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Biomedical subjects

N King

Publications and source records attributed to N King.

At least 19 recordsLinked to original sources

Using fMRI to study recovery from acquired dysphasia.

We have used functional magnetic resonance imaging (fMRI) to characterize brain activations associated with two distinct language tasks performed by a 28-year-old woman after partial recovery from dysphasia due to a left frontal hemispheric ischemic stroke. MRI showed that her ischemic lesion extended posteriorly from the left inferior frontal to the perisylvian cortex. fMRI scans of both language tasks revealed substantial differences in activation pattern relative to controls. The nature of this difference was task-specific. During performance of a verbal semantic decision task, the patient, in contrast to controls, activated a network of brain areas that excluded the inferior frontal gyrus (in either hemisphere). A second task involving rhyme judgment was designed to place a heavier cognitive load on language production processes and activated the left inferior frontal gyrus (Broca's area) strongly in normal controls. During this task, the most prominent frontal activation in the patient occurred in the right homologue of Broca's area. Subsequent analysis of this data by methods able to deal with responses of changing amplitude revealed additional, less sustained recruitment by the patient of cortex adjacent to the infarct in the region inferior to Broca's area during rhyming. These results suggest that in addition to changes in cognitive strategy, recovery from dysphasia could be mediated by both the preservation of neuronal networks in and around the infarct and the use of homologous regions in the contralateral hemisphere.

Adult↗

The effect of body dissatisfaction on women's perceptions of female celebrities.

OBJECTIVE: Research suggests that media exposure causes some women to feel heightened dissatisfaction with their body shape. This study attempts to determine which women are effected as such, by investigating how women feel about their own bodies and how this effects their perceptions of female celebrities in the media. METHOD: Undergraduate females (n = 116) were shown one accurate and six distorted photographs of thin and heavy female celebrities. Each distorted photograph made the celebrity appear thinner or heavier than actuality. Participants chose which photograph portrayed each celebrity's true body shape. Body shape concerns were measured by the Body Shape Questionnaire. RESULTS: Women concerned about their body shape judged thin celebrities as thinner than actuality, whereas unconcerned women judged them accurately. Both groups judged heavy celebrities as heavier than actuality. DISCUSSION: Results suggest certain women are effected by media exposure due to their own perception of females in the media. Prevention strategies, and the media's role in body dissatisfaction and dieting disorders, are discussed.

Adolescent↗

Apoptosis of vascular smooth muscle cells induced by cholesterol and its oxides in vitro and in vivo.

The ability of cholesterol and its oxides to induce apoptosis in vascular smooth muscle cells in tissue culture and in a rabbit model of atherosclerosis was evaluated. Apoptosis was detected using DNA laddering and in situ end-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, were found to inhibit proliferation and induce apoptosis of vascular smooth muscle cells in tissue culture. 7-ketocholesterol was found to be the most potent inhibitor of proliferation, while 25-hydroxycholesterol was found to be the most potent inducer of apoptosis. These data suggest that the inhibition of proliferation and the induction of apoptosis by cholesterol oxides within vascular smooth muscle cells use different pathways, suggesting a differential role for these cholesterol oxides within the arterial wall. Cholesterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we found that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor determining apoptosis in our model was the balloon injury.

Animals↗

Research on the cognitive-behavioral treatment of school refusal: a review and recommendations.

Cognitive-behavior therapy is frequently used in the treatment of school refusal, a challenging problem for mental health professionals and school authorities. We review the clinical and research support for the efficacy of cognitive-behavior therapy using recently published guidelines for determining the level of evidentiary support for psychosocial interventions. Although cognitive-behavior therapy appears to be a useful treatment for school refusal, further research is needed before it can be considered as having "well-established" empirical status. Several other important methodological and theoretical issues are emphasized.

Adolescent↗

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings.

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal:noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.

Appetite↗

Septation, dephosphorylation, and the activation of sigmaF during sporulation in Bacillus subtilis.

Cell-specific activation of transcription factor sigmaF during sporulation in Bacillus subtilis requires the formation of the polar septum and the activity of a serine phosphatase (SpoIIE) located in the septum. The SpoIIE phosphatase indirectly activates sigmaF by dephosphorylating a protein (SpoIIAA-P) in the pathway that controls the activity of the transcription factor. By use of a SpoIIE-GFP fusion protein in time-course and time-lapse experiments and by direct visualization of septa in living cells, we show that SpoIIE is present in the predivisional sporangium, where it often localizes near both cell poles in structures known as E-rings. We also present evidence consistent with the view that SpoIIE is present in both progeny cells after polar division. These findings are incompatible with a model for the control of sigmaF activity in which the phosphatase is simply sequestered to one cell. Instead, we conclude that the function of SpoIIE is subject to regulation, and we present evidence that this occurs in two stages. The first stage, which involves the phosphatase function of SpoIIE, depends on the cell division protein FtsZ and could correspond to the FtsZ-dependent assembly of SpoIIE into E-rings. The second stage occurs after the dephosphorylation of SpoIIAA-P and is dependent on the later-acting, cell-division protein DivIC. Evidence based on the use of modified and mutant forms of the phosphatase protein indicates that SpoIIE blocks the capacity of unphosphorylated SpoIIAA to activate sigmaF until formation of the polar septum is completed.

Bacillus subtilis↗

The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer.

Thirty-four post-menopausal women with early breast cancer who had received 20 mg tamoxifen once daily as adjuvant therapy for at least 10 weeks participated in a randomized, double-blind, parallel-group, multicentre trial. The primary aim of the trial was to determine the effect of anastrozole upon tamoxifen pharmacokinetics, with secondary aims of assessing the tolerability of the two drugs in combination and whether or not tamoxifen had any effect upon the oestradiol suppression seen with anastrozole. Patients were randomized to receive either 1 mg anastrozole (16 patients) or matching placebo (18 patients) once daily on a double-blind basis for 28 days. No significant difference (P = 0.919) was observed in serum tamoxifen concentrations between the anastrozole and placebo groups during the trial. The serum concentration of oestradiol was significantly suppressed (P < 0.0001) in patients co-administered anastrozole compared with placebo in the presence of tamoxifen, confirming that anastrozole remained an effective suppressant of oestradiol in the presence of tamoxifen. The combination of tamoxifen and anastrozole was well tolerated, with very little difference in side-effects reported between anastrozole and placebo. In conclusion, the results of this study confirm that anastrozole does not affect the pharmacokinetics of tamoxifen when the two drugs are given in combination to post-menopausal women with early breast cancer. In addition, the oestradiol suppressant effects of anastrozole appear unaffected by tamoxifen.

Anastrozole↗

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.

BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol x kg(-1) min(-1)) or saline. SUBJECTS: Eight obese (body mass index, BMI, 45.5 +/- 2.3 kg/m2) male subjects. MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique. RESULTS: Hunger ratings were significantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 +/- 0.5 MJ (21 +/- 6%) by GLP-1 infusion (P = 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 +/- 0.35 mmol/L; nadir: 5.3 +/- 0.15 mmol/L). No nausea was recorded during GLP-1 infusion. CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this finding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Adult↗

Investigation of cholecystokinin system genes in panic disorder.

There is evidence for the role of the cholecystokinin (CCK) neurotransmitter system in the neurobiology of panic disorder (PD). The CCK receptor agonist, CCK-tetrapeptide (CCK-4) fulfills criteria for a panicogenic agent and there is evidence that PD might be associated with an abnormal function of the CCK system. For example, PD patients show an enhanced sensitivity to CCK-4, and exhibit lower CSF and lymphocyte CCK concentration as compared to healthy controls (reviewed by Bradwejn et al.). Also, untreated PD patients display an increased CCK-4-induced intracellular Ca2+ mobilization in T cells relative to treated PD, depression and schizophrenia. The CCK receptors have been classified into two subtypes: CCK-A and CCK-B. We report here a study of polymorphisms in the CCK pre-pro hormone gene (CCK), CCK-AR, and CCK-BR in DSM-IV panic patients (n = 99) vs controls matched for gender and ethnicity. The CCK polymorphism revealed no association with PD. We identified a new polymorphism for the CCK-A receptor gene, and tested it in our sample, with negative results. A single nucleotide polymorphism has been found in the coding region of the CCK-B receptor gene (CCK-BR) and D Collier (personal communication) identified a highly polymorphic dinucleotide (CT)n microsatellite in the 5' regulatory region. For the CCK-B receptor gene polymorphism, PD patients showed a significant association. Our genetic dissection of the CCK system thus far suggests that the CCK-B receptor gene variation may contribute to the neurobiology of panic disorder.

Alleles↗

Relationship and family breakdown following acquired brain injury: the role of the rehabilitation team.

Although the literature documents the considerable problems acquired brain injury causes for the survivor's family and close relationships, and the corresponding significantly inflated rate of separation and divorce, few papers offer practical solutions. The objective of this paper is to respond to this gap in the literature by presenting some of the problems raised for the rehabilitation team when a family separates, and some suggestions for ways in which these problems could be overcome. The literature is reviewed briefly, followed by reflections and suggestions which are based on this review and on clinical experience. The discussion indicates that there are a number of practical dilemmas raised for the rehabilitation team when a family already involved in the rehabilitation process starts to break up. Some specific suggestions for addressing these issues are made; further research is needed to evaluate their effectiveness.

Brain Injuries↗

Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia.

Social phobia, particularly the generalized form, is strongly familial and frequently comorbid with major depression, panic disorder, and obsessive-compulsive disorder. It has also recently been shown to be responsive to selective serotonin reuptake inhibitors. We conducted a study to determine if generalized social phobia is genetically linked to either of two candidate genes: the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR) gene. Rates of social phobia (using several phenotype definitions) were ascertained and blood samples obtained from consenting first-degree family members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was performed using the polymerase chain reaction (PCR). Linkage was tested using LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis indicated that failure to find linkage was unlikely due to inadequate statistical power. These findings reasonably exclude linkage between generalized social phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects of 5HT on other neurotransmitter systems may be involved.

Adolescent↗

Effect of regular training on the myocardial and plasma concentrations of taurine and alpha-amino acids in thoroughbred horses.

Exercise induces significant changes in the free intracellular amino acid pool in skeletal muscle but little is known of whether such changes also occur in cardiac muscle. In this study the effect of regular exercise on the size and the constituents of the free amino acid pool in the hearts and in the plasma of thoroughbred horses was investigated. The total free intracellular amino acid pool in the hearts of control horses was 30.9 +/- 1.2 mumol/g wet weight (n = 6). Glutamine but not taurine was present at the highest concentration (13.5 +/- 0.9 and 7.7 +/- 0.69 mumol/g wet weight for glutamine and taurine respectively). As for the rest of the amino acids in the pool, only glutamate and alanine were present at levels greater than 1 mumol/g wet weight (4.6 +/- 0.25 and 1.7 +/- 0.14 for glutamate and alanine respectively). The tissue to plasma ratio was highest for taurine at 155, followed by glutamate at 111, aspartate and glutamine at 37, alanine at 5.8 and ratios of less than 3 for the rest of the amino acids. The total free intracellular amino acid pool in the hearts of exercised horses was slightly but not significantly lower than control (28.1 +/- 1.1 mumol/g wet weight, n = 6). Regular exercise increased the intracellular concentration of threonine, valine, isoleucine, leucine and phenylalanine but was only significant (p < 0.05) for threonine. This work has documented the profile of taurine and protein amino acids in the heart and in the plasma of thoroughbred horses and showed that in contrast to skeletal muscle, heart muscle does not show major changes in amino acids during regular exercise.

Amino Acids↗

Characteristics of L-alanine transport in cardiac sarcolemmal vesicles and into isolated cardiac myocytes.

During cardiac insults, heart cells synthesise and accumulate alanine as a part of the anaerobic energy production pathway. The transport of alanine presumably influences this pathway, making it important to characterise the L-alanine transporter in the heart. In this study, we have investigated the transport of L-alanine across the sarcolemma using a novel approach, namely utilisation of two preparations: cardiac sarcolemmal vesicles and cardiac myocytes. Both preparations were isolated from the heart of the same mammalian species. L-Alanine uptake in both preparations was sodium dependent. In the sarcolemmal vesicles, the sodium dependent component was electrogenic and saturated with an estimated Michaelis-Menten constant (Km) and maximal reaction velocity (Vmax) of 0.48+/-0.18 mM and 279.97+/-64.17 pmol/mg per min respectively at room temperature. In the isolated myocytes, L-alanine uptake was linear in sodium-containing media, with an estimated Km and Vmax of 9.65+/-0. 76 mM and 169.81+/-13.22 pmol/ microl per min respectively at 10 degreesC for the sodium-dependent component. Inhibition of cotransport by a variety of substrates indicated that L-alanine uptake in the heart is mediated by an A- or ASC-like system. These characteristics of L-alanine transport suggest that under ischaemic conditions, L-alanine efflux will be activated, thus allowing for the continuous utilisation of other amino acids for energy production.

Alanine↗

Assessment of long-term psychological well-being following intensive care.

The aim of this research, which remains in progress, has been the examination of long-term psychological consequences for survivors of intensive care. Seventy-two patients were followed up for 1 year, after discharge from the Intensive Care Unit (ICU) at St James's University Hospital in Leeds. Major objectives of the study included assessment of patients' sense of well-being at specified intervals post-discharge, and identification of ICU-related variables which might influence psychological recovery. Psychometric assessments used were the General Health Questionnaire 28-item version, the Rosenberg Self-esteem Scale, and the Impact of Event scale. This paper describes findings from the research so far. An exploratory analysis of the data suggests that distinctions can be drawn among surviving patients with regard to psychological recovery, by way of variables such as type of illness, mode of admission and amount of recall. The work expands previous research into post-ICU psychology and quality of life, and should allow increased understanding of this patient group.

Adult↗

Comparison of the traditional paper visual analogue scale questionnaire with an Apple Newton electronic appetite rating system (EARS) in free living subjects feeding ad libitum.

OBJECTIVE: Assessing the value of a newly developed electronic visual analogue scale questionnaire (Apple Newton Message Pad) with the traditional paper method for appetite rating. DESIGN: In a random, crossover design, subjects completed both electronic and paper questionnaires to compare results obtained by the two methods; individual methods were completed consecutively to assess test-retest reliability; preference was established using a questionnaire. SETTING/SUBJECTS: Healthy, free-living adults were studied for comparison of methods (n = 12), test-retest reliability (n = 8) and preference (n = 13). INTERVENTION: Visual analogue scales were completed each waking hour to assess appetite. Preference was assessed after both methods were completed. RESULTS: There was no significant difference in the hourly results obtained by the paper and electronic methods for 'desire to eat', 'how much can you eat now', 'urge to eat' and 'preoccupation with thoughts of food'. Small differences in 'hunger' and 'fullness' ratings were noted (approximately 5% mean difference between methods, P < 0.05), but patterns of change and sensitivity for these and all other parameters remained similar for both methods across the visual analogue scale. Test-retest reliability demonstrated was similar for both methods. Seven (54%) subjects preferred to use the paper questionnaire, five (38%) the electronic method and one (8%) had no preference. CONCLUSIONS: The electronic Apple Newton questionnaire is as sensitive and reliable as the paper method, has the advantage that it automatically records the time of data acquisition and data collection and processing are more efficient for the researcher. The two methods should not be used interchangeably.

Adult↗

Investigation of dopamine system genes in obsessive-compulsive disorder.

Evidence from anatomical, pharmacological, and animal studies on the involvement of the dopamine system in obsessive-compulsive disorder (OCD) is mounting. This, along with evidence for a genetic diathesis provided by family and twin studies, prompted us to conduct genetic association studies of dopamine system genes in OCD. We genotyped OCD patients (n > 100) and matched controls for four loci: (1) a 40-base-pair repeat in the dopamine transporter gene; (2) the TaqIA polymorphism and the serine/cysteine variation in the D2 dopamine receptor gene; (3) an MscI polymorphism in the D3 dopamine receptor gene; and (4) a 48-base-pair repeat in the D4 dopamine receptor gene. Significant differences in allele frequencies were found between patients and controls for the D4 receptor gene, although replication is required with family-based controls before any conclusions can be entertained. This study represents the first comprehensive assessment of the roles of dopamine system genes in OCD.

Age of Onset↗