Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.     

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure in vitro prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105-135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F1 alpha were generally low. Thromboxane B2 (TXB2) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF1 alpha by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 +/- 4.1 to 43.8 +/- 7.4 ng/g. dry wt./min; 6-oxo-PGF1 alpha production rates increased more than three-fold from 10.0 +/- 2.7 to 34.6 +/- 9.8 ng/g. dry wt./min (means +/- S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB2 by the two groups.     

Sensitive Explosive Vapor Detection with Polyfluorene Lasers

Distributed feedback organic semiconductor lasers based on polyfluorene are shown to be suitable for use as chemical sensors for the detection of nitroaromatic‐based explosive vapors. The laser threshold is increased by a factor of 1.8 and the slope efficiency is reduced by a factor of 3 after exposure to the vapor. The sensing efficiency depends strongly on the excitation energy with a maximum efficiency of 85%. The temporal dynamics of the laser response to the analyte have been investigated. The laser emission falls to 60% of its initial value in 46 s. A model is developed to offer some insight into the diffusion of the vapor molecules inside the polymer layer.     

A computational model for tracking subsurface tissue deformation during stereotactic neurosurgery

Recent advances in the field of stereotactic neurosurgery have made it possible to coregister preoperative computed tomography (CT) and magnetic resonance (MR) images with instrument locations in the operating field. However, accounting for intraoperative movement of brain tissue remains a challenging problem. While intraoperative CT and MR scanners record concurrent tissue motion, there is motivation to develop methodologies which would be significantly lower in cost and more widely available. The approach we present is a computational model of brain tissue deformation that could be used in conjunction with a limited amount of concurrently obtained operative data to estimate subsurface tissue motion. Specifically, we report on the initial development of a finite element model of brain tissue adapted from consolidation theory. Validations of the computational mathematics in two and three dimensions are shown with errors of 1%-2% for the discretizations used. Experience with the computational strategy for estimating surgically induced brain tissue motion in vivo is also presented. While the predicted tissue displacements differ from measured values by about 15%, they suggest that exploiting a physics-based computational framework for updating preoperative imaging databases during the course of surgery has considerable merit. However, additional model and computational developments are needed before this approach can become a clinical reality.     

Transient dynamics of CW intracavity singly resonant opticalparametric oscillators

We study the transient dynamics of CW intracavity, singly-resonant optical parametric oscillators (ICSROs). Relaxation oscillations of the 1064-nm pump light are measured, in both the presence and absence of parametric conversion, in a periodically poled LiNbO₃ (PPLN) CW ICSRO pumped intracavity to a Nd:YVO₄ laser. The presence of parametric conversion is shown to significantly increase both the damping times and oscillation frequencies of the dynamics; at three times the parametric oscillator threshold, these take values of 200 μs and 2 MHz, respectively. Oscillation frequencies are shown to be in good agreement with theoretical values. The influence of energy diffusion and thermal lensing are analyzed to account for discrepences between measured and theoretical damping times. We discuss the implications of the dynamic behavior to the stable-power operation of CW ICSROs     

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.