RESUMEN
Amyloid beta precursor protein (APP) and prion protein (PrP) are cell membrane elements implicated in neurodegenerative diseases. Both proteins undergo endoproteolysis. Evidence is adduced from the literature hinting that the process in the two proteins could be related, their functions may overlap and their distributions coincide. It is proposed that PrP catalyses its own cleavage, the C-terminal fragment functions as an alpha secretase and the N-terminal segment chaperones the active site; the alpha secretase releases anticoagulant and neurotrophic ectodomains from APP. The proposals explain some features of spongiform encephalopathies.
Asunto(s)
Modelos Biológicos , Priones/fisiología , Enfermedad de Alzheimer/etiología , Precursor de Proteína beta-Amiloide/fisiología , Animales , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Enfermedades por Prión/etiología , Priones/química , Conformación ProteicaRESUMEN
We report the cloning and sequencing of vanA genes present in the high-level vancomycin- and teicoplanin-resistant clinical isolates Oerskovia turbata 892 and Arcanobacterium (Corynebacterium) haemolyticum 872. The presence of vanA was detected by Southern blotting and PCR and confirmed by DNA sequencing. vanA-like sequences were encoded on plasmids of 15 and 20 kb respectively. The A. haemolyticum 872 DNA sequence was identical to the published vanA sequence of vancomycin-resistant Enterococcus faecium BM4147, but the O. turbata 892 sequence showed three coding changes. Induction experiments indicated that vancomycin resistance in A. haemolyticum 872 and O. turbata 892 was constitutive. SDS-PAGE analysis of membrane proteins showed the presence of a c. 39 kD protein in both clinical isolates whose expression was unaltered in the presence of vancomycin, while a similar protein in E. faecium BM4147 was inducible. Since A. haemolyticum and O. turbata are naturally susceptible to vancomycin, the high-level constitutive resistance seen in these isolates appears to be mediated by vanA. This is the first report confirming the presence of vanA in genera other than Enterococcus.
Asunto(s)
Actinomycetaceae/genética , Actinomycetales/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno , Genes Bacterianos/genética , Ligasas/genética , Vancomicina/farmacología , Actinomycetaceae/efectos de los fármacos , Actinomycetales/efectos de los fármacos , Infecciones por Actinomycetales/microbiología , Secuencia de Bases , Southern Blotting , Clonación Molecular , Cartilla de ADN , Farmacorresistencia Microbiana/genética , Heces/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Plásmidos , Reacción en Cadena de la PolimerasaRESUMEN
The periventricular region was studied in the brains of 129 cases of multiple sclerosis, with the purpose of establishing the mechanism and order of events in the development of the periventricular plaque, and deciding whether there is any relationship between granular ependymitis and such plaques. Periventricular plaques were found in 82.2% of cases. Observation and computerized morphology showed that the early stage of the periventricular plaque is the formation of a lesion around a subependymal vein and that adjacent lesions later coalesce. These plaques do not appear to arise from the ependyma, which is against any role for the CSF in their initial development. Chronic or burnt-out periventricular lesions often show overlying granular ependymitis (10.9% of cases) and subependymal gliosis (17.8%), presumably as a result of the long-continued low-grade inflammatory process. This process, which is not specific for multiple sclerosis, is sometimes associated with transfer of IgG and C3, as shown with peroxidase methods, across the subependymal vein wall and the ependymal epithelium. Increased permeability of the inflamed ependyma constitutes a possible abnormal entry route from plaque to CSF or, in reverse, from CSF to brain.
Asunto(s)
Ventrículos Cerebrales/patología , Epéndimo/patología , Esclerosis Múltiple/patología , Adulto , Anciano , Anciano de 80 o más Años , Venas Cerebrales/patología , Gliosis/patología , Humanos , Inflamación/patología , Persona de Mediana EdadAsunto(s)
Arteriosclerosis/patología , Hemangioma/patología , Leiomioma/patología , Músculo Liso , Anciano , Humanos , MasculinoAsunto(s)
Síndrome de Behçet/inmunología , Enfermedades del Complejo Inmune/inmunología , Estomatitis Aftosa/inmunología , Complejo Antígeno-Anticuerpo , Quimiotaxis de Leucocito , Humanos , Inmunoglobulinas/inmunología , Lupus Eritematoso Sistémico/terapia , Neutrófilos/fisiología , Fagocitosis , PlasmaféresisRESUMEN
High density lipoprotein (HDL) was found in vitro to form myelin buds (liposomes) from washed crystals of free cholesterol (commercial or atheroma sources). This activity led to the progressive destruction and solubilization of the crystals. Low density and very low density lipoproteins did not have any effect. Liposome formation and solubilization were accelerated by calcium ions, phospholipase A and polyunsaturated lecithin (Lipostabil). Cholesterol crystals were nearly completely destroyed after 18 h incubation with HDL-Lipostabil.
Asunto(s)
Colesterol/metabolismo , Lipoproteínas HDL/farmacología , Arteriosclerosis/metabolismo , Calcio/farmacología , Cristalización , Relación Dosis-Respuesta a Droga , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Liposomas/metabolismo , Proteínas de la Mielina/metabolismo , Fosfatidilcolinas/farmacología , Fosfolipasas/farmacología , Fosfolípidos/metabolismoRESUMEN
Electron microscopy of the reaction product between human pooled high density lipoprotein (HDL) and cholesterol shows that characteristic liposome macromicellar bodies are formed. These bodies vary in size between 30 and 1200 nm. In comparison with HDL, they contain markedly more cholesterol, but less protein and phospholipid. Their phospholipid pattern shows enrichment with sphingomyelin and phosphatidyl serine in comparison with HDL.
Asunto(s)
Colesterol/metabolismo , Lipoproteínas HDL/farmacología , Ésteres del Colesterol/metabolismo , Cristalización , Electroforesis en Gel de Poliacrilamida , Humanos , Lipoproteínas HDL/sangre , Liposomas/metabolismo , Microscopía Electrónica , Proteínas de la Mielina/metabolismo , Fosfolípidos/metabolismoRESUMEN
Chondroitin sulphate was used to isolate from plasma a system that clotted with Russell's viper venom, brain extract and activated contact factors. Clotting appeared to depend on concomitant change in C4, C3 and C1s in the system. Brain extract additionally reacted with C9. Reconstitution of specifically defective plasmas suggested a specific role for each of these complement components in clotting.
Asunto(s)
Coagulación Sanguínea , Proteínas del Sistema Complemento/metabolismo , Reacciones Antígeno-Anticuerpo , Plaquetas/efectos de los fármacos , Sulfatos de Condroitina , Coagulantes/farmacología , Proteínas Inactivadoras del Complemento 1/metabolismo , Complemento C3/metabolismo , Complemento C4/metabolismo , Complemento C5/metabolismo , Complemento C9/metabolismo , Humanos , Técnicas In VitroRESUMEN
Adenosine diphosphate (ADP) stimulates the synthesis of prostaglandin E1 (PGE1) in lysed platelets from normal subjects, patients with affective illness but not in platelets from cases of schizophrenia. The stimulation is concentration-dependent and follows a curve which is mildly sigmoid in the normal, markedly sigmoid in depression and hyperbolic in mania.