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We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n?=?398) and multiple primary melanoma (MPM, n?=?95). The overall frequency of CDKN2A mutations was 15.2, and four-fold higher in MPM than in SPM cases (OR?=?4.27; 95 CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR ?25C?>?T, ?21C?>?T, ?67G?>?C, IVS1 +37G?>?C); the novel 5'UTR ?21C?>?T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7 versus 6.6). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population.

THE presence of androgen receptors on synovial macrophages in human normal and rheumatoid synovial tissues has been described previously. It is now reported that primary cultured human macrophages obtained from normal and rheumatoid synovia express functional androgen receptors. We have investigated the capacity of cultured macrophages to metabolize androgens and have found that these cells were capable of metabolizing testosterone to the bioactive metabolite dihydrotestosterone. Therefore, macrophages contain the key enzymes of steroidogenesis, in particular the 5α-treductase. Furthermore, interleukin-1β production by primary cultured rheumatoid macrophages was analysed, following exposure to physiological concentrations of testosterone (10−8 M). A significant decrease of IL-1β levels in conditioned media after 24 h (p < 0.05) was observed. It is concluded that androgens may act directly on human macrophages and may interfere with some of their functions via receptor-dependent mechanisms.

Summary The in vitro growth of both circulating granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells was assessed in 29 individuals infected with the human immunodeficiency virus (HIV) at different stages of infection. The effects of autologous T lymphocytes, adherent cells, and serum on the in vitro growth of hematopoietic progenitor cells were also investigated. Compared with normal controls, baseline growth was significantly reduced for both CFU-GM and BFU-E in HIV-infected patients, independent of the clinical stage of the disease. In HIV-infected subjects depletion of autologous T cells was associated with a significant increase of progenitor cell growth. Similar results were observed after selective depletion of CD 8 + T cells, while readdition of T cells to T-depleted mononuclear cells reduced the number of CFU-GM. A dose-dependent colony inhibitory activity was found in conditioned medium of T cells from HIV-infected subjects. Neither autologous adherent cells nor serum from either HIV+ or HIV§ubjects had any significant effect on the in vitro growth of CFU-GM. These results indicate that the in vitro growth of circulating hematopoietic progenitor cells is impaired even in the early stages of HIV infection, and that autologous T cells exert an inhibitory effect on the in vitro growth of progenitor cells, possibly via soluble mediator(s).

Adult-onset Still's disease is characterized by high spiking fever, evanescent maculopapular rash and arthritis. Several recent reports have associated its development with a variety of infectious agents. We describe the case of a 25-year old woman presenting high fever, maculopapular rash and seronegative polyarthritis associated with lymphoadenopathy, splenomegaly and neutrophil leucocytosis together with acute acquired toxoplasmosis. Other causes of systemic illness were excluded by appropriate laboratory, radiological and histological investigations. Clinical, radiological and laboratory findings as well as possible etiopathogenetic correlations among both pathological conditions are discussed. Toxoplasma gondii should be considered as a further possible triggering agent associated with the development of adult-onset Still's disease.