bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial pituitary adenomas
Authors: Tichomirowa M. A. , Daly A. F. , Beckers A.
Published: April 2009

The majority of pituitary adenomas occur sporadically, however, about 5% of all cases occur in a familial setting, of which over half are due to multiple endocrine neoplasia type 1 (MEN‐1) and Carney’s complex (CNC). Since the late 1990s we have described non‐MEN1/CNC familial pituitary tumours that include all tumour phenotypes, a condition named familial isolated pituitary adenomas (FIPA). The clinical characteristics of FIPA vary from those of sporadic pituitary adenomas, as patients with FIPA have a younger age at diagnosis and larger tumours. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. This review describes the clinical features of familial pituitary adenomas like MEN1, the MEN 1‐like syndrome MEN‐4, CNC, FIPA, the tumour pathologies found in this setting and the genetic/molecular data that have been recently reported.
The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney–Stratakis syndrome): molecular genetics and clinical implications
Authors: Stratakis C. A. , Carney J. A.
Published: April 2009

Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumours (GISTs) and pulmonary chondromas (PCH). A number of other lesions have been described in the condition including pheochromocytomas, oesophageal leiomyomas and adrenocortical adenomas; CT is a novel form of multiple endocrine neoplasia (MEN), a genetic condition with a female predilection. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC and SDHD have been found in familial and sporadic PGLs, and gain‐of‐function mutations of the oncogenes c‐kit (KIT) and platelet‐derived growth factor receptor A (PDGFRA) cause sporadic and familial GISTs. We recently reported an international series of patients with CT, 34 females and three males (median age of presentation 21 years) who did not carry SDHA, SDHB, SDHC, SDHD, KIT or PDGFRA gene mutations. Comparative genomic hybridization revealed a number of DNA copy number changes. The most frequent and greatest contiguous change was a deletion within the 1pcen13‐q21 region, which harbours the SDHC gene. Another frequent change was loss of 1p. Although GISTs showed more frequent losses of 1p than PGLs, the pattern of chromosomal changes was similar in the two tumours despite their different tissue origin and histology; the findings were consistent with a common genetic aetiology of these two tumours in CT. In a separate condition, in which the association (or dyad) of GISTs with PGLs is inherited in an autosomal dominant manner (Carney–Stratakis syndrome, CSS), germline mutations of the SDHB, SDHC and SDHD genes (but not KIT or PDFGRA) were found; GISTs in this condition were caused by SDH deficiency. We conclude that CT is a novel MEN syndrome whose genetic defect remains elusive. CSS is caused by SDH defects, suggesting that sarcomas (GISTs) can be caused by defective mitochondrial oxidation, consistent with recent data implicating this enzyme in a variety of endocrine and other tumours. The above have clinical implications (i) for patients with GISTs that are cKIT‐ and PDGFRA‐mutation negative: these tumours are usually resistant to treatment with currently available tyrosine kinase inhibitors and may be part of a syndrome such as CT or CSS; and (ii) for patients with an inherited PGL syndrome, family history should be explored to identify any other tumours in the family, and in particular other endocrine lesions and GISTs.
Multiple endocrine neoplasia type 1: a chromatin writer’s block
Authors: Dreijerink K. M. A. , Lips C. J. M. , Timmers H. Th. M.
Published: April 2009

Multiple endocrine neoplasia type 1 (MEN1) is caused by inactivating germ line mutations of the MEN1 tumour suppressor gene. The MEN1 gene product, menin, participates in many cellular processes, including regulation of gene transcription. As part of a protein complex that writes a trimethyl mark on lysine 4 of histone H3 (H3K4me3), menin is involved in activating gene transcription. Several functions of the menin histone methyltransferase complex have been discovered through protein interaction studies. Menin can interact with nuclear receptors and regulate transcription of hormone responsive target genes. Menin regulates transcription of cyclin‐dependent kinase inhibitor and Hox genes via the chromatin‐associated factor LEDGF. Aberrant expression of menin target genes in tumours in MEN1 patients suggests that loss of writing of the H3K4me3 mark contributes to MEN1 tumourigenesis. At present, drugs are being developed that target chromatin modifications. The identification of compounds that could restore H3K4me3 on menin target genes would provide new therapeutic strategies for MEN1 patients.
Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50
Authors: Rosengren A. , Eriksson H. , Hansson P. O. , Svärdsudd K. , Wilhelmsen L. , Johansson S. , Welin C. , Welin L.
Published: April 2009

Objective.  To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined.

Design.  Cross‐sectional studies of five successive cohorts of men aged 50.

Setting.  City of Göteborg, Sweden.

Subjects.  Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953.

Main outcome measures.  Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L−1 over four decades.

Results.  Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m−2 (P < 0.0001), with an increase in the prevalence of obesity (BMI ≥ 30 kg m−2) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L−1 compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L−1 of 8.30 (2.37 to 29.0). However, optimal risk factor status – no smoking, normotension and total serum cholesterol <5 mmol L−1– was still present in less than one in six men in 2003, similar across BMI categories.

Conclusions.  Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.
Expression of biotransformation genes in woodrat (Neotoma) herbivores on novel and ancestral diets: identification of candidate genes responsible for dietary shifts
Authors: MAGNANOU E. , MALENKE J. R. , DEARING M. D.
Published: April 2009

The ability of herbivores to switch diets is thought to be governed by biotransformation enzymes. To identify potential biotransformation enzymes, we conducted a large‐scale study on the expression of biotransformation enzymes in herbivorous woodrats (Neotoma lepida). We compared gene expression in a woodrat population from the Great Basin that feeds on the ancestral diet of juniper to one from the Mojave Desert that putatively switched from feeding on juniper to feeding on creosote. Juniper and creosote have notable differences in secondary chemistry, and thus, should require different biotransformation enzymes for detoxification. Individuals from each population were fed juniper and creosote diets separately. After the feeding trials, hepatic mRNA was extracted and hybridized to laboratory rat microarrays. Hybridization of woodrat samples to biotransformation probes on the array was 87%, resulting in a total of 224 biotransformation genes that met quality control standards. Overall, we found large differences in expression of biotransformation genes when woodrats were fed juniper vs. creosote. Mojave woodrats had greater expression of 10× as many biotransformation genes as did Great Basin woodrats on a creosote diet. We identified 24 candidate genes that may be critical in the biotransformation of creosote toxins. Superoxide dismutase, a free radical scavenger, was also expressed to a greater extent by the Mojave woodrats and may be important in controlling oxidative damage during biotransformation. The results are consistent with the hypothesis that biotransformation enzymes limit diet switching and that woodrats in the Mojave have evolved a unique strategy for the biotransformation of creosote toxins.
A microarray's view of life in the desert: adding a powerful evolutionary genomics tool to the packrat's midden
Authors: MATOCQ MARJORIE D
Published: April 2009

Identifying the genetic architecture of adaptive traits is fundamental to understanding how organisms respond to their environment, over both ecological and evolutionary timeframes. Microarray technology that allows us to capture the simultaneous expression of thousands of genes provides unparalleled insight into how organisms cope with their environment at the transcriptional level. Recent studies in Molecular Ecology demonstrate how microarrays can rapidly identify which genes and pathways allow organisms to face some of the most fundamental physiological challenges posed by the environment, including compensation for the hypoxic and thermal stress of high‐altitudes (Cheviron et al. 2008) and, in this issue, the biotransformation of toxic plant secondary compounds by mammals (Magnanou et al. 2009).

Microarrays (Ekins et al. 1989; Fodor et al. 1991) are glass slides affixed with hundreds to thousands of oligonucleotide or cDNA sequences (probes). Messenger RNA transcripts (typically reverse transcribed to cDNA) are isolated from a tissue/sample of interest and hybridized to the array. Binding to specific probes indicates that a particular gene was transcriptionally active at or near the time of sampling and thus provides a potentially comprehensive measure of gene expression. Although a tremendously powerful tool, commercially produced oligonucleotide arrays are only available for a handful of model organisms. Nonetheless, evolutionary ecologists have exploited this resource by using a cross‐species hybridization approach (e.g. Saetre et al. 2004), that is, hybridizing a model organism array with a nonmodel sample (Bar‐Or et al. 2007). Magnanou et al. (2009) present a novel example of using a model muroid microarray (Agilent Technologies, Rattus) to study physiological response in a wild, nonmodel muroid, Neotoma.
The innate immunity role of cathepsin‐D is linked to Trp‐491 and Trp‐492 residues of listeriolysin O
Authors: Carrasco‐Marín Eugenio , Madrazo‐Toca Fidel , De Los Toyos Juan R. , Cacho‐Alonso Eva , Tobes Raquel , Pareja Eduardo , Paradela Alberto , Albar Juan Pablo , Chen Wei , Gomez‐Lopez Maria Teresa , Alvarez‐Dominguez Carmen
Published: April 2009

Listeriolysin O (LLO) is a thiol‐activated cytolysin secreted by Listeria monocytogenes. LLO and phosphatidylinositol phospholipase C are two essential virulence factors, which this bacterium needs to escape from the phagosomal compartment to the cytoplasm. Cathepsin‐D specifically cleaves LLO, between the Trp‐491 (tryptophan amino acid in three letter nomenclature) and Trp‐492 residues of the conserved undecapeptide sequence, ECTGLAWEWWR, in the domain 4 of LLO (D4). Moreover, these residues also correspond to the phagosomal‐binding epitope. Cathepsin‐D had no effect on phosphatidylinositol phospholipase C. We have observed that cathepsin‐D cleaved the related cholesterol‐dependent cytolysin pneumolysin at the same undecapeptide sequence between Trp‐435 and Trp‐436 residues. These studies also revealed an additional cathepsin‐D cleavage site in the pneumolysin D4 domain localized in the 361‐GDLLLD‐366 sequence. These differences might confer a pathogenic advantage to listeriolysin O, increasing its resistance to phagosomal cathepsin‐D action by reducing the number of cleavages sites in the D4 domain. Using ΔLLO/W491A and ΔLLO/W492A bacterial mutants, we reveal that the Trp‐491 residue has an important role linked to cathepsin‐D in Listeria innate immunity.
Structural and kinetic analysis of an MsrA–MsrB fusion protein from Streptococcus pneumoniae
Authors: Kim Young Kwan , Shin Youn Jae , Lee Won‐Ho , Kim Hwa‐Young , Hwang Kwang Yeon
Published: April 2009

Methionine sulphoxide reductases (Msr) catalyse the reduction of oxidized methionine to methionine. These enzymes are divided into two classes, MsrA and MsrB, according to substrate specificity. Although most MsrA and MsrB exist as separate enzymes, in some bacteria these two enzymes are fused to form a single polypeptide (MsrAB). Here, we report the first crystal structure of MsrAB from Streptococcus pneumoniae (SpMsrAB) at 2.4 Å resolution. SpMsrAB consists of an N‐terminal MsrA domain, a C‐terminal MsrB domain and a linker. The linker is composed of 13 residues and contains one 310‐helix and several hydrogen bonds interacting with both MsrA and MsrB domains. Interestingly, our structure includes the MsrB domain complexed with an SHMAEI hexa‐peptide that is the N‐terminal region of neighbouring MsrA domain. A kinetic analysis showed that the apparent Km of SpMsrAB for the R‐form‐substrate was 20‐fold lower than that for the S‐form substrate, indicating that the MsrB domain had a much higher affinity for the substrate than the MsrA domain. Our study reveals the first structure of the MsrAB by providing insights into the formation of a disulphide bridge in the MsrB, the structure of the linker region, and the distinct structural nature of active site of each MsrA and MsrB domain.
Combined MRI–PET dissects dynamic changes in plant structures and functions
Authors: Jahnke Siegfried , Menzel Marion I. , Van Dusschoten Dagmar , Roeb Gerhard W. , Bühler Jonas , Minwuyelet Senay , Blümler Peter , Temperton Vicky M. , Hombach Thomas , Streun Matthias , Beer Simone , Khodaverdi Maryam , Ziemons Karl , Coenen Heinz H. , Schurr Ulrich
Published: April 2009

Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non‐invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short‐lived radioactive carbon isotope 11C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species‐specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI–PET co‐registration opens the door for non‐invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.
Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta‐analysis
Authors: Anandan C. , Nurmatov U. , Sheikh A.
Published: April 2009

Background:  There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders.

Methods:  We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double‐blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta‐analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity.

Results:  Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta‐analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78–1.54); asthma: RR = 0.81 (95% CI 0.53–1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34–1.89) or food allergy RR = 0.51 (95% CI 0.10–2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56–1.16)] for the prevention of clinical disease.

Conclusions:  Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta‐analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease.
GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma ‘epidemic’
Authors: Bousquet J. , Burney P. G. , Zuberbier T. , Cauwenberge P. v. , Akdis C. A. , Bindslev‐Jensen C. , Bonini S. , Fokkens W. J. , Kauffmann F. , Kowalski M. L. , Lodrup‐Carlsen K. , Mullol J. , Nizankowska‐Mogilnicka E. , Papadopoulos N. , Toskala E. , Wickman M. , Anto J. , Auvergne N. , Bachert C. , Bousquet P. J. , Brunekreef B. , Canonica G. W. , Carlsen K. H. , Gjomarkaj M. , Haahtela T. , Howarth P. , Lenzen G. , Lotvall J. , Radon K. , Ring J. , Salapatas M. , Schünemann H. J. , Szczecklik A. , Todo‐Bom A. , Valovirta E. , Von Mutius E. , Zock J. P.
Published: April 2009

Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA2LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle Allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan‐European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA2LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project‐related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA2LEN are reported in this paper.
Evaluating the potential impact of mismatches outside the antigen recognition site in unrelated hematopoietic stem cell transplantation: HLA‐DRB1*1454 and DRB1*140101
Authors: Xiao Y. , Lazaro A. M. , Masaberg C. , Haagenson M. , Vierra‐Green C. , Spellman S. , Dakshanamurthy S. , Ng J. , Hurley C. K.
Published: April 2009

DNA sequencing of 268 individuals drawn from four US populations carrying two unresolved DRB1*14 alleles differing only outside the antigen recognition site identified DRB1*1454 in the majority. A database of 4222 human leukocyte antigen (HLA)‐matched hematopoietic stem cell transplantation donor–recipient pairs was queried to determine the number likely mismatched for DRB1*140101/DRB1*1454 but matched for class I loci. A power calculation suggests that more than 88,000 transplants among European Americans will be needed to identify sufficient 7/8 allele‐matched pairs to evaluate the impact of the DRB1*140101/DRB1*1454 mismatch on transplant outcome. Molecular modeling of the HLA‐DR interaction with the T‐cell receptor and with CD4 suggests that the amino acid substitution distinguishing the two alleles will have minimal impact on allorecognition.
Identification of a novel allele HLA‐DRB1*0478 by sequence‐based typing in a Chinese individual
Authors: Gao S.‐Q. , Deng Z.‐H. , Xu Y.‐P.
Published: April 2009

A novel allele HLA‐DRB1*0478 is described. This variant has one nucleotide substitution in exon 2. This mutations result in an amino acid substitution at condon 70 (CAG → CGG) from Gln to Arg.
Characterization of three novel HLA alleles, HLA‐B*4613, HLA‐B*4614 and HLA‐B*4618, in Chinese individuals
Authors: Yan L.‐X. , Zhu F.‐M. , Zhang W. , He J.
Published: April 2009

Three novel alleles, human leukocyte antigen (HLA)‐B*4613, HLA‐B*4614 and HLA‐B*4618, were identified in Chinese individuals. HLA‐B*4613 shows four nucleotides difference from B*460101, resulting in two amino acids change from Glu to Val at codon 152 and Trp to Leu at codon 156. HLA‐B*4614 has a single nucleotide difference at position 97 T→C compared with HLA‐B*460101, with an amino acid change from Tyr to His at codon 9. HLA‐B*4618 shares the sequence of exon 2 with B*4601 and sequences of exons 3 and 4 with B*55, B*54 or B*59, together resulting in eight amino acids change compared with HLA‐B*460101.
Characterization of a new HLA‐C allele in a Chinese family by sequence‐based typing: HLA‐Cw*0348
Authors: Zou H.‐Y. , Li Z. , Deng Z.‐H.
Published: April 2009

The novel human leukocyte antigen (HLA)‐Cw*0348 allele was identified by sequence‐based typing in a Chinese family. This allele shows that the sequences of exons 1–3 of HLA‐Cw*0348 are identical to those of HLA‐Cw*030401 except for a nucleotide substitution that changes CCG to CTG at codon 57, resulting in an amino acid change from Pro to Leu in the protein, and this is a unique nucleotide change among the HLA‐C alleles, suggesting a point mutation mechanism. The extended haplotype carrying the new allele was deduced from the family group typing and defined as A*110101, B*1301, Cw*0348, DRB1*0405, and DQB1*0402.
Vaccination status in pediatric liver transplant candidates
Authors: Dehghani Seyed Mohsen , Shakiba Mohammad Ali , Ziaeyan Maziyar , Imanieh Mohammad Hadi , Haghighat Mahmood , Bahador Ali , Nikeghbalian Saman , Salahi Heshmatollah , Alborzi Abdolvahab , Malek‐Hosseini Seyed Ali
Published: April 2009

Abstract:  Infection is a recognized and potentially serious complication in children following solid organ transplantation. This problem is particularly important for young children undergoing any organ transplantation who often have not completed standard childhood immunizations at the time of transplantation and who are therefore at risk for vaccine‐preventable infections. To evaluate the vaccination status in liver transplant candidates, vaccination charts of 100 patients who were referred to Organ Transplant Center of Nemazee Hospital were reviewed and the vaccination status considered appropriate according to the recommendation of NIP and the patients’ age. Fifty‐eight percent of patients were completely vaccinated for HBV, 85% for OPV, 97% for BCG, 63% for DTP, and 58% of the patients were completely vaccinated for MMR. We concluded that the vaccination charts should be periodically reviewed and updated to prevent the vaccine‐preventable disease in liver transplant candidates not only before but also after transplant. Every effort should be made to assure that candidates are immunized early in the course of their disease. Also it may be indicated to recommend a special guideline for immunization of liver transplant candidates and add other vaccines such as Haemophilus influenzae and Streptococcus pneumoniae vaccine to their vaccination program.
Effects of individual and population parameters on reproductive success in three sexually deceptive orchid species
Authors: Vandewoestijne S. , Róis A. S. , Caperta A. , Baguette M. , Tyteca D.
Published: April 2009

Reproductive success (RS) in orchids in general, and in non‐rewarding species specifically, is extremely low. RS is pollinator and pollination limited in food deceptive orchids, but this has rarely been studied in sexually deceptive orchid species. Here, we tested the effects of several individual (plant height, inflorescence size, nearest neighbour distance and flower position) and population (patch geometry, population density and size) parameters on RS in three sexually deceptive Ophrys (Orchidaceae) species. Inter‐specific differences were observed in RS of flowers situated in the upper versus the lower part of the inflorescence, likely due to species‐specific pollinator behaviour. For all three species examined, RS increased with increasing plant height, inflorescence size and nearest neighbour distance. RS generally increased with decreasing population density and increasing patch elongation. Given these results, we postulate that pollinator availability, rather than pollinator learning, is the most limiting factor in successful reproduction for sexually deceptive orchids. Our results also suggest that olfactory ‘display’ (i.e. versus optical display), in terms of inflorescence size (and co‐varying plant height), plays a key role in individual RS of sexually deceptive orchids. In this regard, several hypotheses are suggested and discussed.
Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments
Authors: Rubio de Casas R. , Vargas P. , Pérez‐Corona E. , Cano E. , Manrique E. , García‐Verdugo C. , Balaguer L.
Published: April 2009

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and β‐carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.
Chronic hepatitis B infection in an Australian antenatal population: seroprevalence and opportunities for better outcomes
Authors: Guirgis Marianne , Zekry Amany , Yan Kenneth , Bu Yang Min , Lee Alice
Published: April 2009

Background:  In the antenatal population, screening for Hepatitis B virus (HBV) carrier status is routinely undertaken to guide preventative measures for the newborn. There is scarce information in the literature, however, regarding the subsequent management of Hepatitis B surface antigen (HBsAg) positive mothers.

Aims and Methods:  Thus, we undertook this retrospective study to (i) determine the prevalence of HBsAg positivity among mothers attending two teaching hospital birth centers; (ii) determine whether HBsAg mothers received HBV education and underwent further evaluation of HBV infectivity status; and (iii) determine whether these mothers had further follow up for HBV infection post delivery.

Results:  Between January 2003 and December 2006, 14, 857 mothers were screened for hepatitis B virus infection. Among these, 295 mothers were positive with HBsAg seroprevalence of 2%. A more detailed review of the available 206 medical records revealed that the majority (78%) had previous documentation of infection in earlier pregnancies. However none had received education regarding HBV infectivity. In addition, liver function tests were only performed in 78% of the mothers while Hepatitis B e antigen was tested in 65% of cases. Further, 93% of the mothers had no documentation of further follow up plans or referrals for their HBV infection.

Conclusion:  It is clear that chronic HBV infection is prevalent in the antenatal population. However, there are no strategies to ensure that infected mothers subsequently undergo further education for HBV or evaluation of infectivity. Clearly strategies are required to ensure improved follow up of hepatitis B infected mothers.
Efficacy of a single 24‐hour pre‐anesthetic dose of proton pump inhibitors
Authors: Hirota Kazuyoshi , Imai Atsushi , Kudo Mihoko , Hashimoto Hiroshi , Kushikata Tetsuya
Published: April 2009

Background and Aim:  The H2 receptor antagonist roxatidine is routinely used as an oral pre‐anesthetic medication in surgical patients at night and 2 h before surgery. In the present study, we have compared the effects of roxatidine, rabeprazole and lansoprazole given singly at night as an alternative to the standard double roxatidine medication.

Methods:  120 adult patients undergoing urological surgery were randomly assigned to three groups: roxatidine, rabeprazole and lansoprazole (n = 40 each). Following induction of anesthesia, gastric fluid was obtained by aspiration using a syringe to measure pH and volume of gastric contents.

Results:  Gastric volume (14.1 ± 1.9 mL) in the lansoprazole group was significantly larger than that in roxatidine (8.6 ± 1.7 mL) and rabeprazole (7.5 ± 1.1 mL) groups (P < 0.05). Gastric pH in lansoprazole group (4.10 ± 0.38) was also significantly lower than that in the roxatidine group (5.41 ± 0.31, P < 0.05). The numbers of patients with critical factors for acid aspiration pneumonia (gastric pH < 2.5 or volume > 25 mL) in the lansoprazole group was significantly higher than in the roxatidine group (P < 0.05). Gastric pH and volume in all groups were constant even in the afternoon.

Conclusion:  Single rabeprazole (but not lansoperazole) medication may be a suitable alternative to standard roxatidine for prophylaxis of acid aspiration pneumonia.
Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus‐related cirrhosis
Authors: Toshikuni Nobuyuki , Izumi Akiyoshi , Nishino Ken , Inada Nobu , Sakanoue Ritsuko , Yamato Ryumei , Suehiro Mitsuhiko , Kawanaka Miwa , Yamada Gotaro
Published: April 2009

Background and Aim:  The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far.

Methods:  We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)‐infected patients.

Results:  A total of 227 patients (75 alcoholic and 152 HCV‐infected patients) with compensated cirrhosis were enrolled. The median follow‐up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV‐infected patients (6.8% vs 50.3% at 10 years, P = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan‐Meir analysis). The main causes of death were hepatic failure and non‐hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV‐infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV‐related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non‐abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV‐infected patients.

Conclusions:  Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV‐related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV‐related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.
Prediction of response to combined immunotherapy with interferon‐α and low‐dose interleukin‐2 in metastatic renal cell carcinoma: Expression patterns of potential molecular markers in radical nephrectomy specimens
Authors: Miyake Hideaki , Sakai Iori , Muramaki Mototsugu , Kurahashi Toshifumi , Takenaka Atsushi , Fujisawa Masato
Published: April 2009

Objectives:  To evaluate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) who received combined immunotherapy with interferon‐α (IFN‐α) and low‐dose interleukin‐2 (IL‐2) and to identify factors predicting susceptibility to this therapy.

Methods:  This study included 40 patients with metastatic clear cell RCC undergoing combined immunotherapy with IFN‐α and low‐dose IL‐2 following radical nephrectomy. Expression levels of 10 markers, including Aurora‐A, Bcl‐2, clusterin, heat shock protein 27, heat shock protein 90, Ki‐67, matrix metalloproteinase‐2, matrix metalloproteinase‐9, p53 and vascular endothelial growth factor, in RCC specimens were measured using immunohistochemical staining.

Results:  In this series, one, 10, 15 and 16 patients were diagnosed as showing complete response, partial response, stable disease and progressive disease, respectively. Expression levels of Bcl‐2 and Ki‐67 had significant impacts on the response to this therapy. Furthermore, cancer‐specific survival was significantly associated with the expression levels of Ki‐67 and Bcl‐2 in addition to performance status, presence of metastases at diagnosis, metastatic organ and C‐reactive protein on univariate analysis. Only the presence of metastases at diagnosis and Ki‐67 expression level appeared to be independent predictors of cancer‐specific survival on multivariate analysis.

Conclusions:  It would be useful to consider the expression levels of potential molecular markers, particularly Ki‐67, in addition to clinical parameters, such as the presence of metastases at diagnosis, to select metastatic RCC patients likely to benefit from combined immunotherapy.
ON THE PURPOSES AND ENDS OF NATURAL RHETORIC
Authors: MACIEJEWSKI JEFFREY J.
Published: April 2009

Despite traditional viewpoints that see rhetoric as nothing more than a techné or bios, rhetoric may be viewed as being capable of instantiating basic human goods. This paper proposes that rhetoric motivates our capacities for action and brings the processes involved in action – including the bearing of practical reason on them – into accord with virtue, enabling us to exercise practical wisdom in and through prudential judgments so that when these judgments have a direct bearing on others we may say that they are just.
INQUIRY, CONVERSATION AND THEISTIC BELIEF: WILLIAM JAMES AND RICHARD RORTY GET RELIGION
Authors: NELSON DEREK R.
Published: April 2009

This essay examines William James' view that pragmatic philosophy allows for theistic belief and compares it to Richard Rorty's argument that theistic belief is fundamentally incompatible with pragmatic philosophy. Theism is permissible for James because it is commensurate with his view of philosophy as inquiry. Theism is impermissible for Rorty because it incommensurate with his view of philosophy as conversation. James' arguments are shown to be too generic in their conception of the God in whom theistic belief may be placed, and Rorty's arguments against the desirability of theistic belief are shown to run afoul of his own philosophical program.
JESUS' LANGUAGE‐GAMES: THE SIGNIFICANCE OF THE NOTION OF LANGUAGE‐GAME FOR A REFORMULATION OF ‘NEW TESTAMENT BIBLICAL THEOLOGY’1
Authors: LOCKER MARKUS
Published: April 2009

Despite the exciting consequences of the later Wittgenstein's notion of language‐game for theology in general, one discipline centered on language – exegesis and biblical theology – has remained largely unaffected by this advance. I here show that describing biblical language as a language‐game not only enhances our understanding of biblical texts; it also explodes a long‐term impasse separating the interpretation from the ‘actualization’ of sacred texts. Insights taken from the notion of a language‐game may, as with form of life and grammar, emerge as central building blocks for reformulating the postulates of biblical theology. 2
EVOLUTIONARY PSYCHOLOGY AND THE RATIONALITY OF FAITH
Authors: MURPHY BENJAMIN
Published: April 2009

This paper evaluates the role that evolutionary psychology can play in examining the rationality of faith in the Christian sense. It is argued that because evolutionary psychology enables us to understand human nature, it can help us understand what faith is. I argue that faith is not a universal human instinct that all religions tap into. Rather, we must understand how the early Christian community used the basic building blocks provided by human nature in a particular way. It is argued that it is a misunderstanding of the nature of faith to assert that faith is intrinsically irrational. However, evolutionary psychology cannot tell us whether or not faith is rational.
Assimilation and Otherness: the Theological Significance of Négritude
Authors: WILLIAMS A.N.
Published: April 2009

This article argues that otherness is a root concept in Christian theology, functioning as such in Christology and the doctrines of the Trinity, creation, sanctification and consummation. Recent philosophical and theological treatments of otherness or alterity have, however, focused on its problematic aspects, its link to ills such as racism, sexism and genocide. The thought of the Senegalese statesman and poet Léopold Sédar Senghor (1906–2001) is proposed as an aid in mediating between the tradition's conceptions of otherness and contemporary debates and contexts, illuminating root concepts which have not been recognized as such, their systematic interconnectedness and their enduring relevance.
The “X component” in Shanghai's social security reforms
Authors: Davies Gloria , Nielsen Ingrid , Nyland Chris , Smyth Russell , Zhu Cherrie , Zhu Judith
Published: April 2009

In 2003, the Shanghai Bureau of Labour and Social Security launched the zhenbao (town insurance) programme, now widely known as 25 plus X. This scheme is regarded as an important experiment in social security reform and has been lauded for extending social security to areas where previously only segments of the population had mandatory coverage. Using data from 103,000 individuals enrolled in 25 plus X, we examine the extent to which the scheme represents an extension in social security coverage. Our analysis suggests that while it does represent an extension of benefits for some, for many it represents a considerable dilution in benefits.
Women’s views on the use of decision aids for decision making about the method of delivery following a previous caesarean section: qualitative interview study
Authors: Frost J , Shaw A , Montgomery A , Murphy DJ
Published: April 2009

Objective  To obtain the views of women on their experiences of decision making about the method of delivery following a previous caesarean section and the role of decision aids in this process.

Design  Qualitative study nested within a randomised controlled trial, using repeat semi‐structured interviews conducted pre‐ and postnatally. Data were analysed using a framework approach.

Setting  Three maternity units in south‐west England and Scotland.

Sample  Purposive sample of 30 women participating in a randomised controlled trial of two decision aids for women making a decision about mode of next delivery following a previous caesarean section (Decision Aids for Mode of next Delivery).

Results  Thirty women were interviewed during pregnancy about their experience of decision making about the mode of delivery and 22 were re‐interviewed postnatally. Key themes were: role of decision aids in reducing decisional conflict and uncertainty during the pregnancy; impact of decision aids on knowledge and anxiety; the relationship between prior preferences, decisions and actual outcome; and the mediating role of decision aids.

Conclusions  Women making a decision about mode of delivery following previous caesarean section value some form of structured information to help reduce decisional conflict. Information provision for women making this decision needs to be relevant to their individual needs. Decision analysis may help reconcile prior preferences and the actual mode of delivery.
Occupational predictors of pregnancy outcomes in Irish working women in the Lifeways cohort
Authors: Niedhammer I , O’Mahony D , Daly S , Morrison JJ , Kelleher CC ,   the Lifeways Cross‐Generation Cohort Study Steering Group
Published: April 2009

Objective  The objective of this study was to explore the association between occupational factors and pregnancy outcomes in a prospective cohort of Irish pregnant women.

Design  This study has a prospective design.

Population  The Lifeways cohort included 1124 pregnant women, 676 of whom delivered a single baby and were working at their first prenatal care visit when they filled in a self‐administered questionnaire.

Methods  Occupational factors were measured using this questionnaire and included eight factors describing job and working conditions. Data including pregnancy outcomes were also obtained from clinical hospital records. Logistic regression analysis was used to adjust for well‐known risk factors.

Main outcome measures  Birthweight (≤3000 g and ≤2500 g), preterm delivery (<37 gestation weeks) and small‐for‐gestational‐age.

Results  Significant associations were found between physical work demands and low birthweight (≤2500 g) and working with between a temporary contract and preterm delivery. Trends were also observed between working 40 hours or more a week and shift work, and birthweight of 3000 g or less. The study of a cumulative index showed that being exposed to at least two of these occupational factors significantly predicted birthweight of ≤3000 g (OR = 2.44, 95% CI: 1.17–5.08) and of ≤2500 g (OR = 4.65, 95% CI: 1.08–20.07) and preterm delivery (OR = 5.18, 95% CI: 1.00–27.01).

Conclusions  Our findings suggest that occupational factors may predict birthweight through their predictive effects on preterm delivery. This is one of the few prospective studies on pregnancy outcomes that include working conditions. As they may be modifiable, occupational factors deserve more attention in relation to birth outcomes.
CD36: A multi‐modal target for acute stroke therapy
Authors: Cho Sunghee , Kim Eunhee
Published: April 2009

A role for CD36 in the pathogenesis of atherosclerosis, inflammation and lipid metabolism has been well‐documented. However, little is known about the role of CD36 in cerebral ischemia. The intent of this review is to develop the concept that CD36, whose functions have been implicated in other pathological events, is a prototypic inflammatory receptor that contributes to the pathogenesis of cerebral ischemia. The importance of CD36 as a treatment target is indicated by the fact that many treatment strategies that are effective in experimental models of stroke exhibit little or no efficacy in clinical trials. The failure of clinical trials may be due to the use of animal models of stroke that do not reflect traditional risk factors for stroke in humans. The discussion will be focused on two risk factors, hyperlipidemia and diabetes, that modulate CD36 responses. Blocking the expression and function of CD36 by pharmacological or genetic means will provide insight not only toward identifying CD36 as a novel molecular target but also for developing effective therapeutic strategies to treat stroke victims. More importantly, coupling clinically relevant conditions with CD36‐mediated ischemic injury may provide an appropriate animal model paradigm and develop a scientific understanding that could lead to clinical translational studies involving human subjects.
Protein kinase G is involved in ammonia‐induced swelling of astrocytes
Authors: Konopacka Agnieszka , Konopacki Filip A. , Albrecht Jan
Published: April 2009

Ammonia‐induced swelling of astrocytes is a primary cause of brain edema associated with acute hepatic encephalopathy. Previous studies have shown that ammonia transiently increases cGMP in brain in vivo and in cultured astrocytes in vitro. We hypothesized that protein kinase G (PKG), an enzyme activated by cGMP and implicated in regulation of cell shape, size, and/or volume in peripheral and CNS cells, may play a role in the ammonia‐induced astrocytic volume increase. Treatment of cultured rat cortical astrocytes with 1 or 5 mM NH4Cl (ammonia) for 24 h increased their cell volume by 50% and 80% above control, respectively, as measured by confocal imaging followed by 3D computational analysis. A cGMP analog, 8‐(4‐chlorophenylthio)‐cGMP, increased the cell volume in control cells and potentiated the increase in 1 mM ammonia‐treated cells. A soluble guanylate cyclase inhibitor (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one) abrogated, and a PKG inhibitor [8‐(4‐chlorophenylthio)‐cGMP‐thioate, Rp‐isomer] dose‐dependently reduced the cell volume‐increasing effect of 5 mM ammonia. The results suggest that (i) PKG may play a permissive role in ammonia‐induced astrocytic swelling and (ii) elevation of brain cGMP associated with acute exposure to ammonia in vivo may aggravate the ensuing brain edema.
Now I know my ABC. A systems neurochemistry and functional metabolomic approach to understanding the GABAergic system
Authors: Rae Caroline , Nasrallah Fatima A. , Griffin Julian L. , Balcar Vladimir J.
Published: April 2009

Here, we describe use of a reductionist brain model, the brain tissue slice, to generate snapshots of functional metabolism in response to a pharmacological (GABAergic) perturbation. Tissue slices prepared from Guinea pig cerebral cortex were incubated for 1 h in the presence of [3‐13C]‐pyruvate and ligands with affinity for GABA receptors. The resultant patterns of 13C flux and metabolite levels were measured by 13C/1H NMR spectroscopy, generating ‘metabolic fingerprints’ for each ligand. Effects of agonists and effectors at GABA receptors (A, B, and C types) were examined, compared to those of exogenous GABA and evaluated using multivariate statistical models. Data clusterings did not directly correlate with GABA receptor types but produced at least five distinct groups ranked according to their affinity for GABA. As our experimental model retains, to a large extent, the structure and function of normal brain tissue, the generated database can be used to assess GABAergic ligands and make unique inferences relevant to their modes of action in brain.