bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin Type-1 Receptor A1166C Gene Polymorphism Correlates With Oxidative Stress Levels in Human Heart Failure
Authors: Cameron Vicky A. , Mocatta Tessa J. , Pilbrow Anna P. , Frampton Chris M. , Troughton Richard W. , Richards A. Mark , Winterbourn Christine C.
Published: May 2006

Oxidative stress plays a critical role in the pathogenesis of cardiovascular disease and diabetes. Studies in vascular cells and experimental animals have demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation of reactive oxygen species by activating nicotinamide-adenine dinucleotide phosphate oxidases, but the relevance of this pathway to human heart disease has not been established. Here we demonstrate that a polymorphism in the
AT1R
gene (A1166C), linked to increased receptor activity, is associated with elevated levels of oxidative stress markers in heart failure patients but not in healthy controls. Plasma protein carbonyls (PCs), a marker of oxidative protein modification, were 10-fold higher in heart-failure patients compared with controls [geometric means and 95% CIs for patients, 75 (57 to 100) pmol/mg; controls, 5 (4 to 7) pmol/mg;
P
<0.001]. Moreover, levels of PCs were 50-fold higher in patients homozygous for the polymorphism (CC) than in controls and significantly higher than the AA and AC genotype patient groups [CC: 273 (135–550); AC: 59 (35–98); AA: 65 (40–106) pmol/mg;
P
<0.001]. Levels of myeloperoxidase were also modestly increased in heart-failure patients [51 (46–57) ng/mL] compared with controls [37 (32–44) ng/mL;
P
<0.001], but were especially elevated in patients with a CC genotype [CC: 72 (58–89); AC: 52 (44–61); AA: 39 (34–46) ng/mL;
P
<0.001]. The
AT1R
genotype was demonstrated to be an independent predictor of both PCs and myeloperoxidase levels in heart-failure patients. These findings suggest that oxidative stress in human heart failure is regulated via angiotensin signaling and may involve the nicotinamide dinucleotide oxidase pathway.
Cyclic Guanosine Monophosphate Compartmentation in Rat Cardiac Myocytes
Authors: Castro Liliana R.V. , Verde Ignacio , Cooper Dermot M.F. , Fischmeister Rodolphe
Published: May 2006

Background—

Cyclic guanosine monophosphate (cGMP) is the common second messenger for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides, such as atrial or brain natriuretic peptide, which activate the soluble and particulate forms of guanylyl cyclase, respectively. However, natriuretic peptides and NO donors exert different effects on cardiac and vascular smooth muscle function. We therefore tested whether these differences are due to an intracellular compartmentation of cGMP and evaluated the role of phosphodiesterase (PDE) subtypes in this process.

Methods and Results—

Subsarcolemmal cGMP signals were monitored in adult rat cardiomyocytes by expression of the rat olfactory cyclic nucleotide–gated (CNG) channel α-subunit and recording of the associated cGMP-gated current (
I
CNG
). Atrial natriuretic peptide (10 nmol/L) or brain natriuretic peptide (10 nmol/L) induced a clear activation of
I
CNG
, whereas NO donors (
S
-nitroso-
N
-acetyl-penicillamine, diethylamine NONOate, 3-morpholinosydnonimine, and spermine NO, all at 100 μmol/L) had little effect. The
I
CNG
current was strongly potentiated by nonselective PDE inhibition with isobutyl methylxanthine (100 μmol/L) and by the PDE2 inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (10 μmol/L) and Bay 60-7550 (50 nmol/L). Surprisingly, sildenafil, a PDE5 inhibitor, produced a dose-dependent increase of
I
CNG
activated by NO donors but had no effect (at 100 nmol/L) on the current elicited by atrial natriuretic peptide.

Conclusions—

These results indicate that in rat cardiomyocytes (1) the particulate cGMP pool is readily accessible at the plasma membrane, whereas the soluble pool is not; and (2) PDE5 controls the soluble but not the particulate pool, whereas the latter is under the exclusive control of PDE2. Differential spatiotemporal distributions of cGMP may therefore contribute to the specific effects of natriuretic peptides and NO donors on cardiac function.
Novel Locus for an Inherited Cardiomyopathy Maps to Chromosome 7
Authors: Song Lei , DePalma Steven R. , Kharlap Maria , Zenovich Andrey G. , Cirino Allison , Mitchell Richard , McDonough Barbara , Maron Barry J. , Seidman Christine E. , Seidman J.G. , Ho Carolyn Y.
Published: May 2006

Background—

Genetic mutations are the most common cause of hypertrophic cardiomyopathy (HCM) and an increasingly recognized cause of dilated cardiomyopathy. Autosomal dominant HCM is caused by mutations in sarcomere proteins; such mutations are not universally present, however, and fail to account for &40% of cases of phenotypic HCM. To add further complexity, other genetic origins can mimic the gross clinical phenotype of HCM, and mutations in sarcomere genes have been demonstrated to cause dilated cardiomyopathy.

Methods and Results—

To explore novel genetic causes of inherited cardiomyopathies, genome-wide linkage analysis was used to study one kindred (4 generations, 32 individuals) with predominant clinical features of left ventricular hypertrophy in addition to cardiac dilation, end-stage heart failure, and sudden death. Of note, histopathology from 2 family members did not demonstrate myocyte disarray and fibrosis, indicating that this phenotype is not typical sarcomere mutation HCM. Direct DNA sequencing was performed on sarcomere genes known to cause HCM and dilated cardiomyopathy, and no mutations were identified. Linkage was then established to a novel locus on chromosome 7 (7p12.1-7q21). A maximum 2-point logarithm of odds score of 4.11 was obtained. Recombination events refine the disease interval between
D7S506
and
D7S3314
, corresponding to a distance of 27.2 megabases.

Conclusions—

The discovery of a novel genetic locus in this family provides more evidence that molecular pathways leading to inherited cardiac hypertrophy extend beyond the sarcomere. Identification of the causal gene mutation and additional genotype-phenotype correlation studies will provide fundamental insight into mechanisms of cardiac remodeling.
A critique of the Brushing for Life programme
Authors: Downer Martin C , Drugan Caroline S , Blinkhorn Anthony S
Published: May 2006

Background and objective Brushing for Life is intended to promote regular brushing of children’s teeth with fluoride toothpaste. The programme is delivered by health visitors who provide toothbrushes, toothpaste and dental health education material at children’s 8, 18 and 36 month development checks. The purpose of the present paper was to suggest how all aspects of the programme could be comprehensively assessed; to consider the prospects for its success in the light of evidence from the literature; to review the role of the programme within the wider field of oral health promotion; and to examine appropriate approaches to a quantitative evaluation of its outcome compared with alternatives.

Methods Evaluative reports, and studies of the benefits of toothbrushing in young children published in the literature, were collated. Relevant information was abstracted and assessed and a comprehensive evaluative approach to the programme was constructed and presented.

Results Good practice in dental public health suggested that following implementation, it would be important to ensure that the scheme was fully monitored and evaluated to establish that it was working effectively and giving value for money.

Conclusions Adoption of the programme as a national population-based strategy for the prevention of dental disease in children should depend on its being shown to be effective and economically efficient.
Sex and relationships education in schools - Evaluation of a pilot programme for the certification of community nurses
Authors: Chalmers Helen , Tyrer Paul , Aggleton Peter
Published: May 2006

Objective In support of the UK Government’s teenage pregnancy and sexual health strategies, a certificated programme of professional development for school nurses and other community nurses was developed to provide support for personal, social and health education (PSHE) work, including sex and relationships education (SRE), for young people.

Design and setting This paper reports on findings from a multi-method formative evaluation of the pilot programme, which commenced in June 2003 and focused on six of the nine centres taking part: namely Sunderland, Lancashire, Birmingham, Hertfordshire, Ealing and Plymouth.

Method Face-to-face and telephone interviews took place with national officers, local leads, community nurses on the programme, their line managers, professional colleagues working with the community nurses, and national assessors. Data were collected using semi-structured interview schedules. Partial transcription of tape recordings and notes took place and a thematic analysis was carried out using constant comparative method.

Results The evaluation of the programme suggests considerable benefits for local collaborative working between health and education. In addition, nurses who undertook the programme gained in confidence and skill. Some tensions remain including concern about the need for dedicated time for nurses to complete the programme.

Conclusion Findings suggest that a well-designed scheme of the type described is likely to be well received by community nurses and facilitates cooperative working between health and education in the support of PSHE and SRE. There is a need to respect the unique contribution of the community nurse and to value the one-to-one work that she does.
Motivation for weight-loss diets: A clustering, longitudinal field study using self-esteem and self-determination theory perspectives
Authors: Georgiadis Manolis M , Biddle Stuart JH , Stavrou Nektarios A
Published: May 2006

Background Gradual elevation of body weight leads numerous individuals to dieting and weight loss behaviours. Nevertheless, the prevalence of obesity continues to rise in industrialised countries. The examination of the motivational determinants of dietary modification (‘dieting’) in order to identify clusters of individuals in the first 6 months of their effort to control body weight was the aim of the current study. The theories of self-determination and self-esteem formation guided our analysis.

Methods A longitudinal study was conducted with three data collection points (N1=256; N2=135; N3=75). Data were responses on the Treatment Self Regulation Questionnaire, Social Physique Anxiety Scale, Physical Self-Description Questionnaire, Kaiser Physical Activity Survey Questionnaire, and items assessing expectations of achievement and self-confidence.

Results Cluster analyses provided stable and validated cluster profiles for all data sets. In the 1st and 2nd data sets, results revealed three groups of dieters labelled as ‘media victims’, ‘try to feel nice’ and ‘older and experienced’. For the 3rd data set, results supported a 4-group solution (‘less adaptive profile’, ‘second successful dieters’, ‘successful dieters’, and ‘unsuccessful dieters’). The need for autonomous versus controlling dieting reasons based on Self-Determination Theory, along with the need for an alternative paradigm in weight management, are proposed. Conclusions Psychological theories of self-determination and self-esteem provide important ways of understanding and identifying adaptive and less adaptive weight control strategies.
Redemption for Wrongdoing
Authors: Elster Jon
Published: May 2006

The prosecution of wrongdoers in transitional justice differs from ordinary criminal justice in that defendants can appeal to an argument from redemption: even if they admit to wrongdoing as agents of the autocratic regime during one period of its existence, they may receive lenient treatment on grounds of their later acts of resistance to the regime. Trials and purges of collaborators in France and Norway after World War II provide many examples. The moral and sometimes the legal efficacy of this argument is undermined, however, if the later acts were undertaken for the purpose of redemption. It may also be undermined if the earlier acts were so grave that nothing can wipe them out.
Justice in Transition
Authors: Theidon Kimberly
Published: May 2006

This article draws on anthropological research conducted with communities in Ayacucho, the region of Peru that suffered the greatest loss of life during the internal armed conflict of the 1980s and 1990s. One particularity of internal wars, such as Peru’s, is that foreign armies do not wage the attacks: frequently, the enemy is a son-in-law, a godfather, an old schoolmate, or the community that lies just across the valley. The charged social landscape of the present reflects the lasting damage done by a recent past in which people saw just what their neighbors could do. The author contributes to the literature on transitional justice by examining the construction and deconstruction of lethal violence among “intimate enemies” and by analyzing how the concepts and practices of communal justice have permitted the development of a micropolitics of reconciliation in which campesinos administer both retributive and restorative forms of justice.
Judging Transitional Justice
Authors: Kaminski Marek M. , Nalepa Monika
Published: May 2006

Truth revelation procedures are evaluated according to various normative criteria. The authors find the concepts of false conviction and false acquittal more adequate for such evaluation than the conformity with the rule of law and apply a useful classification of truth revelation procedures into incentive-based (ITRs) and evidence-based ones (ETRs). ITRs induce perpetrators and secret agents of the authoritarian regime to reveal the truth about their past, while ETRs rely exclusively on preserved evidence and victims’ testimonies. Using a simple decision-making model, the authors show that while both procedures are sensitive to the problem of falsified evidence, ITRs perform better with respect to revealing the identity of collaborators whose files were destroyed. Finally, they discuss the connection between ITRs and two modes of coming to terms with the past, endogenous and exogenous.
The Effects of CEO Pay Structure on Corporate Social Performance
Authors: Deckop John R. , Merriman Kimberly K. , Gupta Shruti
Published: May 2006

Corporate social performance (CSP) is increasingly viewed as an important business outcome by researchers, investors, and society as a whole. Furthermore, empirical research indicates that CSP is positively related to corporate financial performance. These considerations lead to the question of whether CEO pay is properly structured to provide incentive to the CEO to improve firm CSP. In a sample of 313 firms, the authors found that a short-term CEO pay focus was negatively related to CSP, whereas a long-term focus was positively related to CSP. Implications of these results for future research and CEO pay design are presented.
Measuring the Relationship Between Managerial Competencies and Performance
Authors: Levenson Alec R. , Van der Stede Wim A. , Cohen Susan G.
Published: May 2006

The use of competency systems to evaluate, reward, and promote managers has become commonplace in many organizations in recent years. Yet, despite their popularity, there is little evidence that competency systems increase managerial effectiveness. In this study, we estimate the relationship between managerial competencies and performance at both the individual and organizational unit levels. We find evidence that competencies are positively related to individual-level performance and that individual managerial performance may be increased by mentoring on a competency system. The evidence of a link between competencies and unit-level performance is weaker.
The Paradox of Dueling Identities: The Case of Local Senior Executives in MNC Subsidiaries
Authors: Zhang Yan , George Jennifer M. , Chan Tsang-Sing
Published: May 2006

This study focuses on how employees cope with dueling social identities when one is of relatively low status compared to the other by studying local senior executives in mulinational corporations’ (MNC’s) subsidiaries who can identify with the local staff and/or headquarters’ management. As hypothesized, perceptions of local staff incompetence are positively related to executives’ turnover intentions. This relationship becomes weaker if they have high-quality communication with, or high levels of trust in, headquarters’ management. Results suggest that employees disidentify with a stigmatized identity group by intending to quit; however, identification with a higher status alternative identity group can mitigate this effect.
Parenting Practices and Child Adjustment in Different Types of Households
Authors: Simons Leslie Gordon , Chen Yi-Fu , Simons Ronald L. , Brody Gene , Cutrona Carolyn
Published: May 2006

This article uses a sample of 867 African American households to investigate differences in parenting practices and child outcomes by type of household. Results indicate that mothers provide similar levels of parenting regardless of family structure. Secondary caregivers, however, show a great deal of variation in quality of parenting. Fathers and grandmothers engage in the highest quality parenting, stepfathers the poorest, with other relatives falling in between. These differences in parenting do not explain family structure differences in child behavior problems. Results suggest that children do best when there are two caregivers in the household, although stepfathers are an exception to this rule. Child behavior problems are found to be no greater in either mother-grandmother or mother-relative families than in households with two biological parents. In terms of risk for child behavior problems, these family forms seem to be functionally equivalent.
Theoretical Postulations on Organization Democracy
Authors: Luhman John Teta
Published: May 2006

In previous research the author conducted a narrative examination of the literature on labor-managed firms to discover the nature of “organization democracy.” The result was a broad conceptual framework. This article builds on the framework by offering two theoretical postulations. First, it offers a substantive theoretical postulation that organization democracy is a conflation of political visions that can be represented by Mannheim’s (1936) four utopian images of anarchism, liberalism, conservatism, and radicalism. Second, it offers a formal theoretical postulation that organization democracy is an additional form of legitimate authority to add to Weber’s (1947, 1978) typology. The author proposes “rational-collective” legitimate authority as the fourth form and ends with a two-dimensional representation of the four types of legitimate authority.
Understanding Mechanisms in Organizational Research
Authors: Anderson Peter J.J. , Blatt Ruth , Christianson Marlys K. , Grant Adam M. , Marquis Christopher , Neuman Eric J. , Sonenshein Scott , Sutcliffe Kathleen M.
Published: May 2006

Social mechanisms are theoretical cogs and wheels that explain how and why one thing leads to another. Mechanisms can run from macro to micro (e.g., explaining the effects of organizational socialization practices or compensation systems on individual actions), micro to micro (e.g., social comparison processes), or micro to macro (e.g., how cognitively limited persons can be aggregated into a smart bureaucracy). Explanations in organization theory are typically rife with mechanisms, but they are often implicit. In this article, the authors focus on social mechanisms and explore challenges in pursuing a mechanisms approach. They argue that organization theories will be enriched if scholars expend more effort to understand and clarify the social mechanisms at play in their work and move beyond thinking about individual variables and the links between them to considering the bigger picture of action in its entirety.
From Nuts and Bolts to Toolkits
Authors: Weber Klaus
Published: May 2006

This essay examines a mechanisms-oriented approach to theory building in organization studies and identifies conditions under which such an approach is likely to be fruitful. Mechanisms-oriented theorizing is a promising path to reviving organization theory but has the potential pitfalls of overly reductionist models of organizations and the complete abandonment of grand theorizing. These undesirable side effects can be reduced when researchers act as playful pragmatists and treat mechanisms as toolkits for working on theoretical puzzles. The article describes some tactics for accomplishing this goal.
Mechanisms and the Theory of Organizations
Authors: Davis Gerald F.
Published: May 2006

The theory in organization theory has become increasingly hard to find in recent empirical research as most current researchers identify their work in terms of the phenomena they study rather than the theoretical tradition in which they operate. This theory drought arguably flows from the limitations that 1970s-era organizational paradigms face in explaining contemporary organizations. This article argues that the greatest strength of organization theory as a field is not particular theoretical paradigms but rather the field’s non-obvious mechanisms of aggregation that generate order, in firms and elsewhere. The thoughtful use of social mechanisms, in service of problem-driven research, can provide a unifying device for the field of organization studies.
What to Do With the Resource-Based View
Authors: Levitas Edward , Ndofor Hermann Achidi
Published: May 2006

The intention of this essay is to point out the key weaknesses of the resource-based view (RBV) and provide prescriptions for curing them. The authors begin with Gibbert’s (this issue) question of whether the RBV is ready for generalization and concluded generalizability is an inappropriate goal for the RBV. Furthermore, they believe that the RBV is simply not ready for generalization. They argue that the quest for generalizability is counter productive when applied to the RBV. Generalizability is not only the least relevant of the external validity criteria but also can only be assessed after valid operationalizations for constructs are developed across different contexts, industries, samples, and so on. Because they believe that RBV researchers have yet to achieve construct validity within their empirical testing, it appears to them that the RBV is simply not ready for generalizability. Finally, when they incorporate RBV developments that have occurred since Barney such as the knowledge-based view and dynamic capabilities, many arguments by Gibbert and others are rendered obsolete.
Exploring photosynthesis evolution by comparative analysis of metabolic networks between chloroplasts and photosynthetic bacteria
Authors: Wang Zhuo , Zhu Xin-Guang , Chen Yazhu , Li Yuanyuan , Hou Jing , Li Yixue , Liu Lei
Published: May 2006

Background

Chloroplasts descended from cyanobacteria and have a drastically reduced genome following an endosymbiotic event. Many genes of the ancestral cyanobacterial genome have been transferred to the plant nuclear genome by horizontal gene transfer. However, a selective set of metabolism pathways is maintained in chloroplasts using both chloroplast genome encoded and nuclear genome encoded enzymes. As an organelle specialized for carrying out photosynthesis, does the chloroplast metabolic network have properties adapted for higher efficiency of photosynthesis? We compared metabolic network properties of chloroplasts and prokaryotic photosynthetic organisms, mostly cyanobacteria, based on metabolic maps derived from genome data to identify features of chloroplast network properties that are different from cyanobacteria and to analyze possible functional significance of those features.

Results

The properties of the entire metabolic network and the sub-network that consists of reactions directly connected to the Calvin Cycle have been analyzed using hypergraph representation. Results showed that the whole metabolic networks in chloroplast and cyanobacteria both possess small-world network properties. Although the number of compounds and reactions in chloroplasts is less than that in cyanobacteria, the chloroplast's metabolic network has longer average path length, a larger diameter, and is Calvin Cycle -centered, indicating an overall less-dense network structure with specific and local high density areas in chloroplasts. Moreover, chloroplast metabolic network exhibits a better modular organization than cyanobacterial ones. Enzymes involved in the same metabolic processes tend to cluster into the same module in chloroplasts.

Conclusion

In summary, the differences in metabolic network properties may reflect the evolutionary changes during endosymbiosis that led to the improvement of the photosynthesis efficiency in higher plants. Our findings are consistent with the notion that since the light energy absorption, transfer and conversion is highly efficient even in photosynthetic bacteria, the further improvements in photosynthetic efficiency in higher plants may rely on changes in metabolic network properties.
Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains
Authors: Farber Charles R , Corva Pablo M , Medrano Juan F
Published: May 2006

Background

High growth (hg) modifier and background independent quantitative trait loci (QTL) affecting growth, adiposity and carcass composition were previously identified on mouse chromosomes (MMU) 1, 2, 5, 8, 9, 11 and 17. To confirm and further characterize each QTL, two panels of speed congenic strains were developed by introgressing CAST/EiJ (CAST) QTL alleles onto either mutant C57Bl/6J-hg/hg (HG) or wild type C57Bl/6J (B6) genetic backgrounds.

Results

The first speed congenic panel was developed by introgressing four overlapping donor regions spanning MMU2 in its entirety onto both HG and B6 backgrounds, for a total of eight strains. Phenotypic characterization of the MMU2 panel confirmed the segregation of multiple growth and obesity QTL and strongly suggested that a subset of these loci modify the effects of the hg deletion. The second panel consisted of individual donor regions on an HG background for each QTL on MMU1, 5, 8, 9, 11 and 17. Of the six developed strains, five were successfully characterized and displayed significant differences in growth and/or obesity as compared to controls. All five displayed phenotypes similar to those originally attributed to each QTL, however, novel phenotypes were unmasked in several of the strains including sex-specific effects.

Conclusion

The speed congenic strains developed herein constitute an invaluable genomic resource and provide the foundation to identify the specific nature of genetic variation influencing growth and obesity.
Experiences and perceptions of people with headache: a qualitative study
Authors: Leiper Deborah A , Elliott Alison M , Hannaford Philip C
Published: May 2006

Background

Few qualitative studies of headache have been conducted and as a result we have little in-depth understanding of the experiences and perceptions of people with headache. The aim of this paper was to explore the perceptions and experiences of individuals with headache and their experiences of associated healthcare and treatment.

Methods

A qualitative study of individuals with headache, sampled from a population-based study of chronic pain was conducted in the North-East of Scotland, UK. Seventeen semi-structured interviews were conducted with adults aged 65 or less. Interviews were analysed using the Framework approach utilising thematic analysis.

Results

Almost every participant reported that they were unable to function fully as a result of the nature and unpredictability of their headaches and this had caused disruption to their work, family life and social activities. Many also reported a negative impact on mood including feeling depressed, aggressive or embarrassed. Most participants had formed their own ideas about different aspects of their headache and several had searched for, or were seeking, increased understanding of their headache from a variety of sources. Many participants reported that their headaches caused them constant worry and anguish, and they were concerned that there was a serious underlying cause. A variety of methods were being used to manage headaches including conventional medication, complementary therapies and self-developed management techniques. Problems associated with all of these management strategies emerged.

Conclusion

Headache has wide-ranging adverse effects on individuals and is often accompanied by considerable worry. The development of new interventions or educational strategies aimed at reducing the burden of the disorder and associated anxiety are needed.
The added value of C-reactive protein to clinical signs and symptoms in patients with obstructive airway disease: results of a diagnostic study in primary care
Authors: Schneider Antonius , Dinant Geert-Jan , Maag Inko , Gantner Lutz , Meyer Joachim Franz , Szecsenyi Joachim
Published: May 2006

Background

To evaluate the diagnostic accuracy of clinical signs and symptoms, C-reactive protein (CRP) and spirometric parameters and determine their interrelation in patients suspected to have an obstructive airway disease (OAD) in primary care.

Methods

In a cross sectional diagnostic study, 60 adult patients coming to the general practitioner (GP) for the first-time with complaints suspicious for obstructive airway disease (OAD) underwent spirometry. Peak expiratory flow (PEF)-variability within two weeks was determined in patients with inconspicuous spirometry. Structured medical histories were documented and CRP was measured. The reference standard was the Tiffeneau ratio (FEV1/VC) in spirometry and the PEF-variability. OAD was diagnosed when FEV1/VC ≤ 70% or PEF-variability > 20%.

Results

37 (62%) patients had OAD. The best cut-off value for CRP was found at 2 mg/l with a diagnostic odds ratio (OR) of 4.4 (95% CI 1.4–13.8). Self-reported wheezing was significantly related with OAD (OR 3.4; CI 1.1–10.3), whereas coughing was inversely related (OR 0.2; CI 0.1–0.7). The diagnostic OR of CRP increased when combined with dyspnea (OR 8.5; 95% CI 1.7–42.3) or smoking history (OR 8.4; 95% CI 1.5–48.9). CRP (p = 0.004), FEV1 (p = 0.001) and FIV1 (p = 0.023) were related with the severity of dyspnea. CRP increased with the number of cigarettes, expressed in pack years (p = 0.001).

Conclusion

The diagnostic accuracy of clinical signs and symptoms was low. The diagnostic accuracy of CRP improved in combination with dyspnea and smoking history. Due to their coherence with the severity of dyspnea and number of cigarettes respectively, CRP and spirometry might allow risk stratification of patients with OAD in primary care. Further studies need to be done to confirm these findings.
AIB1 gene amplification and the instability of polyQ encoding sequence in breast cancer cell lines
Authors: Wong Lee-Jun C , Dai Pu , Lu Jyh-Feng , Lou Mary Ann , Clarke Robert , Nazarov Viktor
Published: May 2006

Background

The poly Q polymorphism in AIB1 (amplified in breast cancer) gene is usually assessed by fragment length analysis which does not reveal the actual sequence variation. The purpose of this study is to investigate the sequence variation of poly Q encoding region in breast cancer cell lines at single molecule level, and to determine if the sequence variation is related to AIB1 gene amplification.

Methods

The polymorphic poly Q encoding region of AIB1 gene was investigated at the single molecule level by PCR cloning/sequencing. The amplification of AIB1 gene in various breast cancer cell lines were studied by real-time quantitative PCR.

Results

Significant amplifications (5–23 folds) of AIB1 gene were found in 2 out of 9 (22%) ER positive cell lines (in BT-474 and MCF-7 but not in BT-20, ZR-75-1, T47D, BT483, MDA-MB-361, MDA-MB-468 and MDA-MB-330). The AIB1 gene was not amplified in any of the ER negative cell lines. Different passages of MCF-7 cell lines and their derivatives maintained the feature of AIB1 amplification. When the cells were selected for hormone independence (LCC1) and resistance to 4-hydroxy tamoxifen (4-OH TAM) (LCC2 and R27), ICI 182,780 (LCC9) or 4-OH TAM, KEO and LY 117018 (LY-2), AIB1 copy number decreased but still remained highly amplified. Sequencing analysis of poly Q encoding region of AIB1 gene did not reveal specific patterns that could be correlated with AIB1 gene amplification. However, about 72% of the breast cancer cell lines had at least one under represented (<20%) extra poly Q encoding sequence patterns that were derived from the original allele, presumably due to somatic instability. Although all MCF-7 cells and their variants had the same predominant poly Q encoding sequence pattern of (CAG)3CAA(CAG)9(CAACAG)3(CAACAGCAG)2CAA of the original cell line, a number of altered poly Q encoding sequences were found in the derivatives of MCF-7 cell lines.

Conclusion

These data suggest that poly Q encoding region of AIB1 gene is somatic unstable in breast cancer cell lines. The instability and the sequence characteristics, however, do not appear to be associated with the level of the gene amplification.
Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group
Authors: Winquist Eric , Waldron Tricia , Berry Scott , Ernst D Scott , Hotte Sébastien , Lukka Himu
Published: May 2006

Background

Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually experience disease progression within 12 to 20 months. New data emerging from randomized controlled trials (RCTs) of chemotherapy provided the impetus for a systematic review addressing the following question: which non-hormonal systemic therapies are most beneficial for the treatment of men with hormone-refractory prostate cancer (HRPC) and clinical evidence of metastases?

Methods

A systematic review was performed to identify RCTs or meta-analyses examining first-line non-hormonal systemic (cytotoxic and non-cytotoxic) therapy in patients with HRPC and metastases that reported at least one of the following endpoints: overall survival, disease control, palliative response, quality of life, and toxicity. Excluded were RCTs of second-line hormonal therapies, bisphosphonates or radiopharmaceuticals, or randomized fewer than 50 patients per trial arm. MEDLINE, EMBASE, the Cochrane Library, and the conference proceedings of the American Society of Clinical Oncology were searched for relevant trials. Citations were screened for eligibility by four reviewers and discrepancies were handled by consensus.

Results

Of the 80 RCTs identified, 27 met the eligibility criteria. Two recent, large trials reported improved overall survival with docetaxel-based chemotherapy compared to mitoxantrone-prednisone. Improved progression-free survival and rates of palliative and objective response were also observed. Compared with mitoxantrone, docetaxel treatment was associated with more frequent mild toxicities, similar rates of serious toxicities, and better quality of life. More frequent serious toxicities were observed when docetaxel was combined with estramustine. Three trials reported improved time-to-disease progression, palliative response, and/or quality of life with mitoxatrone plus corticosteroid compared with corticosteroid alone. Single trials reported improved disease control with estramustine-vinblastine, vinorelbine-hydrocortisone, and suramin-hydrocortisone compared to controls. Trials of non-cytotoxic agents have reported equivocal results.

Conclusion

Docetaxel-based chemotherapy modestly improves survival and provides palliation for men with HRPC and metastases. Other than androgen deprivation therapy, this is the only other therapy to have demonstrated improved overall survival in prostate cancer in RCTs. Further investigations to identify more effective therapies for HRPC including the use of systemic therapies earlier in the natural history of prostate cancer are warranted.
Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls
Authors: Thompson William W , Gottesman Irving I , Zalewski Christine
Published: May 2006

Background

Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam.

Methods

We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models.

Results

Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively.

Conclusion

When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD.
Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS)
Authors: Paradowski Przemyslaw T , Bergman Stefan , Sundén-Lundius Anne , Lohmander L Stefan , Roos Ewa M
Published: May 2006

Background

Self-reported knee complaints may vary with age and gender. Reference data from the adult population would help to better interpret the outcome of interventions due to knee complaints. The objectives of the present study were to describe the variation of self-reported knee pain, function and quality of life with age and gender in the adult population and to establish population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS).

Methods

Population-based cohort retrieved from the national population register. The knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) was mailed to 840 subjects aged 18–84 yrs.

Results

68% response rate. Women in the age group 55–74 reported more knee-related complaints in all the KOOS subscales than age-matched men. The differences were significant for the subscales Pain (p = 0.027), Symptoms (p = 0.003) and ADL function (p = 0.046).

In men, worse ADL and Sport and Recreation function was seen in the oldest age group 75–84 years compared to the younger age groups (p < 0.030). In women, worse Pain (p < 0.007), ADL (p < 0.030), Sport and Recreation (p < 0.001) and QOL (p < 0.002) were seen already in the age group 55–74 compared to the younger age groups.

Conclusion

We found pain and other symptoms, physical function, and knee-related quality of life to vary with age and gender implying the use of age- and gender matched reference values for improved understanding of the outcome after interventions due to knee injury and knee OA.
Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians
Authors: Wasim Hanif , Al-Daghri Nasser M , Chetty Raja , McTernan Phillip G , Barnett A H , Kumar Sudhesh
Published: May 2006

Objectives

South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels.

Methods

In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA).

Results

Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01.

Conclusion

Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance.
Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells
Authors: Belgnaoui S Mehdi , Gosden Roger G , Semmes O John , Haoudi Abdelali
Published: May 2006

Background

Long interspersed nuclear elements (LINEs), Alu and endogenous retroviruses (ERVs) make up some 45% of human DNA. LINE-1 also called L1, is the most common family of non-LTR retrotransposons in the human genome and comprises about 17% of the genome. L1 elements require the integration into chromosomal target sites using L1-encoded endonuclease which creates staggering DNA breaks allowing the newly transposed L1 copies to integrate into the genome. L1 expression and retrotransposition in cancer cells might cause transcriptional deregulation, insertional mutations, DNA breaks, and an increased frequency of recombinations, contributing to genome instability. There is however little evidence on the mechanism of L1-induced genetic instability and its impact on cancer cell growth and proliferation.

Results

We report that L1 has genome-destabilizing effects indicated by an accumulation of γ-H2AX foci, an early response to DNA strand breaks, in association with an abnormal cell cycle progression through a G2/M accumulation and an induction of apoptosis in breast cancer cells. In addition, we found that adjuvant L1 activation may lead to supra-additive killing when combined with radiation by enhancing the radiation lethality through induction of apoptosis that we have detected through Bax activation.

Conclusion

L1 retrotransposition is sensed as a DNA damaging event through the creation DNA breaks involving L1-encoded endonuclease. The apparent synergistic interaction between L1 activation and radiation can further be utilized for targeted induction of cancer cell death. Thus, the role of retrotransoposons in general, and of L1 in particular, in DNA damage and repair assumes larger significance both for the understanding of mutagenicity and, potentially, for the control of cell proliferation and apoptosis.
Phase II Multicenter Study of Arsenic Trioxide in Patients With Myelodysplastic Syndromes
Authors: Schiller Gary J. , Slack James , Hainsworth John D. , Mason James , Saleh Mansoor , Rizzieri David , Douer Dan , List Alan F.
Published: May 2006

Purpose

To evaluate the efficacy and safety of arsenic trioxide monotherapy in patients with myelodysplastic syndromes (MDS).

Patients and Methods

Patients received arsenic trioxide (0.25 mg/kg/d) on 5 consecutive days per week for 2 weeks, followed by 2 weeks’ rest (one cycle). Two patient cohorts were established according to International Prognostic Scoring System risk category: lower-risk (low or intermediate-1) or higher-risk MDS (intermediate-2 or high). For lower-risk MDS, hematologic improvement (HI) was the primary response end point. For higher-risk MDS, additional end points included complete or partial remission. Based on the expected time to response, patients receiving two or more cycles were prospectively evaluated.

Results

Hematologic adverse events included neutropenia, thrombocytopenia, and febrile neutropenia. Two patients died during the study due to treatment-related toxicities. Most common grade 3/4 nonhematologic events were pneumonia, fatigue, hemorrhage, pain, and dyspnea. Among patients who received one or more doses (n = 70) or completed two or more cycles (n = 51), the HI rates were 34% and 39% in lower-risk patients, and 6% and 9% in higher-risk patients, respectively; the overall major HI rates were 20% and 22%. One higher-risk patient achieved a complete remission (3%). Major HIs were observed in all hematologic lineages; erythroid responses were the most common. Transfusion independence or reduction by ≥ 50% occurred in 33% of patients dependent on RBC transfusions. The overall median duration of HI was 6.8 months (range, 2 to 40 months).

Conclusion

Arsenic trioxide monotherapy has moderate activity against MDS, with a manageable adverse effect profile. The further study of arsenic trioxide in MDS, particularly in combination with other agents, is warranted.
Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study
Authors: Vey Norbert , Bosly Andre , Guerci Agnes , Feremans Walter , Dombret Herve , Dreyfus Francois , Bowen David , Burnett Alan , Dennis Mike , Ribrag Vincent , Casadevall Nicole , Legros Laurence , Fenaux Pierre
Published: May 2006

Purpose

Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS).

Patients and Methods

MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation.

Results

Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients.

Conclusion

Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.