RESUMEN
Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo-electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.
Asunto(s)
Proteínas , Microscopía por Crioelectrón , Movimiento (Física) , Proteínas/genéticaRESUMEN
Complement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidase staining using MoAbs reactive with complement-split products. Intense deposition of complement fragments C4d and C3d in peritubular capillaries, indicating activation of the classical pathway, could be detected in the majority of transplanted kidneys with cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biopsies from patients with high 'immunological risk' (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paucity of immunoglobulins in transplant biopsies, antibodies directed against endothelial cell antigens should be considered as a possible cause of classical complement activation.
Asunto(s)
Capilares/inmunología , Activación de Complemento , Complemento C4b , Rechazo de Injerto/inmunología , Inmunidad Celular , Trasplante de Riñón/inmunología , Riñón/irrigación sanguínea , Anticuerpos Monoclonales , Biopsia , Complemento C4/análisis , Ciclosporina/efectos adversos , Glomerulonefritis/inmunología , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina M/análisis , Isquemia/inmunología , Riñón/patología , Fragmentos de Péptidos/análisis , Trasplante Homólogo/inmunologíaAsunto(s)
Ciclosporinas/farmacocinética , Técnica del Anticuerpo Fluorescente , Rechazo de Injerto/efectos de los fármacos , Trasplante de Riñón/inmunología , Azatioprina/administración & dosificación , Ciclosporinas/administración & dosificación , Ciclosporinas/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Polarización de Fluorescencia , Humanos , Riñón/efectos de los fármacos , Metilprednisolona/administración & dosificación , Radioinmunoensayo/métodosRESUMEN
Percutaneous cholecystostomy was performed in 17 poor surgical risk patients. 16 patients developed acute acalculous cholecystitis postoperatively in the intensive care unit, 1 patient had an acute cholecystitis with calculi. Diagnostic imaging using CT and US was specific for acute cholecystitis in 58% only. Percutaneous cholecystostomy was the definitive treatment in 69% of the patients. Additional cholecystectomy was required in 3 patients with complicated cholecystitis, in 1 patient with bile leakage after catheter dislocation and in 1 patient with gallbladder calculi. 3 patients died, 2 of them from reasons unrelated to the gallbladder disease. Radiology-guided percutaneous cholecystostomy performed by a transhepatic approach is a safe and effective procedure for acute cholecystitis in high-risk patients.