Antiphospholipid syndrome presenting as dilated cardiomyopathy in an 11-year-old boy

We report on an 11-year-old Omani boy who presented with acute heart failure due to dilated cardiomyopathy. Examination revealed the presence of left ventricular thrombi on echocardiography and a marked elevation of anticardiolipin antibodies. Subsequently the boy exhibited features of antiphospholipid syndrome including multiple thrombotic episodes involving the brain, and renal and iliac veins. We could not document any underlying cause of the antiphospholipid syndrome. His cardiac status subsequently deteriorated and he expired from multiorgan failure. Resistant heart failure from dilated cardiomyopathy secondary to primary antiphospholipid syndrome is uncommon and has not been reported in children.     

Accidental detection of a giant right atrial aneurysm in an asymptomatic infant

We present a 4-month old infant boy accidentally detected to have cardiomegaly on a chest radiograph, and on further investigation discovered to have a giant right atrial aneurysm and a secundum atrial septal defect. Congenital right atrial aneurysm or diverticulum is a rare anomaly, usually presenting with atrial or supraventricular tachycardia. Previously reported patients did not have any associated congenital heart defect. Although asymptomatic our patient needs close follow-up, and surgical resettion of the aneurysm and closure of the atrial septal defect in view of potential complications.     

Inhibition of type I and type III interferons by a secreted glycoprotein from Yaba-like disease virus

Type I (IFN-alpha/beta) and type III (IFN-lambdas) IFNs are important components of the host antiviral response. Although type III IFNs possess intrinsic antiviral activity similar to that of type I IFNs, they signal through a specific unique receptor complex, and their functional importance for antiviral resistance is largely uncharacterized. Here, we report the first virus defense mechanism that directly targets type III IFNs. Y136 from Yaba-like disease virus, a yatapoxvirus, is a secreted glycoprotein related to protein B18 from Vaccinia virus, a known type I IFN-binding protein and a member of the Ig superfamily. Surprisingly, whereas B18 inhibits only type I IFNs, Y136 inhibits both type I and type III IFNs. Y136 inhibits IFN-induced signaling and suppresses IFN-mediated biological activities including up-regulation of MHC class I antigen expression and induction of the antiviral state. These data demonstrate that poxviruses have developed unique strategies to counteract IFN-mediated antiviral protection and highlight the importance of type III IFNs in antiviral defense. These results suggest that type III IFNs may be an effective treatment for some poxviral infections.     

Lack of association of common cystic fibrosis transmembrane conductance regulator gene mutations with primary sclerosing cholangitis

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease of uncertain etiology. However, the histologic features of PSC liver disease can resemble those in cystic fibrosis (CF), an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to determine if PSC patients have a higher frequency of common CF alleles than disease controls. METHODS: DNA was extracted from peripheral lymphocytes of patients with end-stage liver disease. Samples were obtained before liver transplantation from 59 PSC patients and from three groups of control patients (20 each with primary biliary cirrhosis, autoimmune hepatitis, or hepatitis C). DNA samples were genotyped for 32 common CF mutations, the intron 8 T tract variants, and the M470V variant. RESULTS: One of 59 PSC patients (1.7%) had the common CF mutation (DeltaF508) in one CFTR gene. Two controls (3.3%) carried a single CF mutation (DeltaF508 in one primary biliary cirrhosis patient; W1282X in one hepatitis C patient). These rates do not differ from expected in the general population. The frequency of CFTR variants (5T and M470V) was also similar between PSC patients and controls. CONCLUSIONS: Despite anatomical similarities between CF liver disease and PSC, we could not confirm that PSC patients carried common CF mutations or common CFTR variants in higher than expected frequencies. These data suggest that CFTR dysfunction does not influence the pathogenesis of PSC.     

Increased enzyme binding to substrate is not necessary for more efficient cellulose hydrolysis

Substrate binding is typically one of the rate-limiting steps preceding enzyme catalytic action during homogeneous reactions. However, interfacial-based enzyme catalysis on insoluble crystalline substrates, like cellulose, has additional bottlenecks of individual biopolymer chain decrystallization from the substrate interface followed by its processive depolymerization to soluble sugars. This additional decrystallization step has ramifications on the role of enzyme–substrate binding and its relationship to overall catalytic efficiency. We found that altering the crystalline structure of cellulose from its native allomorph I_β to III_I results in 40–50% lower binding partition coefficient for fungal cellulases, but surprisingly, it enhanced hydrolytic activity on the latter allomorph. We developed a comprehensive kinetic model for processive cellulases acting on insoluble substrates to explain this anomalous finding. Our model predicts that a reduction in the effective binding affinity to the substrate coupled with an increase in the decrystallization procession rate of individual cellulose chains from the substrate surface into the enzyme active site can reproduce our anomalous experimental findings.     

Divergent effects of oxygen therapy in four models of uncontrolled hemorrhagic shock

Treatment with oxygen exerts beneficial effects and prolongs survival in hemorrhagic shock induced by controlled bleeding. We evaluated the effects of inhalation of 100% oxygen in four models of uncontrolled bleeding in rats: amputation of the tail, laceration of two branches of the ileocolic artery, incision of the spleen, and laceration of the lateral lobe of the liver. After tail amputation, oxygen caused a short and transient increase in mean arterial blood pressure (MABP; P < 0.01), decreased distal aorta (DA) blood flow by 27% (P < 0.01), and induced transient redistribution of blood flow to the superior mesenteric artery (SMA; P < 0.01). Later on, MABP in the oxygen group decreased gradually and was significantly lower than in air controls (P < 0.01). Oxygen therapy increased the mean blood loss by 40% (P < 0.01), increased blood lactate (P < 0.01), and shortened the survival time (P < 0.01). After laceration of two branches of the ileocolic artery, oxygen treatment caused a transient increase in MABP and redistribution of blood flow to the SMA that was followed by a comparable decrease in MABP, increase in vascular resistance, and decreased blood flow in the DA and SMA. In this model, oxygen did not affect bleeding volume, blood lactate, or survival. A similar transient regional hemodynamic effect was found when oxygen was administered after spleen or liver injury; however, in both models, oxygen maintained MABP at significantly higher values (P < 0.05). The results point to differential effects of oxygen in uncontrolled bleeding with benefits in bleeding from small parenchymal vessels and possible detrimental effect in bleeding from large size vessels.     

Experimental determination of blood permittivity and conductivity in simple shear flow

The paper is concerned with the determination of blood permittivity and conductivity in Poiseuille and Couette simple shear flows. The experimental procedure, based on dielectric spectroscopy, evidences the sensitivity of blood electric properties to the applied frequency and local shear rate magnitude. The method evidences the possibility to correlate (for well-defined flow geometry) magnitude of shear rate, and consequently the shear stress level, with spectra permittivity of blood.