Grace E Kissling

National Institute of Environmental Health Sciences, Durham, North Carolina, United States

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Publications (150)551.33 Total impact

  • David B Resnik · Ana M Tyler · Jennifer R Black · Grace Kissling
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    ABSTRACT: We analysed the authorship policies of a random sample of 600 journals from the Journal Citation Reports database. 62.5% of the journals we sampled had an authorship policy. Having an authorship policy was positively associated with impact factor. Journals from the biomedical sciences and social sciences/humanities were more likely to have an authorship policy than journals from the physical sciences, engineering or mathematical sciences. Among journals with a policy, the most frequent type of policy was guidance on criteria for authorship (99.7%); followed by guidance on acknowledgments (97.3%); requiring that authors make substantial contributions to the research (94.7%); requiring that authors be accountable for the research as a whole (84.8%); guidance on changes in authorship (77.9%); requiring that authors give final approval to the manuscript (77.6%); requiring that authors draft or critically revise the manuscript (71.7%); providing guidance on corporate authorship (58.9%); prohibiting gift, guest or ghost authorship (31.7%); requiring authors to describe their contributions (5.3%); limiting the number of authors for some types of articles (4.0%) and requiring authors to be accountable for their part in the research (1.1%). None of the policies addressed equal contribution statements. Journals that do not have authorship policies should consider adopting or developing ones.
    No preview · Article · Dec 2015 · Journal of medical ethics
  • Kristie Mozzachio · Alicia B Moore · Grace E Kissling · Darlene Dixon
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    ABSTRACT: Uterine leiomyomas in miniature pet pigs occur similarly to those in women with regard to frequency, age, parity, and cycling. Clinical signs, gross, and histologic features of the porcine tumors closely resemble uterine leiomyomas (fibroids) in women. Although fibroids are hormonally responsive in women, the roles of estrogen and progesterone have not been fully elucidated. In this study, immunohistochemistry was used to assess the expression of the steroid hormone receptors, estrogen receptor alpha (ER-α), estrogen receptor beta (ER-β) and progesterone receptor (PR), and cell proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki-67 in tumor and matched myometrial tissues sampled from miniature pigs. A "quickscore" method was used to determine receptor expression and labeling indices were calculated for the markers. ER-α/β and PR were localized to the nuclei of smooth muscle cells in both tissues. PR expression was intense and diffuse throughout all tissues, with correlation between tumors and matched myometria. Conversely, ER-α expression was variable between the myometrial and tumor tissues, as well as between animals. ER-β expression was low. PCNA and Ki-67 were localized to the nucleus and expression varied among tumors; however, normal tissues were overall negative. These findings support further investigation into the use of the miniature pig as a model of fibroids in women.
    No preview · Article · Dec 2015 · Toxicologic Pathology
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    ABSTRACT: Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. However, cross-model organ pathologies and clinical manifestations are often not compared. We hypothesized that genetic CVD rat models will exhibit baseline pathologies and will thus express varied lung response to acute ozone exposure. Male 12-14-week-old healthy Wistar Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) rats and CVD-compromised spontaneously hypertensive (SH), fawn-hooded hypertensive (FHH), stroke-prone SH (SHSP), obese SH heart-failure (SHHF), obese diabetic JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h and clinical biomarkers, and lung, heart and kidney pathologies were compared immediately following (0-h) or 20-h later. Strain differences were observed between air-exposed CVD-prone and WKY rats in clinical biomarkers and in kidney and heart pathology. Serum cholesterol was higher in air-exposed obese SHHF and JCR compared to other air-exposed strains. Ozone did not produce lesions in the heart or kidney. CVD-prone and SD rats demonstrated glomerulopathy and kidney inflammation (WKY = WIS = SH < SD = SHSP < SHHF < JCR = FHH) regardless of ozone. Cardiac myofiber degeneration was evident in SH, SHHF, and JCR, while only JCR tends to have inflammation in coronaries. Lung pathology in air-exposed rats was minimal in all strains except JCR. Ozone induced variable alveolar histiocytosis and bronchiolar inflammation; JCR and SHHF were less affected. This study provides a comparative account of the clinical manifestations of disease and early-life organ pathologies in several rat models of CVD and their differential susceptibility to lung injury from air pollutant exposure.
    No preview · Article · Dec 2015 · Inhalation Toxicology
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    ABSTRACT: Objective: To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). Methods: The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. Results: The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). Conclusions: These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.
    No preview · Article · Dec 2015 · Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine
  • David B Resnik · J.L. Ariansen · Jaweria Jamal · Grace E Kissling
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    ABSTRACT: Purpose: Institutional conflicts of interest (ICOIs) occur when the institution or leaders with authority to act on behalf of the institution have conflicts of interest (COIs) that may threaten the objectivity, integrity, or trustworthiness of research because they could impact institutional decision making. The purpose of this study was to gather and analyze information about the ICOI policies of the top 100 U.S. academic research institutions, ranked according to total research funding. Method: From May-June 2014, the authors attempted to obtain ICOI policy information for the top 100 U.S. academic research institutions from publicly available Web sites or via e-mail inquiry. If an ICOI policy was not found, the institutions' online COI policies were examined. Data on each institution's total research funding, national funding rank, public versus private status, and involvement in clinical research were collected. The authors developed a coding system for categorizing the ICOI policies and used it to code the policies for nine items. Interrater agreement and P values were assessed. Results: Only 28/100 (28.0%) institutions had an ICOI policy. ICOI policies varied among the 28 institutions. Having an ICOI policy was positively associated with total research funding and national funding ranking but not with public versus private status or involvement in clinical research. Conclusions: Although most U.S. medical schools have policies that address ICOIs, most of the top academic research institutions do not. Federal regulation and guidance may be necessary to encourage institutions to adopt ICOI policies and establish a standard form of ICOI review.
    No preview · Article · Nov 2015 · Academic medicine: journal of the Association of American Medical Colleges
  • C J Willson · G P Flake · R C Sills · G E Kissling · M F Cesta
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    ABSTRACT: o-Nitroanisole is an intermediate in the manufacture of azo dyes. In a National Toxicology Program stop-exposure study, o-nitroanisole induced hyperplasia, papillomas, and papillary carcinomas in the urinary bladder of Fischer 344/N rats. o-Nitroanisole was investigated since occupational or environmental exposure to aniline and azo dyes is a risk factor for urinary bladder cancer in humans. The current study describes the morphology of urinary bladder neoplasms seen in rats with respect to those observed in humans. This study also evaluated immunohistochemical expression of the cell cycle-related proteins cyclin D1 and p53 and the differentiation markers cytokeratin 20 and uroplakin III in hyperplastic (n = 11) and neoplastic (n = 6 papillomas, n = 11 carcinomas) lesions of the urinary bladder epithelium from rats treated with o-nitroanisole and in normal (n = 6) urinary bladders from untreated rats. The tumors observed were more similar to the papillary type rather than the muscle-invasive type of urinary bladder cancer in humans. The preneoplastic and neoplastic lesions observed suggest progression from hyperplasia to papilloma to papillary carcinoma. With neoplastic progression (hyperplasia to papilloma to carcinoma), cyclin D1 immunoreactivity progressively increased in intensity, percentage of cells staining, and distribution. Overexpression of p53 was not found. Cytokeratin 20 staining decreased in superficial cells, while uroplakin III staining increased in intermediate and basal cells with progression from hyperplasia to carcinoma. The results are consistent with increased cell cycle dysregulation or proliferation (cyclin D1), decreased differentiation (cytokeratin 20), and abnormal differentiation (uroplakin III) as lesions progress toward malignancy. © The Author(s) 2015.
    No preview · Article · Aug 2015 · Veterinary Pathology
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    ABSTRACT: Bisphenol A (BPA) is a high production volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products including cash register receipt paper; however little is known about exposure of cashiers to BPA and alternative compounds in receipt paper. To determine if handling receipt paper results in measurable absorption of BPA or the BPA alternatives, bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP). Cashiers (n = 77) and non-cashiers (n=25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analysed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2h after completing a shift) were compared with pre-shift samples (collected ≥ 24 hours after a work shift). Urine levels in cashiers were compared to levels from non-cashiers. Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. Mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as increase after a shift, but the mean post-shift concentration was significantly higher than in non-cashiers. BPSIP was detected more frequently in urine of cashiers handling BPSIP receipts compared to non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently. Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.
    Full-text · Article · Aug 2015 · Environmental Health Perspectives
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    ABSTRACT: Mice exposed to high levels of arsenic in utero are more susceptible to tumors such as hepatic and pulmonary carcinoma when they reach adulthood. However, effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. We evaluated the effect of in utero exposure to inorganic arsenic at the EPA drinking water standard (10 ppb) and tumor-inducing level (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reach adulthood. Pregnant CD-1 mice were exposed to sodium arsenite (0, 10 ppb, or 42.5 ppm) in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) of the exposed females in adulthood. Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10 ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10 ppb and 42.5 ppm groups, exposed females had significantly higher body weight gain, body fat content, and glucose intolerance. Our findings reveal unexpected effects that in utero exposure to arsenic at a human relevant low dose and a tumor-inducing level leads to early onset of vaginal opening and obesity in female CD-1 mice.
    Full-text · Article · Aug 2015 · Environmental Health Perspectives
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    David B Resnik · Elizabeth Wager · Grace E Kissling
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    ABSTRACT: This study gathered information about the retraction policies of the top 200 scientific journals, ranked by impact factor. Editors of the top 200 science journals for the year 2012 were contacted by email. One hundred forty-seven journals (74%) responded to a request for information. Of these, 95 (65%) had a retraction policy. Of journals with a retraction policy, 94% had a policy that allows the editors to retract articles without authors' consent. The majority of journals in this sample had a retraction policy, and almost all of them would retract an article without the authors' permission.
    Full-text · Article · Jul 2015 · Journal of the Medical Library Association JMLA
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    ABSTRACT: Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA. To reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration. We exposed six men and eight women to 100μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates. Mean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711nM (390ng/ml) was observed at Tmax of 1.1±0.50h. Unconjugated d6-BPA appeared in serum within 5-20min of dosing with a mean Cmax of 6.5nM (1.5ng/ml) observed at Tmax of 1.3±0.52h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48h in some subjects at concentrations near the LOD (0.001-0.002ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4±2.0h and 6.2±2.6h, respectively. Recovery of total administered d6-BPA in urine was 84-109%. Most subjects (10 of 14) excreted >90% as metabolites within 24h. Using more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24h. Published by Elsevier Ltd.
    No preview · Article · Jun 2015 · Environment international
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    ABSTRACT: Rodent lung tumors are morphologically similar to a subtype of human lung adenocarcinomas. The objective of this study was to evaluate Kirsten rat sarcoma oncogene homolog (Kras), epidermal growth factor receptor (Egfr), and tumor protein 53 (Tp53) mutations, which are relevant to human lung cancer, in cobalt metal dust (CMD)-induced alveolar/bronchiolar tumors of B6C3F1/N mice and F344/NTac rats. Kras mutations were detected in 67% (mice) and 31% (rats) of CMD-induced lung tumors and were predominantly exon 1 codon 12 G to T transversions (80% in mice and 57% in rats). Egfr mutations were detected in 17% (both mice and rats) of CMD-induced lung tumors and were predominantly in exon 20 with 50% G to A transitions (mice and rats). Tp53 mutations were detected in 19% (mice) and 23% (rats) of CMD-induced lung tumors and were predominant in exon 5 (mice, 69% transversions) and exon 6 (rats, all transitions). No mutations were observed for these genes in spontaneous lung tumors or normal lungs from untreated controls. Ames assay indicated that CMD is mutagenic in the absence but not in the presence of S9 mix. Thus, the mutation data (G to T transversions) and Ames assay results suggest that oxidative damage to DNA may be a contributing factor in CMD-induced pulmonary carcinogenesis in rodents. © 2015 by The Author(s).
    Full-text · Article · Jun 2015 · Toxicologic Pathology
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    David B Resnik · Lisa M Rasmussen · Grace E Kissling
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    ABSTRACT: Research misconduct is an international concern. Misconduct policies can play a crucial role in preventing and policing research misconduct, and many institutions have developed their own policies. While institutional policies play a key role in preventing and policing misconduct, national policies are also important to ensure consistent promulgation and enforcement of ethical standards. The purpose of this study was to obtain more information about research misconduct policies across the globe. We found that twenty-two of the top forty research and development funding countries (55%) had a national misconduct policy. Four countries (18.2%) are in the process of developing a policy, and four (18.2%) have a national research ethics code but no misconduct policy. All twenty-two countries (100%) with national policies included fabrication, falsification, and plagiarism in the definition of misconduct, but beyond that there was considerable diversity. Unethical authorship was mentioned in 54.6% of the misconduct definitions, followed by unethical publication practices (36.4%), conflict of interest mismanagement (36.4%), unethical peer review (31.8%), misconduct related to misconduct investigations (27.3%), poor record keeping (27.3%), other deception (27.3%), serious deviations (22.7%), violating confidentiality (22.7%), and human or animal research violations (22.7%). Having a national policy was positively associated with research and development funding ranking and intensiveness. To promote integrity in international research collaborations, countries should seek to harmonize and clarify misconduct definitions and develop procedures for adjudicating conflicts when harmonization does not occur.
    Full-text · Article · Apr 2015 · Accountability in Research Policies and Quality Assurance
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    David B Resnik · Talicia Neal · Austin Raymond · Grace E Kissling
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    ABSTRACT: In 2000, the U.S. federal government adopted a uniform definition of research misconduct as fabrication, falsification, or plagiarism (FFP), which became effective in 2001. Institutions must apply this definition of misconduct to federally-funded research to receive funding. While institutions are free to adopt definitions of misconduct that go beyond the federal standard, it is not known how many do. We analyzed misconduct policies from 183 U.S. research institutions and coded them according to thirteen different types of behavior mentioned in the misconduct definition. We also obtained data on the institution's total research funding and public vs. private status, and the year it adopted the definition. We found that more than half (59%) of the institutions in our sample had misconduct policies that went beyond the federal standard. Other than FFP, the most common behaviors included in definitions were "other serious deviations" (45.4%), "significant or material violations of regulations" (23.0%), "misuse of confidential information" (15.8%), "misconduct related to misconduct" (14.8%), "unethical authorship other than plagiarism" (14.2%), "other deception involving data manipulation" (13.1%), and "misappropriation of property/theft" (10.4%). Significantly more definitions adopted in 2001 or later went beyond the federal standard than those adopted before 2001 (73.2% vs. 26.8%), and significantly more definitions adopted by institutions in the lower quartile of total research funding went beyond the federal standard than those adopted by institutions in the upper quartiles. Public vs. private status was not significantly associated with going beyond the federal standard.
    Full-text · Article · Jan 2015 · Accountability in Research
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    ABSTRACT: Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17β (HSD17β) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms. © 2014 by The Author(s).
    No preview · Article · Dec 2014 · Toxicologic Pathology
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    Full-text · Dataset · Nov 2014
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    ABSTRACT: Perfluorooctanoic acid (PFOA) is a ubiquitous pollutant that causes liver toxicity in rodents, a process believed to be dependent on peroxisome proliferator-activated receptor-alpha (PPARα) activation. Differences between humans and rodents have made the human relevance of some health effects caused by PFOA controversial. We analyzed liver toxicity at 18 months following gestational PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced effects between strains and in wild type (WT) and PPARα-knockout (KO) 129/Sv mice. Pregnant mice were exposed daily to doses (0.01-5 mg/kg/BW) of PFOA from gestation days 1 to 17. The female offspring were necropsied at 18 months, and liver sections underwent a full pathology review. Hepatocellular adenomas formed in PFOA-exposed PPARα-KO 129/Sv and CD-1 mice and were absent in untreated controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was significantly increased by PFOA exposure in CD-1, and an increased severity was found in WT 129/Sv mice. PFOA significantly increased nonneoplastic liver lesions in PPARα-KO mice (hepatocyte hypertrophy, bile duct hyperplasia, and hematopoietic cell proliferation). Low-dose gestational exposures to PFOA induced latent PPARα-independent liver toxicity that was observed in aged mice. Evidence of liver toxicity in PPARα-KO mice warrants further investigation into PPARα-independent pathways.
    Full-text · Article · Nov 2014 · Toxicologic Pathology
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    ABSTRACT: Background: Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers. objective: We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that infuence benzene-induced genotoxicity. Methods: We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). Te study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis. Results: We observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. Tis estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identifed a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity. Conclusions: The genetically diverse DO mice provided a reproducible response to benzene exposure. Te DO mice display interindividual variation in toxicity response and, as such, may more accurately refect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. Te identifcation of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity. © 2015, Public Health Services, US Dept of Health and Human Services .All rights reserved.
    Full-text · Article · Nov 2014 · Environmental Health Perspectives
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    ABSTRACT: Background: It has been proposed that cadmium (Cd) is an environmental "metalloestrogen" and that its action is mediated via the estrogen receptor (ER). Cd mimics the effects of estrogen in the rat uterus, and blood Cd concentrations positively correlate with ER levels in uteri of women with fibroids. Objectives: In the present study we explored whether Cd could stimulate proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM) cells and uterine smooth muscle cells (ht-UtSMCs) through classical interactions with ERα and ERβ, or by nongenomic mechanisms. Methods: We used estrogen response element (ERE) reporters, phosphorylated receptor tyrosine kinase arrays, Western blot analysis, estrogen binding, and cell proliferation assays to evaluate the effects of Cd on ht-UtLM cells and ht-UtSMCs. Results: Cd stimulated growth of both cell types at lower concentrations and inhibited growth at higher concentrations (≥ 50 μM). Cd did not significantly bind to ERα or ERβ, nor did it show transactivation in both cell types transiently transfected with ERE reporter genes. However, in both cells types, Cd (0.1 μM and 10 μM) activated p44/42 MAPK (ERK1/2), and a MAPK inhibitor (PD98059) abrogated Cd-induced cell proliferation. Cd in ht-UtLM cells, but not in ht-UtSMCs, activated the growth factor receptors EGFR, HGFR, and VEGF-R1 upstream of MAPK. Additional studies in ht-UtLM cells showed that AG1478, an EGFR inhibitor, abolished Cd-induced phosphorylation of EGFR and MAPK. Conclusions: Our results show that low concentrations of Cd stimulated cell proliferation in estrogen-responsive uterine cells by nongenomic activation of MAPK, but not through classical ER-mediated pathways.
    Full-text · Article · Oct 2014 · Environmental Health Perspectives
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    ABSTRACT: Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3, and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA.
    Full-text · Article · Oct 2014 · Toxicologic Pathology
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    ABSTRACT: Sorbitol dehydrogenase (SDH) is a liver-specific enzyme sensitive to the detection of acute hepatocellular injury in rats; however, its usefulness has been questioned as being a highly labile enzyme. The purpose of this study was to determine the stability of serum and plasma SDH activity from both untreated rats and those treated with a single low dose injection of d-(+)-galactosamine hydrochloride, a known hepatotoxicant. After collection and initial SDH activity analysis, aliquots of serum and plasma were stored at 21°C, 4°C, and -80°C and analyzed at various time points. Serum SDH activity was stable for 4 hr at 21°C. At 4°C, serum SDH activity was stable for 24 hr, after which it significantly increased; it was not stable at -80°C. Plasma SDH activity was significantly increased by 4 hr at 21°C and 4°C, and by 48 hr at -80°C. Analysis of plasma SDH activity should occur shortly after blood collection. Analysis of serum SDH activity should occur within 4 hr of collection or stored at 4°C and measured within 24 hr. Extended storage at 4°C or -80°C for the measurement of serum or plasma SDH activity cannot be recommended due to the observed substantial elevations in SDH activity.
    No preview · Article · Oct 2014 · Toxicologic Pathology

Publication Stats

3k Citations
551.33 Total Impact Points


  • 2004-2015
    • National Institute of Environmental Health Sciences
      • • Biostatistics Branch
      • • Cellular & Molecular Pathology Branch
      • • Epidemiology Branch
      Durham, North Carolina, United States
    • National Institutes of Health
      • • Branch of Bio-statistics
      • • Division of Intramural Research
      Maryland, United States
  • 2008-2013
    • Northern Inyo Hospital
      BIH, California, United States
    • George Washington University
      Washington, Washington, D.C., United States
    • University of Cincinnati
      • Department of Biological Sciences
      Cincinnati, Ohio, United States
  • 2011
    • North Carolina Department of Health and Human Services
      Raleigh, North Carolina, United States
  • 2006-2011
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
    • University of Southern Mississippi
      • Gulf Coast Research Laboratory
      HBG, Mississippi, United States
  • 2010
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel