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Biomedical subjects

J D Clark

Publications and source records attributed to J D Clark.

At least 19 recordsLinked to original sources
PubMed1998

Hyperalgesia in mice lacking the Kv1.1 potassium channel gene.

Hyperalgesia and morphine induced antinociception were measured in mice lacking the gene for the Shaker-like voltage-gated potassium channel Kv1.1 alpha subunit. The effects of varying gene dosage were studied by comparing homozygous null (-/-) versus heterozygous (+/-) and wildtype (+/+) littermates. Hyperalgesia was measured using the paw flick assay, hot plate assay and formalin induced hind paw licking. It was observed that null mutant animals had significantly shorter latencies to response in the paw flick (36%) and hot plate (27%) assays while their licking times after hind paw injection of formalin was increased in both the first (74%) and second (65%) phases of the response compared to wildtype controls. Morphine induced antinociception in Kv1.1 null mutant animals was blunted. These studies indicate that Kv1.1 plays an important role in nociceptive and antinociceptive signaling pathways.

Animals↗
PubMed1998

Solution structure and membrane interactions of the C2 domain of cytosolic phospholipase A2.

The amino-terminal, 138 amino acid C2 domain of cytosolic phospholipase A2 (cPLA2-C2) mediates an initial step in the production of lipid mediators of inflammation: the Ca2+-dependent translocation of the enzyme to intracellular membranes with subsequent liberation of arachidonic acid. The high resolution solution structure of this Ca2+-dependent, lipid-binding domain (CaLB) has been determined using heteronuclear three-dimensional NMR spectroscopy. Secondary structure analysis, derived from several sets of spectroscopic data, shows that the domain is composed of eight antiparallel beta-strands with six interconnecting loops that fits the "type II" topology for C2 domains. Using a total of 2370 distance and torsional restraints, the structure was found to be a beta-sandwich in the "Greek key" motif. The solution structure of cPLA2-C2 domain is very similar to the X-ray crystal structure of the C2 domain of phospholipase-C-delta and phylogenetic analysis clarifies the structural role of highly conserved residues. Calorimetric studies further demonstrate that cPLA2-C2 binds two Ca2+ with observed Kds of approximately 2 microM in an entropically assisted process. Moreover, regions on cPLA2-C2 interacting with membranes were identified by 15N-HSQC-spectroscopy of cPLA2-C2 in the presence of low molecular weight lipid micelles. An extended binding site was identified that binds the phosphocholine headgroup in a Ca2+-dependent manner and also interacts with proximal regions of the membrane surface. Based upon these results, a structural model is presented for the mechanism of association of cPLA2 with its membrane substrate.

Amino Acid Sequence↗
PubMed1998

Independent folding and ligand specificity of the C2 calcium-dependent lipid binding domain of cytosolic phospholipase A2.

The Ca(2+)-dependent lipid binding domain of the 85-kDa cytosolic phospholipase A2 (cPLA2) is a homolog of C2 domains present in protein kinase C, synaptotagmin, and numerous other proteins involved in signal transduction. NH2-terminal fragments of cPLA2 spanning the C2 domain were expressed as inclusion bodies in Escherichia coli, extracted with solvent to remove phospholipids, and refolded to yield a domain capable of binding phospholipid vesicles in a Ca(2+)-dependent manner. Unlike other C2 domains characterized to date, the cPLA2 C2 domain bound preferentially to vesicles comprised of phosphatidylcholine in response to physiological concentrations of Ca2+. Binding of the cPLA2 C2 domain to vesicles in the presence of excess Ca2+ chelator was induced by high concentrations of salts that promote hydrophobic interactions. Despite the selective hydrolysis of arachidonyl-containing phospholipid vesicles by cPLA2, the cPLA2 C2 domain did not discriminate among phospholipid vesicles containing saturated or unsaturated sn-2 fatty acyl chains. Moreover, the cPLA2 C2 domain bound to phospholipid vesicles containing sn-1 and -2 ether linkages and sphingomyelin at Ca2+ concentrations that caused binding to vesicles containing ester linkages, demonstrating that the carbonyl oxygens of the sn-1 and -2 ester linkage are not critical for binding. These results suggest that the cPLA2 C2 domain interacts primarily with the headgroup of the phospholipid. The cPLA2 C2 domain displayed selectivity among group IIA cations, preferring Ca2+ approximately 50-fold over Sr2+ and nearly 10,000-fold over Ba2+ for vesicle binding. No binding to vesicles was observed in the presence of greater than 10 mM Mg2+. Such strong selectivity for Ca2+ over Mg2+ reinforces the view that C2 domains link second messenger Ca2+ to signal transduction events at the membrane.

Amino Acid Sequence↗
PubMed1998

How UK orthodontists advise patients on oral hygiene.

In 1993, 1038 UK orthodontists (all the members of the British Association of Orthodontists and the British Society for the Study of Orthodontics) were asked by questionnaire about the oral hygiene advice they gave to patients undergoing routine orthodontic treatment. All the orthodontists gave advice on tooth brushing. Most (89.5 per cent) gave dietary advice and (84 per cent) used disclosing tablets. A fluoride rinse was recommended by 73 per cent and a chlorhexidine mouthwash by 41.9 per cent. Many orthodontists advocate appropriate oral hygiene measures, but the efficacy of such methods is determined by the patient's motivation. The orthodontist therefore requires skills in behavioural management. Oral hygiene measures may be more cost-effective when undertaken by trained auxiliaries.

Counseling↗
PubMed1997

CASES--clinical audit; scenarios for evaluation and study.

CASES, an audit and continuing education programme, evaluated aspects of current orthodontic practice and allowed orthodontists to identify areas where their practice differed from regional and national results. Evaluation of the CASES programme verified its value in audit and continuing education and the authors hope it will encourage similar projects in other disciplines too.

Adolescent↗
PubMed1997

Housing and exercise of dogs: effects on behavior, immune function, and cortisol concentration.

We examined the effect of supplemental exercise (either individually or with a conspecific) on the physical and psychological health of dogs by measuring immune, endocrine, and behavioral responses. Forty purpose-bred adult male beagles were assigned to one of four treatment conditions: exercised individually (EI), exercised with a conspecific (EC), nonexercised (NE), or cage control (CC). Each EI dog was removed from its cage, carried to an empty room, and allowed to exercise alone for 20 min/d 3 days a weeks for 12 weeks. Two EC dogs were allowed to exercise together following a similar schedule. To control for potential handling effects, NE dogs were removed from their cages, carried to the exercise room, but immediately returned to their cages, and CC dogs remained in their cages during scheduled exercise periods. Detailed behavioral observations, humoral immune responses to the antigen keyhole-limpet hemocyanin, peripheral blood mononuclear cell subsets, plasma cortisol concentration, body weight, and total and differential white blood cell (WBC) counts were routinely monitored. Results indicated few significant treatment effects on physiologic or behavioral measures. Specifically, EC dogs had lower percentages of B lymphocytes, and EC and EI dogs barked more than did NE or CC dogs. However, some physiologic and behavioral measures changed as a function of time regardless of treatment condition. Most notably, for all dogs over time, WBC counts, plasma cortisol values, and behavioral measures reflecting inactivity decreased, while measures reflecting high activity and abnormal behaviors increased. We concluded that neither exercise treatment substantially altered the physical health of research dogs, and perhaps more importantly, failed to prevent the development of abnormal behavior.

Animal Husbandry↗
PubMed1997

Animal well-being. I. General considerations.

Recently, interest in and concern about animal well-being has been increasing because of changing views toward nonhuman animals, societal attitudes, legislation, and conduct of quality scientific research and testing. Animal well-being is a vague concept that can neither be viewed in a purely objective manner nor simply described, defined, or assessed. It is not a scientifically or technically precise state, but rather a multidimensional one. Factors such as animal needs and perspective, critical anthropomorphism, and human social and individual values are involved. There are limitations in determining the overall well-being of an animal and comparing well-being in disparate environments. Nevertheless, there is an extensive and ever-growing list of complex factors thought to affect homeostasis, sensitivity, interrelationships, and feedback control mechanisms. Research data from a variety of fields, such as animal biology and behavior, stress biology, and psychoneuroimmunology, increasingly support a holistic view of well-being. Existing data suggest an interactive system linking internal psychologic, neurologic, physiologic, immunologic, endocrine, and biochemical events with the external psychosocial and physical environment. An animal's state of well-being or homeostasis is determined by a multitude of external (psychosocial and physical stimuli) and internal (mental and biological responses) factors and interacting variables and by other aspects such as ethology, genetics, individual variation, social milieu, experience, learning, perception, coping style, and intensity, duration, and frequency of stimuli.

Animal Welfare↗
PubMed1997

Animal well-being. II. Stress and distress.

The concepts of stress and distress are integral parts of consideration of animal well-being. Generally, stress refers to a state of threatened homeostasis, but precise clinical definitions, causes, and biological measurements have been controversial and confusing. Numerous factors associated with needs, life in captivity, threatening events, or aversive stimuli may threaten homeostasis. An animal's well-being or quality of life is an individual's internal somatic and mental state that is affected by what it knows or perceives; its feelings and motivational state; the responses to internal or external stimuli or environments; interacting variables; and phylogeny and ontogeny. Threats to homeostasis activate a complex pattern of behavioral changes and responses in the central and autonomic nervous and endocrine systems. Some responses can be considered normal adaptive and coping activities, satisfactorily handling the threats and therefore contributing to well-being. Other responses may be considered abnormal, maladaptive, and affective disorders. A persistent threat may lead to prolonged hyperactivity of the neuroendocrine system, which impairs rather than contributes to well-being. Except for extremes, differentiation between normal and abnormal internal states is frequently unclear. Individual adapting and coping styles may be more important than the stimuli in determining the varied responses. In animals, perception of a stimulus or life event is as important as the actual situation or environment. As caregivers, humans may know that an event or situation is no threat, but the animal usually does not function with the same information base as humans. A principal component in controlling an animal's response to an external event is determining how the animal perceives a situation. Mental and biological well-being is more likely to exist in animals if they are familiar with their environment, including social groups, and if they can predict or anticipate changes in the environment.

Adaptation, Physiological↗
PubMed1997

Animal well-being. III. An overview of assessment.

Assessment of animal well-being is a complex matter. It is difficult to establish a causal link between stimuli and internal state because of numerous variables and the time interval between cause and effect. Many studies document a correlation rather than a causal relationship among stimuli, responses, and subsequent health, disease, or mental state. Research objectives are often vague, the choice of assessment parameters is perplexing, and the results are difficult to interpret. In general, animal well-being cannot be assessed directly. There are no standardized methods or specific endpoints that provide an objective determination. Overt changes in physical and psychological functions occur only after the animal has experienced a prepathologic state. An animal's response to general arousal, life's events, and aversive stimuli depends on an integrated activation of various neural and endocrine factors. A variety of physiologic, biochemical, and behavioral characteristics change when an animal is exposed to aversive situations and stimuli, although many also change with the onset of positive general arousal, such as play, pleasant experiences, and sexual excitement. There is a need to evaluate numerous criteria (e.g., performance, clinical state, neurochemistry, endocrinology, immunology, morphology, behavior, and ethology) to compile a complete mental and biological profile of animals. The various systems, processes, and individual specific responses are interrelated and interact in a well-structured manner. Given the complexity of the topic and the disparate disciplines involved, developing a comprehensive understanding of animal well-being is not straightforward. Consequently, observers should be cautious. Foremost in any determination of animal well-being is assurance that criteria being used are relevant to well-being.

Animal Welfare↗
PubMed1997

Animal well-being. IV. Specific assessment criteria.

A number of factors have potential use as indicators of animal well-being. Classic and practical criteria for assessing animal well-being are a combination of general health status, clinical signs of disease, and performance. Numerous regulatory mechanisms and systems are responsible for many neurochemical and endocrine changes in response to arousing and stimulating events. Neuroendocrine changes associated with aversive stimuli have been implicated in modulation of immune responses. Animal behavior and preference, which can be observed directly and noninvasively, can be useful in assessment of well-being. Aversive conditions, especially longer term, can cause morphologic and pathologic changes in some tissues.

Animal Diseases↗
PubMed1997

How to do it: making audit work.

The orthodontic Audit Working Party of the Faculty of Dental Surgery, Royal College of Surgeons of England, in collaboration with the Centre for Medical Education, Ninewells Hospital and Medical School, Dundee developed an audit project entitled 'Clinical Audit: Scenarios for Evaluation and Study'. The aim of the project was to contribute to the construction of clinical guidelines for orthodontists. This article, the first of a short series, describes the background to and general results of the study. Further articles will study individual aspects of the project.

Adult↗
PubMed1997

Early treatment of Class III malocclusion? Colin's case.

This is the first of six simulated case reports accompanying the questionnaire detailed in the article 'How to Do It: Making Clinical Audit Work' found earlier in this issue. You will find comprehensive discussion of the problem of making a decision about the early treatment of Class III malocclusion.

Age Factors↗
PubMed1997

An extraction dilemma: Cheryl's case.

This article describes treatment options for a teenager with a mild, although aesthetically unpleasing, malocclusion. The opinions of British orthodontists, as obtained through the CASES project, are summarized and the patient's actual treatment is discussed.

Adolescent↗
PubMed1997

Hypodontia: George's case.

Five questions are posed regarding the treatment of a patient with hypodontia. The treatment options are discussed, and the actual treatment carried out demonstrated. The treatment preferences of British Orthodontists, elicited through the CASES project, are also included.

Anodontia↗
PubMed1996

Practical application of the PAR index: an illustrative comparison of the outcome of treatment using two fixed appliance techniques.

A retrospective assessment of treatment outcome in a group of 82 orthodontic fixed appliance cases was carried out using the Peer Assessment Rating Index (PAR) in order to explore the usefulness of the PAR index as a means of differentiating the change associated with treatment. Two different fixed appliance techniques, the pre-adjusted Edgewise and the Begg appliance had been used to treat these cases, and all had been under the care of one Consultant Orthodontist. The mean percentage reduction in PAR for the group as a whole was 74 per cent. Comparison of the two different appliance types found that the pre-adjusted Edgewise group achieved a significantly greater reduction in PAR score (81 per cent), than the Begg group (65 per cent). Cases with a low PAR score prior to treatment tended to fare more poorly in terms of percentage reduction and this was more marked for those cases treated with the Begg appliance. Although the PAR index has a high degree of reproducibility, it was found that even the small error present can lead to problems of interpretation if the nomogram categories are used as a method of comparison. Some potential problems in undertaking studies such as this using the PAR index to assess treatment outcome are discussed.

Case-Control Studies↗
PubMed1996

"Ovarian asthma"-- act or fancy?

Hormonal interactions have been suspected of worsening airways dysfunction in a subgroup of female asthmatics. Despite reports of fatal and near-fatal asthma attacks associated with menstruation, there is little consensus about the impact of this biologic function on the clinical expression of asthma. The authors present a young asthmatic female whose episodic and potentially fatal worsening of asthma typically occurred within the days prior to her menses in the absence of other trigger factors.

Adult↗