PubMed Health⌕ Search

Biomedical subjects

S Yajima

Publications and source records attributed to S Yajima.

At least 19 recordsLinked to original sources
PubMed2000

The effect of 6-methylthiohexyl isothiocyanate isolated from Wasabia japonica (wasabi) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-buatnone-induced lung tumorigenesis in mice.

The present study was undertaken to estimate the effect of 6-methylthiohexyl isothiocyanate (6MHITC) isolated from Wasabia japonica (wasabi) pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice. Pretreatment with 6MHITC for 4 consecutive days at a daily dose of 5 micromol significantly inhibited NNK-induced O(6)-methylguanine formation in lungs at 4 h after the injection. In conjugation with this inhibitory effect, 6MHITC suppressed the increase in proliferating nuclear cell antigen level as well as ornithine decarboxylase activity at a promotion stage of NNK-induced lung tumorigenesis. Finally, this treatment of 6MHITC suppressed the NNK-induced lung tumorigenesis in mice. These results suggest that 6MHITC inhibits the development of lung tumors in mice treated with NNK, due to the suppression of initiation stage.

Animals↗
PubMed2000

Rifampicin-associated pseudomembranous colitis.

We report a case of pseudomembranous colitis that developed in a patient with liver cirrhosis during anti-tuberculosis therapy with rifampicin and isoniazid. The association between rifampicin and pseudomembranous colitis has been controversial; this report, however, supports the association. Colonoscopy performed 3 days after the onset of the pseudomembranous colitis revealed only reddish patches and a few aphthoid lesions, but 4 days later pseudomembranes were apparent. The pseudomembranous colitis was successfully controlled by discontinuation of the anti-tuberculosis agents, along with the administration of lactic acid bacteria, without vancomycin or metronidazole. Possible predisposing factors for the development of pseudomembranous colitis in this patient are also discussed.

Antibiotics, Antitubercular↗
PubMed1999

Regulation of striatal dopamine receptors by corticosterone: an in vivo and in vitro study.

The effects of chronic corticosterone administration and adrenalectomy on the expression of brain dopamine receptors were studied in rats. In situ hybridization and receptor binding autoradiography were carried out to determine D1, D2 and D3 receptor expression in dorsal and ventral striata. Except for down-regulation of D2 mRNA in dorsal striatum after 2 week corticosterone treatment, no other significant changes were detected. In addition, the transcriptional regulation of D1 and D2 gene promoters by glucocorticoids was studied in neuroblastoma cell lines using transient transfections. While a small segment of the D2-promoter could be activated three-fold by dexamethasone, large fragments of neither D1 or D2 promoters were regulated by this treatment. Glucocorticoids do not appear to have direct overall effects on striatal dopamine receptor expression. The observed down-regulation of D2 receptor mRNA in the dorsal striatum in vivo is likely secondary to increased striatal dopamine release induced by corticosterone.

Adrenal Glands↗
PubMed1999

Regulation of striatal dopamine receptors by estrogen.

The ability of estrogen to modulate the expression of ventral and dorsal striatal dopamine receptors D(1), D(2,) and D(3) was examined in vivo using semi-quantitative in situ hybridization and ligand binding autoradiography. Two-week treatment with subcutaneous pellets of 17beta-estradiol (25 mg) downregulated D(2) dopamine receptor mRNA in both dorsal and ventral striatum (shell and core regions of nucleus accumbens). No significant changes in D(1) or D(3) mRNA expression were detected. Ligand binding autoradiography did not reveal changes in D(1), D(2,) or D(3) receptor protein expression. We also assessed the ability of 17beta-estradiol to regulate D(2) gene promoter activity in NB41A3 neuroblastoma cells that express this gene endogenously using co-transfections with an estrogen receptor expression vector. While a small fragment of the D(2) promoter could be activated 2.5-fold by estrogen, a larger portion of the D(2) gene was not regulated by this treatment. Estrogens do not appear to have a net effect on striatal dopamine receptor expression. The observed downregulation of D(2) receptor mRNA in the dorsal and ventral striatum in vivo could be secondary to the increased striatal dopamine release induced by estrogen. Synapse 34:222-227, 1999. Published 1999 Wiley-Liss, Inc.

Animals↗
PubMed1999

Activation of extracellular signal-regulated kinase in lung tissues of mice treated with carcinogen.

The activation of extracellular signal-regulated kinase (ERK) in lung tissues of mice, as determined by the appearance of phosphorylated form, was observed on day 30 after urethane injection, and the activation also occurred in urethane-induced lung tumors. Immunohistochemical analysis using anti-phosphorylated ERK antibody indicated that the active form of ERK localized in alveolar epithelial cells. Furthermore, we confirmed by immunoprecipitation and immunoblot analysis that other essential components of the ERK cascade, that is, Ras, Raf and MEK (known as ERK kinase) were activated. These results indicate that the activation of the ERK signal in alveolar epithelial cells at the early stage of urethane-induced lung carcinogenesis is an important factor to develop lung tumors.

Animals↗
PubMed1999

Neural cell line-specific regulatory DNA cassettes harboring the murine D1A dopamine receptor promoter.

Transcription in the human and rat D1A dopamine receptor genes proceeds from two distinct promoters in neuronal cells while only the downstream intronic promoter is active in renal cells. To investigate the utility of these promoters in the brain cell-specific expression of transgenes, we now studied the 5' flanking region of the murine D1A gene. We confirmed the presence of two functional promoters utilized for the tissue-specific regulation of this gene similar to its human and rat homologues. The cloned 1.4-kb genomic fragment spans nucleotides - 967 to + 384 relative to the first ATG codon and includes intron 1 between bases -534 to -420. Transient expression analyses using various chloramphenicol acetyltransferase constructs revealed that the murine D1A upstream promoter fused with the human D1A gene activator sequence ActAR1 has potent transcriptional activity in a D1A-expressing neuronal cell line but not in other cell lines tested including renal (OK cells), glial (C6) and hepatic (HepG2), suggesting that this hybrid construct harbors neural cell-specific elements. The availability of potent regulatory DNA cassettes harboring the murine D1A gene promoter could aid testing the neuronal-specific expression of transgenes in vivo.

Amino Acid Sequence↗
PubMed1999

In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid.

A putative transcription factor induced in vitro by glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta was recently cloned and characterized [Yajima S. et al. (1997) J. Neurosci. 17, 8657-8666]. The messenger RNA of this protein, termed murine GDNF-inducible transcription factor (mGIF, hereafter referred to as GIF), is localized within cortical and hippocampal regions of brain, suggesting that GIF might be regulated by perturbations of these brain regions. In an effort to learn more about the role of GIF in vivo, we examined GIF messenger RNA in the brains of rats treated with the glutamatergic agonist kainic acid. This treatment is known to induce seizures and alter the messenger RNA expression of several growth factors, including GDNF, in several brain regions. Rats were given intraperitoneal saline (1 ml/kg) or kainic acid (15 mg/kg) and were killed at various time-points for in situ hybridization of brain sections with a GIF messenger RNA riboprobe. In saline-treated rats, GIF messenger RNA was present at low levels in cerebral cortex, hippocampus and hippocampal remnants such as the taenia tecta. Kainic acid treatment induced robust increases in GIF messenger RNA in several brain regions, including cerebral cortex, hippocampus, caudate-putamen, nucleus accumbens, and several nuclei of the amygdala and hypothalamus. Most brain regions showed the greatest increase in GIF messenger RNA 4-6 h after kainic acid administration and a return towards normal levels at 48 h. The CA3 region of hippocampus, however, showed a more rapid increase in GIF messenger RNA that was also evident 48 h after kainic acid administration. These results demonstrate that GIF messenger RNA can be regulated in vivo, and that this novel factor warrants further study as a central mediator of GDNF and perhaps other neurotrophic factors.

Animals↗
PubMed1999

Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia.

The purpose of this study was to investigate the biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia (ALL). We carried out in vitro tests with a 4-day culture and a methyl-thiazol-tetrazolium assay on bone marrow samples from 209 children newly diagnosed with ALL. After testing the resistance of leukemic cells to 14 drugs, we classified the patients into two groups according to their sensitivity to three drugs (prednisolone, L-asparaginase, and vincristine) used in remission induction therapy. The three-drug resistant group (RR: sensitive to no drugs or to one drug) correlated with both short-term and long-term treatment failure. Three-year event-free survival (95% confidence interval) for the sensitive group (SS: sensitive to two or three drugs) was 0.813 (0.773-0.853) and that of the RR group was 0.616 (0.569-0.669) (P = 0.0001). Univariate analysis showed that Philadelphia-chromosome (Ph1) positivity and immunophenotype of mixed lineage were also prognostic factors in the 209 patients. The prognosis of the SS/RR drug resistance profile within 14 Ph1 patients was marginally significant (P = 0.062). Multivariate Cox regression analysis showed that Ph1 was an overwhelmingly adverse factor in event-free survival, with a relative hazard of 5.37 (2.57-11.21, P < 0.0001), followed by RR, with a relative hazard of 2.98 (1.69-5.25, P = 0.0001). Furthermore, we clarified the characteristics of the RR group by examination of the pattern of drug resistance to other drugs in comparison with the SS group. The leukemic cells of RR patients were more resistant than those of SS patients (P < 0.0001) to all the drugs tested, with resistance ratios of 1.6 to 13.1 (mean 3.4). In conclusion, in vitro three-drug resistance at the initial stage is an important independent predictor of treatment failure for both induction response and long-term outcome in childhood ALL.

Adolescent↗
PubMed1998

Neutral carrier-type ion sensors based on sol-gel-derived membranes incorporating a bis(crown ether) derivative by covalent bonding.

Sol-gel-derived membranes incorporating crown ether neutral carriers by covalent bonding have been designed for durable, nontoxic neutral carrier-type ion sensors by sol-gel processing using tetraethoxysilane, diethoxydimethylsilane, and their corresponding alkoxysilylated neutral carriers. A tetraphenylborate anion was also bound chemically to the neutral carrier-type sol-gel-derived membranes for suppressing anion interference and membrane impedance. Ion-sensitive field effect transistors (ISFETs) based on the sol-gel-derived membranes modified chemically by crown ether derivatives, such as 16-crown-5 and bis(12-crown-4) derivatives, showed high performance, high sensitivity in wide cation activity ranges, short response time, and high electrode durability. Specifically, high ion selectivities of practical use in biological systems were attained in the sodium ISFETs based on the chemically modified bis(12-crown-4), which has been successfully applied to sodium assay in blood sera.

Ethers, Cyclic↗
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

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

Sp family transcription factors regulate expression of rat D2 dopamine receptor gene.

The rat D2 dopamine receptor gene is transcribed from a TATA-less promoter that has an initiator-like sequence and several putative Sp1 binding sites. We previously reported that a negative modulator is located between nucleotides -116 and -76 (D2Neg-B) in this gene and that Sp1 as well as another unknown factor bind to this region (Minowa et al., J. Biol. Chem. 269, 11656, 1994). In the present investigation employing the in situ filter detection method, we identified this factor as Sp3. Anti-Sp3 antiserum used in gel-shift assays also revealed that Sp3 binds to the D2Neg-B sequence. Cotransfection of Drosophila Schneider's SL2 cells with Sp3 or Sp1 expression plasmids in the presence of CAT reporter plasmids containing D2 promoter regions demonstrated that Sp1 increased CAT activity in a dose-dependent manner, whereas Sp3, either alone or in the presence of Sp1, failed to activate or repress transcription. On the other hand, using the TATA-containing reporter plasmid BCAT-2, Sp3 coexpression significantly repressed Sp1-induced trans-activation, although Sp3 alone was ineffective. Thus, the transcriptional activity of Sp3 is dependent on the promoter context, and the negative regulation of D2 gene expression appears quite complex and may not depend simply on known DNA-protein interactions involving only Sp1 and Sp3.

Amino Acid Sequence↗
PubMed1997

Cloning and characterization of murine glial cell-derived neurotrophic factor inducible transcription factor (MGIF).

The potent neurotrophic factor glial cell-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta (TGF-beta) superfamily of proteins. We report a transcription factor that is the first nuclear protein known to be induced by GDNF, thus designated murine GDNF inducible factor (mGIF). The cDNA was cloned in the course of investigating transcription factors that bind to Sp1 consensus sequences, using the in situ filter detection method, and it was found to encode a protein having the same C2-H2 zinc finger motif as Sp1. Sequence analysis indicated that mGIF is homologous to the human TGF-beta inducible early gene (TIEG) and human early growth response gene-alpha (EGR-alpha). mGIF is widely distributed in the adult mouse with high mRNA levels in kidney, lung, brain, liver, heart, and testis. In the adult brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During development, mGIF mRNA also has a wide distribution, including in cerebral cortex, cerebellar primordium, kidney, intestine, liver, and lung. GDNF induces the expression of mGIF rapidly and transiently both in a neuroblastoma cell line and in primary cultures of rat embryonic cortical neurons. Co-transfection of the Drosophila SL2 cells using mGIF expression plasmid and reporter constructs having Sp1 binding sites indicated that mGIF represses transcription from a TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF could be important in mediating some of the biological effects of GDNF.

Amino Acid Sequence↗
PubMed1997

In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia.

It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.

Aclarubicin↗
PubMed1997

Tissue-specific promoter usage in the D1A dopamine receptor gene in brain and kidney.

The D1A dopamine receptor gene consists of a short, noncoding exon 1 separated from a longer coding exon 2 by a small intron. Recently, we found that in addition to its original TATA-less promoter located upstream of exon 1, the human D1A dopamine receptor gene is transcribed in neural cells from a second strong promoter located in its intron. In the present study, we addressed the possibility that these two promoters are used for the tissue-specific regulation of the D1A gene in neuronal and renal cells. Reverse transcription polymerase chain reaction revealed that D1A transcripts in the kidneys of humans and rats lack exon 1. Transient transfection analysis of these two promoters in D1A-expressing cells indicated that the upstream promoter has no detectable activity in the opossum kidney (OK) cell line, in contrast to its strong activity in two neuronal cell lines, SK-N-MC and NS20Y. On the other hand, the D1A intron promoter showed transcriptional activity both in OK cells and in neuronal cells. The activator sequence AR1, which enhances transcription from the upstream promoter in SK-N-MC and NS20Y cells, could not activate this promoter in OK cells. In addition, no protein binding to AR1 could be detected by gel mobility shift assay using nuclear extracts from either OK cells or from rat kidney tissue. These findings indicate that the differential expression of short and long D1A transcripts is due, at least in part, to the tissue-specific expression of the activator protein binding to AR1 driving transcription from the upstream promoter. Absence of this activator protein accounts for the nonfunctional D1A upstream promoter in the kidney.

Animals↗
PubMed1996

Incidence of peroxisomal disorders in Japan.

Japanese patients with peroxisomal disorders in the pediatric field were screened. Very long chain fatty acid analysis in the serum sphingomyelin was introduced since 1987 and was useful for the first screening of peroxisomal disorders. Seventy-five patients were diagnosed since 1980: 15 patients with Zellweger syndrome, 2 with neonatal adrenoleukodystrophy (ALD), 1 with rhizomelic chondrodysplasia punctata, 1 with Zellweger-like syndrome. 2 with acyl-CoA oxidase deficiency, 2 with bifunctional enzyme deficiency and 52 with X-linked ALD. The incidence of peroxisome-deficient disorders was estimated to be approximately 1 in 800,000 births which is far less than that in the USA. However, the incidence in Okinawa Islands was 1 in 30,000. Japanese Zellweger patients belonged to 5 complementation groups (A, B, C, E, F) and the patients in Okinawa Islands belonged to groups A and C. The results of this screening were useful for genetic counseling, prenatal diagnosis, carrier detection and early medical care of patients with peroxisomal disorders.

Adolescent↗
PubMed1996

Carrier identification of X-linked adrenoleukodystrophy by measurement of very long chain fatty acids and lignoceric acid oxidation.

Because identification of carriers of X-linked adrenoleukodystrophy (ALD) results in 5-15% false negatives with very long chain fatty acids (VLCFA) assay in plasma, and mutation analysis of plasma VLCFA combined with of the ALD gene is not always practical, we studied whether the analysis of plasma VLCFA combined with lignoceric acid oxidation study in fibroblasts could improve the rate of carrier detection. Lignoceric acid oxidation was abnormal in 19 out of 19 patients (ALD or adrenomyeloneuropathy) and in three out of three obligate heterozygous women. Among ten women at risk of being a carrier, three women who had normal plasma VLCFA had abnormal lignoceric acid oxidation in fibroblasts. These data suggest that this combined biochemical procedure may help to improve carrier detection in families when the ALD gene mutation has not been identified.

Adrenoleukodystrophy↗