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.     

A mechanical study of six digital pulley reconstruction techniques: Part I. Mechanical effectiveness

A laboratory study on fresh-frozen human cadaver limbs compared six types of flexor tendon pulley reconstruction in the fingers. The reconstructions used were those described by (1) Bunnell, (2) Karev, (3) Weilby, and (4) Lister, and two types developed by us that have not been previously described. The pulleys were studied in specific configurations to determine their effectiveness in transforming tendon excursion into finger flexion. In each finger, comparison was made between the amount of tendon excursion required for full flexion with an intact pulley system versus the various types of reconstructed pulleys. The ratio of these two values was defined as the mechanical effectiveness of the pulley reconstruction. The Karve reconstruction was most effective at 108.2%, which was significantly different from the other five reconstructions (p less than 0.01). The remaining reconstructions ranged in effectiveness from 80.0% to 88.5%.     

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.     

Comparison of Track XI fluorometric immunoassay with Bio-EnzaBead enzyme-linked immunosorbent assay for detection of serum antibody to mouse hepatitis virus.

The Track XI system (Microbiological Associates, Bethesda, Md.) was compared with the Bio-EnzaBead assay (Organon Teknika, Durham, N.C.) for the detection of antibody to mouse hepatitis virus (MHV). Strain A/J mice were inoculated intranasally with MHV type 3. Sera were collected at 1, 2, 4, and 9 weeks postinoculation and tested. Individual serum samples were retested twice by each method. The results suggested that the Track XI system was more sensitive and reliable than the Bio-EnzaBead assay in detecting antibody to MHV type 3 in individual serum samples from A/J mice.     

Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF

BACKGROUND: Lead remains in high levels in the environment and is known to reduce fertility in animal models, but a direct link between lead exposures and human infertility has not yet been established. METHODS: In a prospective, double-blind study of the metal ion levels and sperm function, semen was obtained from partners of 140 consecutive women undergoing their first IVF cycle. Lead in seminal plasma was determined by atomic absorption spectroscopy. Motile sperm populations were assessed for surface receptors for mannose binding, and the ability to undergo premature ('spontaneous'), and free mannose-induced acrosome reactions. Fertile donor (n = 9) sperm were exposed to exogenous lead during capacitating incubations and then assessed for mannose receptor expression and acrosome loss. RESULTS: Lead levels were negatively correlated with IVF rates. Lead levels were negatively correlated to two of the three sperm function biomarkers (mannose receptors, mannose-induced acrosome reactions). Lead levels positively correlated with the spontaneous acrosome reaction. These findings were mimicked by in-vitro exposure of fertile donor sperm to lead. CONCLUSIONS: Multiple sperm parameters are affected as lead levels rise. Increased lead levels may contribute to the production of unexplained male infertility.     

Modeling a medical environment: an ontology for integrated medical informatics design

Modern medical environments have seen an increase in technological complexity and pressures of handling more patients with fewer resources, resulting in higher demands on medical practitioners. Medical informatics designers will have to focus on the problem of organizing medical information more effectively to enable practitioners to cope with these challenges. This article addresses this research problem for the particular area of medical problem solving in patient care. First, we describe a traditional modeling approach for medical reasoning used as a basis for developing some decision support systems. We argue these models may be faithful to what is known about biomedical knowledge, but they have limitations for human problem solving, especially in unanticipated situations. Second, we present an ontological framework, known as the abstraction hierarchy (Rasmussen, IEEE Trans. Man. Cybernetics 15 (1985) 234-243), for integrating patient representations that are faithful to existing biomedical knowledge and that are consistent with what is known about human problem solving. Through an example of a critical event in the operating room, we reveal how this framework can support medical problem solving in unanticipated situations. Third, we show how to use these representations as a frame of reference for mapping medical roles, responsibilities, sensors, and controls in an operating room context. Finally, we provide some insight for medical informatics designers in using this framework to design novel training programs and human-computer displays.     

Lectins in diagnostic microbiology

Current literature suggests that lectins are becoming valuable reagents for the laboratory identification of infectious agents. The identification of bacteria, fungi, or protozoa may be confirmed if they bind to or agglutinate with certain lectins. Assay kits utilizing specific lectin agglutination reactions, coupled with conventional enzyme determinations, have been proposed for several bacteria. Factors such as specificity, stability, assay rapidity, and costs combine to make lectins attractive diagnostic reagents. It is likely that the use of lectins in diagnostic microbiology will continue to grow.