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Biomedical subjects

A Astaldi

Publications and source records attributed to A Astaldi.

At least 37 records · Page 2Linked to original sources

Thymocyte maturation induced by a thymus-dependent serum factor.

By means of direct measurement of intracellular cyclic AMP in thymocytes in vitro we demonstrated the existence in human serum of a thymus-dependent factor (SF). This activity of SF appeared to be due to a very low M.W. (less than 500) peptide distinct from other circulating thymic peptides. SF was found to act selectively on immunologically immature, hydrocortisone (HC)-sensitive peanut lectin-agglutinating thymocytes. In a period of 240 min SF sequentially induces in thymocyte synthesis of cyclic AMP, protein synthesis and synthesis of phosphorylated non-histone chromatin proteins of high molecular weight. Because SF does not induce a change in DNA synthesis, it seems likely that the events induced by SF are associated with a process requiring DNA translation, but not DNA replication. The biochemical events induced by SF are accompanied by the acquisition of immunological maturation by thymocytes. This has been shown by the acquisition of HC resistance, by the expression of FC receptors for IgM, by the decrease of terminal transferase activity and by the induction of the capacity to elicit a graft-versus-host reaction. We conclude that, most likely, SF acts on immature thymocytes inducing a part of them to acquire some properties of mature T cells.

Animals↗

Influence of adult thymectomy on immunocompetence in patients with myasthenia gravis.

The influence of adult thymectomy on several parameters of immunocompetence in patients with myasthenia gravis (MG) was investigated. Since incomplete thymectomy may lead to the presence of thymic remnants, we determined the activity of a thymus-dependent factor in the sera of the MG patients. As measured by several parameters, MG patients showed a normal immunocompetence compared with healthy controls, except in the response to DNCB sensitization in vivo. When tested at least 5 years after thymectomy, MG patients were found to have decreased response to mitogens, and a decreased cytotoxic T cell response in cell-mediated lympholysis. The response to challenge with DNCB in vivo was decreased both in thymectomized and nonthymectomized MG patients. No difference was found in a) the percentage of circulating T, B, non-B/non-T cells; b) the response to allogeneic cells (MLR); c) the antibody-dependent lymphocytotoxicity; d) the production of immunoglobulins in vitro by pokeweed mitogen-stimulated cells; and e) the anamnestic response to antigens in vitro. We conclude that adult thymectomy results in a decrease in the function of some subpopulations of lymphocytes.

Adult↗

Early events in thymocyte activation. II. Changes in nonhistone chromatin proteins induced by a thymus-dependent human serum factor.

Previously, it has been shown that a human thymus-dependent serum factor (SF), isolated from peripheral blood and acting on precursors of mature T lymphocytes, induces an increase in the synthesis of cyclic AMP and proteins in thymocytes. We have now investigated the action of SF on the incorporation of 3H-leucine and 32P-orthophosphate into nuclear proteins of thymocytes after 15 to 240 min of culture. SF induced a rapid increase in the synthesis and phosphorylation of nuclear proteins, especially in the phosphorylated nonhistone chromatin proteins (P-NHCP). Electrophoretic patterns in polyacrylamide gels of the P-NHCP fractions, extracted from the chromatin of the stimulated cells, showed that proteins with m.w. higher than 50 x 10(3) were synthesized to a larger extent as compared with unstimulated cells. These data suggest that SF acts specifically on the synthesis of P-NHCP and may in this way control DNA-template activity.

Chromosomal Proteins, Non-Histone↗

Lymphoid cell surface markers in acute lymphocytic leukaemia.

Peripheral blood lymphoid cells of 29 patients with acute lymphocytic leukaemia (ALL) at onset were studied for characterization of B and T membrane markers and phytohaemagglutinin responsiveness. 24 cases (83%) were classified as "null" cell ALL and 5 (17%) as T-cell ALL. No relationship could be found between cytological presentation and immunological classification. Moreover, no correlation has been demonstrated between clinical-immunological parameters and prognosis, indicating that in our series of patients, assessment of cell size and surface markers were not a reliable predictor of prognosis.

Antineoplastic Agents↗

Experiences with thymosin in primary immunodeficiency disease.

Thymosin has no effect in vitro on cyclic AMP levels in thymocytes. However, when thymosin was injected into patients lacking "serum factor" (SF) activity, it induced the appearance of SF or SF-like activity and the disappearance of target cells for SF among the peripheral blood lymphocytes of the treated patients. On the other hand, when thymosin was injected into one patient with normal SF activity, it induced a marked decrease of SF activity and the appearance of target cells for SF among the peripheral blood lymphocytes of this particular patient.

Animals↗

Effect of a human serum thymic factor on hydrocortisone-treated thymocytes.

A human serum thymic factors (SF) stimulated cyclic adenosine-3' ,5'-monophosphate (cAMP) synthesis in normal mouse thymocytes. Such stimulation was no longer observed when thymocytes were depleted of hydrocortisone (HC)-sensitive cells. It was concluded that SF selectively stimulate cAMP in HC-sensitive cells. Furthermore, incubation of thymocytes with SF enlarged the population of HC-resistant thymocytes. These results suggest that SF might act on HC-sensitive thymocytes increasing their cellular cAMP level and inducing their transformation in HC-resistant cells.

Animals↗

Thymosin-induced human serum factor increasing cyclic AMP.

Thymosin has virtually no in vitro effect on cyclic AMP levels in thymocytes and seems not to react with either the beta-adrenergic receptor or with the putative human serum thymic factor (SF) receptor. However, when thymosin is injected into patients lacking SF activity, it induces the appearance of a serum factor which increases cellular cyclic AMP levels in thymocytes in vitro. This factor appears to act on a membrane site distinct from the beta-adrenergic receptors.

Animals↗

Properties of lymphocytes in chronic HBAg-positive hepatitis. An approach to pathogenetic problems.

Lymphocytes from 22 children affected by chronic hepatitis were studied and a comparison was made with a control group of 32 healthy children in the same age range with respect to PHA dose-response curves. E-rosette formation and membrane immunoglobulin (Ig). From the results it appeared that PHA dose-response curves were displaced to the left (low PHA dose), DNA synthesis was significantly higher for all PHA dosages tested, and that the plasma of chronic hepatitis patients acted neither as inhibitor nor stimulator. The percentage of E-rosette-forming cells decreased, but the total number was normal. The mean percentage of Ig-bearing cells was normal but the single values were spaced over a wide range. It can be assumed that, at least in the chronic stage, there is an enhanced response to PHA and an increased percentage of cells without markers either for T or for B cells.

Antibody Formation↗

Cytoenzymochemical effects of some antiblastic drugs and prediction of response to chemotherapy in acute leukemias.

Over 20 cytoenzymochemical tests were carried out in 152 patients with different types of acute leukemia to estimate the effects of some antiblastic drugs such as L-asparaginase, Purinethol, Methotrexate, Endoxan, Vinchristine, Cytosine Arabinoside a.o. The patients selected for the study were carefully examined before treatment at different moments during and/or at the end of the treatment. The effects of these drugs on the blast cells were mild when the cellular populations had a low rate of nucleic acid synthesis, high glycogenic score and high amounts of lipids or an important oxidative enzymatic activity. The enzymatic prediction tests: the acid phosphate deviation test and the succinic dehydrogenase inhibition test including the variant suggested by some of the authors - the latic dehydrogenase inhibition test - gave satisfactory results only in certain cases of acute leukemia.

Acid Phosphatase↗