Biomedical subjects
Publications and source records attributed to H Endo.
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A phase II study of mitoxantrone (MIT) was performed in 21 patients with hematologic malignancies refractory to combination chemotherapy including anthracyclines. MIT was administered intravenously at doses of 8 to 13 mg/m2 on day 1 for 12 malignant lymphoma patients, and 1 to 3.3 mg/m2 on day 1 through 5 for 7 acute leukemia patients and 2 malignant lymphoma patients. Four malignant lymphoma patients (2 each of Hodgkin's disease and non-Hodgkin's lymphoma) achieved partial response lasting 19, 14, 8+, and 4 weeks, respectively. Although no definite response was obtained in acute leukemia patients, a marked cytoreduction was observed in 2 patients. Myelosuppression was a major toxicity, however, life-threatening toxicities were not observed in this study.
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Cornified layers of newly hatched chick shank skin were solubilized in 8 M urea by reduction followed by S-carboxymethylations. On Sephadex gel chromatography the solubilized proteins were separated into two distinct protein fractions (protein A and protein B). SDS-gel electrophoresis showed that the smaller protein fraction (protein B) contained two molecules with molecular weights of 15,000 and 17,000. Protein B was resolved into several fractions, pI 4.5-5.2, by preparative isoelectric focusing in the presence of 6 M urea and 0.1% Nonidet P-40. The fractions all contained the two molecules (Mr 15,000 and 17,000). The amino acid compositions of these fractions and 2-dimensional electrophoresis of epidermal protein by the method of O'Farrel indicated that the two proteins are each heterogeneous with respect to charge for reasons of microheterogeneity in the amino acid composition and varying extent of phosphorylation. When chick embryonic skin was cultured in a chemically defined medium, hydrocortisone, which induces the synthesis of protein A and results in keratinization of epidermis (Sugimoto, M., Tajima, K., Kojima, A. and Endo, H. (1974) Dev. Biol. 39, 295-307), did not accelerate the accumulation of protein B in epidermis; the normal pattern of protein B was not formed in epidermis of cultured skin with or without the hormone. Actinomycin D did not inhibit the synthesis of protein B, suggesting that the mRNA for this protein has a long life.
When investigating the effects of polyamines on substrate specificity of adenosine cyclic 3', 5'-monophosphate (cAMP) independent nuclear protein kinase NII, we found that the substrate preference of NII was drastically altered in the presence of polyamines. When casein was used as a substrate, spermine stimulated the enzyme activity 7.3-fold at 2 mM, and a 6.5-fold stimulation was observed with 6 mM spermidine. Putrescine was also slightly effective at higher concentrations. With phosvitin as the substrate, however, 2 mM spermine and 4 mM spermidine strongly inhibited the activity by 93% and 80%, respectively, while putrescine showed a weak stimulatory effect. Steady-state kinetics and binding studies suggested that both stimulatory and inhibitory effects of polyamines on NII enzyme activity are probably due to substrate protein-polyamine interactions. The circular dichroism spectrum of phosvitin was apparently altered by spermine, whereas no significant change was observed with casein.
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Langerhans cells were found among bile duct epithelial cells in a biopsy specimen from a patient with chronic liver disease showing cholangitic features. The bile duct was 90 micrometers in diameter and surrounded with mononuclear cell infiltration. Under the electron microscope, the cell had a clear cytoplasm and contained a deeply indented nucleus, a centriole, well-developed Golgi complexes and many rod-shaped bodies (Birbeck granules).
The biochemical effect of a nicotinamide analogue, 6-aminonicotinamide (6-AN), on developing chick embryonic femur was studied. Growth of femur from 9-day-old embryos that had been exposed to 6-AN for 5 days in ovo was not stimulated by PTH in an in vitro culture system. PTH caused a much smaller increase in the cyclic-AMP content in 6-AN-treated femur than in control femur. However, dibutyryl cyclic-AMP stimulated growth of 6-AN-treated femur. A defect in response of 6-AN-treated femur to the growth stimulating action of PTH may explain the production of micromelia by 6-AN.
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Thiolactomycin is a new broad-spectrum antibiotic, active in vitro against many species of Gram-positive cocci, Enterobacteriaceae, Haemophilus, acid-fast bacteria and anaerobic bacteria. However, the activity is generally moderate and bacteriostatic in action. This antibiotic eludes cross resistance with any of the known antibacterial drugs such as ampicillin, carbenicillin or cycloserine. The effect on Gram-negative bacilli in vitro is little affected by the inoculum size, the presence of horse serum, the pH of the medium or the type of medium. When thiolactomycin was added to the assay medium, the minimum inhibitory concentration of ampicillin against inducible beta-lactamase producing strains of Staphylococcus aureus and Pseudomonas aeruginosa was reduced. Thiolactomycin inhibited the production of inducible beta-lactamase in several organisms.
The combined effect of retinol palmitate (RP) and 5-fluorouracil (FUra) was examined with the use of allotransplantable and syngeneic murine tumor systems. The ip combined administration of RP (5,000 IU/kg/day) and FUra (5 mg/kg/day, 20 mg/kg/day, or 20 mg/kg/every 3d day) suppressed the tumor growth in ICR/JCL mice given sc inoculations of 5 X 10(6) allotransplantable sarcoma 180 cells and prolonged the survival time of mice inoculated ip with 10(7) tumor cells, as compared with the survival time of mice given the single administration of either RP or FUra. Similar results were obtained when BALB/c mice were inoculated sc with a syngeneic BALB/c Meth A fibrosarcoma and treated with RP (5,000 IU/kg/day) and FUra (20 mg/kg/every 3d day). The growth of Meth A implanted on day 10, as a rechallenge, was significantly suppressed in the group pretreated with RP alone or both RP and FUra for 9 days from day 1. The growth of Meth 1, another syngeneic tumor of BALB/c origin, inoculated on day 10 as a rechallenge tumor was unaffected by the treatment with RP and/or FUra. An immune response to tumor-specific antigens seemed to be involved in the combined effects of these two drugs.