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Biomedical subjects

K Hanson

Publications and source records attributed to K Hanson.

At least 19 recordsLinked to original sources
PubMed2001

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice.

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.

Journal Article↗
PubMed2001

Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion.

OBJECTIVE: Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Fasting plasma IL-6 concentrations (enzyme-linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). RESULTS: Fasting plasma IL-6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = -0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL-6 was not related to M (partial r = -0.23, p = 0.089). DISCUSSION: Fasting plasma IL-6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL-6 and insulin action seems to be mediated through adiposity.

Adipose Tissue↗
PubMed2001

Ends versus means: the role of markets in expanding access to contraceptives.

Achieving and sustaining universal access to contraceptives are key policy goals of interventions supplying contraceptive commodities. Donor support for contraceptive supplies is substantial and many public and national programmes rely on donated and subsidized supplies of contraceptives. Sustainability of programme benefits is a concern to both national governments and donor agencies. At the same time, market-based provision of contraceptives has become a major source of contraceptives for individuals in a number of countries. While the goals or 'ends' of policy are to increase and sustain universal access to contraceptives, there is debate about the role of markets and their negative impacts on equity and universality. There is also concern that while public programmes supplying free contraceptives may, in the medium-term, achieve high coverage, they may hamper the achievement of long-term sustainability and the development of commercial markets. This paper focuses on the tension between the public health and market paradigms, and uses economic analysis as a framework in order to examine the relative roles or 'means' for subsidized public and commercial private sector supply of contraceptives. The review of the theory and evidence focuses on the trade-offs between public sector and market provision of contraceptives, examining the role for the public sector given the potential for market failures, the impact of public provision on the development of markets, and the role of price in demand. However, because of the potential conflict between these policy objectives, we argue that strategies to deliver contraceptives should be based on the specific characteristics of the context. In particular four variables (contraceptive prevalence rates, HIV prevalence, income level of country, size and geographic spread of private sector development) are important in characterizing this context, and these are highlighted in a matrix of programme priorities. Public choices need to take into account the ways in which they will affect the potential for development of sustainable private sources of supply. Undertaking a 'market assessment' should be a key stage in the analysis of policy options. Such an assessment should address demand factors, health priorities, actual and potential sources of supply and the relationships between public and private supply. Clearly the development of markets for contraceptives is not an end in itself, but may prove an important means of improving the health of women and men.

Contraceptive Agents↗
PubMed2001

Calculating and presenting disability adjusted life years (DALYs) in cost-effectiveness analysis.

Disability adjusted life years (DALYs) are the sum of the present value of future years of lifetime lost through premature mortality, and the present value of years of future lifetime adjusted for the average severity (frequency and intensity) of any mental or physical disability caused by a disease or injury. They have been used as an outcome indicator in micro economic evaluations as well as sectoral prioritization exercises using league tables of cost-effectiveness. However, many of the current analyses are not comparable or transferable because either the assumptions used differ or are unclear, and because results are not presented in a way that allows researchers or policy-makers to re-calculate and re-interpret findings for use in an alternative context. However, at times there have also been miscalculations. This may happen either because evaluators disagree with the assumptions behind DALYs or because the methods of calculation have not been set out clearly. This paper shows how to calculate DALYs for cost-effectiveness analysis using a worked example. It also shows the impact of changing the age weighting and discount rates on estimates of cost-effectiveness, and suggests a set of minimum reporting criteria for using DALYs in cost-effectiveness analysis. Finally, readers are introduced briefly to a selected literature arguing for and against the use of DALYs.

Cost-Benefit Analysis↗
PubMed2001

The relative efficacy of fluoxetine and manual-based self-help in the treatment of outpatients with bulimia nervosa.

A randomized, placebo-controlled study was conducted examining the singular and combined effects of fluoxetine and a self-help manual on suppressing bulimic behaviors in women with bulimia nervosa. A total of 91 adult women with bulimia nervosa were randomly assigned to one of four conditions: placebo only, fluoxetine only, placebo and a self-help manual, or fluoxetine and a self-help manual. Subjects were treated for 16 weeks. Primary outcome measures included self-reports of bulimic behaviors. Fluoxetine and a self-help manual were found to be effective in reducing the frequency of vomiting episodes and in improving the response rates for vomiting and binge-eating episodes. Furthermore, both factors were shown to be acting additively on the primary and secondary efficacy measures in this study. Results are discussed in relation to previous research and the implications for treatment of bulimia nervosa.

Adolescent↗
PubMed2000

Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight.

AIMS/HYPOTHESIS: We aimed to quantify changes in insulin action and insulin secretion associated with long-term gain, loss, regain, and maintenance of body weight in subjects with normal (NGT) or impaired (IGT) glucose tolerance. METHODS: Insulin action (hyperinsulinaemic clamp) and insulin secretion (intravenous glucose challenge) were measured longitudinally in 209 Pima Indians body weight 94.4 +/- 22.8 kg (means +/- SD) 89 women/120 men, 151 NGT/58 IGT[, who either lost (n = 110) or gained (n = 99) weight (-23% to +29%) over 2.6 +/- 2.0 years. Insulin action and insulin secretion were reassessed on a third occasion in 33 subjects who lost at least 5% body weight over 1.5 +/- 0.8 years and then either regained or maintained weight over the subsequent 1.8 +/- 1.1 years. RESULTS: There was a linear negative relation between changes in body weight and changes in insulin-stimulated glucose disposal in subjects with normal glucose tolerance (r = -0.51, p < 0.0001) and impaired glucose tolerance (r = -0.54, p < 0.0001). In contrast, changes in the acute insulin response were positively related to weight changes in subjects with normal glucose tolerance (r = +0.26, p < 0.005) but negatively in those with impaired glucose tolerance (r = -0.51, p < 0.0001). Improvements in insulin action after an average of 10% weight loss were lost with weight regain but largely preserved with weight maintenance. CONCLUSION/INTERPRETATION: Improvements in insulin action are proportional to the amount of weight loss, similar in magnitude to the impairment in insulin action with weight gain, preserved with long-term weight maintenance and similar between subjects with normal and with impaired glucose tolerance. Weight gain could, however, have more detrimental effects in people with impaired glucose tolerance, in whom insulin secretion decreases rather than increases to compensate for the decreased insulin action.

Adult↗
PubMed2000

Phytobilin biosynthesis: the Synechocystis sp. PCC 6803 heme oxygenase-encoding ho1 gene complements a phytochrome-deficient Arabidopsis thalianna hy1 mutant.

The phytobilin chromophores of phycobiliproteins and phytochromes are biosynthesized from heme in a pathway that begins with the opening of the tetrapyrrole macrocycle of protoheme to form biliverdin IXalpha, in a reaction catalyzed by heme oxygenase. An Arabidopsis thaliana hy1 mutant was previously shown to be deficient in phytochrome responses, and these responses were regained when the plants were administered biliverdin IXalpha. A heme oxygenase-encoding gene, ho1, was recently cloned from the cyanobacterium Synechocystis sp. PCC 6803. When ho1 was expressed in Escherichia coli, the cells produced active ferredoxin-dependent soluble heme oxygenase. The open reading frame of ho1 was fused in frame with a chloroplast transit peptide-encoding sequence from the oli gene of Antirrhinum majus. This construct was placed in a binary plasmid vectorcontaining a kanamycin resistance marker and a cauliflower mosaic virus 35S promoter to control expression of the chimeric oli-ho1 gene and used to transform A. thaliana hy1 plants. Two independent transformed lines were obtained that had the phenotype of the parental Landsberg erecta line and expressed the chimeric gene, as indicated by detection of its mRNA by reverse transcriptase-polymerase chain reaction. The results indicate that Synechocystis sp. PCC 6803 heme oxygenase encoded by ho1 can substitute for the defective HY1 gene product and that the only required enzyme activity of the HY1 gene product is heme oxygenase.

Amino Acid Sequence↗
PubMed2000

Newborn screening in Wisconsin: program overview and test addition.

The prevention of congenital anomalies and their sequelae is an important public health objective. One strategy for preventing morbidity and mortality due to congenital disorders is Wisconsin's Newborn Screening Program. Wisconsin has been a national leader in newborn screening since its inception with phenylketonuria screening in 1966. Wisconsin's program is a collaborative effort of the State Maternal and Child Health Program, housed within the Division of Public Health of the Department of Health and Family Services; the State Laboratory of Hygiene; physicians and other health professionals; and families. After in-depth consideration, the Department recently approved the addition of 14 fatty acid oxidation disorders and organic acidemias. This paper provides an overview of the Newborn Screening Program and introduces the disorders that Wisconsin added to the newborn screening panel in April 2000. Technologic advances have provided Wisconsin with yet another tool to improve the health of its citizens and prevent significant morbidity and mortality.

Acetylcarnitine↗
PubMed1998

Cloning and expression of the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA.

Using a cDNA probe from the rat 24-hydrovitamin D3 24-hydroxylase, the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA has been isolated from a chicken kidney lambda gt11 library. The high degree of similarity with the mammalian 24-hydroxylase cDNAs strongly supports the belief that it is the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA. The deduced amino acid sequences are also very well conserved and 325 of them are identical among the four known 25-hydroxyvitamin D3 24-hydroxylases. This cDNA expressed in E. coli produces 24-hydroxylase activity.

Amino Acid Sequence↗
PubMed1998

The prediction of criminal and violent recidivism among mentally disordered offenders: a meta-analysis.

A meta-analysis was conducted to examine whether the predictors of recidivism for mentally disordered offenders are different from the predictors for nondisordered offenders. Effect sizes were calculated for 35 predictors of general recidivism and 27 predictors of violent recidivism drawn from 64 unique samples. The results showed that the major predictors of recidivism were the same for mentally disordered offenders as for nondisordered offenders. Criminal history variables were the best predictors, and clinical variables showed the smallest effect sizes. The findings suggest that the risk assessment of mentally disordered offenders can be enhanced with more attention to the social psychological criminological literature and less reliance on models of psychopathology.

Adolescent↗
PubMed1998

Private health care provision in developing countries: a preliminary analysis of levels and composition.

While the importance of the private sector in providing health services in developing countries is now widely acknowledged, the paucity of data on numbers and types of providers has prevented systematic cross-country comparisons. Using available published and unpublished sources, we have assembled data on the number of public and private health care providers for approximately 40 countries. This paper presents some results of the analysis of this database, looking particularly at the determinants of the size and structure of the private health sector. We consider two different types of dependent variable: the absolute number of private providers (measured here as physicians and hospital beds), and the public-private composition of provision. We examine the relationship between these variables and income and other socioeconomic characteristics, at the national level. We find that while income level is related to the absolute size of the private sector, the public-private mix does not seem to be related to income. After controlling for income, certain socioeconomic characteristics, such as education, population density, and health status are associated with the size of the private sector, though no causal relationship is posited. Further analysis will require more complete data about the size of the private sector, including the extent of dual practice by government-employed physicians. A richer story of the determinants of private sector growth would incorporate more information about the institutional structure of health systems, including provider payment mechanisms, the level and quality of public services, the regulatory structure, and labour and capital market characteristics. Finally, a normative analysis of the size and growth of the private sector will require a better understanding of its impact on key social welfare outcomes.

Delivery of Health Care↗
PubMed1997

Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.

The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Cloning and origin of the two forms of chicken vitamin D receptor.

The cDNA for the chicken vitamin D receptor (VDR) has been cloned in full length by screening cDNA libraries from chicken intestine and chicken kidney. The chicken kidney cDNA library constructed by both oligo(dT) and random primer methods yielded several full-length clones. These contained a 66-bp additional coding sequence at the 5' end in comparison to the cDNAs of human, rat, and mouse VDR. The Japanese quail VDR cDNA was also cloned in full length. We found that the 5' coding sequence reported previously had been artifactually inverted. Both chicken and quail cDNAs have three conserved ATG sites for translation initiation with the 3' one corresponding to the only ATG site found in the mammalian cDNAs. Northern blot analysis showed that the VDR gene is expressed as a single 2.69-kb transcript in chicken intestine and kidney. An analysis of the avian multiple ATG sites revealed that the first ATG is in a suboptimal context of TCCATGT, while the second ATG is in AGC-ATGG, matching the optimal context: R-3NNATGG+4. As a result, the two forms of chicken VDR (cVDR) (form A, 60.3 kDa; form B, 58.6 kDa) likely arise from the first and second ATG sites of a single mRNA during translation. Mutational analysis confirmed this belief. The wild-type construct starting from the first ATG site with its original context was subcloned into pCMV5 expression vector and expressed in COS-1 cells. Two receptor proteins, exactly comigrating with the form A and form B cVDRs isolated from chicken intestine, were detected by immunoblotting. Point mutations optimizing the first ATG context led to exclusive production of form A, while knocking out the first ATG site resulted in the sole generation of form B. Form A translated from the first ATG site has 451 amino acids, and form B from the second ATG has 437 amino acids. Comparison between avian and mammalian VDRs indicated that VDR is essentially conserved in DNA binding and ligand binding domains. The significant difference especially at the N-terminus demonstrates divergence of this receptor during evolution of these species.

Amino Acid Sequence↗
PubMed1997

Disability-adjusted life years: a critical review.

The disability-adjusted life year (DALY) has emerged in the international health policy lexicon as a new measure of the 'burden of disease'. We argue that the conceptual and technical basis for DALYs is flawed, and its assumptions and value judgements are open to serious question. In particular, the implications of age-weighting and discounting are found to be unacceptable. Moreover, the proponents of DALYs do not distinguish between the exercises of measuring the burden of disease and of allocating resources. But the appropriate information sets for the two exercises are quite different. Allocating resources by aggregate DALY-minimization is shown to be inequitable.

Age Factors↗
PubMed1997

Are two interventions worse than none? Joint primary and secondary prevention of eating disorders in college females.

Prevention programs for eating disorders attempt to simultaneously prevent new cases from arising (primary prevention) and encourage students who already have symptoms to seek early treatment (secondary prevention), even though ideal strategies for these 2 types of prevention may be incompatible with each other. In the present study, an eating disorder prevention program was evaluated in a simple of female college freshmen. In the intervention, classmates who had recovered from eating disorders described their experiences and provided information about eating disorders. At follow-up, intervention participants had slightly more symptoms of eating disorders than did controls. The program may have been ineffective in preventing eating disorders because by reducing the stigma of these disorders (to encourage students with problems to seek help), the program may have inadvertently normalized them.

Adaptation, Psychological↗
PubMed1997

Attenuation of phytochrome A and B signaling pathways by the Arabidopsis circadian clock.

In higher plants, environmental cues such as light signals are integrated with circadian clock signals to control precisely the daily rhythms observed for many biological functions. We have used a fusion of the promoter of a chlorophyll a/b binding protein gene, CAB2, with firefly luciferase (cab2::luc) to monitor the detailed kinetics of transcription in response to photoreceptor activation in Arabidopsis. Using this marker in phototransduction and circadian-dysfunctional mutants, we studied how signals from phytochrome and the circadian clock are integrated for the regulation of CAB2 transcription. Results from these mutant studies demonstrate that similar expression features, namely, the acute and circadian responses, are present in both etiolated and green seedlings and that the acute and circadian responses are genetically separable. We also demonstrate that persistent Pfr signaling occurs in red light-pulsed etiolated seedlings, which suggests that the circadian clock antagonizes Pfr-mediated signal transduction. Based on these genetic studies, we propose a model for the regulation of CAB2 transcription in which individual photoreceptors and phototransduction components have been assigned to specific pathways for the regulation of discrete kinetic components of the CAB2 expression pattern.

Arabidopsis↗