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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 667 records · Page 37Linked to original sources
PubMed1984

Immortalization of peripheral blood lymphocytes of cats by human T-cell leukemia virus.

Peripheral blood lymphocytes of domestic cats were co-cultivated with lethally irradiated MT-2 cells, which produced human T-cell leukemia virus type 1 (HTLV-I). Two cat lymphoid cell lines, CaL-1 and CaL-2, established and maintained without exogenously added T-cell growth factor, were characterized after more than 6 months of cultivation. These cells grew in suspension, had a chromosome number of 38 and lacked cytoplasmic and surface immunoglobulins. CaL-2 cells formed E-rosettes. Both cell lines harbored HTLV genomes but not human Alu family sequences, which are highly repetitious in the human genome, suggesting that transfer of human DNA fragments was not necessary for their immortalization or transformation. HTLV antigens were detected in CaL-1 and CaL-2 cells by indirect immunofluorescence assay. CaL-1 and CaL-2 cells both expressed viral proteins with apparent molecular weights of 53 kd, 24 kd and 19 kd, and CaL-2 cells also expressed 28 kd and 20 kd proteins. Reverse transcriptase activity was detected in culture fluid of CaL-2 cells, but not of CaL-1 cells. CaL-2 cells but not CaL-1 cells had syncytium-induced activity. These findings indicated that lymphocytes of cats, especially T lymphocytes, were susceptible to infection with HTLV and to immortalization by HTLV.

Animals↗
PubMed1984

Monoclonal antibodies to poly(adenosine diphosphate ribose) recognize different structures.

Two hybridomas producing monoclonal antibodies to poly(adenosine diphosphate ribose) [poly(ADP-Rib)] were established. One antibody, 10H (IgG3, kappa), bound to most of the poly(ADP-Rib) preparation, which consisted of molecules of various sizes of more than 20 ADP-Rib residues. The binding of this antibody was inhibited by not only poly-(ADP-Rib) but also a monomer unit of poly(ADP-Rib), Ado(P)-Rib-P. The sites protected by antibody 10H were isolated and analyzed by hydrolysis with alkaline phosphomonoesterase and then snake venom phosphodiesterase. The sites contained the same amounts of monomer units and branched portions [Ado(P)-Rib(P)-Rib-P] as the original poly(ADP-Rib) molecules but a lower average number of branched portions per molecule than in the original molecules. The other antibody, 16B (IgM, lambda), reacted with only 50% of the radioactive poly(ADP-Rib), and its binding was not inhibited by a monomer unit. This antibody protected 25% of all the poly(ADP-Rib) molecules from hydrolysis by snake venom phosphodiesterase. The protected sites contained twice as many branched portions per molecule as the original poly(ADP-Rib) molecules. These results show that the two monoclonal antibodies recognize different structures of poly-(ADP-Rib); 10H antibody recognizes the linear structure with ribose-ribose linkages, and 16B antibody may recognize specific structures, including the branched portions of poly-(ADP-Rib).

Animals↗
PubMed1984

Activation of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) by new classes of tumor promoters: teleocidin and debromoaplysiatoxin.

The new potent tumor promoters teleocidin and debromoaplysiatoxin , which are structurally unrelated to phorbol esters, activate Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). The concentrations of 12-O-tetradecanoylphorbol-13-acetate, teleocidin and debromoaplysiatoxin for half-maximum activation of protein kinase C were found to be approximately 3 ng/ml, 40 ng/ml and 400 ng/ml, respectively. These three types of tumor promoters bind to protein kinase C, and appear to exhibit their pleiotropic actions through activation of this enzyme.

Alkaloids↗
PubMed1984

Expressions of the c-Ha-ras and c-myc genes in rat liver tumors.

Expressions of the c-Ha-ras and c-myc genes were studied by Northern blotting of total RNA from primary tumors and non-tumorous parts of the liver of rats given diet containing 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and from established rat hepatoma cell lines. The expression of the c-Ha-ras gene was found to be high in the primary tumors, non-tumorous parts of 3'-Me-DAB-treated livers and hepatoma cell lines. In contrast, the c-myc gene was expressed at a high level only in primary tumors and hepatoma cell lines. During 3'-Me-DAB treatment, the c-Ha-ras mRNA level in the liver increased by day 5 and then remained high. Increase in expression of the c-Ha-ras gene in regenerating liver was confirmed. These findings suggest that increase in expression of the c-Ha-ras gene is related to proliferation of hepatocytes, whereas expression of the c-myc gene is associated with hepatocarcinogenesis.

Animals↗
PubMed1984

A two-stage mouse skin carcinogenesis study of lyngbyatoxin A.

A strong skin irritant, lyngbyatoxin A, isolated from the marine blue-green alga Lyngbya majuscula is structurally related to teleocidin. Since lyngbyatoxin A satisfied our short-term screening tests for possible tumor promoters, viz. irritation of mouse ear, induction of ornithine decarboxylase (ODC) in mouse skin, and adhesion of human promyelocytic leukemia cells (HL-60), a two-stage carcinogenesis experiment was carried out. Tumor incidences in the groups treated with 7,12-dimethylbenz(a)anthracene (DMBA) plus lyngbyatoxin A and with DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA) were 86.7% and 93.3% in week 30, respectively. The average number of tumors per mouse was 3.7 in the former group and 10.5 in the latter group. This paper reports for the first time the potent tumor-promoting activity of lyngbyatoxin A and also the histological examination of tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Formation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in a model system by heating creatinine, glycine and glucose.

A mixture of creatinine, glucose and glycine was heated in diethylene glycol containing 14% water for 2 h at 128 degrees C, and the mutagens formed were purified by XAD-2 column chromatography, acid-base partition, Sephadex LH-20 column chromatography, 'blue cotton' treatment and HPLC. Two mutagenic substances were isolated by HPLC. The major mutagen was identified by its UV absorption and mass and NMR spectra as 2-amino-3,8- dimethylimidazo [4,5-f]quinoxaline, which was originally isolated from fried beef. This finding supported the idea that creatinine, amino acids and sugars present in meat are precursors in the formation of the mutagenic imidazoquinoxaline derivative.

Chemical Phenomena↗
PubMed1984

Mutagenicity of instant coffee on cultured Chinese hamster lung cells.

Coffee showed mutagenic activity in cultured Chinese hamster lung (CHL) cells as assessed by using diphtheria toxin resistance as a selective marker. Most of the mutagenicity was suppressed in the presence of sodium bisulfite. The contribution of methylglyoxal to the total mutagenicity of coffee was less than 3%.

Aldehydes↗
PubMed1984

Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor.

Tyrosine-specific phosphorylation of the epidermal growth factor (EGF) receptor in hormonally stimulated A431 cells is blocked by three chemically distinct classes of tumor promoters. Tumor-promoting esters of the diterpene phorbol (phorbol 12-myristate 13-acetate, beta-phorbol 12,13-dibutyrate, and beta-phorbol 12,13-didecanoate), indole alkaloids (teleocidin and lyngbyatoxin A), and polyacetates ( aplysiatoxin and debromoaplysiatoxin ) all inhibited EGF-stimulated phosphorylation of the receptor. Non-tumor-promoting analogs (beta-phorbol, alpha-phorbol 12,13-didecanoate, and hydrolyzed teleocidin) had no effect on the levels of receptor phosphorylation. The ED50 values of the inhibitory effect (0.1-3 ng/ml) reflected the relative tumor-promoting abilities of these compounds in vivo. None of the tumor promoters tested significantly decreased the overall specific binding of 125I-labeled EGF to A431 cells. Scatchard analysis, however, revealed two apparent EGF receptors in this cell type. The dose-responses for tumor-promoter inhibition of EGF receptor tyrosine phosphorylation and high-affinity EGF binding were similar, suggesting that the same initial event is responsible for both effects. This demonstrates a correlation between modulation of EGF receptor binding and phosphorylation of tyrosine by tumor promoters. The data suggest a possible role for protein kinase C, the putative cellular receptor for these tumor promoters, in the mechanism of action.

Amino Acids↗
PubMed1984

Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient.

The transforming gene of malignant melanoma tissue obtained from a Japanese patient and maintained in nude mice has been cloned in its biologically active form and identified as the c-Ha-ras-1 gene, a homologue of the viral Ha-ras gene. Nucleotide sequence analysis revealed that the genetic alteration responsible for the transforming activity of the melanoma oncogene was localized to a single point mutation in the second exon. The transversion of adenine to thymine results in the substitution of leucine for glutamine as amino acid residue 61 of the predicted p21 protein. Other nucleotide sequences spanning a 2.9-kilobase segment including the entire exons and introns were found to be exactly the same as those in a proto-oncogene from a normal Caucasian reported previously, except for base alterations explained as polymorphic differences.

Base Sequence↗
PubMed1984

Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome.

The nucleic acid sequence of the 3' region of human T-cell leukemia virus type II (HTLV-II) proviral DNA was determined using a HTLV-II proviral clone that could be recovered as infectious, transforming virus. The sequence data indicate a region of unknown function of approximately equal to 1.6 kilobase pairs in the 3' region, analogous to the X region previously identified in human T-cell leukemia virus type I (HTLV-I). Three overlapping open reading frames are present in the X region of HTLV-II. One of these open reading frames, Xc, is most likely to encode a protein product, because it has greater predicted amino acid sequence homology (78%) with the X-IV region of HTLV-I and a greater percentage of its base differences with X-IV at the third nucleotide position of codons than do the other open reading frames. Sequences of the X-region that include the open reading frames are conserved in two deletion mutants of HTLV-II, which are associated with a subline of Mo cells with a decreased dependence on fetal bovine serum.

B-Lymphocytes↗
PubMed1984

Nucleotide sequence analysis of the long terminal repeat of human T-cell leukemia virus type II.

The nucleotide sequence of the human T-cell leukemia virus type II (HTLV-II) long terminal repeat (LTR) and its surrounding regions were determined. Our results show the following structural features: (i) the LTR is 763 base pairs (bp) in length and consists of 314 +/- 1 bp of region U3, 248 +/- 1 bp of region R, and 201 bp of region U5; (ii) the terminal nucleotides in the LTR form an inverted repeat of T-G.....C-A; (iii) 6-bp direct repeats of cellular sequences flanking the provirus were present; and (iv) the putative functional signals for initiation or termination of viral RNA synthesis were identified. Comparison of the HTLV-II LTR sequence with that previously published for adult T-cell leukemia virus (ATLV; HTLV-I) shows that the LTRs are distinct. Some small regions are conserved between HTLV-II and ATLV, involving sequences important for transcription and a sequence of 21 nucleotides repeated three times in U3. This 21-bp repeat may be important in regulating viral transcription in lymphoid cells.

Base Sequence↗
PubMed1984

Potent antitumor promoting activity of N-6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, in mouse skin tumor formation induced by 7,12-dimethylbenz[a]anthracene plus teleocidin.

A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) markedly inhibited the promoting activity of teleocidin on formation of skin tumors in mice initiated by 7,12-dimethylbenz[a]anthracene. This result strongly indicates that the critical action of the Ca2+-calmodulin system is responsible for tumor promotion in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Estimation of tumor promoting activity and structure-function relationships of aplysiatoxins.

Twelve aplysiatoxin compounds have been evaluated as possible tumor promoters in vivo by means of three biological tests: viz. irritation of mouse ear, induction of ornithine decarboxylase in dorsal skin of mice, and inhibition of specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to an epidermal particulate fraction. The potencies of these three biological activities correlate well for each derivative. Bromoaplysiatoxin shows biological activities that are similar to those of the strong tumor promoter, aplysiatoxin. The present studies suggest that the C-3, C-20 and C-30 hydroxyl groups of the aplysiatoxins are involved in binding to the specific receptor of TPA.

Animals↗
PubMed1984

Induction of sarcomas in rats by subcutaneous injection of dinitropyrenes.

The carcinogenicities of potent mutagenic dinitropyrenes were examined by their subcutaneous injections into male F344/ DuCrj rats. Animals were injected with 0.2 mg each of 1,3- and 1,8-dinitropyrenes (1,3- and 1,8- DNPs ) dissolved in 0.2 ml of dimethyl sulfoxide (DMSO) twice a week for 10 weeks. In rats treated with 1,8-DNP, sarcomas were induced at the sites of injection in all 10 animals tested between the 113th and 127th experimental days. In rats treated with 1,3-DNP, 10 of 10 rats developed sarcomas between days 119 and 320. Some tumors induced by these chemicals were transplantable into the same strain of rats. No tumors developed in control rats, which received only DMSO.

Animals↗