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T Yano

Publications and source records attributed to T Yano.

At least 235 records · Page 13Linked to original sources
PubMed1998

Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1.

T cell activation requires the import of NF-AT transcription factors to the nucleus, a process promoted by calcineurin-dependent dephosphorylation and inhibited by poorly understood protein kinases. Here, we report the identification of two protein kinases that oppose NF-AT4 nuclear import. Casein kinase Ialpha directly binds and phosphorylates NF-AT4, resulting in the inhibiton of NF-AT4 nuclear translocation. MEKK1 indirectly suppresses NF-AT4 nuclear import by stabilizing the interaction between NF-AT4 and CKIalpha. CKIalpha thus acts to establish an intramolecular masking of the nuclear location signal on NF-AT4, while MEKK1 augments this mechanism, and may further provide a link to signal transduction pathways regulating NF-AT4.

Amino Acid Sequence↗
PubMed1998

Directed evolution of an aspartate aminotransferase with new substrate specificities.

The substrate specificity of aspartate aminotransferase was successfully modified by directed molecular evolution using a combination of DNA shuffling and selection in an auxotrophic Escherichia coli strain. After five rounds of selection, one of the evolved mutants showed a 10(5)-fold increase in the catalytic efficiency (kcat/Km) for beta-branched amino and 2-oxo acids and a 30-fold decrease in that for the native substrates compared with the wild-type enzyme. The mutant had 13 amino acid substitutions, 6 of which contributed 80-90% to the total effect. Five of these six substitutions were conserved among the five mutants that showed the highest activity for beta-branched substrates. Interestingly, only one of the six functionally important residues is located within a distance of direct interaction with the substrate, supporting the idea that rational design of the substrate specificity of an enzyme is very difficult. The present results show that directed molecular evolution is a powerful technique for enzyme redesign if an adequate selection system is applied.

Amino Acid Sequence↗
PubMed1998

A putative tumor suppressor, TSG101, acts as a transcriptional suppressor through its coiled-coil domain.

TSG101 is thought as a putative tumor suppressor gene, and mutations of this gene were recently found in 7 of 15 breast cancer patients, though the physiological function remains to be elucidated. In this report, we showed that TSG101 protein acts as a transcriptional suppressor for estrogen receptor (ER) as well as other members of the nuclear hormone receptor super-family, VP16, and on its own. The basal promoter activity was also inhibited by TSG101. The suppression of transcription by TSG101 protein required its coiled-coil domain, which is also shown to be required for the tumor suppressive function. Expressed TSG101 protein did not have any histone acetylase nor deacetylase activity, which certain transcriptional co-factors have. The requirement of the same domain in the TSG101 protein for transcriptional suppression and in the tumor suppression indicates a possibility that transcriptional suppression of TSG101 is related to its tumor suppression.

Acetyltransferases↗
PubMed1998

The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in mice based on the regulation of polyamine metabolism.

The present study was carried out in order to estimate a usefulness of vitamin E against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Feeding high doses of vitamin E suppressed the NNK-induced elevation of the activity of ornithine decarboxylase, a key enzyme of polyamine biosynthesis, in the lungs of mice at 4 weeks after injection. In contrast, the vitamin elevated the NNK-induced decrease of the activity of spermidine/spermine N1-acetyltransferase, a key enzyme of polyamine biodegradation. In conjugation with these events, the NNK-increased level of proliferating nuclear cell antigen as a marker of cell proliferation was suppressed by vitamin E treatment. Also, the supply of high doses of vitamin E suppressed NNK-induced lung tumorigenesis in mice. These results suggest that vitamin E inhibits the development of lung tumors in mice treated with NNK, partly due to the regulation of polyamine metabolism.

Animals↗
PubMed1998

Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene.

ALL1, the human homologue of Drosophila trithorax, is directly involved in human acute leukemias associated with abnormalities at 11q23. Using the differential display method, we isolated a gene that is down-regulated in All1 double-knockout mouse embryonic stem (ES) cells. The gene, designated ARP1 (also termed RIEG, Ptx2, or Otlx2), is a member of a family of homeotic genes containing a short motif shared with several homeobox genes. Using a bacterially synthesized All1 polypeptide encompassing the AT-hook motifs, we identified a 0.5-kb ARP1 DNA fragment that preferentially bound to the polypeptide. Within this DNA, a region of approximately 100 bp was protected by the polypeptide from digestion with ExoIII and DNase I. Whole-mount in situ hybridization to early mouse embryos of 9.5-10.5 days indicated a complex pattern of Arp1 expression spatially overlapping with the expression of All1. Although the ARP1 gene is expressed strongly in bone marrow cells, no transcripts were detected in six leukemia cell lines with 11q23 translocations. These results suggest that ARP1 is up-regulated by the All1 protein, possibly through direct interaction with an upstream DNA sequence of the former. The results are also consistent with the suggestion that ALL1 chimeric proteins resulting from 11q23 abnormalities act in a dominant negative fashion.

Amino Acid Sequence↗
PubMed1998

Expression and localization of inducible nitric oxide synthase in the rat ovary: a possible involvement of nitric oxide in the follicular development.

In the present study, using Northern blot analysis, we demonstrated that the level of iNOS mRNA in the ovary of immature rats decreased after 6 h of pregnant mare serum gonadotropin administration and recovered gradually up to the untreated level 48 h after the administration. Both in situ hybridization and immunohistochemistry revealed that iNOS mRNA and protein was predominantly localized in granulosa cells in most of immature follicles, but not in mature follicles with an antrum, which was a consistent finding regardless of gonadotropin treatment. Furthermore, we found that cultured granulosa cells had the ability to express iNOS mRNA in the presence of cytokines such as tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma, which are inherently detectable in the ovary. These results raise the possibility that locally produced NO synthesized by iNOS may be involved in the developmental status of ovarian follicles in concert with gonadotropin.

Animals↗
PubMed1998

Interleukin-6 produced by pancreatic carcinoma cells enhances humoral immune responses against tumor cells: a possible event in tumor regression.

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to the liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 and generates numerous metastases to the liver. An IL-6 high-producer clone (PCI-43h) generated few metastases; IL-6 production thus has a direct effect on metastasis, whereas other transfectants (PCI-43l and PCI-43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. Tumor-reactive IgM was detected in sera from all mice, irrespective of inoculated PCI-43 species, with a slight augmentation being noted in PCI-43h-inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI-43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI-43 transfectants (1 x 10(6)/0.1 ml). Only PCI-43h formed palpable masses in SCID beige mice, whereas it first grew to be palpable but subsequently became not palpable in nude mice, thereby revealing a dual action of tumor-derived IL-6. Thus, tumor-derived IL-6 confers growth promotion in SCID beige mice, while the same cytokine exhibits anti-tumorigenic functions, presumably through humoral immune responses, in nude mice.

Animals↗
PubMed1998

Induction of heme oxygenase-1 in toxic renal injury: mercuric chloride-induced acute renal failure in rat.

It is known that mercuric chloride (HgCl2) is a nephrotoxicant. When HgCl2 (1 mg/kg body weight) was intraperitoneally injected into rats, acute renal failure was induced. Histological changes in the kidneys were exclusively observed in the proximal tubules and the severe necrosis was found as early as 24 h after HgCl2 injection. The heme oxygenase-1 (HO-1) mRNA was strongly and promptly induced at about 2.5 h, the earliest time examined and abruptly decreased after the injection. Whereas the time course of HO-1 protein level was delayed as compared with that of HO-1 mRNA level. The levels of HO-1 mRNA and protein similarly increased with dose-dependent manner. The localization of HO-1 protein was restricted to the tubule cells. These findings suggest the potential involvement of HO-1 induction in the response to HgCl2-induced acute renal injury.

Acute Kidney Injury↗
PubMed1998

Effects of accelerated carbon-ions on growth inhibition of transplantable human esophageal cancer in nude mice.

We have studied the effectiveness of 290 MeV/u carbon-ion (C-) beams (linear energy transfer (LET) of 70 keV/mm) and 200 kVp X-rays on tumor growth inhibition as an in vivo model for radiotherapy of cancer. We measured the size of tumor growth of transplantable human esophageal cancer in nude mice after radiation with C-beams and compared this with X-rays as the control. A significant inhibition of tumor growth was observed by C-beams as compared with X-rays. The relative biological effectiveness (RBE) of C-beams against X-rays was 2.02. Histopathological studies showed that C-beams at 20 Gy induced prominent necrosis in the central region and multinucleate giant cells and inflammatory cells in peripheral regions of the tumor, whereas X-rays at 20 Gy induced only mild necrosis. The high RBE of C-beams obtained in this study provides in vivo evidence that C-beams are more effective than conventional X-rays for radiotherapy of cancer.

Aged↗
PubMed1998

Antitumor spectra of anthracyclines against gastric cancer tissues obtained from surgical specimens with reference to P-glycoprotein expression.

BACKGROUND AND OBJECTIVES: Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression. METHODS: Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP. RESULTS: A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR. CONCLUSIONS: The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Local dynamic changes of the cervix associated with incompetent cervix before and after Shirodkar's operation.

A 31-year-old woman, gravida 2 para 1, visited our clinic for routine follow-up at 20 weeks' gestation. Although she had no abdominal pain or pressure, digital vaginal examination revealed dilatation of the internal cervical os of 1.5 cm, and transvaginal sonography demonstrated dynamic changes in the shape of the cervical canal. The patient underwent Shirodkar's operation. Routine postoperative assessment of the cervix with transvaginal sonography showed dynamic dilatation of the upper cervix (above the cerclage), which was accompanied by a sensation of pelvic pressure but no apparent uterine contractions. A healthy male infant weighing 2,980 g was delivered at 38 weeks' gestation.

Adult↗
PubMed1998

Paragonimiasis westermani presenting as an asymptomatic nodular lesion in the lung: report of a case.

A 57-year-old man with a history of having consumed fresh-water crab 8 months previously presented with a solitary mass lesion in the left lung without any symptoms. Since neoplastic disease could not be ruled out, an open biopsy was performed, and histological examination confirmed a definite diagnosis of paragonimiasis. A high level of the anti-Paragonimus westermani antibody was detected in the sera of the patient, but this level decreased substantially 3 months after chemotherapy with bithionol.

Animals↗
PubMed1998

The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA injury and the fixation of the DNA injury in mouse lungs.

In order to estimate the effect of vitamin E on DNA injury and K-ras point mutation at an early stage of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice, the present study was carried out. Presupplement with vitamin E about 15 times more than control for a week significantly inhibited NNK-induced O6-methylguanine formation in the lungs of mice at 4 and 168 h after the injection. At 30 days after the NNK injection. the activation of K-ras oncogene with a 12th codon GC-->AT transition was detected in 56% of lung samples tested by mutant-allele-specific amplification. Vitamin E supplement reduced the frequency of the mutation to 30%. These results suggest that vitamin E suppresses NNK-induced DNA injury and subsequent fixation of the injury during the initiation and post-initiation phases of the lung tumorigenesis in mice.

Animals↗
PubMed1998

The repetitive activation of extracellular signal-regulated kinase is required for renal regeneration in rat.

In this study, we investigated the activation of p42 extracellular signal-regulated kinase (ERK2) during renal regeneration after HgCl2-induced acute renal failure (ARF) in rat. ERK2 activation was observed at 5 and 29 hr after HgCl2 injection, respectively. The tyrosine phosphorylation of hepatocyte growth factor receptor (c-MET) occurred between 2.5 and 5 hr after the treatment. On the other hand, the phosphorylation of epidermal growth factor receptor (EGFR) was transiently observed at 29 hr after the injection. The peak of ornithine decarboxylase activity as a marker of G1 phase was at 10 hr, and subsequently the labeling index of proliferating cell nuclear antigen as a marker of S phase increased at 53 hr. These results indicate that the repetitive activation of ERK2 related to the phosphorylation of c-MET and EGFR is required for the renal regeneration in HgCl2-induced ARF of rat.

Acute Kidney Injury↗
PubMed1998

HLA class I and class II expression of pulmonary adenocarcinoma cells and the influence of interferon gamma.

BACKGROUND: The clinico-biological significance of HLA (both class I antigen and class II one) expressed on tumor cells still remains controversial. METHODS: Tumor cells were freshly separated from 33 surgical specimens of pulmonary adenocarcinoma. The tumor cells were incubated for 24 h in the presence or absence of IFN-gamma (130 International Units/ml). After incubation, the cells were cytocentrifuged onto glass slides and immunostained with either an anti-HLA class I (A, B, C) monoclonal antibody or anti-HLA class II (DR) one. RESULTS: In 22 of 33 cases (66.7%), the HLA class I were individually expressed by more than 60% of tumor cells while so were the HLA class II in 15 (45.4%). No significant correlation was observed between the HLA class I expression and the HLA class II one. The proportion of HLA class I-positive tumor cells correlated with neither the grade of histological differentiation nor the stage of disease. In contrast, the proportion of HLA class II-positive tumor cells correlated with both the grade of histological differentiation and the stage. In most cases, IFN-gamma was found to increase the proportion of class II-positive tumor cells as well as that of class I-positive cells. CONCLUSIONS: The above findings thus suggested that the HLA class II expression might therefore represent a manifestation of cellular differentiation and that IFN-gamma may, as a result, have the potential to differentiate cancer cells.

Adenocarcinoma↗
PubMed1998

Cytotoxin produced by Escherichia coli isolated from chickens with swollen head syndrome (SHS).

This study was conducted to determine the presence of selected virulence factors in Escherichia coli recovered from swollen head syndrome (SHS) in chickens. Thirty-six (72%) of 50 isolates of E. coli from SHS were shown to produce a cytotoxin that was active on Vero and HeLa but not on Y-1 cells. The toxin was called VT2y because the cytotoxic effect on Vero cells was morphologically similar to that produced by E. coli verotoxins (VTs), and this effect was neutralized by antiserum against VT2 but not by antiserum against VT1. Interestingly, DNA probes for VT1 and VT2 failed to hybridize the VT2y-positive isolates with total DNA. Although the role of this toxin in SHS has yet to be demonstrated, the marked edema which characterizes affected chickens is consistent with the action of a toxin such as verotoxin which targets vascular endothelium.

Animals↗
PubMed1998

Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann-Pick disease type C.

A 15-year-old boy was suffering from splenomegaly and a 10-year history of a neurologic disorder that included mental retardation, vertical supranuclear gaze palsy, dysarthria, ataxia, and dystonia. Bone marrow aspirates revealed foamy cells with storage materials which were positive with filipin staining. Cultured skin fibroblasts derived from the patient showed moderate loss of sphingomyelinase activity and the impairment of cholesterol esterification. The characteristic clinical presentations and typical histochemical findings of this patient met the diagnostic criteria of Niemann-Pick disease type C (NPC). In the fibroblasts from the patient, there was an accumulation of GM2 ganglioside around their cytoplasms. Increased levels of glycolipids. including GM2 ganglioside are reported in the cerebral cortex of NPC, but not in the fibroblasts. The fibroblasts derived from NPC may reflect the abnormal metabolism of glycolipids in the central nervous system of NPC.

Adolescent↗