Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Histopathological changes in the eyes in systemic lupus erythematosus: An electron microscope and immunohistochemical study

This paper reports the histopathological findings in the eyes of a 26-year-old female patient diagnosed with systemic lupus erythematosus (SLE) with peripheral neuropathy. The patient had no significant ocular problems. She died of pneumonia after two years of suffering. The eyeballs were procured at autopsy and the retina, choroid and optic nerve processed for light and electron microscopy, and immunohistochemistry for immunoglobulin G (IgG), glial fibrillary acidic protein (GFAP), calbindin and parvalbumin. Histologically, there was haemorrhaging in the retinal nerve fibre layer. Ultrastructurally, the axons of this layer were swollen, and contained an unusual accumulation of microtubules and smooth endoplasmic reticulum. There were degenerative changes in the pericytes and smooth muscle cells of blood vessels. The capillary lumen was partially obliterated, and contained IgG, which was also detected throughout the choroid and wall of choroidal arterioles. The latter and Bruch’s membrane showed fibrin deposits. The optic nerve showed infiltrated mononuclear cells near the degenerated axons, these axons lacked immunoreactivity to calbindin and parvalbumin. Compared to the control, the connective tissue sheaths of the central retinal vessels possessed a vast number of proliferated fibroblast cells, and trichrome staining showed transmural vessel scarring. Dense GFAP immunoreactivity was observed surrounding the vessel wall. These pathological changes are due to impaired blood circulation caused by haemorrhaging and vasculitis, and vessel occlusion by fibrin. The nature of the changes observed tends to indicate that a regular, thorough ophthalmic examination should be conducted even in the absence of significant ocular symptoms in SLE

Diethylene glycol poisoning in Gurgaon, India, 1998

OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2 months to 6 years who were admitted to two hospitals in Delhi between 1 April and 9 June 1998. METHODS: Data were collected from hospital records, parents and doctors of the patients, and district health officials. Further information was obtained from house visits and community surveys; blood and stool samples were collected from other ill children, healthy family members and community contacts. Samples of drinking-water and water from a tube-well were tested for coliform organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute renal failure developed after an episode of acute febrile illness with or without watery diarrhoea or mild respiratory symptoms for which the children had been treated with unknown medicines by private medical practitioners. On admission to hospital the children were not dehydrated. Median blood urea concentration was 150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6 mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty-three children were known to have died despite being treated with peritoneal dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a company in Gurgaon was found to be contaminated with diethylene glycol (17.5%v/v), but a sample of acetaminophen manufactured by the same company tested negative for contamination when gas-liquid chromatography was used. Thus, poisoning with diethylene glycol seems to be the cause of acute renal failure in these children

Diethylene glycol poisoning in Gurgaon, India, 1998

OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2 months to 6 years who were admitted to two hospitals in Delhi between 1 April and 9 June 1998. METHODS: Data were collected from hospital records, parents and doctors of the patients, and district health officials. Further information was obtained from house visits and community surveys; blood and stool samples were collected from other ill children, healthy family members and community contacts. Samples of drinking-water and water from a tube-well were tested for coliform organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute renal failure developed after an episode of acute febrile illness with or without watery diarrhoea or mild respiratory symptoms for which the children had been treated with unknown medicines by private medical practitioners. On admission to hospital the children were not dehydrated. Median blood urea concentration was 150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6 mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty-three children were known to have died despite being treated with peritoneal dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a company in Gurgaon was found to be contaminated with diethylene glycol (17.5%v/v), but a sample of acetaminophen manufactured by the same company tested negative for contamination when gas-liquid chromatography was used. Thus, poisoning with diethylene glycol seems to be the cause of acute renal failure in these children