CD154 is the ligand for the receptor CD40. This ligand-receptor pair mediates endothelial and antigen-presenting cell activation, and facilitates the interaction of these cells with T cells and platelets. We demonstrate here that administration of a CD154-specific monoclonal antibody (hu5C8) allows for renal allotransplantation in outbred, MHC-mismatched rhesus monkeys without acute rejection. The effect persisted for more than 10 months after therapy termination, and no additional drug was required to achieve extended graft survival. Indeed, the use of tacrolimus or chronic steroids seemed to antagonize the anti-rejection effect. Monkeys treated with antibody against CD154 remained healthy during and after therapy. The mechanism of action does not require global depletion of T or B cells. Long-term survivors lost their mixed lymphocyte reactivity in a donor-specific manner, but still formed donor-specific antibody and generated T cells that infiltrated the grafted organ without any obvious effect on graft function. Thus, therapy with antibody against CD154 is a promising agent for clinical use in human allotransplantation.

To quantify the amount of optic nerve axonal loss associated with the presence of a mild relative afferent pupillary defect (RAPD) in an experimental monkey model. Methods: The right macula of 5 rhesus monkeys (Macaca mulatta) was treated with concentrically enlarging diode laser burns until an RAPD was detected using a transilluminator light and measured with neutral density filters. Intervals between treatments were 3 to 7 days over a period of 2 months. Pupillary responses to light stimulation were recorded with a monocular infrared television pupillometer. Two months after detection of an RAPD, 5 treated and 4 control monkeys underwent euthanasia and enucleation. Histopathologic analysis and quantification of optic nerve axon counts using an image analysis system were performed. Results: No RAPD was observed despite an estimated ganglion cell loss of up to 26%. A 0.6 log unit RAPD was present in 5 monkeys when the laser scar incorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 log units without further laser treatment. Histopathologic evaluation disclosed complete loss of the normal retinal architecture within the macula. The average fiber loss for the 4 treated eyes with 0.6 log unit RAPDs compared with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). The average difference in axon counts between untreated pairs of optic nerves was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of experimental and control eyes was statistically significant (PϽ.001). Conclusion: In rhesus monkeys, an RAPD develops after an approximate unilateral loss between 25% and 50% of retinal ganglion cells. Clinical Relevance: Owing to redundancy in the anterior visual pathways, unilateral retinal ganglion cell loss may occur prior to the observation of an RAPD. The presence of an RAPD measuring 0.6 log units implies that significant retinal ganglion cell injury has occurred.

Strengthened periodic screening for and treatment of confirmed STD, in addition to condom promotion and provision, represent feasible, effective interventions in commercial sex, and time series analyses can provide a useful approach to evaluating new interventions.

No abstract

A short-term, time-dependent smoke exposure of rats in a nose-only chamber to burning wood and 24-h recovery time revealed inflammation of the airways with varying degrees of injury from loss of cilia, degeneration of epithelium, and squamous metaplasia to submucosal edema. These histological changes were reflected in variable expression of the secretory Muc5AC and low expression of membrane-associated Muc4 mucin genes. 20-min smoke exposure in extended recovery experiments showed marked disorder of tracheal epithelium for up to 72 h of recovery with a return to normal by 7 days. Gene expressions were elevated at 24 and 48 h of recovery. 30-min smoke exposure showed a more severe degeneration of the epithelium and a longer recovery time. Muc5AC expression decreased after 72 h of recovery, while there was upregulation of Muc4 gene from 48 through 96 h. Because Muc4 upregulation and histological results correlate and it has reportedly been associated with epithelium renewal, Muc4 gene may be a useful marker for the regeneration of tracheal epithelium.