Impact of low-level exposure to organophosphates on human reproduction and survival

Despite their widespread and longstanding use for the public good, organophosphate (OP) pesticides have led to many adverse effects on human health. Environmental exposure to OPs and adverse reproductive outcomes in men and women working on or living near farms are increasingly reported worldwide. The aim of the current review is to determine whether exposure to OPs, at levels lower than that which results in clinical manifestations of acute OP poisoning, leads to an adverse impact on fertility, growth and development, and to highlight possible effects for further investigation. There is evidence of impaired fertility due to a reduction in semen quality and possibly lower testosterone levels in exposed males. There is also evidence of impairment of fetal growth and development brought about by prenatal exposure to OPs. Paraoxonase gene (PON1) activity in the fetus and during early childhood makes the fetus and child more vulnerable to OP poisoning, suggesting that OP exposure has a greater impact on fetal and infant growth and development than on adults when exposed to the same concentrations of pesticides. This review raises concerns that exposure to OP pesticides at levels currently regarded as safe adversely affect human reproductive function and survival.     

Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays

OBJECTIVE: To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. PATIENTS AND METHODS: We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. RESULTS: The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. CONCLUSION: Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.     

Analysis of Somatic Hypermutation and Antigenic Selection in the Clonal B Cell in Immunoglobulin Light Chain Amyloidosis (AL)

Light chain amyloidosis (AL) is a protein folding disorder with an underlying B cell neoplasia where the monoclonal immunoglobulin light chains (LCs) produced from insoluble amyloid fibrils. The deposition of these fibrillar aggregates in vital organs causes severe organ dysfunction over time and is associated with high mortality. We have identified the postgerminal center status of the B cell clone by evaluating the presence of somatic hypermutation in the variable region of the LC gene in 27 (13 of the lambda and 14 of the kappa subtype) AL patients. Seven of the 27 clones showed statistically significant evidence of antigenic selection, using a multinomial algorithm. The framework region mutations were selected for conservation of protein structure in 13 of the 27 patients. Additionally, mutational clusterspots were identified at specific positions in the nucleotide and deduced protein sequence that could potentially contribute to destabilizing interactions resulting in a propensity to form amyloid.     

Interpretation of Dihydrorhodamine-1,2,3 Flow Cytometry in Chronic Granulomatous Disease: an Atypical Exemplar

Journal of Clinical Immunology - This is a functional characterization of a novel CYBA variant associated with normal DHR flow cytometry. Chronic granulomatous disease (CGD) is an inborn error of...