To address the mechanisms controlling T helper (Th) phenotype development, we used DO10, a transgenic mouse line that expresses the af8 T-cell receptor from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting cells (APCs). We have examined the role of cytokines and APCs in the regulation of Th phenotype development. Interleukin 4 (IL-4) directs development toward the Th2 phenotype, stimulating IL-4 and silencing IL-2 and interferon y production in developing T cells.Splenic APCs direct development toward the Thl phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody. The splenic APCs mediating these effects are probably macrophages or dendritic cells and not B cells, since IL-10 is incapable of affecting Th phenotype development when the B-cell hybridoma TA3 is used as the APC. These results suggest that early regulation of IL-4 and IL-10 in a developing immune response and the identity of the initiating APCs are critical in determining the Th phenotype of the developing T cells.

Activity of the murine interleukin-4 (ILH4) promoter was localized to several cis-acting elements present within the first 300 bp from the transcriptional initiation site. Five repeated elements, P0 to P4, that share the common consensus ATTITCCNNT were located between -40 and -250, and each was shown to interact with the T-cell-specific factor NF(P). These distinct P sites appear functionally interchangeable and cooperatively confer cyclosporin A-sensitive and ionomycin-inducible promoter activity. NF(P)

The authors present recent data on changes under way in and the current status of faculty appointment and tenure policies in U.S. medical schools. The data are drawn from a survey conducted by the Association of American Medical Colleges in 1997, to which deans at all 125 U.S. allopathic medical schools responded, supplemented by follow-up telephone and electronic mail inquiries. Faculty evaluation systems and faculty compensation systems top the list of areas in which medical schools are most frequently making policy changes, with approximately half of the schools involved in each area. Changes in evaluation systems reflect an increasing emphasis on post-tenure review. Changes in compensation systems are characterized by the division of pay into separate components, each with its own financial guarantees and with the level of compensation tied specifically to measures of individual and group productivity. Other policy changes include introducing new faculty tracks and career pathways, redefining or clarifying the portion of salary or compensation that is defined by tenure, lengthening the pre-tenure probationary period, and modifying the link between promotion and tenure. Of the 125 medical schools in the United States, only five do not award tenure, while another six effectively limit eligibility for tenure to basic science faculty. These numbers are unchanged from those reported in 1994. Only two schools indicated that eliminating tenure or ceasing to make tenure-eligible appointments was being considered, and neither reported that a policy change was imminent. Current data on the status of tenure guarantees, tenure probationary periods, other tenure eligibility criteria, and special clinical tracks are provided. Nearly three fourths of the medical schools in the United States now have a separate and distinct faculty track for full-time clinical faculty whose primary responsibilities are in patient care and teaching. The vast majority of these tracks do not permit faculty to be tenured, but 71% require evidence of scholarship for promotion. The authors conclude that faculty personnel policies in medical schools are likely to continue to evolve, consistent with a growing insinuation of the corporate culture into academia.

The authors present data and information about appointment, tenure, and compensation policies to describe how medical schools are redefining the terms under which they relate to their full-time clinical faculties. First, the authors note the increasing differentiation of clinical faculty members into two groups, researchers and clinicians. The present-day competitive realities of both research and clinical enterprises have prompted this change and the principles of mission-based management are reinforcing it. Second, they document the long-term tendency of schools to appoint new clinical faculty members to contract-term (as opposed to tenure) appointments, as special non-tenure-eligible tracks for clinically oriented faculty proliferate. Third, they report on the policies of schools to limit the financial guarantees provided to clinical faculty members who are awarded tenure. For schools that have yet to address this issue, they discuss the various employment and pay arrangements that inform or confuse the question. Fourth, they describe historic problems with clinical faculty compensation arrangements and illustrate, with examples from ten schools, the characteristics of recently implemented performance- and risk-based compensation plans. While these trends in institutional policies and practices may initially concern faculty advocate groups, the authors argue that they may serve the long-term interests of those groups. The terms of relationships between medical schools and their clinical faculties are tied closely to the specifics of organizational structure, which are currently undergoing review and change. The challenge all schools face is to define these terms in ways that allow them to continue to attract high-quality clinical faculty while avoiding an insupportable financial liability.

While a consensus is emerging about the functions of a faculty affairs office, no school has a comprehensive faculty development system, in contrast to most industries, which must be more forward-looking to compete for talent.

Activity of the murine interleukin-4 (IL-4) promoter was localized to several cis-acting elements present within the first 300 bp from the transcriptional initiation site. Five repeated elements, P0 to P4, that share the common consensus ATTTTCCNNT were located between -40 and -250, and each was shown to interact with the T-cell-specific factor NF(P). These distinct P sites appear functionally interchangeable and cooperatively confer cyclosporin A-sensitive and ionomycin-inducible promoter activity. NF(P) may be closely related to the cytoplasmic component of NF-AT (nuclear factor of activated T cells), a T-cell-specific factor essential for IL-2 gene transcription, as judged from indistinguishable molecular weights and protease fragmentation patterns of UV-photolabeled factors. Also, we identified an element in the IL-4 promoter with homology to the Y box common to all major histocompatibility complex class II gene promoters. Our data show that the IL-4 promoter Y box -114CTGATTGG-107 significantly enhances overall promoter activity, since point mutations within this element diminish promoter activity by 85%. The factor binding this region is indistinguishable from the cloned nuclear factor NF-Y, as judged from interactions with specific anti-NF-Y monoclonal and polyclonal antibodies. Last, we point out the presence of two sites that share sequence identity to the OAP region of the ARRE-1 site within the IL-2 promoter (K. S. Ullman, W. M. Flanagan, C. A. Edwards, and G. R. Crabtree, Science 254:558-562, 1991). These regions, -85GTGTAATA-78 and -245GTGTAATT-238, reside adjacent to the NF(P) binding sites P1 and P4 and bind a distinct nuclear factor.

A substantial proportion of U.S. medical schools have taken action to recognize preceptors as a unique faculty group. The comments received indicate that this is an active area of development in faculty affairs policy.

No abstract