Peptic ulcers and erosions are common in Israeli children undergoing upper endoscopy

Background: Peptic ulcers and erosions (PU&E) are thought to be uncommon in children. Patients with early exposure to Helicobacter pylori may be at a higher risk for early onset PU&E. Children in Israel have a high prevalence and early acquisition of Helicobacter pylori (H. pylori) and have easy access to pediatric gastroenterologists and endoscopy. Our aim was to describe the prevalence and characteristics of PU&E in this population referred by Pediatric Gastroenterologists for an upper endoscopy. Methods: We conducted a retrospective study over the years January 2003–May 2006. Over these years we had information on 751 diagnostic upper endoscopies. PU&E was regarded as erosive gastritis/duodenitis or ulcer in either the stomach or duodenum. H. pylori status was assessed using rapid urease test and gastric biopsies. Results: PU&E was detected in 169 (22.5%) patients (ulcers 51 (6.8%), erosions 118 (15.7%)). One hundred twenty‐four had gastric PU&E and 58 had duodenal PU&E. H. pylori was positive in 112 (66.3%). H. pylori‐associated PU&E becomes common after age 10 years, with gastric PU&E presenting much earlier than duodenal disease. Most of the H. pylori‐negative PU&E were idiopathic and improved symptomatically on PPI treatment. Interestingly, 43% of patients with PU&E in our cohort were either immigrants from the former Soviet Union or of Israeli Arab origin. Conclusions: PU&E appears to be common in this selected population with a relatively high incidence of gastric PU&E. H. pylori associated PU&E becomes common after age 10 years with gastric PU&E presenting much earlier than duodenal disease. Non H. pylori PU&E in children comprises approximately a third of all PU&E, are mostly idiopathic and appear earlier than H. pylori associated PU&E.     

Plasmodiophora brassicae: a review of an emerging pathogen of the Canadian canola (Brassica napus) crop

Plasmodiophora brassicae causes clubroot disease in cruciferous plants, and is an emerging threat to Canadian canola (Brassica napus) production. This review focuses on recent studies into the pathogenic diversity of P. brassicae populations, mechanisms of pathogenesis and resistance, and the development of diagnostic tests for pathogen detection and quantification. TAXONOMY: Plasmodiophora brassicae is a soil-borne, obligate parasite within the class Phytomyxea (plasmodiophorids) of the protist supergroup Rhizaria. DISEASE SYMPTOMS: Clubroot development is characterized by the formation of club-shaped galls on the roots of affected plants. Above-ground symptoms include wilting, stunting, yellowing and premature senescence. DISEASE CYCLE: Plasmodiophora brassicae first infects the root hairs, producing motile zoospores that invade the cortical tissue. Secondary plasmodia form within the root cortex and, by triggering the expression of genes involved in the production of auxins, cytokinins and other plant growth regulators, divert a substantial proportion of plant resources into hypertrophic growth of the root tissues, resulting in the formation of galls. The secondary plasmodia are cleaved into millions of resting spores and the root galls quickly disintegrate, releasing long-lived resting spores into the soil. A serine protease, PRO1, has been shown to trigger resting spore germination. PHYSIOLOGICAL SPECIALIZATION: Physiological specialization occurs in populations of P. brassicae, and various host differential sets, consisting of different collections of Brassica genotypes, are used to distinguish among pathotypes of the parasite. DETECTION AND QUANTIFICATION: As P. brassicae cannot be cultured, bioassays with bait plants were traditionally used to detect the pathogen in the soil. More recent innovations for the detection and quantification of P. brassicae include the use of antibodies, quantitative polymerase chain reaction (qPCR) and qPCR in conjunction with signature fatty acid analysis, all of which are more sensitive than bioassays. RESISTANCE IN CANOLA: Clubroot-resistant canola hybrids, recently introduced into the Canadian market, represent an important new tool for clubroot management in this crop. Genetic resistance must be carefully managed, however, as it has been quickly overcome in other regions. At least three resistance genes and one or two quantitative trait loci are involved in conferring resistance to P. brassicae. Root hair infection still occurs in resistant cultivars, but secondary plasmodia often remain immature and unable to produce resting spores. Fewer cell wall breakages occur in resistant hosts, and spread of the plasmodium through cortical tissue is restricted. More information on the genetics of clubroot resistance in canola is needed to ensure more effective resistance stewardship. USEFUL WEBSITES: http://www.canolacouncil.org/clubroot/resources.aspx, http://tu-dresden.de/die_tu_dresden/fakultaeten/fakultaet_mathematik_und_naturwissenschaften/fachrichtung_biologie/botanik/pflanzenphysiologie/clubroot, http://www.ohio.edu/people/braselto/plasmos/     

Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro

The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.     

Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis

Apolipoprotein B (apoB) is the sole protein component of low-density lipoprotein (LDL) and is thought to play an important role in atherogenesis. We performed a meta-analysis of the associations between the three most frequently investigated polymorphisms (XbaI, signal peptide insertion/deletion, EcoRI) in the apolipoprotein B (APOB) gene, lipid parameters, and the risk of ischemic heart disease (IHD). We restricted our analysis to Caucasians. Homozygotes for the XbaI X+ allele had significantly elevated levels of LDL cholesterol (LDL-C) and apoB, but a decreased risk (OR=0.80; 95%CI: 0.66–0.96) of IHD. Homozygosity for the signal peptide deletion allele was associated with similarly increased levels of LDL-C and apoB, and with an increased risk of IHD (OR=1.30; 95%CI: 1.08–1.58). Subjects homozygous for the rare EcoRI allele had significantly decreased levels of total and LDL cholesterol, but unaltered risk of IHD. We conclude that all three polymorphic apoB sites are associated with altered lipid levels, but not necessarily with a consistently altered risk of IHD. These data suggest that the relationship between apoB levels, hypercholesterolemia and IHD risk cannot have a simple molecular basis in the apoB gene.     

Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate

Axl has been a target of interest in the oncology field for several years based on its role in various oncogenic processes. To date, no wild-type Axl crystal structure has been reported. Herein, we describe the structure-based optimization of a novel chemotype of Axl inhibitors, 1H-imidazole-2-carboxamide, using a mutated kinase homolog, Mer(I650M), as a crystallographic surrogate. Iterative optimization of the initial lead compound (1) led to compound (21), a selective and potent inhibitor of wild-type Axl. Compound (21) will serve as a useful compound for further in vivo studies.     

The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway

Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identify the deubiquitinating enzyme USP1 as a novel component of the Fanconi anemia pathway. Inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2. Furthermore, USP1 physically associates with FANCD2, and the proteins colocalize in chromatin after DNA damage. Finally, analysis of crosslinker-induced chromosomal aberrations in USP1 knockdown cells suggests a role in DNA repair. We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2.