Biomedical subjects

John Beard

Publications and source records attributed to John Beard.

At least 19 recordsLinked to original sources

PubMed2007

Iron status of inner-city African-American infants.

The iron status of African-American infants continues to be subject to debate. We characterized the iron status of 198 9-month-old inner-city infants (94% fed iron-fortified formula) using a comprehensive panel of measures and assessing lead and inflammation markers. The proportion with iron deficiency was calculated based on three approaches (> or = 2 abnormal iron measures with or without anemia for MCV model--NHANES II, ferritin model--NHANES III, or Sweden/Honduras study) and a promising new measure-body iron, calculated from ferritin and transferrin receptor (TfR). There were no sex differences for any iron measure. Hb < 110 g/l was observed in 25%; Hb < or = 105 g/l in 10.1%. Free erythrocyte protoporphyrin (FEP) values were elevated without elevated lead concentrations or an inflammatory response: mean FEP = 86.6 microg/dl red blood cells [75.5 micromol/mol heme]; 52.3% were > 80 microg/dl (1.42 micromol/l), almost half of which were accompanied by a second abnormal iron measure. The estimated prevalence of iron deficiency was 14.4, 5.3, and 2.5% for the MCV model, ferritin model, and Sweden/Honduras cutoffs, respectively, and 4.1% for body iron < 0 mg/kg. Regulation of iron storage is immature at < 1 year of age, making estimates of iron deficiency that depend on ferritin, including body iron, suspect in this age period. Thus, the "true" prevalence of iron deficiency could not be established with confidence due to major differences in the results, depending on the guidelines used. Functional indicators of poor iron status in young infants are urgently needed.

Black or African American↗

PubMed2007

Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients.

Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated with beta-amyloid pathology. The proton transverse relaxation rate (R(2)) has a strong linear relationship with iron concentrations in healthy brain tissue; however, an independent test of this relationship has not been extended to AD brain tissue. In this study in vitro single spin-echo (SE) measurements were made on tissue samples from four human AD brains using a 4.7T MRI research scanner. R(2) values were calculated for 14 cortical and subcortical gray matter (GM) and white matter (WM) regions. Atomic absorption spectroscopy was used to measure iron concentrations in the corresponding excised brain regions. Significant positive linear correlations were observed between R(2) values and iron concentrations in GM regions assessed across individual tissue samples and data averaged by brain region. With the use of a predictive model for R(2), a threshold iron concentration of 55 microg Fe/g wet tissue was determined above which R(2) appears to be dominated by the affects of iron in AD brain tissue. High-field MRI may therefore be a useful research tool for assessing brain iron changes associated with AD.

Aged↗

PubMed2006

Iron levels in human retina: sex difference and increase with age.

Oxidative stress is believed to be important in physiological aging and age-related diseases. Iron is a potent pro-oxidant implicated in several age-related diseases. While serum ferritin, as an estimate of body stores of iron, has been shown to increase with age, few studies have directly addressed the effect of age on human neural tissue iron levels. We used atomic absorption spectrophotometry to assess quantitatively iron levels within the eye structures, retina and retinal pigment epithelium/choroid of normal human eyes of various ages and of both sexes. We found that retinal iron increases with age, similar to serum ferritin levels. Women had more retinal iron than men at all ages, suggesting that there may be gender-specific influences on iron regulation.

Adolescent↗

PubMed2006

DDT and human health.

1,1,1-Trichloro-2,2'bis(p-chlorophenyl) ethane (DDT) was the first widely used synthetic pesticide and is extremely persistent in both the environment and the human body. The introduction of DDT revolutionised agricultural production and has been credited with the elimination of malaria from the United States and Europe. However, DDT is also known to have had major environmental consequences and has been associated with dramatic declines in many animal populations. Although DDT use has generally been restricted since the early 1970s, exposure to the pesticide remains widespread. In developed countries, slow elimination from the body means a large proportion of the population still have detectable levels of DDT, or its metabolite DDE, in their serum or adipose tissue. In developing countries, the pesticide continues to be used for vector control and a significant proportion of breast-fed babies has daily intakes above recommended levels. This review considers the epidemiological evidence for possible adverse effects of human exposure to DDT. Much of this research is weakened by methodological flaws. However, recent methods in breast cancer research using nested studies in cohorts with stored biological samples have allowed a more rigorous assessment of a putative role for DDT in disease aetiology. While DDT does not appear to play a causative role in breast cancer development, there is suggestive evidence for a role in the aetiology of other conditions such as pancreatic cancer, neuropsychological dysfunction, and reproductive outcomes. Research into these and other conditions would benefit from the same rigorous approaches used in breast cancer research. Until further high quality evidence is available, it is still too early, even 60 years after the introduction of this once ubiquitous chemical, to pass judgement on the role of DDT in a number of common diseases.

Bone Density↗

PubMed2006

Factor structure and interpretation of the K10.

The Kessler 10 Psychological Distress Scale (K10) is a brief 10-item questionnaire designed to measure the level of distress and severity associated with psychological symptoms in population surveys. It is being used widely, including in the World Health Organization World Mental Health Survey, and as a clinical outcome measure, although little information is available about the structure of the measure. The factorial composition of the K10 was examined in a prospective community survey and cross-validated in a separate large community survey. The K10 was found to consist of 4 factors and a 2-factor second-order factor structure. This was stable across the 2 waves of the prospective study and the Australian National Survey of Mental Health and Well-Being. The 4 factors, labeled Nervous, Negative Affect, Fatigue, and Agitation, were consistent with the original scales from which the items were taken. The 2 second-order factors represent Depression and Anxiety.

Data Interpretation, Statistical↗

PubMed2006

Long-lasting neural and behavioral effects of iron deficiency in infancy.

Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function.

Anemia, Iron-Deficiency↗

PubMed2005

Subcellular localization of iron regulatory proteins to Golgi and ER membranes.

Interaction between iron regulatory proteins and iron responsive elements on certain mRNAs is at the core of regulation of intracellular iron homeostasis. Previous results suggested that in cultured cells iron regulatory proteins (IRPs) exist in cytosolic and microsomal subcellular locations and that this distribution is affected by cellular iron status. In this study, we tested the hypothesis that the membrane-associated fractions of iron regulatory proteins are specifically in the endoplasmic reticulum and Golgi membranes. Confocal microscopy revealed that IRP1 could be co-localized to the endoplasmic reticulum and the Golgi apparatus. To examine the intracellular distribution of IRPs biochemically, we used rats fed normal or iron-deficient diets. As expected, the IRPs were found predominantly in the cytosolic fraction. However, subfractionation of crude microsomal preparations revealed IRP1 in the Golgi apparatus. In animals fed an iron-deficient diet, IRP1 was found in the Golgi apparatus and the endoplasmic reticulum. To identify the mechanisms and factors involved in the localization of iron regulatory proteins in the cytosol and membrane fractions, cells were treated with a phorbol ester, a protein kinase C inhibitor (chelerythrine), hydrogen peroxide, interleukin-1beta, and 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N'N'-tetraacetic acid tetraacetoxy-methyl ester. The results indicate that iron-regulatory-protein-binding activity in the membrane fraction can be altered by cell stress or iron status and that phosphorylation plays a role in the translocation. As a result of this study we propose a novel model for intracellular distribution of IRPs and identify differences between the two iron regulatory proteins.

Alkaloids↗

PubMed2004

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration.

Mechanisms of brain and retinal iron homeostasis have become subjects of increased interest after the discovery of elevated iron levels in brains of patients with Alzheimer's disease and retinas of patients with age-related macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and its homolog hephaestin (Heph) are important for retinal iron homeostasis, we studied retinas from mice deficient in Cp and/or Heph. In normal mice, Cp and Heph localize to Müller glia and retinal pigment epithelium, a blood-brain barrier. Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron. The iron storage protein ferritin was also increased in Cp-/-Heph-/Y retinas. After retinal iron levels had increased, Cp-/-Heph-/Y mice had age-dependent retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor degeneration, and subretinal neovascularization, providing a model of some features of the human retinal diseases aceruloplasminemia and age-related macular degeneration. This pathology indicates that Cp and Heph are critical for CNS iron homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent retinal neurodegeneration, providing a model that can be used to test the therapeutic efficacy of iron chelators and antiangiogenic agents.

Animals↗

PubMed2004

Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome.

Thy-1 is a cell adhesion molecule that plays a regulatory role in the vesicular release of neurotransmitters. The objective of this study is to examine the relationship between iron status and Thy1 expression in neuronal systems of varying complexity. Pheochromocytoma cell (PC12) cells were used to explore whether there was a direct relation between cellular iron status and Thy1 expression. Iron chelation significantly decreased expression of Thy1 in PC12 cells in a dose and time dependent manner. Transferrin receptor expression was increased with iron chelation demonstrating that a global decrease in protein synthesis could not account for the Thy1 changes. We also examined brain homogenates from adult rats that were nursed by dams on an iron deficient (ID) diet and found a significant decrease in Thy1 compared to control rats. Finally, the substantia nigra from individuals with Restless Legs Syndrome reportedly has lower than normal amounts of iron. Therefore, we examined this brain region from individuals with the clinical diagnosis of primary Restless Legs syndrome (RLS) and found the concentration of Thy1 was less than half that of controls. The results of these studies support the novel concept that there is a relationship between Thy1 and iron and point to a novel mechanism by which iron deficiency can affect brain function. They also indicate a possible mechanism by which iron deficiency compromises dopaminergic transmission in RLS, providing a potentially important link between decreased brain iron and the responsiveness to levodopa and iron supplementation treatment in RLS.

Aged↗

PubMed2004

Sustaining evidence-based practice for young people who self-harm: a 4-year follow-up.

OBJECTIVE: In 1998 and 1999, two NSW Area Health Services conducted the Youth At Risk of Deliberate Self Harm (YARDS) project. The YARDS project was designed to implement evidence-based service enhancements for the clinical management of young people with Deliberate Self Harm. This paper examines the extent to which service enhancements implemented during YARDS were maintained 4 years after the conclusion of the project and compares service quality with another NSW Area Health Service that did not participate in the YARDS project. METHOD: Staff from mental health services and emergency departments completed the Service Activity Scale, a measure developed for the YARDS project to assess the quality of health service response to individuals who present following a suicide attempt. RESULTS: RESULTS indicated that the service improvements made during the YARDS project were maintained 4years after the project ended. Furthermore, a significant difference was found between scores for services that participated in YARDS and services that did not participate in YARDS. CONCLUSIONS: These results suggest that projects such as YARDS which support evidence based service nhancements may be useful in improving the management of young people with deliberate self-harm, and that these improvements may be long-lasting.

Emergency Service, Hospital↗

PubMed2004

Factors associated with treatment compliance in young people following an emergency department presentation for deliberate self-harm.

This study investigated factors associated with patient non-compliance with follow-up treatment after a presentation to an Emergency Department (ED) for deliberate self-harm (DSH). 56 patients under 24 years and 20 parents participated in this study. Subjects were interviewed by telephone after they had attended or missed a follow-up appointment following a presentation to an ED for DSH. Convenience of the appointment time and the patients' beliefs about whether counseling would help them were found to differentiate attending and non-attending patients. The attitudes of parents also had a major influence on decisions to attend or not attend an appointment. These results support the use of a therapeutic intervention in the ED, targeting both patients and their parents' attitudes toward counseling.

Journal Article↗

PubMed2004

Regulation of the profile of iron-management proteins in brain microvasculature.

The distribution of brain iron is heterogeneous, but the mechanism by which these regional differences are achieved and maintained is unknown. In this study, the authors test two hypotheses related to brain iron transport. The first is that there is regional variability in the profile of proteins associated with iron transport and storage in the brain microvasculature. The second hypothesis is that the iron status of the brain will dictate the response of the protein profile in the microvasculature to changes in systemic iron status. The profile analysis consists of transferrin (iron transport), ferritin (iron storage), transferrin receptor (iron uptake), and divalent metal transporter 1 (release of iron from endosomes). An additional protein involved in cellular iron efflux, ferroportin, was not detected in brain microvasculature. The results show that there are significantly higher levels of these proteins in the microvasculature from each area of the brain compared to a whole brain homogenate, but no regional differences within the microvasculature. The levels of ferritin observed in the microvasculature indicate that the microvascular endothelial cells have significant iron storage capacity. There are no significant changes in the regional protein profiles in response to systemic iron manipulation when brain iron status was normal. In contrast, in Belgrade rats, whose brain is iron deficient, the expression of both divalent metal transporter 1 and transferrin receptor was increased compared with control in almost all brain regions examined, but not transferrin or ferritin. These findings indicate that regional brain iron heterogeneity is not maintained by differences in microvascular iron-management protein levels. The results also indicate that brain iron status dictates the response of the microvascular protein profile to systemic iron manipulation.

Animals↗

PubMed2004

The role of the public in the management of public health risks.

OBJECTIVE: To critique current models of public involvement in the management of public health risks. METHODS: Two case studies are used to highlight the challenges of contemporary practice. RESULTS: Current models often result in affected communities having perceptions of risk that conflict with those responsible for risk management. This can lead to ineffective decision making. CONCLUSIONS: Involving the public throughout the risk assessment and risk management process may lessen conflict and result in better decisions. IMPLICATIONS: Those responsible for responding to public health risks should aim for transparent processes that highlight assumptions and uncertainties, and involve the public wherever possible.

Australia↗

PubMed2003

Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress.

Several neurodegenerative disorders such as Parkinson's Disease (PD) and Alzheimer's Disease (AD) are associated with elevated brain iron accumulation relative to the amount of ferritin, the intracellular iron storage protein. The accumulation of more iron than can be adequately stored in ferritin creates an environment of oxidative stress. We developed a heavy chain (H) ferritin null mutant in an attempt to mimic the iron milieu of the brain in AD and PD. Animals homozygous for the mutation die in utero but the heterozygotes (+/-) are viable. We examined heterozygous and wild-type (wt) mice between 6 and 8 months of age. Macroscopically, the brains of +/- mice were well formed and did not differ from control brains. There was no evidence of histopathology in the brains of the heterozygous mice. Iron levels in the brain of the +/- and wild-type (+/+) mice were similar, but +/- mice had less than half the levels of H-ferritin. The other iron management proteins transferrin, transferrin receptor, light chain ferritin, Divalent Metal Transporter 1, ceruloplasmin, were increased in the +/- mice compared to +/+ mice. The relative amounts of these proteins in relation to the iron concentration are similar to that found in AD and PD. Thus, we hypothesized that the brains of the heterozygote mice should have an increase in indices of oxidative stress. In support of this hypothesis, there was a decrease in total superoxide dismutase (SOD) activity in the heterozygotes coupled with an increase in oxidatively modified proteins. In addition, apoptotic markers Bax and caspase-3 were detected in neurons of the +/- mice but not in the wt. Thus, we have developed a mouse model that mimics the protein profile for iron management seen in AD and PD that also shows evidence of oxidative stress. These results suggest that this mouse may be a model to determine the role of iron mismanagement in neurodegenerative disorders and for testing antioxidant therapeutic strategies.

Alzheimer Disease↗

PubMed2003

Neonatal iron deficiency results in irreversible changes in dopamine function in rats.

Iron deficiency in human infants and in young animal models produces changes in neural functioning that may be related to monoamine metabolism. This study employed both behavioral and biochemical approaches in a design using cross-fostering to examine alterations in dopamine (DA) function when iron deficiency occurs during the neonatal period. We measured brain Fe, dopamine transporters (DAT) and dopamine receptor density in rats made iron deficient, or not, from postnatal day (PND) 4 to PND 14 or 21. Some pups were then weaned to an iron-deficient diet and others to the control diet to examine the reversibility of these effects. Behaviors related to dopamine function were measured. Dopamine D(2) receptor (D(2)R), D(1)R and iron concentrations were approximately 70, 80 and 30% of control values, respectively, in the nucleus accumbens and striatum in iron-deficient rats at PND 14. The DAT density was also reduced to 50% of control density in the nucleus accumbens but was unchanged in the striatum. By PND 21, there was also a significant 50% lowering of DAT, D(1)R and D(2)R densities in the prefrontal cortex (PFC). Iron repletion at PND 21-49 normalized D(1)R, D(2)R, and DAT levels in the nucleus accumbens, PFC and ventral midbrain but not in the striatum. In summary, neonatal iron deficiency is associated with changes in DA biology that vary with duration of iron deficiency, and are not completely normalized despite replenishment of iron status. Changes in DA-related behaviors that were persistent after postweaning iron repletion suggest the existence of a critical neonatal developmental period that is expressed by alterations in DA functioning.

Animals↗

PubMed2003

Iron deficiency alters brain development and functioning.

Iron deficiency anemia in early life is related to altered behavioral and neural development. Studies in human infants suggest that this is an irreversible effect that may be related to changes in chemistry of neurotransmitters, organization and morphology of neuronal networks, and neurobiology of myelination. The acquisition of iron by the brain is an age-related and brain-region-dependent process with tightly controlled rates of movement of iron across the blood-brain barrier. Dopamine receptors and transporters are altered as are behaviors related to this neurotransmitter. The growing body of evidence suggests that brain iron deficiency in early life has multiple consequences in neurochemistry and neurobiology.

Age Factors↗

PubMed2003

Falls prevention in rural general practice: what stands the test of time and where to from here?

OBJECTIVE: General practitioner recall of the 1992-96 'Stay on Your Feet' (SOYF) program and its influence on practice were surveyed five years post-intervention to gauge sustainability of the SOYF General Practice (GP) component. METHODS: A survey assessed which SOYF components were still in existence, current practice related to falls prevention, and interest in professional development. All general practitioners (GPs) situated within the boundaries of a rural Area Health Service were mailed a survey in late 2001. RESULTS: Response rate was 66.5% (139/209). Of 117 GPs in practice at the time of SOYF, 80.2% reported having heard of SOYF and 74.4% of those felt it had influenced practice. Half (50.9%) still had a copy of the SOYF GP resource and of those, 58.6% used it at least 'occasionally'. Three-quarters of GPs surveyed (75.2%) checked medications 'most/almost all' of the time with patients over 60 years; 46.7% assessed falls risk factors; 41.3% gave advice; and 22.6% referred to allied health practitioners. GPs indicated a strong interest in falls prevention-related professional development. There was no significant association between use of the SOYF resource package and any of the current falls prevention practices (all chi2 > 0.05). CONCLUSIONS AND IMPLICATIONS: There was high recall of SOYF and a general belief that it influenced practice. There was little indication that use of the resource had any lasting influence on GPs' practices. In future, careful thought needs to go into designing a program that has potential to affect long-term change in GPs' falls prevention practice.

Accidental Falls↗

PubMed2003

Health impacts of pesticide exposure in a cohort of outdoor workers.

We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.

Adult↗