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Biomedical subjects

H Endo

Publications and source records attributed to H Endo.

At least 541 records · Page 30Linked to original sources

Synergistic combination therapy of 5-fluorouracil, vitamin A and cobalt-60 radiation upon head and neck tumors.

We have applied a triple combination of 5-fluorouracil (5FU), vitamin A and cobalt-60 radiation (FAR therapy) to clinical treatment of head and neck tumors since 1972. The treatment of 33 patients with cancer of larynx and 15 patients with hypopharyngeal or cervical esophageal cancer with FAR therapy during three years from 1972 to 1974 resulted in highly effective synergism in vivo, and the improved points of this therapy were presented.

Cobalt Radioisotopes↗

Funiculosin, a new antibiotic. II. Structure elucidation and antifungal activity.

Structure elucidation and some biological properties of an antiviral and antifungal antibiotic, funiculosin, are summarized. Funiculosin is a derivative of N-methyl-4-hydroxy-3, 5-disubstituted-2-pyridone containing a novel substituent, cyclopentanetetrol moiety, that is reported here for the first time in a natural product. The antibiotic protects guinea pigs efficiently against experimental trichophytosis. Toxicity of funiculosin is unique and highly selective for animal species.

Animals↗

[Composition of the 32-detector rCBF system (Meditronic) and experience in its use (author's transl)].

Regional cerebral blood flow (rCBF) was measured in patients with no neurological deficit and no abnormal findings of cerebral angiograms except aneurysm itself with Xenon-133 injection technique by using the computerized 32-detector rCBF system (rCBF-322, Meditronic, Denmark). This system consists of a 32-detector head with a concave surface and a 32 pulse height analyser and analog-digital ratemeter as the accumulator connected to display units with an oscilloscope for 32 clearance curves and also a microcomputer programmed for calculating the rCBF initial with the initial slope analysis, for calculating the rCBF 10 with the height-over-area method and the rCBF gray, rCBF white, weight gray and weight white with the SHAM method. The results obtained were as follows: 1) The mean value and SD of rCBF initial was 58.4 +/- 6.2 ml/100 g brain/min; rCBF 10, 50.6 +/- 5.0 ml/100 g brain/min; rCBF gray, 78.0 +/- 14.0 ml/100 g brain/min; rCBF white, 22.1 +/- 6.6 ml/100 g brain/min; weight gray, 49.0 +/- 3.7%; weight white, 51.0 +/- 3.7%. These data should be considered normal values as reported also by others. 2) Reproducibilities were estimated by measuring twice the rCBF initial and the rCBF 10 at rest with closed eyes. The reproducibilities of the rCBF initial eyes 13.55% (P less than 0.05) and one of the rCBF 10 was 8.85% (P less than 0.05). It was concluded that this system should be widely used for measuring the rCBF in patients with various cerebral diseases.

Adult↗

Mode of mutagenic action of methylnitrosocyanamide, a potent carcinogen.

A potent carcinogen, methylnitrosocyanamide was used to induce revertants in a strain of Escherichia coli carrying an amber mutation in a gene for tryptophan (trp) biosynthesis and an ochre mutation in a gene for alkaline phosphatase biosynthesis. Trp+ revertants were purified and classified into seven categories based on their ability to support the growth of particular nonsense mutants of phage lambda and on their content of alkaline phosphatase. About 90% of the Trp+ revertants induced by methylnitrosocyanamide were due to mutations in suppressor genes, and 85% of the suppressor mutations occurred in gene supE. Intragenic reversion cannot occur by a GC leads to AT base substitution mutation, whereas this is the obligate mode of mutation in gene supE. We conclude that methylnitrosocyanamide preferentially induces GC leads to AT transition mutations but that other base substitution mutations are also induced at about 10% of this frequency. N-Methyl-N-nitrosourea and, particularly, N-methyl-N'-nitro-N-nitrosoguanidine also preferentially induce GC leads to AT transition mutations.

Codon↗

Differential control of synergistic effect with polyene macrolide antibiotics upon Chinese hamster cells in vitro.

An amphotericin B-resistant cell (AMBR-1), which was isolated from aneuploid Chinese hamster cells (V79), was found to show much higher resistance than the parent V79 cells to other polyene antibiotics, such as pentamycin and filipin. To obtain the 50 to 60% inhibition of the control protein synthesis activity by a synergistic combination of fusidic acid and amphotericin B, 50 microgram fusidic acid per ml were combined with 10 microgram amphotericin B in V79 cells, whereas in AMBR cells 50 microgram fusidic acid per ml were combined with 100 microgram polyene antibiotic per ml. Bleomycin (10 microgram/ml), which alone did not affect cellular DNA synthesis, inhibited DNA synthesis of V79 cells by more than 90% of the control activity when combined with only 1 microgram pentamycin per ml, whereas a similar extent of inhibition in AMBR cells was observed by combination with more than 5 microgram pentamycin per ml.

Amphotericin B↗

Gene affecting longevity of messenger RNA: a mutant of Escherichia coli with altered mRNA stability.

We have screened 897 temperature sensitive growth mutants of E. coli for mutant strains showing longer mRNA half-life. The fate of pulse-labelled RNA was examined at 42 degrees C after cessation of RNA synthesis and with prior exposure to nonpermissive temperature (42 degrees C). Eight stains showed altered turnover of RNA (presumably mRNA), and further analysis on mutant strain JE15144 indicated that the stability of pulse-labeled RNA as well as of tryptophan (trp) mRNA increased four to seven fold over its parental strain at 42 degrees C. At 4 min or 10 min after addition of rifampicin, some 70 to 80% of polyribosome in the growing cells could still be conserved in JE15144 cultured at the nonpermissive temperature while little, if any, polyribosomes remained in its parental strain (PA3092) under the same condition. Two generation times were required for complete stoppage of growth of this mutant strain after shifting to 42 degrees C, and protein synthesis continued at a significant, but slightly reduced, rate at 42 degrees C. However, functional decay of mRNA in the mutant strain, with respect to the capacity for producing peptides, appeared to be similar to the parent strain, with half-lives of 3.5 min in PA3092 and 4.7 min in JE15144.

Bacterial Proteins↗

A mouse leukemia cell mutant resistant to blasticidin S.

After nitrosoguanidine mutagenesis we isolated from mouse leukemia L5178Y cells a mutant cell (Bla-R) resistant to blasticidin S, an inhibitor of protein synthesis. Neither growth nor leucine incorporation into hot-acid insoluble fraction of Bla-R cell was inhibited by 5 to 20 microgram/ml blasticidin S, which almost completely blocked protein synthesis as well as growth of the parental L5178Y cells. However, other inhibitors such as fusidic acid, cycloheximide, ricin D or L-asparaginase blocked protein synthesis in Bla-R cells to the same extent as in L5178Y cells. Protein synthesis in vitro using S-30 extracts from the parental cell line L5178Y was almost completely blocked in the presence of the antibiotic, while no inhibition by blasticidin S occurred when S-30 extracts -rom Bla-R mutant cells were used. Protein synthesis assays were made by using the S100 fraction from rat liver together with ribosomes from either L5178Y cells or Bla-R cells. Blasticidin S inhibited protein synthesis when ribosomes were derived from L5178Y cells, but not from Bla-R mutant.

Animals↗

Macular cherry-red spots and beta-galactosidase deficiency in an adult. An autopsy case with progressive cerebellar ataxia, myoclonus, thrombocytopathy, and accumulation of polysaccharide in liver.

An adult patient with macular cherry-red spots, a gargoyle-like physical appearance, cerebellar ataxia, myoclonus, convulsive seizures, and pyramidal tract signs showed a profound deficiency of beta-galactosidase in liver and brain. Thrombocytopathy of undetermined etiology was evident since childhood, and the patient died of intracranial bleeding at age 22. Cerebral ganglioside pattern was normal. Hepatic mucopolysaccharides were not increased. GM1-gangliosidosis and mucopolysaccharidosis were ruled out by those analytical data. However, a large amount of amylopectin-like polysaccharide was found to be accumulated in liver. Hepatocyte contained numerous inclusion bodies with granulofibrillary structure similar to Lafora bodies, corpora amylacea, and inclusion bodies in glycogenosis type IV. This case seems to represent a new inborn metabolic disease closely related to GM1-gangliosidosis and mucopolysaccharidosis. The primary metabolic defect is not known at present.

Adult↗

The effect of aurintricarboxylic acid on RNA polymerase from rat liver.

The effect of the dye aurintricarboxylic acid (ATA) on RNA polymerases [EC 2.7.7.6] solubilized from rat liver was studied. Complete inhibition of RNA synthesis in vitro was observed when 3-5 microng/ml of ATA was added to the reaction mixture at time 0, while 40-70 microng/ml of a rifampicin derivative, AF/013, was required to produce the same extent of inhibition. RNA formation, however, continued at a rate of one-half that of the control when ATA was given after the onset of RNA synthesis in a dose capable of completely blocking RNA formation if administered at time 0. ATA was found to interact with RNA polymerizing enzyme itself and competed specifically with the binding of RNA polymerase to template DNA. Preincubation of the enzyme with DNA at 37 degrees before adding dye made the DNA-enzyme complex partly resistant to the drug. RNA-synthesizing activity resistant to ATA increased when nucleoside triphosphates, especially GTP, were added to the preincubation mixture in the presence of Mn2+. However, ATA only slightly affected RNA synthesis in nuclei isolated from rat liver.

Animals↗

A new type of mucolipidosis associated with hereditary thrombocytopathy and color blindness.

Autopsy findings of a 22-year-old Japanese male who showed the symptoms of both mucopolysaccharidosis and sphingolipidosis are reported. The patient had a gargoyle-like face, bone change with cherry-red spot and absence of mucopolysacchariduria, and moreover accompanied by hereditary thrombocytopathy and color blindness. Autopsy findings were almost the same as those of mucopolysaccharidosis, histochemically and electron microscopically. Unique findings were, however, present in the hepatocytes, another inclusion containing dense fine granuloreticular structures was found electron microscopically. Some foamy cells in the lymph nodes, liver including sinusiodal cells, bone marrow and spleen contained intracytoplasmic sudanophilic substance in the form of moderate electron dense globules by electron microscopy. The outstanding finding of the enzymatic activity was the decrease of beta-galactosidase in the liver and brain.

Adult↗