bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Philip Morris’s pursuit of US government regulation of tobacco: Table 1
Authors: McDaniel P A , Malone R E
Published: May 2005

Objective:To investigate Philip Morris’s support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company’s image enhancement strategies.

Data sources:Internal Philip Morris documents released as part of the Master Settlement Agreement.

Methods:Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as “FDA” and “regulatory strategy” and expanding to include relevant new terms.

Results:Philip Morris’s support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company’s stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris’s regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products.

Conclusions:Philip Morris’s ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris’s products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted.
Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats
Authors: Siu Parco M. , Pistilli Emidio E. , Alway Stephen E.
Published: May 2005

Although apoptosis has been demonstrated in soleus during hindlimb suspension (HS), it is not known whether apoptosis is also involved in the loss of muscles dominated by mixed fibers. Therefore, we examined the apoptotic responses in gastrocnemius muscles of young adult and aged Fischer 344 × Brown Norway rats after 14 days of HS. The medial gastrocnemius muscle wet weight significantly decreased by 30 and 32%, and muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively, after HS. The extent of apoptotic DNA fragmentation increased by 119 and 61% in suspended muscles from young and aged rats, respectively. Bax mRNA increased by 73% in young muscles after HS. Bax and Bcl-2 protein levels were greater in suspended muscles relative to control muscles in both age groups. The level of cytosolic mitochondria-housed apoptotic factor cytochrome c was significantly increased in the mitochondria-free cytosol of suspended muscles from young and aged rats. In contrast, the release/accumulation of AIF, a caspase-independent apoptogenic factor, was exclusively expressed in the suspended muscles from aged rats. Our data also show that aging favors the proapoptotic signaling in skeletal muscle by altering the contents of Bax, Bcl-2, Apaf-1, AIF, caspases, XIAP, Smac/DIABLO, and cytochrome c. Furthermore, these results indicate that apoptosis occurs not only in slow-twitch soleus muscle but also in the mixed-fiber (predominately fast fibered) gastrocnemius muscle. Our data are consistent with the hypothesis that apoptotic signaling differs in young adult and aged gastrocnemius muscles during HS.
Cell proliferation and gill morphology in anoxic crucian carp
Authors: Sollid Jørund , Kjernsli Aina , De Angelis Paula M. , Røhr Åsmund K. , Nilsson Göran E.
Published: May 2005

Is DNA replication/cell proliferation in vertebrates possible during anoxia? The oxygen dependence of ribonucleotide reductase (RNR) could lead to a stop in DNA synthesis, thereby making anoxic DNA replication impossible. We have studied this question in an anoxia-tolerant vertebrate, the crucian carp ( Carassius carassius), by examining 5′-bromo-2′-deoxyuridine incorporation and proliferating cell nuclear antigen levels in the gills, intestinal crypts, and liver. We exposed crucian carp to 1 and 7 days of anoxia followed by 7 days of reoxygenation. There was a reduced incidence of S-phase cells (from 12.2 to 5.0%) in gills during anoxia, which coincided with a concomitant increase of G0cells. Anoxia also decreased the number of S-phase cells in intestine (from 8.1 to 1.8%). No change in the fraction of S-phase cells (∼1%) in liver was found. Thus new S-phase cells after 7 days of anoxia were present in all tissues, revealing a considerable rate of DNA synthesis. Subsequently, the oxygen-dependent subunit of crucian carp RNR (RNRR2) was cloned. We found no differences in amino acids involved in radical generation and availability of the iron center compared with mouse, which could have explained reduced oxygen dependence. Furthermore, the amount of RNRR2 mRNA in gills did not decrease throughout anoxia exposure. These results indicate that crucian carp is able to sustain some cell proliferation in anoxia, possibly because RNRR2 retains its tyrosyl radical in anoxia, and that the replication machinery is still maintained. Although hypoxia triggers a 7.5-fold increase of respiratory surface area in crucian carp, this response was not triggered in anoxia.
Why do arms extract less oxygen than legs during exercise?
Authors: Calbet J. A. L. , Holmberg H.-C. , Rosdahl H. , van Hall G. , Jensen-Urstad M. , Saltin B.
Published: May 2005

To determine whether conditions for O2utilization and O2off-loading from the hemoglobin are different in exercising arms and legs, six cross-country skiers participated in this study. Femoral and subclavian vein blood flow and gases were determined during skiing on a treadmill at ∼76% maximal O2uptake (V̇o2 max) and at V̇o2 maxwith different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise), and leg skiing (predominantly leg exercise). The percentage of O2extraction was always higher for the legs than for the arms. At maximal exercise (diagonal stride), the corresponding mean values were 93 and 85% ( n = 3; P < 0.05). During exercise, mean arm O2extraction correlated with the Po2value that causes hemoglobin to be 50% saturated (P50: r = 0.93, P < 0.05), but for a given value of P50, O2extraction was always higher in the legs than in the arms. Mean capillary muscle O2conductance of the arm during double poling was 14.5 (SD 2.6) ml·min−1·mmHg−1, and mean capillary Po2was 47.7 (SD 2.6) mmHg. Corresponding values for the legs during maximal exercise were 48.3 (SD 13.0) ml·min−1·mmHg−1and 33.8 (SD 2.6) mmHg, respectively. Because conditions for O2off-loading from the hemoglobin are similar in leg and arm muscles, the observed differences in maximal arm and leg O2extraction should be attributed to other factors, such as a higher heterogeneity in blood flow distribution, shorter mean transit time, smaller diffusing area, and larger diffusing distance, in arms than in legs.
Lymphocyte responses to influenza and tetanus toxoid in vitro following intensive exercise and carbohydrate ingestion on consecutive days
Authors: Bishop Nicolette C. , Walker Gary J. , Bowley Lee A. , Evans Kate F. , Molyneux Karen , Wallace Fiona A. , Smith Alice C.
Published: May 2005

The effect of carbohydrate (CHO) ingestion on antigen- (rather than mitogen-) stimulated T-cell responses to prolonged, intensive exercise may give a more realistic insight into the effect of CHO on T-cell functional capacity and subsequent infection risk. This study investigated the effect of CHO ingestion during prolonged, intensive exercise on influenza- and tetanus toxoid-stimulated T-cell cytokine mRNA expression and proliferation. Mitogen- [phytohemagglutinin (PHA)] stimulated proliferation was assessed for comparison. Responses were assessed following exercise on consecutive mornings to determine any carryover effect. Fifteen male games players performed two exercise trials in a double-blind, randomized, crossover design. Each trial comprised 90 min of intensive, intermittent running on consecutive mornings, with either CHO (6.4% wt/vol) or placebo (PLA) beverage ingestion before, during, and after each bout of exercise. Postexercise CD3+ cell counts were higher in PLA than CHO on both days ( P < 0.05). Antigen-stimulated T-cell cytokine mRNA expression was unaffected by exercise or CHO ingestion. Before exercise on day 2, T-cell proliferative responses to PHA, influenza, and tetanus toxoid were higher in CHO than PLA by 99, 80, and 58%, respectively ( P < 0.01 for PHA, P < 0.05 for influenza and tetanus toxoid). At 1 h postexercise on day 2, PHA-induced proliferation was 70% higher in CHO than PLA ( P < 0.05), yet there were no differences between trials for antigen-induced proliferative responses. Therefore, mitogen-induced T-cell proliferation following strenuous exercise and CHO does not necessarily reflect responses to specific antigens and, consequently, may not provide a good model for the situation in vivo.
Epithelial lining fluid solute concentrations in chronic obstructive lung disease patients and normal subjects
Authors: Effros Richard M. , Peterson Barry , Casaburi Richard , Su Jennifer , Dunning Marshall , Torday John , Biller Julie , Shaker Reza
Published: May 2005

The exhaled breath condensate (EBC) method represents a new, noninvasive way to detect inflammatory and metabolic markers in the fluid that covers the airways [epithelial lining fluid (ELF)]. However, respiratory droplets represent only a very small and variable fraction of the EBC, most (∼99.99%) of which is water vapor. Our objective was to show that ELF concentrations could be calculated from EBC values by using any of three dilutional indicators (urea, total cations, and conductivity) in nine normal and nine chronic obstructive lung disease (COPD) subjects. EBC concentrations of Na+, K+, Ca2+, Mg2+, total cations, urea, and conductivity varied over a 10-fold range among individuals, but concentrations of these constituents (except Ca2+) remained well correlated ( r2= 0.44–0.83, P < 0.001). Dilution (D) of respiratory droplets in water vapor was calculated by dividing plasma concentrations of the dilutional indicators by EBC concentrations. Estimates of D were not significantly different among these indicators, and urea D averaged 10,800 ± 2,100 (SE) in normal and 12,600 ± 3,300 in COPD subjects. Although calculated Na+concentrations in the ELF were less than one-half those in plasma, and concentrations of K+, Ca2+, and Mg2+exceeded those in plasma, total cation concentrations in ELF were not significantly different from those in plasma, indicating that ELF is isotonic in both normal and COPD subjects. EBC amylase concentrations (measured with an ultrasensitive procedure) indicated that saliva represented <10% of the respiratory (ELF) droplets in all but three samples. Dilutional and salivary markers are essential for interpretation of EBC studies.
Left ventricular size and systolic function in Thoroughbred racehorses and their relationships to race performance
Authors: Young L. E. , Rogers K. , Wood J. L. N.
Published: May 2005

Cardiac morphology in human athletes is known to differ, depending on the sports-specific endurance component of their events, whereas anecdotes abound about superlative athletes with large hearts. As the heart determines stroke volume and maximum O2 uptake in mammals, we undertook a study to test the hypothesis that the morphology of the equine heart would differ between trained horses, depending on race type, and that left ventricular size would be greatest in elite performers. Echocardiography was performed in 482 race-fit Thoroughbreds engaged in either flat (1,000–2,500 m) or jump racing (3,200–6,400 m). Body weight and sex-adjusted measures of left ventricular size were largest in horses engaged in jump racing over fixed fences, compared with horses running shorter distances on the flat (range 8–16%). The observed differences in cardiac morphologies suggest that subtle differences in training and competition result in cardiac adaptations that are appropriate to the endurance component of the horses' event. Derived left ventricular mass was strongly associated with published rating (quality) in horses racing over longer distances in jump races ( P ≤ 0.001), but less so for horses in flat races. Rather, left ventricular ejection fraction and left ventricular mass combined were positively associated with race rating in older flat racehorses running over sprint (<1,408 m) and longer distances (>1,408 m), explaining 25–35% of overall variation in performance, as well as being closely associated with performance in longer races over jumps (23%). These data provide the first direct evidence that cardiac size influences athletic performance in a group of mammalian running athletes.
Netherton Syndrome with Extensive Skin Peeling and Failure to Thrive due to a Homozygous Frameshift Mutation in SPINK5
Authors: Geyer Adam S. , Ratajczak Paulina , Pol-Rodriguez Marlyanne , Millar William S. , Garzon Maria , Richard Gabriele
Published: May 2005

Background: Netherton syndrome (NTS) is a rare autosomal recessive multisystem disorder characterized by congenital erythroderma and ichthyosis, hair shaft abnormalities and immune dysregulation. The disorder is caused by deleterious mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI. Objective: Our objective was to investigate if the erythrodermic variant of peeling skin syndrome is also caused by SPINK5 mutations and to study the consequences of the disease on infantile brain development. Methods: In an infant with extensive erythroderma, peeling skin and failure to thrive, we analyzed the SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed repeated brain MRI studies with diffusion-weighted imaging. Results: We identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which introduces a premature termination codon and appears to be a common mutation among West Indies islanders. MRI analyses revealed a persistent diffuse volume loss. Conclusion: Our results confirm that early truncation mutations of the coding sequence of SPINK5 produce a severe phenotype and that generalized peeling skin is one of the manifestations of NTS. We further demonstrate for the first time that NTS may be associated with MRI abnormalities indicative of a permanent tissue injury of the brain.
Extramammary Paget’s Disease Not Only Mimicking but Also Accompanying Condyloma acuminatum
Authors: Honda Yumi , Egawa Kiyofumi
Published: May 2005

Although its significance remains unknown, it has recently been reported that epidermal papillomatous hyperplasia could be frequently found in extramammary Paget’s disease (EMPD). The simultaneous occurrence of EMPD and various human-papillomavirus (HPV)-associated neoplasms has also been reported. We report a case of a perianal EMPD with multiple verrucous papules on its surface. Histologically, the verrucous papules consisted of two distinct histological patterns; one showed numerous Paget’s cells within the hyperplastic epidermis with papillomatosis, and the other showed the features compatible with condyloma acuminatum (CA). HPV-6 DNA was demonstrated in koilocytic keratinocytes of the CA by in situ hybridization. No positive signal was obtained for targeted HPV type 6/11/16/18/31/33 DNA in either the verrucous or plaque EMPD. Since the verrucous papules were localized on the plaque of EMPD, our case suggests that some undetermined EMPD-related factors may contribute to the development of epithelial hyperplasia, including HPV-associated neoplasms.
The Educational Needs and Professional Roles of Canadian Physicians and Nurses regarding Genetic Testing and Adult Onset Hereditary Disease
Authors: Bottorff Joan L. , Blaine Sean , Carroll June C. , Esplen Mary Jane , Evans Jane , Nicolson Klimek Mary Lou , Meschino Wendy , Ritvo Paul
Published: May 2005

Objective: To investigate the knowledge, professional involvement and confidence of Canadian nurses and physicians in providing genetic services for adult onset hereditary disease. Methods: 1,425 physicians and 1,425 nurses received a mailed questionnaire with reminders. The response rates were 50% (n = 543) and 79% (n = 975), respectively. Results: Forty-eight percent of physicians and 31% of nurses lacked formal education in genetics. Respondents reported being involved in caring for people at risk for adult onset hereditary disease. Their levels of confidence that they could perform tasks, such as counselling about predictive genetic tests, however, were lower than their levels of expectation that it would be important for them to provide these services. Conclusions: The expected roles and educational needs of Canadian nurses and physicians have broad areas of overlap suggesting the possibility of combined professional education programs and multiple ways of organizing teams to provide genetic services to people at risk for adult onset hereditary disease.
Attitudes of Israeli Muslims at Risk of Genetic Disorders towards Pregnancy Termination
Authors: Neter Efrat , Wolowelsky Yael , Borochowitz Zvi U.
Published: May 2005

Objectives: (1) To examine attitudes towards termination of pregnancy (TOP) among high-risk and non-high-risk (for cystic fibrosis) Arab-Muslims, and (2) to examine the effect of an intervention, which among other things related explicitly to TOP. Methods: The study comprised three groups: (1) an intervention group at high risk for CF, which received community genetic counseling; (2) a control group at high risk for CF, and (3) a control group from the general population. The latter two groups were exposed to minimal intervention. Attitudes were measured two or three times during a 1-year period (for the control and intervention groups, respectively). Results: Predictors of an affected fetus being considered a legitimate cause for TOP were religiosity, familiarity with an affected child, and benefits of the test. Predictors of individuals (hypothetically) choosing abortion in the case of an affected fetus were education and age. No change occurred in the attitudes of participants (either experimental or control groups) in the course of 1 year. Conclusions: Other possible intervention options are discussed, and specifically, the advantages of using opinion leaders such as clergy and medical staff.
Bias Correction with a Single Null Marker for Population Stratification in Candidate Gene Association Studies
Authors: Wang Yiting , Localio Russell , Rebbeck Timothy R.
Published: May 2005

Population stratification is a form of confounding by ethnicity that may cause bias to effect estimates and inflate test statistics in genetic association studies. Unlinked genetic markers have been used to adjust for test statistics, but their use in correcting biased effect estimates has not been addressed. We evaluated the potential of bias correction that could be achieved by a single null marker (M) in studies involving one candidate gene (G). When the distribution of M varied greatly across ethnicities, controlling for M in a logistic regression model substantially reduced biases on odds ratio estimates. When M had same distributions as G across ethnicities, biases were further reduced or eliminated by subtracting the regression coefficient of M from the coefficient of G in the model, which was fitted either with or without a multiplicative interaction term between M and G. Correction of bias due to population stratification depended specifically on the distributions of G and M, the difference between baseline disease risks across ethnicities, and whether G had an effect on disease risk or not. Our results suggested that marker choice and the specific treatment of that marker in analysis greatly influenced bias correction.
Insulin-Like Growth Factor-1 and Its Binding Proteins, IGFBP-1 and IGFBP-3, in Adolescents with Type-1 Diabetes mellitus and Microalbuminuria
Authors: Wędrychowicz Anna , Dziatkowiak Hanna , Nazim Joanna , Sztefko Krystyna
Published: May 2005

Background/Aims: Numerous clinical and experimental studies suggest that growth factors may contribute to the development of diabetic microvascular complications. The aim of the study was to test the hypothesis that in adolescents with type-1 diabetes mellitus and microalbuminuria (MA) there are specific disorders of serum insulin-like growth factor-1 (IGF-1) and concentrations of its binding proteins, IGFBP-1 and IGFBP-3, that could be of importance in the pathogenesis of microvascular diabetic complications. Methods: 25 adolescents with MA, 24 adolescents with diabetes without complications, and 17 controls were examined. There were no differences with regard to age, puberty stage, HbA1c and body mass index between the groups examined. Two of the patients in the first group also had diabetic retinopathy. Serum fasting concentrations of IGF-1 and overnight urine albumin concentrations were measured by radioimmunoassay, IGFBP-1 and IGFBP-3 concentrations by immunoradiometric assay and HbA1c by high-performance liquid chromatography methods. Diabetic patients were examined by an experienced ophthalmologist and neurologist. The data were analyzed using Kruskal-Wallis ANOVA and multiple regression analysis. Results: Significantly lower IGF-1 concentrations were found in adolescents with diabetes and MA compared to diabetic patients without complications and healthy contemporaries. IGFBP-1 concentrations were significantly higher and IGFBP-3 concentrations were statistically lower in diabetic patients with MA than in patients without complications. Conclusions: The IGF-IGFBP system is deranged in adolescents with type-1 diabetes mellitus and MA. Our results suggest the participation of circulating IGFBP-1 in the origin of diabetic complications. It could be also possible that IGFBP-3 takes part in the protection from them.
Novel and Recurrent Mutations in Patients with Androgen Insensitivity Syndromes
Authors: Ledig Susanne , Jakubiczka Sibylle , Neulen Joseph , Aulepp Ute , Burck-Lehmann Uta , Mohnike Klaus , Thiele Hannelore , Zierler Hannelore , Brewer Carole , Wieacker Peter
Published: May 2005

Background/Aims: Androgen insensitivity syndrome (AIS) caused by mutations within the androgen receptor gene represents a variety of phenotypes from females with 46,XY karyotype over individuals with ambiguous genitalia to infertile males. Methods: We studied 24 patients with AIS by sequencing androgen receptor gene. 19 of the investigated patients were affected by complete androgen insensitivity syndrome (CAIS) and 5 suffered from partial androgen insensitivity syndrome (PAIS). Results: So far we have detected 12 unreported mutations as well as 9 recurrent mutations (3 recurrent mutations were detected twice) in exons 2–8 of the androgen receptor gene. Three of the novel mutations cause a frameshift with subsequent premature termination and were found in patients with CAIS. These frameshifts were induced by single nucleotide deletion or insertion, or in one case by a 13-bp deletion, respectively. Another premature stop codon found in a CAIS patient results from an already reported nucleotide substitution in exon 5. Furthermore, in a CAIS patient we found a novel duplication of codon 788. All other mutations caused single base substitutions spread through exons 2–8 and were associated with CAIS or PAIS. Conclusions: We report a broad spectrum of different mutations within the AR gene leading to various manifestations of AIS. Apart from truncating mutations, a reliable genotype/phenotype correlation cannot be established. Therefore, modifying factors must be effective.
Role of C-Reactive Protein in Atherogenesis
Authors: Reifenberg Kurt , Lehr Hans-Anton , Baskal Daniela , Wiese Elena , Schaefer Stephan C. , Black Steven , Samols David , Torzewski Michael , Lackner Karl J. , Husmann Matthias , Blettner Maria , Bhakdi Sucharit
Published: May 2005

Objective—Human C-reactive protein (CRP) was reported to accelerate atherosclerotic lesion development in male but not in female apolipoprotein E (apoE) knockout mice. Here, mice expressing rabbit CRP (rbCRP) were crossbred onto apoE knockout animals, and the effect on atherogenesis was studied.

Methods and Results—Hemolytic complement activity could not be detected in apoE knockout mice. Furthermore, in contrast to human complement, neither rabbit nor human CRP complexed to modified low-density lipoprotein–activated murine complement. At 52 weeks, rbCRP levels were similar in male and female transgenic animals. Serum cholesterol levels were equivalent in female animals irrespective of rbCRP expression, whereas rbCRP–positive males had significantly higher serum cholesterol levels than the rbCRP-negative counterparts. All mice exhibited extensive atherosclerotic lesions, as studied en face, and no differences were noted between rbCRP-negative and rbCRP-positive animals. Atherosclerotic luminal obstruction of aortic arch and first-order neck branches did not differ significantly between rbCRP-positive and rbCRP-negative mice. There was no correlation between rbCRP levels and atherosclerotic lesion formation.

Conclusions—No marked effect of rbCRP on the formation of moderately advanced atherosclerotic lesions could be discerned in the apoE knockout mouse. Because of the oddities of the mouse complement system, however, this may not be a good model to investigate the role of CRP in human atherosclerosis.
Mast Cell–Derived Exosomes Activate Endothelial Cells to Secrete Plasminogen Activator Inhibitor Type 1
Authors: Al-Nedawi Khalid , Szemraj Janusz , Cierniewski Czeslaw S.
Published: May 2005

Objective—

Previous studies supported the contribution of exosomes to an acellular mode of communication, leading to intercellular transfer of molecules. In this study we provide evidence that mast cell-derived exosomes induce plasminogen activator inhibitor type 1 (PAI-1) expression in endothelial cells, detectable at the level of PAI-1 mRNA and protein synthesis. The stimulating effect was also measured at the level of PAI-1 promoter activity.

Methods and Results—

To identify components responsible for this activity, exosome proteins were separated by 2-dimensional PAGE, and protein spots were identified by microsequencing using electrospray (ISI-Q-TOF-Micromass) spectrometer. Components of 3 independent systems that can be involved in activation of endothelial cells, namely the prothrombinase complex, tumor necrosis factor-α, and angiotensinogen precursors were identified. Procoagulant activity of exosomes was confirmed by a thrombin generation assay using a specific chromogenic substrate. Because the potential of mast cell-derived exosomes to induce PAI-1 expression was completely abolished by hirudin, thrombin generated on exosomes seems to be responsible for this activity.

Conclusions—

It can be concluded that mast cell-derived exosomes via significant upregulation of PAI-1 secretion from endothelial cells may provide feedback between the characteristically increased PAI-1 levels and procoagulant states, both observed in diverse syndromes manifesting as endothelial cell dysfunction.
Quantification of Calcification in Atherosclerotic Lesions
Authors: Higgins Catherine L. , Marvel Seth A. , Morrisett Joel D.
Published: May 2005

Calcification can be deposited throughout the vasculature in several forms of calcium phosphate, including calcium hydroxyapatite (CHA). Calcium accumulation in arteries by mineralization and calcium loss from bone by osteoporosis often coexist, and vascular calcification may share common mechanisms with bone remodeling. Deposition of calcification in valves and arteries diminishes the valvular or arterial wall elasticity, a major cause of aneurysm and stenosis. Obstruction of arteries by calcification and other components can lead to heart attack and stroke. Mineralization in the femoral arteries can cause intermittent claudication in the legs, causing decreased mobility. Accurate measurement of calcification is essential for identifying other factors associated with this process and ultimately for elucidating the mechanism(s) of calcification. A wide range of methods for visualizing and measuring calcification for diagnosis and treatment in vivo and for studying the calcification process ex vivo are available. This review provides a critical comparison of older established methods and newer evolving technologies for quantifying calcification.
Length of Stay, Discharge Destination, and Functional Improvement
Authors: Tooth Leigh , McKenna Kryss , Goh Kong , Varghese Paul
Published: May 2005

Background and Purpose—

Although implemented in 1998, no research has examined how well the Australian National Subacute and Nonacute Patient (AN-SNAP) Casemix Classification predicts length of stay (LOS), discharge destination, and functional improvement in public hospital stroke rehabilitation units in Australia.

Methods—

406 consecutive admissions to 3 stroke rehabilitation units in Queensland, Australia were studied. Sociodemographic, clinical, and functional data were collected. General linear modeling and logistic regression were used to assess the ability of AN-SNAP to predict outcomes.

Results—

AN-SNAP significantly predicted each outcome. There were clear relationships between the outcomes of longer LOS, poorer functional improvement and discharge into care, and the AN-SNAP classes that reflected poorer functional ability and older age. Other predictors included living situation, acute LOS, comorbidity, and stroke type.

Conclusions—

AN-SNAP is a consistent predictor of LOS, functional change and discharge destination, and has utility in assisting clinicians to set rehabilitation goals and plan discharge.
Global Governance and Labor Rights: Codes of Conduct and Anti-Sweatshop Struggles in Global Apparel Factories in Mexico and Guatemala
Authors: Rodríguez-Garavito César A.
Published: May 2005

Monitoring systems have recently arisen to verify compliance with corporate codes of conduct for labor. This article places codes in the context of broader debates on global governance and argues for an empowered participatory approach to international labor standards focusing on enabling rights. Based on ethnographic research in Mexico and Guatemala on the implementation of codes in the apparel sector and their use in cross-border organizing campaigns, it explores the effect of monitoring on worker empowerment and working conditions in global factories. The analysis highlights institutional designs and political strategies capable of contributing to the protection of international labor rights.
National Model under Globalization: The Japanese Model and Its Internationalization
Authors: Kwon Hyeong-Ki
Published: May 2005

This paper investigates how and why the Japanese model has undergone changes in the context of its internationalization, during which foreign countries, particularly the U.S. and Germany, adopted Japanese methods, departing from their own traditional models at the turn of the twentieth century. By examining the dynamicprocesses of these transformations in national models, this paper critically reviews prevalent paradigms of neoliberalism and institutionalism, proposing an alternative of “mutual learning by reflexive agents.” By exploring the dynamic processes of the Japanese model’s internationalization and transformation, in which the Japanese model fell into crisis and underwent transformation in the changed context of international competition caused by the internationalization of the Japanese model, this paper proposes a new conception of “mutual learning by reflexive agents” in the context of international competition, in which agents, inspired by foreign competitors, critically reconsider their own institutions and, in turn, generate a new divergence in the process of creative learning.
Social Movements and Judicial Empowerment: Courts, Public Policy, and Lesbian and Gay Organizing in Canada
Authors: Smith Miriam
Published: May 2005

This article explores the impact of judicial empowerment on social movement politics and public policy using a case study of the lesbian and gay rights movement in Canada before and after the 1982 constitutional entrenchment of the Canadian Charter of Rights and Freedoms. The expanded role of courts in the Canadian political system has had substantial effects on public policy in the lesbian and gay rights area over a twenty-year period, putting Canada in the forefront of this area of human rights.
Educating European Corporate Communication Professionals for Senior Management Positions
Authors: Forman Janis
Published: May 2005

UCLA’s program in strategic management for European corporate communication professionals provides participants with a concentrated, yet selective, immersion in those management disciplines taught at U.S. business schools, topics that are essential to their work as senior advisors to CEOs and as leaders in the field. The choice of topics represents the close collaboration between the directors of the UCLA and Lugano programs. The UCLA program also encourages the active participation of the professionals by offering an exposure to teaching and classroom communication practices of U.S. business schools that adhere to the case approach to business education and by providing numerous opportunities for participants to present their analyses and application of management topics to their professional roles and responsibilities. Working with European professionals also enables U.S. faculty to reconsider some of their own assumptions about teaching as they train U.S.-based MBA students.
Integrative analysis of multiple gene expression profiles with quality-adjusted effect size models
Authors: Hu Pingzhao , Greenwood Celia MT , Beyene Joseph
Published: May 2005

Background

With the explosion of microarray studies, an enormous amount of data is being produced. Systematic integration of gene expression data from different sources increases statistical power of detecting differentially expressed genes and allows assessment of heterogeneity. The challenge, however, is in designing and implementing efficient analytic methodologies for combination of data generated by different research groups.

Results

We extended traditional effect size models to combine information from different microarray datasets by incorporating a quality measure for each gene in each study into the effect size estimation. We illustrated our method by integrating two datasets generated using different Affymetrix oligonucleotide types. Our results indicate that the proposed quality-adjusted weighting strategy for modelling inter-study variation of gene expression profiles not only increases consistency and decreases heterogeneous results between these two datasets, but also identifies many more differentially expressed genes than methods proposed previously.

Conclusion

Data integration and synthesis is becoming increasingly important. We live in a high-throughput era where technologies constantly change leaving behind a trail of data with different forms, shapes and sizes. Statistical and computational methodologies are therefore critical for extracting the most out of these related but not identical sources of data.
A new approach for the analysis of bacterial microarray-based Comparative Genomic Hybridization: insights from an empirical study
Authors: Taboada Eduardo N , Acedillo Rey R , Luebbert Christian C , Findlay Wendy A , Nash John HE
Published: May 2005

Background

Microarray-based Comparative Genomic Hybridization (M-CGH) has been used to characterize the extensive intraspecies genetic diversity found in bacteria at the whole-genome level. Although conventional microarray analytical procedures have proved adequate in handling M-CGH data, data interpretation using these methods is based on a continuous character model in which gene divergence and gene absence form a spectrum of decreasing gene conservation levels. However, whereas gene divergence may yet be accompanied by retention in gene function, gene absence invariably leads to loss of function. This distinction, if ignored, leads to a loss in the information to be gained from M-CGH data.

We present here results from experiments in which two genome-sequenced strains of C. jejuni were compared against each other using M-CGH. Because the gene content of both strains was known a priori, we were able to closely examine the effects of sequence divergence and gene absence on M-CGH data in order to define analytical parameters for M-CGH data interpretation. This would facilitate the examination of the relative effects of sequence divergence or gene absence in comparative genomics analyses of multiple strains of any species for which genome sequence data and a DNA microarray are available.

Results

As a first step towards improving the analysis of M-CGH data, we estimated the degree of experimental error in a series of experiments in which identical samples were compared against each other by M-CGH. This variance estimate was used to validate a Log Ratio-based methodology for identification of outliers in M-CGH data. We compared two genome strains by M-CGH to examine the effect of probe/target identity on the Log Ratios of signal intensities using prior knowledge of gene divergence and gene absence to establish Log Ratio thresholds for the identification of absent and conserved genes.

Conclusion

The results from this empirical study validate the Log Ratio thresholds that have been used in other studies to establish gene divergence/absence. Moreover, the analytical framework presented here enhances the information content derived from M-CGH data by shifting the focus from divergent/absent gene detection to accurate detection of conserved and absent genes. This approach closely aligns the technical limitations of M-CGH analysis with practical limitations on the biological interpretation of comparative genomics data.
Variability and conservation in hepatitis B virus core protein
Authors: Chain Benjamin M , Myers Richard
Published: May 2005

Background

Hepatitis B core protein (HBVc) has been extensively studied from both a structural and immunological point of view, but the evolutionary forces driving sequence variation within core are incompletely understood.

Results

In this study, the observed variation in HBVc protein sequence has been examined in a collection of a large number of HBVc protein sequences from public sequence repositories. An alignment of several hundred sequences was carried out, and used to analyse the distribution of polymorphisms along the HBVc. Polymorphisms were found at 44 out of 185 amino acid positions analysed and were clustered predominantly in those parts of HBVc forming the outer surface and spike on intact capsid. The relationship between HBVc diversity and HBV genotype was examined. The position of variable amino acids along the sequence was examined in terms of the structural constraints of capsid and envelope assembly, and also in terms of immunological recognition by T and B cells.

Conclusion

Over three quarters of amino acids within the HBVc sequence are non-polymorphic, and variation is focused to a few amino acids. Phylogenetic analysis suggests that core protein specific forces constrain its diversity within the context of overall HBV genome evolution. As a consequence, core protein is not a reliable predictor of virus genotype. The structural requirements of capsid assembly are likely to play a major role in limiting diversity. The phylogenetic analysis further suggests that immunological selection does not play a major role in driving HBVc diversity.
Reporting of unintended events in an intensive care unit: comparison between staff and observer
Authors: Capuzzo Maurizia , Nawfal Imad , Campi Matilde , Valpondi Vanna , Verri Marco , Alvisi Raffaele
Published: May 2005

Background

In order to identify relevant targets for change, it is essential to know the reliability of incident staff reporting. The aim of this study is to compare the incidence and type of unintended events (UE) reported by facilitated Intensive Care Unit (ICU) staff with those recorded concurrently by an observer.

Methods

The study is a prospective data collection performed in two 4-bed multidisciplinary ICUs of a teaching hospital. The format of the UE reporting system was voluntary, facilitated and not necessarily anonymous, and used a structured form with a predetermined list of items. UEs were reported by ICU staff over a period of 4 weeks. The reporting incidence during the first fourteen days was compared with that during the second fourteen. During morning shifts in the second fourteen days, one observer in each ICU recorded any UE seen. The staff was not aware of the observers' study. The incidence of UEs reported by staff was compared with that recorded by the observers.

Results

The staff reported 36 UEs in the first fourteen days and 31 in the second.. The incidence of UE detection during morning shifts was significantly higher than during afternoon or night shifts (p < 0.001). Considering only working day morning shifts, the rate of UE reporting by the staff per 100 patient days was 26.9 (CI 95% 16.9–37.0) in the first fourteen day period and 20.3 (CI 95% 10.3–30.4) in the second. The rate of UE detection by the observers was 53.1 per 100 patient days (CI 95% 40.6–65.6), significantly higher (p < 0.001) than that reported concurrently by the staff. There was excellent agreement between staff and observers about the severity of the UEs recorded (Intraclass Correlation Coefficient 0.869). The observers recorded mainly UEs involving Airway/mechanical ventilation and Patient management, and the staff Catheter/Drain/Probe and Medication errors (p = 0.025).

Conclusion

UE incidence is strongly underreported by staff in comparison with observers. Also the types of UEs reported are different. Invaluable information about incidents in ICU can be obtained in a few days by observer monitoring.
Embolic stroke complicating Staphylococcus aureusendocarditis circumstantially linked to rectal trauma from foreign body: a first case report
Authors: Pandey Braj B , Dang Tuan C , Healy John F
Published: May 2005

Background

Diagnostic and therapeutic instrumentation of the lower gastrointestinal tract has been reported to result in bacteremia and endocarditis. No such case has been reported in persons with a history of rectal foreign body insertion despite its potential for greater trauma.

Case presentation

A 58-year-old male was admitted with confusion and inability to speak. His past history was notable for hospitalization to extract a retained plastic soda bottle from the rectosigmoid two years prior. On examination, he was febrile, tachycardic and hypotensive. There was an apical pansystolic murmur on cardiac examination. He had a mixed receptive and expressive aphasia, and a right hemiparesis. On rectal examination he had perianal erythema and diminished sphincter tone. Magnetic resonance imaging of the brain showed infarction of the occipital and frontal lobes. Transesophageal Echocardiography of the heart revealed vegetations on the mitral valve. All of his blood culture bottles grew methicillin sensitive Staphylococcus aureus. He was successfully treated for bacterial endocarditis with intravenous nafcillin and gentamicin. The rectum is frequently colonized by Staphylococcus aureus and trauma to its mucosa can lead to bacteremia and endocarditis with this organism.

In the absence of corroborative evidence such as presented here, it is difficult to make a correlation between staphylococcal endocarditis and anorectal foreign body insertion due to patients being less than forthcoming

Conclusion

There is a potential risk of staphylococcal bacteremia and endocarditis with rectal foreign body insertion. Further studies are needed to explore this finding. Detailed sexual history and patient counseling should be made a part of routine primary care.
Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney
Authors: Hartner Andrea , Veelken Roland , Wittmann Michael , Cordasic Nada , Hilgers Karl F
Published: May 2005

Background

In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney.

Methods

Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry.

Results

Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals.

Conclusion

Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats.
Accumulation of health risk behaviours is associated with lower socioeconomic status and women's urban residence: a multilevel analysis in Japan
Authors: Fukuda Yoshiharu , Nakamura Keiko , Takano Takehito
Published: May 2005

Background

Little is known about the socioeconomic differences in health-related behaviours in Japan. The present study was performed to elucidate the effects of individual and regional socioeconomic factors on selected health risk behaviours among Japanese adults, with a particular focus on regional variations.

Methods

In a nationally representative sample aged 25 to 59 years old (20,030 men and 21,076 women), the relationships between six risk behaviours (i.e., current smoking, excessive alcohol consumption, poor dietary habits, physical inactivity, stress and non-attendance of health check-ups), individual characteristics (i.e., age, marital status, occupation and household income) and regional (N = 60) indicators (per capita income and unemployment rate) were examined by multilevel analysis.

Results

Divorce, employment in women, lower occupational class and lower household income were generally associated with a higher likelihood of risk behaviour. The degrees of regional variation in risk behaviour and the influence of regional indicators were greater in women than in men: higher per capita income was significantly associated with current smoking, excessive alcohol consumption, stress and non-attendance of health check-ups in women.

Conclusion

Individual lower socioeconomic status was a substantial predictor of risk behaviour in both sexes, while a marked regional influence was observed only in women. The accumulation of risk behaviours in individuals with lower socioeconomic status and in women in areas with higher income, reflecting an urban context, may contribute to their higher mortality rates.