Actinomycins normally contain N-methyl-l-valine and either d-valine, d-alloisoleucine or both amino acids in the molecule. During antibiotic formation in a medium supplemented with one of the four isoleucine stereoisomers, Streptomyces parvulus and S. chrysomallus form complex actinomycin mixtures (C(1), C(2), C(3), E(1), and E(2)-like compounds). Although chromatographic techniques suggested t...

This article presents our current understanding of how actinomycin D binds to DNA and exerts its mechanism of action. Actinomycin is proposed to bind to a premelted DNA-conformation (known as betaDNA) present within the transcription complex. This acts to immobilize the complex, interfering with the elongation of growing RNA chains. Nucleolar (ribosomal) 5S RNA synthesis is particularly sensiti...

Mice (BALB/cJ, C3H/HeN, and C3H/HeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C3H/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an impo...

RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of RG7787, we screened for clinically used drugs t...

The specificity with which actinomycin D is bound to DNA both in vivo and in test tube experiments (for a review, see Reich and Goldberg, 1964) and the recent availability of the drug in tritiated form with high specific activity have suggested its possible usefulness as a means to detect DNA radioautographically in fixed cytological preparations. Brachet and Ficq (1965) had previously employed...

Streptomyces antibioticus produces a family of actinomycin components which differ solely at the "imino acid" site of the molecule; however, new congeners of actinomycin are synthesized when cultures are supplemented with pipecolic acid (PA). The quantitative and qualitative nature of the actinomycins produced differed when cultures were incubated in the presence of either l-, d-, or racemic PA...

The multistranded and double-stranded RNAs synthesized in HeLa cells infected with rhinovirus in the presence and in the absence of actinomycin D have been characterized by polyacrylamide gel electrophoresis and hybridization studies. The replicative form is only found in infected cells treated with actinomycin D, whereas the replicative intermediate is found in both the presence and the absenc...

An actinomycin-D producing strain was isolated from soil and characterized as Streptomyces sindenensis. The culture was subjected to UV irradiation and a mutant with 400% higher actinomycin-D production was isolated (400 mg/l(-1) as compared to 80 mg/l(-1) produced by the parent). Production medium was optimized and antibiotic yield with the mutant was enhanced to 850 mg/l(-1) which is 963% hig...

The ultrastructure of cuticle formation and the effect of actinomycin-D on cuticle formation were examined in the second molt of Nippostrongylus brasiliensis. At the end of the first molt t he rough endoplasmic reticulum of the hypodermis (epidermis) had narrow cisternae. As cuticle formation began the RER cisternae dilated and accumulated a fibrous material. These large fibrous material-contai...

Wilms' tumor in adults is rare, and no treatment guidelines have been established. Spinal cord compression has also been rarely reported in all age groups. In this case report, we present a 19-year-old adolescent with recurrent Wilms' tumor, a paraspinal dumbbell mass, metastatic involvement of the vertebral bodies, lung metastasis, and pregnancy. To our knowledge, this is the first report of a...