bluuebunny/crossref_metadata_2025 huggingface dataset:
Susceptibilities ofCandidaSpecies to Amphotericin B and Fluconazole: The Emergence of Fluconazole Resistance inCandida tropicalis
Authors: Yang Yun-Liang , Ho Yong-An , Cheng Hsiao-Hsu , Ho Monto , Lo Hsiu-Jung
Published: March 2006

Objective:

To determine the susceptibilities ofCandidaspecies isolated from Taiwan to amphotericin B and fluconazole.

Design:

Prospective surveillance study.

Methods:

Each hospital was asked to submit up to 10C. albicansand 40non-albicans Candidaspecies during the collection period, from April 15 to June 15, 1999. One isolate was accepted from each episode of infection. The broth microdilution method was used to determine susceptibilities to amphotericin B and fluconazole.

Results:

Only 3 of 632 isolates, one each ofC. famata, C. krusei,andC. tropicalis,were resistant to amphotericin B. A total of 53 (8.4%) of 632 clinical yeast isolates, consisting of 4%C. albicans,8%C. glabrata,15%C. tropicalis,and 70%C. krusei,were resistant to fluconazole. In contrast, noC. parapsilosisisolate was resistant to fluconazole. Isolates from tertiary-care medical centers had higher rates of resistance to fluconazole than did those from regional and local hospitals (11.4% vs 6.6%). Isolates from different sources showed different levels of susceptibility to fluconazole. All of the isolates with the exception ofC. tropicalisandC. kruseiisolated from blood were susceptible to fluconazole. A pattern of co-resistance to both amphotericin B and fluconazole was observed.

Conclusions:

Non-albicans Candidaspecies had higher rates of resistance to fluconazole than didC. albicans(44 of 395 [11.2%] vs 9 of 237 [3.8%];P= .002). The increasing rate of fluconazole resistance inC. tropicalis(15%) is important becauseC. tropicalisis one of the most commonly isolatednon-albicans Candidaspecies.
Performance Improvement in the Long-Term–Care Setting Building on the Foundation of Infection Control
Authors: Stevenson Kurt B. , Loeb Mark
Published: March 2006

Infection control programs were among the first organized efforts to improve the quality of healthcare delivered to patients and are an excellent model for the development of other healthcare performance improvement activities. Whether labeled as infection control, quality improvement, or patient safety, performance improvement initiatives share similar methods and principles. The quality of care in long-term–care facilities (LTCFs) has been scrutinized foryears and has received renewed attention with the recent initiation of public reporting of quality measures by Medicare. This article reviews the principles of performance improvement, discusses the importance of employing evidence-based interventions, and emphasizes the value of local performance improvement in LTCFs. Residents of LTCFs remain at high risk for the development of nosocomial infections, and among performance improvement initiatives, infection control is recom-mended as a high priority for all LTCFs. Fortunately, infection control contains the essential elements for performance improvement, and a successful infection control program can provide the foun-dation for expanding performance improvement throughout the LTCF. There is still much that needs to be done to determine the best clinical practices for LTCFs, and this should remain a priority for future research. Furthermore, efforts should continue to apply these principles at the local level to ensure that all residents of LTCFs receive the best care possible.
Multicenter Study of the Prevalence of Nosocomial Infections in Italian Hospitals
Authors: Pietrantonj Carlo Di , Ferrara Lorenza , Lomolino G.
Published: March 2006

A point-prevalence study of nosocomial infections was conducted in 10 generai hospitals in northwestern Italy in June and July 2000. Infection rates were compared by type and site among the different hospitals. Urinary tract infections were most frequent, accounting for 57.8% of 128 nosocomial infections.
Wave Action in a Plasma with Coulomb Collisions
Authors: S V Vladimirov  , O Ishihara
Published: March 2006

The influence of Coulomb collisions on the wave propagation in
plasmas is considered. It is demonstrated that the nonlinear coupling
of the nonresonant wave with electric field fluctuations resonant with
the plasma particles as well as contribution of the system
nonstationarity induced by the collisions is crucial to obtain the
correct conservation equation for the wave occupation number. In
contrast to the occupation number, the canonical wave energy changes
because of the nonstationarity of the system. Since the definition of
the wave energy is not necessarily unique and depends on separation
into background and wave subsystems, the result for the change of the
canonical wave energy is not universal. An alternative way of
separation into background and wave subsystems is
discussed.
Feedback-optimized parallel tempering Monte Carlo
Authors: Katzgraber Helmut G , Trebst Simon , Huse David A , Troyer Matthias
Published: March 2006

We introduce an algorithm for systematically improving the efficiency of parallel
tempering Monte Carlo simulations by optimizing the simulated temperature set. Our
approach is closely related to a recently introduced adaptive algorithm that optimizes
the simulated statistical ensemble in generalized broad-histogram Monte Carlo
simulations. Conventionally, a temperature set is chosen in such a way that the
acceptance rates for replica swaps between adjacent temperatures are independent of
the temperature and large enough to ensure frequent swaps. In this paper, we
show that by choosing the temperatures with a modified version of the optimized
ensemble feedback method we can minimize the round-trip times between the lowest
and highest temperatures which effectively increases the efficiency of the parallel
tempering algorithm. In particular, the density of temperatures in the optimized
temperature set increases at the ‘bottlenecks’ of the simulation, such as phase
transitions. In turn, the acceptance rates are now temperature dependent in the
optimized temperature ensemble. We illustrate the feedback-optimized parallel
tempering algorithm by studying the two-dimensional Ising ferromagnet and the
two-dimensional fully frustrated Ising model, and briefly discuss possible feedback
schemes for systems that require configurational averages, such as spin glasses.
Cdc42p GDP/GTP Cycling Is Necessary for Efficient Cell Fusion during Yeast Mating
Authors: Barale Sophie , McCusker Derek , Arkowitz Robert A.
Published: March 2006

The highly conserved small Rho G-protein, Cdc42p plays a critical role in cell polarity and cytoskeleton organization in all eukaryotes. In the yeast Saccharomyces cerevisiae, Cdc42p is important for cell polarity establishment, septin ring assembly, and pheromone-dependent MAP-kinase signaling during the yeast mating process. In this study, we further investigated the role of Cdc42p in the mating process by screening for specific mating defective cdc42 alleles. We have identified and characterized novel mating defective cdc42 alleles that are unaffected in vegetative cell polarity. Replacement of the Cdc42p Val36 residue with Met resulted in a specific cell fusion defect. This cdc42[V36M] mutant responded to mating pheromone but was defective in cell fusion and in localization of the cell fusion protein Fus1p, similar to a previously isolated cdc24 (cdc24-m6) mutant. Overexpression of a fast cycling Cdc42p mutant suppressed the cdc24-m6 fusion defect and conversely, overexpression of Cdc24p suppressed the cdc42[V36M] fusion defect. Taken together, our results indicate that Cdc42p GDP–GTP cycling is critical for efficient cell fusion.
A Critical Role for Tetraspanin CD151 in α3β1 and α6β4 Integrin–dependent Tumor Cell Functions on Laminin-5
Authors: Winterwood Nicole E. , Varzavand Afshin , Meland Marit N. , Ashman Leonie K. , Stipp Christopher S.
Published: March 2006

The basement membrane protein laminin-5 supports tumor cell adhesion and motility and is implicated at multiple steps of the metastatic cascade. Tetraspanin CD151 engages in lateral, cell surface complexes with both of the major laminin-5 receptors, integrins α3β1 and α6β4. To determine the role of CD151 in tumor cell responses to laminin-5, we used retroviral RNA interference to efficiently silence CD151 expression in epidermal carcinoma cells. Near total loss of CD151 had no effect on steady state cell surface expression of α3β1, α6β4, or other integrins with which CD151 associates. However, CD151-silenced carcinoma cells displayed markedly impaired motility on laminin-5, accompanied by unusually persistent lateral and trailing edge adhesive contacts. CD151 silencing disrupted α3β1 integrin association with tetraspanin-enriched microdomains, reduced the bulk detergent extractability of α3β1, and impaired α3β1 internalization in cells migrating on laminin-5. Both α3β1- and α6β4-dependent cell adhesion to laminin-5 were also impaired in CD151-silenced cells. Reexpressing CD151 in CD151-silenced cells reversed the adhesion and motility defects. Finally, loss of CD151 also impaired migration but not adhesion on substrates other than laminin-5. These data show that CD151 plays a critical role in tumor cell responses to laminin-5 and reveal promotion of integrin recycling as a novel potential mechanism whereby CD151 regulates tumor cell migration.
Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP
Authors: Klein Ulf R. , Nigg Erich A. , Gruneberg Ulrike
Published: March 2006

The chromosomal passenger complex (CPC), consisting of the serine/threonine kinase Aurora B, the inner centromere protein INCENP, Survivin, and Borealin/DasraB, has essential functions at the centromere in ensuring correct chromosome alignment and segregation. Despite observations that small interfering RNA-mediated knockdown of any one member of the CPC abolishes localization of the other subunits, it remains unclear how the complex is targeted to the centromere. We have now identified a ternary subcomplex of the CPC comprising Survivin, Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This subcomplex was found to be essential and sufficient for targeting to the centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not required for centromere localization of the subcomplex. We demonstrate that CPC targeting to the centromere does not depend on CENP-A and hMis12, two core components for kinetochore/centromere assembly, and provide evidence that the CPC may be directed to centromeric DNA directly via the Borealin subunit. Our findings thus establish a functional module within the CPC that assembles on the N terminus of INCENP and controls centromere recruitment.
NuSAP, a Mitotic RanGTP Target That Stabilizes and Cross-links Microtubules
Authors: Ribbeck Katharina , Groen Aaron C. , Santarella Rachel , Bohnsack Markus T. , Raemaekers Tim , Köcher Thomas , Gentzel Marc , Görlich Dirk , Wilm Matthias , Carmeliet Geert , Mitchison Timothy J. , Ellenberg Jan , Hoenger Andreas , Mattaj Iain W.
Published: March 2006

Nucleolar and spindle-associated protein (NuSAP) was recently identified as a microtubule- and chromatin-binding protein in vertebrates that is nuclear during interphase. Small interfering RNA-mediated depletion of NuSAP resulted in aberrant spindle formation, missegregation of chromosomes, and ultimately blocked cell proliferation. We show here that NuSAP is enriched on chromatin-proximal microtubules at meiotic spindles in Xenopus oocytes. When added at higher than physiological levels to Xenopus egg extract, NuSAP induces extensive bundling of spindle microtubules and causes bundled microtubules within spindle-like structures to become longer. In vitro reconstitution experiments reveal two direct effects of NuSAP on microtubules: first, it can efficiently stabilize microtubules against depolymerization, and second, it can cross-link large numbers of microtubules into aster-like structures, thick fibers, and networks. With defined components we show that the activity of NuSAP is differentially regulated by Importin (Imp) α, Impβ, and Imp7. While Impα and Imp7 appear to block the microtubule-stabilizing activity of NuSAP, Impβ specifically suppresses aspects of the cross-linking activity of NuSAP. We propose that to achieve full NuSAP functionality at the spindle, all three importins must be dissociated by RanGTP. Once activated, NuSAP may aid to maintain spindle integrity by stabilizing and cross-linking microtubules around chromatin.
Myosin VI Stabilizes an Actin Network duringDrosophilaSpermatid Individualization
Authors: Noguchi Tatsuhiko , Lenartowska Marta , Miller Kathryn G.
Published: March 2006

Here, we demonstrate a new function of myosin VI using observations of Drosophila spermatid individualization in vivo. We find that myosin VI stabilizes a branched actin network in actin structures (cones) that mediate the separation of the syncytial spermatids. In a myosin VI mutant, the cones do not accumulate F-actin during cone movement, whereas overexpression of myosin VI leads to bigger cones with more F-actin. Myosin subfragment 1-fragment decoration demonstrated that the actin cone is made up of two regions: a dense meshwork at the front and parallel bundles at the rear. The majority of the actin filaments were oriented with their pointed ends facing in the direction of cone movement. Our data also demonstrate that myosin VI binds to the cone front using its motor domain. Fluorescence recovery after photobleach experiments using green fluorescent protein-myosin VI revealed that myosin VI remains bound to F-actin for minutes, suggesting its role is tethering, rather than transporting cargo. We hypothesize that myosin VI protects the actin cone structure either by cross-linking actin filaments or anchoring regulatory molecules at the cone front. These observations uncover a novel mechanism mediated by myosin VI for stabilizing long-lived actin structures in cells.
Oxysterol-binding Protein and Vesicle-associated Membrane Protein–associated Protein Are Required for Sterol-dependent Activation of the Ceramide Transport Protein
Authors: Perry Ryan J. , Ridgway Neale D.
Published: March 2006

Sphingomyelin (SM) and cholesterol are coregulated metabolically and associate physically in membrane microdomains involved in cargo sorting and signaling. One mechanism for regulation of this metabolic interface involves oxysterol binding protein (OSBP) via high-affinity binding to oxysterol regulators of cholesterol homeostasis and activation of SM synthesis at the Golgi apparatus. Here, we show that OSBP regulation of SM synthesis involves the endoplasmic reticulum (ER)-to-Golgi ceramide transport protein (CERT). RNA interference (RNAi) experiments in Chinese hamster ovary (CHO)-K1 cells revealed that OSBP and vesicle-associated membrane protein–associated protein (VAP) were required for stimulation of CERT-dependent ceramide transport and SM synthesis by 25-hydroxycholesterol and cholesterol depletion in response to cyclodextrin. Additional RNAi experiments in human embryonic kidney 293 cells supported OSBP involvement in oxysterol-activated SM synthesis and also revealed a role for OSBP in basal SM synthesis. Activation of ER-to-Golgi ceramide transport in CHO-K1 cells required interaction of OSBP with the ER and Golgi apparatus, OSBP-dependent Golgi translocation of CERT, and enhanced CERT–VAP interaction. Regulation of CERT by OSBP, sterols, and VAP reveals a novel mechanism for integrating sterol regulatory signals with ceramide transport and SM synthesis in the Golgi apparatus.
Treaty Interpretation And The Incorporation Of Extraneous Legal Rules
Authors: French Duncan
Published: March 2006

This paper considers under what circumstances, and for what reasons, an international tribunal may want to range beyond the primary text of a treaty to determine its ‘correct’ meaning; such extraneous legal material potentially including rules of customary international law, other treaties between the parties, general principles of law, and documents of a ‘soft law’ nature. The paper suggests a variety of ‘mechanisms’ by which a tribunal may undertake a broader interpretative approach, though all ultimately raise the same inevitable tension between accusations of judicial activism and counter-arguments of inflexibility and insularity. Nevertheless, many tribunals and individual judges continue to utilize such techniques, particularly noticeable in some recent environmental disputes. The paper will conclude with a note of caution; that though such interpretations are becoming an increasingly significant part of modern judicial decision-making—something that is generally to be welcomed—tribunals must concurrently take care to ensure that they remain within the accepted parameters of the adjudicative function.
Binding Armed Opposition Groups
Authors: Sivakumaran Sandesh
Published: March 2006

This article considers how armed opposition groups fighting in an internal armed conflict are bound by the rules of international humanitarian law despite not being party to the relevant treaties. It assesses a number of explanations—customary international law, general principles of international humanitarian law, rules governing treaties and third parties and claims to succession—and argues that each has limited value. The ability of the state to legislate on behalf of all its individuals is considered the best explanation. This principle is explored and objections to it are countered. This article also examines the expressed commitment of armed opposition groups to the rules of international humanitarian law.
UN Convention on State Immunity: Form and Function
Authors: Gardiner Richard
Published: March 2006

The eventual product of the International Law Commission's (ILC) work on state immunity hasbeen in the form of a Convention. This prompts the question whether widespread ratification (or accession etc) will be necessary for clear rules of international law on state immunity to become firmlyestablished or whether a substantial codifying effect could be achieved even if the Convention does not attract a great number of parties. The latter has sometimes been said of much of the Vienna Convention on the Law of Treaties. As the law on state immunity has undergone much of its substantial development by practice of national courts (albeit that the piecemeal adoption and implementation of treaties has played some part), could this process not simply continue with the Convention providing guidance or a model? If the trend from absolute to restrictive immunity could occur by development of customary law, are there not still adequate means of consolidating customary law without the need for states actually to become parties to the treaty?
I. Free Movement of Goods
Authors: Weatherill Stephen
Published: March 2006

The Surveys of the law of the free movement of goods carried in the Quarterly since 1989 have followed a largely consistent pattern. The Court's case law interpreting the nature and purpose of Article 28's legislative institutions. The readier the Court is to treat national measures as barriers to trade, the deeper the incursion of EC law into national regulatory autonomy. And vice versa. The Wider the scope allowed to the possibility to justify barriers to trade, the more room for manoeuvre is handed back to national regulatory autonomy—and the more weight is placed on the process of legislative harmonization or, increasingly, other forms of policy coordination at EC level as the way to advance integration. And vice versa. All these trends are in view in the period covered by this survey. The complex institutional rhythms reveal that the creation of the internal market was not a short-term project that was completed in 1992, nor even an enterprise that gently begged to have a few loose ends tidied up before being triumphantly pronounced historical fact. In reality the internal market, as an exercise in creating a unified economic space underpinned by a constitutionalized system of supra-State legal rules in a politically fragmented but interdependent environment, is one manifestation of the extraordinary exercise in multi-level governance which is evolving in Europe. Systems of this complexity do not stop fluctuating; ‘free’ markets are politically contested.
II AGRICULTURE
Authors: Weatherill Stephen , Cardwell Michael
Published: March 2006

Agriculture continues to maintain a very high profile in the Community, notwithstanding calls that the sector should occupy a place commensurate with its overall contribution to the economy. Such calls grew yet stronger during the United Kingdom Presidency from July to December 2005. Indeed, shortly before the United Kingdom assumed the Presidency, Tony Blair stated that [i]t simply does not make sense, in this new world, for Europe to spend over 40 per cent of its budget on the common agricultural policy, representing 5 per cent. of the EU population producing less than 2 percent. of Europe's output.’1 In similar vein, there has been trenchant criticism of the extent to which agriculture has dominated the Doha Development Round negotiations under the auspices of the World Trade Organization (‘WTO’). For example, Commissioner Mandelson has expressed ‘a real fear that a continuing overnegotiation and overbidding in agriculture will stymite the progress we urgently need to demonstrate across the range of the talks’.2
Identification of Primary Target Genes of Phytochrome Signaling. Early Transcriptional Control during Shade Avoidance Responses in Arabidopsis
Authors: Roig-Villanova Irma , Bou Jordi , Sorin Céline , Devlin Paul F. , Martínez-García Jaime F.
Published: March 2006

The phytochrome (phy) photoreceptors modulate plant development after perception of light. Upon illumination of etiolated seedlings, phys initiate a transcriptional cascade by directly transducing light signals to the promoters of genes encoding regulators of morphogenesis. In light-grown plants, however, little is known about the transcriptional cascade modulated by phys in response to changes in light. The phy entry points in this cascade are completely unknown. We are particularly interested in the shade avoidance syndrome (SAS). Here we describe a subset of six genes whose expression is rapidly modulated by phys during both deetiolation and SAS in Arabidopsis (Arabidopsis thaliana). Using cycloheximide, we provide evidence that four of these phy rapidly regulated (PAR) genes are direct targets of phy signaling during SAS, revealing these genes as upstream components of the transcriptional cascade. Promoter-β-glucuronidase fusions confirmed that PAR genes are photoregulated at the transcriptional level. Analysis of gene expression in light signal transduction mutants showed that COP1 and DET1 (but not DET2 or HY5) play a role in modulating PAR expression in response to shade in light-grown seedlings. Moreover, genetic analyses showed that one of the genes identified as a direct target of phy signaling was phy-interacting factor 3-like-1 (PIL1). PIL1 has previously been implicated in SAS in response to transient shade, but we show here that it also plays a key role in response to long-term shade. The action of PIL1 was particularly apparent in a phyB background, suggesting an important negative role for PIL1 under dense vegetation canopies.
Production and clearance of cyclobutane dipyrimidine dimers in UV‐irradiated skin pretreated with 1% pimecrolimus or 0.1% triamcinolone acetonide creams in normal and atopic patients
Authors: Doelker Laurence , Tran Christian , Gkomouzas Angelos , Grand Denise , Sorg Olivier , Saurat Jean‐Hilaire , Lübbe Jann
Published: March 2006

Background:  Ultraviolet (UV)‐induced pyrimidine dimers are an early step in skin carcinogenesis, which is accelerated in the setting of long‐term immunosuppression with systemic calcineurin inhibitors. It is not known whether topical application of calcineurin inhibitors exposes to a similar risk.

Objective:  To assess the formation and clearance of UV‐induced dipyrimidine dimers in human epidermis treated with topical pimecrolimus as compared to topical steroid, vehicle and untreated control.

Methods:  Pretreated buttock skin of 20 human volunteers with (10) or without (10) atopic dermatitis was exposed to two minimal erythema doses (MED) of simulated solar radiation. DNA was extracted from epidermis 1 and 24 h postirradiation. Pyrimidine dimers were visualized by immuno slot blots and quantified by chemoluminescence image analysis.

Results:  One‐hour postirradiation, pimecrolimus‐treated epidermis contains less DNA damage as compared to untreated control, but there were no statistically significant differences between pimecrolimus, triamcinolone acetonide and vehicle. Dimer levels at 24 h postirradiation showed no significant differences between different treatments.

Conclusion:  Treatment with pimecrolimus cream, triamcinolone acetonide cream and vehicle is not associated with increased epidermal DNA damage at 1 and 24 h post‐UV exposure.
Immune response modifiers – mode of action
Authors: Schiller Meinhard , Metze Dieter , Luger Thomas A. , Grabbe Stephan , Gunzer Matthias
Published: March 2006

Abstract:  The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll‐like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor‐κB activation and the interferon (IFN)‐regulatory factor 3 pathway initiate production of pro‐inflammatory cytokines, such as interleukin‐1 and tumor necrosis factor‐α, and production of type I IFNs (IFN‐α and IFN‐β), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro‐inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN‐producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor‐specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1‐type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2‐type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response.
Vascular endothelial growth factor gene polymorphisms increase the risk to develop psoriasis
Authors: Barile S. , Medda E. , Nisticò L. , Bordignon V. , Cordiali‐Fei P. , Carducci M. , Rainaldi A. , Marinelli R. , Bonifati C.
Published: March 2006

Abstract:  We investigated the relationship between eight polymorphisms in the gene encoding for vascular endothelial growth factor (VEGF) (−1540C > A, −1512Ins18, −1451C > T, −460T > C, −160C > T, −152G > A, −116G > A and +405G > C) and plaque‐type psoriasis stratified for age at onset, gender and family history of dermatosis. For this purpose, 117 patients with chronic plaque‐type psoriasis and 215 healthy subjects were enrolled. We found that being homozygous −1540AA, −1512InsIns, −1451TT, −460CC and −152AA conferred a significant risk in developing psoriasis compared with heterozygous (−1540CA, −1512 + Ins, −1451CT, −460CT and −152AG) and homozygous genotypes (−1540CC, −1512 + +−1451CC, −460TT and −152GG) grouped together [odds ratio (ORs) = 1.73, 1.73, 1.73, 1.77 and 1.87, respectively]. Conversely, having the −116AA or +405GG genotype did not significantly increase the risk of disease expression compared with other genotypes of the same loci. Interestingly, we found that −1540AA, −1512InsIns, −1451TT, −460CC and −152AA homozygous genotypes have a significant two‐fold increased risk in developing psoriasis after the age of 40 years (late‐onset psoriasis) (ORs = 2.19, 2.19, 2.19, 2.05 and 2.26; P = 0.02, 0.02, 0.02, 0.04 and 0.02, respectively) as compared with controls. On the contrary, we found no phenotype–genotype association of the same magnitude among the patients in whom psoriasis developed at or before the age of 40 years (early‐onset psoriasis) compared with controls. Genotype distributions were not significantly different when cases and controls were stratified either by gender or family history of psoriasis. Finally, VEGF plasma concentration was not significantly different between patients and controls and was not correlated with the severity of the disease.
Induction of centrosome amplification in p53 siRNA‐treated human fibroblast cells by radiation exposure
Authors: Kawamura Kenji , Morita Nobuyo , Domiki Chizue , Fujikawa‐Yamamoto Kozaburo , Hashimoto Mitsumasa , Iwabuchi Kuniyoshi , Suzuki Koji
Published: March 2006

Centrosome amplification can be detected in the tissues of p53−/– mice. In contrast, loss of p53 does not induce centrosome amplification in cultured human cells. However, examination of human cancer tissues and cultured cells has revealed a significant correlation between loss or mutational inactivation of p53 and occurrence of centrosome amplification, supporting the notion that p53 mutation alone is insufficient to induce centrosome amplification in human cells, and that additional regulatory mechanisms are involved. It has recently been shown that gamma irradiation of tumor cells induces centrosome amplification. However, the precise mechanism of radiation‐induced centrosome amplification is not fully understood. In the present study, CCD32SK diploid normal human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human p53 (CCD/p53i). There was a small increase in the frequency of centrosome amplification in CCD/p53i cells (4.0%) without irradiation. In contrast, CCD/p53i cells after 5‐Gy irradiation showed a marked increase in abnormal nuclear shapes and pronounced amplification of centrosomes (46.0%). At 12 h after irradiation, irradiated CCD/p53i cells were arrested in G2 phase. By laser scanning cytometry, abnormal mitosis with amplified centrosomes was observed frequently in the accumulating G2/M population at 48 h after irradiation. In the present study, we found that siRNA‐mediated silencing of p53 in normal human fibroblasts, together with DNA damage by irradiation, efficiently induced centrosome amplification and nuclear fragmentation, but these phenomena were not observed with either siRNA‐mediated silencing of p53 or irradiation alone. (Cancer Sci 2006; 97: 252–258)
Infrequent existence of simian virus 40 large T antigen DNA in malignant mesothelioma in Japan
Authors: Aoe Keisuke , Hiraki Akio , Murakami Tomoyuki , Toyooka Shinichi , Shivapurkar Narayan , Gazdar Adi F. , Sueoka Naoko , Taguchi Koji , Kamei Toshiaki , Takeyama Hiroyasu , Sugi Kazuro , Kishimoto Takumi
Published: March 2006

Malignant mesothelioma is the most common primary pleural neoplasm. Association of simian virus 40 (SV40) with malignant mesothelioma has been reported, suggesting that SV40 plays an important role in the origin of a subset of these tumors. However, significant geographic variation is present as to how often this association occurs. As no study concerning SV40 in malignant mesothelioma has been reported from Japan, we examined the frequency of SV40 infection in Japanese malignant mesothelioma cases. In pleural malignant mesothelioma tissue from 35 patients in Japan, we sought the presence of SV40 large T antigen DNA using real‐time polymerase chain reaction (PCR), as well as expression of the viral protein using immunohistological methods. Real‐time PCR demonstrated that two of 35 mesotheliomas contained DNA sequences encoding portions of SV40 large T antigen. None of the 35 malignant mesothelioma specimens showed immunoreactivity for SV40 large T antigen. SV40 infection does not appear to have a major role in the development of malignant mesothelioma in Japan. (Cancer Sci 2006; 97: 292–295)
DMRT‐1 expression during NEC8 human embryonic carcinoma cell differentiation
Authors: Koji Hitoshi , Yamada Akira , Nagasawa Toshihiko , Gamou Shinobu
Published: March 2006

To elucidate the relationship between dsx and mab‐3 related transcription factor 1 (Dmrt‐1) and differentiation, alteration in mRNA levels during differentiation of NEC8 human embryonic carcinoma cells was investigated. After stimulation with 50 nM phorbol 12‐myristate 13‐acetate (PMA), the cells differentiated into cells with mesenchymal characteristics and upregulated Dmrt‐1 mRNA, possibly through the protein kinase C/mitogen‐activated protein kinase/activated protein‐1 signaling pathway. Conversely, knockdown of Dmrt‐1 by small interfering RNA resulted in cell morphology that was different from that after PMA treatment. These results indicated that Dmrt‐1 expression was apparently associated with the differentiation of NEC8, and this cell line may be a helpful in vitro tool to clarify the role of Dmrt‐1 in the differentiation process. (Cancer Sci 2006; 97: 277 –282)
Cervical and corpus cancer survival disparities by socioeconomic status in a metropolitan area of Japan
Authors: Ueda Kimiko , Kawachi Ichiro , Tsukuma Hideaki
Published: March 2006

The purpose of this study was to analyze socioeconomic differences in cervical and corpus cancer survival, and to investigate if the differences are due to differences in age, cancer stage, histology and treatment. A total of 14 055 cases with cervical cancer and 3113 cases with corpus cancer were obtained from the Osaka Cancer Registry. Municipality‐based SES measurements were obtained from the System of Social and Demographic Statistics. Survival analysis was carried out with Kaplan–Meier survival curves. Three types of Cox proportional hazards regression models were tested to assess survival differences among groups and effects of SES on survival, controlling for clinical factors. SES was related to age and cancer stage for cervical and corpus cancer patients, and histology for cervical cancer patients. Differences were observed in cumulative 5‐year survival for cervical cancer patients among low, middle and high unemployment municipalities (68.9%, 64.3% and 50.9%, respectively, P < 0.0001). Differences in cumulative 5‐year survival for cervical cancer patients were also observed among high, middle and low education municipalities (65.1%, 62.2% and 56.1%, respectively, P < 0.0001). Similar patterns in 5‐year survival were also found for corpus cancer patients. After adjusting for age, cancer stage, histology and treatment, survival differences between patients from high and low SES areas still remained. In conclusion, our population‐based analysis of a metropolitan representative sample in Japan has demonstrated, for the first time in Japan, SES differences in survival following cervical and corpus cancer. (Cancer Sci 2006; 97: 283 –291)
Review article: intestinal serotonin signalling in irritable bowel syndrome
Authors: MAWE G. M. , COATES M. D. , MOSES P. L.
Published: March 2006

Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized.

Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5‐hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin‐selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin‐selective reuptake transporter in irritable bowel syndrome. A serotonin‐selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin‐selective reuptake transporter downregulation.

While a psychiatric co‐morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.
Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori?
Authors: GOTTELAND M. , BRUNSER O. , CRUCHET S.
Published: March 2006

Helicobacter pylori is a highly prevalent pathogen considered as an aetiological factor for gastroduodenal ulcers, and a risk factor for gastric adenocarcinoma and lymphoma in humans. Most subjects colonized by this micro‐organism are asymptomatic and remain untreated. In symptomatic patients, the antibiotic treatment has a high cost and is not 100% effective because of resistance to antibiotics and to moderate patient compliance. This review discusses the role of probiotics as alternative solutions to assist in the control of H. pylori colonization in at‐risk populations.

The evidence that some strains of Lactobacillus and Bifidobacterium are able to inhibit H. pylori growth through the release of bacteriocins or organic acids, and may also decrease its adhesion to epithelial cells, is reviewed. In addition, probiotics have a possible role in the stabilization of the gastric barrier function and the decrease of mucosal inflammation. Other aspects that are considered are the contribution of probiotics to the healing of the gastric mucosa linked to their antioxidant and anti‐inflammatory properties.

Clinical trials in colonized adults and children are reviewed, and suggest that probiotics do not eradicate H. pylori but maintain lower levels of this pathogen in the stomach; in combination with antibiotics, probiotics may increase eradication rate and/or decrease adverse effects. Papers suggesting similar effects on H. pylori by foodstuffs such as berry juice and some milk proteins are quoted. Regular intake of these and other dietary products might constitute a low‐cost, large‐scale alternative solution applicable for populations at‐risk for H. pylori colonization.
Oesophagitis is common in patients with achalasia after pneumatic dilatation
Authors: LEEUWENBURGH I. , VAN DEKKEN H. , SCHOLTEN P. , HANSEN B. E. , HARINGSMA J. , SIERSEMA P. D. , KUIPERS E. J.
Published: March 2006

Background  Achalasia, an oesophageal motor disease, is associated with functional oesophageal obstruction. Food stasis can predispose for oesophagitis. Treatment aims at lowering of the lower oesophageal sphincter pressure, enhancing the risk of gastro‐oesophageal reflux. Nevertheless, the incidence of oesophagitis after achalasia treatment is unknown.

Aim  To investigate the incidence and severity of oesophagitis in achalasia patients treated with pneumatic dilatation.

Methods  A cohort of 331 patients with achalasia were treated with pneumatic dilatation and followed. Oesophagitis and stasis were assessed by endoscopy and inflammation was graded by histology.

Results  251 patients were followed for a mean values of 8.4 years (range: 1–26). The average number of endoscopies with biopsy sample sets per patient was 4 (range: 1–17). Three patients had no histological signs of oesophagitis throughout follow‐up, 139 had oesophagitis grade 1, 49 oesophagitis grade 2 and 60 grade 3. Specialized intestinal metaplasia was found in 37 patients. The association between endoscopic food stasis and histological inflammation was significant. The association between endoscopic signs of oesophagitis and histological inflammation was poor.

Conclusions  Forty percent of the achalasia patients develop chronic active or ulcerating oesophagitis after treatment. Inflammation was associated with food stasis. Because the sensitivity of endoscopy to detect inflammation is low, surveillance endoscopy with biopsy sampling and assessment of stasis is warranted to detect early neoplastic changes.
Maintenance infliximab does not result in increased abscess development in fistulizing Crohn's disease: results from the ACCENT II study
Authors: SANDS B. E. , BLANK M. A. , DIAMOND R. H. , BARRETT J. P. , VAN DEVENTER S. J.
Published: March 2006

Background  Rapid fistula healing may predispose Crohn's disease patients to abscess development.

Aim  Data from ACCENT II were analysed to determine whether fistula‐related abscess development is affected by infliximab exposure.

Methods  Following infliximab 5 mg/kg infusions at weeks 0, 2 and 6, patients were evaluated for fistula response for two consecutive visits at least 4 weeks apart. Patients (N = 282) were randomized at week 14 to either placebo or infliximab 5 mg/kg every 8 weeks through week 46. If response was lost at or after week 22, patients could crossover to a 5 mg/kg higher infliximab dose. Fistula‐related abscesses were diagnosed by physical examination or by imaging procedures according to usual practice.

Results  Infliximab exposure was approximately twofold higher for the infliximab maintenance group. Twenty‐one (15%) patients in the infliximab maintenance group had at least one newly developed fistula‐related abscess compared with 27 (19%) in the placebo maintenance group (P = 0.526). The proportion of patients with a new fistula‐related abscess was similar regardless of whether or not patients crossed over to a 5 mg/kg higher infliximab dose. The number of fistula‐related abscesses diagnosed over time did not differ between groups.

Conclusion  Abscess development in patients with fistulizing Crohn's disease is not dependent on cumulative infliximab exposure.
Reinfection after successful eradication of Helicobacter pylori: a 2‐year prospective study in Alaska Natives
Authors: McMAHON B. J. , BRUCE M. G. , HENNESSY T. W. , BRUDEN D. L. , SACCO F. , PETERS H. , HURLBURT D. A. , MORRIS J. M. , REASONOVER A. L. , DAILIDE G. , BERG D. E. , PARKINSON A. J.
Published: March 2006

Background  Limited information exists regarding risk factors for reinfection after cure of Helicobacter pylori infection.

Aim  To determine the 2‐year reinfection rate of H. pylori in a cohort of urban Alaska Natives.

Methods  Participants over 18 years of age undergoing oesophagogastroduodenoscopy had 13C urea breath test, culture, CLOtest and histology performed. Those diagnosed with H. pylori who tested urea breath test‐negative at 8 weeks after treatment were followed prospectively at 4 months, 6 months, 1 year and 2 years. Subjects experiencing H. pylori reinfection as defined by a positive urea breath test were compared with those who did not become reinfected using univariable and multivariable analysis. Risk of reinfection over time was estimated by the Kaplan–Meier method.

Results  Helicobacter pylori reinfection occurred in 14 of 98 subjects successfully treated. The cumulative reinfection rate was 5.1% (95% CI: 0.7%–9.5%) at 4 months, 7.2% (2.0–12.3%) at 6 months, 10.3% (4.2–16.3%) at 1‐year and 14.5% (7.5–21.6%) at 2 years. In multivariable analysis, a history of previous peptic ulcer disease or presence of ulcer at time of study oesophagogastroduodenoscopy were the only risk factors associated with reinfection (P = 0.01).

Conclusions  Based on the findings from our study, subjects with a history of or current peptic ulcer disease should be followed, after successful treatment for H. pylori, with periodic urea breath test to detect reinfection, as reinfection would put them at high risk for ulcer recurrence.
Prokinetic effect of gut‐oriented hypnosis on gastric emptying
Authors: CHIARIONI G. , VANTINI I. , DE IORIO F. , BENINI L.
Published: March 2006

Background  No data are available on the effect of hypnosis on gastric emptying.

Aim  To determine the effect of a hypnosis session on gastric emptying and dyspeptic symptoms.

Methods  We studied emptying by ultrasonography and epigastric sensations in 11 healthy subjects and in 15 patients affected by functional dyspepsia under three conditions according to a fixed schedule: (a) basal, (b) after cisapride and (c) during a 90 min hypnotic trance. Eight healthy subjects repeated an emptying study listening to relaxing music. Statistical analysis was performed using the Friedman test or RM‐anova.

Results  In dyspeptics, the postprandial increase in the antral area was significantly smaller during the hypnosis trance than under the basal and the cisapride conditions. For the patients gastric emptying was significantly shortened by cisapride, and even more by hypnosis (basal 274 ± 16.8 min; cisapride 227 ± 13.2; hypnosis 150 ± 9.7) whereas for healthy subjects it was shortened only by hypnosis. The repeated study in healthy subjects listening to relaxing music showed no significant difference compared with the basal. Epigastric sensations were improved in dyspeptics by hypnosis, but not by cisapride.

Conclusions  Gut‐oriented hypnosis is effective in shortening gastric emptying both in dyspeptic and in healthy subjects.
The usefulness of transabdominal ultrasound for the diagnosis of lower gastrointestinal bleeding
Authors: YAMAGUCHI T. , MANABE N. , HATA J. , TANAKA S. , HARUMA K. , CHAYAMA K.
Published: March 2006

Background  Lower gastrointestinal bleeding is a frequent cause of hospitalization, but diagnostic methods for this condition are not fully established. Transabdominal ultrasound is a widely accepted diagnostic tool in bowel diseases.

Aim  To evaluate the usefulness of transabdominal ultrasound for lower gastrointestinal bleeding.

Methods  We reviewed the medical records of consecutive patients who underwent transabdominal ultrasound as the first diagnostic procedure for acute haematochezia during the period June 1999 to June 2004. The study group comprised 111 patients and all underwent colonoscopy thereafter. Detection and diagnosis of lower gastrointestinal bleeding by ultrasonographic examination were evaluated by comparing the ultrasound diagnosis with the colonoscopic findings and final diagnosis.

Results  The bleeding site was localized by colonoscopy in 90 of the 111 patients (81%). The bleeding site was localized by ultrasound in 59 of the 90 patients (66%). When the bleeding site was in the rectum, ultrasonographic detectability was 30% (10/33); ultrasonographic detectability was 82–100% when the bleeding site was elsewhere. Rectal bleeding and diverticular bleeding were difficult to diagnose by ultrasound, but for the other diseases, diagnosis by ultrasonographic examination was possible in 91–100% of cases.

Conclusions  Ultrasonographic examination may be an effective screening method for lower gastrointestinal bleeding.