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Biomedical subjects

R Giacomelli

Publications and source records attributed to R Giacomelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Soluble CD30 in early rheumatoid arthritis as a predictor of good response to second-line therapy.

OBJECTIVE: To evaluate whether serum levels of the soluble form of CD30 (sCD30) correlate with disease activity in early rheumatoid arthritis (RA) and may have prognostic value in predicting the response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: The levels of sCD30 and C-reactive protein (CRP) were measured in the serum of 14 untreated subjects with early RA, before and during treatment with hydroxychloroquine, for a follow-up period of 8 months. At the end of the study, patients were also evaluated for their response to DMARDs. RESULTS: An inverse correlation between sCD30 and CRP serum values was demonstrated at baseline, but not during the follow-up. Patients who responded to DMARD therapy had higher sCD30 basal levels than non-responders. CONCLUSIONS: The evaluation of sCD30 serum levels in early RA may reflect the attempt by CD30+ T cells to downmodulate inflammation and may be a useful marker to predict a good response to DMARDs.

Adult↗
PubMed1998

Circulating Vdelta1+ T cells are activated and accumulate in the skin of systemic sclerosis patients.

OBJECTIVE: An increased percentage of Vdelta1+/gamma/delta T cells has been detected both in the peripheral blood and bronchoalveolar lavage fluid of patients with systemic sclerosis (SSc). This study evaluated the subset distribution, activation status, and expression of cellular adhesion molecules, such as intercellular adhesion molecule 1 (CD54), very late activation antigen alpha4 (CD49d), and lymphocyte function-associated antigen 1alpha (CD11a), on circulating gamma/delta T cells, as well as their presence in the skin of SSc patients. METHODS: We studied 12 patients with SSc and 16 healthy volunteer donors. The distribution, activation status, and expression of cellular adhesion molecules were studied by flow cytometry; their presence in SSc patient skin was evaluated by immunohistochemistry. RESULTS: We found that the percentages and absolute numbers of peripheral blood gamma/delta T cells, CD16, CD8, CD45RO, CD25, HLA-DR, CD54, and CD11a coexpression did not differ significantly from those of the controls. CD49d gamma/delta T cells were significantly increased in SSc patients (2.3%) compared with controls (0.5%). A marked increase in the ratio of Vdelta1+ cells to gamma/delta cells was observed in the patients (72%) compared with the controls (31%). The Vdelta1+ subset showed a significant expression of both HLA-DR (83% of total Vdelta1+ cells) and CD49d (90% of total Vdelta1+ cells) compared with the controls (20.5% and 60%, respectively). In the skin, the absolute numbers of gamma/delta T cells were found in striking amounts in perivascular areas, particularly in the early edematous phase of SSc (22.58 in patients and 0 in controls); the majority of gamma/delta T cells were Vdelta1+ (19 in patients and 0 in controls). In the advanced phase of SSc, Vdelta1+ T cells were also increased compared with controls (3.5 versus 0). CONCLUSION: Our results show that Vdelta1+ T cells express both adhesion molecules and activation markers, and strongly support gamma/delta T cell homing to sites of inflammation. The increase in the Vdelta1 subset suggests a selective V gene subset expansion.

Adult↗
PubMed1998

The Italian version of the Family Assessment Device.

The aim of the study was to evaluate in a heterogeneous. Italian sample (n = 340) the psychometric properties of the Italian version of the Family Assessment Device (FAD), a 60-item questionnaire assessing family functioning. The questionnaire was administered to psychiatric (n = 116), medical (n = 114) and non-clinical samples (n = 110). In a sample of 30 non-clinical subjects the temporal stability of the FAD was investigated. The results showed a good temporal stability for Problem Solving, General Functioning. Communication, and Affective Responsiveness scales, and a good internal reliability of the scale. Factor analysis of the Italian version provided discrepancies with the hypothesized structure of the instrument, leading to the identification of seven slightly different dimensions. The proposed seven-factor model of the instrument did not provide a good fit to our data. The results of our study suggest the need for a major improvement in the adaptation of the FAD in the Italian setting.

Adult↗
PubMed1998

Serum levels of soluble CD30 are increased in ulcerative colitis (UC) but not in Crohn's disease (CD).

Imbalance in Th1 and Th2 subsets and their derived cytokines seems to be involved in the immune abnormalities underlying UC and CD. CD30 is a member of the tumour necrosis factor/nerve growth receptor superfamily expressed on T cells producing Th2 cytokines and released as a soluble form. In this study high levels of soluble CD30 were found in sera of UC patients independently of disease activity. Furthermore, increased titres of soluble CD30 molecule were shown, in the same patients, by mitogen-stimulated cultures of peripheral blood mononuclear cells. Our data seem to indicate that an activation of Th2 immune response is involved in the pathogenesis of UC, but not of CD. Furthermore, this finding indicates that serum soluble CD30 measurement may be helpful for differentiating these two forms of inflammatory bowel disease.

Adolescent↗
PubMed1997

Circulating levels of soluble CD30 are increased in patients with systemic sclerosis (SSc) and correlate with serological and clinical features of the disease.

Activated Th2 lymphocytes express the surface molecule CD30 and release a soluble form of the same molecule which can be detected both in vivo and in vitro. In the present study, high levels of soluble CD30 were found in the peripheral blood of patients with SSc, and a significant correlation with skin score and erythrocyte sedimentation rate (ESR) was detected. Furthermore, we observed a higher spontaneous release of soluble CD30 in the supernatants of unstimulated cultures of peripheral blood mononuclear cells from our patients compared with healthy controls. Taken together, these data suggest a possible involvement of Th2 cells in the immunopathogenesis of SSc, and the dosage of CD30 soluble in the peripheral blood may be helpful in following the outcome of the disease.

Adult↗
PubMed1996

[Immunosuppressive therapy of vasculitis: current aspects and perspectives].

Vasculitides are a set of serious diseases of unknown aetiology with various immunopathogenetic mechanisms, characterized by inflammation and necrosis of the vessel wall with consequent lumen obliteration. They may be primitive or associated with other diseases, have heterogeneous clinical manifestations and different degrees of severity which may be related to the localization of the interested vessels. Although in the last years many classifications have been proposed, a standardized nomenclature of vasculitides is unquestionably still needed to facilitate the diagnosis and management of patients with the disease. Steroids and immunosuppressant are the conventional therapy, whereas other therapeutic strategies are reserved for the refractory vasculitides to conventional therapies or for intolerant recipients to cytotoxic drugs. New approaches are represented by monoclonal antibodies and drugs which could be effective in the treatment of the trigger factors which activate the immunopathological mechanisms. Current data suggest that, rather than pursuing the idea of a single therapy for vasculitides, an oncological model of combined therapy, to induce both the disease control and maintenance of remission, might be adopted. An improvement of our knowledges on the mechanisms underlying the different entities associated to standardized criteria of activity and remission of disease will lead to an improvement of our therapeutic strategies.

Adrenal Cortex Hormones↗
PubMed1996

Peripheral blood mononuclear cells of patients with systemic sclerosis produce increased amounts of interleukin 6, but not transforming growth factor beta 1.

OBJECTIVE: To assess the ability of peripheral blood mononuclear cells (PBMC) of patients with systemic sclerosis (SSc) to produce interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-beta 1), to identify the IL-6 producer cells in the in vitro model, and to correlate these data with the clinical evidence of our patients. METHODS: We used a sandwich ELISA to quantitate IL-6 and TGF-beta 1 levels in sera, plasma, and supernatants, and an imunofluorescence technique to evaluate IL-6 producing cells in our patients. RESULTS: IL-6 was detected in sera from 8 of 20 patients and no controls (p < 0.05). A significant increase of IL-6 production was observed in both spontaneous and phytohemagglutinin (PHA) induced cultures of PBMC from patients with SSc vs controls. No differences in TGF-beta 1 production were observed, either in sera or supernatants, between patients and controls. A significant increase of IL-6 synthesizing cells was observed after 3 h of PHA stimulation in patients vs controls (p < 0.05). CONCLUSION: Spontaneous IL-6 production and the higher number of IL-6 producing cells in patients with SSc suggest that these cells have been already primed in vivo. The absence of PBMC primed for TGF-beta 1 production supports the hypothesis that cells other than lymphocytes produce and secrete this cytokine in the skin of patients. Higher serum levels of IL-6 observed in a subset of patients did not correlate with either severity or duration of disease.

Adult↗
PubMed1994

Increase of circulating gamma/delta T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease.

In order to study the role of gamma/delta T cells in the pathogenesis of inflammatory bowel disease (IBD) in humans, we measured the percentage of these cells in the peripheral blood, assessed the ratio of the non-disulphide-linked (delta TCS1) type of T cell receptor (TCR) in the total gamma/delta T cells, studied the co-expression of gamma/delta TCR and accessory molecules CD8 and CD16, and compared these data with both the type and the activity of the disease. Percentage levels and absolute numbers of gamma/delta+ T cells were higher in active patients than in controls (P < 0.05), mainly as a result of an increase of V delta 1+ (delta TCS1) T cell subset (P < 0.05). This trend was strongly retained independently of disease activity and clinical picture. An increased percentage of TCR delta 1+/CD16+ cells was observed in our patients compared with controls (P < 0.05). In contrast, no difference was observed as far as the TCR delta 1+/CD8+ cells were concerned. These results suggest that IBD is associated with an expansion of gamma/delta T cells in peripheral blood, which may play a role in the pathogenesis of these disorders.

Adult↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

Natural killer activity and antibody-dependent cellular cytotoxicity in progressive systemic sclerosis.

Enhanced natural killer (NK) activity and normal lymphocyte antibody-dependent cellular cytotoxicity (ADCC) were observed in 16 patients with a diagnosis of progressive systemic sclerosis (PSS). Higher NK activity levels were observed against NK-sensitive K562 target cells, while the NK-resistant P815, Daudi and Raji cell lines were not lysed. Cytofluorimetric studies and morphological analysis of peripheral blood lymphocytes (PBL) showed an increased number of CD16 positive cells and large granular lymphocytes (LGL), indicating that the enhancement observed was probably attributable to an increase in the number of circulating NK cells.

Adult↗
PubMed1990

Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis.

We studied the sera of patients with progressive systemic sclerosis (PSS) for elevated levels of soluble interleukin-2 receptor (sIL-2R), interleukin-2 (IL-2) and interleukin-4 (IL-4). We also measured IL-2, IL-4 and B cell growth factor (BCGF) activity in supernatants of peripheral blood mononuclear cells from the same patients. The finding of elevated serum sIL-2R and IL-2, and the increased levels of IL-2, IL-4 and BCGF activity in culture supernatants indicates that T lymphocyte hyperactivity likely play a major role in PSS. The failure to detect under our experimental conditions a direct proliferative effect of recombinant IL-2 on enriched normal B cells might suggest that IL-4 is the cytokine mainly responsible of the BCGF activity recovered in PSS supernatants.

Adult↗
PubMed1990

Soluble CD8 antigen in systemic sclerosis.

In 15 patients suffering from systemic sclerosis (PSS) the function of CD8+ circulating lymphocytes was assayed by determining soluble CD8 antigen (sCD8) both in sera and in 48 hr PHA-conditioned media of peripheral blood mononuclear cells (PBMCs). Furthermore, the frequency of circulating activated CD8+ cells, which express DR antigens, interleukin-2 receptor, and transferrin-receptor, was determined by cytofluorographic analysis. The results of this preliminary study indicate that only in 6 PSS sera sCD8 was elevated as compared to healthy controls; furthermore, we found slightly increased sCD8 in culture media from PSS patients. The frequency of circulating activated CD8+ cells was similar both in PSS patients and in controls. Overall, our findings suggest that CD8+ cell activation is not a major phenomenon in PSS.

Adult↗
PubMed1990

[Cyclosporin (CyA) and H2 antagonists].

An experimental study on rats in order to discovery any possible interaction between Ciclosporin (CyA) and H2-receptor antagonists has been carried out. The results obtained demonstrated that the serum levels of CyA were higher in rats treated with CyA and Cimetidine or Ranitidine, but not Famotidine. It is probable that the increase of ciclosporinaemia is the consequence of an increased hepatotoxicity due to administration of Cya in association with Cimetidine or Ranitidine.

Animals↗
PubMed1990

Drug interaction between cyclosporin A and nizatidine in Sprague-Dawley rats.

The H2-receptor antagonists seem to be effective in prevention and treatment of stress ulcer in transplant recipients. In a previous study on rats, an increase was observed in cyclosporinaemia and hepatotoxicity after administration of cimetidine or ranitidine in association with cyclosporin A (CyA). On the contrary, famotidine does not influence the blood CyA levels. The aim of the study was to detect the possible synergistic nephro- and hepatotoxicity of nizatidine administered in association with CyA, assaying the serum creatinine, the ALT and AST levels, and histological features of thirty young male Sprague-Dawley rats, divided into 6 groups of five animals each. After 10 days, all the rats were sacrificed, their blood was collected to assay serum creatinine, ALT, AST and serum CyA levels: kidneys and livers were processed for light microscopy. The results obtained demonstrated that, while the level of creatinine was normal in each group, the average level of transaminase and the serum levels of CyA were significantly higher in the animals receiving the association of CyA and nizatidine. Furthermore, this group demonstrated a mild infiltrate of the liver characterized in some cases with eosinophilic polymorphonuclear cells. In light of the results obtained, it is probable that the increase of cyclosporinaemia is the consequence of an enhanced hepatotoxicity due to administration of CyA in association with nizatidine.

Animals↗