bluuebunny/crossref_metadata_2025 huggingface dataset:
Widespread transcriptional changes pre‐empt the critical pelagic–benthic transition in the vetigastropod Haliotis asinina
Authors: WILLIAMS ELIZABETH A. , DEGNAN BERNARD M. , GUNTER HELEN , JACKSON DANIEL J. , WOODCROFT BEN J. , DEGNAN SANDIE M.
Published: February 2009

Larval settlement is a vital transition period for marine invertebrates and can have far‐reaching effects on the ecology and evolution of a species. To explore the molecular mechanisms of this critical process in a nonmodel organism, the abalone Haliotis asinina, we employed cDNA microarrays. By comparing gene expression profiles through mid‐ to late larval development and metamorphosis, we identified 144 genes as candidates for a role in competence and/or metamorphosis. Gene characterization indicates ~60% of these are significantly similar to known genes from other taxa, while ~40% are novel. A high 49.3% of genes are gastropod or abalone specific, but none appears to be Lophotrochozoan specific, even though metamorphosis is thought to have had a separate origin in this group. Differentially expressed larval and postlarval genes can be clustered into five categories that reveal strikingly different temporal transcriptional patterns occurring during this phase of development. Some gene activation is contingent upon exogenous cues and correlates with initiation of settlement. Importantly, there is also extensive gene activity associated with the endogenous attainment of competence, which occurs before, and independent of, the exogenous induction of settlement. Our results show that as the haliotid veliger larva matures, it requires coordinated regulation of temporally different batteries of genes involved in a wide range of physiological and developmental processes associated with benthic colonization. Although the signalling pathways operating at metamorphosis may be conserved across the animal kingdom, it appears they regulate the expression of novel genes specific to abalone, gastropods and molluscs during H. asinina metamorphosis.
Comparative cryo‐electron tomography of pathogenic Lyme disease spirochetes
Authors: Kudryashev Mikhail , Cyrklaff Marek , Baumeister Wolfgang , Simon Markus M. , Wallich Reinhard , Frischknecht Friedrich
Published: February 2009

Spirochetes of the Borrelia burgdorferi sensu lato group, the causative agents of Lyme borreliosis, exhibit a complex biology evolved in its zoonotic cycle. Cryo‐electron tomography was used to investigate structural features of three species, B. burgdorferi, B. garinii and B. afzelii, known to cause different clinical manifestations in humans. All three organisms revealed an overall similar architecture and showed different numbers of periplasmic flagellar filaments, polar periplasmic void regions, vesicles budding from the outer membrane sheath, which was covered by an amorphous slime layer. The latter was shown to be distinct in its density when comparing the three human‐pathogenic Lyme disease spirochetes and Borrelia hermsii, a species causing relapsing fever. Tomograms of dividing bacteria revealed vesicles near the site of division and new basal bodies that were attached at each end of newly establishing cytoplasmic cylinder poles, while periplasmic flagellar filaments still passed the impending site of division. Two different kinds of cytoplasmic filaments showed similarities to MreB or FtsZ filaments of other bacteria. The similar and distinct structural features of Borrelia and the previously investigated pathogenic and non‐pathogenic Treponema species emphasize the importance of further studying phylogenetically distant spirochetes.
FTY720 attenuates lesional interleukin‐17+ cell accumulation in rat experimental autoimmune neuritis
Authors: Zhang Z‐Y. , Zhang Z. , Schluesener H. J.
Published: February 2009

Aims: Experimental autoimmune neuritis (EAN) is a well‐known animal model of human demyelinating polyneuropathies. Here we have studied the spatiotemporal accumulation of interleukin (IL)‐17+ cells in sciatic nerves of EAN rats and effects of FTY720, an agonist of sphingosine‐1‐phosphate (S1P) receptors. Methods: In this study, we examined the spatiotemporal expression of IL‐17 using immunohistochemistry and RT‐PCR, and analysed the IL‐17+ cell proportion in blood and lymph nodes using flow cytometry. Results: In sciatic nerves of EAN rats, IL‐17+ cells were mainly found to concentrate around blood vessels and IL‐17+ cell accumulation was temporally correlated with severity of neurological signs. FTY720, which has been shown to reduce severity of EAN, attenuated accumulation of IL‐17+ cells in sciatic nerves, decreased IL‐17+ cell proportion in peripheral blood, but increased IL‐17+ cell proportion in lymph nodes, suggesting the involvement of S1P signal pathway in regulating IL‐17+ cell trafficking. Conclusions: our data are consistent with the possibility that IL‐17+ cells might contribute to the pathogenesis of EAN and the S1P signal pathway may be involved in the in vivo trafficking of IL‐17+ cells.
Localization and integration of thylakoid protein translocase subunit cpTatC
Authors: Martin Jonathan R. , Harwood Jessica H. , McCaffery Michael , Fernandez Donna E. , Cline Kenneth
Published: February 2009

Thylakoid membranes have a unique complement of proteins, most of which are nuclear encoded synthesized in the cytosol, imported into the stroma and translocated into thylakoid membranes by specific thylakoid translocases. Known thylakoid translocases contain core multi‐spanning, membrane‐integrated subunits that are also nuclear‐encoded and imported into chloroplasts before being integrated into thylakoid membranes. Thylakoid translocases play a central role in determining the composition of thylakoids, yet the manner by which the core translocase subunits are integrated into the membrane is not known. We used biochemical and genetic approaches to investigate the integration of the core subunit of the chloroplast Tat translocase, cpTatC, into thylakoid membranes. In vitro import assays show that cpTatC correctly localizes to thylakoids if imported into intact chloroplasts, but that it does not integrate into isolated thylakoids. In vitro transit peptide processing and chimeric precursor import experiments suggest that cpTatC possesses a stroma‐targeting transit peptide. Import time‐course and chase assays confirmed that cpTatC targets to thylakoids via a stromal intermediate, suggesting that it might integrate through one of the known thylakoid translocation pathways. However, chemical inhibitors to the cpSecA‐cpSecY and cpTat pathways did not impede cpTatC localization to thylakoids when used in import assays. Analysis of membranes isolated from Arabidopsis thaliana mutants lacking cpSecY or Alb3 showed that neither is necessary for cpTatC membrane integration or assembly into the cpTat receptor complex. These data suggest the existence of another translocase, possibly one dedicated to the integration of chloroplast translocases.
AtHMA1 contributes to the detoxification of excess Zn(II) in Arabidopsis
Authors: Kim Yu‐Young , Choi Hyunju , Segami Shoji , Cho Hyung‐Taeg , Martinoia Enrico , Maeshima Masayoshi , Lee Youngsook
Published: February 2009

AtHMA1 is a member of the heavy metal‐transporting ATPase family. It exhibits amino acid sequence similarity to two other Zn(II) transporters, AtHMA2 and AtHMA4, and contains poly‐His motifs that are commonly found in Zn(II)‐binding proteins, but lacks some amino acids that are typical for this class of transporters. AtHMA1 localizes to the chloroplast envelope. In comparison with wild‐type plants, we observed a more pronounced sensitivity in the presence of high Zn(II) concentrations, and increased accumulation of Zn in the chloroplast of T‐DNA insertional mutants in AtHMA1. The Zn(II)‐sensitive phenotype of AtHMA1 knock‐out plants was complemented by the expression of AtHMA1 under the control of its own promoter. The Zn(II)‐transporting activity of AtHMA1 was confirmed in a heterologous expression system, Saccharomyces cerevisiae. The sensitivity of yeast to high concentrations of Zn(II) was altered by the expression of AtHMA1 lacking its N‐terminal chloroplast‐targeting signal. Taken together, these results suggest that under conditions of excess Zn(II), AtHMA1 contributes to Zn(II) detoxification by reducing the Zn content of Arabidopsis thaliana plastids.
High‐throughput linkage analysis of Mutator insertion sites in maize
Authors: Yi Gibum , Luth Diane , Goodman Timothy D. , Lawrence Carolyn J. , Becraft Philip W.
Published: February 2009

Insertional mutagenesis is a cornerstone of functional genomics. High‐copy transposable element systems such as Mutator (Mu) in maize (Zea mays) afford the advantage of high forward mutation rates but pose a challenge for identifying the particular element responsible for a given mutation. Several large mutant collections have been generated in Mu‐active genetic stocks, but current methods limit the ability to rapidly identify the causal Mu insertions. Here we present a method to rapidly assay Mu insertions that are genetically linked to a mutation of interest. The method combines elements of MuTAIL (thermal asymmetrically interlaced) and amplification of insertion mutagenized sites (AIMS) protocols and is applicable to the analysis of single mutants or to high‐throughput analyses of mutant collections. Briefly, genomic DNA is digested with a restriction enzyme and adapters are ligated. Polymerase chain reaction is performed with TAIL cycling parameters, using a fluorescently labeled Mu primer, which results in the preferential amplification and labeling of Mu‐containing genomic fragments. Products from a segregating line are analyzed on a capillary sequencer. To recover a fragment of interest, PCR products are cloned and sequenced. Sequences with lengths matching the size of a band that co‐segregates with the mutant phenotype represent candidate linked insertion sites, which are then confirmed by PCR. We demonstrate the utility of the method by identifying Mu insertion sites linked to seed‐lethal mutations with a preliminary success rate of nearly 50%.
Occult hepatitis B virus infection in liver transplant recipients with recurrent hepatitis C: relationship with donor age and fibrosis progression
Authors: Toniutto Pierluigi , Minisini Rosalba , Fabris Carlo , De Feo Tullia , Marangoni Francesca , Burlone Michela , Avellini Claudio , Bitetto Davide , Fornasiere Ezio , Fumolo Elisa , Baccarani Umberto , Pirisi Mario
Published: February 2009

Abstract:  Liver transplantation (OLT) recipients who receive a graft from donors positive for hepatitis B virus (HBV) anti‐core antibodies may develop overt “de novo” HBV infection. The study was undertaken to explore how often HBV infection may remain occult after OLT for hepatitis C, and whether it may represent a factor of graft fibrosis progression. We studied 30 consecutive patients transplanted for hepatitis C liver disease. Specimens from the native liver and from the graft were searched for occult HBV infection (O‐HBV). In the native liver, 8/30 patients had detectable O‐HBV; during the follow‐up, O‐HBV infection was demonstrated in 14 graft specimens. Graft O‐HBV was associated with older donor age (≥50 yr; 8/9 vs. 6/21, p < 0.005). Recipients with graft O‐HBV and no O‐HBV in the native liver who received their grafts from donors aged >40 yr had faster fibrosis progression than recipients with no post‐transplant O‐HBV, whose grafts came from donors aged >40 yr and recipients whose grafts came from donors aged ≤40 yr (4/7 vs. 1/7 vs. 2/16, p < 0.05). In OLT recipients, O‐HBV is more likely to occur when grafts are obtained from aged donors and may affect the rate of fibrosis progression because of recurrent hepatitis C.
Two yr mycophenolate mofetil plus low‐dose calcineurin inhibitor for renal dysfunction after liver transplant
Authors: Biselli Maurizio , Vitale Giovanni , Gramenzi Annagiulia , Riili Anna , Berardi Sonia , Cammà Carlo , Scuteri Alessandra , Morelli Maria Cristina , Grazi Gian Luca , Pinna Antonio Daniele , Andreone Pietro , Bernardi Mauro
Published: February 2009

Abstract:  We assessed the efficacy and outcome of low through level of calcineurin inhibitors (CNI) and introducing mycophenolate mofetil (MMF) in liver transplant (LT) patients with CNI‐related renal dysfunction. Thirty LT patients were converted to combined therapy and compared with 30 patients used as a contemporary control group receiving CNI only. The two groups were matched for sex, age, months after LT, immunosuppressive treatment, creatinine level, presence of diabetes and calculated glomerular filtration rate (GFR) via Cockroft‐Gault method. After two years, in the MMF serum creatinine decreased from 1.65 mg/dL (range 1.33–3.5) to 1.4 mg/dL (range 0.9–4.7) (p = 0.002) and GFR increased from 51 mL/min (range 18.9–72.2) to 57.6 mL/min (range 16–92.2) (p < 0.001), whereas the controls not showed any improvement. The logistic regression models employing improvement of creatinine and GFR of at least 10% with respect to baseline as dependent variables showed the use of MMF (p = 0.004 and p = 0.019, respectively) as the only statistically significant parameter. Multiple linear regression analysis identified only MMF as independent predictor of Δcreatinine and ΔGFR (p = 0.002 and p < 0.001, respectively). No rejection episode was observed (three in controls). This study demonstrates the medium‐term efficacy and safety of MMF plus low dose CNI in reducing nephrotoxicity in LT recipients.
The relationship of donor source and age on short‐ and long‐term allograft survival in pediatric renal transplantation
Authors: Dale‐Shall A. W. , Smith J. M. , McBride M. A. , Hingorani S. R. , McDonald R. A.
Published: February 2009

Abstract: Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post‐transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18–54 yr‐old LD recipients, 59.1% in ≥55 yr‐old LD, and 45.1% in ≥50 yr‐old DD recipients. An approximate 35% improvement in allograft survival in 18–54 yr‐old LD recipients was observed. Multivariate results showed that recipients of LD 35–49 (aRR 0.66, 95% CI 0.55–0.80) and LD 50–54 (aRR 0.65, 95% CI 0.45–0.94) have a graft survival advantage over the ideal DD. In LD ≥55 yr, no improvement in graft survival was observed when compared with the 18–34 yr‐old DD. In summary, we observed in a pediatric population, <55 yr‐old LD kidneys afford improved long‐term allograft survival when compared with DD kidney recipients. Increasing awareness of the long‐term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority.
Role of polyisoprenoids in tobacco resistance against biotic stresses
Authors: Bajda Agnieszka , Konopka‐Postupolska Dorota , Krzymowska Magdalena , Hennig Jacek , Skorupinska‐Tudek Karolina , Surmacz Liliana , Wójcik Jacek , Matysiak Zdzislaw , Chojnacki Tadeusz , Skorzynska‐Polit Ewa , Drazkiewicz Maria , Patrzylas Pawel , Tomaszewska Monika , Kania Magdalena , Swist Malgorzata , Danikiewicz Witold , Piotrowska Wieslawa , Swiezewska Ewa
Published: February 2009

Infection with avirulent pathogens, tobacco mosaic virus (TMV) orPseudomonas syringaepv. tabaci induced accumulation of polyisoprenoid alcohols, solanesol and a family of polyprenols [from polyprenol composed of 14 isoprene units (Pren‐14) to ‐18, with Pren‐16 dominating] in the leaves of resistant tobacco plantsNicotiana tabacumcv. Samsun NN. Upon TMV infection, solanesol content was increased seven‐ and eight‐fold in the inoculated and upper leaves, respectively, while polyprenol content was increased 2.5‐ and 2‐fold in the inoculated and upper leaves, respectively, on the seventh day post‐infection. Accumulation of polyisoprenoid alcohols was also stimulated by exogenously applied hydrogen peroxide but not by exogenous salicylic acid (SA). On the contrary, neither inoculation of the leaves of susceptible tobacco plants nor wounding of tobacco leaves caused an increase in polyisoprenoid content. Taken together, these results indicate that polyisoprenoid alcohols might be involved in plant resistance against pathogens. A putative role of accumulated polyisoprenoids in plant response to pathogen attack is discussed. Similarly, the content of plastoquinone (PQ) was increased two‐fold in TMV‐inoculated and upper leaves of resistant plants. Accumulation of PQ was also stimulated by hydrogen peroxide, bacteria (P. syringae) and SA. The role of PQ in antioxidant defense in cellular membranous compartments is discussed in the context of the enzymatic antioxidant machinery activated in tobacco leaves subjected to viral infection. Elevated activity of several antioxidant enzymes (ascorbate peroxidase, guaiacol peroxidase, glutathione reductase and superoxide dismutase, especially the CuZn superoxide dismutase isoform) and high, but transient elevation of catalase was found in inoculated leaves of resistant tobacco plants but not in susceptible plants.
Functional annotation of expressed sequence tags as a tool to understand the molecular mechanism controlling flower bud development in tree peony
Authors: Shu Qing Y. , Wischnitzki Elisabeth , Liu Zheng A. , Ren Hong X. , Han Xiao Y. , Hao Qing , Gao Fen F. , Xu Su X. , Wang Liang S.
Published: February 2009

Tree peony (Paeonia suffruticosaAndrews) is an important medicinal and ornamental plant. In China, its root bark is an important ingredient for traditional Chinese medicine. It is valued as an ornamental plant because its flower shows a wide variation in shape and color. We used flower buds at different developmental stages to construct the first cDNA library for this organism. A total of 2241 raw expressed sequence tags (ESTs) were obtained after unidirectional sequencing. After processing and assembly, they resulted in a total of 1300 unigenes [363 contigs with an average size of 3.5 ESTs (ranging from 2 up to 36) and 937 singletons]. Gene Ontology categories were assigned and further summarized into 13 broad families with biological roles according to similar functional characteristics or cellular roles. A total of 185 single nucleotide polymorphisms were detected for all contigs. We were able to detect open reading frames in the consensus sequences of 1268 unigenes. 97.5% of the ESTs showed significant similarity to sequences present in public databases. One hundred and sixty‐seven short sequence repeats were obtained in the whole data set. All the analysis and information will be valuable resources for a better understanding of this important plant and also can be used for functional study in Paeoniaceae.
Epidemiology of dermatophytoses in Sfax, Tunisia
Authors: Neji Sourour , Makni Fattouma , Cheikhrouhou Fatma , Sellami Amira , Sellami Hayet , Marreckchi Slaheddine , Turki Hamida , Ayadi Ali
Published: February 2009

The distribution of dermatophytes varies in different countries and geographical areas depending on several factors. To determine the frequency of aetiological agents and the clinical variants of dermatophytoses, we carried out a study between 1998 and 2007. Out of 25 432 subjects suspected to have superficial mycoses, 9960 (39.2%) were affected with dermatophytoses; 14957 positive samples were obtained. The mean age was 35.7 years (range: 21 days to 97 years). Sex ratio was 0.9. Our patients were from urban regions in 81.9% of cases. The most common type of infection was onychomycosis (30.3%), followed by tinea pedis (24.8%), intertrigo (21.7%), tinea corporis (11.4%) and tinea capitis (9.6%). Fifteen patients had generalised dermatophytosis. Hadida and Schousboe disease was diagnosed in one case with lethal evolution. The most isolated dermatophyte was Trichophyton rubrum (74.5%), followed by T. violaceum (7.9%), T. mentagrophytes (7.5%), Microsporum canis (3.8%), Epidermophyton floccosum (0.7%) and T. verrucosum (0.54%). Other species were occasionally isolated: T. schoenleinii, T. tonsurans, M. audouinii and M. ferrugineum. The prevalence of dermatophytoses remains high in our country (996 cases/year). Trichophyton rubrum is the predominant causal agent. However, zoophilic agents become more prevalent. Epidemiological surveys are an essential tool for developing strategies for infection control.
Risk factors for urinary tract infection in children: A population‐based study of 2856 children
Authors: Sureshkumar Premala , Jones Mike , Cumming Robert G , Craig Jonathan C
Published: February 2009

Aim:  To identify risk factors for urinary tract infection (UTI) in children to inform the development of preventative strategies.

Method:  A validated questionnaire covering demographic factors, perinatal, developmental, bowel and urinary history was sent to a cross‐sectional sample of parents of elementary school children randomly selected from the first 4 years of school. UTI was ascertained by parental report, verified by cross‐referencing with microbiological reports for all positive cases and 50 randomly selected negative cases.

Results:  Parents of 2856 children (mean age 7.3 years, range 4.8–12.8 years) responded. A total of 3.6% of children had a bacteriologically verified UTI, compared with 12.6% by parental report alone. Multivariate polychotomous logistic regression showed that a history of structural kidney abnormalities (odds ratio (OR) 15.7, 95% confidence interval 8.1–30.4), daytime incontinence (OR 2.6, 1.6–4.5), female gender (OR 2.4, 1.5–3.8), and encopresis (OR 1.9, 1.1–3.4) were independently associated with UTI. Daytime incontinence increased risk more in boys (8.3% vs. 1.2%) than girls (8.1% vs. 4.6%), and kidney problems increased risk in older compared with younger children (29% vs. 2% in ≥8 year olds, 0% vs. 4% in 4–6 year olds).

Conclusions:  Parents over‐report UTI by about threefold. Effective treatment of daytime urinary incontinence and encopresis may prevent UTI in children, especially boys.
Management of childhood asthma in Western Australia
Authors: Calogero Claudia , Kusel Merci MH , Van Bever Hugo PS , Sly Peter D
Published: February 2009

Aims:  The study aimed to determine how childhood asthma is managed in Western Australia by general practitioners (GPs) and specialist paediatricians.

Methods:  A questionnaire survey was sent to 992 GPs and specialist paediatricians, asking about practice and preferences regarding maintenance management of childhood asthma and treatment of acute asthma. Questions about asthma in infants, pre‐school and school‐aged children were asked separately.

Results:  The overall response rate was 24.7%, with 188/878 (21.4%) of GPs and 44/62 (71.0%) of paediatricians returning the questionnaire. The decision to start maintenance therapy was generally based on symptom frequency and severity. The first choice for maintenance treatment in all age groups was inhaled corticosteroids (ICS). The second most common treatment varied according to age group, with short‐acting β2‐agonist (SBA) preferred for infants, montelukast or short‐acting β2‐agonist for pre‐schoolers and combination therapy (ICS + long action β2‐agonist) for school‐aged children. Objective monitoring of lung function with peak flow or spirometry, was used by 40% of GPs and 59% of paediatricians. Acute asthma was primarily managed with inhaled salbutamol and oral corticosteroids. There were few differences in treatment choice between GPs and paediatricians. Many GPs indicated that they did not treat asthma in infants without specialist consultation.

Conclusions:  These data show good compliance by the minority of GPs responding to the survey and by paediatricians practising in Western Australia with current Australian asthma management guidelines. Major differences in treatment preferences between the groups were not detected.
Detection of human bocavirus in hospitalised children
Authors: Dina Julia , Vabret Astrid , Gouarin Stephanie , Petitjean Joelle , Lecoq Julie , Brouard Jacques , Arion Alina , Lafay‐Delaire Françoise , Freymuth François
Published: February 2009

Aim:  The objectives of this study are to assess the frequency of human bocavirus (HBoV) infection in hospitalised children and to study the clinical symptoms associated with the detection of HBoV.

Methods:  Two groups of hospitalised children were included in this study: group 1 consisted of 1946 children hospitalised from 1st September 2004 to 30th May 2005, and group 2 consisted of 448 children hospitalised from 1st November 2003 to 30th March 2004. The respiratory specimens were tested by polymerase chain reaction.

Results:  In the first group, HBoV was detected by polymerise chain reaction in 11/828 (1.3%) of nasal specimens that tested negative for other respiratory viruses. One child tested positive for HBoV in both a nasal aspirate and stool sample. In the second group, nasal specimens were tested for all respiratory viruses, including HBoV. The presence of HBoV infection was detected in seven children (1.6%). Detection of a mixed viral population was observed in four of these children. The main symptoms in children infected with HBoV were rhinitis (50%), cough (45%), dyspnoea (28%), wheezing (28%), fever (23%) and diarrhoea (22%). The final clinical diagnoses were bronchiolitis (seven children), rhinopharyngitis (five children), the exacerbation of asthma (two children) and pneumonia (one child). Moreover, four children have associated gastroenteritis.

Conclusion:  These results contribute to the interest in the HBoV detection in children. HBoV detection in hospitalised children with or without any other respiratory virus detection was essentially associated with lower respiratory tract infection and in a lower score with upper respiratory tract infection and gastroenteritis.
Review article: Luminex technology for HLA antibody detection in organ transplantation
Authors: TAIT BRIAN D , HUDSON FIONA , CANTWELL LINDA , BREWIN GEMMA , HOLDSWORTH RHONDA , BENNETT GREG , JOSE MATTHEW
Published: February 2009

Since its inception in the early 1960s, the serologically based complement‐dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre‐transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow‐based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre‐sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA‐DPB1 and HLA‐DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non‐complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re‐evaluation of the role of HLA antibodies in both early and late antibody‐mediated rejection.
Post‐chemotherapy nerve‐sparing retroperitoneal lymph node dissection for advanced germ cell tumor
Authors: Miki Tsuneharu , Mizutani Yoichi , Nakamura Terukazu , Kawauchi Akihiro , Nagahara Akira , Nonomura Norio , Okuyama Akihiko
Published: February 2009

Objective:  To report our experience with post‐chemotherapy nerve‐sparing retroperitoneal lymph node dissection (RPLND) for advanced germ cell tumor (GCT).

Methods:  Between 1994 and 2008, 92 patients with advanced GCT underwent RPLND after multiple treatments with systemic chemotherapy at our institution. A nerve‐sparing RPLND was carried out in 78 patients (84.8%; median age 32 years). Of them, 19 had a seminoma and 59 had a non‐seminoma.

Results:  Lumbar splanchnic nerves controlling ejaculatory function were macroscopically preserved during RPLND. Bilateral and unilateral lumbar splanchnic nerves were preserved in 40 patients and 38 patients, respectively. Sixty‐five patients could be evaluated for ejaculation. Fifty‐four patients (83.1%) achieved antegrade ejaculation with a median postoperative interval of 3 months (range: 1–10 months). Twenty‐eight patients (28/30: 93.3%) and 26 patients (26/35: 74.3%) undergoing bilateral and unilateral nerve‐sparing RPLND had antegrade ejaculation, respectively (P = 0.041). Only two patients (2.6%) had mediastinal and retroperitoneal recurrences during a median follow‐up of 42 months (range: 1–138 months), respectively. However, these patients were cured by chemotherapy and surgery.

Conclusions:  Post‐chemotherapy nerve‐sparing RPLND preserves ejaculatory function in the majority of patients with advanced GCT without increasing the risk of local recurrence.
Prevalence of refractive errors in school‐age children in Morocco
Authors: Anera Rosario G , Soler Margarita , De La Cruz Cardona Juan , Salas Carlos , Ortiz Carolina
Published: February 2009

Abstract

Background:  The prevalence of refractive errors in school‐age children in Morocco was assessed.

Methods:  A total of 545 children (300 boys and 245 girls, between 6 and 16 years of age) attending school were examined to assess their refractive errors in a field study in Morocco (North Africa). The examination included autorefraction under cycloplegia and visual acuity, stereopsis and anterior corneal‐radius measurements .

Results:  We found a low prevalence of myopia (≤−0.5 D SE [spherical equivalent] in at least one eye), i.e. only 6.1%. The prevalence of hyperopia (≥2.0 D SE in at least one eye) was 18.3%. Astigmatism (≤−0.75 D of cylinder in at least one eye) was found in 23.5% of these children. The low prevalence of large refractive errors makes visual acuity in these children very good. In general, the corneal radii did not significantly vary with age. There were no significant differences between the distribution of refractive errors in these children according to gender but there were with respect to age.

Conclusions:  There was a low prevalence of myopia in these African children, astigmatism being the most frequent refractive error. The mean refractive errors found were low, and therefore visual acuity was high in these children.
Lymph node retrieval in colorectal cancer resection specimens: national standards are achievable, and low numbers are associated with reduced survival
Authors: Norwood M. G. A. , Sutton A. J. , West K. , Sharpe D. P. , Hemingway D. , Kelly M. J.
Published: February 2009

Objectives  The current guidelines identify the retrieval of at least 12 lymph nodes as crucial for accurate staging of colorectal cancer. We set out to review our figures from a single centre to see whether this standard has been met, and to examine for factors which may influence the number of lymph nodes retrieved. The influence of a low lymph node harvest on survival in patients with Dukes’ A and B cancers was specifically investigated.

Method  Data were collected from all patients with colorectal cancer undergoing resectional surgery from our prospectively compiled database between June 1998 and May 2007. A multivariate analysis was performed to identify factors resulting in low lymph node yields in those patients undergoing formal resection. Survival analyses were performed in patients with Dukes’ A and B cancers to assess whether a low lymph node yield negatively impacted on survival.

Results  A total of 2449 patients underwent formal resection and were included in the analysis. The median lymph node retrieval was 13 nodes (range 0–136). On multivariate analysis, preoperative chemo‐radiotherapy, operation type, specimen length and patient age all independently influenced lymph node retrieval. Patient gender, ethnicity, operative mode, operative team and consultant presence had no influence. Survival in patients with Dukes’ A and B cancers was significantly reduced if <12 nodes were sampled.

Conclusions  As a unit, we are achieving the national standard for lymph node harvest. This standard was maintained whether the surgeon performing the surgery was a consultant or a trainee, and also when the surgery was performed in the emergency setting. These data support the concept of 12 nodes being required for accurate staging.
Multinationals' Mode of Entry in the Presence of Upstream Spillovers
Authors: BALSVIK RAGNHILD
Published: February 2009

Multinationals' mode of foreign expansion may depend on their expectations of spillovers. I consider a monopolist with a vertical production structure where outsourcing of intermediates to a host country firm is one of three possible entry modes. Spillovers generate threat of entry of a new input producer. With incomplete outsourcing contracts that result in the two firms bargaining over how to share the potential surplus, upstream spillovers do not necessarily benefit the downstream multinational. If the multinational instead allows the supplier to set the price of intermediates (successive monopoly), it clearly benefits from upstream spillovers.
INTERNATIONAL FINANCIAL ASSISTANCE: A LOAN MECHANISM‐DESIGN APPROACH
Authors: MOURMOURAS ALEX , MAYER WOLFGANG
Published: February 2009

International Financial Institutions (IFIs) tie resource transfers to capital‐scarce countries to improvements in their economic policies and institutions. The objective of this assistance is twofold: to augment the recipient's capital base and to improve its allocation of resources. This paper offers a political‐economy explanation for the limited success of some of these loan programs. In our model, governments select policies under the influence of interest groups. Their capacity to absorb IFI loans and their reform efforts are both unobservable to the IFI. An optimally designed loan mechanism must create sufficient incentives – in the form of rewards and punishments – to counter the influence of interest groups on economic policy choices. The loan mechanism is, however, constrained in two ways: it cannot punish a country so severely as to threaten its political stability and it must remain affordable to the IFI. Whenever reform incentives are inadequate, a government will accept the loan but cheat on the implementation of reforms. If, on the other hand, the mechanism design is optimal, it might be so costly to the IFI that a well‐entrenched interest group can block the reform program. Nonetheless, the availability of properly designed loan mechanisms will push governments to implement partial reforms even if the optimal mechanism is too costly for the IFI.
Perineal approach to vascular anatomy during transobturator cystocele repair
Authors: Touboul C , Nizard J , Fauconnier A , Bader G
Published: February 2009

Objective  To evaluate the risk of vascular injury during transobturator approach of cystocele repair.

Design  Dissection of the obturator area by perineal approach was performed after placement of mesh needles used for cystocele mesh repair.

Setting  Surgery school of Paris.

Population or sample  Twenty obturator regions in ten fresh female cadavers.

Methods  Transperineal dissection of the obturator area was conducted in ten fresh female anatomic subjects after inserting anterior Prolift® needles.

Main outcome measures  The vascular anatomy of the obturator region was mapped. Distances between needles and vascular structures of the obturator area were measured three times and averaged for each side.

Results  The anterior cannula‐equipped needle perforated the gracilis and the adductor brevis muscles. The mean (SD) distance to the anterior obturator vessels was 21.2 (1.6) mm on the right side and 20.4 (1.5) mm on the left. The posterior needle perforated the adductor magnus. Its distance to the posterior division of the obturator vessels was 1.8 (1.0) mm on the right side and 1.1 (0.9) mm on the left.

Conclusions  During mesh cystocele repair by transobturator approach, the posterior obturator vessels division seems at risk of injury during the posterior needle insertion.
Prospective randomised trial comparing gonadotrophin‐releasing hormone analogues with triple tourniquets at open myomectomy
Authors: Al‐Shabibi N , Chapman L , Madari S , Papadimitriou A , Papalampros P , Magos A
Published: February 2009

Objective  To compare intra‐operative blood loss with triple tourniquets to occlude uterine blood supply against preoperative treatment with gonadotrophin‐releasing hormone (GnRH) analogues at open myomectomy.

Design  A prospective randomised controlled trial.

Setting  University teaching hospital.

Population  Forty women undergoing open myomectomy for symptomatic fibroids.

Methods  Women due to undergo open myomectomy were randomised to either 3 months pre‐treatment with a GnRH analogue or the intra‐operative application of triple tourniquets (number 1 polyglactin suture [Vicryl®Ethicon Inc., Somerville, NJ, USA] tied around the cervix and a size 10 polythene suction catheter tied around the infundibulo‐pelvic ligaments) to occlude the uterine blood supply.

Main outcome measures  The primary outcome measure was intra‐operative blood loss. Secondary outcome measures included postoperative blood loss, blood transfusion rate and postoperative morbidity.

Results  The two groups were similar in baseline characteristics. An average of 15 and 22 fibroids were removed from the GnRH analogue and tourniquet groups respectively. Intra‐operative estimated blood loss was significantly higher in the GnRH analogue group (median 2482 ml, 75% percentile 1744–3151) than when triple tourniquets were used (median 640 ml, 75% percentile 418–881), giving a difference between means of 1842 ml (P < 0.001). Similarly, significantly more women required blood transfusion in the GnRH analogue group (70 versus 30%, P < 0.025). Postoperative morbidity was similar between the two groups. There were two serious complications in the tourniquet group, but they were not considered to be directly related to occlusion of the uterine blood supply.

Conclusions  Triple tourniquets are significantly more effective than preoperative treatment with GnRH analogues at reducing intra‐operative blood loss at open myomectomy.
Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia
Authors: Gautier Sophie , Ouk Thavarak , Petrault Olivier , Caron Jacques , Bordet Régis
Published: February 2009

Background and purpose:  Polymorphonuclear neutrophils (PMNs) contribute to the vascular damage caused by transient cerebral ischaemia. Here we have evaluated the role of PMNs in intracerebral haemorrhage (ICH) induced in a model of thrombolysis with recombinant tissue plasminogen activator (t‐PA) during the acute phase of cerebral ischaemia.

Experimental approach:  The middle cerebral artery (MCA) of male spontaneously hypertensive rats was occluded for 1 h followed by reperfusion and, 5 h later, infusion of thrombolytic products (generated in vitro by t‐PA on autologous clots). Effects of pretreatment (before the MCA occlusion) with vinblastine (4 days before; 0.5 mg·kg−1), monoclonal anti‐neutrophil antibody (mAbRP3; 12 h, 0.3 mg·kg−1) or saline on ICH, neutrophil infiltration, MCA vascular reactivity and brain infarct volume were assessed, 24 h after the beginning of reperfusion.

Key results:  Depletion of circulating neutrophils significantly reduced t‐PA‐induced ICH (vinblastine, 4.6 ± 1.0; mAbRP3, 5.2 ± 1.0 vs. saline, 10.8 ± 2.7 haemorrhages; P < 0.05). This depletion was associated with a decrease in cerebral infiltration by neutrophils and a decrease of endothelium‐dependent, vascular dysfunction in isolated MCA, induced by the ischaemia/reperfusion and t‐PA treatment. Brain infarct volume was significantly decreased after vinblastine treatment (159 ± 13 mm3 vs. 243 ± 16 mm3 with saline; P < 0.01) but not after depletion with mAbRP3 (221 ± 22 mm3).

Conclusions and implications:  Our results showed that pharmacological depletion of PMNs prevented t‐PA‐induced ICH, in parallel with a decrease in cerebral infiltration by PMNs and a decreased endothelial dysfunction in cerebral blood vessels.

Mandarin translation of abstract
Surveying Recent Literature on the Arabic and Persian Mirrors for Princes Genre
Authors: Marlow L.
Published: February 2009

The study of the medieval Arabic and Persian ‘mirror for princes’ literatures in many respects resembles that of the similarly abundant literatures produced in Byzantium and the Latin West. In earlier scholarship, the predominant approach was that of the history of ideas, and scholars tended to focus on depictions of the ideal ruler and other aspects of the ‘political thought’ expressed in the mirror literatures. A secondary area of interest concerned textual transmission within and across these literatures. More recent scholarship has continued to develop and refine these established approaches, and has also developed new directions of research. Notably, several scholars have explored the Sitz im Leben of individual mirrors, and have studied their meaning and significance in the historical settings in and for which they were composed. Certain recent publications have highlighted the flexibility of mirrors, the multiple purposes they often served, the range of perspectives represented by their authors, and the importance of authors’ choices of language and genre in shaping the composition and reception of their works.
Museums and Museum Studies in New Zealand: A Survey of Historical Developments
Authors: McCarthy Conal , Cobley Joanna
Published: February 2009

What relationship has the university subject of museum studies had with the museum sector? It is often claimed that there is an oversupply of graduates in museum studies ill‐equipped to work in museums, an issue that reveals tensions between understandings of academic study and practical experience. This article addresses these tensions between museums and museum studies through a survey of the historical development of museums and the closely related development of training, professional development and university degrees. The generalist role of the museum worker in the embryonic museums of colonial New Zealand did not require formal academic training. The 1930s witnessed a turning point with grants for professional development from the Carnegie Corporation. The Second World War disrupted the museum sector but from the 1950s museums experienced rapid growth in type and number, developments requiring larger numbers of specialised staff. At the same time the International Council of Museums (ICOM) and the museum branch of UNESCO were formed, along with a national professional body The Art gallery and Museums Association of New Zealand (AGMANZ), which provided an international and local voice and focus for the museum sector. Finally, in the 1960s, only 100 years after the first museum was opened, we see the birth of museum‐centred training programmes first administered by the museum sector and in the late 1980s by the university. The article concludes that the increasingly complex and specialised museum profession and the increasingly sophisticated academic analysis of museums emerged at the same time and are inevitably and necessarily intertwined.
Phosphorylation of p70S6 kinase predicts overall survival in patients with clear margin‐resected hepatocellular carcinoma
Authors: Baba Hideo A. , Wohlschlaeger Jeremias , Cicinnati Vito R. , Hilgard Philip , Lang Hauke , Sotiropoulos Georgios C. , Takeda Atsushi , Beckebaum Susanne , Schmitz Klaus J.
Published: February 2009

Background/Aims: The mammalian target of rapamycin (mTOR) inhibitors play a key role in regulating signal transduction by blocking the mTOR pathway and combining anticancer and immunosuppressive properties. This study was undertaken to determine the prevalence and clinicopathological relevance of phospho‐p70S6 (p‐p70S6) kinase in hepatocellular carcinoma (HCC) and to investigate the effects of rapamycin on HCC in vitro.

Methods: A total of 196 patients with HCCs were treated either with surgical resection (n=106) or liver transplantation (n=90). Tumour tissue was investigated for p‐p70S6, phospho‐AKT, Ki‐67, Cyclin‐D1 and apoptosis, and staining results were correlated with clinicopathologically relevant parameters.

Results: Overall, p‐p70S6 was detected in 24.5% (48/196) of HCCs. In the resection group, 26.4% (28/106) of HCC were positive and 22.2% (20/90) in the transplant group. p‐p70S6 was significantly associated with elevated Cyclin‐D1 immunoexpression and was correlated with decreased overall survival (P=0.011) in patients resected with a clear margin. In multivariate COX regression analysis, p‐p70S6 was identified as an independent prognostic parameter in patients resected with a clear margin. Rapamycin induced apoptosis and growth inhibition by G0/G1 cell cycle arrest in vitro. However, in HCC patients p‐p70S6 kinase was not associated with proliferation or apoptosis.

Conclusions: Activation of p70S6 kinase indicates aggressive tumour behaviour in patients with clear margin‐resected HCC. Identification of p‐p70S6 kinase in HCC selects high‐risk patients who may benefit from drugs targeting the mTOR pathway.
Effects of silymarin on hepatitis C virus and haem oxygenase‐1 gene expression in human hepatoma cells
Authors: Bonifaz Vania , Shan Ying , Lambrecht Richard W. , Donohue Susan E. , Moschenross Darcy , Bonkovsky Herbert L.
Published: February 2009

Background/Aims:Hepatitis C virus (HCV) infection is a global medical problem. The current standard treatment of chronic hepatitis C (CHC), pegylated interferon plus ribavirin, is prolonged, expensive, has serious side effects and, at best, is only 50% effective. Silymarin (SI) is a natural antioxidant often used by patients with CHC, although its efficacy for decreasing HCV levels or ameliorating CHC remains uncertain. HCV infection is associated with increased hepatic oxidative stress, and one of the antioxidant enzymes that protect cells against this stress is haem oxygenase‐1 (HO‐1).

Methods:We investigated effects of SI on HCV and HO‐1 gene expression in Huh‐7 cells, CNS3 and 9‐13 cells (the latter two stably expressing HCV‐proteins).

Results:Silymarin significantly downregulated HCV core mRNA (by 20%–36%) and protein (by 30%–60%) in CNS3 cells. In contrast, SI did not decrease HCV NS5A mRNA or protein expression in 9‐13 cells. HO‐1 mRNA was upregulated (60%–400%) by SI in Huh‐7, CNS3 and 9‐13 cells, whereas BTB and CNC homology 1 and nuclear factor erythroid related factor 2 mRNA levels were not affected. The effect of SI to downregulate HCV core was not related to changes in the Janus‐activated tyrosine kinases–signal transducer and activators of transcription signalling pathway.

Conclusions:Silymarin may be of benefit in CHC, although prospective, randomized, controlled trials are needed to be certain.