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J P Weber

Publications and source records attributed to J P Weber.

At least 19 recordsLinked to original sources
PubMed2004

Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds.

During the past 20 years a number of studies have found neurological and immunological effects in the developing fetus and infants exposed to background or only slightly elevated levels of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). To address concerns arising from possible increased human exposure in the Arctic and possible effects of POPs, all circumpolar countries agreed in 1994 to monitoring of specific human tissues for contaminants in the Arctic under the Arctic Monitoring and Assessment Program (AMAP). Mothers in eight circumpolar countries contributed blood samples that were analysed at a single laboratory for 14 PCB congeners (IUPAC No. 28, 52, 99, 105, 118, 128, 138, 153, 156, 170, 180, 183, 187) and 13 organochlorine pesticides (aldrin, beta-hexachlorocyclohexane (beta-HCH), dichlordiphenyltrichloroethane (p,p'-DDT), diphenyldichloroethylene (p,p'-DDE), dieldrin, heptachlorepoxide, hexachlorobenzene (HCB), mirex, and the chlordane derivatives alpha-chlordane, gamma-chlordane, cis-nonachlor, oxychlordane and trans-nonachlor). Inuit mothers from Greenland and Canada have significantly higher levels of oxychlordane, transnonachlor and mirex than mothers from Norway, Sweden, Iceland and Russia. Inuit mothers from Greenland also have significantly higher levels of these contaminants than Inuit mothers from Canada and Alaska. These differences among Inuit groups may represent regional dietary preferences or different contaminant deposition patterns across the Arctic. Levels of PCBs are also elevated among some arctic populations due to their consumption of marine mammals and are in the range where subtle effects on learning and the immune system have been reported. The Russian mothers who consume mainly food imported from southern Russia have elevated levels of DDT, DDE, beta-HCH and a higher proportion of lower chlorinated PCB congeners. This study has allowed an assessment of the variation of contaminants such as PCBs and various organochlorine pesticides (DDT, chlordane, etc.) in human populations around the circumpolar north.

Adult↗
PubMed2001

Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant.

OBJECTIVE: This study was undertaken to evaluate the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in nonsmoking adult subjects living in the vicinity of a creosote impregnation plant in Delson, Canada. Urinary metabolites of naphthalene, alpha- and beta-naphthol, and pyrene metabolite 1-hydroxypyrene (1-OHP), were used as biomarkers of exposure. METHODS: Morning and evening urine samples were collected in mid-August from 30 exposed individuals living at a distance of 50-360 m downwind of the plant and from a control group in the adjoining municipality residing at a distance of 1.9-2.7 km upwind of the plant. Metabolites were measured by gas chromatography/ mass spectrometry. RESULTS: Excretion values of alpha- and beta-naphthol were significantly higher in the exposed group than in controls (P < 0.04), after accounting for possible confounding variables by multivariate analyses. The respective geometric mean concentrations (5th and 95th percentiles) of alpha-naphthol for the exposed and nonexposed groups were 2.04 (0.55-6.00) and 1.37 (0.39-7.02) micromol/mol creatinine for evening samples, and 2.49 (0.77-8.43) and 1.17 (0.37-6.88) micromol/mol creatinine for morning samples. Corresponding values for beta-naphthol were 1.78 (0.82-3.67) and 1.36 (0.63-5.07) micromol/mol creatinine for evening samples, and 1.94 (1.03-4.96) and 1.08 (0.49-5.05) micromol/mol creatinine for morning samples. On the other hand, no significant difference in 1-OHP excretion was observed between the exposed and the control group (P>0.5). The respective geometric mean concentrations (5th and 95th percentiles) of 1-OHP for these groups were 0.05 (0.01-0.17) and 0.06 (0.01-0.48) micromol/mol creatinine for evening samples, and 0.05 (0.02-0.12) and 0.05 (0.01-0.42) micromol/mol creatinine for morning samples. CONCLUSIONS: The measurement of alpha- and beta-naphthol urinary concentrations appears to be an approach sufficiently sensitive to reveal differences in low exposure levels of volatile PAHs due to creosote impregnation plant emissions. However, uptake of pyrene due to the plant was too small to contribute significantly to 1-OHP excretion.

Adolescent↗
PubMed2000

Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion.

Sickle cell anemia is characterized by painful vaso-occlusive crises. It is hypothesized that monocytes are activated in sickle cell disease and can enhance vaso-occlusion by activating endothelium. To test this hypothesis, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (MVEC) with sickle and normal mononuclear leukocytes were incubated, and endothelial activation was measured. Endothelial cells incubated with sickle mononuclear leukocytes were more activated than those incubated with normal mononuclear leukocytes, as judged by the increased endothelial expression of adhesion molecules and tissue factor and the adhesion of polymorphonuclear leukocytes (PMNL). Monocytes, not lymphocytes or platelets, were the mononuclear cells responsible for activating endothelial cells. Sickle monocytes triggered endothelial nuclear factor-kappa B (NF-kappaB) nuclear translocation. Cell-to-cell contact of monocytes and endothelium enhanced, but was not required for, activation. Antibodies to tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1beta) blocked activation of the endothelium by monocytes. Peripheral blood monocytes from patients with sickle cell disease had 34% more IL-1beta (P =.002) and 139% more TNF-alpha (P =.002) per cell than normal monocytes. Sixty percent of sickle monocytes expressed the adhesion molecule ligand CD11b on their surfaces compared with only 20% of normal monocytes (P =.002). Serum C-reactive protein, a marker of systemic inflammation, was increased 12-fold in sickle serum than in normal serum (P =.003). These results demonstrate that sickle monocytes are activated and can, in turn, activate endothelial cells. It is speculated that vascular inflammation, marked by activated monocytes and endothelium, plays a significant role in the pathophysiology of vaso-occlusion in sickle cell anemia.

Anemia, Sickle Cell↗
PubMed2000

Breast cancer, lactation history, and serum organochlorines.

The authors analyzed the relation between lactation history, organochlorine serum levels-in particular, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)-and the risk of breast cancer within a subsampe from a larger breast cancer case-control study conducted among women living in Mexico City, Mexico, between 1990 and 1995. From the original study, they selected a random sample of 260 subjects (1:1 case/control ratio). Analysis was restricted to 120 cases and 126 controls who had given birth to at least one child and had complete information on all key variables. Serum DDE levels were higher among cases (mean = 3.84 microg/g lipids, standard deviation = 5.98) than among controls (mean = 2.51 microg/g lipids, standard deviation = 1.97). After adjustment for age, age at menarche, duration of lactation, Quetelet index, and serum DDT levels, serum DDE levels were positively related to the risk of breast cancer (adjusted odds ratio (OR)Q1-Q2 = 1.24, 95% confidence interval (CI): 0.50, 3.06; ORQ1-Q3 = 2.31, 95% CI: 0.92, 5.86; ORQ1-Q4 = 3.81, 95% CI: 1.14, 12.80; test of trend, p = 0.02). The increased risk associated with higher serum DDE levels was more apparent among postmenopausal women (ORQ1-Q4 = 5.26, 95% CI: 0.80, 34.30; test of trend p = 0.03). A longer period of lactation was associated with a slightly decreased risk of breast cancer independently of serum DDE levels (OR = 0.91, 95% CI: 0.85, 0.99 change in risk per 10 months of lactation). Serum DDT level was not related to the risk of breast cancer. The data suggest that high levels of exposure to DDE may increase women's risk of breast cancer, particularly among postmenopausal women.

Adult↗
PubMed2000

Gender-related personal attributes and psychological adjustment among U.S. Army soldiers.

Personality characteristics associated with successful adaptation to military life are often described in gender-related terms. However, valid, reliable measures of gender-related personality characteristics have not been established for military populations. The purpose of this study was to validate an instrument for measuring gender-related personality characteristics in an active duty population. The Extended Personal Attributes Questionnaire was administered to 1,060 male soldiers and 305 female soldiers in U.S. Army support units. Results of a factor analysis indicated that there are three separate factors. The first denotes negatively valued aggressive traits (Negative Masculinity), the second denotes negatively valued passive traits (Negative Femininity), and the third combines positive instrumental and positive expressive traits, referred to as the Combined factor. Although positive instrumental traits (referred to as Masculinity) were related to fewer psychological symptoms, Negative Masculinity and Negative Femininity were associated with increased psychological symptoms. Positive expressive traits (referred to as Femininity) were unrelated to psychological symptoms.

Adaptation, Psychological↗
PubMed2000

Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines. Women scheduled for excision biopsy of the breast were enrolled and completed a questionnaire. The biopsy tissue of 217 cases and 213 benign controls frequency matched by study site and age in 5-year groups was analyzed for 14 polychlorinated biphenyl (PCB) congeners, total PCBs, and 10 other organochlorines, including p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene. Multiple logistic regression was used to assess the magnitude of risk. While adjusting for age, menopausal status, and other factors, odds ratios (ORs) were above 1.0 for almost all organochlorines except five pesticide residues. The ORs were above two in the highest concentration categories of PCB congeners 105 and 118, and the ORs for these PCBs increased linearly across categories (Ps for trend < or =0.01). Differences by menopausal status are noted especially for PCBs 105 and 118, with risks higher among premenopausal women, and for PCBs 170 and 180, with risks higher among postmenopausal women. Clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue.

Adipose Tissue↗
PubMed2000

[Biological monitoring of exposure to polycyclic aromatic hydrocarbons among people living nearby an aluminum smelter in the province of Québec].

BACKGROUND: The objective of the study is to estimate the exposure to pyrene, an indicator of polycyclic aromatic hydrocarbons (PAHs) in the general environment, by using the internal dose of 1-hydroxypyrene (1-OHP) among people living nearby an aluminium smelter in the Montérégie area, Province of Québec, Canada. METHODS: This cross-sectional study was done in November and December 1998. Participants were randomly selected according to their environmental exposure to PAHs and were distributed according to three exposure levels (high, low, none). Altogether, 121 non smokers aged between 18 to 70 years were recruited for the study. Persons occupationally exposed to PAHs or using tar-based medications were excluded. Those with personal medical conditions that affect the metabolism of pyrene were also excluded. Urine samples were taken in the morning and analysed by gas chromatography and mass spectrometry (GC-MS) to determine the concentration of the metabolite, 1-OHP. RESULTS: Among the exposed group (n=78), the geometric mean of urinary concentration of 1-OHP was 0.073 micromol/mol creatinine compared to 0.060 micromol/mol creatinine for the control group (n=40). The difference did not reach statistical significance (p=0.09). Geometric means among the three groups of exposure (high, low, none) were respectively 0.079, 0.067 and 0.060 micromol/mol creatinine (p=0.13). Accounting for personal risk factors, such as diet, passive smoke, use of wood heating and time spent at home during the three days prior to urine sampling, did not change previous results. CONCLUSION: This study indicates that the environmental levels of PAH produced by this factory are low and do not contribute significantly to the body burden of PAH as measured by 1-OHP.

Adolescent↗
PubMed1999

Fish consumption and contaminant exposure among Montreal-area sportfishers: pilot study.

A 1995 pilot study assessed sport fish consumption and contaminant exposure among Montreal-area residents fishing the frozen St. Lawrence River. Interviews conducted among 223 ice fishers met on-site were used to create an index of estimated exposure to fish-borne contaminants. A second-stage assessment of sport fish consumption and tissue contaminant burdens included 25 interviewees at the highest level of estimated contaminant exposure (of 38, or 66% of those solicited) and 15 low-exposure fishers (of 41, or 37% of those solicited). High-level fisher-consumers reported eating 0. 92+/-0.99 sport fish meals/week during the previous 3 weeks compared to 0.38+/-0.21 (P<0.05) for the low-level group. Based on the product of consumption frequency times mass of sport fish meals consumed, high-level consumers ate a mean of 18.3 kg of sport fish annually versus 3.3 kg for the low-level consumers. Tissue contaminant assessments showed significant (P<0.05) groupwise differences: 0-1 cm hair mercury (median 0.73 microgram/g for the high versus 0.23 microgram/g for the low group), lipid-adjusted plasma PCB congeners (Aroclor 1260: median 0.77 microgram/g versus 0.47 microgram/g), and lipid-adjusted plasma DDE (median 0.35 microgram/g versus 0.26 microgram/g). No participant had a hair mercury or plasma DDE concentration above Health Canada recommendations but 2/25 high-level participants (8%) had plasma Aroclor 1260 concentrations above recommended limits. The results of this pilot study suggest that a small number of Montreal-area sportfishers consume their catch as often as three times weekly and that those consuming sport fish frequently have significantly higher tissue levels of mercury, PCBs, and DDE than do infrequent consumers. On the other hand, compared to other groups in Quebec, such as the Inuit or commercial fishers on the North Shore of the Gulf of St. Lawrence, Montreal-area sportfishers eat less fish and have lower tissue concentrations of fish-related contaminants.

Adult↗
PubMed1999

Contaminant exposure in Montrealers of Asian origin fishing the St. Lawrence River: exploratory assessment.

Fishing and fish consumption are widely practiced among members of certain ethnocultural groups. Informal assessment led us to ascribe high levels of consumption of locally caught sportfish to Montrealers of Asian origin and to hypothesize that their choices of species and fish organs differ from those of the majority group. An exploratory assessment of contaminant bioindicators reflective of St. Lawrence River fish consumption was conducted in late 1995 among nine Vietnamese and nine Bangladeshi Montreal sportfishers identified by community contacts. Vietnamese participants, six men and three women, were 27-70 (median 36) years of age and had immigrated to Canada 3-20 (median 7) years earlier. In contrast, the nine Bangladeshi males aged 28-41 (median 34) years had been in Canada for 2-13 (median 4) years. Bio-indicator concentrations among Bangladeshi and Vietnamese participants are compared to those found for majority-community Montreal-area high-level consumers recruited on the St. Lawrence River during winter 1995. All results are presented as the median and 90th percentile. Hair mercury concentrations were higher for both Vietnamese (1.2, 4.6 microgram/g) and Bangladeshis (1.1, 2.3 microgram/g) than for majority-community sportfishers (0.7, 1.9 microgram/g). Certain organochlorine levels, specifically total PCB (estimated by plasma Aroclor 1260), p,p'-DDT, p,p'-DDE, and B-BHC, were highest in the Bangladeshis compared to Vietnamese and to majority-community sportfishers. In contrast, plasma levels of other pesticides were low in all three groups, including mirex, chlordane, and cis-nonachlor. A correlation between plasma p,p'-DDT levels and recency of arrival in Canada was found for the Bangladeshis. These data suggest a distinct pattern of tissue organochlorines, which we postulate relates to exposure prior to arrival in Canada and perhaps to the ongoing consumption of foods (other than St. Lawrence River sportfish) specific to these groups.

Adult↗
PubMed1999

Reliability and relative validity of fish consumption data obtained in an exposure assessment study among Montreal-area sportfishers.

A two-season exercise was undertaken in 29 high-level sportfish consumers to evaluate the reliability and accuracy of study instruments. Fishers were invited to participate after completing the main study interview (Time 1) in fall 1995 or winter 1996. Over a 4-week period, they provided a nonconsecutive 7-day weighed food record, kept a fish consumption calendar, and responded to a shortened version of the Time 1 instrument at the end of this period (Time 2). A second blood sample (at Time 2) was analyzed for whole blood mercury (Hg) and the omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) in plasma and erythrocytes. Identical questions were compared in the Time 1 and Time 2 instruments. Reported sportfish consumption assessed by the different instruments was subjected to nutrient analysis. Three estimates of exposure to the target substances were derived from the dietary intake estimates and correlated with their respective Time 2 plasma (EPA, DHA) or blood (Hg) values, and with a kinetically derived interval-specific plasma/blood uptake value. Remarkable similarities were observed for the data derived from like questions in the Time 1 and 2 questionnaires in both seasons. However, frank discrepancies between some portion size estimates and measured values may signal cause for concern. The strongest correlations between the Time 2 plasma DHA and EPA, and blood Hg, and the three exposure indices emerged between estimates of retrospective DHA intake and DHA fish calendar values and their corresponding Time 2 plasma levels, and for Hg estimated both retrospectively and from the fish consumption calendar and correlated with Time 2 blood Hg, especially in the winter 1996 dataset. Overall, the results suggest that the main study instrument provides a reliable and relatively accurate indication of sportfishers' fishing practices, species selection, and sportfish consumption habits.

Adult↗
PubMed1999

Blood PCB, p,p'-DDE, and mirex levels in Great Lakes fish and waterfowl consumers in two Ontario communities.

PCB, p,p'-DDE, and mirex levels were examined in blood plasma samples of 232 anglers from Cornwall and Mississauga, Ontario, in a pilot study to establish the feasibility and suitability of using a cohort of Ontario fish license holders for large-scale health studies. Great Lakes fish, waterfowl, and ocean fish consumption were examined as predictors of contaminant levels using regression analysis, with adjustment for age, gender, and community. Levels of Great Lakes fish and waterfowl consumption and contaminant levels were generally low in comparison with those observed in other Great Lakes studies. However, even within these low levels, Great Lakes fish consumption was associated with increased blood plasma PCB levels in men and mirex levels in both men and women. Waterfowl consumption was associated with higher plasma PCB (men and women), DDE (men only), and mirex levels (men and Cornwall women), and requires further exploration. We conclude that other study designs are required (to identify high consumers) for carrying out studies of health effects associated with high levels of Great Lakes fish and waterfowl consumption.

Adult↗
PubMed1999

Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland.

Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher than those measured using the same analytical method in samples from Canadians in Quebec City, Quebec. Brain lipids contained lower concentrations of all organochlorines than lipids extracted from other tissues. Organochlorine residue levels in lipid extracts from liver, omental fat, and subcutaneous abdominal fat samples were similar, with the exception of ss-hexachlorocyclohexane, which reached a greater concentration in liver lipids than in lipids from both adipose tissues (4-fold; p < 0. 05). Comparisons with available international data on adipose tissue levels reveal that the organochlorine body burden in the Inuit population of Greenland is presently among the highest resulting from environmental exposure.

Adipose Tissue↗
PubMed1998

New patterns of drinking-water consumption: results of a pilot study.

A pilot study on water consumption was carried out in the Québec City region in April and May 1996 with 125 people using a 24-h recall plus a 2-day diary. Consumption of drinking water via liquid and food was assessed as well as the type of water consumed (tap, bottle or filtered water) and place of consumption (home or away from home). Most of the people (56%) were drinking some bottled water or filtered tap water and 25% of water intake was away from home. Food consumption was found to be a non-significant source of drinking-water intake. The average water consumption was nearly similar in exclusively tap-water consumers and bottled- or filtered-water consumers (1.5 vs. 1.7 l/day, P = 0.29) but two-thirds of the consumption in this last group is natural water, while it is mixed water in the bottled/filtered-water group. No significant difference in amounts consumed were found according to age, but older people drank hot beverages and soup more often. The present pilot-study was weakened by a low participation rate (14%). Incentive might be necessary to improve participation rate and data collection methods must also be simplified. A 24-h recall plus a 1-day diary seem sufficient and data on consumption could be limited to liquids, soups and cereals.

Adult↗
PubMed1996

Effect of transient moderate hyperventilation on dynamic cerebral autoregulation after severe head injury.

OBJECTIVE: This study was undertaken to evaluate the effect of acute moderate hyperventilation on cerebral autoregulation in head-injured patients. METHODS: Dynamic cerebral autoregulation was analyzed by use of transcranial doppler ultrasonography before and after hyperventilation in 10 patients with severe head injury. All of the patients were artificially ventilated and underwent continuous monitoring of arterial blood pressure, intracranial pressure, and end-tidal carbon dioxide. To test autoregulation, rapid transient decreases in systemic blood pressure were achieved by quickly releasing large blood pressure cuffs that were inflated around both thighs. This resulted in a drop of 24 +/- 6 mm Hg in mean systemic blood pressure, which lasted an average of 49 +/- 24 seconds. Cerebral blood flow velocity was monitored continuously in both middle cerebral arteries by use of transcranial doppler ultrasonography. The percentage change in middle cerebral artery velocity was used as an index of the change in cerebral blood flow during the autoregulatory response. The change in estimated cerebrovascular resistance, immediately after the blood pressure drop, or the rate of regulation was used to analyze the effectiveness of the cerebral autoregulation. This value was calculated by determining the rate of increase in middle cerebral artery velocity during the 1st 5 seconds after a blood pressure drop, relative to the rate of increase of the cerebral perfusion pressure. RESULTS: The average rate of regulation during normocapnia at pCO2 of 37 mm Hg was 11.4 +/- 5% per second. After reduction of the pCO2 to 28 mm Hg, the average rate of regulation improved significantly (P < 0.001) to 17.7 +/- 6% per second. Autoregulation improved, despite no significant change in the cerebral perfusion pressure during hyperventilation. The degree of improvement in autoregulation was significantly correlated with the CO2 reactivity (r = 0.45, P < 0.05) but did not correlate (r = -0.23, P = 0.33) with the change in arterial pH value after hyperventilation. CONCLUSION: These results confirm the finding that dynamic autoregulation is disturbed in severe head injury and that moderate transient hyperventilation can temporarily improve the efficiency of the autoregulatory response, probably as a result of a transient increase in vascular tone.

Acid-Base Equilibrium↗
PubMed1996

Quality in environmental toxicology measurements.

From the clinical chemist's point of view, environmental toxicology can be defined as the identification or quantitation or both of environmental toxicants, their metabolites, and the biochemical consequences in easily accessible human specimens. Requirements as to specificity, accuracy, precision, and sensitivity will vary depending on the purpose of the analysis (e.g., diagnosis of acute intoxication vs. population baseline study). Laboratories must therefore clearly indicate the scope of their analytic methods. To ensure consistency of results, quality guidelines, such as International Standards Organization (ISO) guide 25, should be adhered to. However, to demonstrate accuracy, external proficiency assessment is required. Interlaboratory comparison programs, by using representative reference material, can document laboratory performance over time. Examples taken from the Quebec Toxicology Centre's program for toxic metals in biologic fluids indicate that laboratory performance has improved in recent years. The quality of results is generally adequate for most applications of environmental toxicology measurements.

Environmental Monitoring↗
PubMed1996

Polychlorinated biphenyl (PCB) and dichlorodiphenyl dichloroethylene (DDE) concentrations in the breast milk of women in Quebec.

OBJECTIVES: This study documented the concentration of polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethylene (DDE) in the breast milk of women from Quebec, Canada, and assessed the impact of various sociodemographic and lifestyle factors on these levels. METHODS: From 1988 to 1990, milk samples were obtained from 536 Quebec women and analyzed for seven PCB congeners and p,p'-DDE. Information was obtained on subjects' physical, sociodemographic, and lifestyle characteristics. RESULTS: Mean concentrations were 0.52 mg/kg lipids (95% confidence interval [CI] = 0.50, 0.54) and 0.34 mg/kg lipids (95% CI = 0.32, 0.35) for PCBs (Aroclor 1260) and DDE, respectively. Age and history of breast-feeding showed statistically significant correlations with PCB and DDE concentrations. CONCLUSIONS: Concentrations of PCBs and DDE measured in this study are at the lower end of the concentration range recently reported for women living in industrialized countries. The modulating factors identified here should be considered when conducting studies on organochlorine exposure and disease.

Adolescent↗
PubMed1994

A novel mechanism for coupling of m4 muscarinic acetylcholine receptors to calmodulin-sensitive adenylyl cyclases: crossover from G protein-coupled inhibition to stimulation.

Muscarinic m4 acetylcholine receptors are normally coupled through Gi to inhibition of adenylyl cyclases. In the olfactory bulb and some cultured cells, however, m4 receptors can couple to stimulation of adenylyl cyclase activity. In this study, m4 receptors and specific isozymes of adenylyl cyclases were coexpressed in HEK-293 cells to characterize the mechanism(s) for m4 receptor stimulation of adenylyl cyclases. The calmodulin-sensitive type I and type III adenylyl cyclases were chosen for this study because neither enzyme is stimulated by the beta/gamma complex of G coupling proteins. M4 receptors exhibited either inhibition or stimulation of type I and III adenylyl cyclases depending upon receptor density and agonist concentration. Inhibition of adenylyl cyclase was apparently due to M4 coupling through Gi. Adenylyl cyclase stimulation through m4 receptors was not due to increases in intracellular Ca2+ and stimulation of the calmodulin-sensitive enzymes since it was evident in isolated membranes in the absence of free Ca2+ and with whole cells preloaded with the Ca2+ chelator BAPTA/AM. Stimulation of adenylyl cyclase activities by m4 receptors was apparently mediated via Gs since it was GTP-dependent, was insensitive to pertussis toxin, and was not due to beta/gamma stimulation. Synthetic peptides derived from a G protein activating region of the m4 receptor mimicked the m4-mediated stimulation of adenylyl cyclase activity. These data demonstrate a novel mechanism for muscarinic regulation of adenylyl cyclases that may involve crossover from inhibitory to stimulatory G protein coupling.

Adenylyl Cyclases↗