bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontal lobe syndrome or adolescent‐onset schizophrenia? A case report
Authors: Ferrara M , Freda F. , Massa R. , Carratelli T. J.
Published: October 2006

Objective:  To highlight the difficulties that abound in making a clinical distinction between early‐onset schizophrenia (EOS) and juvenile frontal dementia early in the course of illness.

Method:  Clinical information and data from investigations in single case was collated and reviewed.

Results:  A 15‐year‐old girl was admitted to our psychiatric unit because of cognitive decline and formal thought disorder with echopraxia, echolalia and palilalia, and a lack of flexibility in the use of cognitive and motor strategies that culminated in psychosis. A single photon emission computerized tomography scan showed marked frontal lobe hypoperfusion; however, on proton spectroscopy there was no differential in N‐acetyl aspartate levels.

Conclusion:  Hypofrontality in EOS is well established and the association of frontal functional alterations, neuropsychological impairment and psychotic symptomatology is suggestive of frontal lobe prodrome that precedes the onset of psychosis.
The Ulva connection: marine algae subsidize terrestrial predators in coastal Peru
Authors: Catenazzi Alessandro , A. Donnelly Maureen
Published: October 2006

How can terrestrial animals survive in a desert with scant primary productivity? The Peruvian coastal desert is hyper‐arid, but faces one of the world's most productive marine ecosystems, the Peru–Chile cold current. Given the stark difference in productivity between these adjacent ecosystems, we expected to find strong linkages connecting the terrestrial and marine food web. We investigated how marine resources are incorporated in the diet, and influence the distribution of terrestrial consumers (geckos, scorpions, solifuges and darkling beetles). Stomach contents from geckos, and δ13C and δ15N values of geckos and other terrestrial consumers suggest that marine green algae of the genus Ulva provide energy and nutrients to the terrestrial food web. Isotopic values suggest that amphipods, which feed on stranded Ulva, make marine resources available to terrestrial predators by moving between the intertidal and supratidal zones. The relative contribution of terrestrial and algal carbon sources varied among terrestrial predators, because scorpions assimilated a lower proportion of energy from Ulva than did geckos and solifuges. These δ13C patterns reflected differences in the spatial distribution of consumers. Our study supports the idea that in places where ecosystems with contrasting productivity levels are spatially juxtaposed, it is not possible to understand the structure and dynamics of food webs without taking into account the effects of energy and nutrients flowing from adjacent ecosystems. In contrast to other studied systems, especially those in Baja California, our site in Peru receives very little rainfall and the amount of precipitation is not affected by El Niño events. The near absence of rainfall promotes an extreme dependence of terrestrial consumers on marine resources, and causes permanent indirect food‐web effects that are affected by temporal variability in marine productivity, rather than temporal patterns of plant growth.
Evenness–invasibility relationships differ between two extinction scenarios in tallgrass prairie
Authors: Losure David A. , Wilsey Brian J. , Moloney Kirk A.
Published: October 2006

Experiments that have manipulated species richness with random draws of species from a larger species pool have usually found that invasibility declines as richness increases. These results have usually been attributed to niche complementarity, and interpreted to mean that communities will become less resistant to invaders as species go locally extinct. However, it is not clear how relevant these studies are to real‐world situations where species extinctions are non‐random, and where species diversity declines due to increased rarity (i.e. reduced evenness) without having local extinctions. We experimentally varied species richness from 1 to 4, and evenness from 0.44 to 0.97 with two different extinction scenarios in two‐year old plantings using seedling transplants in western Iowa. In both scenarios, evenness was varied by changing the level of dominance of the tall grass Andropogon gerardii. In one scenario, which simulated a loss of short species from Andropogon communities, we directly tested for complementarity in light capture due to having species in mixtures with dissimilar heights. We contrasted this scenario with a second set of mixtures that contained all tall species. In both cases, we controlled for factors such as rooting depth and planting density. Mean invader biomass was higher in monocultures (5.4 g m−2 week−1) than in 4‐species mixtures (3.2 g m−2 week−1). Reduced evenness did not affect invader biomass in mixtures with dissimilar heights. However, the amount of invader biomass decreased by 60% as evenness increased across mixtures with all tall species. This difference was most pronounced early in the growing season when high evenness plots had greater light capture than low evenness plots. These results suggest that the effect of reduced species diversity on invasibility are 1) not related to complementarity through height dissimilarity, and 2) variable depending on the phenological traits of the species that are becoming rare or going locally extinct.
Evolution as It Appears to the Paleontologist
Authors: Osborn Henry Fairfield
Published: October 2006

The following facts are those which are put forth through paleontological observation, for verification by others:

1. That many origins of new characters are through some internal action in heredity.

2. That many important adaptive characters arise determinately, definitely, but by extremely slow stages.

3. That degrees of similarity in such origins correspond with degrees of kinship. 4. That degrees of kinship also affect to a certain extent, but not absolutely the time of appearance, or the time of the origin, or the rate of evolution.

5. That such origins find expression not spontaneously, or irrespective of conditions, or from purely internal mechanical causes, but through some entirely unknown and at present inconceivable relation to ontogeny (habit and use), to environment (external conditions), and to selection.

6. That if such origins do spring from internal hereditary principles, as they appear to do in many cases, slow origins (mutations of de Vries) may be simply due to the same law operating with a different velocity.
Erratum: Report of the General Secretary of the American Association for the Advancement of Science for the Chicago Meeting, Convocation Week, 1907-8
Authors: McNair F. W.
Published: October 2006

In the report of the general secretary of the American Association for the Advancement of Science there is an error on page 43. Sections A and D joined with the Chicago section of the American Mathematical Society in the discussion of the teaching of mathematics to engineers, not A and B, as appears in the report.
The Homologue ofhet-cofNeurospora crassaLacks Vegetative Compatibility Function inFusarium proliferatum
Authors: Kerényi Zoltán , Oláh Brigitta , Jeney Apor , Hornok László , Leslie John F.
Published: October 2006

For two fungal strains to be vegetatively compatible and capable of forming a stable vegetative heterokaryon they must carry matching alleles at a series of loci variously termedhetorvicgenes. Clonedhet/vicgenes fromNeurospora crassaandPodospora anserinahave no obvious functional similarity and have various cellular functions. Our objective was to identify the homologue of theNeurospora het-cgene inFusarium proliferatumand to determine if this gene has a vegetative compatibility function in this economically important and widely dispersed fungal pathogen. InF. proliferatumand five other closely relatedFusariumspecies we found a few differences in the DNA sequence, but the changes were silent and did not alter the amino acid sequence of the resulting protein. Deleting the gene altered sexual fertility as the female parent, but it did not alter male fertility or existing vegetative compatibility interactions. Replacement of the allele-specific portion of the coding sequence with the sequence of an alternate allele inN. crassadid not result in a vegetative incompatibility response in transformed strains ofF. proliferatum. Thus, thefphchgene inFusariumappears unlikely to have the vegetative compatibility function associated with its homologue inN. crassa. These results suggest that the vegetative compatibility phenotype may result from convergent evolution. Thus, the genes involved in this process may need to be identified at the species level or at the level of a group of species and could prove to be attractive targets for the development of antifungal agents.
Molecular Comparisons of Freshwater and Marine Isolates of the Same Morphospecies of Heterotrophic Flagellates
Authors: Scheckenbach Frank , Wylezich Claudia , Mylnikov Alexander P. , Weitere Markus , Arndt Hartmut
Published: October 2006

Heterotrophic flagellates are key components of all ecosystems. Understanding the patterns of biodiversity of these organisms is thus particularly important. Here we analyzed the intraspecific diversity of 10 morphospecies of heterotrophic flagellates comprising representatives of the Apusozoa (2 morphospecies) and Kinetoplastea (8 morphospecies), all belonging to the most common flagellates with worldwide distribution. Most morphospecies showed a mixing of lineages isolated from diverse habitats, indicating that some lineages of these morphospecies had been able to colonize different habitats several times. Furthermore, our results revealed remarkable levels of genetic divergence within most of the morphospecies studied, underlining the difficulty of correctly determining species by means of morphology alone. Many cryptic or pseudocryptic species seem to occur. Our results revealed clear divergence between marine and freshwater lineages of the morphospecies
Ancyromonas sigmoides
, showing that freshwater lineages have not been able to colonize marine environments and marine lineages have not been able to colonize freshwater environments for a long time.
Accuracy of Cefoxitin Disk Testing for Characterization of Oxacillin Resistance Mediated by Penicillin-Binding Protein 2a in Coagulase-Negative Staphylococci
Authors: Perazzi B. , Fermepin M. Rodríguez , Malimovka A. , García S. D. , Orgambide M. , Vay C. A. , de Torres R. , Famiglietti A. M. R.
Published: October 2006

The Clinical and Laboratory Standards Institute (CLSI) proposed, beginning in 2004, the use of cefoxitin disks to predict resistance mediated by the
mecA
gene in all species of coagulase-negative staphylococci (CoNS). The aim of this work was to evaluate the efficiency of the cefoxitin disk and of oxacillin-salt agar screening (MHOX) to characterize the oxacillin resistance mediated by the
mecA
gene in CoNS. One hundred seven CoNS isolates from different clinical samples were studied. Detection of the
mecA
gene by PCR was considered the “gold standard.” The susceptibility to oxacillin and cefoxitin was detected by the disk diffusion and agar dilution tests, as described by the CLSI. MHOX was also performed with 6 μg/ml of oxacillin and 4% NaCl. The sensitivities of the oxacillin and cefoxitin disks for all CoNS species were 88% and 80%, respectively, whereas the specificities were 63% and 100%, respectively. The sensitivities of the agar dilution test for oxacillin and cefoxitin (for proposed breakpoints of ≥4 μg/ml for resistance and ≤2 μg/ml for susceptibility) were 90% and 85%, respectively, whereas the specificities were 76% and 98%, respectively. MHOX showed a sensitivity of 90% and a specificity of 95% for all CoNS species. Both the MHOX and the cefoxitin disk results indicate that these are appropriate methods for the evaluation of oxacillin resistance mediated by the
mecA
gene in all CoNS species.
Evaluation of Molecular-Beacon, TaqMan, and Fluorescence Resonance Energy Transfer Probes for Detection of Antibiotic Resistance-Conferring Single Nucleotide Polymorphisms in Mixed
Mycobacterium tuberculosis
DNA Extracts
Authors: Yesilkaya Hasan , Meacci Francesca , Niemann Stefan , Hillemann Doris , Rüsch-Gerdes Sabine ,   LONG DRUG Study Group, Barer Michael R. , Andrew Peter W. , Oggioni Marco R.
Published: October 2006

The ability of fluorescence resonance energy transfer, molecular-beacon, and TaqMan probes to detect single nucleotide polymorphism (SNP) in the presence of a wild-type allele was evaluated using drug resistance-conferring SNPs in mixed
Mycobacterium tuberculosis
DNA. It was found that both the absolute quantity and the ratio of alleles determine the detection sensitivity of the probe systems.
Identification of
Borrelia burgdorferi
Ribosomal Protein L25 by the Phage Surface Display Method and Evaluation of the Protein's Value for Serodiagnosis
Authors: Mueller Markus , Bunk Sebastian , Diterich Isabel , Weichel Michael , Rauter Carolin , Hassler Dieter , Hermann Corinna , Crameri Reto , Hartung Thomas
Published: October 2006

The phage surface display technique was used to identify
Borrelia burgdorferi
antigens. By affinity selection with immunoglobulin G from pooled sera of six Lyme borreliosis (LB) patients, the ribosomal protein L25 was identified. The diagnostic value of L25 was investigated by an enzyme-linked immunosorbent assay, using sera from 80 LB patients and 75 controls, and the use of the protein resulted in a specificity of 99% and a 23% sensitivity, which qualify L25 as a useful antigen when combined with others.
In Vitro Activities of Daptomycin, Ciprofloxacin, and Other Antimicrobial Agents against the Cells and Spores of Clinical Isolates of
Bacillus
Species
Authors: Citron Diane M. , Appleman Maria D.
Published: October 2006

Daptomycin inhibited 67 of 70 clinical isolates of
Bacillus
species at ≤1 μg/ml and 100% of them at ≤2 μg/ml. It showed bactericidal activity similar to that of ciprofloxacin against vegetative cells but not against spores. For 2 strains, the ciprofloxacin MICs were >4 g/ml, and 10 strains were resistant to erythromycin.
Candida albicansStrain Maintenance, Replacement, and Microvariation Demonstrated by Multilocus Sequence Typing
Authors: Odds F. C. , Davidson A. D. , Jacobsen M. D. , Tavanti A. , Whyte J. A. , Kibbler C. C. , Ellis D. H. , Maiden M. C. J. , Shaw D. J. , Gow N. A. R.
Published: October 2006

We typed 165Candida albicansisolates from 44 different sources by multilocus sequence typing (MLST) and ABC typing of rRNA genes and determined their homozygosity or heterozygosity at the mating-type-like locus (MTL). The isolates represented pairs or larger sets from individual sources, which allowed the determination of strain diversity within patients. A comparison of replicate sequence data determined a reproducibility threshold for regarding isolates as MLST indistinguishable. For 36 isolate sets, MLST and ABC typing showed indistinguishable or highly related strain types among isolates from different sites or from the same site at different times from each patient. This observation included 11 sets with at least one isolate from a blood culture and a nonsterile site from the same patient. For one patient, strain replacement was evidenced in the form of two sets of isolates from different hospital admissions where the strain types within each set were nearly identical but where the two sets differed both by MLST and ABC typing. MLST therefore confirms the existing view ofC. albicansstrain carriage. Microvariation, evidenced as small differences between MLST types, resulted in most instances from a loss of heterozygosity at one or more of the sequenced loci. Among isolate sets that showed major strain type differences, some isolates could be excluded as likely examples of handling errors during storage. However, for a minority of isolates, intermittent differences in ABC type for tightly clustered MLST types and intermittent appearances of MTL homozygosity lead us to propose that someC. albicansisolates, or all isolates under yet-to-be-determined conditions, maintain a high level of genetic diversity by mechanisms such as recombination, gene conversion, or chromosomal ploidy change.
Identification of Clinical Isolates of Indole-Positive and Indole-Negative
Klebsiella
spp
Authors: Alves Maria Silvana , Dias Rubens Clayton da Silva , de Castro Angela Christina Dias , Riley Lee W. , Moreira Beatriz Meurer
Published: October 2006

Biochemical methods employed to classify bacterial species have limitations and may have contributed to the taxonomic complexity recently reported for the genus
Klebsiella
. The objective of the present study was to apply a simple biochemical test panel to classify a collection of human
Klebsiella
isolates. We found that with only three additional tests, it is possible to place most isolates in a defined species. Analysis of a 512-bp sequence of the
rpoB
gene was used as the reference. A total of 16 conventional and 4 supplementary tests were used to evaluate 122 recent isolates identified as
Klebsiella
from 120 patients, isolated at the clinical laboratory of a university hospital in Minas Gerais, Brazil. Of these, 102 (84%) isolates were identified as
Klebsiella pneumoniae
or
Klebsiella variicola
, 19 (15%) as
Klebsiella oxytoca
, and 1 (1%) as
Raoultella planticola
. Enterobacterial repetitive intergenic consensus-PCR typing revealed a diversity of genotypes.
rpoB
gene sequencing confirmed the phenotypic identification and detected five
K. variicola
isolates among the
K. pneumoniae
/
K. variicola
group. Three additional tests that include growth at 10°C and histamine and
d
-melezitose assimilation should be considered essential tests for the typing of
Klebsiella
isolates.
Unusually High Prevalence of Nosocomial Panton-Valentine Leukocidin-Positive
Staphylococcus aureus
Isolates in Cape Verde Islands
Authors: Aires-de-Sousa M. , Conceição T. , de Lencastre H.
Published: October 2006

Characterization of nosocomial methicillin-susceptible
Staphylococcus aureus
isolates from Cape Verde showed that (i) Panton-Valentine leukocidin genes were present in 35% of the isolates and (ii) half of the collection had the same genetic background as methicillin-resistant pandemic clones. Introduction of the staphylococcal chromosome cassette
mec
(SCC
mec
) into virulent and epidemic isolates could pose serious threats to public health.
Use of Pulsed-Field Gel Electrophoresis for Comparison of Similar but Distinguishable Isolates of
Shigella sonnei
Collected in Ireland and Italy
Authors: De Lappe N. , Doran G. , Connor J. O. , Mammina C. , Cormican M.
Published: October 2006

Comparison of pulsed-field gel electrophoresis patterns (generated with XbaI and BlnI) of
Shigella sonnei
isolates from Ireland and Italy suggests that two possibly distantly related lineages are present in both countries. Smaller, more closely related groups, including isolates from Ireland and Italy, were also noted. These groups raise the possibility that the dissemination of clonal groups of
S. sonnei
may have occurred in recent years.
Beijing and Haarlem Genotypes Are Overrepresented among Children with Drug-Resistant Tuberculosis in the Western Cape Province of South Africa
Authors: Marais Ben J. , Victor Tommie C. , Hesseling Anneke C. , Barnard Madeleine , Jordaan Annemie , Brittle Wendy , Reuter Helmuth , Beyers Nulda , van Helden Paul D. , Warren Rob M. , Schaaf H. Simon
Published: October 2006

Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic.
Pancreatic polypeptide cell hyperplasia of the pancreas
Authors: Albazaz R , Da Costa P E , Verbeke C S
Published: October 2006

A case of pancreatic polypeptide cell hyperplasia in a 76-year-old man who presented with subacute bowel pseudo-obstruction is reported. A computed tomography scan incidentally showed a pancreatic head lesion that was resected by pancreaticoduodenectomy. Histological examination showed expansion of the endocrine pancreas with increased numbers of pancreatic polypeptide cells in irregularly enlarged islets, ragged endocrine cell clusters, ductulo-insular complexes and microadenomas. The clinicopathological features of this rare and poorly understood condition are discussed.
Diagnosis and grading of dysplasia in Barrett’s oesophagus
Authors: Odze R D
Published: October 2006

This review focuses on the pathological features of dysplasia in Barrett’s oesophagus. Two categorisation schemes are used for grading dysplasia in the gastrointestinal tract, including Barrett’s oesophagus. The inflammatory bowel disease dysplasia morphology study group system is the one most commonly used in the USA. However, some European and most far Eastern countries use the Vienna classification system, which uses the term “non-invasive neoplasia” instead of low-grade dysplasia (LGD) or high-grade dysplasia (HGD) and also uses the term “suspicious for invasive carcinoma” for lesions that show equivocal cytological or architectural features of tissue invasion. The degree of dysplasia is based on a combination of cytological and architectural atypia. However, the precise number of HGD crypts that is necessary to upgrade a biopsy from LGD to HGD has never been investigated and varies widely among expert gastrointestinal pathologists. The extent of dysplasia, particularly LGD, has also been recognised recently as an important prognostic parameter in Barrett’s oesophagus. Other problematic areas of dysplasia interpretation include differentiation of regenerating epithelium versus LGD and separating HGD from carcinoma. Dysplasia associated with macroscopically visible lesions, such as ulcers, nodules or polyps, carry a high risk of synchronous or metachronous adenocarcinoma. Recently, immunostaining for α-methylacyl-CoA-racemase has been shown to have a high degree of specificity for detection of dysplasia in Barrett’s oesophagus and may be used to help distinguish negative from positive biopsies in this condition. In this review, the problematic areas in dysplasia interpretation are outlined and a specific approach to these issues is discussed.
A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy
Authors: Lee Myung-Ja , Feliers Denis , Mariappan Meenalakshmi M. , Sataranatarajan Kavithalakshmi , Mahimainathan Lenin , Musi Nicolas , Foretz Marc , Viollet Benoit , Weinberg Joel M. , Choudhury Goutam Ghosh , Kasinath Balakuntalam S.
Published: October 2006

We tested the hypothesis that AMP-activated protein kinase (AMPK), an energy sensor, regulates diabetes-induced renal hypertrophy. In kidney glomerular epithelial cells, high glucose (30 mM), but not equimolar mannitol, stimulated de novo protein synthesis and induced hypertrophy in association with increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2, regulatory events in mRNA translation. These high-glucose-induced changes in protein synthesis were phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR) dependent and transforming growth factor-β independent. High glucose reduced AMPK α-subunit theronine (Thr) 172 phosphorylation, which required Akt activation. Changes in AMP and ATP content could not fully account for high-glucose-induced reductions in AMPK phosphorylation. Metformin and 5-aminoimidazole-4-carboxamide-1β-riboside (AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2. Expression of kinase-inactive AMPK further increased high-glucose-induced protein synthesis. Renal hypertrophy in rats with Type 1 diabetes was associated with reduction in AMPK phosphorylation and increased mTOR activity. In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia. AMPK is a newly identified regulator of renal hypertrophy in diabetes.
Expression of Terminally Glycosylated Calcitonin Receptor–Like Receptor in Uterine Leiomyoma: Endothelial Phenotype and Association with Microvascular Density
Authors: Nikitenko Leonid L. , Cross Tanya , Campo Leticia , Turley Helen , Leek Russell , Manek Sanjiv , Bicknell Roy , Rees Margaret C.P.
Published: October 2006

Purpose: The role for the hypoxia-inducible angiogenic factor adrenomedullin (AM) in tumor growth and progression has been suggested. Calcitonin receptor–like receptor (CL) is a G protein–coupled receptor (GPCR) that mediates effects of AM, but little information is available on its expression and functional state in human tumors. The present study attempted to determine CL potential for antiangiogenic therapy of uterine leiomyoma.

Experimental Design and Results: GPCR CL is transported to the cell surface and recognized by AM only when terminally/mature glycosylated. The presence and localization of this form of the receptor in tumor and surrounding myometrial tissues obtained from leiomyoma-bearing uteri were examined using deglycosylation, immunoblotting, and immunofluorescence analysis. The mature CL glycoprotein was expressed in both tissues and localized exclusively in normal and tumor endothelium within leiomyoma-bearing uteri. The functionality of the receptor expressed in myometrial microvascular endothelial cells (MMVEC) was examined in vitro using receptor internalization and angiogenic assays. The mature CL glycoprotein expressed by primary MMVECs was functional because AM interacted with this GPCR and induced its internalization as well as angiogenic effects (proliferation and migration) in MMVECs in vitro. Finally, the levels of tissue-expressed mature CL glycoprotein as a functional form of this GPCR were analyzed by immunoblotting. The expression of this functional form of the receptor in vivo was significantly decreased (P = 0.01) in leiomyoma tissue, and this was concurrent with the decrease in microvascular density (measured by Chalkley counting) in tumor compared with surrounding myometrium (P = 0.031).

Conclusions: Our findings suggest that GPCR CL mediates angiogenic effects of AM in myometrium and that further evaluation of the properties of the CL expressed in both normal and tumor endothelium in vivo may be essential before targeting this endothelial GPCR for antiangiogenic therapies.
Interphase Fluorescence In situ Hybridization Analysis of Chromosome 12p Abnormalities Is Useful for Distinguishing Epidermoid Cysts of the Testis from Pure Mature Teratoma
Authors: Cheng Liang , Zhang Shaobo , MacLennan Gregory T. , Poulos Christopher K. , Sung Ming-Tse , Beck Stephen D. , Foster Richard S.
Published: October 2006

Purpose: The distinction of epidermoid cyst of the testis from teratoma is of critical importance because the former is benign and the latter is a malignant tumor that may have associated metastasis of either teratomatous or non–teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the vast majority of testicular germ cell tumors of adults and are present in all histologic subtypes. In this study, we investigated the clinical utility of interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p abnormalities for distinguishing epidermoid cysts of the testis from pure mature teratoma.

Experimental Design: Sixteen testicular epidermoid cysts and 17 testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p overrepresentation using interphase FISH analysis.

Results: Neither i(12p) nor 12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p) was detected in 76% of teratomas and 12p overrepresentation was identified in 29% of teratomas. Overall, 88% of testicular teratomas had chromosome 12p abnormalities.

Conclusions: FISH identification of i(12p) and/or 12p overrepresentation in routinely processed surgical specimens is a useful ancillary diagnostic tool in distinguishing testicular epidermoid cysts from teratoma.
Cotreatment with Vorinostat (Suberoylanilide Hydroxamic Acid) Enhances Activity of Dasatinib (BMS-354825) against Imatinib Mesylate–Sensitive or Imatinib Mesylate–Resistant Chronic Myelogenous Leukemia Cells
Authors: Fiskus Warren , Pranpat Michael , Balasis Maria , Bali Purva , Estrella Veronica , Kumaraswamy Sandhya , Rao Rekha , Rocha Kathy , Herger Bryan , Lee Francis , Richon Victoria , Bhalla Kapil
Published: October 2006

Purpose: We determined the effects of vorinostat [suberoylanilide hydroxamic acid (SAHA)] and/or dasatinib, a dual Abl/Src kinase (tyrosine kinase) inhibitor, on the cultured human (K562 and LAMA-84) or primary chronic myelogenous leukemia (CML) cells, as well as on the murine pro-B BaF3 cells with ectopic expression of the unmutated and kinase domain-mutant forms of Bcr-Abl.

Experimental Design: Following exposure to dasatinib and/or vorinostat, apoptosis, loss of clonogenic survival, as well as the activity and levels of Bcr-Abl and its downstream signaling proteins were determined.

Results: Treatment with dasatinib attenuated the levels of autophosphorylated Bcr-Abl, p-CrkL, phospho-signal transducer and activator of transcription 5 (p-STAT5), p-c-Src, and p-Lyn; inhibited the activity of Lyn and c-Src; and induced apoptosis of the cultured CML cells. Combined treatment of cultured human CML and BaF3 cells with vorinostat and dasatinib induced more apoptosis than either agent alone, as well as synergistically induced loss of clonogenic survival, which was associated with greater depletion of Bcr-Abl, p-CrkL, and p-STAT5 levels. Cotreatment with dasatinib and vorinostat also attenuated the levels of Bcr-AblE255K and Bcr-AblT315I and induced apoptosis of BaF3 cells with ectopic expression of the mutant forms of Bcr-Abl. Finally, cotreatment of the primary CML cells with vorinostat and dasatinib induced more loss of cell viability and depleted Bcr-Abl or Bcr-AblT315I, p-STAT5, and p-CrkL levels than either agent alone.

Conclusions: As shown here, the preclinical in vitro activity of vorinostat and dasatinib against cultured and primary CML cells supports the in vivo testing of the combination in imatinib mesylate–sensitive and imatinib mesylate–resistant CML cells.
Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study
Authors: Moreau Lisa A. , McGrady Patrick , London Wendy B. , Shimada Hiroyuki , Cohn Susan L. , Maris John M. , Diller Lisa , Look A. Thomas , George Rani E.
Published: October 2006

Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins.

Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with currently used risk group stratification variables and patient outcome were assessed.

Results: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN amplification. Among the 677 tumors for which the pattern of amplification was known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs. Although MYCN amplification is associated with older age, higher stage, and unfavorable histology, whether the amplification occurred as dmins or HSRs did not significantly affect these risk factors. There were no differences in the event-free survival (EFS) or overall survival in patients with MYCN amplification manifested as either dmins or HSRs (5-year EFS, 35 ± 3% versus 38 ± 15%; P = 0.59). Although the eight patients with dmins + HSRs fared worse than either of the individual subgroups (EFS, 18 ± 16% versus 35 ± 3% for dmins and 38 ± 15% for HSRs), these differences were not significant.

Conclusions: MYCN amplification in any form (HSRs or dmins) is associated with a poor outcome.
J-integral of a Penny-shaped Crack on the End of Stiff Cylindrical Cord Embedded in Rubbery Materials
Authors: Yang Kyeong Jin
Published: October 2006

The general purpose of this study is the determination of J-integral when dealing with fracture of a penny-shaped crack on the end of the stiff cylindrical cord embedded in rubber matrix. The dimensional analysis is applied to derive a general equation of J-integral, and then it is assumed that the equation of J-integral can be separated into the deformation and geometry functions, the validity of which is proved by using separation parameter. The J-integral is expressed in a multiplicative form in which the geometry calibration function (or factor) is introduced in order to take into account the finite dimensions. The values of the J-integral for the rubber-cord composites with various crack and specimen radius are obtained by using finite element analysis (FEA), and these results are used for concretely determining the geometry calibration function, which, in this work, is expressed in a polynomial form of fourth order. The deformation calibration function, which is a constant for a linear elastic materials, characterizing the large deformable nonlinear effect in rubbery materials is obtained by comparing the equation of J-integral with the ones for the linear elastic deformation. As we approach the infinitesimal strain, the value of the deformation calibration function comes close to the result of linear elastic fracture mechanics (LEFM).
Novel Amino Acid-constructed Polyalkenoates for Dental Glass-ionomer Restoratives
Authors: Xie Dong , Park Jong-Gu , Faddah Mona , Zhao Jun , Khanijoun Harleen K.
Published: October 2006

Several methacrylate or acrylate derivatives of natural amino acids were synthesized and characterized. Based upon these derivatives, novel amino acid-constructed polyalkenoic acids were prepared and used to formulate glass-ionomer cements (GICs) with Fuji II glass filler. The effects of type of derivatives, molar ratio, molecular weight, and powder/liquid ratio were investigated. The results show that amino acid-constructed polyalkenoic acids can be formed only from amino acid methacrylate derivatives or by copolymerization of methacrylate with acrylate derivatives. Strong hydrogen bond interactions failed the polymer formation from acrylate derivatives. The cement composed of poly(methacryloyl glutamic acid-co-acryloyl beta-alanine) with the molar ratio of 8:2 demonstrated the best mechanical strengths along with a workable viscosity. By using the powder/liquid ratio of 3.0/1, the experimental cement exhibited a significantly higher FS (27.7 MPa), and nearly the same CS (198.5 MPa) and DTS (11.8 MPa), as compared to Fuji II (18.9 for FS, 189.1 for CS, and 11.4 MPa for DTS). During aging, the cement showed a significant increase in strength over 24 h, followed by a slow increase over 6 months.
Chemo-mechanical Model for Actuation Based on Biological Membranes*
Authors: Sundaresany Vishnu Baba , Leo Donald J.
Published: October 2006

Plants have the ability to develop large mechanical force from chemical energy available with bio-fuels. The energy released by adenosine tri-phosphate (ATP) hydrolysis assists the transport of ions and fluids to achieve volumetric expansion and homeostasis. Materials that develop pressure and hence strain similar to bio-materials are classified as nastic materials. Recent calculations for controlled actuation of an active material inspired by biological transport mechanism demonstrated the feasibility of developing such a material with actuation energy densities on the order of 100 kJ/m3. The initial investigation was based on capsules that generate pressure, thus causing strain in the surrounding matrix material. This paper focuses on our efforts to fabricate a representative actuation structure and describes the chemo-mechanical constitutive equation for such a material. The actuator considered in this work is a laminated plate dispersed with biological transporters. The initial design and a mathematical model to predict the fluid flux and strain developed in such an actuator are presented here.
Simulations and games
Authors: Lean Jonathan , Moizer Jonathan , Towler Michael , Abbey Caroline
Published: October 2006

This article explores the use of simulations and games in tertiary education. It examines the extent to which academics use different simulation-based teaching approaches and how they perceive the barriers to adopting such techniques. Following a review of the extant literature, a typology of simulations is constructed. A staff survey within a UK higher education (HE) institution is conducted to investigate the use of the different approaches identified within the typology. The findings show significant levels of use of both computer and non-computer-based simulations and games. The main barrier to teaching with simulations, as perceived by the respondents, is the availability of resources. However, further analysis indicates that use of simulations is not associated with perceptions of resource issues, but rather is influenced by views on the suitability of, and risk attached to, such learning methods. The study concludes by recommending improved promotion of simulation-based teaching through enhanced information provision on the various techniques available and their application across subject areas.
Activated AKT/PKB signaling in C. elegansuncouples temporally distinct outputs of DAF-2/insulin-like signaling
Authors: Gami Minaxi S , Iser Wendy B , Hanselman Keaton B , Wolkow Catherine A
Published: October 2006

Background

In the nematode,Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling inC. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype ofage-1(mg109)animals.

Results

This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype ofage-1(mg109). Two mutations corresponded to alleles ofdaf-16. Two mutations were gain-of-function alleles in the genes,akt-1andpdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation,mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting thatmg227may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development inage-1(mg109);akt-1(mg247)animals was dependent on the presence ofpdk-1. Similarly, reproductive development inage-1(mg109);pdk-1(mg261)animals was dependent onakt-1. However, reproductive development inage-1(mg109); mg227animals required onlyakt-1, andpdk-1activity was dispensable in this background. Interestingly, whilemg227suppressed dauer arrest inage-1(mg109)animals, it enhanced the long lifespan phenotype. In contrast,akt-1(mg247)andpdk-1(mg261)did not affect lifespan or stress resistance, while bothdaf-16alleles fully suppressed these phenotypes.

Conclusion

A screen for suppressors of PI3K mutant phenotypes identified activating mutations in two known pathway components, providing insights into their regulation. In particular, the interdependence ofakt-1andpdk-1, even in activated forms, supports the existence of AGE-1-independent pathways for these phospholipid-dependent kinases. Phenotypic analysis of these alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable in these mutants.
Metabolic changes after polytrauma: an imperative for early nutritional support
Authors: Hasenboehler Erik , Williams Allison , Leinhase Iris , Morgan Steven J , Smith Wade R , Moore Ernest E , Stahel Philip F
Published: October 2006

Major trauma induces marked metabolic changes which contribute to the systemic immune suppression in severely injured patients and increase the risk of infection and posttraumatic organ failure. The hypercatabolic state of polytrauma patients must be recognized early and treated by an appropriate nutritional management in order to avoid late complications. Clinical studies in recent years have supported the concept of "immunonutrition" for severely injured patients, which takes into account the supplementation of Ω-3 fatty acids and essential aminoacids, such as glutamine. Yet many aspects of the nutritional strategies for polytrauma patients remain controversial, including the exact timing, caloric and protein amount of nutrition, choice of enteral versus parenteral route, and duration. The present review will provide an outline of the pathophysiological metabolic changes after major trauma that endorse the current basis for early immunonutrition of polytrauma patients.
Early postoperative serum S100β levels predict ongoing brain damage after meningioma surgery: a prospective observational study
Authors: Einav Sharon , Shoshan Yigal , Ovadia Haim , Matot Idit , Hersch Moshe , Itshayek Eyal
Published: October 2006

Introduction

Elevated serum levels of S100β, an astrocyte-derived protein, correlate with unfavourable neurological outcomes following cardiac surgery, neurotrauma, and resuscitation. This study evaluated whether pre-/postoperative serum S100β levels correlate with unfavourable clinical and radiological findings in patients undergoing elective meningioma resection.

Methods

In 52 consecutive patients admitted for meningioma surgery, serum S100β levels were determined upon admission and immediately, 24 hours, and 48 hours after surgery. All patients underwent complete pre- and postoperative neurological examination and mini-mental state examination. Radiological evaluation included preoperative magnetic resonance imaging (MRI) and postoperative computed tomography. Tumour volume, brain edema, and bleeding volume were calculated using BrainSCAN™ software.

Results

Preoperative S100β levels did not correlate with the tumour characteristics demonstrated by preoperative MRI (for example, tumour volume, edema volume, ventricular asymmetry, and/or midline shift). Preoperative serum S100β levels (0.065 ± 0.040 μg/l) were significantly lower than the levels measured immediately (0.138 ± 0.081 μg/l), 24 hours (0.142 ± 0.084 μg/l), and 48 hours (0.155 ± 0.119 μg/l) postoperatively (p < 0.0001). Significantly greater postcraniotomy S100β levels were observed with prolonged surgery (p = 0.039), deterioration in the mini-mental state examination (p = 0.005, 0.011, and 0.036 for pre versus immediate, 24 hours, and 48 hours postsurgery, respectively), and with postoperative brain computed tomography evidence of brain injury; bleeding was associated with higher serum S100β levels at 24 and 48 hours after surgery (p = 0.046, 95% confidence interval [CI] -0.095 to -0.001 and p = 0.034, 95% CI -0.142 to -0.006, respectively) as was the presence of midline shift (p = 0.005, 95% CI -0.136 to -0.025 and p = 0.006, 95% CI -0.186 to -0.032, respectively). Edema was associated with higher serum S100β levels immediately (p = 0.022, 95% CI -0.092 to -0.007) and at 48 hours after surgery (p = 0.017, 95% CI -0.142 to -0.026). The degree of elevation in S100β levels at 24 and 48 hours after surgery also correlated with the severity of midline shift and edema.

Conclusion

In patients with meningioma, serum S100β levels perform poorly as an indicator of tumour characteristics but may suggest ongoing postcraniotomy injury. Serum S100β levels may serve as a potentially useful early marker of postcraniotomy brain damage in patients undergoing elective meningioma resection.
Acoustic neuroma suspicion index: An aid to investigation and diagnosis
Authors: Windle‐Taylor Paul C. , Dhillon Ramindar S. , Kenyon Guy S. , Morrison Andrew W.
Published: October 2006

A clinical scale, the Acoustic Neuroma Suspicion Index (ANSI) is presented. It was based initially on the retrospective analysis of 397 patients suspected of having an acoustic neuroma of whom, following full investigation, 263 (66%) were found to have space occupying lesions. After minor modifications, the Index was re‐tested on 98 patients of whom 56 proved to have tumors while 47, who did not, formed a control group. All tumor cases were confirmed surgically.

Neuro‐otological investigations can be expensive, time consuming and occasionally unpleasant for patients; furthermore they are not always readily available. Though the diagnosis of an acoustic tumor or other cerebellopontine angle lesion is often straightforward, atypicality of presentation occurs often. The ANSI uses simple selected data from the history and clinical examination, with routine audiological, vestibular and radiological investigations to calculate a score. If this score exceeds the predetermined threshold, further investigations should be undertaken.