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T Sugimura

Publications and source records attributed to T Sugimura.

At least 307 records · Page 17Linked to original sources
PubMed1994

Role of fat and calcium in cancer causation by food mutagens, heterocyclic amines.

We investigated the modulation by dietary corn oil and calcium levels of carcinogenesis by heterocyclic amines (HCA), a new class of important carcinogens in the human nutritional environment, since they are formed during cooking. Two approaches involved (i) a chronic bioassay in male and female F344 rats, and (ii) an abbreviated test, the induction of foci of aberrant crypts in the colon in male F344 rats. One typical HCA, 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was fed at 75 ppm for 12 months to male and female rats that were held three and six months longer, respectively, on control diets. Neoplasms were induced in the Zymbal gland, skin (predominantly in male rats), liver, mammary and preputial glands, colon, and lung. Diets with 23.5% corn oil increased carcinomas in the liver in males, and in the mammary gland in females, compared with a 5% corn oil diet. Males on the low-fat diet had more cancers in the lip, and females had more ear duct cancers, than did rats on the high-fat diet. Another HCA, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), fed at 400 ppm for nine weeks induced foci of aberrant crypts in the lower intestinal tract of male F344 rats. There were significantly more aberrant crypts on the high-fat than on the low-fat diet. On the low-fat diet, there were fewer aberrant crypts on the higher calcium level. Thus, dietary fat modulates the carcinogenic action of HCA food carcinogens in specific organs of male and female F344 rats. Also, both fat and calcium affected the induction of aberrant crypts in the distal intestinal tract of male F344 rats.

Amines↗
PubMed1994

[The utilization of categorical knowledge in story inference of young children].

Hundred-seventy-nine children, 5- and 6-year-olds, were assigned to one of three groups; basic-context group (BC), intermediate-context group (IC), and superordinate-context group (SC). Each child listened to the first half of a story, which was the same for three groups except that it contained a basic-level word (e.g. apple) for BC group, an intermediate-level word (e.g. fruit) for IC group, and a superordinate-level word (e.g. food) for SC group. Immediately after the listening the child was asked to infer the later half of the story. Main findings were as follows: (1) in BC and IC conditions 6-year-olds made more inferences based on the informed concept-level than 5-year-olds, but in SC condition the age difference was not observed; (2) both error analysis and verbal report showed that most inference errors resulted from the overextension beyond the informed concept-level.

Child↗
PubMed1994

[Kawasaki vasculitis].

Kawasaki disease is an acute febrile illness recognized most often in children under 4 years of age. It is characterized by mucosal inflammation, indurative edema of the hands and feet, skin rash and cervical lymphadenopathy. This is an acute systemic vasculitis syndrome of unknown etiology which has been recognized not only in Japan but all over the world. This article reports on the clinical spectrum of Kawasaki disease, analysis of coronary artery and other lesions, and long-term cardiovascular problems including premature atherosclerosis. The etiology and pathogenesis of this disease are still unknown. Current hypotheses and leading studies on the etiology and the pathogenesis of Kawasaki disease are also reviewed.

Coronary Angiography↗
PubMed1993

Molecular cloning of a cDNA encoding an inducible calmodulin-dependent nitric-oxide synthase from rat liver and its expression in COS 1 cells.

Calmodulin-dependent nitric-oxide synthase, with an apparent molecular mass of 125 kDa, was induced in the liver of rats treated with Propionibacterium acnes and Escherichia coli lipopolysaccharide. Clones were isolated from a cDNA library obtained from induced rat liver using oligonucleotide probes which were synthesized based on the amino acid sequences of peptides of the purified enzyme. Four overlapping cDNA clones for a 3.8-kbp region were isolated and the nucleotide sequences were determined. These clones encompassed an open-reading frame of 3441 bases encoding 1147 amino acids. The deduced amino acid sequence of the cDNA suggested that the protein contains binding sites for NADPH, FAD and FMN. The structure of the possible calmodulin-binding site, consisting of a strongly hydrophobic region surrounded by basic amino acids, is present. The full-length cDNA was expressed in COS 1 cells under the control of a cytomegalovirus promoter and the expressed enzyme was found to be a calmodulin-dependent nitric-oxide synthase. A structural comparison suggested that the liver nitric-oxide synthase is the same as the macrophage enzyme. Northern-blot analysis showed that the mRNA in the liver is approximately 4.2 kb long and is induced transcriptionally by treatment with P. acnes and lipopolysaccharide.

Amino Acid Oxidoreductases↗
PubMed1993

Increment of the cyclin D1 mRNA level in TPA-treated three human myeloid leukemia cell lines: HEL, CMK and HL-60 cells.

To study the involvement of cyclins in cell-cycle progression, changes of mRNA levels for three G1 cyclins (cyclin C, D1 and E) and cyclin A were studied in a leukemia cell line, HEL cells, before and after incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, the cyclin D1 mRNA level markedly increased in the HEL cells when the cells were growth-arrested by TPA, while the amounts of cyclin E and A mRNAs decreased to an almost undetectable level in HEL cells after incubation with TPA. The similar marked increment of the cyclin D1 mRNA level was observed in other leukemia cell lines, CMK and HL-60 cells, after incubation with TPA. The cyclin C mRNA was not detected in HEL cells before and after incubation with TPA.

Base Sequence↗
PubMed1993

Germ-line p53 mutation is uncommon in patients with triple primary cancers.

We examined five patients with multiple primary cancers who had a history of three different types of primary cancers for germ-line p53 mutations. The germ-line p53 mutation was detected in a patient who conformed to the Li-Fraumeni syndrome, but not in the other four patients. The diagnosis of these four patients did not fall in the category of Li-Fraumeni syndrome. This result indicates that germ-line p53 mutations are uncommon even in patients with triple primary cancers.

Female↗
PubMed1993

Protein phosphatase 1 gamma 2 is associated with nuclei of meiotic cells in rat testis.

We have shown that there are at least 4 isotypes of the catalytic subunit of type 1 protein phosphatase (PP1), PP1 alpha, PP1 gamma 1, PP1 gamma 2 and PP1 delta by rat cDNA cloning. Among these, PP1 gamma 2 mRNA was found to be abundant in rat testis. To study the roles of PP1 gamma 2 in rat spermatogenesis, we raised an antibody against a synthetic 21 mer peptide corresponding to the predicted amino acid sequence of the C-terminal region of the PP1 gamma 2. The antibody interacted with a testicular protein of 39-kDa prepared from rats after puberty (25 days after birth). However, the antibody did not interact with proteins extracted from the immature testes or from other tissues examined. Indirect immunofluorescent staining of PP1 gamma 2 of the seminiferous tubules from rats of various ages and costaining with DNA showed that the protein is located in the nuclei of late spermatocytes and of early spermatids. We suggest that PP1 gamma 2 plays some role in meiotic division during spermatogenesis.

Amino Acid Sequence↗
PubMed1993

Reduction in formation and growth of 1,2-dimethylhydrazine-induced aberrant crypt foci in rat colon by docosahexaenoic acid.

The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 times a week for 4, 8, or 12 weeks from the day before the first carcinogen treatment. The numbers of DMH-induced aberrant crypt foci per colon after 4, 8, and 12 weeks of DHA treatment were approximately 40% of those in the respective control groups, and the differences were statistically significant. The numbers of foci reached plateau levels at 8 weeks in both the DHA-treated and control groups. The mean number of aberrant crypts per focus was also significantly smaller in the group given DHA than that in the control group at each time. These results suggest that DHA suppresses the formation and growth of aberrant crypt foci and has a preventive effect on colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1993

Expression of PP2A B regulatory subunit beta isotype in rat testis.

We isolated a rat cDNA encoding part of the beta-isotype of the B regulatory subunit (BR beta) of protein phosphatase 2A (PP2A). The isolated cDNA encoded the region corresponding to amino acids positions 8(R) to 177(N) of human BR beta. The identities of the nucleotide and amino acid sequences of the rat and human BR beta s were 95.7% and 100%, respectively. The BR beta mRNA was specifically expressed in rat brain and testis, the lengths of mRNAs in these two organs being different. In the testis, the BR beta mRNA was first detected 40 days after birth, increasing gradually thereafter, and was expressed specifically in elongated spermatids, while mRNA of the alpha-isotype (BR alpha) was expressed equally in all spermatogenic cells. After meiosis, round spermatids change morphologically to elongated spermatids. BR beta may regulate the activity of the PP2A catalytic subunit in spermatids, and be involved in spermatogenic maturation, especially spermatid elongation.

Aging↗
PubMed1993

c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase.

c-erbB3 product is moderately expressed in gastric mucosa, especially in parietal cells. Northern blot analysis revealed that 6.2-kb c-erbB3 transcript was expressed in all gastric cancer cell lines examined, and that 1.4-kb c-erbB3 transcript was expressed as highly as 6.2-kb transcript in MKN45 cells. erbB3-S cDNA, corresponding to 1.4-kb c-erbB3 transcript, was cloned by rapid amplification of cDNA ends. Sequence analysis of erbB3-S cDNA showed that this 1.4-kb c-erbB3 mRNA encoded a secreted receptor. Analysis of partial genomic structure of c-erbB3 gene revealed that the exon specific to secreted receptor was identical with the 5' portion of the intron in c-erbB3 gene. c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase due to alternative splicing.

Amino Acid Sequence↗
PubMed1993

Identification of PP1 catalytic subunit isotypes PP1 gamma 1, PP1 delta and PP1 alpha in various rat tissues.

cDNA clones for 4 rat protein phosphatase 1 (PP1) catalytic subunit isotypes, PP1 alpha, PP1 gamma 1, PP1 gamma 2 and PP1 delta, were isolated (K. Sasaki et al., Jpn. J. Cancer Res. 81, 1272-1280, 1990). Antibodies were raised to determine the physiological functions of 4 isotypes. Among these isotypes, the PP1 gamma 2 protein was detected specifically in rat testis (H. Shima et al., Adv. Prot. Phosphatases, vol. 7, in press). On the other hand, PP1 gamma 1, PP1 delta and PP1 alpha were detected as 36kDa, 37kDa and 38kDa proteins in several rat organs by immunoblot analysis. All three isotypes were found in both soluble and particulate fractions. PP1 gamma 1 was predominant in the brain and PP1 delta in the brain, lung and small intestine, but the levels of both were low in the liver and muscle. It became evident that PP1 alpha was not a predominant isotype in any tissue examined.

Amino Acid Sequence↗
PubMed1993

Cloning of cDNA encoding Drosophila poly(ADP-ribose) polymerase: leucine zipper in the auto-modification domain.

We have isolated cDNA clones for a Drosophila poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) by screening a lambda gt11 cDNA library with a Drosophila partial cDNA fragment. The Drosophila PARP probe was obtained by the polymerase chain reaction with heterologous primers deduced from conserved amino acids in the mammalian, chicken, amphibian, and fish sequences. The Drosophila PARP mRNA is 3.2 kb in length and is expressed in the early stages of development. The PARP protein of 994 amino acids contains two zinc-finger motifs and an NAD-binding motif, which are conserved among different species. Interestingly, the heptad leucine repeat in an alpha-helix was found in Drosophila PARP. Alignments of the auto-modification domains of various species showed the repeated hydrophobic amino acids on the same face of the helix that make the coiled-coil configuration in the mammalian and chicken sequences. The presence of a leucine-zipper motif in the auto-modification domain suggests that this motif might be responsible for protein-protein interaction between PARP and physiological acceptors. PARP may have novel functions, possibly involving its homo- and/or heterodimerization with other nuclear leucine-zipper proteins and its regulation by ADP-ribosylation.

Amino Acid Sequence↗
PubMed1993

Isolation of the complementary DNA encoding a mouse heparin-binding growth factor receptor with the use of a unique kinase insert sequence.

With the use of reverse transcriptase-polymerase chain reaction techniques focused on a unique kinase insert sequence, the complementary DNA for a mouse tyrosine kinase receptor gene, designated sam3, was isolated from a mouse brain complementary DNA library as a member of the heparin-binding growth factor receptor family or fibroblast growth factor receptor family. The kinase insert region was selected as the probe synthesized by polymerase chain reaction techniques because it composes a unique structure in this receptor family. The sam3 protein, 800 amino acids long, has high homology to mouse K-sam/bek (67%) and N-sam/flg (63%), which we also cloned as the mouse counterparts of human K-sam/bek and N-sam/flg genes, other members of this family. The sam3 protein also has high homology to human FGFR3 (92%) and chicken cek2 (80%) proteins. The sam3 protein is most likely to be a mouse counterpart of human FGFR3 and chicken cek2 proteins. mRNAs of K-sam/bek, N-sam/flg, and sam3/FGFR3 genes were detected in mouse embryo through some adult tissues. The relative amounts of these mRNAs were different depending on the organs examined. Thus, these gene products may have different biological functions in organ development including the central nervous system.

Amino Acid Sequence↗
PubMed1993

Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma.

To identify genetic alterations associated with acquisition of metastatic ability in colorectal carcinoma, 31 liver metastases and 40 primary tumors of colorectal carcinoma from 55 patients were analyzed for loss of chromosomal heterozygosity using 46 polymorphic DNA markers covering 15 chromosomes. Loss of heterozygosity (LOH) and/or rearrangement at the TP53 and DCC loci were detected in all liver metastases (10 of 10 at TP53 and 19 of 19 at DCC), and were observed in 59% (10 of 17) at TP53 and 75% (18 of 24) at DCC respectively in the primary tumors. Furthermore, the incidence of LOH on chromosomes 13q and 14q was higher than that on other chromosomes in liver metastasis, and it was higher in liver metastases than in primary tumors (20/30 vs. 18/39, p = 0.072 on chromosome 13q and 21/31 vs. 16/40, p = 0.018 on chromosome 14q). In 4 cases, LOH or rearrangement at loci on chromosomes 13q, 14q and 18q not detected in primary tumors was observed in liver metastases from the same patients. These results suggest that concordant p53 and DCC alterations and inactivation of several other tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential of colorectal carcinoma.

Alleles↗
PubMed1993

Rare frequency of activation of the Ki-ras gene in rat colon tumors induced by heterocyclic amines: possible alternative mechanisms of human colon carcinogenesis.

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.

Adenocarcinoma↗
PubMed1993

Mutations of the p53 tumor suppressor gene and the ras gene family in intrahepatic cholangiocellular carcinomas in Japan and Thailand.

The incidence and pattern of mutations of the ras oncogenes and the p53 tumor suppressor gene have been shown to differ among different cancer types and even among the same cancer types with different etiological backgrounds. For example, in a previous study we showed that not only the etiology but also the incidence of point mutation of the c-Ki-ras oncogene in cholangiocellular carcinomas (CCCs) differ between Japanese and Thai patients. In the study presented here, we examined the incidence of mutations in the ras gene family and the p53 gene in CCCs of both Japanese and Thai patients by single-strand conformation polymorphism and direct sequencing analyses and compared the pattern of p53 mutation between these two CCC groups. Although the incidence of ras mutation differed markedly between Japanese (seven of 12, 58%) and Thai (two of 26, 8%) cases, the incidence of p53 mutation was similar: four of 12 (33%) and nine of 26 (35%), respectively. Except for one case in which deletion-insertion was detected in the second exon of the N-ras gene, all ras mutations occurred at codon 12 or 13 of the c-Ki-ras gene. All p53 mutations but one were detected in a highly conserved region, and the predominant form of the mutations was G:C-->A:T transition at CpG sites in both Japanese and Thai cases, similar to that reported for colorectal cancers. Therefore, in contrast to the ras oncogenes, mutation of the p53 gene was frequently involved in the development of CCCs in both Japanese and Thai patients, irrespective of any difference in etiology.

Adult↗