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Biomedical subjects

F Lauria

Publications and source records attributed to F Lauria.

At least 127 records · Page 7Linked to original sources

Hairy-cell leukemia complicating coeliac disease: report of a case and discussion of possible pathogenetic mechanisms.

10-28% of the patients with chronic coeliac disease develop a second malignancy, such as non-Hodgkin's lymphomas, particularly of the histiocytic type, and adenocarcinomas. The second tumor may arise in the intestinal tract or in other organs. We describe here a patient who developed a tartrate-resistant, acid phosphatase-positive, hairy-cell leukemia after a history of chronic coeliac disease. In the literature, no similar case has been described as yet.

Celiac Disease↗

Different stages of B cell differentiation in non-T acute lymphoblastic leukemia.

Immunoglobulin heavy chain gene rearrangement was evaluated in 19 cases of acute lymphoblastic leukemia (ALL) and correlated with the immunological phenotypic expression on primary or phorbol diester (12-O-tetradecanoylphorbol-13-acetate [TPA])-induced cells. One case of common ALL (cALL), one case of T-ALL, and one undifferentiated acute leukemia that responded to anti-myeloid drugs after unsuccessful anti-lymphoid induction therapy, had germ line heavy chain genes. Rearranged immunoglobulin genes were instead found in 15 of the 16 cALL cases studied and in a case of non-T, non-B, non-common ("null") ALL, which suggested the B cell origin of the neoplastic cells. All cases bearing a heavy chain gene rearrangement were HLA-DR positive. However, the unique cALL case with a germ line configuration was also HLA-DR positive, which confirmed that both the cALL antigen and HLA-DR antigen were not per se expression of B cell commitment. On the other hand, a complete search for B cell-related markers (BA-1 and B1 monoclonal antibodies, as well as cytoplasmic immunoglobulins [CyIg]) in the cALL cases showed that at least one B cell marker could be detected either on primary or on TPA-induced cells in all cases in which a gene rearrangement had occurred. Incubation with TPA allowed the detection of one B cell marker in a case in which the primary cells were negative, and increased the expression of B cell markers in all but one of the cALLs tested. The only cALL case that was not rearranged expressed no B cell markers either on primary or on TPA-induced cells. The non-T, non-B, non-common ("null") case that was rearranged also showed no phenotypic evidence of B cell markers on primary and induced cells. These findings indicate that: (a) practically all cases of cALL appear to be of B cell origin as shown by gene rearrangement analysis; (b) DNA studies are relevant for a more precise characterization of individual cases of undifferentiated acute leukemia; (c) a complete survey for B cell markers may establish the B cell origin of the cALL blasts, as long as the analysis on primary cells is complemented by differentiation induction assessment; and (d) most cases of non-T ALL appear to be characterized by the expansion of neoplastic cells "frozen" at different levels along the B cell differentiation pathway, the first detectable marker being heavy chain gene rearrangement, followed by BA-1, B1, and CyIg expression.

Antigens, Surface↗

Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease.

The distribution of T lymphocyte subsets was assessed using monoclonal antibodies (MoAbs) in 44 untreated patients with multiple myeloma (MM) subdivided according to the clinical stage of the disease. A significant reduction (P less than 0.001) of T lymphocytes was observed only in stage II and III patients. The proportion and absolute number of OKT4 positive cells (helper/inducer phenotype) were significantly reduced in all stages of the disease; this quantitative abnormality was more pronounced in advanced disease. While the proportion of OKT8 positive cells (suppressor/cytotoxic phenotype) was increased above normal in all stages, the absolute number (of OKT8 positive cells) was high only in stage I patients; on the contrary in stage II-III patients the total OKT8 count was reduced compared with normal controls. A significantly reduced OKT4/OKT8 ratio was found in both groups of patients (P less than 0.005). Functional studies, carried out on the unfractionated T cells of patients with MM, demonstrated a consistent helper defect in the ability to induce the differentiation of normal B lymphocytes into antibody producing cells in a pokeweed mitogen driven system. However, the removal of OKT8 positive cells produces a significant increase in helper capacity, suggesting that the reduced helper function of T lymphocytes in toto is probably due to excessive suppressor activity. The possible immunoregulatory role of MM T cell disease is discussed.

Antibodies, Monoclonal↗

Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies.

Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.

Aged↗

Increased proportion of suppressor/cytotoxic (OKT8+) cells in patients with Hodgkin's disease in long-lasting remission.

The distribution of T-lymphocyte subsets in patients with Hodgkin's disease (HD) at diagnosis and in those disease-free off-therapy for over 5 years, was assessed with OKT monoclonal antibodies. In patients at diagnosis, T-cell subsets appeared substantially balanced with only a moderate reduction in the proportion and absolute number of OKT4 (helper/inducer) positive cells, suggesting that the lymphopenia, constantly associated with HD at diagnosis, is mainly due to a reduction in the helper/inducer T-cell subpopulation. In patients off-therapy, a reduced proportion, but normal absolute number, of OKT4+ cells was constantly accompanied by a significant increase in the proportion and absolute number of OKT8+ cells, compared with patients at diagnosis and normal controls (40% +/- 11 versus 24% +/- 7 and versus 23 +/- 6, respectively). Consequently the OKT4/OKT8 ratio, normal or near normal in patients at diagnosis (1.70 versus 2.00), was significantly reduced in patients off-therapy (0.78 versus 2.00, P less than 0.001). These data suggest that in patients with HD at diagnosis, T-cell subpopulations are substantially normal, while a significant abnormality was observed in patients with HD off-therapy and potentially "cured." Further investigations will better elucidate these findings probably related to the cytotoxic radiotherapy and chemotherapy.

Adolescent↗

T lymphocytes in B-cell chronic lymphocytic leukemia: characterization by monoclonal antibodies and correlation with Fc receptors.

In 35 patients with B-cell chronic lymphocytic leukemia (B-CLL), T lymphocytes were characterized by their ability to react with OKT-4 and OKT-8 monoclonal antibodies. These T-cell subsets were also compared with the expression of Fc receptors. An imbalance in the distribution of OKT-4 and OKT-8 lymphocyte subpopulations was observed, with an overall significant reduction in the OKT-4/OKT-8 ratio. When the patients were subdivided according to Rai's staging classification, the OKT-4/OKT-8 ratio was more severely impaired in stages III and IV than in stages 0, I, and II. The correlation between the expression of Fc receptors and monoclonal antibodies revealed in both systems an increase in cells bearing suppressor phenotypes (OKT-8+ and TG+ cells) and a decrease in cells bearing helper phenotypes (OKT-4+ and TM+). However, a strict correlation between cells defined by the two assays could not be found in individual cases. In some cases a proportion of T lymphocytes (E+ and OKT-3+) did not express the OKT-4 and OKT-8 determinants; possible implications of this finding are discussed. These data provide further evidence of the T-cell abnormality in B-CLL and emphasize the importance of T-cell subsets in this disease.

Aged↗

T-cell functional abnormality in B-chronic lymphocytic leukaemia: evidence of a defect of the T-helper subset.

The helper and suppressor capacity of T, T mu (T non gamma) and T gamma cells was assessed in a group of patients with B-cell chronic lymphocytic leukaemia (B-CLL) in a pokeweed mitogen (PWM) stimulated system. The enriched T-cells (E-rosette positive) from all B-CLL cases showed a reduced capacity to induce the differentiation of normal B-lymphocytes compared with normal T-cells (P less than 0.005). After enrichment of the T mu cells, the helper/inducer capacity was still significantly depressed compared with the same fraction from normal controls (P less than 0.01). On the other hand, enriched T gamma cells from B-CLL were effective in suppressing the differentiation of normal B-lymphocytes to a similar degree as normal T gamma cells. These findings are indicative of a deficient T-cell helper function in B-CLL, which appears to be unrelated to the clinical stage of the disease. The fractionation experiments suggest that this functional impairment is not only due to the abnormal T-cell subset distribution seen in the majority of cases, but point to a possible intrinsic defect within the T mu cell population.

Aged↗

Prognostic significance of large mediastinal involvement in Hodgkin's disease.

Relapse rates of 75 patients with previously untreated Hodgkin's disease with stages I and II nodular sclerosis were analyzed according to the mediastinal involvement. The overall relapse rate was 22.6%. The probability of relapse was much greater for patients with large mediastinal involvement (66.6%) compared with 17% for patients with small mass, and 11.7% of patients without mediastinal involvement (P less than 0.001). There was no significant difference in recurrence rates between patients without mediastinal mass and patients with a small mass, and in these patients adjuvant chemotherapy MOPP after radiotherapy showed an evident benefit in reducing the relapse rate. On the other hand, no beneficial effect of adjuvant chemotherapy was observed in patients with large mediastinal involvement. Finally, in the 17 relapsing patients, 'salvage' chemotherapy was less effective in patients with large mediastinal mass than in those with small or no mediastinal involvement.

Adolescent↗

Normal helper T-cell function in hairy-cell leukaemia.

The function of peripheral blood T-lymphocytes was tested in a series of untreated patients with hairy-cell leukaemia (HCL). The in vitro T-colony forming capacity fell within the normal range in 20 of the 22 cases studied. No difference in colony growth was found between splenectomized and non splenectomized patients. The ability to induce differentiation of normal B-lymphocytes into antibody producing plasma cells, in a pokeweed mitogen (PWM) stimulated system, was similar to that of normal T-cells in all 6 cases studied. Both the T-colony growth and the helper capacity were unrelated to the distribution of T-lymphocyte subsets defined by monoclonal antibodies, despite an increase in OKT8+ cells (suppressor/cytotoxic phenotype) and a decrease in OKT4+ cells (helper/inducer phenotype) in 44% of the patients. The significance of these findings is discussed in relation to T-cell abnormalities previously described in other B-cell leukaemias, chiefly chronic lymphocytic leukaemia (B-CLL). The preserved T-cell function in HCL correlates well with the normal humoral immunity found in this disease.

Antibodies, Monoclonal↗

HLA in familial Hodgkin's disease.

We report HLA genotypes in four familial cases of Hodgkin's disease (HD), Nodular Sclerosis (NS) histological subtype, where all patients showed B18 antigen. This finding, although statistically not supported, confirms the possible correlation between HD and B18 antigen which carries a high relative risk in international data.

Adolescent↗

Reduced T-colony forming capacity in B-chronic lymphocytic leukaemia.--II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia.

The T-colony forming capacity of T-lymphocytes from 33 cases of B-chronic lymphocytic leukaemia (B-CLL) and five of B-prolymphocytic leukaemia (B-PLL) was studied. An absent or reduced (less than 50) colony growth was observed in 21 of the 33 B-CLL and in four of the five B-PLL studied. Seven of the nine stage 0 patients (77.7%) according to Rai's clinical staging) gave rise to more than 50 colonies, compared with five out of 24 (20.9%) in stages I-IV patients. Furthermore, the mean number of colonies was significantly (p less than 0.01) higher in stage 0 patients (57 +/- 33.6), compared with more advanced stages (22 +/- 29.9). Since in normal peripheral blood, T-colony formation appears to be a property of T mu lymphocytes, and T gamma cells are significantly increased in B-PLL and B-CLL, mainly in advanced disease, the T-colony growth was correlated with the percentage of T gamma cells. Despite a negative trend, a statistical correlation was not observed. Our findings are suggestive of a functional defect of the T-cell population in the majority of cases of B-CLL, with a partial sparing in stage 0 patients. This abnormality, apparently unrelated to the T mu: T gamma ratio, is probably due to an intrinsic defect of the T mu cell population.

B-Lymphocytes↗

Characterization of T-lymphocyte subsets in hairy-cell leukaemia (HCL) by monoclonal antibodies: comparison with Fc gamma, Fc mu receptors and correlation with disease activity.

T lymphocytes from 22 patients with hairy-cell leukaemia (HCL) were assessed on the basis of their ability to bind the Fc receptors for IgM (T mu) or IgG (T gamma), and by the capacity to react with OKT monoclonal antibodies. T-cell subsets defined by the presence of Fc receptors for IgM or IgG showed an overall increase in the proportion of T gamma cells and a non-significant decrease of T mu cells, regardless of the clinical state of the disease. Results with monoclonal antibodies showed that in patients with HCL in clinical remission T-cell subsets were normally balanced, while in patients with active disease the distribution and absolute number of T-cell subpopulations appeared markedly impaired, with a significant increase of OKT8 positive cells (suppressor/cytotoxic) and a significant reduction of OKT4 positive cells (helper/inducer) compared both with active disease patients and with normal controls. The OKT4+/OKT8+ ratio was also significantly reduced in patients with active disease compared with those in clinical remission and with controls (0.96 v 1.63 and v 1.94, respectively). Our findings confirm the heterogeneity of T-cell subset positivity defined by monoclonal antibodies and by Fc mu and Fc gamma receptors and suggest that in patients with HCL the distribution of OKT4 and OKT8 positive cells is closely correlated to the clinical state of the disease.

Antibodies, Monoclonal↗

Reduced T lymphocyte colonies in B chronic lymphocytic leukaemia. III. Evidence of a proliferative abnormality of the T helper cell population.

The functional capacity of T and T mu (helper) cells from six untreated cases of B cell chronic lymphocytic leukaemia (B-CLL) was assessed in a double layer T colony forming assay. T lymphocytes from B-CLL originated few T colonies compared with normal T cells (35 +/- 25.9 vs 118 +/- 33.7). After enrichment of the T mu cells, colony growth in B-CLL was still reduced compared with the same cell fraction from normal controls (55 +/- 28.6 vs 90 +/- 35.6). When analysed independently, the three B-CLL cases with the lowest colony forming capacity, after enrichment of the T mu cells showed only a slight increase in growth, still well below the normal range. The two cases with normal or near normal colony growth, gave rise to similar results after T mu enrichment, indicating that, as in normal blood, B-CLL residual T colony formation is a property of the T mu cell population. In only one case was a significant increase and a normalization of the colony growth observed. It is suggested that the functional abnormality of T lymphocytes frequently observed in B-CLL patients, is not due only to the marked imbalance in T cell subsets, with a significant increase in T suppressor/cytotoxic cells and a reduction in T helper/inducer cells, but in many cases to an intrinsic defect of the T mu (helper/inducer) cell population.

B-Lymphocytes↗