Publications

We characterized the effects of Leishmania infection on activation-induced translocation of protein kinase C (PKC) isoforms in murine bone marrow-derived macrophages. Although PKC-dependent gene expression was attenuated by infection, the distribution and translocation of PKC isoforms were unaffected. However, subsequent dissociation from membranes was substantially delayed for some isoforms, particularly PKCbeta.

BACKGROUND

Several changes can be anticipated in the practice of communicable disease control as a result of the health care delivery system's transition from a predominantly fee-for-service system to a predominantly managed care system. These changes will clearly involve clinical services provided by public health agencies, such as immunizations and diagnosis and treatment of tuberculosis and sexually transmitted diseases, as well as those that do not involve direct patient care, such as public health surveillance, disease investigation, outbreak control, contact tracing, public health laboratory services, and health education.

METHODS

In this paper I review the potential impact of managed care on each of these areas of communicable disease control and suggest strategies for minimizing adverse effects and maximizing potential areas of cooperation.

RESULTS

Examples of successful strategies include California's Medi-Cal managed care expansion, which allows local public health agencies to bill managed care organizations for the sexually transmitted disease, immunization, and confidential HIV services they provide to managed care beneficiaries. A different strategy is illustrated by the Pacific Business Group on Health, an employer-based purchasing group, that uses purchasing power to standardize the clinical preventive services benefit across all plans with which it contracts and to promote immunization goals.

CONCLUSION

This analysis and these examples suggest that the emergence of managed care as the predominant form of health care financing and delivery in the United States offers an important opportunity for public health.

MRL/lpr mice spontaneously develop an autoimmune disease with features of systemic lupus erythematosus. They also develop a lymphoproliferative disorder characterized by a massive accumulation of double-negative (DN) T cells that lack both CD4 and CD8. To clarify the role of CD4 in autoimmunity and lymphoproliferation in these mice, CD4-deficient MRL/lpr mice were generated. CD4-deficient MRL/lpr mice developed massive expansion of DN T cells in the blood, spleen, and lymph nodes, which significantly exceeded the degree of lymphoproliferation in CD4-expressing control MRL/lpr mice. Despite this lymphoproliferation, CD4-deficient MRL/lpr mice produced little, if any, antibodies to double-stranded DNA, and they had prolonged survival relative to CD4-expressing littermates. However, they eventually developed moderately severe nephritis, characterized by immunoglobulin and complement deposition in glomeruli, vasculitis, and renal infiltration by CD8+ T cells. These findings indicate that (1) lymphoproliferation in MRL/lpr mice does not require the expression of CD4; (2) autoantibody production in MRL/lpr mice is dependent on the expression of CD4 and not on the accumulation of DN T cells; and (3) the development of nephritis in MRL/lpr mice involves both CD4-dependent and CD4-independent mechanisms.

The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family. In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure. These rodents also show hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and infertility due to hypogonadotropic hypogonadisms. In humans, leptin deficiency due to a mutation in the leptin gene is associated with early-onset obesity. Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains. In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced. These results indicate that leptin is an important physiological regulator of several endocrine functions in humans.