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Biomedical subjects

M Tanaka

Publications and source records attributed to M Tanaka.

At least 19 recordsLinked to original sources

A TBP complex essential for transcription from TATA-less but not TATA-containing RNA polymerase III promoters is part of the TFIIIB fraction.

The TATA box-binding protein TBP directs transcription by all three eukaryotic RNA polymerases. In mammalian cells, TBP is found in at least three different complexes: SL1, D-TFIID, and B-TFIID. While SL1 and D-TFIID are involved in RNA polymerase I and II transcription, respectively, no unique function has been assigned to the B-TFIID complex. Here we show that the TFIIIB fraction required for RNA polymerase III transcription contains two separable components, one of which is a TBP-containing complex that may correspond to B-TFIID. For transcription of TATA-less RNA polymerase III genes such as the VAI, 5S, and 7SL genes, this complex cannot be replaced by either TBP alone or the D-TFIID complex. In contrast, TBP alone is active for basal transcription from the TATA-containing U6 promoter. This indicates different requirements for recruiting TBP to TATA-less and TATA-containing RNA polymerase III promoters.

Base Sequence

A novel orally active inhibitor of IL-1 generation: synthesis and structure-activity relationships of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acid derivatives.

A new series of 3-(4-hydroxy-1-naphthalenyl)-2-propenoic acids was prepared and the inhibitory activities of its members on IL-1 generation were evaluated both by in vitro systems using human monocytes and/or rat exudated macrophages stimulated with LPS, and by an in vivo system using the rat CMC-LPS air-pouch model. Many compounds in this series were found to be potent inhibitors of IL-1 generation both in vitro and in vivo. Structure-activity relationships indicated that in the rat CMC-LPS air-pouch model by oral administration the (Z)-2-substituted propenoic acids with 3-alkoxy, 5-alkyl, and 4-hydroxy substituents on the naphthalene ring exhibit optimal inhibition. Among the compounds evaluated, (Z)-3-(5-ethyl-4-hydroxy-3-methoxy-1-naphthalenyl)-2-methyl-2-propeno ic acid (20a), which inhibited IL-1 generation from human monocytes with an IC50 value of 3.0 microM and had an IC50 value of 1.4 microM for rat exudated macrophages, showed the most potent inhibitory activity in the rat CMC-LPS model by oral administration. Compound 20a also showed antiinflammatory effects in animal models of inflammation.

Acrylates

L-threo-3,4-dihydroxyphenylserine, a noradrenaline precursor, inhibits dopamine release and metabolism in the rat striatum in vivo.

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.

Animals

Attenuation of the inhibitory effect of dynorphin on dopamine release in the rat nucleus accumbens by repeated treatment with methamphetamine.

Dynorphin (1-100 nM) dose dependently inhibited both spontaneous and electrically evoked endogenous dopamine (DA) release from slices of the nucleus accumbens of untreated rats. When this inhibitory effect was compared, it was significantly reduced in rats pretreated (for 9 days) with methamphetamine (6 mg/kg per day i.p.) relative to rats treated with saline. These findings indicate that dynorphin inhibits DA release from the nucleus accumbens, and that treatment with methamphetamine reduces the modulatory action of dynorphin on DA release. It is possible that repeated administration of methamphetamine leads to attenuation of the inhibition of DA release from the nucleus accumbens via presynaptic dynorphin-sensitive receptors.

Animals

Double antenna structure of chicken prolactin receptor deduced from the cDNA sequence.

Chicken prolactin receptor (cPRLR) deciphered from the cDNA sequence showed a unique double antenna structure in its extracellular domain. The predicted cPRLR preprotein was composed of 831 amino acids and contained a signal peptide and a transmembrane region. The extracellular domain comprised 438 residues, and was divided into two tandemly repeated, highly homologous units, each of which corresponded to the extracellular domains of mammalian prolactin receptors. Both extracellular units of cPRLR possessed two structural features characteristic of the ligand binding units of cytokine/prolactin receptor family, namely two pairs of cysteine residues and a WSXWS motif. These findings strongly suggest that cPRLR contains two repeated ligand binding units, that is a double antenna structure. The cPRLR gene is expressed in a wide range of tissues of laying hen.

Amino Acid Sequence

The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy.

In hepatocellular carcinoma (HCC), it has been strongly suggested that as the tumor increases in size, foci of less-differentiated malignant tissues arise in the well-differentiated tumor and increase until they replace the well-differentiated tumor tissues. It has also been suggested that tumor growth is attributed to such dedifferentiation. In the current study, the individual histologic features of ultrasound-guided fine-needle biopsy specimens, taken from 12 small HCC in an early stage, were compared with those of autopsy to confirm the dedifferentiation of HCC. In all 12 cases, autopsy was performed 6 months or more after the initial biopsy. Dedifferentiation was demonstrated in 9 of 12 cases (75.0%). Most of the biopsy specimens from minute HCC were well-differentiated. All tumors that had been well-differentiated when evaluated by biopsy were found to have become moderately differentiated at autopsy. This comparative study confirmed the dedifferentiation of HCC with tumor growth.

Aged

Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein-associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth.

Herbimycin A, a benzoquinoid ansamycin antibiotic, was demonstrated to decrease intracellular phosphorylation by protein tyrosine kinase (PTK). In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis. However, the same dose of herbimycin A did not inhibit in vitro growth of a broad spectrum of Ph1-negative human leukemia cells, and several other protein kinase antagonists also displayed no preferential inhibition. Furthermore, we demonstrated that herbimycin A has an antagonizing effect on the growth of transformed cells by a transfection of retroviral amphotrophic vector expressing P210bcr/abl into a murine interleukin (IL)-3-dependent myeloid FDC-P2 cell line. This inhibition was abrogated by the addition of sulfhydryl compounds, similar to the reaction previously described for Rous sarcoma virus transformation. The inhibitory effect of herbimycin A on the growth of Ph1-positive cells was associated with decreased bcr/abl tyrosine kinase activity, but no decrease of bcr-abl mRNA and protein, suggesting that the inactivation of bcr-abl tyrosine kinase activity by herbimycin A may be induced by its binding to the bcr-abl protein portion that is rich with sulfhydryl groups. The present study indicates that herbimycin A is a beneficial agent for the investigation of the role of the bcr-abl gene in Ph1-positive leukemias and further suggests that the development of agents inhibiting the bcr-abl gene product may offer a new therapeutic potential for Ph1-positive leukemias.

Benzoquinones

Glucagonlike peptide-1(7-36)amide suppresses glucagon secretion and decreases cyclic AMP concentration in cultured In-R1-G9 cells.

We previously reported that GLP-1(7-36)amide had glucagonostatic action as well as insulinotropic action in the perfused rat pancreas. In this study, we examined the effect of GLP-1(7-36)amide on glucagon secretion and cAMP concentration in glucagon-secreting cell line, In-R1-G9. GLP-1(7-36)amide (1nM) significantly suppressed glucagon secretion and decreased cAMP concentration in the cells. GLP-1(1-37) did not affect glucagon secretion. It is suggested that inhibitory effect of GLP-1(7-36)amide on glucagon secretion is at least partly mediated by adenylate cyclase system.

1-Methyl-3-isobutylxanthine

Pig testicular 20 beta-hydroxysteroid dehydrogenase exhibits carbonyl reductase-like structure and activity. cDNA cloning of pig testicular 20 beta-hydroxysteroid dehydrogenase.

cDNA inserts encoding 20 beta-hydroxysteroid dehydrogenase (EC 1.1.1.53) were, for the first time, isolated and cloned from a pig testis cDNA library using synthetic oligonucleotides deduced from the partially determined amino acid sequences. The cDNA contains an open reading frame predicted to encode 289 amino acid residues. Surprisingly, it has 85% amino acid homology to human carbonyl reductase. The purified enzyme exhibited carbonyl reductase activity. Adenine-rich sequence was located in the 3'-untranslated nine-rich sequence was located in the 3'-untranslated region, which may mean that the gene originates by retroposition. RNA transcripts of 1.3, 3, and 6 kilobases were detected in poly(A)+ RNA extracted from pig testis by Northern blot hybridization. The steady-state level of the RNA species increased to a maximum in testes from 10-day-old pigs, but rapidly declined thereafter to the same levels found in testes of mature animals.

Alcohol Oxidoreductases

[Study on 27 surgical cases of hypertrophic pyloric stenosis at Kyoto City Hospital].

Twenty-seven patients of hypertrophic pyloric stenosis operated on at our hospital between 1977 and 1991 were reviewed. The patients consisted of 22 boys and 5 girls, with males accounting for 81%. Seventeen of the 27 patients were the first children of their mothers. Vomiting was first noted between 10 and 58 days after birth with a mean of 26.5 days, and neonatal onset was observed in 67% of all patients. The body weight decreased after the onset in 17 patients, including 1 in which it decreased below the birth weight. Hypochloremia was the most frequent preoperative electrolyte imbalance, being observed in 41% of all patients. Alkalosis was noted in 17 of the 22 patients in which arterial blood gas analysis could be performed. The olive was palpated preoperatively in 24 (89%) of the 27 patients. The body weight increased in all patients after operation, and the mean daily increase was 26.7 g. The mean period of hospitalization after operation was relatively short at 8.3 days. Postoperative vomiting was observed in 16 patients (59%), with its mean duration being 26 days. All patients showed normal growth after operation, and no postoperative complications were noted.

Female

Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer.

Eight complementary DNA (cDNA) clones highly expressed in fetal rat stomach but not in normal adult rat stomach were isolated after screening 2 x 10(4) independent recombinants from a subtracted cDNA library. The cDNA library was first prepared from RNAs of total stomach at 16 days gestational period, and this cDNA library was subtracted by cDNAs prepared from adult rat total stomach RNA, using a novel PCR-based cDNA subtraction method. Northern blot analysis revealed that as many as six of eight clones thus isolated were overexpressed in at least some of the human or rat gastric cancers. From analysis of partial nucleotide sequence, four cDNA clones were identified as profilin, pro-alpha 1 (1) collagen, nucleolar protein B23.2, and elongation factor 1 alpha subunit. The remaining two clones were derived from novel genes. These novel genes, L-1 and L-2, are developmentally well regulated in the stomach. The present results clearly show that genes expressed preferentially in embryo stomach are most likely to be highly expressed in gastric cancer. The method described here provides us with a rapid method for identification of genes with significantly increased expression in cancer.

Animals

Combined histochemical and biochemical demonstration of nigral vulnerability to lipid peroxidation induced by dopa and iron.

Using a newly developed lipid peroxidation-inducing system composed of DOPA and iron, we examined the vulnerability of substantia nigra to peroxidation in comparison with that of caudate-putamen obtained from normal or vitamin E-deficient animals. Histochemical detection of lipid peroxidation revealed that substantia nigra was far more susceptible than caudate putamen to DOPA and iron treatment, which was biochemically supported by measurements of thiobarbituric acid-reactive substances. Vitamin E deficiency accelerated such susceptibility of substantia nigra but had no influence on the histochemical findings observed in caudate-putamen.

Adenosine Diphosphate

Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors.

The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation.

Animals

Eating and drinking cause increased dopamine release in the nucleus accumbens and ventral tegmental area in the rat: measurement by in vivo microdialysis.

Dopamine (DA) release was simultaneously monitored in the nucleus accumbens (NAC) and ventral tegmental area (VTA) of conscious rats using in vivo microdialysis. During dialysis perfusion, rats were allowed access to food or water for 20 min following a 36 h food and water deprivation period. DA release increased significantly in the NAC and VTA in response to eating and drinking. The increases in both regions continued until 20-60 min after the end of the feeding or drinking session. These results show that the mesolimbic DA pathway is activated in response to ingestive behavior, and that DA release occurs in the cell body (A10) region as well as in the mesolimbic DA nerve terminals.

Animals