CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPalpha 1.

The rat OX41 antigen is a cell surface protein containing three immunoglobulin superfamily domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM). It is a homologue of the human signal-regulatory protein (SIRP) also known as SHPS-1, BIT or MFR. Cell activation-induced phosphorylation of the intracellular ITIM motifs induces association with the tyrosine phosphatases SHP-1 and SHP-2. To identify the physiological OX41 ligand, recombinant OX41-CD4d3+4 fusion protein was coupled to fluorescent beads to produce a multivalent cell binding reagent. The OX41-CD4d3+4 beads bound to thymocytes and concanavalin A-stimulated splenocytes. This interaction was blocked by the monoclonal antibody (mAb) OX101. Affinity chromatography with OX101 mAb and peptide sequencing revealed the rat SIRP ligand to be CD47 (integrin-associated protein). A direct interaction between human SIRP and human CD47 was demonstrated using purified recombinant proteins and surface plasmon resonance ruling out the involvement of other proteins known to be associated with CD47. The affinity of the SIRP/CD47 interaction was K(d) approximately 8 microM at 37 degrees C with a k(off )>/=2.1 s(-1). The membrane-distal SIRP V-like domain was sufficient for binding to CD47.

Homicide or suicide: the killing of suicidal persons by law enforcement officers.

This paper presents 15 deaths of suicidal persons in Oregon and Florida who, by their behavior, sufficiently provoked law enforcement officers into killing them. Four deaths were certified as suicide, one as undetermined and ten as homicide. All of the deaths are individually described in detail and their case characteristics are presented in a table. The method of study is a descriptive analysis of the case characteristics, including 21 variables which are determined to be relevant to the classification of death. The variables were grouped into six categories: (a) personal information; (b) criminal behavior during the fatal incident; (c) dangerous behavior during the fatal incident; (d) toxicological data; (e) mental illness information; and (f) certification data. From the analysis, reasons for the opinions on manner of death classification are presented. All incidents were perceived as life-threatening to law officers, family members, or hostages. All victims were male except one, and all were Caucasian except two. All victims resisted arrest and verbally threatened homicide during the fatal incident. Two-thirds of the victims took hostages. All victims possessed an apparent handgun or other weapon (knife, iron bar). All victims posed their weapon and threatened others during the incident, 60% of victims actually used the weapon with apparent intent to inflict damage to others. 40% of victims were intoxicated with alcohol but other drug-involvement was uncommon. Seven of 15 had previous suicide attempts, 40% had medically documented psychiatric diagnoses and 60% had reasonable historical evidence of psychiatric diagnoses, most commonly depression or substance abuse. One of the co-authors presents the case for some of the deaths to be certified as suicides, whereas two present the case for all to be certified as homicide. A brief discussion of psychiatric issues is also presented concerning individuals who use others to commit suicide and who may engage in dangerous and/or criminal behavior to do so. A major conclusion is that there is lack of a unified opinion on death certification procedures for individuals who have provoked law enforcement officers to kill them. For such cases, it is recommended that professional organizations of medical examiners/coroners develop guidelines to promote consistency in death certification practices including manner of death classification and selection of death certificate wording so that "police-assisted suicide" may be appropriately reported and studied.