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Biomedical subjects

S Nishimura

Publications and source records attributed to S Nishimura.

At least 775 records · Page 43Linked to original sources
PubMed1985

Activation of c-Ki-ras gene in human pancreatic cancer.

DNA isolated from a lymph node with metastasis from pancreatic adenocarcinoma in a Japanese male patient transformed NIH3T3 cells upon transfection by the calcium-phosphate precipitation technique. Analysis of DNA from the transformant revealed the presence of an activated human c-Ki-ras gene, which is considered to be responsible for the transformation of the NIH3T3 cells.

Adenocarcinoma↗
PubMed1985

Transforming activity of the c-Ha-ras oncogene having two point mutations in codons 12 and 61.

A recombinant plasmid carrying the human c-Ha-ras gene with two point mutations in codons 12 and 61 was constructed and its transforming activity on mouse NIH 3T3 cells was compared with those of genes with a single mutation in either codon 12 or 61. Quantitative analyses revealed that the gene with two mutations had essentially the same transforming activity as the genes with single mutations. These results indicate that a single mutation of the c-Ha-ras gene in either codon 12 or 61 is sufficient to activate the gene and that neither of the two mutation sites involved in activation of the gene needs to be intact for transforming activity.

Animals↗
PubMed1985

Lymphatic distribution of an anti-tumor agent in postoperative adjuvant chemotherapy in gastric cancer: fat-emulsified preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil in lymph.

In 8 postoperative patients with gastric cancer the effectiveness of fat emulsification of tegafur as a means of improving the drug distribution in the lymphatic tissue was studied. A water-in-oil type of emulsion of tegafur (FT-w/o) and an oil-in-water type of emulsion of tegafur (FT-o/w) were orally administered. A fistula in the thoracic duct, prepared in advance, was used to collect lymph. The concentrations of tegafur and 5-FU were compared in simultaneously obtained specimens of lymph and peripheral blood. In the case of FT-w/o, the tegafur concentration at 30-60 min after administration was significantly higher in both the lymph and plasma than that found using FT-o/w. In the case of FT-w/o, the 5-FU concentration at 30-120 min after the administration was significantly higher than that found with FT-o/w in both the lymph and the plasma. Thus, FT-w/o shows excellent distribution in both lymph and blood, and is considered useful as an adjuvant chemotherapeutic agent in the postoperative treatment of gastric cancer patients.

Administration, Oral↗
PubMed1985

[Left ventricular diverticulum: a report of two cases].

Left ventricular diverticulum is a rare congenital cardiac malformation, and is classified as muscular and fibrous. Muscular diverticula are usually associated with thoracoabdominal defects and arise from the cardiac apex. We encountered two cases of muscular left ventricular diverticulum without other congenital anomalies during the review of 3,000 left ventriculograms. Both patients were men and their diverticula were located along the inferior left ventricular wall. No symptoms were associated with the diverticula. In both cases, two-dimensional echocardiography detected the diverticula, thus this is regarded as a useful method for the diagnosis and screening of this anomaly. In one of our cases, thallium myocardial imaging also demonstrated a characteristic abnormal bulge corresponding to the diverticulum. We subsequently detected two more cases of muscular left ventricular diverticula among 300 left ventriculograms. Thus, we detected four cases of left ventricular diverticula among 3,300 left ventriculograms. Although only 11 cases of muscular left ventricular diverticulum previously have been reported, this anomaly is not so rare as previously supposed, and it should be distinguished from left ventricular aneurysm.

Adult↗
PubMed1985

[Histological features of apical hypertrophic cardiomyopathy].

Biopsy specimens of 16 patients diagnosed by cardiac catheterization and angiography as having primary hypertrophic cardiomyopathy were examined. They were categorized as apical hypertrophy type in six, septal hypertrophy type in five, and others in five. Histological examinations disclosed edema, fibrosis, disorganization and bizarre nuclei in the myocardium in all types of disease entity, and it was possible to diagnose histologically primary cardiomyopathy in three each of the apical and other types. The remaining cases, however, did not show histological findings compatible with cardiomyopathy. We concluded that primary cardiomyopathy cannot always be diagnosed by biopsy data alone, and echocardiography and angiography are essential for its diagnosis.

Biopsy↗
PubMed1985

Monoclonal antibodies to queuine.

Monoclonal antibodies specific for queuine have been prepared. Synthetic 9-(5-carboxypentyl)queuine (cp9Q) was conjugated with bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH), and the conjugate was used to immunize BALB/c mice by intraperitoneal and subcutaneous injection. Monoclonal antibodies were subsequently obtained by fusion of spleen cells and the mouse myeloma cell line X63Ag8U1. An enzyme-linked immunoabsorbent assay (ELISA) using o-phenylenediamine as peroxidase substrate was used for screening of clones and characterization of antibodies. Inhibition experiments with various homologous nucleosides revealed that the monoclonal antibody designated as 2D8E6 has no cross-reactivity with guanosine, adenosine or 7-methylguanosine.

Animals↗
PubMed1984

A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer.

Amplifications of two oncogenes, c-K-ras-2 and c-myc, were found in a human lung giant cell carcinoma (LGCC) Lu-65, which is maintained in nude mice. The extent of c-K-ras-2 and myc amplifications were estimated to be 10- and 8-fold, respectively, by means of the Southern hybridization procedure. In addition, NIH3T3 cells were transformed by transfection of Lu-65 DNA and the transforming gene was identified as c-K-ras-2. c-K-ras-2 genes were cloned from a gene library of Lu-65 and a single point mutation causing a substitution of cysteine for glycine in codon 12 was found by DNA sequencing. It was concluded that the amplification of the c-myc and c-K-ras-2 genes are accompanied by point mutational activation of c-K-ras-2 in the human LGCC Lu-65. This is the first report of multiple gene amplification accompanied by a point mutation of oncogenes in human cancer cells, providing further support for the idea that co-operation of at least two activated cellular oncogenes is required for carcinogenesis.

Amino Acid Sequence↗
PubMed1984

The adsorption of bovine blood proteins onto the surface of O-(carboxymethyl)chitin.

Chitin was found to interact with bovine blood proteins and the affinities of these proteins for chitin tended to be decreased by the introduction of O-carboxymethyl (CM) groups onto the chitin surface, especially with fibrinogen. As the adsorption of blood proteins to the CM-chitin (d.s. 0.35) was assumed to follow an isothermal adsorption-curve, the adsorption coefficients were estimated by applying the Langmuir equation. Bovine serum albumin showed the highest affinity among the proteins applied in this experiment [KBSA (bovine serum albumin); 20.0, KB gamma G (bovine gamma globulin); 1.96, KBF (bovine fibrinogen); 1.20]. The binding site of BSA for CM-chitin was assumed to be regulated not only by the cationic groups of BSA but also by other factors such as the recognition capacity of BSA to bind to GlcNAc residues in CM-chitin.

Adsorption↗
PubMed1984

Nucleotide sequence of initiator tRNA from Mycobacterium smegmatis.

The nucleotide sequence of initiator tRNA from Mycobacterium smegmatis was determined to be pCGCGGGGUGGAGCAGCUCGGDAGCUCGCUGGGCUCAUAACCCAGAGm7GUCG CAGGU psi CGm1AAUCCUGUCCCCGCUACCAOH . The nucleotide sequence of Mycobacterium initiator tRNA was found to be the same as that of Streptomyces initiator tRNA, except that G46 and A57 were replaced by m7G46 and G57 , respectively. The striking feature of Mycobacterium initiator tRNA is the absence of ribothymidine at residue 54, and the presence of 1-methyladenosine at residue 58 which makes the sequence of this tRNA similar to that of eukaryotic initiator tRNA.

Adenosine↗
PubMed1984

Purification and some properties of delta 2-isopentenylpyrophosphate:5'AMP delta 2-isopentenyltransferase from the cellular slime mold Dictyostelium discoideum.

delta 2-Isopentenylpyrophosphate:5'AMP delta 2-isopentenyltransferase, which catalyzes the formation of isopentenyl-AMP from delta 2-isopentenylpyrophosphate and 5'AMP, was purified 6800-fold from the fruiting body of the cellular slime mold Dictyostelium discoideum using several separation procedures including 5'AMPox-red AH-Sepharose 4B affinity column chromatography. The final preparation was very unstable and lost its activity in a day. Various properties of the 1000-fold-purified enzyme preparation were examined. The molecular mass was 40,000 +/- 2000 Da, as determined by Sephadex G-100 superfine gel filtration. The divalent metal ions Mn2+, Zn2+, and Mg2+ profoundly affected the enzymatic activity depending on their concentration, and also altered the optimum pH and temperature. Of the compounds tested, 5'AMP was the best acceptor of the isopentenyl group and, interestingly, ADP also served as a substrates, being 60-80% as effective as 5'AMP. Adenine, adenosine, and ATP were not substrates for this enzyme. Under the optimum assay conditions (pH 7.0, 1 mM Zn2+, and 25 degrees C) the Km values for 5'AMP and delta 2-isopentenylpyrophosphate were 1.0 X 10(-7)M and 2.2 X 10(-6)M, respectively.

Alkyl and Aryl Transferases↗
PubMed1984

Detection and identification of mutagens and carcinogens as their adducts with guanosine derivatives.

For use in screening for environmental mutagens and carcinogens, a highly fluorescent derivative of guanosine, 2'-deoxy-2'-(2",3"-dihydro-2",4"-diphenyl-2"-hydroxy-3"-oxo-1"-pyrrol yl) guanosine (FG), was synthesized. When incubated with FG in aqueous solution, mutagens form adducts that can be analyzed with an HPLC-fluorescence detector-system. By this method, mutagens such as glyoxal, methylglyoxal, 2-(2-furyl)-3-(5-nitrofuryl) acrylamide and 4-nitroquinoline-N-oxide, used as model compounds, were detected rapidly with high sensitivity. Reaction with isopropylideneguanosine (IPG), followed by isolation and characterization of the mutagen-IPG-adduct was found to be a useful method for identifying unknown mutagens in crude samples. This method was successfully applied in identification of the mutagens in heated glucose (200 degrees C, 20 min); glyoxal-IPG and 8-hydroxy-IPG were identified in the reaction mixture.

Carcinogens↗
PubMed1984

Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents.

The C-8 position of deoxyguanosine (dGuo) was hydroxylated by ascorbic acid in the presence of oxygen (O2) in 0.1 M phosphate buffer (pH 6.8) at 37 degrees C. Addition of hydrogen peroxide (H2O2) remarkably enhanced this hydroxylation. The Udenfriend system [ascorbic acid, FeII, ethylenediaminetetraacetic acid (EDTA) and O2] was also effective for hydroxylation of dGuo in high yield. Guanine residues in DNA were also hydroxylated by ascorbic acid. Other reducing agents, such as hydroxylamine, hydrazine, dihydroxymaleic acid, sodium bisulfite and acetol, were also effective for the hydroxylation reaction, as were metal-EDTA complexes (FeII-, SnII-, TiIII-, CuI-EDTA). An OH radical seemed to be involved in this hydroxylation reaction in most of the above hydroxylating systems, but another reaction mechanism may also be involved, particularly when dGuo is hydroxylated by ascorbic acid alone or ascorbic acid plus H2O2. The possible biological significance of the hydroxylation of guanine residues in DNA in relation to mutagenesis and carcinogenesis is discussed.

8-Hydroxy-2'-Deoxyguanosine↗