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Biomedical subjects

J A Bush

Publications and source records attributed to J A Bush.

50 records · Page 3Linked to original sources

New mitomycin analogs produced by directed biosynthesis.

When the normal fermentation medium for the production of mitomycin C with Streptomyces caespitosus is supplemented with a number of primary amines, two new types of mitomycin analogs described as Type I and Type II are produced. Type I analogs are related to mitomycin C with the amine substitution at position C7 on the mitosane ring. Type II analogs also contain the same substitutions at C7 but the conformation of the mitosane ring is related to mitomycin B having an OH at positions C9a and a methyl substituted aziridine. The products obtained from the supplementation of the medium with methylamine, ethylamine, propylamine, propargylamine and 2-methylallylamine were isolated and characterized. In all cases the Type I analogs are more active in a prophage induction test and against L1210 lymphatic leukemia in mice. A number of other amines have been tested and shown to yield new products that have not yet been isolated. No secondary amines are incorporated.

Animals↗

Production and biological activity of marcellomycin, an antitumor anthracycline antibiotic, and taxonomy of the producing organism.

An actinomycete, isolated from a soil sample from Ontario, Canada, was studied taxonomically and named Actinosporangium bohemicum sp. nov. strain C-36,145. This strain was found to produce a complex mixture of e-pyrromycinone glycosides having antitumor properties. Marcellomycin, a member of this complex, was selected for further study. Conditions for production of this antibiotic were developed in flask studies and scaled-up to the 3,000-liter fermentor stage.

Actinomycetales↗

Use of covalently closed circular deoxyribonucleic acid for prescreening for antitumor compounds.

The interactions of PM-2 deoxyribonucleic acid (DNA) with 20 known antineoplastic agents were studied using agarose gel electrophoresis and fluorescence assay systems. Actinomycin D and adriamycin (and all other anthracyclines studied) induced superhelical conformational changes in PM-2 DNA. Bleomycin A2, tallysomycin, neocarzinostatin, macromomycin, and hedamycin degraded PM-2 DNA under various conditions. The potential utility of PM-2 DNA as an antitumor antibiotic prescreening tool was further studied by examining the effects of 200 broths on PM-2 DNA employing both fluorescence and agarose gel electrophorectic assays. The assays were shown to be sensitive and rapid and to provide information not provided by other prescreens with which the PM-2 DNA assays were compared.

Antineoplastic Agents↗

Similarities and differences in precipitating events between black and anglo suicide attempts.

The rapid rise in suicide among young Blacks in American the past decade is of increasing concern to mental health practitioners and suicidologists. While there are some similarities among suicide attempts by Blacks and Whites, the pattern is that Black suicide attempters are distinctly more youthful. This exploratory study tests the hypothesis that the precipitating events for young Blacks who consider, plan, and attempt suicide is more likely to be "the loss or threatened loss of a love partner in the context of a negative value-orientation and intragroup pressures" than among Anglo suicide attempters. Specific strategies are recommended that use a family perspective for assisting Blacks who consider, plan and attempt suicide.

Adult↗

Suicide and blacks: a conceptual framework.

Suicide among black Americans has risen sharply in this decade. The suicide pattern differs from that of white Americans in that black suicide is mainly a youth phenomenon and the rates between black females and black males are relatively equal. The lack of research into these phenomena is highlighted along with an exploration of current explanations. A specific conceptual framework is proposed that includes extragroup pressure, intragroup pressure, and value orientation. The framework is extended into the area of mental health planning, as well as behavioral science practice.

Black or African American↗

A comparison of the performance of some similarity and dissimilarity measures in the automatic classification of chemical structures.

A group of 39 structures with local anesthetic activity has been classified automatically by calculating similarity or dissimilarity coefficients between pairs of structure diagrams and applying cluster analysis to the results. The performance of a number of similarity and dissimilarity coefficients has been compared using the relationship between structure and property. Simple coefficients and a distance function give more satisfactory results than functions using probabilistic weighting or standardized distance.

Anesthetics, Local↗

Fermentation, isolation, and antitumor activity of sterigmatocystins.

In a screening program for antitumor substances from microbial fermentations, a compound was isolated from the mycelium of an Aspergillus species which proved to be the mycotoxin 5-methoxysterigmatocystin. This and the subsequently isolated sterigmatocystin gave significant inhibition of the transplanted mouse leukemias P-388 and L-1210. Preparation and testing of several derivatives of 5-methoxysterigmatocystin suggest that certain functions in the molecule are essential for tumor inhibition. Although slight antitumor effects have been reported for the chemically related aflatoxins, we believe this is the first report of antitumor activity of sterigmatocystins.

Animals↗

Anchorage-independent growth of p53-knockout dermal fibroblasts is reversed by wild-type p53.

BACKGROUND: p53 is a 393-residue nuclear phosphoprotein. Mutation of p53 occurs in over half of all human cancers and thus is a crucial step in the process of cell transformation and tumorigenesis. Since tumorigenesis is a multistep process, it generally requires the mutation of certain key oncogenes and/or tumor-suppressor genes. Using p53-deficient mice, we can investigate the p53-dependent mechanisms leading to tumorigenesis. OBJECTIVE: To examine the unique anchorage-independent growth characteristics of dermal fibroblasts isolated from p53-deficient mice. METHODS: The growth characteristics of highly confluent cultured dermal fibroblasts from wild-type (p53+/+) and p53-deficient (p53-/-) mice were compared by DNA fragmentation assay, colony formation in soft agar, and overexpression of a wild-type p53 transgene in p53-deficient cells. RESULTS: p53-/- fibroblasts have a growth rate dramatically higher than p53+/+ cells and detach from plastic cultureware at high density. The detachment of p53-/- cells is not due to apoptosis. Furthermore, these cells have the capacity to grow in soft agar-a hallmark of cell transformation-and this anchorage-independent growth can be reversed by the introduction of a wild-type p53 transgene. CONCLUSION: Dermal fibroblasts isolated from p53-deficient mice show anchorage-independent growth. Therefore, the absence of p53 is sufficient for the initiation of cell transformation in this cell type and establishes this model system as an excellent tool to dissect the molecular steps involved in oncogenesis.

Animals↗