In brief

The UK Post Office has rolled out a wide area network encryption technology to protect its connections to the Link ATM network as it upgrades from X.25 to IP. This coincides with a major programme that the Post Office has introduced for the payment of state benefits electronically.     

Radiosensitization and apoptosis

The toxicity of radiation to living tissues was discovered soon after the discovery of radioactivity itself and this toxicity is the basis for cancer therapy with radiation. Although this mode of therapy is often effective, its success is far from assured. One major difficulty in the implementation of radiotherapy is that normal tissues are also sensitive to killing by radiation so that treatment is often limited by the tolerance of normal tissues for radiation. Thus methods that sensitize tumor cells while sparing normal tissues could potentially lead to greater success with radiation as a therapy. Oncogenes are frequently altered in tumors, but are not in normal tissue making them potential targets for altering radiosensitivity and apoptosis in tumors.     

Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle

Four calves were experimentally infected via aerosol with foot-and-mouth disease virus. Two were infected with a wild-type virus derived from a full-length infectious clone (A12-IC), and two were infected with a clone-derived virus lacking the leader gene (A12-LLV2), with euthanasia and tissue collection at 24 and 72 h postexposure (hpe). Clinical disease was apparent only in the animal given A12-IC and euthanized at 72 hpe. In situ hybridization revealed that the animal infected with A12-IC and euthanized at 24 hpe had abundant viral nucleic acid in the lung, present in clusters of positive cells in the respiratory bronchiolar epithelium and associated subepithelial regions. At 72 hpe in the A12-IC-infected calf, viral nucleic acid in the lung was present in interstitial areas, and in addition, viral nucleic acid was detectable in epithelial tissues around histologically apparent vesicles. In animals infected with A12-LLV2, viral nucleic acid was detectable in the lung at both 24 and 72 hpe, but staining revealed a more localized distribution with less nucleic acid than was found in animals given A12-IC. Therefore, it appears that after aerosol exposure to A12-IC, early replication is in the region of the lung, with subsequent dissemination to distal sites. In comparison, the A12-LLV2 virus is much less widely disseminated in the lung at 24 hpe, with no lesions or virus detectable in secondary sites at 72 hpe. The greatly reduced pathogenicity of A12-LLV2 may make it an excellent candidate for a modified live viral vaccine.     

The measurement of bioreductive capacity of tumor cells using methylene blue

PURPOSE: Methylene blue (MB) can be used as an intracellular electron acceptor. The purpose of this study was to demonstrate the usefulness of MB for the determination of total bioreductive capacity of cell suspensions. METHODS AND MATERIALS: We measured oxygen consumption by Clark electrode and pentose cycle activity by release of 14CO2 from 1-14C-glucose. RESULTS: Methylene blue catalyzes the reaction of intracellular reductants NADPH, NADH, and reduced glutathione (GSH) with oxygen, causing the production of hydrogen peroxide. The reaction rate correlates with the negative charge of molecule (NADPH(-4) > NADH(-2) > GSH(-1)), suggesting that reaction with positively charged oxidized MB is the limiting step of the reaction. In a cellular system MB causes the electron flow from cellular endogenous substrates to oxygen. It is activated by the disruption of the NADP+/NADPH ratio due to several processes. These are direct oxidation of NADPH and GSH, the GSH peroxidase catalyzed reaction of GSH with H2O2, followed by NADPH oxidation by oxidized glutathione (GSSG). This results in increased cellular oxygen consumption and stimulation of the oxidative limb of pentose cycle (PC) in the presence of MB. The cellular effect of MB differs from other electron accepting drugs. Diamide and tert-butylhydroperoxide act as direct oxidants, while MB is an electron carrier to oxygen. Accordingly, MB shows the highest effect on PC activation and oxygen consumption. CONCLUSIONS: Our results indicate that MB may be used for the determination of the total bioreductive capacity of the cells, measured by oxygen consumption and PC activation.     

A novel insertional mutation in loricrin in Vohwinkel's Keratoderma

A mutation in the gene encoding loricrin has recently been reported in a subset of patients with Vohwinkel's Keratoderma manifesting an associated ichthyosiform dermatosis. We have studied a further kindred with this clinical phenotype. Microsatellite marker analysis was consistent with linkage to chromosome 1q21 and direct sequencing of loricrin identified a heterozygous mutation with an insertion of a T residue at codon 209. This mutation is predicted to produce a mutant protein with a frameshift of its terminal 107 amino acids and to be 22 amino acids longer than the wild-type protein due to a delayed termination codon. The only previously reported mutation is a G insertion producing a frameshift after codon 231. The novel mutation we report is likely to have a similar functional effect on cornified envelope formation, with disturbance of transglutaminase-mediated cross-linking of envelope components, and serves to confirm the predicted role of insertional mutations in Vohwinkel's Keratoderma associated with ichthyosis.     

Spot and Aspirated Laser Smoke Detection in Telecommunications Facilities

Full-scale, in-situ comparison tests of spot and aspirated laser detection systems in an active telephone switch center were conducted to compare the response times of spot and aspirated smoke detection systems when exposed to a variety of smoke sources and ventilation conditions. The report documents the performance of multiple systems varying in detector type, detector spacing and detector locations (i.e., mounted on the ceiling versus on return air grills). The work provides data intended to guide system designers in the selection and use of very early warning smoke detection systems.