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Biomedical subjects

G Dighiero

Publications and source records attributed to G Dighiero.

154 records · Page 9Linked to original sources

Contribution of quantitative immunocytology to the study of lymphoid hemopathies.

Forty-three patients with a lymphoid hemopathy, three with agammaglobulinemia and six normal controls were investigated with regard to their blood lymphocyte membrane-associated light chains. Detection and quantitation of antigenic determinants were performed by means of peroxidase-labeled antibodies. Compared to normal controls, values found in chronic lymphocytic leukemia (CLL) were very low (tenfold decrease). The number of antigenic determinants on lymphoid cells from patients with blast crises supervening in CLL, prolymphocytic leukemia, Waldenström's macroglobulinemia and Burkitt-cell acute leukemia were significantly higher than those seen in patients with CLL. The data obtained in this investigation through quantitative immunocytology constitutes a new parameter for the classification of lymphoid hemopathies and for an approach to their pathogenesis, in particular if the quantity of membrane immunoglobulin correlates with the stage of cell maturation.

Adult↗

Variations in lymphocyte counts four hours after administration of hydrocortisone in patients with chronic lymphocytic leukemia.

The peripheral lymphocyte count and the number of large unstained cells (LUC) were investigated prior to and 4 hr after a single intravenous injection of 400 mg of hydrocortisone in 23 controls and 51 patients with lymphoid disorders (43 chronic lymphocytic leukemia, 3 cases of Waldenström macroglobulinemia, 2 hairy cell leukemias, 1 Sézary syndrome, and 2 cases of infectious mononucleosis). A reduction in both the peripheral lymphocyte counts and the number of LUC was observed in all normal controls, the mean decrease being 54% and greater than 60%, respectively, with differences according to age. In chronic lymphocytic leukemia (CLL), the peripheral lymphocyte count showed a variable response: decrease, no change, or increase. A correlation was shown to exist between a decrease in peripheral lymphocyte counts and anatomical-clinical staging: patients with involvement restricted to blood and bone marrow very often exhibited a drop in their peripheral lymphocyte count (p less than 0.01). In addition, the percentage of circulating T lymphocytes was higher (54%) in CLL patients whose peripheral lymphocyte count dropped than in other CLL patients (p less than 0.001).

Age Factors↗

[Lymphography in chronic lymphocytic leukemia (author's transl)].

Sixty-seven lymphangiograms were performed in 58 patients with chronic lymphocytic leukemia. These patients were classified according to a new anatomico-clinical staging system which has previously been shown to bear prognostic significance. The lymphangiograms were divided into four groups on the basis of lymph node size and each group was further divided into subgroups (12). Each subgroup corresponded to a different roentgenographic picture. A good correlation was observed between lymphangiographic and anatomico-clinical staging: lymphangiogram groups 3 and 4, anatomico-clinical stage III and IV (p less than 0.001). The absence of normal lymph nodes in all patients, the diversity of lymphangiographic appearance from one patient to another and even the diversity from one region to another in the same patient should be stressed.

Adult↗

Comparison of normal and chronic lymphocytic leukemia lymphocyte surface Ig determinants using peroxidase-labeled antibodies. II. quantification of light chain determinants in atypical lymphocytic leukemia.

Five cases of atypical lymphocytic leukemia were investigated with regard to their membrane-associated light chains. Detection and quantitation of antigenic determinants were performed by means of peroxidase-labeled antibodies according to Avrameas et al. The cases studied had clinical and cytologic features in common: an active clinical course, marked splenomegaly, severe anemia and thrombocytopenia, little or no lymph node enlargement, and very high white blood counts with small mature lymphocytes and poorly differentiated lymphoid cells. Blood lymphocytes of all patients carried a single type of light chain, and 90%-100% of the cells were stained. The average number of antigenic sites per cell was 72,500 (range 40,000-97,500). These results differed from those previously found in typical CLL (mean value 9000) and approached the values of normal peripheral blood lymphocytes (90,000). The criteria investigated in this study could be of value for the diagnosis and prognosis of some atypical forms of lymphocytic leukemia.

Aged↗

Patient accrual and interim statistical analysis in long-term randomized clinical trials: the French chronic lymphocytic leukemia CLL 80 protocol as a case study.

The CLL 80 clinical trial of treatment for chronic lymphocytic leukemia was designed using a three-stage prognostic classification. Within each stage patients received one of two treatments allocated by randomization, two adjacent stages having a common treatment. The fixed-sample design required 850 patients entered over a period of 8.5 years. Active patient recruitment led to 741 patients being randomized in four years. The first interim analysis, carried out at this point, showed a treatment difference in one stage which was statistically significant (p = 0.001) and justified an early termination of the protocol. This paper discusses practical aspects of patient accrual and interim analysis in this study.

Antineoplastic Combined Chemotherapy Protocols↗

5th International Workshop on Chronic Lymphocytic Leukemia.

In the past few years important advances have been made in our understanding of the biology and natural history of CLL; also, new strategies and agents offer promise in the treatment of this form of leukemia. Now, patients can be treated on a more rationale basis and with real prospects for a sustained control of their disease, and improved quality of life. Hopefully, progresses in CLL will continue to accumulate in the coming years.

Animals↗

Natural antibodies against tubulin, actin myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenström's macroglobulinemia may express similar antibody specificities.

Sera from a pool of 800 healthy donors and from 3 individual healthy donors were passed through tubulin, actin, thyroglobulin, myoglobin, fetuin, transferrin and albumin immunoadsorbents. Proteins were eluted in all the immunosorbents and were found to be essentially composed of the three major Ig classes and albumin. The isolated Ig fractions were shown to react specifically, via their Fab fragment with the antigens and were specifically inhibited by them. These results strongly suggest that natural antibodies against the seven antigens are present in normal human serum, and probably against a high variety of self antigens. These results prompted us to search in the sera of patients with monoclonal gammapathies, paraproteins having natural antibody-like function. Among the 62 sera studied 3 were shown to react with actin and 1 with tubulin. Most important, these 4 monoclonal immunoglobulins exhibited similar specificities to that found with natural antibodies. This seems to indicate, that at least for some patients, the monoclonal immunoglobulins produced may represent the expansion of a clone producing a natural antibody.

Actins↗

Expression of VH11-gene family in hybridoma collections from peritoneum and spleen: differential correlation with BrMRBC reactivity.

Hybridoma collections from spleen or peritoneal cells of newborn or adult individuals were screened by RNA hybridization for expression of the VH11-gene family using a V-region probe VCP12, which encodes anti-BrMRBC antibodies. No VH11 expression was observed in hybridomas derived from newborn spleen cells in either BALB/c, NZB or (CBA/N x BALB/c) F1 mice (0/93). Adult NZB and BALB/c spleen cell collections contained only one hybridoma expressing VH11 (1/242). Interestingly, however, the VH11-positive hybridoma showed no anti-BrMRBC reactivity, while one anti-BrMRBC clone in the same collection expressed a Q52 VH gene. In contrast, hybridomas derived from peritoneal cells showed an absolute correlation between expression of VH11 genes and anti-BrMRBC reactivity (15/32). The high expression in the peritoneal cavity of such cells is likely the result of local positive selection.

Animals↗