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Biomedical subjects

A J Sinclair

Publications and source records attributed to A J Sinclair.

At least 55 records · Page 3Linked to original sources
PubMed1999

The metabolism of native and randomized butterfat chylomicrons in the rat is similar.

Reportedly, randomly rearranging the position of fatty acids (FA) in butterfat triacylglycerol (TAG) by interesterification, thereby lowering the proportion of saturated FA in the sn-2 position, reduces its hypercholesterolemic and hypertriglyceridemic properties when fed to humans. The aim of this work was to determine if these reductions in plasma cholesterol and TAG could be explained by an improved rate of clearance from the plasma of chylomicrons composed of randomized butterfat, using a rat model. Acute chylomicron clearance studies demonstrated no differences in fractional clearance rates of cholesteryl esters and TAG from the plasma of rats infused with chylomicrons produced from gastric feeding of either native (NBF) or randomized (RBF) butterfat. Although there was a 14% decrease in the level of saturated FA occupying the sn-2 position of TAG in RBF compared with NBF, this difference became negligible (approximately 5%), following digestion of the fat and subsequent repackaging of TAG into chylomicrons. These observations suggest that the previously observed reduction in hypercholesterolemic properties of randomized butterfat in rat is unlikely to be explained by improved clearance of chylomicron TAG.

Animals↗
PubMed1999

Quality of life in elderly subjects with a diagnostic label of asthma from general practice registers.

The aim of this study was to assess health-related quality of life (QoL) in elderly subjects with a diagnostic label of asthma from a general practice population, and to determine the main contributory factors. Sixty people aged > or =70 yrs with a primary care diagnostic label of asthma, and 43 control subjects were recruited. Assessment of bronchodilator response, and oral steroid trials were conducted where possible. The main outcome measures were QoL scores for the Short Form (SF)-36 and the St George's Respiratory Questionnaire (SGRQ). In the asthma group, 29 subjects demonstrated a significant airway response to bronchodilators or steroids. Mean SF-36 scores were significantly worse in the total asthma group for components of physical function, physical role limitation, and general health, although psychological scores were similar. QoL remained worse than controls in those subjects with a significant bronchodilator response. Dyspnoea and depression accounted for 61% of the variance in the SGRQ, but forced expiratory volume in one second was not an independent variable. Quality of life is impaired in elderly people with a diagnosis of asthma, including those with demonstrable airway variability. Many older subjects with asthma note a variety of symptoms, highlighting the need for further research into the adequacy and efficacy of their treatment.

Aged↗
PubMed1999

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies.

Human cancers frequently sustain genetic mutations that alter the function of their G1 cell cycle control check point. These include changes to the retinoblastoma gene and to the genes that regulate its phosphorylation, such as the cyclin-dependent kinase inhibitor p16INK4a. Altered expression of retinoblastoma protein (pRb) is associated with non-Hodgkin's lymphoma, particularly centroblastic and Burkitt's lymphomas. pRb is expressed in normal B-cells and its regulatory phosphorylation pathway is activated in response to a variety of stimuli. Since human B-lymphoma-derived cell lines are often used as in vitro model systems to analyse the downstream effects of signal transduction, we examined the functional status of pRb in a panel of human B-cell lines. We identified eleven cell lines which express the hyperphosphorylated forms of pRb. Furthermore, we suggest that the pRb protein appears to be functional in these cell lines.

Burkitt Lymphoma↗
PubMed1999

The effect of diet on plasma homocysteine concentrations in healthy male subjects.

OBJECTIVE: To determine the effect of habitual omnivorous and vegetarian diets on folate and vitamin B12 status and the subsequent effect on homocysteine concentration. DESIGN: Cross-sectional comparison of free-living habitual meat-eaters and habitual vegetarians. SETTING: The study was conducted at RMIT University, Melbourne. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n=18, ovolacto vegetarians n=43, moderate meat-eaters n=60 and high meat-eaters n=18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Fasting plasma or serum from each subject was analysed for folate, vitamin B12 and homocysteine concentration. A semi-quantitative Food Frequency Questionnaire was completed by a subset of subjects from each group to determine methionine intake. RESULTS: The two meat eating groups consumed significantly greater levels of methionine (P<0.001). There was no clear trend in plasma folate status between groups, however the plasma vitamin B12 concentration decreased progressively from the high-meat-eating group to vegans (P<0.05). An inverse trend was observed with plasma homocysteine concentration, with vegans showing the highest levels and high meat eaters the lowest (P<0.05). CONCLUSIONS: Dietary methionine intake has no observable effect on plasma homocysteine concentration. In habitual diets, where folate intake is adequate, lowered vitamin B12 intake from animal foods leads to depleted plasma vitamin B12 concentration with a concomitant increase in homocysteine concentration. The suggested mechanism is the failure to transfer a methyl group from methyl tetrahydrofolate by vitamin B12 in the remethylation of homocysteine to methionine.

Adult↗
PubMed1999

Divergent requirements for the MAPK(ERK) signal transduction pathway during initial virus infection of quiescent primary B cells and disruption of Epstein-Barr virus latency by phorbol esters.

Quiescent primary B lymphocytes and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines express components of the extracellular response kinase arm of the mitogen-activated protein kinase (MAPK(ERK)) signal transduction pathway and transmit signals through the pathway when exposed to appropriate stimuli. Although the MAPK(ERK) pathway is activated following infection with EBV, MAPK/ERK kinase (MEK1) activity is not required to drive the proliferation of infected cells. However, MEK1 contributes to EBV latency control.

B-Lymphocytes↗
PubMed1999

Diabetes in the elderly: A perspective from the United Kingdom.

Within some parts of the United Kingdom major deficiencies in diabetes care for older adults exist; these include lack of screening for the disorder, failure to evaluate complications, lack of individual management plans, and failure to appreciate the role of informal caregivers. The prevalence of diabetes in the elderly varies from 3% to 9% among the indigenous population, which, although considerably lower than in other European countries, may be a tremendous health care burden in the next century. Several community surveys testify to the high level of macrovascular and microvascular complications present in the older patient with diabetes, but the impact on patients' lives (and their caregivers' lives) often is underestimated, especially as a result of unrecognized disability. Premature death in aging diabetics also requires highlighting. Identifying the most suitable care model for managing the elderly diabetic is the subject of interest in the United Kingdom, with momentum growing to facilitate shared care between the family practitioner and the hospital specialist (diabetologist or geriatrician).

Age Factors↗
PubMed1999

Effects of dietary n-3 fatty acid deficiency and repletion in the guinea pig retina.

PURPOSE: To investigate the nature and reversibility of biochemical and functional changes in the retina encountered over a single generation of dietary n-3 polyunsaturated fatty acid deficiency in guinea pigs. METHODS: Dunkin-Hartley guinea pigs were fed for 16 weeks after weaning with diets supplemented with safflower seed oil (n-3 deficient) or canola oil (n-3 sufficient, control). A number of deficient animals were repleted at 6 weeks with canola oil for 5 or 10 weeks, or at 11 weeks for 5 weeks. Electroretinograms (0.8 and 4.3 log scot td x sec) were collected at 6, 11, and 16 weeks after weaning. Conventional waveforms (a- and b-waves), oscillatory potentials, and receptoral and postreceptoral subcomponents (PIII and PII, respectively) were evaluated. Cone pathway function was assessed with 30-Hz flicker at the brighter intensity. Retinal phospholipid fatty acids were measured by capillary gas-liquid chromatography. RESULTS: Electroretinographic amplitudes showed statistically significant losses in b- and a-waves after 6 and 16 weeks of dietary n-3 deficiency, respectively. The response amplitude to 30-Hz flicker was reduced 42% after 16 weeks. Retinal docosahexaenoic acid (DHA) levels of animals maintained on the safflower oil diet for 16 weeks were 42% of levels in age-matched control subjects. There were significant losses in maximum response amplitudes (R(mPIII) and R(mPII)), although the major effect was a reduction in sensitivity of the receptoral response. Complete functional recovery was observed only in animals repleted for 10 weeks. CONCLUSIONS: Functional deficits in PIII and PII of the electroretinogram were apparent in first-generation guinea pigs fed an n-3 deficient diet. These losses showed a correlation with age and retinal DHA level, although varying degrees of dependence on the DHA level were found. All functional deficits were reversed after 10 weeks of dietary n-3 repletion. The results suggest that DHA may serve several functional and structural roles in the retina and further emphasize the requirement for DHA in the normal development of vision.

Animals↗
PubMed1998

Serum hyaluronic acid in Down's syndrome.

In agreement with previous studies we show an age-related increase in serum levels of hyaluronic acid in healthy individuals. Levels in Down's syndrome persons were slightly higher, especially in those with hypothyroidism. This provides further evidence that the normal ageing process is accelerated in Down's syndrome.

Adult↗
PubMed1998

Cell cycle arrest following exposure of EBV-immortalised B-cells to gamma irradiation correlates with inhibition of cdk2 activity.

The exposure of Epstein-Barr virus immortalised B cells (LCLs) to the genotoxic effects of gamma irradiation causes a decreased proliferation of the cells. The early events in this process have been investigated here. The induction of p53 expression correlates with a cell cycle arrest in the G1 and G2/M phases of the cell cycle within 24 h of exposure. The molecular mechanism governing the decreased proliferation appears to involve the induction of the cyclin dependent kinase (cdk) inhibitor p21CIP1 and its functional association with cdk2.

Apoptosis↗
PubMed1998

Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.

Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies after exposure to bovine thrombin preparations, or in factor V-deficient patients after plasma therapy. Clinical manifestations range from asymptomatic laboratory abnormalities to life-threatening hemorrhage. We have characterized the anti-factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8 patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin-induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and 2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the factor Va light chain, but only the 8 IgG fractions associated with hemorrhage inhibited factor V activity in a prothrombinase assay. Nine IgG fractions, including the 8 patients with hemorrhage, immunoprecipitated the isolated second C-type domain (C2). The 8 IgG fractions from the symptomatic patients also immunoprecipitated recombinant chimeras containing only the N-terminal third of the factor V C2 domain, and isolated recombinant C2 domain abrogated the inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked binding of factor V to phosphatidylserine. These results suggest that inhibitory anti-factor V antibodies are associated with hemorrhagic manifestations and frequently bind to a common region within the C2 domain, whether originating spontaneously or after exposure to bovine thrombin.

Adolescent↗
PubMed1998

The efficient and rapid import of a peptide into primary B and T lymphocytes and a lymphoblastoid cell line.

Lymphocytes are notoriously difficult to transfect. The favoured technique, electroporation, has three major disadvantages: it is highly disruptive, causing large scale cell death; it is inefficient; quiescent primary lymphocytes are refractory to electroporation unless they have been partially activated. We have investigated the cellular import of the third helix of the Antennapedia homeodomain protein (pAntp) as an alternative method for introducing peptides into primary lymphocytes and lymphoid cell lines. The pAntp peptide is taken up rapidly into the cytoplasm and nucleus of the cells where it is retained for at least 48 h. The system displays none of the disadvantages of electroporation; no toxicity of the pAntp peptide was detected at the concentrations tested and the process was efficient with up to 95% of lymphocytes importing the pAntp peptide. Finally, quiescent primary lymphocytes were as efficient as activated primary lymphocytes and a lymphoid cell line at importing the pAntp peptide. This demonstrates that the pAntp peptide delivery system has major advantages over electroporation as a method of delivering molecules to lymphocytes and a lymphoid cell line.

Amino Acid Sequence↗
PubMed1998

British Diabetic Association guidelines on genetic and immune screening for type 1 diabetes mellitus.

The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

Autoantibodies↗
PubMed1998

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia.

OBJECTIVES: Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. DESIGN: Cross-sectional comparative study. SETTING: Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. METHODS: Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). RESULTS: Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p = 0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p = 0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p = 0.046). There were no significant differences in LP or TAC between the three groups. CONCLUSIONS: Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation.

Aged↗
PubMed1998

Contribution of meat fat to dietary arachidonic acid.

Arachidonic acid (AA) in the diet can be efficiently absorbed and incorporated into tissue membranes, resulting in an increased production of thromboxane A2 by platelets and increased ex vivo platelet aggregability. Results from previous studies have shown that AA is concentrated in the membrane phospholipids of lean meats. However, the concentration of AA in the visible fat portion of meats also may be significant despite being ignored in most studies. The aim of this study was to accurately quantitate the AA content of visible fat and the lean portion of beef, lamb, pork, chicken, duck, and turkey. The visible fat of meat contained a significant quantity of AA, ranging from 20 to 180 mg/100 g fat, whereas the AA content of the lean portion of meat was lower, ranging from 30 to 99 mg/100 g lean meat. Beef and lamb meats contained lower levels of AA in both the visible fat and lean portion than that from the other species. The highest level of AA in lean meat was in duck (99 mg/100 g), whereas pork fat had the highest concentration for the visible fats (180 mg/100 g). The lean portions of beef and lamb contained the higher levels of n-3 polyunsaturated fatty acids (PUFA) compared with white meats which were high in AA and low in n-3 PUFA. The present data indicate that the visible meat fat can make a contribution to dietary intake of AA, particularly for consumers with high intakes of fat from pork or poultry meat.

Adipose Tissue↗
PubMed1998

Nutrition, ageing and ill health.

There are physical, mental, social and environmental changes which take place with ageing; for example, decreased physical activity, increase in body fat, decrease in lean body mass and consequently decreased energy intake may be associated with physiological functions that affect metabolism, nutrient intake, physical activity and risk of disease. There are now many studies which have found that undernutrition is prevalent and often unrecognized in patients admitted to hospitals and institutions. There is also evidence which links protein-energy undernutrition or its markers with clinical outcomes in acute and non-acute hospital settings and that nutritional supplements can improve outcomes in some of these settings. However, most clinically-available nutrition screening instruments lack sensitivity and specificity, and abnormal nutritional indicators may simply reflect effects of age, functional disability, or severe underlying disease. Thus, causal relationship cannot be assumed without a sufficiently powerful intervention study which adequately adjusts for the effects of non-nutritional factors, such as the number and severity of co-morbid conditions on clinical outcome.

Aged↗
PubMed1998

Comparison of guinea pig electroretinograms measured with bipolar corneal and unipolar intravitreal electrodes.

This study considers the precision and accuracy of bipolar corneal electrodes compared with unipolar intravitreal methods in collecting electroretinographic (ERG) recordings from a small animal. Flash ERGs were obtained from 9 adult guinea pigs on three occasions. Corneal bipolar (Burian-Allen) electrodes were used to collect data on the first two occasions whereas unipolar intravitreal electrodes were used on the last. We identified the a-wave, b-wave, oscillatory potentials, PIII and PII responses. Intensity-response functions were fit using a Naka-Rushton relationship with a bootstrap estimating the 95% confidence limits. Discrepancy analysis was applied to determine the coefficient of agreement. We found significantly larger amplitudes with unipolar intravitreal electrodes (ANOVA; a-wave, p<0.002; b-wave, p<0.001; Oscillatory potentials (OPs), p<0.005) especially at high intensities. Implicit times showed little differences between electrodes for the a-wave, significantly faster (p<0.03) b-waves at some intensities, and significantly slower (p<0.005) OP implicit times across all intensities. The PIlI amplitude (log microV), sensitivity and timing were not significantly different (p>O.05) if expressed in logarithmic units but PII amplitude (log microV) was significantly smaller with corneal electrodes. We suggest that a conversion factor (x1.35) should be applied to data collected with bipolar corneal electrodes to estimate the amplitudes of the modelled parameters accurately. The corneal electrode gave a precision of +/-39 microV which yields a statistical power of 0.90 for a sample size of 7 subjects. We conclude that bipolar corneal electrodes provide smaller electroretinogram amplitudes due to their location and reduced span of the retinal generators.

Animals↗