A multicenter, double-blind, placebo-controlled trial of autologous fibroblast therapy for the treatment of nasolabial fold wrinkles.

BACKGROUND: Changes associated with aging are partly due to loss of collagen and elastin. Treatment with autologous fibroblasts grown in culture (azficel-T) can help correct the appearance of aging by replacing lost dermal constituents. OBJECTIVE: To demonstrate the safety and effectiveness of autologous fibroblasts in the treatment of nasolabial fold (NLF) wrinkles. METHODS AND MATERIALS: Adults with moderate to very severe NLF wrinkles were randomized to receive three treatments with autologous fibroblasts or placebo at 5-week intervals. Blinded evaluators and subjects assessed efficacy using a validated wrinkle assessment scale. RESULTS: Three hundred seventy-two subjects were enrolled and underwent treatment. Seventy-eight percent of subjects treated with autologous fibroblast therapy and 48% of subjects treated with placebo achieved at least a 1-point improvement on the subject assessment at 6 months (p < 0.001), and 64% of subjects treated with autologous fibroblast therapy and 36% of those treated with placebo showed at least a 1-point improvement evaluator's assessment (p < 0.001). Adverse events were generally mild, and the treatment was well tolerated. CONCLUSION: Autologous fibroblast therapy is safe and effective for the treatment of NLF wrinkles. The availability of autologous cell therapy marks the beginning of a new phase in aesthetic therapy.

Meeting report on protein particles and immunogenicity of therapeutic proteins: filling in the gaps in risk evaluation and mitigation.

This meeting was successful in achieving its main goals: (1) summarize currently available information on the origin, detection, quantification and characterization of sub-visible particulates in protein products, available information on their clinical importance, and potential strategies for evaluating and mitigating risk to product quality, and (2) foster communication among academic, industry, and regulatory scientists to define the capabilities of current analytical methods, to promote the development of improved methods, and to stimulate investigations into the impact of large protein aggregates on immunogenicity. There was a general consensus that a considerable amount of interesting scientific information was presented and many stimulating conversations were begun. It is clear that this aspect of protein characterization is in its initial stages. As the development of these new methods progress, it is hoped that they will shed light on the role of protein particulates on product quality, safety, and efficacy. A topic which seemed appropriate for short term follow up was to hold further discussions concerning the development and preparation of one or more standard preparations of protein particulates. This would be generally useful to facilitate comparison of results among different studies, methods, and laboratories, and to foster further development of a common understanding among laboratories and health authorities which is essential to making further progress in this emerging field.

Social integration in employment settings: application of intergroup contact theory.

This study used a survey of 106 employment specialists to test the ability of intergroup contact theory to explain social integration outcomes of employees with disabilities. Contact theory suggests that coworkers are more accepting of employees with disabilities if they have sufficient opportunities to interact with them, equal status and interdependent working relationships, and supervisors who support equality and acceptance. The contact model and an expanded model that includes workplace culture significantly predicted not only coworker attitudes toward employees with disabilities but also the employees' level of social participation and feelings of social support. In addition, outcome dependency moderated the relation between the vocational competence of employees with disabilities and coworker attitudes toward them. Study findings have practical implications for facilitating social relationships in the supported workplace.

Characterization of lethal factor binding and cell receptor binding domains of protective antigen of Bacillus anthracis using monoclonal antibodies.

Lethal toxin from Bacillus anthracis is composed of protective antigen (PA) and lethal factor (LF). Anti-PA mAbs that neutralized lethal toxin activity, either in vivo or in vitro, identified three non-overlapping antigenic regions on PA. Two distinct antigenic regions were recognized by the four mAbs that neutralized lethal toxin activity by inhibiting the binding of 125I-LF to cell-bound PA. Mapping showed that one mAb, 1G3PA63, recognized an epitope on a 17 kDa fragment located between amino acid residues Ser-168 and Phe-314. The three other mAbs, 2D3PA, 2D5PA and 10D2PA, recognized an epitope between amino acids Ile-581 and Asn-601. A single antigenic region was recognized by the three mAbs, 3B6PA, 14B7PA and 10E10PA63, that inhibited binding of 125I-PA to cells. This region was located between amino acids Asp-671 and Ile-721. These results confirm previously defined functional domains of PA and suggest that LF may interact with two different sites on PA to form lethal toxin.