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T Sugimura

Publications and source records attributed to T Sugimura.

At least 361 records · Page 20Linked to original sources
PubMed1992

Localization of HstI transcripts to the apical ectodermal ridge in the mouse embryo.

The HstI gene is a transforming gene, coding for a protein of the fibroblast growth factor family (Sakamoto et al., 1986). Previous RNA hybridization studies with the mouse homolog demonstrated the presence of a 3.0-kb transcript in Day 11 and 14 mouse embryos. Here we detect a 3.0-kb transcript in the limb and body of the dissected Day 11 mouse embryo. PCR amplification using HstI-specific primers also showed comparable results. In order to localize the HstI transcripts during development, corresponding HstI cDNA was isolated, and an HstI-specific region was used as a probe for in situ hybridization analysis. Serial sections of embryos from Day 8 (early-somite stages) through Days 9, 10, 11, and 12 of gestation were examined. With the antisense probe, a signal was detected in the Day 11 and 12 embryo, where it was localized to the apical ectodermal ridge (AER) of the limb bud. This structure is well known for its role in promoting the distal outgrowth of the developing limb bud. Signal was detected in both fore- and hindlimbs during the period of rapid distal growth. This restricted localization suggests a role for HstI in normal embryogenesis, including outgrowth of the limb bud.

Animals↗
PubMed1992

Anticarcinogenic effects of (-)-epigallocatechin gallate.

BACKGROUND: Our research objective is to develop nontoxic cancer chemopreventive agents and to apply these agents in treating humans. We are identifying agents that inhibit the process of tumor promotion in two-stage carcinogenesis experiments on mouse skin. METHODS: We review (a) the inhibitory effect of penta-O-galloyl-beta-D-glucose (5GG) on tumor promotion by teleocidin, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (5GG is structurally similar to (-)-epigallocatechin gallate (EGCG) and is isolated from hydrolyzed tannic acid); (b) the inhibitory effects of EGCG, the main constituent of Japanese green tea, on tumor promotion with two tumor promoters, teleocidin and okadaic acid, a non-TPA-type tumor promoter; (c) the mechanisms of action of EGCG, a single application of which reduced the specific binding of [3H]TPA and [3H]okadaic acid to a particulate fraction of mouse skin; and (d) the anticarcinogenic effects of EGCG on duodenal carcinogenesis induced by N-ethyl-N'-nitro-N-nitrosoguanidine in male C57BL/6 mice. EGCG is a nontoxic compound. CONCLUSION: We believe that the main constituent of Japanese green tea, EGCG, is a practical cancer chemopreventive agent available in everyday life.

Animals↗
PubMed1992

Ordering of human chromosome 3p markers by radiation hybrid mapping.

To construct a panel of radiation hybrids (RHs) for human chromosome 3p mapping, mouse microcell hybrid cells, A9(neo3/t)-5, containing a single copy of human chromosome 3p with pSV2neo plasmid DNA integrated at 3p21-p22 were irradiated and fused to mouse A9 cells. A panel of 96 RHs that retain several sizes and portions of human chromosome 3p segments was used to map 25 DNA markers for chromosome 3p. Eight of them, H28, H29, H32, H33, H35, H38, H48, and H64, were cloned from Alu-primed PCR products using A9(neo3/t)-5 cell DNA as a template. The most likely order of the 24 markers, except for H28, based on the statistical ordering method proposed by Falk, was cen-D3S4-D3S3-D3S30-H29-D3S13-D3S2-+ ++H48-D3F15S2-D3S32-D3S23-CCK-H35-H33- D3S11-D3S12-RARB-THRB(ERBA2-pBH302)- H64-H38-RAF1-D3S18-H32-D3S22-pter. The order and location of these markers were in good agreement with those previously determined by other mapping methods, suggesting that a panel of these 96 RHs is a valuable source for a rapid mapping of human chromosome 3p markers.

Chromosome Mapping↗
PubMed1992

Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate.

OBJECTIVE: To determine coronary artery diameter change before and after an intracoronary infusion of isosorbide dinitrate in patients who have had Kawasaki disease, we performed coronary angiography in 188 such patients. PATIENTS AND METHODS: Four patient groups were studied. Groups 1 to 3 consisted of patients with Kawasaki disease: group 1 (the "normal" group; n = 65) had no coronary artery lesions; patients in group 2 had regression to normal of a coronary artery aneurysm after Kawasaki disease and were divided, according to the time since onset, into two subgroups, group 2-a (n = 20) being at an early stage after regression to normal (followed for 1.7 +/- 0.7 years) and group 2-b (n = 34) being at a later stage after regression (followed for 8.7 +/- 2.9 years); and group 3 (the "abnormal" group; n = 25) had persistent coronary artery aneurysm or stenosis or both. Group 4, the control group (n = 44), consisted of patients without Kawasaki disease who had congenital heart disease with normal coronary arteries. The coronary artery diameter change was calculated by the following formula: Percentage of change = (Diameter after infusion - Diameter before infusion)/Diameter before infusion x 100. RESULTS: The percentages of change in the coronary artery diameter after isosorbide dinitrate infusion were 16.2% +/- 13.4% (normal group), 11.3% +/- 7.2% (early-regression group), 7.8% +/- 8.3% (late-regression group), 6.8% +/- 7.8% (abnormal group), and 15.2% +/- 11.8% (control group). In the abnormal group, there was significantly poorer dilation than in the control and normal groups. The late-regression group also had significantly less change in diameter than did the control and normal groups (p < 0.05). CONCLUSIONS: These data suggest (1) that the coronary artery after Kawasaki disease becomes stiff not only in patients with persistent abnormal lesions but also in those with regressed aneurysms and (2) that stiffness of the coronary artery may be a risk factor for atherosclerosis.

Child↗
PubMed1992

Induction of preneoplastic lesions by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the livers of rats treated with carbon tetrachloride.

The multifactorial nature of carcinogenesis in man has impelled us to study the effects of various chemicals and conditions in combination. In the present investigation, we examined the effects of low doses of 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) in combination with carbon tetrachloride (CCl4) on the formation of glutathione S-transferase placental form (GST-P)-positive foci in rat liver. Administration of diet containing MeIQx at 0.4, 4 or 40 p.p.m., representing one-thousandth, one-hundredth and one-tenth of the dose proved to induce hepatocellular carcinomas (400 p.p.m.), for 8 or 12 weeks did not induce GST-P-positive foci. However, 40 p.p.m. of MeIQx when co-administered with CCl4 (0.7 ml/kg, s.c. twice a week) induced preneoplastic lesions: 7- and 3-fold increases in the numbers and areas of GST-P positive foci in week 8, and 8- and 6-fold increases respectively in week 12, over those with CCl4 alone. Furthermore, a marked increase in the number of hyperplastic nodules was observed in this group of rats in week 12. No significant increases of GST-P-positive foci were observed at doses of 0.4 or 4 p.p.m. MeIQx in combination with CCl4. Thus, it is predicted that chronic exposure to 40 p.p.m. of MeIQx eventually results in induction of hepatocellular carcinomas in injured rat liver.

Animals↗
PubMed1992

Determination of human exposure to the dietary carcinogen 3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) from hemoglobin adduct: the relationship to DNA adducts.

A quantitative method for estimation of the exposure of the food-borne carcinogen, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), was developed by the analysis of its hemoglobin binding in rats. This method was then applied to show the presence of Trp-P-1-hemoglobin adducts in human blood. In rat experiments, 0.2 and 0.07% of the administered [14C]Trp-P-1 formed stable covalent adducts with blood hemoglobin and plasma proteins respectively. Subsequent strong acidic treatment (6 N HCl, 110 degrees C, 24 h) of the Trp-P-1-hemoglobin adducts cleaved peptide bonds of globin, and yielded mainly three derivatives of Trp-P-1. One of them (TPHB) represented approximately 50% of the total Trp-P-1-hemoglobin adducts and was suitable for detection through its strong fluorescence. TPHB was used as a surrogate marker of the Trp-P-1-hemoglobin adducts. Linear dose dependency of Trp-P-1 binding to liver DNA and hemoglobin in rats was confirmed by 32P-postlabeling analysis and TPHB assay. The absence of Trp-P-1-DNA adducts and TPHB in nontreated rats was also confirmed. Using TPHB as a tool for human dosimetry of Trp-P-1, human blood samples from four healthy individuals were examined. TPHB was detected in all samples ranging from 0.23 to 4.33 pmol/g hemoglobin. These results suggest human exposure to Trp-P-1, probably from cooked foods or cigarette smoke, and its possible relationship to human carcinogenesis.

Adult↗
PubMed1992

Suppression of spontaneous hepatocellular carcinoma development in C3H/HeNCrj mice by the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611).

The study was performed to examine the effects of the lipophilic ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), with a strong scavenging capacity for active oxygen species, on the spontaneous development of liver tumors in male C3H/HeNCrj mice. Animals were given a diet containing 0.1% CV-3611 for a total experimental period of 16 months. Hepatocellular carcinomas developed in 2/39 (5%) of these experimental mice and in 11/43 (26%) of control mice fed a basal diet. The numbers of carcinoma per mouse were 0.05 +/- 0.22 and 0.33 +/- 0.61 respectively. Thus, CV-3611 clearly suppressed the development of hepatocellular carcinomas. However, the scavenger did not affect either the incidence or the number of hepatocellular adenomas, suggesting that active oxygen species might be involved in the conversion of adenomas to carcinomas in spontaneous liver carcinogenesis in C3H/HeNCrj mice.

Animals↗
PubMed1992

Dose-dependent formation of preneoplastic foci and DNA adducts in rat liver with 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Dose responses to two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in induction of glutathione S-transferase placental form positive liver cell foci (GST-P+ foci) and DNA adduct formation in the liver were examined in male F344 rats. Beginning 2 weeks after a single diethylnitrosamine (DEN) injection (200 mg/kg, i.p.), rats received MeA alpha C or PhIP in the diet at various doses for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) 1 weeks after the test agents were added to the diet and were killed 8 weeks after DEN initiation. MeA alpha C (100, 200, 400 and 800 p.p.m.) significantly increased numbers and areas of GST-P+ foci over control levels in all dose groups with a clear dose-response. In contrast, PhIP (50, 100, 200 and 400 p.p.m.) only equivocally increased foci development in the highest dose group and rather was associated with decrease in the lower dose groups. DNA adduct formation assessed by 32P-postlabeling demonstrated a dose-dependent increase with both chemicals, the levels being much higher with MeA alpha C. Thus, two highly mutagenic heterocyclic amines that are produced in broiled foodstuffs exerted different influence on GST-P+ foci development and DNA adduct formation; these findings are consistent with liver carcinogenicity in rats and/or mice.

Animals↗
PubMed1992

Detection of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine in broiled beef.

2-Amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) showed mutagenicity in Salmonella typhimurium TA98 in the presence of S9 mix, inducing 180 revertants per 100 micrograms. Since creatinine, tyrosine and glucose, which are present in meat, are expected to be involved in the formation of 4'-OH-PhIP, its presence in broiled beef was examined. 4'-OH-PhIP was detected in broiled beef by high-performance liquid chromatography and UV-spectrometry after extraction with 0.1 N HCl and purification by blue cotton treatment and ion exchange column chromatography. Its level was estimated to be 21.0 ng per g of broiled beef, which is comparable to that of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Animals↗
PubMed1992

Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters.

We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.

Acetic Anhydrides↗
PubMed1992

Species difference among experimental rodents in induction of P450IA family enzymes by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Rats, mice, hamsters and guinea pigs were given an i.p. injection of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), a protein-derived pyrolysate component present in cooked foods, and inductions of cytochrome P450 (P450) in the liver and kidney of these animals were examined. The activity and amount of P450s corresponding to the rat P450IA1 and P450IA2 were assessed by means of a bacterial mutation test using 3 carcinogenic heterocyclic aromatic amines including PhIP as substrates and by Western blotting with a monoclonal antibody reactive with both P450IA1 and P450IA2. In rats, PhIP induced P450IA1, P450IA2 and a new but unspecified P450 isozyme in the liver, and induced P450IA1 in the kidney. However, PhIP induced none of these P450 isozymes in mice, hamsters and guinea pigs.

Amines↗
PubMed1992

Multiple genetic alterations in human carcinogenesis.

Cancer development in man appeared to be a multistage process as suggested by epidemiological studies on commonly occurring gastric, colon, and breast cancers and also on human retrovirus-related leukemia, and by the finding by physicians and surgeons of precancerous lesions for many types of neoplasias. In the last 10 years it has become evident that human cancers have multiple genetic alterations caused by point mutations, recombinations, amplifications, and/or deletions. The genes affected include both oncogenes and tumor-suppressor genes and genes that accelerate cell proliferation and metastasis. Cancers with more malignant properties and poorer prognosis are generally associated with larger numbers of genetic alterations. These multiple genetic alterations are considered to be a direct reflection of the multiple steps involved in carcinogenesis. The multiple genetic alterations are caused by multiple environmental carcinogenic substances or factors, each of which usually exists only at minute concentrations and does not exert any major impact alone except under particular occupational, iatrogenic, and locally geographic conditions. The fact that carcinogenesis is a multistep process involving multiple genetic alterations clearly needs to be taken into consideration in assessing the risks of environmental carcinogenic substances or factors. The increasing incidence of multiple primary cancers is also most easily understood from the viewpoint of multiple steps in carcinogenesis. Possible multiple approaches to cancer prevention should therefore be considered in relation to multistep carcinogenesis and multiple carcinogenic factors.

Animals↗
PubMed1992

Anti-tolA antibody in non-A, non-B chronic liver disease.

We constructed a cDNA library against the plasma obtained from the patient with acute exacerbation of non-A, non-B liver cirrhosis, and immunoscreened this library with the sera obtained from the patients with non-A, non-B chronic liver disease. One positive clone lambda 22C containing about 1.2 kb cDNA insert was isolated from 10(6) clones. Nucleotide sequence determination and subsequent homology search revealed its identity to the tolA gene of Escherichia coli. Anti-tolA antibody was detected in 54.5% of the patients with NANB chronic liver disease whose sera were negative for antibody to hepatitis C virus (anti-C100). In contrast, anti-tolA was detected only of 14.6% patients with anti-C100 positive NANB chronic liver disease, 10.5% with hepatitis B surface antigen-positive chronic liver disease, 7.7% with alcoholic liver disease and 4.2% in normal control, and no positive case in acute hepatitis of etiology and in primary biliary cirrhosis. However, antibody to the core protein of hepatitis C virus (anti-JCC) was detected 50% of the patients whose sera were negative for anti-C100 but positive for anti-tolA. Recently, it has been reported that hepatitis C virus is rich in mutations and has some variants. These results indicated the presence of a common epitope between the tolA protein and some agent related to non-A, non-B hepatitis, especially to anti-C100 negative non-A, non-B hepatitis such as variants of hepatitis C virus which have mutations in C100 coded region.

Antibodies↗
PubMed1992

Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma.

To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Allelic losses and mutations of the p53 gene were detected in 24 out of 25 informative cases (96%) and 23 out of 27 cases (85%) respectively. Simultaneous losses and mutations were detected in all 16 stage III-IV tumors, while these alterations were detected only in 3 of 6 stage I-II tumors. When allelic losses and/or mutations were detected in the primary tumors, the same alterations were always maintained in the process of metastasis. In three cases, identical p53 alterations were detected among different organ metastases. The mutations detected in five cell lines were also detected in the corresponding original tumors. These results suggest that the alterations of the p53 gene are common and early events, but probably not the first events, in the development of SCLC, and that these alterations are essential for the maintenance of malignant phenotypes in the progression of SCLC.

Base Sequence↗
PubMed1992

Identification and analysis of the ret proto-oncogene promoter region in neuroblastoma cell lines and medullary thyroid carcinomas from MEN2A patients.

The human ret proto-oncogene (proto-ret), encoding a receptor tyrosine kinase, is highly expressed in neuroblastomas, medullary thyroid carcinomas (MTCs) and pheochromocytomas, which are all tumors of cells originating from the neural crest. In studies on the transcription mechanism of proto-ret, we identified the transcription start site and the promoter region by chloramphenicol acetyl transferase (CAT) assay. A sequence upstream from the transcription start site (-167 to +98 bp) showed definite promoter activity in both proto-ret mRNA-positive neuroblastoma NB39-nu cells and proto-ret mRNA-negative HeLa cells. The promoter sequence had a high GC content and contained four tandemly repeated GC boxes without a TATA box. Putative binding sequences for SP-1, AP-2 and epidermal growth factor receptor-specific transcription factor (ETF) and also the transcription-suppressing factor, GC factor (GCF), were found in the repeated GC box region. Southern blot analysis of DNAs of neuroblastoma cell lines and primary MTCs showed that the high proto-ret expression in these tumors is not caused by gross genetic changes in the promoter region, suggesting the possible involvement of a region(s) other than the sequence from -167 to +98 bp or a minor genetic change(s) in the promoter region.

Amino Acid Sequence↗
PubMed1992

Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization.

The hst-2 gene was previously identified by its close homology to the hst-1 gene. Cosmid clones containing the hst-2 gene were cloned from a normal human genomic library. Focus-forming activity was observed for the hst-2 cosmids when NIH3T3 transfection assay was performed in a serum-free medium, whereas induction of morphological transformation was difficult to detect in an ordinary serum-supplemented medium. The hst-2 cDNA was cloned from the NIH3T3 transformant. Nucleotide sequence analysis of the cDNA indicates that the hst-2 gene encodes a 198 amino acid transforming protein containing a signal peptide with the characteristics of a heparin-binding growth factor. The coding sequence was almost identical to the published portion of the exon sequence of the FGF-6 gene, indicating that hst-2 is identical to FGF-6. The hst-2 cDNA fragment, when inserted into an expression vector, was able to transform NIH3T3 cells effectively, and the resulting transformant formed a well-vascularized tumor in nude mice, thus suggesting an angiogenic property similar to some other members of the family. RNA blot analysis revealed the expression of the hst-2 gene in human leukemia cell lines with platelet/megakaryocytic differentiation potential.

Animals↗