bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold-pressed flaxseed oil reverses age-associated depression in a primary cell-mediated adaptive immune response in the mouse
Authors: Hillyer L. M. , Sandiford A. M. , Gray C. E. , Woodward Bill
Published: February 2006

The objective of this investigation was to determine the influence of flaxseed oil on responses representative of primary humoral and cell-mediated adaptive immune competence in immunosenescent mice. Male and female C57BL/6J mice, 85 weeks old, were randomized between two complete purified diets differing only in oil source (cold-pressed safflower or flaxseed). After 8 weeks, humoral competence was assessed in six mice per group as the serum haemagglutinin titre to sheep red blood cells (SRBC) and cell-mediated competence was assessed, in an additional six mice per group, as the delayed hypersensitivity response to SRBC. A zero-time control group (88 weeks old) and a young adult positive control group (12 weeks old) were each tested similarly (six per immune response), revealing age-related depression in both antibody and cell-mediated competence at 88 weeks of age. After the 8-week experimental period, the antibody response of the two test groups of geriatric mice remained below the young adult level (P=0·04) and the cell-mediated response of the saffloweroil group also continued to exhibit age-related depression (20% of young adult level,P=0·0002). By contrast, the anti-SRBC delayedhypersensitivity response of the flaxseed group no longer differed from the response of the young adults but exceeded that of the safflower and zero-time control senescent groups (P=0·0002). Depression in primary cell-mediated competence, the most outstanding aspect of immunosenescence, can be addressed by means of a dietary source of 18:3n-3 without longer-chain PUFA.
The facilitative effects of glucose ingestion on memory retrieval in younger and older adults: is task difficulty or task domain critical?
Authors: Riby Leigh M. , McMurtrie Hazel , Smallwood Jonathan , Ballantyne Carrie , Meikle Andrew , Smith Emily
Published: February 2006

The ingestion of a glucose-containing drink has been shown to improve cognitive performance, particularly memory functioning. However, it remains unclear as to the extent to which task domain and task difficulty moderate the glucose enhancement effect. The aim of this research was to determine whether boosts in performance are restricted to particular classes of memory (episodicv. semantic) or to tasks of considerable cognitive load. A repeated measures (25g glucosevsaccharin), counterbalanced, double-blind design was used with younger and older adults. Participants performed a battery of episodic (e.g. paired associate learning) and semantic memory (e.g. category verification) tasks under low and high cognitive load. Electrophysiological measures (heart rate and galvanic skin response) of arousal and mental effort were also gathered. The results indicated that whilst glucose appeared to aid episodic remembering, cognitive load did not exaggerate the facilitative effect. For semantic memory, there was little evidence to suggest that glucose can boost semantic memory retrieval even when the load was manipulated. One exception was that glucose facilitated performance during the difficult category fluency task. Regardless, the present findings are consistent with the domain-specific account in which glucose acts primarily on the hippocampal region, which is known to support episodic memory. The possible contribution of the hippocampus in semantic memory processing is also discussed.
Soil contamination with ascarid eggs in playgrounds in Kirikkale, Turkey
Authors: Aydenizöz Özkayhan M.
Published: February 2006

Contamination of soil with feline and canine ascarid eggs in eight playgrounds in Kırıkkale, Turkey was investigated monthly from February 2003 to January 2004. Dog faeces were also collected and all samples were examined using the zinc sulphate centrifugal flotation method. Eggs ofToxocarawere observed in 5 of 8 (62.5%) of playgrounds examined and in 15.6% of 480 soil samples. The number of eggs varied from 1 to 11. Eggs were observed in soil samples collected in February, March to June, August and November, with embryonated eggs appearing in June and August. Eggs ofToxascaris leoninaandTaeniaspp. and oocysts ofIsosporaspp. were also found in 1.5%, 1.0% and 0.2% of soil samples, respectively. Of 26 samples of dog faeces collected, 7.7% were contaminated withToxocaraspp. and 11.5% withTaeniaspp. The presence ofToxocaraeggs in the city playgrounds and dog populations suggests a potential human health hazard due to toxocariasis.
Comparative study on DNA sequences of ribosomal DNA and cytochrome c oxidase subunit 1 of mitochondrial DNA among five species of gnathostomes
Authors: Ando K. , Tsunemori M. , Akahane H. , Tesana S. , Hasegawa H. , Chinzei Y.
Published: February 2006

The nucleotide sequences of partial 18S, complete internal transcribed spacer region 1 (ITS1), complete 5.8S, complete ITS2 and partial 28S of ribosomal DNA (rDNA) and cytochrome c oxidase subunit 1 of mitochondrial DNA (MCOI) from five species of gnathostomes (G. spinigerum, G. doloresi, G. nipponicum, G. hispidum and G. binucleatum with the former four species being distributed in Japan and Asia) that cause human gnathostomiasis were compared by direct polymerase chain reaction cycle-sequencing. The nucleotide sequences of each region of the18S (613 bp), 5.8S (158 bp) and 28S (598 bp) rDNA from the five species were almost identical. The ITS1 region was different in length for the five species. The nucleotide sequences of each region of ITS2 and partial MCO1 regions were different among the five species. Therefore, these two regions can be used as genetic markers for identification of worms.
Diversity of Dilepididae (Cestoda: Cyclophyllidea) revealed by cytogenetic analysis
Authors: Petkevičiūtė R. , Binkienė R. , Komisarovas J.
Published: February 2006

Karyotypes of three dilepidid species: Molluscotaenia crassiscolex, Anomotaenia bacilligera and Dilepis undula, which have not been recorded previously, were studied using conventional Giemsa staining and comparative karyometric analysis. Twelve small biarmed chromosomes were observed in mitotic cells of M. crassiscolex, 16 biarmed chromosomes of gradually decreasing size were found in cells of A. bacilligera, while 18 elements were characteristic for D. undula. These data, together with information available in literature, prove the heterogeneity and possible polyphyletic nature of the family Dilepididae.
Sodium dodecyl sulphate as a rapid clearing agent for studying the hard parts of monogeneans and nematodes
Authors: Wong W.L. , Tan W.B. , Lim L.H.S.
Published: February 2006

Hard structures of helminths have often been used for taxonomic identification but are usually not clearly defined when treated with conventional methods such as ammonium picrate-glycerin for monogeneans and glycerin for nematodes. The present study reports a rapid and simple technique to better resolve the hard parts of selected monogeneans and nematodes using 5–10% alkaline sodium dodecyl sulphate (SDS). In comparison with established methods, SDS-treated worms become more transparent. In monogeneans treated with SDS, clear details of the hooks, hook filaments, anchors, bars and the sclerotized copulatory organs could be observed. In SDS-treated nematodes, spicules and ornamentations of the buccal capsules could be clearly seen.
Unusual finding of Trichobilharzia sp. in Motacilla alba in the Czech Republic
Authors: Rudolfová J. , Sitko J. , Horák P.
Published: February 2006

Adult male worms of Trichobilharzia sp. recovered from a pied wagtail (Motacilla alba) in the Czech Republic were found to belong to a new species of the genus. The finding of Trichobilharzia sp. in a passeriform bird in Europe represents an important discovery, as only anseriform birds have thus far been reported as final hosts of the European Trichobilharzia species.
Toxocara canis infections in a pig model: immunological, haematological and blood biochemistry responses
Authors: Sommerfelt I.E. , Santillán G. , Mira G. , Ribicich M. , Betti A. , De Torres R.
Published: February 2006

The immunological, haematological and enzymatic responses to the inoculation in pigs of 100,000 embryonated eggs of Toxocara canis were studied. Fifteen females were inoculated and three remained as controls. Haematological values were analysed from day 7 p.i. until day 126 p.i. In the inoculated group, white blood cells were raised on day 14 p.i. and eosinophil values on days 7, 14, 21, 35 and 49 p.i. showing significant differences compared with controls (P<0.05). Absolute eosinophil counts (per ml) presented two rises, the first on days 7, 14 and 21 p.i. and the second on days 35 and 49 p.i. Blood biochemistry was maintained within normal values. Serological examination by ELISA to determine antibody levels against Toxocara canis L2/L3 excretory–secretory (ES) antigens showed values higher than the positive cut-off (1:32) from day 7 p.i. and until the end of the study on day 126 p.i., presenting two peaks: one on day 28 p.i. and the second covering days 49 to 56 p.i. Western blots of sera of inoculated animals presented, from day 7 p.i., two polypeptide bands of 55 and 70 kDa MW and, from day 56 p.i., an additional band of 120 kDa MW, all of which persisted until the end of the study. Immunological responses were sustained over time. No direct correlation was observed between the rise in eosinophils and antibody titres. To validate the conclusions, more studies are required on the polypeptide bands.
Molecular identification of Anisakis species from Pleuronectiformes off the Portuguese coast
Authors: Marques J.F. , Cabral H.N. , Busi M. , D'Amelio S.
Published: February 2006

Anisakid nematodes belonging to the Anisakis simplex complex are highly prevalent in several fish species off the coast of Portugal and are an important zoonotic problem in the Iberian Peninsula. Two reproductively isolated sibling species of the Anisakis simplex complex were identified from Pleuronectiformes inhabiting the Portuguese coast using restriction fragment length polymorphism (RFLP). Recombinant genotypes corresponding to presumptive Anisakis simplex sensu stricto and Anisakis pegreffii hybrids were also detected by this technique, as well as the species Anisakis typica. Although 25 species of Pleuronectiformes were investigated, Anisakis spp. larvae were only found in seven: Arnoglossus imperialis, Arnoglossus laterna, Lepidorhombus boscii, Citharus linguatula, Platichthys flesus, Dicologlossa cuneata and Solea senegalensis. The occurrence of hybrids in relatively sedentary fishes such as the Pleuronectiformes suggests that the Portuguese coast may constitute an area of hybridization and, therefore, is of particular interest for the study of the process of hybridization and speciation for these anisakids.
Fertilization state of Ascaris suum determined by electrorotation
Authors: Dalton C. , Goater A.D. , Smith H.V.
Published: February 2006

Electrorotation is a non-invasive technique that is capable of detecting changes in the morphology and physicochemical properties of microorganisms. The first detailed electrorotation study of the egg (ovum) of a parasitic nematode, namely Ascaris suum is described to show that electrorotation can rapidly differentiate between fertilized and non-fertilized eggs. Support for this conclusion is by optical microscopy of egg morphology, and also from modelling of the electrorotational response. Modelling was used to determine differences in the dielectric properties of the unfertilized and fertilized eggs, and also to investigate specific differences in the spectra of fertilized eggs only, potentially reflecting embryogenesis. The potential of electrorotation as an investigative tool is shown, as undamaged eggs can be subjected to further non-destructive and destructive techniques, which could provide further insight into parasite biology and epidemiology.
Helminth fauna of Talpa spp. in the Palaearctic Realm
Authors: Ribas A. , Casanova J.C.
Published: February 2006

The helminth fauna of the genus Talpa in the Palaearctic Realm is reviewed. Several helminth species reported in Talpa spp. by a number of authors are discussed, with reference to host specificity, parasite biology, and host ethology, ecology and phylogeny. Twelve species of cestodes were found, two of which exhibit stenoxenous specificity (Staphylocystis bacillaris and Multitesticulata filamentosa). Only three species of trematodes, Ityogonimus lorum, Ityogonimus ocreatus and Combesia macrobursata, are exclusive parasites of Talpa spp. The largest group are nematodes, with 37 species. Species of Tricholinstowia are parasites of holarctic talpids and several species of distinct genera, such as Capillaria, Soboliphyme and Trichuris, are found only in Talpa spp. Only acanthocephalans of the genus Moniliformis have been reported in moles of the genus Talpa. On the basis of these helminthological findings, the close phylogenetic relationship between moles (Talpidae) and shrews (Soricidae) supports the separation of the ordinal levels Soricomorpha and Erinaceomorpha.
Influence of season and host age on wild boar parasites in Corsica using indicator species analysis
Authors: Foata J. , Mouillot D. , Culioli J.-L. , Marchand B.
Published: February 2006

The indicator value (Ind Val) method which combines measures of fidelity and specificity has been used in a study on wild boar parasites in Corsica during 2001–2003. Because of its resilience to changes in abundance, IndVal is a particularly effective tool for ecological bioindication. The Ind Val method showed how season can influence the occurrence of parasite species in the wild boar, and also identified parasites as bioindicators relative to host age. The randomization test identified five parasite species having a significant indicator value for the season (the ticks, Hyalomma aegyptium and Rhipicephalus sanguineus, the louse, Haematopinus suis and the nematodes Globocephalus urosubulatus and Ascaris suum and two indicator species of an age class (the nematodes G. urosubulatus and Metastrongylus sp.). Data on species composition and infection levels would help improve the monitoring and management of parasitism in Suidae populations.
Complete differentiation of CD8+ T cells activated locally within the transplanted liver
Authors: Klein Ingo , Crispe Ian Nicholas
Published: February 2006

The transplanted liver elicits systemic tolerance, and the underlying mechanism may also account for the persistence of liver infections, such as malaria and viral hepatitis. These phenomena have led to the hypothesis that antigen presentation within the liver is abortive, leading to T cell tolerance or apoptosis. Here we test this hypothesis in an optimized orthotopic liver transplantation model. In direct contradiction to this model, the liver itself induces full CD8+ T cell activation and differentiation. The effects of microchimerism were neutralized by bone marrow transplantation in the liver donor, and the lack of liver-derived antigen-presenting cells was documented by eight-color flow cytometry and by sensitive functional assays. We conclude that local antigen presentation cannot explain liver tolerance. On the contrary, the liver may be an excellent priming site for naive CD8+ T cells.
Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons
Authors: Pilling Aaron D. , Horiuchi Dai , Lively Curtis M. , Saxton William M.
Published: February 2006

To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150Gluedsuggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings (“organelle jams” or “clogs”) caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration.
Splicing Speckles Are Not Reservoirs of RNA Polymerase II, but Contain an Inactive Form, Phosphorylated on Serine2Residues of the C-Terminal Domain
Authors: Xie Sheila Q. , Martin Sonya , Guillot Pascale V. , Bentley David L. , Pombo Ana
Published: February 2006

“Splicing speckles” are major nuclear domains rich in components of the splicing machinery and polyA+RNA. Although speckles contain little detectable transcriptional activity, they are found preferentially associated with specific mRNA-coding genes and gene-rich R bands, and they accumulate some unspliced pre-mRNAs. RNA polymerase II transcribes mRNAs and is required for splicing, with some reports suggesting that the inactive complexes are stored in splicing speckles. Using ultrathin cryosections to improve optical resolution and preserve nuclear structure, we find that all forms of polymerase II are present, but not enriched, within speckles. Inhibition of polymerase activity shows that speckles do not act as major storage sites for inactive polymerase II complexes but that they contain a stable pool of polymerase II phosphorylated on serine2residues of the C-terminal domain, which is transcriptionally inactive and may have roles in spliceosome assembly or posttranscriptional splicing of pre-mRNAs. Paraspeckle domains lie adjacent to speckles, but little is known about their protein content or putative roles in the expression of the speckle-associated genes. We find that paraspeckles are transcriptionally inactive but contain polymerase II, which remains stably associated upon transcriptional inhibition, when paraspeckles reorganize around nucleoli in the form of caps.
H-Ras, R-Ras, and TC21 Differentially Regulate Ureteric Bud Cell Branching Morphogenesis
Authors: Pozzi Ambra , Coffa Sergio , Bulus Nada , Zhu Wenqin , Chen Dong , Chen Xiwu , Mernaugh Glenda , Su Yan , Cai Songmin , Singh Amar , Brissova Marcela , Zent Roy
Published: February 2006

The collecting system of the kidney, derived from the ureteric bud (UB), undergoes repetitive bifid branching events during early development followed by a phase of tubular growth and elongation. Although members of the Ras GTPase family control cell growth, differentiation, proliferation, and migration, their role in development of the collecting system of the kidney is unexplored. In this study, we demonstrate that members of the R-Ras family of proteins, R-Ras and TC21, are expressed in the murine collecting system at E13.5, whereas H-Ras is only detected at day E17.5. Using murine UB cells expressing activated H-Ras, R-Ras, and TC21, we demonstrate that R-Ras–expressing cells show increased branching morphogenesis and cell growth, TC21-expressing cells branch excessively but lose their ability to migrate, whereas H-Ras–expressing cells migrated the most and formed long unbranched tubules. These differences in branching morphogenesis are mediated by differential regulation/activation of the Rho family of GTPases and mitogen-activated protein kinases. Because most branching of the UB occurs early in development, it is conceivable that R-Ras and TC-21 play a role in facilitating branching and growth in early UB development, whereas H-Ras might favor cell migration and elongation of tubules, events that occur later in development.
Yeast Nuclear Envelope Subdomains with Distinct Abilities to Resist Membrane Expansion
Authors: Campbell Joseph L. , Lorenz Alexander , Witkin Keren L. , Hays Thomas , Loidl Josef , Cohen-Fix Orna
Published: February 2006

Little is known about what dictates the round shape of the yeast Saccharomyces cerevisiae nucleus. In spo7Δ mutants, the nucleus is misshapen, exhibiting a single protrusion. The Spo7 protein is part of a phosphatase complex that represses phospholipid biosynthesis. Here, we report that the nuclear protrusion of spo7Δ mutants colocalizes with the nucleolus, whereas the nuclear compartment containing the bulk of the DNA is unaffected. Using strains in which the nucleolus is not intimately associated with the nuclear envelope, we show that the single nuclear protrusion of spo7Δ mutants is not a result of nucleolar expansion, but rather a property of the nuclear membrane. We found that in spo7Δ mutants the peripheral endoplasmic reticulum (ER) membrane was also expanded. Because the nuclear membrane and the ER are contiguous, this finding indicates that in spo7Δ mutants all ER membranes, with the exception of the membrane surrounding the bulk of the DNA, undergo expansion. Our results suggest that the nuclear envelope has distinct domains that differ in their ability to resist membrane expansion in response to increased phospholipid biosynthesis. We further propose that in budding yeast there is a mechanism, or structure, that restricts nuclear membrane expansion around the bulk of the DNA.
Regulated Phosphorylation of Budding Yeast's Essential Myosin V Heavy Chain, Myo2p
Authors: Legesse-Miller Aster , Zhang Sheng , Santiago-Tirado Felipe H. , Van Pelt Colleen K. , Bretscher Anthony
Published: February 2006

The tail of the yeast myosin V encoded by Myo2p is known to bind several receptors for cargo delivery along polarized actin cables. However, it is not known how Myo2p activity is regulated or how it selects between cargos. Here we show that Myo2p is reversibly phosphorylated in vivo. A short peptide at the N-terminal end of the cargo-binding domain contains three residues contributing to single or doubly phosphorylated species. We confirm that the tail consists of two proteolytically resistant subdomains and identify a functionally important region N-terminal to sudomain 1 that includes the phosphorylation sites. Mutagenesis of the phosphorylation sites to alanine abolished a mobility shift diagnostic of phosphorylation, whereas mutagenesis to glutamic acid produced the shift and the formation of an additional phosphorylated species. These substitutions did not affect overall cell growth. However, one of the sites is predicted to be a substrate of cAMP-dependent protein kinase (PKA), and yeast expressing Myo2p with alanine substitutions is resistant to otherwise lethal overexpression of PKA, whereas the glutamic acid mutant is supersensitive to overexpression of PKA. These results suggest that in yeast, Myo2p is subject to phosphoregulation involving a PKA-related signaling pathway.
Rad22Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease
Authors: Coulon Stéphane , Noguchi Eishi , Noguchi Chiaki , Du Li-Lin , Nakamura Toru M. , Russell Paul
Published: February 2006

Slx1 and Slx4 are subunits of a structure-specific DNA endonuclease that is found in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and other eukaryotic species. It is thought to initiate recombination events or process recombination structures that occur during the replication of the tandem repeats of the ribosomal DNA (rDNA) locus. Here, we present evidence that fission yeast Slx1-Slx4 initiates homologous recombination events in the rDNA repeats that are processed by a mechanism that requires Rad22 (Rad52 homologue) but not Rhp51 (Rad51 homologue). Slx1 is required to generate ∼50% of the spontaneous Rad22 DNA repair foci that occur in cycling cells. Most of these foci colocalize with the nucleolus, which contains the rDNA repeats. The increased fork pausing at the replication fork barriers in the rDNA repeats in a strain that lacks Rqh1 DNA helicase is further increased by expression of a dominant negative form of Slx1. These data suggest that Slx1-Slx4 cleaves paused replication forks in the rDNA, leading to Rad22-dependent homologous recombination that is used to maintain rDNA copy number.
CLIP-170 Homologue and NUDE Play Overlapping Roles in NUDF Localization inAspergillus nidulans
Authors: Efimov Vladimir P. , Zhang Jun , Xiang Xin
Published: February 2006

Proteins in the cytoplasmic dynein pathway accumulate at the microtubule plus end, giving the appearance of comets when observed in live cells. The targeting mechanism for NUDF (LIS1/Pac1) of Aspergillus nidulans, a key component of the dynein pathway, has not been clear. Previous studies have demonstrated physical interactions of NUDF/LIS1/Pac1 with both NUDE/NUDEL/Ndl1 and CLIP-170/Bik1. Here, we have identified the A. nidulans CLIP-170 homologue, CLIPA. The clipA deletion did not cause an obvious nuclear distribution phenotype but affected cytoplasmic microtubules in an unexpected manner. Although more microtubules failed to undergo long-range growth toward the hyphal tip at 32°C, those that reached the hyphal tip were less likely to undergo catastrophe. Thus, in addition to acting as a growth-promoting factor, CLIPA also promotes microtubule dynamics. In the absence of CLIPA, green fluorescent protein-labeled cytoplasmic dynein heavy chain, p150Glueddynactin, and NUDF were all seen as plus-end comets at 32°C. However, under the same conditions, deletion of both clipA and nudE almost completely abolished NUDF comets, although nudE deletion itself did not cause a dramatic change in NUDF localization. Based on these results, we suggest that CLIPA and NUDE both recruit NUDF to the microtubule plus end. The plus-end localization of CLIPA itself seems to be regulated by different mechanisms under different physiological conditions. Although the KipA kinesin (Kip2/Tea2 homologue) did not affect plus-end localization of CLIPA at 32°C, it was required for enhancing plus-end accumulation of CLIPA at an elevated temperature (42°C).
The Labor Market Effects of Sex and Race Discrimination Laws
Authors: Neumark David , Stock Wendy A.
Published: February 2006

We study the effects of state sex and race discrimination laws that were passed prior to federal antidiscrimination legislation. State sex discrimination laws targeted discrimination in pay only. Because an equal pay constraint raises the relative price of female labor, we would expect the relative employment of females to decline. We find robust evidence that state equal pay laws for women reduced relative employment of both black women and white women. We also find some evidence of positive effects of race discrimination laws on earnings of blacks relative to whites, although no evidence of employment effects. (JEL J15, J16, J18, J23)
Analysis of allelic differential expression in human white blood cells
Authors: Pant P.V. Krishna , Tao Heng , Beilharz Erica J. , Ballinger Dennis G. , Cox David R. , Frazer Kelly A.
Published: February 2006

Allelic variation of gene expression is common in humans, and is of interest because of its potential contribution to variation in heritable traits. To identify human genes with allelic expression differences, we genotype DNA and examine mRNA isolated from the white blood cells of 12 unrelated individuals using oligonucleotide arrays containing 8406 exonic SNPs. Of the exonic SNPs, 1983, located in 1389 genes, are both expressed in the white blood cells and heterozygous in at least one of the 12 individuals, and thus can be examined for differential allelic expression. Of the 1389 genes, 731 (53%) show allele expression differences in at least one individual. To gain insight into the regulatory mechanisms governing allelic expression differences, we analyze a set of 60 genes containing exonic SNPs that are heterozygous in three or more samples, and for which all heterozygotes display differential expression. We find three patterns of allelic expression, suggesting different underlying regulatory mechanisms. Exonic SNPs in three of the 60 genes are monoallelically expressed in the human white blood cells, and when examined in families show expression of only the maternal copy, consistent with regulation by imprinting. Approximately one-third of the genes have the same allele expressed more highly in all heterozygotes, suggesting that their regulation is predominantly influenced by cis-elements in strong linkage disequilibrium with the assayed exonic SNP. The remaining two-thirds of the genes have different alleles expressed more highly in different heterozygotes, suggesting that their expression differences are influenced by factors not in strong linkage disequilibrium with the assayed exonic SNP.
Diglossia and register variation in Singapore English
Authors: Zhiming Bao , Huaqing Hong
Published: February 2006

Abstract: Colloquial Singapore English is an outer‐circle variety that exhibits contact‐induced linguistic change. It has been characterized as the L variant in diglossic opposition to standard English. In this paper, we address two related issues: (1) the extent to which the Singapore English diglossia is supported by corpus data, and (2) the extent to which the diglossia is reducible to register variation. We investigate the usage pattern of two linguistic variables which have acquired novel grammatical meanings, and show that our data support the Singapore English diglossia, but the variation is greater than what is normal in register variation. The diglossia of which one variant is an outer‐circle variety does not reduce easily to register variation.
Antitumor activity of sequence‐specific alkylating agents: Pyrolle‐imidazole CBI conjugates with indole linker
Authors: Shinohara Ken‐ichi , Bando Toshikazu , Sasaki Shunta , Sakakibara Yogo , Minoshima Masafumi , Sugiyama Hiroshi
Published: February 2006

DNA‐targeting agents, including cisplatin, bleomycin and mitomycin C, are used routinely in cancer treatments. However, these drugs are extremely toxic, attacking normal cells and causing severe side effects. One important question to consider in designing anticancer agents is whether the introduction of sequence selectivity to DNA‐targeting agents can improve their efficacy as anticancer agents. In the present study, the growth inhibition activities of an indole‐seco 1,2,9,9a‐tetrahydrocyclopropa[1,2‐c]benz[1,2‐e]indol‐4‐one (CBI) (1) and five conjugates with hairpin pyrrole‐imidazole polyamides (2–6), which have different sequence specificities for DNA alkylation, were compared using 10 different cell lines. The average values of – log GI50 (50% growth inhibition concentration) for compounds 1–6 against the 10 cell lines were 8.33, 8.56, 8.29, 8.04, 8.23 and 8.83, showing that all of these compounds strongly inhibit cell growth. Interestingly, each alkylating agent caused significantly different growth inhibition patterns with each cell line. In particular, the correlation coefficients between the – log GI50 of compound 1 and its conjugates 2–6 showed extremely low values (R < 0). These results suggest that differences in the sequence specificity of DNA alkylation lead to marked differences in biological activity. Comparison of the correlation coefficients between compounds 6 and 7, with the same sequence specificity as 6, and MS‐247, with sequence specificity different from 6, when used against a panel of 37 human cancer cell lines further confirmed the above hypothesis. (Cancer Sci 2006; 97: 219–225)
Depression and survival in patients with non‐small cell lung cancer after curative resection: a preliminary study
Authors: Nakaya Naoki , Saito‐Nakaya Kumi , Akizuki Nobuya , Yoshikawa Eisho , Kobayakawa Makoto , Fujimori Maiko , Nagai Kanji , Nishiwaki Yutaka , Fukudo Shin , Tsubono Yoshitaka , Uchitomi Yosuke
Published: February 2006

Psychological depression is thought to be a predictor of poor survival among cancer patients. The objective of the present study was to investigate the association between depression and survival in surgically treated Japanese patients with non‐small cell lung cancer (NSCLC). From June 1996 through April 1999, a total of 229 patients with postoperative lung cancer were enrolled. Three months after the patients’ surgery, the Structured Clinical Interview for DSM‐III‐R (SCID) and the Profile of Mood States (POMS) were used to assess the patient for depression, based on the interviewers’ rating and a self‐report, respectively. The follow‐up period consisted of a total of 14 342 person‐months (median = 69 months). As of January 2004, 55 deaths had occurred within the follow‐up period. A Cox regression was used to estimate the hazard ratio (HR) of mortality adjusting for age, sex, smoking status, occasion of diagnosis, pathological stage and preoperative percentage forced expiratory volume in 1 s. The depression‐dejection subscale on the POMS was divided into three score levels. The multivariate HR of survival for individuals with depression, as diagnosed by the SCID, was 2.2 (95% confidence interval 0.8–6.0) (P‐value = 0.14), compared with individuals without depression. The multivariate HR of survival for subjects in the highest level of the POMS Depression–Dejection subscale was 1.4 (0.7–2.6), compared with in the lowest level (trend P‐value = 0.0502). This prospective cohort study in Japan does not support the hypothesis that depression is associated with survival among NSCLC patients after curative resection, but further analysis involving a long‐term follow‐up period is needed. (Cancer Sci 2006; 97: 199–205)
A survey of oesophageal cancer: pathology, stage and clinical presentation
Authors: SCHLANSKY B. , DIMARINO A. J. , LOREN D. , INFANTOLINO A. , KOWALSKI T. , COHEN S.
Published: February 2006

Background  Oesophageal adenocarcinoma is the sixth leading cause of cancer‐related mortality worldwide. Previously, oesophageal cancer was mainly squamous cell, presenting late with dysphagia and weight loss.

Aims  To examine the distribution of oesophageal cancer histopathology at a large, urban hospital; to determine the tumour stage and symptoms at presentation; and to evaluate the impact of endoscopic surveillance in Barrett's oesophagus.

Methods  From 1999 to 2004, all patients diagnosed with oesophageal cancer were evaluated retrospectively for demographics and tumour stage at presentation using endoscopic ultrasonography and computerized tomography.

Results  A total of 131 patients were included. 81% of tumours were adenocarcinomas; most localized to the distal oesophagus (97%). Patients presented with dysphagia (56%), pain (30%) and/or weight loss (16%). Irrespective of histology, locally advanced lesions accounted for most cases. Thirteen patients had lesions detected in Barrett's surveillance; these were early or intermediate stage in nine patients, but late stage in four patients.

Conclusions  Adenocarcinoma has become the dominant histologic subtype, comprising 81% of proven malignancies. Despite a change in histopathology, most cancers are diagnosed at an advanced stage, presenting with dysphagia, pain and/or weight loss. Endoscopic surveillance of Barrett's oesophagus allows earlier diagnosis of cancer in most, but not all, patients.
Despite high satisfaction, majority of gastro‐oesophageal reflux disease patients continue to use proton pump inhibitors after antireflux surgery
Authors: MADAN A. , MINOCHA A.
Published: February 2006

Background  While antireflux surgery is effective in controlling symptoms of gastro‐oesophageal reflux, its role in eliminating the use of antireflux medicines after surgery and as such its long‐term cost‐effectiveness remains controversial.

Aim  To assess the patient satisfaction and the continued medication use following laparoscopic Nissen fundoplication at a tertiary level community hospital.

Methods  Adult patients who underwent laparoscopic Nissen fundoplication at our institution over a period of over 3 years were asked to complete a questionnaire recording their demographic information, date and reason for the surgery, preprocedure and postprocedure symptoms, smoking and alcohol use, and medication use preoperatively and post‐operatively. Patients were also asked about their satisfaction with surgery.

Results  One hundred patients participated in the study. Overall, 90% patients experienced satisfaction with their surgery. Eighty percentage patients were willing to undergo surgery again, if needed. Over two‐thirds (67%) patients had decrease in the severity of their symptoms. None of the patients had worsening of symptoms post‐operatively. However, 80% patients were still taking antireflux medications including proton pump inhibitors (53%).

Conclusions  Most patients continue to use antireflux medications including after laparoscopic Nissen fundoplication despite high satisfaction with surgery.
The effect of over‐the‐counter ranitidine 75 mg on night‐time heartburn in patients with erosive oesophagitis on daily proton pump inhibitor maintenance therapy
Authors: VAKIL N. , GUDA N. , PARTINGTON S.
Published: February 2006

Background  H2‐receptor antagonists are widely used with proton pump inhibitors.

Aim  To determine if H2‐receptor antagonists used in conjunction with proton pump inhibitors were effective for nocturnal heartburn in patients taking proton pump inhibitors.

Methods  We evaluated 386 patients with erosive oesophagitis documented at endoscopy who were receiving single daily maintenance proton pump inhibitor therapy to determine if they had symptoms of nocturnal heartburn. Patients with two or more episodes of night‐time a week were invited to participate in the study. Patients were randomly assigned to a single dose of an over‐the‐counter preparation of ranitidine 75 mg at bedtime or matching placebo for 14 days.

Results  The prevalence of nocturnal symptoms was 10.6%. Mean symptom scores on the first day of the trial (baseline) were similar between the treatment group (1.1 ± 0.9) and the placebo group (1.1 ± 1.1). On day 3, symptom scores were significantly lower in the ranitidine group (0.71 ± 0.69) compared with the control group (1.4 ± 1.2; P = 0.045). On day 14, mean symptom scores were similar in the ranitidine group (0.82 ± 0.95) and the control group (1 ± 0.84).

Conclusions  Nocturnal heartburn is uncommon on proton pump inhibitor therapy; the addition of ranitidine at bedtime resulted in a decrease in symptom scores on day 3 but there were no differences on day 14.
Haemodynamic instability during thyroid surgery: a baroreflex‐mediated neurogenic phenomenon?
Authors: Nouraei S. A. R. , Davies M. R. , Obholzer R. , Sandhu G. S. , Porter F.
Published: February 2006

We present a case of marked intra‐operative blood pressure instability in a euthyroid, fit 33‐year‐old female undergoing elective hemithyroidectomy. This led to significant haemodynamic compromise, cardiac failure and end‐organ damage. There was no evidence of a vasoactive endocrine cause, and the nature and timing of the event strongly pointed towards baroreflex‐mediated neurogenic sympathetic dysfunction. This can occur during carotid surgery and neck dissection. Although haemodynamic fluctuations may happen during thyroid surgery, their severity in this case was unusual. We believe this could have been a rebound phenomenon in response to acute decompression of the carotid artery which had been compressed by an enlarging cyst. We suggest that in similar cases blockade of the carotid sinus could attenuate such responses.
Impact of introducing a sedation management guideline in intensive care
Authors: Adam C. , Rosser D. , Manji M.
Published: February 2006

To ensure that sedative agents in the intensive care unit are used for maximum benefit, a guideline that promotes the accurate and continuous assessment of patients' needs is indicated. This observational 24‐month prospective study investigated the effect of introducing a sedation management guideline into a 10‐bedded multidisciplinary intensive care unit on length of stay, severity of illness, mortality and the number of bed days provided. Costs for all sedative drugs were calculated as cost per bed day. Intensive care unit mortality remained constant before and after guideline introduction. The length of stay of non‐cardiac surgery patients was mean (SD) 4.6 (4.4) and 5.1 (4.3) days, respectively (p = 0.2). Monthly sedative cost before guideline introduction was £6285 compared to £3629 afterwards (p≤0.0001), representing a real saving of £63 759 in sedative costs over the 2 years following introduction of the guideline.

Guideline‐directed management for sedation significantly reduces the cost of sedative drugs per bed day without any negative effect on length of ICU stay and outcome.
A study of codispensing with sodium alendronate in Australia
Authors: Boyd Ian W. , McEwen John , Calcino Lisa J.
Published: February 2006

Aim

To estimate the percentage of patients dispensed alendronate who were also dispensed another drug for treatment of an upper gastrointestinal disorder (‘GI’ drug).

Methods

The Australian Health Insurance Commission (HIC) Pharmaceutical Benefits Scheme (PBS) database was searched to identify a cohort of patients for whom alendronate or calcitriol had been dispensed and had also been dispensed a GI drug.

Results

The number of patients dispensed a GI drug were 6.7% for alendronate and 7.5% for calcitriol with H2‐receptor antagonists accounting for the majority of usage. This difference of − 0.8% (95% confidence interval −1.6, 0.1) is not significant.

Conclusion

There was no excess use of GI drugs in patients taking alendronate compared with those taking calcitriol and the Australian HIC PBS database is useful for identifying large numbers of patients who have been dispensed combinations of drugs.
The c.−1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients
Authors: Montes Ramón , Ruiz de Gaona Estefanía , Martínez‐González Miguel Ángel , Alberca Ignacio , Hermida José
Published: February 2006

Much of the variability in the sensitivity to warfarin in anticoagulated patients is associated with the c.−1639G > A polymorphism of the vitaminK‐epoxide reductase (VKORC1) gene. However, its association with the acenocoumarol dose in patients under anticoagulant therapy has not been studied. The c.−1639G > A genotype of VKORC1 was determined in 113 patients on stable anticoagulation requiring low (n = 42), medium (n = 42) or high (n = 21) acenocoumarol doses. To evaluate the association between acenocoumarol requirements and the c.−1639G > A variant, multivariate logistic regression models were fitted, adjusting for age, gender, and the c.430C > T and c.1075A > C variants of cytochrome P450 2C9 (CYP2C9). A total of 90·5% of the patients in the low acenocoumarol dose group carried the A allele of VKORC1:c.−1639G > A. The A allele independently increased the odds of requiring a low acenocoumarol dose [odds ratio (OR) 9·4; 95% confidence interval (CI) 1·9–46·4; P = 0·006], especially when the homozygous form was present (OR 44·2; 95% CI 5·5–354·6; P < 0·001). The A allele was less frequent in the high dose group showing an inverse association with the requirement for high doses (OR 0·04; 95% CI 0·01–0·22; P < 0·001). The A allele of the c.−1639G > A polymorphism of VKORC1 is therefore associated with a low‐dose requirement for acenocoumarol in patients receiving anticoagulant therapy.
Apolipoprotein E genotype is related to plasma levels of C‐reactive protein and lipids and to longevity in nonagenarians
Authors: Rontu Riikka , Ojala Petri , Hervonen Antti , Goebeler Sirkka , Karhunen Pekka J. , Nikkilä Matti , Kunnas Tarja , Jylhä Marja , Eklund Carita , Hurme Mikko , Lehtimäki Terho
Published: February 2006

Objective  Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C‐reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians.

Design and patients  This cross‐sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40‐year‐olds, and 70‐year‐olds).

Results  In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of ɛ2/2, ɛ2/3, ɛ3/3, ɛ2/4, ɛ3/4 and ɛ4/4. Total (P= 0.009) and low‐density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the ɛ4 allele carriers. In newborns, the ɛ4 frequency was 0.192, in 40‐year‐olds 0.181, in 70‐year‐olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the ɛ4 allele frequency in the elderly was more clearly seen in women than in men.

Conclusions  APOEɛ4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some ɛ4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.
Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial
Authors: Eustatia‐Rutten C. F. A. , Corssmit E. P. M. , Pereira A. M. , Frölich M. , Bax J. J. , Romijn J. A. , Smit J. W. A.
Published: February 2006

Objective  The impact of prolonged subclinical hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH‐suppressive thyroxine therapy as a model for subclinical hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life.

Design  We performed a prospective, single‐blinded, placebo‐controlled, randomized trial of 6 months’ duration with two parallel groups.

Patients and methods  Twenty‐four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH‐suppressive therapy with L‐thyroxine completed the study. L‐thyroxine dose was replaced by study medication containing L‐thyroxine or L‐thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low‐TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires.

Results  At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low‐TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low‐TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index‐20, P = 0·003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form‐36; P = 0·050) was observed. No improvement in the SDQ score was observed.

Conclusion  In summary, quality of life in patients with DTC and long‐term subclinical hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.