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T L Webb

Publications and source records attributed to T L Webb.

6 recordsLinked to original sources
PubMed1996

Mechanism of site-selective DNA nicking by the hydrodioxyl (perhydroxyl) radical.

In previous studies, the ability of the hydrodioxyl (perhydroxyl) radical [HOO., the conjugate acid of superoxide (O2.-] to "nick" DNA under biomimetic conditions was demonstrated, and a sequence selectivity was observed. A background level of nonspecific nicking also was noted. This paper provides support for 5'-hydrogen atom abstraction from the deoxyribose ring as the initial event in the sequence-selective nicking by 02.-/HOO.. Two experiments support the proposed mechanism. First, using a defined sequence 5'-32P-labeled restriction fragment as the DNA substrate, only free (unalkylated) 3'-phosphate is produced at the site of nicking. Second, using poly (dA).poly (T) as the substrate, furfural is formed in the reaction from deoxyribose ring breakdown. Both results are consistent with 5'-hydrogen atom abstraction for initiation of the site-selective nicking. Hydrogen atom abstraction at other sites of the deoxyribose ring and/or base oxidation and loss followed by strand scission likely are responsible for the nonspecific nicking. The 5'-abstraction mechanism contrasts to those elicited by other 02-derived and metal-associated oxidants, which may provide a biomarker for the reactivity of HOO. in vivo.

Binding Sites↗
PubMed1995

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Adolescent↗
PubMed1981

Regrowth of Pseudomonas aeruginosa and other bacteria after the bactericidal action of carbenicillin and other beta-lactam antibiotics.

Exposure of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus to bactericidal concentrations of beta-lactam antibiotics in broth culture resulted in a decrease in viability over the first 6--8 hr, followed by regrowth which was not due to the selection of resistant variants or loss of antibiotic potency. During incubation, bacteria adhered to the surface of the culture vessel and multiplied despite the presence of bactericidal concentrations of antibiotic in the medium. It is concluded that the phenomenon of "regrowth" results from such adhesion and the subsequent dispersal of some of these cells into the culture medium. The significance of these findings is discussed in relation to the treatment of infection, the determination of minimal bactericidal concentrations, and the phenomena of tolerance and persisters.

Carbenicillin↗
PubMedDate not supplied

Time-activity patterns and diurnal variation of respiratory status in a panel of asthmatics: implications for short-term air pollution effects.

To understand the short-term health risks to people from air pollution exposure, we investigated time-activity patterns and temporal variation of the respiratory status in 49 asthmatic Los Angeles area residents 18-50 years old. During the summer (May-September) and winter (November-March), subjects measured their lung function two to four times daily at home for one week periods, and every hour recorded their symptoms, medication, and activity hourly in diaries. Almost all subjects recorded heart rates (HR), which were converted to ventilation rate (VR) estimates using individual laboratory exercise data. Most subjects' lung function and symptoms varied diurnally, and were worst in early morning. For subjects with clinically mild asthma, diurnal forced expired volume in 1 sec (FEV1) changes averaged 7%, versus 12% in those with moderate symptoms, and 18% in severely asthmatic subjects. Lung function was similar in summer and winter, but symptoms and medication use decreased in winter. In the aggregate, subjects reported spending 75% of waking hours indoors at self-rated slow activity and 11% in vehicles. HR records usually corroborated reports of medium or fast activity. Mean estimated VR at slow, medium, and fast activity was 19, 37, and 61 L/min for men, and 16, 24, and 32 L/min for women. Outdoor fast activity, representing the greatest vulnerability to outdoor pollution, occupied approximately 0.2% of waking hours (2 min/day on average); outdoor medium activity occupied about 2% of waking hours (19 min/day on average). Estimated cumulative ventilation was higher than that of previous healthy panels because of asthmatics' higher VR at slow activity. If these activity patterns are typical, asthmatics may be especially vulnerable to pollutants with effects dependent on cumulative inhaled dose. Effects dependent on high inhaled dose rates over a short period, e.g., sulfur dioxide effects, would be unlikely, except perhaps for uncommonly active individuals in uncommonly polluted areas.

Adolescent↗