Trypsin interaction with the senile plaques of Alzheimer disease is mediated by β-protein precursor

In this study we demonstrate byin situ binding that trypsin interacts with the senile plaques found in Alzheimer disease. Characterization of various potential trypsin binding proteins shows that trypsin binding is mediated by β-protein precursor (βPP)—the progenitor of amyloid-β in senile plaques. Using specific antisera against various proteins to sterically block trypsin blocking, we found that only those antibodies raised against proteins or peptides containing the Kunitz protease inhibitor domain were able to abolish binding. By analogy with other protease/inhibitor interactions, we speculate that the binding of trypsin to βPP could involve concomitant βPP cleavage. Therefore, βPP in protecting against potentially damaging proteolysis could simultaneously liberate βPP fragments or intermediate precursors of amyloid-β deposits.     

An unusual rotational fracture-dislocation of the thoracic spine without neurologic sequelae internally fixed with a combined anterior and posterior approach

A rare complete lateral dislocation of the thoracic spine with preservation of neurologic function is reported. Anatomic reduction was obtained using an anterior approach and Harrington distraction rods for reduction followed by a broad plate and subsequent posterior segmental fixation and fusion. Long-term followup showed an excellent result.     

Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat

The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress-strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis.     

Autotomy and the sciatic functional index

The rat sciatic nerve serves as a good model of nerve regeneration and, as such, is often used in investigations of nerve repair. After transection of the sciatic nerve, rodents frequently scratch and bite their anesthetic foot, resulting in amputation of one or more toes. This is termed autotomy or autophagy. When these rats are part of a study using the sciatic functional index (SFI), autotomy results in unusable data, since necessary foot landmarks have been removed. It would be helpful, therefore, to be familiar with the phenomenon of autotomy and to know which rats are least likely to mutilate themselves. In our experiment involving 64 rats in which the sciatic nerve was transected and repaired, we found that female Sprague-Dawley rats were significantly less likely to perform autotomy than males (33% vs. 65%, P =.04). In addition, we noted that two-thirds of the autotomies that occurred did so by postoperative week 4 and that tabasco sauce did not decrease this activity. We present our experience and a survey of the literature on autotomy and the SFI. © 1993 Wiley-Liss Inc.     

Brief report: Does fenfluramine treatment enhance the cognitive and communicative functioning of autistic children?

This project was supported by two separate research grants from the Trust Fund Board, Washington Association for Retarded Citizens to Richard Neel and Truman E. Coggins. The research was also supported by a training grant to the University of Washington entitled Comprehensive Training in Mental Retardation and Other Handicapping Conditions (MCH-000913, Clifford J. Sells, M.D., Principal investigator); and, a training grant to the University of Arizona entitled Doctoral and Post-Doctoral Leadership Training and Clinical Research, Teaching and Administration: Clinical Language Research Center (G008630088, Linda Swisher, Ph.D., principal investigator). We are indeed grateful to the parents of our five subjects for their patience, understanding, and commitment. Finally, we express our appreciation to Arelene Chaussee for her technical expertise and untiring spirit.     

Evaluation of several film/screen combinations for megavoltage radiation therapy treatment field verification

The introduction of a lower cost alternative to a film commonly used for megavoltage radiation therapy port films led to a comparison of two films (Kodak X-TL and X-OMAT G) in four metal screen cassette configurations. In addition to determination of H-D curves and point spread functions, images of humanoid phantom sections were obtained and evaluated for clinical "usefulness." The X-OMAT G film-screen combinations compared favorably with the X-TL film combinations with respect to the H-D Curves and point spread functions but there was a slight preference for X-TL film. There were no differences noted whether the film was used in the standard "ready pack" or naked in the cassettes.