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L Biancone

Publications and source records attributed to L Biancone.

At least 55 records · Page 3Linked to original sources
PubMed1999

Perceptual defense mechanisms in Crohn's disease and panic disorder.

The defense organization of Crohn's disease and Panic Disorder was studied with a well-validated tachistoscopic paradigm, the Defense Mechanism Test. Three sex- and age-matched groups of 34 subjects (Crohn, Panic, and Nonclinical) were compared on the main codings of defense. Crohn patients were characterized by stereotypy and lack of recognition of the threat. The Panic group presented clearly higher frequencies of protocols with repression, isolation, and disappearance of the threat. Especially was the strongest variant of isolation, barrier-isolation, typical of the defensive substructure of panic patients.

Adult↗
PubMed1999

CD40-CD154 interaction in experimental and human disease (review).

Cell-to-cell signals between T lymphocytes and antigen-presenting cells strictly regulate the development of the immune response. It has clearly emerged that among these signals few cell surface receptor-ligand pairs, such as CD40 and its ligand, CD154, are mandatory for the induction of lymphocyte activation. The early observation that mutations of CD154 gene are responsible for a human severe immunodeficiency primed an impressive number of studies aimed to functionally characterize this receptorial system in view of therapeutically exploiting its properties. Indeed, various approaches aimed to disrupt natural CD40-CD154 interaction were highly effective in the prevention and treatment of several experimental models of autoimmune disease and transplant rejection. In parallel, abnormalities of this pathway were constantly found in several immunologically-mediated human diseases. Furthermore, a number of studies have dissected the role of CD40 and its ligand in the immune response against various microbial and viral pathogens. Since these molecules are often expressed by tumor cells, it is not surprising that great efforts have been made to address their function also in the development of cancer. Most recent data strongly suggest an involvement of endothelial CD40 in the vascular processes that lead to atherogenesis. This review focuses on the most significant advances in the understanding of the molecular regulatory events involving CD40 and its ligand in experimental and human disease.

Animals↗
PubMed1998

HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation.

HIV-infected patients suffer several renal syndromes, which can progress rapidly from renal insufficiency to end-stage renal disease. Histologically, HIV-induced nephropathy is characterized by prominent tubulopathy with apoptosis of tubular cells. Clinical and experimental evidence suggests that renal injury may be directly related to virus infection. Although HIV-1 is a polytropic and not solely lymphotropic pathogen, the susceptibility of renal cells to HIV-1 remains to be determined. This paper demonstrates in vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 and describes the effects of PTEC infection to explain the pathogenesis of tubular damage in vivo. The results indicate that PTEC express HIV-specific receptor and coreceptors and sustain virus replication. We observed that HIV-1 infection causes the death of tubular cells by triggering an apoptotic pathway involving caspase activation. Fas upregulation but not Fas ligand expression was found in the infected PTEC. However, after HIV-1 infection, tubular cells became susceptible to apoptosis induced through Fas stimulation. Caspase inhibition prevented the death of the infected PTEC in spite of persistent viral replication. These findings may explain the prominent histopathology of HIV-associated nephropathy and demonstrate that the apoptosis of nonlymphoid cells can be directly induced by HIV-1.

Apoptosis↗
PubMed1998

Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity.

In vitro experiments indicate that components of the host present in body fluids may prevent the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells. Fibronectin (Fn), a dimeric 440-kDa extracellular matrix adhesion protein, is secreted by mesenchymal cells and assembled into insoluble matrices. Fn exerts important effects on cell growth and differentiation through a number of discrete functional domains. Several microorganisms are known to bind Fn. We show that, under physiological conditions, HIV-1 gp120 and gp160 are capable of binding plasma and cellular Fn as well as laminin and vitronectin. Experiments were set up to analyze in detail the binding of HIV gp120 and gp160 to Fn. The gp120 and gp160 specifically recognize the C-terminal heparin-binding domain of Fn (Fn-CTHBD) with a calculated KD of 2.8 x 10(-7) M for gp160. Binding of gp160 to Fn-CTHBD is a saturable and specific process that is blocked by antibodies to Fn-CTHBD and by heparin and is inhibited to a minor extent by heparan sulfate and dextran sulfate. These observations suggest that gp120/160 specifically recognize the III15 repeat within Fn-CTHBD. Intact Fn and Fn-CTHBD strongly inhibit the interaction of gp120/160 with soluble CD4 and, under low serum conditions, are capable of neutralizing the infectivity of HIV-1 for CD4-positive T cells. Thus, Fn that is present in plasma and mucinous secretions may well affect HIV infectivity and virus distribution in vivo.

Antibodies↗
PubMed1998

Tropomyosin isoforms in intestinal mucosa: production of autoantibodies to tropomyosin isoforms in ulcerative colitis.

BACKGROUND & AIMS: Autoantibodies against tropomyosins (TMs) have been reported in ulcerative colitis (UC). In this study the hTM isoforms (hTM1-5) present in intestinal epithelial cells and in smooth muscle were investigated, and the immunoreactivity against hTMs by immunoglobulin G (IgG) produced in vitro by colonic mucosal lymphocytes (LPMCs) from patients with UC, Crohn's disease (CD), and controls was examined. METHODS: TMs were extracted from colonic and jejunal epithelial cells and smooth muscle, and hTM isoforms were identified using isoform-specific monoclonal antibodies by enzyme-linked immunosorbent assay and transblot analysis. The immunoreactivity of IgG produced by colonic LPMCs was analyzed against the recombinant hTM isoforms. RESULTS: The major hTM isoforms present in colonic and jejunal epithelial cells are hTM5 and hTM4, whereas intestinal smooth muscle contains the hTM1-3 isoforms. The IgG synthesized in vitro by LPMCs from UC (n = 19) recognized hTM5 and hTM1, more significantly (P < 0.04 to <0.001) when compared with CD (n = 12) and controls (n = 17). However, IgG produced by LPMCs from CD did not show such anti-hTM reactivity. Mucosal anti-hTM IgG mainly belonged to the IgG1 subclass. CONCLUSIONS: Intestinal epithelial cells and smooth muscle have distinct hTM isoforms. Patients with UC, and not CD, show mucosal autoantibody response against hTM isoforms, particularly hTM5 and hTM1.

Adult↗
PubMed1998

Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives.

Autoimmunity to cytoskeletal protein tropomyosin (TM) has been demonstrated in UC. However, the TM isoforms involved in this IgG-mediated autoimmune response in UC and the possible presence of serum IgG antibodies against TM (hTMs IgG) in unaffected UC relatives are unknown. The aim of this study was to investigate the human TM (hTM) isoforms recognized by serum IgG from UC and to explore whether hTM IgG antibodies are present in healthy UC relatives. We studied 33 UC patients with 58 unaffected relatives, 31 Crohn's disease (CD) patients with 31 unaffected relatives and 20 controls (C). Serum IgG against four recombinant hTM isoforms (hTM1, 2, 3, 5) were tested by ELISA. p-ANCA were tested by ELISA and immunofluorescence. Serum hTM1 and hTM5 IgG were higher in UC patients than in CD and C (P<0.005). Among UC patients 52% were seropositive for hTM1 and 64% for hTM5 (P<0.001 versus CD and C). In UC, hTM5 IgG were higher in p-ANCA+ than in ANCA- patients (P=0.04). In UC relatives hTM1 IgG were higher than in CD relatives and C (P<0.01). UC relatives were more frequently seropositive for hTM1 than hTM5 IgG (P=0.001). while probands were more frequently seropositive for hTM5 IgG (P=0.008). We conclude that autoimmunity to hTMI and hTM5 is a feature of UC, while hTM1 IgG differentiate UC relatives from controls. A genetic susceptibility to immune recognition of hTM isoforms in UC is suggested.

Adolescent↗
PubMed1998

Expression of inducible lymphocyte costimulatory molecules in human renal allograft.

BACKGROUND: CTLA-4/CD28-B7 and CD40-CD40L interactions constitute two key costimulatory pathways in lymphocyte signalling during experimental allograft rejection. Studies on the expression of these molecules in human transplant rejection are still lacking. METHODS: The immunohistochemical study was performed on renal biopsies obtained for various clinical complications from 25 renal transplant patients. Expression of B7-1 and B7-2 and their counter-receptor CTLA-4, and of CD40 and its counter-receptor CD40L was examined. RESULTS: In acute rejection a focal intense infiltration of B7-1+ and B7-2+ cells (mainly CD20- CD14+) and of CTLA-4+ T lymphocytes (mainly CD8+) was present. In contrast, CD40 and CD40L were rarely expressed. Accumulations of T lymphocytes were found in the interstitium in the same area containing B7-1+ and B7-2+ cells. The scattered CD40L+ cells found in the T-cell infiltrate exhibited the CD4+ phenotype. In chronic rejection only a few B7-1+, B7-2+ or CTLA-4+ cells were detectable. In contrast, several CD40L+CD4+ cells were present both in the interstitium and in glomeruli. Moreover, an intense expression of CD40 on the endothelium was observed. In patients with cyclosporin nephrotoxicity cells positive for B7-1, B7 2, CTLA-4, CD40, or CD40L were absent. CONCLUSIONS: These results demonstrate a differential expression of costimulatory molecules in renal biopsies of allograft recipients undergoing acute or chronic rejection. Moreover, their detection may prove useful to discriminate rejection from cyclosporin nephrotoxicity.

Abatacept↗
PubMed1998

Mucosal and systemic antibody levels against Helicobacter pylori do not parallel gastric inflammatory changes.

BACKGROUND AND AIMS: Mucosal and systemic antibodies against Helicobacter pylori have been detected but their role in the natural history of Helicobacter pylori-related diseases is unclear. In this study, the levels of Helicobacter pylori IgG and IgA were related to the grade of gastritis. PATIENTS AND METHODS: A series of 152 dyspeptic patients underwent gastroscopy with biopsies. Helicobacter pylori was detected in 131 (86%) patients. Samples of serum and unstimulated saliva were collected. Helicobacter pylori IgG and IgA were measured in homogenised gastric biopsies, saliva and serum by an in-house enzyme linked immunosorbent assay. RESULTS: Levels of gastric mucosa, salivary and serum Helicobacter pylori IgG were higher (p < or = 0.01) in Helicobacter pylori positive than negative patients. Likewise, levels of gastric mucosa and serum Helicobacter pylori IgA were higher (p < 0.01) in Helicobacter pylori positive patients. Gastric mucosa, saliva and serum Helicobacter pylori antibody levels did not differ between superficial and atrophic, active and inactive Helicobacter pylori positive gastritis. CONCLUSIONS: These data indicate that gastric inflammatory changes may not necessarily be related to the antibody response against Helicobacter pylori.

Adult↗
PubMed1997

Development of inflammatory angiogenesis by local stimulation of Fas in vivo.

Fas-Fas ligand interaction is thought to be a crucial mechanism in controlling lymphocyte expansion by inducing lymphocyte apoptosis. However, Fas is also broadly expressed on nonlymphoid cells, where its function in vivo remains to be determined. In this study, we describe the development of inflammatory angiogenesis induced by agonistic anti-Fas mAb Jo2 in a murine model where Matrigel is used as a vehicle for the delivery of mediators. The subcutaneous implants in mice of Matrigel containing mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalization of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected in the inflammatory infiltrate. The phenomenon was dose and time dependent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogenesis was restricted to the agonistic anti-Fas mAb and it was absent in lpr Fas-mutant mice. Apoptotic cells were not detectable at any time inside the implant or in the surrounding tissue, suggesting that angiogenesis and cell infiltration did not result from recruitment of phagocytes by apoptotic cells but rather by a stimulatory signal through Fas-engagement. These findings suggest a role for Fas-Fas ligand interaction in promoting local angiogenesis and inflammation.

Animals↗
PubMed1997

Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells.

BACKGROUND & AIMS: Cell-mediated immunity is a feature of Crohn's disease (CD). The heterodimer interleukin (IL)-12, produced by phagocytes, induces T-cell cytokines, primarily interferon (IFN)-gamma. This study examined whether CD lamina propria mononuclear cells (LPMCs) express and release bioactive IL-12. METHODS: LPMCs were isolated from 13 patients with CD, 9 with ulcerative colitis (UC), and 13 controls. Messenger RNA for p40 and p35 IL-12 subunits was evaluated by reverse-transcription polymerase chain reaction. IL-12 was measured by enzyme-linked immunosorbent assay in LPMC culture supernatants. The INF-gamma-inducing effect of unstimulated LPMC supernatants was evaluated. RESULTS: Messenger RNA for both IL-12 subunits was detected in LPMCs of 11 of 13 patients with CD, 1 of 9 patients with UC, and 1 of 13 controls (P < 0.001). IL-12 was measured (10.5 +/- 2 pg/mL at 24 hours) in unstimulated CD LPMCs and was enhanced by pokeweed mitogen, lipopolysaccharide, and staphylococcal enterotoxin B. No IL-12 was detectable in 8 of 9 patients with UC and 12 of 13 control-unstimulated LPMCs. IL-12 induced by pokeweed mitogen and staphylococcal enterotoxin B in UC was lower than in CD and did not differ from controls. An IFN-gamma-inducing effect was restricted to unstimulated CD LPMC supernatants and was inhibited by an anti-IL-12 antibody in a dose-dependent fashion. CONCLUSIONS: IL-12 transcripts are expressed in CD intestinal tissues. CD LPMCs are up-regulated in their capability of releasing bioactive IL-12. Expression and release of bioactive IL-12 seem to differentiate CD from UC.

Blood Cells↗
PubMed1997

99mTc-HMPAO granulocyte scintigraphy in the early detection of postoperative asymptomatic recurrence in Crohn's disease.

The usefulness of 99mTc-HMPAO scintigraphy in the early detection of postoperative recurrence of Crohn's disease was evaluated in 17 patients undergoing ileocecal resection and prospectively followed up for one year. Scintigraphy was performed 6 and 12 months after surgery and recurrence assessed by colonoscopy within two weeks. As controls, four patients with ileocecal resection for cecal carcinoma were studied. To perform scintigraphy, autologous granulocytes were labeled with 99mTc-HMPAO, injected, and tau-camera images acquired after 30 min and 3 hr. Six months after surgery, 4/8 Crohn's disease patients showed endoscopic recurrence, and 30-min scintigraphy was positive only in these four patients (four true positives, four true negatives). At 12 months, endoscopic recurrence was detected in 10/14 Crohn's disease patients, and 30-min scintigraphy was positive in 9/14 patients (eight true positives, three true negatives, two false negatives, one false positive). Scintigraphy at 3 hr showed a lower specificity in detecting CD recurrence both at 6 and 12 months. The endoscopic and 30-min scintigraphic score were significantly correlated both at 6 and 12 months (P = 0.007; P = 0.04). Scintigraphy was negative in 4/4 controls at 30 min (four true negatives) and positive in 1/4 (one false positive) at 3 hr. We conclude that 99mTc-HMPAO scintigraphy at 30 min is a sensitive technique for the early detection of Crohn's disease recurrence in patients under regular follow-up after surgery.

Adult↗
PubMed1997

Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells.

BACKGROUND: Proximal tubular epithelial cells express a surface C3-convertase activity which induces C fixation and insertion of the C5b-9 membrane attack complex (MAC) into the cell plasma membrane. The physiopathological consequences of this phenomenon are unknown. METHODS: The effect of C fixation on the production of inflammatory mediators by human proximal tubular epithelial cells in culture was explored. RESULTS: Proximal tubular epithelial cells incubated with a sublytic amount of normal human serum as a source of C, but not with heat-inactivated human serum, showed a time-dependent calcium influx and a concomitant release of 14C-arachidonic acid (14C-AA). Eicosanoid synthesis following the arachidonic acid mobilization was studied as prostaglandin E2 release. Mg2+/EGTA, which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl bromide a phospholipase A2-inhibitor, inhibited mobilization of 14C-AA. These results suggest the activation of an extracellular Ca(2+)-dependent, phospholipase A2. Complement fixation was associated with the synthesis of proinflammatory cytokines such as IL-6 and TNF-alpha. Experiments with C6-deficient sera indicated that the release of 14C-AA and the production of cytokines were dependent on the insertion of the terminal components of complement in the plasma membrane. Indeed, the reconstitution of normal haemolytic activity of C6-deficient sera with purified C6 restored also the release of 14C-AA and the production of cytokines. CONCLUSIONS: In vitro complement activation on the proximal tubular cell surface triggers the generation of proinflammatory mediators, which may potentially contribute to the pathogenesis of tubulointerstitial injury.

Arachidonic Acid↗
PubMed1997

Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells.

The six group B coxsackieviruses (CVBs) are highly prevalent human pathogens that cause viremia followed by involvement of different organs. Clinical and experimental evidence suggests that CVBs can induce kidney injury, but the susceptibility of human renal cells to these viruses is unknown. By using pure cultures of human glomerular and tubular cells, we demonstrated that all CVBs are capable of productively infecting renal cells of three different histotypes. Distinct pathogenic effects were observed. Proximal tubular epithelial cells and, to a lesser extent, glomerular podocytes were highly susceptible to CVBs; in both cases, infection led to cytolysis. In contrast, glomerular mesangial cells supported the replication of the six CVBs but failed to develop overt cytopathologic changes. Mesangial cells continued to produce infectious progeny for numerous serial subcultures (i.e., more than 50 days), especially with type 1, 3, 4, and 5 viruses. In the above cells, persistent infection induced the de novo synthesis of platelet-derived growth factor A/B and enhanced the release of transforming growth factor beta1/2. These two factors are important mediators of progression from glomerular inflammation to glomerulosclerosis. CVB replication appeared also to impair the phagocytic and contractile activity of mesangial cells. Loss of these properties--which are important in glomerular physiopathology--may contribute to the development of progressive nephropathy. The results show that CVBs induce distinct effects in different types of cultured renal cells and suggest that CVB infections may be associated with both acute and progressive renal injury.

Cytokines↗
PubMed1997

The role of E-selectin for neutrophil activation and tumor metastasis in vivo.

The selectin class of adhesion molecules plays a critical role in facilitating leukocyte adhesion to and subsequent transmigration of endothelium. On this basis, selectins have been suggested to promote metastasis of certain types of tumors, although direct evidence is lacking. To explore this hypothesis two sets of transgenic mice were developed, one TgNES, which constitutively expresses cell surface E-selectin in all tissues, the other TgNEsol, which expresses truncated, soluble E-selectin in the liver. Both transgenic mice showed apparently normal phenotype. However in TgNES mice, but not in TgNEsol mice, the number of neutrophil decreased to 50% compared with that in their negative littermate. And also these neutrophils were markedly activated. On the other hand, B16 F10 melanoma cells were stably transfected with alpha 1-3/4 fucosyltransferase-specific cDNA (B16F10 ft), allowing them to express E-selectin ligands. Normal mice injected with B16F10 ft developed lung tumors exclusively. In contrast, TgNES mice developed massive, infiltrating liver tumors. TgNEsol mice also developed liver tumors that grow more slowly. These observations suggest the important role of E-selectin for neutrophil activation and tumor metastasis in vivo.

Actins↗
PubMed1996

In vivo modulation of CD26 (dipeptidyl peptidase IV) in the mouse: effects of polyreactive and monoreactive antibodies.

We previously reported that intravenous injections in rabbits or guinea pigs of divalent antibodies to purified protein or carbohydrate antigens located mainly on endothelial cells induce acute pulmonary edema, which is often lethal. Surviving animals develop resistance to the injurious effect of subsequent injection of antibodies (adaptation), associated with shedding of antigen-antibody complexes from endothelial cells. In the present study, we investigated and compared in mice the effects of 3-day multiple injections of two different rabbit antibody (IgG) preparations against antigens expressed mainly at the surface of epithelial cells. The first preparation contained antibodies to a single transmembrane protein, CD26 (dipeptidyl peptidase IV [DPP IV]) (monoreactive anti-DPP IV IgG); the second contained antibodies against multiple antigens of the renal tubular brush border (BB), including DPP IV (polyreactive anti-BB IgG). Both IgG preparations caused loss of DPP IV from the organs studied, as shown by reduction in enzyme activity in tissue homogenates and by immunofluorescence microscopy, which showed loss of DPP IV from cell surface. However, the monoreactive anti-DPP IV IgG induced considerably greater reduction than polyreactive anti-BB IgG. Loss of DPP IV from the cell surface probably occurred by shedding of immune complexes into vascular and extravascular fluids, including bile and urine. The results may have relevance to hyperacute rejection of xenografts, as from pigs to primates. Since human natural antibodies that bind to porcine cells are polyreactive, a new prophylactic strategy for hyperacute rejection might be based on down-regulation of the major xenogeneic antigen, alpha-galactosyl, by injecting donor animals with monoreactive alpha-galactosyl antibodies before transplantation.

Amino Acid Sequence↗
PubMed1996

Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes.

CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, for receptorglobulin) we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induce transient expression of CD5L on B lymphocytes that lasts for approximately 72 h. Binding of CD5Rg to activated splenocytes is trypsin resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF on N-glycanase completely abrogates its ability to bind activated splenocytes. It addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of immune responses.

Animals↗
PubMed1996

Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease.

We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28-B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40-L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2-associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium.

Animals↗