Radionuclide Concentrations in Different Water Sources From Nigeria.

Gamma spectrometric analysis was done on all the different sources of water samples in the rural communities of Egbeda Local Government Area of Oyo State in Nigeria. Water samples were collected from 6 boreholes, 11 streams, 5 taps, and 41 hand-dug wells. The water samples were analyzed using a high-purity germanium detector at the National Institute of Radiation Protection and Research, Ibadan, Nigeria. Radionuclides found in the water samples include K, Th, and U. The average amount of K found in the borehole, stream, tap, and well water is 3.22, 2.23, 2.11, and 1.77 Bq L, respectively. The average amount of Th found in the borehole, stream, tap, and well water is 0.57, 0.46, 0.47, and 0.55 Bq L, respectively. The average amount of U found in the borehole, stream, tap, and well water is 0.54, 0.27, 0.29, and 0.61 Bq L, respectively. The annual effective doses calculated from radionuclides in the water are 0.11, 0.09, 0.09, and 0.11 mSv for borehole, stream, tap, and well, respectively.

Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody.

Monocyte chemoattractant proteins (MCPs) are cytokines that direct immune cells bearing appropriate receptors to sites of inflammation or injury and are therefore attractive therapeutic targets for inhibitory molecules. 11K2 is a blocking mouse monoclonal antibody active against several human and murine MCPs. A 2.5 A structure of the Fab fragment of this antibody in complex with human MCP-1 has been solved. The Fab blocks CCR2 receptor binding to MCP-1 through an adjacent but distinct binding site. The orientation of the Fab indicates that a single MCP-1 dimer will bind two 11K2 antibodies. Several key residues on the antibody and on human MCPs were predicted to be involved in antibody selectivity. Mutational analysis of these residues confirms their involvement in the antibody-chemokine interaction. In addition to mutations that decreased or disrupted binding, one antibody mutation resulted in a 70-fold increase in affinity for human MCP-2. A key residue missing in human MCP-3, a chemokine not recognized by the antibody, was identified and engineering the preferred residue into the chemokine conferred binding to the antibody.

Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma.

Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed. Our understanding of its activity is complicated by the possibility that TIM-1 possesses multiple and diverse binding partners. In order to delineate the function of TIM-1, we generated monoclonal antibodies directed to a cleft formed within the IgV domain of TIM-1. We have shown here that antibodies that bind to this defined cleft antagonize TIM-1 binding to specific ligands and cells. Notably, these antibodies exhibited therapeutic activity in a humanized SCID model of experimental asthma, ameliorating inflammation, and airway hyperresponsiveness. Further experiments demonstrated that the effects of the TIM-1-specific antibodies were mediated via suppression of Th2 cell proliferation and cytokine production. These results demonstrate that modulation of the TIM-1 pathway can critically influence activated T cells in a humanized disease model, suggesting that TIM-1 antagonists may provide potent therapeutic benefit in asthma and other immune-mediated disorders.