At least three distinct beta-adrenergic recep-

To determine the effects, if any, of the Zn-metalloprotease on virulence of Legionella pneumophila infection, an isogenic mutant deficient in protease (encoded by the proA gene) was tested in an Acanthamoeba cell model, in guinea-pig macrophages, and in a guinea-pig pneumonia model. The cloned proA gene was completely inactivated by insertion of a kanamycin-resistance cassette into the protease gene of L. pneumophila AA100. This mutated gene was then introduced into the L. pneumophila chromosome by allelic exchange to form the isogenic ProA- mutant AA200. AA200 showed no difference in its ability to enter, survive, or grow in Acanthamoeba and explanted guinea-pig macrophages; neither light nor electron microscopy revealed morphological differences in the eukaryotic cells infected with the protease mutant or the wild-type strains. The proA gene was found to be expressed in L. pneumophila during intracellular growth in amoebae by measuring the light produced from a truncated luxC gene fusion with the proA promoter. Virulence of the protease mutant was attenuated when tested in a guinea-pig model of infection employing the intratracheal inoculation method. AA200 was slower to cause death, grew to lower numbers in the lungs, resulted in less necrotic debris and a larger macrophage infiltrate, and was more likely to be found in association with macrophage vacuoles than the parent strain. Although deletion of the protease was not sufficient to completely abolish virulence in a guinea-pig model, the mutation caused a delay in the lethal effects of L. pneumophila and attenuated the infection.

No abstract

The nodular form of lymphocyte predominance Hodgkin's disease has been shown to be immunophenotypically distinct from the histologically diffuse form and from other types of Hodgkin's disease. We undertook a clinicopathological study of 73 cases to determine whether any clinical differences between the nodular and diffuse subtypes could be discerned. Patients with the diffuse form (n = 41) tended to have a course similar to that of other types of Hodgkin's disease; there were few relapses and only two deaths due to Hodgkin's disease. In contrast, patients with the nodular form (n = 32) had significantly more relapses, which were independent of stage or treatment and equally distributed up to 10 years after initial therapy. Despite the frequent relapses, patients with the nodular form had an indolent course, and there was only one death due to Hodgkin's disease. There were seven fatal second cancers and two non-neoplastic treatment-related deaths, equally distributed between the nodular and diffuse groups. We conclude that nodular lymphocyte predominance Hodgkin's disease may have important clinical as well as immunophenotypic differences from other forms of Hodgkin's disease, and that patients with this condition should be followed carefully because of the possibility of late relapse.