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Biomedical subjects

A Pignone

Publications and source records attributed to A Pignone.

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

Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis.

OBJECTIVE: Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produced by fibroblasts and cleaving a large number of neuropeptides. We previously found increased plasma circulating levels of NEP in patients with systemic sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset NEP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. METHODS: Fibroblasts, derived from biopsies taken from affected skin of 8 patients with the limited subset and 5 with the diffuse subset, were grown in vitro and intracellular levels of NEP activity were measured with a fluorometric method, while CD10 surface expression was evaluated by FACS analysis. Cell proliferation was assessed by 3HThymidine incorporation. RESULTS: Intracellular NEP activity was significantly increased in diffuse (7.02+/-4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11+/-2.0) and control fibroblasts (1.41+/-0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3+/-15%) compared to controls (74.6+/-11%) and the limited subset (82.7+/-11%). Cell proliferation of diffuse SSc fibroblasts was strikingly higher than controls and limited SSc fibroblasts. CONCLUSION: These results confirm that NEP is produced by fibroblasts and indicate that in diffuse SSc fibroblasts NEP is produced in higher quantities, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides.

Cell Division↗
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

Synoviocytes from osteoarthritis and rheumatoid arthritis produce plasminogen activators and plasminogen activator inhibitor-1 and display u-PA receptors on their surface.

The production of plasminogen activators and their inhibitors was studied in vitro in osteoarthritic (OA) and rheumatoid arthritic (RA) synovial fibroblasts (SF), obtained from RA and OA patients undergoing joint surgery. Subcultured SF were cultivated for 2, 4, 6, 8, 10 and 13 days and the medium assayed for the presence of both plasminogen activators (PAs) and plasminogen activator inhibitor-1 (PAI-1). The presence of urokinase-Plasminogen Activator (u-PA) receptors (u-PAR) on the surface of synovial cells was investigated by radio-ligand binding assay and cross-linking and by transmission electron microscopy (TEM) of a gold-u-PA complex. Our results showed a low production of tissue-type-Plasminogen Activator (t-PA) in both OA and RA SF, but relatively high levels of u-PA, until confluence, both in OA and in RA. SF were also able to produce plasminogen activator inhibitor in large amounts, in particular in RA since the very beginning of the culture. Receptors for u-PA were evident on both RA and OA SF. Our data show that SF in vitro produce mainly u-PA, the most important plasminogen activator involved in tissue modifications. The demonstration of u-PA receptors on the surface of OA and RA SF represents a step forward in the understanding of the possible role of fibrinolytic and tissue destructive proteinase cascade in joint inflammation.

Arthritis, Rheumatoid↗
PubMed1997

New approaches to Raynaud's phenomenon [corrected].

Dysfunction of vascular tone control is mainly caused by the derangement of endothelium and of the peripheral nervous system. Studies have suggested changes in the nervous system at either the peripheral level (loss of sensory motor nerves, increased alpha 2-receptor activity, and so on) or the central level (impaired thermoregulation), always linked to the profound abnormality of endothelial function. This dual involvement consistently affects the blood flow, which can be measured with several tools (laser Doppler velocimetry, digital blood pressure response, and so on). Studies have analyzed serologic and instrumental predictors of a possible development of a connective tissue disease in Raynaud's phenomenon. A new wave of studies addressed the role of reperfusion injury and oxygen radicals in provoking chromosomal breakage and generating an immune response through fragmentation of autoantigens in the presence of metals. Antioxidants have been proposed as efficacious treatment of Raynaud's phenomenon. The continued study of regeneration of vessels (therapeutic angiogenesis) may open a new avenue for the treatment of Raynaud's phenomenon and the loss of angiogenesis as in diffuse scleroderma.

Connective Tissue Diseases↗
PubMed1997

Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis.

The pattern of cytokine production of skin-infiltrating T cells from patients with progressive systemic sclerosis was investigated. Most CD4+ T-cell clones generated from skin biopsy specimens showed a type 2 helper (Th2) cytokine profile (production of interleukin-4, but no interferon (IFN)-gamma). High interleukin-4 but little or no IFN-gamma mRNA expression was found by in situ hybridization in skin perivascular mononuclear cell infiltrates. The immunohistochemical analysis revealed CD30 expression by high numbers of CD4+ T cells in the same specimens. Finally, the great majority of patients with diffuse disease had elevated levels of soluble CD30 in their sera. These data suggest the existence in patients with progressive systemic sclerosis of a predominant activation of Th2-like T cells, which may account for the major alterations (endothelial cell injury, fibrosis, and autoantibody production) occurring in this disease.

Adult↗
PubMed1996

The nervous system in systemic sclerosis (scleroderma). Clinical features and pathogenetic mechanisms.

The involvement of the nervous system in SSc is well recognized today. Different pathogenetic mechanisms are suggested that may alternatively explain the multiform appearance of the clinical spectrum (mononeuritis, mononeuritis multiplex, carpal tunnel syndrome, and so forth). It is now clear that the ANS is the earliest structure targeted by the disease in the gastrointestinal tract. The importance of this observation has not yet been adequately interpreted but may, together with the increasing evidence of the nervous system involvement in SSc, become a leading factor in understanding of the importance of the nervous system in the onset, development, and maintenance of the disease.

Autonomic Nervous System Diseases↗
PubMed1996

Increased circulating nerve growth factor is directly correlated with disease activity in juvenile chronic arthritis.

OBJECTIVE: To determine the circulating serum concentrations of nerve growth factor (NGF) and compare them with indices of disease activity in juvenile chronic arthritis. METHODS: NGF concentrations were evaluated with a two site immunoenzymatic assay (ELISA), in 17 children with systemic, 39 with polyarticular, and 24 with pauciarticular onset juvenile chronic arthritis. Each subset was divided according to different variables, appropriate to each subset, reflecting active and inactive disease. RESULTS: NGF concentrations were significantly higher in children with systemic [254 (SD 256.1) pg ml-1; P < 0.001], polyarticular [165.2 (300.8) pg ml-1; P < 0.05], and pauciarticular [106.8 (111.8) pg ml-1; P < 0.005] onset juvenile chronic arthritis than in controls. In all subsets, NGF concentrations were higher in the active than in the inactive phase of the disease. A significant direct correlation between NGF concentrations and erythrocyte sedimentation rate was found both in the systemic and in the polyarticular onset juvenile chronic arthritis. CONCLUSIONS: The increase in NGF concentrations in all juvenile chronic arthritis subsets and the correlation with disease activity suggest that NGF may take an active part in joint inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Nerve growth factor circulating levels are increased in Kawasaki disease: correlation with disease activity and reduced angiotensin converting enzyme levels.

OBJECTIVE: To investigate the serum levels of nerve growth factor (NGF) and their possible relationship with disease activity in Kawasaki disease. METHODS: Twelve children with Kawasaki disease, 12 healthy children (afebrile controls), and 12 children with high fever related to upper respiratory tract viral infections (URTVI) were enrolled in the study. Serum NGF levels were measured by an ELISA method before and after therapy. In addition, angiotensin converting enzyme (ACE), and erythrocyte sedimentation rate (ESR), complete hemochrome, and C-reactive protein were tested as indicators of endothelial injury and disease activity, respectively. RESULTS: NGF levels were strikingly increased in the acute phase of Kawasaki disease (1219.54 +/- 1660.29 pg/ml) and decreased in the inactive phase of the disease (277.08 +/- 245.64 pg/ml), while remaining significantly higher than controls (6.5 +/- 2.03 pg/ml). In febrile patients with URTVI, NGF levels (30.18 +/- 44.70 pg/ml) were moderately but significantly increased compared to afebrile controls, but remarkably lower in respect to active and inactive Kawasaki disease. In active Kawasaki disease, ACE values were significantly lower than in healthy children (2.8 +/- 1.7 vs 10.1 +/- 4.2 pmol/ml/min; p < 0.001) and increased during the inactive phase, but remaining lower than in controls (4.8 +/- 2.7 pmol/ml/min); ESR, hemoglobin level, and platelet count showed significant correlation with NGF, while ACE levels showed a significant inverse correlation with ESR and NGF. CONCLUSION: In Kawasaki disease, NGF increased together with decreased ACE may be linked to a diffuse vascular inflammatory process. NGF and ACE levels remained abnormal even when there was no clinical sign of disease activity. This may indicate that the disease process is not in complete remission and suggests careful and prolonged cardiac followup until their normalization.

Child, Preschool↗
PubMed1995

The central role of the endothelium in the pathogenesis of vasculitides.

The pathogenesis of vasculitides is poorly understood. A growing body of evidence indicates that endothelium injury is a fundamental step in the development of all types of vasculitides. In the recent years, it has become evident that endothelial cell is responsible for a multiplicity of functions such as several immunological activities and the control of the vascular tone. The alteration of endothelium may result in metabolic and biologic disorders leading to pathologic changes. Even though the importance of endothelial cell is now demonstrated, the pathophysiological mechanisms able to induce the vascular damage are still not completely defined. In the next years, the better knowledge of the physiology of the endothelium might lead to a more appropriate therapy of vasculitis.

Endothelium, Vascular↗
PubMed1994

[Expression of p53 in the skin in systemic sclerosis. Immunohistochemical study of 8 cases].

P53 gene belongs to the family of "Tumor suppressor gene". It encodes a nuclear phosphoprotein involved in cell proliferation control; mutations of p53 gene are the most common genetic alterations found in human tumors. These mutations may cause the production of an altered protein that usually loses its physiological function. The mutant p53 protein is more stable than the wild type form and it is immunohistochemically detectable. Systemic Sclerosis is characterized by activation of fibroblasts, endotheliocytes and lymphocytes; furthermore, in this disease, a proto-oncogenic activation has already been shown in fibroblasts and lymphocytes. The aim of this study was to verify p53 expression in the skin of SSc patients. Eight patients, all classified in the limited cutaneous subset of SSc, after informed consent, underwent skin biopsies of the affected and apparently unaffected skin. P53 was investigated by immunohistochemistry, using a monoclonal anti-p53 antibody (DO-7), on formalin fixed, paraffin embedded tissue. P53 immunoreactive cells were found in 4 out of 8 biopsies; in all cases the positivity was confined to cells of the basal layer of the epidermis, histologically identified as keratinocytes. A large case series and a molecular biology approach are needed to support these preliminary observations.

Adult↗
PubMed1993

Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation?

In recent years the role of the peripheral nervous system has been focused on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstrated to be involved in cartilage breakdown [13]. The aim of our work was to study the levels of SP and its peptidases, neutral endopeptidase (3.4.24.11) (NEP) and angiotensin-converting enzyme (ACE), in the synovial fluid and plasma of 30 patients with RA and 14 patients with osteoarthritis (OA). ACE and NEP were determined with a fluorimetric assay and SP with a radioimmunoassay (RIA) method. ACE levels were normal in the plasma of patients with RA and OA (6.1 +/- 1.9 and 6.7 +/- 1.4 pmol/ml/min, respectively); we found no differences in the values, of ACE between RA and OA synovial fluid (5.7 +/- 4.2 and 5.5 +/- 4.1 pmol/ml/min, respectively). NEP levels were significantly increased in plasma (139.3 +/- 36 pmol/ml/min) and synovial fluid (133.8 +/- 32 pmol/ml/min) of patients with RA when compared to patients with OA (73.4 +/- 22 in plasma and 15.2 +/- 10.8 pmol/ml/min in synovial fluid) and healthy controls (89.7 +/- 14 pmol/ml/min in plasma). In synovial fluid, SP was significantly higher in RA patients (43.1 +/- 16.6 pg/ml) than in OA patients (12 +/- 13.1 pg/ml), while plasma levels did not show any difference (RA: 14.4 +/- 10.2; OA: 13.6 +/- 10.6; healthy subjects: 11.3 +/- 3.9 pg/ml). The only relationship detected in controls and in OA was among plasma NEP and ESR (P < 0.05) and synovial fluid NEP (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Chronobiology in epidemiology and preventive medicine.

Many of the known cardiovascular risk factors, such as hormones, metabolic parameters, lifestyle, blood pressure, fibrinogenesis, fibrinolytic activity, etc., and also the reactivity of the organism to stimuli, are periodical and therefore require adequate measures at specific times in appropriate frequencies. The presence of circadian, circannual or other wide frequency rhythms may lead to contradiction in the evaluation of a potential risk factor. Chronobiological analysis shows fine differences within a "risk variable", defining some characters which may imply the alteration of a parameter only at certain times. Periodical risk factors may therefore be foreseen and sometimes prevented. Moreover, chronobiological approach may show another peculiar relation between risk factors; this is the so-called chronorisk. The convergence, in certain periods of time, of the phases of various risk factors, may strengthen their combined value. On the other hand, the phases of the protective factors, in the same period of time, may contribute to reduce or strengthen this combined value. From this point of view combined risk, apparently unimportant, appears highly increased, as compared with the normal homeostatic value. At equal levels of risk factors, different distribution and amplitude of the phases implies great differences in final combined risk values. Acute heart attack has a daily, seasonal and perhaps ultradian rhythm; other cardiological events, such as angina pectoris and sudden death, have circadian rhythms. Also cerebral vascular events have daily, seasonal, weekly and monthly variations. The periodical variations of acute vascular events and of the related risk factors, near and far, implies many complex interrelations in timing of biological structures, which are still perceived by the physician only as "noise".

Chronobiology Phenomena↗
PubMed1993

[The enzymatic mechanisms involved in the pathogenesis of rheumatoid arthritis and arthrosis. The role of metalloproteases and serine proteases in the breakdown of articular cartilage].

Rheumatoid arthritis and osteoarthritis, expression, respectively, of inflammatory and degenerative articular involvement, are the most important diseases affecting joint cartilage. Proteolytic enzymes are the effectors of the articular damage: their increased production by chondrocytes and synoviocytes leads to cartilage breakdown. These enzymes, whose structure and specific activities have been defined in the recent years, carry out their action in the extracellular matrix. They are characterized by the presence of a particular element at the active site, that allows to distinguish four different families. The most studied and the best known among them are metalloproteinases, represented by several enzymes with common features, and serinoproteinases, some members of which, particularly urokinase and tissue-type plasminogen activator, are recently indicated as potential responsible for articular destruction. Activators, and inhibitors of proteinases play a fundamental role: a fine balance, that controls the mechanisms of activation and inhibition, seems to take place at transcriptional level. Any factor able to modify the cellular shape and the cytoskeleton, gives rise to lytic enzyme expression at the genomic level. With the progress of knowledges, serinoproteinases are assuming an increasing relevance, particularly the components of the fibrinolytic pathway.

Arthritis, Rheumatoid↗
PubMed1992

High resolution computed tomography in systemic sclerosis. Real diagnostic utilities in the assessment of pulmonary involvement and comparison with other modalities of lung investigation.

The real utility of high resolution computed tomography (HRCT) for early detection of lung involvement was investigated in eighteen patients affected with systemic sclerosis (SSc). The results obtained from HRCT have been compared with traditional (chest radiographs, pulmonary function tests (PFT)) and nontraditional (ventilation and perfusion scintiscan) modalities of lung investigation. A significant statistical correlation (p < 0.001) between HRCT scans and chest radiographs was observed. Moreover, HRCT was more sensitive in the detection of early pulmonary interstitial involvement and more accurate in the assessment of interstitial fibrosis in cases with severe lung involvement. A statistical correlation (P < 0.001) between HRCT and the modalities of investigation of alveolo-capillary membrane--as PFT and ventilation scintiscan--was also observed. These results indicate that in SSc HRCT may be a useful technique for assessing early pulmonary involvement and for complementing other methodologies of investigation of lung function.

Adult↗