Biomedical subjects
Publications and source records attributed to M Ferrarini.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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In previous studies we described a patient with Burkitt's lymphoma and AIDS, whose cells recognized a molecule expressed by normal and malignant breast cells. In the present study, we identified this antigen by two-dimensional (2-D) electrophoresis and Western blotting using the antibody produced by lymphoma cells. The antigen so identified consisted of two clusters of spots with a molecular mass (Mr) of 60 and 50 kDa, respectively. Preparative immobilized pH gradient (IPG) was subsequently used to isolate the clusters of spots of higher molecular masses, from which peptide fragments of approximately 10 aa were separated on reverse-phase chromatography and sequenced. This procedure enabled the identification of the antigen recognized by the lymphoma cells as HSP-60. By means of serological analyses it was possible to identify the lower molecular mass cluster of spots as a molecule related to HSP-60. It is hypothesized that this molecule is a membrane form of HSP-60 that differs from HSP-60 in a COOH terminal portion.
Athymic nude (nu/nu) mice are widely employed for the heterotransplantation of human tumor cell lines established in vitro and tumor cells directly grafted from patients. By contrast, hemopoietic malignancies have consistently proved difficult to transplant and well-characterized human leukemias suitable for studies in nude mice are scarce. We report here our experience with subcutaneous xenotransplantation of human neoplastic cells into nu/nu mice immunosuppressed through sublethal irradiation and splenectomy (SI-nu/nu) and with an additional injection of anti-Asialo-GM1 antibodies (SIA-nu/nu) in order to eliminate natural killer activity. Thirteen out of 16 continuous cell lines established in vitro from solid tumors and 7 out of 14 human tumors obtained from fragments of surgical specimens formed a progressively growing tumor in SI-nu/nu mice. Six out of 8 in vitro established human leukemic cell lines and 5 out of 18 neoplastic hematopoietic cells directly xenotransplanted from the patient grew SIA-nu/nu mice. When the membrane and chromosome markers of neoplastic cells that grew into the mice were evaluated, only marginal differences with those of the original tumors were found. In addition, when interfering factors alter the histological aspect of the primary tumor, xenotransplantation may also be of some help in histological diagnosis. By using SI- and SIA-nu/nu mice, it is thus possible to build up several new in vivo experimental systems with fresh human tumors that may be of value in studying the efficacy of differentiation factors and immunological maneuvers on the in vivo growth of human tumors.
Human NK cells, besides mediating cytotoxic functions, can exert a number of regulatory activities on the proliferation and maturation of hematopoietic stem cells through the release of soluble factors. A preliminary characterization of these factors demonstrates that NK cell-derived colony stimulating activities (CSA) are represented by GM-CSF and IL3, whereas the colony inhibiting activity (CIA) produced by NK cells is identifiable as TNF. CSA is mainly released by resting NK cells, while, following appropriate activation, the latter cells produce large amounts of CIA. NK cells also influence B cell activation by releasing a 50 kd BCGF and a 26 kd BCDF. The latter factor, which is active in vitro only in the presence of IL2, is identifiable as IL6. The production of regulatory cytokines by NK cells may have some bearing on the pathogenesis of a number of autoimmune disorders.
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Two different methods, immunofluorescence and lactoperoxidase-catalysed radioiodination, were used to investigate mIg on two different myeloma cell lines. The data indicate that, even though both techniques are highly sensitive, different results can be obtained in the same cell line depending on the technique employed.
In this study we have investigated the efficacy and safety of cyclosporin A (CyA) in a group of pediatric patients with juvenile chronic arthritis (JCA, 9 cases) and polymyositis-dermatomyositis (PM-DM, 3 cases). Of the 9 JCA patients, 7 had the systemic and 2 the polyarticular form of the disease. All of the patients received CyA after the failure of corticosteroids and/or cytotoxic drugs. CyA was administered for 9 to 48 months at a mean dose of 5 mg/kg/day. Ten patients received corticosteroids with CyA. The results of CyA treatment were satisfactory overall, both in the PM-DM patients and in the JCA patients, as assessed by clinical and laboratory evaluation. CyA-related side effects included alopecia, hypertension, hypertrichosis, tremors, and hirsutism. One JCA patient developed polyserositis with hypoproteinemia of unknown origin while receiving CyA. CyA blood levels did not correlate with clinical efficacy and/or side effects. This study suggests that CyA represents a promising agent for the treatment of JCA and childhood PM-DM.
BACKGROUND AND OBJECTIVE: The lymph nodes involved in classic Hodgkin's disease (HD), i.e. mixed cellularity (MC) and nodular sclerosis (NS) subtypes, usually contain few (1-2%) Reed-Sternberg (RS) cells scattered in a background of lymphocytes, eosinophils, plasma cells and neutrophils. CD4+ T-lymphocytes are increased in number, express activation markers and cluster around RS cells. The presence of eosinophilia in most HD patients and the presence of hyper-IgE in a subset of them may suggest that activated lymph node T cells release large amounts of IL5 and IL4, respectively. METHODS: The expression of four T-cell-associated cytokine genes, i.e. interleukin (IL)2, IL4, IL5 and interferon (IFN)-gamma, in frozen sections of 14 HD (7 MC, 7 NS) and 10 reactive lymph nodes was investigated by qualitative and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). T-cell clones were also raised from purified CD4+ lymphocytes of one HD lymph node and one reactive lymph node and tested for IL2, IL4, IL5 and IFN-gamma secretion in culture supernatants by immunoassays. RESULTS: The transcripts of all the cytokine genes were detected in every lymph node irrespective of the HD or reactive nature. HD or reactive lymph node-derived CD4+ T-cell clones released the four cytokines according to a predominant T-helper (Th)0-type pattern. In more than half of the lymph nodes of either HD or reactive nature, there was a predominance of IL4 over IFN-gamma mRNA production (Th2-type pattern). In the remaining HD or reactive lymphadenopathies, either a balanced IL4/IFN-gamma mRNA ratio (Th0-type pattern) or a predominance of IFN-gamma over IL4 mRNA expression (Th1-type pattern) was observed. INTERPRETATION AND CONCLUSIONS: The overall pattern of cytokine gene expression in classic HD is similar to that detected in reactive lymph nodes. Further studies are needed to determine whether differences in the absolute concentrations of cytokines released in HD versus reactive lymph nodes and the long-standing course of HD versus the self-limiting nature of reactive adenopathies may explain certain peculiar features of HD, such as eosinophilia, for example.