On the quantification of prothrombin from different species using echis carinatus as activator

The generation of thrombin-like activity from rat, human, bovine and mouse prothrombin by Echis carinatus venom (ECV) treatment was compared using a partially purified system (i.e. whole ECV and isolated prothrombin). A rapid increase in coagulant activity was obtained within 0.5 to 2 min., being constant upon further incubation for 60 min. A large variation in coagulant activity of the ECV generated thrombin from the four species was found, whereas no differences were found for the amidolytic activities. The coagulant activities of the ECV generated thrombin was also low compared with the corresponding thrombin activities obtained by physiological activation. Coagulant activity of the ECV generated thrombin levelled off at increasing concentration of prothrombin in the sample as measured by the one-stage coagulation assay. By measuring amidolytic activity a linear relationship to the concentration of prothrombin was found, however. These findings indicate that ECV converts prothrombin from the four different species to a thrombin-like protein with properties distinct from -thrombin. The lack of linearity in the ECV generated clot activity with increasing concentration of prothrombin could be explained by assuming a dimerization of the thrombin like protein molecules making them less accessible to fibrinogen. The significance of these observations for the quantification of prothrombin from different species is discussed.     

Training Synergies Between Medical Informatics and Health Services Research: Successes and Challenges

Stanford''s two decades of success in linking medical informatics and health services research in both training and investigational activities reflects advantageous geography and history as well as natural synergies in the two areas. Health services research and medical informatics at Stanford have long shared a quantitative, analytic orientation, along with linked administration, curriculum, and clinical activities. Both the medical informatics and the health services research curricula draw on diverse course offerings throughout the university, and both the training and research overlap in such areas as outcomes research, large database analysis, and decision analysis/decision support. The Stanford experience suggests that successful integration of programs in medical informatics and health services research requires areas of overlapping or synergistic interest and activity among the involved faculty and, hence, in time, among the students. This is enhanced by a mixture of casual and structured contact among students from both disciplines, including social interactions. The challenges to integration are how to overcome any geographic separation that may exist in a given institution; the proper management of relationships with those sub-areas of medical informatics that have less overlap with health services research; and the need to determine how best to exploit opportunities for collaboration that naturally occur.Training in medical informatics and health services research has been closely linked at Stanford University for almost two decades. Although the close linkage was deliberate, it was facilitated by historical circumstances, in particular the common academic structures in which both programs arose. In this paper, we describe some of that rationale and history, identifying the areas of overlap that we have pursued in coordinating the training opportunities for graduate students and fellows in both areas of study. As we shall note, the synergies have been great, and in some cases trainees have collaborated closely on research while also taking some of the same courses. We believe that these interactions can be a model for the design of training programs that encourage scholarly interactions between medical informatics and health services research. Although our initial charge was to describe both the successes and failures in integrating the programs, we found that we could not identify any outright failures and that it would be better to delineate the complexities and challenges that we have faced in bringing together these two disciplines.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Sex effects in defensive behavior: Baseline differences and drug interactions

Female rats consistently show a pattern of differences in defensive behaviors compared to males which parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat, a factor which probably also reflects ceiling or floor effects in situations involving very intense defensiveness. In addition, pharmacological studies indicate sex differences in the effects of selective serotonin (5-HT) receptor agonists and antagonists on defensive responding. These findings indicate that sex effects must be considered in studies of the pharmacological control of defensive behaviors, and suggest that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety.     

Theoretical calculation of relative binding affinity in host-guest systems.

The relative free energy of binding the anions Cl- and Br- to the macrotricyclic receptor SC24 in water has been computed by a computer simulation technique. This result and an incidental result for the relative free energy of hydration of the anions are in excellent agreement with experimental data. The simulation approach to ligand-receptor interactions that is described here has significant potential as a predictive tool in chemistry, biochemistry, and pharmacology.     

Comparisons of Pooled Polyclonal Rabbit Anti-Human C3d with Four Monoclonal Mouse Anti-Human C3ds

Performance characteristics of pooled rabbit IgG polyclonal anti-C3d are compared with one mouse IgM and three mouse IgG monoclonal anti-C3d antibodies (MAs). IgG MA,s employed singly or in combination, failed to precipitate C3d; by contrast, IgM MA and polyclonal anti-C3d precipitated C3d. Measurements of polyclonal anti-C3d concentration by chemical means and by 125I-C3d radioimmunoassay (RIA) agreed closely. RIA values were 50% of chemical measurement values for three of the four MAs. Use of sucrose density gradient ultracentrifugation to assess MA C3d/anti-C3d molar combining ratios for soluble anti-C3d/C3d was not possible because fast-sedimenting multimeric C3d/anti-C3d complexes did not form. Dissociation and competitive binding studies indicate that (1) two MAs had substantially lower affinities than the other anti-C3d antibodies, and (2) polyclonal anti-C3d recognizes more C3d epitopes than are recognized by individual MAs. The results demonstrate antigenic complexity of C3d fragment and illustrate the difficulties of predicting individual MA performance based on prior experience with polyclonal antibodies.