bluuebunny/crossref_metadata_2025 huggingface dataset:
A double‐blind randomized controlled trial investigating the effectiveness of topical bupivacaine in reducing distress in children following extractions under general anaesthesia
Authors: GAZAL G. , BOWMAN R. , WORTHINGTON H. V. , MACKIE I. C.
Published: December 2004

Objective.  This study was designed to investigate the effectiveness of topical bupivacaine (0·25%) in reducing postoperative distress following extraction of teeth under general anaesthesia in children.

Design.  The study was a double‐blind randomized controlled trial.

Setting.  The study was conducted in a dental hospital.

Sample.  The sample comprised 135 children aged between 2 and 12 years of age who were undergoing outpatient general anaesthesia for simple dental extractions.

Methods.  The children were randomly allocated to one of two groups: the bupivacaine group (the study group) comprised 68 children whilst the sterile water group (the control group) comprised 67. Following the extraction of their teeth, children had swabs soaked in the appropriate solution placed over the exposed teeth sockets. A five‐point face scale was employed by an independent observer to evaluate the distress for each child. Evaluation of distress was made preoperatively, on recovery from the general anaesthetic, and again, 15 min following recovery from the anaesthetic.

Results.  There were no statistically significant differences between the mean distress scores for the bupivacaine and sterile water groups preoperatively, postoperatively or 15 min postoperatively. For both groups, however, there were significant increases in distress scores between the preoperative and 15 min postoperative assessment scores.

Conclusion.  Extraction of teeth under general anaesthesia does cause distress in children. There is no evidence that topical bupivacaine reduces this distress when compared to sterile water.
A modern pollen–climate calibration set from northern Europe: developing and testing a tool for palaeoclimatological reconstructions
Authors: Seppä Heikki , Birks H. J. B. , Odland Arvid , Poska Anneli , Veski Siim
Published: December 2004

Aims and location The potential of pollen records in quantitative climate reconstructions has been widely debated but seldom tested. Our aim is to develop a pollen–climate transfer function for northern Europe and test its performance and inference power by numerical cross‐validation with modern climate data. Annual mean temperature (Tann) was assessed as the critical climatic variable becauseTannhas a distinct south–north gradient (5.5 to −4.7 °C) in the study region with a corresponding zonal vegetation gradient from the hemiboreal zone in the south to the northern boreal zone in the north.

Methods We collected 137 pollen surface samples from small‐ to medium size lakes from southern Estonia to northern Finland. The transfer function forTannwas developed with weighted averaging partial least squares (WA‐PLS) regression. All 102 terrestrial pollen and spore types were included in the calculation sum and all 137 surface samples and all 102 taxa were included in the transfer function. The performance of the WA‐PLS transfer function was evaluated by leave‐one‐out cross‐validation.

Results A cross‐validated root mean square error of prediction (RMSEP) of our model is 0.89 °C and the coefficient of determination (r2) between the observed meteorologicalTannvalues and those predicted by the model in leave‐one‐out cross‐validation is 0.88. The RMSEP as a percentage of the gradient length ofTannis 8.8%. These figures indicate high performance statistics for our transfer function compared with other inference models. This is probably because of standardization of our surface‐sampling and pollen‐analytical procedures, careful selection of the surface sample sites with consideration of the relevant pollen source area, the simple patterns of vegetation zones and climate in the study area, and the mostly natural floristic composition of the forests in northern Europe. However, we also demonstrate the limitations of our model in reliably detecting fine‐scale climatic variability.

Main conclusions The study shows the strong influence ofTannon modern pollen composition and demonstrates the potential of pollen data for long‐term climate reconstructions in northern Europe. It also provides evidence against simple interpretations of fine‐scale variations in a single climate reconstruction. In particular, our results highlight the importance of careful study design and implementation in the construction of pollen–climate transfer functions.
Trauma and tribulation: the experiences and attitudes of operating room nurses working with organ donors
Authors: Regehr Cheryl , Kjerulf Maria , Popova Svetlana R , Baker Andrew J
Published: December 2004

Background. In the past two decades, significant medical advances have resulted in remarkable success and survival rates for organ recipients. However, the rates of donation have not kept pace with the demand, resulting in a critical shortage of available healthy organs. It has been suggested that the attitudes of medical personnel towards organ retrieval is a key success factor in improving organ donation. Yet there is evidence that those closest to the process of procurement are the most negative.

Aims and objectives. This study sought to examine the attitudes towards organ donation of operating room nurses and their experiences of participating in the procurement of organs for transplant, in order to unravel factors that contribute to their attitudes.

Methods. This study relied upon in‐depth qualitative interviews with 14 operating room nurses who participated in organ procurement in a large urban trauma centre.

Results. The results of this study suggest that the process of organ procurement is highly stressful and raises many concerns for operating room nurses. Factors, which added to participants’ distress, include organizational factors such as strained relationships within surgical teams, concerns about the dignity of the patient and the well‐being of the family and exposure to death and trauma.

Conclusions. Experiences of nurses participating in surgical removal of organs for transplantation resulted in personal feelings of distress and negative attitudes to the issue of organ donation which may be transmitted to others and undermine organ procurement efforts.

Relevance to clinical practice. The concerns of these vital members of the organ procurement team should be heeded and actions taken to reduce their distress and improve their attitudes towards donation.
Kidney transplantation: determination of the problems encountered by Turkish patients and their knowledge and practices on healthy living
Authors: Talas Melek Serpil , Bayraktar Nurhan
Published: December 2004

Background. Although renal transplantations remove many limitations, dialysis can improve quality life in patients with end‐stage renal disease, once transplantation has been performed and the patient has been discharged with a functioning graft, life with a chronic illness continues.

Aims and objectives. This study was carried out to define problems encountered by patients undergoing kidney transplantation and their knowledge and practices on healthy living.

Design. This study was designed as a retrospective and descriptive survey.

Methods. This study was performed on 125 patients who were followed at Social Insurance Institute's Ankara Speciality Hospital Transplantation Clinic between March and August 2001. A convenience sample was drawn from the population of renal transplant patients. A questionnaire was prepared based on the literature, which included patients’ socio‐demographic information, physiological problems, diseases and repeated hospitalizations; side‐effects and usage of immunosuppressive drugs, knowledge and practices of patients regarding healthy living and their knowledge needs. Data were collected through interviews. Percentage and chi‐square test were used in evaluation of the data.

Results. Physiological problems and diseases after renal transplantations were seen such as 38.4% had infections in urinary and respiratory tract. Some had hypertension (22.4%) hypercholesterolaemia (26.5%) and 5.6% had malignancy. Most (67.2%) developed antirejection drugs side‐effects. About 55.2% were admitted to hospital after renal transplantation and 68.8% had not received any training after transplantation from a health professional. Only 35.2% knew the signs and symptoms of rejection entirely or partly. It was determined that 55.2% stated that they avoid sunlight and 56% stated that they exercise regularly. Only 26.8% of female patients do regular breast self‐examination. While 52.8% listed the forbidden foods correctly, only 27.2% could list the forbidden beverages accurately.

Conclusions. According to the results, patients undergoing renal transplantation experience various problems that may influence their quality of life adversely and their knowledge and practice is not adequate for them to continue to lead healthy lives.

Relevance to clinical practice. In accordance with the results of the study, offering continuing education and counselling services, preparing training guides, brochures, video cassettes and CDs for patient education, improving the national web sites to inform the public and creation of a home care system were suggested.
Raised platelet levels in diabetes mellitus complicated with nephropathy
Authors: Sterner G. , Carlson J. , Ekberg G.
Published: December 2004

Abstract. Sterner G, Carlson J, Ekberg G (Malmö University Hospital, Malmö, Sweden). Raised platelet levels in diabetes mellitus complicated with nephropathy. J Intern Med 1998; 244: 437–41.

Objectives To study if elevated platelet levels are found in early and late diabetic nephropathy.

Design A retrospective study was performed of platelet count in different subgroups of patients with insulin‐dependent diabetes mellitus, including patients with long and short duration of diabetes and with early signs of nephropathy. Patients with severe renal failure subjected to renal transplantation were also included.

Results The results suggest that raised platelet levels were associated with early signs of diabetic nephropathy and with female gender. Amongst diabetics progressing to uraemia leading to renal transplant, the platelet level was 50% higher than in non‐diabetic uraemic patients.

Conclusion It is concluded that raised platelet levels are a common finding in patients with diabetes mellitus complicated by nephropathy.
Absorption and urinary excretion of the coffee diterpenes cafestol and kahweol in healthy ileostomy volunteers
Authors: De Roos B. , Meyboom S. , Kosmeijer‐Schuil T. G. , Katan M. B.
Published: December 2004

Abstract. de Roos B, Meyboom S, Kosmeijer‐Schuil TG, Katan MB (Wageningen Agricultural University, Wageningen, The Netherlands). Absorption and urinary excretion of the coffee diterpenes cafestol and kahweol in healthy ileostomy volunteers. J Intern Med 1998; 244: 451–60.

Objectives To determine the absorption and urinary excretion of the cholesterol‐raising coffee diterpenes cafestol and kahweol in humans.

Subjects and design Nine healthy ileostomists consumed a dose of one, two or three cups of French‐press coffee together with a standardized breakfast on three separate days in random order. Subsequently, ileostomy effluent was collected for 14 h and urine for 24 h. Stability of cafestol and kahweol was also assessed under simulated gastrointestinal tract conditions.

Main outcome measures Absorption of diterpenes, stability of diterpenes during incubation with gastrointestinal fluids, and urinary excretion of diterpenes.

Results Corrected mean absorptions expressed as percentages of the amount consumed and the amount entering the duodenum were 67 and 88%, respectively, for cafestol, and 72 and 93%, respectively, for kahweol. We found losses of diterpenes during incubation in vitro with gastric juice (cafestol, 24%; kahweol, 32%), during storage with ileostomy effluent (cafestol, 18%; kahweol, 12%), and during freeze‐drying (cafestol, 26%; kahweol, 32%). Mean excretion of glucuronidated plus sulphated conjugates in urine was 1.2% of the ingested amount for cafestol and 0.4% of the ingested amount for kahweol.

Conclusions About 70% of the ingested cafestol and kahweol is absorbed in ileostomy volunteers. Possibly, undetected metabolites are present in ileostomy effluent, resulting in lower absorption percentages. Only a small part of the diterpenes is excreted as a conjugate of glucuronic acid or sulphate in urine. Therefore, these compounds are extensively metabolized in the human body.
Endocrine manifestations of Erdheim–Chester disease (a distinct form of histiocytosis)
Authors: Tritos N. A. , Tritos N. A. , Weinrib S. , Kaye T. B
Published: December 2004

Abstract. Tritos NA, Weinrib S, Kaye TB (Lahey Hitchcock Clinic, Burlington; Beth Israel Deaconess Medical Center, Boston; and Joslin Diabetes Center, Boston, Massachusetts, USA). Endocrine manifestations of Erdheim–Chester disease (a distinct form of histiocytosis) (Case Report). J Intern Med 1998; 244: 529–35.

Erdheim–Chester disease (ECD) is a disorder of unclear aetiology, characterized by exuberant histiocyte proliferation and a variable clinical course. We report the case of a woman with multi‐organ involvement secondary to ECD. Central diabetes insipidus (CDI), hyperprolactinaemia, gonadotropin insufficiency and decreased insulin‐like growth factor I levels were present, suggesting hypothalamic–pituitary dysfunction. The high‐intensity signal of the posterior pituitary on T1‐weighted images was absent on magnetic resonance imaging, but no sellar mass lesions or stalk thickening were apparent. Additionally, our patient had bilateral adrenal enlargement. Even though ECD is a rare cause of neuroendocrine dysfunction or adrenal enlargement, it should be considered in patients with these disorders in the setting of multiorgan disease.
Early participation in an HIV cohort study slows disease progression and improves survival
Authors: Battegay M. , Wirz M. , Steuerwald M. H. , Egger M. , Egger M.
Published: December 2004

Battegay M, Wirz M, Steuerwald MH, Egger M, Swiss HIV Cohort Study (University Hospital of Basel, Basel, University of Berne, Berne, and University of Lausanne, Lausanne, Switzerland; and University of Bristol, Bristol, UK). Early participation in an HIV cohort study slows disease progression and improves survival. J Intern Med 1998; 244: 479–87.

Background Different levels of experience of physicians caring for patients with HIV infection have been found to be associated with differences in survival amongst their patients. We examined whether early participation in the Swiss HIV Cohort Study (SHCS), an ongoing prospective study with regular follow‐up visits at specialized clinics, improved survival of HIV‐infected patients.

Methods We studied 3553 HIV‐infected individuals who joined the Swiss HIV Cohort Study (SHCS) with different levels of immunosuppression: mild (CD4 count above 500 × 106 cells L−1; n × 2038); severe (100–199 cells; n = 960); and very severe (50–99 cells; n = 555). Characteristics at different CD4 cell levels were compared and Cox proportional hazards regression was used to examine the mortality experience during a total of 16 201 person‐years of follow‐up.

Results Participants joining the cohort early with mild immunodeficiency were younger, more likely to be female, and more likely to have a history of intravenous drug use. At CD4 cell counts below 200 × 106 cells L−1, they were less likely to have a history of Pneumocystis carinii pneumonia or AIDS, more likely to be on prophylaxis against P. carinii and more likely to be on antiretroviral therapy than those joining with severe or very severe immunodeficiency. For example, at the time of the first CD4 cell count in the range of 50–99 × 106 cells L−1, 8.9, 15.0 and 21.6% of participants who joined with mild, severe and very severe immunodeficiency had suffered an episode of P. carinii pneumonia. In Cox models adjusted for CD4 cell count at entry and other relevant baseline differences, mortality was increased amongst participants who joined with severe and very severe immunodeficiency. Hazard ratios (95% confidence intervals (CI)) were 1.71 (1.21–2.42) for participants with severe immunodeficiency at entry and 2.61 (1.70–4.01) for those with very severe immunodeficiency, compared with 1.0 for those with mild immunodeficiency at entry.

Conclusions Individuals who were seen regularly at specialized HIV units from early stages of the infection onwards were, at comparable levels of immunodeficiency, less likely to progress to AIDS, and mortality during subsequent follow‐up was reduced. This is likely to be explained by better access to prophylactic regimens and antiretroviral therapy.
Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function
Authors: Müller S. , Ronfani L. , Bianchi M. E.
Published: December 2004

High mobility group box protein 1 (HMGB1) has been considered as a ubiquitous nuclear protein with an architectural function, but even early reports have described its presence outside of the nucleus. Today, we have only started to understand the extranuclear and extracellular functions of HMGB1: we know that it participates in developmental and differentiation processes, triggers and modulates many of the inflammatory cascades in the body, and may even be involved in the metastatic invasion programme of cancer cells. Given such diverse roles, it is important to know which cells express HMGB1, where, and how much. The present review deals with the expression pattern of HMGB1 and provides evidence that, far from being housekeeping, the HMGB1 gene is tightly regulated. This can have implications for therapeutic intervention on inflammatory diseases as well as cancer.
Mating system and population structure of the primitively eusocial waspRopalidia revolutionalis: a model system for the evolution of complex societies
Authors: Henshaw Michael T. , Crozier Ross H.
Published: December 2004

Mating systems are important determinants of genetic structure in cooperative groups, and their effects can influence profoundly the interactions of group members. The primitively eusocial wasp,Ropalidia revolutionalis, has an interesting genetic and social structure that makes it an excellent model system for examining the evolution of more complex societies. In particular, its colonies sometimes have multiple queens, a key characteristic of more advanced wasp societies. In this study, we have characterized the mating system of the social waspRopalidia revolutionalisto understand better its colony genetic structure.R. revolutionalisfemales nearly always mate singly and they are unrelated to their mates. However, different females in the same colony do mate with males, on average, who are related as cousins. Single mating will help to maintain high relatedness, which should be important for continued cooperation in multiple queen societies, but it creates potential conflicts in single queen colonies over the production of males as well as over the timing of male production. We have also characterized the population structure ofR. revolutionalisfrom Townsville, in tropical north Queensland, to Brisbane in the subtropics. Even at such a large scale, the population is remarkably unstructured with an averageFSTof 0.0546. There is weak isolation by distance, and evidence for subtle differentiation between a southern region with no dry season, which extends as far north as Rockhampton, and a northern region with a severe to moderate dry season. This may reflect historical effects of extreme aridity on the population structure.
Geographic genetic architecture of pocket gopher (Thomomys bottae) populations in Baja California, Mexico
Authors: ALVAREZ‐CASTAÑEDA SERGIO TICUL , PATTON JAMES L.
Published: December 2004

Phylogenetic analyses of complete mitochondrial cytochrome b sequences support the monophyly of pocket gopher (Thomomys bottae) populations from the 1000 km length of the Baja California peninsula of Mexico, relative to other geographical segments of the species range in western North America. The Baja California peninsula is an area that encompasses considerable ecomorphological and infraspecific diversity within this pocket gopher species. However, detailed population analyses encompassing 35 localities distributed over the southern half of the peninsula reveal only trivial phylogeographical structure. Rather, most of the 72 unique 500‐base pair haplotypes examined from 142 individuals is restricted to single populations, although a few haplotypes are shared broadly across geography. Individual populations are typically comprised of haplotype sets from different branches in a network of relationships. Analysis of molecular variance (amova) indicates that approximately half of the total pool of variation is contained among individuals within local populations, and that only about 25% can be explained by the regional subdivisions of current subspecies distributions or physiographic realms. A hypothesized historical vicariant event that has been causally linked to the phylogeographical structure of other, codistributed species has had little influence on these pocket gopher populations, explaining only 13% of the total variation. The temporal depth, estimated by coalescence parameters, of the haplotype lineage in Baja California is relatively recent, approximately 300 000 generations; both the mismatch distribution of pairwise comparisons and a significantly positive exponential growth estimate support a recent history of expanding populations; but current, or recent past, migration estimates have remained small, are largely unidirectional from north to south, and weak isolation by distance is present. All data suggest that pocket gophers have relatively recently invaded the southern half of peninsular Baja California, with the genetic signature of expansion still evident but with sufficient time having lapsed to result in a weak isolation by distance pattern. The geographical assemblage of sampled populations thus appears as a meta‐population, with limited gene flow contrasting with random haplotype loss due to drift in small, localized populations.
Microsatellite and mitochondrial DNA analyses of Atlantic bluefin tuna (Thunnus thynnus thynnus) population structure in the Mediterranean Sea
Authors: CARLSSON JENS , McDOWELL JAN R. , DÍAZ‐JAIMES PÍNDARO , CARLSSON JEANETTE E. L. , BOLES SANDRA B. , GOLD JOHN R. , GRAVES JOHN E.
Published: December 2004

Genetic variation was surveyed at nine microsatellite loci and the mitochondrial control region (868 bp) to test for the presence of genetic stock structure in young‐of‐the‐year Atlantic bluefin tuna (Thunnus thynnus thynnus) from the Mediterranean Sea. Bluefin tuna were sampled over a period of 5 years from the Balearic and Tyrrhenian seas in the western basin of the Mediterranean Sea, and from the southern Ionian Sea in the eastern basin of the Mediterranean Sea. Analyses of multilocus microsatellite genotypes and mitochondrial control region sequences revealed no significant heterogeneity among collections taken from the same location in different years; however, significant spatial genetic heterogeneity was observed across all samples for both microsatellite markers and mitochondrial control region sequences (FST = 0.0023, P = 0.038 and ΦST = 0.0233, P = 0.000, respectively). Significant genetic differentiation between the Tyrrhenian and Ionian collections was found for both microsatellite and mitochondrial markers (FST = 0.0087, P = 0.015 and ΦST = 0.0367, P = 0.030, respectively). These results suggest the possibility of a genetically discrete population in the eastern basin of the Mediterranean Sea.
Expression of the INO2 regulatory gene of Saccharomyces cerevisiae is controlled by positive and negative promoter elements and an upstream open reading frame
Authors: Eiznhamer David A. , Ashburner Brian P. , Jackson John C. , Gardenour Kyle R. , Lopes John M.
Published: December 2004

The INO2 gene encodes a transcriptional activator of the phospholipid biosynthetic genes of Saccharomyces cerevisiae. Complete derepression of phospholipid biosynthetic gene expression in response to inositol/choline deprivation requires both INO2 and INO4. Ino2p dimerizes with Ino4p to bind the upstream activating sequence (UAS)INO element found in the promoters of the target genes. We have demonstrated previously that transcription from the INO2 promoter is autoregulated 12‐fold in a manner identical to that of the target genes. Here, we show that this regulation occurs at the levels of transcription and translation. Transcription accounts for fourfold regulation, whereas translation accounts for an additional threefold regulation. Regulation of transcription requires a UASINO element. Additional promoter elements include an upstream essential sequence (UES) located upstream of the UASINO element and a negative regulatory element in the vicinity of the UASINO element. Regulation of translation is dependent on an upstream open reading frame (uORF) in the INO2 leader. These data support the model that regulatory gene promoters may display unusual organizations and may be subject to multiple levels of regulation. We have shown previously that the UME6 gene positively regulates INO2 expression. Here, we limit the UME6‐responsive region of the INO2 promoter to nucleotides −217 to −56.
Switching the polarity of a bacteriophage integration system
Authors: Smith Matthew C. A. , Till Rob , Smith Margaret C. M.
Published: December 2004

During lysogenic growth many temperate bacteriophage genomes are integrated into the host's chromosome and efficient integration and excision are therefore an essential part of the phage life cycle. The Streptomyces phage φC31 encodes an integrase related to the resolvase/invertases and is evolutionarily and mechanistically distinct from the integrase of phage λ. We show that during φC31 integration the polarity of the recombination sites, attB and attP, is dependent on the sequences of the two base pairs (bp) where crossover occurs. A loss or switch in polarity of the recombination sites can occur by mutation of this dinucleotide, leading to incorrectly joined products. The properties of the mutant sites implies that φC31 integrase interacts symmetrically with the substrates, which during synapsis can align apparently freely in either of two alternative forms that lead to correct or incorrect joining of products. Analysis of the topologies of the reaction products provided evidence that integrase can synapse and activate strand exchange even when recombinant products cannot form due to mismatches at the crossover site. The topologies of the recombination products are complex and indicative of multiple pathways to product formation. The efficiency of integration of a φC31 derivative, KC859, into an attB site with switched polarity was assayed in vivo and shown to be no different from integration into a wild‐type attB. Thus neither the host nor KC859 express a factor that influences the alignment of the recombination sites at synapsis.
Blue light stimulates cyanobacterial motility via a cAMP signal transduction system
Authors: Terauchi Kazuki , Ohmori Masayuki
Published: December 2004

The participation of cAMP in photosignal transduction in cyanobacteria was investigated. When cells of the cyanobacterium Synechocystis sp. PCC 6803 were exposed to light, cellular cAMP contents increased within a few minutes. Among incident monochromatic lights, blue light (450 nm) markedly increased cellular cAMP content, while red (630 nm) and far‐red (720 nm) lights did not. Disruption of the cya1 gene encoding an adenylate cyclase caused the insensitivity of cellular cAMP level to blue light. Treatment of wild‐type cells with the flavin antagonist phenylacetic acid inhibited this blue light effect. The motility of wild‐type cells was enhanced by blue light, whereas that of cya1 mutant cells was not. Based on these results, we concluded that a blue light–cAMP signal transduction system stimulates the motility of Synechocystis sp. PCC 6803.
Conjugation mediates transfer of the Ll.LtrB group II intron between different bacterial species
Authors: Belhocine Kamila , Plante Isabelle , Cousineau Benoit
Published: December 2004

Some self‐splicing group II introns (ribozymes) are mobile retroelements. These retroelements, which can insert themselves into cognate intronless alleles or ectopic sites by reverse splicing, are thought to be the evolutionary progenitors of the widely distributed eukaryotic spliceosomal introns. Lateral or horizontal transmission of introns (i.e. between species), although never experimentally demonstrated, is a well‐accepted model for intron dispersal and evolution. Horizontal transfer of the ancestral bacterial group II introns may have contributed to the dispersal and wide distribution of spliceosomal introns present in modern eukaryotic genomes. Here, the Ll.LtrB group II intron from the Gram‐positive bacterium Lactococcus lactis was used as a model system to address the dissemination of introns in the bacterial kingdom. We report the first experimental demonstration of horizontal transfer of a group II intron. We show that the Ll.LtrB group II intron, originally discovered on an L. lactis conjugative plasmid (pRS01) and within a chromosomally located sex factor in L. lactis 712, invades new sites using both retrohoming and retrotransposition pathways after its transfer by conjugation. Ll.LtrB lateral transfer is shown among different L. lactis strains (intraspecies) (retrohoming and retrotransposition) and between L. lactis and Enterococcus faecalis (interspecies) (retrohoming). These results shed light on long‐standing questions about intron evolution and propagation, and demonstrate that conjugation is one of the mechanisms by which group II introns are, and probably were, broadly disseminated between widely diverged organisms.
Secretory protein trafficking in Giardia intestinalis
Authors: Hehl Adrian B. , Marti Matthias
Published: December 2004

Early diverged extant organisms, which may serve as convenient laboratory models to look for and study evolutionary ancient features of eukaryotic cell biology, are rare. The diplomonad Giardia intestinalis, a protozoan parasite known to cause diarrhoeal disease, has become an increasingly popular object of basic research in cell biology, not least because of a genome sequencing project nearing completion. Commensurate with its phylogenetic status, the Giardia trophozoite has a very basic secretory system and even lacks hallmark structures such as a morphologically identifiable Golgi apparatus. The cell's capacity for protein sorting is nevertheless unimpeded, exemplified by its ability to cope with massive amounts of newly synthesized cyst wall proteins and glycans, which are sorted to dedicated Golgi‐like compartments termed encystation‐specific vesicles (ESVs) generated from endoplasmic reticulum (ER)‐derived transport intermediates. This soluble bulk cargo is kept strictly separate from constitutively transported variant surface proteins during export, a function that is dependent on the stage‐specific recognition of trafficking signals. Encysting Giardia therefore provide a unique system for the study of unconventional, Golgi‐independent protein trafficking mechanisms in the broader context of eukaryotic endomembrane organization and evolution.
Inventory and functional analysis of the large Hrp regulon in Ralstonia solanacearum: identification of novel effector proteins translocated to plant host cells through the type III secretion system
Authors: Cunnac Sébastien , Occhialini Alessandra , Barberis Patrick , Boucher Christian , Genin Stéphane
Published: December 2004

The ability of Ralstonia solanacearum strain GMI1000 to cause disease on a wide range of host plants (including most Solanaceae and Arabidopsis thaliana) depends on genes activated by the regulatory gene hrpB. HrpB controls the expression of the type III secretion system (TTSS) and pathogenicity effectors transiting through this pathway. In order to establish the complete repertoire of TTSS‐dependent effectors belonging to the Hrp regulon and to start their functional analysis, we developed a rapid method for insertional mutagenesis, which was used to monitor the expression of 71 candidate genes and disrupt 56 of them. This analysis yielded a total of 48 novel hrpB‐regulated genes. Using the Bordetella pertussis calmodulin‐dependent adenylate cyclase reporter fusion system, we provide direct biochemical evidence that five R. solanacearum effector proteins are translocated into plant host cells through the TTSS. Among these novel TTSS effectors, RipA and RipG both belong to multigenic families, RipG defining a novel class of leucine‐rich‐repeats harbouring proteins. The members of these multigenic families are differentially regulated, being composed of genes expressed in either an hrpB‐dependent or an hrpB‐independent manner. Pathogenicity assays of the 56 mutant strains on two host plants indicate that, with two exceptions, mutations in individual effectors have no effect on virulence, a probable consequence of genetic and functional redundancy. This large repertoire of HrpB‐regulated genes, which comprises > 20 probable TTSS effector genes with no counterparts in other bacterial species, represents an important step towards a full‐genome understanding of R. solanacearum virulence.
Hypoxia‐inducible factor 1α/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis
Authors: Korkolopoulou P. , Patsouris E. , Konstantinidou A. E. , Pavlopoulos P. M. , Kavantzas N. , Boviatsis E. , Thymara I. , Perdiki M. , Thomas‐Tsagli E. , Angelidakis D. , Rologis D. , Sakkas D.
Published: December 2004

Hypoxia‐inducible factor (HIF)‐1α is a transcription factor that promotes ischaemia‐driven angiogenesis. The aim of this study was to determine the relation of HIF‐1α to vascular endothelial growth factor (VEGF; an important angiogenic molecule in brain tumours), p53 expression, angiogenesis, proliferative potential and clinical outcome in a large series of diffuse astrocytomas. Expression of HIF‐1α, VEGF, Ki‐67 (a proliferation‐associated marker) and p53 was determined immunohistochemically in 83 adult patients with supratentorial diffuse astrocytomas. Microvessels, highlighted by means of anti‐CD34 immunohistochemistry, were enumerated with computer‐assisted image analysis. Although HIF‐1α and VEGF were expressed in the majority of cases, their levels increased significantly with increasing grade and proliferative potential. HIF‐1α positively correlated with microvessel counts and VEGF with total vascular area and the presence of rounder vessel sections. There was a positive correlation of VEGF with p53 expression in astrocytomas and anaplastic astrocytomas. In univariate analysis, both VEGF and HIF‐1α were associated with shortened survival in the entire cohort, but lost significance when grades II/III and grade IV were analysed separately. Multivariate analysis revealed that the combination of HIF‐1α with grade was a significant prognostic indicator. HIF‐1α expression may be used to refine the prognostic information provided by grade in patients with diffuse astrocytomas. Its adverse prognostic effect is most likely mediated by hypoxia, the driving force for HIF‐1α accumulation.
Why has the Stability and Growth Pact Failed?
Authors: De Haan Jakob , Berger Helge , Jansen David‐Jan
Published: December 2004

This paper evaluates the Stability and Growth Pact. After briefly examining the rules in place and the experience so far, the Pact is analysed from a political economy perspective, focusing on the choice of hard versus soft law and drawing inferences from characteristics of successful fiscal rules at the state level in the USA. The main argument of the paper is that the Pact's enforcement mechanisms are too weak. It is also argued that big countries are less likely to adhere to the fiscal policy rules in place. Reform of the Pact should aim at stricter, instead of more flexible, rules and should not rely on cyclically adjusted deficit estimates.
On the Relationship Between Short‐ and Long‐term Interest Rates*
Authors: Kobayashi Teruyoshi
Published: December 2004

This paper addresses issues regarding the relationship between short‐ and long‐term interest rates. In the real world, an expansionary (contractionary) policy is normally followed by a fall (rise) in long‐term rates. However, there exist exceptional cases in which short‐ and long‐term rates move in opposite directions. This paper attempts to provide a formal explanation for such unusual phenomena using a variety of new Keynesian models. It turns out that the simultaneous occurrence of different economic shocks, to which the central bank should react, can explain this behaviour of long rates.
Creola bodies in wheezing infants predict the development of asthma
Authors: Yamada Yumi , Yoshihara Shigemi , Arisaka Osamu
Published: December 2004

Creola bodies (CrBs) have been shown to be present specifically in the sputum of adults with asthma, and are clinically useful in the estimation of airway hyper‐responsiveness through correlation with the levels of eosinophil cationic protein in the sputum. Our aim was to investigate whether CrBs can be detected in the sputum of wheezing infants, and the clinical significance of CrBs in wheezing infants in the development of asthma. Twenty‐three wheezing infant patients, mean age 5.3 months, were studied. The presence of CrBs in the sputum was determined by Papanicolau's stain. The patients were divided into two groups: CrB positive [CrB(+)] and CrB negative [CrB(−)]. In addition, we examined the relationship between the presence of CrBs and the asthma symptom scores that occurred during a 1‐month post‐discharge period. The following results were obtained: (i) CrBs were detected in 15 of 23 (65%) wheezing infants; (ii) the asthma symptom scores after discharge was significantly higher in the CrB(+) group than in the CrB(−) group (p < 0.001); (iii) in the infants experiencing their first episode of wheezing, the asthma symptom scores during the post‐discharge period was also significantly higher in the CrB(+) group than in the CrB(−) group (p < 0.05). Furthermore, infantile asthma was diagnosed in 12 (80.0%) infants in the CrB(+) group during the following 2‐yr period, but none in the CrB(−) group. These findings suggest that CrBs detected in the sputum of wheezing infants may be used to identify the progression to infantile asthma.
Red & black or black & white? Phylogeny of the Araschnia butterflies (Lepidoptera: Nymphalidae) and evolution of seasonal polyphenism
Authors: Fric Z. , Konvicka M. , Zrzavy J.
Published: December 2004

Phylogeny of the butterfly genera Araschnia, Mynes, Symbrenthia and Brensymthia (Lepidoptera: Nymphalidae: Nymphalini) is reconstructed, based on 140 morphological and ecological characters. The resulting tree shows that Araschnia is a sister group of the clade including Symbrenthia, Mynes and Brensymthia (Symbrenthia is paraphyletic in the respect of remaining genera; Symbrenthia hippalus is a derived species of Mynes). The species-level relationships within Araschnia are robustly supported as follows: (A. davidis (prorsoides ((zhangi doris) (dohertyi (levana burejana))))). Analysis of the wing colour-pattern characters linked with the seasonal polyphenism in the Araschnia species suggests that the black and white coloration of the long-day (summer) generation is apomorphic. Biogeographically, the origin of polyphenism in Araschnia predates the dispersal of some Araschnia species towards the Palaearctic temperate zone, and the ecological cause of the polyphenism itself is then probably not linked with thermoregulation. The possible mimetic/cryptic scenarios for the origin of Araschnia polyphenism are discussed.
Evolutionary mode, tempo, and phylogenetic association of continuous morphological traits in the aquatic moss genusAmblystegium
Authors: Vanderpoorten A. , Jacquemart A.-L.
Published: December 2004

Evolutionary significance of morphological characters that have traditionally been used for species delineation in the aquatic moss genus Amblystegium was tested by partitioning the environmentally and genetically induced morphological variation and focusing on morphological evolution using comparative methods. Cultivation experiments under controlled condition showed that most of the morphological variation in nature resulted from plasticity. Information regarding genetically fixed morphological variation and genetic similarity derived from polymorphic inter-simple sequence repeat markers was combined into an explicit model of morphological evolution. Maximum likelihood estimates of the model parameters indicated that evolution of most characters tended to accelerate in the most recent taxa and was often independent from the phylogeny. Constraining the different characters to be independent from each other most often produced a less likely result than when the characters were free to evolve in a correlated fashion. Thus, the morphological characters that have traditionally been used to circumscribe different Amblystegium species lack the independence, diagnostic value for specific lineages, and stability that would be required for distinguishing different species.
Conclusions and Activities of Previous Expert Groups: The Scientific Steering Committee of the EU
Authors: Fries R.
Published: December 2004

In 1998, the EU Commission consulted its Scientific Steering Committee (SSC) to give advice on actions against anti‐microbial resistance based on scientific evidence. The SSC set up a working group and adopted in 1999 an Opinion on Antimicrobial Resistance. Statements given in the well‐structured document are clear, and precise recommendations were proposed. Summarizing, the Committee stated: There is evidence to suppose a continuous flow of resistance genes between pathogenic and commensal bacteria and of transfer of these bacteria between different compartments of the biosphere, thus changing the genetic resources continuously. There exist numerous factors which influence the emergence and spread of anti‐bacterial resistance. However, it is likely that restriction in the use of anti‐microbials will lead to a containment or a reduction of the drug resistance problem. Actions should be taken promptly to reduce the overall use of anti‐microbials in a balanced way in all areas: human medicine, veterinary medicine, animal production and plant protection.
Expression of cyclooxygenase‐2 (COX‐2) in human esophageal cancer and in vitro inhibition by a specific COX‐2 inhibitor, NS‐398
Authors: YU HONG‐PING , SHI LU‐YUAN , LU WEN‐HONG , SU YAN‐HUA , LI YUAN‐YUAN , XU SHUN‐QING
Published: December 2004

Background:  The purpose of the present paper was to study the expression of cyclooxygenase‐2 (COX‐2) in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX‐2 in esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a COX‐2 inhibitor, NS‐398, in inducing growth inhibition and apoptosis of human esophageal cancer cells.

Methods:  Biopsy specimens of esophageal dysplasia (n = 21), and surgical resections of SCC (n = 37) were compared with normal esophagus (n = 37) and analyzed by RT‐PCR. Human esophageal cells were used for the study. Anti‐proliferative effect was measured by MTT, apoptosis was determined by DNA fragmentation assay.

Results:  Marked COX‐2 expression was shown in SCC and esophageal squamous dysplasia, and no marked COX‐2 expression was observed in the normal squamous epithelium, respectively. NS‐398 could inhibit esophageal cells growth in a dose‐dependent manner, induce apoptosis, and elevate caspase‐3 activity in vitro.

Conclusions:  This study provides evidence that COX‐2 is upregulated in the majority of cases of squamous dysplasia and SCC of esophagus, and that NS‐398 can inhibit growth and induce apoptosis via activating caspase‐3 activity in vitro. These results suggest that selective inhibitors of COX‐2 may be an effective preventive and therapeutic option for esophageal carcinoma.
Efficacy of electrolyzed acid water in reprocessing patient‐used flexible upper endoscopes: Comparison with 2% alkaline glutaraldehyde
Authors: LEE JUN HAENG , RHEE POONG‐LYUL , KIM JEONG HWAN , KIM JAE J , PAIK SEUNG WOON , RHEE JONG CHUL , SONG JAE‐HOON , YEOM JOON SUP , LEE NAM YONG
Published: December 2004

Background and Aim:  Two percent glutaraldehyde, the most widely used liquid chemical germicide (LCG), may be hazardous to patients and medical personnel. Alternatives to glutaraldehyde, such as electrolyzed acid water (EAW), are being developed, but data from well‐controlled studies with patient‐used endoscopes are rare. The purpose of the present paper was to evaluate the high‐level disinfection capability of EAW and compare it with glutaraldehyde.

Methods:  A random sample of 125 endoscopes was collected immediately after upper endoscopic examination. After careful manual cleaning, endoscopes were divided into a glutaraldehyde and EAW group. After the disinfection procedure, samples from working channel (S‐1), insertion tube (S‐2), umbilical cord (S‐3), and angulation knob (S‐4) were taken and cultured. Another twenty endoscopes were experimentally contaminated with hepatitis B virus (HBV) and samples were collected after contamination (T‐1), after manual cleaning (T‐2), and after final disinfection (T‐3). Polymerase chain reaction (PCR) for HBV‐DNA was performed.

Results:  In the EAW group, culture‐positive rates were 3.2% in S‐1, 9.5% in S‐2, 3.2% in S‐3, and 27.0% in the S‐4 samples. There was no significant difference between the EAW and glutaraldehyde groups for all sampling sites. However, in both groups, disinfection of the angulation knobs (S‐4) was less efficient than the others. For the T‐1 site, HBV‐DNA was detected from all of them, and in 95% (19/20) of T‐2. However, HBV‐DNA was not detected from T‐3 samples.

Conclusions:  Electrolyzed acid water is as efficient as glutaraldehyde in eliminating bacteria from patient‐used endoscopes. After disinfection procedures using both methods, HBV‐DNA was not detected from any endoscopes experimentally contaminated with HBV‐positive mixed sera. However, some bacteria may remain on the surface of the endoscopes. Therefore, more careful precleaning of the endoscopes may help achieve high‐level disinfection in the clinical setting.
Small renal oncocytoma with central cystic degeneration
Authors: KODAMA KOICHI , NAGANO KEN‐ICHI , AKIMOTO MANABU , SUZUKI SHIOTO
Published: December 2004

Abstract  A case of a small renal oncocytoma with central cystic degeneration, 15 mm in diameter, is reported. Contrast‐enhanced computed tomography showed the tumor contained a central hypoattenuating region and had an irregular, heterogeneously enhanced wall. Magnetic resonance images showed a well‐circumscribed lesion and the T1‐weighted image indicated medium signal intensity, whereas the T2‐weighted image indicated slight hypointensity. Both T1‐ and T2‐weighted images showed central hyperintensity. Our preoperative diagnosis was renal cell carcinoma originating in a renal cyst wall or cystic renal cell carcinoma. Nephrectomy was performed because frozen‐section examination did not completely rule out malignancy. The final pathological diagnosis of the entire surgical specimen was renal oncocytoma with cystic degeneration. To our knowledge, this is the 14th case of renal oncocytoma with central cystic degeneration reported in the published works. We discuss herein the variant forms of oncocytoma and difficulties with their preoperative diagnosis, especially when the tumor is small.