F Navaglia

Publications (36)90.38 Total impact

• Article: Antigastric autoantibodies inHelicobacter pylori infection: role in gastric mucosal inflammation

  D. Basso, N. Gallo, C. -F. Zambon, M. Baron, F. Navaglia, E. Stockreiter, F. Di Mario, M. Rugge, M. Plebani
  [show abstract] [hide abstract]
  ABSTRACT: The aim of the study was to ascertain whether there is an association between the presence of serum parietal cell autoantibodies The aim of the study was to ascertain whether there is an association between the presence of serum parietal cell autoantibodies (PCA) and: (1)Helicobacter pylori infection; (2) de presence and degree of gastritis and intestinal metaplasia; and (3) theH. pylori infecting strain. Gastric mucosal biopsies were obtained from 49 consecutive patients in order to assess and grade gastritis, (PCA) and: (1)Helicobacter pylori infection; (2) de presence and degree of gastritis and intestinal metaplasia; and (3) theH. pylori infecting strain. Gastric mucosal biopsies were obtained from 49 consecutive patients in order to assess and grade gastritis, make a histological diagnosis, and culture and genotypeH. pylori. H. pylori infection was present in 26 patients (group 1), had been present in 17 patients (group 2), and the remaining 6 (group 3) make a histological diagnosis, and culture and genotypeH. pylori. H. pylori infection was present in 26 patients (group 1), had been present in 17 patients (group 2), and the remaining 6 (group 3) had never had the infection. The infecting strain wascagA positive in 21 of 26 group 1 patients. Positive PCA results were found in 84%, 76%, and 14% of patients in groups 1, 2, and had never had the infection. The infecting strain wascagA positive in 21 of 26 group 1 patients. Positive PCA results were found in 84%, 76%, and 14% of patients in groups 1, 2, and 3, respectively. PCA results were correlated with anti-H. pylori antibody titers (P<0.05). In group 2 patients, PCA were associated with the degree of antral gastritis (Fisher’s exact testP<0.05).cagA status was not associated with the presence of PCA (X2=0.68, NS). The frequency of positive findings for PCA in group 2 was higher in patients with (90%) than in those without 3, respectively. PCA results were correlated with anti-H. pylori antibody titers (P<0.05). In group 2 patients, PCA were associated with the degree of antral gastritis (Fisher’s exact testP<0.05).cagA status was not associated with the presence of PCA (X2=0.68, NS). The frequency of positive findings for PCA in group 2 was higher in patients with (90%) than in those without (50%) intestinal metaplasia. In conclusion: (1)H. pylori infection is associated with the production of PCA, which, after eradication of the infection, persist and might contribute (50%) intestinal metaplasia. In conclusion: (1)H. pylori infection is associated with the production of PCA, which, after eradication of the infection, persist and might contribute to the persistent antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions associated with infections sustained to the persistent antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions associated with infections sustained by the morevirulentH. pylori strains do not appear to be due to the induction of antigastric autoantibodies. by the morevirulentH. pylori strains do not appear to be due to the induction of antigastric autoantibodies.
  International Journal of Clinical & Laboratory Research 04/2012; 30(4):173-178.
• Article: Heat-induced transcription of diphtheria toxin A or its variants, CRM176 and CRM197: implications for pancreatic cancer gene therapy.

  P Fogar, F Navaglia, D Basso, C-F Zambon, L Moserle, S Indraccolo, A Stranges, E Greco, E Fadi, A Padoan, G Pantano, M C Sanzari, S Pedrazzoli, C Montecucco, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: Vectors combining the heat shock proteins (HSPs) promoter with the catalytic subunit A of the diphtheria toxin (DTA) or its variants, cross-reacting material (CRM) 176 and 197, were engineered to investigate the effect of bacterial toxins on pancreatic cancer (PC) cells. Three heat-inducible enhanced green fluorescent protein (eGFP)-expression vectors were obtained: V1 (91% homology to HSPA6), V2 (five heat shock elements upstream the minimal HSPA6 promoter) and V3 (V1 and V2 combined). The highest eGFP transcription and translation levels were found in V3 transfected PC cells. The V3 promoter was used to control DTA, CRM176 and CRM197 expression, treatment response being investigated in four PC cell lines. DTAwt or CRM176 transfected cell growth was completely arrested after heat shock. CRM197 toxin presumed to be inactive, caused mild distress at 37 degrees C and induced a 25-50% reduction in cell growth after heat shock. Preliminary in vivo findings showed that heat treatment arrests tumor growth in DTA197 stably transfected PSN1 cells. In conclusion, the efficient HSP promoter identified in this study may be extremely useful in controlling the transcription of toxins such as CRM197, which have lethal dose-related effects, and may thus be a promising tool in PC gene therapy in vivo.
  Cancer gene therapy 08/2009; 17(1):58-68. · 3.13 Impact Factor
• Article: An open population screening study for HFE gene major mutations proves the low prevalence of C282Y mutation in Central Italy.

  A Floreani, E Rosa Rizzotto, D Basso, F Navaglia, M Zaninotto, I Petridis, O DI Andrea, R Testa, M Marra, V Baldo, M Chiaramonte
  [show abstract] [hide abstract]
  ABSTRACT: The C282Y mutation in the HFE gene is responsible for most cases of hereditary haemochromatosis. To investigate the allele frequency of HFE mutations and the associations between mutations and cases of iron overload or liver diseases in an open population of Central Italy. A total of 502 individuals over 8 years of age, comprising 203 males and 299 females, who were residents in Arsita (a small town in Central Italy), were assayed for: C282Y, H63D and S65C mutations of the HFE gene by TaqMan probes; body mass index, serum ferritin, transferrin saturation, transaminases, GGT, glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, HBV and HCV serum markers. Information was obtained on alcohol intake. Liver ultrasound was performed in 334 (67%) subjects. The allele frequencies for C282Y, H63D and S65C were 2%, 15%, and 0.01%, respectively. C282Y/wt was found in 19 subjects (4%), H63D/wt in 127 (25%), H63D/H63D in 11 (2%) and S65C/wt in one (2.0 per thousand). No homozygosity for C282Y or compound mutation (C282Y/H63D) was found in the study population, but 27 subjects (5%) had TfSat >45% (including 10 subjects with high serum ferritin). Overall, 49 subjects (9.8%) were HCV-RNA-positive. Logistic regression analysis indicated that male gender (P = 0.000) and hepatic steatosis (P = 0.017) were independent variables correlating to a high serum ferritin. C282Y HFE mutation is less frequent in Central Italy than in Northern Italy.
  Alimentary Pharmacology & Therapeutics 08/2007; 26(4):577-86. · 3.77 Impact Factor
• Article: Insights in the laboratory diagnosis of celiac disease.

  D Basso, G Guariso, P Fogar, F Navaglia, C-F Zambon, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: The present report focuses on the diagnosis of celiac disease and its pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8 haplotypes), gluten ingestion and T cell activation, type II transglutaminase (TG2), the autoantigen recognized by the antiendomysial antibody playing a key role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2) antigens are present in the sera of patients with celiac disease. The anti-TG2 antibody has the best available diagnostic accuracy, especially when measured employing second generation ELISA tests, which use the human TG2 antigen, or immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac disease must always be confirmed by the histological evaluation of multiple duodenal mucosa specimens, and serology is recommended for follow-up controls.
  Lupus 02/2006; 15(7):462-5. · 2.34 Impact Factor
• Article: Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals.

  F Navaglia, D Basso, C-F Zambon, E Ponzano, L Caenazzo, N Gallo, A Falda, C Belluco, P Fogar, E Greco, F Di Mario, M Rugge, M Plebani
  Journal of Medical Genetics 07/2005; 42(6):503-10. · 6.36 Impact Factor
• Article: Killer genes in pancreatic cancer therapy.

  P Fogar, E Greco, D Basso, F Navaglia, M Plebani, S Pedrazzoli
  [show abstract] [hide abstract]
  ABSTRACT: This review describes: 1. The main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. The use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. The implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. Viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.
  Cellular and molecular biology (Noisy-le-Grand, France) 02/2005; 51(1):61-76. · 1.46 Impact Factor
• Article: Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination.

  S Fracalanza, T Prayer-Galetti, F Pinto, F Navaglia, E Sacco, M Ciaccia, M Plebani, F Pagano, D Basso
  [show abstract] [hide abstract]
  ABSTRACT: We ascertained whether plasma chromogranin A enhances the power of serology assessing prostate cancer (PC). We studied 56 PC and 83 benign prostatic hyperplasia (BPH) patients. In the sera we measured total prostate-specific antigen (tPSA) and free PSA (fPSA) and calculated the ratio between fPSA and tPSA (f/tPSA). In plasma samples the levels of chromogranin A (CgA) were also assayed. PC patients had higher CgA (p < 0.005) and tPSA (p < 0.05) levels, and a lower f/tPSA ratio (p < 0.001), than BPH patients. When f/tPSA and CgA were combined, the diagnostic sensitivity was enhanced (57-73%), while the specificity had only an 8% reduction (from 89 to 80%). CgA was only correlated to the Gleason PC score (p < 0.05). CgA determination in PC may enhance the diagnostic accuracy of the f/tPSA assay and provides useful information on the tumor grade.
  Urologia Internationalis 01/2005; 75(1):57-61. · 0.99 Impact Factor
• Article: Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes.

  D Basso, C Millino, E Greco, C Romualdi, P Fogar, A Valerio, M Bellin, C-F Zambon, F Navaglia, N Dussini, A Avogaro, S Pedrazzoli, G Lanfranchi, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.
  Gut 09/2004; 53(8):1159-66. · 10.11 Impact Factor
• Article: Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model.

  P Fogar, E Greco, D Basso, W Habeler, F Navaglia, C-F Zambon, D Tormen, N Gallo, A Cecchetto, M Plebani, S Pedrazzoli
  [show abstract] [hide abstract]
  ABSTRACT: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.
  European Journal of Surgical Oncology 12/2003; 29(9):721-30. · 2.50 Impact Factor
• Article: Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia.

  C-F Zambon, F Navaglia, D Basso, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: To determine any associations between the Helicobacter pylori genes babA2, oipA, cagA and the s and m alleles of vacA. In addition, to verify whether these genes work synergistically or independently in causing gastritis, peptic ulcer, and intestinal metaplasia. One hundred and sixty seven H pylori positive patients were studied (52 antral gastritis, 41 diffuse gastritis, 41 peptic ulcer, and 33 duodenitis). Helicobacter pylori virulence genes were amplified by means of the polymerase chain reaction. Significant associations were found between babA2 and the other H pylori genes studied. When considered singly, all the genes were associated with disease diagnosis, inflammation, and intestinal metaplasia. Four H pylori groups were defined. Group A: cagA-, s2m2, babA2-; group B: cagA+, s1m1, babA2+; group C: cagA+, s1m2, babA2+; group D: cagA+, s1m2, babA2-. Group A infecting strains were associated with less severe endoscopic and inflammatory conditions, whereas group B strains were associated with the worst endoscopic and inflammatory findings. Intestinal metaplasia was a rare finding in group A infected patients (< 10%), whereas it was frequent in those infected with group B strains (48%). The H pylori genes cagA, oipA "on", s1 and m1 vacA, and babA2 are associated with each other, possibly as a result of shared selective pressure. When coexpressed by the same H pylori strain, cagA, s1 and m1 vacA, and babA2 work synergistically in worsening inflammation. Infections caused by strains coexpressing cagA, s1m1 vacA, and babA2 are those at higher risk for intestinal metaplasia.
  Journal of Clinical Pathology 04/2003; 56(4):287-91. · 2.31 Impact Factor
• Article: Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia.

  C-F Zambon, D Basso, F Navaglia, G Germano, N Gallo, M Milazzo, E Greco, P Fogar, S Mazza, F Di Mario, G Basso, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.
  Cytokine 07/2002; 18(5):242-51. · 3.02 Impact Factor
• Article: [Diagnosis of Helicobacter pylori infection: comparison of techniques].

  N Gallo, D Basso, C F Zambon, F Navaglia, F Di Mario, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: Several diagnostic assays are available for evaluating Helicobacter pylori infection: histological examination, culture of gastric biopsies, urea breath test and serology. Recently a new enzyme immunoassay has been introduced for the detection of H. pylori antigens in stool samples (HpSA). The aim of our study was to evaluate and compare diagnostic efficacy of HpSA with histological examination, culture, urea breath test and serology in a group of 95 patients. Patients were classified H. pylori positive (43) or negative (52) on the basis of histology, culture and urea breath test. HpSA optical densities were significantly higher in infected patients compared to those obtained in H. pylori-negative patients (t = 5.47, p < 0.001). Overall, with a fixed cut-off of 0.1 unit of optical density, the sensitivity was 79% and the specificity 100%. In the H. pylori positive patients, HpSA optical density correlated with bacterial load histologically evaluated in the gastric antrum (r = 0.405, p < 0.05) and was inverse correlated with levels of serum IgG elicited against H. pylori (r = -0.315, p < 0.05). Considering patients with a positive HpSA finding and/or levels of anti-H. pylori antibodies upper than 30 U/mL, sensitivity in detecting infected patients was 98%. In conclusion: (1) immunodetection of H. pylori antigens in stools is a good alternative of breath test; (2) a reduction in H. pylori density grade might be accompanied by low HpSA optical density, leading to a false negative result and (3) combining the HpSA determination with the serum detection of anti-H. pylori antibodies a better clinical sensitivity is obtained.
  Recenti progressi in medicina 05/2001; 92(5):332-5.
• Article: Different effects of H. pylori water extracts on cytokines, pepsinogen C and gastrin mucosal release in patients with or without duodenal ulcer.

  D Basso, N Gallo, C F Zambon, F Navaglia, E Stockreiter, F Di Mario, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: In the present study we ascertained whether cagA positive and negative H. pylori strains release water soluble products that can influence the production of gastric mucosal cytokines and endocrine (gastrin) or exocrine (pepsinogen C) secretion in 23 H. pylori positive and 19 H. pylori negative patients. Antral biopsies were obtained to classify inflammation, activity, atrophy, intestinal metaplasia and H. pylori density grade. The cagA gene was identified by means of the polymerase chain reaction (PCR) in H. pylori positive colonies after culture of mucosal samples. Three antral biopsies from each patient were incubated with (1.) Water extracts from cagA positive, (2.) Water extracts from cagA negative strains or (3.) H2O (control) at 37 degrees C in a CO2 incubator for 24 hrs. Gastrin, pepsinogen C, IL-1 beta, IL-8, GMCSF, and TNF alpha were measured in the supernatants and mucosal homogenates. H. pylori infection was significantly associated with an increased antral inflammation and activity (chi 2 = 21.7, p < 0.001 and chi 2 = 42.0, p < 0.001), and increased mucosal levels of IL-1 beta, IL-8 and TNF alpha. Water extracts from cagA positive strains enhanced the release of PGC in mucosal biopsy supernatants (p < 0.05) when patients were considered overall and the release of TNF alpha (p < 0.05) when only patients with duodenal ulcer were considered. Water extracts from cagA negative strains stimulated gastrin secretion (p < 0.05). None of the remaining cytokines were influenced by H. pylori water extracts. In conclusion, pepsinogen C and TNF alpha can be induced by cagA positive water extracts and may contribute to damage the gastric and duodenal mucosa. Our findings indicate that in patients with H. pylori infection the increase of the mucosal levels of IL-1 beta and IL-8 does not depend on H. pylori water soluble products, but probably depends on the entire bacterium.
  Journal of medicine 01/2001; 32(1-2):97-112.
• Article: ME-PCR for the identification of mutated K-ras in serum and bile of pancreatic cancer patients: an unsatisfactory technique for clinical applications.

  C Zambon, F Navaglia, D Basso, N Gallo, E Greco, M G Piva, P Fogar, C Pasquali, S Pedrazzoli, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: Our aim was to assess the clinical reliability of mutated K-ras detection in serum or bile for the diagnosis of pancreatic cancer using ME-PCR. DNA was extracted from 1 ml serum obtained from 29 patients with pancreatic cancer and 12 control subjects. ME-PCR was optimized using a mixture of normal DNA added with different amounts of mutated DNA. The analysis of sera obtained from the 29 patients and of bile obtained from 11 pancreatic cancer patients demonstrated the presence of mutated K-ras in two (6.9%) and four cases (36%). By contrast K-ras was not amplifiable in any of the 12 serum samples obtained from healthy controls. In conclusion the DNA obtained from pancreatic cancer patients' sera is suitable for K-ras amplification and for the identification of codon 12 point mutations. However ME-PCR alone has an unsatisfactory sensitivity for the detection of pancreatic cancer using serum DNA as starting template.
  Clinica Chimica Acta 01/2001; 302(1-2):35-48. · 2.54 Impact Factor
• Article: CEA mRNA identification in peripheral blood is feasible for colorectal, but not for gastric or pancreatic cancer staging.

  M G Piva, F Navaglia, D Basso, P Fogar, G Roveroni, N Gallo, C F Zambon, S Pedrazzoli, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (chi(2) = 14.6, p<0.01), lymph node (chi(2) = 18.95, p<0.001) and distant metastasis (chi(2) = 11.3, p<0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.
  Oncology 12/2000; 59(4):323-8. · 2.27 Impact Factor
• Article: Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: which is clinically effective and when?

  D Basso, P Fogar, M G Piva, F Navaglia, S Mazza, T Prayer-Galetti, E Castellucci, F Pagano, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.
  Urology 06/2000; 55(5):710-5. · 2.43 Impact Factor
• Article: Antigastric autoantibodies in Helicobacter pylori infection: role in gastric mucosal inflammation.

  D Basso, N Gallo, C F Zambon, M Baron, F Navaglia, E Stockreiter, F Di Mario, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: The aim of the study was to ascertain whether there is an association between the presence of serum parietal cell autoantibodies (PCA) and: (1) Helicobacter pylori infection; (2) the presence and degree of gastritis and intestinal metaplasia; and (3) the H. pylori infecting strain. Gastric mucosal biopsies were obtained from 49 consecutive patients in order to assess and grade gastritis, make a histological diagnosis, and culture and genotype H. pylori. H. pylori infection was present in 26 patients (group 1), had been present in 17 patients (group 2), and the remaining 6 (group 3) had never had the infection. The infecting strain was cagA positive in 21 of 26 group 1 patients. Positive PCA results were found in 84%, 76%, and 14% of patients in groups 1, 2, and 3, respectively. PCA results were correlated with anti-H. pylori antibody titers (P<0.05). In group 2 patients, PCA were associated with the degree of antral gastritis (Fisher's exact test P<0.05). cagA status was not associated with the presence of PCA (chi2=0.68, NS). The frequency of positive findings for PCA in group 2 was higher in patients with (90%) than in those without (50%) intestinal metaplasia. In conclusion: (1) H. pylori infection is associated with the production of PCA, which, after eradication of the infection, persist and might contribute to the persistent antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions associated with infections sustained by the more-virulent H. pylori strains do not appear to be due to the induction of antigastric autoantibodies.
  International Journal of Clinical & Laboratory Research 01/2000; 30(4):173-8.
• Article: [Biochemical markers of gastric functioning].

  D Basso, A L Stefani, N Gallo, L Brigato, F Navaglia, P Fogar, M G Piva, E Greco, A Toma, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: The serum determination of pepsinogen A (PGA) and pepsinogen C (PGC) might indicate gastric mucosal inflammation and atrophy. Body gastric mucosa produces both PGA and PGC, while antral mucosa produces only PGC. Therefore, diseases involving mainly the antrum, such as H. pylori infection, are mainly indicated by the variations in serum PGC than in serum PGA. In agreement, when the antral mucosa is infected by the more virulent cagA positive H. pylori strains, which cause severe inflammation, serum PGC significantly increases. Another indirect indicator of gastric inflammation is polymorphonuclear (PMN) oxidative burst after the stimulation with water extracts from H. pylori culture: this parameter is significantly increased in infected if compared to non-infected subjects. The higher oxidative burst response of peripheral PMN in infected patients, possibly consequent to the release of specific cytokines able to prime PMN towards H. pylori products, is unable to eliminate the infection, but it might concur in damaging the gastric mucosa.
  Recenti progressi in medicina 07/1999; 90(6):342-6.
• Article: Polymorphonuclear oxidative burst after Helicobacter pylori water extract stimulation is not influenced by the cytotoxic genotype but indicates infection and gastritis grade.

  D Basso, A Stefani, N Gallo, L Brigato, F Navaglia, A Toma, F Zancanaro, F Di Mario, G De Franchis, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: H. pylori-associated gastric mucosal inflammation is characterized by the presence of polymorphonuclear (PMN) leukocyte infiltrate, which is more severe when the infecting strain is cagA positive. After appropriate stimuli, such as bacterial products, PMN release large amounts of oxygen derived free radicals and proteases, to kill the bacterium. H. pylori seems to be particularly resistant to the oxidative machinery of PMN, which can in turn damage the host gastric mucosa. We evaluated peripheral PMN oxidative burst response after stimulation with water extracts from cagA positive (WEcagA+) or negative (WEcagA-) H. pylori strains in infected (n=31) and non-infected patients (n=32) in comparison with healthy controls (n=16); the influence of gastric mucosal inflammatory infiltrate and activity grade on PMN oxidative burst were also assessed. PMN oxidative burst was measured by FACS analysis. H. pylori water extracts were obtained from bacterial culture. H. pylori genotype was determined by means of the polymerase chain reaction. The PMN oxidative burst in H. pylori infected patients was significantly higher than that in H. pylori negative or healthy controls, no differences being found when the results following WEcagA+ and WEcagA- stimulation were compared. The difference in PMN oxidative burst obtained after WEcagA- and E. coli (standard stimulus for PMN oxidative burst) stimulation discriminated H. pylori infected from non-infected patients with a sensitivity of 90% and a specificity of 97%. The grade of PMN oxidative burst correlated with PMN infiltration grade of the gastric mucosa. Our findings allow to conclude that PMN oxidative burst activation by H. pyloriWE is species- but not strain-correlated. PMN priming, probably consequent to the action of soluble mediators released by mononuclear cells, makes PMN hyper-responsive to H. pylori products, thus favoring the release in the gastric mucosa of infected patients of large amounts of oxygen-derived free radicals, which are not enough to eliminate the infection, but may contribute to damaging the gastric mucosa itself. Peripheral PMN oxidative burst response to H. pyloriWE might furthermore be of help in diagnosing H. pylori infection.
  Clinical Chemistry and Laboratory Medicine 04/1999; 37(3):223-9. · 2.15 Impact Factor
• Source

  Available from: bmj.com

  Article: Helicobacter pylori non-cytotoxic genotype enhances mucosal gastrin and mast cell tryptase.

  D Basso, F Navaglia, L Brigato, F Di Mario, M Rugge, M Plebani
  [show abstract] [hide abstract]
  ABSTRACT: To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine. 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies. 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer. The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.
  Journal of Clinical Pathology 04/1999; 52(3):210-4. · 2.31 Impact Factor