Managing uncertainty: intermediate organizations as triple agents.
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Consumer Behavior↗
Biomedical subjects
L Casalino
Publications and source records attributed to L Casalino.
Executives with white coats--the work and world view of managed-care medical directors. Second of two parts.
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Budgets↗
Executives with white coats--the work and world view of managed-care medical directors. First of two parts.
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Career Mobility↗
Primary care physicians should be coordinators, not gatekeepers.
Primary care gatekeeping, in which the goal of the primary care physician (PCP) is to reduce patient referrals to specialists and thereby reduce costs, is not an adequate system in which to practice medicine. However, returning to the pre-managed care model of uncoordinated open access to specialists is a poor solution. The primary care model should be retained, but PCPs should be transformed from gatekeepers into coordinators of care, in which the goal of the PCP is to integrate both primary and specialty care to improve quality. Changes in the PCP's daily work process, as well as the referral and payment processes, need to be implemented to reach this goal. This model would eliminate the requirement that referrals to specialists be authorized by the primary care physician or managed care organization. Financial incentives would be needed, eg, to encourage PCPs to provide management of complex cases and discourage both over-referral and underreferral to specialists. Budgeting specialists should control excess costs that might be created by the elimination of the primary care gatekeeper. Pilot projects are needed to test and refine this model of PCP as coordinator of care.
Case Management↗
Role of distinct mitogen-activated protein kinase pathways and cooperation between Ets-2, ATF-2, and Jun family members in human urokinase-type plasminogen activator gene induction by interleukin-1 and tetradecanoyl phorbol acetate.
We have investigated the in vivo and in vitro regulation of the human urokinase-type plasminogen activator (uPA) gene by interleukin-1 (IL-1) and analyzed the transcription factors and signalling pathways involved in the response of the -2.0-kb uPA enhancer to IL-1 induction and to tetradecanoyl phorbol acetate (TPA) induction. Mutational analysis showed the cooperative activity of the Ets-binding site (EBS) and the two AP-1 elements of the enhancer. The results reveal that the EBS is required for the response to both inducers mediated by Ets-2, which is regulated at a level subsequent to DNA binding, by an IL-1- and phorbol ester-inducible transactivation domain. Both the IL-1 and the TPA-mediated induction result in a drastic increase of AP-1 binding to the downstream site of the enhancer (uPA 3' TPA-responsive element), while a mostly qualitative change, resulting from the interplay between ATF-2 homodimers and c-Jun-ATF-2 heterodimers, takes place at the upstream AP-1 element. The analysis of two distinct mitogen-activated protein kinase pathways shows that stress-activated protein kinase-Jun N-terminal kinase activation, resulting in the phosphorylation of ATF-2, c-Jun, and JunD, is required not only for the IL-1- but also for the TPA-dependent induction, while the extracellular signal-related kinase 1 (ERK-1) and ERK-2 activation is involved in the TPA- but not in the IL-1-dependent stimulation of the uPA enhancer.
Activating Transcription Factor 2↗
Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression.
We have investigated the role of the NFkappaB complex in the process of thyroid carcinogenesis by analysing thyroid carcinoma cell lines. A significant increase in p65 NFkappaB mRNA and protein expression, compared to normal thyroid cultures or tissue, was found in all of the cancer cell lines. Conversely, only a modest increase in the p50 NFkappaB mRNA and protein was found in most, but not all carcinoma cell lines. The block of p65 protein synthesis with specific antisense oligonucleotides greatly reduced the ability of two undifferentiated carcinoma cell lines to form colonies in agar and reduced their growth rate. On the other hand, no effect was observed in the same cell lines when treated with p50 specific antisense oligonucleotides. These inhibitory effects seem to be mediated by the suppression of c-myc gene expression, since treatment with antisense oligonucleotides for p65 gene interfered negatively with c-myc gene expression. Our results indicate that activation of the NFkappaB complex by overexpression of p65 plays a critical role in the process of thyroid cell transformation.
Down-Regulation↗
Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.
The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.
Animals↗
NF-kappa B-mediated regulation of urokinase gene expression by PMA and TNF-alpha in human A549 cells.
Binding sites for different transcription factors have been identified in the regulatory region of the human uPA gene. We investigated the role of NF-kappa B and AP-1 families of transcription factors in the induction of uPA mRNA by TNF-alpha and PMA in the A549 cell line constitutively expressing uPA mRNA and protein. Using the protein synthesis inhibitor cycloheximide and the antioxidant PDTC, that have an opposite effect on NF-kappa B and AP-1 activation, we showed that uPA mRNA induction by TNF-alpha and PMA in the A549 cell line is mainly due to NF-kappa B activation.
Antioxidants↗
Canaries in a coal mine: California physician groups and competition.
Health care organizations may compete by developing organized processes to improve quality and increase efficiency, or may focus on growing to increase negotiating leverage and on controlling costs through withholding appropriate care and avoiding sick patients. This paper describes key ways in which public and private policy decisions create incentives that influence the competitive focus of physician groups in California, a state in which physician groups and health maintenance organizations are prevalent. These policies do not manage competition in optimal ways: They reward groups for market leverage and controlling costs while failing to fully reward quality and efficiency.
California↗