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Biomedical subjects

J B Ward

Publications and source records attributed to J B Ward.

At least 55 records · Page 3Linked to original sources
PubMed1991

Epidemic keratoconjunctivitis at a U.S. military base: Republic of the Philippines.

Between August 1988 and January 1989, 2,603 cases of acute conjunctivitis occurred at Clark Air Base in the Philippines. Clinical features of the disease were consistent with epidemic keratoconjunctivitis. Adenovirus types 19 and 8, as well as enteroviruses, were isolated from conjunctival swabs. Approximately 18% of 9,167 active duty personnel were affected. In an attempt to contain the outbreak, active cases were isolated from the workplace, resulting in 9,038 personnel-days lost. Military preparedness was significantly impacted. A case-control study revealed multiple risk factors for acquisition of the disease.

Adenovirus Infections, Human↗
PubMed1989

A combined testing protocol for assessing genotoxicity in individual animals: application to environmental toxicology.

A multiple end-point approach to assessing genetic toxicity (the combined testing protocol, CTP) was evaluated in male and female CD-1 mice exposed subacutely (3 and 6 weeks) to low levels of a custom-blended gas mixture (epichlorohydrin, benzene, chloroprene and xylene, at 50, 100, 100, and 100 ppb, respectively, as the low dose, with concentration levels 10-fold and 100-fold higher as the intermediate and high doses, or 0.1, 1 and 10 ppm of benzene). Urine mutagenicity was tested in the Salmonella/microsome assay, chromosome aberrations were examined in bone marrow and spleen lymphocytes, micronuclei were measured in bone marrow and peripheral erythrocytes, and cytochrome P450 and glutathione S-transferases were measured in the liver. Structural aberrations in alveolar macrophages and spermatocytes, and thioguanine resistance in spleen lymphocytes were examined for their suitability for incorporation into the overall protocol. Spleen lymphocytes were the most sensitive indicator cells, and showed a dose-related increase (P less than 0.01) in structural chromosome aberrations and in cytotoxicity after 6 weeks of exposure. Analysis of micronucleus formation and metaphase aberrations in the bone marrow, and micronuclei in peripheral erythrocytes showed an overall statistically non-significant but positive trend at the high dose. No mutagenicity was detected in pooled urine samples. Liver microsomal cytochrome P450 was not increased, but cytosolic glutathione S-transferases were significantly increased in a dose-related manner. Since the probability of detecting a genotoxic effect increases with the number of endpoints and tissues examined, this approach should be applicable to many situations without having to perform separate experiments for each tissue examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗
PubMed1989

Genotoxic effects of fly ash in bacteria, mammalian cells and animals.

The increasing use of fossil fuels has raised concerns about possible deleterious health effects of the final combustion product, fly ash. Seven ash samples from coal sources obtained from Battelle Columbus Laboratories were evaluated in the Salmonella/mammalian microsome mutagenicity assay to determine their mutagenic potential. While dimethyl sulfoxide extracts of five samples showed no mutagenicity, sample 102 caused an increase in the number of revertants per plate over controls in TA100 and TA98 with activation by liver homogenate (2-fold and 2.4-fold, respectively), and without (2-fold and 6-fold). This ash was thus evaluated in whole animal studies. Animals treated by inhalation or oral gavage were assayed for the presence of mutagens in the urine, micronuclei in polychromatic erythrocytes, and chromosomal aberrations in metaphase bone marrow cells. Those animals treated by inhalation were also examined for local damage in the lung. The assay for mutagens in the urine was negative as shown by the Ames assay with TA100 and TA98 and there was no increase in micronuclei or in metaphase aberrations. Histological sections from the animals treated by inhalation did not show the presence of particles, macrophage infiltrations and generalized lung damage. We tested the same fly ash with an in vitro cell transformation assay with the cell line Balb/c 3T3 subclone A31-1-13. Although there was not an increase in Type III foci, there was a dose-dependent increase of Type II foci in the treated cells over the controls. In one assay, there was approximately a 14-fold increase in Type II foci in the highest dose (2 mg/ml) compared to the solvent control. One other ash sample induced cell transformation without being markedly cytotoxic, while a third sample was highly toxic but did not induce transformation.

Animals↗
PubMed1989

Cross-linking and O-acetylation of newly synthesized peptidoglycan in Staphylococcus aureus H.

Staphylococcus aureus H growing exponentially was labelled with N-acetyl[14C]glucosamine, which became incorporated into the peptidoglycan. The portion of peptidoglycan not linked to teichoic acid (60-75% of the whole) was degraded with Chalaropsis muramidase to yield disaccharide-peptide monomers and dimers, trimers and oligomers formed by biosynthetic cross-linking of the monomers. The degree of O-acetylation of these fragments was also examined. Pulse-chase experiments showed that the proportion of label initially in the monomer fraction immediately after the 1 min pulse declined rapidly during a 3 min chase, while the oligomer fraction (fragments greater than trimer) gained the radioactivity proportionately. The radioactivity of the dimer and trimer fractions remained virtually unchanged. At 4 min after the commencement of labelling (i.e. approx. one-tenth of a generation time) final values had been reached. The O-acetylation of all fragments had achieved final values even at 1 min, except for the monomer fraction, which showed an increase from 40% to 60% during the first 3 min of chase. Although O-acetylation was clearly a very rapid process, no O-acetylated peptidoglycan lipid-intermediates could be detected.

Acetylation↗
PubMed1988

Genotoxic effects of a sub-acute low-level inhalation exposure to a mixture of carcinogenic chemicals.

A study was conducted using a combined testing protocol (CTP), to determine whether short-term biological end-points, singly or in combination, are sufficiently sensitive to identify damage induced by exposure to ambient levels of industrial chemicals. A small-scale inhalation set-up which is both economical and easy to assemble was designed. Mice were exposed to 4 concentrations of a custom-blend mixture of benzene, chloroprene, epichlorohydrin and xylene in a ratio of 2:2:1:2, respectively. The concentrations for benzene, chloroprene and xylene were 0, 0.1, 1.0 and 10 ppm each. Concentrations for epichlorohydrin were half those for the other components. Groups of 22 males and 22 female mice were exposed to each concentration of the mixture for 3 and 6 weeks. Selected biological end-points including urine mutagenesis, bone marrow cell aberrations and micronuclei, spleen lymphocyte aberrations and liver enzyme induction were monitored. The spleen lymphocyte aberrations and liver enzyme induction were the most sensitive end-points. The lymphocytes showed a significant induction of chromosome aberrations from exposure for 3 weeks to all 3 concentrations of the mixtures. After 6 weeks of exposure, significant induction of aberrations was observed after exposure to low and medium concentrations but not to the high concentration. This lack of response at the high concentration after 6 weeks exposure, appeared to correlate with a significant induction of glutathione S-transferase in the liver. Since this enzyme is known to detoxify 3 of the 4 chemicals in our mixture, it may indicate a detoxification mechanism after enzyme induction. The present study indicates that the CTP is sufficiently sensitive to identify toxicological effects after exposure to ambient levels of a gas mixture.

Administration, Inhalation↗
PubMed1988

Elevated frequencies of 6-thioguanine-resistant lymphocytes in multiple sclerosis patients treated with cyclophosphamide: a prospective study.

An autoradiographic assay for 6-thioguanine-resistant (TGr) lymphocytes was used to determine the frequency of in vivo derived variant T lymphocytes in peripheral blood from multiple sclerosis (MS) patients treated with monthly intravenous infusions of 750 mg/m2 of cyclophosphamide (CP). To analyze the time-course of response to CP, the MS patients were studied prospectively. Samples were obtained from the patients before the beginning of CP therapy, 4-5 times during the course of treatment, and, finally, 2 or 3 months after the completion of therapy. 2 weeks after the first CP infusion, the variant frequencies (Vfs) of the MS patients were significantly increased (p less than 0.05) above their pre-treatment values, but by 4 weeks following the first CP infusion the Vfs had fallen to normal or near-normal levels. After subsequent treatments, the frequencies of variant TGr cells were again higher than pre-treatment Vfs. However, within 7-13 weeks after the cessation of CP therapy, the Vfs of all subjects had returned to normal levels. The transient nature of the response indicates rapid in vivo selection against CP-induced TGr mutant cells. The mean pre-treatment Vf of the 4 MS patients who were cigarette smokers was 6.56 X 10(-6) which was significantly greater (p less than 0.05) than the mean Vf (1.52 X 10(-6) of the 4 MS patients who were non-smokers. The mean Vf from 8 assays of healthy non-smokers was 1.92 X 10(-6).

Autoradiography↗
PubMed1988

Development of a rodent lung macrophage chromosome aberration assay.

Lung macrophages are the first line of defense against inhaled xenobiotics. They are able to accumulate airborne particulates as well as having metabolic capability. They may thus be sensitive indicator cells for detecting inhalation exposure to environmental mutagens. Their usefulness as a short-term in vivo genotoxic assay has not, however, been adequately explored. We have systematically investigated the feasibility of developing a lung macrophage chromosome-aberration assay. It was found that with different types of spindle-binding chemicals (vinblastine and vincristine), and with improved harvesting procedures, an adequate number of metaphase cells can be collected from mice and Chinese hamsters. The chromosome aberration frequencies in macrophages from control mice and Chinese hamsters were found to be 1.2 +/- 2.3 and 0.75 +/- 2.2 per 100 cells respectively. These frequencies are within normal ranges for other somatic cells. After inhalation exposure to an occupational-exposure level of benzene (0, 0.1 and 1 ppm), significant dose-dependent induction of aberrations (1.2 +/- 2.3, 5.7 +/- 6.3 and 6.8 +/- 6.2 chromatid deletions per 100 cells resp.) were observed in the macrophages. Thus, these cells can be used as one of a battery of in vivo assays for inhalation exposure studies.

Animals↗
PubMed1988

Sperm evaluation in human genetic monitoring.

Health hazards, including reproductive hazards, resulting from exposure to mutagenic chemical or physical agents are a major concern. Human genetic monitoring is a relatively new approach to the evaluation of human population exposure to mutagens that is based on the use of short-term tests with human cells (including sperm), tissues, and body fluids for genetic damage. Evaluation of sperm for count, percentage of morphologically abnormal forms, and frequency of heads containing zero, one, or two fluorescent bodies have been incorporated in genetic monitoring studies. In this paper, the application of human genetic monitoring to the evaluation of germ cell mutagen exposure is discussed. The purposes and limitations of human genetic monitoring studies are presented. Some of the practical issues involved in the use of sperm studies in genetic monitoring are described through the examples of two studies in different settings that were conducted by the author's laboratory. The first was a study of Autopsy Service workers within the resident institution of the laboratory. The second was a study of workers exposed to coal tar pitch volatiles at an industrial plant approximately 1,000 miles from the laboratory.

Genetic Testing↗
PubMed1988

Fluorescent body distribution in spermatozoa in the male with exclusively female offspring.

Fluorescent (F) body distribution was determined in a group of men who did not have a fertility problem, but rather had fathered exclusively female offspring. The study was designed to analyze spermatozoa for the frequency of zero F-body (X-bearing) and one F-body (Y-bearing) spermatozoa. Semen samples were separated (processed) for Y-bearing spermatozoa enrichment and reanalyzed for fluorescent body distribution. The study consisted of 50 control (10 males) samples (unprocessed), 35 preseparation (35 patients) samples (unprocessed), and 18 postseparation (18 patients) samples (processed). A significantly higher frequency (P less than 0.05) of zero F-body spermatozoa were observed in the preseparation samples when compared with the control samples. The presence of more spermatozoa without fluorescent body correlates with the occurrence of more female births.

Fathers↗
PubMed1988

Calcium regulation of pigment transport in vitro.

Calcium has been implicated in the regulation of many cellular motility events. In this study we have examined the role of different Ca2+ concentrations on the in vitro transport of pigment within cultured chromatophores. Cells treated with Brij detergent for 1-2 min were stripped of their plasma membranes, leaving their cytoskeleton and associated pigment granules exposed to the external milieu. We found that retrograde pigment transport (aggregation) is induced upon addition of 1 mM MgATP2- with 10(-7) M free Ca2+, while an orthograde transport (redispersal) of pigment results from lowering the concentration of free Ca2+ to 10(-8) M while maintaining 1 mM MgATP2-. These Ca2+-regulated movements are ATP dependent but are apparently independent of cAMP and insensitive to calmodulin inhibitors. The observations reported here provide novel evidence that the concentration of free Ca2+ acts to regulate the direction of intracellular organelle transport.

Adenosine Triphosphate↗
PubMed1987

Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs.

The effects of laudanosine, a metabolite of atracurium, on the behaviour of conscious mice, rats and dogs, and on cardiovascular function in conscious and anaesthetized dogs have been evaluated: EEG studies were performed in anaesthetized dogs. In mice and rats, i.v. bolus doses of laudanosine 10-20 mg kg-1, caused convulsions and hind limb extensions; these effects were prevented by pretreatment with diazepam. After the continuous infusion of laudanosine to conscious dogs, plasma concentrations in the order of 1.2 micrograms ml-1 did not cause behavioural disturbances. In anaesthetized dogs, laudanosine plasma concentrations of more than 6 micrograms ml-1 caused hypotension and bradycardia, laudanosine concentrations greater than 10 micrograms ml-1 induced epileptic EEG spiking and plasma concentrations greater than 17 micrograms ml-1 produced prolonged seizures. There is a wide difference between laudanosine plasma concentrations in patients given atracurium by bolus injection or by short-term infusion for surgical use and those required to induce epileptic activity in dogs. However, during the prolonged infusion of atracurium to patients this difference will be decreased. It is unlikely that the use of atracurium, in patients, would result in plasma concentrations of laudanosine capable of producing neurological or cardiovascular disturbances.

Action Potentials↗
PubMed1987

The correlation between DNA adducts and chromosomal aberrations in the target organ of benzidine exposed, partially-hepatectomized mice.

An experimental system was developed to test the association between benzidine--DNA adduct levels and chromosome aberrations in the target organ, the liver, of mice. A 2/3 partial hepatectomy was performed (0 h), then the animals were treated with benzidine (0, 7.8, 19.5, 38.2 or 97.8 mg/kg, i.p.) and an agar-coated 50 mg 5-bromodeoxyuridine tablet was implanted subcutaneously (58 h). Colcemid was given at 4 mg/kg i.p. (70 h), and the animals were sacrificed 2 h later. The liver from each animal was divided, with portions allocated for cytogenetics and DNA adduct analysis. DNA adducts were analyzed with the 32P-postlabeling technique. DNA adduct and chromosomal aberration data were available on a total of 43 animals. Benzidine was shown to be a potent clastogen in liver, the target organ, as opposed to its reported weak activity in the bone marrow. A linear dose response was demonstrated for benzidine--DNA adducts found in the liver. The correlation between adduct levels and aberrations in individual animals was 0.43 (P less than 0.05). However, most of the residual variance was due to four outlying cases. When these cases were removed from the data set and the analysis repeated, the linear correlation coefficient increased to 0.74. When the data were analyzed by dose groups, the correlation was 0.91. These data support the hypothesis that carcinogen-DNA adducts are responsible for the induction of chromosomal aberrations, and perhaps other genotoxic events, including neoplasia.

Animals↗
PubMed1985

Absence of mutagenicity in the urine of autopsy service workers exposed to formaldehyde: factors influencing mutagenicity testing of urine.

Hospital autopsy service workers and a matched control group were studied using a battery of genetic monitoring tests performed on samples of blood, semen and urine. The results of the analysis of urine for mutagens are described in this report. The participants in the study were matched with the controls for sex, age and their use of alcohol, tobacco and marijuana. Information was collected on general health, usage of medications and any exposure which might affect the outcome of the study. Individuals were sampled three times at approximately two month intervals. Time weighed average exposures to formaldehyde in the work areas were estimated at 0.61 to 1.32 ppm. Additionally, studies were carried out which examined various parameters affecting the testing of human urine samples for mutagenicity. No increase in mutagenicity was seen in the autopsy workers as compared to the control group. One individual who was receiving metronidazole and one control who smoked two packs of cigarettes per day had significantly mutagenic urine. A large proportion of the exposed individuals had toxic urine while only two of the control individuals had similar toxic urine. The material responsible for the toxicity has been isolated and purified but does not appear to be related to the formaldehyde exposure. Studies on the parameters affecting mutagenicity testing of urine with Salmonella typhimurium suggest that in the plate incorporation assay, TA100, but not TA98, can be affected by exogenous histidine. Furthermore, with the conditions employed in this study, 3 to 4% of labeled histidine added to urine samples was retained by the XAD-2 and subsequently eluted in the urine concentrate. Urinary histidine levels of unconcentrated samples ranged from 112 to 2614 nmol per ml (mean 994 nmol per ml) and the amount of histidine present correlated with the corresponding increases in histidine revertants with strain TA100.

Adult↗
PubMed1985

Genetic monitoring of aluminum workers exposed to coal tar pitch volatiles.

A group of 50 workers exposed to coal tar pitch volatiles (CTPV) in an aluminum reduction plant and a group of 50 non-exposed workers were selected to evaluate the genotoxic effects of CTPV exposure. A battery of tests was performed on 3 different body fluids; urine, blood and semen. Urine samples were evaluated for mutagenic constituents using the Ames/Salmonella assay. Cultured lymphocytes from blood samples were used to perform cytogenetic analysis. Semen samples were used to measure sperm count, percent abnormal sperm morphology and frequency of sperm carrying double fluorescent bodies (2-F). 14 of 28 (50%) exposed workers and 7 of 36 (19.4%) non-exposed workers had mutagenic urine. This difference was significant (p less than 0.01). Among the non-smokers a significantly higher percentage of workers who were exposed had positive urine (36%) compared to the non-exposed workers (5%) (p less than 0.05). Among the exposed group, more mechanics had mutagenic urine than did other types of workers. Overall chromosome aberration rates were similar in both exposed and non-exposed workers. Among exposed workers a significant inverse correlation (p less than 0.05) between age and chromatid aberration rate was observed. Results of semen analysis failed to detect differences between exposed and non-exposed workers. Results of these tests lend support to a battery approach to genetic monitoring and suggest a link between exposure to CTPV and genotoxic effects. Detection of exposure to mutagens at an early time offers an opportunity for disease prevention by the reduction of exposure.

Adult↗