A 75-year-old man presented with dysarthria and left facial paralysis. Brain diffusion-weighted MRI revealed a highsignal intensity in the right precentral gyrus, and he was hospitalized under the diagnosis of cerebral infarction. His symptoms worsened and brain MRI findings were consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) JC virus (JCV) was undetectable in the DNA polymerase chain reaction (PCR) test four times, but brain biopsy revealed typical PML histopathology. He had no human immunodeficiency virus infection and history of immunosuppressive treatment, but he was found to have CD4+ lymphocytopenia. He was treated with mefloquine and mirtazapine, and died 29 months after symptoms onset. In cases whose repeated DNA PCR results are negative for CSF JCV, brain biopsy may be useful for the diagnosis of PML.
Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers: Hirotaka Sato, et al. Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences
Objective
Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present crosssectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low‐level OPs.
Methods
Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 ± 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos‐methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography‐mass spectrometry.
Results
The maximum differences in enzyme activities between individuals were 64.6‐, 6.3‐, 7.7‐, and 2.0‐fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE.
Conclusions
While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.
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