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M Walker

Publications and source records attributed to M Walker.

At least 181 records · Page 10Linked to original sources
PubMed1999

Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years.

Factors operating in fetal life or during childhood may be important in determining fibrinogen and factor VII concentrations in adult life, and particularly in explaining social gradients in cardiovascular disease risk. In 1994, the authors measured fibrinogen and factor VIIc levels in 641 children aged 10-11 years (61% response rate) from schools in five towns in England and Wales. Birth weight was obtained by maternal recall, and other data on measures of fetal growth were obtained from birth records. Fibrinogen levels were higher in girls (258.8 mg/dl) than in boys (245.4 mg/dl) (95% confidence interval (CI) for difference: 5.5, 21.5). Fibrinogen and factor VIIc levels were linearly related to adiposity, rising by 37.1 mg/dl (95% CI: 24.7, 49.5) and 13.0% of standard (95% CI: 6.3, 19.7), respectively, between the bottom and top quintiles of ponderal index (weight (kg)/height (m)3). Fibrinogen was independently related to heart rate (p < 0.001) and was negatively but nonsignificantly related to measures of physical activity. Factor VIIc was positively correlated with total cholesterol (p < 0.001). No relations were found with measures of fetal growth or social class. These data do not support the concept that fibrinogen or factor VII levels are determined in utero or by social factors in childhood. Adiposity and physical training appear to be the important determinants of fibrinogen and factor VII levels in childhood.

Adipose Tissue↗
PubMed1999

Nonrandom tissue distribution of mutant mtDNA.

Heteroplasmic mitochondrial DNA (mtDNA) defects are an important cause of inherited human disease. On a cellular level, the percentage of mutant mtDNA is the principal factor behind the expression of the genetic defect. Marked variation in the level of mutant mtDNA among tissues is thought to be responsible for the diverse clinical phenotypes associated with the same pathogenic mtDNA mutation. This study was designed to determine whether the percentage level of a pathogenic mtDNA molecule is determined by a purely random process. The tissue distribution of the A3243G MELAS point mutation was analyzed in five individuals who were members of a family with maternally inherited diabetes and deafness. The level of mutant mtDNA was measured in four tissues in three individuals and three tissues in two individuals. The highest level of mutant mtDNA occurred in skeletal muscle, followed by hair follicles, and then buccal mucosa, with the lowest levels in blood (leucocyte/platelet fraction). The probability of observing any strict hierarchy in family is 4.82 x 10(-5). These results indicate that the distribution of the A3243G mutation is not solely determined by random processes.

Adult↗
PubMed1999

Absolute configurations of Emycin D, E and F; mimicry of centrosymmetric space groups by mixtures of chiral stereoisomers.

The crystal structures of Emycin E (1), di-o-bromobenzoyl-Emycin F (2) and o-bromobenzoyl-Emycin D (3) have been determined by X-ray analysis at low temperature. Emycin E and o-bromobenzoyl-Emycin D both crystallize with two molecules in a triclinic unit cell. These two structures can be solved and refined either in the centrosymmetric space group P1;, with apparent disorder localized at or around the expected chiral centre, or in the non-centrosymmetric space group P1 as mixtures of two diastereomers without disorder. Only the latter interpretation is consistent with the chemical and spectroscopic evidence. Refinements in the centrosymmetric and non-centrosymmetric space groups are compared in this paper and are shown to favour the chemically correct interpretation, more decisively so in the case of the bromo derivative as a result of the anomalous dispersion of bromine. Structures (1) and (3) provide a dramatic warning of the dangers inherent in the conventional wisdom that if a structure can be refined satisfactorarily in both centrosymmetric and non-centrosymmetric space groups, the former should always be chosen. In these two cases, despite apparently acceptable intensity statistics and R factors (5.87 and 3.55%), the choice of the centrosymmetric space group leads to the serious chemical error that the triclinic unit cell contains a racemate rather than two chiral diastereomers! The weakest reflections are shown to be most sensitive to the correct choice of space group, underlining the importance of refining against all data rather than against intensities greater than a specified threshold. The use of similar-distance restraints is shown to be beneficial in both P1 refinements. Di-o-bromobenzoyl-Emycin F crystallizes in the monoclinic space group P2(1) with one molecule in the asymmetric unit and so does not give rise to these problems of interpretation. The absolute configuration of the two bromo derivatives, and hence the Emycins in general, was determined unambiguously as S at the chiral centre C3.

Journal Article↗
PubMed1999

Observation of transient disorder during myosin subfragment-1 binding to actin by stopped-flow fluorescence and millisecond time resolution electron cryomicroscopy: evidence that the start of the crossbridge power stroke in muscle has variable geometry.

The mechanism of binding of myosin subfragment-1 (S1) to actin in the absence of nucleotides was studied by a combination of stopped-flow fluorescence and ms time resolution electron microscopy. The fluorescence data were obtained by using pyrene-labeled actin and exhibit a lag phase. This demonstrates the presence of a transient intermediate after the collision complex and before the formation of the stable "rigor" complex. The transient intermediate predominates 2-15 ms after mixing, whereas the rigor complex predominates at time >50 ms. Electron microscopy of acto-S1 frozen 10 ms after mixing revealed disordered binding. Acto-S1 frozen at 50 ms or longer showed the "arrowhead" appearance characteristic of rigor. The most likely explanation of the disorder of the transient intermediate is that the binding is through one or more flexible loops on the surfaces of the proteins. The transition from disordered to ordered binding is likely to be part of the force-generating step in muscle.

Actins↗
PubMed1999

Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of Type II (non-insulin-dependent) diabetic parents: evidence of several aberrations.

AIMS/HYPOTHESIS: Insulin resistance is a common feature in relatives of patients with Type II (non-insulin-dependent) diabetes mellitus and abnormalities in beta-cell function can also exist. Insight into non-fasting carbohydrate metabolism in these potentially prediabetic subjects relies almost exclusively on studies in which glucose is infused or ingested or both. We aimed to characterize insulin secretion and aspects of hormonal and metabolic patterns in relatives using a physiological approach. METHODS: We examined profiles of insulin, C peptide, proinsulin, gut incretin hormones and fuel substrates in 26 glucose tolerant but insulin resistant (clamp) relatives and 17 control subjects during a 24-hour period including three meals. RESULTS: During the day plasma glucose was slightly raised in relatives (p < 0.05). Overall insulin secretion calculated on the basis of C peptide kinetics were increased in relatives (p < 0.0005) whereas incremental insulin secretion after all three meals were similar. Peak incremental insulin secretion tended, however, to be reduced in relatives (p < 0.10). Despite considerably increased insulin concentrations in relatives (70 %, p < 0.001), serum NEFA did not differ. Postprandial proinsulin concentrations (p < 0.05), but not proinsulin:insulin ratios, were increased in relatives. After meals concentrations of glucose-dependent-insulinotropic polypeptide (p < 0.05) were increased in relatives. Glucagon-like peptide-1 concentrations were similar. CONCLUSION/INTERPRETATION: Several hormonal and metabolic aberrations are present in healthy relatives of Type II diabetic patients during conditions that simulate daily living. Increased concentrations of glucose-dependent-insulinotropic polypeptide could indicate a beta-cell receptor defect for glucose-dependent-insulinotropic polypeptide in the prediabetic stage of Type II diabetes. Incremental insulin secretion after mixed meals appear normal in relatives, although a trend towards diminished peak values possibly signifies early beta-cell dysfunction. [Diabetologia (1999) 42: 1314-1323]

Adult↗
PubMed1999

Accelerated healing of Dacron grafts seeded by preclotting with autologous bone marrow blood.

> Studies have suggested that bone marrow-derived cells in the circulation may have the capacity and potential to endothelialize and heal vascular graft surfaces. We have investigated whether accelerated endothelialization could be achieved for Dacron grafts seeded by preclotting with bone marrow blood (BMB). Five 8 mm x 6 cm Dacron grafts seeded and preclotted with BMB and four controls preclotted with peripheral blood were implanted in the descending thoracic aorta (DTA) of mongrel dogs for 2 and 4 weeks. Two additional BMB DTA grafts were studied for 3 months. Five pairs of BMB and control grafts (4 mm x 6 cm) were bilaterally implanted into the carotids of dogs for 1 week and five pairs for 4 weeks. All grafts remained patent. BMB seeding/preclotting was a simple, effective method to accelerate early graft endothelialization without increasing thrombogenicity. Further studies are needed before clinical application can be recommended.

Animals↗
PubMed1999

Neuropsychiatric aspects of Alzheimer's disease.

The increase in research studies focusing on neuropsychiatric symptoms over the last decade has greatly increased our knowledge base, particularly with regard to the frequency of these symptoms and their impact on both patients and carers. We still have a poor understanding of the natural course of these symptoms and their biologic correlates, however, and more specific treatment studies are needed to inform clinical management.

Aged↗
PubMed1999

Acetylcholine in mind: a neurotransmitter correlate of consciousness?

The cholinergic system is one of the most important modulatory neurotransmitter systems in the brain and controls activities that depend on selective attention, which are an essential component of conscious awareness. Psychopharmacological and pathological evidence supports the concept of a 'cholinergic component' of conscious awareness. Drugs that antagonize muscarinic receptors induce hallucinations and reduce the level of consciousness, while the nicotinic receptor is implicated as being involved in the mechanism of action of general (inhalational) anaesthetics. In degenerative diseases of the brain, alterations in consciousness are associated with regional deficits in the cholinergic system. In Alzheimer's disease (AD), there is a loss of explicit (more than implicit) memory and hypoactivity of cholinergic projections to the hippocampus and cortex, while the visual hallucinations experienced by subjects with Dementia with Lewy bodies (DLB) are associated with reductions in neocortical ACh-related activity. In Parkinson's disease, the additional loss of pedunculopontine cholinergic neurones, which control REM (rapid eye movement) sleep or dreaming, is likely to contribute to REM abnormalities, which also occur in DLB. Widespread basal-forebrain and rostral brainstem cholinergic pathways, which include converging projections to the thalamus, appear to be located strategically for generating and integrating conscious awareness. Alleviation of a range of cognitive and non-cognitive symptoms by drugs that modulate the cholinergic system, which are being developed for the treatment of AD and related disorders, could be caused by changes in consciousness.

Acetylcholine↗
PubMed1999

Reply to Holscher

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Validity of a self-reported history of doctor-diagnosed angina.

The objective of this study was to assess the validity of a self-reported history of doctor-diagnosed angina in population-based studies in men. Subjects were 5789 men from the British Regional Heart Study who reported being without an angina diagnosis at entry (1978-1980) and were alive at the end of 1992, aged 52 to 75 years. In 1992, subjects were asked in a self-administered questionnaire if they recalled ever having had a doctor diagnosis of angina. Self-report of diagnosed angina was compared with general practice (GP) record of angina obtained from reviews of medical records from study entry to the end of 1992. Men were followed for a further 3 years from 1992 for major ischemic heart disease events. The prevalence of diagnosed angina in 1992 was 10.1% according to self-reported history and 8.9% according to GP record review. There was substantial agreement between the two sources of information: 80% of men with a GP record of angina reported their diagnosis, and 70% of men who reported an angina diagnosis had confirmation of this from the record review. When all ischemic heart disease (angina or myocardial infarction) was considered, agreement was higher. Genuine angina was likely in many of the 177 men who had self-reported angina not confirmed by the GP record review: 78 had an ischemic heart disease history (myocardial infarction or coronary revascularization) identified by the review, and 31 had a GP record of angina after 1992. Angina symptoms, nitrate use, cardiological investigation, and surgical intervention for angina compared between agreement groups showed a very consistent pattern. All these indicators of angina were most common in men with both self-report and GP record of angina, least common in men with neither self-report nor GP record of angina, but had a substantially higher prevalence in men with self-reported angina only than in those with GP-recorded angina only. After 3 years follow-up from 1992, 9.5% of men with both self-report and GP record of angina, and 11.3% of men with self-reported angina only had experienced a new major ischemic heart disease event; compared to 5.7% of men with a GP record of angina only and 2.7% of those without angina by either criteria. This pattern of risk remained similar after adjustment for age and previous myocardial infarction. These results suggest that self-reported history of a doctor diagnosis of angina is a valid measure of diagnosed angina in population-based studies in men.

Adult↗
PubMed1999

Functional status and health service planning.

Functional status indicators have been proposed as instruments to aid health service planning for patients. This study examines functional status at three points surrounding an acute health episode: admission, discharge and 3 months post discharge from a community hospital. The aim of the study is to determine the most appropriate time to measure functional status to assist health service planning. A longitudinal cohort study was conducted at Manly Hospital, Australia. Four hundred patients aged 65 years and over representing a 10% random sample of all hospital admissions in a 10-month period were interviewed on admission, discharge and 3 months post discharge. Repeated measure multiple analysis of variance identified a decline in functional status between admission and discharge. At 3 months post discharge functional status had improved to levels higher than admission. Functional status assessment at discharge can assist consumers, clinicians, health planners and health insurers to make effective decisions to maximize health outcomes.

Activities of Daily Living↗
PubMed1999

HTLV-I infection and the low prevalence of Helicobacter pylori infection in Japan.

HTLV-I retrovirus infection and Helicobacter pylori infection are common in Japan; however a report in this issue shows a significantly low prevalence of H. pylori in patients infected with HTLV-I. The reasons for this may be due to differences in genetic susceptibility of the infections, the gastric milieu in HTLV-I being unable to support H. pylori, or because antimicrobial therapy in HTLV-I infection has eradicated H. pylori in this susceptible population. Similarities between HIV-1, another retroviral infection, and the prevalence of H. pylori are noted.

Comorbidity↗
PubMed1999

Role of risk factors for major coronary heart disease events with increasing length of follow up.

BACKGROUND: It has been suggested that the predictive value of certain risk factors for coronary heart disease (CHD) measured at one point in time diminishes with increasing length of follow up. DESIGNS AND METHODS: The relation was examined between a wide range of risk factors and the risk of major CHD events over 15 years' total (cumulative) follow up and for three separate five year periods (0-5.0, 5.1-10.0, and 10.1-15.0 years) in men with and without diagnosed CHD in a large prospective study of 7735 men aged 40-59 years. SETTING: General practices in 24 towns in the UK. RESULTS: The cumulative CHD event rate for all men was 9.4/1000 person-years for the 15 years of follow up. In men with no recall of a diagnosis of CHD, the established risk factors-serum total cholesterol, high density lipoprotein cholesterol, systolic and diastolic blood pressure, physical activity, body mass index (BMI), alcohol intake, diabetes mellitus, parental history, and evidence of CHD on chest pain questionnaire or on ECG-were predictive of CHD events occurring in the three specific periods after baseline measurement. Blood pressure (systolic and diastolic) was still predictive of events occurring 10.1-15.0 years later with some attenuation in the relative risk associated with systolic blood pressure. The risks associated with blood glucose and serum insulin concentration, factors measured with greater imprecision, attenuated with longer follow up and were not predictive of events occurring 10. 1-15.0 years later. In men with recall of diagnosed CHD, the absolute risk was very high (38.8/1000 person-years); only cigarette smoking, BMI, total cholesterol, and serum insulin were predictive of CHD events occurring 10.1-15.0 years later. CONCLUSION: In men without recall of diagnosed CHD most major risk factors measured in middle age predict risk of CHD events occurring in up to 15 years of follow up, both cumulatively and in the three separate five year periods. Risk factors measured at one point in time in middle age may be regarded as reliable indicators for long term prognosis of major CHD events on a group basis, despite the changes that may take place in these risk factors in some individuals during prolonged follow up.

Adult↗
PubMed1999

Serum total homocysteine and coronary heart disease: prospective study in middle aged men.

OBJECTIVES: To examine the prospective relation between total homocysteine and major coronary heart disease events. DESIGN: A nested case-control study carried out within the British regional heart study, a prospective investigation of cardiovascular disease in men aged 40-59 years at entry. Serum total homocysteine concentrations were analysed retrospectively and blindly in baseline samples from 386 cases who had a myocardial infarct during 12.8 years of follow up and from 454 controls, frequency matched by age and town. RESULTS: Geometric mean serum total homocysteine was slightly higher in cases (14.2 micromol/l) than in controls (13.5 micromol/l), a proportional difference of 5.5% (95% confidence interval (CI) -0.02% to 10.8%, p = 0.06). Age adjusted risk of myocardial infarction increased weakly with log total homocysteine concentration; a 1 SD increase in log total homocysteine (equivalent to a 47% increase in total homo cysteine) was associated with an increase in odds of myocardial infarction of 1.15 (95% CI 1.00 to 1. 32; p = 0.05). The relation was particularly marked in the top fifth of the total homocysteine distribution (values >16.5 micromol/l), which had an odds ratio of 1.77 (95% CI 1.28 to 2.42) compared with lower levels. Adjustment for other risk factors had little effect on these findings. Total homocysteine concentrations more than 16.5 micromol/l accounted for 13% of the attributable risk of myocardial infarction in this study population. Serum total homocysteine among control subjects varied between towns and was correlated with town standardised mortality ratios for coronary heart disease (r = 0.43, p = 0.08). CONCLUSIONS: Serum total homocysteine is prospectively related to increased coronary risk and may also be related to geographical variation in coronary risk within Britain. These results strengthen the case for trials of total homocysteine reduction with folate.

Adult↗