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J K Bell

Publications and source records attributed to J K Bell.

5 recordsLinked to original sources
PubMed2005

A repetitive movement detector used for automatic monitoring and quantification of scratching in mice.

We have designed an economical non-invasive movement detector for small animal studies and used it for monitoring and quantifying itch in mice. The system is based on a sensitive force transducer positioned below a recording platform holding a lightweight polystyrene recording box in which an animal is placed. A programmed micro-controller is used to discriminate between non-specific movement, grooming behaviour, and scratching movements made by the animal's hind limb. Following sub-dermal injection of histamine receptor agonists into the neck of a mouse, dose-related scratching occurred which was detected and quantified. There was 91% correlation between bouts of scratching as counted manually from playback of the video recording and recorded by the detector. The detector was also able rapidly to count the individual scratch movements of the hind limb that comprise a bout, with 95% accuracy in comparison with manual counting during slow motion playback of video tape, something that is impossible for an unaided observer to achieve because individual scratch movements are too fast to discriminate by eye. Separate detectors were used for the efficient non-invasive study of four animals simultaneously, and this number could easily be increased by adding more platforms. The system could also be modified to record the animal's position within the box, which would be of value in studies involving exploratory behaviour. In summary, the non-invasive multichannel repetitive movement detector will be very useful for accurate measurement of scratching during pruritus studies in small animals, with considerable savings in staff time and effort. It should therefore be a valuable tool for helping to investigate pruritus and in the evaluation of anti-pruritic drugs.

Animals↗
PubMed2004

Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice.

The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.

Animals↗
PubMed2004

Bispectral index monitoring for conscious sedation in intervention: better, safer, faster.

AIM: The aim of this study was to compare subjective (Ramsay sedation score, RSS) with objective electroencephalogram-based bispectral index (BIS) assessment, and to validate the appropriate BIS range for measurement of conscious sedation in interventional procedures. MATERIALS AND METHODS: One hundred patients undergoing sedo-analgesia (midazolam and fentanyl) for interventional gastrointestinal procedures were divided into two groups. In group A (n=30) sedation was guided by the RSS with the operator blinded to the BIS recording. In group B (n=70) the operator titrated intravenous sedation to maintain an optimal BIS, predetermined from the results in group A. Recovery time, procedure duration, physiological parameters and unplanned events were recorded in both groups. RESULTS: There was a significant correlation between the BIS and RSS (p<0.001). BIS values of 87.2 and 80.9 corresponded to an RSS of 3 and 4, respectively. The optimal BIS level was defined as 80-85. Fifty-seven point five percent of readings were within this range in group B compared with 26.5% in group A (p<0.001). Sedation approaching general anaesthesia (BIS<60) occurred in 5.5% of patients in group A but not in group B. Mean recovery time, duration of procedure, midazolam and fentanyl doses were significantly reduced in group B. Unplanned events were reduced from 27 to 17%, but this was not statistically significant (p=0.29). CONCLUSION: BIS monitoring enables more effective titration of sedatives to maintain a suitable level of consciousness, whilst reducing procedure time. The BIS offers an objective, safe and reliable measure of sedation, without disturbing either patient or operator. BIS monitoring raises the standard of patient care, and in our view, should be used to augment standard assessment.

Aged↗
PubMed2001

Structural analyses of a malate dehydrogenase with a variable active site.

Malate dehydrogenase specifically oxidizes malate to oxaloacetate. The specificity arises from three arginines in the active site pocket that coordinate the carboxyl groups of the substrate and stabilize the newly forming hydroxyl/keto group during catalysis. Here, the role of Arg-153 in distinguishing substrate specificity is examined by the mutant R153C. The x-ray structure of the NAD binary complex at 2.1 A reveals two sulfate ions bound in the closed form of the active site. The sulfate that occupies the substrate binding site has been translated approximately 2 A toward the opening of the active site cavity. Its new location suggests that the low catalytic turnover observed in the R153C mutant may be due to misalignment of the hydroxyl or ketone group of the substrate with the appropriate catalytic residues. In the NAD.pyruvate ternary complex, the monocarboxylic inhibitor is bound in the open conformation of the active site. The pyruvate is coordinated not by the active site arginines, but through weak hydrogen bonds to the amide backbone. Energy minimized molecular models of unnatural analogues of R153C (Wright, S. K., and Viola, R. E. (2001) J. Biol. Chem. 276, 31151-31155) reveal that the regenerated amino and amido side chains can form favorable hydrogen-bonding interactions with the substrate, although a return to native enzymatic activity is not observed. The low activity of the modified R153C enzymes suggests that precise positioning of the guanidino side chain is essential for optimal orientation of the substrate.

Binding Sites↗