bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-visiting Luck’s classification: a histological analysis of Dupuytren’s disease
Authors: Lam W. L. , Rawlins J. M. , Karoo R. O. S. , Naylor I. , Sharpe D. T.
Published: February 2010

Luck (1959) described a histological staging system for Dupuytren’s disease, classifying the disease into three stages. Previous biochemical and immunochemical studies have detailed the decrease in type III/I collagen ratio with disease progression. Herovici (1963) described a histological stain that produced a differential red/purple and blue colour for type I and III collagen respectively. We stained 15 specimens of Dupuytren’s disease and quantified the different collagen types in each using computer analysis. We found a corresponding decrease in the amount of type III collagen as a percentage of the total collagen with disease progression: stage I range 35–49% (mean 38%); stage 2 range 21–33% (mean 27%) and stage 3 range 11–19% (mean 14%). We propose a new staging system based on the relative amount of type III collagen, where stage 1: >35%, stage 2: >20% and <35%, and stage 3: <20%.
Treatment of Painful Pediatric Flatfoot With Maxwell-Brancheau Subtalar Arthroereisis Implant A Retrospective Radiographic Review
Authors: Scharer Brandon M. , Black Brian E. , Sockrider Nathan
Published: February 2010

The purposes of this study were to evaluate the outcome of pediatric patients who have undergone Maxwell-Brancheau arthroereisis (MBA) subtalar implants for the treatment of painful pediatric flatfoot deformities. In a retrospective study, 39 patients (68 feet) were evaluated clinically and radiographically. The mean age of the patients was 12 years (range, 6-16 years). The mean period of follow-up was 24 months (range, 6-61 months). Statistical evaluation was performed on all radiographic measurements. Additional surgical procedures (gastrocnemius recession, Achilles tendon lengthening, Kidner posterior tibial tendon advancement) were performed in 22 of 68 feet. There were 10 (15%) complications, which consisted of 10 reoperations in 10 feet. Implants were exchanged in 9 feet because of implant migration, undercorrection, and overcorrection. There was 1 reoperation (in 1 foot) for implant removal because of persistent sinus tarsi pain. Radiographic evaluation demonstrated an improvement of all parameters determined. The parameters that were evaluated include talonavicular joint coverage, as well as lateral and anterior-posterior talocalcaneal angles. There were significant changes noted in pre- and postoperative measurements (P < .001). The MBA implant is effective for the correction of painful, flexible flatfoot deformity in children in short-term follow-up. However, this is a multiplanar deformity, and additional procedures may be needed in addition to the MBA.
In vivo targeting of B-cell lymphoma with glycan ligands of CD22
Authors: Chen Weihsu C. , Completo Gladys C. , Sigal Darren S. , Crocker Paul R. , Saven Alan , Paulson James C.
Published: February 2010

Antibody-mediated cell depletion therapy has proven to provide significant clinical benefit in treatment of lymphomas and leukemias, driving the development of improved therapies with novel mechanisms of cell killing. A current clinical target for B-cell lymphoma is CD22, a B-cell–specific member of the sialic acid binding Ig-like lectin (siglec) family that recognizes α2-6–linked sialylated glycans as ligands. Here, we describe a novel approach for targeting B lymphoma cells with doxorubicin-loaded liposomal nanoparticles displaying high-affinity glycan ligands of CD22. The targeted liposomes are actively bound and endocytosed by CD22 on B cells, and significantly extend life in a xenograft model of human B-cell lymphoma. Moreover, they bind and kill malignant B cells from peripheral blood samples obtained from patients with hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia. The results demonstrate the potential for using a carbohydrate recognition–based approach for efficiently targeting B cells in vivo that can offer improved treatment options for patients with B-cell malignancies.
SpectraClassifier 1.0: a user friendly, automated MRS-based classifier-development system
Authors: Ortega-Martorell Sandra , Olier Iván , Julià-Sapé Margarida , Arús Carles
Published: February 2010

Background

SpectraClassifier (SC) is a Java solution for designing and implementing Magnetic Resonance Spectroscopy (MRS)-based classifiers. The main goal of SC is to allow users with minimum background knowledge of multivariate statistics to perform a fully automated pattern recognition analysis. SC incorporates feature selection (greedy stepwise approach, either forward or backward), and feature extraction (PCA). Fisher Linear Discriminant Analysis is the method of choice for classification. Classifier evaluation is performed through various methods: display of the confusion matrix of the training and testing datasets; K-fold cross-validation, leave-one-out and bootstrapping as well as Receiver Operating Characteristic (ROC) curves.

Results

SC is composed of the following modules: Classifier design, Data exploration, Data visualisation, Classifier evaluation, Reports, and Classifier history. It is able to read low resolution in-vivo MRS (single-voxel and multi-voxel) and high resolution tissue MRS (HRMAS), processed with existing tools (jMRUI, INTERPRET, 3DiCSI or TopSpin). In addition, to facilitate exchanging data between applications, a standard format capable of storing all the information needed for a dataset was developed. Each functionality of SC has been specifically validated with real data with the purpose of bug-testing and methods validation. Data from the INTERPRET project was used.

Conclusions

SC is a user-friendly software designed to fulfil the needs of potential users in the MRS community. It accepts all kinds of pre-processed MRS data types and classifies them semi-automatically, allowing spectroscopists to concentrate on interpretation of results with the use of its visualisation tools.
The chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites
Authors: Tenin Gennady , Wright David , Ferjentsik Zoltan , Bone Robert , McGrew Michael J , Maroto Miguel
Published: February 2010

Background

Somitogenesis is the earliest sign of segmentation in the developing vertebrate embryo. This process starts very early, soon after gastrulation has initiated and proceeds in an anterior-to-posterior direction during body axis elongation. It is widely accepted that somitogenesis is controlled by a molecular oscillator with the same periodicity as somite formation. This periodic mechanism is repeated a specific number of times until the embryo acquires a defined specie-specific final number of somites at the end of the process of axis elongation. This final number of somites varies widely between vertebrate species. How termination of the process of somitogenesis is determined is still unknown.

Results

Here we show that during development there is an imbalance between the speed of somite formation and growth of the presomitic mesoderm (PSM)/tail bud. This decrease in the PSM size of the chick embryo is not due to an acceleration of the speed of somite formation because it remains constant until the last stages of somitogenesis, when it slows down. When the chick embryo reaches its final number of somites at stage HH 24-25 there is still some remaining unsegmented PSM in which expression of components of the somitogenesis oscillator is no longer dynamic. Finally, we identify a change in expression of retinoic acid regulating factors in the tail bud at late stages of somitogenesis, such that in the chick embryo there is a pronounced onset of Raldh2 expression while in the mouse embryo the expression of the RA inhibitor Cyp26A1 is downregulated.

Conclusions

Our results show that the chick somitogenesis oscillator is arrested before all paraxial mesoderm is segmented into somites. In addition, endogenous retinoic acid is probably also involved in the termination of the process of segmentation, and in tail growth in general.
Molecular evolution of the crustacean hyperglycemic hormone family in ecdysozoans
Authors: Montagné Nicolas , Desdevises Yves , Soyez Daniel , Toullec Jean-Yves
Published: February 2010

Background

Crustacean Hyperglycemic Hormone (CHH) family peptides are neurohormones known to regulate several important functions in decapod crustaceans such as ionic and energetic metabolism, molting and reproduction. The structural conservation of these peptides, together with the variety of functions they display, led us to investigate their evolutionary history. CHH family peptides exist in insects (Ion Transport Peptides) and may be present in all ecdysozoans as well. In order to extend the evolutionary study to the entire family, CHH family peptides were thus searched in taxa outside decapods, where they have been, to date, poorly investigated.

Results

CHH family peptides were characterized by molecular cloning in a branchiopod crustacean, Daphnia magna, and in a collembolan, Folsomia candida. Genes encoding such peptides were also rebuilt in silico from genomic sequences of another branchiopod, a chelicerate and two nematodes. These sequences were included in updated datasets to build phylogenies of the CHH family in pancrustaceans. These phylogenies suggest that peptides found in Branchiopoda and Collembola are more closely related to insect ITPs than to crustacean CHHs. Datasets were also used to support a phylogenetic hypothesis about pancrustacean relationships, which, in addition to gene structures, allowed us to propose two evolutionary scenarios of this multigenic family in ecdysozoans.

Conclusions

Evolutionary scenarios suggest that CHH family genes of ecdysozoans originate from an ancestral two-exon gene, and genes of arthropods from a three-exon one. In malacostracans, the evolution of the CHH family has involved several duplication, insertion or deletion events, leading to neuropeptides with a wide variety of functions, as observed in decapods. This family could thus constitute a promising model to investigate the links between gene duplications and functional divergence.
Flux of transcript patterns during soybean seed development
Authors: Jones Sarah I , Gonzalez Delkin O , Vodkin Lila O
Published: February 2010

Background

To understand gene expression networks leading to functional properties of the soybean seed, we have undertaken a detailed examination of soybean seed development during the stages of major accumulation of oils, proteins, and starches, as well as the desiccating and mature stages, using microarrays consisting of up to 27,000 soybean cDNAs. A subset of these genes on a highly-repetitive 70-mer oligonucleotide microarray was also used to support the results.

Results

It was discovered that genes related to cell growth and maintenance processes, as well as energy processes like photosynthesis, decreased in expression levels as the cotyledons approached the mature, dry stage. Genes involved with some storage proteins had their highest expression levels at the stage of highest fresh weight. However, genes encoding many transcription factors and DNA binding proteins showed higher expression levels in the desiccating and dry seeds than in most of the green stages.

Conclusions

Data on 27,000 cDNAs have been obtained over five stages of soybean development, including the stages of major accumulation of agronomically-important products, using two different types of microarrays. Of particular interest are the genes found to peak in expression at the desiccating and dry seed stages, such as those annotated as transcription factors, which may indicate the preparation of pathways that will be needed later in the early stages of imbibition and germination.
Modulation of iron homeostasis in macrophages by bacterial intracellular pathogens
Authors: Pan Xin , Tamilselvam Batcha , Hansen Eric J , Daefler Simon
Published: February 2010

Background

Intracellular bacterial pathogens depend on acquisition of iron for their success as pathogens. The host cell requires iron as an essential component for cellular functions that include innate immune defense mechanisms. The transferrin receptor TfR1 plays an important part for delivering iron to the host cell during infection. Its expression can be modulated by infection, but its essentiality for bacterial intracellular survival has not been directly investigated.

Results

We identified two distinct iron-handling scenarios for two different bacterial pathogens.Francisella tularensisdrives an active iron acquisition program via the TfR1 pathway program with induction of ferrireductase (Steap3), iron membrane transporter Dmt1, and iron regulatory proteins IRP1 and IRP2, which is associated with a sustained increase of the labile iron pool inside the macrophage. Expression of TfR1 is critical forFrancisella'sintracellular proliferation. This contrasts with infection of macrophages by wild-typeSalmonella typhimurium, which does not require expression of TfR1 for successful intracellular survival. Macrophages infected withSalmonellalack significant induction of Dmt1, Steap3, and IRP1, and maintain their labile iron pool at normal levels.

Conclusion

The distinction between two different phenotypes of iron utilization by intracellular pathogens will allow further characterization and understanding of host-cell iron metabolism and its modulation by intracellular bacteria.
Potential chromosomal introgression barriers revealed by linkage analysis in a hybrid of Pinus massoniana and P. hwangshanensis
Authors: Li Shuxian , Chen Ying , Gao Handong , Yin Tongming
Published: February 2010

Background

Exploring the genetic mechanisms underlying speciation is a hot topic in modern genetics and evolutionary studies. Distortion of marker transmission ratio is frequently ascribed to selection against alleles that cause hybrid incompatibility. The natural introgression between P. massoniana and P. hwangshanensis and their distribution ranges lead to the emergence of the two species as desirable organisms to study the genetic mechanisms for speciation.

Results

Using seeds sampled from trees at different elevations, we consistently detected sharp decreases in seed germination rates of trees in the hybrid zone, which might be due largely to the hybrid incompatibility. A genetic map was established using 192 megagametophytes from a single tree in the hybrid zone of the two species. Segregation distortion analysis revealed that the percentage of significant-segregation-distortion (SSD) markers was extremely high, accounting for more than 25% of the segregating markers. The extension range, the distortion direction, and the distortion intensity of SSD markers also varied dramatically on different linkage groups.

Conclusions

In this study, we display the potential chromosomal introgression barriers between P. massoniana and P. hwangshanensis. Our study provides a valuable platform for conducting genome-wide association of hybrid incompatible QTLs and/or candidate genes with marker transmission ratio distortion in the hybrid.
Immunoscreening of the extracellular proteome of colorectal cancer cells
Authors: Klein-Scory Susanne , Kübler Salwa , Diehl Hanna , Eilert-Micus Christina , Reinacher-Schick Anke , Stühler Kai , Warscheid Bettina , Meyer Helmut E , Schmiegel Wolff , Schwarte-Waldhoff Irmgard
Published: February 2010

Background

The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.

Methods

For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.

Results

From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.

Conclusions

Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.
Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays
Authors: Qing Yi , Yang Xue-Qin , Zhong Zhao-Yang , Lei Xin , Xie Jia-Yin , Li Meng-Xia , Xiang De-Bing , Li Zeng-Peng , Yang Zhen-Zhou , Wang Ge , Wang Dong
Published: February 2010

Background

The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes.

Methods

HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR.

Results

The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated.

Conclusions

Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer.
Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells
Authors: Kim Kyu Kwang , Lange Thilo S , Singh Rakesh K , Brard Laurent
Published: February 2010

Background

Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).

Methods

Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)

Results

HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.

Conclusions

The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.
Hepatitis B and liver cancer knowledge and practices among healthcare and public health professionals in China: a cross-sectional study
Authors: Chao Jonathan , Chang Ellen T , So Samuel KS
Published: February 2010

Background

Chronic hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer and a major source of health-related discrimination in China. To better target HBV detection and prevention programs, it is necessary to assess existing HBV knowledge, educational resources, reporting, and preventive practices, particularly among those health professionals who would be responsible for implementing such programs.

Methods

At the China National Conference on the Prevention and Control of Viral Hepatitis on April 26-29, 2004, the Asian Liver Center at Stanford University partnered with the China Foundation for Hepatitis Prevention and Control to distribute a voluntary written questionnaire to Chinese healthcare and public health professionals from regional and provincial Chinese Centers for Disease Control and Prevention, health departments, and medical centers. Correct responses to survey questions were summed into a total knowledge score, and multivariate linear regression was used to compare differences in the score by participant characteristics.

Results

Although the median score was 81% correct, knowledge about HBV was inadequate, even among such highly trained health professionals. Of the 250 participants who completed the survey, 34% did not know that chronic HBV infection is often asymptomatic and 29% did not know that chronic HBV infection confers a high risk of cirrhosis, liver cancer, and premature death. Furthermore, 34% failed to recognize all the modes of HBV transmission and 30% did not know the importance of the hepatitis B vaccine in preventing liver disease. Respondents who reported poorer preventive practices, such as not having personally been tested for HBV and not routinely disposing of used medical needles, scored significantly lower in HBV knowledge than those who reported sound preventive practices. Of note, 38% of respondents reported positive HBsAg results to patients' employers and 25% reported positive results to patients' schools, thereby subjecting those with positive results to potential discriminatory practices.

Conclusions

These results indicate that there is a need for development of effective educational programs to improve HBV knowledge among health professionals and the general public to avoid missed vaccination opportunities, reduce misconceptions, and eliminate discrimination based on chronic hepatitis B in China.
Systems genetics analyses predict a transcription role for P2P-R: Molecular confirmation that P2P-R is a transcriptional co-repressor
Authors: Peidis Philippos , Giannakouros Thomas , Burow Matthew E , Williams Robert W , Scott Robert E
Published: February 2010

Background

The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations.

Results

GeneNetwork and associated gene ontology links were used to investigate the coexpression of P2P-R with distinct functional sets of genes in an adipocyte genetic reference panel of HXB/BXH recombinant strains of rats and an eye genetic reference panel of BXD recombinant inbred strains of mice. The results establish that biological networks of 75 and 135 transcription-associated gene products that include P2P-R are co-expressed in a genetically-defined manner in rat adipocytes and in the mouse eye, respectively. Of this large set of transcription-associated genes, >10% are associated with hormone-mediated transcription. Since it has been previously reported that P2P-R can bind the SRC-1 transcription co-regulatory factor (steroid receptor co-activator 1, [Ncoa1]), the possible effects of P2P-R on estrogen-induced transcription were evaluated. Estrogen-induced transcription was repressed 50-70% by the transient transfection of P2P-R plasmid constructs into four different cell types. In addition, knockdown of P2P-R expression using an antisense oligonucleotide increased estrogen-mediated transcription. Co-immunoprecipitation assays confirmed that P2P-R interacts with SRC-1 and also demonstrated that P2P-R interacts with estrogen receptor α.

Conclusions

The findings presented in this study provide strong support for the value of systems genetics, especially GeneNetwork, in discovering new functions of genes that can be confirmed by molecular analysis. More specifically, these data provide evidence that the expression of P2P-R co-varies in a genetically-defined manner with large transcription networks and that P2P-R can function as a co-repressor of estrogen-dependent transcription.
Bayesian closed-skew Gaussian inversion of seismic AVO data for elastic material properties
Authors: Karimi Omid , Omre Henning , Mohammadzadeh Mohsen
Published: February 2010

Bayesian closed-skew Gaussian inversion is defined as a generalization of traditional Bayesian Gaussian inversion, which is used frequently in seismic amplitude-versus-offset (AVO) inversion. The new model captures skewness in the variables of interest; hence, the posterior model for log-transformed elastic material properties given seismic AVO data might be a skew probability density function. The model is analytically tractable, and this makes it applicable in high-dimensional 3D inversion problems. Assessment of the posterior models in high dimensions requires numerical approximations, however. The Bayesian closed-skew Gaussian inversion approach has been applied on real elastic material properties from a well in the Sleipner field in the North Sea. A comparison with results from traditional Bayesian Gaussian inversion shows that the mean square error of predictions of P-wave and S-wave velocities are reduced by a factor of two, although somewhat less for density predictions.
Hydroxysteroid (17β) Dehydrogenase 7 Activity Is Essential for Fetal de Novo Cholesterol Synthesis and for Neuroectodermal Survival and Cardiovascular Differentiation in Early Mouse Embryos
Authors: Jokela Heli , Rantakari Pia , Lamminen Tarja , Strauss Leena , Ola Roxana , Mutka Aino-Liisa , Gylling Helena , Miettinen Tatu , Pakarinen Pirjo , Sainio Kirsi , Poutanen Matti
Published: February 2010

Hydroxysteroid (17β) dehydrogenase 7 (HSD17B7) has been shown to catalyze the conversion of both estrone to estradiol (17-ketosteroid reductase activity) and zymosterone to zymosterol (3-ketosteroid reductase activity involved in cholesterol biosynthesis) in vitro. To define the metabolic role of the enzyme in vivo, we generated knockout mice deficient in the enzyme activity (HSD17B7KO). The data showed that the lack of HSD17B7 results in a blockage in the de novo cholesterol biosynthesis in mouse embryos in vivo, and HSD17BKO embryos die at embryonic day (E) 10.5. Analysis of neural structures revealed a defect in the development of hemispheres of the front brain with an increased apoptosis in the neuronal tissues. Morphological defects in the cardiovascular system were also observed from E9.5 onward. Mesodermal, endodermal, and hematopoietic cells were all detected by the histological analysis of the visceral yolk sac, whereas no organized vessels were observed in the knockout yolk sac. Immunohistological staining for platelet endothelial cell adhesion molecule-1 indicated that the complexity of the vasculature also was reduced in the HSD17B7KO embryos, particularly in the head capillary plexus and branchial arches. At E8.5–9.5, the heart development and the looping of the heart appeared to be normal in the HSD17B7KO embryos. However, at E10.5 the heart was dilated, and the thickness of the cardiac muscle and pericardium in the HSD17B7KO embryos was markedly reduced, and immunohistochemical staining for GATA-4 revealed that HSD17B7KO embryos had a reduced number of myocardial cells. The septum of the atrium was also defected in the knockout mice.
Angiotensin II-Induced Expression of Brain-Derived Neurotrophic Factor in Human and Rat Adrenocortical Cells
Authors: Szekeres Mária , Nádasy György L. , Turu Gábor , Süpeki Katinka , Szidonya László , Buday László , Chaplin Tracy , Clark Adrian J. L. , Hunyady László
Published: February 2010

Angiotensin II (Ang II) is a major regulator of steroidogenesis in adrenocortical cells, and is also an effective inducer of cytokine and growth factor synthesis in several cell types. In microarray analysis of H295R human adrenocortical cells, the mRNA of brain-derived neurotrophic factor (BDNF), a neurotrophin widely expressed in the nervous system, was one of the most up-regulated genes by Ang II. The aim of the present study was the analysis of the Ang II-induced BDNF expression and BDNF-induced effects in adrenocortical cells. Real-time PCR studies have shown that BDNF is expressed in H295R and rat adrenal glomerulosa cells. In H295R cells, the kinetics of Ang II-induced BDNF expression was faster than that of aldosterone synthase (CYP11B2). Inhibition of calmodulin kinase by KN93 did not significantly affect the Ang II-induced stimulation of BDNF expression, suggesting that it occurs by a different mechanism from the CYP11B2-response. Ang II also caused candesartan-sensitive, type-1 Ang II receptor-mediated stimulation of BDNF gene expression in primary rat glomerulosa cells. In rat adrenal cortex, BDNF protein was localized to the subcapsular region. Ang II increased BDNF protein levels both in human and rat cells, and BDNF secretion of H295R cells. Ang II also increased type-1 Ang II receptor-mediated BDNF expression in vivo in furosemide-treated rats. In rat glomerulosa cells, BDNF induced tropomyosin-related kinase B receptor-mediated stimulation of EGR1 and TrkB expression. These data demonstrate that Ang II stimulates BDNF expression in human and rat adrenocortical cells, and BDNF may have a local regulatory function in adrenal glomerulosa cells.
Real-Time Monitoring of Chemical Transmission in Slices of the Murine Adrenal Gland
Authors: Petrovic Jelena , Walsh Paul L. , Thornley Keith T. , Miller Charles E. , Wightman R. Mark
Published: February 2010

The real-time electrochemical detection of catecholamine secretion from murine adrenal slices using fast-scan cyclic voltammetry (FSCV) and amperometry at carbon fiber microelectrodes is described. Bright-field and immunofluorescent microscopy supported that chromaffin cells in the adrenal medulla are organized into clusters and positively stain for tyrosine hydroxylase confirming that they are catecholaminergic. Spontaneous exocytotic catecholamine events were observed inside chromaffin cell clusters with both FSCV and amperometry and were modulated by the nicotinic acetylcholine receptor antagonist hexamethonium and low extracellular calcium. Reintroduction of extracellular calcium and pressure ejection of acetylcholine caused the frequency of spikes to increase back to predrug levels. Electrical stimulation caused the synchronous secretion from multiple cells within the gland, which were modulated by nicotinic acetylcholine receptors but not muscarinic receptors or gap junctions. Furthermore, electrically stimulated release was abolished with perfusion of low extracellular calcium or tetrodotoxin, indicating that the release requires electrical excitability. An extended waveform was used to study the spontaneous and stimulated release events to determine their chemical content by FSCV. Consistent with total content analysis and immunohistochemical studies, about two thirds of the cells studied spontaneously secreted epinephrine, whereas one third secreted norepinephrine. Whereas adrenergic sites contained mostly epinephrine during electrical stimulation, noradrenergic sites contained a mixture of the catecholamines showing the heterogeneity of the adrenal medulla.
Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts
Authors: Xia Sheng , Li Xiaogang , Johnson Teri , Seidel Chris , Wallace Darren P. , Li Rong
Published: February 2010

Polycystin 1 and polycystin 2 are large transmembrane proteins, which, when mutated, cause autosomal dominant polycystic kidney disease (ADPKD), a highly prevalent human genetic disease. The polycystins are thought to form a receptor-calcium channel complex in the plasma membrane of renal epithelial cells and elicit a calcium influx in response to mechanical stimulation, such as fluid flow across the apical surface of renal epithelial cells. The functional role of the polycystins in mechanosensation remains largely unknown. Here, we found that myocyte enhancer factor 2C (MEF2C) and histone deacetylase 5 (HDAC5), two key regulators of cardiac hypertrophy, are targets of polycystin-dependent fluid stress sensing in renal epithelial cells in mice. We show that fluid flow stimulation of polarized epithelial monolayers induced phosphorylation and nuclear export of HDAC5, which are crucial events in the activation of MEF2C-based transcription. Kidney-specific knockout of Mef2c, or genetrap-inactivation of a MEF2C transcriptional target, MIM, resulted in extensive renal tubule dilation and cysts, whereas Hdac5 heterozygosity or treatment with TSA, an HDAC inhibitor, reduced cyst formation in Pkd2−/− mouse embryos. These findings suggest a common signaling motif between myocardial hypertrophy and maintenance of renal epithelial architecture, and a potential therapeutic approach to treat ADPKD.
Discretionary Disclosure of Proprietary Information in a Multisegment Firm
Authors: Arya Anil , Frimor Hans , Mittendorf Brian
Published: February 2010

The seminal “unraveling” result in the disclosure literature posits that discretion inevitably leads to full disclosure, even when such disclosure has detrimental consequences. In this paper, we revisit optimal disclosure of proprietary information when firms compete in multiple markets. The analysis demonstrates that in the presence of multiple segments, the unraveling result applies at the firmwide level but not necessarily segment by segment. Instead, when the firm has an ex ante desire to withhold information and segments are sufficiently similar, the ex post disclosure equilibrium entails aggregation of segment details. Aggregation arises because any ex post temptation to disaggregate and reveal particularly favorable news in one segment entails revealing unfavorable news in another segment. A desire to balance profits across segments then leads a firm to disclose firmwide information (a temptation that cannot be avoided), but only in the aggregate.
A General Index of Absolute Risk Attitude
Authors: Denuit Michel M. , Eeckhoudt Louis
Published: February 2010

Many results involving expected utility theory call upon the notions of absolute risk aversion, prudence, and/or temperance. This paper exploits a representation of the Friedman–Savage utility premium (Friedman, M., L. J. Savage. 1948. The utility analysis of choices involving risk. J. Political Econom. 56(4) 279–304) to give a general foundation for such coefficients and for their higher-order extensions.
Alendronate-Induced Asthma Proton Pump Inhibitor–Induced Acute Interstitial Nephritis Mesalazine and Hypereosinophilia Tardive Dyskinesia Associated with Aripiprazole Atrial Fibrillation and Coronary Vasospasm Caused by Ondansetron Doxycycline-Induced Pseudotumor Cerebri Excellent Review: Antipsychotic-Induced Hyperprolactinemia
Authors: Shuster Joel
Published: February 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215–947–7797; fax: 215–914–1492; e-mail: joel.shuster@temple.edu ). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.
Docetaxel and Estramustine for Prostate Cancer
Authors: Solimando Dominic A. , Waddell J. Aubrey , Watts Andrew J.
Published: February 2010

The complexity of cancer chemotherapy requires that pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparing, dispensing, and administering antineoplastic therapy and to the agents, commercially available and investigational, used to treat malignant diseases.
Lacosamide
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E.
Published: February 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The June 2009 monograph topics are everolimus; Japanese encephalitis vaccine, inactivated; inhaled insulin; pitavastatin; and dabigatran etexilate. The DUE is on plerixafor.
Electronic Forms in a Hospital and Hospital-Based Outpatient Clinical Research Environment to Maximize Patient Safety
Authors: Formea Christine M. , Griffin Monica G. , Picha Andrew F. , Schaller Jane A. , Lee Mary R.
Published: February 2010

Patient safety is a complex issue that is constantly evolving. Communication via standardized drug ordering is recognized as one of the key elements for providing a safer hospital stay, as well as a stronger patient outcome. This feature provides examples of standardized drug prescribing and a forum for discussion. If you have a template that you believe may be beneficial to other hospital pharmacies, please submit it along with answers to the questions (as shown in the text of this article) to Joyce Generali, Director of Drug Information, Kansas University Medical Center, 3901 Rainbow Boulevard, Mail Stop 4040, Kansas City, KS 66160 or e-mail jgeneral@kumc.edu .
New distributional records from central-eastern Madagascar and patterns of morphological variation in the endangered shrew tenrec Microgale jobihely (Afrosoricida: Tenrecidae)
Authors: Soarimalala Voahangy , Raheriarisena Martin , Goodman Steven M.
Published: February 2010

Microgale jobihely (Afrosoricida: Tenrecidae) was described in 2006 based on 12 specimens from the southwestern flank of Tsaratanana Massif in northern Madagascar. This species is considered Endangered by the IUCN. During small mammal surveys conducted in central-eastern Madagascar within the Ambatovy Forest between June 2007 and February 2009, six specimens allocated to M. jobihely were collected. This site is 485 km southeast of the holotype locality and rests on ultrabasic soils associated with nickel and cobalt deposits. Morphological studies of the Ambatovy and Tsaratanana material provide insights into patterns of variation in this taxon. Notable size variation occurs between the northern and southern populations, as well as differences in craniodental morphology. A portion of the Ambatovy site will be cleared as a result of mineral exploitation and even with the discovery of a second population of this taxon, its conservation status remains Endangered.
Species limits and distribution of the Malagasy carnivoran genus Eupleres (Family Eupleridae)
Authors: Goodman Steven M. , Helgen Kristofer M.
Published: February 2010

A review was conducted of members of the endemic Malagasy carnivoran genus Eupleres (family Eupleridae) based on published and unpublished records and museum specimens. Classically, one species has been recognized in this poorly known genus – E. goudotii, divided into two geographical forms with non-overlapping distributions: E. g. goudotii distributed in the mesic forests of the east and E. g. major found in the dry areas of the northwest. Drawing on external and craniodental comparisons, we demonstrate that these two forms are highly distinctive morphologically and can be readily distinguished from each another. Furthermore, there is some evidence that they both can occur on the slopes of Montagne d'Ambre in the far north of the island. On this basis, we recognize these taxa as distinct species, E. goudotii and E. major.
Embrittlement Correlation Method for the Japanese Reactor Pressure Vessel Materials
Authors: Soneda Naoki , Dohi Kenji , Nomoto Akiyoshi , Nishida Kenji , Ishino Shiori
Published: February 2010

A new embrittlement correlation method developed for the Japanese reactor pressure vessel (RPV) steels is presented. The Central Research Institute of Electric Power Industry and the Japanese electric utilities conducted a project to develop a new embrittlement correlation method for the Japanese RPV steels based on the understandings on the mechanisms of the RPV embrittlement. In addition to the information from the literatures, we generated new information by characterizing the microstructural changes in the surveillance materials of the Japanese commercial reactors. We found that in low Cu materials, solute atom clusters containing little or no Cu atoms are formed at relatively low fluence of 3×1019 n/cm2, E>1 MeV. The volume fraction of the solute atom clusters has a good correlation with the Charpy transition temperature shift regardless of the Cu content. We also found that the microstructure of the boiling water reactor surveillance material is different from that of the archive material irradiated in material testing reactor. The understandings on the RPV embrittlement mechanisms were formulated using a set of rate equations, and the coefficients of the equations were optimized using the ΔRTNDT values of the Japanese surveillance database. This method considers the effect of neutron flux. Only one set of coefficients was developed, and they are independent of the product form. Predictions of the new embrittlement correlation method were compared with those of the recent U.S. correlation method as well as the U.S. surveillance data. The comparison shows the characteristics of the present method.
Are ACL Injuries Related to Perceived Fatigue in Female Skiers?
Authors: Ruedl G. , Schranz A. , Fink C. , Pocecco E. , Nachbauer W. , Burtscher M.
Published: February 2010

In alpine skiing, knee injuries show marked sex differences, as female recreational skiers have a twofold greater incidence of knee injuries and a threefold higher anterior cruciate ligament (ACL) injury risk than male skiers. General preventive recommendations to reduce the incidence of ski injuries include avoiding fatigue. However, no study has yet examined to which extent ACL injuries in female recreational skiers are related to perceived fatigue. Therefore, 68 ACL injured female skiers and 136 matched controls were interviewed about skiing time and perception of fatigue in legs and the whole body at the time point of accident and questioning, respectively. In addition, skiing ability, self estimated fitness level, quantity and quality of breaks per run, sleeping quality, and group skiing and skill level of group members have been recorded. Patients and controls differ significantly regarding the duration of skiing as about 81 % of ACL injuries occurred within the first 3 h (odds ratio=4.4; P<0.001). In patients about 71 % and in controls about 27 % felt no fatigue or a trace of fatigue in their legs at the time of injury and questioning, respectively (P<0.001) . No other factors showed a significant difference. Therefore, fatigue seems no major risk factor for an ACL injury in female recreational skiing.
Simulation-Based Maximum Likelihood Median Pragmatic A-Basis and B-Basis Statistical Tolerance Limits Given Fatigue Datum Values with No Censoring or with Potential or Actual Type I Censoring
Authors: Little R. E.
Published: February 2010

This technical note introduces the author’s simulation-based maximum likelihood median pragmatic A-basis or B-basis statistical tolerance limit calculation methodology. It presents websites that provide exemplar outputs of microcomputer programs that employ this methodology to compute these statistical tolerance limits given (i) replicate Weibull and loge-normal fatigue life datum values pertaining to a material without an endurance limit and (ii) s-N data with either linear and quadratic models pertaining to a material without an endurance limit or with a two-segment straight-line model pertaining to a material with an endurance limit.