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Biomedical subjects

M Massaia

Publications and source records attributed to M Massaia.

At least 73 records · Page 4Linked to original sources
PubMed1988

Biochemical and immunologic abnormalities in peripheral blood T lymphocytes of patients with hemophilia A.

Subset distribution, ecto-5'nucleotidase (5'NT) activity, and the generation of allospecific cytotoxic T lymphocytes (CTL) were investigated in peripheral blood T lymphocytes from 39 hemophilia A patients divided into three groups: group A and group B (HIV-patients with CD4:CD8 ratio less than 1 and greater than 1 respectively), and group C (HIV + patients). 5'NT activity was significantly decreased compared with healthy controls in groups B and C. In group B, this deficiency was attributable to expansion of CD8 + CD11 + suppressor cells. In group C, activated (HLA-DR+) CD8+ cells were also present and contributed to 5'NT deficiency. The suppressor cell expansion seemed to be mainly related to AHF infusions, whereas HLA-DR expression was related to HIV infection. CD11+ and HLA-DR+ cells were also expanded in the CD4+ subpopulation of all three groups, whereas CD4+ CD28+ lymphocytes were significantly decreased in group C only. Lastly, alloreactive cytotoxicity was decreased in group B and was normal in groups A and C.

Cytotoxicity, Immunologic↗
PubMed1988

Emergence of activated lymphocytes in CD4 and CD8 subpopulations of multiple myeloma: correlation with the expansion of suppressor T-cells (CD8+ OKM1+) and ecto-5'nucleotidase deficiency.

This study of CD4 and CD8 lymphocyte subpopulations in MM revealed increased proportions of cells expressing OKM1, Leu7, and HLA-DR antigens. In CD8 lymphocytes, there was a direct correlation between OKM1 and HLA-DR positivity. Two-colour analysis of purified CD8 subpopulations showed that HLA-DR was preferentially expressed by OKM1+ lymphocytes (suppressor cells), but a significant proportion of OKM1-lymphocytes (cytotoxic precursor cells) were also HLA-DR+. A significant proliferative activity found in CD2 lymphocytes was directly correlated with the proportion of HLA-DR+ cells in CD8 subpopulations only. CD8 lymphocytes displayed significantly lower 5'NT activity than those of normal subjects. This enzyme deficiency was correlated with the expansion of CD8 OKM1+ and HLA-DR+ cells; the increase in suppressor cells, as well as the emergence of activated cells, are associated with CD8 5'NT deficiency. In conclusion, the immunological pattern of CD4 and CD8 subpopulations in MM is significantly different from that in normal subjects. The implications of these data for the immune dysregulation occurring in MM are discussed.

5'-Nucleotidase↗
PubMed1988

Activated idiotype-reactive cells in suppressor/cytotoxic subpopulations of monoclonal gammopathies: correlation with diagnosis and disease status.

The phenotypic pattern of peripheral blood T (PBT) lymphocytes was correlated with diagnosis and clinical status in 63 patients with monoclonal gammopathies (MGs). The numbers of lymphocytes expressing activation and CD11 determinants were significantly increased in suppressor/cytotoxic and helper/inducer subpopulations of patients with multiple myeloma (MM) and MG of undetermined significance (MGUS). The number of activated suppressor/cytotoxic cells was closely correlated with diagnosis and disease status. These cells were significantly higher in MM at diagnosis (160 +/- 88) than MGUS patients (61 +/- 79; P less than .01). Their number decreased to MGUS levels in MM in stable remission (58 +/- 53), but not in MM with tumor progression (172 +/- 102; P less than .001). In individual patients, part of these cells specifically adhered to dishes precoated with the related M-protein. No monoclonal T-beta gene rearrangement was detected in PBT and cytotoxic/suppressor subpopulations from two patients with a large proportion of activated cells.

Blood Proteins↗
PubMed1988

Defective generation of alloreactive cytotoxic T lymphocytes (CTL) in human monoclonal gammopathies.

The generation of cytotoxic T lymphocytes (CTL) towards allogeneic cells was investigated in 19 patients with monoclonal gammopathy of undetermined significance (MGUS) and 31 patients with multiple myeloma (MM). This function was significantly decreased in all patients. The cytotoxic deficiency was more pronounced in MM with poor prognosis than MM with good prognosis and MGUS patients. A phenotypic analysis of PBT lymphocytes showed that poor prognosis MM also had the highest proportions of activated cells (HLA-DR+) in CD8+ subpopulations. CTL were generated after depletion of CD11+ lymphocytes (including suppressor cells) or after inhibition of suppressor function with deoxyguanosine. No increase of cytotoxicity was detected under these conditions. Exogenous supplementation of recombinant interleukin 2 (rIL-2) was also ineffective. These data indicate that MG PBT lymphocytes are unable to fully differentiate into CTL following allogeneic stimulation. This deficiency is most evident in MM patients already showing the poorest prognosis and the most altered T cell phenotype.

Antigens, Surface↗
PubMed1987

Immunologic and virologic findings in hemophiliacs do not correlate with ecto-5'nucleotidase activity of peripheral blood lymphocytes. A difference with homosexual men.

It has been recently demonstrated that ecto-5'nucleotidase (5'NT) activity is significantly decreased in the peripheral blood lymphocytes (PBL) of homosexual men. This paper reports a study of PBL 5'NT activity in 38 hemophiliacs at risk for the acquired immunodeficiency syndrome (AIDS). The enzyme activity was correlated to the immunologic and virologic data. T-cell subset distribution was unbalanced and directly correlated with the cumulative amount of AHF infused. PBL 5'NT activity, however, was similar to that of healthy controls. 6 patients displayed serum antibodies to the human immunodeficiency virus (HIV) but no decrease in PBL 5'NT activity. In conclusion, these data indicate that both heavily treated and seropositive as well as untreated hemophiliacs have normal PBL 5'NT activity. This striking dissimilarity between homosexual men and hemophiliacs suggests that some immunologic alterations leading to 5'NT deficiency occur in the former only.

5'-Nucleotidase↗
PubMed1987

Lack of correlation between plasma cell thymidine labelling index and serum beta-2-microglobulin in monoclonal gammopathies.

Simultaneous evaluation of bone marrow plasma cell thymidine labelling index (LI) and serum beta-2-microglobulin (SB2M) was performed in 146 patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS). Eighty patients had MM on diagnosis, 11 were in relapse and 12 were in remission phase; 43 patients had MGUS. All the evaluated patients had normal renal function with a creatinine level less than 1.4 mg%. Overall there was no direct correlation between LI% and SB2M. LI% best reflected the proliferative capacity of the tumor clone itself being less than or equal to 1% in MGUS and MM in remission, but greater than 2% at relapse of MM. SB2M correlated best with the stage of disease and tumor burden. These two factors therefore have different clinical utility: LI is a useful parameter to detect disease stability (e.g., MGUS) or highly proliferative disease (aggressive MM at diagnosis or early relapse). SB2M remains the best single predictor of patient tumor burden and associated survival duration.

Bone Marrow↗
PubMed1987

Cytobiological studies in multiple myeloma.

Multiple myeloma (MM) is a heterogeneous disease in which the median survival time varies from a few months to more than 10 years. Clinical, kinetic, and immunological studies reflected such a heterogeneity. In clinical studies beta 2-microglobulin (beta 2-M), which is a well-known prognostic factor, was evaluated as an expression of tumor burden: a linear increase has been observed from stage I to stage III. No clear cutoff was detected between monoclonal gammopathy of undetermined significance (MGUS) and stage I MM. Kinetic studies have been performed by 3[H]thymidine or 5-bromo-2-deoxyuridine incorporation in bone marrow plasma cells. An analysis has been carried out between beta 2-M and the labeling index (LI). No correlation has been observed between these 2 parameters which identify different subgroups of poor prognosis patients. MGUS always showed an LI less than 1% allowing a clear distinction from stage I MM. A reduced survival time has been observed in patients with an LI greater than 2%. A subgroup of MM patients characterized by an LI greater than 2% and a decrease of M component greater than 50% within 3 months (early responders) has been identified. These patients showed a median survival time of about 10 months. Immunological studies identified a sharp decrease of 5' nucleotidase (5'NT) enzymatic activity in peripheral blood lymphocytes. This enzymatic defect is the biochemical marker of the expansion of a T subpopulation expressing low levels of 5'NT. This subpopulation was characterized by monoclonal antibodies and is represented by activated suppressor cells (OKM1+, DR+). Such an unbalancement in the T cell subpopulation was evident in poor prognosis patients. Clinical, kinetic and immunological studies identified new prognostic parameters that will be useful in the future therapeutic strategy of MM.

5'-Nucleotidase↗
PubMed1987

Multiple myeloma: ecto-5' nucleotidase deficiency of suppressor/cytotoxic (CD8) lymphocytes is a marker for the expansion of suppressor T cells.

In this study, 5'NT activity was investigated by radiochemical and cytochemical assays in T cell subpopulations of patients with multiple myeloma (MM). Cytotoxic/suppressor (CD8) and helper/inducer (CD4) lymphocytes were separated from peripheral blood by the panning technique, or sorted with a fluorescein activated cell sorter. 5'NT activity was significantly decreased in MM CD8 lymphocytes compared with the controls. By contrast, it was comparably low in CD4 subpopulations of normal controls and MM patients. The cytochemical assay indicated that a decreased number of 5'NT+ cells rather than a decreased activity per cell was responsible for 5'NT deficiency in MM CD8 lymphocytes. CD8 lymphocytes with the suppressor phenotype (OKMI+, granular cells) were significantly increased in MM. These data provide a phenotypic explanation for the enhanced suppressor activity displayed by T lymphocytes in MM. A significant correlation was found between the increase of suppressor cells and the decrease of 5'NT+ cells. 5'NT deficiency of CD8 lymphocytes can be a biochemical marker for the expansion of suppressor T cells.

5'-Nucleotidase↗
PubMed1986

Differential expression of ecto-5' nucleotidase activity by functionally and phenotypically distinct subpopulations of human Leu-2+/T8+ lymphocytes.

Subsets of Leu-2+/T8+ cytotoxic/suppressor T lymphocytes were isolated by using various methods of purification and were investigated for expression of ecto-5' nucleotidase (5'NT) enzyme activity by radiochemical, cytochemical, and ultrastructural techniques. By using both the radiochemical and the cytochemical methods. T4-OKM1- cells displayed higher 5'NT activity in comparison with the entire T4- subpopulation. Analyses of the subpopulations of T4- (and predominantly Leu-2+) cells defined by the Leu-15 or Lyt-1 (9.3) monoclonal antibodies demonstrated that T4-Leu-15- and T4-Lyt-1+ cells displayed high 5'NT activity, whereas virtually no activity was present in T4-Leu-15+ and T4-Lyt-1-cells. At the ultrastructural level, the 5'NT reaction product was detected on the plasma membrane of a proportion of nongranular Leu-2+/T8+ lymphocytes, but no activity was found on cells with a granular lymphocyte (GL) morphology. 5'NT activity was also analyzed in peripheral blood mononuclear cells from one patient with expanded numbers of GL and two patients with GL leukemia. The enzymatic activity was significantly lower in these patients than in normal controls. This study provides new cytochemical evidence demonstrating the heterogeneity of Leu-2+/T8+ cells, and indicates that the population with the suppressor phenotype and function (Leu-15+/Lyt-1-, GL morphology) displays low or absent 5'NT activity, whereas the population composed of cytotoxic cell precursors (Leu-15-/Lyt-1+, nongranular morphology) has high 5'NT activity. Implications of these data for the interpretation of low 5'NT activity described in several immunodeficiency states and lymphoproliferative disorders are discussed.

5'-Nucleotidase↗
PubMed1985

Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics.

Ecto-5'nucleotidase (5'NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5'NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5'NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5'NT on LI% which was statistically significant: the higher the LI%, the lower the 5'NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5'NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5'NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5'NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5'NT deficiency of unseparated T lymphocytes.

5'-Nucleotidase↗
PubMed1984

Soluble factor(s) released by Concanavalin A activated lymph node lymphocytes induce proliferation and maturation of chronic lymphocytic leukaemia (CLL) B lymphocytes.

An active supernatant (Ly Con A) was prepared by stimulating the normal human lymph node lymphocytes with Concanavalin A (Con A). Peripheral blood lymphocytes (PBL) from 3 healthy subjects and from 8 patients with chronic lymphocytic leukaemia (CLL) were cultured in the presence of Con A and Ly Con A. The latter induced a significant DNA synthesis both in normal and CLL lymphocytes. A proliferative response was still present in CLL after T lymphocytes depletion. The Con A and Ly Con A treatment also induced morphological changes in CLL lymphocytes consistent with plasma cell differentiation. In 3 cases the appearance of cytoplasmic light chains was detected by immunofluorescence. These findings suggest that peripheral blood B lymphocytes from CLL patients can be stimulated to maturation when helper factor(s) released by mitogen activated lymph node lymphocytes are provided.

Antibody-Producing Cells↗
PubMed1983

Comparison of purine degradative enzymes and terminal deoxynucleotidyl transferase in T cell leukaemias and in normal thymic and post-thymic T cells.

Adenosine deaminase (ADA), ecto 5' nucleotidase (5'NT), purine nucleoside phosphorylase (PNP) and terminal deoxynucleotidyl transferase (TdT) were measured in the cells of patients with acute or chronic T cell leukaemia and compared with normal putative prothymocytes (large, blast-like cortical thymocytes), cortical and medullary thymocytes and peripheral blood T lymphocytes. Distinct patterns of enzyme activities were found in the individual types of T cell leukaemia. Mean ADA, TdT and 5'NT activities in thymic acute lymphoblastic leukaemia (Thy-ALL) were 41.9 u/10(8) cells, 31.1 u/10(8) cells and 4.7 u/10(6) cells respectively; in chronic T cell leukaemia they were 7.1 u/10(8) cells, 0.6 u/10(8) cells and 18.1 u/10(6) cells respectively. Mean PNP activity was similar between these two groups of leukaemia (68.6 u/10(6)cells in Thy-ALL and 77.9 u/10(6) cells in chronic T cell leukaemia). The activities of these four enzymes in OKT4+ chronic T cell leukaemia did not differ significantly from those in the OKT8+ chronic T cell leukaemia cases. The activities of TdT, ADA, PNP and 5'NT in Thy-ALL closely resembled those in normal immature thymocytes, and in the chronic T cell leukaemias showed a similar pattern of enzyme activities to that of mature T lymphocytes. These findings are consistent with surface phenotypic studies of T cell malignancies which suggest that different T cell leukaemias represent malignant proliferation of T cell clones arrested at different stages of T cell differentiation. They also demonstrate the value of biochemical markers in defining the different subtypes of acute and chronic leukaemia.

5'-Nucleotidase↗
PubMed1983

Kinetics of circulating B lymphocytes in human myeloma.

The tritiated thymidine labeling index (LI%) of peripheral B lymphocytes was studied in eight myeloma patients using simultaneous immunofluorescence and autoradiography. The LI% values were low (0.3%-5.1%), but significantly increased as compared to normal controls. In addition, there was excellent correlation between the LI% values and myeloma disease activity: lowest LI% values were observed in remission patients and the highest at the time of relapse. Simultaneous LI% evaluation of bone marrow myeloma cells in five patients gave concordant results, indicating the same kinetic behavior in both these compartments, particularly in the relapse phase. These data indicate both that circulating B lymphocytes include the neoplastic clone and that these B lymphocytes and bone marrow myeloma cells have similar kinetics.

B-Lymphocytes↗
PubMed1983

Changes in SRBC binding capacity and T-surface antigen expression on human peripheral blood lymphocytes stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA).

The expression of surface markers was analyzed on human peripheral blood lymphocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter which is known to have a mitogenic effect on human T-cells. A significant decrease in the proportion of cells capable of binding to SRBC under different experimental conditions (active (EA), high affinity (EH), total (ET) rosettes) was observed after 20 hr exposure to TPA. After 4 days incubation, the ability to form EH and ET rosettes was recovered, while a significant increase in the proportion of EA and temperature stable (ES) rosettes compared with control cultures was observed. Using monoclonal antibodies directed against different T-lymphocyte subpopulations, a depression in the proportion of cells reacting with OKT3 (pan T) and OKT4 (helper/inducer) antibodies was observed, after both early and late exposure to TPA. On the contrary, the positivity with OKT8 (suppressor/cytotoxic) antibody was not affected at any time of culture. These findings suggest that, in normal blood, TPA can modulate the expression of T-cell receptors, and that T-lymphocytes with helper/inducer phenotype appear to be the target of the TPA-induced membrane changes.

Antibodies, Monoclonal↗
PubMed1983

The idiotypic specificities of lymphocytes in human monoclonal gammopathies: analysis with the fluorescence activated cell sorter.

Four monoclonal IgG kappa gammopathies were studied with anti-idiotypic sera and the percentage of lymphocytes bearing such idiotypes was evaluated with a fluorescence activated cell sorter (FACS). A large percentage (10-15%) of peripheral lymphocytes bearing receptors with the same idiotypic specificities as the M component was observed in multiple myeloma (MM) and in monoclonal gammopathy of undetermined significance (MGUS), suggesting a malignant origin for both these diseases. Capping-endocytosis and resynthesis experiments showed that these idiotypic receptors were not simply adsorbed on the cell membrane, but actually synthesized by the cells bearing them. Experiments performed after effective conventional chemotherapy showed a strong reduction of the idiotypic compartment in only one MM patient.

Antibodies, Monoclonal↗
PubMed1982

5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia.

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.

Acute Disease↗