The histamine H 4 receptor is a novel G-protein-coupled receptor with a unique pharmacological profile. The distribution of H 4 mRNA suggests that it may play a role in the regulation of immune function, particularly with respect to allergy and asthma. To define the histamine-binding site of this receptor, molecular modeling and site-directed mutagenesis were used to predict and alter amino acids residing in the histaminebinding pocket. The effects of these alterations on histamine binding and receptor activation were then assessed. (6.52) in TM6 play a role in receptor activation but are not involved in histamine binding. Taken together, these data indicate that although histamine seems to bind to the H 4 receptor in a fashion similar to that predicted for the other histamine receptor subtypes, there are also important differences that can probably be exploited for the discovery of novel H 4 -selective compounds.

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ABSTRACT1. Assessments of anthropogenic impacts on cetaceans are often constrained by limited data on the extent to which these species use particular areas.2. Timing porpoise detectors (T-PODs) are autonomous data recorders for detecting cetacean echolocation clicks, potentially providing cost-effective opportunities for monitoring cetacean occurrence.3. The performance of T-PODs was assessed in three areas off the Scottish east coast, where the relative occurrence of bottlenose dolphins and harbour porpoises was known to differ. Land-based observations in one area compared visual and acoustic detections of dolphins, while direct hydrophone recordings of dolphin echolocation clicks were compared with T-POD detections during boat surveys.4. Land-based surveys recorded 89 groups of dolphins within 900 m of the T-POD. All groups spending 430 min in the area were detected on the T-POD, and the probability of detection declined in relation to distance from the recording site.5. The number of dolphin clicks recorded on the independent hydrophone system was significantly related to the number detected by a T-POD. Between pairs of T-PODs, there was also significant correlation with the numbers of clicks recorded in each hour, both for channels set to detect bottlenose dolphins and for channels set to detect harbour porpoises.6. Year-round deployments of paired T-PODs detected significant geographical variation in detections for both bottlenose dolphins and harbour porpoises. This pattern reflected published data from visual surveys, where dolphins occurred most regularly within the Moray Firth Special Area of Conservation, and porpoises were sighted more regularly in offshore waters.7. T-PODs do not detect all cetaceans in the area, and care must be taken when interpreting data from mixed species communities. Nevertheless, these results confirm that T-PODs provide an effective method for monitoring the occurrence of bottlenose dolphins and harbour porpoises, and provide excellent potential for collecting baseline data from poorly studied areas and monitoring long-term temporal change in key areas of interest.

Hepatitis C infection is widespread throughout the community. This study aimed to assess the status of oral health of persons infected with hepatitis C. DMFT and CPITN indices were recorded at a clinic providing priority dental care for people with hepatitis C infection. The data were compared with information from an existing survey of general dental patients. Social impact Profile questionnaire. The DMFT index differed significantly between hepatitis C and general patients. The number of decayed and missing teeth was greater in those infected with hepatitis C for all patients aged between 25 and 50 years. Although there was no significant difference in CPITN categories for subjects evaluated, a marked trend for poor periodontal health was noted for those individuals with hepatitis C. Salivary flow was reduced in 50 per cent of hepatitis C infected subjects. Social impact was significantly affected with 71 per cent of hepatitis C subjects reporting painful aching in the mouth and 56 per cent having difficulty in relaxing. In conclusion, the results from the project strongly indicate an urgent need for priority delivery of dental care for people with hepatitis C infection.

AD101 and SCH-C are two chemically related small molecules that inhibit the entry of human immunodeficiency virus type 1 (HIV-1) via human CCR5. AD101 also inhibits HIV-1 entry via rhesus macaque CCR5, but SCH-C does not. Among the eight residues that differ between the human and macaque versions of the coreceptor, only one, methionine-198, accounts for the insensitivity of macaque CCR5 to inhibition by SCH-C. Thus, the macaque coreceptor engineered to contain the natural human CCR5 residue (isoleucine) at position 198 is sensitive to HIV-1 entry inhibition by SCH-C, whereas a human CCR5 mutant containing the corresponding macaque residue (methionine) is resistant. Position 198 is in CCR5 transmembrane (TM) helix 5 and is not located within the previously defined binding site for AD101 and SCH-C, which involves residues in TM helices 1, 2, 3, and 7. SCH-C binds to human CCR5 whether residue 198 is isoleucine or methionine, and it also binds to macaque CCR5. However, the binding of a conformation-dependent monoclonal antibody to human CCR5 is inhibited by SCH-C only when residue 198 is isoleucine. These observations, taken together, suggest that the antiviral effects of SCH-C and AD101 involve stabilization, or induction, of a CCR5 conformation that is not compatible with HIV-1 infection. However, SCH-C is unable to exert this effect on CCR5 conformation when residue 198 is methionine. The region of CCR5 near residue 198 has, therefore, an important influence on the conformational state of this receptor.