Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

Prevalence of primary monofixation syndrome in parents of children with congenital esotropia.

The prevalence of primary monofixation syndrome (MFS) in the general population is approximately 1%. This study was performed to determine the prevalence of primary monofixation in biological parents of children with congenital esotropia. Ninety children with congenital esotropia were seen between November 1991 and June 1992 by one ophthalmologist (M.M.P.). One hundred and twenty-nine biological parents of these children were screened for sensorimotor abnormalities. Twelve parents were found to have secondary MFS and were removed from the analysis. This left 78 apparently non-strabismic families consisting of a total of 117 parents. Seven parents were identified as having primary MFS. The prevalence of primary MFS in this population is 9% of families and 6% of parents. Congenital esotropia is believed to be inherited in a multifactorial fashion. We believe that this increase in the prevalence of primary MFS compared to the general population lends support to the hypothesis that primary MFS may be a mild (subthreshold) effect of the "gene(s)" that cause congenital esotropia.

Potent neutralizing activity associated with anti-glycoprotein D specificity among monoclonal antibodies selected for binding to herpes simplex virions.

Thirty-three monoclonal antibodies were selected for ability to bind to purified virions of herpes simplex virus and were shown by immunoprecipitation to react with one or another of the envelope glycoproteins. Only six of these antibodies exhibited potent neutralizing activity, and all six were specific for glycoprotein D. Two other anti-glycoprotein D antibodies and 25 antibodies specific for four other viral glycoproteins had much less potent, if any, neutralizing activity.

Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1.

Monoclonal antibodies directed against glycoprotein D of herpes simplex virus completely inhibited fusion of Vero cells infected with type 1 virus. In contrast, several monoclonal antibodies directed against other viral glycoproteins, including B, were ineffective or were only minimally inhibitory at the highest concentrations tested.