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R Consolini

Publications and source records attributed to R Consolini.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Brief analytical review of additional possible mechanisms in the pathogenesis of AIDS].

It is generally agreed that HIV itself has the primary role in the initiation and propagation of the pathogenic process of the infection. Nonetheless, a number of important issues concerning the pathogenesis of HIV infection remain unresolved. For example, it remains unclear how CD4+ T cells are lost after HIV infection. The low frequency of infected cells seen even in advanced infection implies that a direct cythopathic effect of HIV on infected CD4+ T cells cannot explain their disappearance. Multiple and diverse mechanisms have been proposed as supplements to the HIV in the destruction of CD4+ cells and the pathogenesis of AIDS. However, it is not yet possible to state confidently which additional mechanism(s) is important. Identification of the nature of this supplemental process has become essential for successful, non-harmful intervention. We propose here a short analytical review of the possible supplemental mechanisms of immunological destruction in AIDS in order to emphasize the complexity of the pathogenesis of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Human rIL4 fails to differentiate leukemic B-cell progenitors growing upon S17 stromal cell line.

Stromal cells appear to be key regulatory elements in hematopoiesis and lymphopoiesis. Several stromal cell lines can support B lineage by creating a hematopoietic microenvironment via cell contact or regulatory humoral molecules. These activities have been efficiently mediated by an adipocytic stromal cell line 14F1.1 on infant leukemia cells expressing a hybrid pre-B myeloid phenotype. Several murine cell clones, however, are known to have different ability to support growth and/or differentiation of leukemic cells depending on the maturational stage in which malignant cells are frozen. Pre-B-cell lines and fresh leukemias were therefore cultivated on S17 stromal cell line, before and after exposure to human recombinant interleukin 4 (rIL4), a cytokine whose effects on the growth and differentiation of the B-cell compartment depend on the developmental stage of the target B cell. In the present work, leukemic cells, both in suspension and in close contact with stromal cells, maintained their original phenotype throughout the whole period of co-culture with S17, either before or after exposure to human rIL4.

Cell Differentiation↗
PubMed1987

Thymic dysfunction in histiocytosis-X.

In some patients with histiocytosis-X there is a deficiency of suppressor T cells, which is corrected in vitro by incubation with either crude calf thymic extract or thymostimulin. This finding suggests that a thymus deficiency could be involved in this disease. Low levels of serum thymic factor (FTS) are found in patients with histiocytosis-X. Their plasma contain factors capable of inhibiting biological activity of FTS in vitro. Elucidation of the mechanism by which FTS is inhibited would be helpful in understanding the immunological defect in histiocytosis-X. The presence of evidence of thymic dysfunction and the fact that patients respond to thymic hormone therapy suggest that histiocytosis-X could be due to a primary immunodeficiency syndrome. Thymulin, which stimulates the generation of suppressor T cells, could be of benefit in therapy.

Adolescent↗
PubMed1987

Heterogeneity of TdT+, HLA-DR+ acute leukaemia: immunological, immunocytochemical and clinical evidence of lymphoid and myeloid origin.

15 cases of acute leukemia (AL) displaying a TdT+, HLA-DR+ phenotype were studied; surface immunoglobulins, T cell markers and the common acute lymphoblastic leukaemia (c-ALL) antigen were negative, as were peroxidase and non-specific esterase cytochemical reactions. All cases were extensively investigated by conventional immunofluorescence (IF) and immunoperoxidase (IP), with a panel of monoclonal antibodies (MoAb), using both light and electron microscopy, and for ultrastructural myeloperoxidase (MPO). 8 cases, which were OKB2+, BA1+, B4+, J5- and BA2- by IF, expressed the J5 antigen in IP. These cases were therefore re-classified as ALL with a weak expression of the C-ALL antigen. The other 7 cases showed an OKB2-, BA1-, B4+, BA2+ phenotype at IF and were also positive for 1 or more anti-myeloid MoAb. These features were confirmed by IP study. 4 patients also presented ultrastructural positivity to MPO. These cases were considered as proliferations of early precursor cells capable of expressing both myeloid and lymphoid features. This study, while demonstrating the heterogeneity of TdT+, HLA-DR+ AL, suggests that the cell origin of many cases may be defined by extensive immunotyping at both IF and IP level. The prognostic and therapeutic implications of these findings are discussed, also in view of the poor prognosis often observed in the more undifferentiated cases of AL.

Acute Disease↗
PubMed1986

Abnormal in vitro differentiation of peripheral blood clonogenic B cells in common acute lymphoblastic leukemia during complete remission.

An in vitro B cell colony assay system was used to evaluate B cell growth from peripheral blood precursors in common acute lymphoblastic leukemia (CALL) patients in remission during maintenance therapy and in normal controls. Major differences between the two groups were found in the phenotypic and morphologic features of pooled colony cells. In both cases, the cells were E-. Controls' cells were surface immunoglobulin (sIg)-positive, and some (mean, 25%) expressed la determinants. By Wright-Giemsa staining, they appeared as plasmacytoid cells. In contrast, patients' cells had predominantly a lymphoblastoid appearance, fewer cells had developed sIg, and a large fraction (mean, 43%) were Ia-positive. Moreover, the CALL antigen (CALLA) was expressed by a mean of 18% (range, 2% to 72%) of the patients' colony cells, whereas CALLA was never found in control colonies. Thus, cells with immature features persist in the colonies of CALL patients. Secondary colonies could be generated from the patients' cultured cells, indicating their self-renewal capacity. CALLA + cells were also present in the secondary colonies. Finally, cytogenetic studies showed that a fraction of the patients' colony cells had karyotypic abnormalities similar to that of the original lymphoblasts. It is believed that in CALL patients this B cell assay permits the clonal expansion of residual circulating cells linked to malignant clones that are not detectable by classic hematologic and cytologic methods.

Adolescent↗
PubMed1986

Circulating thymic hormone activity in young cancer patients.

We measured serum levels of Facteur Thymique Sérique (FTS) in 56 young cancer patients compared to normal controls. All patients who received immunosuppressive therapy had low age-corrected titres of FTS. Low levels were also found at diagnosis and off therapy. Plasma from 22 patients contained factors capable of inhibiting biological activity of FTS in vitro. The nature of this inhibitor has not been elucidated. No zinc deficiency was found in the patients studied, suggesting that FTS is secreted in its active form. Our study points out the importance of monitoring FTS activity in young cancer patients for its implications on immunological surveillance. The practical applications of thymic hormone therapy in cancer patients are discussed.

Adolescent↗
PubMed1985

Characterization of normal peripheral blood T- and B-cell colony-forming cells: growth factors(s) and accessory cell requirements for their in vitro proliferation.

The biological properties of normal peripheral lymphoid precursors were studied using separate colony assays for T- and B-cell colony-forming cells (T-CFC and B-CFC, respectively). Cell fractions, selected by complement-mediated cytotoxicity with monoclonal antibodies, were cultured in methylcellulose using different sources of growth factors containing (PHA-LCM2 and PHA-LCM7) or not (PHA-TCM) Interleukin-2 (IL-2). Well-differentiated T-cell colonies were only observed with IL-2-containing conditioned media (CM). Normal T-CFC displayed either an immature (E-T11-OKT3-Ia-) or mature (E+) phenotype, were quiescent cells presenting different radiosensitivity (D0 = 80 and 155 rads, respectively). B-CFC displayed the E-T11-OKT3-B1-Ia+ surface phenotype, were in DNA synthesis and were more radioresistant (D0 = 300 rads) than T-CFC. B-cell colonies could be obtained in the presence of allogeneic irradiated T cells and PHA-TCM, but not with IL-2-containing CM. When E-T11-OKT3- cells were seeded with PHA-TCM supplemented with increasing amounts of semipurified IL-2 in the presence of a fixed number of irradiated T cells, the B-cell colony growth (as assessed by the frequency of sIg+ colony cells) progressively decreased whereas that of T-cell colonies increased. IL-2-free CM (PHA-TCM) was able to induce T-cell colony growth from E-T11-OKT3- cells but addition of allogeneic irradiated T cells induced B-cell colony formation in a dose-dependent manner. Conversely, T cells enhanced T-cell colony growth in the presence of IL-2-containing CM. Furthermore, adherent cell depletion of E-T11-OKT3- cells inhibited T- but not B-cell colony growth. These results taken together suggest that T- and B-cell colonies derive from different progenitor cells which have different growth factor(s) and accessory cell requirements and indicate that T-cell colony growth is associated with inhibition of B-cell colony formation.

Antigen-Presenting Cells↗
PubMed1985

Bone marrow necrosis foreshadowing acute lymphoid leukemia.

Necrosis of the bone marrow is rarely observed during life. Less than 50 cases have been reported, for the most part in patients with leukemia. The finding of bone marrow necrosis in children is even more rare. Of the seven cases reported, six patients had acute lymphoid leukemia and one patient had lymphocytic lymphoma. The occurrence of marrow necrosis diagnosed by aspirate and by biopsy in a child 18 months of age is presented. The necrosis was present several months before the appearance of acute lymphoid leukemia. The reasons for the presumed rarity of this pathological finding, its relationship with bone or joint pain and fever, hypotheses concerning pathogenesis, and its prognostic value are discussed.

Biopsy, Needle↗
PubMed1985

T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia.

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non-Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

Acid Phosphatase↗
PubMed1984

Analytical infrared spectral differences between human normal and leukaemic cells (CLL)--I.

Two series of normal and leukaemic lymphocytes were examined by infrared spectroscopy in order to try to find spectral differences connected with chemical and biological modifications. The bands at 965 and 530 cm-1 present only in the spectra of leukaemic lymphocytes, assume particular significance. The C-H stretching region furnishes useful indications about the different ratios of the methyl groups compared with the methylene ones in the two cases. The infrared bands characteristic of the leukaemic lymphocytes seem to be due to chemical modifications not involving the DNA chain.

Humans↗
PubMedDate not supplied

Psoralen and UVA light: an in vitro investigation of multiple immunological mechanisms underlying the immunosuppression induction in allograft rejection.

Photopheresis (ECP) is a novel immunomodulatory therapy effectively used to treat several T-cell-mediated diseases and to reverse allograft rejection after organ transplantation. It consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and extracorporeally incubated with 8-methoxypsoralen (8-MOP). In this study we explored the potential immunological events for therapeutic efficacy of photopheresis in preventing allograft rejection by evaluating in vitro the combined effects of 8-MOP and UVA (PUVA) on multiple immunological parameters, such as induction of apoptosis, production of soluble mediators, and expression of cell antigens. Peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects were treated with 8-MOP and UVA at the same doses as those clinically used in ECP. We demonstrate that PUVA treatment induced leukocyte hyporesponsiveness and a decrease in expression of co-stimulatory and adhesion molecules as well as of cytokine levels. Additionally, PUVA treatment induced apoptosis in both mononuclear cells (possibly through the Fas/FasL system and/or the CD38 pathway) and purified monocytes. In conclusion, our work focuses attention on the initial phase of immune response and identifies some new targets of therapy (e.g., costimulatory molecules) able to trigger final effects underlying therapeutic efficacy of photopheresis.

Adolescent↗
PubMedDate not supplied

Thymic dysfunction in childhood T-acute lymphoblastic leukemia: a possible linkage with a primary thymus involvement.

Experimental 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 Sérique (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.

Adolescent↗
PubMedDate not supplied

Abnormal in vitro differentiation of clonogenic B-cells in common acute lymphoblastic leukemia in complete remission. A marker for minimal residual disease?

An in vitro B-cell colony assay system was used to evaluate B-cell differentiation from peripheral blood precursors in common acute lymphoblastic leukemia (cALL) patients in remission as compared to normal controls. Significant differences in the morphologic and phenotypic features of pooled colony cells were found between the two groups. The morphology and surface markers of control-cultured cells were those of young plasmocytes. In contrast, patients' cells had predominantly a lymphoblastoid appearance and a mean of 18% (2-72%) of the cells expressed the cALL (CALLA) antigen. This marker, known to be present on normal pre-B-cells and malignant cALL cells, was not found on control colony cells. Cytogenetic studies performed in four cases showed that a fraction of the patients' colony cells had karyotypic abnormalities similar to that of the original lymphoblasts. These data suggest that the cells with immature features persisting in the colonies of cALL patients are the progeny of residual circulating cells linked to the malignant clone which cannot be detected in the fresh sample and are clonally expanded during the culture.

Antigens, Differentiation↗