Search results for "PATHOGENESIS"
showing 10 items of 761 documents
OP0299 Serum and glomerular expression of IL32 in lupus nephritis
2017
Background Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Several cytokines and chemokines are secreted locally in case of glomerular inflammation. Interleukin 32 (IL32) is a newly described cytokine that exhibits several properties typical of proinflammatory cytokines. Ex vivo and in vitro studies supported the role of Toll like receptors (TLRs) in LN pathogenesis and recent investigations demonstrated that Poly I:C, a ligand for (TLR) 3, strongly induced IL32 production from several cell populations. Objectives To investigate serum and urinary levels of IL32 in a cohort of LN patients compared to SLE patients without renal involvement and he…
The Expanding Spectrum of Mutations in Hereditary Angioedema.
2021
The evolution in the knowledge of rare genetic diseases such as hereditary angioedema (HAE) has increased at a parallel pace with the development of new molecular tools. The deficiency of C1 inhibitor (C1-INH) has been recognized as the main cause of HAE (HAE-C1-INH) since the 1960s, but the discovery of the wide spectrum of mutations affecting the C1-INH gene (SERPING1) was possible only from the late 1980s, when Sanger sequencing became available and more accessible worldwide. Nevertheless, the involvement of other genes in HAE was discovered only in 2006 with the description of mutations in the F12 gene in patients with HAE and normal C1-INH. In the last 3 years, advanced next-generation…
Involvement of IL-6 in the Pathogenesis of Inflammatory Bowel Disease and Colon Cancer
2005
Inflammatory bowel disease (IBD), which consists of Crohn’s disease and ulcerative colitis, is defined as a chronic inflammation of the gastrointestinbal tract. The etiopathogenetic mechanisms underlying the development of IBD are still not completely understood, and the therapeutic strategies used thus far have been limited to mostly evidence-based principles. There is growing evidence that the pro-inflammatory cytokine interleukin (IL)-6 plays a crucial part in the uncontrolled intestinal inflammatory process, which is a main characteristic of IBD. There is elevated production of IL-6 and its soluble receptor (sIL-6R) by intestinal macrophages and CD4+ T-cells. The increased formation of …
Staphylococcal alpha-toxin provokes neutrophil-dependent cardiac dysfunction: role of ICAM-1 and cys-leukotrienes.
2002
The role of polymorphonuclear neutrophils (PMN) in septic myocardial dysfunction is presently unknown. Staphylococcus aureus infections are frequently associated with septic sequelae. Therefore, we perfused isolated rat hearts with low doses of α-toxin, the major staphylococcal exotoxin, followed by application of human PMN, N-formyl-methionyl-leucyl-phenylalanine, and arachidonic acid. In contrast to sham-perfused hearts (no α-toxin), a rise in coronary perfusion pressure (CPP) and a reduction of contractile function were noted, and cardiac expression of intercellular adhesion molecule (ICAM)-1 was detected by immunohistochemical methods and real-time PCR. Histological analysis and myelope…
Vibrio vulnificus biotype 2 serovar E gne but not galE is essential for lipopolysaccharide biosynthesis and virulence
2008
ABSTRACT This work aimed to establish the role of gne (encoding UDP-GalNAc 4-epimerase activity) and galE (encoding UDP-Gal-4-epimerase activity) in the biosynthesis of surface polysaccharides, as well as in the virulence for eels and humans of the zoonotic serovar of Vibrio vulnificus biotype 2, serovar E. DNA sequence data revealed that gne and galE are quite homologous within this species (≥90% homology). Mutation in gne of strain CECT4999 increased the surface hydrophobicity, produced deep alterations in the outer membrane architecture, and resulted in noticeable increases in the sensitivity to microcidal peptides (MP), to eel and human sera, and to phagocytosis/opsonophagocytosis. Furt…
Cationic Proteins Inhibit l-Arginine Uptake in Rat Alveolar Macrophages and Tracheal Epithelial Cells
1999
Eosinophil-derived cationic proteins play an essential role in the pathogenesis of bronchial asthma. We tested whether cationic proteins interfere with the cationic amino-acid transport in alveolar macrophages (AMPhi) and tracheal epithelial cells, and whether L-arginine-dependent pathways were affected. The effect of cationic polypeptides on cellular uptake of [(3)H]-L-arginine, nitrite accumulation, and the turnover of [(3)H]-L-arginine by nitric oxide (NO) synthase and arginase (formation of [(3)H]-L-citrulline and [(3)H]-L-ornithine, respectively) were studied. Poly-L-arginine reduced [(3)H]-L-arginine uptake in rat AMPhi and tracheal epithelial cells in a concentration-dependent manner…
Overview of the pathology of three widely used animal models of acute lung injury
2007
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute diffuse damage to the pulmonary parenchyma by a variety of local or systemic insults. Increased alveolar capillary membrane permeability was recognized as the common end organ injury and a central feature in all forms of ALI/ARDS. Although great strides have been made in understanding the pathogenesis of ALI/ARDS and in intensive care medicine, the treatment approach to ARDS is still relying on ventilatory and cardiovascular support based on the recognition of the clinical picture. In the course of evaluating novel treatment approaches to ARDS, 3 models of ALI induced in different species, i.e. the…
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
2015
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study
2017
Background and aims Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. Methods This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. Results Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic …
Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease.
2020
Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17…