bluuebunny/crossref_metadata_2025 huggingface dataset:
World class manufacturing and accountability
Authors: Hopper Trevor , Jazayeri Mostafa , Westrup Chris
Published: May 2008

Purpose

The paper's aim is to establish how world class manufacturing (WCM) was diffused to some small‐ and medium‐sized enterprises in the NW of England and the network of institutions involved ranging from the state to firms, and to iterate the results with Miller and O'Leary's work on accounting practices and governance.

Design/methodology/approach

This followed an actor network theory approach of “following the actors and actants” using interviews and documentation.

Findings

Three accountabilities (financial, production, and idealised customer) at firm and state levels were linked through agencies like consultants, academics, and employer federations, and quasi‐governmental organisations like training and enterprise councils. New discourses and programmes of governance associated with competitiveness fostered changes in accountability locally and nationally. Competitiveness, WCM, and occasional allies like activity‐based costing lacked stable and consistent definition. They are adopted and circulate because their plasticity helps actors redefine themselves within translation and mediation processes.

Research limitations/implications

Shop floor workers were not directly studied. Hence, observations on resistance and enactment are tentative.

Practical implications

Continual translations within large networks shape new techniques of management and governance.

Originality/value

The paper shows that programmes and discourses of governance over time are reciprocally linked in a constellation of state institutions and firms.
A rationale for stakeholder‐based management in developing nations
Authors: Joseph George
Published: May 2008

Purpose

The paper aims to provide a rationale for stakeholder‐based management in developing countries. To implement the objectives, the paper contrasts the implications of agency and stakeholder theories as they apply to developing countries and highlight “total wealth creation” and “purposive adaptation” that support developmental goals of developing countries. This “purposive adaptation” also implicates the use of management accounting tools in a flexible way to meet the needs of the strategy.

Design/methodology/approach

The paper uses conceptual analysis and the case study approach

Findings

The Tata Steel case illustrates the normative stakeholder approach in the developing country context. Specifically, the case highlights strategy developed through “stakeholder engagement” and the application of the balanced scorecard to address stakeholder issues in implementing the strategy, illustrating the rationale underlying the stakeholder approach in addressing developmental concerns through more dispersed and larger wealth creation.

Research limitations/implications

There is limited scope to use methods other than illustrating the theory using specific instances of its application, as in the case approach.

Practical implications

The paper illustrates long‐term implications on sustainable development.

Originality/value

Few papers consider contextualizing theoretical implications of management to developing countries. This is important as the theory has implications on development in such aspects as environmental costs, increasing inequality, and associated issues. The paper directs attention to the importance of identifying theory that addresses the unique management challenges in developing countries and can potentially enable further research to systematize and generalize management approaches in developing countries.
Predicting change in bank efficiency in Jordan: a data envelopment analysis
Authors: Bdour Jamal I. , Al‐khoury Abeer F.
Published: May 2008

Purpose

This study aims to investigate the relative efficiency pattern of Jordanian banks during the period between 1998 and 2004.

Design/methodology/approach

The deterministic data envelopment analysis (DEA) as a quantitative approach was used to obtain the efficiency of individual commercial banks in Jordan.

Findings

The results of the DEA Charnes, Cooper and Rhodes model show an increase in bank efficiency in the entire period except in 2003 and 2004 where a decrease in bank efficiency was shown for few banks in the sample. The total efficiency scores suggest that the liberalisation programme has provided the anticipated efficiency gains. Most efficiency scores showed consistent increases after the introduction of the policy with the exception of few banks which have responded differently and shown decreased in efficiency. This may be taken to imply that the banks have responded differently to the new system. The analysis further shows that both assets utilisation and the labour factor had an adverse effect on bank efficiency, especially in terms of number of employees.

Research limitations/implications

The effect of the Jordanian Government liberalisation programme may not be readily discerned in such a relatively short period of time, which may require that a longer time period elapses before this effect becomes noticeable.

Originality/value

The paper analyses the performance of Jordanian banks with regard to their efficiency.
Institutional differences in EU countries and their relationship with earnings management differences
Authors: Reverte Carmelo
Published: May 2008

Purpose

The paper seeks to highlight the differences among EU countries in a series of institutional factors (e.g. enforcement, securities regulation, investor protection and ownership concentration) in order to test whether these differences are associated with the European variability in earnings management practices and, as a result, in the quality of financial information.

Design/methodology/approach

The approach is to use cluster analysis and regression analysis.

Findings

The results of the study confirm the main hypothesis in that earnings management practices are significantly lower in those EU countries with an institutional framework more favourable to a high quality of financial reporting (i.e. in those countries with a higher level of enforcement of the rules, stricter securities regulation, lower ownership concentration and a higher degree of investor protection).

Research limitations/implications

The study presents the limitations typical from cross‐country studies. Moreover, the results should be interpreted cautiously as earnings management is difficult to measure. Future research should explore further the theoretical relations among institutional factors and earnings management practices by taking into consideration potential endogeneity issues.

Practical implications

The results of the study suggest that a single EU financial market should be based not only on a harmonization of financial reporting standards (such as the International Reporting Financing Standards issued by the International Accounting Standards Board) but also on a harmonization of enforcement rules, investor protection mechanisms, and securities regulation.

Originality/value

The main contribution is to justify from an empirical point of view the necessity of the recent EU convergence regulatory initiatives in the areas of shareholder protection, enforcement and securities regulation to facilitate the construction of the pan‐European stock market.
Removal of distal protein–water hydrogen bonds in a plant epoxide hydrolase increases catalytic turnover but decreases thermostability
Authors: Thomaeus Ann , Naworyta Agata , Mowbray Sherry L. , Widersten Mikael
Published: May 2008

A putative proton wire in potato soluble epoxide hydrolase 1, StEH1, was identified and investigated by means of site‐directed mutagenesis, steady‐state kinetic measurements, temperature inactivation studies, and X‐ray crystallography. The chain of hydrogen bonds includes five water molecules coordinated through backbone carbonyl oxygens of Pro186, Leu266, His269, and the His153 imidazole. The hydroxyl of Tyr149 is also an integrated component of the chain, which leads to the hydroxyl of Tyr154. Available data suggest that Tyr154 functions as a final proton donor to the anionic alkylenzyme intermediate formed during catalysis. To investigate the role of the putative proton wire, mutants Y149F, H153F, and Y149F/H153F were constructed and purified. The structure of the Y149F mutant was solved by molecular replacement and refined to 2.0 Å resolution. Comparison with the structure of wild‐type StEH1 revealed only subtle structural differences. The hydroxyl group lost as a result of the mutation was replaced by a water molecule, thus maintaining a functioning hydrogen bond network in the proton wire. All mutants showed decreased catalytic efficiencies with the R,R‐enantiomer of trans‐stilbene oxide, whereas with the S,S‐enantiomer, k cat/K M was similar or slightly increased compared with the wild‐type reactions. k cat for the Y149F mutant with either TSO enantiomer was increased; thus the lowered enzyme efficiencies were due to increases in K M. Thermal inactivation studies revealed that the mutated enzymes were more sensitive to elevated temperatures than the wild‐type enzyme. Hence, structural alterations affecting the hydrogen bond chain caused increases in k cat but lowered thermostability.
Determinants of plasma apolipoprotein A‐V and APOA5 gene transcripts in humans
Authors: Hahne P. , Krempler F. , Schaap F. G. , Soyal S. M. , Höffinger H. , Miller K. , Oberkofler H. , Strobl W. , Patsch W.
Published: June 2008

Objective.  Apolipoprotein A‐V (apoAV) contributes to the regulation of triglyceride metabolism, which plays a role in the pathogenesis of atherosclerotic diseases. We therefore ascertained determinants of hepatic APOA5 transcript and apoAV plasma levels in humans.

Design.  We determined influences of anthropometric variables, biochemical factors related to lipid and glucose metabolism, hepatic mRNA levels transcribed from the APOA1/C3/A4/A5 cluster and transcription factor genes implicated in the regulation of APOA5 as well as common single nucleotide polymorphisms (SNPs) at the APOA5 locus on APOA5 expression in 89 obese patients and 22 non‐obese controls.

Results.  Mean, age and sex adjusted, hepatic APOA5 mRNA or apoAV plasma levels did not differ by obesity status, homoeostasis model assessment insulin resistance or inflammatory markers. In multivariate regression models, the c56C > G SNP, plasma apoCIII, plasma nonesterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels. Hepatic transcript levels of carnitine palmitoyltransferase 1 (CPT1A1) and peroxisome proliferator‐activated receptor alpha (PPARA), plasma nonesterified fatty acids and the c56C > G SNP explained 48% of the variance in hepatic APOA5 transcript levels.

Conclusion.  Apolipoprotein A‐V plasma levels are independently associated with plasma free fatty acid and hepatic APOA5 mRNA levels. Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism.
Maternal vitamin D deficiency, ethnicity and gestational diabetes
Authors: Clifton‐Bligh R. J. , McElduff P. , McElduff A.
Published: June 2008

Aims  Vitamin D deficiency has been linked to impaired glucose metabolism. We determined whether serum 25‐hydroxyvitamin D (25OHD) is associated with glucose metabolism in pregnant women and the effect of ethnicity on this relationship.

Methods  We analysed serum 25OHD concentrations in 307 pregnant women attending a metropolitan obstetric clinic between October 2003 and May 2005. Measurements from 264 of the women were taken at the time of glucose tolerance testing at mid‐gestation, a population therefore at increased risk for gestational diabetes. Pearson correlation analysis was used to test for univariate linear relationships between the natural log of serum 25OHD (ln‐25OHD) and other variables. Multiple regression analysis was used to adjust for confounding factors.

Results  Mean serum 25OHD concentration was 53.8 ± 23.9 nmol/l (sd). Ln‐25OHD was negatively correlated with serum parathyroid hormone as expected (r −0.24, confidence intervals −0.35 to −0.12). Ln‐25OHD was also negatively correlated with fasting plasma glucose (r−0.20, −0.31 to −0.08), fasting insulin (r −0.20, −0.31 to −0.08) and insulin resistance as calculated by homeostatis model assessment (r −0.21, −0.32 to −0.09). The association between fasting glucose and log‐transformed 25OHD concentration was of borderline significance after accounting for ethnicity, age and body mass index in multivariate analyses (−0.13, −0.26 to 0.01). The odds ratio of gestational diabetes in women with 25OHD < 50 nmol/l did not reach statistical significance (1.92, 95% confidence interval 0.89–4.17).

Conclusions  Maternal 25OHD concentrations are inversely related to fasting glucose, although further studies are required to establish whether this is independent of the effects of ethnic background.
The Pro12Ala polymorphism of the PPARG gene is not associated with the metabolic syndrome in an urban population of middle‐aged Swedish individuals
Authors: Montagnana M. , Fava C. , Nilsson P. M. , Engström G. , Hedblad B. , Lippi G. , Minuz P. , Berglund G. , Melander O.
Published: June 2008

Background  To determine if the common Pro12Ala polymorphism (rs1801282) of the peroxisome proliferator‐activated receptor (PPARG) gene is associated with the metabolic syndrome (MetS) or with its individual components in middle‐aged Swedish individuals.

Methods  MetS was defined according to the National Cholesterol Education Program/Adult Panel III (NCEP/ATP III), the International Diabetes Federation (IDF) and the European Group for the Study of Insulin Resistance (EGIR) criteria in a population‐based sample of nearly 5000 subjects participating in the Malmö Diet and Cancer‐cardiovascular arm.

Results  Of the subjects included in the analysis, 21.8, 29.4 and 20.4% had MetS according to the NCEP/ATP III, IDF and EGIR (only in subjects without diabetes) definitions, respectively. The Pro12Ala was not associated with MetS or with its individual components. These results were similar when patients with diabetes were excluded. Hypertensive and obese ala‐carriers had lower fasting glucose and hypertensive ala‐carriers also had lower level triglycerides (P < 0.05).

Conclusions  Our data do not support a major role for the Pro12Ala variant of the PPARG gene in MetS and its individual components. The modest difference in triglyceride and glucose levels, restricted to hypertensive and obese subjects in our cohort, suggests that the polymorphism has a minor effect on glucose and lipid metabolism, particularly in individuals at risk for gluco‐metabolic disturbances.
Educational interventions for migrant South Asians with Type 2 diabetes: a systematic review
Authors: Khunti K. , Camosso‐Stefinovic J. , Carey M. , Davies M. J. , Stone M. A.
Published: June 2008

Aims  To conduct a systematic review to determine the scope of published assessments of educational initiatives for South Asians with Type 2 diabetes living in Western countries and to consider the effectiveness of reported interventions.

Methods  A range of electronic databases was searched using Medical Subject Headings (MeSH) and free text terms; papers published up to the end of 2007 were considered. Two researchers independently reviewed titles and abstracts and the full text of selected citations. Reference list review and consultation with experts in the field were used to check for completeness of the final sample of studies prior to data extraction.

Results  Only nine studies, including five randomized controlled trials with a combined total of 1004 cases, met our inclusion criteria. The quality of reporting in some studies was limited, e.g. omission of detailed information about ethnicity. Selected studies included a range of group and one‐to‐one interventions with varied knowledge, psychological and biomedical outcome measures. The effectiveness of the interventions was also variable, and the low number and heterogeneity of the studies made identification of factors linked to effectiveness difficult and meta‐analysis inappropriate. However, it appeared that improvements in knowledge levels may be easier to achieve than positive biomedical outcomes, and the need for tailored approaches was suggested.

Conclusions  Our findings confirm the difficulty of designing, assessing and achieving an impact through educational interventions for migrant South Asians with Type 2 diabetes and emphasize the need for good‐quality studies in these high‐risk populations.
DEMAND THRESHOLD, ZERO EXPENDITURE AND HIERARCHICAL MODEL OF CONSUMER DEMAND
Authors: Chattopadhyay Nachiketa , Majumder Amita , Coondoo Dipankor
Published: June 2008

Consumer expenditure surveys often show households reporting zero consumption of some commodities. Three reasons for this are recognized in the literature: (i) infrequency of purchase, (ii) a strong brand preference for differentiated products and (iii) misreporting. However, sometimes the number of households reporting zero consumption is seen to decline with income. To capture this phenomenon, which does not fall into any of the categories mentioned above, we propose a hierarchical preference structure and identify a class of recursive utility functions representing this structure. An empirical illustration based on Indian consumer expenditure data is provided.
Long‐term trends for socio‐economic differences in prenatal diagnosis of Down syndrome: diffusion of services or persistence of disparities?
Authors: Khoshnood B , De Vigan C , Blondel B , Vodovar V , Cadio E , Goffinet F
Published: June 2008

Objective  To assess long‐term trends in disparities for prenatal diagnosis of Down syndrome in relation to policy changes.

Design  Population‐based observational study.

Setting  Paris.

Population  Residents of Paris who gave birth or had a termination of pregnancy in Paris during 1983–2003 (approximately 23 000 births per year).

Methods  Using population‐based data from the Paris Registry of Congenital Malformations on 1934 cases of Down syndrome, we assessed differences in prenatal diagnosis proportions by maternal profession and geographical origin for the years 1983–2003. Analyses included locally weighted scatter plot smoother curves and binomial regression.

Main outcome measure  Trends in proportion of Down syndrome cases diagnosed prior to birth for different maternal occupation groups and women of different geographical origins.

Results  The proportion of prenatally diagnosed cases increased substantially, reaching to about 85–90% of cases in 2003 for most socio‐economic groups. This increase was accompanied by a significant decrease in disparities in prenatal diagnosis. Nonetheless, the proportion of prenatally diagnosed cases remained 12% lower for women without a profession compared with those in the highest occupational category (maternal age‐adjusted risk difference −12.0%, 95% CI −17.1 to −6.9).

Conclusions  Together with the implementation of policies aimed at providing access to prenatal screening for all women, socio‐economic differences in prenatal diagnosis of Down syndrome decreased over time. These trends need to be monitored, particularly in light of technical advances and alternative strategies for prenatal testing. However, while monitoring the proportion of cases with prenatal diagnosis is important, the ideal evaluation of prenatal testing programmes should also include measures of informed choice.
Behavioral sensitization to Δ9‐tetrahydrocannabinol and cross‐sensitization with morphine: differential changes in accumbal shell and core dopamine transmission
Authors: Cadoni Cristina , Valentini Valentina , Di Chiara Gaetano
Published: May 2008

Although cannabinoid‐induced behavioral sensitization and cross‐sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Δ9‐tetrahydrocannabinol (Δ9‐THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Δ9‐THC and morphine in the NAc shell and core. Different groups of male Sprague–Dawley rats were administered twice daily for 3 days with increasing doses of Δ9‐THC (2, 4, and 8 mg/kg i.p.), morphine (10, 20, and 40 mg/kg s.c.), and vehicle. After 14–20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc shell and the other at the core. The following day animals pre‐treated with Δ9‐THC and vehicle controls were challenged with 150 μg/kg i.v. of Δ9‐THC or 0.5 mg/kg i.v. of morphine. Animals pre‐treated with morphine and their vehicle controls were administered with 150 μg/kg i.v. of Δ9‐THC. Rats pre‐exposed to Δ9‐THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc shell and an increased stimulation in the NAc core in response to Δ9‐THC challenge. Pre‐exposure to Δ9‐THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc shell was observed. Animals pre‐treated with morphine showed behavioral sensitization and differential changes of DA in the NAc shell and core in response to Δ9‐THC challenge with a decreased response in the shell and an increased response in the core. The results show that Δ9‐THC‐induced behavioral sensitization is associated with changes in the responsiveness of DA transmission in the NAc subdivisions that are similar to those observed in the sensitization induced by other drugs of abuse.
Huperzine A exhibits anti‐inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia
Authors: Wang Zhi‐Fei , Wang Juan , Zhang Hai‐Yan , Tang Xi‐Can
Published: May 2008

Huperzine A, a reversible and selective acetylcholinesterase (AChE) inhibitor, has been reported to display neuroprotective properties. The present study investigated the protective effects of huperzine A in a rat model of transient focal cerebral ischemia created by middle cerebral artery occlusion (MCAO). Huperzine A (0.1 mg/kg), administrated intraperitoneally at the onset of occlusion and 6 h later, markedly restored regional cerebral blood flow, reduced infarct size, and decreased neurological deficit score at 24 h after reperfusion. Along with inhibiting AChE activity, huperzine A inhibited nuclear translocation of transcription factor nuclear factor‐kappa B, decreased overexpression of proinflammatory factors in both ipsilateral cortex and striatum, and suppressed activation of glial cells in the ischemic penumbra. Neurological deficit and glial cells activation were also reduced by daily administration of huperzine A for 14 days. Mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, totally abolished the inhibitory effects of huperzine A on ischemia‐induced glial cells activation. Meanwhile, mecamylamine partially reversed the infarct size‐reducing effects of huperzine A. In conclusion, our results demonstrate that huperzine A exhibits neuroprotective effects against transient focal cerebral ischemia‐induced brain injury and suggest that the protection mechanism may involve a cholinergic anti‐inflammatory pathway, in which nAChR plays an essential role.
NELL2 participates in formation of the sexually dimorphic nucleus of the pre‐optic area in rats
Authors: Jeong Jin Kwon , Ryu Byung Jun , Choi Jungil , Kim Dong Hee , Choi Eun Jung , Park Jeong Woo , Park Joong Jean , Lee Byung Ju
Published: May 2008

Formation of the sexually dimorphic nucleus of the pre‐optic area (SDN‐POA) in the rat hypothalamus shows a sexually differential development of neurons. Volume of the SDN‐POA in males is much bigger than that in females which is because of a neuroprotective effect of estradiol converted from circulating testosterone during a critical period of brain development. We found that neural epidermal growth factor‐like like‐2 (NELL2), a neural tissue‐enriched protein, is a potential downstream target of estrogen. In this study, we examined a possible role of NELL2 in the development of the SDN‐POA and in the normalcy of sexual behavior in the male rats. NELL2 was expressed and co‐localized with estrogen receptor alpha in the SDN‐POA. A blockade of NELL2 synthesis in the brain during postnatal day 0 (d0) to d4 by an intracerebroventricular injection of an antisense NELL2 oligodeoxynucleotide, resulted in a decrease in volume of the SDN‐POA in males. Interestingly, it reduced some components of the male sexual behavior such as mounting and intromission, but not the sexual partner preference in adulthood. In vitro study using the hippocampal neuroprecursor HiB5 cells showed that NELL2 has a protective effect from a cell death condition. These data suggest that a relevant expression of NELL2 in the neonatal brain is important for the estrogen‐induced normal development of the SDN‐POA and the normalcy of sexual behavior in male rats.
Altered aminergic neurotransmission in the brain of organic cation transporter 3‐deficient mice
Authors: Vialou Vincent , Balasse Laure , Callebert Jacques , Launay Jean‐Marie , Giros Bruno , Gautron Sophie
Published: May 2008

Organic cation transporters (OCTs) are carrier‐type polyspecific permeases known to participate in low‐affinity extraneuronal catecholamine uptake in peripheral tissues. OCT3 is the OCT subtype most represented in the brain, yet its implication in central aminergic neurotransmission in vivo had not been directly demonstrated. In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non‐aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus and cortex. Although OCT3 was found mainly in neurons, it was also occasionally detected in astrocytes in the SNr, hippocampus and several hypothalamic nuclei. In agreement with this distribution, OCT3/Slc22a3‐deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. The behavioral characterization of these mutants reveal subtle behavioral alterations such as increased sensitivity to psychostimulants and increased levels of anxiety and stress. Altogether our data support a role of OCT3 in the homeostastic regulation of aminergic neurotransmission in the brain.
Expression of E‐FABP in PC12 cells increases neurite extension during differentiation: involvement of n‐3 and n‐6 fatty acids
Authors: Liu Jo‐Wen , Almaguel Frankis G. , Bu Liming , De Leon Daisy D. , De Leon Marino
Published: May 2008

Epidermal fatty acid‐binding protein (E‐FABP), a member of the family of FABPs, exhibits a robust expression in neurons during axonal growth in development and in nerve regeneration following nerve injury. This study examines the impact of E‐FABP expression in normal neurite extension in differentiating pheochromocytoma cell (PC12) cultures supplemented with selected long chain free fatty acids (LCFFA). We found that E‐FABP binds to a broad range of saturated and unsaturated LCFFAs, including those with potential interest for neuronal differentiation and axonal growth such as C22:6n‐3 docosahexaenoic acid (DHA), C20:5n‐3 eicosapentaenoic acid (EPA), and C20:4n‐6 arachidonic acid (ARA). PC12 cells exposed to nerve growth factor (NGFDPC12) exhibit high E‐FABP expression that is blocked by mitogen‐activated protein kinase kinase (MEK) inhibitor U0126. Nerve growth factor‐differentiated pheochromocytoma cells (NGFDPC12) antisense clones (NGFDPC12‐AS) which exhibit low E‐FABP expression have fewer/shorter neurites than cells transfected with vector only or NGFDPC12 sense cells (NGFDPC12‐S). Replenishing NGFDPC12‐AS cells with biotinylated recombinant E‐FABP (biotin‐E‐FABP) protein restores normal neurite outgrowth. Cellular localization of biotin‐E‐FABP in NGFDPC12 was detected mostly in the cytoplasm and in the nuclear region. Treatment of NGFDPC12 with DHA, EPA, or ARA further enhances neurite length but it does not trigger further induction of TrkA or MEK phosphorylation or E‐FABP mRNA observed in differentiating PC12 cells without LCFFA supplementation. Significantly, DHA and EPA neurite stimulating effects are higher in NGFDPC12‐S than in NGFDPC12‐AS cells. These findings are consistent with the scenario that neurite extension of differentiating PC12 cells, including further stimulation by DHA and EPA, requires sufficient cellular levels of E‐FABP.
Altered phosphorylation and localization of the A‐type channel, Kv4.2 in status epilepticus
Authors: Lugo Joaquin N. , Barnwell Lyndon Forbes , Ren Yajun , Lee Wai Ling , Johnston Lisa Danielle , Kim Rebecca , Hrachovy Richard A. , Sweatt John David , Anderson Anne E.
Published: May 2008

Extracelluar signal‐regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down‐regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho‐ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole‐cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A‐current, which could lead to altered intrinsic membrane excitability during SE.
Tyrosine hydroxylase activity is regulated by two distinct dopamine‐binding sites
Authors: Gordon Sarah L. , Quinsey Noelene S. , Dunkley Peter R. , Dickson Phillip W.
Published: May 2008

Tyrosine hydroxylase (TH), the rate‐limiting enzyme in the biosynthesis of the catecholamines dopamine, noradrenaline and adrenaline, is regulated acutely by feedback inhibition by the catecholamines and relief of this inhibition by phosphorylation of serine 40 (Ser40). Phosphorylation of serine 40 abolishes the binding of dopamine to a high affinity (KD < 4 nM) site on TH, thereby increasing the activity of the enzyme. We have found that TH also contains a second low affinity (KD = 90 nM) dopamine‐binding site, which is present in both the non‐phosphorylated and the Ser40‐phosphorylated forms of the enzyme. Binding of dopamine to the high‐affinity site decreases Vmax and increases the Km for the cofactor tetrahydrobiopterin, while binding of dopamine to the low‐affinity site regulates TH activity by increasing the Km for tetrahydrobiopterin. Kinetic analysis indicates that both sites are present in each of the four human TH isoforms. Dissociation of dopamine from the low‐affinity site increases TH activity 12‐fold for the non‐phosphorylated enzyme and 9‐fold for the Ser40‐phosphorylated enzyme. The low‐affinity dopamine‐binding site has the potential to be the primary mechanism responsible for the regulation of catecholamine synthesis under most conditions.
Expression of cyclooxygenase‐2 and peroxisome proliferator‐activated receptor gamma during malignant melanoma progression
Authors: Lee Carolyn , Ramirez James A. , Guitart Joan , Diaz Leslie K.
Published: June 2008

Background:  Cancer chemoprevention using nonsteroidal anti‐inflammatory drugs is frequently attributed to cyclooxygenase‐2 (COX‐2) inhibition, although recent studies suggest that peroxisome proliferator‐activated receptor gamma (PPARγ) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high‐risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX‐2 and PPARγ immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers.

Methods:  COX‐2 and PPARγ immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas.

Results:  There was a significant increase in both COX‐2 and PPARγ immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARγ‐immunopositive cells. They were also more likely to express COX‐2 than primary melanomas. Neither COX‐2 nor PPARγ expression was associated with a specific pathologic subtype.

Conclusions:  COX‐2 and PPARγ may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery.
Effect of high dose, repeated intra‐cerebrospinal fluid injection of sulphamidase on neuropathology in mucopolysaccharidosis type IIIA mice
Authors: Hemsley K. M. , Beard H. , King B. M. , Hopwood J. J.
Published: June 2008

Mucopolysaccharidosis type IIIA (MPS IIIA) is an inherited neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Reduced activity of sulphamidase (N‐sulphoglucosamine sulphohydrolase; SGSH; EC 3.10.1.1) results in intracellular accumulation of heparan sulphate (HS), with the brain as the primary site of pathology. We have used a naturally occurring MPS IIIA mouse model to determine the effectiveness of SGSH replacement through the cerebrospinal fluid (CSF) to decrease neuropathology. This is a potential therapeutic option for patients with this disorder. Mice received intra‐CSF injections of recombinant human SGSH (30, 50 or 70 μg) fortnightly from 6 to 18 weeks of age, and the cumulative effect on neuropathology was examined and quantified. Anti‐SGSH antibodies detected in plasma at euthanasia did not appear to impact upon the health of the mice or the experimental outcome, with significant but region‐dependent and dose‐dependent reductions in an HS‐derived oligosaccharide observed in the brain and spinal cord using tandem mass spectrometry. SGSH infusion reduced the number of storage inclusions observed in the brain when visualized using electron microscopy, and this correlated with a significant decrease in the immunohistochemical staining of a lysosomal membrane marker. Reduced numbers of activated isolectin B4‐positive microglia and glial fibrillary acidic protein‐positive astrocytes were seen in many, but not all, brain regions. Significant reductions in the number of ubiquitin‐positive intracellular inclusions were also observed. These outcomes show the effectiveness of this method of enzyme delivery in reducing the spectrum of neuropathological changes in murine MPS IIIA brain.
Intramedullary spinal cord tumors: Patterns of care in Victoria from 1998–2000
Authors: ROSENTHAL Mark A , ASHLEY David M , DRUMMOND Katharine , DALLY Michael , MURPHY Michael , CHER Lawrence , THURSFIELD Vicky , GILES Graham G
Published: June 2008

Aim:  This study describes the management of and outcomes for adult patients with newly diagnosed intramedullary spinal cord tumors during 1998–2000 in Victoria.

Methods:  The adult patients were identified in a retrospective cohort study conducted by surveying doctors involved in managing incident glioma cases identified from the population‐based Victorian Cancer Registry.

Results:  Sixteen patients were considered eligible for this review. Of these 15 (94%) had a histological diagnosis: an ependymoma was diagnosed in 13 patients (81%). A complete macroscopic resection was achieved in eight patients (50%). A variety of tumor types and grades were observed with surgery and radiotherapy the mainstays of therapy. One patient received chemotherapy (7%). One patient died from disease within six months of diagnosis. Of the remaining 15 patients, all were alive at 5 years and 10 (63%) remain disease free.

Conclusion:  This review documents characteristics of a rare condition and suggests that, overall, prognosis is excellent.
Unusual responses to thalidomide in refractory solid tumors
Authors: RANGARAJU Ranga Rao , ANIL Konnpal , VENNIYOOR Ajit , SINGH Harinder , RANJAN Subhash , KAPUR B
Published: June 2008

Despite the positive impact of newer chemotherapeutic agents on responses and survival in patients with solid tumors, challenges in recurrent and metastatic solid tumors include acquired drug resistance, poor responses and poor tolerance by the patient. Use of antiangiogenic agents appears to be a logical, rational and effective approach. Of these agents, thalidomide has shown to specifically inhibit endothelial cell growth in various experimental animals. The advantages of thalidomide include the convenience of the oral route of administration and low toxicity profile. Furthermore, thalidomide has been found to be effective in cancer cachexia syndrome, chronic nausea, insomnia, profuse sweating and pain, which are often part of advanced malignancies. In this case report of six patients, we present encouraging responses to thalidomide used in a dose of 200 mg in patients with refractory solid tumors.
Paraneoplastic encephalomyelitis associated with motor neuron disease causing respiratory failure in the setting of occult small cell lung carcinoma
Authors: SIVA Shankar , TALMAN Paul , BROAD Adam , NORDEN Sam
Published: June 2008

A 72‐year‐old female smoker presented with widespread wasting, fasciculation, rapidly evolving motor paralysis and respiratory failure. An initial chest X‐ray and thorax computed tomography (CT) failed to demonstrate any lung pathology. Serum Anti‐Hu antibodies were elevated. An occult small cell lung carcinoma and a paraneoplastic encephalomyelitis were detected at autopsy. Paraneoplastic encephalomyelitis associated motor neuron disease is an uncommon association with cryptic small cell carcinoma of the lung that carries poor prognosis. In addition, serum anti‐Hu antibodies are strongly associated with small cell carcinoma. We suggest in the clinical setting of anti‐Hu antibody associated paraneoplastic motor neuron disease that empirical chemotherapy directed against small cell carcinoma be considered.
Ten‐year trends and 20‐year projections of the incidence of lip and tongue cancer in Western Australia
Authors: KRUGER Estie , TENNANT Marc
Published: June 2008

Aim:  Lip and tongue cancer account for about 40 and 14%, respectively, of all oral cancers in Western Australia. The aim of this study is to report on the trends in incidence rates of lip and tongue cancer in Western Australia over the last ten years, and to generate incidence projections up to the year 2025.

Methods:  Incidence data for the current analysis were obtained from the Western Australian Cancer Registry for the period 1995 to 2004.

Results:  Two projection methods indicate an increase in the numbers and rates of lip and tongue cancer cases over the next 19 years, showing that the number of lip cancer patients will increase from 122 in 1995 to between 395 and 477 in 2025, and the number of tongue cancer patients will increase from 41 in 1995 to between 112 and 135 in 2025.

Conclusion:  The projections indicate there will be increasing rates of lip and tongue cancer in Western Australia, especially in older people. With an ageing population this implies significantly increased caseloads of the most common oral cancers and planning future resource allocation should be considered.
EFFECT OF YAM VARIETY ON THE PASTING PROPERTIES AND SENSORY ATTRIBUTES OF TRADITIONAL DRY‐YAM AND ITS PRODUCTS
Authors: BABAJIDE J.M. , HENSHAW F.O. , OYEWOLE O.B.
Published: June 2008

Six varieties of yam were processed into traditional dry‐yam slices. The pasting properties and sensory attributes of dry‐yam samples, flour and paste from the flour were investigated. Significant differences (P ≤ 0.05) were observed in the pasting properties of flour from different yam varieties. “Ijedo,” the commonly used variety, had the highest peak, trough and final viscosities. There was no significant difference in the viscosities of “Efuru” (206.04 rapid viscosity analyzer), “Ise‐Osi” (242.75 rapid viscosity unit [RVU]) and “Abuja” (241.25 RVU) varieties. Samples of dry yam made from “Efuru,”“Ise‐Osi” and “Abuja” yams were not significantly different (P > 0.05) from “Ijedo” in terms of instrumental color measurement, as their degree of brownness (100 − L*) were 21.53, 19.21, 20.87 and 22.42, respectively. There was no significant difference (P > 0.05) in color, taste and moldability of the paste made from “Efuru,”“Ise‐Osi,”“Ijedo” and “Abuja” yams. There was no significant difference (P > 0.05) between the hardness of dry yams made from “Ise‐Osi,”“Ijedo” and “Abuja.” There were positive correlations between the yam paste moldability, peak, trough and final viscosities for the different yam varieties. “Ise‐Osi,”“Efuru” and “Abuja” varieties were found to be suitable for dry‐yam processing in terms of sensory property and pasting of dry‐yam slices and their products, which were not significantly different from those of “Ijedo” variety – the commonly used yam.

PRACTICAL APPLICATIONS

The study revealed that dry‐yam processors and potential dry‐yam processors in Nigeria can use other white yam varieties, such as “Abuja,”“Ise‐Osi” and “Efuru,” apart from “Ijedo” variety – the commonly used yam variety. These yam varieties were also acceptable in terms of the sensory and pasting properties of dry‐yam slices and their products. Thus, the general knowledge that white yams are good for dry‐yam processing has been scientifically verified.
SENSORY ATTRIBUTES AND ANTIOXIDANT CAPACITY OF SPANISH HONEYS
Authors: GONZÁLEZ LORENTE MONTSERRAT , DE LORENZO CARRETERO CRISTINA , PÉREZ MARTÍN ROSA ANA
Published: June 2008

Twenty‐two honey samples from Spain have been assayed in relation to (1) their sensory and physicochemical characteristics; and (2) their radical‐scavenging capacity against the stable free radical DPPH. Sensory analysis has been carried out by means of descriptive profiling with a trained panel. In previous studies, a strong correlation of the physicochemical parameters, (1) net absorbance and (2) electrical conductivity, was observed, with the radical‐scavenging capacity. Interestingly, some correlations were also observed between the mentioned radical‐scavenging capacity and some sensory parameters. Statistical analysis showed that sensory parameters of bitterness and color were directly correlated with the honey antioxidant capacity, whereas the parameters sweetness and crystallization degree were negatively correlated. In terms of sensory appreciation, bitterness and dark color are sensory parameters indicative of the honey scavenging capacity, which is greater in dark honeys, mainly honeydews.

PRACTICAL APPLICATIONS

The main weight of this work is devoted to the sensory analysis of honeys by the use of objective scales, and to study the relation between these appreciations with the antioxidant properties of artisanal honeys. The main practical application is to improve the knowledge of the consumer about honey, its characteristics and properties, in order to provide criteria for selection. The direct correlation established between some sensory parameters and the antioxidant capacity of honey may enable the consumer to have an idea about the antioxidant capacity of the product. So, the intake of darker and less sweet honeys, which have higher antioxidant activities, in combination with other natural and better‐known foodstuffs rich in antioxidants (fruit, vegetables, olive oil, red wine, among others), can be introduced in the frame of an adequate diet.
3D Reconstruction from temporal bone histological sections – is it now possible?
Authors: Ahmad N. , Tan A.C. , Gardner A. , Wright A.
Published: June 2008

Objectives.  Current 3D temporal bone models have either lacked the resolution (if volume‐rendered from imaging)1 or lacked the interactivity (if surface‐rendered from sections)2 necessary for surgical training. The objective was to produce a 3D volume‐rendered temporal bone model from serial sections.

Method.  High resolution images were acquired from serial histological sections of the temporal bone using a Canon SLR digital 8‐megapixel camera. Image registration was performed by aligning in Adobe Photoshop on a PC with a 256 Mb graphics card. Segmentation of surgically relevant anatomical structures was performed followed by 3D volumetric reconstruction. The model was finally checked for anatomical accuracy and interactivity by practicing otologists.

Results.  An anatomically accurate, high resolution 3D volume‐rendered model of the temporal bone was produced, containing many of the surgically relevant structures the otologist may come across during surgery. The course of the facial nerve, the labyrinth, internal carotid artery, jugular vein and all the ossicles where visualised (including the stapes footplate) along with the internal and external auditory meati and even the chorda tympani nerve in some projections. The model was interactive with the ability to rotate it in any plane, zoom into areas of interest and ‘cut’ volume to reveal underlying structures.

Conclusions.  To the best of our knowledge, this is the world's first 3D volume‐rendered model of the temporal bone from histological sections. At a time of difficulty in procuring cadaveric bones, this model could be a major aid to improving the future training of surgeons performing procedures on the temporal bone.

References.  1 Wiet G.J., Schmalbrock P., Powell K. & Stredney D. (2005) Use of ultra‐high‐resolution data for temporal bone dissection simulation. Otolaryngol. Head Neck Surg. 133, 911–915

2 Mason T.P., Applebaum E.L., Rasmussen M., Millman A., Evenhouse R. & Panko W. (2000) Virtual temporal bone: creation and application of a new computer‐based teaching tool. Otolaryngol. Head Neck Surg. 122, 168–173
Endoscopic dewaxing in primary care – a replacement for syringing?
Authors: Pothier D.D.
Published: June 2008

Objectives.  To investigate the feasibility and effectiveness of endoscopic dewaxing1 in primary care as a replacement for syringing or irrigation of the external auditory meatus.

Method.  Case control pilot study. Seven practice nurses from General Practices in the Wiltshire area completed a training course in the technique of endoscopic dewaxing. After training the group dewaxed 100 sequential ears using irrigation followed by 100 ears using endoscopic dewaxing. Data on patient feedback, time and difficulty were recorded. To account for the learning curve associated with the technique, the endoscopically dewaxed ears were analysed in two groups, the first 50 performed and the last 50 performed by the nurses.

Results.  There was no significant in difference in pain or satisfaction scores between the first 50 endoscopic dewaxes and irrigation (P = 0.21, P = 0.31). The level of satisfaction with the second group of endoscopic dewaxes was 95.5 (sd = 42.7) compared to irrigation at 65.5 (sd = 28.9) (P < 0.001). The mean time take to perform irrigation was 10.8 min, very similar to both groups of endoscopic dewaxing (11.8 min and 10.3 min respectively, P = 0.3)

Conclusions.  Endoscopic dewaxing can be successfully introduced into primary care and represents a technique performed under direct vision. It takes a similar length of time and is associated with greater patient satisfaction. It can be effectively performed without prior wax softening and is likely to be safer than irrigation, particularly where there is undiagnosed tympanic membrane pathology.

Reference.  1 Pothier D.D. (2006) How we do it: technical note: endoscopic removal of cerumen. Clin. Otolaryngol. 31, 153–155