Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: Implications for pathogenesis.

OBJECTIVE: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis (LCH) of unknown etiology, characterized by diffuse histiocyte infiltration of bones and soft tissue. The purpose of this study was to assess cell proliferation and expression of cytokines, chemokines, and chemokine receptors that may potentially be important in histiocyte accumulation in ECD lesions. METHODS: Biopsies were performed on 3 patients with ECD. The diagnosis of the disease was based on clinical signs including typical radiologic osteosclerosis, and on the detection of foamy CD68+,CD1a- non-Langerhans' cell histiocytes on histologic examination. The expression of the proliferation marker Ki-67 as well as of selected chemokine/chemokine receptor pairs and cytokines was analyzed by immunohistochemistry. RESULTS: In all samples, Ki-67 was undetectable in CD68+ histiocytes. Conversely, these cells expressed the chemokines CCL2 (monocyte chemotactic protein 1), CCL4/macrophage inflammatory protein 1beta (MIP-1beta), CCL5/RANTES, CCL20/MIP-3alpha, and CCL19/MIP-3beta, and their counter-receptors CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Moreover, ECD histiocytes expressed interferon-gamma-inducible 10-kd protein (CXCL10), which is specifically induced by interferon-gamma, and interleukin-6 and RANKL, which are both implicated in bone remodeling. Finally, all cases showed a Th1-type lymphocyte infiltrate. CONCLUSION: Our data indicate that, similar to LCH, ECD lesions are characterized by a complex cytokine and chemokine network, which may orchestrate histiocyte activation and accumulation through an autocrine loop and contribute to the pathogenesis of the disease

Microbiological and calorimetric investigations on degraded marbles from the C\ue0 d'Oro facade (Venice)

Microbiological, physicochemical and biochemical investigations were carried out on degraded marble samples from the Ca d'Oro facade (Venice) in order to verify the presence of biodeterioration agents. The aerobic heterotrophic bacteria (mean value 10(5) CFU/g marble), which were also observed by scanning electron microscope (SEM), were characterized as belonging to the Micrococcus and Bacillus genera. Nitrifying and sulphooxidizing bacteria were not found in any samples. The fungi (mean value 10(2) CFU/g marble) were attributed to the Penicillium and Aspergillus genera. Enrichment cultures revealed the presence of photosynthetic microorganisms belonging to the div. Cyanophyta and Chlorophyta. The metabolic activity of the microorganisms derived from the cultural tests, was confirmed by the ATP content extracted directly from the powdered marble samples (average 3170 pg ATP per g marble). Microbiological alterations of stone are the result of the metabolic activity of the microorganisms, whose heat production is an expression of this activity. Confirmation of the presence of the microorganisms on the degraded marble samples was, therefore, obtained by calorimetric investigations, which revealed that the process is completely exothermic and can be divided into two phases: the first showed the attainment of a plateau, typical of a zero-order reaction; the second was characterized by a peak followed by an abrupt arrest

Research on chromatic alterations of marbles from the fountain of Villa-Litta (Lainate, Italy)

The fountain of Galatea at Villa Litta (Lainate, Milan) showed abundant flowerings of black spots accompanied by little red spots on the marble surface. On these altered areas no chemolithotrophic bacteria were found, although many heterotrophic microorganisms were present. The high number of colonies of Alternaria alternata isolated by black spots may induce us to believe that this fungal strain is the cause of such alteration. From the red areas however, in spite of the high number of heterotrophic bacteria (10(6) CFU/g marble), only a few red pigmented microbial strains classified as Micrococcus roseus, Flavobacterium sp. and Rhodotorula minuta were isolated. The resonance Raman spectra carried out on the red spots showed the absence of carotenoids, whilst the normal Raman spectra showed the presence of minium (Pb3O4). The lead probably derives from the pipes of the fountain. Two biocides, Neo-Desogen and Cequartyl, were tested by minimum inhibitory concentration on the isolated microorganisms: R. minuta showed a higher sensitivity to both biocides compared with A. alternata, whilst M. roseus and Flavobacterium sp. showed more sensitivity towards Cequartyl. Three years after treatment with Neo-Desogen, small black and red spots were found. Microbiological analyses and ATP determination showed a new colonization of the heterotrophic bacteria (10(6) CFU/g) corresponding to the red spots, and of Mycetes (10(3) CFU/g) corresponding to the black ones

IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients

<p><b>Objectives</b>: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre.</p> <p><b>Method</b>: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as ‘definite’ or ‘possible’ according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI).</p> <p><b>Results</b>: Forty-one patients (15 females, 26 males) were included in this study: 26 with ‘definite’ IgG4-RD and 15 with ‘possible’ IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24–51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking.</p> <p><b>Conclusions</b>: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.</p