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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 19 recordsLinked to original sources
PubMed2006

Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins.

Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediate phenotypes of asthma. Using population-based data collected from a sample of twins, the present authors estimated the relative contribution of genes, family environment and nonshared environmental influences to variations in eNO and airway responsiveness (AR). In addition, the genetic and environmental sources of covariation between these two asthma-related phenotypes were investigated. The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. The main outcome variables were eNO and AR to methacholine. Genetic effects accounted for 60% of the variation in eNO. Family environment accounted for 30% of the variation in AR, while nonshared environmental influences explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects for atopy and smoking. The small, but significant association between eNO and AR was primarily explained by genetic factors. Sub-analyses restricted to atopic and nonsmoking twins strengthened the observation. In conclusion, variations in exhaled nitric oxide and airway responsiveness appear to be explained by different genetic and environmental variance structures. Variation in exhaled nitric oxide is explained by genetic and nonshared environmental effects, whereas an environmental model best explains the variation in airway responsiveness. Common genetic effects explain the small but significant association between exhaled nitric oxide and airway responsiveness.

Adult↗
PubMed2006

Irritable bowel syndrome in twins: genes and environment.

BACKGROUND AND AIMS: Both environmental and genetic factors may contribute to irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental factor, seems to influence the development of chronic diseases later in life, such as coronary heart disease, hypertension, and non-insulin diabetes. This population based twin study evaluated the association between intrauterine growth, measured by weight and gestational age, and IBS. Structural equation analyses were conducted to analyse genetic and environmental sources of variation in liability to IBS. METHODS: A postal questionnaire was sent to 12 700 Norwegian twins born between 1967 and 1979. The questionnaire included a checklist of 31 illnesses and symptoms, including IBS. The influence of birth weight on developing IBS was tested in four weight groups. Disease discordant monozygotic (MZ) pairs were analysed to test the association between intrauterine growth and IBS. RESULTS: Concordance for IBS was significantly greater (p = 0.011) in monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the development of IBS, which appeared 7.7 years earlier than in higher weight groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were significantly lighter than twins without disease (190.6 g; p = 0.02). CONCLUSION: The present study demonstrates that restricted fetal growth has a significant influence on the development of IBS later in life. Weight below 1500 g influences age at onset. Genetic contribution appears to be important for IBS among females.

Age of Onset↗
PubMed2006

Subjective well-being: genetic and environmental contributions to stability and change.

BACKGROUND: Previous cross-sectional studies have found substantial genetic influences on individual variation in subjective well-being (SWB), and evidence for sex-specific genetic effects has been reported. However, the genetic and environmental influences on stability and change in SWB over time are largely unexplored. METHOD: Questionnaire data on SWB from a population-based sample of Norwegian twins born 1967 to 1979, initially surveyed in 1992 (T1) and re-surveyed in 1998 (T2), were analysed using structural equation modelling to explore the relative effects of genetic and environmental influences on phenotypic stability and change. RESULTS: The phenotypic cross-time correlations for SWB were 0.51 and 0.49 for males and females respectively. The best-fitting longitudinal model specified only additive genetic and individual environmental effects with qualitative and quantitative sex-specific genetic influences. For both males and females, the additive genetic factors influencing SWB were largely stable, although some time-specific genetic contributions were indicated. Cross-time correlations for genetic effects were 0.85 and 0.78 for males and females respectively. The individual environmental influences were primarily time-specific. Additive genetic effects explained approximately 80% of the phenotypic cross-time correlation. For females, the magnitude of the additive genetic effects decreased significantly from T1 to T2, whereas for males, the estimates generally remained unchanged. CONCLUSIONS: For both males and females, long-term stability of SWB was mainly attributable to stable additive genetic factors, whereas susceptibility to change was mostly related to individual environmental factors. However, both stable environmental contributions and emerging genetic influences were indicated.

Attitude to Health↗
PubMed2005

Psoriasis in Norway as observed in a population-based Norwegian twin panel.

BACKGROUND: Psoriasis is a chronic T-cell-mediated immunological skin disease. The occurrence of the disease appears to differ with geography and ethnicity. There is a need for epidemiological data obtained from defined population-based studies, and the sex-specific differences observed in the natural history of the disease require more attention. OBJECTIVES: To describe the occurrence and risk of psoriasis in Norway by age and sex. PATIENTS/METHODS: A population-based health survey was conducted in 1998 in Norwegian twins aged 19-31 years. The present study is based upon the self-reported history of psoriasis among the 8045 questionnaire responders. RESULTS: Altogether, 334 (4.2%) reported a positive history of psoriasis. There were no sex differences in the overall prevalence rates, but significantly higher point-prevalences emerged in females in the teenage-year intervals. A fairly linear increase in incidence rates by every 4-year age-interval peaked at a lower age in females. The mean age at onset was also significantly lower in females (14.8 years) than in males (17.3 years). The absolute risk of developing psoriasis appeared higher for females across the entire age range. However, by the age of 31 the cumulative risks were similar in females and males (0.056 and 0.053, respectively). CONCLUSIONS: In this historical cohort of Norwegian twins, we find a high prevalence of psoriasis in congruence with previously reported data among whites in north-western Europe. We have found sex-specific characteristics in point-prevalences and incidence rates which may contribute to the understanding of the earlier age at onset of the disease in females.

Adult↗
PubMed2005

The University of Maryland electron ring: a platform for study of galactic dynamics on a laboratory scale.

The University of Maryland electron ring (UMER) is a novel experimental storage ring designed to investigate the dynamics of large systems of collisionless particles that nevertheless interact via collective mechanisms. Heavily diagnosed and designed to circulate a 100 mA electron beam at 10 keV for several turns, UMER allows us to follow the evolution of the beam over a large number of dynamical periods. Given the similarity of dynamics between the Coulomb forces and gravitational forces, it is possible to design beam experiments that will simulate such astrophysical events as galactic merger, for instance. The cross-comparison of beam experiments with accelerator simulation codes provides invaluable benchmarks of transient processes akin to, for example, violent relaxation in stellar systems that are otherwise impossible to obtain.

Journal Article↗
PubMed2004

Amylopectin: a major component of the residual body in Cryptosporidium parvum oocysts.

Amylopectin is used for carbohydrate storage in different life-stages of a number of apicomplexan parasites. We have performed an ultrastructural analysis of amylopectin granules from the oocyst residual body and sporozoites of Cryptosporidium parvum. Amylopectin granules were studied in situ and after isolation from 'French' press disrupted parasites, by conventional transmission electron microscopy (TEM) of sectioned oocysts and various negative staining and cryoelectron microscopy techniques. Within the membrane-enclosed oocyst residuum large amylopectin granules (0.1-0.3 microm) can be found besides a characteristic large lipid body and a crystalline protein inclusion. Smaller granules were detected in sectioned sporozoites. Negative staining of isolated amylopectin granules revealed some ultrastructural features not readily visible in sectioned material. The large amylopectin granules had a smooth surface with a 'ball of string'-like inner structure. Granules isolated from sporozoites were more irregularly shaped and showed a rod-like particulate composition. With the exception of alpha-amylase, which led to some degree of damage of the surface of the particles, treatment of amylopectin granules with other glycohydrolases had little effect on the overall structure. However, granules adhered to one another. Only when the granules were boiled did the 'ball of string' structure gradually dissolve.

Amylopectin↗
PubMed2003

Gender differences in binge-eating: a population-based twin study.

OBJECTIVE: To assess whether genetic and environmental effects on liability to binge-eating (BE) are of equal importance for males and females and whether the same genetic risk factors predispose to BE in the two sexes. METHOD: Questionnaire data on 8045 same sex and opposite sex twins, aged 19-31 years, from a population-based Norwegian registry, was used to estimate the relative contribution of genetic and environmental factors to liability for BE utilizing structural equation modeling. RESULTS: In the best-fitting model, the magnitude of genetic and environmental effects on BE was the same for males and females. Heritability was 51%. The correlation between genetic risk factors in men and women was estimated to be +0.57. CONCLUSION: Binge-eating appears to be equally heritable in males and females. Although the majority of the genetic risk factors are shared between the sexes, there may exist gender-specific genetic effects on liability.

Adult↗
PubMed2002

In vitro fibrillogenesis of the amyloid beta 1-42 peptide: cholesterol potentiation and aspirin inhibition.

Understanding the formation of extracellular amyloid neurofibrillar bundles/senile plaques and their role in the development of Alzheimer's disease is of considerable interest to neuroscientists and clinicians. Major components of the extracellular neurofibrillar bundles are polymerized amyloid beta (Abeta) peptides (1-40), (1-42) and (1-43), derived in vivo from the soluble amyloid precursor protein (sAPP) by proteolytic (beta- and gamma-secretase) cleavage. The Abeta(1-42) peptide is widely considered to be of greatest significance in relation to the pathogenesis of Alzheimer's disease. A well-defined ultrastructural characteristic within Alzheimer dense plaques is the presence of helical fibrils that are believed to consist of polymerized amyloid beta, together with other associated proteins such as the serum amyloid P protein, apolipoprotein E isoform epsilon 4, alpha1-anti-chymotrypsin, catalase, glycoproteins, proteoglycans, cholesterol and other lipids. The spontaneous in vitro fibrillogenesis of chemically synthesized Abeta(1-42) peptide (rat sequence), following 20h incubation at 37 degrees C, has been assessed from uranyl acetate negatively stained specimens studied by transmission electron microscopy (TEM). Amyloid beta(1-42) peptide fibrillogenesis in the presence of cholesterol has been investigated using aqueous suspensions of microcrystalline cholesterol and cholesteryl acetate, globular particles of cholesteryl oleate, a soluble (micellar) cholesterol derivative (polyoxyethyl cholesteryl sebacate/cholesteryl PEG 600 sebacate), cholesterol-sphingomyelin liposomes and sphingomyelin liposomes. In all these cases, with the exception of cholesteryl oleate, considerable potentiation of long smooth helical fibril formation occurred, compared to 20h 37 degrees C control samples containing the Abeta(1-42) peptide alone. The binding of polyoxyethyl cholesteryl sebacate micelles to helical Abeta fibrils/filaments and the binding of fibrils to the surface of cholesterol and cholesteryl acetate microcrystals, and to a lesser extent on cholesteryl oleate globules, indicates an affinity of the Abeta peptide for cholesterol. This potentiation of Abeta(1-42) polymerization is likely to be mediated at the molecular level via hydrophobic interaction between the amino acid side chains of the peptide and the tetracyclic sterol nucleus. Addition of cupric sulphate (0.1mM) to the Abeta solution produced large disorganized fibril aggregates. Inclusion of 1mM aspirin (sodium acetylsalicylate) in the Abeta peptide alone and as an addition to Abeta peptide solution containing cholesterol, cholesteryl acetate, soluble cholesterol, sphingomyelin and sphingomyelin-cholesterol liposomes, and to 0.1mM cupric sulphate solution, completely inhibited fibrillogenesis. Instead, only non-crystalline diffuse, non-filamentous microaggregates of insoluble Abeta particles were found, free and attached to the sterol particles. The in vitro system presented here provides a way to rapidly monitor at the structural/TEM level other compounds (e.g. chelating agents, drugs, beta-sheet breaking peptides and anti-oxidants) for their effects on amyloid beta peptide fibrillogenesis (and on preformed fibril disassembly) in parallel with in vitro biochemical studies and in vivo studies using animal models of Alzheimer's disease as well as studies on man.

Alzheimer Disease↗
PubMed2002

Back-neck pain and symptoms of anxiety and depression: a population-based twin study.

BACKGROUND: Clinical and epidemiological studies have shown an association between anxiety and depression and pain in the back and neck. The nature of this relationship is not clear. This study aimed to investigate the extent to which common genetic and environmental aetiological factors contribute to the covariance between symptoms of anxiety and depression and back-neck pain. METHODS: Measures of back-neck pain and symptoms of anxiety and depression were part of a self-report questionnaire sent in 1992 to twins born in Norway between 1967 and 1974 (3996 pairs). Structural equation modelling was applied to determine to what extent back-neck pain and symptoms of anxiety and depression share genetic and environmental liability factors. RESULTS: The phenotypic correlation between symptoms of anxiety and depression and back-neck pain was 0.31. Individual differences in both anxiety and depression and back-neck pain were best accounted for by additive genetic and individual environmental factors. Heritability estimates were 0.53 and 0.30 respectively. For back-neck pain, however, a model specifying only shared- and individual environmental effects could not be rejected. Bivariate analyses revealed that the correlation between back-neck pain and symptoms of anxiety and depression was best explained by additive genetic and individual environmental factors. Genetic factors affecting both phenotypes accounted for 60% of the covariation. There were no significant sex differences. CONCLUSION: The results support previous findings of a moderate association between back-neck pain and symptoms of anxiety and depression, and suggest that this association is primarily due to common genetic effects.

Adolescent↗
PubMed2002

Dynamic performance of the mechanism of an automatically deployable ROPS.

The mechanism for an automatically deployable ROPS (AutoROPS) has been designed and tested. This mechanism is part of an innovative project to provide passive protection against rollover fatality to operators of new tractors used in both low-clearance and unrestricted-clearance tasks. The device is a spring-action, telescoping structure that releases on signal to pyrotechnic squibs that actuate release pins. Upper post motion begins when the release pins clear an internal piston. The structure extends until the piston impacts an elastomeric ring and latches at the top position. In lab tests the two-post structure consistently deployed in less than 0.3 s and latched securely. Static load tests of the telescoping structure and field upset tests of the fully functional AutoROPS have been successfully completed.

Accidents, Occupational↗
PubMed2002

Static load test performance of a telescoping structure for an automatically deployable ROPS.

The automatically deployable ROPS was developed as part of an innovative project to provide passive protection against overturn fatality to operators of new tractors used in both low-clearance and unrestricted-clearance tasks. The primary objective of this phase of the research was to build a telescoping structure that would prove that a ROPS can be built that will (1) reliably deploy on signal, (2) rise in a sufficiently short amount of time, (3) firmly latch in its deployed position, and (4) satisfy SAE J2194 testing requirements. The two-post structure had previously been found to meet deployment time criteria, and design analyses indicated that neither the slip-fit joint nor the latch pins would fail at test loading. Four directions of static loading were applied to the structure to satisfy SAE requirements. For the series of static loading tests, the raised structure was found to maintain a protective clearance zone after all loads were applied. The structure is overly stiff and should be redesigned to increase its ability to absorb ground-impact energy. Results of dynamic tests and field upset tests are reported in companion articles. The next phase of development is to optimize the structure so that it will plastically deform and absorb energy that would otherwise be transferred to the tractor chassis.

Accidents, Occupational↗
PubMed2001

Comparison of the decameric structure of peroxiredoxin-II by transmission electron microscopy and X-ray crystallography.

The decameric human erythrocyte protein torin is identical to the thiol-specific antioxidant protein-II (TSA-II), also termed peroxiredoxin-II (Prx-II). Single particle analysis from electron micrographs of Prx-II molecules homogeneously orientated across holes in the presence of a thin film of ammonium molybdate and trehalose has facilitated the production of a >/=20 A 3-D reconstruction by angular reconstitution that emphasises the D5 symmetry of the ring-like decamer. The X-ray structure for Prx-II was fitted into the transmission electron microscopic reconstruction by molecular replacement. The surface-rendered transmission electron microscopy (TEM) reconstruction correlates well with the solvent-excluded surface of the X-ray structure of the Prx-II molecule. This provides confirmation that transmission electron microscopy of negatively stained specimens, despite limited resolution, has the potential to reveal a valid representation of surface features of protein molecules. 2-D crystallisation of the Prx-II protein on mica as part of a TEM study resulted in the formation of a p2 crystal form with parallel linear arrays of stacked rings. This latter 2-D form correlates well with that observed from the 2.7 A X-ray structure of Prx-II solved from a new orthorhombic 3-D crystal form.

Crystallography, X-Ray↗
PubMed2001

Radiation therapy impairs endothelium-dependent vasodilation in humans.

OBJECTIVES: The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation. BACKGROUND: Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS: Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured. RESULTS: Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (-0.4 +/- 0.4% vs. 3.2 +/- 0.8% p < 0.001) and also compared with control subjects' arteries (-0.4 +/- 0.4% vs. 2.5 +/- 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 +/- 0.5% vs. 2.0 +/- 0.4%, p < 0.05) and also compared with control arteries (3.8 +/- 0.5% vs. 2.5 +/- 0.4%, p < 0.05). CONCLUSIONS: External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.

Aged↗
PubMed2001

Marine tumor vaccine carriers: structure of the molluscan hemocyanins KLH and htH.

Keyhole limpet hemocyanin (KLH) is a well-established immune stimulant and hapten carrier, and Haliotis tuberculata hemocyanin (HtH) is a related product. Biologically, KLH and HtH are blue copper proteins which serve as oxygen carriers in the blood of the keyhole limpet Megathura crenulata and the abalone H. tuberculata, respectively, two marine gastropods. Both hemocyanins occur as two distinct isoforms, termed KLH1 KLH2, HtH1, and HtH2. Each of these molecules is based on a very large polypeptide chain, the subunit (molecular mass ca 400 kDa), which is folded into a series of eight globular functional units (molecular mass ca 50 kDa each). Twenty copies of this subunit form a cylindrical quaternary structure (molecular mass ca 8 MDa). This article reviews the recent data on the biosynthesis, quaternary structure, subunit architecture, amino acid sequence, gene structure, and recombinant production of KLH and HtH.

Adjuvants, Immunologic↗
PubMed2001

Reviews of evidence regarding interventions to reduce tobacco use and exposure to environmental tobacco smoke.

This report presents the results of systematic reviews of effectiveness, applicability, other effects, economic evaluations, and barriers to use of selected population-based interventions intended to reduce tobacco use and exposure to environmental tobacco smoke. The related systematic reviews are linked by a common conceptual approach. These reviews form the basis of recommendations by the Task Force on Community Preventive Services (TFCPS) regarding the use of these selected interventions. The TFCPS recommendations are presented on page 67 of this supplement.

Adolescent↗
PubMed2001

Performance measures: are we measuring what matters?

BACKGROUND: The ultimate intent of healthcare performance measures is to improve health status by stimulating improvements to healthcare quality. This report evaluates how well current performance measurement sets address the leading causes of illness and death in the United States, using the Health Plan Employer Data and Information Set (HEDIS) as an example. METHODS: We assessed whether HEDIS measures exist for the leading causes of illness and death according to five commonly used indices: physiologic cause of death, underlying cause of death, disability-adjusted life years, healthcare expenditures, and missed work days. RESULTS: Fewer than one half of the leading causes of morbidity and mortality are addressed by current measures. CONCLUSIONS: The opportunities for using accurate and meaningful measurement for disease prevention and health promotion are substantial, yet this potential remains only partly realized and depends on further expansion of performance measurement efforts.

Cause of Death↗
PubMed2001

Priorities among recommended clinical preventive services.

BACKGROUND: Many recommended clinical preventive services are delivered at low rates. Decision-makers who wish to improve delivery rates, but face competing demands for finite resources, need information on the relative value of these services. This article describes the results of a systematic assessment of the value of clinical preventive services recommended for average-risk patients by the U.S. Preventive Services Task Force. METHODS: The assessment of services' value for the U.S. population was based on two dimensions: burden of disease prevented by each service and cost effectiveness. Methods were developed for measuring these criteria consistently across different types of services. A companion article describes the methods in greater detail. Each service received 1 to 5 points on each of the two dimensions, for total scores ranging from 2 to 10. Priority opportunities for improving delivery rates were determined by comparing the ranking of services with what is known of current delivery rates nationally. RESULTS: The highest ranked services (scores of 7+) with the lowest delivery rates (< or =50% nationally) are providing tobacco cessation counseling to adults, screening older adults for undetected vision impairments, offering adolescents an anti-tobacco message or advice to quit, counseling adolescents on alcohol and drug abstinence, screening adults for colorectal cancer, screening young women for chlamydial infection, screening adults for problem drinking, and vaccinating older adults against pneumococcal disease. CONCLUSIONS: Decision-makers can use the results to set their own priorities for increasing delivery of clinical preventive services. The methods provide a basis for future priority-setting efforts.

Adult↗