Directed selection of recombinant human monoclonal antibodies to herpes simplex virus glycoproteins from phage display libraries.

Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome

THE AIM OF THE STUDY There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. RESULTS Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. CONCLUSIONS Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.

Comentarios de la guerra de España e historia de su rey Phelipe V el animoso desde el principio de su reynado hasta la Paz General del año 1725 : dividido en dos tomos /

Se publicaron diversas ediciones desde 1725.

[Tomo segundo de los comentarios de la guerra de España /

Mode of access: Internet.

[Comentarios de la guerra de España e historia de su Rey Phelipe V, el Animoso, desde el principio de su reynado hasta la paz general del año 1725. Dividido en dos tomos /

Según Palau, II, p. 2 hay una reimpresión conservando el nombre del ed. italiano: "En Sevilla, por Matheo Garvizza", sin año. Coinciden las pág.

Memorias políticas y militares : para servir de continuación a los Comentarios del Marques de San Felipe... /

Mode of access: Internet.

Comentarios de la guerra de España e historia de su rey Phelipe V el animoso desde el principio de su reynado hasta la Paz general del año de 1725 : dividido en dos tomos /

Mode of access: Internet.

Comentarios de la guerra de España, e historia de su Rey Phelipe V El Animoso, desde el principio de su reynado, hasta la paz general del año de 1725 : dividido en dos tomos /

Mode of access: Internet.

Memorias politicas y militares : para servir de continuacion a los comentarios del Marques de S. Phelipe /

Mode of access: Internet.

Comentarios de la guerra de España e historia de su rey Phelipe V el animoso desde el principio de su reynado hasta la Paz General del año 1725 : dividido en dos tomos /

Se publicaron diversas ediciones desde 1725.

Comentarios de la guerra de España, e historia de su Rey Phelipe V el animoso, desde el principio de su reynado, hasta la paz general del año de 1725 : dividido en dos tomos /

Mode of access: Internet.

Los Tobias : su vida, escrita en octavas /

Mode of access: Internet.