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Biomedical subjects

G Tonietti

Publications and source records attributed to G Tonietti.

11 recordsLinked to original sources

Natural killer cell frequency and function in patients with monoclonal gammopathies.

We evaluated the frequency and the functional activity of peripheral blood mononuclear cells (PBMCs) with natural killer (NK) cell phenotype in patients with monoclonal gammopathies. CD16+ and CD56+ PBMCs were strongly increased in monoclonal gammopathies of undetermined significance (MGUS) and multiple myeloma (MM). Furthermore, increased frequency of CD16+/CD3+ PBMCs was found in 7/15 patients with MGUS, indicating that T lymphocytes with NK-like phenotype are expanded in at least a subset of these patients. However, despite the increased frequency of PBMCs with natural killer phenotype, the functional NK activity was as comparable in both MGUS and MM patients as in normal individuals. The discrepancy between the expansion of circulating NK cells and the normal NK activity in patients with monoclonal gammopathies requires further investigation. However, at least in some MGUS patients, this discrepancy could be accounted for by the expansion of PBMCs with the rare phenotype CD16/CD3 which have been reported not to mediate significant NK activity.

Aged

[The expansion of NK CD56+ cells with reduced cytotoxicity in a female patient with systemic sclerosis].

An absolute and relative increase of circulating CD56+ (NKH1, Leu19) natural killer cells has been found in a patient with systemic sclerosis. The expanded natural killer cells exhibited reduced natural killer activity and antibody-dependent cell-mediated cytotoxicity. Furthermore, the limiting dilution analysis of spontaneous in vitro immunoglobulin synthesis demonstrated that the precursor frequency of immunoglobulin-secreting cells and the "single-hit" kinetics of the titration curve were similar to healthy controls, but strongly different from previously reported patients in whom CD16+NK cell subset was expanded. Thus, our findings might suggest that expanded CD56+ natural killer cells exhibit unique regulatory properties on B cell function in systemic sclerosis.

Aged

Modulation by ST 789 of in vitro lymphocyte activation and cytokine production.

Our results indicate that ST 789 exhibits complex immunomodulant properties. In fact, we found that ST 789 inhibits the expression of activation antigens, such as interleukin-2 and transferrin receptors by peripheral blood mononuclear cells (PBMCs) from healthy subjects following mitogen stimulation, but we were not able to detect under the same experimental conditions any effect on the in vitro production of soluble CD8 antigen and of interleukin-4 as well as on the proliferative response of antigen-specific and autoreactive human T cell lines. Finally, we showed that ST 789 is able to strongly enhance the in vitro production of interleukin-6 by PHA-stimulated PBMCs. The reduced expression of activation antigens in the presence of ST 789 does not seem to be mediated by CD8+ suppressor T lymphocytes, as indicated by the normal soluble CD8 levels in culture media, but rather reflects a direct inhibitory action on T helper proliferation and likely on interleukin-2 secretion. The strong enhancement by ST 789 of the in vitro interleukin-6 production seems to indicate the most relevant possibility of clinical applications in human diseases.

Adjuvants, Immunologic

Clinical results of a multicenter study with sulbactam/ampicillin for the treatment of patients with lower respiratory and urinary tract infections.

A total of 124 patients with lower respiratory tract (44) or urinary tract infections (80) were enrolled in an open, multicenter study to evaluate the efficacy and tolerability of sulbactam/ampicillin, administered at the dosage of 3 g/die by intramuscular route. Pretreatment pathogens from patients with lower respiratory tract infections included: Streptococcus alpha-haemolyticus in 8 cases, Streptococcus beta-haemolyticus in 2 cases, Staphylococcus albus in 7 cases, Haemophilus influenzae in 7 cases, Staphylococcus aureus in 6 cases, Klebsiella oxytoca in 5 cases, Staphylococcus epidermidis in 3 cases, Streptococcus pneumoniae in 3 cases, Escherichia coli in 2 cases; in one subject (2.75%), no microorganisms were isolated. In vitro, 36 isolates (84%) were sensitive to SA and 7 (16%) were resistant. At the end of therapy, all the causative pathogens sensitive to sulbactam/ampicillin were eliminated. In patients with urinary tract infections, pretreatment pathogens were: E. coli in 40 cases, S. albus in 16 cases, Proteus mirabilis in 8 cases, Enterobacter agglomerans in 6 cases, Proteus vulgaris in 3 cases, Streptococcus faecalis in 3 cases, Streptococcus liquefaciens in 2 cases, Pseudomonas aeruginosa in 2 cases. In vitro, 64 isolates (80%) were sensitive to sulbactam/ampicillin and 16 (20%) were resistant. At the end of therapy, 63 out of the 64 pathogens sensitive to sulbactam/ampicillin were eliminated; in one case the therapy was interrupted due to adverse effect. Clinical efficacy: in subjects with lower respiratory tract infections, sulbactam/ampicillin cured 32 patients (72.72%) and ameliorated the clinical status of 8 patients (18.18%); efficacy rate: 90.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Cytokine production in patients with monoclonal gammapathies.

Increased interleukin-6 levels in culture media of mitogen-driven non adherent peripheral blood mononuclear cells were measurable in patients with monoclonal gammapathies of unknown significance but not in patients with multiple myeloma, indicating that in the former circulating mononuclear cells other than monocytes are involved in producing interleukin-6. Increased interleukin-4 levels were detected in supernatants of mitogen-driven peripheral blood mononuclear cells from patients with monoclonal gammapathies of unknown significance and from patients with multiple myeloma. The further increased interleukin-4 content in supernatants of non adherent cell cultures of multiple myeloma patients only suggests a somewhat inhibitory role of monocytes on interleukin-4 production, at least in multiple myeloma. Undetectable interleukin-2 levels in culture media were found in patients with monoclonal gammapathies of unknown significance and in patients with multiple myeloma. Serum levels of interleukin-6 and interleukin-2 were not measurable in either group, and interleukin-4 was detected only in a few patients. Our study suggests that in monoclonal gammapathies peripheral blood mononuclear cells could participate in producing cytokines involved in the regulation of B lymphocyte proliferation and differentiation. However, the pathophysiologic role in these patients of IL-6 and IL-4 in vitro, and possibly in vivo, produced by circulating lymphocytes remains to be established.

Aged

Immuno-electronmicroscopic study of human EA rosettes.

The immuno-electronmicroscopic study of human EA rosettes, using ferritin-labelled anti-human IgG antiserum, showed clusters of ferritin granules at the points of contact between erythrocytes and lymphoid cells, indicating that the links between Fc fragment of IgG on the surface of erythrocytes and specific receptor on the surface of lymphoid cell correspond to the sites of morphological interaction between the 2 cell types.

Erythrocytes

Ultrastructure of cell-mediated immunity. I. Comparison between E and EA rosettes.

The ultrastructural comparison between E and EA rosettes showed that, in the former, the rosetting lymphocytes are mostly round in shape and their interaction with sheep erythrocytes only consists of limited areas of membrane contact, in the latter, rosetting lymphocytes are mostly in the shape of uropods and surrounding ox red cells show pseudopods protruding towards the lymphocyte and coming into contact with it.

Animals

Ultrastructure of lymphocyte-mediated cytotoxicity. I. Interaction between phytohaemagglutinin-stimulated human lymphocytes and chicken erythrocytes.

The ultrastructural appearances of the interaction between normal phytohaemagglutinin (PHA)-stimulated human lymphocytes and chicken red cells (ChRBC) were studied. Close contact between ChRBC and control non-stimulated lymphocytes was often observed indicating that this is a non-specific phenomenon. In mixtures of PHA-stimulated lymphocytes and ChRBC, time-dependent development of interdigitating pseudopods between the two cell types was observed which was not seen in controls. Their development followed the same time-course as release of 51Cr when the ChRBC were pre-labelled with this marker. The findings suggest a relationship between the morphorlogical changes observed and the destruction of the target cells (ChRBC).

Animals