Biomedical subjects

G Peri

Publications and source records attributed to G Peri.

At least 19 recordsLinked to original sources

PubMed2006

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.

Age Factors↗

PubMed2001

PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.

OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.

Acute Disease↗

PubMed2001

Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration.

Pentraxin 3, a prototypic long pentraxin, is induced by proinflammatory signals in the brain. Inflammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, specific neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 -/- mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.

2-Amino-5-phosphonovalerate↗

PubMed2001

Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells.

Human natural killer (NK) cells constitutively express the beta- and gamma-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the beta(2)-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the alpha-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.

Apoptosis↗

PubMed2001

Evaluation of recovery methods to detect faecal streptococci in polluted waters.

AIMS: This paper compares the faecal streptococci count on 25 samples of polluted waters obtained with three techniques: most probable number (MPN), membrane filtration (MF) and pour plate (PP) methods. Although the PP method is a simple technique, familiar to water bacteriologists, it is not recommended in the international methods. METHODS AND RESULTS: For the MPN method, azide dextrose broth and ethyl violet azide broth were employed. For the MF technique, Millipore filters were placed onto azide maltose agar (KF agar), while for the PP method, 1 ml of a decimal water dilution was added to (Kennel Faecal) KF medium. Regression analysis and Friedman's ANOVA were performed to determine the relationship between faecal streptococci counts obtained with the three techniques. Statistical analysis of the results showed that the MPN, MF and PP techniques were equally valid with respect to faecal streptococci enumeration in polluted waters. CONCLUSION: Since the PP method was found to be as good as the other techniques, it may be preferred in polluted waters. It is more economical in terms of both time and materials than the MPN count, and it is as accurate as the MF count. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that the PP method, although not recommended internationally, is a reliable alternative to MF and MPN.

Bacteriological Techniques↗

PubMed2001

Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients.

OBJECTIVE: To evaluate the recently discovered long pentraxin PTX3 in plasma of critically ill patients and to compare it with the classic short pentraxin C-reactive protein and with other indicators of inflammation. DESIGN: A cohort study on plasma samples. SETTING: Medical intensive care unit (ICU) of the University Hospital of Basel. PATIENTS: A total of 101 consecutive critically ill patients admitted to the medical ICU. INTERVENTIONS: Venous blood samples were routinely obtained at entry, on day 2, and at discharge or before death. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained from 101 consecutive critically ill patients admitted to the ICU with systemic inflammatory response syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme-linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock. PTX3 levels correlated with clinical scores reflecting severity of disease (e.g., Acute Physiology and Chronic Health Evaluation II: p =.00097). In addition, high levels of PTX3 were associated with unfavorable outcome. CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection. Compared with the short pentraxin C-reactive protein, PTX3 may be a more direct indicator of tissue involvement by inflammatory and infectious processes.

Acute-Phase Proteins↗

PubMed2001

[Role of inflammation mediators in the pathogenesis of heart failure].

A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.

Cytokines↗

PubMed2000

Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians.

Several lines of evidence point to a profound remodelling of the cytokine network in healthy elderly subjects, with decreased type-1 cytokine production (IL 2) and a shift to type 0 and 2. We have also observed an increase of proinflammatory cytokines (IL-1, IL-6, TNF-alpha) in vitro, and an increase of circulating stem cell factor in vivo. In this setting, we studied changes of chemokines (MCP-1 and RANTES) with aging, as well as other molecules, namely, sTNF-RI and sTNF-RII, and the soluble form of the CD30 molecule (sCD30), involved in the pro- and antiinflammatory cytokine balance. The subjects enrolled in the study belonged to three different selected healthy groups of young, aged and centenarians. The presence of rheumatoid factor (RF) and antinuclear antibodies (ANA) was simultaneously assessed. The results show that MCP-1 serum levels were higher in the healthy aged and lowest in the young, while RANTES increased exclusively in centenarians. Only centenarians had autoantibodies (ANA and RF). sTNF-RI and sTNF-RII were significantly elevated in healthy old subjects compared to the young, and even higher in selected centenarians compared to the other age groups. sCD30 serum levels were significantly raised in centenarians compared to the young, despite absence of circulating CD30+ cells in the peripheral blood of the whole study population. No relationship among serum values of these different members of the TNF-R family was found, despite a strong correlation for sTNF-RI and sTNF-RII in all groups. We hypothesize that the increased chemokine levels in aged people, and raised sCD30 levels in centenarians, may reflect a general shift towards type 0/2 cytokines in normal aging, which may be responsible, at least in part, for the appearance of circulating autoantibodies without definite clinical consequences at advanced age.

Adult↗

PubMed2000

The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells.

Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1 beta, and tumor necrosis factor-alpha, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 cross-linking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues. (Blood. 2000;96:4300-4306)

Acute-Phase Reaction↗

PubMed2000

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Aged↗

PubMed2000

Changing epidemiology of dengue fever in travelers to Thailand.

A study was conducted to evaluate the incidence and seasonal pattern of dengue fever occurring among Israeli travelers to Southeast Asia. The illness was diagnosed by Israeli physicians stationed abroad and by serological methods carried out in Israel. Between 1994 and 1998 dengue fever was confirmed in 103 travelers, 80 of whom were diagnosed in Israel. A sharp increase in the incidence was noted in 1998 as compared with the previous 4 years. The attack rate during 1998 in a defined group of travelers was 3.4/1,000 and reached a peak of 5/1,000 during the dry season of 1998.

Dengue↗

PubMed2000

Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA).

PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1beta and tumour necrosis factor-alpha (TNF-alpha), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cytokines including IL-1beta and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.

Arthritis, Rheumatoid↗

PubMed2000

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease.

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 +/- 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 +/- 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation co-localized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD.

Adult↗

PubMed1999

[Severe psychiatric disorders during trips to the Far East].

8 cases of acute mental disorders among Israelis travelling in the Far East are presented. The most common symptoms were hallucinations, paranoid delusions, agitation and depression. The important precipitating factors were drug abuse, reaction to the foreign environment and malarial prophylaxis. Treatment included creating a nonhostile environment, the presence of a Hebrew-speaking physician, psychopharmacotherapy and prompt evacuation to Israel. Most patients improved markedly and returned to normal functioning.

Adult↗

PubMed1999

Characterization of type II intracellular IL-1 receptor antagonist (IL-1ra3): a depot IL-1ra.

Three molecular forms of the IL-1 receptor antagonist (IL-1ra) have been identified and cloned. Secreted IL-1ra (sIL-1ra or IL-1ra1) contains a classical leader peptide giving a released mature protein. Two intracellular isoforms, icIL-1ra type I (IL-1ra2) and icIL-1ra type II (IL-1ra3), have no leader sequence, thus predicting that these proteins remain intracellular. In an effort to define its biological role, we structurally and functionally characterized IL-1ra3. Endogenous immunoreactive IL-1ra3 was detected in a variety of inflammatory cells and tissues. We used a gene transfer strategy to explore the possible intracellular functions of IL-1ra3 (and IL-1ra2) and the cell-associated agonist IL-1alpha. The intracellular IL-1ra3 isoform, as well as IL-1ra2, does not block the action of exogenous and endogenous IL-1 under these conditions. Intact IL-1ra3 was released from the cells killed by NK effectors. The intracellular isoforms may represent a reservoir of IL-1ra, released upon cell death, whose function is to limit the pro-inflammatory action of cell debris.

Animals↗

PubMed1998

Interferon-gamma inhibits expression of the long pentraxin PTX3 in human monocytes.

PTX3 is a prototypic long pentraxin expressed by various cell types, most prominently monocytes and endothelial cells, in response to interleukin-1 (IL-1), tumor necrosis factor (TNF) and bacterial products. In the present report, we show that interferon-gamma (IFN-gamma) inhibits the expression of the PTX3 gene induced by exposure to IL-1, TNF or lipopolysaccharide in human monocytes. This effect is dose dependent and observable when IFN-gamma is added from 24 h before up to 3 h after the addition of IL-1. While the time course of the IL-1-induced PTX3 mRNA expression is not affected, IFN-gamma reduces the stability of the PTX3 mRNA as well as its transcription. The inhibition of PTX3 expression is restricted to monocytes in that no inhibition occurs in cytokine-stimulated fibroblasts and endothelial cells. Under the same conditions, as expected, IFN-gamma augmented monocyte chemotactic protein-1 expression in the same cell preparations. PTX3 protein secretion by activated monocytes is also suppressed by exposure to IFN-gamma. Altogether, these data identify a negative pathway of regulation mediated by IFN-gamma, which may occur under inflammatory conditions.

C-Reactive Protein↗

PubMed1998

The monocyte chemotactic protein a (MCP-1) and interleukin 8 (IL-8) in Hodgkin's disease and in solid tumours.

AIMS: Monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) are small, inducible proteins with chemotactic activity for specific subsets of leucocytes. The possibility that MCP-1 and IL-8 are produced in tissues involved by Hodgkin's disease, thus contributing to the inflammatory-type background of the lesion, was investigated. METHODS: The presence of RNA transcripts for MCP-1 and IL-8 was investigated in biopsy samples of 24 cases of Hodgkin's disease, 17 non-Hodgkin's malignant lymphomas, 30 solid tumours, and 30 histologically normal tissues by means of reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot analysis. RESULTS: MCP-1 expression was detected in 23 of 24 cases of Hodgkin's disease, in seven of 17 cases of B cell non-Hodgkin's lymphoma, and in seven of 14 cases of reactive lymphoid hyperplasia. IL-8 was present in six of 14 cases of Hodgkin's disease, and was seen only rarely in B cell non-Hodgkin's lymphoma and in reactive lymphoid tissues. MCP-1 and IL-8 RNA transcripts were detected in 13 of 25 carcinomas originating from the lung, breast, thyroid, and ovary. CONCLUSIONS: These findings are consistent with the possibility that MCP-1 and IL-8 are two additional cytokines involved in the pathogenesis of Hodgkin's disease.

Blotting, Southern↗

PubMed1998

[Cervical ganglioneuroma. Review, apropos of a case].

We describe a case of cervical ganglioneuroma, an uncommon benign tumor which develops slowly, predominantly in females and infants. Ganglioneuromas have a neuroectodermic origin and are localized along the sympathetic trunk. Most are unmasked fortuitously by palpation or by high serum catecholamine levels proportional to tumor size. After radiographic exploration and surgical excision, a pathologic study of the surgical specimen is required to identify this very differentiated tumor stemming from the neural crest.

Catecholamines↗