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Biomedical subjects

G Gasparotto

Publications and source records attributed to G Gasparotto.

At least 19 recordsLinked to original sources

Childhood onset cyclic neutropenia: G-CSF therapy restores neutrophil count but does not influence superoxide anion and cytokine release by neutrophils.

In this paper we describe the case of a 16-year-old boy with childhood onset cyclic neutropenia (CN) with a 21 d cycle who was successfully treated with recombinant granulocyte-colony stimulating factor (G-CSF). Cyclic therapy with G-CSF (5 micrograms/kg/d s.c. for 1 week every 21 d) maintained peripheral neutrophil count above the normal range, reduced the incidence of severe infections and significantly improved the patient's performance status throughout an 18-month follow-up. Phenotypic analysis of circulating lymphocytes demonstrated that G-CSF treatment does not modify the phenotypic profile of circulating B, T and NK cell populations. Circulating neutrophils released normal amounts of cytokines (including IL-1 beta, IL-8, TNF alpha) and superoxide anion during G-CSF therapy.

Adolescent↗

Phenotypic and functional characterization of cytotoxic cells derived from endomyocardial biopsies in human cardiac allografts.

This study was undertaken to characterize the phenotype and function of lymphocytes derived from endomyocardial biopsies in heart transplant patients. To this aim, tissue infiltrating lymphocytes were derived from seven heart transplant patients and were analyzed for the expression of a panel of markers, including CD3, CD4, CD8, CD16, CD56, CD45RA, CD45RO, alpha/beta and gamma/delta T cell receptor, and for their ability to lyse a series of targets, including NK-sensitive K-562 targets, NK-resistant Raji targets, donor related, and unrelated normal splenocytes. Our data show that the majority of cultured lymphocytes expressed the CD3+ phenotype and the alpha/beta T cell receptor. The CD4 and CD8 molecules were heterogeneously expressed among T cell lines tested. Concerning cytotoxic related markers, a significant percentage of cells were CD56+. The evaluation of CD45 isoforms showed that both "naive" and "memory" cells were present among heart TIL. Cytotoxic in vitro studies demonstrated that all our T cell lines showed an efficient cytotoxic machinery when tested against NK-sensitive targets. A marked lysis of donor-related splenocytes was demonstrated in all patients tested. To investigate the role of CD3 and HLA class I molecules in the cytotoxic mechanisms taking place in human heart allograft rejection mechanisms, TIL were assessed for their lytic activity against different targets in the presence of anti-CD3 and anti-HLA class I monoclonal antibodies (mAbs). Although donor-specific cytotoxicity was considerably inhibited by the anti-CD3 mAb, no inhibitory effect was displayed by this antibody on TIL-mediated cytotoxicity against donor-unrelated splenocytes. Anti-HLA class I mAb was able to inhibit both allospecific and nonallospecific cytotoxicity. These data suggest that different types of cytotoxic cells may be propagated from biopsy specimens of heart transplant patients.

Adult↗

Cytotoxic in vitro function in the lymphoproliferative disease of granular lymphocytes.

In 20 patients with lymphoproliferative disease of granular lymphocytes (LDGL) the cytotoxic in vitro function of peripheral blood mononuclear cells was studied against both NK sensitive (K-562) and NK resistant target cells (Daudi). Cytotoxicity was analysed at resting conditions and after in vitro pre-incubation with recombinant alpha 2-interferon, gamma-interferon and interleukin 2. At resting conditions, a heterogeneous cytotoxic picture was observed against the K-562 targets, with 11 of the 20 patients showing a normal or increased NK activity, and nine an impaired function. Against the Daudi targets, unstimulated cells from all patients displayed a normal cytotoxic activity. Following in vitro stimulation, an increased lytic function against K-562 cells was demonstrated in six of the nine patients with low basal values, in three after boosting with all lymphokines tested and in three with interleukin 2. In three of these six patients incubation with interleukin 2 also produced an increased cytotoxic function against Daudi target cells; this phenomenon may be associated to the lymphokine-activated killer (LAK) system. The importance of investigating the cytotoxic in vitro function in LDGL patients to further characterize the biological features of GL and its relevance to better define the nature of this disease are discussed.

Adult↗

The acquired immunodeficiency syndrome (AIDS): insights into the immunopathogenesis of the pulmonary involvement.

The lung is involved in more than 50 per cent of patients with the acquired immune deficiency syndrome (AIDS), and pulmonary abnormalities can be easily investigated using the bronchoalveolar lavage (BAL). Besides providing information on the type of infecting microorganism, BAL has been used to characterize immunocompetent cells from the lower respiratory tract in these patients. This allows new insights into the immunopathogenetic mechanism involved in the persistence of opportunistic pulmonary infections and in the uncontrolled viral replication. This paper emphasizes the value of BAL evaluation as a simple and useful method for investigating the involvement of the distal respiratory tract in AIDS patients. A particular attention is payed on the immunological pulmonary abnormalities of this epidemic immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

Adolescent↗

Impaired production of interleukin-2 in peripheral blood of patients with sarcoidosis.

In twelve patients with active sarcoidosis we attempted to explain the nature of reduced release on interleukin-2 (IL-2) and the consequent impairment in lymphoproliferative in vitro responses. The addition of exogenous IL-2 containing supernatants was unable to completely restore the defective uptake of 3H-Thymidine suggesting that an impairment of IL-2 producer cells is not enough to explain the in vitro hyporesponsiveness of sarcoid lymphocytes. We also found a reduced number of precursors of IL-2 responder cells, as defined by peripheral blood lymphocytes bearing Tac determinant following in vitro stimulation with mitogens. The abnormalities of both IL-2 producer cells and precursors of IL-2 responder cells in peripheral blood of patients with sarcoidosis are discussed, stressing the importance of the concept of compartmentalization of T lymphocytes in this disease.

Adult↗

Distribution of natural killer cells in sarcoidosis.

A number of immunological abnormalities have been reported in sarcoidosis. In this paper an excess of Natural killer (NK) cells, as defined by the reactivity with HNK-1 monoclonal antibody, is demonstrated in peripheral blood of these patients. On the contrary, only a few HNK-1+ cells have been found among mononuclear cells infiltrating and/or surrounding sarcoid granulomas in the lungs, lymph nodes and skin. While NK cell activity may represent one of the first lines of natural resistance against foreign antigens, the lack of killing in involved tissue gives no support for control of sarcoidosis by NK cells at sites of disease activity. Possible interpretations of these findings are discussed.

Adult↗

Immunologic evaluation of T chronic lymphocyte leukemia cells: correlations among phenotype, functional activities, and morphology.

Chronic lymphocytic leukemia of T-cell origin (T-CLL), a rare variant of CLL, appears to be a clonal proliferation of mature T cells of one of several subsets. In the cells of 7 T-CLL patients, surface markers (including those reacting with a panel of monoclonal antibodies), functional activities, and electron microscopic morphology were evaluated. The phenotypic patterns of circulating T-CLL cells correspond to those of normal mature T-cell subsets. The cells of three patients demonstrated at least one marker reported to be expressed by suppressor/cytotoxic T cells: those of three patients expressed markers apparently linked with T-helper activity. Cells from one patient appeared to be a heterogeneous proliferation of more than one T-cell subset. These T-CLL cells may also retain some of the functional activity of the normal T subpopulations. Our data indicate that a combination of several tests should be used to characterize the proliferating cells in T-CLL.

Aged↗

T-lymphocyte subpopulations in chronic lymphocytic leukemia: a quantitative and functional study.

In the peripheral blood of patients with chronic B-cell lymphocytic leukemia (B-CLL) absolute numbers of E-rosetting lymphocytes were increased. The proportions of TG and TM cell subsets were analyzed, as were their effects on the pokeweed mitogen (PWM)-dependent differentiation of normal allogenic B cells or of autologous leukemic cells. The TG lymphocyte subset was further studied for its cytotoxic activity in antibody-dependent cellular cytotoxicity (ADCC). A marked increase both in percentages and in absolute numbers of TG cells was found. TM lymphocytes percentages were normal, but because of the T lymphocytosis occurring in all patients, the absolute numbers of TM were increased. TM and TG subsets showed helper and suppressor activity, respectively, in PWM-induced B-cell differentiation. TG cells displayed effector cell activity in ADCC. The results provide further evidence that T lymphocytes from patients with B-CLL are functionally normal. However, a noticeable increase of the T-cell subset having suppressor and cytotoxic activity in ADCC was observed. This may be the consequence of a normal immune reaction to the leukemic population.

Aged↗

Subpopulations of T-lymphocytes in multiple myeloma.

The percentage and absolute numbers of T lymphocytes bearing Fc receptor for IgG and IgM were evaluated in 13 patients with multiple myeloma and in a group of controls of the same age range. An increase in the percentage of the TG cells was found, whereas TM cell numbers were not different from those of the controls. In order to better define the properties of the TG lymphocytes, their ability to suppress the PWM-induced B cell differentiation was tested in an in vitro experimental assay. TG cells from multiple myeloma exert a suppressor activity as the TG of the controls in this system. The possible interpretation of suppressor T cell increases in these patients is discussed.

Aged↗

B lymphocytes in newborns.

B lymphocyte markers in 24 full term newborn infants were evaluated within four days after birth. It was demonstrated that the percentage of cells with surface immunoglobulins (SmIg) in the blood of these subjects was normal when the lymphocytes were stained with polyvalent as well as monospecific antisera. The percentage of cells bearing Fc receptors were found to be slightly, but not significantly, reduced. The ability of newborn lymphocytes to form rosettes with mouse erythrocytes was significantly reduced. The hypothesis that the B dependent system reaches complete maturity already at the first days after birth is discussed.

Animals↗

[Juvenile rheumatoid arthritis appearing after hepatitis. Causal or casual relationship].

High fever, spleen and lymph node enlargement, and joint pains that assumed the character of rheumatoid arthritis in the ensuing months were noted after a viral hepatitis episode in a 21-year-old woman. Serious anaemia and myocarditis also appeared when the picture was at its worst. A lymphoma was suspected, and the spleen and some abdominal lymph nodes were removed. These displayed signs of intense follicular reaction unaccompanied by atypia. The possibility that juvenile rheumatoid arthritis may be triggered by hepatitis is examined.

Adult↗