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Biomedical subjects

R Consolini

Publications and source records attributed to R Consolini.

At least 19 recordsLinked to original sources
PubMed2005

Circulating epstein-barr virus in children living in malaria-endemic areas.

Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase in the number of EBV-carrying B cells in the circulation. To further understand the potential influence of malarial infection on the EBV persistence in children living in malaria-endemic areas, we studied the occurrence and quantified cell-free EBV-DNA in plasma from 73 Ghanaian children with and without acute malarial infection. Viral DNA was detected in 40% of the samples (47% in the malaria-infected and 34% in the nonmalaria group) but was absent in plasma from Ghanaian adults and healthy Italian children. These findings provide evidence that viral reactivation is common among children living in malaria-endemic areas, and may contribute to the increased risk for endemic BL. The data also suggest that the epidemiology of EBV infection and persistence varies in different areas of the world.

Burkitt Lymphoma↗
PubMed2001

Effects of vitamin D on the growth of normal and malignant B-cell progenitors.

As the effects of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) (VD, calcitriol) on the proliferation and differentiation potential of normal and leukaemic cells in vitro of myeloid lineage are known, we investigated the response to VD on the growth of both normal and malignant lymphoid progenitors. Effects of vitamin D on normal human lymphoid progenitors and B lineage acute lymphoblastic leukaemia (ALL) progenitors were assessed by using an in vitro cell colony assay specific for either B or T cell lineages. The expression of VDR on B untreated malignant progenitors at diagnosis was investigated by RT-PCR analysis. VD induced a significant inhibition of normal lymphoid cell progenitors growth of both T and B lineage. VD inhibited significantly also the growth of malignant B cell lineage lymphoid progenitors, without inducing cytotoxic effect. As it has been reported that VD effects on activated lymphocytes are mediated by 1,25-(OH)2-D3 nuclear receptor (VDR), we investigated VDR expression on malignant B cell progenitors. We did not detect VDR expression on these cells examined at diagnosis. We demonstrated that VD inhibited in vitro the clonogenic growth of both normal and malignant lymphoid B cell progenitors and that this inhibitory effect on malignant B cell progenitors was not related to VDR. Our work contributes to understanding of the mechanism of action of this hormone in promoting cellular inhibition of clonal growth of malignant lymphoid B cell progenitors, suggesting that the regulation of some critical growth and differentiation factor receptors could be a key physiological role of this hormone.

B-Lymphocytes↗
PubMed2001

Immunological evaluation of patients with beta-thalassemia major.

Abnormalities in the immune system and zinc homeostasis in patients with beta-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.

Adolescent↗
PubMed2001

[The hematopoietic stem cell: biology and clinical applications].

The 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.

Animals↗
PubMed2001

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.

BACKGROUND AND OBJECTIVES: The transplantation of mobilised peripheral progenitor cells has resulted in shortening of neutrophil and platelet engrafment times following high-dose chemotherapy. Since reticulated platelet percentage (PR%) 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 RP. The correlation between CD34(+) cell subsets and the time of highest percentage of RP was also evaluated. RESULTS: The percentage of RP increases since day +8 after single transplant reaching the peak (3.4%) at day +10. In the group of patients receiving double transplant, the RP value of peak observed after second transplant is not significantly different from that one 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 correlate 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.

Adult↗
PubMed2000

Distribution of age-related thymulin titres in normal subjects through the course of life.

The 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).

Adolescent↗
PubMed2000

Primary thymic endocrine failure in HIV-1-infected children.

Thymulin, an essential hormone for the T lymphocyte differentiation process and function, was evaluated to asses thymic endocrine function in a cohort of 17 HIV-1-infected children aged between 2 months and 14 years, 18 seroreverted subjects and 47 normal controls. The rosette inhibition assay by Dardenne and Bach (1975) is the only method available to evaluate the biologically active form of this hormone (thymulin or Zn-facteur thymique sérique, Zn-FTS), as immunoassays cannot discriminate between thymulin and the inactive form of the hormone not containing Zn (FTS). HIV-1 patients presented undetectable or significantly lowered plasma levels of thymulin. Plasma zinc levels were significantly reduced in patients although inactive, zinc-unbound thymulin molecules were not demonstrated. The investigation of inhibitory anti-thymulin molecules performed in all patients was negative. Thymulin titers did not correlate with CD4+ lymphocyte count at the different disease stages. This study suggests that a primary thymic endocrine deficiency is present in HIV children. The critical importance of these results in assessing disease progression and a potential therapeutic approach are discussed.

Adolescent↗
PubMed1999

The c-kit receptor and its ligand stem cell factor in childhood malignant lymphoid precursors.

The c-kit receptor (CD117) and its ligand stem cell factor (SCF) play an important role in the development, differentiation, and survival of normal and malignant hematopoietic cells. The aim of this work is to review the cellular distribution of this receptor and the effect of SCF on the hematopoietic system, particularly among lymphoid lineage, either in normal or malignant cell progenitors. We examined reports and results in the field and articles or abstracts published in journals covered by MEDLINE. Additionally, we evaluated CD117 expression on fresh blast cells of 376 newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL) that were referred to centers affiliated with the Italian Association for Pediatric Hematology and Oncology (AIEOP). In view of our data, approximately 11% of ALL are CD117 positive. In particular, this receptor can be expressed in 10% and 11.5% of T-lineage and B-lineage ALL, respectively. Its expression is associated with an intermediate/mature phenotype in T-lineage ALL, whereas in B-lineage ALL, the majority of the positive cases are classified as early B ALL. The effect of SCF on malignant hematopoiesis and its potential clinical uses are reviewed.

Cell Lineage↗
PubMed1998

Expression of myeloid markers lacks prognostic impact in children treated for acute lymphoblastic leukemia: Italian experience in AIEOP-ALL 88-91 studies.

The importance of coexpression of myeloid antigens in childhood acute lymphoblastic leukemia (ALL) has long been debated; results are conflicting. We studied children with ALL treated at Italian Association for Pediatric Hematology-Oncology (AIEOP) institutions over 6 years with Berlin-Frankfurt-Muenster (BFM)-based protocols and have analyzed the incidence of coexpression of six MyAg (CD11b, CD13, CD14, CD15, CD33, CD65w) to determine its prognostic impact. Criteria for MyAg coexpression (MyAg+ALL) included positivity to one or more MyAg on at least 20% of blasts and confirmation of coexpression at double-fluorescence analysis. A total of 291 of 908 cases were MyAg+ALL (32%). Incidence was similar in B-ALL and T-ALL; among common, pre-B, and pre-pre-B-ALL. CD13 and CD33 were most common. Patients with MyAg+ALL had presenting features similar to MyAg-ALL. They entered standard or intermediate risk protocols more frequently and had better prednisone response, but similar complete remission rates. Six-year event-free survival (EFS) was 69.0% in 291 MyAg+ALL cases and 65.3% in 617 MyAg-ALL cases, without significant difference. Cases expressing two or more MyAg presented similar clinical features and treatment response. MyAg+ALL had worse EFS only in infants (0% v 47%) (P = .01). Therefore, in this series of homogeneously diagnosed and treated ALL, coexpression of MyAg was not associated with prognostic significance, without relevance for clinical purposes or for patient stratification, except for infants.

Antigens, CD↗
PubMed1998

In vitro cytotoxicity of docetaxel in childhood acute leukemias.

PURPOSE: In seeking to identify novel effective antileukemic agents, we assessed the in vitro activity of the taxoid docetaxel (Taxotere; Rhone-Poulenc Rorer, Antony, France) in primary leukemic cells supported in culture by bone marrow-derived stromal layers. MATERIALS AND METHODS: Bone marrow samples from children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were cultured on allogeneic bone marrow-derived stromal layers and exposed to various concentrations of docetaxel. After 7 days of culture, the number of viable leukemic cells were counted by flow cytometry and compared with that in parallel cultures without drugs. RESULTS: In 20 samples tested (15 B-lineage ALL, one T-lineage ALL, and four AML), the median cytotoxicity was 78% after a 7-day culture in the presence of 100 ng/mL docetaxel (range, 54% to 95%). The effects were dose-dependent and extended to all five ALL samples with the t(9;22)(q34;q11) (Philadelphia chromosome) or 11q23 abnormalities, karyotypes associated with an unfavorable outcome. Studies with continuously growing cell lines demonstrated that docetaxel exerted its cytotoxic effect by inducing apoptosis, and was consistently more effective than paclitaxel (Taxol; Bristol-Myers Squibb, Wallingford, CT) (mean 50% cell kill [LC50], 6.93 v 12.86 ng/mL in six leukemic cell lines). The antileukemic activities of docetaxel and vincristine were synergistic. While the mean (+/- SD) cytotoxicity of vincristine (0.1 ng/mL) was 11.2% +/- 7.3% and that of docetaxel (10 ng/mL) was 19.3% +/- 17.5% in CEM-C7 cells after 24 hours, combining the two agents increased the cytotoxicity to 62.5% +/- 20.7% (P = .003). CONCLUSION: Docetaxel, at concentrations achievable in vivo, is cytotoxic to ALL and AML cells. These results provide a rationale for clinical trials of docetaxel in patients with acute leukemia.

Acute Disease↗
PubMed1998

Clinical relevance of CD10 expression in childhood ALL. The Italian Association for Pediatric Hematology and Oncology (AIEOP).

BACKGROUND AND OBJECTIVE: Previous studies have considered the prognostic significance of CD10 expression in childhood acute lymphoblastic leukemia (ALL) and showed its linkage to a more favorable prognosis. The aim of this study was to assess the independent significance of CD10 expression in a large population of ALL patients. DESIGN AND METHODS: We revised the independent clinical relevance of CD10 expression in 2038 children with acute lymphoblastic leukemia (ALL), who were consecutively entered in 4 sequential trials of the Italian Association for Pediatric Hematology and Oncology (i.e. AIEOP studies 82, 87, 88, 91); 1142 were males and 896 females, age ranged between 1 and 14 years (yrs) at diagnosis. Of the whole group, 1471 children (72.2%) were defined as having standard risk, 567 (27.8%) as having a high risk. RESULTS: CD10 was detected in blast cells from 1706 of 1784 (95.6%) patients with B-lineage ALL and 46 of 254 (18.1%) with T-cell ALL. In the B-lineage subgroup CD10 expression was associated with presenting features such as age < 9 yrs and inclusion in the standard risk category. No significant differences were found between CD10+ and CD10- cases in T-lineage ALL, concerning presenting features, except for FAB L2 in the former group. We compared the event-free survival (EFS) rates for patients with T-ALL or B-lineage ALL, regarding CD10 positivity, overall and by individual study. Patients with T-ALL fared worse than those with B-lineage ALL (5 and 10 yrs EFS: 46.8% vs. 68.5% and 44.5% vs. 63.7% respectively, p = 0.0001). In multivariate analysis of B-lineage subgroup poorer EFS was associated with male sex, higher WBC (> or = 20 x 10(9)/L), age > 9 yrs. Only WBC > or = 20 x 10(9)/L and age > 9 yrs were parameters linked to poorer EFS in the T-lineage subgroup. Finally, we compared EFS rates for four groups of patients categorized as having high or standard risk, and according to CD10+ and CD10- expression. High-risk patients fared statistically worse than standard risk patients both in the CD10- and in the CD10+ groups (42% vs. 50.7% and 63.6% vs. 66.8%, respectively). INTERPRETATION AND CONCLUSIONS: CD10 expression does not have independent prognostic significance in either the larger subgroup of B-ALL patients or in T-cell ALL.

Adolescent↗
PubMed1997

The effect of cytokines, including IL4, IL7, stem cell factor, insulin-like growth factor on childhood acute lymphoblastic leukemia.

We have investigated the effects of some interleukins, such as interleukin (IL) 4, IL7, stem cell factor (SCF) and insulin-like growth factor (IGF-1), known to be involved in human lymphopoiesis, on proliferation, clonal growth and differentiation of cells from two acute lymphoblastic leukemia (ALL) derived pre-B cell lines, that is, Nalm 1, Nalm 6 and purified blasts from 37 childhood ALL. IL4 did not display any promoting activity, an inhibitory effect being observed in two patients. IL7 showed an heterogeneous responsiveness, not related to immunophenotype or cytogenetic features, proliferation and clonal growth being observed in a minority of ALL. In other patients no or even inhibitory effects on proliferation were observed. In one case this inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of surface immunoglobulins (slg); other IL7 treated samples failed to express slg, but showed a decreased expression of terminal deoxynucleotidyl transferase and cALL antigen, suggesting that the cells have a potential of limited maturation by IL7. SCF, known to synergize with IL7 in the most primitive stages of normal B cell development, did not enhance the IL7 response in B cell precursor ALL. Finally IGF-1 failed to induce a proliferative response and clonal growth in BCP ALL either alone or in combination with IL7.

Adolescent↗
PubMed1997

[Effect of cytokines on the growth of human B-cell precursors, purified and in the presence of stromal (CD13+) components].

As 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.

B-Lymphocytes↗
PubMed1996

Lymphokine release during co-culture of human lympho-mononuclear cells and fresh or cultured human, porcine and bovine pancreatic islets.

In this study we evaluated whether isolated human (HI), porcine (PI) and bovine (BI) islets, either fresh (Fr) or cultured for 4 weeks (4 w) affect cytokine release from human lymphomononuclear cells (LMC) differently. We prepared LMC from peripheral blood by density gradient purification and co-cultured 1 x 10(6) LMC for 24 h with 100 hand-picked islets, either within 48 h of isolation or after culture for 4 weeks. Soluble interleukin-2 receptor (IL-2R), interferon-gamma (IFN), interleukin-4 (IL-4) and interleukin-10 (IL-10) were measured by sandwich enzyme-linked immunoadsorbent assay. Compared with controls (Ctrl, LMC without islets), Fr-HI, Fr-PI and Fr-BI caused a similar increase of IL-2R and IFN release, whereas 4 w-HI and 4 w-BI did not lead to any significant production of these two cytokines. IL-10 concentrations increased with Fr-PI and Fr-BI, but not with Fr-HI, and no major effect of the 4-week culture was seen. IL-4 levels were below the detection limit of the method used in these experiments. Thus, fresh allo- and xeno-islets caused a similar increase of the release of cytokines known to be markers of Th1 activation, whereas the release of IL-10, a marker of Th2 activation, increased with xeno-, but not with allo-islets; culturing the islets for 4 weeks decreased Th1, but not Th2 activation.

Animals↗
PubMed1996

[Serum lactate-dehydrogenase isoenzymes in HIV positive children. A longitudinal study].

The impairment of humoral immunity with rapid turn-over of cellular B clones in children with HIV infection is known as well as the conduct of LDH isoenzymes in B cell lymphoproliferative diseases like Burkitt's lymphoma. Therefore, serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes have been evaluated twice (within 12 months) in 11 children with HIV infection with respect to a control group (30 subjects). Furthermore, the relationship between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC 1987) has been studied. HIV infected children have shown a significant decrease in LD1 rates, which was directly correlated to CD4/CD8 values. After the follow-up, this correlation became even more significant. Thus, these findings may suggest the usefulness of LDH isoenzymes evaluation as a marker of disease activity in children with HIV infection.

Antibody Formation↗
PubMed1994

B cell colony assay improves the sensitivity of the cytogenetic analysis in common acute lymphoblastic leukemia.

The 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.

B-Lymphocytes↗