End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with ...dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented.
Because the mutations are expected to affect both actin and myosin light chain interactions, they are likely to have a cumulative detrimental effect on myosin function.\n Examples of two mutations ...within an FHC family have been described, but these have not been found through further analysis of the same allele. The second mutation in these examples has been either non-pathogenic, 8 situated in a different FHC disease gene, that is, leading to double heterozygosity, 15 or identical by descent in consanguineous families. 16 Although such double heterozygous and autozygous subjects are of interest, the two mutations are unlikely to cosegregate in many members of a family. ...these phenomena may contribute to discordant phenotypes in particular subjects with FHC, but will not have a systematic impact on genotype-phenotype correlation.
The aim of the present study was to determine the flavor-active compounds responsible for the "sulfur" and "bitter" flavors of cooked cauliflower potentially implicated in cauliflower rejection by ...consumers. Eleven varieties of cauliflower were cooked and assessed by a trained sensory panel for flavor profile determination. Among the 13 attributes, the varieties differed mainly according to their "cauliflower odor note" and their "bitterness". Various glucosinolates were quantified by HPLC and correlated with bitterness intensity. The results showed that neoglucobrassicin and sinigrin were responsible for the bitterness of cooked cauliflower. Application of Dynamic Headspace GC-Olfactometry and DH-GC-MS showed that allyl isothiocyanate (AITC), dimethyl trisulfide (DMTS), dimethyl sulfide (DMS), and methanethiol (MT) were the key odorants of cooked cauliflower "sulfur" odors. Moreover, these volatile compounds corresponded to the main compositional differences observed between varieties. Finally, AITC, DMTS, DMS, MT, sinigrin, and neoglucobrassicin were shown to be potential physicochemical determinants of cooked cauliflower acceptance.
Diseases of gut inflammation such as neonatal necrotizing enterocolitis (NEC) result after an injury to the mucosal lining of the intestine, leading to translocation of bacteria and endotoxin ...(lipopolysaccharide). Intestinal mucosal defects are repaired by the process of intestinal restitution, during which enterocytes migrate from healthy areas to sites of injury. In an animal model of NEC, we determined that intestinal restitution was significantly impaired compared with control animals. We therefore sought to determine the mechanisms governing enterocyte migration under basal conditions and after an endotoxin challenge. Here we show that the cytoskeletal reorganization and stress fiber formation required for migration in IEC-6 enterocytes requires RhoA. Enterocytes were found to express the endotoxin receptor Toll-like receptor 4, which served to bind and internalize lipopolysaccharide. Strikingly, endotoxin treatment significantly inhibited intestinal restitution, as measured by impaired IEC-6 cell migration across a scraped wound. Lipopolysaccharide was found to increase RhoA activity in a phosphatidylinositol 3-kinase-dependent manner, leading to an increase in phosphorylation of focal adhesion kinase and an enhanced number of focal adhesions. Importantly, endotoxin caused a progressive, RhoA-dependent increase in cell matrix tension/contractility, which correlated with the observed impairment in enterocyte migration. We therefore conclude that endotoxin inhibits enterocyte migration through a RhoA-dependent increase in focal adhesions and enhanced cell adhesiveness, which may participate in the impaired restitution observed in experimental NEC.
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