ABSTRACT
En los EE.UU., el traumatísmo craneoencefálico (TCE) es la principal causa mortis entre individuos de 10 a 44 años y constituye por más del 50 por ciento de los órbitos por trauma alcanzado, por lo tanto, una importante parcela económicamente activa de la población. El uso de vehículos de dos ruedas, sea como medio de transporte, recreación o para la práctica de deportes, no está exento de accidentes, siendo el TCE relevante consecuencia de esa práctica y la principal causa de muerte e invalidez. Se realizó un estudio prospectivo de 20 pacientes atendidos en el Hospital Universitario Vírgen de la Arrixaca, Murcia, España, con diagnóstico de TCE por caída de vehículo de dos ruedas, en el período de enero a junio de 2002, utilizando un protocolo patrón, el cual fue rellenado por el autor o por el equipo del hospital. En nuestra muestra, hubo una nítida predominancia del sexo masculino (95 por ciento de los casos), siendo el grupo más afectado el de los jóvenes de 11 a 20 años, con el 65 por ciento de los casos. Hubo 17 accidentes por motocicleta y tres por bicicleta. En el primer grupo, siete (41,2 por ciento) usaban casco y entre los usuarios de bicicleta, dos (67 por ciento). En todo el muestreo, el uso de casco fue relatado por el 45 por ciento de los pacientes. La tomografía computarizada (TC) fue el método de elección para la evaluación de esos pacientes, pues es un método rápido que tiene la posibilidad de reconocer a los pacientes que necesitan intervención quirúrgica. En cuanto a las lesiones encontradas en las imágenes por TAC, el 85 por ciento del muestreo evidenció la presencia de lesiones intracraneales, siendo el hematoma subdural la más frecuente, seguido de la hemorragia subaracnoidea, la contusión cerebral y el edema cerebral. El tratamiento instituído fue conservador en la mayoría de los casos, siendo en apenas 5 pacientes (25 por ciento) necesaria la cirugía. El tiempo medio de internación fue significativamente más alto en los pacientes sometidos a tratamiento quirúrgico en relación al grupo sometido a tratamiento conservador (26,6 días y 15,3 días, respectivamente). La mortalidad fue de 10 por ciento (2 pacientes). La atención en el lugar del accidente es de importancia fundamental para reducir el número de óbitos y secuelas después del traumatísmo en general y el TEC en particular.
Subject(s)
Humans , Craniocerebral Trauma , Motor Vehicles , Tomography, Emission-Computed , SpainABSTRACT
El compromiso óseo craneal asociado a tumores cerebrales primarios es de ocurrencia rara. Entre los gliomas de crecimiento lento que pueden cursar con erosión craneána están el astrocitoma, oligodendroglioma, ependimoblastoma, oligoastrocitoma, glioblastoma multiforme, meningiomas, metástasis y sarcomas. Su fisiopatología se debe probablemente a evolución lenta y localización superficial en el cerebro, lo que ocasiona elevación progresiva de la presión intracraneal. Los autores relatan un caso de ependimoma parietal posterior derecho con perforación de la duramadre y extensión extracraneal.
Subject(s)
Humans , Adult , Female , Brain Neoplasms , Ependymoma , Neoplasms, Unknown Primary , Tomography, X-Ray ComputedABSTRACT
Los quístes dermoides en la región de la fontanela anterior son raros constituyendo alrededor de 0,1 porciento de todos los tumores craneales. Son tumores relacionados con el desarrollo, que aparecen frecuentemente en la región axial del neuro-eje o en la línea de fusión embriológica. Son diagnósticados y tratados por cirugía en los primeros añós de vida, razón por la cual este tipo de patologíaes raramente observada en la edad adulta. Para s diagnóstico son necesarios radiografía simple y tomografía computarizada con o sin contraste. Los autores relatan un caso de Quiste Dermoide de Inclusión Congénita (DIC) ubicado en la fontanela anterior en un paciente adulto, y discuten su aspecto histopatológico, diagnóstico diferencial y tratamiento.
Subject(s)
Humans , Male , Adult , Skull/abnormalities , Skull/surgery , Dermoid Cyst/surgery , Dermoid Cyst/diagnosis , Dermoid Cyst/pathology , Tomography, Emission-Computed , Tomography, X-Ray Computed , Diagnosis, DifferentialABSTRACT
PSD-95/SAP90 is a member of the MAGUK superfamily. In excitatory synapses, PSD-95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules. We have determined the crystal structures of the apo and GMP-bound forms to 2.3 and 2.0 A resolutions, respectively, of a fragment containing the SH3, HOOK, and guanylate kinase (GK) domains of PSD-95. We observe an intramolecular interaction between the SH3 and GK domains involving the formation of a beta sheet including residues N- and C-terminal to the GK domain. Based on amino acid conservation and mutational data available in the literature, we propose that this intramolecular interaction is a common feature among MAGUK proteins.
Subject(s)
Catalytic Domain , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Nucleoside-Phosphate Kinase/chemistry , Nucleoside-Phosphate Kinase/metabolism , src Homology Domains , Amino Acid Sequence , Animals , Apoenzymes/chemistry , Apoenzymes/metabolism , Binding Sites , Crystallography, X-Ray , Disks Large Homolog 4 Protein , Guanosine Monophosphate/metabolism , Guanylate Kinases , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Models, Molecular , Molecular Sequence Data , Protein Binding , Protein Structure, Quaternary , Protein Structure, Secondary , Protein Structure, Tertiary , Rats , Sequence Alignment , Static Electricity , Structure-Activity RelationshipABSTRACT
The three-dimensional structure of the major horse allergen Equ c 1 has been determined at 2.3 A resolution by x-ray crystallography. Equ c 1 displays the typical fold of lipocalins, a beta-barrel flanked by a C-terminal alpha-helix. The space between the two beta-sheets of the barrel defines an internal cavity that could serve, as in other lipocalins, for the binding and transport of small hydrophobic ligands. Equ c 1 crystallizes in a novel dimeric form, which is distinct from that observed in other lipocalin dimers and corresponds to the functional form of the allergen. Binding studies of point mutants of the allergen with specific monoclonal antibodies raised in mouse and IgE serum from horse allergic patients allowed to identify putative B cell antigenic determinants. In addition, total inhibition of IgE serum recognition by a single specific monoclonal antibody revealed the restricted nature of the IgE binding target on the molecular surface of Equ c 1.
Subject(s)
Allergens/chemistry , Glycoproteins/chemistry , Allergens/immunology , Amino Acid Sequence , Animals , Antibodies, Monoclonal/chemistry , Binding Sites , Carrier Proteins/chemistry , Crystallography, X-Ray , Dimerization , Glycoproteins/immunology , Horses , Immunoglobulin E/blood , Immunoglobulin E/immunology , Lipocalins , Mice , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Point Mutation , Protein Conformation , Protein Structure, Secondary , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
The intracellular parasite Trypanosoma cruzi, the etiological agent of Chagas disease, sheds a developmentally regulated surface trans-sialidase, which is involved in key aspects of parasite-host cell interactions. Although it shares a common active site architecture with bacterial neuraminidases, the T.cruzi enzyme behaves as a highly efficient sialyltransferase. Here we report the crystal structure of the closely related Trypanosoma rangeli sialidase and its complex with inhibitor. The enzyme folds into two distinct domains: a catalytic beta-propeller fold tightly associated with a lectin-like domain. Comparison with the modeled structure of T.cruzi trans-sialidase and mutagenesis experiments allowed the identification of amino acid substitutions within the active site cleft that modulate sialyltransferase activity and suggest the presence of a distinct binding site for the acceptor carbohydrate. The structures of the Trypanosoma enzymes illustrate how a glycosidase scaffold can achieve efficient glycosyltransferase activity and provide a framework for structure-based drug design.
Subject(s)
Neuraminidase/metabolism , Sialyltransferases/metabolism , Trypanosoma/enzymology , Animals , Binding Sites , Crystallography, X-Ray , Models, Molecular , Mutagenesis, Site-Directed , Neuraminidase/genetics , Protein Conformation , Sialyltransferases/genetics , Trypanosoma/geneticsABSTRACT
The secreted protein Equ c 1 is the major component responsible for the induction of specific IgE antibodies in patients sensitized to horse allergens. Equ c 1 belongs to the lipocalin superfamily of hydrophobic ligand-binding proteins, which also includes other known allergens. Equilibrium sedimentation and gel-filtration studies demonstrate that both the glycosylated form of Equ c 1 purified from horse salivary glands and the non-glycosylated recombinant form expressed in bacteria exist predominantly as dimers in solution. As observed for other dimeric lipocalins, acidic pH and low protein concentration favour dimer dissociation. The recombinant form of Equ c 1 has been crystallized using ammonium sulfate as a precipitant. The crystals belong to the tetragonal space group P41212 with cell parameters a = b = 84.0, c = 56.1 A, and contain a single molecule in the asymmetric unit. A complete data set from native crystals was collected at the synchrotron source in Hamburg to 2.9 A resolution using a frozen crystal, and structure determination is in progress.
Subject(s)
Allergens/chemistry , Glycoproteins/chemistry , Horses/immunology , Allergens/genetics , Allergens/isolation & purification , Animals , Crystallization , Crystallography, X-Ray , Dimerization , Glycoproteins/genetics , Glycoproteins/isolation & purification , Lipocalins , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purificationABSTRACT
The quaternary organization of the cellulosome, a multi-enzymatic extracellular complex produced by cellulolytic bacteria, depends on specific interactions between dockerin domains, double EF-hand subunits carried by the catalytic components, and cohesin domains, individual receptor subunits linearly arranged within a non-catalytic scaffolding polypeptide. Cohesin-dockerin complexes with distinct specificities are also thought to mediate the attachment of cellulosomes to the cell membrane. We report here the crystal structure of a single cohesin domain from the scaffolding protein of Clostridium thermocellum. The cohesin domain folds into a nine-stranded beta-sandwich with an overall "jelly roll" topology, similar to that observed in bacterial cellulose-binding domains. Surface-exposed patches of conserved residues promote extensive intermolecular contacts in the crystal, and suggest a possible binding target for the EF-hand pair of the cognate dockerin domain. Comparative studies of cohesin domains indicate that, in spite of low sequence similarities and different functional roles, all cohesin domains share a common nine-stranded beta-barrel fold stabilized by a conserved hydrophobic core. The formation of stable cohesin-dockerin complexes requires the presence of Ca2+. However, the structure of the cohesin domain reported here reveals no obvious Ca2+-binding site, and previous experiments have failed to detect high affinity binding of Ca2+ to the unliganded dockerin domain of endoglucanase CelD. Based on structural and biochemical evidence, we propose a model of the cohesin-dockerin complex in which the dockerin domain requires complexation with its cohesin partner for protein stability and high-affinity Ca2+ binding.
Subject(s)
Bacterial Proteins/chemistry , Membrane Proteins/chemistry , Amino Acid Sequence , Bacterial Proteins/metabolism , Binding Sites , Cellulose/metabolism , Clostridium , Crystallography, X-Ray , Membrane Proteins/metabolism , Models, Molecular , Molecular Sequence Data , Molecular Structure , Protein Conformation , Sequence AlignmentABSTRACT
The lectin from the seeds of Cratvlia mollis shows strong binding to human malignant cancerous tissues, particularly those from many glands, uterus, rectum and brain. The C. mollis lectin has been crystallized using the hanging-drop method with polyethylene glycol 6000 as a precipitant. Two different crystal forms were grown from the same drops and they belong to space groups I222 and P2(1)2(1)2(1), respectively. The cell parameters obtained were a = 63.26 (4), b = 77.45 (8) and c = 105.22 (8) A, for the I222 form, and a = 88.83 (5), b = 183.24 (9) and c = 61.70 (2) A for the P2(1)2(1)2(1) crystals. The solution of both structures is currently being attempted by means of molecular replacement techniques.
