Elevated serum macrophage inhibitory factor-related protein (MRP) 8/14 levels in advanced HIV infection and during disease exacerbation.

UNLABELLED: To assess the value of MRP 8, MRP 14, and MRP 8/14 serum concentrations as markers of disease progression in HIV infection and as markers of intercurrent infections. DESIGN: We measured MRP 8, MRP 14, and MRP 8/14 serum concentrations in 184 HIV-infected patients in various stages of disease with or without disease exacerbation and in 50 healthy control subjects. In clinically stable HIV-infection correlations of MRP levels with stage of HIV disease, CD4 counts, p24 antigen, and beta-2 microglobulin levels were studied. In patients with intercurrent illnesses, correlations of MRP levels with type of disease exacerbation and with CRP were calculated and compared with those found in stable HIV infection. RESULTS: MRP 8/14 levels were significantly elevated and MRP 8 levels slightly decreased in stable HIV infection compared with HIV-negative controls. The CD4 cell count and MRP 8/14 levels correlated significantly in patients with AIDS. Despite higher values of MRP 8/14 during advanced disease, these were not significant predictors of progression to death. In patients with acute infections, MRP 8/14 levels were significantly elevated, compared with patients with illnesses of noninfectious origin. Levels of MRP 8/14 associated with acute infections were significantly higher in patients with AIDS than in patients during earlier stages of HIV infection. CONCLUSIONS: Both stable HIV infection and advanced immunedeficiency are associated with an elevation of the MRP 8/14 complex and probably with a decline of MRP 8 serum levels. MRP 8/14 is preserved as a marker of acute infection in immunecompromised patients.

A phase I/IIA clinical study with a chimeric mouse-human monoclonal antibody to the V3 loop of human immunodeficiency virus type 1 gp120.

A phase I/IIA clinical trial with the chimeric mouse-human monoclonal antibody CGP 47,439 to the principal neutralization determinant in the V3 region of human immunodeficiency virus type 1 (HIV-1) strain IIIB envelope protein gp120 is reported. The trial was an uncontrolled single-center, open-label, multidose tolerability, immunogenicity, and pharmacokinetic study in homosexual men with advanced HIV disease. Patient groups were formed on the basis of the reactivity of the antibody with the gp120 of their HIV-1 isolates. Intravenous infusions of 1, 10, and 25 mg of antibody were followed by seven escalated doses of 50, 100, and 200 mg, every 3 weeks. The antibody was well tolerated; no toxicity was observed. Some patients showed a transient but insignificant antibody response to the antibody with no apparent adverse reactions or accelerated elimination of it. Substantial serum levels of the antibody were maintained with a mean t1/2 beta of 8-16 days. A virus burden reduction was observed in some patients.

Mutations in the hormone regulatory element of mouse mammary tumor virus differentially affect the response to progestins, androgens, and glucocorticoids.

Transcription of the mouse mammary tumor virus DNA is known to be induced by several steroid hormones. Using chimeric MMTV plasmids containing mutations within the hormone regulatory element, we have previously studied the regions required for the glucocorticoid response in mouse fibroblasts. Here we report the characterization of elements essential for the stimulation by progestins and androgens as compared with glucocorticoids. The same set of mutant plasmids was transfected into the human mammary tumor cell line T47D, and the specific transcripts were analyzed by an S1 nuclease protection assay. Androgen-mediated stimulation, although weak, showed an extended sensitivity to mutations, with a slight preference for the proximal region. The results with progestin suggest that sequences within all the described sites protected by the receptor in vitro are required and that the promoter-proximal region (-128 to -78 from the RNA start site) is more important than the distal one (-190 to -160). Moreover, a binding site for nuclear factor I was not required for the progestin response, whereas it was required for glucocorticoids. Thus, the various steroid receptors play a role in the differential regulation of mouse mammary tumor virus transcription by recognizing distinct sequence differences in the hormone regulatory element and interacting with different factors bound to the promoter.