Aged Drivers May Experience Decreased Visual Function While Driving.

PURPOSE: To investigate conventional visual acuity (VA) and changes therein over time in older drivers. DESIGN: A cross-sectional study. METHODS: One hundred twenty-four drivers (41 younger drivers aged 21-39 years, 40 middle-aged drivers aged 40-59 years, and 43 older drivers aged 60-77 years) who consented to undergo conventional and functional VA testing, perform the Trail Making Test B, and complete a questionnaire on visual performance while driving at an expressway rest stop in Ashigara, Japan, were studied. RESULTS: The overall proportion of the study subjects with a decimal bilateral VA less than 0.7, the Japanese threshold score for obtaining and renewing a driver's license, was 10%. The number of the subjects with decimal functional VA scores and minimum VA scores less than 0.7 was significantly higher in the older group than in the younger group (P < 0.05), although the conventional VA scores did not differ significantly between the older and younger groups (P = 0.621). The Trail Making Test B scores were significantly higher in the older group than in the younger and middle-aged groups (P < 0.05). The total score of the "visual performance during driving at night" category correlated significantly with the logMAR functional VA and logMAR minimum VA (P < 0.05) but not the logMAR VA. CONCLUSIONS: Older drivers might experience decreased functional VA and increased frequency of transient decreases in VA while driving. The functional VA test might capture visual impairment among older drivers that went undetected by the conventional VA test.

Plasmacytoid dendritic cells employ multiple cell adhesion molecules sequentially to interact with high endothelial venule cells--molecular basis of their trafficking to lymph nodes.

Plasmacytoid dendritic cells (pDCs) are natural type I IFN-producing cells found in lymphoid tissues, where they support both innate and adaptive immune responses. They emigrate from the blood to lymph nodes, apparently through high endothelial venules (HEVs), but little is known about the mechanism. We have investigated the molecular mechanisms of pDC migration using freshly isolated DCs and HEV cells. We found that pDCs bound avidly to HEV cells and then transmigrated underneath them. Two observations suggested that these binding and migration steps are differentially regulated. First, treatment of pDCs with pertussis toxin blocked transmigration but not binding. Second, pDCs were able to bind but not to transmigrate under non-HEV endothelial cells, although the binding was observed to both HEV and non-HEV endothelial cells. Antibody inhibition studies indicated that the binding process was mediated by alphaL and alpha4 integrins on pDCs and by intercellular adhesion molecule (ICAM)-1, ICAM-2 and vascular cell adhesion molecule-1 on HEVs. The transmigration process was also mediated by alphaL and alpha4 integrins on pDCs, with junctional adhesion molecule-A on HEV cells apparently serving as an additional ligand for alphaL integrin. These data show for the first time that pDCs employ multiple adhesion molecules sequentially in the processes of adhesion to and transmigration through HEVs.

Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.

Lymphocyte trafficking to lymph nodes (LNs) is initiated by the interaction between lymphocyte L-selectin and certain sialomucins, collectively termed peripheral node addressin (PNAd), carrying specific carbohydrates expressed by LN high endothelial venules (HEVs). Here, we identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches [PPs]), that is expressed in LN HEVs but not detectable in PP HEVs at the protein level. Unlike conventional sialomucins, nepmucin contains a single V-type immunoglobulin (Ig) domain and a mucin-like domain. Using materials affinity-purified from LN lysates with soluble L-selectin, we found that two higher molecular weight species of nepmucin (75 and 95 kD) were decorated with oligosaccharides that bind L-selectin as well as an HEV-specific MECA-79 monoclonal antibody. Electron microscopic analysis showed that nepmucin accumulates in the extended luminal microvillus processes of LN HEVs. Upon appropriate glycosylation, nepmucin supported lymphocyte rolling via its mucin-like domain under physiological flow conditions. Furthermore, unlike most other sialomucins, nepmucin bound lymphocytes via its Ig domain, apparently independently of lymphocyte function-associated antigen 1 and very late antigen 4, and promoted shear-resistant lymphocyte binding in combination with intercellular adhesion molecule 1. Collectively, these results suggest that nepmucin may serve as a dual-functioning PNAd in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains.