The cytotoxic effect of anthrax lethal toxin on human lung cells in vitro and the protective action of bovine antibodies to PA and LF.

The excretion of protein toxins by vegetative cells of Bacillus anthracis is critical to the development of the lethal consequences of anthrax, particularly inhalational anthrax. Whilst the lung macrophages and other phagocytic cells transfer the spores from the lung cavities into the lymphatic system, and provide an initial germination site for the proliferation of the vegetative cells, it appears that much of the tissue pathology at the time of the host's death could be due to the action of the toxins, especially lethal toxin-protective antigen (PA) plus lethal factor (LF). The widespread tissue oedema and hypoxia may in part reflect a direct attack by lethal toxin on vascular endothelial cells.

Monoclonal antibodies to ricin: in vitro inhibition of toxicity and utility as diagnostic reagents.

Monoclonal antibodies (MAbs) against ricin toxin (RT) and its subunits were produced in mice. The MAbs were initially selected based upon the ability to either bind ricin or the individual subunits in a solid-phase enzyme-linked immunosorbent assay (ELISA). Several candidates were selected for further evaluation, including their ability to inhibit ricin intoxication in vitro and their utility as immunodiagnostic reagents.

Therapy and prophylaxis of inhaled biological toxins.

This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors.

Characterization of the Asialofetuin microtitre plate-binding assay for evaluating inhibitors of ricin lectin activity.

Optimum conditions for the binding of ricin to the glycoprotein asialofetuin immobilized on microtitre plates were investigated for the purpose of evaluating inhibitors of ricin B-chain lectin activity. Such inhibitors are of potential value in the use of immunotoxins based on ricin. This assay was first reported in 1986, but has not been characterized fully.

Blockade of cardiac nicotinic responses by anticholinesterases.

1. Tacrine (10 microM) and physostigmine (10 microM) completely inhibited the positive chronotropic and inotropic actions of acetylcholine (ACh) or nicotine in the atropinized guinea pig right atria. 2.

Biosensors for chemical and biological agents of defence interest.

This review discusses current developments in biosensors for toxic materials of defence interest with particular emphasis on the biological element of such devices. A wide variety of synthetic chemicals, toxins of plant or animal origin and biological materials--including various disease micro-organisms as well as some bacterial exotoxins--have either been used as warfare agents or are perceived as having the potential to be used for that purpose. Although an enormous effort is being put into developing biosensors, relatively few analytes, especially toxic materials, can yet be measured by commercially available devices.

Simple high-performance liquid chromatographic method for assessing the deterioration of atropine-oxime mixtures employed as antidotes in the treatment of nerve agent poisoning.

A set of reversed-phase HPLC conditions for determining the degradation of atropine and the oxime (pralidoxime, obidoxime, or HI-6) in autoinjectors designed for use against nerve agent poisoning is described. The assay conditions for atropine do not require its prior separation from the large molar excess of oxime since both the atropine and tropic acid peaks elute well clear of the oxime and its degradation products and the phenolic preservatives. Further dilution of the sample and simple changes to the mobile phase then provide conditions for the oxime and its major degradation products to be quantitated.

A scanning fluorometer for imaging ischaemic areas in traumatized muscle.

The criteria used to evaluate the state of muscle surrounding a bullet wound are: a lack of contractility, a lack of capillary bleeding, and changes in colour and consistency. Muscle with all these properties may be assumed to be irreversibly damaged. However, the boundary between such tissue and tissue with potentially reversible levels of damage may not be clear cut.

Scanning fluorometer for the rapid assessment of pyridine nucleotide and flavoprotein fluorescence changes in tissues in vivo.

This paper describes a scanning fluorometer which produces images in real time of the distribution of pyridine nucleotide or flavoprotein fluorescence at the surface of tissues in vivo. The basic difference between this device and others reported in the literature is that fluorescence changes at any selected point within the image can be quantified as they occur. We suggest that the apparatus has potential application in those areas of surgery where vascular replacement or repair is required and where it would be advantageous to have an immediate measure of the cellular response to a return of blood flow.

A cytoplasmic component of pyridine nucleotide fluorescence in rat diaphragm: evidence from comparisons with flavoprotein fluorescence.

Pyridine nucleotide (PN) and flavoprotein (Fp) fluorescence were monitored in the isolated intact rat diaphragm. A substantial increase in PN fluorescence occurred when N2 replaced O2 in glucose medium. This response was much reduced in pyruvate medium and/or by pretreatment with iodoacetic acid (IAA).

Fine-structure studies of experimental skeletal muscle trauma.

A study was made of damage to skeletal muscle caused by a high-velocity rifle bullet. Such damage extends peripherally from the permanent wound cavity and is focal in nature. A fine-structure investigation of this region suggests that some components of the muscle are more susceptible to the wounding process than others.

Evidence that prostaglandin is responsible for the 'rebound contraction' following stimulation of non-adrenergic, non-cholinergic ('purinergic') inhibitory nerves.

The prostaglandin synthesis inhibitor, indomethacin, blocks the "rebound contractions" which characteristically follow the inhibitory responses of the guinea-pig taenia coli to non-adrenergic, non-cholinergic (purinergic) nerves and to exogenously applied ATP, without affecting the responses to periaterial adrenergic nerves. Since adenine nucleotides are known to induce prostaglandin synthesis, this result is consistent with the purinergic hypothesis and suggests that purinergic nerves may form a link with prostaglandin in the physiological regulation of a variety of organs.