bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular analysis of the barley cv. ‘Valticky’ and its X‐ray‐derived semidwarf‐mutant ‘Diamant’
Authors: Mlčochová L. , Chloupek O. , Uptmoor R. , Ordon F. , Friedt W.
Published: October 2004

The outstanding semidwarf spring barley cultivar ‘Diamant’ was derived from the cv.‘Valticky’ by X‐ray mutagenesis. More than 120 European spring barley varieties trace back to ‘Diamant’. This variety and nine German spring barley cultivars having ‘Diamant’ in their pedigree, as well as four cultivars not related to ‘Diamant’, were analysed by amplified fragment length polymorphisms (AFLPs) and simple sequence repeats (SSRs) in order to identify genomic regions associated with traits derived from ‘Diamant’. The total number of SSRs tested was 122, of which 88 were polymorphic taking all varieties into account, with 51 for ‘Valticky’ and ‘Diamant’, i.e. 42.8%. A varying level of polymorphism was detected on individual chromosomes (11.1–78.6%). In addition, AFLP revealed a high level of polymorphism. Out of the total number of 1591 bands, 670 were polymorphic for all varieties studied with 182 for ‘Valticky’ and ‘Diamant’, i.e. 11.4%. Based on SSR and AFLP data UPGMA cluster analysis was carried out, but no grouping according to the relatedness with ‘Diamant’ or ‘Valticky’, respectively, was found. It is concluded from these results that the mutagenic effect leading to the development of ‘Diamant’ out of ‘Valticky’ affected many genetic loci and is thus larger than expected.
Genetic transformation of pigeonpea with rice chitinase gene
Authors: Kumar S. M. , Kumar B. K. , Sharma K. K. , Devi P.
Published: October 2004

With a long‐term plan to develop transgenic pigeonpea with resistance to fungal disease, the transfer of a rice chitinase gene to pigeonpea [Cajanus cajan (L.) Millsp.] is reported here. The rice chitinase gene harboured in the plasmid pCAMBIA 1302:RChit was delivered via the Agrobacterium‐mediated method to the cotyledonary node explants followed by subsequent regeneration of complete plants on selection media containing hygromycin. Putative transformed pigeonpea plants were recovered with stringent selection pressure and confirmed using molecular techniques. Stable integration and expression of the chitinase gene has been confirmed in the T0 and T1 transgenics through molecular analysis.
Additive effects of dexamethasone in nebulized salbutamol or l‐epinephrine treated infants with acute bronchiolitis
Authors: Kuyucu Semanur , Unal Selma , Kuyucu Necdet , Yi̇lgor Esat
Published: October 2004

Abstract
Background
: Although it is the most common lower respiratory infection of infancy, the optimal treatment for acute bronchiolitis is still controversial. The aim of this study was to compare the early and late effects of nebulized l‐epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators alone in outpatients with acute bronchiolitis.

Methods
: A total of 69 infants aged 2−21 months who were admitted to the Pediatrics Department of the Faculty of Medicine, Mersin University, with acute bronchiolitis were included in a randomized, placebo‐controlled, prospective trial study. Patients were assigned to receive either nebulized l‐epinephrine (3 mg) or salbutamol (0.15 mg/kg) and 15 min later, either dexamethasone 0.6 mg/kg or placebo (PLA), intramuscularly, in a double‐blind randomized fashion. The study groups were: epinephrine + dexamethasone group (group 1, n = 23), salbutamol + dexamethasone group (group 2, n = 23), epinephrine + placebo group (group 3, n = 11), and salbutamol + placebo group (group 4, n = 12). The outcome measures were heart rate, respiratory rate and Respiratory Distress Assessment Instrument (RDAI) score determined at 30, 60, 90 and 120 min, 24 h, and 5 days after the first therapy. Patients were then followed‐up during the subsequent 2 months for the prevalance of respiratory complaints regarding bronchial hyperreactivity.

Results
: There were no significant differences between the outcome variables of the four groups within the first 120 min and at 24 hours, or between the rates of requirement of a second dose of the same bronchodilator. However, fifth day RDAI score values of both DEX groups were significantly lower than that of SAL + PLA group (P = 0.000 and P = 0.01, respectively). The fifth day score value of group 1 was also significantly better than that value of EPI + PLA group but not different from group 2.

Conclusions
: A single dose of intramuscular dexamethasone added to nebulized l‐epinephrine, or salbutamol therapies resulted in better outcome measures than bronchodilators alone in the late phase (fifth day) of mild to moderate degree bronchiolitis attack. However, effects of EPI + DEX combination was not different from SAL + DEX combination.
Effects of leptin and dexamethasone on long and short leptin receptor mRNA
Authors: Liu Zheng‐Juan , Endoh Akira , Li Renshan , Ohzeki Takehiko
Published: October 2004

Abstract
Background
: Leptin exerts its effects by using both long (OB‐Rb) and short (OB‐Ra) receptors. Although leptin resistance or insensitivity is reported to be a cause of human obesity, there have not been enough studies to clarify regulation of leptin receptors.

Methods
: The authors studied leptin receptor regulation by leptin and dexamethasone in the human hepatocellular carcinoma cell (HepG2). Using a quantitative RT‐PCR technique, the authors demonstrate expression of OB‐Ra and OB‐Rb mRNA after the incubation for 24 h with leptin or dexamethasone at various concentrations (10‐9−10‐6 M).

Results
: Leptin (10‐7−10‐6 M) significantly inhibited expression of OB‐Rb mRNA, with maximum inhibition (43% of control) at 10−6 M. Expression of OB‐R219.1 and OB‐R219.3, two short isoforms of leptin receptor, were also reduced in cells treated with leptin most remarkably at 10−7 M for OB‐R219.1 (44% of the control) and at 10−6 M for Ob‐R219.3 (49% of the control). In contrast, dexamethasone (10‐8−10‐6 M) significantly increased OB‐Rb mRNA levels, with a maximum increase (204% of the control) at 10−7 M, and OB‐R219.1 and OB‐R219.3 mRNA expression was also markedly increased at 10‐9−10‐6 M. The peak values were 254% of the control for OB‐R219.1 and 246% of the control for OB‐R219.3 at 10−7 M.

Conclusions
: In HepG2 cells, leptin inhibits and dexamethasone increases OB‐Ra and OB‐Rb mRNA expression. It is suggested that glucocorticoids as well as leptin itself contribute to regulatory effects of leptin through changes in gene expression of leptin receptors.
Non‐specific host response markers in the differentiation between pneumococcal and viral pneumonia: What is the most accurate combination?
Authors: Korppi Matti
Published: October 2004

Abstract
Background
: Serum C‐reactive protein (CRP), blood white cell count (WBC), serum procalcitonin (PCT) and erythrocyte sedimentation rate (ESR) were measured in 132 children hospitalized for community‐acquired pneumonia. Serological evidence for viral infection was found in 38 cases and for pneumococcal infection in 41 cases, and the infiltrate was alveolar in 46 cases and interstitial in 86 cases. The aim of the present paper was to determine if there is a combination of these four host response markers and chest radiograph findings suitable for differentiating pneumococcal from viral etiology of pneumonia.

Methods
: The 50th, 75th and 90th percentiles of CRP, WBC, ESR and PCT in the total group of 132 patients were calculated. By using these cut‐off limits, the likelihood ratios of a positive test result were calculated for the possible combinations of CRP, WBC, ESR and PCT, and the likelihood ratio was 1.50 or more for six combinations.

Results
: The highest likelihood ratio (1.74) was achieved with the combination CRP > 90th (80 mg/L) or WBC > 75th (17.0 × 109/L) or PCT > 75th (0.84 µg/L) or ESR > 90th (63 mm/h) percentile. For this combination, the sensitivity was 61% and the specificity 65%. When the 90th percentile cut‐off limit was applied also for WBC (>22 × 109/L) and PCT (>1.8 µg/L), the specificity increased to 76%, but the sensitivity decreased to 37%. When the presence of an alveolar infiltration was included in the combination, the likelihood ratio was 1.89; the specificity was as high as 82% and the sensitivity as low as 34%.

Conclusions
: CRP, PCT, WBC and ESR have only limited value in differentiating pneumococcal or other bacterial pneumonia from viral pneumonia. If there was a high value in at least one of the markers (CRP > 80 mg/L, PCT > 1.8 µg/L, WBC > 22 × 109/L or ESR > 60 mm/h), viral infections were rare. There was no combination of these markers which was sufficiently sensitive and specific to be used in clinical pediatric practice.
Rapid diagnosis of bacterial meningitis by using multiplex PCR and real time PCR
Authors: Uzuka Rina , Kawashima Hisashi , Hasegawa Daisuke , Ioi Hiroaki , Amaha Masahiro , Kashiwagi Yasuyo , Takekuma Kouji , Hoshika Akinori , Chiba Katsumi
Published: October 2004

Abstract
Background
: The purpose of the present study was to improve a method for a rapid identification of bacteria in bacterial meningitis by using multiplex polymerase chain reaction (PCR).

Methods
: Ten species of bacteria which cause meningitis in children were investigated, and cerebrospinal fluid from patients with purulent meningitis was studied. The ribosomal RNA genes of bacteria are essential, and are highly conserved in the bacterial kingdoms with consensus region. The 23S rRNA region shows a larger variation among species than in the 16S rRNA region. The authors set primers in the universal region and specific region of 23S rRNA, then amplified these regions by multiplex PCR and real‐time PCR.

Results
: All species of bacteria showed one band by PCR using universal primer. Haemophilus influenzae and Streptococcus pneumoniae showed two bands by multiplex PCR using a combination of universal primers and specific primers. The authors detected H. influenzae within 15 min by using real‐time PCR.

Conclusion
: It was possible to identify clinically significant bacterial species in cerebrospinal fluid by multiplex PCR, and to identify H. influenzae by real‐time PCR within a short period.
Effect of total attending period on infection episode rate in a child‐care center
Authors: YalçIn S. Songül , Tuğrul Belma , Çeti̇nkaya Semra , Çakir Banu , Yilmaz Ayşe
Published: October 2004

Abstract
Background
: Attendance to a child‐care facility is known to be associated with increased rate of episodes of infectious diseases in children. This retrospective cohort study investigates the infection episode rate and the effect of total attending period on infection episode rates in a child‐care center (Gülveren Child‐Care Center, Ankara, Turkey), at a stable environmental condition, over a 7‐year follow‐up period.

Methods
: During the study period, 288 children attended the center and enrolled. Sex, total duration of breastfeeding, starting age at the center, total duration of attendance, and the type and frequency of infections diseases were recorded. Episode rates were calculated for each child.

Results
: The mean starting age at the child care center was 4.1 ± 0.7 years (range: 2.5–5.8 years); the mean total duration of attendance at the center was 20.4 ± 9.9 months. Over the study period, 1000 infection episodes were detected. The general infection episode rate was calculated as 2.04/child per year. In bivariate analysis, children with longer attendance period (≥12 months), and a younger starting age at the center (<4 years of age) had lower ‘moderate general infection’ (≥3 episode/child per year) episode rates than those of other groups. In multiple logistic regression analysis, only total attending period in the center was significantly associated with ‘moderate’ level general infection episode rate. The presence of asthma slightly increased the lower respiratory tract infections episode rate in bivariate analysis, and was the only significant predictor of LRTI episode rate in multivariate analysis.

Conclusions
: The results of the present study show that among children attending a single facility, longer periods of attendance at the facility was associated with a decreased risk of general infection episode, regardless of starting age at the center. Additional cohort studies are needed to determine whether this reduction in general infection episode rate extends into school‐age years and whether children moving between different centers affects the incidence of infectious episodes.
Serum leptin concentrations in children with mild protein‐energy malnutrition and catch‐up growth
Authors: Büyükgebiz Benal , Öztürk Yesim , Yilmaz Sebnem , Arslan Nur
Published: October 2004

Abstract
Background
: The aim of the present study was to clarify the relationship between changing nutritional anthropometric data and serum leptin concentrations during the catch‐up growth process in children.

Methods
: Thirty children with mild protein‐energy malnutrition (PEM) were followed for 6 months and their anthropometric measurements and serum leptin concentrations were recorded during follow up.

Results
: Twenty‐two (73.3%) of the 30 children showed catch‐up growth. All parameters and serum leptin concentrations increased during the period of catch‐up growth. In the remaining eight children, weight for height, percentage standard body mass index, percentage standard body height and mean serum leptin concentrations did not show any significant increase at the 6 month follow‐up. Mean serum leptin concentration was higher in children with catch‐up growth than in the controls.

Conclusion
: During recovery from malnutrition, leptin concentrations increase in relation to fat mass if the fat mass reaches a critical point, and leptin might trigger catch‐up growth with its regulator effects on growth. Although weight gain was noted in both groups, an increase in leptin concentration was observed only in children who showed catch‐up growth. More interestingly, the mean leptin concentration was much higher in children with PEM who had catch‐up growth compared to the control group and in children who failed to have catch‐up growth. In children with catch‐up growth, the higher serum leptin concentrations compared to healthy children and to children without catch‐up growth despite significant weight gain suggests that leptin affects nutritional status in catch‐up growth as a dynamic process, rather than merely being an index of body fat content.
Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants
Authors: Li Yudong , Shimizu Toshiaki , Hosaka Atsuto , Kaneko Noritsugu , Ohtsuka Yoshikazu , Yamashiro Yuichiro
Published: October 2004

AbstractBackground: It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases. Because bacterial populations develop during the first day of life, the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants.

Methods: The effects of oral administration ofBifidobacterium breve (B. breve)supplements were studied in a controlled trial with low birth weight infants (average birth weight 1489 g). The infants were divided into three groups: Group A and B received a dose of 1.6 × 108cells ofB. brevesupplement twice a day, commencing either from several hours after birth (group A) or 24 h after birth (group B). Group C, the control group, received no supplement.

Results: There were no significant differences in birth weight, treatment with antibiotics, and the starting time of breast‐feeding among the three groups. ABifidobacterium‐predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B, while noBifidobacteriumwas isolated in eight out of 10 infants in group C during the observation period of 7 weeks. In comparison between group A and B,Bifidobacteriumwas detected significantly earlier in group A, and the number ofEnterobacteriaceaepresent in the infants at 2 weeks after birth was significantly lower in group A.

Conclusion: The results of the present study suggest that very early administration ofB. breveto low birth weight infants is useful in promoting the colonization of theBifidobacteriumand the formation of a normal intestinal flora.
Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy
Authors: Tanaka Hiroshi , Suzuki Koichi , Nakahata Tohru , Tsugawa Koji , Konno Yuki , Tsuruga Kazushi , Ito Etsuro , Waga Shinobu
Published: October 2004

Abstract
Background
: It has been reported that combined therapy of angiotensin converting enzyme inhibitor and angiotensin receptor blocker significantly decreases proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic alterations following the therapy have not been reported.

Methods
: A total of nine Japanese children with severe proteinuric IgA nephropathy who received a prompt immunosuppressive therapy were enrolled the study, four of whom received a combined therapy of angiotensin converting enzyme inhibitor, enalapril and angiotensin receptor blocker, losartan (Group A), while the remaining five did not (Group B). All underwent renal biopsy before and approximately 12 months after the first renal biopsy.

Results
: At presentation, urine protein excretion and the histologic indices of mean activity index, mean chronicity index and tubulointerstitial scores did not show a statistical difference between the two groups: Group A (2.6 ± 0.6 g/day; mean activity index, 5.0 ± 1.0; mean chronicity index, 5.0 ± 1.0; tubulointerstitial scores, 4.3 ± 1.0) and Group B (2.2 ± 0.6 g/day; mean activity index, 4.8 ± 0.8; mean chronicity index, 4.8 ± 1.3; tubulointerstitial scores, 3.6 ± 0.5, respectively). All had normal blood pressure and renal function. Urine protein excretion and the activity index decreased at the second renal biopsy, while the chronicity index and the tubulointerstitial scores slightly increased or remained unchanged. In comparison with Group B, a significant suppression in increasing the chronicity index and the tubulointerstitial scores obtained at the second renal biopsy were observed in Group A [Group A: 4.3 ± 1.2 and 3.0 ± 0.0, respectively, vs Group B: 6.0 ± 0.7 and 4.4 ± 0.9, respectively (P < 0.05)]. One patient in Group B developed chronic renal insufficiency thereafter.

Conclusions
: Although only a small number of patients were examined, these clinical findings suggest that a combined therapy of enalapril and losartan may attenuate histologic progression in at least a proportion of patients with severe proteinuric IgA nephropathy.
Gastroesophageal reflux disease beyond infancy
Authors: Lin Yu‐Cheng , Ni Yen‐Hsuan , Chang Mei‐Hwei
Published: October 2004

Abstract
Background
: Children beyond infancy (>12 months of age) rarely have gastroesophageal reflux disease (GERD). Underlying diseases may contribute to the persistence of GERD from infancy to childhood. This study compares the clinical course of children with GERD with and without underlying diseases.

Methods
: The authors studied the role of underlying diseases responsible for GERD in children beyond infancy by a retrospective analysis. From 1985 to 2000, GERD was confirmed in 34 children beyond infancy in the National Taiwan University (median age 2.5 years, range 1.1–9.7 years), according to the inclusion criteria of reflux symptoms and the fraction of pH < 4 above 5% in the 24‐h esophageal pH study. The patients were divided into two groups: those without underlying diseases (n = 10) and those with underlying diseases (n = 24). The follow‐up duration was 0.5–17.1 years (median 4.5 years).

Results
: The underlying diseases responsible for GERD in 24 children included neurological impairment (n = 14), repaired esophageal atresia (n = 2), hiatal hernia (n = 3), repaired congenital diaphragmatic hernia (n = 2), and congenital heart disease (n = 3). At the end of the study, 9 of 10 children with GERD beyond infancy and without underlying diseases were free of symptoms without any need for further medical treatment. In contrast, 10 of 14 children with neurological disorders had persisting reflux symptoms (Kaplan–Meier analysis, P = 0.02, log‐rank test).

Conclusions
: Neurological impairment and esophageal or diaphragmatic anatomic abnormalities were frequently associated with GERD beyond infancy. Children with underlying diseases, especially with neurological impairment, ran a refractory course, while those without underlying diseases enjoyed a longer symptom‐free life.
Abnormal steroidogenesis in three patients with Antley–Bixler syndrome: Apparent decreased activity of 17α‐hydroxylase, 17,20‐lyase and 21‐hydroxylase
Authors: Adachi Masanori , Asakura Yumi , Tachibana Katsuhiko , Shackleton Cedric
Published: October 2004

Abstract
Background
: Antley–Bixler syndrome (ABS) is characterized mainly by abnormal skeletal morphonogenesis such as craniosynostosis and radiohumeral synostosis, and by ambiguous genitalia in some cases. The mechanisms resulting in these deformities have not been determined.

Methods
: The adrenal and gonadal function of three Japanese ABS patients were evaluated. Patient 1 (17‐year‐old‐male) had bilateral cryptoorchidism, delayed puberty and symptoms of glucocorticoid deficiency. Patient 2 (14‐year‐old male) and patient 3 (4‐year‐old female) presented with emaciation. Additionally, patient 3 had partial labial fusion and common urogenital sinus. In each patient, blood sampling for steroid analysis before and after rapid adrenocorticotropic hormone (ACTH) stimulation was carried out. Additionally, urinary steroids were quantified. Molecular analysis of CYP17 and CYP21A2 were also performed.

Results
: All patients showed elevated basal 17α‐deoxysteroid levels. Although the 17α‐deoxysteroid levels further increased after rapid ACTH stimulation, 17α‐hydroxysteroids including cortisol did not respond, suggesting impaired 17α‐hydroxylation. Patient 1 and patient 2 showed low adrenal androgen blood levels both before and after rapid ACTH stimulation. Patient 3 showed lower than normal excretions of urinary androgens. Additionally, a prolonged ACTH stimulation in patient 3 failed to elicit significant increase of adrenal androgens. These findings suggested impaired 17,20‐lyase activity. In contrast to attenuated 17α‐hydroxycorticosteroids, notably cortisol, elevated 17α‐hydroxyprogesterone (17OHP) levels were observed, not only in pubertal patients (1 and 2) but also in prepubertal patient 3, indicating impaired 21‐hydroxylation. This assumption was supported by increased urinary 21‐deoxycortisol metabolite excretion in patients 2 and 3. With the exception of a heterozygous mutation of CYP17 in one of the patients, other mutations of this gene or CYP21A2 were identified in any of the patients.

Conclusion
: Combined decreased 17α‐hydroxylation, 17,20‐lyase activity and 21‐hydroxylation was detected in three ABS patients. Considering that the enzymes responsible are all cytochrome P450 enzymes and that another cytochrome P450 enzyme, lanosterol 14α‐demethylase, has recently been shown to be impaired in an ABS patient, we speculate that dysfunction of a system which commonly regulates cytochrome P 450 activity may be responsible for the ABS phenotype.
The role of top management teams in formulating and implementing turnaround strategies: a review and research agenda
Authors: Lohrke Franz T. , Bedeian Arthur G. , Palmer Timothy B.
Published: October 2004

Both business commentators and scholarly researchers have acknowledged the key role that top management teams (TMTs) play in reversing the fortunes of failing firms. Nonetheless, relatively few empirical studies have investigated the importance of TMTs in turnaround situations. To encourage such studies, we draw upon the multiple theories employed in TMT research as a guide to review studies that have examined how TMTs formulate and implement turnaround strategies. Based on this review, we highlight TMT topics that have received limited attention in the turnaround literature and, thus, represent opportunities for future research. We conclude by discussing methodological issues that should be considered when examining a TMT's role in a turnaround situation.
Toxic Ethics: Environmental Genomics and the Health of Populations
Authors: Robert Jason Scott , Smith Andrea
Published: October 2004

Dealing primarily with implications rather than foundations, and focusing downstream at the expense of upstream prevention, mainstream bioethics is at a toxic watershed. Through an extended analysis of the Environmental Genome Project (EGP), we offer new tools from the philosophy of science and from critical epidemiology to help bioethics to move ahead. Our aim in this paper is not to resolve the moral and conceptual problems we reveal, but rather to outline ways to prevent such problems from arising in future research.
What's Wrong with Corporate Governance: a note
Authors: Leblanc Richard W.
Published: October 2004

Greater use of qualitative research methods – including observing boards in real time and interviewing directors – needs to occur to advance the field. Quantitative researchers are, it would seem, measuring variables in respect of “structural independence,” rather than board and individual director effectiveness, per se. Once “board effectiveness” and “director effectiveness” variables are able to be measured, together with their interaction, a greater likelihood of distilling a more definitive relationship between corporate governance and corporate financial performance may occur.
A Framework for Diagnosing Board Effectiveness
Authors: Nicholson Gavin J. , Kiel Geoffrey C.
Published: October 2004

Pressure on boards to improve corporate performance and management oversight has led to a series of inquiries and reports advocating governance reform. These reports largely reflect an agency perspective of governance and seek to ensure greater board independence from and control of management.

While board independence is important to good governance, we contend that frameworks, models and advice centred on one element of governance ignore the complexity of how boards work. We develop a holistic board framework based upon the concept of board intellectual capital to address this concern.

Our framework proposes a series of inputs (e.g. company history, company constitution, legal environment) that lead to a particular mix of board intellectual capital. We contend that the balance of the different elements of board intellectual capital will lead to a series of board behaviours. Further, the board needs to mobilise its intellectual capital to carry out a series of roles. The exact nature of these roles will depend on the company's requirements. Thus, the governance outputs of organisational performance, board effectiveness and director effectiveness will depend on the match between the board's intellectual capital and the roles required of it.

We conclude by demonstrating the benefits of this framework as a diagnostic tool. We outline how boards wishing to improve their governance systems can diagnose common governance problems by evaluating their own board's capabilities in relation to the different components of the framework.
Why So Few Women Directors in Top UK Boardrooms? Evidence and Theoretical Explanations
Authors: Singh Val , Vinnicombe Susan
Published: October 2004

Using evidence from a survey of women directors in FTSE 100 companies, this paper considers possible explanations for the persistent homogeneity of top UK boards. Only 61 per cent of the top 100 companies had female directors in 2002, down from 64 per cent in 1999. Women held only 3 per cent of executive (= US inside) directorships, and there were only 15 women executive directors in total. Explanations usually include women's lack of ambition, lack of experience and lack of commitment. These have been disproved by research, but underlying theories of social exclusion may provide insight into this persistent phenomenon.
The Role of the Board in Firm Strategy: integrating agency and organisational control perspectives
Authors: Hendry Kevin , Kiel Geoffrey C.
Published: October 2004

The role of the board of directors in firm strategy has long been the subject of debate. However, research efforts have suffered from several deficiencies: the lack of an overarching theoretical perspective, reliance on proxies for the strategy role rather than a direct measure of it and the lack of quantitative data linking this role to firm financial performance. We propose a new theoretical perspective to explain the board's role in strategy, integrating organisational control and agency theories. We categorise a board's approach to strategy according to two constructs: strategic control and financial control. The extent to which either construct is favoured depends on contextual factors such as board power, environmental uncertainty and information asymmetry.
The Paradox of Proportional Representation: The Effect of Party Systems and Coalitions on Individuals' Electoral Participation
Authors: Brockington David
Published: October 2004

Empirical findings based on aggregate data have found that proportional representation (PR) has a mixed relationship with electoral participation. Large party systems, thought to be one of the benefits of PR in increasing turnout, instead depress turnout. This article examines two theories that seek to account for this paradox – that coalition governments resulting from larger party systems serve to depress turnout, and that larger party systems increase the complexity of the decision environment for voters. By combining individual-level data from the Comparative Study of Electoral Systems with contextual measures of effective number of parties, coalition structure and disproportionality, this article tests for interactions between the characteristics and attitudes of individuals and the contextual influences on electoral participation. The frequency of coalitions that violate the minimal-winning rule depresses turnout, especially among supporters of major parties. By accounting for variations in coalition governments, larger party systems appear, on balance, to enhance, rather than depress, individuals' propensity to vote. Limited evidence is reported that indicates that this participation-enhancing role of larger party systems is not evenly distributed across the electorate, as those lacking a university degree may find the decision environment created by larger party systems more complex.
Problems of Descriptive Representation in Dutch Works Councils
Authors: Engelen Ewald
Published: October 2004

In political theory, descriptive representation as a corrective to structural asymmetries within society is usually debated against the background of formal political institutions. It is discussed in this paper as a means to enhance the declining legitimacy of Dutch works councils as important sites of democratic decision-making in their own right. The aim is to show that the moral requirements of democratic inclusion have to be weighed against the functional requirements of effective representation, concluding that in some cases the costs in terms of effectiveness exceed the gains in terms of inclusiveness. Hence, the debate about descriptive representation is clearly in need of a more contextualized assessment of its pros and cons.
UK Initiatives on Forced Marriage: Regulation, Dialogue and Exit
Authors: Phillips Anne , Dustin Moira
Published: October 2004

The literature on feminism and multiculturalism has identified potential conflicts between the recognition of cultural diversity and securing women's equality. Three broad approaches to this dilemma have emerged in the practices of contemporary states: regulation, working with the communities, and exit. Each of these is apparent in current initiatives regarding forced marriage, but the overwhelming emphasis in the UK has been on enabling individuals to exit from the threat or reality of a forced marriage. In assessing these initiatives, this paper highlights the limitations of exit and the danger of moving towards immigration regulation as the preferred solution.
Modulation of NMDA receptor function by cyclic AMP in cerebellar neurones in culture
Authors: Llansola Marta , Sánchez‐Pérez Ana M. , Montoliu Carmina , Felipo Vicente
Published: October 2004

The signal transduction pathways involved in NMDA receptor modulation by other receptors remain unclear. cAMP could be involved in this modulation. The aim of this work was to analyse the contribution of cAMP to NMDA receptor modulation in cerebellar neurones in culture. Forskolin increases cAMP and results in increased intracellular calcium and cGMP that are prevented by blocking NMDA receptors. Similar effects were induced by two cAMP analogues, indicating that cAMP leads to NMDA receptor activation. It has been reported that phosphorylation of Ser897 of the NR1 subunit of NMDA receptors by cAMP‐dependent protein kinase (PKA) activates the receptors. Forskolin increases Ser897 phosphorylation. Neither Ser897 phosphorylation nor cGMP increase induced by forskolin are prevented by four inhibitors of PKA, suggesting that NMDA receptor activation is dependent on cAMP but not on PKA. Inhibition of Akt prevents forskolin‐induced phosphorylation of Ser897, suggesting a role for Akt in the mediation of the modulation of NMDA receptors by cAMP. Pituitary adenylate cyclase‐activating polypeptide (PACAP) activates its receptors, increasing cAMP and also leading to phosphorylation of Ser897 of NR1 and activation of NMDA receptors. These results indicate that cAMP modulates NMDA receptor in cerebellar neurones and may play a role in NMDA receptor modulation by other receptors.
Differential modulation of evoked and spontaneous glycine release from rat spinal cord glycinergic terminals by the cyclic AMP/protein kinase A transduction cascade
Authors: Katsurabayashi Shutaro , Kubota Hisahiko , Moorhouse Andrew J. , Akaike Norio
Published: October 2004

The mechanisms underlying cyclic AMP modulation of action potential‐dependent and ‐independent (spontaneous) release of glycine from terminals synapsing onto sacral dorsal commissural nucleus neurons of lamina X were studied in spinal cord slices using conventional patch‐clamp recordings. 3‐Isobutyl‐1‐methylxanthine (IBMX), a phosphodiesterase inhibitor, and forskolin increased the amplitude of evoked inhibitory postsynaptic currents (eIPSCs) in a sensitive manner to protein kinase A (PKA) inhibition (with KT‐5720). Direct activation (with adenosine 3′,5′‐cyclic‐monophosphothioate, Sp‐isomer) and inhibition (with adenosine 3′,5′‐cyclic‐monophosphothioate, Rp‐isomer) of PKA increased and decreased the eIPSC amplitude, respectively. Paired pulse experiments and direct injection of PKA inhibitor fragment 6–22 amide (PKI6−22) into the recording neuron revealed that these effects on eIPSC amplitude occurred presynaptically, indicating that evoked glycine release is regulated by presynaptic cAMP via changes in PKA activity. Increasing cAMP also increased spontaneous release of glycine, causing an increased frequency of miniature IPSCs (mIPSCs). In contrast to the effects on evoked release, this response was not solely mediated via PKA, as it was not occluded by PKA inhibition, and both direct inhibition and direct activation of PKA actually enhanced mIPSC frequency. Direct inhibition of cAMP (with SQ 22536) did, however, reduce mIPSC frequency. These results suggest cAMP modulation of evoked and spontaneous release involves different presynaptic mechanisms and proteins.
Role of extracellular signal‐regulated protein kinase in neuronal cell death induced by glutathione depletion in neuron/glia mesencephalic cultures
Authors: De Bernardo S. , Canals S. , Casarejos M. J. , Solano R. M. , Menendez J. , Mena M. A.
Published: October 2004

To date, glutathione (GSH) depletion is the earliest biochemical alteration shown in brains of Parkinson's disease patients, but the role of GSH in dopamine cell survival is debated. In this study we show that GSH depletion, produced with GSH synthesis inhibitor, l‐buthionine‐(S,R)‐sulfoximine (BSO), induces selectively neuronal cell death in neuron/glia, but not in neuronal‐enriched midbrain cultures and that cell death occurs with characteristics of necrosis and apoptosis. BSO produces a dose‐ and time‐dependent generation of reactive oxygen species (ROS) in neurons. BSO activates extracellular signal‐regulated kinases (ERK‐1/2), 4 and 6 h after treatment. MEK‐1/2 and lipoxygenase (LOX) inhibitors, as well as ascorbic acid, prevent ERK‐1/2 activation and neuronal loss, but the inhibition of nitric oxide sintase (NOS), cyclo‐oxygenase (COX), c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (p38 MAPK) does not have protective effects. Co‐localization studies show that p‐ERK‐1/2 expression after BSO treatment increased in astrocytes and microglial cells, but not in neurons. Selective metabolic impairment of glial cells with fluoroacetate decreased ERK activation. However, blockade of microglial activation with minocycline did not. Our results indicate that neuronal death induced by GSH depletion is due to ROS‐dependent activation of the ERK‐1/2 signalling pathway in glial cells. These data may be of relevance in Parkinson's disease, where GSH depletion and glial dysfunction have been documented.
Autoreceptor‐mediated inhibition of norepinephrine release in rat medial prefrontal cortex is maintained after chronic desipramine treatment
Authors: Garcia April S. , Barrera Gabe , Burke Teresa F. , Ma Shuaike , Hensler Julie G. , Morilak David A.
Published: October 2004

Alterations in noradrenergic neurotransmission are important in the mechanism of action of many antidepressant drugs, including selective norepinephrine (NA) reuptake inhibitors such as desipramine (DMI). It has been suggested that chronic NA reuptake blockade induces a desensitization of inhibitory α2‐adrenergic autoreceptors. This hypothesis was tested in experiment 1 using in vivo microdialysis to examine the degree of α2‐autoreceptor‐mediated inhibition of NA release in rat medial prefrontal cortex exerted by endogenous NA following chronic treatment with vehicle or DMI. This was accomplished by measuring the elevation of extracellular NA levels induced by acute administration of the α2‐receptor antagonist yohimbine. An 8‐fold increase in basal NA levels was observed after 21 days of DMI treatment. Further, acute yohimbine administration induced a robust elevation in NA levels which was not attenuated, and in fact at lower doses was greater in DMI‐treated rats compared with vehicle‐treated controls. In experiment 2, we addressed directly the functional status of terminal α2‐autoreceptors in frontal cortex in vitro, in the absence of potentially confounding competition from elevated levels of endogenous NA, after chronic reuptake blockade. We observed no difference in the degree to which the α2‐receptor agonist clonidine inhibited potassium‐evoked [3H]‐NA release from cortical slices taken from DMI‐ or vehicle‐treated rats. Together, these data suggest that endogenous activation of α2‐autoreceptors persists in restraining NA neurotransmission in the face of tonically elevated basal NA levels following chronic reuptake blockade.
Septin 3 (G‐septin) is a developmentally regulated phosphoprotein enriched in presynaptic nerve terminals
Authors: Xue Jing , Tsang Christopher W. , Gai Wei‐Ping , Malladi Chandra S. , Trimble William S. , Rostas John A. P. , Robinson Phillip J.
Published: October 2004

The septins are GTPase enzymes with multiple roles in cytokinesis, cell polarity or exocytosis. The proteins from the mammalian septin genes are called Sept1–10. Most are expressed in multiple tissues, but the mRNA for Sept5 (CDCrel‐1) and Sept3 (G‐septin) appear to be primarily expressed in brain. Sept3 is phosphorylated by cGMP‐dependent protein kinase I (PKG‐I) and the cGMP/PKG pathway is involved in presynaptic plasticity. Therefore to determine whether Sept3 specifically associates with neurones and nerve terminals we investigated its distribution in rat brain and neuronal cultures. Sept3 protein was detected only in brain by immunoblot, but not in 12 other tissues examined. Levels were high in all adult brain regions, and reduced in those enriched in white matter. Expression was developmentally regulated, being absent in the early embryo, low in late embryonic rat brain and increasing after birth. Like dynamin I, Sept3 was specifically enriched in synaptosomes compared with whole brain, and was only found in a peripheral membrane extract and not in the soluble or membrane extracts. Sept3 was particularly abundant in mossy fibre nerve terminals in the hippocampus. In primary cultured hippocampal neurones Sept3 immunoreactivity was punctate in neurites and predominantly localized to presynaptic terminals, strongly colocalizing with synaptophysin and dynamin I. The specific nerve terminal localization was confirmed by immunogold electron microscopy. Together this shows that Sept3 is a neurone‐specific protein highly enriched in nerve terminals which supports a secretory role in synaptic vesicle recycling.
Pyrrolidine dithiocarbamate inhibits translocation of nuclear factor kappa‐B in neurons and protects against brain ischaemia with a wide therapeutic time window
Authors: Nurmi Antti , Vartiainen Nina , Pihlaja Rea , Goldsteins Gundars , Yrjänheikki Juha , Koistinaho Jari
Published: October 2004

Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibitor of transcription factor nuclear factor kappa‐B (NF‐κB). Because the role of NF‐κB in brain injury is controversial and another NF‐κB inhibiting thiocarbamate, DDTC, was recently shown to increase ischaemic brain damage, we investigated the effect of PDTC on transient brain ischaemia. Ischaemia was induced by occlusion of the middle cerebral artery (MCAO). In Wistar rats, the PDTC treatment started even 6 h after MCAO reduced the infarction volume by 48%. PDTC protected against MCAO also in spontaneously hypertensive rats and against forebrain ischaemia in Mongolian gerbils. PDTC prevented NF‐κB activation in the ischaemic brain as determined by reduced DNA binding and nuclear translocation of NF‐κB in neurons. PDTC had anti‐inflammatory effect by preventing induction of NF‐κB‐regulated pro‐inflammatory genes. In ischaemic rats, NF‐κB was localized in cyclo‐oxygenase‐2‐immunoreactive neurons. Blood cytokine levels were not altered by ischaemia or PDTC. When cultured neurons were exposed to an excitotoxin, no production of reactive oxygen species was detected, but PDTC provided protection and prevented nuclear translocation of NF‐κB. The clinically approved PDTC and its analogues may act as anti‐inflammatories and may be safe therapies in stroke with a wide time window.
A role for semaphorin 3A signaling in the degeneration of hippocampal neurons during Alzheimer's disease
Authors: Good Paul F. , Alapat Daisy , Hsu Amy , Chu Caryn , Perl Daniel , Wen Xiaping , Burstein David E. , Kohtz D. Stave
Published: October 2004

Among the earliest invariant neuropathological changes in Alzheimer's disease (AD) is the degeneration of vulnerable hippocampal CA1 and subicular pyramidal neurons. Semaphorin 3A (Sema3A) is a secreted protein that functions in signaling growth cone collapse, chemorepulsion and neuronal apoptosis during early development of the central nervous system. In this report we show that accumulation of an internalized form of Sema3A is associated with degeneration of neurons in vulnerable fields of the hippocampus during AD. Accumulation of Sema3A overlaps the appearance of phosphorylated MAP1B and tau in many neurons, suggesting that Sema3A signaling at some level may be coupled to these previously identified cytoskeletal markers of neurodegeneration. Consistent with this, we isolated and partially characterized a multiprotein complex from the hippocampus of patients with AD that contains phosphorylated MAP1B, collapsin‐response mediator protein 2 (CRMP‐2), Plexins A1 and A2, and a processed form of Sema3A. A model is presented in which aberrant release of Sema3A from expressing neurons in the subiculum during AD results in the internalization and transport of Sema3A from this field to CA1. Within the context of the myriad of potential insults that contribute to Alzheimer's and other neurodegenerative diseases, the bioactivity of Sema3A may contribute either directly to neurodegeneration by inducing neuronal collapse, or indirectly by abrogating the recovery capabilities of adult neurons faced with these insults.
Nitric oxide‐induced increase of excitatory amino acid levels in the trigeminal nucleus caudalis of the rat with tactile hypersensitivity evoked by the loose‐ligation of the inferior alveolar nerves
Authors: Fujita Toyohiro , Kamisaki Yoshinori , Yonehara Norifumi
Published: October 2004

To investigate whether or not N‐methyl‐d‐aspartate (NMDA)/nitric oxide (NO) pathway in the trigeminal system is involved in the development and/or maintenance of such pathological pain states as the hyperalgesia and allodynia observed after dental surgery, we examined the alteration patterns of excitatory amino acid (EAA) level in the superficial layer of subnucleus caudalis of the brain‐stem trigeminal sensory nuclear complex (SpVc‐I,II) by in vivo microdialysis. A very high EAA release response was observed immediately after the start of the perfusion in ligated animals compared with sham‐operated rats. The EAA level evoked by application of the 40‐V tooth pulp‐stimulation or 1% capsaicin cream was significantly higher in the ligated animals than those in the sham‐operated animals. This increase of EAA level induced by capsaicin cream was inhibited by adding carboxy‐PTIO (100 µm) to the perfusate. The applications of SNAP (2 mm) into the perfusate enhanced the level of EAAs in ligated animals and sham‐operated animals. However, SNAP‐evoked EAA levels in ligated animals were not significantly different compared with those of sham‐operated animals. These results suggest that alterations in the stimulus‐evoked raised EAA levels that occur in the site of the first synaptic relay of the dental pain pathway and which are expressed via endogenous NO, and which play an important role in development and/or maintenance of pathological pain states following dental peripheral nerve injury.
Up‐regulation of the Kv3.4 potassium channel subunit in early stages of Alzheimer's disease
Authors: Angulo Ester , Noé Véronique , Casadó Vicent , Mallol Josefa , Gomez‐Isla Teresa , Lluis Carmen , Ferrer Isidre , Ciudad Carlos J. , Franco Rafael
Published: October 2004

Gene expression throughout the different stages of Alzheimer's disease was analysed in samples from cerebral cortex. The gene encoding the voltage‐gated potassium channel Kv3.4 was already overexpressed in early stages of the disease, and in advanced stages Kv3.4 was present at high levels in neurodegenerative structures. This subunit regulates delayed‐rectifier currents, which are primary determinants of spike repolarization in neurones. In unique samples from a patient with Alzheimer's disease whose amount of amyloid plaques was decreased by β amyloid immunization, Kv3.4 was overexpressed. The channel subunit was expressed in the neuropil, in the remaining conventional plaques in the frontal cortex and in collapsed plaques in the orbitary cortex. Therefore, amyloid deposition in plaques does not seem to be responsible for the increase in Kv3.4 levels. Nevertheless, Kv3.4 up‐regulation is related to amyloid pathology, given that transgenic mice with the Swedish mutation of amyloid precursor protein showed increased expression of Kv3.4. Up‐regulation of voltage‐gated potassium channel subunits alters potassium currents in neurones and leads to altered synaptic activity that may underlie the neurodegeneration observed in Alzheimer's disease. Thus, Kv3.4 likely represents a novel therapeutic target for the disease.