bluuebunny/crossref_metadata_2025 huggingface dataset:
Neospora caninum and bone marrow‐derived dendritic cells: parasite survival, proliferation, and induction of cytokine expression
Authors: STROHBUSCH M. , MÜLLER N. , HEMPHILL A. , MARGOS M. , GRANDGIRARD D. , LEIB S. , GREIF G. , GOTTSTEIN B.
Published: March 2009

Dendritic cells (DCs) represent the first line defence of the innate immune system following infection with pathogens. We exploratively addressed invasion and survival ability of Neospora caninum, a parasite causing abortion in cattle, in mouse bone marrow DCs (BMDCs), and respective cytokine expression patterns. Immature BMDCs were exposed to viable (untreated) and nonviable parasites that had been inactivated by different means. Invasion and/or internalization, as well as intracellular survival and proliferation of tachyzoites were determined by NcGRA2‐RT‐PCR and transmission electron microscopy (TEM). Cytokine expression was evaluated by reverse transcription (RT)‐PCR and cytokine ELISA. Transmission electron microscopy of DCs stimulated with untreated viable parasites revealed that N. caninum was able to invade and proliferate within BMDCs. This was confirmed by NcGRA2‐RT‐PCR. On the other hand, no viable parasite organisms were revealed by TEM when exposing BMDCs to inactivated parasites (nonviability demonstrated by NcGRA2‐RT‐PCR). Cytokine expression analysis (as assessed by both RT‐PCR and ELISA) demonstrated that both viable and nonviable parasites stimulated mBMDCs to express IL‐12p40, IL‐10 and TNF‐α, whereas IL‐4 RNA expression was not detected. Thus, exposure of mBMDCs to both viable and nonviable parasites results in the expression of cytokines that are relevant for a mixed Th1/Th2 immune response.
Randomized trial to compare the dosage of darbepoetin alfa by administration route in haemodialysis patients
Authors: KIM CHAN‐DUCK , PARK SUN‐HEE , KIM DAE‐JOONG , PARK JONG‐WON , DO JUN‐YOUNG , SHIN SUK‐KYUN , KIM BEOM‐SEOK , SEO JUNG‐JU , KIM YONG‐LIM
Published: March 2009

Aim:  The doses of darbepoetin alfa required to maintain target haemoglobin levels after s.c. or i.v. administration when recombinant human erythropoietin (rHuEpo) treatment was replaced by darbepoetin alfa treatment in haemodialysis (HD) patients were compared.

Methods:  In this prospective, randomized, open‐label study, 65 HD patients who were receiving stable SC doses of rHuEpo were switched to an equivalent dose of darbepoetin alfa at a reduced frequency by s.c. or i.v. administration. Patients were randomly assigned to the s.c. group (n = 32) or the i.v. group (n = 33). Darbepoetin alfa doses were titrated to maintain target haemoglobin levels of 8.0–11.0 g/dL for up to 24 weeks. A period of 20 weeks was used for dose titration and haemoglobin stabilization. This was followed by a 4 week evaluation period.

Results:  The mean haemoglobin concentration during the evaluation period was similar in the s.c. and i.v. groups. The mean dose and mean weight‐standardized dose of darbepoetin alfa during the evaluation period tended to be lower in the s.c. group than the i.v. group, although these differences were not statistically significant. The mean weekly darbepoetin alfa dose requirements during the evaluation period significantly decreased in both groups compared to the dose requirements at randomization.

Conclusion:  There is a possibility that s.c. administration of darbepoetin alfa is more efficacious than i.v. administration, but a definite benefit cannot be demonstrated with the current sample size. A bigger sample size is needed to confirm the result.
Potential for erythropoietin synthesis in kidney of uraemic rat alters depending on severity of renal failure
Authors: SANADA SATORU , TOYAMA HIROAKI , EJIMA YUTAKA , MATSUBARA MITSUNOBU
Published: March 2009

Aim:  Renal anaemia is a common early complication of chronic renal failure (CRF) that is characterized by relative erythropoietin (EPO) deficiency. Although a lowered renal function is considered to induce limited EPO production, potential EPO production capacity in CRF remains unclear. The aim of this study was to determine the mechanisms underlying this relative deficiency.

Methods:  Male Sprague–Dawley rats were underwent 5/6 nephrectomy with different severities of CRF. These rats were assigned to two groups – mild CRF or advanced CRF – and subjected to haemodilution by exchange of blood with Ringer's solution or haemoconcentration by blood transfusion. Serum EPO and EPO transcript levels in remnant kidney were examined. Expression levels of hypoxia‐related genes, including heme oxygenase‐1 (HO‐1) and glucose transporter‐1 (Glut‐1), were also examined.

Results:  Haemodilution increased both serum EPO and EPO transcript levels in mild CRF, as observed in sham‐operated controls, whereas the extents of such increases were significantly smaller in advanced CRF. HO‐1 and Glut‐1 transcript levels also increased by haemodilution in mild CRF, but not in advanced CRF. Haemoconcentration markedly decreased serum EPO and EPO transcript levels in mild CRF as in controls. Rats with advanced CRF did not survive after blood transfusion.

Conclusion:  Potential EPO regulation capacity in mild CRF is as conserved as that in normal control, whereas that in advanced CRF is impaired, suggesting that underlying mechanisms of low EPO production alters according to the stage of CRF.
Review article: Early detection of chronic kidney disease in Australia: Which way to go?
Authors: MATHEW TIMOTHY , CORSO OLIVIA
Published: March 2009

Early detection of chronic kidney disease (CKD) followed by appropriate clinical management appears the only means by which the increasing burden on the health‐care system and affected individuals will be reduced. The asymptomatic nature of CKD means that early detection can only occur through testing of individuals. The World Health Organization principles of screening for chronic disease can now be largely fulfilled for CKD. The risk groups to be targeted, the expected yield and the tests to be performed are reviewed. For a screening programme to be sustainable it must carry a greater benefit than risk of harm for the participant and be shown to be cost‐effective from the community point of view. Whole population screening for CKD is impractical and is not cost‐effective. Screening of those at increased risk of CKD could occur either through special events run in the community, workplace or in selected locations such as pharmacies or through opportunistic screening of high‐risk people in general practice. Community screening programmes targeted at known diabetics, hypertensives and those over 55 years have been described to detect 93% of all CKD in the community. The yield of CKD stages 3–5 from community screening has been found to vary from 10% to 20%. The limitations of screening programmes including the cost and recruitment bias are discussed. The most sustainable and likely the most cost‐efficient model appears to be opportunistic general practice screening. The changing structure of general practice in Australia lends itself well to the requirements for early detection of CKD.
Diagnostic accuracy of blood qualitative nucleic acid testing for polyomavirus‐associated nephropathy in kidney recipients
Authors: CROSS NICHOLAS B , WEBSTER ANGELA C , O'CONNELL PHILIP J , JEOFFREYS NEISHA , DWYER DOMINIC E , CRAIG JONATHAN C
Published: March 2009

Aim:  Polyomavirus‐associated nephropathy (PVAN) is an important cause of graft loss following kidney transplantation and may only be diagnosed with kidney transplant biopsy. Early detection may improve outcomes by enabling early intervention. Serum polyomavirus polymerase chain reaction (PVPCR) has been used to identify patients at risk of PVAN, but prior studies have not assessed all patients with negative PVPCR with transplant biopsy, potentially overestimating test performance.

Methods:  We assessed the diagnostic accuracy of qualitative PVPCR for detection of PVAN in a population undergoing protocol biopsies. We included all patients receiving kidney or kidney‐pancreas transplants and followed at Westmead Hospital, Sydney, Australia, between May 2002 and March 2007, excluding those with graft loss prior to 1 month post transplant or without PVPCR testing in the first 12 months. We compared PVPCR to contemporaneous transplant biopsies assessed with light microscopy and immunohistochemistry.

Results:  Of the 257 included patients, 246 (96%) underwent biopsy within 30 days of PVPCR. Eight of 36 patients with positive PVPCR had PVAN and one of 210 patients with negative PVPCR had PVAN. The point prevalence of PVAN was therefore 3.7%, with PVPCR sensitivity 89% (95% CI 57% to 99%) and specificity 88% (95% CI 83% to 92%). The negative predictive value is 99.5% (95% CI 97.3% to 100.0%).

Conclusion:  Qualitative PVPCR on serum is a reliable triage test for excluding the presence of PVAN. Screening for PVAN need not include biopsy in patients with negative PVPCR.
Serum phosphate is an important determinant of corrected serum calcium in end‐stage kidney disease
Authors: FERRARI PAOLO , SINGER RICHARD , AGARWAL AANCHAL , HURN ANNE , TOWNSEND MARY A , CHUBB PAUL
Published: March 2009

Background:  Approximately 12% of bound blood calcium is linked to various anions including phosphate. In patients with end‐stage kidney disease (ESKD), serum phosphate is highly variable. We propose that establishing a formula to calculate albumin‐ and phosphate‐corrected total calcium would be more appropriate to estimate free calcium in ESKD patients.

Methods:  In 82 haemodialysis patients, serum ionized calcium (Caion) and pH were measured by blood gas analyser with ion‐selective electrodes at the point‐of‐care, while bicarbonate, phosphate, albumin, magnesium and total calcium (Catot) were measured at the central laboratory. Linear regression analysis of measured variables was used to best fit adjusted calcium versus Caion.

Results:  The most parsimonious multiple linear regression model (r2 = 0.81) of variables associated with Caion included Catot (coeff 0.820, P < 0.0001), albumin (coeff −0.016, P < 0.0001) and phosphate (coeff −0.063, P < 0.002). Modelling of available variables yielded the following equation to adjust calcium for albumin and phosphate: CaalbPh = Catot + (0.015 × (40 − [albumin]) + 0.07 × (1.5 − [phosphate])). At an ambient albumin of 40 g/L, CaalbPh would be 0.07 mmol/L lower than Catot for every mmol/L of phosphate. In vitro data using three different albumin levels and increasing phosphate concentrations demonstrated this relationship, with the slope of the phosphate effect being stronger at lower albumin concentrations.

Conclusion:  Because guidelines recommendations indicate that corrected serum calcium should be maintained within the normal range in ESKD patients, inclusion of phosphate to correct Catot in these patients may have clinical implications on the choice of phosphate binders and the prescription of vitamin D or calcimimetic agents.
Left ventricular function by ‘conventional’ and ‘tissue Doppler’ echocardiography in paediatric dialysis patients
Authors: CIVILIBAL MAHMUT , CALISKAN SALIM , OFLAZ HUSEYIN , SEVER LALE , CANDAN CENGİZ , CANPOLAT NUR , KASAPCOPUR OZGUR , ARISOY NIL
Published: March 2009

Aim:  Cardiovascular abnormalities are common in children with chronic kidney disease (CKD). Left ventricular (LV) structure and functions have been extensively studied by conventional pulse‐wave Doppler echocardiography (cPWD), however, tissue Doppler imaging (TDI) is a relatively new echocardiography method. The aims of this study were to evaluate LV diastolic function in paediatric dialysis patients using cPWD and TDI methods, and to compare the findings obtained with two modalities.

Methods:  This study included 38 children and adolescents on dialysis (14 haemodialysis and 24 peritoneal dialysis, duration of dialysis 58.0 ± 32.8 months) and 16 age‐ and sex‐matched healthy subjects.

Results:  The mean left ventricular mass index (LVMI) was significantly higher in the patient group (P < 0.001) and the most common cardiac geometry was concentric LV hypertrophy (55%). There was no significant difference in LV systolic function between patient and control groups. However, dialysis patients had worse LV diastolic function both according to cPWD (lower E/A ratio) and TDI (lower Em/Am ratio) than the healthy subjects (P < 0.001 and P = 0.001, respectively). Also, the index of LV filling pressure (E/Em ratio) obtained by the combination of cPWD and TDI was significantly higher in the patients (P < 0.001). Cumulative dose of calcium‐based phosphate binder (CBPB), diastolic blood pressure and LVMI were the independent predictors of E/Em ratio.

Conclusion:  Our study shows that LV diastolic dysfunction is common in paediatric dialysis patients and TDI findings correlate well with cPWD findings. Similarly, higher dose intake of CBPB, hypertension and LV hypertrophy have a negative effect on LV filling pressure suggesting diastolic function.
Cardio‐selective and non‐selective beta‐blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise
Authors: Chang C. L. , Mills G. D. , McLachlan J. D. , Karalus N. C. , Hancox R. J.
Published: March 2009

Background: Patients with chronic obstructive pulmonary disease (COPD) often have co‐existing cardiovascular disease and may require beta‐blocker treatment. There are limited data on the effects of beta‐blockers on the response to inhaled β2‐agonists and exercise capacity in patients with COPD.

Objective: To determine the effects of different doses of cardio‐selective and non‐selective beta‐blockers on the acute bronchodilator response to beta‐agonists in COPD, and to assess their effects on exercise capacity.

Methods: A double‐blind, randomized, three‐way cross‐over (metoprolol 95 mg, propranolol 80 mg, placebo) study with a final open‐label high‐dose arm (metoprolol 190 mg). After 1 week of each treatment, the bronchodilator response to salbutamol was measured after first inducing bronchoconstriction using methacholine. Exercise capacity was assessed using the incremental shuttle walk test.

Results: Eleven patients with moderate COPD were recruited. Treatments were well‐tolerated although two did not participate in the high‐dose metoprolol phase. The area under the salbutamol–response curve was lower after propranolol compared with placebo (P = 0.0006). The area under the curve also tended to be lower after high‐dose metoprolol (P = 0.076). The per cent recovery of the methacholine‐induced fall was also lower after high‐dose metoprolol (P = 0.0018). Low‐dose metoprolol did not alter the bronchodilator response. Oxygen saturation at peak exercise was lower with all beta‐blocker treatments (P = 0.046).

Conclusion: Non‐selective beta‐blockers and high doses of cardio‐selective beta‐blockers may inhibit the bronchodilator response to β2‐agonists in patients with COPD. Beta‐blockers were also associated with lower oxygen saturation during exercise. The clinical significance of these adverse effects is uncertain in view of the benefits of beta‐blocker treatment for cardiovascular disease.
Biodiversity maintenance mechanisms differ between native and novel exotic‐dominated communities
Authors: Wilsey Brian J. , Teaschner Terri B. , Daneshgar Pedram P. , Isbell Forest I. , Polley H. Wayne
Published: March 2009

In many systems, native communities are being replaced by novel exotic‐dominated ones. We experimentally compared species diversity decline between nine‐species grassland communities under field conditions to test whether diversity maintenance mechanisms differed between communities containing all exotic or all native species using a pool of 40 species. Aboveground biomass was greater in exotic than native plots, and this difference was larger in mixtures than in monocultures. Species diversity declined more in exotic than native communities and declines were explained by different mechanisms. In exotic communities, overyielding species had high biomass in monoculture and diversity declined linearly as this selection effect increased. In native communities, however, overyielding species had low biomass in monoculture and there was no relationship between the selection effect and diversity decline. This suggests that, for this system, yielding behaviour is fundamentally different between presumably co‐evolved natives and coevolutionarily naive exotic species, and that native‐exotic status is important to consider.
Biodiversity, productivity and the temporal stability of productivity: patterns and processes
Authors: Isbell Forest I. , Polley H. Wayne , Wilsey Brian J.
Published: March 2009

Theory predicts that the temporal stability of productivity, measured as the ratio of the mean to the standard deviation of community biomass, increases with species richness and evenness. We used experimental species mixtures of grassland plants to test this hypothesis and identified the mechanisms involved. Additionally, we tested whether biodiversity, productivity and temporal stability were similarly influenced by particular types of species interactions. We found that productivity was less variable among years in plots planted with more species. Temporal stability did not depend on whether the species were planted equally abundant (high evenness) or not (realistically low evenness). Greater richness increased temporal stability by increasing overyielding, asynchrony of species fluctuations and statistical averaging. Species interactions that favoured unproductive species increased both biodiversity and temporal stability. Species interactions that resulted in niche partitioning or facilitation increased both productivity and temporal stability. Thus, species interactions can promote biodiversity and ecosystem services.
External Imbalances and the US Current Account: How Supply‐Side Changes Affect an Exchange Rate Adjustment*
Authors: Engler Philipp , Fidora Michael , Thimann Christian
Published: March 2009

The influential work of Obstfeld and Rogoff argues that a closing‐up of the US current account deficit involves a large exchange rate adjustment. However, the Obstfeld–Rogoff model works exclusively via demand‐side channels and abstracts from possible supply‐side changes. We extend the framework to allow for endogenous supply‐side changes and show that this fundamentally alters the mechanism of the adjustment process. Allowing for such an extension attenuates quite significantly the implied exchange rate adjustment. The paper also provides some empirical evidence of variations in the supply‐side structure and correlations with the exchange rate and the current account. The policy implications are that measures to foster a supply‐side reaction would facilitate the external adjustment by alleviating an exclusive reliance on demand and exchange rate changes, with the latter being potentially destabilizing for the global financial system.
Tariff Elimination and the Wage Gap in an Industrial Specific Factors Model*
Authors: Thompson Henry , Francis John
Published: March 2009

A specific factors model of 458 US manufacturing industries simulates the effects of eliminating manufacturing tariffs on unskilled and skilled wages. The model assumes constant elasticity substitution, industry‐specific capital inputs, and mobile unskilled and skilled labor. Tariff elimination slightly lowers both unskilled and skilled wages, and increases the skilled wage gap. Industry outputs and capital returns absorb the negative impact of the falling tariffs with losses concentrated in more highly protected industries and most industries enjoying small positive outcomes.
Gains from Trade in a Differential Game Model of Asymmetric Oligopoly
Authors: Fujiwara Kenji
Published: March 2009

This paper revisits a classical topic of trade gains in a differential game model of oligopoly in which Home and Foreign firms differ in the number and cost. After deriving the feedback Nash equilibrium, we provide examples to consider how the difference in the number of firms or costs affects gainfulness of trade. We prove that feedback strategies can result in implications for trade gains which are sharply different from the open‐loop case.
The significance of organizational factors for the incidence of bullying
Authors: AGERVOLD MOGENS
Published: March 2009

It is frequently assumed that a poor psychosocial working environment will create conditions that encourage bullying. However, few studies have examined this assumption while comparing work environment ratings of bullied and non‐bullied employees who work in the same organization and/or department. The objective of this study was to examine the relationship between organizational factors and the incidence of acts of bullying based on two different approaches: the first by comparing bullied with no‐bullied, the second by comparing departments with widespread bulling with departments with little bulling. The study was a part of a general survey study of the work environment and employee well‐being in 12 different local social security offices. A total of 898 persons participated in the study (a response rate of 88%).

First, the results showed a clear relationship between bullying and fear of organizational change; secondly, weak, but significant, correlations between bullying and other organizational factors; thirdly, the subsequent analyses compared departments in which bullying were most widespread with the rest of the departments. The results supported the hypothesis that departments that suffer from much bullying also have a poorer psychosocial work environment, results that support the assumption that organizational factors such as changes in one's position, pressure of work, performance demands, autocratic management and role conflict and lack of role clarity, as well as a poor social climate can contribute to the emergence of higher incidences of bullying.
Military leaders and followers – do they have different decision styles?
Authors: THUNHOLM PETER
Published: March 2009

There are five different, although not mutually exclusive, styles exhibited by military officers when making decisions: rational, intuitive, dependent, avoidant, and spontaneous (Scott & Bruce, 1995). The purpose was to investigate if elected leaders of military planning teams had a different configuration of decision‐making styles than their team members. Participants were 98 army captains organized in 16 brigade‐level planning teams. The results indicate that team leaders tended to be more spontaneous and less rational, dependent and avoidant in their style configuration than their team members. One possible explanation is that the style configuration exhibited by many of the elected leaders comes through to others as forcefulness and decisiveness and that such a profile is in line with a general leadership culture. The results also provide support for the General Decision‐Making Style inventory as a measurement of decision styles, because they suggest that the self‐reports coincide with displayed, observable behavior.
Welfare State, Gender, and Reconciliation of Work and Family in Poland: Policy Developments and Practice in a New EU Member
Authors: Plomien Ania
Published: March 2009

In the context of welfare state change and European Union and national debates on activation, this article engages in a systematic analysis of the reconciliation of work and family policies in Poland, and their implications regarding the gendered division of labour. Examination of three areas of reconciliation, that is, childcare services, maternity and parental leaves, and parent‐friendly organization of work, reveals strong tensions between the unpaid labour of care and paid market labour. Reconciliation of work and family appears challenging for mothers and fathers alike, but the nature of the problem differs – women face greater obstacles to paid employment and men to involvement in family and care. Assessed against EU prescriptions in this area, Poland's performance is mixed. Based on policy developments and practice, Poland is far from achieving Barcelona targets for the provision of childcare services, it complies with EU regulations on maternity and parental leave arrangements but also compares unfavourably with the member states which provide special arrangements for fathers, and, finally, lags behind employment goals and parent‐friendly organization of work. Although participation in the Lisbon Strategy has proved important for raising the visibility of the reconciliation of work and family policies on the national political agenda, recent policy reforms have been either inconsistent or too modest in light of EU policy goals. Therefore, it is too soon to argue that parents’ ability to reconcile work and care has improved or that greater equality in the gendered division of labour has been attained.
Neo‐liberalism by Decay? The Evolution of the Czech Welfare State
Authors: Saxonberg Steven , Sirovátka Tomáš
Published: March 2009

In this article we analyse the evolution of the Czech welfare state and we examine the factors explaining its path. We show that although the Czech welfare regime exhibits a ‘mixed profile’ that includes conservative and universalist elements, it is increasingly moving in a more liberal, residualist direction – not because of conscious steps but rather through decay. Governments have often zig‐zagged in their policies and resorted to symbolic reforms at times rather than implementing ideologically based, consistent policies. We argue that historical and sociological institutionalism combined with a social‐capital approach can explain this decay better than the more common arguments about economic pressures combined with ideological hegemony or the protest‐avoidance strategy. In particular, the social capital approach adds to our institutional framework by explaining why cutbacks in welfare programmes have not met much opposition, even though public opinion surveys consistently show support for more generous welfare policies, and why policies have deviated so much from political rhetoric.
Modern Statistics: The Myth and the Magic
Authors: Hand David J.
Published: March 2009

The paper is a personal exploration of the puzzling contradiction between the fundamental excitement of statistics and its poor public image. It begins with the historical foundations and proceeds through the role of applications and the dramatic impact of the computer in shaping the discipline. The mismatch between the reality of statistics and its public perception arises from a number of dichotomies, some of which are explored. In particular, although statistics is perhaps typically seen as an impersonal discipline, in some sense it is very personal, and many of its applications are aimed at providing unique benefit to individuals. This benefit depends on the creation of detailed data sets describing individuals, but the contrary view is that this represents an invasion of privacy. Some observations on statistical education are made, and issues which will affect the future health of the discipline are examined.
Rapid constitutive and ligand‐activated endocytic trafficking of P2X3 receptor
Authors: Vacca Fabrizio , Giustizieri Michela , Ciotti Maria Teresa , Mercuri Nicola Biagio , Volonté Cinzia
Published: March 2009

P2X receptors mediate a variety of physiological actions, including smooth muscle contraction, neuro‐endocrine secretion and synaptic transmission. Among P2X receptors, the P2X3 subtype is expressed in sensory neurons of dorsal root‐ and trigeminal‐ganglia, where it performs a well‐recognized role in sensory and pain transmission. Recent evidence indicates that the strength of P2X3‐mediated responses is modulated in vivo by altering the number of receptors at the plasma membrane. In the present study, we investigate the trafficking properties of P2X3 receptor in transfected HEK293 cells and in primary cultures of dorsal root ganglion neurons, finding that P2X3 receptor undergoes rapid constitutive and cholesterol‐dependent endocytosis. We also show that endocytosis is accompanied by preferential targeting of the receptor to late endosomes/lysosomes, with subsequent degradation. Furthermore, we observe that at steady state the receptor localizes predominantly in lamp1‐positive intracellular structures, with a minor fraction present at the plasma membrane. Finally, the level of functional receptor expressed on the cell surface is rapidly up‐regulated in response to agonist stimulation, which also augments receptor endocytosis. The findings presented in this work underscore a very dynamic trafficking behavior of P2X3 receptor and disclose a possible mechanism for the rapid modulation of ATP‐mediated responses potentially relevant during physiological and pathological conditions.
Activation of dopamine D1 receptors blocks phencyclidine‐induced neurotoxicity by enhancing N‐methyl‐D‐aspartate receptor‐mediated synaptic strength
Authors: Lei Gang , Anastasio Noelle C. , Fu Yu , Neugebauer Volker , Johnson Kenneth M.
Published: March 2009

Early postnatal blockade of NMDA receptors by phencyclidine (PCP) causes cortical apoptosis in animals. This is associated with the development of schizophrenia‐like behaviors in rats later in life. Recent studies show that the mechanism involves a loss of neurotrophic support from the phosphoinositol‐3 kinase/Akt pathway, which is normally maintained by synaptic NMDA receptor activation. Here we report that activation of dopamine D1 receptors (D1R) with dihydrexidine (DHX) prevents PCP‐induced neurotoxicity in cortical neurons by enhancing the efficacy of NMDAergic synapses. DHX increases serine phosphorylation of the NR1 subunit through protein kinase A activation and tyrosine phosphorylation of the NR2B subunit via Src kinase. DHX enhances recruitment of NR1 and NR2B, but not NR2A, into synapses. DHX also facilitated the synaptic response in cortical slices and this was blocked by an NR2B antagonist. DHX pre‐treatment of rat pups prior to PCP on postnatal days 7, 9 and 11 inhibited PCP‐induced caspase‐3 activation on PN11 and deficits in pre‐pulse inhibition of acoustic startle measured on PN 26‐28. In summary, these data demonstrate that PCP‐induced deficits in NMDA receptor function, neurotoxicity and subsequent behavioral deficits may be prevented by D1R activation in the cortex and further, it is suggested that D1R activation may be beneficial in treating schizophrenia.
Slow release properties and liver‐targeting characteristics of methotrexate erythrocyte carriers
Authors: Yuan Sheng‐Hua , Ge Wei‐Hong , Huo Jing , Wang Xiao‐Hai
Published: March 2009

To study the releasing properties and tissue‐targeting characteristics of methotrexate‐loaded red blood cells (MTX‐RBCs), pharmacokinetics and tissue distributions of intravenous injected MTX‐RBCs and free MTX were compared. MTX‐RBCs were made from rat erythrocytes using a hypertonic method. After i.v. injection of MTX‐RBCs or free MTX to rats, both plasma and tissue homogenate samples at each time‐point were collected and analyzed by RP‐HPLC. From this data, pharmacokinetic parameters and tissue distributions of MTX were obtained. MTX‐RBCs were successfully produced by the hypertonic method. After i.v. injection, MTX‐RBCs displayed more than three times longer half‐life and MRT than free MTX, and the velocity of MTX clearance from plasma was much slower. The ratio of area under the concentration time curve (AUC)tissue to AUCplasma in the liver was clearly higher than that for other organs after MTX‐RBCs administration; MRT in the liver was also longer. This study has demonstrated that the hypertonic method for making MTX‐RBCs has led to a preparation with slow release properties as well as liver‐targeting characteristics in rats. This approach offers considerable potential for the treatment of tumors in liver, which would merit further investigation.
Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in mice
Authors: Susa Denis , Mitchell James R. , Verweij Marielle , Van De Ven Marieke , Roest Henk , Van Den Engel Sandra , Bajema Ingeborg , Mangundap Kirsten , IJzermans Jan N. M. , Hoeijmakers Jan H. J. , De Bruin Ron W. F.
Published: March 2009

Cockayne syndrome and other segmental progerias with inborn defects in DNA repair mechanisms are thought to be due in part to hypersensitivity to endogenous oxidative DNA damage. The accelerated aging‐like symptoms of this disorder include dysmyelination within the central nervous system, progressive sensineuronal hearing loss and retinal degeneration. We tested the effects of congenital nucleotide excision DNA repair deficiency on acute oxidative stress sensitivity in vivo. Surprisingly, we found mouse models of Cockayne syndrome less susceptible than wild type animals to surgically induced renal ischemia reperfusion injury, a multifactorial injury mediated in part by oxidative damage. Renal failure‐related mortality was significantly reduced in Csb−/– mice, kidney function was improved and proliferation was significantly higher in the regenerative phase following ischemic injury. Protection from ischemic damage correlated with improved baseline glucose tolerance and insulin sensitivity and a reduced inflammatory response following injury. Protection was further associated with genetic ablation of a different Cockayne syndrome‐associated gene, Csa. Our data provide the first functional in vivo evidence that congenital DNA repair deficiency can induce protection from acute stress in at least one organ. This suggests that while specific types of unrepaired endogenous DNA damage may lead to detrimental effects in certain tissues, they may at the same time elicit beneficial adaptive changes in others and thus contribute to the tissue specificity of disease symptoms.
Recent Studies of African History in Japan
Authors: Philips John Edward
Published: March 2009

African history in Japan is a tiny part of the total output of history in Japan. It is difficult to categorize within the traditional divisions of history in Japan, and it is somewhat of an orphan, although it has been recognized as a subfield. Sub‐Saharan Africa in precolonial times is considered the domain of anthropology, not history, despite the fact that Japanese archeology is considered history rather than anthropology. Most historical works concerning sub‐Saharan Africa in Japan are concerned with colonialism and/or economic history, although such recent trends as subaltern studies and gender studies have also had an impact. The traditional history of North Africa and Northern, Semitic Ethiopia is also considered history in Japan.
Correlation between BNP Levels and Doppler Echocardiographic Parameters of Left Ventricle Filling Pressure in Patients with Chagasic Cardiomyopathy
Authors: Oliveira Bráulio M.R. , Botoni Fernando A. , Ribeiro Antonio L.P. , Pinto Airandes S. , Reis Adelina M. , Nunes Maria do Carmo P. , Rocha Manoel O.C.
Published: March 2009

Cardiomyopathy is the most important manifestation of Chagas' disease. Brain natriuretic peptide (BNP) level and Doppler echocardiographic parameters for diastolic dysfunction have shown correlation with left ventricle (LV) filling pressures. Objectives: The purpose of this study is to compare BNP levels with Doppler echocardiographic parameters in patients with chagasic cardiomyopathy. Methods: Forty‐three patients (69.8% men; mean age 41.0 ± 10.4 years) were submitted to an echocardiographic study and 39 had their BNP levels measured. Results: BNP levels increased with the deterioration of the diastolic function (P=0.025). Pulmonary venous flow parameters were correlated with BNP levels, but E/E′ratio (E′measured at the inferior mitral annulus) was the only diastolic parameter that remained an independent predictor of elevated BNP levels in the multivariate analysis. The area under the receiver‐operating curve for BNP to detect E/E′ >15 was 0.875. A BNP value of 280.4 pg/ml had a sensitivity of 96% and a specificity of 75% for predicting E/E′ >15. Conclusions: In a group of patients with chagasic cardiomyopathy, BNP levels correlated with diastolic function patterns regardless of systolic function. The E/E′ratio (inferior wall) was the only isolated parameter of diastolic function that was independently associated with BNP levels.
Large Obstructive Cardiac Myxofibrosarcoma Is Nearly Invisible on Transthoracic Echocardiogram
Authors: Heletz Ido , Abramson Sandra V.
Published: March 2009

Malignant primary cardiac tumors are exceptionally rare, and the most common of these are sarcomas. We present a case of a patient who was found to have a large mass in the left atrium causing obstruction of mitral inflow. Only selected views on a transthoracic echocardiogram reveal the mass and its hemodynamic effect. Although the mass was sizeable, it could be easily overlooked on cursory review of the echocardiogram. After surgical resection, the mass was proven to be a myxofibrosarcoma. We review the etiologies and possible solutions for the imperfect sensitivity of transthoracic echocardiography for cardiac masses.
The effects of phototherapy on the numbers of circulating natural killer cells and T lymphocytes in psoriasis
Authors: Tobin A. M. , Maguire B. , Enright H. , Kirby B.
Published: March 2009

The innate immune system is believed to be important in the pathogenesis of psoriasis and natural killer (NK) have been found in increased numbers in psoriatic plaques. Alterations in the numbers of NK cells in peripheral blood have been reported. We investigated the effect of phototherapy on levels of peripheral NK cells and lymphocytes in patients with psoriasis. In nine patients whom we followed before, during and after narrowband ultraviolet B (UVB) treatment there were no differences in the numbers of circulating lymphocytes, lymphocyte subsets or cells expressing NK markers and controls. Treatment with narrowband UVB did, however, significantly lower circulating CD4 counts which gradually recovered posttreatment.
Direct Hemoperfusion With a β2‐Microglobulin‐selective Adsorbent Column Eliminates Inflammatory Cytokines and Improves Pulmonary Oxygenation
Authors: Kono Keiichi , Toda Shigeru , Hora Kazuhiko , Kiyosawa Kendo
Published: March 2009

Abstract:  Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by a high mortality rate; therefore, ARDS/ALI in humans is a leading cause of morbidity and mortality in critically ill patients. As previously reported, cytokines play a critical role as signaling molecules that initiate, amplify, and perpetuate inflammatory responses on a local and systemic basis, and the polymyxin‐B immobilized direct hemoperfusion system (PMX–DHP) is effective for the treatment of ARDS/ALI. Furthermore, another direct hemoperfusion system using the β2‐microglobulin‐selective adsorbent column, Lixelle, the direct hemoperfusion treatment (Lixelle–DHP), has been applied in some cases to patients who are affected with systemic inflammatory response syndrome. The aim of this study is to evaluate the therapeutic efficacy of Lixelle–DHP in the treatment of ARDS/ALI. Four patients, aged 67–79 years old (mean 72 ± 6.2 years), diagnosed with ARDS/ALI were treated with Lixelle–DHP. The PaO2/fraction of inspired oxygen (FiO2) ratio (PF ratio) was 90.0 ± 22.9 before the treatment, and it increased to 129.9 ± 5.6 at 72 h afterward the start of treatment. Inflammatory cytokines such as interleukin (IL)‐1β, IL‐6, soluble intercellular adhesion molecule 1 (sICAM‐1) decreased significantly after the treatment. All patients were still alive after one month. However, while IL‐2 had decreased significantly after the treatment, it had returned by the next treatment. It is possible that Lixelle–DHP might be able to improve the PF ratio and mortality rate as a result of decreased cytokines, and it has been suggested that Lixelle–DHP has a beneficial influence in the treatment of ARDS/ALI.
Fresh‐frozen, optimal cutting temperature (OCT) compound‐embedded bone marrow aspirates: a reliable resource for morphological, immunohistochemical and molecular examinations
Authors: LIM J. , KIM Y. , LEE W. , KIM M. , LEE E. J. , KANG C. S. , HAN K.
Published: March 2009

The usefulness of fresh‐frozen, optimal cutting temperature (OCT) compound‐embedded (FFOE) bone marrow (BM) aspirates was evaluated as a reliable resource for morphological, immunohistochemical and molecular examinations. One hundred BM aspirates were collected in polypropylene tubes and immediately frozen for 2 h in a deep freezer. Frozen BM was transferred to a cryomold filled with OCT compound and the prepared samples were stored in a deep freezer. Histological examination and immunohistochemical staining, polymerase chain reaction (PCR), sequencing and reverse transcription (RT)‐PCR were performed to evaluate the quality of the FFOE BM sections in 10% of randomly selected samples. FFOE BM sections revealed better morphologies than paraffin‐embedded clot sections in haematoxylin and eosin staining because mature erythrocytes were removed during the staining process in frozen BM sections. Immunohistochemical staining for CD34 revealed excellent staining quality and oil red O staining showed that fat vacuoles in cells were well preserved. The quality of genomic DNA in FFOE BM sections was suitable for obtaining about 2000 bp PCR product for the human leucocyte antigen‐A locus followed by direct sequencing of the sample, and the quality of total RNA was suitable for detection of BCR‐ABL fusion transcript. FFOE BM aspirates are a reliable resource for various laboratory tests of diagnostic and research arenas.
Characterization of microsatellite loci for the western cherry fruit fly, Rhagoletis indifferens (Diptera: Tephritidae)
Authors: MAXWELL SHERI A. , RASIC GORDANA , KEYGHOBADI NUSHA
Published: March 2009

The western cherry fruit fly (Rhagoletis indifferens) is a major pest of cherry crops in western North America, yet relatively little is known about its population structure or movement patterns due to the difficulty of studying these parameters directly in the field. We isolated and characterized a set of 16 polymorphic microsatellite loci specific to R. indifferens that display sufficient polymorphism to assess genetic structure and movement patterns. All 16 loci amplified in one or more other Rhagoletis species, indicating that they are useful tools for genetic analysis in other members of the genus, many of which are also agricultural pests.
Isolation and characterization of polymorphic microsatellite loci for the three‐toed box turtle (Terrapene carolina triunguis) and cross‐amplification in other Terrapene species
Authors: BUCHMAN A. B. , DEATON R. , RANDLE C. P. , BRUMMEL T. , WILSON E. D. , LUTTERSCHMIDT W. I.
Published: March 2009

We isolated and characterized eight polymorphic microsatellite loci for a Texas population of three‐toed box turtle, Terrapene carolina triunguis, using a refined hybridization capture procedure. All eight primer pairs amplified successfully at all loci in seven Texas ornate box turtles (T. ornata ornata). Due to the decline and conservation concerns of North American box turtles, these isolated microsatellites may be a most valuable tool for evaluating baseline population genetic structure for threatened box turtle populations.
Novel microsatellite DNA loci for Bombus terrestris (Linnaeus, 1758)
Authors: STOLLE ECKART , ROHDE MANDY , VAUTRIN DOMINIQUE , SOLIGNAC MICHEL , SCHMID‐HEMPEL PAUL , SCHMID‐HEMPEL REGULA , MORITZ ROBIN F. A.
Published: March 2009

We present details and characteristics of 123 novel polymorphic microsatellite DNA loci for Bombus terrestris. Thirty‐four of these loci have been tested in nine other Bombus species and 25 of them showed polymorphisms in at least one species. These microsatellite DNA loci together with the already established 60 loci will be useful for characterizing wild and managed populations of B. terrestris and other Bombus species as well as for detailed genetic studies in including mapping studies and genome annotations.
Single molecule measurements of mechanical interactions within ternary SNARE complexes and dynamics of their disassembly: SNAP25 vs. SNAP23
Authors: Montana Vedrana , Liu Wei , Mohideen U. , Parpura Vladimir
Published: March 2009

Regulated exocytosis is a crucial event for intercellular communication between neurons and astrocytes within the CNS. The soluble N‐ethylmaleimide‐sensitive fusion protein attachment protein receptor (SNARE) complex, composed of synaptobrevin 2, syntaxin and synaptosome‐associated protein of 25 kDa or 23 kDa (SNAP25 or SNAP23), is essential in this process. It was reported that SNAP25 and SNAP23 have distinct roles in exocytotic release, where SNAP25, but not SNAP23, supports an exocytotic burst. It is not clear, however, whether this is due to the intrinsic properties of the ternary SNARE complex, containing either SNAP25 or SNAP23, or perhaps due to the differential association of these proteins with ancillary proteins to the complex. Here, using force spectroscopy, we show from single molecule investigations of the SNARE complex, that SNAP23A created a local interaction at the ionic layer by cuffing syntaxin 1A and synaptobrevin 2, similar to the action of SNAP25B; thus either of the ternary complexes would allow positioning of vesicles at a maximal distance of ∼13 nm from the plasma membrane. However, the stability of the ternary SNARE complex containing SNAP23A is less than half of that for the complex containing SNAP25B. Thus, differences in the stability of the two different ternary complexes could underlie some of the SNAP25/23 differential ability to control the exocytotic burst.
Developmental change of T‐type Ca2+channel expression and its role in rat chromaffin cell responsiveness to acute hypoxia
Authors: Levitsky Konstantin L. , López‐Barneo José
Published: March 2009

Neonatal chromaffin cells of the adrenal medulla (AM) are intrinsic chemoreceptors that secrete catecholamines in response to hypoxia, thus contributing to fetal adaptation to extrauterine life. In most mammals studied, oxygen sensitivity of AM cells disappears a few days after birth, possibly due to innervation of the adrenal gland by the cholinergic fibres of the splanchnic nerve (∼postnatal day 7 in the rat). The mechanisms underlying these homeostatic changes in chromaffin cells are unknown. Low voltage‐activated, T‐type, Ca2+channels regulate cell excitability and their expression is up‐regulated by hypoxia. Hence, we hypothesized that these channels contribute to the developmental changes in the chemoreceptive properties of AM chromaffin cells. Using electrophysiological, immunocytochemical and molecular biology methodologies we show here that neonatal AM chromaffin cells express T‐type Ca2+channels (of α1H or Cav3.2 sub‐type) and that the function of these channels is necessary for catecholamine release in response to acute hypoxia. T‐type Ca2+channel expression, as well as chromaffin cell responsiveness to hypoxia, decrease with postnatal maturation. Adult chromaffin cell sensitivity to hypoxia reappears after AM denervation in parallel with the recruitment of T‐type Ca2+channels. These observations indicate that T‐type Ca2+channels are essential for the acute response of chromaffin cells to hypoxia and help explain the disappearance of O2sensitivity in adult AM chromaffin cells. Our results may also be relevant for understanding the pathogenesis of disorders associated with chronic hypoxia or maternal nicotine consumption.