Helicobacter pylori protein oxidation influences the colonization process

Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of membrane and exported proteins. Here we examined the role of DsbI protein in Helicobacter pylori pathogenesis and demonstrated that a dsbI mutant impaired in disulfide bond formation revealed a greatly reduced ability to colonize mice gastric mucosa.     

Respiratory changes in a murine model of spontaneous systemic lupus erythematosus

The pathophysiology of systemic lupus erythematosus (SLE) has been very well described in many organs. However, the relation between extracellular matrix changes and lung dynamic mechanical behaviour deserves elucidation. To that end, pulmonary mechanics, lung morphometry and the amount of collagen and elastic fibres in the alveolar septa were analysed in mice with SLE [NZB/W (New Zealand Black/White) F1] and non-diseased NZW mice (control). Static (E(st)) and dynamic (E(dyn)) elastances, difference between dynamic and static elastances (DeltaE), airway resistance (R(aw)) and viscoelastic/inhomogeneous pressure (DeltaP(2)) were determined by the end-inflation occlusion method. Lungs were removed and prepared for histology. E(st), E(dyn), DeltaE and DeltaP(2) were higher in SLE than in control group, while R(aw) was similar in both groups. SLE group showed alveolar collapse and increased amount of elastic and collagen fibres. In conclusion, SLE mice showed an increase in elastic and viscoelastic/inhomogeneous pressures that was accompanied by deposition of collagen and elastic fibres in the alveolar septa.     

Genetic variation of NSP1 and NSP4 genes among serotype G9 rotaviruses causing hospitalization of children in Melbourne, Australia, 1997-2002

Serotype G9 rotaviruses have emerged as one of the leading causes of gastroenteritis in children worldwide. We examined 29 representative G9 rotavirus isolates from a 6-year collection (1997-2002) and determined the level of variation in genes encoding non-structural proteins, NSP1 and NSP4. Northern hybridization analysis with a whole genome probe derived from the prototype G9 strain, F45, revealed that the NSP1 gene (gene 5) of two isolates (R1 and R14) did not exhibit significant homology. Complementary DNA probes of R1 and R14 genes 5 were used in Northern blot hybridization and indicated the presence of at least two gene 5 alleles among Melbourne G9 rotaviruses. Nucleotide sequence analysis revealed that isolates carrying the R14 gene 5 shared 94-98% sequence identities with one another, while sequence identity to R1 was 78%. Surprisingly, R1 displayed 96% nucleotide identity with the prototype serotype G1 strain, Wa. The detection of different alleles of NSP1 genes prompted us to investigate the level of variation in another non-structural protein, NSP4, a multifunctional protein and the first viral-encoded enterotoxin. Phylogenetic analysis indicated that while all isolates clustered into one group containing the Wa NSP4 allele (genotype 1), isolate R1 was most closely related to Wa. This study reveals new information about the diversity of non-structural proteins of G9 rotaviruses.     

Neoplastic pericarditis--the role of different diagnostic procedures

The aim of the study was to assess the role of different diagnostic procedures in the recognition of malignant pericarditis. Consecutive medical records of the patients with pericardial effusion treated with pericardiocentesis or pericardioscopy in the period of 1982-2002 were analyzed retrospectively. Criteria of neoplastic pericarditis were: positive result of pericardial fluid cytology and/or neoplastic infiltration found in pericardial biopsy specimen. Criteria of non-neoplastic pericarditis were: negative result of pericardial fluid cytology and pericardial biopsy specimen, no neoplastic disease diagnosed at presentation and during 3-years of follow up. Malignant pericarditis was diagnosed in 47 patients (pts), nonmalignant in 51. Echocardiographic signs of cardiac tamponade were found in 80% of pts with neoplastic pericarditis and 40% of pts with non-malignant disease (p = 0.0001). Chest CT scan revealed the presence of enlarged mediastinal lymph nodes in 94% of pts with malignant pericarditis and only 11% of pts with non-malignant disease (p = 0.00001). Pericardial thickness on CT scan exceeded 8 mm in 75% of the pts with malignant pericarditis and 8% of pts with nonmalignant disease (p = 0.0003). Pericardial fluid (pf) CEA concentration was significantly higher in the patients with neoplastic pericarditis than in the pts with non-malignant process. CEA > 5 ng/ml and Cyfra 21-1>50 ng/ml were found in 43% of the pts with malignant pericarditis and none of the pts with benign pericarditis. Thus we recommend chest CT scan and pericardial fluid tumor markers (CEA and Cyfra 21-1) assessment as the procedures helpful in the recognition of malignant pericarditis.     

Lack of intestinal mucosal toxicity of Triticum monococcum in celiac disease patients

OBJECTIVE: The treatment of celiac disease is based on lifelong withdrawal of foods containing gluten. Unfortunately, compliance with a gluten-free diet has proved poor in many patients (mainly due to its low palatability), emphasizing the need for cereal varieties that are not toxic for celiac patients. In evolutionary terms, Triticum monococcum is the oldest and most primitive cultivated wheat. The aim of this study was to evaluate the toxicity of T. monococcum on small intestinal mucosa, using an in vitro organ culture system. MATERIAL AND METHODS: Distal duodenum biopsies of 12 treated celiac patients and 17 control subjects were cultured for 24 h with T. aestivum (bread) gliadin (1 mg/ml) or with T. monococcum gliadin (1 mg/ml). Biopsies cultured with medium alone served as controls. Each biopsy was used for conventional histological examination and for immunohistochemical detection of CD3 + intraepithelial lymphocytes (IELs) and HLA-DR. Secreted cytokine protein interferon-gamma (IFN-gamma) was measured in the culture supernatant using an enzyme-linked immunoadsorbent assay. RESULTS: Significant morphological changes, HLA-DR overexpression in the crypt epithelium and an increased number of CD3 + IELs, found after bread gliadin exposure, were not observed in celiac biopsies cultured with T. monococcum gliadin. In contrast, with bread gliadin, there was no significant IFN-gamma response after culture with monococcum gliadin. Similarly, biopsies from normal controls did not respond to bread or monococcum gliadin stimulation. CONCLUSIONS: These data show a lack of toxicity of T. monococcum gliadin in an in vitro organ culture system, suggesting new dietary opportunities for celiac patients.     

Complete repair in total atrioventricular canal defect with cyanosis

Atrioventricular septal defects account for 4% of congenital cardiac malformations and over 50% of cardiac defects seen in Down syndrome. Clinical presentation is marked by congestive heart failure early in infancy. Cyanosis is rarely found in infants and suggests irreversible pulmonary hypertension or associated cardiac defects as tetralogy of Fallot, double outlet right ventricle, Ebstein anomaly, persistent left superior vena cava draining in the left atrium (Barbero Marcial, personal communication). Children with Down's syndrome is particularly difficult to assess because they often suffer from upper airways obstruction, which may contribute to the increased pulmonary vascular resistance determined at cardiac catheterization. This association of factors becomes a challenge for operability and, we will report one such case.     

Comparative evaluation of p53 mutation in pancreatic adenocarcinoma and chronic pancreatitis

BACKGROUND/AIMS: Pancreatic adenocarcinoma (PA) has a very poor prognosis. In patients suffering from chronic pancreatitis (CP) the risk for the PA development is higher than in the general population. The purpose of the study was to compare the prevalence of p53 mutations in PA and CP in order to evaluate their usefulness in differential diagnosis of those diseases. METHODOLOGY: We examined 49 patients who underwent Whipple resection or distal pancreatectomy for pancreatic adenocarcinoma (26 subjects) or chronic pancreatitis (23 subjects). DNA from pancreatic tissue was analyzed for p53 mutations with PCR/SSCP methods. RESULTS: The p53 gene mutation has been shown in 16 (61.5%) of the PA patients (9 in exon 5 and 7 in exon 7) and in 2 (8.6%) of CP patients (1 in exon 5 and 1 in exon 8; p < 0.001). There was a significant correlation between p53 mutation and G3 tumor differentiation (p < 0.01). Overall median survival in patients with PA was 8.5 months. No relationship between presence of p53 mutation and survival time in PA patients has been observed. CONCLUSIONS: The specificity of p53 mutation for pancreatic cancer is very high. Our results indicate that p53 gene mutation may provide an additional tool in differential diagnosis of CP and PC.     

Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved

The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3–6 μg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3–1 μg/paw), disappearing within 24 h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5–10 μg/site) induced MCs degranulation and release of PGD₂. Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom.