Biomedical subjects

D E House

Publications and source records attributed to D E House.

At least 19 recordsLinked to original sources

PubMed1992

The differential hepatotoxicity and cytochrome P450 responses of Fischer-344 rats to the three isomers of dichlorobenzene.

The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate the onset of toxicity and to further elucidate the role of cytochrome P450 in the metabolism and toxicity of these compounds. In a study design employing one animal per dose level, Fischer-344 rats were gavaged with up to 25 different dosages, then evaluated 24 h later. Hepatic necrosis, serum alanine aminotransferase, and serum aspartate aminotransferase exhibited similar patterns demonstrating that ortho-DCB (o-DCB) was the most toxic in terms of both earliest onset and degree of response at higher dosages. For these three endpoints, meta-DCB (m-DCB) exhibited a lesser toxicity. Para-DCB (p-DCB) did not cause changes in these three endpoints, but hepatic degenerative changes were found. Total hepatic cytochrome P450 responses were also different after treatment with each isomer. The o-DCB produced a dose-dependent decrease in P450 beginning at dosages lower than the onset of necrosis and appeared to be a suicide substrate for P450. The m-DCB treatment increased P450 at dosages below the onset of necrosis and decreased P450 at higher dosages, with the decline preceding the onset of hepatocyte death. Treatment with p-DCB increased P450 beginning at 380 mg/kg. The combination of toxicity and P450 profiles has provided a framework for interpreting literature data on the metabolism and toxicity of the DCBs in rats. It is also noteworthy that o-DCB and p-DCB were administered at dosages several times the oral rat LD-50 (RTECS) without any lethality.

Alanine Transaminase↗

PubMed1992

Comparison of open and blind histopathologic evaluation of hepatic lesions.

This paper explores the controversy among scientists on whether microscopic evaluation of tissue slides should be done in an open or blind fashion. Definitions are given and discussed that provide a better focus to the problem. An experiment was conducted in which hepatocellular degeneration and necrosis in rats were assessed both openly and blindly. The results indicate that 'simple bias' is present when the slides are read openly. Valid comparisons among treatment groups are possible in the presence of simple bias, provided appropriate control groups have been incorporated into the experimental design.

Animals↗

PubMed1992

Evaluation of high volume particle sampling and sample handling protocols for ambient urban air mutagenicity determinations.

An investigation of high volume particle sampling and sample handling procedures was undertaken to evaluate variations of protocols being used by the U.S. Environmental Protection Agency. These protocols are used in urban ambient air studies which collect ambient and source samples for subsequent mutagenicity analysis of the organic extracts of the aerosol fraction. Specific protocol issues investigated include: (a) duration of sampling period, (b) type of filter media used to collect air particles, (c) necessity for cryogenic field site storage and dry ice shipping of filter samples, and (d) sample handling at the receiving laboratory. Six PM10 Hi-Vol samplers were collocated at an urban site in downtown Durham, North Carolina and operated simultaneously to evaluate 12 h versus 24 h collection periods and filter media choices of glass fiber, Teflon impregnated glass fiber (TIGF), and quartz fiber. Filters from the samplers plus field blanks were collected during each of 25 sampling periods. TIGF filters from two samplers were immediately placed on dry ice in the field and transported directly to cryogenic storage. TIGF, quartz, and glass fiber filters from three samplers were transported at ambient and maintained at room temperature for three to six days prior to cryogenic storage. One TIGF sample, which was collected on a previously tared filter, was subjected to controlled environment equilibration (40 percent relative humidity, 22 degrees C) for 8 to 24 h and weighed prior to cryogenic storage. All filters were subsequently stored at -70 degrees C to -80 degrees C prior to a one-time extraction and Salmonella (Ames) mutagenicity bioassay of the entire sample set.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

PubMed1992

Hepatotoxic interactions of ethanol with allyl alcohol or carbon tetrachloride in rats.

To assess whether potential toxic interactions occur between ethanol and allyl alcohol or carbon tetrachloride following subacute, concurrent chemical exposure, male Fischer 344 rats, approximately 70 d of age, were given ethanol at 0, 0.05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 d (ETOH group), or the same levels of ethanol with 21 mg allyl alcohol/kg (ALAC group), or the same levels of ethanol with 20 mg carbon tetrachloride/kg (CCL4 group). Hepatic response was assessed 24 h after the last dose. Interactions were evaluated by comparing the ETOH group with either the ALAC group or the CCL4 group using multivariate analysis of variance procedures. No statistically significant interaction was seen between the ETOH group and the ALAC group at the dosages used. Although an interaction between ethanol and carbon tetrachloride given simultaneously was not statistically significant, a small interactive effect on weight gain from d 0 to termination was apparent (p = .057). Exposure to ethanol alone resulted in a concentration-dependent decrease in absolute and relative liver weight, with a threshold between 0.05 and 0.1 ml/kg. There was no histopathological evidence of hepatic damage with ethanol alone, and no effect on hepatic cytochrome P-450 and glutathione levels or on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALK). Exposure to allyl alcohol alone resulted in significant increases in absolute and relative liver weights, liver glutathione, and periportal hepatocellular vacuolar degeneration. Exposure to carbon tetrachloride alone resulted in significant increases in absolute and relative liver weight, serum levels of ALT, AST, and ALK, and centrilobular hepatocellular vacuolar degeneration and necrosis. These observations indicate that subacute, concurrent exposure of ethanol with carbon tetrachloride or allyl alcohol at ethanol levels comparable to those reported in gavage vehicles did not result in interactive toxicity.

1-Propanol↗

PubMed1991

The influence of temperature during electric- and magnetic-field-induced alteration of calcium-ion release from in vitro brain tissue.

A technique based on release of calcium ions from in vitro preparations of avian brain tissues has been used by several investigators to demonstrate a biological effect of weak electric and magnetic fields. When the tissues have been exposed to ELF-modulated, VHF or UHF fields, enhanced release of calcium ions has resulted. In contrast, when the tissues have been exposed directly to an ELF field, outcomes have differed. Both inhibition and enhancement in release of calcium ions have been reported. We now find that either outcome--or a null result--is possible, depending on the temperature of tissue samples before and during exposure. Avian-brain tissues were exposed to 16-Hz sinusoidal electromagnetic fields at 14.1 Vrms/m (in air) and 64 nTrms. During 20-min exposures, as tissue-sample temperature rose by 0.7 to 2.5 degrees C to a final temperature of 35, 36, or 37, but not of 38 or 39 degrees C, an enhanced release of ions was observed. When the temperature was stable during exposure (i.e., constant within +/- 0.3 degrees C) at a final value of 36 or 37, but not of 35 or 38 degrees C, the quantity of ions released was reduced. And when descending by 0.7 to 1.5 degrees C to any final temperature from 35 to 38 degrees C, a null result occurred. These findings may reconcile the apparent disagreement in the direction of a field-induced response, and they may explain why experimental outcomes have been difficult to confirm in some laboratories. Of greater importance, the findings may also provide insight into the mechanism of the field-induced phenomenon.

Animals↗

PubMed1991

Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung.

An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

Adolescent↗

PubMed1990

Importance of alignment between local DC magnetic field and an oscillating magnetic field in responses of brain tissue in vitro and in vivo.

The frequency dependence of the electric and magnetic (EM)-field-induced release of calcium ions from an in vitro brain tissue preparation has been shown to be a function of the density of the local DC magnetic field (Bdc). In this study, we demonstrate that the relative orientation of the Bdc and the magnetic component (Bac) of a 315-Hz EM signal (15 Vrms/m and 61 nTrms) are crucial for the induced release to be observed. The induced release occurs only when the Bdc and the Bac are perpendicular, and not when they are parallel. This finding is consistent with a magnetic resonance-like transduction mechanism for the conversion of EM energy into a physicochemical change, and contrasts with the requirement for parallel Bdc and Bac components in the diatom-mobility experiments of Smith et al. A review of the exposure conditions in the rat behavioral experiments conducted by Thomas et al. identifies unhydrated calcium and zinc ions as alternatives to lithium ions as candidates for interaction under parallel magnetic-field orientations but fails to reject perpendicular orientations as an alternative basis for the phenomenon. Investigators that attempt to confirm the rat behavioral experiments should be aware of the conflicting exposure conditions that can be assumed to be operative, and they should design their experiments to test all conditions accordingly.

Animals↗

PubMed1990

Exposure of frog hearts to CW or amplitude-modulated VHF fields: selective efflux of calcium ions at 16 Hz.

Isolated frog hearts were exposed for 30-min periods in a Crawford cell to a 240-MHz electromagnetic field, either continuous-wave or sinusoidally modulated at 0.5 or 16 Hz. Radiolabeled with calcium (45Ca), the hearts were observed for movement of Ca2+ at calculated SARs of 0.15, 0.24, 0.30, 0.36, 1.50, or 3.00 mW/kg. Neither CW radiation nor radiation at 0.5 Hz, which is close to the beating frequency of the frog's heart, affected movement of calcium ions. When the VHF field was modulated at 16 Hz, a field-intensity-dependent change in the efflux of calcium ions was observed. Relative to control values, ionic effluxes increased by about 18% at 0.3 mW/kg (P less than .01) and by 21% at 0.15 mW/kg (P less than .05), but movement of ions did not change significantly at other rates of energy deposition. These data indicate that the intact myocardium of the frog, akin to brain tissue of neonatal chicken, exhibits movement of calcium ions in response to a weak VHF field that is modulated at 16 Hz.

Animals↗

PubMed1989

Multiple power-density windows and their possible origin.

We have previously reported that in vitro exposure of chick forebrain tissue to 50-MHz radiofrequency (RF) electromagnetic radiation, amplitude modulated (AM) at 16 Hz, would enhance the efflux of calcium ions within only two power-density ranges: one from 1.44 to 1.67 mW/cm2, and the other including 3.64 mW/cm2. No effect on efflux occurred at 0.37, 0.72, 2.17, and 4.32 mW/cm2. We confirmed and extended these results by testing at another set of power densities, which included the range of the previous study. Forebrain tissue from 1-7-day-old chickens was labeled in vitro with radioactive calcium ions (30 min, at 37 degrees C), rinsed, placed in a physiological salt solution, and then exposed for 20 min to 50-MHz radiation, AM at 16 Hz, in a transverse electric and magnetic field (TEM) cell maintained at 37 degrees C. The solution was then assayed for radioactive calcium activity. A power-density series was tested. An enhanced efflux of calcium ions was found at 1.75, 3.85, 5.57, 6.82, 7.65, 7.77, and 8.82 mW/cm2; no change was observed at 0.75, 2.30, 4.50, 5.85, 7.08, 8.19, 8.66, 10.6, and 14.7 mW/cm2. Power density is converted to specific absorption rate (SAR) by 0.36 mW/kg per mW/cm2. Even the highest SAR tested (0.005 W/kg) is much too low to result in generalized heating of the sample and thus to be the underlying cause of the enhanced response. A hypothetical mechanism is proposed involving dynamic systems that may account for the power-density dependency as well as for part of the frequency dependency observed with both modulated RF radiation and extremely-low-frequency (ELF) fields.

Animals↗

PubMed1989

Ozone-induced inflammation in the lower airways of human subjects.

Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1988

Effect of ambient levels of power-line-frequency electric fields on a developing vertebrate.

Fertilized eggs of Gallus domesticus were exposed continuously during their 21-day incubation period to either 50- or 60-Hz sinusoidal electric fields at an average intensity of 10 Vrms/m. The exposure apparatus was housed in an environmental room maintained at 37 degrees C and 55-60% relative humidity (RH). Within 1.5 days after hatching, the chickens were removed from the apparatus and tested. The test consisted of examining the effect of 50- or 60-Hz electromagnetic fields at 15.9 Vrms/m and 73 nTrms (in a local geomagnetic field of 38 microT, 85 degrees N) on efflux of calcium ions from the chicken brain. For eggs exposed to 60-Hz electric fields during incubation, the chicken brains demonstrated a significant response to 50-Hz fields but not to 60-Hz fields, in agreement with the results from commercially incubated eggs [Blackman et al., 1985a]. In contrast, the brains from chicks exposed during incubation to 50-Hz fields were not affected by either 50- or 60-Hz fields. These results demonstrate that exposure of a developing organism to ambient power-line-frequency electric fields at levels typically found inside buildings can alter the response of brain tissue to field-induced calcium-ion efflux. The physiological significance of this finding has yet to be established.

Animals↗

PubMed1988

Influence of electromagnetic fields on the efflux of calcium ions from brain tissue in vitro: a three-model analysis consistent with the frequency response up to 510 Hz.

The frequency dependence of electromagnetic field-induced calcium-ion efflux from chicken brain tissues has been examined at 15-Hz intervals over the range 1-510 Hz. The electric field component was 15 Vrms/m and the magnetic component varied between 59 and 69 nTrms. No patterns of response as a function of frequency could be readily discerned when the differences in mean efflux values between exposed and sham samples were compared. However, the calculated P-value, a function that combines at each frequency the difference between the means of the exposed and sham groups with the variance of each group, does provide a basis for hypothesizing the existence of three frequency-dependent patterns in the data. One pattern includes all the highly significant (P less than .01) responses which occur between 15 and 315 Hz, at 30-Hz intervals; two independent trials at 165 Hz, giving nonsignificant responses (P greater than .5), break this pattern into two groups of five frequencies each, which is contrary to the expected result for a simple Lorentz-force interaction. However, another pattern of significant results at 60, 90, and 180 Hz, but not at 300 Hz, is consistent with a Lorentz-force model. A third pattern, composed of only one significant response at 405 Hz, is very close to the resonance predicted on a linear extrapolation from high-frequency data for 13carbon atoms. This hypothetical ordering of the frequency-response profile provides the basis for future experimental designs to test each possible interaction model and for their connection to the calcium-ion efflux endpoint.

Animals↗

PubMed1988

Extrathoracic and intrathoracic removal of O3 in tidal-breathing humans.

We measured the efficiency of O3 removal from inspired air by the extrathoracic and intrathoracic airways in 18 healthy, nonsmoking, young male volunteers. Removal efficiencies were measured as a function of O3 concentration (0.1, 0.2, and 0.4 ppm), mode of breathing (nose only, mouth only, and oronasal), and respiration frequency (12 and 24 breaths/min). Subjects were placed in a controlled environmental chamber into which O3 was introduced. A small polyethylene tube was then inserted into the nose of each subject, with the tip positioned in the posterior pharynx. Samples of air were collected from the posterior pharynx through the tube and into a rapidly responding O3 analyzer yielding inspiratory and expiratory O3 concentrations in the posterior pharynx. The O3 removal efficiency of the extrathoracic airways was computed with the use of the inspiratory concentration and the chamber concentration, and intrathoracic removal efficiency was computed with the use of the inspiratory and expiratory concentrations. The mean extrathoracic removal efficiency for all measurements was 39.6 +/- 0.7% (SE), and the mean intrathoracic removal efficiency was 91.0 +/- 0.5%. Significantly less O3 was removed both extrathoracically and intrathoracically when subjects breathed at 24 breaths/min compared with 12 breaths/min (P less than 0.001). O3 concentration had no effect on extrathoracic removal efficiency, but there was a significantly greater intrathoracic removal efficiency at 0.4 ppm than at 0.1 ppm (P less than 0.05). Mode of breathing significantly affected extrathoracic removal efficiency, with less O3 removed during nasal breathing than during either mouth breathing or oronasal breathing (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Evaluating the toxicity of urban patterns of oxidant gases. II. Effects in mice from chronic exposure to nitrogen dioxide.

The study reported herein evaluates the influence of a chronic exposure to an urban pattern of NO2 (continuous baseline exposure of 0.2 ppm, on which were superimposed two 1-h spikes of 0.8 ppm NO2, 5 d/wk) as compared to the baseline exposure to determine the contribution of the spikes to toxicity. Mice were exposed for up to 52 wk with interim examinations. Multivariate analysis of variance revealed a statistically significant treatment effect on infectivity (p = 0.05) and pulmonary function (p = 0.03) parameters. Infectivity mortality of mice in the spiked exposure regimen was significantly greater than that in either the NO2-background-exposed mice or in control mice. Four of the pulmonary function variables exhibited the greatest differences among the treatment groups: end expiratory volume, vital capacity, respiratory-system compliance, and multiple-breath nitrogen washout. Results from the pulmonary-function analyses indicate that the spiked exposures to 0.8 ppm NO2 may have induced a subtle lesion. The chronic study results indicate that the presence of spikes of NO2 is contributing significantly to effects on antibacterial lung defenses and pulmonary function of mice.

Administration, Inhalation↗

PubMed1987

Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice.

The nitrogen dioxide (NO2) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO2 peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO2 exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO2 concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O3) and NO2, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO2 and O3, synergistic results were obtained for streptococcal-induced mortality.

Air Pollutants↗

PubMed1986

A nonparametric version of Williams' test for a randomized block design.

A large-sample nonparametric version of Williams' test for comparing increasing doses of a substance with a zero-dose control response is given for observations from a randomized block experimental design. The method is based on Friedman-type ranks. Williams' test and the nonparametric equivalent for a one-way design are briefly described. The validity of the new method is shown and a numerical example is given.

Animals↗

PubMed1985

Effects of ELF (1-120 Hz) and modulated (50 Hz) RF fields on the efflux of calcium ions from brain tissue in vitro.

We have previously shown that 16-Hz, sinusoidal electromagnetic fields can cause enhanced efflux of calcium ions from chick brain tissue, in vitro, in two intensity regions centered on 6 and 40 Vp-p/m. Alternatively, 1-Hz and 30-Hz fields at 40 Vp-p/m did not cause enhanced efflux. We now demonstrate that although there is no enhanced efflux associated with a 42-Hz field at 30, 40, 50, or 60 Vp-p/m, a 45-Hz field causes enhanced efflux in an intensity range around 40 Vp-p/m that is essentially identical to the response observed for 16-Hz fields. Fields at 50 Hz induce enhanced efflux in a narrower intensity region between 45 and 50 Vp-p/m, while radiofrequency carrier waves, amplitude modulated at 50 Hz, also display enhanced efflux over a narrow power density range. Electromagnetic fields at 60 Hz cause enhanced efflux only at 35 and 40 Vp-p/m, intensities slightly lower than those that are effective at 50 Hz. Finally, exposures over a series of frequencies at 42.5 Vp-p/m reveal two frequency regions that elicit enhanced efflux--one centered on 15 Hz, the other extending from 45 to 105 Hz.

Animals↗

PubMed1985

A role for the magnetic field in the radiation-induced efflux of calcium ions from brain tissue in vitro.

Two independent laboratories have demonstrated that electromagnetic radiation at specific frequencies can cause a change in the efflux of calcium ions from brain tissue in vitro. In a local geomagnetic field (LGF) at a density of 38 microTesla (microT), 15- and 45-Hz electromagnetic signals (40 Vp-p/m in air) have been shown to induce a change in the efflux of calcium ions from the exposed tissues, whereas 1- and 30-Hz signals do not. We now show that the effective 15-Hz signal can be rendered ineffective when the LGF is reduced to 19 microT with Helmholtz coils. In addition, the ineffective 30-Hz signal becomes effective when the LGF is changed to +/- 25.3 microT or to +/- 76 microT. These results demonstrate that the net intensity of the LGF is an important variable. The results appear to describe a resonance-like relationship in which the frequency of the electromagnetic field that can induce a change in efflux is proportional to a product of LGF density and an index, 2n + 1, where n = 0,1. These phenomenological findings may provide a basis for evaluating the apparent lack of reproducibility of biological effects caused by low-intensity extremely-low-frequency (ELF) electromagnetic signals. In future investigations of this phenomenon, the LGF vector should be explicitly described. If the underlying mechanism involves a general property of tissue, then research conducted in the ambient electromagnetic environment (50/60 Hz) may be subjected to unnoticed and uncontrolled influences, depending on the density of the LGF.

Animals↗