PubMed Health⌕ Search

Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 253 records · Page 14Linked to original sources
PubMed1995

Frequent development of murine T-cell lymphomas with TcR alpha/beta+, CD4-/8- phenotype after implantation of human inflammatory breast cancer cells in BALB/c nude mice.

Tumors developed quite frequently in some of the visceral organs, including spleen and liver, in BALB/c nude mice upon subcutaneously xenografting surgical specimens from five different inflammatory breast cancer patients. All of these tumors developed within two and a half months to one year after the subcutaneous inoculation of surgical specimens. From these tumors, five independent transplantable tumors, including tMK-2, tHK-1, tYK-1, tYK-2 and tTY-1 have been established. Chromosome analysis, morphologic studies by light and electron microscopy and phenotype analysis indicated that these tumors are of mouse origin. The tMK-2 tumor was highly metastatic to the spleen and liver when it was subcutaneously transplanted into the right scapular region. In addition, the region where the tMK-2 tumor cells were subcutaneously inoculated showed an apparently inflammatory process represented by erythema. After subcutaneous inoculation into the right scapular region, tHK-1, tYK-1, 2, and tTY-1 tumors also metastasized to some of the visceral organs, including spleen and liver. From these tumors, in vitro cell lines were established. The cells grew in a stromal-cell dependent manner under in vitro culture conditions. The cells were again tumorigenic at the inoculated region and metastasized to various organs, including liver and spleen, of BABL/c nude mice. Histological examination revealed that the tumors showed features of malignant lymphoma. Phenotypically, these five tumors expressed early T lymphocyte markers as revealed by anti-mouse anti-TcR alpha/beta, anti-CD3, CD4 and CD8 monoclonal antibodies. To our knowledge, these cell lines are the first T-cell lines showing the phenotype of extrathymically differentiated T-cells in the liver.

Animals↗
PubMed1995

Presence of Streptococcus DNA sequence in surgical specimens of gastric cancer.

In Southern blot analysis using Mycoplasma 16S ribosomal DNA (rDNA) as a probe, positive signals were detected in DNA samples from surgical specimens of gastric cancers. The DNA that hybridized to Mycoplasma 16S rDNA was eluted from the gel, cloned and sequenced. The cloned sequence was identical to 16S rDNA of Streptococcus anginosus. In Southern blot analysis with the S. anginosus 16S rDNA fragment as a new probe, positive signals were detected in 9 (20%) out of 43 cases of gastric cancer.

Adenocarcinoma↗
PubMed1995

Effective prevention of thrombocytopenia in mice using adenovirus-mediated transfer of HST-1 (FGF-4) gene.

HST-1 (FGF-4) gene product is a member of the fibroblast growth factor family with a signal peptide and plays a crucial role in limb development. We showed previously that an intraperitoneal injection of replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into normal mice caused a twofold increase in peripheral platelet count. To investigate whether Adex1HST-1 could effectively prevent experimentally induced thrombocytopenia in mice, we injected Adex1HST-1 intraperitoneally into thrombocytopenic mice induced by administration of a chemotherapeutic agent and/or by irradiation. A single Adex1HST-1 injection caused continuously increased levels of serum HST-1 protein for at least 30 d and increased the count of large megakaryocytes in bone marrow, which specifically recovered platelet counts and more efficiently diminished the extent and duration of thrombocytopenia than any other reported cytokine or any combination of cytokines so far. In the other peripheral hematological parameters, no discernible differences were detected. No other apparent side effects were observed. Therefore, this method could be useful for treatment and/or prevention of thrombocytopenia induced by chemotherapy and/or irradiation for cancer treatment.

Adenoviruses, Human↗
PubMed1995

Kawasaki disease.

Explore the source record for details and available documents.

Coronary Aneurysm↗
PubMed1995

Etiology and prognosis of liver cirrhosis in elderly patients.

We compared the etiology and prognosis of liver cirrhosis in patients age 60 and older with that of patients under age 60 during the 1980s (1981-89, n = 207). Non-A, non-B hepatitis (NANB) was significantly more prevalent in the elderly (p < 0.05), and the mean age of NANB and alcoholic cirrhosis (Alc) were significantly older than those with hepatitis B virus (HBV) (p < 0.05). Evaluation using hepatitis C virus (HCV) antibody also revealed significantly higher mean age of HCV (p < 0.05). Male patient was predominant in the younger patients than in the elderly patients. (M/F = 2.94 and 1.33, respectively) The estimated 5-year survival rate was 73.1% in the younger patients and 60.2% in the elderly patients (p < 0.05). Multivariate analysis revealed that male sex, a lower serum albumin level, and the presence of the encephalopathy were significantly associated with poor prognosis in the elderly, while a lower serum cholinesterase level and a higher indocyanin green retention rate at 15 minutes (ICGR15) were significantly associated with poor prognosis in younger patients. However, causes of deaths were not significantly different between the younger patients and the elderly patients, the proportion of deaths unrelated to liver disease predominated in the elderly patients. Thus, the etiology and the prognostic factors of liver cirrhosis in elderly patients differ from those in younger patients.

Age Factors↗
PubMed1995

Dietary modulation of the carcinogenicity of the heterocyclic amines.

UNLABELLED: Heterocyclic amines (HCAs) are potent mutagens and carcinogens formed during cooking of meats or fish. They are, therefore, widely consumed by humans. PURPOSE: A series of studies explore modulation of the mutagenicity and carcinogenicity of typical HCAs like 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP), through dietary fat, green or black tea, and tea polyphenols like epigallocatechin gallate (EGCG) and theaflavin gallate (TFG). Also examined was the carcinogenicity of the bacterial metabolite of IQ, 7-oxo-IQ. METHODS: Male and female F344 rats were fed diets with 75 ppm IQ for 12 months, and containing 5% or 20% corn oil. Complete necropsies after 15 months (males), or 18 months (females) were performed. Modification of the action of IQ and of PhIP in tests for bacterial mutagenicity (Ames test) or DNA repair in male rat hepatocytes (Williams test) by teas, EGCG or TFG was studied. Also compared was the activity of IQ and of 7-oxo-IQ in the tests of Ames and of Williams, and their carcinogenicity in male F344 rats upon intrarectal infusion. RESULTS: A high fat diet increased the carcinogenicity of low levels of IQ at several target organs. Multiple benign and malignant sebaceous skin tumors were noted in males but not in females. Green or black teas, EGCG, and TFG sharply reduced the mutagenicity of IQ and PhIP, and especially lowered the activity of IQ and of PhIP in the Williams test. 7-Oxo-IQ was active only in the Ames test, but not in the Williams test. Also, it was not carcinogenic, confirming that chemicals positive in the Ames test but negative in the Williams test are not likely carcinogens. CONCLUSIONS: The in vitro and in vivo effects of HCAs can be modified by dietary components such as fats or teas. An understanding of the underlying mechanisms may provide practical and realistic means of risk assessment, and may lower the risk associated with these nutritional carcinogens widespread in the human environment.

Amines↗
PubMed1995

Studies on the carcinogenic and myocardial effects of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in nonhuman primates.

The heterocyclic aromatic amine 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) is one of three heterocyclic amine mutagens currently being evaluated for carcinogenic activity in nonhuman primates, primarily cynomolgus monkeys. IQ was administered by gavage five times a week at doses of 10 or 20 mg/kg. Thus far IQ induced tumors in 50 percent of the monkeys at the 10 mg/kg dose and in 85 percent of the monkeys at the 20 mg/kg dose. Because H and E sections of the myocardium from IQ-treated animals demonstrated inflammatory infiltrate and studies of IQ-DNA adducts in monkeys, by the 32P-postlabeling method, showed high levels of adducts in the heart a systematic study of cardiac pathologic changes associated with chronic administration of IQ was undertaken. Both light and electron microscopic abnormalities were seen. The possibility exists that heterocyclic aromatic amines may be etiologic factors for human cancer and myocardial disease.

Administration, Oral↗
PubMed1995

Genetic alterations in HCA-induced tumors.

Accumulating evidence from molecular oncology indicates that carcinogens may induce tumors through characteristic mutations in characteristic genes for each agent. Identification of specific mutations induced by heterocyclic amines (HCAs), food-borne carcinogens, should facilitate risk assessment of HCAs in man. Identification of characteristic genes affected by HCAs will lead to identification of the genes involved in human carcinogenesis. We therefore examined tumors induced by various HCAs from these two viewpoints. With regard to forestomach tumors induced in CDF1 mice by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), mutations of Ha-ras and p53 were observed in four of eight and two of four tumors, respectively. One papilloma examined had mutations in both Ha-ras and p53, whereas two carcinomas had only one or the other. For Zymbal gland tumors induced in F344 rats by IQ, mutations of Ha- or Ki-ras were observed in both of two papillomas and in 10 of 13 squamous cell carcinomas (SCCs), while p53 mutations were limited to only four of the SCCs. The ras mutation was thus suggested to be an early event, while p53 mutation was more associated with malignancy. In liver tumors induced in F344 rats by 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), mutations of p53 were observed in one of two moderately-differentiated and two of two poorly-differentiated hepatocellular carcinomas (HCCs). No such changes were found in any of nine well-differentiated HCCs, suggesting p53 mutation to be a very late event. In colon tumors induced in F344 rats by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (nine adenocarcinomas), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (two adenomas and nine adenocarcinomas), or 2-amino-6-methyldipyrido[1,2-a:3', 2'-d]imidazole (Glu-P-1) (seven adenocarcinomas), a Ki-ras mutation was found in only one Glu-P-1-induced adenocarcinoma. No p53 mutations could be detected. In mammary gland carcinomas induced in F344 rats by PhIP, Ha-ras was activated in three of 17 carcinomas and p53 was mutated in one of 10 carcinomas. We therefore concluded that other genes were involved in colon and mammary carcinomas. G:C base pairs were involved in all 42 positive cases of the present study, and 36 of them were guanine base mutations. This indicates that the changes in IQ, MeIQx, PhIP and Glu-P-1 tumors were mainly caused by non-transcribed strand modifications through their major DNA adducts, N2-(guanin-8-yl)HCAs. Ha-ras mutations in the forestomach tumors induced by MeIQ were all G to T transversions at the second position of codon 13. Mutation sites of p53 did not appear to be specific in the forestomach, Zymbal gland and liver tumors.

Animals↗
PubMed1995

Sampling method as a key factor in identifying K-ras oncogene mutations in preneoplastic colorectal lesions.

The development of sensitive polymerase chain reaction (PCR)-based techniques in recent years has enabled us to verify the possible presence of mutated oncogenes and tumor suppressor genes in stages preceding tumor formation. Early detection of mutants serves as a powerful tool for detecting exposure to carcinogens and can assist in diagnosis. In studies performed in the past few years, we have identified mutant ras alleles in preneoplastic samples of patients with and without colorectal cancer. Our studies have shown (i) that mutant ras alleles are present at low incidence in normal appearing tissues of patients with colorectal cancer. Such mutations are also found in colonic effluents of patients at risk for developing this tumor type; and (ii) that the method of sampling is critical to ensure true representation of the entire colonic mucosa. The implications of identifying ras mutations in patients without evidence for neoplasma are discussed.

Biomarkers, Tumor↗
PubMed1994

Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of platelet count in vivo.

The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a variety of cell types of mesodermal and neuroectodermal origin, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in the number of platelets in the peripheral blood. The number of platelets reached twice the pretreated level by 12 days after the virus injection and the increased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the platelet count. The number of megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was increased compared with the control animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of platelet count by HST-1 protein remain to be elucidated, these findings also suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.

Adenoviridae↗
PubMed1994

Instability of microsatellites in rat colon tumors induced by heterocyclic amines.

Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/mircrosatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f] quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis.

Animals↗
PubMed1994

Highly efficient method for obtaining a subtracted genomic DNA library by the modified in-gel competitive reassociation method.

A highly efficient method to obtain a subtracted genomic DNA library using 1 microgram of target DNA was developed by modification of the previously reported in-gel competitive reassociation procedure. The modified method was based on polymerase chain reaction amplification after selective purification of a target-target reassociated molecule of subtracted DNA fragments to increase cloning efficiency. For a model experimental system, the subtracted DNA library was constructed after two cycles of subtractive reassociation between cervical cancer DNA fragments containing human papilloma virus DNA and the 100-fold excess of dephosphorylated normal tissue DNA fragments which were size-fractionated in agarose gel. Colony hybridization using human papilloma virus DNA as a probe revealed that a more than 500-fold enrichment of human papilloma virus DNA sequences in the subtracted DNA library could easily be obtained. This simple and efficient method will enable us to isolate an unknown foreign DNA fragment and an unknown amplified DNA fragment which might be present in cancer.

Base Sequence↗
PubMed1994

Characterization of the PP2A alpha gene mutation in okadaic acid-resistant variants of CHO-K1 cells.

Okadaic acid (OA)-resistant variants of Chinese hamster ovary cells, clones CHO/OAR6-6 and CHO/OAR2-3, were isolated from a CHO-K1 culture. These variant cells were 17- to 26-fold more resistant to OA than the parental cells. The phosphorylase phosphatase activity of the variant cell extracts was 2- to 4-fold more resistant to OA than that of the parental cells in the presence of inhibitor 2, a specific inhibitor of type 1 protein serine/threonine phosphatase (PP1). Nucleotide sequencing of PP2A alpha (an isotype of PP2A catalytic subunit) cDNA demonstrated that both variants have a T-->G transversion at the first base of codon 269 (805 nt), which results in substitution of glycine for cysteine. We expressed in COS-1 cells a mutant PP2A alpha tagged with the influenza hemagglutinin epitope. The recombinant mutant PP2A alpha protein immunoprecipitated with an anti-influenza hemagglutinin antibody was more resistant than the wild type to OA, their IC50 values being 0.65 nM and 0.15 nM, and their IC80 values being 4.0 nM and 0.45 nM, respectively. The cysteine at residue 269 present only in highly OA-sensitive protein serine/threonine phosphatase catalytic subunit isozymes, PP2A alpha, PP2A beta, and PPX, is suggested to be involved in the binding of OA. CHO/OAR6-6 and CHO/OAR2-3 cells also overexpressed the P-glycoprotein, and the efflux of OA was more rapid. It is suggested that the PP2A alpha mutation in cooperation with a high level of P-glycoprotein makes the CHO-K1 variants highly resistant to OA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines.

To study the involvement of the p16 tumor suppressor gene in esophageal cancer development, we examined homozygous deletion of the p16 gene in 13 human esophageal cancer cell lines and 9 gastric cancer cell lines, in which some of genetic alterations have already been characterized. By Southern blot analysis, homozygous deletion was observed in 12 out of the 13 esophageal cancer cell lines (92%), in 2 out of a total of 9 gastric cancer cell lines (22%). It was also found that the p16 gene loss, cyclin D1 amplification and p53 gene mutations occurred independently in these cell lines. These findings suggest that loss or mutations of the p16 gene are involved in most esophageal cancers and that mutation of this gene plays a critical role in the development of esophageal cancer.

Blotting, Southern↗
PubMed1994

Chinese hamster ovary cells resistant to okadaic acid express a multidrug resistant phenotype.

Two Chinese hamster ovary cell clones resistant to okadaic acid (OA) were isolated. The OA-resistance was associated with resistance to colchicine, Vinca alkaloids and inhibitors of DNA topoisomerase (topo) II. Drug accumulation assays showed that the intracellular levels of OA, vinblastine and vincristine, but not the topo II inhibitor etoposide, were significantly lowered in the OA-resistant mutants than in the parental cells. These results, together with the finding of an increased level of P-glycoprotein (P-gp) in the mutant cells, indicate that the resistances to OA, Vinca alkaloids and colchicine are due to a P-gp-mediated mechanism. Resistance to topo II inhibitors, however, was associated with reduced activity of topo II. Thus, at least two events, overexpression of P-gp and reduction of topo II activity, occurred in a single OA-resistant cell line, contributing to expression of the MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Dietary carcinogens and mammary carcinogenesis. Induction of rat mammary carcinomas by administration of heterocyclic amines in cooked foods.

Grilled or fried meat and fish contain various mutagenic heterocyclic amines, and structures of at least 19 compounds have already been determined. Among these, 10 have been examined for long term carcinogenicity, all proving to be positive. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), for example, preferentially induced mammary adenocarcinomas in 47% of Fischer 344 female rats when supplemented into the diet at a concentration of 400 parts per million (ppm) for 52 weeks. Moreover, 100 ppm of PhIP for 104 weeks yielded the same incidence. PhIP in the diet for 48 weeks also induced mammary cancer in Sprague-Dawley female rats with incidences of 72 and 25% at 200 ppm and 100 ppm. 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline in the diet at 300 ppm also induced a 25% incidence of mammary adenocarcinomas within 40 weeks. Analysis of PhIP-induced rat mammary carcinomas for ras mutations by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing revealed Ha-ras activation in 3 of 17 carcinomas; all were G-->A transitions at the second letter of codon 12 replacing glycine by glutamic acid. A p53 gene mutation was also found in 1 of 10 carcinomas examined; a G-->T transversion was detected at the third letter of codon 130, with a substitution of asparagine for lysine. PhIP is the most abundant mutagenic and carcinogenic heterocyclic amine in grilled meat, and, therefore, a role for this compound in human carcinogenesis is strongly implied.

Adenocarcinoma↗