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G Pizzolo

Publications and source records attributed to G Pizzolo.

At least 109 records · Page 6Linked to original sources
PubMed1990

Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms.

Abnormal immunoreaction associated with increased cell activation phenomena might play a role in the pathogenetic events leading to the development of angioimmunoblastic lymphadenopathy (AILD). In the present study we investigated the serum levels of some soluble molecules related to cell activation in 24 patients with AILD at presentation. In particular, we measured by immunoenzymatic or immunoradiometric techniques the levels of the Tac peptide (sIL-2R), soluble CD30 (sCD30) and CD8 (sCD8) antigens, and gamma-IFN (gIFN). The results show that all the above molecules are increased as compared to normal controls, with a different pattern of increase for the different molecules. The sIL-2R levels were very high in all cases with no overlap between AILD and control samples (mean 6315 +/- 3374 U/ml, controls 271 +/- 112 U/ml, P less than 0.001). Very high values of the sCD30 antigen (722 +/- 895 U/ml) were detected in all cases but five, as opposed to the lack of detectable levels in controls. A significant increase of sCD8 (978 +/- 646 U/ml, controls 334 +/- 95 U/ml, P less than 0.01) and gIFN (329 +/- 236 U/ml, controls 97 +/- 43 U/ml, P less than 0.01) was also observed with some overlap between AILD samples and controls. The above findings further support the view that a condition of abnormally enhanced cell activation is likely to play a central role in the pathogenetic events leading to the composite clinicopathological picture of AILD.

Antigens, CD↗
PubMed1990

Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.

We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.

Adolescent↗
PubMed1989

Evaluation of serum levels of soluble interleukin-2 receptor in patients with chronic lymphoproliferative disorders of T-lymphocytes.

Serum levels of soluble interleukin-2 receptor (sIL-2R) have been evaluated in 33 patients with chronic lymphoproliferative disorders of T-lymphocytes, including 12 T-helper phenotype chronic lymphocytic leukemias (Th-CLL) and 21 lymphoproliferative diseases of granular lymphocytes (LDGL). All Th-CLL cases were negative for antibodies against type I human T-leukemia virus (HTLV-I). Serum levels of sIL-2R were significantly increased in patients with Th-CLL with respect to controls (P less than 0.02) and this increase was related to the clinical course of the disease. In fact, patients with rapidly progressive disease (mean survival, 11.6 +/- 3 months) showed significantly higher concentrations of sIL-2R than patients with less aggressive disease (mean survival, 39.5 +/- 5 months) (16,223 U/ml +/- 5612 versus 1447 U/ml +/- 817; P less than 0.05). A significant positive correlation was found between sIL-2R concentrations and the number of CD4-positive cells (r = 0.64; P less than 0.05). These data point to the possible use of sIL-2R levels as a marker of active malignancy in patients with Th-CLL. Patients with LDGL showed increased sIL-2R values (721 U/ml +/- 112) with respect to controls (334 U/ml +/- 28; P less than 0.005). However, the sIL-2R levels were lower than those detected in Th-CLL patients (P less than 0.05). Among the different correlations the authors tried to establish, the only observed difference was found between serum sIL-2R levels in the group of CD3+ LDGL patients with respect to CD3- LDGL cases (P less than 0.05).

Antigens, CD↗
PubMed1989

Functional analysis of cytotoxic cells in patients with acute nonlymphoblastic leukemia in complete remission.

In the current study, we investigated the cytotoxic ability of peripheral blood mononuclear cells (PBMC) recovered from patients with acute nonlymphoblastic leukemia (ANLL) in complete remission (CR) against natural killer (NK)-sensitive, NK-resistant, autologous and allogeneic leukemic target cells taken at diagnosis. Our purpose was to define the role played by cytotoxic mechanisms in the control of leukemic cell growth in ANLL. Experiments were carried out at resting conditions and after in vitro activation with recombinant interleukin-2 (rIL-2) and anti-CD3 monoclonal antibody (moAb). At resting conditions, PBMC recovered from ANLL patients displayed a NK function that was not significantly different from controls (mean +/- standard error of the mean [SEM]: 21.9% +/- 3.9% versus control values of 27.5% +/- 2.9%; the P value was not significant [NS]), but they were unable to show cytotoxic activity against autologous and allogeneic leukemic cells. After in vitro boosting with rIL-2, PBMC were able to generate lymphokine activated killer (LAK) cells, as demonstrated by an increased killing of NK-resistant Daudi targets (16.3% +/- 2.7%). Although LAK activity was quantitatively lower than in control subjects (mean +/- SEM: 16.3% +/- 2.7% versus control values of 79.8% +/- 3.1%; P less than 0.001), it still exerted a cytotoxic effect against autologous and allogeneic leukemic cells. Similar results were obtained when anti-CD3 moAb was used as a stimulus in vitro. Our data suggest that nonspecific cytotoxic cells may be triggered to exert an in vitro cytotoxic effect on leukemic cells, which could possibly play a key role in vivo in the control of leukemic cell growth regulation.

Adult↗
PubMed1989

Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis.

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HBeAg/anti-HBe status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HBeAg-positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum sIL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.

Acute Disease↗
PubMed1989

Hairy cell sensitivity to the lysis in vitro. Role of the anti-CD3 antibody in generating a susceptibility to the lysis.

Experiments herein reported were designed to clarify the degree of sensitivity of hairy cells to lysis in vitro. The cytotoxic capacity of peripheral blood lymphocytes from hairy cell leukemia patients against autologous and/or allogenic hairy cells was tested both at resting conditions and after in vitro stimulation. While effectors activated by interferon alpha, lectins, or interleukin-2 were unable to induce a lysis of hairy cells, in some cases we were successful in eliciting a definite lysis of these cells by triggering the effector cells with anti-CD3 monoclonal antibodies. Our results favour the interpretation that hairy cells are relatively, but not completely resistant to in vitro lysis. Furthermore, the evidence that anti-CD3 antibodies increase the efficacy of the cytotoxic machinery might support the use of these molecules in designing new immunotherapeutic approaches against tumor targets.

Aged↗
PubMed1989

Release of natural killer cytotoxic factor in patients with lymphoproliferative disease of granular lymphocytes.

To further investigate the mechanisms accounting for defective natural killer (NK) activity observed in the majority of patients with lymphoproliferative disease of granular lymphocytes (LDGL), we have studied the generation of natural killer cytotoxic factor (NKCF) from peripheral blood lymphocytes recovered from twelve LDGL patients. On the basis of their cytotoxic activity against the K-562 target cells, cases under study were separated in two groups. Cells from five patients, referred to as NK+, were found to exhibit high levels of NK-cell mediated cytotoxicity; cells from seven patients, referred to as NK-, despite their ability to bind to the K-562 targets, displayed a defective NK function. The coculture of cells from NK+ patients with NK sensitive K-562 cells triggered a significantly higher production of NKCF with respect to NK- patients (p less than 0.001 at 1:2 dilution). Using phytohemagglutinin (PHA) as the NKCF stimulator, differences between the groups were not significant, due to a recovery of NKCF generation in NK- patients. Furthermore, a consistent lectin (PHA) dependent cellular cytotoxicity (LDCC) was exhibited by both groups of patients. The addition of gamma-interferon (IFN-gamma) or interleukin-2 (IL-2) during NKCF generation did not significantly modify the production of this factor. Our data point out that (a) NKCF is involved in the lytic activity of LDGL patients' cells, (b) a constitutional impairment in the generation of NKCF is not present in NK- patients, since recovery of lytic function occurs after PHA stimulation, and (c) IL-2 and IFN-gamma do not play a relevant role in triggering NKCF production when added during the generation of this factor. These studies help to clarify the factors involved in the cytotoxic machinery of LDGL patients' cells, suggesting that the defect of the cytotoxic function observed in some LDGL patients could lie at the level of target recognition.

Adult↗
PubMed1989

Increased levels of soluble interleukin-2 receptor in non-Hodgkin's lymphomas. Relationship with clinical, histologic, and phenotypic features.

In this study the authors investigated the serum levels of the released soluble form of interleukin-2 receptor (sIL-2R) in patients with non-Hodgkin's lymphomas (NHLs). Data were evaluated in relationship to the morphologic and immunophenotypic heterogeneity of NHL at diagnosis and in progressive advanced diseases. Increased sIL-2R levels were found in most cases, when compared with levels observed in healthy controls. No obvious statistical correlation has been observed between sIL-2R values in different NHL subtypes as defined by current classifications. On the other hand, major significance was related to the extent of the disease. Very high values, comparable to those observed in hairy cell leukemia, were observed in a number of large cell NHLs complicating low-grade B-cell lymphoproliferations and in a single case of T-cell Kil+ NHL. The authors' findings suggest that the detection of sIL-2R in NHL may represent a good marker in improving risk assignment of single cases and/or for monitoring remissions and exacerbations during the treatment of cases with very high levels at diagnosis. Nevertheless, the observed overlap between groups on an individual case basis can render the clinical application of this marker problematic.

B-Lymphocytes↗
PubMed1988

Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.

In this study we investigated the serum levels of a released soluble form of the interleukin-2 receptor (sIL-2R) in 42 patients with rheumatoid arthritis and in 12 cases of systemic lupus erythematosus. Data were evaluated in relationship to the clinical phase and compared with those observed in normal controls (N = 56) and in osteoarthritis (N = 7). Increased levels were observed in both rheumatoid arthritis (mean +/- SE, 604 +/- 49 U/ml) and systemic lupus erythematosus (1438 +/- 481 U/ml). These values were significantly higher than in control (256 +/- 15 U/ml; P less than 0.001) and in osteoarthritis (298 +/- 33 U/ml; P less than 0.001) groups. In addition, the highest values were associated with the active phases of both rheumatoid arthritis (active vs inactive, 771 +/- 78 vs 451 +/- 39 U/ml; P less than 0.001) and systemic lupus erythematosus (active vs inactive, 2108 +/- 489 vs 499 +/- 75 U/ml; P less than 0.001). Our findings suggest that the detection of sIL-2R in rheumatoid arthritis and in systemic lupus erythematosus may represent a good marker of disease activity, which indirectly indicates the ongoing activation and/or proliferation of immunoreactive cells which are involved in the pathogenetic events of these autoimmune conditions.

Acute Disease↗
PubMed1988

Natural killer cell function and lymphoid subpopulations in acute non-lymphoblastic leukaemia in complete remission.

A long term follow-up study has been undertaken in 33 patients with acute non-lymphoblastic leukaemia (ANLL) in order to establish whether a correlation exists between the clinical course and the immunologic pattern of lymphoid subpopulations. Peripheral blood lymphoid cells have been investigated longitudinally (each 1 to 4 months) during complete remission (CR), by morphologic, phenotypic and functional analyses. Particular attention has been paid to the evaluation of the natural killer (NK) cell compartment, by the detection of cells expressing an NK-related phenotype and by NK in vitro assay. Among the patients so far evaluable, 20 relapsed (R) and 10 are long survivors in CR 'off therapy' (LS). The most relevant finding was represented by statistically higher values of NK activity observed in LS vs. R patients (P less than 0.01). The removal of adherent cells before the NK assay, performed to investigate the possible inhibitory effect on NK function played by the macrophage component, abolished this difference, due to a selective increase of NK function in the R group. The longitudinal study revealed that NK activity tended to decrease in individual patients who subsequently relapsed. These data suggest a possible role of NK cells in the relapse control of ANLL, although it cannot be excluded that the low level of NK activity observed in the R group is the result of impending relapse rather than its cause.

Adolescent↗
PubMed1988

Immunohistochemical analysis of sarcoid granulomas. Evaluation of Ki67+ and interleukin-1+ cells.

Proliferating cells have been immunophenotypically characterized in lymph node and bronchoalveolar lavage (BAL) samples obtained from patients with active and inactive sarcoidosis with the cell-cycle-related antigen Ki67. Ki67 monoclonal antibody was used by combined immunohistochemical methods together with antibodies recognizing macrophage- and T-cell-subset-related antigens using avidin-biotin peroxidase (ABC) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) systems. Many proliferating Ki67+ cells were found in affected mediastinal lymph nodes. These cells were mainly located around granulomas and exhibited phenotypical markers of helper/inducer T cells (CD3+, CD4+). Ki67+ macrophages could not be detected in the same lesions with this technique. A different picture was found in BAL preparations where proportions of both T lymphocytes and macrophages were Ki67+. The presence of replicating lymphocytes could be correlated to disease activity, whereas the proportions of Ki67+ macrophages did not show significant differences between active and inactive disease. Interleukin-1 (IL-1) expression was investigated in the same samples with a specific antiserum. Epithelioid macrophages in granulomas and BAL macrophages in all cases exhibited cytoplasmic staining revealing an activated status. Interestingly, giant cells in granulomas were mainly devoid of IL-1 immunoreactivity. These studies support the concept that activated cells at different sites of ongoing inflammation play a central role in the mechanisms accounting for granuloma formation.

Adult↗
PubMed1987

The lymphoproliferative disease of granular lymphocytes. A heterogeneous disorder ranging from indolent to aggressive conditions.

A multiparameter analysis, which included the evaluation of clinical features, cell morphology, karyotype, phenotypic and functional immunologic findings, and T-cell receptor beta-chain configuration was performed on 34 patients with lymphoproliferative disease of granular lymphocytes (LDGL). The two-fold aim of the study was to identify the most useful tools that would more accurately characterize these patients and to deal with the problem of classifying these lymphoproliferative disorders. The data presented in this article suggest that a single parameter may not be sufficient to define the nature of the proliferating cells or to predict the clinical course of the disease and prognosis for the patient. The use of a multiparameter approach, however, may reach this goal, thus providing important prognostic and therapeutic information. Our study supports the concept that lymphoproliferative disease of granular lymphocytes is a heterogeneous disorder that ranges from indolent and possibly reactive conditions to the manifestation of aggressive malignancies.

Adult↗
PubMed1987

Immunologic abnormalities in angioimmunoblastic lymphadenopathy.

In this study we describe the results of phenotypic, serologic, and functional analyses performed in nine patients with angioimmunoblastic lymphadenopathy (AILD). The study investigates the nature of the T-cell defects which seem to represent a consistent feature in this disease. The study, based on the analysis of T-cell subsets with monoclonal antibodies and on functional in vitro tests, showed the following main abnormalities: reduction of the absolute number of circulating T-cells; inversion of the CD4/CD8 ratio, both in the peripheral blood and in the involved lymph nodes; high percentages of activated T-cells (CD8+/HLA-DR+); defective T-cell response in vitro to the PHA mitogen; and minimal helper and enhanced in vitro suppressor functions. Some of these immunologic dysfunctions are also observed in acquired immune deficiency syndrome (AIDS) which has in common with AILD several clinical features. However, no evidence of HTLV-III infection could be demonstrated in our patients with AILD.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia.

The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)-positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh-rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T-ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid-related features, is characterized by cells molecularly committed along the B cell lineage.

Adolescent↗
PubMed1987

Alpha-interferon activated cytotoxic lymphocytes in hairy cell leukemia patients: evaluation of cytotoxic events.

To further define the mechanisms responsible for the alpha-interferon (alpha-IFN) efficacy in the treatment of hairy cell leukemia (HCL), experiments were carried out to specify the cytotoxic events taking place following this type of therapy. Although an increased natural killer (NK) activity was demonstrable after alpha-IFN treatment, evidence has been provided that hairy cells were not specifically lysed either by fresh autologous/allogenic NK lymphocytes or by lymphokine activated killer (LAK) cells. This property could not be induced in vitro by alpha-IFN or by interleukin-2 (IL-2). Our data favour the hypothesis that the increase of NK cell activity observed following alpha-IFN therapy has not a direct antineoplastic effect but is likely to be of relevance for a non-specific enhancement of the host immune system. In alpha-IFN treated HCL this latter property may account for the better resistance to infections which usually represents the major cause of mortality in these patients.

Adult↗