bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Ovarian Actinomycosis
Authors: Iwasaki Masahiro , Nishikawa Akira , Akutagawa Noriyuki , Fujimoto Takashi , Teramoto Mizue , Kudo Ryuichi
Published: September 2005

Background: Pelvic actinomycosis is uncommon and often presents as a complication of an intrauterine device
(IUD). A diagnosis of actinomycosis can be made from the finding of sulfur granules within inflammatory exudate
on histologic examination after surgery. However, it may be possible to diagnose actinomycosis before surgery
by finding Actinomyces‐like organisms on Papanicolaou smears.

Case: A 41‐year‐old woman had been diagnosed as having a pelvic abscess, and bilateral salpingo‐oophorectomy
was performed. She had been an IUD user for 6 years. Actinomyces‐like organisms were detected in her previous
Papanicolaou cervical smears. If the patient had been treated when the Actinomyces‐like organisms were detected
by Papanicolaou smears, the serious ovarian actinomycosis might have been avoided.

Conclusion: We suggest that routine cervical examinations are important for women who are IUD users.
The Efficacy of Vaginal Clindamycin for the Treatment ofAbnormal Genital Tract Flora in Pregnancy
Authors: Lamont Ronald F. , Jones Brian M. , Mandal Debashis , Hay Philip E. , Sheehan Marie
Published: September 2005

Objective: To assess the efficacy of 2% clindamycin vaginal cream (CVC) to treat bacterial vaginosis (BV) in
pregnancy.

Methods: A prospective, randomized, double‐blind, placebo‐controlled, tricenter study. Four hundred and four
women with BV on Gram stain at their first antenatal clinic visit were randomized to receive a 3‐day course of
2% CVC or placebo. The outcome was assessed using an intention to treat analysis at 3 weeks and 6 weeks
post‐treatment according to three different diagnostic methods based on five criteria (Gram stain and all four
elements of clinical composite criteria: vaginal discharge, abnormal vaginal pH, clue cells, amine odor), three
criteria (vaginal pH, clue cells, amine odor) or two criteria (clue cells and amine odor) to reflect stringency of
diagnosis, historical precedence and government agency recommendations respectively.

Results: Using five diagnostic criteria, 18% of CVC patients were cured and 70.8% either cured and/or improved
compared to 1.6% and 12% of placebo patients respectively (p < 0.0001). Using three diagnostic criteria, 44.8%
of CVC patients were cured and 77.3% were either cured and/or improved compared to 9.3% and 28.8% of
placebo patients respectively (p < 0.0001). Using two diagnostic criteria, 75.0% of CVC patients were cured
compared to 18.0% of placebo patients (p < 0.0001). Recurrence rates in those CVC patients successfully treated
were approximately 6% at 6 weeks post baseline and 10% at 28 to 34 weeks gestation.

Conclusions: A 3‐day course of CVC appears to be well tolerated by the mother and statistically significantly
more efficacious than placebo in the treatment of BV during the second trimester of pregnancy.
Angiopoietin Affects Neutrophil Migration
Authors: STURN DANIEL H. , FEISTRITZER CLEMENS , MOSHEIMER BIRGIT A. , DJANANI ANGELA , BIJUKLIC KLAUDIJA , PATSCH JOSEF R. , WIEDERMANN CHRISTIAN J.
Published: September 2005

Objective: After an ischemic event vascular growth factors are involved in regulating leukocyte infiltration in inflammatory processes. This study focused on effects of 2 other angiogenic growth factors, angiopoietin‐1 and angiopoietin‐2, on human neutrophils and on the involvement of the angiopoietin receptor Tie‐2.

Methods: Neutrophils were from venous blood of healthy donors and cell migration was studied by micropore filter assays. Receptor expression was investigated by reverse transcriptase–polymerase chain reaction (PCR) for mRNA and fluorescence‐activated cell‐sorter scanner (FACS) analysis. Signaling mechanisms required for angiopoietin‐dependent effects were tested functionally by using signaling enzyme blockers.

Results: The angiopoietins were chemotactic for neutrophils. They showed antagonistic effects on each other and both inhibited VEGF‐directed migration of neutrophils. The effects of both angiopoietins were Tie‐2 dependent. Tie‐2 receptor immunoreactivity was confirmed on neutrophils by FACS. De novo synthesis is suggested by Tie‐2 receptor mRNA expression as demonstrated by reverse transcriptase PCR.

Conclusions: Data suggest that a Tie‐2 receptor is expressed by human neutrophils whose active site ligation with either angiopoietin‐1 or angiopoietin‐2 exerts migratory effects on the one hand and arrests VEGF‐mediated chemotaxis on the other. These effects suggest a role of angiopoietins in modulating neutrophilic inflammation.
TaqMan Applications in Genetic and Molecular Toxicology
Authors: Watson David E. , Li Baohui
Published: September 2005

Quantification of nucleic acids has become a common procedure in many toxicology laboratories. Among the technologies that accomplish this is the fluorogenic 5 ′-nuclease assay, commonly known as TaqMan. Three TaqMan applications for genetic and molecular toxicology are presented in this article: quantification of gene expression, detection of genetic polymorphisms, and quantification of chromosomal DNA deletions. Of these, quantification of gene expression is the most widely used, and established TaqMan as a benchmark technology for nucleic acid quantification. Two additional applications, polymorphism detection and quantification of DNA deletions, demonstrate the flexibility and quantitative strengths that make TaqMan so powerful, including high precision, excellent sensitivity, and broad linear dynamic range. These and similar applications improve our ability to investigate genetic and molecular dimensions of toxicological phenomena, and have promoted the widespread use of TaqMan in toxicology departments in the pharmaceutical industry. In addition to presenting these applications, the authors discuss some of the challenges of integrating TaqMan and other new technologies into the drug development process.
How does bupropion work as a smoking cessation aid?
Authors: Warner Charlotte , Shoaib Mohammed
Published: September 2005

Bupropion exhibits reasonable efficacy as a smoking cessation aid, yet its precise mechanisms of action remain unclear. This review evaluates the mechanism of action of bupropion by considering the clinical evidence in combination with results from pre‐clinical experiments in vivo and in vitro. Bupropion is a weak inhibitor of dopamine and noradrenaline reuptake, and has also been shown to antagonise nicotinic acetylcholine receptor function. It is extensively metabolized in humans, its major metabolites reaching levels higher than those of bupropion itself. These metabolites share many of the pharmacological properties of bupropion, so they may play an important role in its clinical activity, yet they have been neglected in investigations into bupropion action. This review led to several conclusions: (1) the principal mode of bupropion action is upon the withdrawal symptoms following smoking cessation; (2) during withdrawal, bupropion may attenuate symptoms by mimicking nicotinic effects on dopamine and noradrenaline; (3) its ability to antagonize nicotinic receptors may prevent relapse by attenuating the reinforcing properties of nicotine, but probably cannot acutely reduce smoking; and (4) further exploration of bupropion metabolites and its role in withdrawal and relapse, within more appropriate animal models, could be crucial in the determination of the precise mechanisms by which bupropion exerts its activity in smoking cessation. Greater elucidation of the exact mechanisms of action of bupropion could lead to the development of new drugs even more beneficial in promoting smoking abstinence.
Tryptophan hydroxylase gene 1 polymorphisms are not associated with suicide attempts in alcohol‐dependent individuals
Authors: Koller G , Engel RR , Preuss UW , Karakesisoglou A , Zill P , Bondy B , Soyka M
Published: September 2005

A serotonergic dysfunction was suggested to be involved into the biological susceptibility of suicidal behaviour. Tryptophan hydroxylase (TPH), the rate‐limiting enzyme in serotonin biosynthesis, is a significant regulating factor in the serotonergic system. Recently the A‐6526G, and G‐5806T and A‐779C polymorphisms of the TPH 1 gene were identified and suggested to be associated with suicidal behaviour, but study results are conflicting. We examined a possible association of the A‐6526G, and G‐5806T and A‐779C polymorphisms with suicide attempts in a sample of 80 alcohol‐dependent individuals with a history of at least one suicide attempt. This group was analysed in comparison with 241 alcohol‐dependent subjects without such a history. No significant relationship between haplotype and genotype distribution and allele frequencies of these polymorphisms with suicide attempts were detected. Furthermore, no association with number of suicide attempts and TPH haplotypes were found. Our data do not support the hypothesis of A‐6526G, G‐5806T or A‐779C polymorphisms to be associated with suicide attempts in alcohol‐dependent individuals.
Effects of acute administration of methamphetamine on Narp mRNA in rat brain
Authors: Fukumoto Makoto , Iwata Masaaki , Shinbori Chiko , Hazama Gen‐i , Shirayama Yukihiko , Kawahara Ryuzou
Published: September 2005

Narp (neuronal activity‐regulated pentraxin) is a secreted immediate early gene product functioning as a cluster factor for the AMPA receptor subtype of glutamate receptors. This study was designed to examine the effects of acute administration of methamphetamine (MAP) on the Narp gene in rat brain using reverse transcription – polymerase chain reaction (RT‐PCR). Acute administration of MAP [4.6?mg/kg, intraperitoneally (i.p.)] increased Narp mRNA in the prefrontal cortex, whereas the same treatment with MAP decreased Narp mRNA in the hippocampus. Therefore, Narp gene could be involved in the MAP‐induced effects.
TRANSITION FROM SCHOOL TO WORK IN TRANSITION ECONOMIES
Authors: Kogan Irena , Unt Marge
Published: September 2005

This paper explores school-to-work transitions in three new EU Member states, Hungary, Slovenia and Estonia, focusing on the effect of the level of education and social background on the timing of the first significant employment and the match between educational qualifications and occupation among school leavers. So-called cohort effects are a focal point as well, since transition process and outcomes seem to be largely influenced by the dynamics of economic and social changes in the transition economies. To explore the early career developments of job entrants in the three transition countries during the 1990s, the study utilizes the European Union Labour Force Survey ad hoc module on school-to-work transitions, which has been launched in Hungary, Slovenia in 2000 and in Estonia in 2002. Event history methods are applied to explore transition to first significant employment, while the match of educational qualification and occupational attainment is modelled using multinomial logistic regression techniques.
Counsellors' experiences of working with suicidal clients: An exploratory study
Authors: Reeves Andrew , Mintz Rita
Published: September 2005

Counselling is increasingly available in a wide variety of contexts, including mental health and psychiatric services. As a consequence, counsellors increasingly work with clients who present with suicidal ideation, expressing either suicidal thought and/or intent in the counselling session. This paper describes an exploratory study that examined the experience of counsellors when working with suicidal clients. The paper considers counsellors' behavioural, cognitive and emotional responses to such suicidal expression, both on a personal and professional level. The research employed semi‐structured interviews. A constant comparative method was used in analysing the transcribed interview text. Results suggest that counsellors experience a range of responses when their clients express suicidal thought, including fear, anxiety, anger and professional impotence. The interviewees also expressed self‐doubts about their professional competence. In addition, they identified the threat of litigation for negligent practice and the lack of confidence in appropriate risk assessment approaches as significant causes for concern. The implications for further research, and practice, are discussed.
Paradoxes of qualitative research
Authors: Elliott MS , Williams DI
Published: September 2005

In qualitative research paradoxes abound in research design, sampling, generalisation, ethics and the behaviour of the researcher. The ultimate paradox is that qualitative inquiry is impossible — both conceptually and practically — yet it still goes on. It must do so if the professions of counselling and psychotherapy are to advance.
Research in person‐centred, experiential and humanistic counselling and psychotherapy: Meeting new challenges
Authors: McLeod John
Published: September 2005

As a result of the programme of research into client‐centred therapy led by Carl Rogers, the humanistic therapies could claim, in the 1950s, to possess a comprehensive evidence base. Over the following decades, however, there was a marked decline in the productivity and influence of research into person‐centred and humanistic therapies. The present paper celebrates the publication of three books that mark a resurgence in research into these approaches, and comments on emerging themes and trends.
Beyond resolution of presenting issues: Clients' experiences of an in‐house police counselling service
Authors: Millar Anne
Published: September 2005

The availability of counselling services for employees has expanded significantly in recent years. However, despite an increase in appreciation of the value of counselling within the police service, there has been little research into the effectiveness of counselling with police personnel. The present study assesses an in‐house counselling service provided by the welfare and counselling department of a Scottish police force. Thirteen former clients (including both police officers and civilian support staff) were interviewed about their views on four areas of the counselling provision: how they entered counselling, the issues they brought, their experiences during counselling, and their assessment of the impact of counselling on their lives. Interviews were analysed using a grounded theory approach, which identified four main categories: initial engagement, learning by participating, experiencing moments of deep self‐examination, and moving beyond resolution of presenting problems. All of those who were interviewed appreciated the provision of a counselling service within their employment, and the majority reported that they had not only been helped to resolve their presenting problems, but had also made important gains in self‐awareness and work effectiveness. Findings are discussed in terms of implications for service delivery and future research.
The therapeutic alliance: Adolescent perspectives
Authors: Everall Robin D. , Paulson Barbara L.
Published: September 2005

This paper presents a conceptualisation of the therapeutic alliance from the adolescent perspective and discusses implications for practitioners. The main aim of the study was to focus on the factors that participants identified as important in relationship formation and maintenance. Eighteen individuals were interviewed using a semi‐structured format. Three major themes were identified: therapeutic environment, uniqueness of the therapeutic relationship, and therapist characteristics. Participants identified both positive and negative aspects of the therapeutic relationship. A strong alliance was found to be necessary in that the perception of the therapist as accepting, supportive and trustworthy influenced the adolescent's evaluation of the appropriateness of therapeutic tasks and goals. Participants stressed the importance of the supportive nature of the relationship in their willingness to collaborate in therapeutic interventions.
Therapist perspectives on using silence in therapy: A qualitative study
Authors: Ladany Nicholas , Hill Clara E , Thompson Barbara J , O'Brien Karen M
Published: September 2005

Twelve experienced therapists were interviewed about their perceptions of why they used silence in therapy. Qualitative analyses revealed that these therapists typically perceived themselves as using silence to convey empathy, facilitate reflection, challenge the client to take responsibility, facilitate expression of feelings, or take time for themselves to think of what to say. Therapists generally indicated that a sound therapeutic alliance was a prerequisite for using silence, and they typically educated their clients about how they used silence in therapy. Therapists typically believed they did not use silence with clients who were psychotic, highly anxious, or angry. They typically thought they now used silence more flexibly, comfortably, and confidently than when they began doing therapy. Therapists typically believed they learned how to use silence from their own experience as a client and from supervision.
A Reactive Soil Moisture Sensor Network: Design and Field Evaluation
Authors: Cardell-Oliver Rachel , Kranz Mark , Smettem Keith , Mayer Kevin
Published: September 2005

Wireless sensor network technology has the potential to reveal finegrained, dynamic changes in monitored variables of an outdoor landscape. But there are significant problems to be overcome in order to realize this vision in working systems. This paper describes the design and implementation of a reactive, event driven network for environmental monitoring of soil moisture and evaluates its effectiveness. A novel feature of our solution is its reactivity to the environment: when rain falls and soil moisture is changing rapidly, measurements are collected frequently, whereas during dry periods, between rainfall, measurements are collected less often. Field trials demonstrating the reactivity, robustness, and longevity of the network are presented and evaluated, and future improvements proposed.
Power Aware Chain Routing Protocol for Data Gathering in Sensor Networks
Authors: Pham Minh-Long , Kim Daeyoung , Yoo Seong-Eun , Doh Yoonmee
Published: September 2005

To prolong the network lifetime, we propose an energy efficient chain-based routing scheme and a distributed algorithm for constructing the routing chain based on the minimum cost tree. The chain construction algorithm calculates the transmission cost based on optimal transmission power. Therefore, it does not require global knowledge of location information of notes and provides more accurate communication cost calculation among nodes under different practical deployment environments. The proposed power aware mechanism for leader node election in the chain ensures more uniform energy consumption among nodes. The simulation shows the new scheme provides more uniform energy consumption among nodes and better active network lifetime in different network settings as compared to previous chain-based protocols.
p53 isoforms can regulate p53 transcriptional activity
Authors: Bourdon Jean-Christophe , Fernandes Kenneth , Murray-Zmijewski Fiona , Liu Geng , Diot Alexandra , Xirodimas Dimitris P. , Saville Mark K. , Lane David P.
Published: August 2005

The recently discovered p53-related genes, p73 and p63, express multiple splice variants and N-terminally truncated forms initiated from an alternative promoter in intron 3. To date, no alternative promoter and multiple splice variants have been described for the p53 gene. In this study, we show that p53 has a gene structure similar to the p73 and p63 genes. The human p53 gene contains an alternative promoter and transcribes multiple splice variants. We show that p53 variants are expressed in normal human tissue in a tissue-dependent manner. We determine that the alternative promoter is conserved through evolution from Drosophila to man, suggesting that the p53 family gene structure plays an essential role in the multiple activities of the p53 family members. Consistent with this hypothesis, p53 variants are differentially expressed in human breast tumors compared with normal breast tissue. We establish that p53β can bind differentially to promoters and can enhance p53 target gene expression in a promoter-dependent manner, while Δ133p53 is dominant-negative toward full-length p53, inhibiting p53-mediated apoptosis. The differential expression of the p53 isoforms in human tumors may explain the difficulties in linking p53 status to the biological properties and drug sensitivity of human cancer.
A pathway for the biogenesis of trans-acting siRNAs in Arabidopsis
Authors: Yoshikawa Manabu , Peragine Angela , Park Mee Yeon , Poethig R. Scott
Published: August 2005

The Arabidopsis genes, TAS2 and TAS1a, produce structurally similar noncoding transcripts that are transformed into short (21-nucleotide [nt]) and long (24-nt) siRNAs by RNA silencing pathways. Some of these short siRNAs direct the cleavage of protein-coding transcripts, and thus function as trans-acting siRNAs (ta-siRNAs). Using genetic analysis, we defined the pathway by which ta-siRNAs and other short siRNAs are generated from these loci. This process is initiated by the miR173-directed cleavage of a primary poly(A) transcript. The 3′ fragment is then transformed into short siRNAs by the sequential activity of SGS3, RDR6, and DCL4: SGS3 stabilizes the fragment, RDR6 produces a complementary strand, and DCL4 cleaves the resulting double-stranded molecule into short siRNAs, starting at the end with the miR173 cleavage site and proceeding in 21-nt increments from this point. The 5′ cleavage fragment is also processed by this pathway, but less efficiently. The DCL3-dependent pathway that generates long siRNAs does not require miRNA-directed cleavage and plays a minor role in the silencing of these loci. Our results define the core components of a post-transcriptional gene silencing pathway in Arabidopsis and reveal some of the features that direct transcripts to this pathway.
Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor α1 can be ameliorated by T3 treatment
Authors: Venero César , Guadaño-Ferraz Ana , Herrero Ana Isabel , Nordström Kristina , Manzano Jimena , de Escobar Gabriella Moreale , Bernal Juan , Vennström Björn
Published: August 2005

The transcriptional properties of unliganded thyroid hormone receptors are thought to cause the misdevelopment during hypothyroidism of several functions essential for adult life. To specifically determine the role of unliganded thyroid hormone receptor α1 (TRα1) in neuronal tissues, we introduced a mutation into the mouse TRα1 gene that lowers affinity to thyroid hormone (TH) 10-fold. The resulting heterozygous mice exhibit several distinct neurological abnormalities: extreme anxiety, reduced recognition memory, and locomotor dysfunction. The anxiety and memory deficiencies were relieved by treatment with high levels of TH in adulthood, an effect that correlated with a normalization of GABAergic inhibitory interneurons in the hippocampal CA1 region. In contrast, a post-natal TH treatment was necessary and sufficient for ameliorating the adult locomotor dysfunction. Here, the hormone treatment normalized the otherwise delayed cerebellar development. The data thus identify two novel and distinct functions of an unliganded TRα1 during development and adulthood, respectively.
ARE LIFE HISTORY CHARACTERISTICS GOOD PREDICTORS OF GENETIC DIVERSITY AND STRUCTURE? A CASE STUDY OF THE INTERTIDAL ALGA FUCUS SPIRALIS (HETEROKONTOPHYTA; PHAEOPHYCEAE)1
Authors: Coleman Melinda A. , Brawley Susan H.
Published: August 2005

Characteristics of an organism's life history are often good predictors of genetic diversity and genetic structure. We tested hypotheses about genetic structure and diversity in an intertidal alga based on life history and life form. Fucus spiralis L. is a perennial monoecious alga that is abundant on the shores of Maine. Reproduction in fucoids is highly sensitive to water motion, resulting in fertilization success close to 100%. Given these life history characteristics, we predicted genetic structure among populations to be high and genetic diversity within populations to be low. We used five microsatellite loci to analyze genetic structure and diversity in F. spiralis from four sites on each of two coastal points, Maine, USA. Observed heterozygosities were relatively low (0.23 to 0.56), and FIS estimates were usually significantly large, ranging from 0.021 to 0.476. This suggests that selfing and/or inbreeding may occur. Contrary to predictions, genetic differentiation between the two coastal points was insignificant. Moreover, few sites were genetically different from one another. Pairwise tests revealed complex patterns among sites. Genetic differentiation was not correlated with distance (P>0.05). Life history characteristics are good predictors of genetic diversity but not of population genetic structure in F. spiralis. We suggest that long distance dispersal of F. spiralis via drifting algal rafts increases gene flow. In addition, low levels of genetic structure may arise due to episodic recruitment or recent recolonization events. We discuss the implications of our results in terms of using life history characteristics as predictors of genetic diversity and structure in algae.
MOLECULAR PHYLOGENY OF STAURASTRUM MEYEN EX RALFS AND RELATED GENERA (ZYGNEMATOPHYCEAE, STREPTOPHYTA) BASED ON CODING AND NONCODING RDNA SEQUENCE COMPARISONS1
Authors: Gontcharov Andrey A. , Melkonian Michael
Published: August 2005

Nuclear‐encoded small subunit rDNA, 1506 group I intron, and internal transcribed spacer sequences were obtained from 39 strains representing five core desmid genera, Staurastrum, Staurodesmus Teil., Cosmarium Corda ex Ralfs, Xanthidium Ehr. ex Ralfs, and Euastrum Ehr. ex Ralfs (Desmidiaceae, Zygnematophyceae), and used individually and concatenated to assess phylogenetic relationships between putatively allied members of the family. To identify positional homology between divergent noncoding sequences, secondary structure models were generated and their reliability assessed by screening the alignment for compensating base changes. The phylogeny based on coding and noncoding sequence comparisons confidently resolved a monophyletic core of the genus Staurastrum but also revealed the artificial nature of the traditional genus. Twenty distinct species representing a wide range of morphotypes of Staurastrum formed a strongly supported generic clade that was further split into three well‐resolved lineages. The phylogenetic relationships revealed within Staurastrum were in conflict with all previous formal or informal classifications of the genus. The genera Staurodesmus and Cosmarium were shown to be highly polyphyletic, and some morphologically similar taxa displayed high sequence divergence that exceeded generic boundaries. Apparently, the taxonomic significance of some morphological characters in Staurastrum and other desmid genera has been greatly overestimated.
OXYGEN MICROSENSOR STUDIES ON ZOOXANTHELLATE CLIONAID SPONGES FROM THE COSTA BRAVA, MEDITERRANEAN SEA1
Authors: Hanna Christine , Schönberg Lydia , De Beer Dirk , Lawton Angela
Published: August 2005

Photosynthetic properties of two symbiotic demosponges were compared using Clark‐type oxygen microsensors. The putatively distinct sponge species,Cliona viridis(Schmidt, 1862) andCliona nigricans(Schmidt, 1862) were discriminated by their mean megasclere lengths of 296 and 387 μm, respectively. Photosynthetic behavior was used to generate additional taxonomic information. Sponge–dinoflagellate symbioses were well adapted to low light due to the hosts' endolithic lifestyle. Both sponges reached light compensation and saturation at similar light levels with means close to 10 and 30 μmol photons·m−2·s−1, respectively. The gross photosynthetic activity was closely related to symbiont cell density in the sponge surface tissue. Mean symbiont densities, chlacontent, and gross photosynthesis were about six times higher inC. viridisthan inC. nigricans, with respective values of 3000 and 440 symbiont·mm−2, 1.3 and 0.2 μg chla·g−1, and 5.4 and 1.0 μmol O2·cm−3·s−1gross photosynthesis. Net photosynthesis and respiration could not be calculated accurately from the oxygen gradients, because significant gas exchange occurs through the pumping activity. Thus, assumptions of diffusional oxygen exchange via the surface do not hold for sponges. Combined data of this study indicate that the metabolic activity ofC. viridisdepends on photosynthetic activity of its symbionts, whereasC. nigricansappears to have a higher pumping intensity and is more actively filter feeding. The difference in photosynthetic activities is not caused by different light adaptations but provides new evidence against the conspecifity ofC. viridisandC. nigricans.
SYMBIODINIUM (PYRRHOPHYTA) GENOME SIZES (DNA CONTENT) ARE SMALLEST AMONG DINOFLAGELLATES1
Authors: LaJeunesse Todd C. , Lambert Georgina , Andersen Robert A. , Coffroth Mary Alice , Galbraith David W.
Published: August 2005

Using flow cytometric analysis of fluorescence, we measured the genome sizes of 18 cultured “free‐living” species and 29 Symbiodinium spp. isolates cultured from stony corals, gorgonians, anemones, jellyfish, and giant clams. Genome size directly correlated with cell size, as documented previously for most eukaryotic cell lines. Among the smallest of dinoflagellates, Symbiodinium spp. (6–15 μm) possessed the lowest DNA content that we measured (1.5–4.8 pg·cell−1). Bloom‐forming or potentially harmful species in the genera Alexandrium, Karenia, Pfiesteria, and Prorocentrum possessed genomes approximately 2 to 50 times larger in size. A phylogenetic analysis indicated that genome/cell size has apparently increased and decreased repeatedly during the evolution of dinoflagellates. In contrast, genome sizes were relatively consistent across distantly and closely related Symbiodinium spp. This may be the product of intracellular host habitats imposing strong selective pressures that have restricted symbiont size.
DISSECTION OF TWO DISTINCT DEFENSE‐RELATED RESPONSES TO AGAR OLIGOSACCHARIDES IN GRACILARIA CHILENSIS (RHODOPHYTA) AND GRACILARIA CONFERTA (RHODOPHYTA)1
Authors: Weinberger Florian , Leonardi Patricia , Miravalles Alicia , Correa Juan A. , Lion Ulrich , Kloareg Bernard , Potin Philippe
Published: August 2005

The two agar‐producing red algae, Gracilaria chilensis C. J. Bird, McLachlan & E. C. Oliveira and Gracilaria conferta (Schousboe ex Montagne) Montagne, responded with hydrogen peroxide (H2O2) release when agar oligosaccharides were added to the medium. In G. conferta, a transient release was observed, followed by a refractory state of 6 h. This response was sensitive to chemical inhibitors of NADPH oxidase, protein kinases, protein phosphatases, and calcium translocation in the cell, whereas it was insensitive to inhibitors of metalloenzymes. Transmission electron microscopic observations of the H2O2‐dependent formation of cerium peroxide from cerium chloride indicated oxygen activation at the plasma membrane of G. conferta. A putative system, consisting of a receptor specific to agar oligosaccharides and a plasma membrane‐located NADPH oxidase, appears to be responsible for the release of H2O2 in G. conferta. Subcellular examination of G. chilensis showed that the H2O2 release was located in the cell wall. It was sensitive to inhibitors of metalloenzymes and flavoenzymes, and no refractory state was observed. The release was correlated with accumulation of an aldehyde in the algal medium, suggesting that an agar oligosaccharide oxidase is present in the apoplast of G. chilensis. The presence of this enzyme could also be demonstrated by polyacrylamide electrophoresis under nondenaturating conditions and proven to be variable. Cultivation of G. chilensis at 16 to 17°C resulted in significantly stronger expression of agar oligosaccharide oxidase than cultivation at 12°C, which indicates that the enzyme is used under conditions that generally favor microbial agar macerating activity.
INHIBITION OF ASTAXANTHIN SYNTHESIS UNDER HIGH IRRADIANCE DOES NOT ABOLISH TRIACYLGLYCEROL ACCUMULATION IN THE GREEN ALGA HAEMATOCOCCUS PLUVIALIS (CHLOROPHYCEAE)1
Authors: Zhekisheva Mirash , Zarka Aliza , Khozin‐Goldberg Inna , Cohen Zvi , Boussiba Sammy
Published: August 2005

Under stress conditions, Haematococcus pluvialis Flotow accumulates fatty acid–esterified astaxanthin, in extraplastidial lipid globules. The enhanced accumulation of fatty acids, mainly in triacylglycerols (TAG), among which oleic acid predominates, is linearly correlated with that of astaxanthin. We used inhibitors of either carotenoid or lipid biosynthesis to assess the interrelationship between carotenogenesis and TAG accumulation under high light irradiance as the stress factor. The two carotenogenesis inhibitors used—norflurazon, an inhibitor of phytoene desaturase, and diphenylamine (DPA), an inhibitor of β‐carotene C‐4 oxygenase—suppressed the accumulation of astaxanthin in a concentration‐dependent manner. Concurrently, the accumulation of neutral lipids was significantly less affected. The lipid biosynthesis inhibitor sethoxydim, which inhibits acetyl‐CoA carboxylase, significantly decreased de novo fatty acid synthesis and, in concert, drastically inhibited astaxanthin formation. In the presence of various concentrations of the three inhibitors, the inhibition of astaxanthin was not accompanied by a proportional decrease in oleic acid, which was used as a marker for TAG fatty acids. When astaxanthin synthesis was completely inhibited, the volumetric content of oleic acid was about 60% of the control value when the two carotenogenesis inhibitors (0.05 μM norflurazon or 20 μM DPA) were used and 27% of the control when the lipid‐synthesis inhibitor (50 μM) was used. We suggest therefore that TAG accumulation under high irradiance is not tightly coupled with astaxanthin accumulation, although the correlation between these two processes was demonstrated earlier. Furthermore, we propose that the accumulation of a certain amount of TAG is a prerequisite for the initiation of fatty acid–esterified astaxanthin accumulation in lipid globules.
An exploration of decision‐making factors regarding advance directives in a long‐term care facility
Authors: White Carol
Published: August 2005

Purpose

To explore the experiences of residents who had signed an advance directive on admission to a long‐term care facility and apply the Advance Directive Decision‐Making Model to this process.

Data sources

Interactive interviews with 13 elders. Questions related to how each felt about their life and death, how each perceived the advance directive discussion, and what factors influenced their decisions were discussed.

Conclusions

The thematic analysis suggested that the decision regarding advance directives was multifaceted and complex. It required preparation, understanding, and time. Decision‐making ability was sometimes compromised by the other stressors associated with the move to a long‐term care facility.

Implications for practice

Nurse practitioners will have an easier time discussing medical conditions and choices regarding end‐of‐life care with residents and their families if advance directives are discussed thoroughly on admission to a long‐term care facility and are updated routinely.
Measurement of nurse practitioner job satisfaction in a midwestern state
Authors: Kacel Barbara , Miller Mary , Norris Diane
Published: August 2005

Purpose

To describe the current level of job satisfaction of nurse practitioners (NPs) in one Midwestern state.

Data sources

This study utilized descriptive correlation design to examine factors that lead to job satisfaction and dissatisfaction among a randomized sample of licensed NPs from a Midwestern state. The sample of 147 NPs (63% return rate) completed self‐administered questionnaires about various characteristics of their jobs. Descriptive statistics and correlations were used to analyze the data. The theoretical foundation for the study was Herzberg's Dual Factor Theory of Job Satisfaction.

Conclusions

Overall job satisfaction of NPs was minimally satisfied to satisfied. NPs were most satisfied with intrinsic factors and least satisfied with extrinsic factors of their jobs. Factors NPs were most satisfied with were sense of accomplishment, challenge in work, level of autonomy, patient mix, and ability to deliver quality care. NPs were least satisfied with time off to serve on professional committees, reward distribution, amount of involvement in research, opportunity to receive compensation for services outside normal duties, and monetary bonuses available in addition to salary. NPs with 0–1 year practice experience were the most satisfied with their jobs, but satisfaction scores fell steadily with each additional year of experience, reaching a plateau between the 8th to 11th years of practice.

Implications for practice

Improving job satisfaction for NPs is critical to recruit and retain advanced practice nurses to enhance access to quality, cost‐effective care for all patient populations. Satisfied NPs can potentially reduce healthcare costs associated with employee turnover. Employers must look at extrinsic factors such as compensation and opportunities for professional growth to enhance NP job satisfaction.
Monoclonal antibodies as effective therapeutic agents for solid tumors
Authors: Hinoda Yuji , Sasaki Shigeru , Ishida Tadao , Imai Kohzoh
Published: August 2005

Monoclonal antibodies (mAbs) against growth factors or their receptors have been revealed to be effective therapeutic agents for solid tumors. Trastuzumab (humanized anti‐HER2 mAb) is the first mAb approved for the treatment of a solid tumor, metastatic breast cancer. Large‐scale phase III clinical trials are now ongoing to further evaluate the additive effects on chemotherapy and the efficacy as a maintenance monotherapy. Another anti‐HER2 mAb CH401 that we developed also seems to have good potential. This chimeric mAb completely suppressed the growth of established human tumor xenografts in SCID mice after a single injection. Furthermore, CH401 characteristically showed much stronger induction of apoptosis in HER2‐overexpressing gastric cancer cells compared to trastuzumab. Additional targets now being intensively evaluated are epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). Both cetuximab (chimeric anti‐EGFR mAb) and bevacizumab (humanized anti‐VEGF mAb) have recently been shown to be of clinical value for metastatic colorectal cancer. Anti‐idiotype mAbs are unique as active immunotherapeutic agents, and survival benefits have been observed in clinical trials for solid tumors.
Tumorigenesis facilitated by Pten deficiency in the skin: Evidence of p53‐Pten complex formation on the initiation phase
Authors: Komazawa Nobuyasu , Suzuki Akira , Sano Shigetoshi , Horie Kyoji , Matsuura Nariaki , Mak Tak Wah , Nakano Toru , Takeda Junji , Kondoh Gen
Published: August 2005

Pten, a tumor suppressor gene, is mutated in various human cancers and in hereditary cancer syndromes, such as Cowden disease. We have previously developed a knockout mouse in which Pten is specifically disrupted in the skin, resulting in hyperproliferation and spontaneous tumorigenesis of the skin keratinocytes. In this study, we further clarified the effects of Pten deficiency in tumorigenesis, by using a two‐step model in intact skin of Pten knockout mouse. Although the conventional protocol requires serial exposures to DMBA and TPA, mice deficient for Pten developed skin papilloma within 6 weeks after a single exposure to DMBA, indicating that loss of Pten has a tumor‐promoting effect. Serial exposure to DMBA‐TPA ointments produced 10‐fold more papillo mas in the skin of knockout mice than in the wild‐type counterpart, suggesting an increased rate of initiation. Therefore, we precisely examined the effect of DMBA. This treatment was highly apoptotic in wild‐type mice, whereas the number of apop totic cells was diminished in Pten‐deficient skin. Moreover, primary keratinocytes isolated from Pten‐deficient mice were also resistant to the apoptotic effect of DMBA. The status of p53, Pten proteins and downstream targets of p53, such as p21, 14–3–3a, and Reprimo, were also examined, and we found that accumulation of p53 protein and up‐regulation of p53 targets were delayed in Pten‐knockout skin. These observations suggest that Pten is involved in rapid recruitment of p53 in the tumor initiation phase.
Reactive oxygen species (ROS) control the expression of Bcl‐2 family proteins by regulating their phosphorylation and ubiquitination
Authors: Li Dechao , Ueta Eisaku , Kimura Tsuyoshi , Yamamoto Tetsuya , Osaki Tokio
Published: August 2005

We examined the influence of ROS on the phosphorylation and complex formation of Bcl‐2 family proteins in Mn‐superoxide dis‐mutase (SOD) antisense‐transfected squamous cell carcinoma cells, OSC‐4 cells. The increase of intracellular ROS level induced by cis‐diamminedichloroplatinum (CDDP) and γ‐ray treatment was greater in antisense‐transfected cells than in control vector‐trans‐fected cells, and apoptosis was more extensively induced in the former. Antisense‐transfected cells expressed high levels of Bax and Bak, but low levels of Bcl‐2 and Bcl‐XL when treated with CDDP, peplomycin, 5‐fluorouracil or γ‐rays. After treatment with these agents, the phosphorylation of protein kinase A, Bcl‐2 (Thr56) and Bad (Ser155) was increased, especially in antioxidant (N‐acetylcysteine and pyrrolidine dithiocarbamate)‐pretreated control cells, but the phosphorylation levels were very low in the antisense‐transfected cells. Bcl‐2 ubiquitination was increased, but ubiquitination of Bad and Bax was decreased in the antisense‐transfected cells, although their ubiquitination was increased by the antioxidants. These results reveal that ROS induce apoptosis by regulating the phosphorylation and ubiquitination of Bcl‐2 family proteins, resulting in increased proapoptotic protein levels and decreased antiapoptotic protein expression.
Biophoton detection as a novel technique for cancer imaging
Authors: Takeda Motohiro , Kobayashi Masaki , Takayama Mariko , Suzuki Satoshi , Ishida Takanori , Ohnuki Kohji , Moriya Takuya , Ohuchi Noriaki
Published: August 2005

Biophoton emission is defined as extremely weak light that is radiated from any living system due to its metabolic activities, without excitation or enhancement. We measured biophoton images of tumors transplanted in mice with a highly sensitive and ultra‐low noise CCD camera system. Cell lines employed for this study were AH109A, TE4 and TE9. Biophoton images of each tumor were measured 1 week after carcinoma cell transplantation to estimate the tumor size at week 1 and the biophoton intensity. Some were also measured at 2 and 3 weeks to compare the biophoton distribution with histological findings. We achieved sequential biophoton imaging during tumor growth for the first time. Comparison of microscopic findings and biophoton intensity suggested that the intensity of biophoton emission reflects the viability of the tumor tissue. The size at week 1 differed between cell lines, and the biophoton intensity of the tumor was correlated with the tumor size at week 1 (correlation coefficient 0.73). This non‐invasive and simple technique has the potential to be used as an optical biopsy to detect tumor viability.
Docetaxel enhances the cytotoxicity of cisplatin to gastric cancer cells by modification of intracellular platinum metabolism
Authors: Maeda Shingo , Sugiura Tsudoi , Saikawa Yoshiro , Kubota Tetsuro , Otani Yoshihide , Kumai Koichiro , Kitajima Masaki
Published: August 2005

We have examined the combined anticancer effects of docetaxel (DOC) and cisplatin (CDDP) in vitro using the gastric cancer cell lines MKN‐45, MKN‐74, and TMK‐1. Treatment of the cell lines with 30 μg/ml of DOC for 24 h followed by incubation with 3 or 10 μg/ml of CDDP for 24 h showed a clear synergistic effect. Sequence dependency of the agents was observed in these cell lines: DOC followed by CDDP (DC) showed a stronger antitumor effect than CDDP followed by DOC (CD) in all cell lines. To clarify the mechanism of action of the DC combination, total intracellular platinum (Pt) levels were evaluated after treatment with CDDP alone or combined with DC. For the MKN‐45 and ‐74 cell lines, cells treated with DOC (10 μg/ml for 12 h) and then CDDP showed significantly increased intracellular Pt accumulation compared to cells treated with CDDP alone. We also investigated alterations in intracellular glutathione (GSH) concentration in response to DOC and CDDP. MKN‐45 and ‐74 cells pretreated with DOC (10 μg/ml for 12 h) showed significantly increased intracellular GSH levels compared to cells administered CDDP only. To explain these findings, messenger RNA (mRNA) levels for multidrug resistance‐associated protein‐1 (MRP‐1), the ATP‐dependent pump for Pt‐GSH complexes, were quantified in CDDP‐treated MKN‐45 cells with and without DOC pretreatment. While CDDP administration increased MRP‐1 mRNA expression in MKN‐45 cells, MRP‐1 was not up‐regulated after CDDP administration in DOC pretreated MKN‐45 cells. Our results suggested that the enhanced CDDP toxicity due to DOC pretreatment may be related to the accumulation of intracellular Pt‐GSH complexes, because DOC appears to suppress the MRP‐1 up‐regulation induced by CDDP exposure in gastric cancer cells.
Antitumor activity of pyrvinium pamoate, 6‐(dimethylamino)‐2‐[2‐(2,5‐dimethyl‐1‐phenyl‐1H‐pyrrol‐3‐yl)ethenyl]‐1‐methyl‐quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation
Authors: Esumi Hiroyasu , Lu Jie , Kurashima Yukiko , Hanaoka Tomoyuki
Published: August 2005

An anthelminthic, pyrvinium pamoate (PP), 6‐(dimethylamino)‐2‐[2‐(2,5‐dimethyl‐1‐phenyl‐1H‐pyrrol‐3‐yl)ethenyl]‐1‐methyl‐quino‐linium pamoate salt, has been found to be extremely toxic to PANC‐1 cells in glucose‐free medium, but not to be toxic to the same cells cultured in ordinary medium, Dulbecco's modified Eagle's medium (DMEM). It showed the same preferential toxicity for various cancer cell lines during glucose starvation. When 0.1 μg/ml PP was added to the medium, spheroid growth of human colon cancer cell line WiDr was strongly inhibited to a diameter of 750 μm, and this finding is consistent with the concept of anti‐austerity. PP was also found to exert antitumor activity against human pancreatic cancer cell line PANC‐1 in nude mice and SCID mice when it was administered subcutaneously or orally. Regarding the mechanism of PP action, inhibition of Akt phosphoryla‐tion, which has been found to be essential for the austerity mechanism, was observed in vitro and in vivo. These findings indicate that PP may be useful for anticancer therapy and that anti‐austerity therapy could be a novel strategy for anticancer therapy.