Biomedical subjects

K Morgan

Publications and source records attributed to K Morgan.

At least 109 records · Page 6Linked to original sources

PubMed1998

The Nottingham Longitudinal Study of Activity and Ageing: a methodological overview.

OBJECTIVES: first, to describe the background and methodological approach to the assessment of customary physical activity, health and psycho-social status used by the Nottingham Longitudinal Study of Activity and Ageing; second, to provide information on the sampling strategy and survey response rates for three waves of data collection; and, third, to provide information on the reliability and validity of the survey assessments. DESIGN: longitudinal study. SUBJECTS: 1042 people originally aged 65 and over, randomly sampled from general practitioner lists in Nottingham, UK. METHODS: a descriptive overview of response rates (%), instrument reliability (alpha coefficients) and intercorrelations among measured outcomes (correlation coefficients and principal components analysis). MAIN OUTCOME MEASURES: questionnaire-assessed levels of physical activity; instrumental measurements of handgrip strength, weight, demi-span and shoulder flexibility; brief assessments of depression, social engagement, life-satisfaction and cognitive impairment. RESULTS: the study achieved a baseline (TI) response rate of 80%, with re-interview rates of 88% and 73% for T2 (1989) and T3 (1993) surveys respectively. For both men and women, factor scores derived from first principal components extracted from T1 survey data showed significant (r > or = 0.4; P < 0.001) product moment correlations with instrumental measurements of handgrip strength and shoulder flexibility. All the brief assessment measures showed satisfactory levels of reliability (alpha > or = 0.7).

Activities of Daily Living↗

PubMed1998

Growth response of human coronary smooth muscle cells to angiotensin II and influence of angiotensin AT1 receptor blockade.

BACKGROUND: The renin-angiotensin system has been implicated in the development of vascular wall thickening in cardiovascular disease, through the growth-promoting actions of the vasoconstrictive agent, angiotensin II, on vascular smooth muscle cells. OBJECTIVE: To investigate the effect of angiotensin II on growth of human coronary artery smooth muscle cells (cSMCs) in culture, and to identify the angiotensin receptor(s) mediating such a response. METHODS: Human cSMCs were isolated from coronary arteries of recipient hearts obtained during transplantation, and characterized by immunohistochemistry. The effect of angiotensin II on protein synthesis by cSMCs was measured by [3H]leucine incorporation and protein concentration assays. Human cSMC proliferation was assessed by [3H]thymidine incorporation assay and cell count. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect angiotensin receptor expression. Transient increases in intracellular calcium concentration in cSMCs in response to angiotensin II stimulation were visualized under fura-2 fluorescence microscopy. RESULTS: Angiotensin II (1 nmol/l-10 mumol/l) stimulated protein synthesis in cSMCs (maximum 24 +/- 2% increase in incorporation of [3H]leucine over 48 h; n = 4, P < 0.01). An increase in cellular protein content was also measured. However, angiotensin II had no effect on proliferation of quiescent cSMCs. The increased protein synthesis was completely inhibited by pretreatment with the angiotensin AT1 receptor antagonist, losartan, but not the AT2 receptor antagonist, PD123319. Expression of the angiotensin AT1 receptor subtype was detected in cSMCs by RT-PCR. Angiotensin II stimulation of cells triggered transient increases in intracellular calcium concentration, which were abolished by losartan, but were insensitive to PD123319 and pertussis toxin. CONCLUSIONS: The results of this study in human coronary VSMCs indicate that angiotensin II and the AT1 receptor may be involved in the development of coronary artery disease in man.

Angiotensin II↗

PubMed1998

A salmonellosis outbreak linked to internally contaminated pork meat.

In August 1995, we investigated an outbreak of salmonellosis among patrons who attended a church camp in southern Sydney. Of the 73 attendees interviewed, 22 reported a gastroenteritis illness within two days of the conclusion of the camp, with one attendee hospitalised. Two stool specimens, one from each of two attendees, were both positive for Salmonella typhimurium phage type 9. A cohort study of 68 attendees established a statistically significant association between illness and the consumption of de-boned roast pork (estimated relative risk infinite, p = 0.03) and between illness and the degree of cooking of the pork meat (chi 2 for trend 5.8, p < 0.02). The outbreak was most likely caused by consumption of roast pork that had been internally contaminated during the de-boning process. Meat and meat products that may be internally contaminated, such as de-boned meats, should be thoroughly cooked. Guidelines about minimum cooking temperatures of meats liable to internal contamination should be developed for commercial food handlers in Australia.

Adolescent↗

PubMed1998

The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression.

The extra sex combs (esc) and Enhancer of zeste [E(z)] proteins are members of the Drosophila Polycomb group (Pc-G) of transcriptional repressors. Here we present evidence for direct physical interaction between the esc and E(z) proteins using yeast two-hybrid and in vitro binding assays. In addition, coimmunoprecipitation from embryo extracts demonstrates association of esc and E(z) in vivo. We have delimited the esc-binding domain of E(z) to an N-terminal 33-amino-acid region. Furthermore, we demonstrate that site-directed mutations in the esc protein previously shown to impair esc function in vivo disrupt esc-E(z) interactions in vitro. We also show an in vitro interaction between the heed and EZH1 proteins, which are human homologs of esc and E(z), respectively. These results suggest that the esc-E(z) molecular partnership has been conserved in evolution. Previous studies suggested that esc is primarily involved in the early stages of Pc-G-mediated silencing during embryogenesis. However, E(z) is continuously required in order to maintain chromosome binding by other Pc-G proteins. In light of these earlier observations and the molecular data presented here, we discuss how esc-E(z) protein complexes may contribute to transcriptional silencing by the Pc-G.

Amino Acid Sequence↗

PubMed1998

Food safety knowledge and practice among elderly people living at home.

OBJECTIVE: To assess the food storage knowledge and practice of elderly people living at home. METHODS: Three phase survey data collection: face to face interviews; dietary diaries with a food frequency questionnaire; and follow up interviews. SETTING: Urban Nottingham. PARTICIPANTS: 809 elderly people (aged 65+) randomly selected from general practitioner lists. MAIN OUTCOME MEASURES: Respondent's refrigerator temperature; knowledge of freezer star rating; understanding of "use by" and "sell by" dates; reported ability to read food product safety labels. RESULTS: From a weighted total of 645 refrigerators measured, 451 (70%) were too warm for the safe storage of food (> or = 6 degrees Celsius). Only 41% of respondents (n = 279) knew the star rating of their freezer. Within a smaller sub-sample knowledge of the "use by" and "sell by" dates was good, but 45% of these respondents reported difficulty reading food labels. The storage of foods at inappropriate temperatures was not independent of socioeconomic or demographic status, and tended to be more likely among the poorer and those not living alone. CONCLUSIONS: Food storage practices among the majority of elderly people interviewed in this study do not meet recommended safety standards to minimise the risk of food poisoning.

Aged↗

PubMed1998

Genetic risk factors in Alzheimer's disease.

Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease.

Aged↗

PubMed1998

Information skills for distance learning.

In spring 1997, the Education Services department at the University of North Carolina at Chapel Hill (UNC-CH) Health Sciences Library (HSL) developed six Web-based tutorials designed to teach information skills. This paper describes how the modules were created.

Academic Medical Centers↗

PubMed1998

The interaction of physical, psychological, socioeconomic and sociodemographic variables on the Body Mass Index (MINDEX) of the community-dwelling elderly.

Two cohorts of older people 65-74, and 75 or more years of age living at home in Nottingham or in a nearby rural area in the UK were interviewed and anthropometric measurements were taken (n=1037). Bivariate analyses showed significant relationships between mindex and variables previously associated with food choice. Those with a mindex above the 95th percentile were more likely to live in a rural area, and were less likely to smoke than those between the 5th and 95th percentiles. Those with a low mindex, below the 5th percentile, were more likely to smoke than those between the 5th and 95th percentiles (45% compared to 17%), and were also more likely to live in an urban area, to have difficulty carrying shopping bags, not to use a car for shopping, to have a poorer appetite, and to live alone. Those overweight and underweight had lower levels of social engagement and were more likely to be of a lower social class. In multivariate analysis, socioeconomic variables and psychosocial variables were not significantly associated with mindex, when controlling for physical and sociodemographic variables. Advancing age, female gender, smoking and decreased appetite were significantly associated with decreased mindex (Adjusted R2 = .168).

Aged↗

PubMed1998

Differential distribution of angiotensin AT2 receptors in the normal and failing human heart.

Cardiac expression of angiotensin II (Ang II) AT1 and AT2 receptor subtypes is species dependent, and changes in their relative proportion may influence myocardial hypertrophy and fibrosis. Regional differences in the distribution of Ang II receptors in the normal and failing human heart were assessed using 125I-(Sar1,Ile8)Ang II binding and quantitative autoradiography. Receptor subtypes were distinguished by their affinity for selective nonpeptide antagonists (losartan and PD123319) and sensitivity to dithiothreitol. Ventricular and atrial tissues displayed a heterogeneous distribution of ligand binding sites. AT2 receptors predominated, representing 70% to 77% of the sites in normal and noninfarcted myocardium. Endocardial, interstitial, perivascular and infarcted regions in the ventricles of patients with end-stage ischemic heart disease or dilated cardiomyopathy exhibited a significantly greater density (P < .001) of high affinity AT2 binding sites (Kd = 0.57 nmol/liter) compared with adjacent noninfarcted myocardium. Regions displaying the relative increase in AT2 binding sites corresponded to areas of fibroblast proliferation and collagen deposition, shown by picrosirius red staining. AT1 binding sites were localized to nerves, occurred at relatively low density in coronary vessels and represented only 23% to 29% of myocardial 125I-(Sar1,Ile8)Ang II binding sites. The border zone between infarcted and noninfarcted myocardium characteristically contained numerous microvessels, exhibiting perivascular AT2 receptors and endothelial angiotensin converting enzyme activity, as demonstrated by binding of 125I-351A. Specific myocardial AT2 receptor mRNA transcripts (approximately 3 kb) were identified and exhibited alternative splicing of untranslated 5' exons. The differential distribution of cardiac Ang II receptor subtypes and selective increase in binding to AT2 sites in the diseased heart suggest that cells bearing the AT2 receptor represent a significant target for Ang II, possibly contributing to its growth-related actions.

Adolescent↗

PubMed1998

Characterization of two corneal epithelium-derived antigens associated with vasculitis.

PURPOSE: In a previous investigation into corneal autoimmunity, it was demonstrated that a putative autoantigen, a protein of 66 kDa, present in bovine corneal epithelium, binds circulating autoantibodies in approximately 60% of patients with Wegener's granulomatosis (WG). The aim of the present study was to characterize and identify the 66-kDa protein. METHODS: A purification protocol was established for the 66-kDa protein using standard chromatography techniques. During the purification procedure it became clear that the 66-kDa protein detected in patients' sera was in fact two proteins, both running at 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, that eluted in different fractions on DE-52 chromatography columns. These two proteins have been labeled bovine corneal epithelial antigen-A and -B (BCEA-A and BCEA-B). Further investigations of antibody binding have demonstrated that patients' sera bind to either one or the other of these proteins with no cross-reactivity between them. Separated BCEA-A and BCEA-B protein extracts were immunoblotted with 27 WG patients' sera, 10 Churg-Strauss syndrome (CSS) patients' sera, 31 rheumatoid arthritis (RA) patients' sera, and 40 healthy control subjects' sera from the blood bank. RESULTS: Forty-six percent of WG patients' sera had antibodies to one of the 66-kDa antigens, whereas none of the healthy control subjects' sera had 66-kDa antibodies (P < 10(-5)). In the WG group, 31% were positive to BCEA-A (versus controls, P = 0.0023), and 15% were positive to BCEA-B. WG patients with peripheral ulcerative keratitis (PUK) had a significant association with anti-BCEA-A antibodies when compared with healthy control subjects (50%, P < 10(-6)). However, in the RA group with no eye disease there was an association with BCEA-A (25%, P = 0.011) but not in the RA group with PUK. The frequency of anti-BCEA-B antibodies was significantly increased in patients with CSS (60%, P < 10(-7)). CONCLUSIONS: In summary, it has been shown that vasculitis patients have antibodies to two 66-kDa corneal antigens and that autoantibodies to these antigens are mutually exclusive. It has also been shown that antibodies to BCEA-B are associated with CSS, whereas BCEA-A antibodies are associated with WG and RA.

Adult↗

PubMed1997

Mutation in an alpha1-antitrypsin enhancer results in an interleukin-6 deficient acute-phase response due to loss of cooperativity between transcription factors.

We previously reported that a mutation in a 3' enhancer region of the alpha1-antitrypsin (AAT) gene is associated with chronic obstructive airways disease (COAD). During the acute-phase response the plasma concentration of AAT increases approximately 3-fold and this effect is mediated primarily by interleukin-6 (IL-6). We demonstrate, by transfection of Hep G2 cells, that the AAT gene contains at least two enhancers, one at the 5' end of the gene which is dominant under basal conditions, and another at the 3' end of the gene which exhibits weak basal activity. However, both enhancers must be present to modulate the IL-6-induced response which is diminished as a consequence of the 3' enhancer mutation. These results suggest that the 3' enhancer modulates the IL-6 response through an interaction with the 5' enhancer. The mutation occurs at a DNA binding site for the ubiquitous transcription factor octamer-1 (Oct-1) and results in a loss of cooperativity between Oct-1 and the tissue-specific transcription factor, NF-IL6 (C/EBPbeta), a member of the C/EBP family of transcription factors. NF-IL6 is a key transcription factor for a major pathway through which IL-6 mediates its effects. These observations provide a novel mechanism for a diminished IL-6-induced response.

Acute-Phase Reaction↗

PubMed1997

Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci.

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders affecting primarily the shoulder and pelvic girdles. Autosomal dominant and recessive forms have been identified; 8 have been mapped and 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives with only mildly elevated CK levels were assigned an unknown phenotype to prevent their possible misclassification. Two-point linkage analysis of the disease locus against markers linked to 7 of the known LGMD loci and 3 other candidate genes yielded lod scores of < or = -2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD.

Adolescent↗

PubMed1997

SMN(T) and NAIP mutations in Canadian families with spinal muscular atrophy (SMA): genotype/phenotype correlations with disease severity.

Childhood-onset spinal muscular atrophy (SMA) is an autosomal recessive neuropathy characterized by selective degeneration of alpha-motor neuron cells of the spinal cord. Age of onset and motor development varies greatly among patients, but the molecular basis of this variability remains unclear. The SMA locus contains two copies of a 500-kb element and deletions within the telomeric element have been shown to be the most common cause of SMA. To study the relationship between genotype and phenotype, 60 SMA families, all but two of which are of French Canadian origin, were screened for deletions in the telomeric survival motor neuron (SMN(T)) and the intact neuronal apoptosis inhibitory protein (NAIP) genes. Combining these results with those obtained for the multicopy microsatellite marker Ag1-CA (D5S1556) indicated that there are at least two types of SMA alleles. Most type I SMA patients are homozygous for large scale deletions involving the entire SMN(T) gene as well as exons 5 and 6 of the NAIP gene. The strong association between the 100-bp allele of Ag1-CA and large scale deletions in populations of diverse ethnic origin suggests that this allele marks an unstable or founder SMA chromosome. In contrast, most chronic SMA patients have at least one SMA allele with either an intragenic SMN(T) deletion or a SMN(C):SMN(T) chimeric gene which replaces the normal SMN(T) gene. The broad continuum of disease presentation in chronic SMA is most likely a consequence of the interaction between different SMA alleles.

Canada↗

PubMed1997

Lack of association between bipolar disorder and tyrosine hydroxylase: a meta-analysis.

Tyrosine hydroxylase (TH) is a candidate gene extensively explored in several association studies of bipolar disorder (BD). However, because of conflicting results of independent studies and low statistical power of individual studies to detect small differences between cases and controls, reliable conclusions are difficult to formulate. A method to obtain more reliable conclusions about the involvement of the TH locus in the etiology of BD is meta-analysis. We undertook a meta-analysis of studies that investigated the association between BD and TH genetic markers. The studies were identified by means of computerized searches of several databases, and the scanning of review articles and the reference lists of the primary articles identified. More than 60 publications were reviewed, and 9 relevant articles were included in this meta-analysis, with an overall sample of 1,069 subjects (547 cases and 522 normal controls). The overall odds ratio (and confidence interval) based on combining the results of the studies was 1.02 (0.68-1.54). Test of the null hypothesis that the mean log odds ratio equals zero (chi2 = 0.11; 5 df; P > 0.05) indicated that there was no overall association between bipolar disorder and tyrosine hydroxylase.

Bipolar Disorder↗

PubMed1997

Schizophrenia and chromosome 6p.

Several studies have recently reported genetic linkage between markers located on the short arm of chromosome 6 and schizophrenia. Valid conclusions, however, are difficult to formulate because chromosomal markers that yielded positive results span a relatively large region of chromosome 6, and studies did not necessarily obtain consistent results with regard to the particular loci tested. Here, we report a meta-analysis of the results of linkage studies of schizophrenia that used chromosome 6p markers. After conducting a systematic search, nine different studies were selected for the analysis using defined criteria. Pooled P values were obtained for all common markers investigated and provided additional support for a major susceptibility locus for schizophrenia in this region. In addition, two markers located 2 cM apart, D6S274 and D6S285, provided the most significant results. These findings may help narrow the chromosomal region in the search for a major gene implicated in schizophrenia.

Chromosomes, Human, Pair 6↗

PubMed1997

Modeling the phenotype in parametric linkage analysis of bipolar disorder.

The definition of phenotype is a major problem in genetic studies of psychiatric disorders. Most linkage studies in bipolar disorder have defined the phenotype as a dichotomous trait and have usually employed different hierarchical classifications in order to overcome uncertainty resulting from phenotypic variability. In this study we explored the advantages of maximizing the evidence for linkage over different phenotypic definitions when conducting parametric linkage analysis of a complex trait. The GAW10 Problem 1 was used, focusing on chromosome 18 data sets. Three major phenotypic models were analyzed: quasi-quantitative, liability-based and affection-status models. Overall, no single phenotypic model performed consistently better than the others (i.e., lod scores greater than 1.0). Each model yielded higher lod scores than the others in particular instances, suggesting that it might be useful in exploratory data analysis, where the phenotype is variable, to maximize evidence for linkage over different phenotypic models.

Bipolar Disorder↗

PubMed1997

T cell responses to human type II collagen in patients with rheumatoid arthritis and healthy controls.

OBJECTIVE: To study the prevalence of T cell responses to human type II collagen (CII) in patients with rheumatoid arthritis (RA) with or without antibodies to CII, and in healthy controls. METHODS: Assays were performed to study T cell proliferative responses to CII in peripheral blood from 69 patients with RA (11 with anti-CII antibodies and 58 without) and 28 healthy controls. Further analysis was made of the time course of the response and the epitopic specificity, using peptides derived from the cyanogen bromide 11 (CB11) fragment of CII. RESULTS: Significant proliferative responses to CII were found in 50% of patients with anti-CII, 5.3% of RA patients without these antibodies, and 35.7% of healthy controls. Responses in RA patients differed from those in healthy controls; the former had kinetics suggestive of a recall response and the latter that of a primary response. Some common epitopes within CB11 were recognized by T cells from patients and controls. CONCLUSION: Proliferative T cell responses to CII occur in some healthy individuals, suggesting that thymic tolerance for this antigen may be incomplete. Most patients with RA have no evidence of a T cell response to CII, possibly indicating the development of peripheral tolerance to this antigen as a consequence of cartilage breakdown. However, in a minority of patients, T and B cell responses to CII persist, and may contribute to joint damage.

Adult↗

PubMed1997

Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion.

We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.

Adolescent↗