681 research outputs found
THYMIC DYSFUNCTION IN CHILDHOOD T-ACUTE LYMPHOBLASTIC-LEUKEMIA - A POSSIBLE LINKAGE WITH A PRIMARY THYMUS INVOLVEMENT
No full textExperimental models, clinical and histopathological observations suggest a thymic origin of childhood T acute lymphoblastic leukemia (T-ALL).
We studied thymic epithelial function in childhood T-ALL as compared to normal controls in order to improve our understanding of the cellular immunodeficiency mechanisms operating in a thymus-linked malignant process. The levels of Facteur Thymique Serique (FTS) were measured in 9 patients at diagnosis, according to the rosette inhibition assay of Dardenne & Bach (1975). This method is based on the capacity of human serum containing FTS activity to confer on rosette-forming cells (RFC) from adult thymectomized mice a sensitivity to azathioprine identical to that of normal mouse RFC.
All patients presented low age-corrected titres of FTS. No zinc deficiency was found, suggesting that low FTS levels are not related to unexpressed FTS biological activity. Plasma from all the children studied contained factors capable of inhibiting the biological activity of FTS in vitro. However, the nature of this inhibitor has not yet been elucidated.
Our study shows the presence of a thymic dysfunction in childhood T-ALL, which could partially explain the immunodeficiency described in these patients. The linkage of the leukemic process with a primitive thymic involvement is discussed
EFFETTI DI CITOCHINE SULLA CRESCITA DI PRECURSORI CELLULARI B UMANI PURIFICATI E IN PRESENZA DI COMPONENTE (CD13+) STROMALE
No full textAs reproducible models for examining human early B-cell progenitors (BCPs) are poorly developed, the cells and molecules regulating their growth and differentiation are still incompletely characterized. We used a recently published short term culture system, using immunomagnetic beads and negative selection, in order to isolate an early BCPs enriched population from human fetal tissues that support further studies on B cell proliferation or differentiation events. This purified population was incubated with or without human recombinant Interleukin-4 (rIL4), and its capability to proliferate and differentiate was followed. We found that rIL4 did not induce either proliferation or differentiation of purified human BCPs. Furthermore in the presence of stromal cells (CD13+) it was able to enhance cy mu + cells and to induce the expression of surface Ig (sIg), surface CD22 on in vitro TdT + CD19 + CD10 + sIg-fetal liver cells. Human recombinant interleukin-7 (rIL-7) promoted the proliferation and the clonal growth of Tdt + CD19 + CD10 + fetal BCPs, confirming its critical role at early stages of human B lymphopoiesis. Furthermore rIL7 also induced growth of CFU-GM when unseparated fetal tissues or myeloid/monocytic contaminated BCPs were used as a target populations, probably by indirect mechanism. Transforming growth factor -beta (TGF-beta 1) partially inhibited the stromal cell-dependent rIL4 induced differentiation and rIL7 clonal growth and proliferation of fetal BCPs. Our study contributes to elucidate the growth factor requirements that characterize normal human B-cell ontogeny, suggesting another mechanism for the linkage between lymphopoiesis and myeloid/macrophagic micro-environment. The in vivo implications of this study are discussed
[The hematopoietic stem cell: biology and clinical applications] La cellula staminale emopoietica: biologia e applicazioni cliniche (Editoriale)
No full textThe hematopoietic stem cells (HSCs) are defined as cells that are able of both self-renewal and multilineage reconstitution of the hematopoietic system. Their biological properties and, similarly, the gene regulation, the positive and negative factors of the hematopoietic progenitor cells and the models of the hematopoietic amplification in the murine system are described. The clinical relevance of HCS has been obtained by the characterization and function of the CD34 cell surface molecule. The methods of isolation, selection and purification of HCS, the clinical use (particularly the mobilization of peripheral CD34+ cells) are detailed. Finally the potential advantages and use of HCS in vivo expansion are described
The effects of zoledronate on monocyte-derived dendritic cells from melanoma patients differ depending on the clinical stage of the disease.
No full textZoledronic acid has shown indirect anticancer effects on angiogenesis, the tumor microenvironment and immune responses. Its immunological action is exerted, at least in part, via its modulating properties. The aim of this study was to investigate the in vitro effects of zoledronic acid on the dendritic cells of melanoma patients. Peripheral blood samples were collected from 26 patients with melanoma and 11 healthy donors. Dendritic cells were derived from purified monocytes, and zoledronic acid (ZA) was added on the first day of culture. The phenotype and function of the generated cells were evaluated by flow cytometry. The ZA-treated monocytes from patients with early-stage disease generated DCs characterized by reduced endocytic activity and increased allostimulatory capacity compared with the untreated samples, allowing restoration of the DC function observed in normal subjects. In contrast, the ZA-treated monocytes from patients at stage III generated cells with higher CD14 antigen expression and endocytosis than the untreated samples. Therefore, in melanoma patients, the in vitro ZA effects differ according to the progression of the disease. In addition, our preliminary results appear to suggest that ZA effects are also influenced by the expression of CD14 antigen, indicating that the DC phenotype together with clinical characteristics must be considered in the choice of patients to be treated with ZA. Our work focus on the effect of ZA on monocyte-derived DCs from melanoma patients, showing that the effects of therapeutic doses of this drug might be mediated at least in part by modulation of myeloid cell function
Numerical defect of circulating dendritic cell subsets and defective dendritic cell generation from monocytes of patients with advanced melanoma.
No full textThe behaviour of circulating dendritic cells (DCs) and DC generation from monocytes in melanoma patients during the progression of disease have not been described. We report a significant decrease in the absolute number of total DCs, which mainly affects plasmacytoid DCs in stage IV. Additionally, monocyte-DC generation is less efficient in advanced stages, resulting in DCs that exhibit increased phagocytic capacity, potentially indicating a less mature state. These findings elucidate aspects of basic tumour-mediated immunosuppression, which may have implications for immunotherapeutic approaches, suggesting that the selection of patients for immunotherapy should also be made on the basis of their immune status
Immunological evaluation of patients with beta-thalassemia major
No full textAbnormalities in the immune system and zi nc homeostasis in patients with P-thalassemia major (TM) have been reported. Since zinc ion is essential for the efficiency of the immune system and is required to induce biological activity to thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22 normal controls of the same age, Inhibitory molecules anti-thymulin and the distribution of lymphocyte subsets were also analyzed. Patients with TM presented significantly lowered plasma zinc and thymulin levels when compared to normal subjects, The significant enhancement of the active form of the hormone after zinc addition in vitro suggests that low thymulin values found in TM are due not to a thymic failure in synthesizing and secreting the thymic hormone, but a defect in zinc saturation of the hormone. An impairment of cell subset distribution was also demonstrated. This study shows that zinc and thymulin deficiency contribute to the complex mechanisms underlying immune dysfunction in TM
Effetti in vitro di 8-MOP e UVA su cellule mononucleate ottenute da pazienti con GVHD cronica
No full textDistribution of age-related thymulin titres in normal subjects through the course of life
No full textThe thymus has a dominant immunological role in utero and in early childhood, being a primary source of T lymphopoiesis, and its investigation may be particularly relevant for the immunological study of paediatric patients. Thymulin, a nonapeptide secreted by the thymus, is an essential hormone for T lymphocyte differentiation and function. As thymulin values in the normal population have not been well documented, especially for children under the age of 1 year, we detail thymic endocrine function by presenting age-related plasma thymulin levels in a large series (n = 93) of healthy individuals, ranging from birth to old age. We demonstrate that thymulin is already detectable at birth; it then gradually increases with age, reaching the highest level in children aged 5-10 years. Starting at adolescence, thymulin titres gradually start to fall, reaching the lowest value at 36 years of age and remaining steady until 80 years (the oldest person tested)
Evaluation of thrombopoiesis kinetics by measurement of reticulated platelets and CD34+ cell subsets in patients with solid tumors following high dose chemotherapy and autologous peripheral blood progenitor cell support
No full textBackground and Objectives. The transplantation of mobilized peripheral progenitor cells has resulted in shortening of neutrophil and platelet engraftment times following high-dose chemotherapy. Since reticulated platelet percentage (RP%) has been established as a measure of bone marrow platelet production, we performed this type of analysis on the thrombopoietic compartment during transplant-related chemotherapy.
Design and Methods. Kinetics of thrombopoiesis of 19 patients with solid tumors undergoing a single or double autologous peripheral blood progenitor cell transplant was characterized by evaluating the level of RR The correlation between CD34(+) cell subsets and the time of highest percentage of RP was also evaluated.
Results. The percentage of RP increased from day +8 after single transplant reaching the peak (3.4%) at day +10. In the group of patients receiving double transplant, the peak RP value of observed after the second transplant is not significantly different from that observed after the first transplant (3 vs 3.7%). In a subgroup of patients both the number of CD34+ cells/Kg infused and the percentage of CD34(+)CD61(+) cell subsets correlated with the day of RP peak.
Interpretation and Conclusions. These results suggest that RP measurement is an early indicator of engraftment. Additionally, the observation that RP percentage is high at the time of platelet transfusion in 13 out of 20 cases of transfusions (the 7 cases with low RP value being transfused during the period of obligate thrombocytopenia) suggests that the evaluation of this parameter, together with the platelet count, can be used to monitor, the need for platelet transfusion
B cell colony assay improves the sensitivity of the cytogenetic analysis in common acute lymphoblastic leukemia.
No full textThe recognition and identification of subtle chromosomal changes in leukemic cells has greatly been facilitated since the advent of high-resolution banding techniques. However efficient utilization of these methods is often hampered by the paucity of leukemic cells during clinical remission, the variability of cell cycle length and tissue culture conditions. Therefore the detection of minimal residual disease in acute lymphoblastic leukemia by cytogenetic methods requires a preselection of material to be examined. In this preliminary report analyzable metaphases could be obtained in cultured cells from a colony assay for malignant peripheral B cell progenitors, whereas in marrow samples direct or 24 hours G-banding technique had failed to reveal metaphases in common Acute Lymphoblastic Leukemia patients during complete remission. It is believed that in common Acute lymphoblastic Leukemia patients this B cell colony assay permits the clonal expansion of residual circulating cells linked to malignant clone that are not detectable by classic hematologic and cytologic methods. In addition, this culture procedure substantially improves the sensibility of cytogenetic approach to the study of minimal residual disease in acute lymphoblastic leukemia during complete remission
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