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W Stewart

Publications and source records attributed to W Stewart.

At least 19 recordsLinked to original sources
PubMed1995

Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers.

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.

Adult↗
PubMed1995

Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II.

Insulin-like growth factors (IGFs) are polypeptides that play an important role in cellular proliferation and differentiation. The present study examines the role of IGFs in the growth of mesothelial cells. Cell lines derived from normal rat mesothelium as well as lines derived from spontaneous rat mesotheliomas were found to express RNA transcripts for IGF-II. In contrast, cell lines derived from asbestos-induced rat mesotheliomas did not express this growth factor. All cell lines expressed receptors for IGF-I and IGF-II, as well as insulin receptors. Coexpression of IGF-II and its cognate receptor suggested that IGF-II was acting as an autocrine growth factor in the spontaneously immortalized cells and the cells derived from the spontaneous tumors. The biological activity of IGF-II secreted by the cell lines into conditioned medium could be neutralized using an IGF-II-specific antibody. Growth was inhibited in a dose-dependent manner; at the highest antibody concentration used (100 micrograms anti-IGF-II/ml), cell growth was decreased to 47% of control values. This inhibition was partially reversible by treatment of the cultures with IGF-II (91% of the control). These data suggest that IGF-II expression may be involved in the spontaneous alteration of rat mesothelial cells and may function as an autocrine or paracrine growth factor to modulate the growth of these cells in vitro and in vivo. Ubiquitous expression of IGF-II by cells that have not been exposed to asbestos and the lack of IGF-II expression by asbestos-transformed cells suggest that the mechanisms of changes in growth factor expression differ in mesothelial cells transformed by different pathways.

Animals↗
PubMed1995

Autocrine growth stimulation by transforming growth factor alpha in asbestos-transformed rat mesothelial cells.

Although the association between asbestos exposure and mesothelioma development has been established for decades, very little is known regarding the molecular mechanism(s) by which asbestos fibers induce this disease. In this series of experiments, the potential for transforming growth factor alpha (TGF-alpha) to act as an autocrine growth factor in transformed mesothelial cells was examined in rats, a model system frequently used to assess the tumorigenic potential of fibrous particulates. Both asbestos-transformed cells and spontaneously transformed cells expressed functional EGF receptors, although only the asbestos-transformed cells expressed TGF-alpha. Expression of TGF-alpha transcripts was correlated with secretion of picogram amounts of growth factor into conditioned medium by the asbestos-transformed cells. In addition, whereas TGF-alpha inhibited the growth of spontaneously transformed mesothelial cells, it stimulated the growth of asbestos-transformed cells. Neutralizing antibody that recognized TGF-alpha secreted by the asbestos-transformed cells was able to inhibit the growth of these cells. Taken together, these data indicate that TGF-alpha acts as an autocrine growth factor for asbestos-transformed rat mesothelial cells. Therefore, in asbestos-transformed mesothelial cells, altered production and responsiveness to TGF-alpha distinguish these cells from spontaneously transformed mesothelial cells. These data suggest that differences in mesothelioma etiology may be reflected in differences in the molecular alterations present in these tumors.

Animals↗
PubMed1995

Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents.

The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of < or = 10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of > or = 18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study.

Adult↗
PubMed1995

A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers.

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographic (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses > or = 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolastron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.

Adolescent↗
PubMed1995

Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites.

OBJECTIVES--To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. METHODS--34 male lead workers in the Republic of Korea were given a single oral dose of 10 mg/kg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours. RESULTS--Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0.76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSA-chelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper dose-response relation between these two measures. CONCLUSIONS--The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead.

Adult↗
PubMed1995

Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: an epidemiological review.

OBJECTIVES: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults. METHODS: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption. RESULTS: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure. CONCLUSION: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure.

Age Factors↗
PubMed1994

Rater agreement for the Rey-Osterrieth Complex Figure Test.

This report assesses the intrarater and interrater reliability of quantitatively scoring the Rey-Osterrieth Complex Figure Test (RCF). The intrarater correlation coefficients were .96, .99, and .96, and the interrater correlation coefficients were .88, .97, and .96 for the Copy, Immediate Recall, and Delayed Recall, respectively. However, statistically significant mean differences in score were found between raters on the Copy, Immediate, and Delayed Recall. Though the majority of structural units within the RCF are reliably scored, several units had a greater magnitude of observed scoring differences compared to the other units after adjusting for expected differences. Overall, reliability estimates demonstrate high intrarater reliability and acceptable interrater reliability except for the potential for systematic scoring differences.

Adolescent↗
PubMed1994

Molecular cytogenetic analysis of a duplication Xp in a male: further delineation of a possible sex influencing region on the X chromosome.

We describe a male infant with severe mental retardation and autism with a duplication of the short arm of the X chromosome. Chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified one copy of the zinc finger protein on the X chromosome (ZFX) and two copies of the steroid sulfatase gene (STS), further delineating the breakpoints. Based on cytogenetic and molecular comparisons of cases from the literature of sex-reversal in dup(X),Y patients and our patient, we suggest that a possible secondary sex-influencing gene involved in the regulation of sex determination or testis morphogenesis is present at the distal Xp21.1 to p21.2 region.

Autistic Disorder↗
PubMed1994

Comparison of measures of lead exposure, dose, and chelatable lead burden after provocative chelation in organolead workers.

OBJECTIVES: To describe 6 h urinary lead excretion (6 h PbU) after 1 g intravenous ethylene diamine tetraacetic acid (EDTA) in organolead manufacturing workers with mixed exposure to organic and inorganic lead; to determine the predictors of lead excretion (PbU); and to determine the extent to which internal lead stores and ongoing external exposure govern blood concentrations of lead (PbB). METHODS: A case series of 21 active workers were studied. Personal industrial hygiene data, grouped by 29 exposure zones, in combination with personal interviews about work location and times were used to derive several measures of recent and cumulative exposure to organic and inorganic lead. The average exposure intensities assigned to the 29 zones ranged from 4 to 119 micrograms/m3 (0.02-0.57 mumol/m3 as lead) for organic lead and from 1 to 56 micrograms/m3 (0.004-0.27 mumol/m3) for inorganic lead. RESULTS: After controlling for age, 6 h PbU was significantly and positively correlated with summary measures of PbB--for example, lifetime peak PbB, time weighted PbB--and zinc protoporphyrin concentrations--for example, lifetime peak zinc protoporphyrin, time weighted zinc protoporphyrin--but not with measures of estimated external exposure--for example, duration of exposure and cumulative exposure to inorganic or organic lead. Among workers with higher chelatable lead burdens (6 h PbU > or = 212.4 micrograms (1.03 mumol) divided at the median), there was no apparent relation between recent inorganic lead exposure and PbB at the time of chelation. Among workers with lower chelatable lead burdens (6 h PbU < 212.4 micrograms (1.03 mumol) however, there was a significant relation between exposure and effect between recent exposure to inorganic lead and PbBs. CONCLUSION: These findings are consistent with the concept of physiological dampening. The high chelatable lead burden, a source of internal exposure, dampens the effect of external exposure on PbBs. The data suggest that in organolead workers with high chelatable lead burdens, PbBs may be more influenced by internal lead stores than by variations in airborne exposure to organic and inorganic lead.

Adult↗
PubMed1994

Comorbidity of migraine and panic disorder.

Clinical and epidemiologic evidence suggests that migraine co-occurs with psychopathology, including specific anxiety disorders. To examine this association, survey data from a population-based study of more than 10,000 respondents were used to determine if individuals with a history of panic attacks were at greater risk of having specific headaches in the week preceding an interview. Four types of headache were defined. Of these, only migraine was strongly associated with panic attacks. Given the high prevalence of both migraine and panic attacks and evidence that they often co-occur, treatment implications are discussed for this comorbidity.

Adolescent↗
PubMed1992

Is there etiologic heterogeneity between upper and lower neural tube defects?

Neural tube defects are thought to arise from two different embryologic mechanisms depending on the level of the defect: neurulation defects associated with anencephaly and upper spina bifida and canalization defects associated with lower spina bifida. To investigate whether the risk profiles of neural tube defect cases differ according to the level of the defect, the authors examined data from the Atlanta Birth Defects Case-Control Study. Cases were infants live- or stillborn from 1968 to 1980 with these defects, and controls were infants without defects randomly selected and frequency matched to cases by race, birth year, and hospital of birth. By multivariate polychotomous logistic regression, 1,186 controls were compared with cases: 145 with anencephaly, 59 with upper spina bifida (cervical/thoracic lesions), and 100 with lower spina bifida (lumbar/sacral lesions). Infant's sex and sibling recurrence of neural tube defects were the only factors for which the case subgroups significantly differed in risk. The risks associated with selected maternal exposures during the first trimester of pregnancy did not differ among the case subgroups. Although these results do not support the concept that upper and lower neural tube defects differ in risks from exogenous factors, differences in sibling recurrence and in risks by sex between the two groups suggest an underlying heterogeneity in genetic susceptibility factors.

Anencephaly↗
PubMed1992

Genetic-epidemiologic study of omphalocele and gastroschisis: evidence for heterogeneity.

On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, omphalocele (OM) and gastroschisis (GA) are considered casually and pathogenetically distinct abdominal wall defects. More than 50% of infants with OM have additional defects, but only about 15% of those with GA do. To evaluate whether there is heterogeneity between isolated and multiply affected cases of OM and GA, we analyzed epidemiologic characteristics and familial risks of major defects for 82 OM and 81 GA cases drawn from a population-based study in the Maryland-Washington, DC-Northern Virginia area and born from 1980 through June 1987. We examined year of birth, sex, race, and maternal age distributions after stratifying the infants into isolated and multiple defect groups. We found significant differences in maternal age between cases with isolated OM and GA, but not between cases with GA or OM who had other defects. Using regressive logistic models, we analyzed familial aggregation of birth defects among relatives of infants with OM and GA. An autosomal recessive model of inheritance was found to be the most parsimonious explanation for the families of infants with isolated OM or GA. However, for families of infants with multiple defects, a sporadic or nongenetic model fit best. These findings are not only useful for estimating familial risk of major birth defects, but they also suggest further heterogeneity of infants with OM and GA according to the presence of other malformations.

Abdominal Muscles↗
PubMed1992

Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma.

Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos-induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (Kd = 0.5 nM) and receptor number was 1.6 x 10(5)/cell. Western analysis using antibodies specific for either the alpha-type or beta-type PDGF receptor and Northern analysis using probes specific for alpha- and beta-type receptor RNA transcripts indicated that these cells expressed beta-type PDGF receptors but that alpha-type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain-containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific.

Animals↗
PubMed1992

Biotic and abiotic parameters associated with an epizootic of Coelomomyces punctatus in a larval population of the mosquito Anopheles quadrimaculatus.

Biotic and abiotic parameters associated with an epizootic of the fungus Coelomomyces punctatus in larval populations of the mosquito Anopheles quadrimaculatus were investigated for three mosquito breeding seasons (1986-1988) in two adjacent farm ponds in North Carolina. In the first pond, the prevalence of infected larvae averaged 42% (range 0-85%) for collections made weekly from May 1 to November 20, 1986, but larvae did not occur in this pond in 1987. Infection rates in the adjacent pond, sampled during the mosquito breeding seasons of 1987 and 1988, declined from 10.9% (range 0-27.5%) in 1987 to 2.5% (range 0-14.2%) in 1988. Correlation analyses between the number of female copepods and fungal infection rates in sentinel mosquitoes were significant (P < 0.01) for Acanthocyclops robustus but insignificant for eight other species. Infections obtained in sentinel larvae placed in the ponds for 3 hr intervals indicated that C. punctatus infected larvae around sundown. Infection rates for field-collected larvae increased with the stage of larval development. However, experiments with sentinel larvae showed that early instars were more susceptible to infection than later instars, suggesting that the higher infection rates in late instars resulted from individual larvae being infected by two or more zygotes during larval development. Standard multiple regression analyses, used to determine the relationship between seasonal infection rates and water chemistry, weather variables, and the abundance of early and late instar larvae, showed that the abundance of late instars was the only independent variable common to linear models. The models only accounted for 20 and 9% of the variation in larval infection rates for 1987 and 1988, respectively. These results indicate that of the parameters examined, the seasonal abundance of the copepod, A. robustus, was the most important factor (or variable) correlated with the prevalence of mosquito infection.

Animals↗
PubMed1992

Evidence for the copepods Acanthocyclops robustus and Mesocyclops edax as competent intermediate hosts for Coelomomyces punctatus during an epizootic in a larval population of the mosquito Anopheles quadrimaculatus.

Field and laboratory experiments were conducted during an epizootic of Coelomomyces punctatus (Chytridiomycetes: Blastocladiales) in a population of the mosquito Anopheles quadrimaculatus in a North Carolina farm pond to examine the interactions of several potential copepod hosts with the mosquito and fungus. The diel vertical migratory behavior of the copepod species Acanthocyclops robustus, Eucyclops serrulatus, Macrocyclops albidus, and Mesocyclops edax were monitored in relation to infection rates in sentinel mosquito larvae. Mosquito infection occurred primarily around dusk, the same period during which A. robustus and E. serrulatus were most abundant near the surface of the pond. However, exposure of A. robustus, E. serrulatus, M. albidus, M. edax, Microcyclops varicans, and Paracyclops poppei to fungal meiospores in the laboratory showed that only A. robustus and M. edax were competent intermediate hosts for C. punctatus. Laboratory studies of the diel periodicity of gametangial dehiscence in A. robustus and M. edax infected with C. punctatus revealed that gamete release and zygote formation also occurred around dusk. The combined results of the laboratory and field studies on copepod abundance, susceptibility to infection, and periodicity of gametangial dehiscence suggest that A. robustus was the principal intermediate host for C. punctatus during the epizootic, though it is probable that M. edax also contributed importantly to the overall rate of larval infection.

Animals↗
PubMed1992

Measurement of pharyngeal transit time by electrical impedance tomography.

The feasibility of using electrical impedance tomography (EIT) for measuring pharyngeal transit time has been investigated. Imaging sequences were obtained on the neck in a group of eight healthy subjects when swallowing solutions of different electrical conductivities. The solutions used were aqueous Dioralyte (1.5 S m-1) and tap water (0.04 S m-1). The effects of movement upon the images were large compared with the changes due to the solutions, but these were cancelled by a subtraction technique. The mean value of the EIT pharyngeal transit time parameter was 370 +/- 120 ms. EIT has the advantage that repeated measurements could be performed without fear of hazard in contrast to the established technique of video fluoroscopy which involves ionising

Adult↗