Biomedical subjects

W G Landis

Publications and source records attributed to W G Landis.

10 recordsLinked to original sources

PubMed1992

Initial characterization of the organophosphate acid anhydrase activity of the chicken, Gallus domesticus.

1. Supernatant solutions from kidney and liver homogenates of the chicken, Gallus domesticus, were found to hydrolyze the organophosphate (OP) compound diisopropylfluorophosphate (DFP). The activity on DFP as substrate was heat-inactivated and was characterized for temperature and pH optima, enzyme kinetics, and requirements for manganous ion. 2. Gel column chromatography indicated that the DFPase in both tissues is in the range of 82,100 to 93,300 D. This activity is strongly inhibited by N,N'-diisopropylphosphorodia-midofluoridate (mipafox). 3. The chicken has organophosphate acid (OPA) anhydrase activity comparable to other eucaryotic sources in its ability to hydrolyze DFP. Although birds may not have paraoxonase activity comparable to mammalian species, they do not differ significantly in the ability to hydrolyze DFP and probably related compounds.

Animals↗

PubMed1990

Inactivation of organophosphorus nerve agents by the phosphotriesterase from Pseudomonas diminuta.

The phosphotriesterase from Pseudomonas diminuta was tested as a catalyst for the hydrolysis of phosphofluoridates. The purified enzyme has been shown to hydrolyze the phosphorus-fluorine bond of diisopropyl fluorophosphate, isopropyl methylphosphonofluoridate, and 1,2,2-trimethylpropylmethylphosphonofluoridate at pH 7.0, 25 degrees C, with turnover numbers of 41, 56, and 5 s-1, respectively. The enzymatic rate enhancement for the hydrolysis of sarin at pH 7.0 is 2.2 X 10(7). The turnover number for paraoxon hydrolysis is 2100 s-1. The enzyme does not hydrolyze methanesulfonyl fluoride, phenylmethylsulfonyl fluoride, or O-p-nitrophenyl phenylsulfonate nor do these compounds inactivate or inhibit the ability of the enzyme to hydrolyze diethyl p-nitrophenyl phosphate. The breadth of substrate utility and the efficiency of the hydrolytic reaction exceed the more limited abilities of other prokaryotic and eukaryotic enzymes that catalyze similar reactions. The substantial rate enhancement exhibited by this enzyme for the hydrolysis of a wide variety of organophosphorus nerve agents make this enzyme the prime candidate for the biological detoxification of insecticide and mammalian acetylcholinesterase inhibitors.

Animals↗

PubMed1988

Organofluorophosphate-hydrolyzing activity in an estuarine clam, Rangia cuneata.

1. The bivalve Rangia cuneata can enzymatically detoxify the organophosphorus acetylcholinesterase inhibitors DFP and soman. 2. Digestive gland homogenates contained Mazur-type DFPases based on response to Mn2+ ions, and relative rates of DFP: soman hydrolysis. Squid-type DFPase contributed little to the total organophosphate acid (OPA) anhydrase activity of these preparations. 3. The natural substrate(s) and physiological role(s) of OPA anhydrase in R. cuneata has yet to be determined; however, DFPase specific activity was pronounced in the digestive gland, the primary organ involved in bioconcentration and biotransformation of xenobiotics, and in the gills, which are in continuous contact with water-borne chemicals.

Animals↗

PubMed1987

Discovery of multiple organofluorophosphate hydrolyzing activities in the protozoan Tetrahymena thermophila.

Recently it has been found that homogenates of Tetrahymena thermophila can hydrolyze the potent acetylcholinesterase inhibitors O,O-diisopropylphosphofluoridate (DFP) and O-1,2,2-trimethylpropylmethylphosphonofluoridate (soman). Upon purification of the DFP hydrolyzing activity 10-fold it had been noted that the soman hydrolyzing activity increased only 2-3 fold. Treatment with manganous ion and comparison of the soman and DFP hydrolysis rates of the homogenate indicated that a mixture of the squid-type and Mazur-type DFPases may be present. Subsequent purification of the enzymatic activities within the Tetrahymena-homogenate demonstrated that there are at least five functioning proteins of molecular weights 67,000 to 96,000. None are directly homologous to the DFPases found in hog kidney or squid. The enzymatic activities are designated DFPase-1 through DFPase-5. A hypothesis is presented that the functions of DFPases are in the normal metabolism of organophosphates naturally synthesized by T. thermophila.

Animals↗

PubMed1987

Factors determining the frequency of the killer trait within populations of the Paramecium aurelia complex.

The factors maintaining the cytoplasmically inherited killer trait in populations of Paramecium tetraurelia and Paramecium biaurelia were examined using, in part, computer simulation. Frequency of the K and k alleles, infection and loss of the endosymbionts, recombination during conjugation and autogamy, cytoplasmic exchange and natural selection were incorporated in a model. Infection during cytoplasmic exchange at conjugation and natural selection were factors that would increase the proportion of killers in a population. Conversely, k alleles reduced the proportion of killers in a population, acting through conjugation and autogamy. Field studies indicate that the odd mating type is prevalent in P. tetraurelia isolated from nature. Conjugation and therefore transmission by cytoplasmic transfer would be rare. Competition studies indicate a strong selective disadvantage for sensitives at concentrations found in nature. Natural selection must therefore be the factor maintaining the killer trait in P. tetraurelia.

Alleles↗

PubMed1986

Acute toxicity of brass particles to Daphnia magna.

The aquatic toxicity of brass particles was examined. Acute, 48 hour bioassays were performed using the water flea, Daphnia magna. Tests were conducted with uniform suspensions of uncoated brass particles, brass particles coated with a Teflon solution, silica particles, and titanium dioxide particles. The Teflon coating solution and the supernatant of the brass suspension (after settling of the brass) also were tested. All tests were conducted according to guidelines set forth by the US Environmental Protection Agency and the Organization for Economic Cooperation and Development. Mean EC50 determinations of 20.0 micrograms l-1 and 23.6 micrograms l-1 were calculated for uncoated brass particles and coated brass particles, respectively. The silica, titanium dioxide, and Teflon each had an EC50 greater than 1 g l-1. Chemical fate studies demonstrated that the brass dissociated to its ionic components of copper and zinc quickly at pH 2.0. At pH 5.0 and 6.5, the dissociation occurred too slowly to account for the observed toxicity. The data suggested that the toxicity is due to filtration by the daphnids and subsequent ingestion. EC50 determinations for the brass particles are nearly identical with published EC50 values for copper salts.

Alloys↗

PubMed1986

The toxicity of brass dust to the microalgae Ankistrodesmus falcatus and Selenastrum capricornutum.

The toxicity of brass dust was examined by conducting 96 h growth inhibition tests. Two species of algae were used, Ankistrodesmus falcatus (EC50 = 0.316 mg brass/l) and Selenastrum capricornutum (EC50 = 0.056 mg brass/l). Brass dissociates into two components, Cu (68.5%) and Zn (27.5%). Enhanced algal growth was exhibited at concentrations of 0.01 and 0.001 mg brass/l. Available literature on the toxicity of copper to S. capricornutum (EC50 = 0.047 mg Cu/l), indicate that the toxicity of brass dust is due to the ionized copper. Reported toxicities of zinc are orders of magnitude lower than copper. The ionization of the brass is dependent on pH and hardness. The literature cites cases in which copper toxicity varies with pH, clay content and dissolved organics. At present little is known of the fate and distribution of brass dust upon the release into the environment. However, the presence of heavy metals has consistently been shown to impact aquatic systems.

Chemical Phenomena↗

PubMed1986

Kinetics of the DFPase activity in Tetrahymena thermophila.

Crude homogenates of the ciliate protozoon, Tetrahymena thermophila, can hydrolyze the potent acetylcholinesterase inhibitors O,O-diisopropylphosphorofluoridate (DFP) and O-1,2,2-trimethylpropylmethylphosphonofluoride (soman). Characterization of the enzymatic activity of the homogenate has been performed. The DFPase operates over a pH range of 4 to 10 and an ionic range of 0-500 mM NaCl. Rate of reaction increases three- to four-fold from 25 degrees C to 40 degrees C and is still present at 55 degrees C. These results indicate that the enzymatic activity operates over a broad range of environmental conditions, making it an attractive material for use in the detoxification and detection of organofluorophosphates. DFPases may be important in the metabolism of naturally occurring organophosphates.

Animals↗

PubMed1985

An organofluorophosphate-hydrolyzing activity in Tetrahymena thermophila.

An enzymatic activity that hydrolyzes O,O-diisoproplyphosphofluoridate (DFP) and O-1,2,2-trimethylpropylmethylphosphonofluoridate (Soman) was discovered in the ciliate protozoan Tetrahymena thermophila. The enzymatic activity classifies the protein as Mazur-type similar to that found in hog kidney and Escherichia coli. The rate of hydrolysis of Soman by the Tetrahymena-extract is the highest, on a per gram of extract basis, of any eucaryote. The molecular weight is approximately 75,400 as determined by Sephacryl column chromatography. A maximum fifteen-fold purification has been achieved. Potential exists for the detoxification and one-step detection of common organofluorophosphate pollutants. Additionally, Tetrahymena should prove an easier subject for manipulation than mammalian or squid sources. Protozoa may be a potentially important source of detoxification and degradation enzymes for other environmental contaminants.

Animals↗

PubMed1983

Mutagenicity (Ames): a structure-activity model.

A statistical structure-activity model of the Salmonella typhimurium (Ames) test has been devised based on 472 chemicals for which this endpoint has been measured. The model uses substructural fragments as the independent parameters to explain the difference in mutagenicity of the different chemicals. The model is able to classify 86% of the chemicals into their correct categories; the false-positive rate is 4.7%, and the false-negative rate 5.3%. Approximately 10% of the chemicals cannot be classified by the existing equation. This structure-activity model can be used as a preliminary screen prior to other testing as well as for setting priorities for more detailed investigations.

False Negative Reactions↗