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Angiogenin (ANG), a 14‐kDa pro‐angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detected elevated levels of secreted and cell surface‐bound ANG in highly invasive metastatic breast cancer cells. ANG was also detected at very high levels in the tumor cells in infiltrating ductal carcinomas. By immunofluorescence and immunoprecipitation analysis, ANG was detected at the leading edges of the cell surfaces where it colocalized and interacted with members of the plasminogen activation system (PAS) such as annexin A2 (A2), calpactin (S100‐A10) and urokinase plasminogen activator receptor (uPAR). Analysis of lipid raft (LR) and non‐lipid raft (NLR) regions of the cell membranes showed the predominance of ANG, A2 and S100‐A10 in the LR regions. In contrast, uPAR was detected predominantly in the NLR fractions, suggesting that ANG interacts with uPAR at the junctions of LR and NLR regions. ANG knockdown in T47D and MDA‐MB‐231 breast cancer cell lines did not affect the cellular expression of A2, S100‐A10 and uPAR but decreased cell migration and plasmin formation. Neutralization of ANG with monoclonal antibodies similarly decreased the migration of MDA‐MB‐231 cells. In the presence of ANG, uPAR was observed to interact with uPA, which is necessary for plasmin formation. Conversely, in the absence of ANG, uPAR did not interact with uPA and FAK and Src kinases were observed to be dephosphorylated. Exogenous addition of recombinant ANG to ANG knocked down MDA‐MB‐231 cells restored FAK phosphorylation, uPAR interactions with uPA, plasmin formation as well as migration of these cells. Taken together, our results identified a novel role for ANG as a member of the uPAR interactome that facilitates the interaction of uPAR with uPA, leading to plasmin formation and cell migration necessary for tumor invasion and metastasis of breast cancer cells. Highlights: Invasive metastatic breast cancer cells have high levels of cell surface bound ANG.Cell surface ANG interacts with members of the plasminogen activation system (PAS).PAS member uPAR interacts with plasminogen receptor Annexin A2 and S100‐A10 via ANG.ANG is required for interaction between uPAR and uPA.Depletion of cell surface ANG causes inhibition of plasmin formation and cell motility. [ABSTRACT FROM AUTHOR]

HLA-DRB4 gene is associated with Churg-Strauss syndrome (CSS), a systemic eosinophilic vasculitis with a prodromal phase characterized by severe asthma, eosinophilia, nasal polyposis, and sinusitis. Aim of this study was to evaluate if the presence of HLA-DRB4 in asthmatic patients is associated with a clinical picture resembling that of the prodromal phase of CSS. HLA-DRB1 was determined in a cohort of 159 asthmatic patients and its frequency was compared with that of 1808 blood donors. HLA-DRB4 presence/absence was correlated with clinical features, including sinusitis, nasal polyposis, eosinophils, antiasthmatic drugs, asthma severity, and pulmonary function tests. HLA-DRB4 gene was associated with severe persistent asthma before treatment (P < 0.02), near fatal or severe hypoxemic asthma (P < 0.01), sinusitis (P < 0.01), nasal polyposis (P < 0.01), number of patients with eosinophils >1000/µl: (P < 0.05), need of beclomethasone >1000-2000 µg/daily (P < 0.001), use of a third controller (P < 0.05), and oral prednisone (P < 0.02). HLA-DRB4 gene is associated in asthmatic patients with a clinical picture characterized by asthma severity, sinusitis, nasal polyposis, and eosinophilia closely resembling that of the prodromal phase of CSS and might be useful to suspect corticosteroids-masked cases of CSS. [ABSTRACT FROM AUTHOR]

The article presents a study on the significance of using size fractionation, scanning electron microscopy, and x-ray absorption spectroscopy to examine zinc (Zn) speciation in pig slurry. Zn has high quantity in pig slurry for it is used as an essential nutrient in animal feeds. The soil surface layers are measured for Zn accumulation, phytotoxicity, and groundwater quality degradation. Size fractionation was performed to determine the complexity of pig slurry. Scanning electron microscopy and x-ray absorption spectroscopy were performed to assess Zn speciation. It found out that the organic matter has 49% Zn, 37% amorphous Zn hydroxides, and 14% sphalerite.

Background:  The asthmatic-prodromal phase of Churg–Strauss syndrome (CSS) is usually considered allergic, but data about the involved allergens are scarce. The aim of our work was to examine the prevalence of allergy in a group of CSS patients and in two control groups of persistent asthmatic subjects selected for eosinophilia >10% [first control group patients (CGP1)] and eosinophils <6% [second control group patients (CGP2)]. Methods:  The respiratory symptoms, and the results of prick test and/or RAST for the common allergens, performed before the vasculitic phase in 51 CSS, were retrospectively evaluated and compared with those of 46 CGP1 and 50 CGP2. Results:  31.4% of CSS vs 67.4% of CGP1 ( P = 0.0004) and vs 58.0% CGP2 ( P = 0.007) were allergic. The number of subjects with seasonal allergies was lower in CSS vs CGP1 ( P = 0.0069) and vs CGP2 ( P = 0.0002). The number of perennial allergies was significantly higher in CSS than in both control groups (CSS vs CGP1, P = 0.0108; CSS vs CGP2, P = 0.0079). The subjects allergic to Dermatophagoides were prevalent in CSS vs CGP1 ( P = 0.0045) but not vs CGP2. Conclusions:  The evidence of allergy, considered as the demonstration of specific IgE consistent with the clinical history, is present in less than one-third of CSS and the higher prevalence of seasonal allergies in the controls disagrees with persistent asthma. Allergy may be only one of several mechanisms triggering exacerbation of asthma or supporting chronic airway inflammation as in asthma in general. Alternatively, unidentified allergens may play a role. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Churg-Strauss syndrome (CSS) is classified among the so-called antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75-95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features. METHODS: Immunofluorescence and enzyme-linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status. RESULTS: ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti-MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042). CONCLUSION: ANCAs are present in approximately 40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA-positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis. [ABSTRACT FROM AUTHOR]

Four endodontic surgical cases are presented in which low-temperature thermoplasticized gutta-percha was used for obturation. In 3 of them, after the retrograde instrumentation of the root canals, thermoplasticized gutta-percha was employed as a retrofilling material; in the fourth tooth, the material was used for retrofilling of an external resorption lacuna. The possibility for using this filling technique in different endodontic surgical procedures is suggested, based on the clinical success obtained in these cases. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease., Methods: Low-resolution genotyping of HLA-A, HLA-B, and HLA-DR loci and genotyping of TNFA -238A/G and TNFA -308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls., Results: The frequency of the HLA-DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; chi(2) = 12.64, P = 0.0003, corrected P [P(corr)] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47-3.99). The HLA-DRB4 gene, present in subjects carrying either HLA-DRB1*04, HLA-DRB1*07, or HLA-DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; chi(2) = 16.46, P = 0.000058, P(corr) = 0.000232, OR 2.49, 95% CI 1.58-3.09). Conversely, the frequency of the HLA-DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; chi(2) = 7.62, P = 0.0057, P(corr) = 0.0228, OR 0.54, 95% CI 0.35-0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)-positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA-DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001)., Conclusion: These findings indicate that HLA-DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.