1,721,043 research outputs found
Response letter to the Editor RE: Formaldehyde and leukemia: Missing evidence!
No full textNo abstrac
Critical review and synthesis of the epidemiologic evidence on formaldehyde exposure and risk of leukemia and other lymphohematopoietic malignancies
No full textPurpose Recent epidemiologic studies indicate elevated risks for some lymphohematopoietic malignancies (LHM) related to formaldehyde exposure. We performed a systematic review of literature to assess the strength and consistency of associations. Methods We summarized published literature in the PubMed database of the National Library of Medicine during 1966-2012. Literature was categorized according to study design and population: industrial cohort studies, professional cohort studies, and population-based case- control studies. Results Findings from occupational cohort and population-based case-control studies were very inconsistent for LHM, including myeloid leukemia. Apart from some isolated exceptions, relative risks were close to the null, and there was little evidence for dose-response relations for any of the LHM. Conclusions At present, there is no consistent or strong epidemiologic evidence that formaldehyde is causally related to any of the LHM. The absence of established toxicologicalmechanisms further weakens any arguments for causation. To be informative, future epidemiologic research should improve on formaldehyde exposure assessment and apply modern diagnostic schemes for specific LHM. © 2012 Springer Science+Business Media B.V
Genetic polymorphisms in Parkinson's disease
No full textThe search for genetic polymorphisms relevant to Parkinson's disease etiology and pathogenesis has been motivated by recent thinking emphasizing the potential significance of gene-environment interactions. Especially influential to this research have been the MPTP model of PD induction, hypotheses concerning oxidative stressor reactions, and epidemiological observations of an inverse relation between cigarette smoking and PD risk. This brief review summarizes trends in genetic polymorphism research, with examples provided by investigations of cytochrome P450 enzymes, monoamine oxidase, superoxide dismutase, and mitochondrial genes
Platelet monoamine oxidase B activity in workers exposed to styrene
No full textA cross-sectional study was conducted to evaluate monoamine oxidase type B (MAO-B) activity in platelets as a biomarker of effect of styrene and perchloroethylene exposures. MAO-B is an enzyme system involved in dopamine catabolism, the impairment of which has been postulated as a mechanism of styrene-induced neurotoxicity. We previously observed an inverse association between blood styrene and MAO-B among reinforced plastics manufacturing workers. The present study included 59 male boat plant workers exposed to styrene (exposure range < 1-144 ppm, 8-h TWA). Two comparison groups comprised six male dry cleaning workers exposed to perchloroethylene (PCE; exposure range < 2-37 ppm) and 14 male laundry workers not exposed to either agent. Respiratory protection was not used by any of the styrene- or PCE-exposed workers; thus, air concentrations were regarded as valid exposure indicators. MAO-B activity (pmol/10(8) cells/h) was measured in peripheral blood platelets, using phenylethylamine as substrate. Only small overall mean differences in MAO-B were observed among the three groups; mean values were 4.21, 4.51, and 4.12 for the styrene-exposed, PCE-exposed, and laundry workers, respectively. Despite the absence of gross differences among the groups, styrene exposure was inversely related to MAO-B. Mean values for four increasing exposure group quartiles were: 5.60, 4.13, 3.69, and 3.44. The Spearman rank correlation coefficient for styrene with MAO-B was -0.41. Adjustment for age, medication use, smoking, and alcohol consumption had only a minimal effect on this trend.(ABSTRACT TRUNCATED AT 250 WORDS
Characterization of the in vitro transcriptional activity of polymorphic alleles of the human monoamine oxidase-B gene
No full textThe activity of monoamine oxidase-B (MAO-B) enzyme has a high degree of heritability, although no common genetic polymorphisms are present in the MAO-B coding region. The only known polymorphisms in MAO-B gene are a C-1, 114T in the 5' region, a variable number of GT repeats in intron 2, and a G/A change in intron 13. The genetically determined differences in MAO-B activity among subjects most likely derive from functional differences conferred by these three MAO-B genetic polymorphisms, or by polymorphisms in trans-acting factors that regulate MAO-B expression. In order to identify differences in transcriptional activity conferred by the MAO-B genetic variants, we cloned alternative alleles at the three polymorphic loci in -1,114, intron 2 and intron 13, and tested them in transfection-luciferase assays in HepG2 hepatoma and 1321N1 astrocytoma cells. The mutant -1, 114 allele T had higher activity than allele C in both cell lines, when cloned in pGL3Enhancer. Significant differences in trascriptional activity by intron 2 GT repeat allele were also observed, and varied by cell type and reporter construct. Allele G of intron 13 had significantly higher activity than allele A in both cell lines. These results indicate transcriptional activity differences between MAO-B variant alleles that are naturally occurring in the populatio
Peripheral markers of neurochemical function among workers exposed to styrene
No full textA cross sectional study of biological markers of neurochemical function in peripheral blood cells, and self reported nervous system symptoms, was conducted among 60 workers exposed to styrene in three reinforced plastics plants and 18 reference workers not exposed to styrene or other solvents. Concentrations of styrene in the air at the plants ranged from less than 1 to 160 ppm. Biomarkers of neurochemical function measured were: sigma receptor binding in lymphocytes, monoamine oxidase type B (MAO-B) activity in platelets, and serotonin uptake by platelets. Blood styrene concentration was used as the exposure index to take account of the use of protective equipment and dermal uptake. Four blood styrene exposure groups were defined as: non-exposed (reference) and exposed to less than 0.05, 0.05-0.19, and greater than or equal to 0.20 micrograms/ml. The prevalences of headache, dizziness, light headedness, fatigue, irritability, memory loss, and feeling "drunk" at work increased with increasing blood styrene concentration. No effect on sigma receptor binding was seen. A slight positive correlation was found for uptake of serotonin, which has been used as an exposure related effect indicator in previous studies of workers exposed to solvents. The MAO-B activity decreased with increasing blood styrene concentration; the mean (SE) MAO-B values for the four groups were 34.2 (3.0), 28.1 (5.3), 20.1 (4.8), and 16.9 (7.7) pmol/10(7) cells/min. The MAO-B activity also correlated negatively with the number of reported nervous system symptoms, whereas no associations were seen between prevalence of symptoms and either serotonin uptake or sigma receptor binding. The findings for MAO-B activity are consistent with previously reported experimental data, and suggest that MAO-B may be a useful marker of styrene neurotoxicity
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