Maternal genes with localized mRNA and pattern formation of the ascidian embryo.
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Amino Acid Sequence↗
Biomedical subjects
S Yoshida
Publications and source records attributed to S Yoshida.
Expression of fas (CD95/APO-1) antigen induced by radiation therapy for diffuse B-cell lymphoma: immunohistochemical study.
Most malignant lymphomas show relatively high degrees of radiosensitivity, in which apoptosis has been shown to play an important role. Recently, the Fas (CD95/APO-1)/Fas ligand system has been identified as a key regulator of apoptosis in some types of lymphoma cell lines. In this study, we aimed to determine whether Fas antigen expression is induced by radiotherapy for malignant lymphoma and to clarify its possible correlation with the therapeutic effect of radiation therapy. Fifty-six patients with tumors of the tongue, oropharynx, and maxillary sinus were examined; four were confirmed as malignant lymphoma, and the rest were identified as squamous cell carcinoma. After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and specimens were preserved in liquid nitrogen until further examination. Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against Fas. Two of the four patients with malignant lymphoma showed Fas antigen expression on their tumor tissue at 4 and 10 Gy of radiotherapy. These tumors showed high radiosensitivity and disappeared at a dose of 20 Gy of radiotherapy. In samples from these two patients, DNA ladder formation was identified at 10 Gy. In 52 squamous cell carcinomas, staining for the Fas antigen showed negative or only slightly positive results. However, in one of the cases of squamous cell carcinoma, lymphocytes infiltrating into cancer tissue showed Fas antigen expression at 4 Gy of irradiation, and these lymphocytes disappeared on the tumor tissue at 10 Gy. Therefore, the high radiosensitivity of malignant lymphoma among our samples could be explained by the overexpression of Fas antigen induced by small doses of radiation therapy, and Fas ligand could be produced by infiltrating lymphocytes or may be expressed simultaneously on the lymphoma cells.
Aged↗
Immunohistochemical study of c-fos-positive lymphocytes infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance.
C-fos has been reported to be one of the immediate early genes in signal transduction systems after many kinds of stresses, including ionizing radiation. Changes in c-fos expression induced by radiation therapy in tumor tissues have not yet been reported. In this study, we have attempted to determine whether c-fos expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between c-fos expression and the therapeutic effects of radiation therapy. Twenty-seven patients with tumors of the oral cavity, oropharynx, and maxillary sinus were examined, all of which were confirmed as squamous cell carcinomas. After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and the specimens were preserved in liquid nitrogen for further examination. Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against c-fos. Three of the 27 patients with squamous cell carcinoma showed slight expression of c-fos in their tumor cells before and/or at 4 or 10 Gy of radiotherapy. The tumors showed high radiosensitivity. Concerning tumor-infiltrating lymphocytes, the rate of moderate or remarkable grades of c-fos-positive lymphocytes before radiotherapy and at radiation doses of 4, 10, and 20 Gy was 8.0, 29.2, 4.8, and 0%, respectively. The relationship between the immunohistochemical findings and the antitumor effect at a radiation dose of 20 Gy was examined on the corresponding H&E-stained sections. In patients whose infiltration of c-fos-positive lymphocytes into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy, the tumors responded significantly well to radiation therapy (P < 0.025, chi2 test), and the patients took a significantly favorable clinical course (P < 0.05, chi2 test). In a sample from one of the patients, c-fos-positive lymphocytes were identified as CD4 positive and CD8 negative. Therefore, the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of c-fos in the tumor-infiltrating lymphocytes induced by small doses of radiation therapy, and these activated lymphocytes exerted a cytotoxic effect against the cancer cells.
Adult↗
Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and clinical stages of primary ovarian tumors.
To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and clinical stages of ovarian tumors, we analyzed homozygous deletion and somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of the 5'-CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6 ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of p16/CDKN2 was found in only 1 primary tumor, but mutation of p15/MTS2 was not detected in any sample. None of the 28 primary tumors or 6 cell lines was hypermethylated at the 5'-CpG island of p16/CDKN2. The incidence of inactivation of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7 of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2 and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear-cell (1 of 4) carcinomas. However, only normal sequences of these genes were detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus was detected in 1 of 19 (5%) tumors, but no change at the D9S171 locus was observed in 17 tumors. These results suggest that: (i) homozygous deletion is the main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the histological type-specific events involved in ovarian tumorigenesis; and (iii) inactivation of p16/CDKN2 is potentially involved in the progression of ovarian tumors in advanced stages.
Carcinoma↗
Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1.
The expression of vascular endothelial growth factor (VEGF) has been implicated in brain tumor angiogenesis, and the promoter region for the VEGF gene contains several SP-1 and AP-1 (c-Fos and c-Jun) binding motifs. Among eight human glioma cell lines, cellular mRNA levels of transcription factors SP-1 and AP-1 (c-Fos and c-Jun) were found to be closely correlated with those of VEGF. VEGF expression appears to be highly susceptible to hypoxia or exogenous cytokines and growth factors. Of various cytokines and growth factors, basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-alpha), and interleukin 1 most potently enhanced VEGF mRNA levels of a glioma cell line, U251. Incubation of the glioma cells with bFGF or TNF-alpha increased both VEGF and SP-1 mRNA at 30 min and c-Fos mRNA at 1-3 h, over 5-fold. Nuclear run-on assays showed an apparent increase of the transcription of the VEGF gene as well as the SP-1 gene by bFGF or TNF-alpha. Gel mobility shift assays demonstrated that only SP-1 binding activity was increased 1 h after exposure to bFGF or TNF-alpha, and also that AP-1, but not SP-1, activity was significantly activated by hypoxia. Mithramycin, an inhibitor of SP-1, at 1-10 nM inhibited activation of the VEGF gene by bFGF or TNF-alpha but not that by hypoxia. Western blot analysis also demonstrated an increase in cellular amounts of VEGF by TNF-alpha and a decrease by co-administration with mithramycin. The promoter activity of the VEGF gene, which contains five SP-1 binding sites and one AP-1 binding site but not hypoxia regulatory elements, was enhanced by bFGF or TNF-alpha but not by hypoxia. The chloramphenicol acetyltransferase assay with VEGF promoter deletion constructs demonstrated that four clusterized SP-1 binding sites in the proximal promoter were essential for the basal transcription and the TNF-alpha-dependent activation. These data indicated that the expression of the VEGF gene enhanced by bFGF or TNF-alpha appeared to be mediated in part through the transcription factor SP-1, suggesting a different mechanism from that for hypoxia-induced activation of the VEGF gene.
Antineoplastic Agents↗
A possible origin of newly-born bacterial genes: significance of GC-rich nonstop frame on antisense strand.
Base compositions were examined at every position in codons of more than 50 genes from taxonomically different bacteria and of the corresponding antisense sequences on the bacterial genes. We propose that the nonstop frame on antisense strand [NSF(a)] of GC-rich bacterial genes is the most promising sequence for newly-born genes. Reasons are: (i) NSF(a) frequently appears on the antisense strand of GC-rich bacterial genes; (ii) base compositions at three positions in the codon are nearly symmetrical between the gene having around 55% GC content and the corresponding NSF(a); (iii) amino acid compositions of actual proteins are also similar to those of hypothetical proteins from the GC-rich NSF(a); and (iv) proteins from NSF(a) of 60% or more GC content are flexible enough to adapt to various molecules encountered as novel substrates, due to the high glycine content. To support our proposition, using a computer we generated hypothetical antisense sequences with the same base compositions as of NSF(a) at each base position in the codon, and examined properties of resulting proteins encoded by the imaginary genes. It was confirmed that NSF(a) of GC-rich gene carrying about 60% GC content is competent enough for a newly-born gene.
Amino Acids↗
Positron emission tomography study of the alterations in brain distribution of [11C]methamphetamine in methamphetamine-sensitized dog.
We newly prepared a MAP-sensitized dog by repeated MAP treatment and studied the brain distribution of [11C]MAP in the normal and the MAP-sensitized dog using PET. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. No difference was found in the metabolism of MAP between the two conditions. The significant increase of [11C]MAP in the MAP-sensitized brain indicates that subchronic MAP administration causes some functional change in the uptake site of MAP. The pharmacokinetic change may, in part, account for behavioral sensitization.
Animals↗
Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis.
Using 39 clinical isolates of Mycobacterium strains with a broad range of susceptibility to rifampicin, we examined the relationship between the degree of resistance to rifampicin and mutational sites of the rpoB gene. All rifampicin-resistant strains had missense mutations. Twenty strains (95%) had a mutation in the cluster I region, which has also been reported in Escherichia coli [Jin and Gross (1988) J. Mol. Biol. 202, 45-58], and the remaining one strain had a mutation at codon 381 [Ala-->Val] in the N-terminal region, which has not been reported in E. coli. Among 18 rifampicin-susceptible strains, two had a mutation in the cluster I region and the other three strains had a mutation in the cluster III region. The mutations at codons 513 (5%), 526 (33%) or 531 (43%) in the cluster I region led to high level resistance to rifampicin (50 micrograms ml-1 < or = MIC). The mutations at the other sites, in the cluster III region (codons 679 or 687) and even in the cluster I region (codon 514, 521, or 533), showed low level (MIC = 12.5 micrograms ml-1) or no (MIC < 0.39 microgram ml-1) resistance to rifampicin. These results suggest that mutations in the rpoB gene are, mostly, but not necessarily, associated with rifampicin resistance of M. tuberculosis, and the sites of mutations on the rpoB gene will affect the level of resistance to rifampicin.
Amino Acid Sequence↗
Lack of relationship between soluble erythropoietin receptor levels and erythroid parameters in anemic patients.
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Amino Acid Sequence↗
Purification and characterization of nuclear alkaline phospholipase A2 in rat ascites hepatoma cells.
The alkaline phospholipase A2 (PLA2) was purified from nuclei of rat ascites hepatoma cells (AH7974) by column chromatography with a Sephacryl S-300 column and an immunoadsorbent using anti-group II PLA2 monoclonal antibody. From these two columns, the alkaline PLA2 was eluted in parallel with a 17-kDa protein which is reactive to another anti-group II PLA2 polyclonal antibody. Approximately 80% of nuclear PLA2 was inhibited by this antibody. The alkaline PLA2 was found in association with the chromatin fraction among subnuclear fractions. By an immunocytochemical staining, the nuclei of AH7974 were stained more strongly than other parts of cells with anti-group II PLA2 antiserum.
Animals↗
Down-regulation of telomerase activity is an early event in the differentiation of HL60 cells.
Telomerase has been shown to be essential for unlimited cell proliferation and has been linked to immortality. However, still very little is known about the mechanism by which this enzyme is activated or inactivated. To investigate its regulation, we closely monitored telomerase activity during HL60 cell differentiation induced by either 1 alpha,25-dihydroxyvitamin D3 or all-trans retinoic acid. To that effect, we used a new combination of TRAP assay and SPA, which provides reproducible data for the quantitation and detection of variations in enzyme activity. We thereby observed that the decrease in telomerase activity after induction of differentiation by either of these agents is an early event of the differentiation process rather than its consequence, and that it is independent of the growth arrest pathway. It is neither due to a reduced expression of its RNA component nor to the appearance of a telomerase inhibitor in differentiating cells but is parallel to an increase in p21 and Rb mRNA expression.
Base Sequence↗
Fatty acids selectively inhibit eukaryotic DNA polymerase activities in vitro.
The in vitro relationship between eukaryotic DNA polymerases and fatty acids was investigated. Some fatty acids strongly inhibited the activities of DNA polymerase alpha and/or beta in vitro. The kinetics of inhibition by linoleic acid showed that DNA polymerase alpha was non-competitively inhibited with respect to the DNA template and substrate (dTTP), while DNA polymerase beta was inhibited competitively with both DNA and substrate.
Animals↗
[Mixed connective tissue disease: progress in diagnosis and treatment. III. Treatment. 3. Clinical aspects and treatment of specific conditions. 5) Peripheral circulatory dysfunction].
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Humans↗
[Case of sarcoidosis diagnosed by myocardial biopsy].
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Adult↗
Possible Clustering of the Most Energetic Cosmic Rays within a Limited Space Angle Observed by the Akeno Giant Air Shower Array.
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Journal Article↗
Kindling induces neuropsin mRNA in the mouse brain.
Neuropsin mRNA expression was analyzed and mapped in the mouse brains after kindling epileptogenesis by using in situ hybridization histochemistry. Dynamic increases of the neuropsin mRNA were observed in the layer II of prelimbic, somatosensory, auditory, perirhinal, entorhinal, and piriform cortices in an activity-dependent manner, though no neuropsin gene was expressed in these areas in control mice. In addition to the confirmation of our previous studies showing increases of mRNA in the hippocampus and amygdaloid complex, there were also remarkable increases of the neuropsin mRNA in the limbic areas, such as the accessory olfactory nucleus, the medial and lateral septal nucleus, the nucleus of diagonal band, the substantia innominata and the zona incerta. The dynamic activity-dependent changes of the gene expression and the site-specificity of neuropsin localization are suggesting that this molecule is implicated in cortical- and limbic-specific neuronal reorganization.
Animals↗
Occupation of the QB-binding pocket by a photosystem II inhibitor triggers dark cleavage of the D1 protein subjected to brief preillumination.
The D1 protein of the photosystem (PS) II reaction center turns over very rapidly in a light-dependent manner initiated by its selective and specific cleavage. The cleavage of D1 was studied by using a PS II inhibitor, N-octyl-3-nitro-2,4,6-trihydroxybenzamide (PNO8), as a molecular probe. The following results were obtained. (i) D1 was selectively cleaved into 23-kDa N-terminal and 9-kDa C-terminal fragments in complete darkness by PNO8 at a single site in a D-E loop connecting membrane-spanning helices D and E. (ii) The cleavage was markedly enhanced when PS II was illuminated for a brief period before the addition of PNO8 in darkness. (iii) The effect of preillumination was slowly lost during incubation in the dark, with a decay half-time of approximately 1 h at 25 degrees C. (iv) The light intensity of preillumination required for the cleavage was much lower than that required for O2 evolution. (v) The light-triggered cleavage of D1 was observed in thylakoids, PS II membranes, and PS II core particles, but not in purified PS II reaction centers. More than 60% of D1 was cleaved into the two fragments with no other by-products. (vi) The cleavage reaction revealed a marked pH dependence that was considerably different from that for inhibition of PS II activity. The results are interpreted as indicating that the binding of PNO8 to the QB-binding pocket triggers proteolytic cleavage of D1 that has been previously modified during illumination.
Benzamides↗
Dissociated release of tetrahydrobiopterin and nitric oxide by lipopolysaccharide from mouse neuroblastoma cells.
We examined the release of tetrahydrobiopterin ((6R)-L-erythro-dihydroxypropyl-2-amino-4-hydroxy-5,6,7, 8-tetrahydropteridine; BH4) and nitric oxide induced by lipopolysaccharide from mouse neuroblastoma N1E-115 cells by measuring BH4 and nitric oxide derivatives, nitrites and nitrates, harbored in the conditioned media. The stimulation of the cells by 1 microgram/ml of lipopolysaccharide for 24 h induced 2-fold increase in the release of BH4 from the cells, but did not induce the nitric oxide release from the cells. Although such increase in BH4 release from the cells was blocked by the inhibitors of nuclear factor-kappa B or protein tyrosine kinases, the release of nitric oxide was not affected by such inhibitors. Our results may suggest that the inductions of BH4 and nitric oxide in this neuroblastoma cell line are processed in different ways and that this cell line is also different from the immune cells in the central nervous system such as microglia in this respect.
Animals↗