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Biomedical subjects

F Minonzio

Publications and source records attributed to F Minonzio.

27 records · Page 2Linked to original sources

Effect of pirprofen on polymorphonuclear leukocyte functions in vitro.

The action of the new non-steroidal anti-inflammatory drug (NSAID) pirprofen on different functions of human polymorphonuclear leukocytes (PMNs) has been studied. The chemotaxis of PMNs was found to be affected by pirprofen in a dose-dependent fashion; at a concentration of 2 micrograms/ml (10 times lower than the therapeutic blood levels) it significantly inhibited PMN locomotion toward two different chemoattractants. Moreover pirprofen inhibited the chemiluminescent response in a dose- and stimulus-dependent way. In fact the drug inhibited the chemiluminescence induced by the soluble stimuli FMLP or PMA, but it was ineffective when zymosan particles were used. The phagocytosis and adhesion functions of the PMNs were not modified by pirprofen at the concentrations tested. These experimental results suggest that a reduction of the accumulation and activation of inflammatory cells in tissues may represent another way, together with cyclooxygenase inhibition, by which pirprofen realizes its antiinflammatory activity in vivo.

Cell Adhesion↗

Chronic granulomatous disease in a 23-year-old female.

A 23-year-old girl with clinical and laboratory findings characteristic of chronic granulomatous disease is described. The patient was admitted to hospital because of severe disseminated aspergillosis. Studies of neutrophils showed normal phagocytosis but impaired microbicidal killing and a failure of the respiratory burst activity as measured by NBT-reduction, superoxide generation, chemiluminescence and antibody-dependent cell mediated cytotoxicity. Patient's neutrophils had normal chemotactic responsiveness but a marked impairment in the level of serum chemotactic activity was observed. Neutrophils from the parents and 2 maternal aunts showed normal values for all the determinations. The lack of evidence for a carrier state in all the family members studied together with the inability to detect a mixed population of neutrophils in our patient are in contrast with the Lyon's hypothesis of X-chromosome inactivation. Our findings suggest an autosomal recessive inheritance in this female with chronic granulomatous disease.

Adult↗

Effect of ambroxol on human phagocytic cell function.

The in vitro effects of ambroxol on phagocytic and microbicidal activities of human neutrophils and monocytes have been studied. Preincubation of neutrophils with ambroxol (10 to 100 ng/ml) had no effect on their phagocytic or microbicidal capacities. On the other hand, when monocytes were preincubated for 24 hours with ambroxol a significant increase of their microbicidal activity was observed, without effect on the phagocytic properties.

Ambroxol↗

Plasma ACTH-response to the corticotropin releasing factor in patients with Cushing's disease. Comparison with the lysine-vasopressin test.

In three female patients with Cushing's disease, 100 micrograms of synthetic ovine corticotropin releasing factor (CRF) were administered before surgery and 1 week after transsphenoidal microadenomectomy. In these patients a test with lysine-vasopressin (LVP), 10 U intramuscularly, was also performed before and after pituitary surgery. Before surgery, both stimuli induced a clear increase in plasma ACTH and cortisol in all patients; the response of ACTH to CRF was of greater magnitude. Postoperatively, the responses were virtually absent in two patients, but were still present in the third one in whom the removal of adenoma had been partially unsuccessful. The CRF test was also performed in a female patient with Cushing's syndrome due to adrenal adenoma; in this patient no responses of plasma ACTH and cortisol to CRF were recorded. This paper demonstrates that pituitary microadenomas causing Cushing's disease may retain the ability to respond to CRF; this stimulus may be useful in the differential diagnosis between ACTH-dependent and independent Cushing's syndrome; the lack of response after microadenomectomy indicates successful removal of the tumor. CRF is more potent than LVP in releasing ACTH at the doses employed.

Adenoma↗

CD69 expression on neutrophils from patients with rheumatoid arthritis.

OBJECTIVE: Since the early activation antigen CD69 has been implicated in the pathogenesis of some inflammatory diseases, we evaluated the expression of the molecule on peripheral blood (PB) and synovial fluid (SF) neutrophils obtained from RA patients and its possible correlation with PB and SF cytokine concentration. METHODS: CD69 membrane expression (and CD11b as control marker) was assessed by indirect immunofluorescence and flow cytometry analysis on purified PB and SF neutrophils. Cytokine levels (GM-CSF, IFN-gamma, TNF-alpha) in plasma and SF supernatants were measured by ELISA. RESULTS: CD69 was absent on control neutrophils, while it was expressed on PB neutrophils from RA patients although no detectable GM-CSF, IFN-gamma or TNF-alpha was observed in their plasma. CD69 expression was still more evident on SF neutrophils from RA patients; 59% had detectable levels of INF-gamma in their SF while GM-CSF and TNF-alpha were detectable in SF from 95% and 33% of RA patients, respectively. However, no correlation was observed between cytokine concentrations and CD69 expression on SF neutrophils. SF but not PB neutrophils from RA patients expressed increased amounts of CD11b when compared to control PB neutrophils without any correlation with CD69 membrane expression. CONCLUSION: The activation antigen CD69 is significantly expressed on PB and SF neutrophils from RA patients. However, the mechanism(s) of induction and its possible role in the pathogenesis of RA remain to be defined.

Adolescent↗

Immunostimulation of neutrophil phagocytic function by RU41740 (Biostim) in elderly subjects.

On this randomized, double-blind trial we investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae, on human neutrophil function after oral administration to elderly subjects with a previously demonstrated phagocytic defect. Six subjects were given RU41740 orally at a daily dose of 2 mg for one week the first month and of 1 mg for one week the second month, while six subjects received placebo. Already after the first week of treatment with RU41740 (T1) and more evidently 3 weeks after the last administration of the first course of therapy (T2), a significant improvement of the neutrophil phagocytic capacity was observed; at the time T2, as well as at the end of the second course of therapy (T3), the phagocytic capacity was completely restored with no differences between control and aged subjects. Similar results were obtained in the chemiluminescence assays. As expected, placebo had no significant effect on neutrophil functions. No significant differences were observed between the two group of elderly subjects for total or differential leukocyte number. These results suggest that RU41740 exerts, almost in part, its clinical effect, i.e. the prevention of recurrent infections, by stimulating blood neutrophil phagocytic function.

Adjuvants, Immunologic↗

Clinical and laboratory findings in a new case of leukocyte adhesion deficiency.

We describe a child suffering from recurrent bacterial infections whose cells exhibited laboratory findings compatible with the leukocyte adhesion deficiency (LAD) syndrome. Surface marker analysis with monoclonal antibodies (MAbs) to the individual alpha and beta chains of LFA-1/Mac-1/p150,95 antigens revealed that the patient's neutrophils did not express the common beta chain and LFA-1/p150,95 alpha subunits, but reacted weakly with four different MAbs specific for the Mac-1 alpha chain; however, no glycoprotein was immunoprecipitated from the patient's cells using the same anti-Mac-1 alpha MAbs. Functional analysis of the patient's phagocytes revealed many of the defects in adherence-dependent functions (adherence, chemotaxis and phagocytosis) described in patients with LAD. The studies performed on the phagocytes of the patient's relatives showed normal phenotypes and function, suggesting the possibility of a non heritable form of disease in this family.

Antigens, CD↗

Abnormal neutrophil chemotaxis in bone marrow transplant patients correlates with impaired 31D8 monoclonal antibody binding.

BACKGROUND: 31D8 monoclonal antibody (mAb) has been shown to bind heterogeneously to human neutrophils, identifying subsets of cells which differ in their functional response to chemotactic stimuli. In this study we used 31D8 mAb to determine whether differences in neutrophil subpopulations might explain the long-lasting decreased chemotaxis observed in bone marrow transplant recipients. METHODS: Thirty patients with self-sustaining hematopoiesis 1 to 5 years bone marrow transplantation (BMT) (15 allogeneic and 15 autologous) performed for acute lymphocytic leukemia (ALL, 10 patients) or acute myelogenous leukemia in complete remission (8 patients), Hodgkin's lymphoma (2 patients), chronic myeloid leukemia (8 patients) and severe aplastic anemia (2 patients) were included in the study. Neutrophil chemotaxis was evaluated using a modified Boyden chamber assay and 31D8 binding was determined by indirect immunofluorescence and cytofluorimetric analysis. RESULTS: Neutrophil chemotaxis was significantly impaired in the BMT group with respect to controls. The chemotactic defect strikingly correlated with autologous BMT and, in particular, with ALL as the pre-existing disease. No differences between patients and controls were observed in the percentage of 31D8 bright and dull neutrophils. However, when mean fluorescence intensity (MFI) was analyzed as a relative measure of 31D8 antigen expression on the overall neutrophil population, a significant decrease was observed in neutrophils from BMT patients with respect to controls. As for chemotaxis, the impairment of 31D8 binding was more evident in autologous BMT and strikingly correlated with ALL as the pre-existing disease regardless of age, sex and time since BMT. Moreover, a significant positive correlation between impaired chemotaxis and decreased 31D8 binding was found in our patients. CONCLUSIONS: These findings suggest that the decreased neutrophil chemotaxis observed in some BMT patients may be due in part to circulating 31D8 dull neutrophils, although the causes for the decreased 31D8 binding and for the quite pronounced neutrophil defect in ALL patients remain unknown.

Adolescent↗