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Biomedical subjects

W E White

Publications and source records attributed to W E White.

At least 19 recordsLinked to original sources
PubMed2003

An evaluation of the genetic stability and pathogenicity of the Russian cold-adapted influenza A donor strains A/Leningrad/134/17/57 and A/Leningrad/134/47/57 in ferrets.

The influenza A components of live attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47), and virulent epidemic strains. The lesions responsible for attenuation within the six internal genes of each donor strain have been sequenced and described, but relatively little is known as to their stability before and after passage in susceptible hosts. In the work reported in this paper, RT-PCR restriction analysis and limited sequencing of individual genes were used to evaluate the stability of lesions in stocks of the both donor strains after passage in ferrets, which have been used widely as susceptible hosts for assessment of the virulence of influenza strains. Len/47 was shown to possess expected lesions by RT-PCR and restriction analysis. Substitution at position 1066 of the NP gene, which has been previously reported to be unique to Len/47 [Klimov et al., Virology 186 (1992) 795], was also shown to be present in all clones of Len/17. This change was confirmed by limited sequence analysis and was shown to be retained in progeny viruses isolated from the lungs and turbinates of inoculated ferrets. Two other changes in the PB2 and PB1 genes that were present in Len/47 were detected by limited sequence analysis alone. Further previously unreported minor changes were shown to be present for Len/17 and Len/47, but not both, and their significance is unknown. Limited replication of each donor strain occurred in ferrets and minimal clinical signs and histopathology were present. By contrast, the parental strain Len/57 and the recent epidemic strain A/Sydney/6/97 induced clinical signs and histopathology that were typical of influenza disease.

Adaptation, Physiological↗
PubMed2001

A computational study of the reactions of thiiranes with ammonia and amines.

The relative rates of reaction of thiirane and thiirane derivatives with NH3, a series of secondary amines including aziridine, and trimethylamine were determined in the gas phase by means of B3LYP/6-31+G(d)//HF/6-31+G(d) computations and transition state theory. Convergence of the results was selectively tested using the 6-311++G(d,p) basis set. Comparison with MP2/6-31 + G(d)//MP2/6-31G(d) computations was made in model cases. These results are significant in that they supplement the only reported gas-phase experimental study of this type of reaction. The reaction rates of thiirane with secondary amines can best be rationalized by means of an interplay of steric and polarizability effects. While beta-halo substituents retard S(N)2 reactions in solution, both 2-fluorothiirane and its acyclic model react more than l0(6) times faster with NH3 than the unsubstituted compounds in the gas phase. 2-Fluorothiirane was calculated to react with NH3 at C2 by a factor of 0.142 with respect to thiirane itself; attack at C3 was found to be 3.42 x 10(6) times faster than the parent compound. 2-Methylthirane reacts with NH3 at 0. 230 the rate of thiirane with a 12.8-fold regioselectivity for C3. In the reaction of 2,2-dimethylthirane and NH3, this preference for C3 increases to a factor of 124. Ground-state destabilization of cis-2,3-dimethylthiirane is sufficient to account for its calculated rate acceleration with respect to the trans isomer.

Journal Article↗
PubMed1999

Fragmentation of an alkali metal-attached peptide probed by collision-induced dissociation fourier transform mass spectrometry and computational methodology.

Collision-induced dissociation of metal-cationized N-CBZ-Gly-Pro-Gly-Pro-Ala was studied by Fourier transform mass spectrometry. Lithium-, sodium-, potassium- and rubidium-cationized peptide species were generated by matrix-assisted laser desorption/ionization (MALDI) using 2,5-dihydroxybenzoic acid as matrix, together with appropriate metal salts. The experimental mass spectrometric results were interpreted with the aid of Monte Carlo conformational searches using the Amber(*) force field, together with ab initio molecular orbital calculations with Gaussian-94 for the singly lithium- and potassium-cationized peptides. It is concluded that metal coordination plays a key role in guiding the gas-phase fragmentation of the cationized peptide. In contrast to lithium and sodium, potassium and rubidium apparently do not coordinate to the C-terminal carbonyl. When the peptide is cationized with the two smaller alkali metals, losses corresponding to alanine and CBZ are observed, while the coordination of potassium and rubidium results in only CBZ loss upon dissociation.

Amino Acid Sequence↗
PubMed1999

Effects of chemical reactivity of the toxicity of phosphorus fluoridates.

Semiempirical quantum calculations were performed on a series of organophosphorus fluoridates to determine the relative reactivity for hydrolysis. This value was determined by subtracting the energy of the metastable intermediate from the energy of the stable molecule. Plotting this relative reactivity for each compound vs. its toxicity resulted in a parabolic curve with nerve agents and other similarly toxic compounds in the center. The more reactive phosphinates and less reactive phosphates were at the edges of the graph in the region of lower toxicity. The results indicate that for compounds meeting minimal structural requirements, chemical reactivity is the principal determinant of cholinesterase inhibition.

Animals↗
PubMed1993

Precise ablation of skin with reduced collateral damage using the femtosecond-pulsed, terawatt titanium-sapphire laser.

BACKGROUND AND DESIGN: The precise ablation of skin was studied using an ultrashort-pulsed, high-intensity titanium-sapphire (Ti:Al2O3) laser capable of peak intensities of tens of terawatts (TW; 1 TW = 10(12) watts [W]) per square centimeter. Rat skin was exposed in vitro to femtosecond-pulsed Ti:Al2O3 laser radiation at 800 nm, while varying the number of pulses and the intensity up to 46 TW/cm2. Ablation was evaluated by monitoring the amount of tissue removed per pulse as a function of energy, and by light microscopic examination of damage to adjacent, nonirradiated tissue. OBSERVATIONS: Ablation depth per pulse was 0.1 micron at threshold intensity, and it was increased with both the energy per pulse and the number of pulses. Minimal damage to adjacent healthy tissue was observed, varying 0 to 30 microns. CONCLUSION: The results suggest that ablation of skin with femtosecond-pulsed, terawatt Ti:Al2O3 laser may have potential for precision cutaneous surgery, and in vivo studies are indicated.

Animals↗
PubMed1991

Effects of typhus rickettsiae on peritoneal and alveolar macrophages: rickettsiae stimulate leukotriene and prostaglandin secretion.

Monolayers of mouse resident peritoneal macrophages were incubated with typhus rickettsiae, and macrophage secretion of leukotriene B4 (LTB4) was assessed. Macrophages incubated with native rickettsiae, but not those incubated with hemolytically inactivated rickettsiae, secreted significantly more LTB4 than did sham-treated macrophages. Antirickettsial antiserum was opsonic and blocked hemolysis, and macrophages incubated with rickettsiae in the presence of antiserum did not secrete more LTB4 than those incubated with buffer alone. Native rickettsiae also stimulated alveolar macrophages to secrete LTB4 and prostaglandin E2 (PGE2), but inactivated rickettsiae had no effect. Finally, because trifluoperazine did not alter macrophage LTB4 secretion in the presence of rickettsiae, but inhibited PGE2 secretion, it was suggested that the mechanisms by which rickettsiae stimulated production of these autacoids may have differed.

Analysis of Variance↗
PubMed1987

Bacterial detoxification of diisopropyl fluorophosphate.

The ability of 18 gram-negative bacterial isolates to detoxify diisopropyl fluorophosphate, a structural analog of the agents soman and sarin, was investigated. Detoxification by both frozen cell sonicates and acetone powders was assayed by two methods, i.e., the hydrolytic release of fluoride, measured by a fluoride-specific ion electrode, and the disappearance of acetylcholinesterase inhibition in vitro. Frozen cell sonicates for all strains exhibited some activity (F- ion release). In general, acetone powder preparations produced higher activity than frozen cell sonicates did, and the highest activities were exhibited by strains with known parathion hydrolase activity. Two ranges in activity were observed, low level, ranging from 0.1 to 7.0 mumol/min per g of protein, and high level, detected only in parathion hydrolase-producing strains, from 47 to greater than 300 mumol/min per g of protein. Results indicate that parathion hydrolase was nonspecific in phosphoesterase activity. Also, it was an effective detoxicant at low concentrations and near-neutral pH.

Biodegradation, Environmental↗
PubMed1984

Differentiating violent and nonviolent opiate-addicted reformatory inmates with the MMPI.

Used multivariate profile analysis and stepwise discriminant analysis in an effort to discriminate among four groups of male opiate-addicted reformatory inmates (N = 193) classified according to degree of criminal violence: (1) Bodily Violent (N = 19); (2) Potentially Bodily Violent (N = 25); (3) Materially Violent (N = 113); and (4) Nonviolent (N = 36). Profile analysis indicated that the four groups were very similar; a stepwise discriminant analysis significantly distinguished the Bodily Violent group from each of the other groups, but failed to differentiate successfully among the remaining three groups. A second stepwise discriminant analysis, in which Groups 2, 3 and 4 were combined, produced a significant discriminant function and correctly classified 68.4% of the Bodily Violent group and 75.9% of the combined Nonbodily Violent groups. The MMPI scales that contributed most to the latter prediction of group membership, in relative order of discriminating power, were: F, MA, D, PD, HS, PA and SI.

Adolescent↗
PubMed1983

Peroxidase-thiocyanate-peroxide antibacterial system does not damage DNA.

The hypothiocyanite ion (OSCN(-)) is a normal component of human saliva. It is a highly reactive oxidizing agent, and at concentrations above the values normally found in human saliva, it inhibits the growth and metabolism of oral bacteria. This finding has led to the suggestion that antibacterial properties of human saliva might be enhanced in vivo by appropriate supplements which elevate OSCN(-) concentrations. Since DNA is sensitive to oxidizing agents (hydrogen peroxide attacks nucleosides), high concentrations of OSCN(-) in human saliva might damage DNA and produce deleterious effects on the oral mucosa. In the present study, the effect of high OSCN(-) concentrations on several mutagen-sensitive Salmonella typhimurium strains was determined. These strains are used to detect base-pair substitutions and frameshift mutations. We also studied the effects of OSCN(-) on a Saccharomyces cerevisiae (yeast) strain commonly employed as a test cell for evaluating the potential of a compound to produce gene conversion, mitotic crossing-over, or reverse mutation. By recording the UV spectra of mixtures of calf thymus DNA and OSCN(-), we explored the possible in vitro reactions of this oxidizing agent with eucaryotic genetic material. Our results show that, at concentrations above 10 muM, OSCN(-) is toxic for the tested Salmonella typhimurium strains. The mutant strains with defects in cell wall lipopolysaccharides are killed more readily by OSCN(-) than is the strain lacking these defects. However, OSCN(-) was not mutagenic for any of the tested strains. Saccharomyces cerevisiae was not affected by OSCN(-) even at concentrations above 800 muM. Calf thymus DNA was not oxidized by OSCN(-). We conclude that the elevated concentrations of OSCN(-) required to produce antibacterial effects in the human mouth pose no threat to the genetic material of host tissues.

Anti-Bacterial Agents↗
PubMed1983

Effect of growth phase and cell envelope structure on susceptibility of Salmonella typhimurium to the lactoperoxidase-thiocyanate-hydrogen peroxide system.

The lactoperoxidase-thiocyanate-hydrogen peroxide system was found to have both bacteriostatic and bactericidal activities against strains of Salmonella typhimurium. The bactericidal activity was clearly dependent on the permeability of the bacterial cell envelope. The deep rough mutant TA1535, with the most permeable cell envelope, was killed both at neutral and acid pH, whereas very little or no killing was observed with the intact cells of the parent strain hisG46. The delta gal mutant, TA1530, representing an intermediate in cell envelope permeability, was inhibited to a much lesser extent than TA1535. Bacteria in log phase of growth were more sensitive to the bactericidal effects than were those in stationary phase. Growth phase had little influence on the bacteriostatic effects. The hisG46 strain produced significant quantities of acid in the presence of glucose. This acid production was inhibited by the lactoperoxidase-thiocyanate-hydrogen peroxide system, and, in contrast to results obtained with several strains of streptococci, this inhibition was not reversed by addition of a reducing agent (2-mercaptoethanol).

Cell Membrane Permeability↗
PubMed1983

Mutagenesis of nitro-dibenzo-p-dioxins.

Two dioxins, 2-nitro-dibenzo-p-dioxin (I) and 2,3 dichloro-7-nitro-dibenzo-p-dioxin (II), were prepared by condensing 3,4 dichloro nitrobenzene with the dipotassium salts of catechol and 4,5-dichloro-catechol, respectively. Both compounds were very mutagenic for Salmonella typhimurium TA1538, but only weakly mutagenic for TA1537. Compound II, but not compound I, also induced a few (approximately 100 revertants at near toxic doses) point mutations in strain TA1535.

DNA, Bacterial↗
PubMed1981

Characterization of an unusual isoenzyme of N-acetyl-beta-D-hexosaminidase from a human colonic carcinoma cell line.

A sub-line with increased metastatic ability was previously isolated from an established human colonic carcinoma cell line [Kimball & Brattain (1980) Cancer Res. 40, 1574-1579]. The separation and characterization of the isoenzymes of N-acetyl-beta-D-hexosaminidase from each cell line are reported. The parental cell line contained A and B isoenzymes. The sub-line lacked the A-isoenzyme activity and contained an atypical B isoenzyme that was thermolabile, susceptible to alkylation and of lower molecular weight.

Cell Line↗
PubMed1981

Lack of comutagenicity by norharman and other compounds on revertants induced by photolabeling with 2-azido-9-fluorenone oxime.

Mutations were induced by photolabeling 2-azido-9-fluorenone oxime in Salmonella typhimurium tester strain TA1538. Since the critical adducts were formed directly by the photogenerated nitrene, metabolic activation was bypassed. The bacteria themselves possessed the deep rough cell wall and uvrB- mutations, thereby minimizing comutagenic effects resulting from transport or DNA repair. This technique thus permitted detection of comutagenicity resulting from alteration in the binding of the mutagen to its critical receptor. No compound tested increased mutagenicity. Cholic acid had no effect at low dose, but inhibited mutagenicity at 10(-4) M, while trans-retinol no effect at any concentration. Harman, norharman and ethidium reduced the number of mutants only slightly at concentrations from 10(-6) to 10(-5) M.

Alkaloids↗
PubMed1981

Fluorescence of yeast vitally stained with ethidium bromide and propidium iodide.

Both ethidium bromide and propidium iodide stain growing yeast. As visualized in the fluorescence microscope, ethidium stains the nucleus and cytoplasm in wild type yeast and in those grown in 10% dextrose, with brightly fluorescent cytoplasmic granules being present in both. Under the latter conditions, the mitochondria are repressed but not absent. In rho 0 cells, in which the mitochondrial DNA is absent, ethidium appears to bind to the cell wall or membrane preferentially with no cytoplasmic granules being visible. In all cell types, propidium appears to bind the cell wall or membrane with no cytoplasmic granules being visible in any cell. The staining patterns thus suggest greater differences in the binding of these two types to mitochondrial DNA in situ than is suggested by their in vitro behavior. These differences in binding could explain their different mutagenic capacities..

Cell Nucleus↗
PubMed1980

Mutations and cell transformation with 2-azido-9-fluorenone oxime.

When photolyzed in situ for as little as 15 s 2-azido-9-fluorenone oxime causes Type II and Type III transformation in C3H 10T 1/2 CL8 cells. In the yeast strain Saccharomyces cerevisiae D-7, simple reversions and gene conversions occurred and also mitotic crossing over, to a lesser extent, but no mitochondril "petite" mutants occurred. No mutations or transformations were induced in the dark or by the light itself.

Animals↗
PubMed1980

Mutagenesis by photoaffinity labeling using selected azidofluorenes.

Several 2-azidofluorenes have been synthesized for use as photoaffinity labels inside bacteria. In the dark they were not mutagenic for any Salmonella typhimurium tested. When photolyzed inside the bacteria, all were mutagenic for strain TA1538 to varying degrees, and were considerably less mutagenic in the corresponding repair positive TA1978. None were mutagenic for strain TA1535 or TA1537, although most compounds were toxic for those strains when photolyzed.

Affinity Labels↗