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F Adami

Publications and source records attributed to F Adami.

At least 37 records · Page 2Linked to original sources

Leukemic cells in hairy cell leukemia and B cell chronic lymphocytic leukemia release soluble TNF receptors.

The two tumor necrosis factor receptors (TNF-Rs) exist in their soluble form in different biological fluids. In this study we investigated the concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) in the culture supernatants of leukemic cells and in the serum obtained from 33 patients: 12 with hairy cell leukemia (HCL) and 21 with B cell chronic lymphocytic leukemia (B-CLL). In seven patients with HCL, sTNF-Rs were also evaluated following in vivo treatment with interferon-alpha (IFN-alpha). Purified leukemic cells from patients with HCL and B-CLL spontaneously released sTNF-R75 but not sTNF-R55. The levels of sTNF-R75 were higher in supernatants obtained from cultured hairy cells than from cultures of B-CLL cells. The shedding of sTNF-R75 was further increased both in HCL and B-CLL subjects by some B cell-related stimuli, including BCGF, PMA, SAC and was partially inhibited by IFN-alpha in patients with HCL. Sera from HCL patients presented increased levels of both sTNF-Rs with respect to normal controls. Treatment of HCL patients with IFN-alpha resulted in a decrease in serum levels of sTNF-Rs, particularly sTNF-R75. These findings suggest that leukemic cells account for the increased serum levels of sTNF-R75 observed in patients with HCL and B-CLL, but not for sTNF-R55.

Antigens, CD↗

Expression and regulation of tumor necrosis factor, interleukin-2, and hematopoietic growth factor receptors in B-cell chronic lymphocytic leukemia.

Leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) express tumor necrosis factor (TNF) and interleukin-2 (IL-2) receptors, but only a low proliferative response can be elicited in vitro by TNF alpha and IL-2. To investigate the functional properties of IL-2 and TNF alpha on leukemic B cells, we evaluated (1) the regulation of expression of TNF receptors (TNF-R) and IL-2 receptors on leukemic B cells after culture with TNF alpha and IL-2; (2) the effect of the combination of TNF alpha and IL-2 in a proliferative in vitro assay; and (3) the expression and regulation by these cytokines of receptors for hematopoietic factors, including IL-3, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Flow cytometry analysis showed that freshly isolated leukemic cells from B-CLL patients bear the 75-kD TNF-R and the 55-kD IL-2R; TNF alpha was able to upregulate the 55-kD IL-2R but not the 75-kD TNF-R. On the other hand, IL-2 was not able to modify the expression of the above-mentioned receptors. Although each cytokine alone was unable to induce a relevant proliferation of leukemic cells, a synergistic proliferative effect was detected when these cytokines were used in combination. Leukemic B cells from B-CLL patients bear receptors for hematopoietic factors (IL-3, G-CSF, and GM-CSF) that were upregulated in vitro by IL-2 via the 55-kD IL-2R. On the contrary, TNF alpha was unable to affect the expression of the above-mentioned receptors. These results indicate (1) that IL-2 and TNF receptors are related to each other on leukemic cells in B-CLL and (2) that the IL-2R is involved in the regulation of other structures, ie, CSF receptors, thus pointing to another functional role of this receptor complex and the related cytokine in leukemic cells.

Aged↗

Serum levels of tumour necrosis factor-alpha in patients with B-cell chronic lymphocytic leukaemia.

Serum levels of tumour necrosis factor-alpha (TNF-alpha) have been evaluated in the peripheral blood of 91 patients with B-cell chronic lymphocytic leukaemia (B-CLL), and have been correlated with the clinical stage (according to Rai's staging system) and relevant haematological and immunological data. Increased values were detected, compared to 36 normal age-matched controls (36 pg/ml +/- 5 versus 0.11 pg/ml +/- 0.08; P < 0.05). An increase of TNF-alpha serum levels was observed in all stages including stage 0, with a progressive increase in relation to the stage of the disease. A significant relationship between serum TNF-alpha levels and the number of circulating monocytes (P < 0.002) and an inverse correlation with the level of the haemoglobin (P < 0.001) was established, as defined by the Pearson's correlation test. In contrast, no correlation was observed between TNF-alpha serum levels and the other parameters taken into account, including the white blood cell and platelet counts, the absolute number of peripheral blood (PB) lymphocytes, CD5+ B lymphocytes, CD57+ lymphocytes, serum levels of lactic dehydrogenase, total serum immunoglobulins and the serum levels of IgG, IgA and IgM. These data suggest that, in addition to the B-CLL neoplastic cells, the PB monocytes may be involved in the release of TNF-alpha.

Aged↗

Expression and functional role of tumor necrosis factor receptors on leukemic cells from patients with type B chronic lymphoproliferative disorders.

Two receptors for tumor necrosis factor (TNF) with different molecular weight (75-Kd and 55-Kd) and binding affinity have been recently discovered. To investigate the distribution and the functional role of these receptors on leukemic B cells from hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL) patients, we evaluated: (1) the cytofluorimetric pattern of uncultured and cultured leukemic B cells incubated with utr-1 and htr-9 monoclonal antibodies (MoAbs), which specifically recognize the 75-Kd and 55-Kd TNF receptors (TNFR), respectively; (2) the effect of TNF-alpha and TNF-beta on leukemic B cells in an in vitro proliferation assay; (3) the role of anti-TNFR MoAbs on TNF-alpha and TNF-beta-driven B-cell growth; and (4) the proliferative effect of utr-1 and htr-9 MoAbs on in vitro cultured leukemic cells. Our study shows that the high affinity (75-Kd) but not the low affinity (55-Kd) TNFR molecules are expressed on freshly isolated leukemic B cells recovered from HCL and B-CLL patients. The expression of these receptors was neither upregulated nor downregulated by different stimuli, including TNF-alpha, TNF-beta, B-cell growth factor, and interleukin-2. TNF-alpha efficiently triggers the proliferation of HC and, to a lesser extent, the growth of B-CLL cells. TNF-beta was also able to transduce the proliferative signal in HCL, but not in B-CLL patients. TNF-alpha- and TNF-beta-driven B-cell proliferation was inhibited by the preincubation of leukemic B cells with utr-1 but not htr-9 MoAb. Moreover, anti-75-Kd, but not anti-55-Kd TNFR MoAb, was able to trigger the proliferation of leukemic B cells, and in particular of HC. These results show that leukemic B cells from patients with HCL and B-CLL are equipped with a fully functional high affinity TNFR.

Aged↗

A CD5+ leukemic lymphoma with monocytoid features: an unusual B-cell lymphoma mimicking hairy-cell leukemia.

A case of lymphoma presenting with features shared by hairy cell leukemia (HCL) and its variant, intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) is described. Clinical presentation and the morphological findings observed in peripheral blood and in bone marrow biopsy suggested an HCL; however, the tartrate-resistant acid phosphatase negativity of peripheral blood lymphocytes, the histologic pattern observed in the spleen, and the immunophenotyping of peripheral blood, spleen and bone marrow neoplastic lymphocytes (expression of CD5 and lack of CD25), were strongly against this hypothesis. The clinical course was aggressive. This report emphasizes the concept of the equivocal presentation of some 'low-grade' B-cell lymphomas. It is further pointed out that, even with complete and exhaustive morphological and immunological analyses, atypical cases may be encountered.

Aged↗

Expression and functional role of the p75 interleukin 2 receptor chain on leukemic hairy cells.

Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2 receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain which binds IL-2 with intermediate affinity and plays a crucial role in transducing the message to the cell. For this purpose, we tested highly enriched leukemic HC from six hairy cell leukemia patients for the presence of IL-2R transcripts and for the expression of the p55 and p75 IL-2R chains on their surface membrane by flow cytometry and immunoprecipitation analyses. The functional role of IL-2 in the regulation of HC proliferation was also investigated. Our results indicate that freshly isolated HC express detectable messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A mixture of two specific mAb was able to immunoprecipitate detectable amounts of p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of several concentrations of IL-2 a low proliferative response was observed. Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75 IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide direct evidence of the expression of different IL-2 receptors on leukemic HC and suggest that these molecules might play a role in leukemic cell growth.

Adult↗

Transbronchial biopsy in sarcoidosis: the role of immunohistochemical analysis for granuloma detection.

In this study 27 transbronchial biopsy specimens obtained from patients with clinical and/or laboratory features suggestive for sarcoidosis were analysed with conventional morphology and immunohistochemistry comparing the sensitivity and reproducibility of the two methods. A limited panel of monoclonal antibodies recognizing epitopes resistant to conventional fixation and embedment procedures were used (CD45R0, CD68, anti-cheratin, anti-collagen IV). All specimens were independently observed by two different pathologists. On the basis of the recognition of bona-fide noncaseating granulomas, 9 cases were uniformly judged as positive, 10 cases as negative, but 8 cases were considered doubtful. Immunohistochemical analysis reliably demonstrated the presence of epithelioid cells in 3 of these cases and absence in 5. These data suggest that the use of a limited immunohistochemical analysis can significantly improve histological diagnosis of sarcoidosis on small transbronchial biopsies using conventional routine material.

Antigens, CD↗

Tumor necrosis factor-alpha and B-cell growth factor induce leukemic hairy cells to proliferate in vitro.

To clarify the mechanisms accounting for the hairy cell proliferation, in five patients with hairy cell leukemia (HCL), we evaluated the ability of neoplastic cells to proliferate in vitro in response to tumor necrosis factor-alpha (TNF-alpha), B-cell growth factor (BCGF), and interleukin 4 (IL-4). In addition, supernatants recovered from cultures of unstimulated hairy cells were tested for the capability to induce the proliferation of allogeneic hairy cells. We demonstrated that TNF-alpha and BCGF were able to induce the in vitro growth of hairy cells (stimulation index (SI) ranging, at different concentrations, from 1.6 to 10.7 and from 1.6 to 25.1 for TNF-alpha and BCGF, respectively). IL-4 did not show any proliferative effect on hairy cells. When unstimulated hairy cell supernatants were tested for the proliferative activity on allogeneic hairy cells, we demonstrated a low proliferative effect that was not inhibited by an anti-TNF-alpha antibody. Our findings demonstrate that unstimulated hairy cells proliferate in vitro in response to TNF-alpha and BCGF, thus suggesting that these cytokines could be involved in an autocrine model of cell proliferation.

Cell Division↗

Serum levels of soluble CD8 are increased in patients with B chronic lymphocytic leukemia.

Serum levels of the soluble form of the CD8 (s-CD8) antigen were evaluated in the peripheral blood of 44 patients with B-CLL, using an enzyme-linked immunosorbent assay, and were correlated with clinical features and relevant hematological and immunological data. Increased values were observed with respect to normal age-matched controls (mean +/- S.E.M. 603 U/ml +/- 81 vs. 315 U/ml +/- 31, respectively; P less than 0.0001). This increase was observed in all stages of the disease, excluding stage 0 (mean 277 U/ml +/- 45). A general trend pointing to lower values overall in patients with less invasive disease was observed. In fact, the rank correlation test showed that the serum levels of s-CD8 correlate significantly with the WBC counts, the CD4/CD8 ratio, and also with the levels of serum immunoglobulins. On the contrary, no correlation was observed between s-CD8 levels and the absolute number of circulating CD8+ cells in individual cases. Therefore, the increase of s-CD8 is unlikely to be a mere expression of the increase of the CD8 cell number, but seems related to an increase of the activation phenomena involving the CD8+ T cell subset.

Antigens, Differentiation, T-Lymphocyte↗

[Juvenile rheumatoid arthritis appearing after hepatitis. Causal or casual relationship].

High fever, spleen and lymph node enlargement, and joint pains that assumed the character of rheumatoid arthritis in the ensuing months were noted after a viral hepatitis episode in a 21-year-old woman. Serious anaemia and myocarditis also appeared when the picture was at its worst. A lymphoma was suspected, and the spleen and some abdominal lymph nodes were removed. These displayed signs of intense follicular reaction unaccompanied by atypia. The possibility that juvenile rheumatoid arthritis may be triggered by hepatitis is examined.

Adult↗

PHA-induced, antibody-mediated and spontaneous cellular cytotoxicity toward chicken red blood cells in solid carcinomas and glioblastomas.

In 29 bronchogenic, 22 esophageal carcinomas and 17 glioblastoma peripheral mononuclear cells cytotoxicity toward chicken red blood cells was studied under three different sets of conditions: spontaneously induced, PHA induced, or mediated by antibodies toward target cells lysis. Cultures were 48 hours. While the cytotoxicity induced by mitogen and that medicated by antibody are diminished when compared to the control groups, spontaneous cytotoxicity shows values significantly higher in all the tumoral forms examined. Kinetically this type of lysis shows an already increased release of isotope after 24 hours and a steady rise in the successive hours. After depletion of adherent cells the mononuclear elements lose most of their lytic power. This datum, which contrasts with the diminished spontaneous cytotoxicity toward tumoral cells frequently described in the course of neoplasm, underlines the heterogenicity of the element responsible for SCMC and the diverse effects that the disease provokes on cell function.

Animals↗