Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.

Chemokines have been shown to play an important role in both the adhesion and migration of numerous leukocytic cell types, including granulocytes, monocytes, mast cells, and T lymphocytes. However, the biologic effects of chemokines on NK cells remain to be defined. Chemotaxis studies using purified human NK cells and a panel of human recombinant chemokines revealed that macrophage inflammatory protein (MIP)-1 alpha and IFN-inducible protein-10 (IP-10) are potent NK cell chemoattractants in vitro.

Rational drug design: the proteinase inhibitors.

Human immunodeficiency virus (HIV) proteinase is a promising target for the rational development of drugs against the acquired immunodeficiency syndrome (AIDS), since this enzyme is necessary for viral maturation, and its inhibition could lead to cessation of viral replication. Rational drug design combines chemical synthesis of compounds with structure determination methods, including protein crystallography. When the crystal structure of the HIV proteinase was determined, many research laboratories began designing drugs that would be effective inhibitors of the enzyme, and many such inhibitors were produced.

Protective effects of selenium on cadmium toxicity in rats: role of altered toxicokinetics and metallothionein.

Selenium prevents the toxicity of the carcinogenic metal cadmium through undefined mechanisms. In this study, we determined the effects of selenium on cadmium toxicokinetics and on the ability of cadmium to induce metallothionein, a metal-binding protein that is thought to confer tolerance to cadmium toxicity. To assess the acute protective effects of selenium, male Wistar (WF/NCr) rats were given selenium (as SeO2; 10 mumol/kg, sc) at -24, 0, and +24 h relative to cadmium (as CdCl2; 45 mumol/kg, sc).

A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants.

Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.

Crystal structure of recombinant rabbit interferon-gamma at 2.7-A resolution.

The crystal structure of recombinant rabbit interferon-gamma was solved by the multiple isomorphous replacement technique at 2.7-A resolution and refined to a crystallographic R-factor of 26.2%.

Phase I evaluation of recombinant tumor necrosis factor given in combination with recombinant interferon-gamma.

In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.

Gene regulation and genetic susceptibility to neoplastic transformation: AP-1 and p80 expression in JB6 cells.

The mouse epidermal JB6 cell system consists of clonal genetic variants that are sensitive (P+) or resistant (P-) to the promotion of neoplastic transformation by phorbol esters and other tumor-promoting agents. P+ cells display AP-1-dependent phorbol-ester-inducible transactivation of gene expression, whereas P- cells have a defect in transactivation. Transfection of promotion sensitivity gene pro-1 into P- cells reconstituted both P+ phenotype and AP-1-dependent phorbol-ester-inducible transactivation.

Prevention of nickel subsulfide carcinogenesis by local administration of Mycobacterium bovis antigen in male F344/NCr rats.

This study was designed to determine the effect of local inflammation on nickel subsulfide (Ni3S2) carcinogenesis. Male F344/NCr rats, 6-week-old, 20 rats/group, received a single i.m.

Mechanisms of nickel carcinogenesis. Interaction of Ni(II) with 2'-deoxynucleosides and 2'-deoxynucleotides.

Interactions of Ni(II) with the base moieties of 2'-deoxynucleosides and 2'-deoxynucleotides were studied by means of UV difference spectroscopy in order to elucidate the mechanisms of site-specific enhancement by Ni(II) of DNA base oxidation with active oxygen species, observed previously (Kasprzak et al., Cancer Res., 49 (1989) 5964; Carcinogenesis, 11 (1990) 647).

Binding of trans-dominant mutant Rev protein of human immunodeficiency virus type 1 to the cis-acting Rev-responsive element does not affect the fate of viral mRNA.

The binding of Rev protein of human immunodeficiency virus type 1 (HIV-1) to the cis-acting Rev-responsive element (RRE) was compared to the binding of a trans-dominant Rev mutant. RevBL, which inhibits Rev function. Rev and RevBL expressed in bacteria were purified and shown to bind in vitro to the RRE with similar affinities.