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C Tortorella

Publications and source records attributed to C Tortorella.

83 records · Page 5Linked to original sources

Redistribution of natural killer (NK) cell frequency and NK cytotoxic activity in primary IgA nephropathy.

Recent findings have indicated an imbalance of immune responsiveness in primary IgA nephropathy (IgAN). Thus natural killer (NK) cell frequency and NK cytotoxicity were evaluated in fifteen IgAN patients. CD8+, CD11+, CD56+ and CD57+ lymphocyte percentages in IgAN individuals fell within normal values, while a significant decrease of CD16+ cells was observed in the same group of patients. In contrast, NK activity overlapped that seen in controls as assessed by an agarose-single cell cytotoxic assay. To further investigate the discrepancy between CD16+ cell level and NK cytotoxic activity in IgAN, the proportion of CD11+ CD57+, CD56+ CD16+ and CD57+ CD16+ lymphocytes was determined. In spite of the unaffected CD56+ CD16+ cell frequency, IgAN subjects exhibited a significant decrease of CD11+ CD57+ and CD57+ CD16+ lymphocyte percentages in comparison to controls. It is suggested that a redistribution of NK lymphocyte subsets occurs in IgAN. This may have an important role in the impairment of the immunoregulatory network.

Adult↗

Role of interleukin 2, interleukin 4 and interleukin 5 in the T helper cell-driven B cell polyclonal differentiation in the elderly.

There is evidence for an impaired T cell-mediated B cell response during senescence. In thirty aged donors, pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by B cells co-cultured with autologous enriched CD4+ lymphocytes and low amounts of monocytes, was evaluated. Under such experimental conditions, elderly cultures displayed a reduced IgG and/or IgM production when compared with the younger counterpart. Moreover, interleukin (IL)-2 and/or IL-5 addition to cultures led to an enhancement of Ig release. In contrast, IL-4 supplementation failed to positively modulate B cell differentiation. At the same time, aged cells cultured in the presence of IL-2 + IL-5 exhibited an increased Ig synthesis, while the addition of IL-2 + IL-4 or IL-4 + IL-5 mixtures did not induce any significant effect in comparison with homologous untreated samples. The results suggest a critical role for IL-2, IL-4 and IL-5 in the modulation of T helper cell-driven B cell polyclonal responsiveness in the elderly.

Aged↗

[The role of free oxygen radicals in myocardial damage from ischemia/reperfusion, in chronic obstructive bronchopneumopathy and in aging].

During the last few years, several observations point out that oxygen-free radicals may play a pivotal role in the development of myocardial ischaemic/reperfusion injury, chronic obstructive pulmonary disease (COPD) and aging. With particular reference to acute myocardial ischaemic syndrome, these compounds may account for reperfusion-mediated ventricular arrhythmias, myocardial stunning and cell death. Such molecules may also be involved in lung damage during the course of COPD. In this regard, polymorphonuclear cell (PMN) recruitment at myocardial and/or lung level play an important role in oxygen-free radical overproduction. Several factors may, in fact, trigger PMN adhesion, respiratory burst and/or lysosomal enzyme release, this leading to a deleterious effect for the host. As far as elderly is concerned, evidence has been provided for a strict relationship between oxygen-free radical generation and metabolic rate. Nevertheless, the occurrence of PMN impaired functions and malnutrition in aged subjects gives rise to an enhanced synthesis of these compounds. All together, these findings outline the toxicity of oxygen-derived radicals and suggest the usefulness of a therapeutical approach to antagonize their effects.

Aging↗

Modulating effects on CD25 and CD71 antigen expression by lectin-stimulated T lymphocytes in the elderly.

During the last few years, several observations outline that the impaired T lymphocyte proliferative capacity in the elderly is due to a reduced interleukin 2 (IL-2) release. To further investigate the activation process during lectin stimulation, aged peripheral blood mononuclear cells (PBMC) were stimulated with phytohemagglutinin (PHA) and assessed for CD25 (IL-2 receptor) and CD71 (transferrin receptor) expression at different intervals of time. Our results provided evidence for a significant decline of both structure induction, above all in the later phase of culture. Indomethacin (INDO) treatment gave rise to an enhancement of CD71 antigen expression only, while prostaglandin E2 (PGE2) supplementation to culture media further decreased either CD25 or CD71 receptor induction. Interferon (IFN)-alpha and IFN-gamma treatment failed to modulate the frequency of CD25+ and/or CD71+ cells. Finally, the expression of CD71 receptor was increased by deferoxamine supplementation, this suggesting a partial involvement of iron overload in the depressed function. Although further studies are required to evaluate at a molecular level the decreased antigen expression, these findings indicate that several mechanism are involved in the elderly-related decline of T lymphocyte activation structures during lectin stimulation.

Aged↗

Role of bacterial lipopolysaccharides in the development of natural antibacterial activity mediated by human peripheral blood T lymphocytes.

The role of bacterial lipopolysaccharides (LPS) has been evaluated for their influence on the human T cell-mediated anti-Salmonella typhi activity. In nonendemic areas for salmonellosis this activity is exerted by CD4+ lymphocytes armed by IgA, whereas in endemic zones besides these cells also CD8+ lymphocytes armed by IgG display an elevated anti bacterial activity. These results suggest that, in endemic regions, continuous antigenic challenge and, in particular, that exerted by lipid A (the active moiety of LPS) may play a role in triggering this activity. In other series of experiments, pretreatment of endemic peripheral blood lymphocytes (PBL) with smooth and rough (Rb and Re) forms of Salmonella LPS leads to the inhibition of antibacterial activity. In this respect, Re-LPS, which contains lipid A covalently linked to the core-chetodeoxyoctonate, gives rise to the maximum of inhibition. Finally, fractionation of PBL by means of S. minnesota R345 (Rb) cytoadherence has led to the conclusion that anti bacterial activity is present in the Rb-unbound population, thus indicating that bacterial adherence to PBL is a distinct phenomenon from natural anti-S. typhi activity. The overall results suggest that lipid A is able to modulate the expression of antibacterial activity exerted by human peripheral blood T cells.

Adult↗

Serum suppressive factors may account for the reduced polymorphonuclear cell function in haemophilia.

Haemophiliacs exhibit a broad range of immune defects. In this regard we have investigated the functional capacity of purified polymorphonuclear (PMN) cell suspensions in a group of Human Immunodeficiency Virus (HIV)+ or HIV- patients. Our results provide evidence for a significant reduction of PMN-mediated chemotactic responsiveness, phagocytosis and killing in haemophiliacs regardless of HIV infection. The depressed response does not reflect a PMN intrinsic dysfunction, since respiratory burst activity and lysosomal enzyme release from haemophilic PMN are unaffected in comparison to healthy donors. Quite interestingly the pretreatment of PMN from normal donors with either HIV+ or HIV- haemophilic sera gives rise to a reduction of PMN activity. Moreover, the suppressive effect is abrogated by serum heat inactivation. Taken together, these findings indicate a role for serum suppressive factors in the imbalance of PMN functional capacity in haemophilia regardless of HIV infection.

Adolescent↗

Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade.

Orexins-A and B are two novel hypothalamic peptides, which, like leptin and neuropeptide-Y (NPY), are involved in the central regulation of feeding. Since leptin and NPY were found to modulate adrenal function, we have examined whether orexins are able to directly affect rat adrenal steroid secretion. Both orexin-A and orexin-B raised basal corticosterone secretion of dispersed rat zona fasciculata-reticularis (ZF/R) cells, their maximal effective concentration being 10(-8) M. In contrast, orexins did not affect either maximally ACTH (10(-9) M)-stimulated corticosterone production by ZF/R cells or the basal and agonist-stimulated aldosterone secretion of dispersed zona glomerulosa cells. The ACTH-receptor antagonist corticotropin-inhibiting peptide (10(-6) M) annulled corticosterone response of ZF/R cells to ACTH (10(-9) M), but not to orexins (10(-8) M). Orexins (10(-8) M) enhanced cyclic-AMP release by ZF/R cells, and the selective inhibitor of protein-kinase A (PKA) H-89 (10(-5) M) abolished corticosterone responses to both ACTH (10(-9) M) and orexins (10(-8) M). A subcutaneous injection of both orexins (5 or 10 nmol/kg) evoked a clear-cut increase in the plasma concentration of corticosterone (but not aldosterone), the effect of orexin-A being significantly more intense than that of orexin-B. Collectively, these findings suggest that orexins exert a selective and direct glucocorticoid secretagogue action on the rat adrenals, acting through a receptor-mediated activation of the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗

Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation.

BACKGROUND AND PURPOSE: The extent of abnormalities on T2-weighted MR images of the brain of patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) at presentation is associated with an increased risk of developing clinically definite MS (CDMS). We evaluated whether subtle changes outside T2-visible lesions are present in the brain of these patients and whether their extent increases the risk of subsequent development of CDMS. METHODS: Dual-echo, T1-weighted, and magnetization transfer (MT) images of the brain were obtained from 24 patients with CIS at presentation. These patients were followed up for a mean period of 33 months (range, 25-42 months). Twenty age- and sex-matched healthy volunteers served as control subjects. To create MT histograms of the normal-appearing brain tissue (NABT), macroscopic lesions were segmented from dual-echo images, were superimposed automatically, and were nulled out from the coregistered and scalp-stripped MT ratio (MTR) maps. The following MTR histogram-derived measures were considered: average MTR, MTR(25), MTR(50), MTR(75), peak height, and peak position. T2 and T1 lesion loads, average lesion MTR, and brain volume were also measured. RESULTS: Patients with CIS had lower average NABT-MTR (P < .0001) and peak position (P = .002) than did control volunteers, but patient brain size was similar to that of volunteers. At follow-up, 10 (41%) patients developed CDMS. Patients who developed CDMS during the follow-up period had higher T2 lesion volume (P = .003) and lower average NABT-MTR (P = .005) and peak position (P = .006) than did those who did not develop CDMS. T2 lesion volume (odd ratio, 3.54; P = .0005) and average NABT-MTR (odd ratio, 0.81; P = .01) were independent predictors of the subsequent development of CDMS. CONCLUSION: Subtle changes occur outside lesions visible on conventional MR images among patients with CIS suggestive of MS at presentation. The greater the extent of such abnormalities is, the higher is the risk of subsequent development of CDMS.

Adult↗

Oxidative burst and lysosomal enzyme release by polymorphonuclear cells in type IIa, type IIb and type IV primary hyperlipoproteinaemia.

Several findings pint out the occurrence of a strict relationship between lipoproteins and immunoresponsiveness. In this regard, in vitro lipoproteins pretreatment of mononuclear cell suspensions leads to an inhibition of Natural Killer (NK) cytotoxicity or T- and B-mediated immune functions. These results have an in vivo counterpart, since an impairment of either T-driven B cell polyclonal differentiation or phagocyte chemotaxis, phagocytosis and killing has been shown in patients with type IIa and type IIb primary hyperlipoproteinaemia. On the contrary, these activities fall within normal range in type IV hyperlipoproteinaemic subjects. To further address the potential role of polymorphonuclear cells (PMN) in atherosclerotic process, in the present report PMN-mediated superoxide anion (O2-) generation, hydrogen peroxide (H2O2) production, beta-glucuronidase and myeloperoxidase release have been assessed in similar groups of patients. Results provide a clearcut evidence for a significant enhancement of oxidative metabolism by either suspended or adherent to plastic PMN in type IIa primary hyperlipoproteinaemia only. These data were further confirmed by the observation that the same cell suspensions exhibit a significant increase of H2O2 generation and/or beta-glucuronidase and myeloperoxidase release. By contrast, PMN metabolic pathway in type IIb and type IV patients mimics that observed in healthy individuals. In the light of the well known increase of serum low-density lipoproteins (LDL) in type IIa primary hyperlipoproteinaemia, these findings suggest that also PMN may play an important role in the development of atherosclerosis. The augmented oxidative responsiveness may, in fact, give rise to LDL oxidation, which is in turn responsible for foam cell generation through an exaggerated uptake of oxidized LDL by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗