Search PubMed⌕ Search

Biomedical subjects

R F Anderson

Publications and source records attributed to R F Anderson.

At least 73 records · Page 4Linked to original sources

Effect of lipophilicity of nitroimidazoles on radiosensitization of hypoxic bacterial cells in vitro.

The effect of radiosensitization of hypoxic bacterial cells by 9 nitroimidazoles was measured in the bacterial strains E. coli AB 1157 and S. lactis 712. Seven of these compounds were similar to misonidazole in their redox properties, but differed widely in their lipophilicites. The dependence of sensitization enhancement on reduction potential was similar to that reported in mammalian cells. The efficiency of sensitization was similar for compounds of low lipophilicity, but increased if the octanol: water partition coefficients of the compounds were higher than about 3.5. With one compound, otherwise similar to misonidazole, the increased lipophilicity led to about one order of magnitude lower concentration achieving the same degree of radiosensitization.

Anaerobiosis↗

Results of eleven years' experience with heated perfusion for melanoma of the extremities.

Eleven years have elapsed since we first added heat to regional perfusion for treatment of melanoma of the extremities. This report describes briefly our laboratory findings and our technique of hyperthermic perfusion and brings up to date the survival figures for the 165 patients (185 perfusions) which were originally reported in 1975 (Stehlin et al., Surg. Gynecol. Obstet., 122: 3--14, 1966). A dramatic increase in the survival rate is documented for those patients with recurrent melanoma confined to the extremities.

Chemotherapy, Cancer, Regional Perfusion↗

Radiosensitization of Serratia marcescens by nitropyridinium compounds.

The two nitropyridinium compounds tested sensitize hypoxic Serratia marcescens to irradiation up to the oxygen enhancement level by two components which can be separated as a function of compound concentration. Sensitization above the initial plateau level is in order of their determined one-electron reduction potentials, Ro 03-5580 (E 7 1 = -335 mV) being more efficient than Ro 03-5637 (E 7 1 = -358 mV). Additivity in sensitization up to a maximum enhancement level of 2.1 +/- 0.1 is found on combining these hydrophilic compounds at concentrations to give sensitization at the plateau level, with the hydrophobic sensitizer paranitroacetophenone (PNAP). It is concluded that the nitropyridinium compounds and PNAP sensitize the same site.

Acetophenones↗

Radiosensitization of Serratia marcescens by bipyridinium compounds.

Bipyridinium compounds (viologens) have been shown to radiosensitize hypoxic Serratia marcescens cells by two components. These can be separated on the basis that only the one-electron reduced form of the compounds can penetrate the bacterium cell wall. One component is associated with sensitization at the membrane and the other with an internal site. The efficiency of sensitization at the membrane-associated site follows the order of increasing one-electron reduction potentials of the compounds. The one-electron reduced forms of the bipyridinium compounds are involved in a mechanism that reduces the initial level of sensitization. No additivity in sensitization is found on combining the bipyridinium compounds with other radiosensitizers, PNAP and Ro 07-0582 at concentrations of each, which will give sensitization to the level associated with the membrane site. It is concluded that all these electron-affinic compounds sensitize this site. The protective effect of added glycerol on sensitization by viologens is related to protection at the membrane-associated site.

Drug Combinations↗

Critical residues in D-amino acid oxidase. A pulse-radiolysis and inactivation study.

The enzyme D-amino acid oxidase and its apoenzyme have been irradiated at pH 5.5--10 under conditions designed to assess the inactivating effect of OH radicals and the selective free radicals Br2- and (SCN)2-. Near neutral pH, removal of the coenzyme FAD from the enzyme results in greater inactivation by selective free-radical attack. From pulse-radiolysis spectra, this increase is associated with attack on tyrosine and tryptophan residues in the protein. A large increase in inactivation of both the haloenzyme and apoenzyme by selective free-radical attack is seen with increasing alkalinity. This is consistent with attack on tyrosine being of major importance.

Amino Acids↗

Soft tissue sarcomas of the extremity. Multidisciplinary therapy employing hyperthermic perfusion.

Cultured human sarcomatous cells that have been tested in our laboratory are more sensitive to the lethal effects of heat than are the normal cells from which they are derived. During an eight year period from March 1967 to March 1975, thirty-seven patients with soft tissue sarcomas of the extremities were treated with hyperthermic perfusion and, when possible, radiation therapy and radical local excision. Despite the fact that these tumors arise on the extremity, diagnosis was often delayed. With meticulous attention to all details, hyperthermic perfusion was performed with a minimum of morbidity and mortality. The combined use of hyperthermic perfusion, radiation therapy, and delayed excision has greatly reduced the necessity for amputation. Many useful limbs, heretofore not considered salvageable, can be saved with this method of treatment. Also, the possibility exists that destruction of tumor within the extremity followed by delayed excision enhances the immune response of the patient.

Adolescent↗

Results of hyperthermic perfusion for melanoma of the extremities.

Our studies show that the malignant melanoma cell in human beings is more sensitive to the lethal effect of heat than its normal counterpart, the melanocyte. Malignant melanoma of the extremities presents unique problems; at times, local control can be extremely difficult. The addition of heat to regional perfusion with melphalan has dramatically improved the objective response of melanoma. Complications rise as the tempreature and duration of perfusion increase. These risks must be weighed carefully against the volume and extent of tumor. One hundred and eighty-five hyperthermic perfusions have been perfomed on 165 patients. When done with meticulous attention to details, this procedure is accompanied by minimal morbidity and mortality. Hyperthermic perfusion is currently the best treatment for recurrent melanoma of the extremities and has almost eliminated the necessity for amputation. Perfusion is recommended as a prophylactic measure for the more deeply invasive primary lesions. It reduces the incidence of regional recurrence. A retrospective statistical analysis of survival rates of patients treated with nonheated and heated perfusion for recurrent melanoma, State IIIA, was conducted. If the experience of the heated group continues, which from a clinical standpoint appears likely, then a striking advantage of heated perfusion over nonheated perfusion will be demonstrated. This superiority in survival rates for the heated group is now three to one or 300 per cent. The most reasonable explanation for the improvement in survival time of patients in State IIIA is stimulation of the immune response. As a result of our experience with heated perfusion of limbs, we are investigating the possibility that systemic hyperthermia may enhance the antitumor effects of various chemotherapeutic agents on melanoma.

Acute Kidney Injury↗

Polymer-Producing Species of Arthrobacter.

Gasdorf, Helen J. (Northern Regional Research Laboratory, Peoria, Ill.), R. G. Benedict, M. C. Cadmus, R. F. Anderson, and R. W. Jackson. Polymer-producing species of Arthrobacter. J. Bacteriol. 90:147-150.1965.-Two slime-producing microorganisms, designated as NRRL B-1973 and NRRL B-1797, were isolated from a Guatemalan soil sample. Their morphological and physiological characteristics permit their assignment to the genus Arthrobacter. Both cultures produce a large amount of extracellular polysaccharide, the maximal amount being 1.4 g per 3 g of glucose. The carbohydrate constituents of B-1973 polysaccharide are galactose, glucose, and mannuronic acid; those of B-1797 are galactose, glucose, and glucuronic acid. The organisms are morphologically and physiologically alike. The differences between these two cultures and previously described species of Arthrobacter appear sufficient to designate a new species. The name Arthrobacter viscosus sp. n. is proposed.

Journal Article↗

Production of Fumaric Acid in 20-Liter Fermentors.

The conditions necessary for the production of fumaric acid in 20-liter fermentors by fermentation of glucose with Rhizopus arrhizus strain NRRL 2582 were determined. Continuous neutralization of fumaric acid was necessary for optimal yields. Yields of the calcium salt were in excess of 65 g of fumaric acid from 100 g of sugar consumed during fermentation of sugar concentrations of 10 to 16%. Conditions established for calcium fumarate production include a simple mineral salts medium, 0.5 v:v:min aeration rate, 300 rev/min agitation rate in a baffled tank, 33 C incubation temperature, CaCO(3) to neutralize the acid formed, and a 4 to 5% (v/v) vegetative inoculum. A suitable procedure and medium for the preparation of a vigorous vegetative inoculum were established. The tendency for calcium fumarate fermentations to foam excessively was controlled with a proper antifoam agent added prior to sterilization of the medium and again at daily intervals during fermentation. The production of soluble sodium or potassium fumarates was inhibited when the concentration of fumarates reached 3.5 to 4.0%. No means of overcoming this inhibition was found. Starches and certain other grain-derived carbohydrates were fermented to form calcium fumarate in flask experiments with approximately the same efficiency as was glucose.

Journal Article↗

Radiosensitization by non-nitro compounds.

The effects of 23 non-nitro compounds on the radiosensitivity of hypoxic Chinese hamster V79-379A or E. coli AB 1157 cells in vitro are outlined. Imidazole derivatives substituted with several alternative electron-withdrawing groups are described; the dicyanovinyl function conferred considerable radiosensitizing activity. 2,4,5-Tribromoimidazole and 2,4-dinitrophenol may show unusual radiosensitizing activity because of interference with oxidative phosphorylation. Attempts to influence radiosensitivity by compounds potentially capable of depleting intracellular sulphydryls are also described.

Animals↗

Reduction of nitroimidazoles in model chemical and biological systems.

Some chemical and biological properties of intermediates obtained during reduction of nitroimidazoles are discussed. These include: rate data for the decay of the nitro radical-anion, stoichiometry and absorption spectra for reduction via the radical-anion or using dithionite, stoichiometry with other reducing agents, and rate of reduction by xanthine/xanthine oxidase. Increased radiosensitization by misonidazole is seen upon prolonged pre-irradiation incubation using E. coli, enabling demonstration that a freely-diffusable metabolite is responsible for this effect. Preliminary experiments designed to extend studies of the radiobiological properties of extracellularly-added metabolites to mammalian cells and the use of liver perfusion to generate metabolites are described.

Animals↗