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Biomedical subjects

F Pallone

Publications and source records attributed to F Pallone.

At least 91 records · Page 5Linked to original sources
PubMed1995

Salivary-specific immunoglobulin G in the diagnosis of Helicobacter pylori infection in dyspeptic patients.

OBJECTIVES: Helicobacter pylori infection is arguably the most common chronic bacterial infection in humans. The high prevalence and the association with peptic ulceration and gastric cancer indicate that simple, noninvasive methods for diagnosis of the infection are needed. In this study, the accuracy of salivary diagnosis for H. pylori infection was assessed. METHODS: Saliva and serum samples of 152 dyspeptic patients were tested for H. pylori IgG and IgA by an in-house ELISA. All patients underwent gastroscopy with biopsy. RESULTS: One hundred thirty-one patients (86%) were found to be H. pylori positive on histology. Duodenal ulcer was found in 67 patients; 85 had no macroscopic lesion. Salivary and serum H. pylori IgG as well as serum H. pylori IgA titers were significantly higher in H. pylori-positive than in H. pylori-negative patients. The sensitivity and specificity of salivary H. pylori IgG were 82% and 71%, respectively; the positive and negative predictive values were 95% and 40%, respectively; and the accuracy 81%. The corresponding figures for serum H. pylori IgG were 97% and 91%; 98% and 83%; and 96%. Those for serum H. pylori IgA were 80% and 52%; 91% and 30%; and 76%. The sensitivity of salivary H. pylori IgG in detecting duodenal ulcer was 83% (56/67) that of serum H. pylori IgG was 97% (65/67) (odds ratio = 0.15; confidence interval = 0.02-0.8; p = 0.02). CONCLUSIONS: Salivary H. pylori IgG was a fairly sensitive and accurate indicator of gastric H. pylori colonization, with a high positive predictive value in our population. Data, however, suggest that salivary H. pylori IgG measurements do not compare favorably with serology.

Adult↗
PubMed1994

Vasoactive intestinal polypeptide modulates the in vitro immunoglobulin A production by intestinal lamina propria lymphocytes.

BACKGROUND/AIMS: Vasoactive intestinal polypeptide (VIP) modulates the immunoglobulin (Ig) synthesis in the peripheral blood of humans and in various lymphoid organs of other species. Because VIP receptors have been shown on lamina propria mononuclear cells (LPMC), the effects of graded doses of VIP on the in vitro Ig production by normal human LPMC was investigated. METHODS: Colonic LPMC were cultured with or without graded doses of VIP (1 pmol/L-1 mumol/L). The concentrations of Ig A, G, and M in the 12 days supernatants were quantitated by an enzyme-linked immunosorbent assay, and the effects of VIP were characterized by limiting dilution analysis (LDA). RESULTS: The addition of VIP was associated with a significant increase in the production of IgA, whereas IgG levels were significantly reduced. Both these effects were restricted to LPMC. LDA showed that the IgA-enhancing effect was associated with an increase in the number of IgA-producing precursor cells and with variation in the regulatory phenomena involved in IgA production. CONCLUSIONS: In humans, a major function of the mucosal immune system (i.e., the synthesis of IgA) is modulated by VIP. Data suggest that VIP may either act as an indirect switch factor or increase the clone size of pre-committed cells.

Cells, Cultured↗
PubMed1994

Interferon expression in Crohn's disease patients: increased interferon-gamma and -alpha mRNA in the intestinal lamina propria mononuclear cells.

The in vivo interferon (IFN) activation in Crohn's disease was evaluated by measuring the relative amounts of IFN-alpha and -gamma mRNA in freshly isolated human lamina propria mononuclear cells (LPMC) from patients with Crohn's disease and controls. Both IFN-gamma and IFN-alpha mRNA, as estimated by dot blot analysis, were increased in Crohn's disease (LPMC), although the relative amounts of IFN mRNA appeared to differ among patients. Appreciable amounts of IFN-gamma mRNA were found in Crohn's disease peripheral blood mononuclear cells (PBMC) extracts, whereas the same cells were negative for IFN-alpha mRNA. Only minute amounts of IFN-gamma RNA were found sporadically in control LPMC while no IFN-alpha was detected. Control PBMC were shown to be virtually negative for both IFN-alpha and IFN-gamma mRNA. These data suggest that IFN induction in the normal human gut is a well-controlled function and that in Crohn's disease tissues, both IFN-gamma and IFN-alpha production are dysregulated. The increased IFN activity may represent a major feature in the induction and perpetuation of the chronic inflammatory process in Crohn's disease.

Crohn Disease↗
PubMed1994

Oral mesalazine (5-aminosalicylic acid; Asacol) for the prevention of post-operative recurrence of Crohn's disease. Gruppo Italiano per lo Studio del Colon e del Retto (GISC).

METHODS: A multicentre randomized controlled trial was conducted to evaluate the efficacy of oral mesalazine (5-aminosalicylic acid) for the prevention of post-operative recurrence in 110 patients operated on for Crohn's disease by first intestinal resection. Patients were randomly allocated to receive 2.4 g/day of mesalazine, or no treatment at all. The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter. Recurrence was defined on the basis of endoscopic criteria and classified as mild or severe. RESULTS: The demographic and pre-trial characteristics were very similar in the two groups of patients. The cumulative proportion of recurrence at 6, 12 and 24 months was significantly lower in the mesalazine group than in untreated group (P = 0.002). At 24 months the cumulative proportions of endoscopic recurrence were 0.52 +/- 0.12 (+/- S.E.M.) and 0.85 (+/- 0.07), respectively. At the same time the cumulative proportions of symptomatic recurrence were 0.18 +/- 0.09 and 0.41 +/- 0.09 (P = 0.006). The cumulative proportions of the severe recurrence was also significantly lower in the mesalazine group (0.17 +/- 0.09 vs. 0.38 +/- 0.09; P = 0.021). CONCLUSIONS: The preliminary results of this study show that administration of oral mesalazine soon after surgery is effective in preventing post-operative endoscopic recurrence in Crohn's disease over a 2-year period. It is estimated that this treatment prevents 39% of all recurrences and 55% of the severe recurrences.

Administration, Oral↗
PubMed1994

Multinucleated giant cells generation induced by interferon-gamma. Changes in the expression and distribution of the intercellular adhesion molecule-1 during macrophages fusion and multinucleated giant cell formation.

BACKGROUND: Multinucleated giant cells (MGC), interferon-gamma (IFN-gamma) production, and increased expression of adhesion molecules are features of granulomatous reactions. IFN-gamma induces the fusion of macrophages and the subsequent MGC generation in vitro. Moreover, IFN-gamma increases ICAM-1 expression on lymphoid cells and an important role for adhesion molecules in MGC generation has been proposed. EXPERIMENTAL DESIGN: The time course of the IFN-gamma-driven MGC generation was investigated in slide-chamber cultures of adherence-purified human monocytes. The fusion index, the monocytes clustering the total number of MGC were determined. The expression of intercellular cell adhesion molecule-1 (ICAM-1), LFA-1 and HLA-DR was investigated by immunohistochemistry. The effect of anti-ICAM-1, anti-LFA-1 and anti-HLA-DR monoclonal antibodies on IFN-gamma-induced MGC generation was also examined. RESULTS: IFN-gamma enhanced the generation of MGC in a dose- and time-dependent fashion. In all experiments, MGC formation was preceded by a sequence of changes in the morphology of cultured monocytes. Cell clustering occurred as early as 3 days after IFN-gamma stimulation and was followed by the adhesion of cells that eventually fused. Immunohistochemistry showed that ICAM-1 was increased by IFN-gamma and constantly polarized on a cell uropode. When monocytes clustered, ICAM-1 was localized on the membrane where the cell-to-cell contact occurred. In newly formed MGC, ICAM-1 stained in the center of the giant cell. The cellular distribution of LFA-1 on cultured monocytes was not modified by IFN-gamma. HLA-DR expectedly enhanced by IFN-gamma was mostly cytoplasmic and tended to disappear when MGC formed. Finally, anti-LFA-1 and anti-ICAM-1 monoclonal antibodies variably inhibited IFN-gamma-induced MGC generation. CONCLUSIONS: Taken together, these data add support to the concept that IFN-gamma is essential for MGC generation by promoting cell clustering and cell-to-cell adhesion. The present data also indicate that among the mechanisms by which IFN-gamma exert such a promoting effect, changes in the ICAM-1 expression and cellular distribution are included. The observation that ICAM-1 appears to be trapped in the cytoplasm of IFN-gamma-driven MGC and that HLA-DR tend to disappear from macrophages undergoing MGC formation, also suggest changes in the functional properties of these cells.

Cell Fusion↗
PubMed1994

Circulating D dimer in inflammatory bowel disease.

An activated thrombogenesis has been reported in inflammatory bowel disease (IBD). In this study we evaluated whether a fibrin degradation product, the D dimer, is increased in patients with IBD. D dimer plasma levels were evaluated by sandwich ELISA in patients with Crohn's disease (24), ulcerative colitis (25), gastrointestinal (GI) disease controls (10), hospital controls (13) and healthy subjects (14). Circulating D dimer was significantly higher in ulcerative colitis (median 651; 95% CI 89-1275 ng/ml) than in healthy subjects (median 412; 95% CI 112-672 ng/ml; p = 0.002), Crohn's disease (median 466; 95% CI 6-931 ng/ml; p = 0.005) and GI disease controls (median 446; 95% CI 196-688 ng/ml; p = 0.023). In ulcerative colitis, plasma D dimer was related to inflammatory parameters such as C-reactive protein (p < 0.01) and seromucoids (p < 0.001). Circulating D dimer was age-related in all groups (p < 0.05). Fibrin degradation, as reflected by plasma D dimer, is detected in patients with ulcerative colitis exhibiting a marked acute phase response.

Adult↗
PubMed1993

Continuous in vivo activation and transient hyporesponsiveness to TcR/CD3 triggering of human gut lamina propria lymphocytes.

Three-color immunofluorescence and flow cytometric analysis showed that the vast majority of normal human T-lamina propria lymphocytes (LPL) expressed high levels of the early activation antigen CD69, together with CD45R0, irrespective of their CD4, CD8 or gamma/delta-TcR phenotype, indicating that they are continuously stimulated in vivo. Importantly, measurement of cytoplasmic [Ca2+]i showed that T-LPL had significantly higher basal [Ca2+]i levels, compared to autologous peripheral blood lymphocytes (PBL). Both cytoplasmic [Ca2+]i elevation and inositol (1,4,5) trisphosphate generation following CD3 cross-linking by monoclonal antibodies in vitro were essentially abolished in T-LPL, as compared to autologous T-PBL. Moreover, freshly isolated LPL could be induced to proliferate by CD2- or CD28-mediated signals, but not by CD3-mediated signals. Surprisingly however, impairment in TcR/CD3-mediated early signaling and proliferation in T-LPL could be completely reversed by 24 h incubation of the cells at 37 degrees C in culture medium, a condition which allowed basal intracellular [Ca2+]i to return to levels comparable to peripheral T cells. Our data suggest that selective hyporesponsiveness to TcR/CD3-mediated signaling may represent a transient event during continuous in vivo activation of mucosal lymphocytes.

Calcium↗
PubMed1993

Lansoprazole and Helicobacter pylori infection.

Helicobacter pylori-associated gastritis is present in virtually all patients with duodenal ulcer (DU). Eradication of H pylori is associated with a highly significant decline in the recurrence rates of DU, indicating that treatments aimed at eradicating H pylori are mandatory in these patients. The novel proton pump inhibitor lansoprazole exhibits a potent antiulcer effect and, in vitro, a direct antibacterial effect against H pylori. Conflicting data have been reported on the question of whether lansoprazole is bactericidal against H pylori in vivo when administered alone. The aim of this double-blind trial was to address this issue further by comparing the effects of two different 4-week regimens (lansoprazole alone or in combination with amoxicillin) on H pylori infection in patients with DU. Patients were assessed before and after the 4-week treatment and 3 months after stopping the study medication. The ulcer healing rates at 4 weeks were similar for the two treatments while there was a trend for higher recurrence rates at 4 months in patients receiving lansoprazole alone. The frequency of high-grade H pylori infection was significantly lower in the lansoprazole and amoxicillin group both at 4 weeks (84% clearing) and 4 months. After 4 weeks of treatment there were no patients with residual H pylori-positive active antral gastritis in the lansoprazole and amoxicillin group compared with 25% in the lansoprazole alone group. Neither treatment significantly affected the IgG antibody response to H pylori either at the circulatory or the mucosal level. In contrast, the mucosal H pylori-specific IgA response was significantly enhanced after 4 weeks and more markedly after treatment with lansoprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Serum angiotensin converting enzyme activity in Crohn's disease and ulcerative colitis.

The relationship between serum angiotensin-converting enzyme activity (SACE) and inflammatory bowel disease was investigated in 30 patients with active Crohn's disease (CD) (CDAI > 150), 12 patients were not taking active medication, while 11 were on prednisone and 7 on mesalazine (5-ASA). Of 12 patients with active ulcerative colitis (UC), 4 patients were without treatment, 4 were on prednisone and 4 on mesalazine. Twelve patients with acute pulmonary sarcoidosis and 25 healthy subjects were studied. SACE levels in CD were not significantly different compared to healthy subjects and did not appear to be affected by the anti-inflammatory therapy. The average levels of SACE in UC were significantly higher than those of healthy subjects and CD (p < 0.005). Among the UC patients there was a trend for lower levels in the group treated with prednisone. In patients with active sarcoidosis SACE levels were extremely elevated and were significantly higher than in all other groups examined (p < 0.0001). The granulomatous inflammation in Crohn's disease differs from that of sarcoidosis, in which there is a striking elevation of angiotensin converting enzyme in serum. In other words, SACE levels seem to differentiate patients with active CD from patients with UC.

Adult↗
PubMed1992

Modulation of human natural killer activity by vasoactive intestinal peptide (VIP) family. VIP, glucagon and GHRF specifically inhibit NK activity.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide, which also modulates some immune functions. Natural killer (NK) cell activity was already found to be diminished by VIP. In the present paper we report that VIP is able to decrease NK cell activity of human large granular lymphocytes (LGL), showing maximal inhibition at doses ranging from 10(-8) to 10(-6) M. Some neuropeptides, belonging to the VIP family (secretin, glucagon, peptide histidine isoleucine, PHI and human growth hormone releasing factor, GHRF), were also tested. Among these peptides, secretin and PHI were shown to be uneffective on NK cell activity whereas glucagon and GHRF were inhibitory. The D50 of GHRF was similar to that of VIP (10(-9) M), the D50 of glucagon was 10(-8) M. A recently synthesized VIP-antagonist (4Cl-D-Phe6-Leu17) was then used to assess its ability to reverse the VIP-mediated inhibition of NK activity. The antagonist was able to completely reverse the inhibitory effect of VIP on NK activity. The VIP-antagonist was also able to reverse the inhibitory effect of glucagon and GHRF, even though to a lesser extent than for VIP. Our data provide a new physiological observation regarding the functional activity of LGL, supporting the presence of a receptor for VIP on human LGL with NK activity.

Cell Line↗
PubMed1992

Analysis of clinical course of postoperative recurrence in Crohn's disease of distal ileum.

In the present study we have investigated whether in patients with Crohn's Disease the clinical course remains the same from the initial disease to postoperative recurrent disease. Fifty-eight resected patients who developed a postoperative recurrence were followed for 4.2 +/- 3 years (median 3 years). The yearly frequency of flare-up was 1.9 +/- 1.0 (median 1.5) in the initial disease and 1.7 +/- 1.0 (median 1.7) in recurrent disease. In patients who experienced complications during the initial disease, the frequency of complications during the course of recurrent disease was significantly higher than in the others (27/42 vs 3/16, P = 0.002). The frequency of obstruction and extraintestinal manifestations in the recurrent disease was higher in patients who suffered these complications in the initial disease than in those who did not (19/29 vs 6/29, P = 0.0006, and 4/5 vs 4/53, P = 0.0008). The cumulative probability of complication during the course of recurrent disease was higher in patients with complications during the initial disease (P less than 0.001). The survival analysis showed that the cumulative probability of obstruction and extraintestinal complication in recurrent disease was higher in patients who suffered these complications in the initial disease (P less than 0.005). These data indicate that the clinical course of Crohn's disease of the distal ileum remains the same from the initial disease to postoperative recurrent disease. This study also suggests that the short-term course of recurrent disease can reasonably be predicted.

Adult↗
PubMed1992

Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn's disease.

A randomized, placebo-controlled multicenter trial was conducted to evaluate the efficacy and safety of a delayed-release formulation of 5-aminosalicylic acid (5-ASA) (Asacol; Giuliani & Bracco, Milan, Italy) for prevention of clinical relapse in 125 patients with inactive Crohn's disease. Patients in remission [Crohn's Disease Activity Index (CDAI) less than 150] between 3 months and 2 years were randomly allocated to receive either 800 mg 5-ASA three times daily (n = 64) or placebo (n = 61) for up to 12 months or until relapse of symptoms. Relapse was defined by a CDAI greater than 150, with a minimum increase of 100 points over the baseline value. The cumulative relapse rates were 12% in the 5-ASA group and 22% in the placebo group at 3 months [95% confidence interval (CI) for the difference, -4 to 24]; 28% and 41%, respectively, at 6 months (95% CI, -4 to 30); and 34% and 55%, respectively, at 12 months (95% CI, 3-39; P = 0.02, log rank test). Significant decrease in the risk of relapse was found in patients with ileitis, in those with previous bowel resection and, in those with prolonged prestudy remission. Eight patients (5 on 5-ASA, 3 on placebo) withdrew from the study because of adverse reactions, but no major clinical or laboratory adverse effect was observed. It is concluded that oral 5-ASA coated with Eudragit S (Rohn Pharma GmbH, Wieterstadt, Germany), 2.4 g daily, is safe and seems superior to placebo in preventing or delaying clinical relapse in Crohn's disease, especially in milder cases and in ileal disease.

Adolescent↗
PubMed1992

Absence of circulating interferon in patients with inflammatory bowel disease. Suggestion against an autoimmune etiology.

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.

Autoantibodies↗
PubMed1992

Gliadin induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with coeliac disease mucosa.

Jejunal biopsies from 16 treated coeliac disease patients and from nine controls were cultured with and without a peptic-tryptic digest of gliadin. Cultures with a peptic-tryptic digest of maize prolamins were also undertaken. Frozen sections of baseline and cultured mucosa were stained by immunofluorescence with an anti-HLA-DR monoclonal antibody. Before culture the villous epithelium from both controls and treated coeliac disease expressed DR molecules while the crypt epithelium did not. When biopsies from treated coeliac disease were cultured with gliadin the expression of DR was enhanced in the crypt epithelium in eight of 14 cultures and in 11 of 14 was reduced or absent on the villous epithelium. No change was observed in control cultures. We conclude that gliadin is capable of inducing HLA-DR on the crypt epithelium of in vitro cultured coeliac disease mucosa, providing indirect evidence that gliadin may activate cell mediated immune mechanisms within the small bowel mucosa. This model could prove useful in identifying the immunogenic sequence(s) of gliadins and related prolamins.

Celiac Disease↗
PubMed1992

Interferon-alpha (IFN-alpha) production by human intestinal mononuclear cells. Response to virus in control subjects and in Crohn's disease.

The virus induced production of interferon alpha by human intestinal lamina propria mononuclear cells was investigated. Intestinal and autologous peripheral cells from control subjects and patients with Crohn's disease were cultured in vitro with and without stimulation with the Newcastle disease virus. Interferon alpha was measured and characterised in the culture supernatants after 12 hours and the kinetics of production was evaluated over the following four days of culture. No detectable interferon alpha was found in cultures of unstimulated intestinal and autologous peripheral mononuclear cells from controls and Crohn's disease whereas interferon alpha was released in all cultures stimulated with the virus. In all 12 hours experiments in both groups, virus stimulated intestinal mononuclear cells yielded significantly less interferon alpha than the autologous peripheral cells. The kinetics experiments showed that control intestinal mononuclear cells appeared to be poorly responsive to virus stimulation showing a release of interferon alpha significantly lower than that of the autologous peripheral cells. The interferon alpha release at day 4 by control cells (either intestinal or peripheral) did not differ from that measured after the first 12 hours. In contrast, the interferon alpha produced by Crohn's disease cells progressively increased during the culture period and the amount of interferon alpha measured at day 4 was significantly higher than that released at 12 hours. These data suggest that normal human intestinal mononuclear cells are down regulated in their capability of producing interferon alpha and that in Crohn's disease their activation for this function is enhanced. These data also suggest that in Crohn's disease intestinal mononuclear cells exhibit a transient hyporesponsiveness to in vitro stimulation possibly related to massive in vivo exposure to interferon alpha inducers.

Cells, Cultured↗
PubMed1991

Usefulness of fecal alpha 1-antitrypsin clearance and fecal concentration as early indicator of postoperative asymptomatic recurrence in Crohn's disease.

The aim of this study was to evaluate in Crohn's disease the possible usefulness of alpha 1-antitrypsin clearance and fecal concentration in the early detection of postoperative asymptomatic recurrence. Eleven adult patients with small bowel Crohn's disease undergoing elective resection were enrolled in the study and prospectively followed for one year. Three, six, and 12 months after surgery the alpha 1-antitrypsin clearance and fecal concentration were measured, and the disease activity was assessed. All patients were free of active symptoms throughout the study. One year after surgery small bowel radiology was performed in all patients. Radiographic evidence of recurrent macroscopic disease was found in five of the 11 patients. Three months after surgery both alpha 1-antitrypsin clearance and fecal concentration were significantly lower (P less than 0.01) than before surgery. There was no difference at this time between patients with recurrence and those with no recurrence. In patients with recurrence both alpha 1-antitrypsin clearance and fecal concentration significantly increased at six months in comparison with the values at three months (P less than 0.02). Both measurements were significantly higher at six and 12 months in this group of patients than in those with no recurrence and in normal controls (P less than 0.01). At six and 12 months alpha 1-antitrypsin clearance was above the upper normal limit in all patients with recurrence. We conclude that fecal alpha 1-antitrypsin clearance is a noninvasive, inexpensive, sensitive marker of asymptomatic recurrence in CD patients who are under regular supervision after surgery.

Adult↗