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Biomedical subjects

M Ciancarelli

Publications and source records attributed to M Ciancarelli.

9 recordsLinked to original sources

Dimethyl sulfoxide induces programmed cell death and reversible G1 arrest in the cell cycle of human lymphoid pre-T cell line.

In human B- and T-differentiated lymphoid cell lines DMSO was found to arrest the proliferation at the G1 stage of the cell cycle, without any detectable differentiation and DMSO itself was found to prevent apoptosis. Programmed cell death, or apoptosis, is now thought to be an important regulatory process in normal hemopoiesis and in the lymphoid system this program is started in the immune process such as autoreactive T-cell elimination in the thymus, and antigen-driven B-cell selection in the terminal centre. For this purpose, we have analysed the effect of DMSO using undifferentiated pre-B (KM-3) and pre-T (RPMI-8402) human lymphoid cells. Results obtained by multiparametric analyses show that DMSO affect only the pre-T cell line inducing a reversible G1 arrest of the cell cycle with a significant presence of apoptotic cells and modification of terminal transferase (TdT) expression. Pre-B cell line is resistant to DMSO treatment. These data provide evidence of a new model for the study of the selective cell type depending effect of DMSO in the immune system.

Apoptosis↗

Intravenous immunoglobulins suppress the recurrences of genital herpes simplex virus: a clinical and immunological study.

Effective treatment is not currently available for suppressing the recurrence of genital herpes simplex virus (HSV) infections. Since intravenous immunoglobulins (IVIG) proved useful against HSV in experimental models, we treated patients with very high frequency of HSV genital recurrences (more than 15 episodes per year) with IVIG (400 mg/Kg every fourth week). The control group was treated with intermittent oral acyclovir (800 mg twice a day for one week every month). Both groups were treated for six months and, then, patients were followed-up to further six months. Both IVIG and acyclovir were effective in reducing the frequency of HSV genital recurrences as compared to base-line. However, patients treated with IVIG had a more striking reduction in the frequency of recurrences as well as both a shorter mean duration and a minor severity of the lesions as compared to acyclovir-treated patients. Furthermore, we found a trend indicating IVIG as more effective in reducing the viral load. Since in IVIG-recipients we found a strong increase of peripheral blood lymphocytes with natural killer (NK) surface phenotype, we suggest that the clinical effectiveness of IVIG treatment is probably mediated via the expansion of NK cell populations. Our study indicates that the treatment with IVIG is an effective and safe tool for suppressing the recurrences of genital HSV infections.

Acyclovir↗

Cytokines and programmed cell death in burkitt lymphoma cells.

Tumour necrosis Factor (TNF), Interleukin 1alpha and beta (IL-alpha and IL-beta), Interleukin 7 (IL-7) and Stem Cell Factor (SCF) are cytokines synthesized by immune system cells under stimulation of various agents. Apoptosis, or programmed cell death, is a process that appears in response to specific stimuli, apparently following an intrinsic program. In this work we examined, in RA-1 human lymphoblastoid B cell line, the effect induced by different cytokines in cell proliferation and in programmed cell death. After 48 hours of treatment is present an antiproliferative affects, detected by 3H-thymidine incorporation and morphological changes related to apoptotic process.

Apoptosis↗

Allogeneic bone marrow transplantation for Fanconi anemia.

Five patients (age range 7-14 years) received allogeneic bone marrow transplantation (BMT) for Fanconi anemia (FA). All patients showed progressive pancytopenia associated with congenital malformations. Diagnosis was confirmed by studies of cellular hypersensitivity to the clastogenic effect of the DNA crosslinking agent diepoxybutane. The conditioning regimen consisted of low dose cyclophosphamide (5 mg/kg x 4) and fractionated total body irradiation (167 cGy x 3). For graft-versus-host disease prophylaxis one patient was given cyclosporin alone while the remaining four patients received a combination of cyclosporin and two doses of methotrexate. Marrow was given unmanipulated from HLA-identical siblings. All patients are alive 18-67 months after grafting with Karnofsky scores of 100% and normal hemopoiesis of donor origin. Modifications in transplant protocols such as those here described have resulted in a decreased risk of severe transplant-related complications. These results confirm that BMT is a curative therapy in FA patients and should be considered as a first choice treatment if an HLA-identical donor is available.

Adolescent↗

Cytogenetics in patients with chronic myelogenous leukemia treated with bone marrow transplantation.

Cytogenetic data are reported from 16 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) treated with bone marrow transplantation (BMT). The usefulness of cytogenetic investigations for the assessment of marrow engraftment is stressed. The significance of persistence or reappearance of Ph after BMT, possibly due to a defective leukemic clone eradication by the conditioning regimen, is also discussed. Generally, Ph-positive cells are damaged and disappear within the first year of BMT. Sometimes, however, the cells may repair the damage and proliferate again, resulting in disease relapse. Rarely, clinical and hematologic relapse does not follow Ph-positive clone expansion although leukemic cells represent more than 50% of marrow metaphases examined. Finally, the effect of interferon on Ph-positive clones after BMT and random chromosome changes, that appear transiently after BMT and are of uncertain significance, are discussed.

Adolescent↗

TCR and immunophenotype changes in dimethyl sulfoxide-dependent programmed cell death.

In the thymus most deleted cells are immature thymocytes and the high rate of cell death within the thymus is involved in the development of the initial T-cell receptor repertoire. Functional T-cell receptor recognition units are created by somatic rearrangements of gene segments, and the expression of successfully assembled TCR complex is the key to molecular events that culminate in T-cell activation, growth and differentiation. Previously, we reported that DMSO induces apoptosis in RPMI-8402 human pre-T cells. Here we examine the fate of pre-T cells undergoing negative selection analysing the responsiveness to DMSO-enforced TCR expression and immunophenotype modulation. Our results demonstrate that DMSO induces cell growth inhibition, cell phenotype changes, with down-regulation of CD2 and CD7, and increases in alpha/beta or gamma/delta TCR chains led by TdT, RAG-1 and RAG-2 activity. These modifications are associated with an apoptotic program. Taken together, these data suggest the existence of an early checkpoint that ensures in vivo the effective intrathymic differentiation supported from another point of view, the linkage between immunophenotypes and TCR regulation in T-cell differentiation and programmed cell death.

Antigens, CD↗