bluuebunny/crossref_metadata_2025 huggingface dataset:
Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2
Authors: Matthews Megan L. , Neumann Christopher S. , Miles Linde A. , Grove Tyler L. , Booker Squire J. , Krebs Carsten , Walsh Christopher T. , Bollinger J. Martin
Published: October 2009

The α-ketoglutarate-dependent hydroxylases and halogenases employ similar reaction mechanisms involving hydrogen-abstracting Fe(IV)-oxo (ferryl) intermediates. In the halogenases, the carboxylate residue from the His
2
(Asp/Glu)
1
“facial triad” of iron ligands found in the hydroxylases is replaced by alanine, and a halide ion (X
−
) coordinates at the vacated site. Halogenation is thought to result from “rebound” of the halogen radical from the X-Fe(III)-OH intermediate produced by hydrogen (H
•
) abstraction to the substrate radical. The alternative decay pathway for the X-Fe(III)-OH intermediate, rebound of the hydroxyl radical to the substrate radical (as occurs in the hydroxylases), reportedly does not compete. Here we show for the halogenase SyrB2 that positioning of the alkyl group of the substrate away from the oxo/hydroxo ligand and closer to the halogen ligand sacrifices H
•
-abstraction proficiency for halogen-rebound selectivity. Upon replacement of
l
-Thr, the C4 amino acid tethered to the SyrB1 carrier protein in the native substrate, by the C5 amino acid
l
-norvaline, decay of the chloroferryl intermediate becomes 130× faster and the reaction outcome switches to primarily hydroxylation of C5, consistent with projection of the methyl group closer to the oxo/hydroxo by the longer side chain. Competing H
•
abstraction from C4 results primarily in chlorination, as occurs at this site in the native substrate. Consequently, deuteration of C5, which slows attack at this site, switches both the regioselectivity from C5 to C4 and the chemoselectivity from hydroxylation to chlorination. Thus, substrate-intermediate disposition and the carboxylate → halide ligand swap combine to specify the halogenation outcome.
Zinc and cognitive development
Authors: Bhatnagar Shinjini , Taneja Sunita
Published: October 2009

Cognition is a field of thought processes by which an individual processes information through skills of perception, thinking, memory, learning and attention. Zinc deficiency may affect cognitive development by alterations in attention, activity, neuropsychological behavior and motor development. The exact mechanisms are not clear but it appears that zinc is essential for neurogenesis, neuronal migration, synaptogenesis and its deficiency could interfere with neurotransmission and subsequent neuropsychological behavior. Studies in animals show that zinc deficiency during the time of rapid brain growth, or during the juvenile and adolescent period affects cognitive development by decreasing activity, increasing emotional behavior, impairing memory and the capacity to learn. Evidence from human studies is limited. Low maternal intakes of zinc during pregnancy and lactation were found to be associated with less focused attention in neonates and decreased motor functions at 6 months of age. Zinc supplementation resulted in better motor development and more playfulness in low birth weight infants and increased vigorous and functional activity in infants and toddlers. In older school going children the data is controversial but there is some evidence of improved neuropsychological functions with zinc supplementation. Additional research is required to determine the exact biological mechanisms, the critical periods, the threshold of severity and the long-term effects of zinc deprivation on cognitive development.
Micronutrient deficiency in children
Authors: Bhan Maharaj K , Sommerfelt Halvor , Strand Tor
Published: October 2009

Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to humans, the biology of deficiency as well as excess of micronutrients in humans must continue to be investigated with vigour.
Phonological neighbourhood effects in French spoken-word recognition
Authors: Dufour Sophie , Frauenfelder Ulrich H.
Published: October 2009

According to activation-based models of spoken-word recognition, words with many and high-frequency phonological neighbours are processed more slowly than words with few and low-frequency phonological neighbours. Although considerable empirical support for inhibitory neighbourhood density effects has accumulated, especially in English, little or nothing is known about the effects of neighbourhood frequency and its interaction with neighbourhood density. In this study we examine both effects first separately and then simultaneously in French lexical decision experiments. As in English, we found that words in dense neighbourhoods are recognized more slowly than words in sparse neighbourhoods. Moreover, we showed that words with higher frequency neighbours are processed more slowly than words with no higher frequency neighbours, but only for words occurring in sparse neighbourhoods. Implications of these results for spoken-word recognition models are discussed.
Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes
Authors: Hu Chih-Chi Andrew , Dougan Stephanie K. , Winter Sebastian Virreira , Paton Adrienne W. , Paton James C. , Ploegh Hidde L.
Published: October 2009

Shiga-toxigenic Escherichia coli (STEC) use subtilase cytotoxin (SubAB) to interfere with adaptive immunity. Its inhibition of immunoglobulin secretion is both rapid and profound. SubAB favors cleavage of the newly synthesized immunoglobulin heavy chain–binding protein (BiP) to yield a C-terminal fragment that contains BiP’s substrate-binding domain. In the absence of its regulatory nucleotide-binding domain, the SubAB-cleaved C-terminal BiP fragment remains tightly bound to newly synthesized immunoglobulin light chains, resulting in retention of light chains in the endoplasmic reticulum (ER). Immunoglobulins are thus detained in the ER, making impossible the secretion of antibodies by SubAB-treated B cells. The inhibitory effect of SubAB is highly specific for antibody secretion, because other secretory proteins such as IL-6 are released normally from SubAB-treated B cells. Although SubAB also causes BiP cleavage in HepG2 hepatoma cells, (glyco)protein secretion continues unabated in SubAB-exposed HepG2 cells. This specific block in antibody secretion is a novel means of immune evasion for STEC. The differential cleavage of newly synthesized versus “aged” BiP by SubAB in the ER provides insight into the architecture of the ER compartments involved.
Qupe—a Rich Internet Application to take a step forward in the analysis of mass spectrometry-based quantitative proteomics experiments
Authors: Albaum Stefan P. , Neuweger Heiko , Fränzel Benjamin , Lange Sita , Mertens Dominik , Trötschel Christian , Wolters Dirk , Kalinowski Jörn , Nattkemper Tim W. , Goesmann Alexander
Published: October 2009

Motivation: The goal of present -omics sciences is to understand biological systems as a whole in terms of interactions of the individual cellular components. One of the main building blocks in this field of study is proteomics where tandem mass spectrometry (LC-MS/MS) in combination with isotopic labelling techniques provides a common way to obtain a direct insight into regulation at the protein level. Methods to identify and quantify the peptides contained in a sample are well established, and their output usually results in lists of identified proteins and calculated relative abundance values. The next step is to move ahead from these abstract lists and apply statistical inference methods to compare measurements, to identify genes that are significantly up- or down-regulated, or to detect clusters of proteins with similar expression profiles.

Results: We introduce the Rich Internet Application (RIA) Qupe providing comprehensive data management and analysis functions for LC-MS/MS experiments. Starting with the import of mass spectra data the system guides the experimenter through the process of protein identification by database search, the calculation of protein abundance ratios, and in particular, the statistical evaluation of the quantification results including multivariate analysis methods such as analysis of variance or hierarchical cluster analysis. While a data model to store these results has been developed, a well-defined programming interface facilitates the integration of novel approaches. A compute cluster is utilized to distribute computationally intensive calculations, and a web service allows to interchange information with other -omics software applications. To demonstrate that Qupe represents a step forward in quantitative proteomics analysis an application study on Corynebacterium glutamicum has been carried out.

Availability and Implementation: Qupe is implemented in Java utilizing Hibernate, Echo2, R and the Spring framework. We encourage the usage of the RIA in the sense of the ‘software as a service’ concept, maintained on our servers and accessible at the following location: http://qupe.cebitec.uni-bielefeld.de

Contact:  stefan.albaum@cebitec.uni-bielefeld.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pathway identification by network pruning in the metabolic network of Escherichia coli
Authors: Gerlee P. , Lizana L. , Sneppen K.
Published: October 2009

Motivation: All metabolic networks contain metabolites, such as ATP and NAD, known as currency metabolites, which take part in many reactions. These are often removed in the study of these networks, but no consensus exists on what actually constitutes a currency metabolite, and it is also unclear how these highly connected nodes contribute to the global structure of the network.

Results: In this article, we analyse how the Escherichia coli metabolic network responds to pruning in the form of sequential removal of metabolites with highest degree. As expected this leads to network fragmentation, but the process by which it occurs suggests modularity and long-range correlations within the network. We find that the pruned networks contain longer paths than the random expectation, and that the paths that survive the pruning also exhibit a lower cost (number of involved metabolites) compared with random paths in the full metabolic network. Finally we confirm that paths detected by pruning overlap with known metabolic pathways. We conclude that pruning reveals functional pathways in metabolic networks, where currency metabolites may be seen as ingredients in a well-balanced soup in which main metabolic production lines are immersed.

Contact:  gerlee@nbi.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Exon Array Analyzer: a web interface for Affymetrix exon array analysis
Authors: Gellert Pascal , Uchida Shizuka , Braun Thomas
Published: October 2009

Summary: The Exon Array Analyzer (EAA) is a web server, which provides a user-friendly interface to identify alternative splicing events analyzed with Affymetrix Exon Arrays. The EAA implements the Splice Index algorithm to identify differential expressed exons. The use of various filters allows reduction of the number of false positive hits. Results are presented with detailed annotation information and graphics to identify splice events and to facilitate biological validations. To demonstrate the versatility of the EAA, we analyzed exon arrays of 11 different murine tissues using sample data provided by Affymetrix (http://www.affymetrix.com). Data from the heart were compared with other tissues to identify exons that undergo heart-specific alternatively splicing, resulting in the identification of 885 differentially expressed probe sets in 649 genes.

Availability: The web interface is available at http://EAA.mpi-bn.mpg.de/. Detailed documentation is available on the EAA web site (http://EAA.mpi-bn.mpg.de/supp.php) including screen shots, example analyzes and step by step instructions.

Contact:  thomas.braun@mpi-bn.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
When Should Political Scientists Use the Self-Confirming Equilibrium Concept? Benefits, Costs, and an Application to Jury Theorems
Authors: Lupia Arthur , Levine Adam Seth , Zharinova Natasha
Published: October 2009

Many claims about political behavior are based on implicit assumptions about how people think. One such assumption, that political actors use identical conjectures when assessing others' strategies, is nested within applications of widely used game-theoretic equilibrium concepts. When empirical findings call this assumption into question, the self-confirming equilibrium (SCE) concept provides an alternate criterion for theoretical claims. We examine applications of SCE to political science. Our main example focuses on the claim of Feddersen and Pesendorfer that unanimity rule can lead juries to convict innocent defendants (1998. Convicting the innocent: The inferiority of unanimous jury verdicts under strategic voting.American Political Science Review92:23–35). We show that the claim depends on the assumption that jurors have identical beliefs about one another's types and identical conjectures about one another's strategies. When jurors' beliefs and conjectures vary in ways documented by empirical jury research, fewer false convictions can occur in equilibrium. The SCE concept can confer inferential advantages when actors have different beliefs and conjectures about one another.
A Comprehensive Transcriptomic Analysis of the Effect of Silicon on Wheat Plants Under Control and Pathogen Stress Conditions
Authors: Chain F. , Côté-Beaulieu C. , Belzile F. , Menzies J. G. , Bélanger R. R.
Published: October 2009

The supply of soluble silicon (Si) to plants has been associated with many benefits that remain poorly explained and often contested. In this work, the effect of Si was studied on wheat plants under both control and pathogen stress (Blumeria graminis f. sp. tritici) conditions by conducting a large transcriptomic analysis (55,000 unigenes) aimed at comparing the differential response of plants under four treatments. The response to the supply of Si on control (uninfected) plants was limited to 47 genes of diverse functions providing little evidence of regulation of a specific metabolic process. Plants reacted to inoculation with B. graminis f. sp. tritici by an upregulation of many genes linked to stress and metabolic processes and a downregulation of genes linked to photosynthesis. Supplying Si to inoculated plants largely prevented disease development, a phenotypic response that translated into a nearly perfect reversal of genes regulated by the effect of B. graminis f. sp. tritici alone. These results suggest that Si plays a limited role on a plant's transcriptome in the absence of stress, even in the case of a high-Si-accumulating monocot such as wheat. On the other hand, the benefits of Si in the form of biotic stress alleviation were remarkably aligned with a counter-response to transcriptomic changes induced by the pathogen B. graminis f. sp. tritici.
The Two Conserved Cysteine Residues of the Triple Gene Block Protein 2 Are Critical for Both Cell-to-Cell and Systemic Movement of Bamboo mosaic virus
Authors: Tseng Yang-Hao , Hsu Hsiu-Ting , Chou Yuan-Lin , Hu Chung-Chi , Lin Na-Sheng , Hsu Yau-Heiu , Chang Ban-Yang
Published: October 2009

The triple gene block protein 2 (TGBp2) of Bamboo mosaic virus (BaMV) is a transmembrane protein which is known to be required for the cell-to-cell movement of potexviruses. This protein has two conserved Cys residues, Cys-109 and Cys-112, at its C-terminal tail, which is supposed to be exposed on the outer surface of the endoplasmic reticulum (ER) membrane and ER-derived granular vesicles. In this study, we investigated the importance of these two Cys residues on the cell-to-cell and systemic movement of BaMV. Our results indicate that the Cys-to-Ala substitutions in TGBp2 make the cell-to-cell movement of BaMV relatively inefficient and the systemic movement of BaMV severely inhibited. Moreover, the defect in systemic movement is attributed to the inefficient transport of viral RNA in the phloem of petiole. Clearly, TGBp2 is critical not only for the cell-to-cell but also for the systemic movement of BaMV. In addition, the conserved Cys residues are important for the functioning of TGBp2.
The Pepper Calmodulin Gene CaCaM1 Is Involved in Reactive Oxygen Species and Nitric Oxide Generation Required for Cell Death and the Defense Response
Authors: Choi Hyong Woo , Lee Dong Hyuk , Hwang Byung Kook
Published: October 2009

Calcium signaling has emerged as an important signal transduction pathway of higher plants in response to biotic and abiotic stresses. Ca2+-bound calmodulin (CaM) plays a critical role in decoding and transducing stress signals by activating specific targets. Here, we isolated and functionally characterized the pathogen-responsive CaM gene, Capsicum annuum calmodulin 1 (CaCaM1), from pepper (C. annuum) plants. The cellular function of CaCaM1 was verified by Agrobacterium spp.-mediated transient expression in pepper and transgenic overexpression in Arabidopsis thaliana. Agrobacterium spp.-mediated transient expression of CaCaM1 activated reactive oxygen species (ROS), nitric oxide (NO) generation, and hypersensitive response (HR)-like cell death in pepper leaves, ultimately leading to local acquired resistance to Xanthomonas campestris pv. vesicatoria. CaCaM1-overexpression (OX) Arabidopsis exhibited enhanced resistance to Pseudomonas syringae and Hyaloperonospora parasitica, which was accompanied by enhanced ROS and NO generation and HR-like cell death. Treatment with the calcium-channel blocker suppressed the oxidative and NO bursts and HR-like cell death that were triggered by CaCaM1 expression in pepper and Arabidopsis, suggesting that calcium influx is required for the activation of CaCaM1-mediated defense responses in plants. Upon treatment with the CaM antagonist, virulent P. syringae pv. tomato-induced NO generation was also compromised in CaCaM1-OX leaves. Together, these results suggest that the CaCaM1 gene functions in ROS and NO generation are essential for cell death and defense responses in plants.
SOD1-Targeted Gene Disruption in the Ericoid Mycorrhizal Fungus Oidiodendron maius Reduces Conidiation and the Capacity for Mycorrhization
Authors: Abbà S. , Khouja H. R. , Martino E. , Archer D. B. , Perotto S.
Published: October 2009

The genome sequences of mycorrhizal fungi will provide new opportunities for studying the biology and the evolution underlying this symbiotic lifestyle. The generation of null mutants at the wild-type loci is one of the best methods for gene-function assignment in the post-genomic era. To our knowledge, the generation of superoxide dismutase 1 (SOD1)-null mutants in the ericoid mycorrhizal fungus Oidiodendron maius is the first example of a gene-targeted disruption via homologous recombination in a mycorrhizal fungus. The disruption of OmSOD1 by Agrobacterium-mediated transformation resulted in the presence of oxidative stress markers, even in the absence of external superimposed stresses, and an increased sensitivity to reactive oxygen species (ROS)-generating substances, especially to menadione. A reduction in conidiation and in the percentage of mycorrhization of Vaccinium myrtillus roots was also observed. The latter findings establish the pivotal role of SOD1 as an important factor in the relationship between O. maius and its symbiotic partner. The lack of this ROS-scavenger may cause an imbalance in the redox homeostasis during host colonization and an alteration in the delicate dialogue between the fungus and its host plant.
The Absence of Nops Secretion in Sinorhizobium fredii HH103 Increases GmPR1 Expression in Williams Soybean
Authors: López-Baena Francisco Javier , Monreal José Antonio , Pérez-Montaño Francisco , Guasch-Vidal Beatriz , Bellogín Ramón A. , Vinardell José María , Ollero Francisco Javier
Published: October 2009

Sinorhizobium fredii HH103 secretes through the type III secretion system at least eight nodulation outer proteins (Nops), including the effector NopP. These proteins are necessary for an effective nodulation of soybean. In this work, we show that expression of the nopP gene depended on flavonoids and on the transcriptional regulators NodD1 and TtsI. Inactivation of nopP led to an increase in the symbiotic capacity of S. fredii HH103 to nodulate Williams soybean. In addition, we studied whether Nops affect the expression of the pathogenesis-related genes GmPR1, GmPR2, and GmPR3 in soybean roots and shoots. In the presence of S. fredii HH103, expression of pathogenesis-related (PR) gene PR1 was induced in soybean roots 4 days after inoculation and it increased 8 days after inoculation. The absence of Nops provoked a higher induction of PR1 in both soybean roots and shoots, suggesting that Nops function early, diminishing plant defense responses during rhizobial infection. However, the inactivation of nopP led to a decrease in PR1 expression. Therefore, the absence of NopP or that of the complete set of Nops seems to have opposite effects on the symbiotic performance and on the elicitation of soybean defense responses.
Advances in experimental methods for the elucidation of Pseudomonas syringae effector function with a focus on AvrPtoB
Authors: MUNKVOLD KATHY R. , MARTIN GREGORY B.
Published: October 2009

Pseudomonas syringae infects a wide range of plant species through the use of a type III secretion system. The effector proteins injected into the plant cell through this molecular syringe serve as promoters of disease by subverting the plant immune response to the benefit of the bacteria in the intercellular space. The targets and activities of a subset of effectors have been elucidated recently. In this article, we focus on the experimental approaches that have proved most successful in probing the molecular basis of effectors, ranging from loss‐of‐function to gain‐of‐function analyses utilizing several techniques for effector delivery into plants. In particular, we highlight how these diverse approaches have been applied to the study of one effector—AvrPtoB—a multifunctional protein with the ability to suppress both effector‐triggered immunity and pathogen (or microbe)‐associated molecular pattern‐triggered immunity. Taken together, advances in this field illustrate the need for multiple experimental approaches when elucidating the function of a single effector.
Diversity and composition of trees and shrubs in Kasagala forest: a semiarid savannah woodland in central Uganda
Authors: Gwali Samson , Okullo Paul , Hafashimana David , Byabashaija Denis Mujuni
Published: October 2009

The diversity and composition of trees and shrubs of ≥5 cm diameter at breast height (DBH) were investigated in Kasagala woodland in central Uganda using 1 ha permanent sample plots. A total of 2745 trees and shrubs with a mean stem density of 686 ha−1 were recorded. These included 69 tree species belonging to 28 families and 47 genera. There was a larger number of small stems compared with that of larger stems. There was significant variation in stem size class distribution between the plots (F = 3.14, P = 0.027). The variation in stem densities (counts) across different size classes was significant (F = 8.31, P < 0.001). Species diversity was higher in the low lands compared with that in the elevated sites in the woodland. The species encountered were unevenly distributed across the plots. Species abundance was not significantly different across the sample plots (F = 2.63, P = 0.053). We suggest that the structure of the forest is typical of any regenerating forest, but other human influences may have played a part in the dominance of size classes <10 cm DBH. The causes of the present status and composition of the woodland require further investigation.
Response of waterbird species to fluctuating water levels in tropical coastal wetlands
Authors: Gbogbo Francis , Oduro William , Oppong Samuel Kingsley
Published: October 2009

Recent upsurges in the incidence of dam construction over rivers for farming and hydro electric power in the West African sub‐region is a known promoter of fluctuating water levels on tropical coastal wetlands. Waterbirds, being one of the dominant fauna on wetlands, are key species that can be affected by fluctuating water levels. Waterbird census and water level monitoring at four coastal wetlands in Ghana revealed that different guilds (species assemblages) of waterbirds responded differently to fluctuating water levels. The populations density of birds in guilds 1 (ducks and cormorants), 3 (tactile surface foraging waders), 4 (pelagic foraging waders) and 5 (stalking herons and egrets) significantly (P < 0.05) increased linearly with decreasing water levels. The population density of birds in guilds 2 (visual surface foraging waders) and 7 (fishing terns) responded significantly (P < 0.05) in a second order polynomial function with optimum numbers occurring when water levels were neither too high nor too low. As far as farming and energy requirement are met from these dams, it is important that the ecological needs of waterbirds on wetlands are incorporated into the management of these dams so as to maintain appropriate water levels beneficial to waterbird populations.
Variability in survival and mortality of Acacia drepanolobium Sjøstedt following prescribed burning at Olpejeta Conservancy, Kenya
Authors: Wahungu Geoffrey M. , Mureu Lucy K. , Macharia Paul G.
Published: October 2009

Mortalities to Acacia drepanolobium, a main item in the diet of the eastern black rhino (Diceros bicornis Michaeli) in Olpejeta conservancy, Kenya, are caused by three main factors: drought, browsers and fire. The effect of controlled fires on A. drepanolobium was examined by monitoring survival and growth in experimental plots before and after fire episodes between 2003 and 2007. Density, survival and growth in A. drepanolobium trees were compared eighteen months before and after burning. Tall trees were more likely to die from fire compared to short trees (R2 = 0.575; df = 6; P = 0.048), while seedling densities increased after fire (χ2 = 36.57; df = 1; P = 0.001). Even with increased seedling densities, burned areas attracted large numbers of seedling predators, lowering the possibility of seedling recruitment into adult, as mean seedling heights reduced significantly (ANOVA, F = 204.42; df = 1; P = 0.036). Fires also significantly lowered flowering (F = 346; df = 1; P < 0.05) in A. drepanolobium, thereby affecting fruit production. Although fires caused mortalities to adult A. drepanolobium, the most significant effect was tree reversals into seedling height class as trees resprouted. Although fire may increase browse biomass of A. drepanolobium available for black rhino, it is not an appropriate black rhino habitat management tool because burnt areas attract many seedling predators that lower seedling recruitment into adult trees.
3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing’s syndrome
Authors: Erickson Dana , Erickson Bradley , Watson Robert , Patton Alice , Atkinson John , Meyer Fredric , Nippoldt Todd , Carpenter Paul , Natt Neena , Vella Adrian , Thapa Prabin
Published: October 2009

Objective  We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o‐CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH‐dependent Cushing’s syndrome (CS).

Design and patients  We prospectively identified 23 patients over a 2‐year period with clinical and biochemical evidence of ACTH‐dependent CS with no lesion (n = 11) or equivocal lesion (n = 10) on 1·5T MRI. Subsequently, two additional MRIs were performed in random order: 3T nonstimulated MRI or 3T MRI with o‐CRH in all patients. Three neuroradiologists reviewed all examinations in a randomized blinded fashion. Patients were divided into four groups, depending on the outcome of their evaluation and treatment for CS. Two patients had to be excluded, and so we report on 21 subjects.

Measurements and results  Both 3T MRI without (P < 0·016) and with o‐CRH stimulation (P < 0·013) was significantly more sensitive for detection of pituitary microadenomas than 1·5T MRI for Group 1 (definitive proof of Cushing’s disease, n = 10). Group 2 (those in group 1, plus three patients where dynamic/invasive testing suggested pituitary source) also showed a significant (P < 0·012) advantage for 3T. There was no difference between the 3T and the 3T o‐CRH examinations for any of the pulse sequences. We did not observe a statistically significant difference in other patient groups [patients with recurrent CD (n = 6) and patients with ectopic CS (n = 2)].

Conclusions  The results of our prospective blinded studies suggest that 3T MRI of pituitary gland should be considered in evaluation of patients with ACTH‐dependent CD when 1·5T imaging is negative or equivocal.
Efficacy and safety of highly purified, doubly virus‐inactivated VWF/FVIII concentrates in inherited von Willebrand’s disease: results of an Italian cohort study on 120 patients characterized by bleeding severity score
Authors: FEDERICI A. B. , BARILLARI G. , ZANON E. , MAZZUCCONI M. G. , MUSSO R. , TARGHETTA R. , MANNUCCI P. M.
Published: October 2009

Summary.  The efficacy of highly purified VWF/FVIII concentrates with standardized ristocetin cofactor content (VWF:RCo) has been already proven in patients with von Willebrand’s disease (VWD). Aim of this retrospective study is to confirm efficacy and safety of two highly purified, doubly virus‐inactivated VWF/FVIII concentrates in a large cohort of patients with VWD who were characterized at enrolment by bleeding severity score. Study drugs Alphanate or Fanhdi were given to 120 cases (51 males, 69 females, median age 50 years, range 6–83 years). Patients had VWD3 (10), VWD2A (19), VWD2B (25), VWD2M (10) and DDAVP‐unresponsive VWD1 (56) and a median bleeding severity score of 8 (range 0–27). A total of 114 bleeding episodes in 55 cases and 131 surgical procedures in 85 cases could be analysed. Excellent‐good clinical responses were seen in 97% of bleeding episodes and in 99% of surgical procedures. To prevent recurrent gastrointestinal (GI) bleeding, cerebral (CNS) haemorrhage, haemarthroses, urogenital or multisite bleeding in more severe patients, secondary prophylaxis was also carried out in 15 cases with VWD3 (3), VWD2A (3), VWD2B (2), VWD1 (7). A median dose of 42 IU VWF:RCo kg−1 given every other day or twice a week over a median period of 334 days (range 24–799) prevented bleeding completely in 13 cases and reduced its incidence in the remaining two. These results confirm the efficacy and safety of the study concentrates, not only in the management of bleeding and surgery but also in secondary prophylaxis of severe VWD.
IgG4‐related systemic sclerosing disease – an emerging and under‐diagnosed condition
Authors: Bateman Adrian C , Deheragoda Maesha G
Published: October 2009

Autoimmune pancreatitis was first described in 1961, although it was not more widely recognized as an autoimmune condition until 1995. It has now become apparent that this form of pancreatitis is part of a clinical syndrome that is commonly multisystem in nature. One of the most common histopathological features is the presence of IgG4+ plasma cells within involved tissues. Many terms have been proposed to describe the condition, but ‘IgG4‐related systemic sclerosing disease’ appears most appropriate. Commonly affected extrapancreatic tissues include the biliary tract, liver, kidneys and lung, but a wide range of other sites may be involved. Histological examination reveals features that are not entirely disease‐specific, but that are often sufficiently characteristic to provide useful support to a clinicopathological diagnosis. The disease often responds well to systemic steroid therapy, unlike some of the conditions that it may simulate clinically. The emergence of this disease as a specific and treatable entity has favourably altered the clinical outlook for patients in whom steroid therapy might not previously have been considered appropriate.
Histogenesis‐specific expression of fibroblast activation protein and dipeptidylpeptidase‐IV in human bone and soft tissue tumours
Authors: Dohi Osamu , Ohtani Haruo , Hatori Masahito , Sato Elichi , Hosaka Masami , Nagura Hiroshi , Itoi Eiji , Kokubun Shoichi
Published: October 2009

Aims:  Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase‐IV (DPP‐IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP‐IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP‐IV and the malignant potential of tumours.

Methods and results:  This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase‐polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP‐IV in all individuals. Immunohistochemistry using pre‐fixed frozen sections revealed that FAP was positive in low‐grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing’s sarcomas and rhabdomyosarcomas. DPP‐IV showed similar immunohistochemical results. Among benign tumours, non‐ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP‐IV. Giant cells expressed DPP‐IV in giant cell tumours.

Conclusions:  Our data suggest that FAP and DPP‐IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP‐IV is also expressed in monocyte–macrophage lineage cells.
Breast cancer in the elderly: a histological assessment
Authors: Tse Gary M , Tan Puay‐Hoon , Lau Kin‐Mang , De Andrade Victor Piana , Lui Philip C W , Vong Joaquim S , Chaiwun Benjaporn , Lam Christopher C , Yu Alex M , Moriya Takuya
Published: October 2009

Aims:  To understand the correlation between the expression status of different biological markers in breast cancers in the elderly.

Methods and results:  Three hundred and ninety‐seven cases were evaluated for expression of hormone receptors [oestrogen receptors (ER) α and β, progesterone receptor (PR)], basal markers [p63, cytokeratin (CK) 5/6 and CK14] and others (HER2/neu, synaptophysin and chromogranin). The expression rates were 60, 29, 25, 6, 14, 8, 28, 17 and 5%, respectively, for these markers. The expression of ER α and β, PR, synaptophysin and chromogranin at any level correlated with low nuclear or tumour grades, whereas the expression of HER2/neu, CK5/6 and CK14 at any level correlated with high nuclear grade. By using hierarchical clustering, groups of HER2, luminal and basal types were identified. In addition, a neuroendocrine group was also identified, being characterized by expression of synaptophysin, chromogranin, ER and PR, but not HER2/neu, and other basal cytokeratins. This group was associated with lower nuclear grade, and hence better prognosis.

Conclusions:  Breast cancer in the elderly shows similar molecular groupings as other breast cancers, with an additional neuroendocrine group that is associated with a favourable biological marker profile.
Tumour regression grade (TRG) analyses in patients with resectable gastro‐oesophageal adenocarcinomas treated with platinum‐based neoadjuvant chemotherapy
Authors: Fareed Khaleel R , Ilyas Mohammad , Kaye Philip V , Soomro Irshad N , Lobo Dileep N , Parsons Simon L , Madhusudan Srinivasan
Published: October 2009

Aims:  Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro‐oesophageal adenocarcinoma. The aims were to validate the utility of the tumour regression grade (TRG) in patients who have received chemotherapy and to investigate if (i) TRG correlates with tumour downstaging and (ii) TRG could provide a comparative platform for future predictive biomarker investigations.

Methods and results:  Three pathologists were blinded to the treatment approaches. Review included diagnosis, tumour grade, TNM staging, vascular invasion, perineural invasion, resection margin involvement and histopathological response to chemotherapy, as measured by TRG. In the neoadjuvant chemotherapy (CS) group (n = 84), 46.7% of gastric/gastro‐oesophageal junction adenocarcinomas, and 45.5% of lower third oesophageal adenocarcinomas had TRG 1, 2 or 3 compared with 13.7% in the primary surgery group (n = 124) (P < 0.001 and P = 0.006, respectively). In the CS group, responders (TRG 1, 2 or 3) showed significant tumour downstaging [early ypT‐stage disease (P = 0.002)]. In gastric cancers specifically, additional associations were seen with negative nodal disease (P = 0.044) and absence of vascular invasion (P = 0.027).

Conclusions:  TRG may reflect response to chemotherapy. In addition, positive correlations between TRG and ypTNM staging were demonstrated that would suggest tumour downstaging.
The impact of the 2005 International Society of Urological Pathology (ISUP) consensus on Gleason grading in contemporary practice
Authors: Zareba Piotr , Zhang Jianguo , Yilmaz Asli , Trpkov Kiril
Published: October 2009

Aims:  To investigate the impact of the 2005 International Society of Urological Pathology (ISUP) Gleason grading consensus in contemporary practice.

Methods and results:  The Gleason scores (GS) were compared in two consecutive patient cohorts with matched biopsies and prostatectomies: (i) 908 patients evaluated before the ISUP consensus (July 2000–June 2004) and (ii) 423 patients evaluated after the ISUP consensus (October 2005–June 2007). All biopsies and prostatectomies were performed and scored in one institution and were sampled and processed identically. There was a higher percentage of biopsy and prostatectomy specimens with GS ≥ 7 after the ISUP consensus (GS ≥ 7 on biopsy in 32% before ISUP versus 46% after ISUP; GS ≥ 7 on prostatectomy in 53% before ISUP versus 68% after ISUP; P < 0.001). No significant difference in the complete and ±1 unit Gleason agreement was found before and after the ISUP consensus. There was a trend towards better complete agreement for GS ≥ 7 after the ISUP consensus.

Conclusions:  There was a shift towards higher GS on biopsy and prostatectomy in our practice after the ISUP consensus, although – there was no significant impact on the biopsy–prostatectomy Gleason agreement. The significance of this shift for patient management and prognosis is uncertain.
Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversal
Authors: Lohiya N. K. , Suthar R. , Khandelwal A. , Goyal S. , Ansari A. S. , Manivannan B.
Published: October 2009

The functional success of the reversal of vas occlusion by styrene maleic anhydride (RISUG), using the solvent vehicle, Dimethyl Sulphoxide (DMSO), has been investigated. Reversal with DMSO was carried out in Wistar albino rats 90 days after bilateral vas occlusion. The body weight, organ weight, sperm characteristics, fertility test and teratology, including skeletal morphology were evaluated in vas occlusion and reversal animals and in F1 progenies to assess the functional success of the occlusion and reversal. Body weight, organ weight and the cauda epididymal sperm characteristics of vas occlusion and reversal animals and of F1 progenies were comparable to control. Ejaculated spermatozoa in the vaginal smear showed detached head/tail, acrosomal damage, bent midpiece, bent tail and morphological aberrations in sperm head after vas occlusion, which returned to normal, 90 days after reversal. Monthly fertility test, post‐injection showed 0% fertility, which improved gradually and 100% fertility was achieved 90 days after reversal. The fertility/pregnancy/implantation record and skeletal morphology of the offspring were comparable to control. The results suggest functional success and safety of vas occlusion reversal by DMSO.
Adaptation, postpartum concerns, and learning needs in the first two weeks after caesarean birth
Authors: Weiss Marianne , Fawcett Jacqueline , Aber Cynthia
Published: October 2009

Aims.  The purpose of this Roy Adaptation Model‐based study was to describe women’s physical, emotional, functional and social adaptation; postpartum concerns; and learning needs during the first two weeks following caesarean birth and identify relevant nursing interventions.

Background.  Studies of caesarean‐delivered women indicated a trend toward normalisation of the caesarean birth experience. Escalating caesarean birth rates mandate continued study of contemporary caesarean‐delivered women.

Design.  Mixed methods (qualitative and quantitative) descriptive research design.

Methods.  Nursing students collected data from 233 culturally diverse caesarean‐delivered women in urban areas of the Midwestern and Northeastern USA between 2002–2004. The focal stimulus was the planned or unplanned caesarean birth; contextual stimuli were cultural identity and parity. Adaptation was measured by open‐ended interview questions, fixed choice questionnaires about postpartum concerns and learning needs and nurse assessment of post‐discharge problems. Potential interventions were identified using the Omaha System Intervention Scheme.

Results.  More positive than negative responses were reported for functional and social adaptation than for physical and emotional adaptation. Women with unplanned caesarean births and primiparous women reported less favourable adaptation than planned caesarean mothers and multiparas. Black women reported lower social adaptation, Hispanic women had more role function concerns and Black and Hispanic women had more learning needs than White women. Post‐discharge nursing assessments revealed that actual problems accounted for 40% of identified actual or potential problems or needs. Health teaching was the most commonly recommended postpartum intervention strategy followed by case management, treatment and surveillance interventions.

Conclusions.  Caesarean‐delivered women continue to experience some problems with adapting to childbirth. Recommended intervention strategies reflect the importance of health teaching following hospital discharge.

Relevance to clinical practice.  Women who experience caesarean birth require comprehensive assessment during the early postpartum period. Nurses should devise strategies to continue care services for these women following hospital discharge.
Geostatistical analysis of the distribution of Leptosphaeria species causing phoma stem canker on winter oilseed rape (Brassica napus) in England
Authors: Stonard J. F. , Marchant B. P. , Latunde‐Dada A. O. , Liu Z. , Evans N. , Gladders P. , Eckert M. R. , Fitt B. D. L.
Published: October 2009

In June/July 2001, 2002, 2003 and 2006, regional variation in distribution of the pathogens Leptosphaeria maculans and L. biglobosa that are causally associated with phoma stem canker was surveyed on winter oilseed rape crops in England. In 2001–2003, when isolates from basal cankers were visually identified as L. maculans or L. biglobosa based on cultural morphological characteristics, 70% were L. maculans and 30%L. biglobosa. In 2001, 2002, 2003 and 2006, when amounts of DNA of each species in basal cankers were determined by quantitative PCR, the abundance of L. maculans DNA was greater than that of L. biglobosa DNA in 77% of samples. When regional differences in amounts of L. maculans and L. biglobosa DNA were mapped geostatistically, quantities of L. maculans DNA were greater in cankers from southern England and those of L. biglobosa DNA were greater in northern England. A comparison with geostatistically mapped predictions made using a weather‐based model describing stages in development of phoma stem canker epidemics suggested that these differences in Leptosphaeria populations may have been a consequence of differences in temperature after onset of leaf spotting between northern and southern England. Both PCR and morphological evidence suggested that the abundance of L. maculans in England has increased since the last surveys in the 1980s. Implications of these surveys for control of phoma stem canker are discussed.
Patient factors in the implementation of decision aids in general practice: a qualitative study
Authors: Bhavnani Vanita , Fisher Brian
Published: October 2009

Background  Decision aids (DAs) have been developed to help patients make treatment decisions. Research shows that they are effective in increasing patients’ knowledge of treatment options without raising anxiety or conflict. However, they have not been routinely adopted for use in general practice in the UK and there are few reports addressing strategies to introduce them.

Objective  To examine patients’ views about a variety of DAs for different conditions (heart disease, osteoporosis, osteoarthritis and breast cancer) in order to inform a strategy to introduce them into general practice.

Setting and participants  General practice patients over the age of 18 years being or having been treated for one of the conditions above.

Methods  Qualitative study involving 12 focus groups with 77 patients evaluating decision aids relevant to their conditions. A semi‐structured interview guide was used to generate discussions about the applicability of the DAs in routine general practice.

Results  Patients welcomed DAs for their educational and informational content. Reactions to the DAs were influenced by patients’ own personal desires for involvement. The main concerns were that the use of DAs would potentially shift the onus of decision making responsibility on to the patient and about the practical challenges to implementation.

Conclusions  Clinicians will need to make explicit to patients that DAs are an adjunct to routine care and not a replacement, and therefore do not represent a derogation of responsibility. DAs need to be used as an integral part of the communication and support process for patients who want them.