Nicholas Edward Sargent

Breath monitoring of inhalation and dermal methanol exposure

Abstract A fundamental assumption of monitoring breath for a toxicant is that the concentration of the toxicant in breath is proportional to the concentration in blood. The present study was designed, in part, to assess the conditions under which measurement of methanol in breath would be useful for estimating the blood concentration of methanol following inhalation or dermal exposures to methanol. Paid volunteer subjects underwent controlled inhalation exposure to methanol vapor at various concentrations for 8 hours, or dermal exposures (without inhalation exposure) to methanol for varying periods of time. Blood and end-expiratory air were analyzed for methanol from samples obtained prior to exposures, and at various times during and after exposures. The results demonstrate that blood and breath concentrations of methanol are disproportional for varying periods of time during and following cessation of methanol exposure, depending on the route of exposure (dermal versus inhalation). In settings where the...

IgG antibody and antibody–antigen complex imaging by scanning tunneling microscopy

We have examined two preparations of biomolecules labeled with colloidal gold markers using scanning tunneling microscopy. In the first preparation, we studied gold labeled IgG antibodies. In the second preparation, we studied unlabeled IgG antibodies which were complexed with gold labeled antigen (bovine serum albumin). Images of these noncrystalline biological specimens, obtained under atmospheric conditions, revealed features on a nanometer scale. The images show details of molecular organization in addition to the classical antibody configuration.

Pulmonary response to ozone: Reaction of bronchus-associated lymphoid tissue and lymph node lymphocytes in the rat

The purpose of this work is to assess the effect of ozone, a reactive product of environmental photochemical oxidation, on lymphocytes of the lung. We exposed male Fischer rats to ozone at a concentration of 0.5 ppm for 20 hr/day for 1-14 days. Animals were treated with radioactive thymidine and were sacrificed at Day 1, 2, 3, 7, or 14 of exposure. Lungs and mediastinal lymph nodes were removed and prepared for histologic examination, evaluation of labeling indexes, and morphometric measurement. We examined two components of the lymphocyte response of the lung: the airway-related response, represented by the reaction of the bronchus-associated lymphoid tissue (BALT), and the deep lung-related response, represented by reaction of the mediastinal lymph node. Lymphocytes of both the BALT and the mediastinal lymph node showed elevated radioactive thymidine uptake; however, no evidence of cell death was observed at either site. The cells of the specialized epithelium covering the BALT (lymphoepithelium) showed increased vacuolization, indicating altered cellular function. The average size of BALTs was unchanged by ozone exposure. Under experimental conditions ozone can affect a variety of cells in the lung including bronchial epithelial cells, macrophages, and Type 1 cells. We have shown for the first time that in addition to these cells, the rat BALT also proliferates in response to ozone. In addition we confirm previous work in the mouse which shows that the mediastinal lymph node reacts as well. The airways can be affected by inflammation, can be targets of infection, and can respond to chemical irritants with bronchoconstrictive responses. They are an important target organ for hypersensitivity responses and are a primary site for pulmonary cancer formation. A role for lymphocytes has been implicated in each of these processes. Therefore, the clinical significance of ozone on BALT and mediastinal lymph node responses could be appreciable in terms of potentiation of, or protection against, such responses.

The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function

The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing [14C]serotonin or [14C]hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.

Evaluation of Methanol and Formate in Urine as Biological Exposure Indices of Methanol Exposure

Abstract Biological monitoring of exposure to industrial chemicals commonly involves laboratory analyses of a toxicant or metabolites in urine. The American Conference of Governmental Industrial Hygienists has recommended biological exposure indices for methanol exposure based on methanol and formate in urine. The present study was designed primarily to evaluate methanol in urine and other potential biological determinants of methanol exposure. Volunteer subjects underwent controlled exposure to methanol vapor at different concentrations for approximately 8 hours to simulate a standard work shift. Urine was collected immediately prior to exposure sessions, during exposures, and immediately following cessation of exposures. Samples were analyzed for methanol, formate, specific gravity (SpGr), and creatinine. The following biological determinants were examined: total methanol excreted during the shift; mean concentration of methanol excreted during the shift (uncorrected, and corrected for SpGr and creatini...