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Biomedical subjects

Kevin Morgan

Publications and source records attributed to Kevin Morgan.

11 recordsLinked to original sources
PubMed2003

Predicting longer-term outcomes following psychological treatment for hypnotic-dependent chronic insomnia.

OBJECTIVES: To identify predictors of treatment adherence, patient dropout, and treatment response among long-term hypnotic users recruited into a randomized controlled trial of psychological treatment for insomnia. METHODS: Of 108 treatment and 101 control patients initially recruited, 37 treatment group patients (34.3%) failed to complete all 6 sessions (i.e., were nonadherent), while across both groups 61 (29.2%) patients failed to return postal assessments at 3-month follow-up (i.e., dropped out). Relationships between baseline characteristics and adherence (adherent vs. nonadherent) and attrition (dropout vs. nondropout) were examined in discriminant models. Relationships between baseline characteristics and treatment response (sleep quality, sleep latency, sleep efficiency, and hypnotic drug use) were examined in a series of multiple regression models. RESULTS: Adherent patients showed a significantly greater severity of pretreatment sleep disturbance, as measured by the Pittsburgh Sleep Quality Index (PSQI). Dropout at 3 months was associated with significantly lower perceived health status at baseline. In the regression models, lower Cure/Control subscale scores from the Illness Perception Questionnaire (IPQ) predicted greater posttreatment improvements in sleep efficiency and PSQI scores, while lower baseline anxiety scores predicted a posttreatment increase in hypnotic-free nights/week. CONCLUSION: In routine clinical practice settings, higher anxiety and a less positive attitude towards symptom control were associated with poorer treatment response. Adherence and attrition show a different pattern of associations, with greater need (as indexed by insomnia severity) predicting higher levels of service uptake and poorer general health predicting a higher likelihood of dropout.

Adult↗
PubMed2003

Survival in a population sample is predicted by proportions of lymphocyte subsets.

Comparisons of lymphocyte subsets show that the ratio of CD4 to CD8 is usually greater than one. Inversion of this ratio was found to predict survival in a Swedish octogenarian sample (n=27 deaths), although individual lymphocyte subsets did not predict survival. We have examined these relationships in a larger sample (n=153 deaths). Inversion of the CD4 to CD8 ratio was present in 16% of the sample and predicted survival when adjusted for age but not when adjusted for sex. For individual lymphocyte subsets, higher CD4 and CD19 percentages were associated with better survival, but only the CD19 percentage remained significant when adjusted for age and sex.

Aged↗
PubMed2003

Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer's disease.

The processing of amyloid precursor protein (APP) generates amyloid-beta (Abeta) peptides 1-40 and 1-42. The latter is neurotoxic and its accumulation results in amyloid fibril formation and the generation of senile plaques, the hallmark of Alzheimer's disease (AD). Whilst there has been considerable progress made in understanding the generation of Abeta by alpha-, beta- and gamma-secretase activity on APP, recently enzymes involved in the degradation of Abeta have been identified including neprilysin and insulin-degrading enzyme (IDE). We review the pathways involved in proteolytic processing of APP and discuss the potential implications of aberrant proteolysis on neurodegeneration. It is conceivable that single nucleotide polymorphisms (SNPs) in the regulatory regions of genes in these proteolytic cascades, which alter their expression, could contribute to some of the age-related changes seen in AD.

Alzheimer Disease↗
PubMed2003

Serpins: structure, function and molecular evolution.

The superfamily of serine proteinase inhibitors (serpins) are involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression and are expressed in a cell-specific manner. The average protein size of a serpin family member is 350-400 amino acids, but gene structure varies in terms of number and size of exons and introns. Previous studies of all known serpins identified 16 clades and 10 orphan sequences. Vertebrate serpins can be conveniently classified into six sub-groups. We provide additional data that updates the phylogenetic analysis in the context of structural and functional properties of the proteins. From these, we can conclude that the functional classification of serpins relies on their protein structure and not on sequence similarity.

Animals↗
PubMed2003

Daytime activity and risk factors for late-life insomnia.

Laboratory evidence linking exercise with improved sleep quality raises the possibility that the lower levels of physical activity characteristic of older age groups may contribute to late-life insomnia. While support for this hypothesis appears to come from epidemiological surveys, few such studies have distinguished satisfactorily between social and physical activities which differ widely in terms of energy cost and theoretical significance. The present analyses were, therefore, designed to assess the independent influence of physical and social activity levels on the prevalence and natural history of late-life insomnia. Survivors from a nationally representative UK sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). Detailed assessments of physical and social activities, mental and physical health status, and sleep quality were made at each survey wave. Logistic regression models, adjusted for age, sex and health status, were used to assess relationships between activity levels and the prevalence, remission/persistence, and incidence of late-life insomnia. Lower physical health, depressed mood and lower physical (but not social) activity levels consistently emerged as significant risk factors for prevalent, persistent and incident insomnia. Age was unrelated to insomnia variables in all the cross-sectional models, but did emerge as a significant risk for cumulative 4-8-year insomnia incidence. These findings suggest that, independent of those activities more closely associated with social engagement, higher levels of customary physical activity per se appear to be protective against incident and chronic late-life insomnia.

Aged↗
PubMed2003

A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12.

GnRH-II peptide hormone exhibits complete sequence conservation across vertebrate species, including man. Type-II GnRH receptor genes have been characterized recently in nonhuman primates, but the human receptor gene homolog contains a frameshift, a premature stop codon (UGA), and a 3' overlap of the RBM8A gene on chromosome 1q.12. A retrotransposed pseudogene, RBM8B, retains partial receptor sequence. In this study, bioinformatics show that the human receptor gene promoter overlaps the peroxisomal protein 11-beta gene promoter and the premature UGA is positionally conserved in chimpanzee. A CGA [arginine (Arg)] occurs in porcine DNA, but UGA is shifted one codon to the 5' direction in bovine DNA, suggesting independent evolution of premature stop codons. In contrast to marmoset tissue RNA, exon- and strand-specific probes are required to distinguish differently spliced human receptor gene transcripts in cell lines (HP75, IMR-32). RBM8B is not transcribed. Sequencing of cDNAs for spliced receptor mRNAs showed no evidence for alteration of the premature UGA by RNA editing, but alternative splicing circumvents the frameshift to encode a two-membrane-domain protein before this UGA. A stem-loop motif resembling a selenocysteine insertion sequence and a potential alternative translation initiation site might enable expression of further proteins involved in interactions within the GnRH system.

Adenoma↗
PubMed2003

Type II gonadotrophin-releasing hormone (GnRH-II) in reproductive biology.

Humans may be particularly unusual with respect to the gonadotrophin-releasing hormone (GnRH) control of their reproductive axis in that they possess two distinct GnRH precursor genes, on chromosomes 8p11-p21 and 20p13, but only one conventional GnRH receptor subtype (type I GnRH receptor) encoded within the genome, on chromosome 4. A disrupted human type II GnRH receptor gene homologue is present on chromosome 1q12. The genes encoding GnRH ligand precursors and GnRH receptors have now been characterized in a broad range of vertebrate species, including fish, amphibians and mammals. Ligand precursors and receptors can be categorized into three phylogenetic families. Members of each family exist in primitive vertebrates, whereas mammals exhibit selective loss of ligand precursor and receptor genes. One interpretation of these findings is that each ligand-cognate receptor family may have evolved to fulfil a separate function in reproductive physiology and that species-specific gene inactivation, modification or loss may have occurred during evolution when particular roles have become obsolete or subject to regulation by a different biochemical pathway. Evidence in support of this concept is available following the characterization of the chromosomal loci encoding the human type II GnRH receptor homologue, a rat type II GnRH receptor gene remnant (on rat chromosome 18) and a mouse type II GnRH ligand precursor gene remnant (on mouse chromosome 2). Whether type I GnRH and type II GnRH peptides elicit different signalling responses in humans by activation of the type I GnRH receptor in a cell type-specific fashion remains to be shown. Recent structure-function studies of GnRH ligands and GnRH receptors and their expression patterns in different tissues add further intrigue to this hypothesis by indicating novel roles for GnRH such as neuromodulation of reproductive function and direct regulation of peripheral reproductive tissues. Surprises concerning the complexities of GnRH ligand and receptor function in reproductive endocrinology should continue to emerge in the future.

Amino Acid Sequence↗
PubMed2002

Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer.

alpha(1)-Antitrypsin (AAT) is the major serine proteinase inhibitor (SERPIN A1) in human plasma. Its target proteinase is neutrophil elastase and its main physiological function is protection of the lower respiratory tract from the destructive effects of neutrophil elastase during an inflammatory response. Circulating levels of AAT rise 2-3-fold during inflammation and the liver produces most of this increase. The cytokines oncostatin M (OSM) and interleukin-6 have been shown to be mainly responsible for this effect, which is mediated via the interaction of cytokine-inducible transcription factors with regulatory elements within the gene. In the present study, we report for the first time that OSM stimulation of hepatocyte AAT occurs via an interaction between the hepatocyte promoter and an OSM-responsive element at the 3'-end of the AAT gene. This effect is mediated by the transcription factor signal transducer and activator of transcription 3 ('STAT 3') binding to an OSM-responsive element (sequence TTCTCTTAA), and this site is distinct from, but close to, a previously reported interleukin-6-responsive element.

Base Sequence↗
PubMed2002

Transcriptional and physiological responses of HepG2 cells exposed to diethyl maleate: time course analysis.

Expression levels of 767 genes were measured in HepG2 cells at eight time points (0, 0.5, 1, 6, 12, 16, 20, and 24 h) following exposure to the oxidizing agent, diethyl maleate (DEM). DEM treatment caused an immediate and sustained loss of intracellular GSH, with a concomitant increase in GSSG. From 6-12 h after exposure, there was a substantial increase in the percentage of cells undergoing S phase arrest and apoptosis. Expression profiles of approximately 90% of the genes fell into one of five clusters generated using hierarchical-clustering software, indicating the well-ordered nature of the stress response. The directional movement and timing of induction for many genes matched closely the known physiological role of the proteins they encode. Inhibitors of the cell cycle (CDKN1, CDKN4D, ATM) were induced, whereas cyclins [proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin K] were downregulated during the period from 6--20 h. Likewise, pro-apoptotic genes such as the caspases (CASP9, CASP3, CASP2) and apoptotic protease activating factor (APAF) were induced during the same period. Results of this study indicate that there is a good correlation between time-dependent physiological, biochemical, and gene expression data.

Apoptosis↗
PubMed2002

A functional magnetic resonance imaging study of overt letter verbal fluency using a clustered acquisition sequence: greater anterior cingulate activation with increased task demand.

Regional cerebral activation during a cognitive task can vary with task demand and task performance. In a functional magnetic resonance imaging study, we examined the effect of manipulating task demand on activation during verbal fluency by using "easy" and "hard" letters. A "clustered" image acquisition sequence allowed overt verbal responses to be made in the absence of scanner noise which facilitated "on-line" measurement of task performance. Eleven right-handed, healthy male volunteers participated. Twice as many errors were produced with hard as with easy letters (20.8 +/- 13.6 and 10.1 +/- 10.7% errors, respectively). For both conditions, the distribution of regional activation was comparable to that reported in studies of covert verbal fluency, but with greater engagement of subcortical areas. The hard condition was associated with greater dorsal anterior cingulate activation than the easy condition. This may reflect the greater demands of the former, particularly in terms of arousal responses with increased task difficulty and the monitoring of potential response errors.

Adult↗