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Biomedical subjects

A Atkinson

Publications and source records attributed to A Atkinson.

At least 19 recordsLinked to original sources
PubMed2000

Bacterial, viral and parasitic aetiology of paediatric diarrhoea in the highlands of Papua New Guinea.

Enteropathogens and clinical features associated with diarrhoea were investigated in 1526 children admitted over a 5-year period to the paediatric ward of a hospital in the highlands of Papua New Guinea. Overall, a recognized pathogen was isolated from 39 per cent of the children admitted with diarrhoea. The most commonly isolated agents were rotavirus (23 per cent), Shigella spp. (13 per cent), Campylobacter spp. (12 per cent), Cryptosporidium parvum (10 per cent) and enteropathogenic Escherichia coli (8 per cent). The clearest clinical associations were rotavirus with vomiting, and Shigella with blood and pus in the stool. A control series of children admitted with other complaints was also included, and the odds ratios for diarrhoea for the above five pathogens were 18.2, 9.6, 3.7, 2.2, and 1.6, respectively.

Bacterial Infections↗
PubMed2000

Kinetics of L-[1-(13)C]leucine when ingested with free amino acids, unlabeled or intrinsically labeled casein.

In two groups of five adults, each adapted to two different dietary regimens for 6 days, the metabolic fate of dietary [1-(13)C]leucine was examined when ingested either together with a mixture of free amino acids simulating casein (extrinsically labeled; condition A), along with the intact casein (extrinsically labeled; condition B), or bound to casein (intrinsically labeled; condition C). Fed state leucine oxidation (Ox), nonoxidative leucine disposal (NOLD), protein breakdown, and splanchnic uptake have been compared using an 8-h oral [1-(13)C]leucine and intravenous [(2)H(3)]leucine tracer protocol while giving eight equal hourly mixed meals. Lower leucine Ox, increased NOLD, and net protein synthesis were found with condition C compared with condition A (19.3 vs. 24.9; 77 vs. 55.8; 18.9 vs. 12.3 micromol. kg(-1). 30 min(-1); P < 0.05). Ox and NOLD did not differ between conditions B and C. Splanchnic leucine uptake calculated from [1-(13)C]- and [(2)H(3)]leucine plasma enrichments was between 24 and 35%. These findings indicate that the form in which leucine is consumed affects its immediate metabolic fate and retention by the body; the implications of these findings for the tracer balance technique and estimation of amino acid requirements are discussed.

Adult↗
PubMed2000

Cyclophosphamide and water retention: mechanism revisited.

We describe an 8 year-old girl with established diabetes insipidus who developed cyclophosphamide-associated antidiuresis. The patient had received cyclophosphamide as part of a high-dose chemotherapy regimen for recurrent suprasellar dysgerminoma prior to autologous bone marrow transplantation. Urinary output decreased and specific gravity increased shortly after a 1 hour i.v. infusion of 50 mg/kg cyclophosphamide and the effect lasted some 5 hours. No other drug could be implicated. This response, occurring in a patient with no ability to secrete vasopressin, suggests a direct tubular effect of one or more cyclophosphamide metabolites. Administering i.v. cyclophosphamide requires careful monitoring of fluid balance in order to avoid water intoxication. Further research is warranted both into the mechanism of this effect and the metabolite responsible for it.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease.

PURPOSE: To assess the mutation spectrum in the ABCR gene and clinical phenotypes in Italian families with autosomal recessive Stargardt disease (STGD1) and fundus flavimaculatus (FFM). METHODS: Eleven families from southern Italy, including 18 patients with diagnoses of STGD1, were clinically examined. Ophthalmologic examination included kinetic perimetry, electrophysiological studies, and fluorescein angiography. DNA samples of the affected individuals and their family members were analyzed for variants in all 50 exons of the ABCR gene by a combination of single-strand conformation polymorphism analysis and direct sequencing techniques. RESULTS: TenABCR variants were identified in 16 (73%) of 22 mutant alleles of patients with STGD1. Five mutations of 10 that were found had not been previously described. The majority of variants represent missense amino acid substitutions, and all mutant alleles cosegregate with the disease in the respective families. These ABCR variants were not detected in 170 unaffected control individuals (340 chromosomes) of Italian origin. Clinical evaluation of these families affected by STGD1 showed an unusually high frequency of early age-related macular degeneration (AMD) in parents of patients with STGD1 (8/22; 36%), consistent with the hypothesis that some heterozygous ABCR mutations enhance susceptibility to AMD. CONCLUSIONS: Patients from southern Italy with Stargardt disease show extensive allelic heterogeneity of the ABCR gene, concordant with previous observations in patients with STGD1 from different ethnic groups. Half the mutations identified in this study had not been previously described in patients with STGD1. Screening of increasingly large numbers of patients would help to determine whether this can be explained by ethnic differences, or is an indicator of extensive allelic heterogeneity of ABCR in STGD1 and other eye diseases. In 6 (55%) of 11 families, the first-degree relatives of patients with STGD1 were diagnosed with early AMD, supporting the previous observation that some STGD1 alleles are also associated with AMD.

ATP-Binding Cassette Transporters↗
PubMed1999

Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.

Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category.

Adult↗
PubMed1999

Determination of glucosinolates using their alkaline degradation and reaction with ferricyanide.

Glucosinolates, a group of naturally occurring thioglucosides, are significant factors impairing the nutritional quality of rapeseed and postextraction rapeseed meal, restricting its use as high-quality protein animal feed. Currently, the European Community standards and Canola definition are being brought in line recommending cultivation and marketing of rapeseed with a glucosinolate content below 18 micromol of total glucosinolates per gram of seeds. Furthermore, some glucosinolates are of increasing interest in Brassica vegetables due to their proven cancer-preventing activities. A novel approach to the analysis of total glucosinolates is reported in this paper based on their alkaline degradation and subsequent reaction of released 1-thioglucose with ferricyanide. The reaction was followed spectrophotometrically using sinigrin and glucotropeaolin as model glucosinolates. The applicability of the method was demonstrated using rapeseed extracts after reducing the interfering effect of phenolics by their adsorption onto polyvinylpolypyrrolidone. Good agreement with official ISO methods was shown.

Brassica↗
PubMed1999

Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice.

The effect of mercuric chloride (HgCl2) on the activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and its effect on glutathione (GSH) content were evaluated in different organs (liver, kidneys, and brain) of mice after administration at 0, 0.25, 0.5 and 1.0 mg/kg/day for 14 days. The uptake of mercury shows that the kidneys accumulated the highest levels of mercury compare to brain and liver. The enzyme levels varied in mercury treated organs compare to control. A dose dependent increase of antioxidant enzymes occurred in the liver and kidneys. The increase in enzyme activities correlated with highest mercury accumulation in the kidneys and liver. Mercury is known to generate reactive oxygen species (ROS) in vivo and in vitro, therefore, it is likely that enzyme activities increased to scavenge ROS levels produced as a result of mercury accumulation. Glutathione content increased in liver and kidneys of mercury treated mice compare to control. The results showed that the highest oral dose of mercury significantly increased antioxidant enzymes in kidneys and liver. The increased antioxidant enzymes enhance the antioxidant potential of the organs to reduce oxidative stress.

Animals↗
PubMed1999

CYP2D6 is associated with Parkinson's disease but not with dementia with Lewy Bodies or Alzheimer's disease.

The similarities between the clinical and pathological findings of dementia with Lewy Bodies (DLB) with Alzheimer's disease and Parkinson's disease are complex, and their significance for pathogenesis is unresolved. It is likely that DLB shares common disease determinants with both Alzheimer's disease and Parkinson's disease. Clinically DLB shows the presence of dementia similar, though not identical, to that found in Alzheimer's disease. A parkinsonian movement disorder is present in a proportion of DLB cases. Pathologically DLB shows senile plaques, as with Alzheimer's disease, and also substantia nigra neurone loss and Lewy bodies, as with Parkinson's disease. At a genetic level, DLB shows an elevated Apolipoprotein E epsilon4 frequency as described in Alzheimer's disease, but this is absent in Parkinson's disease. An elevated frequency of the CYP2D6*4 allele has been found in Parkinson's disease and we have therefore genotyped a large series of clinically and neuropathologically confirmed cases of DLB, Alzheimer's disease, Parkinson's disease and age-matched control individuals for the CYP2D6*4 allele. Whilst an elevated frequency of the CYP2D6*4 allele was found in Parkinson's disease, no such elevations were found in DLB or Alzheimer's disease. Stratification of the CYP2D6*4 allele with respect to the Apolipoprotein E epsilon4 also did not show any significant associations with the CYP2D6*4 allele. The CYP2D6*4 allele is not a major genetic determinant of DLB and the results place DLB with Alzheimer's disease rather than Parkinson's disease on a genetic level.

Aged↗
PubMed1999

The Arabidopsis FILAMENTOUS FLOWER gene is required for flower formation.

A screen for mutations affecting flower formation was carried out and several filamentous flower (fil) alleles were identified. In fil mutants, floral primordia occasionally give rise to pedicels lacking flowers at their ends. This defect is dramatically enhanced in fil rev double mutants, in which every floral primordium produces a flowerless pedicel. These data suggest that the FIL and REV genes are required for an early step of flower formation, possibly for the establishment of a flower-forming domain within the floral primordium. The FIL gene is also required for establishment of floral meristem identity and for flower development. During flower development, the FIL gene is required for floral organ formation in terms of the correct numbers and positions; correct spatial activity of the AGAMOUS, APETALA3, PISTILLATA and SUPERMAN genes; and floral organ development.

AGAMOUS Protein, Arabidopsis↗
PubMed1998

Representations of self in women sexually abused in childhood.

OBJECTIVE: This exploratory study examined the self representations of 27 women sexually abused in childhood and their association with symptomatology. METHOD: Twenty-seven self-identified female survivors of childhood sexual abuse completed the Trauma Symptom Checklist-40, Beck Depression Inventory, State-Trait Anxiety Inventory and a measure designed to elicit subjects' self-generated descriptors of selves. RESULTS: Discrepancies in views of current self when compared to ideal or future selves were positively correlated with all symptom measures. Discrepancies in representations of current self compared to views of who they were when they were with their perpetrator were negatively correlated with trait anxiety. Self integration, as defined in this study, was negatively correlated with symptoms. CONCLUSIONS: This study suggests that cognitive representations of self are an important indicator of adjustment in survivors of childhood sexual abuse.

Adult↗
PubMed1998

Twenty-four-hour intravenous and oral tracer studies with L-[1-13C]-2-aminoadipic acid and L-[1-13C]lysine as tracers at generous nitrogen and lysine intakes in healthy adults.

BACKGROUND: This is a continuation of investigations of the relations between amino acid kinetics and amino acid dietary requirements in healthy adults. OBJECTIVE: The aim was to investigate the 24-h pattern and rate of the metabolism of an L-[1-13C]-2-aminoadipic acid ([13C]AAA) tracer and of whole-body L-[1-13C]lysine ([13C]lysine) oxidation and balance in healthy, young adults receiving a generous intake of lysine. DESIGN: Thirteen healthy adults were given an adequate, L-amino acid-based diet supplying 77 mg lysine x kg(-1) x d(-1) for 6 d before the tracer studies. Two subjects received [13C]AAA intravenously and 2 received it orally; 3 subjects received [13C]lysine intravenously and 6 received it orally. We measured 13CO2 output, plasma [13C]AAA and [13C]lysine enrichment, and urinary [13C]AAA. RESULTS: [13C]AAA oxidation was estimated to be higher after the orally administered than after the intravenously administer tracer; plasma [13C]AAA was similar to urinary [13C]AAA. Whole-body lysine oxidation showed a rhythm that was induced by meal feeding. The intravenous [13C]lysine tracer gave mean estimates of lysine balances (lysine intake minus oxidation) that apparently were too low (-15.7 mg x kg(-1) x d(-1)) or too high (16.6 mg x kg(-1) x d(-1), P < 0.05 from zero balance) on the basis of urinary [13C]AAA or plasma [13C]lysine estimates of oxidation, respectively. For the orally administered tracer and plasma [13C]lysine enrichment, the mean balance was slightly positive (8.7 mg x kg(-1) x d(-1), P < 0.05 from zero). CONCLUSIONS: Use of urinary [13C]AAA as an index of the enrichment of the precursor pool did not appear to significantly improve the estimate of the fasting and feeding components of daily lysine balance. For estimates of daily, whole-body lysine oxidation, we propose use of plasma [13C]lysine with a 24-h, orally administered tracer protocol.

2-Aminoadipic Acid↗
PubMed1997

Biochemical and molecular changes at the cellular level in response to exposure to environmental estrogen-like chemicals.

Estrogen-like chemicals are unique compared to nonestrogenic xenobiotics, because in addition to their chemical properties, the estrogenic property of these compounds allows them to act like sex hormones. Whether weak or strong, the estrogenic response of a chemical, if not overcome, will add extra estrogenic burden to the system. At elevated doses, natural estrogens and environmental estrogen-like chemicals are known to produce adverse effects. The source of extra or elevated concentration of estrogen could be either endogenous or exogenous. The potential of exposure for humans and animals to environmental estrogen-like chemicals is high. Only a limited number of estrogen-like compounds, such as diethylstilbestrol (DES), bisphenol A, nonylphenol, polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (DDT), have been used to assess the biochemical and molecular changes at the cellular level. Among them, DES is the most extensively studied estrogen-like chemical, and therefore this article is focused mainly on DES-related observations. In addition to estrogenic effects, environmental estrogen-like chemicals produce multiple and multitype genetic and/or nongenetic hits. Exposure of Syrian hamsters to stilbene estrogen (DES) produces several changes in the nuclei of target organ for carcinogenesis (kidney): (1) Products of nuclear redox reactions of DES modify transcription regulating proteins and DNA; (2) transcription is inhibited; (3) tyrosine phosphorylation of nuclear proteins, including RNA polymerase II, p53, and nuclear insulin-like growth factor-1 receptor, is altered; and (4) DNA repair gene DNA polymerase beta transcripts are decreased and mutated. Exposure of Noble rats to DES also produces several changes in the mammary gland: proliferative activity is drastically altered; the cell cycle of mammary epithelial cells is perturbed; telomeric length is attenuated; etc. It appears that some other estrogenic compounds, such as bisphenol A and nonylphenol, may also follow a similar pattern of effects to DES, because we have recently shown that these compounds alter cell cycle kinetics, produce telomeric associations, and produce chromosomal aberrations. Like DES, bisphenol A after metabolic activation is capable of binding to DNA. However, it should be noted that a particular or multitype hit(s) will depend upon the nature of the environmental estrogen-like chemical. The role of individual attack leading to a particular change is not clear at this stage. Consequences of these multitypes of attack on the nuclei of cells could be (1) nuclear toxicity/cell death; (2) repair of all the hits and then acting as normal cells; or (3) sustaining most of the hits and acting as unstable cells. Proliferation of the last type of cell is expected to result in transformed cells.

Animals↗
PubMed1997

Moderate exercise at energy balance does not affect 24-h leucine oxidation or nitrogen retention in healthy men.

Short-term metabolic experiments have revealed that physical exercise increases the oxidation of leucine, which has been interpreted to indicate an increased requirement for dietary protein in physically active subjects. Because it may be inaccurate to extrapolate measurements of amino acid oxidation made over a few hours to the entire day, we have carried out a continuous 24-h intravenous [1-13C]leucine/[15N]urea tracer study in eight healthy adult men. Their diet supplied 1 g protein.kg-1.day-1, and exercise (mean maximal O2 consumption 46%) was for 90 min during the 12-h fast and 12-h fed periods of the day. Subjects were adapted to the diet and exercise regimen for 6 days. Then, on day 7, they were dressed in the University of Uppsala energy metabolic unit's direct calorimeter suit, were connected to an open-hood indirect calorimeter, and received the tracers. Exercise increased leucine oxidation by approximately 50 and 30% over preexercise rates for fast and fed periods, respectively. This increase amounted to approximately 4-7% of daily leucine oxidation. Subjects remained in body leucine equilibrium (balance -4.6 +/- 10.5 mg.kg-1.day-1; -3.6 +/- 8.3% of intake; P = not significant from zero balance). Therefore, moderate exercise did not cause a significant deterioration in leucine homeostasis at a protein intake of 1 g.kg-1.day-1. These findings underscore the importance of carrying out precise, continuous, 24-h measurements of whole body leucine kinetics; this model should be of value in studies concerning the quantitative interactions among physical exercise, energy/protein metabolism, and diet in humans.

Adult↗
PubMed1997

Effectiveness of a training program for enhancing therapists' understanding of the supportive-expressive treatment model for breast cancer groups.

This study evaluated a training program for leaders of supportive-expressive psychotherapy groups for breast cancer patients. Twenty-four mental health/medical cancer care professionals completed two training phases and were tested for their understanding of the treatment model. Participants' understanding was enhanced as a result of the training program. This study demonstrates that a brief training program can improve therapists' understanding of the treatment model and demonstrates an effective method of evaluation. Future research should examine how performance on these tests generalizes to performance when leading a supportive-expressive group.

Adult↗
PubMed1996

Plasma glycocalicin levels are not elevated in patients with a history of transient ischaemic event and are normal in aspirinated normal volunteers.

Glycocalicin (GC) is the soluble portion of platelet membrane protein GP1b, and may be cleaved from the platelet surface during platelet activation. Previous study has indicated that plasma glycocalicin/platelet (GC/plt) levels are elevated in patients presenting with acute stroke. The present study was undertaken to determine the GC/plt levels in patients being treated for transient ischaemic episodes, to assess whether the elevated GC/plt level in acute stroke is due to a detectable, constitutive premorbid state of platelet activation. In sixteen consecutive patients attending a vascular surgery clinic, GC levels were measured on a citrated plasma sample, and corrected for circulating platelet count. Since 15 of 16 patients were taking aspirin when seen at clinic, a control study was undertaken to assess the effect of aspirin on sequential plasma GC/plt levels measured over 10 days--5 pre and post daily aspirin for 5 days, 4 acting as non-aspirinated controls. Plasma GC/plt levels in normal plasma were 21.6 +/- 8.0 fg; mean +/- SD. In the 16 patients the GC/plt levels were 13.1 fg/plt; SD 5.4, range 2.9-24.3. All platelet counts were in the normal range in all patients involved. While a masking effect due to aspirin cannot be completely ruled out, these studies indicate that plasma GC/plt level is not useful as a predictor of acute stroke in the premorbid population.

Aspirin↗
PubMed1996

Effects of age on energy expenditure and substrate oxidation during experimental overfeeding in healthy men.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of overfeeding on changes in energy expenditure, substrate oxidation, and energy deposition between young men (age 23.7 +/- 1.1 [SEM] years) and older men (age 70.0 +/- 7.0) of normal body weight who were leading unrestricted lives. Changes in total energy expenditure, resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient (RQ), and body energy content were determined in response to overeating by 4.09 +/- 0.07 Megajoule (MJ)/day for 21 days in 16 healthy subjects consuming a typical diet. After excluding data from one young subject with unusual results and adjusting for individual differences in excess energy intake, there was a tendency towards a smaller increase in REE in older men compared to the young men (p = .07) which was accounted for by their lower fat-free mass (p = .016). There was also a significantly smaller increase in resting energy expenditure averaged over fasting and fed states (i.e, REE + TEF) with overfeeding in older men than in young men (p < .01). Combined, these smaller increases in energy expenditure with overfeeding in the older subjects averaged an estimated 365 kilojoule (kJ)/day (8.9% of the excess energy intake) (p < .02). There were also significant effects of age on fasting RQ (p < .001) and the change in RQ with overfeeding (p < .001), but no significant increase in energy expenditure for physical activity and thermoregulation with overfeeding in either age-group. These results are consistent with the suggestion that older individuals experience both a reduction in the ability to increase energy expenditure, and an alteration in the pattern of substrate utilization, in response to overfeeding. These changes may promote cumulative increases in body energy during normal cycles of positive energy balance unless compensated for by adaptive variations in energy intake.

Adult↗