Xa-mediated activation of prothrombin.

We investigated the ability of polyethylene glycol 4000 to accelerate thrombin generation in a mixture of prothrombin and factor X at concentrations of 1-30%. In the presence of 5 mM of CaCl2, polyethylene glycol 4000 promoted prothrombin activation at concentrations above 1%. The peak of activation was seen at levels of 14 and 20% of polyethylene glycol 4000. The effect of the polyethylene glycol was remarkably dependent on its molecular weight; molecular weights greater than 2000 were required for accelerating thrombin generation. Under optimal conditions, polyethylene glycol 4000, in the presence of CaCl2, promoted conversion of all of the prothrombin into thrombin and its derivatives. We conclude that polyethylene glycol 4000, at concentrations ranging from 14 to 20%, effectively accelerates thrombin generation in the presence of 5 mM of CaCl2. This new method for preparing thrombin is based on the use of polyethylene glycol 4000 and CaCl2 and is applicable to the manufacture of thrombin.

Calcium Chloride↗
PubMed1998

Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene sensitizes cancer cells to low concentrations of 5-fluorouracil.

5-fluorouracil (5-FU), although a widely used chemotherapeutic agent, has a limited effect in the treatment of human solid tumors due to their resistance to the cytotoxic effects of 5-FU. Escherichia coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that catalyzes the synthesis of UMP from uracil and 5-phosphoribosyl-alpha-1-diphosphate. The present study demonstrates that adenovirus-mediated transduction of E. coli UPRT gene results in marked sensitization of colon, gastric, liver, and pancreas cancer cell lines to low concentration of 5-FU in vitro. The in vitro bystander effect was observed when only 10% of the hepatoma Hep3B cells were infected with UPRT-expressing adenovirus. In addition, 5-FU treatment of human hepatoma or gastric cancer xenografts in nude mice transduced with UPRT was demonstrated to result in significant in vivo antitumor effects. The adenovirus vector transduction of the UPRT gene followed by 5-FU administration is representative of a new chemosensitization strategy for cancer gene therapy.

Adenoviridae↗
PubMed1998

A live non-neurovirulent herpes simplex virus vector expresses beta-galactosidase in the nervous system of the Wistar and Sprague-Dawley strain rat for a prolonged period.

We have constructed a live non-neurovirulent herpes simplex virus vector expressing beta-galactosidase under the control of the latency associated transcript promoter without inducing inflammation. Pathogenicity of the recombinant virus (betaH1) was not observed in the cutaneous, intravenous and intracerebral infection in mice. When betaH1 was inoculated at the caudate putamen of rats, beta-galactosidase activity was observed in neurons at the inoculation site and its projecting frontal cortex. Expression of beta-galactosidase was observed in the neurons of the innervating dorsal root ganglia 45 days after inoculation of betaH1 into the hind paws of the rats. Neither inflammation nor tissue destruction was observed in both neural tissues in this study. Thus this non-neurovirulent recombinant virus is a suitable vector for expressing the foreign genes in the nervous system for the prolonged period.

Animals↗
PubMed1998

Genomic structure and promoter activity of the mouse polysialic acid synthase (mST8Sia IV/PST) gene.

The mouse gene encoding ST8Sia IV/PST, one of two polysialic acid synthases, was isolated and characterized. The mST8Sia IV/PST gene was found to comprise over 60 kilobases and to be composed of five exons. Primer extension analysis revealed that transcription started from 333 nucleotides upstream of the translational initiation site. Transfection with nested deletion mutants of the 5'-flanking region fused to the luciferase reporter gene revealed that the promoter activity of the -107/+145 region was correlated with the gene expression of mST8Sia IV/PST in embryonal carcinoma P19 and neuroblastoma F11 cells. This proximal promoter region lacks an apparent TATA box but has putative binding sites for transcription factors Sp1 and NF-Y (CCAAT binding protein) at nucleotide positions -66/-57 and -47/-37, respectively. Individual deletions and mutations of the inverted Sp1 binding site or inverted NF-Y binding site caused significant reduction of the promoter activity, indicating that each binding site was involved in essential transcription control. Mobility shift assaying also revealed that Sp1 and NF-Y in a nuclear extract of P19 cells bind to the promoter region of the mST8Sia IV/PST gene. Deletion of the region from -60 to -40, which contains parts of both the Sp1 and NF-Y binding sites, completely abolished the promoter activity, suggesting that both Sp1 and NF-Y are synergetically involved in transcription regulation of the mST8Sia IV/PST gene in P19 and F11 cells. Although the overall structures of the two polysialic acid synthase genes (ST8Sia II/STX and IV/PST) are very similar, there is no extensive sequence homology between the 5'-flanking regions of the ST8Sia II/STX and IV/PST genes, suggesting that these two genes are expressed under different regulatory systems.

Animals↗
PubMed1998

The primary site of CD4- 8- B220+ alphabeta T cells in lpr mice: the appendix in normal mice.

There have been no reports on an abundance of CD4- 8- B220+ alphabeta T cells, seen in autoimmune mice carrying the lpr gene (abnormal Fas gene), in any immune organs of normal mice. We herein report, however, that such alphabeta T cells were abundant at intraepithelial sites of the appendix in normal mice. They lacked the expression of NK1.1 Ags (C57BL/6 mice), but had the morphology of granular lymphocytes and contained forbidden T cell clones in the minor lymphocyte-stimulating antigen (Mls) system (C3H/He mice with Mls-1b2a). In other words, many properties of intraepithelial T cells in the appendix resembled those ascribed to abnormal alphabeta T cells, which expand in the lymph nodes and spleen of lpr mice. In the case of lpr mice, CD4- 8- B220+ alphabeta T cells first expanded in the appendix and then extended to other organs. CD4- 8- B220+ alphabeta T cells seemed to originate in situ from c-kit+ stem cells in the appendix. These results suggest that the appendix is one of the primary sites in which CD4- 8- B220+ alphabeta T cells exist, and that these cells carry many primordial properties as prototype T cells.

Animals↗
PubMed1998

Midkine exists in astrocytes in the early stage of cerebral infarction.

Midkine (MK), a heparin-binding neurotrophic factor, is expressed in the early stage of experimental cerebral infarction in the zone surrounding the infarct. Double immunostaining with anti-MK and anti-glial fibrillary acidic protein showed existence of MK in astrocytic cytoplasm on postoperative day 2. Immunoelectron microscopic analysis revealed the presence of MK in the swollen astrocytic processes on postoperative day 4.

Acute Disease↗
PubMed1998

Infrequent inactivation of DCC gene in replication error-positive colorectal cancers.

Colorectal cancers with and without the replication error (RER) exhibit fundamental differences in genotype and phenotype. While alterations in APC, p53, and K-ras genes have been characterized between RER+ and RER- colorectal cancers, the status of deleted in colorectal carcinomas (DCC) gene has not been yet. Alterations of DCC gene were analyzed in stage-matched two panels of 30 RER+ and 30 RER- colorectal cancers using semiquantitative reverse transcription-PCR and PCR-LOH analyses. Loss or reduction of DCC mRNA expression and allelic loss at the DCC locus were significantly less frequent in RER+ cancers than in RER- cancers. Interestingly, reduced DCC mRNA expression was observed in all 5 RER- cancers with liver metastasis. Our results support the concept that RER+ and RER- colorectal cancers represent different pathways of carcinogenesis and may give a hint for clarifying the specific mechanism of DCC inactivation in RER- colorectal cancers.

Colorectal Neoplasms↗
PubMed1998

Auxiliary heterotopic liver transplantation in the rat: a simplified model using cuff technique and application for congenitally hyperbilirubimemic Gunn rat.

To study the immunological and metabolic effects of auxiliary liver transplantation (ALT), a simple ALT model in rats was developed using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubin concentrations in Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained within normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubin levels did not return to the preoperative value of the Gunn rats. It is possible that hepatic stem cells included in ALT liver migrated to the host liver and differentiated into cells capable of producing certain enzymes.

Analysis of Variance↗
PubMed1998

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Adult↗
PubMed1998

Pathological analyses of early recurrence and malignant transformation in meningiomas.

We investigated factors of the early recurrence and malignant transformation of histologically benign meningiomas using immunohistochemistry for MIB-1 positive indices (PI) and p53 protein expression, a flow cytometric DNA analysis, and the examination of numerical chromosomal aberrations detected by fluorescence in situ hybridization using an alpha-satellite DNA probe and a bcr gene locus-specific probe. Twenty-six meningiomas of 23 patients were classified into two groups: the 3 patients in whom a recurrence was defined within two years after initial surgery and who showed histologically malignant features were classified as the early recurrent group, and the other 20 patients in whom recurrence did not develop during the same period were classified as the nonrecurrent group. DNA aneuploidy was observed in 40% of the nonrecurrent patients and in 67% of the early recurrent patients. Loss of chromosome 22 was the most common numerical aberration, but the aberrations characteristic of early recurrent meningiomas were not detected. The MIB-1 PI values of the early recurrent meningiomas were higher than those of nonrecurrent meningiomas, suggesting that MIB-1 PI is very important for biological and histopathological analyses and prediction of the future recurrence of meningiomas.

Aneuploidy↗