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Biomedical subjects

C Agostini

Publications and source records attributed to C Agostini.

At least 163 records · Page 9Linked to original sources

Peripheral blood NK cells in patients with extrinsic allergic alveolitis: phenotype and function.

Peripheral blood mononuclear cells obtained from patients with extrinsic allergic alveolitis were tested with a series of monoclonal antibodies against natural killer cells, including HNK-1, NK-15, Ab8.28, OKM1 reagents. An NK in vitro functional evaluation of these cells was associated to the phenotypic analysis. Our data demonstrated an increase, with respect to controls, of the percentage and absolute number of HNK-1 positive cells in the blood of these patients. This increase was consistent with an enhanced cytotoxic in vitro activity. These findings provide evidence that in patients with extrinsic allergic alveolitis, the exposition to antigenic stimuli triggers the NK system. Possible immunopathogenetic mechanisms, especially in comparison with other interstitial lung disorders, are discussed.

Adolescent↗

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↗

Alpha-interferon activates the natural killer system in patients with hairy cell leukemia.

To elucidate the mechanisms of alpha-interferon's (alpha-INF) therapeutic effect on clinical and laboratory findings in hairy cell leukemia, we sequentially monitored different immunologic parameters in three patients treated with recombinant alpha-INF. The most evident effect of this treatment on the immune system was the recovery of natural killer (NK) cell in vitro activity of peripheral blood lymphocytes, which was severely impaired before therapy. In particular, NK function began to improve after 3 months, and a complete recovery was obtained after 6 months in all cases. This increase parallels the improvement in clinical and laboratory findings.

Adult↗

The analysis of expanded cells from patients with lymphoproliferative disorders of granular lymphocytes may help to clarify the NK cell differentiation.

Surface phenotype and functional in vitro activities were studied in 2 cases of lymphoproliferative disorders of granular lymphocytes. Cells from both patients presented the same, previously unreported, surface phenotype (i.e. T3+, T8+, T4-, HNK-1-, NK-15+, M1-), were unable to display either Natural Killer (NK) activity or suppressor function in a poke-weed-driven system, and showed a defective response to phytohemagglutinin (PHA). On the basis of available schemes for NK cells ontogenesis, we will discuss the phenotype and functional activities of patients' cells suggesting that the cell population expressing the T3+, T8+, HNK-1-, NK-15+, M1- phenotype might represent a discrete stage along the NK-cell differentiation pathway.

Antigens, Surface↗

Phenotypical and functional analysis of natural killer cells in sarcoidosis.

The frequency of cells reactive with natural killer (NK)-related monoclonal antibodies (MoAbs) HNK-1, NKP-15, B73.1, VEP-13, Ab8.28 has been evaluated in the peripheral blood and bronchoalveolar lavage (BAL) fluid of 39 patients with pulmonary sarcoidosis (including 19 cases with active sarcoidosis and 20 cases with inactive disease). This phenotypic analysis was carried out together with the NK in vitro functional evaluation of cell populations from peripheral blood and BAL fluid. In addition, inhibition studies were performed in order to evaluate the ability of alveolar macrophages (M phi) to modulate NK activity. Data from peripheral blood showed an increased number of mononuclear cells bearing HNK-1, NKP-15, Ab8.28, VEP-13, and B73.1 determinants in patients with active sarcoidosis with respect to patients with inactive disease and controls. The majority of HNK-1-positive cells lacked both Leu2 and Leu3 antigens when investigated in a double marker system. A parallel increase in the in vitro cytotoxicity assay has been demonstrated. On the other hand, only a few mononuclear cells recovered from BAL fluid displayed a surface pattern of NK cells. This small population of HNK-1-positive cells expresses the HNK-1/Leu3 phenotype and does not exhibit NK activity. The alveolar M phi from sarcoid patients, as well as alveolar M phi from controls, have the property of inhibiting the NK activity of autologous peripheral blood lymphocytes. The lack of lung NK function in patients with active sarcoidosis may be related to the presence of immature forms of NK cells and/or to the release of soluble factors by alveolar macrophages.

Adult↗

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↗

Non-T, non-B childhood acute lymphoblastic leukemia. Correlation between cytochemical markers and first complete remission.

The positivity for four cytochemical reactions, acid phosphatase (AcP), alpha-naphtyl acid acetate esterase (ANAE), beta-glucuronidase (BG), and N-acetyl beta-glucosaminidase (NABG) was correlated to first remission duration in 120 children affected with non-T, non-B acute lymphoblastic leukemia (ALL). The percentages of patients remaining in complete remission at 72 months were always higher for children whose blasts lacked these enzymatic reactions; however, a statistical difference was found only between BG+ and BG- ALL. It also appears that more complete enzymatic patterns of leukemic cells are associated with a poorer prognosis. The percentage of patients still in their first remission was 89% for leukemias with no cytochemical markers, 59% when one reaction was present, but less than 39% when two or more enzymes were detected in the blasts. It is noteworthy that the blasts of patients with more severe prognosis demonstrated a simultaneous positivity for AcP-ANAE or BG-NABG cytochemical reactions. The possible usefulness of these cytochemical markers to detect subsets of patients with different prognostic significance among non-T, non-B ALL is discussed.

Acid Phosphatase↗

B cells in chronic lymphocytic leukaemia. Comparative analysis of blood and bone marrow.

A study was performed on cell suspension from peripheral blood and bone marrow aspirates and on cryostat sections from bone marrow biopsies in order to investigate the membrane phenotype of neoplastic B cells in chronic lymphocytic leukaemia (B-CLL). The immunological analyses, performed on 43 patients, included rosetting ability with sheep and mouse erythrocytes, evaluation of surface immunoglobulins and reactivity with anti-HLA-DR, UCHT 1 (OKT-3 like) and RFA-1 (OKT-1 like) monoclonal antibodies. The results demonstrate that neoplastic B lymphocytes in B-CLL display an identical phenotype in peripheral blood and bone marrow. Possible interpretations on the origin of proliferating cells in B-CLL are discussed.

Adult↗

Evidence of cells bearing interleukin-2 receptor at sites of disease activity in sarcoid patients.

The frequency of cells reactive with anti-Tac monoclonal antibody (MoAb), which recognizes the interleukin-2 (IL-2) receptor, has been evaluated in cell suspensions from peripheral blood and bronchoalveolar lavage (BAL), and in frozen sections from involved tissues in 18 patients with active sarcoidosis. Peripheral blood lymphocytes of sarcoid patients do not bear Tac determinant and reduced numbers of Tac+ cells are inducible following PHA stimulation. On the other hand, significant numbers of lymphocytes reactive with anti-TacMoAb are present in the cells obtained from the BAL and a number of Tac+ cells infiltrate the lung, lymph node and conjunctiva. The finding of Tac+ cells in the BAL fluid and in other organs in patients with sarcoidosis provides evidence that some T cells in these involved tissues have the characteristics of IL-2 responder cells and thus the potential to absorb IL-2, supporting the hypothesis that T lymphocytes replicate in situ at sites of disease activity.

Adult↗

Abnormal expansions of polyclonal large to small size granular lymphocytes: reactive or neoplastic process?

Morphological, immunologic, and functional properties of peripheral blood cells from two patients with chronic proliferations of granular lymphocytes are described. Cells from both patients showed a heterogeneous pattern from both a morphological and immunologic standpoint, indicating a polyclonal, rather than a monoclonal, expansion of these cells. In fact, both large and small-to-medium-sized granular lymphocytes were observed, and different percentages of positivity were found in the analysis with a large panel of monoclonal antibodies. Serologic and histologic features support the hypothesis that this lymphocytosis could be secondary to bacterial or viral infections rather than a primary event, suggesting that these patients may have chronic reactive immunoregulatory disorders.

Acid Phosphatase↗

Effects of cimetidine and ranitidine on the "lipoperoxide" and lipid content of liver of rats treated with CCl4, colchicine, ethanol, ethionine and emetine.

Ranitidine increases liver "lipoperoxide" content of colchicine-treated rats while decreasing that of rats given emetine. Lipid content is increased by ranitidine in livers of rats dosed with ethanol. No significant effects of ranitidine were observed under the other conditions here studied. Cimetidine does never provoke significant modifications.

Animals↗

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↗

Effects of various agents on the in vivo "lipoperoxide" content of rat liver and kidney and on the "lipoperoxide" and lipid content of liver slices.

"Lipoperoxide" content increases in rat livers 2h after emetine and glucosamine and 24h after CCl4, cycloheximide, colchicine, emetine and ethionine administration. Renal "lipoperoxides" decrease 24h after glucosamine and 24h and 72h after X-rays. In liver slices thiobarbituric acid values are increased by diethyl maleate, glucosamine and puromycin. Loss in lipid content is accelerated in liver slices by cycloheximide, emetine, FeCl3 but counteracted by colchicine and ethanol.

Animals↗

Binding of sheep erythrocytes in chronic lymphocytic leukemias of B-cell origin.

Two patients with B chronic lymphocytic leukemia having leukemic cells that bind sheep red blood cells by different mechanisms are described. In the first case, rosette formation was mediated by the anti-sheep erythrocyte activity of a monoclonal surface IgMk, related to Forssman antigen. In the second, E-rosette formation was found to be independent of both surface immunoglobulins and the classic E-rosette receptor since the leukemic cells were recognized neither by the OKT-11 monoclonal antibody nor by other markers specific to T-cell lineage. Evaluation of these rare cases emphasizes that detection of surface immunoglobulins and spontaneous rosetting are not sufficient for the characterization of leukemic clones and raises some doubts concerning the use of available surface markers in the characterization of lymphoproliferative disorders.

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↗