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M Massaia

Publications and source records attributed to M Massaia.

78 records · Page 5Linked to original sources

Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes.

Terminal deoxynucleotidyl transferase (TdT) and purine metabolic enzymes were examined in subsets of human infant thymocytes (defined by surface cell antigens) and normal peripheral T lymphocytes. Putative prothymocytes (RFB-1+, HTA-1+/- large blast-like cells), medium and high density cortical thymocytes (RFB-1+, HTA-1+), and medullary thymocytes (RFB-1-, HTA-1-, OKT3+) were isolated by density gradient centrifugation, monoclonal antibody and complement-mediated cytolysis, and cell-antibody affinity chromatography. Peripheral T lymphocytes were isolated from normal adult mononuclear cells using nylon fiber technique. Adenosine deaminase (ADA) and TdT were highest in prothymocytes 48.8 +/- 14.7 mumol/hr/10(8) cells (mean +/- SE) and 22.9 +/- 1.4 U/10(8) cells, respectively. Both enzymes decreased progressively down the maturation pathway. In peripheral T lymphocytes, ADA was 3.9 +/- 1.5 mumol/hr/10(8) cells, and TdT was undetectable. Purine nucleoside phosphorylase (PNP) and ecto-5'nucleotidase (5'NT) were lowest in cortical thymocytes (27.5 +/- 11.0 nmol/hr/10(6) cells and 2.8 +/- 1.3 nmol/hr/10(6) cells, respectively) and increased with T cell maturation. The PNP level was 124.9 +/- 17.2 nmol/hr/10(6) cells and 5'NT was 30.1 +/- 3.9 nmol/hr/10(6) cells in peripheral T lymphocytes. The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets. The proliferative activity (labeling index) was highest in the prothymocyte fraction and lowest in peripheral T cells. Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency.

Adenosine Deaminase↗

Enzymes of purine metabolism in human peripheral lymphocyte subpopulations.

Ecto-5'nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and deoxycytidine (CdR), deoxyguanosine (GdR), deoxyadenosine (AdR) and adenosine (AR) kinases have been measured in subpopulations of peripheral blood lymphocytes of eight healthy volunteers. The separation of B, T, T helper/inducer and T suppressor/cytotoxic cells was performed by means of density gradient centrifugation, E rosetting, passage through a nylon-wool column and antibody affinity chromatography utilising OKT8 and OKT4 monoclonal antibodies. ADA was significantly higher in T lymphocytes and 5'NT in B lymphocytes. Among T cell subpopulations, 5'NT activity was significantly higher (P less than 0 . 01) in T suppressor/cytotoxic (OKT8+) cells (32 . 9 units/10(6) cells than in T helper/inducer (OKT4+) cells (9 . 7 units/10(6) cells). Indeed, the 5'NT activity in T suppressor cells was similar to that in B cells. T helper cells tended, however, to have higher PNP and ADA activities than T suppressor cells but the differences were not statistically significant. No major differences were noted in kinase activities between any of the lymphocyte subpopulations.

5'-Nucleotidase↗

Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass.

BACKGROUND: IFN-alpha has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-alpha exerts its effect directly on the myeloma cells or is mediated by modulation of the host response. METHODS: The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha 2b (IFN-alpha) therapy. RESULTS: Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-alpha treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease at the sixth month of IFN-alpha therapy. CONCLUSIONS: i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.

Antigens, CD↗

Multiple myeloma: altered CD4/CD8 ratio in bone marrow.

The expression of CD3, CD4 and CD8 antigens was simultaneously evaluated in peripheral blood and bone marrow lymphocytes from 22 multiple myeloma (MM) patients. The coexpression of CD11b and HLA-DR antigens was also analyzed within the CD4+ and CD8+ subpopulations in 4 MM patients. In peripheral blood the percentage of CD3+ and CD8+ cells was in the normal range, and the percentage of CD4+ was slightly reduced, leading to an altered CD4/CD8 ratio (less than 1) in only 7 patients. On the contrary, in bone marrow the percentage of CD4+ was profoundly reduced, leading to an altered CD4/CD8 ratio in all MM patients. As we previously reported in peripheral blood, an expansion of the CD11b+ and HLA-DR+ lymphocytes was observed within the CD4+ and CD8+ bone marrow T-cell subpopulations. A T-lymphocyte subset imbalance is more evident in bone marrow than in peripheral blood, and it is not due to a different lymphocyte distribution within the hematological compartments.

Antigens, CD↗