Dallas M. Purnell

The effects of specific auxotrophic mutations on the virulence of Aspergillus nidulans for mice.

The paper describes studies of the influence of a number of genetically-mapped auxotrophic mutations on the virulence ofAspergillus nidulans for DBA/2J male mice. Specific mutations were found to be either neutral in regard to the character of virulence, i.e., strains carrying such mutations had a virulence similar to that of prototrophic strains, or were associated with significantly decreased virulence or avirulence. These data provide the first extensive information concerning the effects of auxotrophic mutation on the virulence of a mycotic pathogen of animals.

Immunogenicity of “viable” tumor cells after storage in liquid nitrogen

SummaryInjection of vaccines containing BCG and irradiated L10 hepatoma cells into strain 2 guinea pigs led to arrest and regression of viable L10 cells injected contralateral to and simultaneous with the vaccine. If the tumor cells in the vaccine had been stored in LN2, the vaccine was significantly less effective. The diminished immunogenicity of the stored cells could not be attributed to the sequence of freezing and irradiation, nor to the presence of dead cells which had been killed during cryopreservation. We concluded that cells which had been stored in LN2 had undergone changes which decreased their immunogenicity but which did not alter permeability to trypan blue.

Heterozygous diploid strains of Aspergillus nidulans: Enhanced virulence for mice in comparison to a prototrophic haploid strain

The paper describes quantitative studies of the virulence for DBA/2J mice of three heterozygous diploid strains ofAspergillus nidulans synthesized from avirulent auxotrophic haploid strains, and auxotrophic strains of reduced virulence. These studies demonstrate that the heterozygous diploid strains possess an unusually high virulence for mice in comparison to a haploid prototrophic strain ofA. nidulans employed as a virulence standard.

Immunotherapeutic effectiveness of BCG inactivated by various modalities

Factors responsible for the limited effectiveness of Bacillus Calmette‐Guérin (BCG) immunotherapy are not completely understood. One limitation is that although the effect is dose‐related, high‐dose administration increases the risk of BCG toxicity, possibly the result of disseminated BCG infection. In the present study, we compared the relative effectiveness of Tice lyophilized BCG which was inactivated by heat, sonication, irradiation, streptomycin, or isoniazid (INH). The model systems were the 13762A rat mammary adenocarcinoma and the line 10 guinea pig hepatoma. In the 13762A system, tumors were injected on day 7 with living or killed BCG preparations, or with Corynebacterium parvum as a positive control. Tumors were excised on day 20. Rats treated with surgery alone usually died within 40–50 days with extensive metastases to lymph nodes, lungs, and viscera. Guinea pig line 10 hepatoma was treated with vaccine containing irradiated tumor cells and BCG. In both the rat and guinea pig models, BCG inactivated by means of irradiation was as effective as viable BCG and heat‐killed BCG also had a strong effect. Streptomycin treatment diminished the efficacy of the BCG and sonication destroyed BCG effectiveness even though the organisms were not all killed. The INH treatment of tumor‐bearing rats did not alter the benefits of single or repeated injections of high‐dose viable BCG, irradiated BCG, or C parvum. We conclude that inactivation of BCG with heat, irradiation, or INH host treatment preserves but does not improve the immunotherapeutic benefits of BCG. Cancer 46:480–487, 1980.

A morphologic mutation in Aspergillus nidulans associated with increased virulence for mice.

Studies of the virulence for inbred mice of a morphologic mutant ofAspergillus nidulans and the morphologically-normal strain from which it was isolated as a spontaneous variant are described. The study demonstrates that the single gene difference known to exist between the two strains is associated with increased virulence. This is the first example of a mutation inA. nidulans associated with increased virulence.

Genetic and cytoplasmic control of undifferentiated growth in Aspergillus nidulans.

Abstract Undifferentiated, infiltrative variants of Aspergillus nidulans with aberrant pattens of mycelial growth arose spontaneously from genetically marked parental strais. These abnormalities of growth and develpment, reminiscent of neoplasms of higher organisms, could be transmitted to normal strains via heteokaryosis. Preliminary genetic analysis suggests that there is a gene or linkage group VIII necessary for the expression of this somatic variation.

Treatment of cancer using Corynebacterium parvum: similarity of two preparations in four animal tumor models.

The tumor inhibitory properties of Corynebacterium parvum obtained from Burroughs Wellcome (CP‐BW) or from Institut Merieux (CP‐IM) were compared in four animal tumor models: the CaD2 mouse mammary carcinoma treated by intravenous (I.V.) or intratumoral (I.T.) injection of C. parvum; 13762A rat mammary adenocarcinoma treated by I.T. injection of C. parvum either alone or combined with excision of the primary tumor; LSTRA murine leukemia and line 10 cavian hepatoma, each treated with vaccines containing irradiated tumor cells and C. parvum. Both preparations were active against each tumor. In most comparisons the potency of the two materials was not different, but in a few cases the CP‐BW was effective at a lower dose than was the CP‐IM. These results demonstrate the versatility of C. parvum for use in a variety of immunotherapy procedures and show that the potencies of the two major types of C. parvum are very similar.