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Biomedical subjects

M R Montgomery

Publications and source records attributed to M R Montgomery.

At least 19 recordsLinked to original sources
PubMed1995

Detection of hydroxyl radicals upon interaction of ozone with aqueous media or extracellular surfactant: the role of trace iron.

As part of a study on mechanisms modulating ozone-induced surfactant perturbations, we used the electron paramagnetic resonance (EPR) spin trapping technique to determine the type and origin of radicals generated following interaction of ozone with aqueous solutions and cell-free bronchoalveolar lavage fluid (BAL) fractions. All aqueous media were exposed to ozone at 25 degrees C with or without added chelator, 1 mM diethylenetriaminepentaacetic acid, and spintrap, 100 mM 5,5'-dimethyl-1-pyrroline-1-oxide (DMPO). Exposure of distilled water to 0.5, 1.0, 2.0, and 3.0 ppm ozone for 1 h yielded four-line spectra, 1:2:2:1, consistent with hydroxyl radical adduct formation (DMPO-OH), the amplitudes of which increased with the ozone concentration. No signals were obtained from air-exposed samples. Similar four-line spectra were also produced following interaction of 3 ppm ozone with Hank's balanced salt solution (HBSS) alone or containing BAL fractions. Addition of the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) to the incubation medium strongly inhibited formation of DMPO-OH adduct during ozone exposure. As an alternate method of demonstrating the generation of hydroxyl radicals, aqueous solutions of 1 mM L-phenylalanine were exposed to high concentrations of ozone and shown, using ion-exchange chromatography, to contain small amounts of L-tyrosine. Production of hydroxyl radicals upon interaction of ozone and water was further substantiated using the spintrap PBN (phenyl-N-tert-butylnitrone) in the presence of DMSO which reacts with the hydroxyl radical resulting in the formation of methyl radical. The methyl radical subsequently reacts with spintrap PBN, yielding PBN-methyl adduct. In the absence of DMSO there was no detectable formation of methyl radical adduct. EPR double distilled water containing DMPO showed a small amount of DMPO-OH adduct upon exposure to ozone. Addition of 10 microM ferrous sulfate to this mixture produced a 10-fold increase of the signal, which was attenuated in the presence of 1500 U catalase, strongly attenuated with 50-500 microM deferoxamine or 8000 U catalase and abolished by higher concentration of deferoxamine (1 mM). The signal was not influenced by 1000 U superoxide dismutase. These results indicate that hydroxyl radicals are produced via iron-dependent reactions during the initial interaction of ozone with aqueous media, including bronchoalveolar fluid.

Animals↗
PubMed1994

Ozone increases amino- and carboxy-terminal atrial natriuretic factor prohormone peptides in lung, heart, and circulation.

Ozone can cause pulmonary edema and simultaneously decrease blood pressure. Atrial natriuretic peptides may mediate both of these effects in that they increase pulmonary capillary permeability resulting in edema formation and are potent vasodilating peptides. To examine this possibility, the lungs of Fischer 344 rats were exposed to ozone (0.5 ppm) for 8 hours which resulted in a three- to fourfold increase in atrial natriuretic peptides. Ozone also increased atrial natriuretic peptides in the heart two- to fivefold from 266 +/- 25, 226 +/- 22, and 288 +/- 40 ng/g (room air) to 716 +/- 26, 471 +/- 14, and 1473 +/- 235 ng/g recognized by the proANFs 1-30 and 31-67 and atrial natriuretic factor radioimmunoassays, respectively. Ozone also doubled the concentrations of pro-ANFs 1-30, 31-67, and 1-98 and ANF in the circulation. This study demonstrates that ozone increases atrial natriuretic peptides within the heart, lung, and circulation, suggesting that atrial natriuretic peptides may mediate the decreased blood pressure and pulmonary edema observed with ozone exposure. Since the proANF 31-67 radioimmunoassay exclusively recognizes the ANF prohormone within the heart, this study further indicates that ozone can increase the synthesis of the ANF prohormone.

Animals↗
PubMed1994

Ozone increases atrial natriuretic peptides in heart, lung and circulation of aged vs. adult animals.

Ozone can cause pulmonary edema and simultaneously decrease blood pressure. Atrial natriuretic peptides may mediate both of these affects since they increase pulmonary capillary permeability and are potent vasodilating peptides. To examine this possibility and determine if aged animals respond differently to ozone, adult (4-6 months old) and aged (24-26 months old) Fischer 344 rats were exposed to ozone (0.5 parts per million) for 8 h. Ozone increased atrial natriuretic peptides recognized by the proANF 1-30, proANF 31-67, and atrial natriuretic factor (ANF) radioimmunoassays in lung from 3.7 +/- 0.2, 3.5 +/- 0.1, and 3.0 +/- 0.2 ng/g of lung, respectively, to 9.7 +/- 1.0, 9.2 +/- 0.4, and 13.3 +/- 2.7 ng/g in adult rats (n = 6) and from 3.6 +/- 0.1, 3.5 +/- 0.1, and 3.2 +/- 0.1 ng/g of lung of aged rats (n = 6) to 10.2 +/- 0.3, 10.0 +/- 0.2, and 12.6 +/- 0.2 ng/g. Ozone increased the content of these peptides in the heart 2- to 5-fold from 266 +/- 25, 226 +/- 22, and 288 +/- 40 ng/g of heart to 716 +/- 26, 471 +/- 14, and 1,473 +/- 235 ng/g in the same adult animals and from 495 +/- 17, 483 +/- 22, and 501 +/- 18 ng/g to 903 +/- 16,879 +/- 21, and 1,489 +/- 31 ng/g of heart in the aged animals. Ozone also doubled the concentration of these atrial natriuretic peptides in the circulatory system. This study demonstrates that ozone increases atrial natriuretic peptides in the lung, heart, and circulation of equal magnitude in aged versus adult animals, indicating an equal response to ozone with aging. This study further suggests that atrial natriuretic peptides may mediate the decreased blood pressure and pulmonary edema observed with ozone exposure.

Aging↗
PubMed1994

Increase in atrial natriuretic factor in the lungs, heart, and circulatory system owing to ozone.

Ozone can cause pulmonary edema and simultaneously decrease blood pressure. Atrial natriuretic factor (ANF) may mediate both of these effects in that it increases pulmonary capillary permeability resulting in edema formation and vasodilates the vascular system. The present investigation was designed to test directly the effect of ozone on the content of ANF in the lungs, heart, and the circulatory system. Ozone (0.5 ppm) exposure for 8 h increased ANF content in the lungs fourfold (13.33 +/- 2.7 ng/g tissue) in six Fischer 344 rats compared with ANF content (3.03 +/- 0.2 ng/g tissue) in six Fischer 344 rats exposed only to room air. Ozone increased ANF content in the heart fivefold in the same animals from 288 +/- 39.6 ng/g tissue in the rats exposed to room air to 1,473 +/- 234.8 ng/g tissue in those exposed to ozone. Ozone also doubled the concentration of ANF in the circulatory system. This study demonstrates that ozone does increase ANF in the lungs, heart, and circulatory system, suggesting that ANF may mediate the decreased blood pressure and pulmonary edema observed with ozone exposure.

Animals↗
PubMed1994

A toxicologic approach for evaluating cases of sick building syndrome or multiple chemical sensitivity.

The nonspecificity of symptoms and exposures commonly reported as "sick building syndrome" is very similar to that reported for the condition termed "multiple chemical sensitivity (MCS)." In many instances health care practitioners are divided on the reality of the latter. As in all scientific cases of possible cause-and-effect relationships, an organized, dispassionate approach should be used to evaluate each claim of MCS. Most obviously, known medical conditions must be ruled out before chemical "sensitivity" is proposed. Also, several questions on the toxicology of the chemical exposure must be addressed. Although temporality may be apparent (toxicity followed exposure), the time frame for the appearance of symptoms must be appropriate to the exposure conditions and chemical(s) involved. The chemical(s) must have known or reasonably inferred properties to cause the claimed effect. The dose(s) received must be adequate to effect a response (dose-response characteristics). Alternate causation must be evaluated thoroughly, that is, are there other more logical explanations for the symptoms? In contrast to single-chemical exposures, exposure to mixtures of chemicals, as commonly found in sick buildings, is very difficult to evaluate. However, a rational, scientific approach to cause-and-effect questions will help avoid erroneous and subjective decision making.

Air Pollution, Indoor↗
PubMed1993

Increased atrial natriuretic factor prohormone peptides with aging in the heart, but not in lung, liver, or intestine.

Atrial natriuretic factor (ANF) has been found to be increased in the circulation of aged rats. The present investigation was designed to determine if the N-terminal ANF prohormone peptides with blood pressure lowering properties are increased in the circulation of "aged" (24-26 months) versus "adult" (4-6 month old) Fisher 344 rats. We utilized two sensitive and specific radioimmunoassays that immunologically recognize the 98 amino acid (a.a.) N-terminus (proANF 1-98) and a.a. 31-67 (proANF 31-67, Vessel dilator) from the midportion of the N-terminus of the 126 a.a. ANF prohormone. ProANF 1-98, and proANF 31-67, as well as ANF, were found to be elevated in the circulation of aged versus adult animals with proANF 31-67 and ANF elevations being significant at p < 0.05. To determine the potential source of the increased atrial natriuretic peptides in aged animals four tissue sources (liver, lung, heart, and intestine) from both adult and aged animals were examined. Hearts of aged animals contained significantly (P < 0.05; ANOVA) more proANF 1-98, proANF 31-67, and ANF than hearts of adult animals. There was no significant difference in the concentration of proANF 1-98, proANF 31-67, or ANF in the lung, liver, or intestine of the aged versus the adult animals. These results indicate that aged animals contained increased N-terminal and C-terminal ANF prohormone peptides in the circulation. The source of these increased peptides appears to be the heart.

Aging↗
PubMed1992

Acute ozone-induced lung injury in rats: structural-functional relationships of developing alveolar edema.

As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH2O/kg) from a control value of 0.84 +/- 0.02 (SEM) to 0.72 +/- 0.04 and 0.57 +/- 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO2 to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H2O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.

Animals↗
PubMed1992

Retrograde extrapolation of blood alcohol data: an applied approach.

Retrograde extrapolation is a mathematical process, based on sound scientific principles, that is used routinely in pharmacology, toxicology, and clinical medicine. This process may be applied to the situation of ethyl alcohol consumption with reliability when reasonable assumptions are made concerning absorption rates, elimination rates, and patterns of alcohol consumption, including drinking duration and volume consumed. By utilizing an established range of values for the elimination rate of alcohol of 0.015-0.020 g/dl/h, a relatively narrow range of extrapolated blood alcohol concentrations (BACs) can be determined in situations where the time frame in question is after peak alcohol absorption into the blood. A wider range of elimination rates of 0.01-0.03 g/dl/h may be applied and will satisfy the possibility of nonlinear kinetics within an individual; however, this wider range will have little practical effect on the predicted BACs. When the time point in question is prior to peak absorption, a wider range of predicted BAC values will result. The extent of this range will be influenced by the amount of information available concerning the temporal pattern of alcohol consumption. Reported drinking volumes are notoriously inaccurate and, in fact, are of little practical use. Given the parameters of body weight and time duration between initiation of drinking and determination of the BAC, the number of "drinks" consumed may be reliability calculated. Retrograde extrapolation is applicable in the forensic setting with scientific reliability when reasonable and justifiable assumptions are utilized.

Absorption↗
PubMed1992

Immunocytochemical localization of lysozyme and surfactant protein A in rat type II cells and extracellular surfactant forms.

Using immunogold labeling of fixed, cryosubstituted tissue sections, we compared the distribution of lysozyme, an oxidant-sensitive lamellar body protein, with that of surfactant protein A (SP-A) in rat Type II cells, extracellular surfactant forms, and alveolar macrophages. Morphometric analysis of gold particle distribution revealed that lysozyme and SP-A were present throughout the secretory and endosomal pathways of Type II cells, with prominent localization of lysozyme in the peripheral compartment of lamellar bodies. All extracellular surfactant forms were labeled for both proteins with preferential labeling of tubular myelin and unilamellar vesicles. Labeling of tubular myelin for SP-A was striking when compared with that of lamellar bodies and other extracellular surfactant forms. Lamellar body-like forms and multilamellar structures were uniformly labeled for lysozyme, suggesting that this protein is rapidly redistributed within these forms after secretion of lysozyme-laden lamellar bodies. By contrast, increased labeling for SP-A was observed over peripheral membranes of lamellar body-like forms and multilamellar structures, apparently reflecting progressive SP-A enrichment of these membranes during tubular myelin formation. The results indicate that lysozyme is an integral component of the lamellar body peripheral compartment and secreted surfactant membranes, and support the concept that lysozyme may participate in the structural organization of lung surfactant.

Animals↗
PubMed1991

Recovery of lung pyridine nucleotides following acute exposure of adult and aged rats to ozone.

Male, pathogen-free Fischer 344 rats aged 6 and 24 mo were exposed to 1.5 or 3.0 ppm for 8 h and recovery rates of diphosphonucleotides (NAD+ and NADH) and triphosphonucleotides (NADP+ and NADPH) were measured and compared to controls. Recovery after 0.5 ppm was not examined because no significant changes occurred in either age group after this lower exposure. At zero time (immediately after exposures) both concentrations are depressed in adults and aged animals except for NADH in aged animals at 3.0 ppm; NADP+ in adults at 1.5 and 3.0 ppm was decreased, but not significantly. For NAD+ and NADH, recovery of whole lung concentrations is complete by 24 h following an 8-h exposure to 1.5 or 3.0 ppm of ozone. Only after 3.0 ppm of ozone was the ratio of the reduced to oxidized form (NADH/NAD+) still elevated after 24 h; however, it also returned to control levels by 96 h. For the triphosphonucleotides, an 8-h exposure to 1.5 ppm of ozone resulted in a sustained depression of whole lung concentrations of NADPH throughout the 96-h recovery period. Also, only after the 1.5 ppm exposure was the reduced to oxidized ratio (NADPH/NADP+) significantly depressed throughout the 96-h recovery period. Unexpectedly, recovery of whole lung levels returned to normal within 24 h after the 8-h exposure to both the 1.5 and the 3.0 ppm concentrations. With the exception of the sustained effect on NADPH levels, these data indicate that di- and triphosphonucleotide concentrations rapidly return to normal in the lung after severe, acute oxidant injury. There were no differences in recovery rates between the adult and the aged groups.

Aging↗
PubMed1991

Ozone stress initiates acute perturbations of secreted surfactant membranes.

To identify the early changes of surfactant secretion in response to acute oxidant stress, the authors evaluated morphometrically centriacinar type II cells and lavage fluid surfactant forms obtained immediately after exposure of adult rats to 3 ppm ozone for 1, 2, 4, or 8 hours. In this model, the rat lung develops progressive alveolar edema with significant elevation of lavage fluid proteins at 2 to 8 hours of exposure. Ultrastructural changes in type II cells at 1 and 2 hours included enhanced lamellar body (LB) fusion with significant increase in the compound and vacuolated LB compartments. Parallel changes of lavage fluid surfactant membranes included a sustained, twofold increase in the proportion of loosely coiled multilamellar structures at 1 to 8 hours, with reciprocal decrease in the proportion of tubular myelin from control value of 56% to 34%. The proportion of densely coiled LB-like forms in lavage fluid increased significantly at 4 and 8 hours, whereas the proportions of unilamellar structures remained unchanged. The results indicate that ozone-induced alveolar injury initiates time-dependent defects in the organization of stored and secreted surfactant membranes. The acute ozone stress inhibits unfolding of secreted lamellar body membranes as well as their organization into tubular myelin, thereby perturbing the proportions of extracellular surfactant membranes that are available for adsorption onto the surface film.

Animals↗
PubMed1989

Age-related difference in bioenergetics of lung and heart mitochondrial from rats exposed to ozone.

Bioenergetics of isolated lung and heart mitochondria from adult and aged rats were examined in the presence of glutamate (NAD-linked substrate) or succinate + rotenone (FAD-linked substrate) following ozone exposure (3.0 ppm, 8 hr). In controls, several differences were observed between adults and aged in both organ preparations. Following exposure, all bioenergetic parameters were decreased significantly in lung preparations from both adult and aged rats. In heart mitochondria, the respiration rates in state 3 and in uncoupled state, and the ADP/O ratio were decreased significantly in both exposed age groups. The respiratory control ratio (RCR) was decreased significantly only in the aged exposed rats. These results suggest that acute exposure to high levels of ozone alters energy production in both lung and heart mitochondria of adult and aged rats.

Aging↗
PubMed1989

Dynamic behavioural models and contraceptive choice.

Dynamic models of contraceptive use fill a theoretical gap. They bring behavioural content to the mathematically elegant Markov models of family building. They meet the criterion that Bulatao (1989) advances that method use, discontinuation and switching be considered not in isolation, but with reference to individual reproductive goals. Dynamic models help to link the literature on method choice with the literature on method effectiveness. These theoretical advantages are, at present, counter-balanced by empirical limitations. This article explores the theoretical and empirical underpinnings of dynamic contraceptive choice models.

Abortion, Legal↗
PubMed1989

Sequential changes of lamellar body hydrolases during ozone-induced alveolar injury and repair.

Lamellar body hydrolases in acutely damaged and regenerating type II cells were determined using an established rat model with well-defined stages of bronchiolo-alveolar injury and repair. Lamellar bodies were isolated from control and ozone-exposed (3.0 ppm for 8 hours) adult male rats by sucrose density gradient centrifugation and analyzed for their content of six different lysosomal hydrolases. Immediately after 3 ppm ozone exposure (zero-time) there was a significant decrease in specific enzyme activity (units/mg protein) of five lamellar body hydrolases and these activities remained depressed for at least 24 hours after exposure. In addition, total enzyme activity (units/lung) was reduced at zero-time for beta-hexosaminidase and at 24 hours postexposure for alpha-mannosidase and alpha-L-fucosidase. During the reparative and recovery stages (48 to 96 hours) the hydrolases demonstrated variable elevations in both specific activity and total activity (units/lung). Characteristically, beta-hexosaminidase and beta-galactosidase reached supranormal values at 96 hours, whereas alpha-mannosidase remained below normal levels through the recovery stage. Moreover, at 24 to 48 hours the lamellar body fraction demonstrated prominent enzyme depletion relative to the expanding pool of stored surfactant. It is concluded that acute ozone stress initiates the development of hydrolase deficiency within the lamellar bodies of injured and regenerating type II cells. This deficiency state is followed by asynchronous lamellar body hydrolase elevations that reflect distinct patterns of response rather than uniform return to normal condition. The lysosomal enzyme changes of lamellar bodies may be pathogenetically linked to the development of associated alterations in the storage and secretion of surfactant.

Animals↗
PubMed1988

Influence of bipyridylium compounds on microsomal mixed-function oxidation activities.

The two principal bipyridyl herbicides, paraquat and diquat, were investigated for their influence on microsomal mixed-function oxidation (MFO) activities and on NADPH oxidation rates in lung, liver, and kidney preparations. In lung microsomal preparations, benzphetamine N-demethylation was found to be inhibited by paraquat and diquat in a concentration-dependent manner, but ethylmorphine N-demethylation was unaffected by these bipyridyls. In liver microsomal fractions, both benzphetamine and ethylmorphine N-demethylases were inhibited by paraquat and diquat. Neither bipyridyl affected MFO activity in kidney preparations. A kinetic investigation of the enzyme inhibition showed that only Vmax was affected by paraquat and diquat, providing the first evidence for noncompetitive inhibition by the bipyridyls. In all microsomal preparations, NADPH oxidation was stimulated significantly by paraquat and to an even greater extent by diquat in the absence or presence of benzphetamine or ethylmorphine. The influence of MFO substrates on the stimulation varied widely among the three organ systems. In lung, paraquat- or diquat-mediated stimulation of NADPH oxidation was equal in the absence of MFO substrates and in the presence of ethylmorphine, but the stimulation was increased in the presence of benzphetamine. Stimulation of NADPH oxidation by the bipyridyls, in liver as well as in kidney preparations, was equal in all situations in the absence of MFO substrates and in the presence of benzphetamine or ethylmorphine, although the quantity of this stimulation was greater in liver than in kidney fractions. It is apparent that the bipyridyls are potent stimulators of in vitro NADPH oxidation in microsomal preparations from several organs. The quantity of the NADPH oxidation stimulation seems to be a decisive factor in the inhibition of xenobiotic metabolism. Whether the stimulation of NADPH oxidation and the non-competitive inhibition of xenobiotic metabolism play a significant role in bipyridyl toxicity are under further investigation.

Animals↗
PubMed1988

Artifacts in the determination of microsomal xenobiotic N-demethylation in the presence of ascorbic acid tris buffer and Nash reagent.

1. During investigation of microsomal xenobiotic N-demethylation in the presence of ascorbic acid, large increases in apparent enzymic activity were observed. 2. Examination of incubation components indicated that a non-enzymic interaction between ascorbic acid and Tris buffer, in the presence of acetylacetone and ammonium acetate (Nash reagent), was occurring. 3. The resulting chromophore had an absorption maximum at 412 nm that coincided with the absorption for the chromophore resulting from the interaction of the Nash reagent with the product (formaldehyde) of the enzymic reaction. 4. Strict controls of ascorbic acid potential chemical interaction with incubation components are required in enzymic studies.

Acetates↗