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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 451 records · Page 25Linked to original sources

Anorexia nervosa presenting in a prepubertal boy.

A case of anorexia nervosa that presented in a prepubertal boy is reported. It seemed that particular maternal attitudes towards dieting, paternal criticism of the boy's body shape and size, and severe family disruption were the major factors in the aetiology of this disorder. If such attitudes to food intake and body size and shape and major family disruptions become more prevalent in the community, then one might expect to see an increase in the prevalence of this serious disorder in younger children, which results in serious physical and psychological sequelae.

Anorexia Nervosa↗

Young children's understanding of the say-mean distinction in referential speech.

Four experiments were conducted to investigate 6-year-old children's understanding of the say-mean distinction in referential speech. In Experiments 1 to 3, children heard stories in which a listener found an object that only approximated a speaker's description. They were subsequently asked if the object was the one the speaker had intended. When cues prominently indicated that the object was the referent, 6-year-olds often judged that it was the one that the speaker had intended. Thus, children displayed an awareness of intended meaning as distinct from message meaning. Consistent with this, 6-year-olds in Experiment 4 associated "saying X by accident" with "making a slip of the tongue." Thus, the children appeared to be aware of a factor which can result in message meaning deviating from intended meaning. However, unlike older children, 6-year-olds did not vary between literal and nonliteral interpretations of a message in accordance with information relevant to the speaker's state of memory. We conclude that young children are ineffective at utilizing others' informational states in deciding whether a literal or nonliteral message interpretation is appropriate.

Child↗

American Association of Critical-Care Nurses demonstration project: patients' recollections of critical care.

Although more patients are surviving illness that requires critical care, little is known about the impact of the critical care experience on patients as they recall it. In this study we describe 59 patients' recollections of the critical care experience within 24 to 48 hours after transfer from the unit. Responding to an open-ended series of questions, patients accurately identified why they were admitted to critical care units. Actions related to observations, technical care, alleviation of concerns, and self-care promotion were recalled by patients. Nurses were the persons most frequently associated with such actions. In contrast, physicians were most frequently cited as the source of information about their health condition. Almost half of the patients who were willing and able to be interviewed described the impact of the experience as positive or neutral. Pain and sleeplessness were the major problems identified by patients.

Critical Care↗

Effect of epidural lidocaine on spinal cord blood flow.

The effect of epidural lidocaine on spinal cord blood flow (SCBF) was measured in mongrel dogs. Spinal evoked potentials were used to measure spinal cord conduction and enabled us to time the measurement of SCBF associated with maximum reduction in latency and amplitude of spinal evoked potentials produced by instillation of 5 ml of 2% lidocaine in the epidural space. We used the radioactive microsphere technique to quantitate SCBF in the cervical, upper thoracic, lower thoracic, and lumbar regions of the spinal cord. A narcotic/relaxant technique was used to eliminate SCBF changes associated with other anesthetic agents. Other parameters known to affect SCBF were kept constant and within normal physiologic values. As compared with saline solution controls, there were significant decreases in SCBF in all the four areas of spinal cord in animals given epidural lidocaine, most marked in the lumbar area.

Anesthesia, Epidural↗

The location of CuA in mammalian cytochrome c oxidase.

Imposition of a protonmotive force across the inner membrane of coupled cyanide-inhibited, beef heart mitochondria by addition of ATP causes reduction of cytochrome c and CuA with concomitant oxidation of haem aA. The data are consistent with previous demonstrations of an intramembrane location of haem aA but further indicate that CuA is very close to the cytosolic surface of the membrane. The implications of this finding for electron transfer route and the site of the proton pumping chemistry are discussed.

Adenosine Triphosphate↗

Strategy of research on the chemiosmotic mechanism of cytochrome oxidase.

In recent papers on protonmotive redox mechanisms in cytochrome oxidase in [(1987) FEBS Lett. 222, 235-245] and [Glynn Biological Research Reports (1987) 3, 1-7], I have suggested that a copper centre may enable the H2O/OH or H2O/O couple to act as the hydrogen-carrying arm of a redox loop by means of a (CuOH2)+/(CuOH)+ or (CuOH2)+/(CuO)+ system at the centre. I here explain that critical comments by Malmström [(1988) FEBS Lett. 231, 268-269] on the first of these papers, which might also be levelled at the second, depend on a misunderstanding. I also respond to Malmström's comment about testing conformationally coupled proton-pump mechanisms.

Electron Transport Complex IV↗

Electron conduction between b cytochromes of the mitochondrial respiratory chain in the presence of antimycin plus myxothiazol.

The b haems of the bc1 complex of bovine heart mitochondria were poised with succinate and fumarate so that only the high-potential haem (b-562) was reduced, and then isolated from further redox exchange with the ubiquinone pool by adding antimycin and myxothiazol. A transmembrane electric potential difference was then developed, either by electron flow from [Ru(NH3)6]Cl2 to oxygen or by ATP hydrolysis. The small difference spectrum, caused by the electric field, indicated 32-55% oxidation of b-562 with concomitant reduction of b-566. No lag greater than 0.1 s was detectable between the initiation of respiration and the development of the difference spectrum, thus providing a direct demonstration of (fairly) rapid electron transfer between the b haems.

Animals↗

The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide.

BRL 34778, exo-4-amino-5-chloro-2-methoxy-N-[9-(4-fluorophenylmethyl)-9-azabi cyclo(3.3.1) non-3-yl]-benzamide, is a very potent and specific dopamine D2-receptor antagonist. It exhibits a Ki value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(Ki 5700 nM) and for many other receptor types. Its action is potent and of long duration in models for antipsychotic activity (4 h ED50s PO are 0.017 mg/kg for antagonism of apomorphine-induced climbing in mice and 0.028 mg/kg for antagonism of amphetamine-induced locomotion in rats). In contrast to its high potency in models for antipsychotic activity, BRL 34778 is much weaker in models for extrapyramidal effects and sedation (4 h ED50s PO are 2.4 mg/kg for inducing catalepsy in rats and 1.14 mg/kg for inhibition of rearing behaviour in rats). These data indicate potent activity of BRL 34778 in models for antipsychotic activity but low activity in models for extrapyramidal effects and sedation.

Adenylyl Cyclase Inhibitors↗

Risk factors for community- and household-acquired pertussis during a large-scale outbreak in central Wisconsin.

To identify risk factors associated with community- and household-acquired pertussis, we studied 61 households (HHs) with members with culture-positive illnesses and compared their characteristics with 58 neighborhood control-HHs and 62 randomly selected control-HHs. Case-HHs were more likely than either control group to have members 12-18 y of age (P less than .01); these individuals accounted for 34% of all primary cases. A history of exposure outside the home was the most important predictor of community-acquired infection (P less than .001), with adolescents being at higher risk than other age-groups (odds ratio, 3.2; P less than .001). After known exposure to a culture-positive case in the same HH, the risk of illness was unrelated to age; lengthy delays in initiating erythromycin therapy and prophylaxis were the only factors associated with secondary spread (P less than .01). The risk of pertussis may be related more to the likelihood of exposure than to age-related increases in susceptibility, and the risk can be reduced with appropriate use of erythromycin.

Adolescent↗

Cleaning procedures for small dental instruments prior to sterilization.

Observations were made in an institutional setting on the quality of cleaning of dental burs. Assessments were made by scanning electron microscopy of surface contamination and change to the surface quality of burs before and after use, and as a result of different cleaning procedures. The most significant finding was the corrosive action on carbon steel burs of a phosphoric acid based cleaning solution in routine use at the time. We show by comparison the effectiveness and non-corrosive nature of an alternative detergent based on sulfamic acid, and propose a suitable cleaning routine. Two other findings are presented: new burs as unpackaged are unacceptable for use without first being subjected to a cleaning process (we recommend a suitable procedure); and there is a need for distilled water rather than tap water rinsing after detergent use. It is an important part of an institution's responsibility to monitor cleaning, sterilizing and supply services; the scanning electron microscope is a valuable adjunct in this aspect of quality assurance.

Communicable Disease Control↗

Protonmotive stoichiometry of rat liver cytochrome c oxidase: determination by a new rate/pulse method.

The stoichoimetry of vectorial H+ ejection coupled to electron flow through the cytochrome c oxidase (EC 1.9.3.1) of rat liver mitochondria was determined by a new rate/pulse method. This is a modification of the oxygen-pulse method. Electron flow through the oxidase is initiated by adding oxygen to suspensions of anaerobic mitochondria at a known and constant rate. Cytochrome c oxidase was examined directly or in combination with cytochrome c reductase (ubiquinol:ferricytochrome c oxidoreductase). In both cases the----H0+/2e- ratio was found to be constant during the time-course of oxygen reduction, and thus independent of delta pH. The stoichiometries observed were consistent with mechanistic stoichiometries of 2 and 6 for cytochrome c oxidase alone and cytochrome c oxidase together with cytochrome c reductase, respectively. The stoichiometry of cytochrome c reductase alone was also examined, by using ferricyanide in place of oxygen. The results obtained were consistent with the accepted mechanistic stoichiometry of 4 for this enzyme.

Animals↗

A new redox loop formality involving metal-catalysed hydroxide-ion translocation. A hypothetical Cu loop mechanism for cytochrome oxidase.

A new hypothetical type of redox loop is described, which translocates hydroxide instead of protons. Conventional protonmotive redox loops use carriers of protons with electrons (e.g. QH2/Q systems) to couple electron transfer to the translocation of protons. The putative hydroxidemotive redox loop uses carriers of hydroxide ions against electrons (e.g. transition-metal centres) to couple electron transfer to the translocation of hydroxide ions. This simple idea leads to the proposal of a hydroxidemotive Cu loop mechanism that may possibly be applicable to the CuA or CuB centre of cytochrome oxidase, and might thus account for the coupling of electron transfer to net proton translocation in that osmoenzyme.

Copper↗

Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements.

The enhancer-binding protein AP-1 has been purified to greater than 95% homogeneity from HeLa cells by sequence-specific DNA affinity chromatography and identified as a 47 kd polypeptide. Purified AP-1 activates transcription in vitro of the wild-type human metallothionein IIA (hMT IIA) gene but not mutant hMT IIA promoters lacking AP-1 recognition sites. DNAase I protection analysis indicates that genetically defined enhancer elements in hMT IIA, SV40, and the human collagenase gene contain high-affinity AP-1-binding sites, each with a conserved recognition motif, TGACTCA. These three genes are transcriptionally induced by treatment of cells with the tumor promoter TPA. Here we demonstrate that multiple synthetic copies of the consensus AP-1-binding site can act as TPA-inducible enhancers in various plasmid constructs after transfection into HeLa cells. These findings suggest that AP-1 is a transcription factor that functions by interacting with a specific enhancer element, and that its activities may be modulated by treatment of cells with TPA, known to stimulate protein kinase C.

Base Sequence↗

The pharmacological treatment of tricyclic-resistant depression: review and management guidelines.

Despite the introduction of a wide range of antidepressant drugs since the late 1950s, approximately 30-50% of depressed subjects do not respond to these agents. Various treatment strategies, both pharmacological and non-pharmacological, have been proposed for treatment-resistant depression. This paper critically reviews the studies of single and combined pharmacological treatments for tricyclic-resistant patients, with a particular discussion of lithium augmentation. The major inadequacies of these studies have been the frequent lack of definitions of treatment resistance, the heterogeneity of the depressed samples, and the infrequent use of double-blind, placebo-controlled designs. Two central issues, definition of treatment resistance and clinical predictors of response to pharmacological treatments, are discussed in detail. Finally, a suggested guideline for the management of tricyclic-resistant depression is proposed.

Antidepressive Agents↗