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T Sugimura

Publications and source records attributed to T Sugimura.

At least 451 records · Page 25Linked to original sources
PubMed1990

Carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in nonhuman primates: induction of tumors in three macaques.

The carcinogenic potential of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was evaluated in cynomolgus monkeys. Monkeys received IQ, beginning at the age of one year, at doses of 10 or 20 mg/kg by gavage. Thus far, IQ has induced hepatocellular carcinoma in three monkeys with a latent period of 27 to 37 months. Metastases to the lung occurred in two of the three monkeys. Microscopically, the hepatocellular carcinoma in all three cases demonstrated a trabecular pattern. These data demonstrate that IQ is a potent carcinogen in nonhuman primates and support the idea that it is a potential carcinogen for humans.

Animals↗
PubMed1990

Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma.

By restriction fragment length polymorphism analysis, we examined loss of heterozygosity at 34 loci on 23 chromosomes in 35 surgically resected human hepatocellular carcinomas. Allele losses at the HP locus on chromosome 16q22 and at the MT2P1 locus on chromosome 4p11-q21 were detected in 57% (8/14) and 50% (8/16) of cases, respectively. Loss of heterozygosity on chromosomes 16q and 4 occurred simultaneously in 4 of 7 informative cases for both loci, and seemed to be important in the development of human hepatocellular carcinoma irrespective of the presence of hepatitis B virus infection. In contrast, the incidence of allele loss was low at the other loci, e.g., chromosome 1p, 3p, 11p, 13q or 17p, where one allele is frequently lost in other cancers.

Carcinoma, Hepatocellular↗
PubMed1990

Expression of ret proto-oncogene in human neuroblastomas.

We examined the expression of ret proto-oncogene (proto-ret) in surgically resected human neuroblastomas. Slot blot RNA hybridization revealed that all 29 neuroblastomas examined expressed the proto-ret, the relative intensity of the hybridization ranging from 1 to 48. No correlation was found between the level of expression of proto-ret and the clinical stage. The level of expression was also not correlated with N-myc amplification, the patient's age or the histological type of the tumor. Based on the previous finding that proto-ret expression is very rarely detected in tumor cell lines other than those of neuroblastoma, proto-ret expression was suggested to be a characteristic of neuroblastomas, and possibly to be involved in the genesis of neuroblastomas.

Actins↗
PubMed1990

DNA adducts formed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rat liver: dose-response on chronic administration.

The effect of administration of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) at various doses on DNA adduct formation in male rats was examined by 32P-postlabeling analysis. Administration of MeIQx in the diet at 0.4 ppm, 4 ppm, 40 ppm and 400 ppm for one week resulted in the formations of 0.04, 0.28, 3.34 and 39.0 adducts per 10(7) nucleotides in rat liver cells. Continuous administration of 400 ppm of MeIQx in the diet for 61 weeks to rats induced hepatocellular carcinomas in all rats. The carcinogenicity of MeIQx at doses of 40 ppm or less is not known yet, but the above results show a linear relationship between the level of MeIQx administered and the adduct level. In rats treated with low doses of 0.4, 4 and 40 ppm of MeIQx, adduct levels increased linearly with time of treatment, the levels in week 12 being two to three times those in week 1. In contrast, on treatment with 400 ppm of MeIQx, the adduct level in the liver increased until week 4, when it was 110 adducts per 10(7) nucleotides, and then remained constant for the next 8 weeks. Induction of the multidrug-resistance gene was suggested to be involved in development of this plateau level.

Animals↗
PubMed1990

Two-dimensional electrophoretic analysis of hepatitis-associated polypeptides in liver of LEC rats developing spontaneous hepatitis.

High-resolution two-dimensional polyacrylamide gel electrophoresis in combination with silver staining was used to analyze between 800 and 1000 cytosolic and particulate polypeptides from age-matched livers of normal male Long-Evans rat with Agouti coat color (LEA) and Long-Evans rat with Cinnamon-like coat color (LEC) rats with hereditary trait of hepatitis at ages long before, immediately prior to, and just after the onset of hepatitis. Although the electrophoretic patterns of polypeptide expression were very similar with respect to the overall spot patterns, a number of polypeptides which differed either qualitatively or quantitatively were noted. Two constitutively expressed cytosolic polypeptides, P29.5 (Mr 29.5 kDa/pI 6.73) and P30 (30 kDa/6.70), were not detected in livers of LEC animals at any age. In the normal LEA rats both P29.5 and P30 were detected as early as one day after birth and both were expressed at similar concentrations at all ages. In the LEC rats P30-C (30 kDa/6.68) was constitutively expressed in close proximity to the expected position of P30, and P30-C was not detected in the LEA rats. By means of non-equilibrium pH gradient electrophoresis two relatively basic polypeptides were detected in the LEC rats. P18ne was detected immediately prior to and P27ne immediately after the clinical manifestation of hepatitis. Experiments in F1 backcross ([LEA x LEC] x LEC) animals, however, failed to demonstrate any genetic link between either the expression or lack of expression of P29.5, P30, P30-C, or P18ne and hepatitis development. P27ne was detected in all backcross animals exhibiting hepatitis, but was never observed in LEC rats prior to the onset of hepatitis. Although we were unable to identify any unique loss of expression of polypeptides which are genetically linked to hepatitis susceptibility in LEC rats, specific subsets of quantitatively modulated polypeptides were detected.

Animals↗
PubMed1990

Isolation of an amplified DNA sequence in stomach cancer.

By use of the in-gel DNA renaturation method, the presence of amplified DNA sequences was demonstrated in KATO-III, a cell line established from a signet ring cell carcinoma of the stomach. A DNA fragment from one of these amplified regions in KATO-III cells was cloned and designated SAM0.2; the locus containing the SAM0.2 fragment was referred to as SAM. The SAM locus was shown to be amplified not only in KATO-III cells, but also in three of 24 surgical specimens of stomach cancers and in two of 13 xenografts of human stomach cancers, all of these specimens being poorly differentiated adenocarcinoma or mucinous adenocarcinoma of the stomach. The SAM locus was not amplified in 14 cell lines of cancers of other organs or in 42 surgical specimens of lung cancers.

Adenocarcinoma↗
PubMed1990

Frequent detection of hepatitis C virus US strain in Japanese hemophiliacs.

Hemophiliacs have been found to be at high risk of hepatitis. Hemophiliacs in Japan receive imported clotting factors as well as domestic ones. Recently we found that hepatitis C virus (HCV) could be classified into at least two types, HCV-US and HCV-J, depending on the nucleotide sequence. We analyzed the nucleotide sequences of virus RNAs from the plasma of patients with hemophilia A or B and found HCV-US in 3 of 4 Japanese hemophiliacs examined.

Adolescent↗
PubMed1990

Identification of members of the protein phosphatase 1 gene family in the rat and enhanced expression of protein phosphatase 1 alpha gene in rat hepatocellular carcinomas.

We isolated four kings of cDNA clones of isotypes of catalytic subunits of protein phosphatase 1 (PP-1) from rat liver and testis cDNA libraries. For the cloning, cDNA fragments of dis2ml and dis2m2, which encode mouse PP-1 catalytic subunit, were used as probes. Two of the four isotypes were thought to be derived from the same gene and produced by alternative splicing. Based on the comparative study of their nucleotide and deduced amino acid sequences with those reported, these cDNA clones were named rat PP-1 alpha, PP-1 gamma 1, PP-1 gamma 2 and PP-1 delta. The deduced amino acid sequences of these four cDNA clones showed about 90% identity. Their amino-terminal regions were highly conserved, and their differences were mainly in the carboxy-terminal regions. Furthermore, several amino acids located in the middle regions of the peptides were conserved in all the isotypes of the catalytic subunits of PP-1, PP-2A, PP-2B and PP-2C. These conserved regions are suggested to be the functional domains of the catalytic subunits of protein phosphatases. Rat hepatocellular carcinomas induced by a food mutagen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline showed increased expression of PP-1 alpha, but no increased expression of PP-1 gamma 1, PP-1 gamma 2 or PP-1 delta. Involvement of PP-1 alpha in hepatocarcinogenesis or in hepatic cell proliferation was suspected.

Amino Acid Sequence↗
PubMed1990

Correlation between blood prostaglandins, plasma lipids and atherosclerosis in dialyzed patients.

The correlations between the degree of atherosclerosis, plasma prostaglandins (PGs) and plasma lipids were examined in maintenance hemodialyzed patients with and without diabetes mellitus. The degree of atherosclerosis was evaluated by pulse wave velocity (PWV) of the aorta. Plasma PGs were radioimmunoassayed. PWV was significantly higher in hemodialyzed patients compared to sex- and age-matched healthy controls. PWV correlated with the plasma thromboxane A2 (TXB2) level and TXB2/6-keto-PGF1 alpha ratio in hemodialyzed patients, without a significant difference between the diabetic and nondiabetic groups. The plasma lipid profile was type IV of the WHO classification in both the diabetic and nondiabetic groups, and PWV did not correlate with these lipid abnormalities. Though not significantly, the decreases in plasma PGE2 and 6-keto-PGF1 alpha and the increase in TXB2 correlated with the degree of type IV hyperlipidemia. The results suggest that plasma PG abnormalities might correlate with the degree of atherosclerosis in hemodialyzed patients.

Adult↗
PubMed1990

Estimation of 140S particles in foot-and-mouth disease virus (FMDV) vaccine by using the computer analyzing system.

The quantity of 140S particles in inactivated foot-and-mouth disease virus (FMDV) vaccine samples produced in Foot-and-Mouth Disease Vaccine Production Center (FMD Vaccine Production Center) in Thailand was estimated by the sucrose gradient ultracentrifugation and optical density analysis by using the computer applying system. The soft ware; Chromato Data System (CDS) (Nihon Chromato Works Co., Ltd. Japan) which is prepared for the analysis of chromatography, was applied for the estimation of 140S particles in FMDV vaccine. The quantity of 140S particles in each vaccine sample measured by CDS was mostly ranged from 2-4 micrograms/ml and this quantity was consistent with the results of the other reports. This method is considered to be the available method for estimation of 140S particles in FMDV vaccine as routine assay.

Aphthovirus↗
PubMed1990

Partial purification and properties of cathepsin G-like proteinase of mouse myeloid leukemia M1 cells.

A proteinase extracted with 1M NaCl from particulate fraction of the postnuclear fraction of mouse myeloid leukemia M1 cells was partially purified by Bio-Gel HTP treatment and Sephadex G-75 gel filtration. The apparent molecular mass of the proteinase was 26,000 Da and the isoelectric point was about pH 10. The enzyme activity was inhibited by phenylmethanesulfonylfluoride, chymostatin, and soy-bean trypsin inhibitor. It hydrolysed specifically Suc-Ala2-Pro-Phe-4-methylcoumaryl-4-amide (MCA). NaCl and KCl enhanced several times the activity for Suc-Ala2-Pro-Phe-MCA, but not that for fluorescein-labeled albumin and fibrinogen. These enzymic properties of the major proteinase are similar to those of chymotrypsin and cathepsin G. The role of a cathepsin G-like proteinase in relation to M1 cell differentiation is discussed.

Amino Acid Sequence↗
PubMed1990

[Holistic and analytic modes in classification learning of young children].

To examine the factors underlying children's categorization modes (holistic vs. analytic) and ease of classification learning, 5-6 year-olds were given a classification task of schematic faces with two values in each of five dimensions. The tasks varied on the similarity between sample and learning exemplars (high vs. low) and the number of categories to be classified (one vs. two), and could classify either by holistic or analytic mode. The subjects were trained on one of the four tasks and tested the categorization modes after reaching each of three learning criteria (4/4, 8/8, and 8/8 + 8 correct). The results showed that (a) with increasing training trials, the number of subjects who used the analytic mode increased while that who used the holistic mode decreased, (b) the number of subjects who used the analytic mode was greater for the low-similarity than the high-similarity tasks, and (c) the task with two categories was learned faster than that with one category.

Child↗
PubMed1990

Detection of endotoxin antibody in long-term dialysis patients.

Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 10(8). These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophan and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers.

Antibodies↗
PubMed1990

Heterocyclic amines produced in cooked food: unavoidable xenobiotics.

Humans are continuously exposed to naturally occurring and industrial xenobiotics in their daily lives. Heterocyclic amines, which are formed during the cooking of proteinaceous foods, have been categorized as a new class of naturally occurring xenobiotics. They are divided into 2-amino-3-methylimidazo[4,5-f] quinoline (IQ)- and non-IQ-types. The amounts and proportion of total mutagenicity contributed by the IQ-type heterocyclic amines in cooked food are greater than those of the non-IQ-types. Precursors of the IQ-type heterocyclic amines including IQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are creatinine, amino acids and sugars in meat and fish. Both types of heterocyclic amines are carcinogenic in mice and rats. All heterocyclic amines except PhIP frequently induce cancers in the liver, while PhIP induces lymphomas in mice and carcinomas of the colon and mammary gland in rats. Based on quantitative analysis of heterocyclic amines in cooked food and levels of excretion of unchanged heterocyclic amines in human urine, total heterocyclic amine intake was calculated to be around 0.4-16 micrograms/person per day. As in the case of other naturally occurring xenobiotics, and degree of exposure is small and is presumably insufficient alone to account for the development of human cancer. Nevertheless, a linear relationship has been demonstrated between DNA adduct levels and a wide range of doses of MeIQx in animals. In addition, combined treatment with five heterocyclic amines yielded additive or synergistic effects in the development of glutathione S-transferase placental form (GST-P) positive foci. Taking these results and current observations of multiple genetic alterations in human cancers into consideration together, heterocyclic amines are probably involved in the development of human cancer in the presence of other carcinogens, tumor promoters and factors stimulating cancer progression.

Amines↗
PubMed1990

Metabolic processing and carcinogenicity of heterocyclic amines in nonhuman primates.

The potential for human exposure to heterocyclic amine (HAA) mutagens derived from cooking food prompted an evaluation of the disposition and carcinogenicity of three of the HAAs in nonhuman primates, especially cynomolgus monkeys. The three HAAs currently under study are 2-amino-3-methylimidazo [4, 5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo [4,5,b]pyridine (PhIP). These three HAAs were selected on the basis of several factors including structure, mutagenic activity in vitro, concentration in cooked meat, activity in rodent carcinogenicity tests and availability. Studies on the disposition of IQ demonstrated that it was extensively metabolized in monkeys and excreted in urine and feces as metabolites. These metabolites represent predominantly detoxification products of IQ. The extent of in vivo activation of IQ and PhIP was assessed by measuring DNA adducts in various tissues and white blood cells of monkeys following administration of the compounds. Both compounds form high levels of DNA adducts in a number of organs, particularly the liver, kidney, and heart. The carcinogenicity of IQ, 8-MeIQx and PhIP in nonhuman primates has been under study for 5 years, 24 months, and 7 months, respectively. Thus far, IQ has induced hepatocellular carcinoma in 3 of 20 monkeys at doses of 10 mg/kg daily, 5 days/week and in 10 of 20 monkeys at 20 mg/kg on the same schedule. Thus, IQ is a potent liver carcinogen in nonhuman primates and a potential carcinogen for humans.

Animals↗
PubMed1990

Variable mutations of the RB gene in small-cell lung carcinoma.

Loss of heterozygosity for chromosome 13q including the RB locus is a common genetic alteration in small-cell lung carcinoma (SCLC) as well as in retinoblastoma. We examined the RB cDNA sequences of exon 13 to 18 and exon 19 to 23 in 9 SCLC cell lines to detect mutations which cause inactivation of the remaining allele of the RB gene. Internal deletions of RB cDNA were observed in 3 of the 9 SCLC cell lines. In the Lu-24 cell line, a 114 base pairs (bp) deletion corresponding to exon 22 was due to abnormal splicing, which probably resulted from a two-base mutation within genomic exon 22, and aberrant 105 kilodaltons RB protein was detected by immunoprecipitation analysis. A base pair deletion within exon 20 in the Lu-135 cell line and a 1 bp deletion within exon 23 in the Lu-141 cell line were due to the deletions of the corresponding genomic DNA, and each deletion resulted in formation of a premature termination codon. These results indicate that both alleles of the RB genes are inactivated in SCLC by several different mechanisms, including small deletion, mutation and chromosomal loss.

Alleles↗
PubMed1990

Characterization of ret proto-oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line.

The ret proto-oncogene expresses four major mRNA species of different lengths in human malignant cell lines and rat tissues. We isolated ret proto-oncogene cDNA clones from a cDNA library of a human neuroblastoma line, Nagai, which over-expressed these mRNAs. Four cDNA clones differing from each other in their 3' portions were analysed. The sequence of the region common to the cDNA clones is essentially identical to a reported cDNA sequence derived from THP-1 monocytic leukemia cells, that encodes a protein with characteristic features of receptor-type tyrosine kinase. From the 3' heterogeneity, two isoforms of the ret proto-oncogene product of 1072 and 1114 residues that differed from each other in their 9 and 51 C-terminal amino acids are predicted. Comparison of the structures of cDNA clones with that of the genomic clone showed that the 3' heterogeneity is produced by alternative polyadenylation and splicing of mRNA. Northern blot analysis using various fragments of cDNA indicated that the 4.5 kb, 3.9 kb and possibly 7.0 kb transcripts may encode a protein of 1072 residues, while the 6.0 kb transcript and a (minor) 4.6 kb transcript may encode a protein of 1114 residues.

Amino Acid Sequence↗