bluuebunny/crossref_metadata_2025 huggingface dataset:
Least squares inversion of self‐potential (SP) data and application to the shallow flow of ground water in sinkholes
Authors: Jardani A. , Revil A. , Akoa F. , Schmutz M. , Florsch N. , Dupont J. P.
Published: October 2006

We propose a least squares inversion algorithm to determine the spatially variable depth of the water table in shallow unconfined aquifers using self‐potential signals measured on the ground surface. Traditionally, the water table is determined only at few locations using piezometers. Our approach relates its shape with the distribution of the self‐potential signals according to a Fredholm equation of the first kind. The latter is discretized to obtain a linear matrix formulation of the forward problem. This new formulation is very general and can account for the resistivity distribution of the vadose zone. It is used to setup the inverse problem using the approach of Tarantola (1987) for a test site located in Normandy (France) where 225 self‐potential measurements were performed over an area of 15,400 m2. Ground water flows through the loess overlying a low permeability clay‐with‐flint weathered chalk, at a depth between 1 to 7 meters, into sinkholes in chalk bedrock. The method determines the water table with a precision of 0.4 m.
A Rabbit Langendorff Heart Proarrhythmia Model: Predictive Value for Clinical Identification of Torsades de Pointes
Authors: Lawrence C L , Bridgland‐Taylor M H , Pollard C E , Hammond T G , Valentin J‐P
Published: October 2006

Background and purpose:

The rabbit isolated Langendorff heart model (SCREENIT) was used to investigate the proarrhythmic potential of a range of marketed drugs or drugs intended for market. These data were used to validate the SCREENIT model against clinical outcomes.

Experimental approach:

Fifty‐five drugs, 3 replicates and 2 controls were tested in a blinded manner. Proarrhythmia variables included a 10% change in MAPD60, triangulation, instability and reverse frequency‐dependence of the MAP. Early after‐depolarisations, ventricular tachycardia, TdP and ventricular fibrillation were noted. Data are reported at nominal concentrations relative to EFTPCmax. Proarrhythmic scores were assigned to each drug and each drug category.

Key results:

Category 1 and 2 drugs have the highest number of proarrhythmia variables and overt proarrhythmia while Category 5 drugs have the lowest, at every margin. At 30‐fold the EFTPCmax, the mean proarrhythmic scores are: Category 1, 101±24; Category 2, 101±14; Category 3, 72±20; Category 4, 59±16 and Category 5, 22±9 points. Only drugs in Category 5 have mean proarrhythmic scores, below 30‐fold, that remain within the Safety Zone.

Conclusions and Implications:

A 30‐fold margin between effects and EFTPCmax is sufficiently stringent to provide confidence to proceed with a new chemical entity, without incurring the risk of eliminating potentially beneficial drugs. The model is particularly useful where compounds have small margins between the hERG IC50 and predicted EFTPCmax. These data suggest this is a robust and reliable assay that can add value to an integrated QT/TdP risk assessment.

British Journal of Pharmacology (2006) 149, 845–860. doi:10.1038/sj.bjp.0706894
Scenarios of Poiesis: Italian New Media (1994–2004)
Authors: Campbell Timothy C.
Published: October 2006

This essay attempts to read a number of interventions in Italian new media over the last decade as both a response to and an implicit critique of posthumanism. After a brief discussion of the principal terms in question—new media, interaction, and posthumanism—and a survey of the most important contributors to the discourse of posthumanism in Italy, the essay maps the principal features of Italian media as embodied by the works of three contemporary new media artists. These characteristics include the privileging of a prosthetic model for understanding interaction and more generally the staging of interaction as moments ofpoiesis. They also include more recently the cancellation of the boundaries between ‘scientific’ and cultural images. The essay insists that by foregrounding the primacy of Italian cultural patterns for determining how meaning is generated in new media, Italian new media artists implicitly critique a reifying tendency among posthuman observers in Italy. The essay concludes with a broad assessment of the importance of poiesis for an Italian technological imaginary.
Autonomia and the Political: An Italian Cycle of Contention, 1972–1979
Authors: Edwards Philip
Published: October 2006

Sidney Tarrow has identified a ‘cycle of contention’ taking place in Italy between 1966 and 1972; Tarrow characterises the left-wing terrorism of the late 1970s as an after-effect of this cycle. However, there was a second cycle of contention between 1972 and 1979, incorporating the left-wing ‘armed struggle’ milieu alongside a group of related mass movements (notably the ‘area of Autonomia’, the ‘movement of 1977’ and the ‘proletarian youth movement’). The second cycle, unlike the first, was met with repression, and with the exclusion of its ideological and tactical innovations from the political mainstream. The difference between the two cycles relates to the role played by the Italian Communist Party, which functioned as a ‘gatekeeper’ in each case; the party's engagement with the first cycle can be characterised as inclusive, while its engagement with the second cycle was unremittingly exclusive.
‘Neither Fish nor Fowl’? The Correspondence of Lorenzo Valerio, 1825–1849
Authors: Thom Martin
Published: October 2006

Lorenzo Valerio (1810–1865), though a key figure in Piedmontese and Italian politics, a newspaper editor of note and a leading light of both the Associazione Agraria and the Associazione Italo-Slava, has not been accorded in recent years the attention he merits. With the publication, however, of the first four volumes of his correspondence, it is now possible to map more precisely Valerio's activities and influence, in Risorgimento Italy and far beyond it. These letters provide their principal editor, Adriano Viarengo, with the opportunity to review a number of crucial historiographical questions in Risorgimento scholarship, among them, the nature of moderate hegemony, the political vision of the Sinistra subalpina, and the complex relations between Italian patriots and Slav Romantic nationalists active within the Austrian Empire. This article is designed both to portray Valerio and his world, and to reflect upon the contribution Viarengo has made, whether in his introductions to the correspondence or in his ancillary essays, to the study of the Risorgimento.

‘… a good enough sort, but neither fish nor fowl …’ Giuseppe Mazzini [Letter, 6 March 1851, to his mother]
Transient anchorage of cross-linked glycosyl-phosphatidylinositol–anchored proteins depends on cholesterol, Src family kinases, caveolin, and phosphoinositides
Authors: Chen Yun , Thelin William R. , Yang Bing , Milgram Sharon L. , Jacobson Ken
Published: October 2006

How outer leaflet plasma membrane components, including glycosyl-phosphatidylinositol–anchored proteins (GPIAPs), transmit signals to the cell interior is an open question in membrane biology. By deliberately cross-linking several GPIAPs under antibody-conjugated 40-nm gold particles, transient anchorage of the gold particle–induced clusters of both Thy-1 and CD73, a 5′ exonucleotidase, occurred for periods ranging from 300 ms to 10 s in fibroblasts. Transient anchorage was abolished by cholesterol depletion, addition of the Src family kinase (SFK) inhibitor PP2, or in Src-Yes-Fyn knockout cells. Caveolin-1 knockout cells exhibited a reduced transient anchorage time, suggesting the partial participation of caveolin-1. In contrast, a transmembrane protein, the cystic fibrosis transmembrane conductance regulator, exhibited transient anchorage that occurred without deliberately enhanced cross-linking; moreover, it was only slightly inhibited by cholesterol depletion or SFK inhibition and depended completely on the interaction of its PDZ-binding domain with the cytoskeletal adaptor EBP50. We propose that cross-linked GPIAPs become transiently anchored via a cholesterol-dependent SFK-regulatable linkage between a transmembrane cluster sensor and the cytoskeleton.
Mapping the assembly pathways that specify formation of the trilaminar kinetochore plates in human cells
Authors: Liu Song-Tao , Rattner Jerome B. , Jablonski Sandra A. , Yen Tim J.
Published: October 2006

We report the interactions amongst 20 proteins that specify their assembly to the centromere–kinetochore complex in human cells. Centromere protein (CENP)-A is at the top of a hierarchy that directs three major pathways, which are specified by CENP-C, -I, and Aurora B. Each pathway consists of branches that intersect to form nodes that may coordinate the assembly process. Complementary EM studies found that the formation of kinetochore trilaminar plates depends on the CENP-I/NUF2 branch, whereas CENP-C and Aurora B affect the size, shape, and structural integrity of the plates. We found that hMis12 is not constitutively localized at kinetochores, and that it is not essential for recruiting CENP-I. Our studies also revealed that kinetochores in HeLa cells contain an excess of CENP-A, of which ∼10% is sufficient to promote the assembly of normal levels of kinetochore proteins. We elaborate on a previous model that suggested kinetochores are assembled from repetitive modules (Zinkowski, R.P., J. Meyne, and B.R. Brinkley. 1991. J. Cell Biol. 113:1091–110).
Rapid Growth in Infancy
Authors: Weaver Lawrence T.
Published: October 2006

Low birth weight is associated with a number of immediate adverse consequences, and it has been assumed that "catch‐up" growth is a "good thing" because "better" nutritional status is associated with greater childhood health and survival. The same thinking applies to infants who suffer malnutrition and growth faltering during weaning. Recent studies suggest that the rapid postnatal growth of babies is associated with an enhanced risk for obesity, diabetes, hypertension, cardiovascular disease and osteopenia in later life. If this is true, it has implications for our recommendations for infant feeding. Insights from evolutionary biology, life cycle theory, animal husbandry, epidemiology and comparative zoology suggest that the energetic feeding of underweight infants should be considered in the context of the whole life cycle and balance the interests of the child with its likely fortunes in adulthood. Before we revise our current recommendations, we must consider the meaning of catch‐up growth, what it involves in terms of tissues gained (fat, muscle and bone) and to what degree association represents causation. In the meantime, it will be prudent to balance the short‐ and long‐term interests of the child by endeavoring to (1) optimize maternal nutrition and health, to avoid low birth weight, (2) breast‐feed ideally, (3) consider birth weight, gestation and future "nutritional environment" when making decisions about infant feeding, (4) use appropriate growth charts, (5) avoid excessive postnatal weight gain, (6) think about the whole life span and (7) extrapolate from animal studies cautiously.
Long‐term Lamivudine Therapy for Chronic Hepatitis B Infection in Children Unresponsive to Interferon
Authors: Hartman Corina , Berkowitz Drora , Eshach‐Adiv Orly , Hino Bian , Rimon Nurit , Satinger Iehudith , Kra‐Oz Tzipi , Shamir Raanan
Published: October 2006

Objectives:

Prolonged lamivudine treatment in adults has been shown to improve hepatitis B e (HBe) seroconversion rates in patients with chronic hepatitis B. This prospective open study reports the results of prolonged lamivudine treatment in a group of children with chronic hepatitis B.

Patients and Methods:

Twenty‐two children and adolescents age 13.2 years (range, 9.5‐18 years), who have been treated with lamivudine for 1 year, continued treatment with lamivudine (3 mg/kg/day, up to 100 mg/d) as long as there was evidence of continued biochemical and virological benefit compared with baseline. We evaluated virological and biochemical responses, the occurrence of YMDD mutants and adverse effects during 4 years of follow‐up.

Results:

After 4 years on lamivudine, only 4 patients (18%) underwent HBe seroconversion. In addition, in 3 patients (13%), the treatment was stopped when lamivudine's lack of efficacy became evident. During the 4‐year study period, we recorded a continuing decline in the participants' number, mostly because of lack of compliance with treatment (9/22, 41%). Only 5 children were still receiving lamivudine and showing benefit after 4 years. In 2 children, treatment termination and YMDD mutant emergence were associated with hepatitis flare. Besides subclinical elevation of creatine phosphokinase, no other adverse events were recorded during the study period.

Conclusions:

Four years after starting lamivudine treatment, most children from this study were off lamivudine, mainly because of lack of compliance and poor HBe seroconversion. These findings suggest that continuing treatment with lamivudine for undefined periods is hard to implement and does not improve HBe seroconversion.
In Vivo and In Vitro Effects of Tea Extracts on Enterotoxigenic Escherichia coli‐induced Intestinal Fluid Loss in Animal Models
Authors: Bruins M.J. , Cermak R. , Kiers J.L. , van der Meulen J. , van Amelsvoort J.M.M. , van Klinken B.J.W.
Published: October 2006

Objectives:

Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of dehydrating diarrhoea in infants and early‐weaned piglets living under subhygienic conditions. We studied the effect of different tea types and subfractions on the intestinal fluid and electrolyte losses involved in ETEC diarrhoea.

Materials and Methods:

Jejunal segments of anaesthetised piglets were infected with ETEC or ETEC heat‐labile toxin (LT) and subsequently perfused for 8 hours with control or tea solutions containing green or black tea extract (BTE) or 3 different BTE subfractions containing small‐size, large‐size or no phenolics. Changes in intestinal fluid and electrolyte net absorption were measured. To assess the antisecretory effects of tea, BTE was incubated before or after administration of the secretagogue forskolin in rat jejunal tissue placed in Ussing chambers and Cl− secretion measured as changes in short‐circuit current (ISC).

Results:

Enterotoxigenic E. coli infection of piglet jejunal segments significantly reduced net absorption of fluid, Na+ and Cl− and increased net secretion of K+ compared with controls. Perfusion of the ETEC‐infected segments with both 3 g/L green tea extract and BTE significantly inhibited these disturbances in fluid and electrolyte balance. The BTE subfraction rich in polymeric phenolics but not the other subfractions improved the fluid and electrolyte balance. Addition of forskolin to rat jejunal tissue induced a significant increase in ISC. Pretreating but not posttreating the jejunal tissue with BTE inhibited the forskolin‐induced increase in ISC.

Conclusions:

Tea may inhibit net fluid and electrolyte losses involved in secretory diarrhoea from ETEC.
Identification of a cytotoxic T-lymphocyte (CTL) epitope recognized by Gag-specific CTLs in cynomolgus monkeys infected with simian/human immunodeficiency virus
Authors: Negri Donatella R. M. , Borghi Martina , Baroncelli Silvia , Macchia Iole , Buffa Viviana , Sernicola Leonardo , Leone Pasqualina , Titti Fausto , Cara Andrea
Published: October 2006

Infection ofMacaca fascicularis(cynomolgus monkey) with chimeric simian/human immunodeficiency virus (SHIV) provides a valuable experimental animal model of AIDS and is widely used for the development of human immunodeficiency virus vaccine strategies. In these settings, analysis of CD8+T-cell responses during infection represents one of the key parameters for monitoring the evaluation of containment of virus replication. The generation of Gag-specific CD8+T cells was reported previously from a cynomolgus monkey infected with SHIV89.6P by taking advantage of a B-lymphoblastoid cell line transduced with a retroviral vector expressing simian immunodeficiency virus (SIV) Gag. Here, it was shown that these cytotoxic T lymphocytes (CTLs) demonstrated specificity for a single 9 aa peptide (NCVGDHQAA) spanning aa 192–200 of the SIVmac239 p55gagprotein. Furthermore, a positive response was found against the same epitope in one of six other SHIV-infected monkeys. This newly identified SIV Gag CTL epitope in SHIV-infected cynomolgus monkeys will be a useful tool for monitoring and evaluating Gag-specific immune responses during vaccination and infection in the cynomolgus monkey model of AIDS.
Adenovirus type 5 fiber knob domain has a critical role in fiber protein synthesis and encapsidation
Authors: Henning Petra , Lundgren Emma , Carlsson Mattias , Frykholm Karolin , Johannisson Jenny , Magnusson Maria K. , Tång Erika , Franqueville Laure , Hong Saw See , Lindholm Leif , Boulanger Pierre
Published: October 2006

Adenovirus serotype 5 (Ad5) vectors carrying knobless fibers designed to remove their natural tropism were found to have a lower fiber content than recombinant Ad5 with wild-type (WT) capsid, implying a role for the knob-coding sequence or/and the knob domain in fiber encapsidation. Experimental data using a variety of fiber gene constructs showed that the defect did not occur at the fiber mRNA level, but at the protein level. Knobless fiber proteins were found to be synthesized at a significant slower rate compared with knob-carrying fibers, and the trimerization process of knobless fibers paralleled their slow rate of synthesis. A recombinant Ad5 diploid for the fiber gene (referred to as Ad5/R7-ZZwt/E1 : WT-fiber) was constructed to analyse the possible rescue of the knobless low-fiber-content phenotype by co-expression of WT fiber. Ad5/R7-ZZwt/E1 : WT-fiber contained a knobless fiber gene in its natural location (L5) in the viral genome and an additional WT fiber gene in an ectopic position in E1. Knobless fiber was still synthesized at low levels compared with the co-expressed E1 : WT fiber and the recovery of the two fiber species in virus progeny reflected their respective amounts in the infected cells. Our results suggested that deletion of the fiber knob domain had a negative effect on the translation of the fiber mRNA and on the intracellular concentration of fiber protein. They also suggested that the knob control of fiber protein synthesis and encapsidation occurred as aciseffect, which was not modified by WT fiber protein providedin transby the same Ad5 genome.
Feline calicivirus replication: requirement for polypyrimidine tract-binding protein is temperature-dependent
Authors: Karakasiliotis Ioannis , Chaudhry Yasmin , Roberts Lisa O. , Goodfellow Ian G.
Published: October 2006

The interaction of host-cell nucleic acid-binding proteins with the genomes of positive-stranded RNA viruses is known to play a role in the translation and replication of many viruses. To date, however, the characterization of similar interactions with the genomes of members of the familyCaliciviridaehas been limited toin vitrobinding analysis. In this study,Feline calicivirus(FCV) has been used as a model system to identify and characterize the role of host-cell factors that interact with the viral RNA. It was demonstrated that polypyrimidine tract-binding protein (PTB) interacts specifically with the 5′ sequences of the FCV genomic and subgenomic RNAs. Using RNA interference it was shown that PTB is required for efficient FCV replication in a temperature-dependent manner. siRNA-mediated knockdown of PTB resulted in a 15- to 100-fold reduction in virus titre, as well as a concomitant reduction in viral RNA and protein synthesis at 32 °C. In addition, virus-induced cytopathic effect was significantly delayed as a result of an siRNA-mediated reduction in PTB levels. A role for PTB in the calicivirus life cycle was more apparent at temperatures above and below 37 °C, fitting with the hypothesis that PTB functions as an RNA chaperone, potentially aiding the folding of RNA into functional structures. This is the first functional demonstration of a host-cell protein interacting with a calicivirus RNA.
Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis
Authors: Ren Wuze , Li Wendong , Yu Meng , Hao Pei , Zhang Yuan , Zhou Peng , Zhang Shuyi , Zhao Guoping , Zhong Yang , Wang Shengyue , Wang Lin-Fa , Shi Zhengli
Published: October 2006

Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus. These viruses, together with SARS coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively named group 2b (G2b). In this study, complete genome sequences of two additional group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b-CoV isolates have an identical genome organization and share an overall genome sequence identity of 88–92 % among themselves and between them and the human/civet isolates. The most variable regions are located in the genes encoding nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists in the bat habitat and has evolved from a common ancestor of SARS-CoV.
Parvoviral nuclear import: bypassing the host nuclear-transport machinery
Authors: Cohen Sarah , Behzad Ali R. , Carroll Jeffrey B. , Panté Nelly
Published: October 2006

The parvovirus Minute virus of mice (MVM) is a small DNA virus that replicates in the nucleus of its host cells. However, very little is known about the mechanisms underlying parvovirus' nuclear import. Recently, it was found that microinjection of MVM into the cytoplasm of Xenopus oocytes causes damage to the nuclear envelope (NE), suggesting that the nuclear-import mechanism of MVM involves disruption of the NE and import through the resulting breaks. Here, fluorescence microscopy and electron microscopy were used to examine the effect of MVM on host-cell nuclear structure during infection of mouse fibroblast cells. It was found that MVM caused dramatic changes in nuclear shape and morphology, alterations of nuclear lamin immunostaining and breaks in the NE of infected cells. Thus, it seems that the unusual nuclear-import mechanism observed in Xenopus oocytes is in fact used by MVM during infection of host cells.
Anti‐tumor effect in an in vivo model by human‐derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties
Authors: Yagi Hiroshi , Ueda Masakazu , Jinno Hiromitsu , Aiura Koichi , Mikami Shuji , Tada Hiroko , Seno Masaharu , Yamada Hidenori , Kitajima Masaki
Published: October 2006

It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h‐bFGF) was inserted genetically into the Gly89 position of cross‐linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross‐linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional‐fusion protein (CL‐RFN89) was active both as h‐bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h‐bFGF domain. In the present study, the effect of the resultant protein, CL‐RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL‐RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL‐RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL‐RFN89 reduced tumor vascularization. These findings identify CL‐RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent. (Cancer Sci 2006; 97: 1315–1320)
Acute lung injury following pancreas ischaemia‐reperfusion: role of xanthine oxidase
Authors: Flaishon R. , Szold O. , Weinbroum A. A.
Published: October 2006

Background  Acute pancreatitis can lead to increased pulmonary vascular permeability and respiratory failure. Oxidants (and their generator, xanthine oxidase (XO)) play an important role in injuring the structural integrity of the pulmonary epithelium and endothelium, but their importance in the induction of acute lung injury following pancreas ischaemia‐reperfusion (IR) has not been defined.

Materials and methods  Rats (n = 48) received a regular or a tungsten (oxidoreductase inhibitor)‐enriched diet for 14 days. Their isolated pancreases were then either perfused (controls) or made ischaemic (IR) for 40 min (12 replicates/group). This was followed by in‐series pancreas plus normal isolated lung reperfusion for 15 min. Lungs only were subsequently perfused with the 15‐min accumulated pancreas effluents for 45 min.

Results  Injury was induced in all IR pancreases as expressed by reperfusion pressure, wet‐to‐dry ratio and amylase and lipase concentrations. Tissue XO activity was high and reduced glutathione pool was low in the tungsten‐free IR pancreases. Pulmonary plateau pressure increased by 46% and final PO2/FiO2 decreased by 24%. Capillary pressure and weight rose two‐ to fourfold in lungs paired with IR non‐treated pancreases. Twofold increases in bronchoalveolar lavage volume and contents, including XO, were also recorded in this group of lungs. Lungs exposed to tungsten‐treated ischaemic pancreas effluents were minimally damaged and tissue XO content was low compared to controls.

Conclusions  Ex‐vivo acute pancreatitis induces acute lung injury via oxidants/antioxidants misbalance, which may be prevented by attenuating pancreas oxidative stress.
Pathogenicity of Edwardsiella tarda to olive flounder, Paralichthys olivaceus (Temminck & Schlegel)
Authors: Han H‐J , Kim D‐H , Lee D‐C , Kim S‐M , Park S‐I
Published: October 2006

The LD50 and cytotoxic and enzymatic activities of both cells and extracellular products (ECPs) of eight Edwardsiella tarda strains were determined and their bacterial superoxide dismutase gene (sodB) and catalase gene (katB) were sequenced. Strains were also examined for their ability to resist the immune responses of olive flounder, Paralichthys olivaceus. LD50 values of strains (FSW910410, KE1, 2, 3, 4, 5 and 6) in olive flounder ranged between 102.5 and 105.3 cfu (colony forming units) per fish. Unlike the avirulent strain SU100 (LD50 ≥ 107), all pathogenic strains were able to survive in flounder serum and head kidney leucocytes (except for KE2). The virulent strains possessed type I sodB and katB, whereas SU100 had type II sodB but not katB. However, there was no difference between avirulent and virulent strains in haemolytic and cytotoxic activities. The results of this study demonstrated that the ability of E. tarda to resist complement activity and phagocytosis is conferred by its superoxide dismutase and catalase, which thus play an essential role in the pathogenicity of this bacterium. In addition genotyping of sodB and kat B proved to be a very useful tool to distinguish virulent from avirulent strains.
A high‐positive patch test load correlates with further positive patch test reactions irrespective of their location
Authors: Brasch J. , Geier J. , Schnuch A. , Uter W. ,   [for the German Contact Dermatitis Research Group (DKG) and the Information Network of Departments of Dermatology (IVDK)]
Published: October 2006

Background:  Patch testing is the standard clinical procedure to prove contact sensitization. It is a common practice to attach multiple patch tests at the same time. However, synchronous reactions to unrelated allergens may not be completely unassociated. If so, the reaction in a given test field might be influenced by other positive test reactions in a distance‐related degree. This article analyses whether there is a distance‐related effect of synchronous positive patch test reactions on the outcome of a target patch test.

Methods:  Data collected from patients patch tested for diagnostic purposes with 15 standard allergens attached in a specific pattern between 1992 and 2004 in 20 centres in a Central European network were retrospectively evaluated. The association between the target patch test result (allergic vs negative reaction to the thiuram mix) and the number and cumulated strength of synchronous positive reactions (positive patch test load) to allergens placed in nearby or distant positions to the target patch was analysed by using logistic regression analysis.

Results:  The likelihood of a positive reaction to thiuram mix significantly increased with an increasing synchronous positive patch test load generated by positive reactions to allergens unrelated to thiuram mix. The effect of allergens neighbouring the target allergen was not significantly stronger than that of allergens placed in distant positions.

Conclusion:  For the interpretation of patch test results, the potentially enhancing effects of a synchronous positive patch test load should be considered. The local distribution of the patches on the back is, however, not critical.
Release of prostaglandin D2 and leukotriene C4 in response to hyperosmolar stimulation of mast cells
Authors: Gulliksson M. , Palmberg L. , Nilsson G. , Ahlstedt S. , Kumlin M.
Published: October 2006

Background:  Mannitol‐induced bronchoconstriction in subjects with exercise‐induced asthma is associated with increased urinary excretion of 9α, 11β‐PGF2, a metabolite of prostaglandin D2 (PGD2) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD2 and leukotriene C4 (LTC4) after osmotic challenge with mannitol in vitro.

Methods:  Cord blood‐derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD2, LTC4 and histamine contents with enzyme immunoassays.

Results:  Significant release of de novo synthesized eicosanoids, predominantly PGD2 [12 (8.8, 14) pmol/106cells; median (25th, 75th percentile) but also LTC4 (0.1 (0.08, 0.15) pmol/106 cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD2 and LTC4, following immunological stimulation.

Conclusion:  The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.
Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options
Authors: Bircher A. J. , Harr T. , Hohenstein L. , Tsakiris D. A.
Published: October 2006

Anticoagulants, including heparins, coumarins, hirudins, and some of the previously used plasma volume expanders, belong to the most widely used drugs. Hypersensitivity reactions from these agents are uncommon. However, they may have a considerable impact on patient safety and treatment decisions. Therefore, early diagnosis of potentially life‐threatening adverse events and identification of alternatives is clinically important. This review contains an update on current knowledge about hypersensitivity reactions caused by the different anticoagulants. In addition, it discusses pathophysiologic mechanisms, diagnostic possibilities, and management options. The most common hypersensitivity reactions are erythematous plaques, occurring with a delay after subcutaneous application of heparins. Seldom they turn into maculopapular exanthema. Other hypersensitivity reactions are rare but may be life‐threatening, e.g. skin necrosis because of heparin‐induced thrombocytopenia. Skin and provocation tests with immediate and late readings are the most reliable diagnostic tools for heparin‐ or hirudin‐induced urticaria/anaphylaxis or heparin‐induced delayed plaques. If necrosis from heparins or coumarins is suspected, skin tests are contraindicated. In anaphylactic reactions caused by dextrans or hydroxyethyl starch skin tests are useless. Most in vitro tests have a low sensitivity and are not generally available. Therefore, in some anticoagulant‐associated hypersensitivity reactions detailed allergologic investigation may help to identify safe treatment alternatives. However, several tests may be needed, and the procedures are usually time‐consuming.
Is Preening Behaviour Sexually Selected? An Experimental Approach
Authors: Griggio Matteo , Hoi Herbert
Published: October 2006

Elaborate or colourful feathers are important traits in female mate choice in birds but little attention has been given to potential costs of maintaining these traits in good condition with preening behaviour. Recent studies indicate that the time and energy required to maintain ornamental plumage in good condition reinforces the honesty of plumage trait. It has been proposed that some behaviours, whose primary function is not to transfer information, can also evolve as signalling components. Here we investigate whether the preening behaviour intensity has a signalling component: we hypothesized that if only high quality males can invest a lot of time in preening, this behaviour may be used by females as a quality signal (attractive preening hypothesis). We tested this hypothesis by using female budgerigars in mate‐choice tests in captivity. We tried to experimentally manipulate the preening behaviour of two groups of budgerigar males (treatment and control group). The proportion of time in which treated males preened in front of females was statistically higher than for control males, however, females spent similar amounts of time with treated males and control males. Moreover, males did not show significant quantitative changes in preening (for both groups) when females were present, suggesting that male budgerigars did not use this behaviour to convey information. These results are inconsistent with the ‘attractive preening’ hypothesis which predicts that preening behaviour itself provides information on condition and is used in female choice.
Impact of Exogenous ACTH During Pro‐Oestrus on Endocrine Profile and Oestrous Cycle Characteristics in Sows
Authors: Einarsson S , Ljung A , Brandt Y , Häger M , Madej A
Published: October 2006

Contents

Sows housed in freely moving groups have elevated cortisol levels until the rank order is established, which takes place within approximately 48 h. The aim of this investigation was to study the effect of repeated administration of synthetic adrenocorticotropic hormone (ACTH; Synacthen Depot®), during the follicular phase (pro‐oestrus) on oestrus, ovulation and endocrine parameters. Four multiparous sows were used. Follicular growth and ovulation were recorded by ultrasonography. The first oestrous cycle after weaning was used as control cycle. Onset of oestrus in the sow occurs 3–4 days after the time when plasma progesterone reaches a concentration of 8 nmol/l. The progesterone profile in the control cycle of the individual sow was used for estimation when the ACTH injections should start. In the third pro‐oestrus ACTH (2.5 μg/kg) was given via an indwelling catheter every 2 h for 48 h. The sows were euthanased 4–6 days after onset of the third oestrus and the ovaries were examined. Cortisol levels were elevated during the treatment period (p < 0.05). The second cycle, in which the sows were injected with ACTH, was prolonged with 2.5 days compared with the control cycle (p < 0.05). The oestradiol pattern during oestrus was similar in the control and the treatment cycle in ovulating sows. Three sows had ovulated (fresh corpora lutea), but the ovaries contained additionally one or several luteinized follicles/cysts. In conclusion, ACTH administration during pro‐oestrus caused a prolongation of the oestrous cycle and a disturbed follicular development.
Endo16 is required for gastrulation in the sea urchin Lytechinus variegatus
Authors: Romano Laura A. , Wray Gregory A.
Published: October 2006

The Endo16 gene encodes a large extracellular protein with several functional domains that provide some insight into the role of this protein during embryonic development. We isolated the full‐length cDNA sequence from Lytechinus variegatus and utilized morpholinos to further investigate the role of Endo16 during embryonic development in this species. Endo16‐deficient embryos failed to undergo gastrulation and the blastocoele became filled with dissociated cells after 24 h of incubation. Moreover, there was a delay in endoderm differentiation as assayed by staining with an antibody that recognizes Endo1. The differentiation of other cell types including oral ectoderm, primary mesenchymal cells (PMC) and secondary mesenchymal cells (SMC) appeared to be normal, although the patterns of protein expression did not resemble control embryos due to the gross morphological abnormalities elicited by the LvEndo16 morpholino. Microinjection of full‐length EGFP mRNA with the LvEndo16 morpholino‐targeted sequence confirmed that this phenotype can be attributed specifically to the loss of Endo16 protein. Taken together, our data suggest that Endo16 may be required for the cell–extracellular matrix (ECM) interactions that are required for endoderm differentiation in the sea urchin embryo.
Retroperitoneal anomalies in men with testicular germ cell tumours
Authors: Holt Peter J. , Adshead Jim M. , Filiadis Ioannis , Christmas Timothy J.
Published: October 2006

OBJECTIVES

To assess whether vascular and other retroperitoneal anomalies are more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic testicular tumours (when retroperitoneal masses persist after chemotherapy) than would be expected, based on the initial observations from one centre with a large experience of RPLND in the UK.

PATIENTS AND METHODS

A prospective series of 278 consecutive patients treated with RPLND for testicular tumours comprised the sample population. For each patient the presence or absence of four factors from the history was recorded. Each patient then underwent RPLND. During surgery, a template was constructed of the anatomy of the retroperitoneum and the information stored. Eight different retroperitoneal anatomical anomalies were identified in the sample population; the incidence of each was then compared with the largest available study of a normal population, and differences analysed statistically.

RESULTS

Of the 278 patients who had RPLND, 55 had 59 anomalies (21%), found by history and as retroperitoneal vascular and urological anomalies; cryptorchidism was present in 7.6%, 9.5 times the incidence in the control population (P < 0.01). A left‐sided inferior vena cava was present in 3.6% of patients, 21 times the incidence in the control population (P < 0.001); a retro‐aortic left renal vein in 3.2%, four times that in the control population (P < 0.05); and ipsilateral renal agenesis had an incidence of 1% in the test population, 11 times greater than in the control population (P < 0.01).

CONCLUSIONS

This prospective study of 278 RPLNDs provides evidence that some retroperitoneal anatomical anomalies are associated with testicular germ cell tumours. The link between maldescent and testicular tumours, rather than an isolated association, should be considered as part of a spectrum of retroperitoneal anomalies that occur in these men.
A clinical assessment of the performance of a sensor to detect crystalline biofilm formation on indwelling bladder catheters
Authors: Stickler David J. , Jones Steven M. , Adusei Gabriel O. , Waters Mark G. , Cloete Jenny , Mathur Sunil , Feneley Roger C.L.
Published: October 2006

OBJECTIVES

To test the ability of a sensor developed to signal infection by the organisms that generate the crystalline biofilms that encrust catheters, to give an early warning that encrustation was occurring on patients’ catheters, as the care of many patients undergoing long‐term bladder catheterization is complicated by the encrustation and blockage of their catheters

PATIENTS AND METHODS

Twenty patients were followed prospectively for the lifetime of one of their catheters. Sensors based on cellulose acetate/bromothymol blue were placed in the urine‐collection bags, which were changed as usual at weekly intervals. The bacteriology was assessed and pH determined weekly on urine samples. Photographic records were made of the sensors twice weekly. On removal, each catheter was examined for encrustation and blockage.

RESULTS

Proteus mirabilis was not isolated from five patients and in these cases the sensor colour remained golden‐yellow to brown. The catheters drained for the scheduled period and showed no signs of encrustation. By contrast, the sensors turned dark blue/black in the urine of all 15 patients infected with P. mirabilis. All these patients’ catheters were encrusted and in 12 the catheters blocked. The mean interval between the sensor signalling and the catheter blocking was 12 days.

CONCLUSION

The cellulose acetate/bromothymol blue sensors placed in the urine collection bags are capable of signalling infection by P. mirabilis. They also signal the early stages of catheter encrustation and allow catheter replacement in ample time to avoid the clinical crises and emergency referrals caused by catheter blockage.
Accomplicity: Britain, Torture and Terror
Authors: Danchev Alex
Published: October 2006

Britain has been chief accomplice in the ‘global war on terror’ (GWOT) from the outset. This article examines the underside of that voluntary servitude—the complicity in torture and abuse, humiliation and rendition. It asks, inter alia, what we know, and how we know, and why we should care.
CI Implementation: An Empirical Test of the CI Maturity Model
Authors: Jørgensen Frances , Boer Harry , Laugen Bjørge Timenes
Published: October 2006

There are a number of tools available for organizations wishing to measure and subsequently develop Continuous Improvement (CI). In this article, we review and evaluate a well‐accepted CI development model, namely the CI Maturity Model (Bessant and Caffyn, 1997), against data collected from the 2nd Continuous Improvement Network Survey and a number of empirical cases described in the literature. While the CI Maturity Model suggests that CI maturation ought to be a linear process, the findings in this article suggest that there are feasible alternatives for companies to develop CI capability.
Mast cell tryptase and microphthalmia transcription factor effectively discriminate cutaneous mast cell disease from myeloid leukemia cutis
Authors: Sundram Uma N. , Natkunam Yasodha
Published: October 2006

Background:  Cutaneous mast cell disorders are uncommon, but a subset, especially mastocytoma and mast cell leukemia, can histologically mimic myeloid leukemia cutis. Our objective was to employ a panel of cytochemical and immunohistochemical markers to determine which ones would be most useful in separating these two entities.

Methods:  We stained 17 cases of cutaneous mast cell disease and 20 cases of myeloid leukemia cutis with Giemsa, toluidine blue, or pinacyanol erythrosinate (PE), as well as with antibodies against mast cell tryptase, microphthalmia transcription factor (MiTF), CD117 (c‐kit), myeloperoxidase, CD43, CD25, CD2, and CD68.

Results:  Mast cell tryptase and MiTF emerged as highly sensitive and specific markers for mast cell disease in this context, as both antibodies stained all cases of mast cell diseases but none of myeloid leukemia cutis. Although CD117 stained all cases of mast cell disease, it also stained 2 of 18 cases of myeloid leukemia cutis. PE appeared to be specific for mast cell disease, as 11 of 12 cases stained with this marker, compared with 0 of 18 cases of myeloid leukemia cutis.

Conclusions:  Our results show that mast cell tryptase and MiTF are equally effective in distinguishing mast cell disease from myeloid leukemia cutis.
Diagnosing Sjögren–Larsson syndrome in a 7‐year‐old Moroccan boy
Authors: Bernardini M. L. , Cangiotti A. M. , Zamponi N. , Porfiri L. , Cinti S. , Offidani A.
Published: October 2006

Abstract:  Sjögren–Larsson syndrome (SLS) is an autosomal recessively inherited neurocutaneous disorder characterized by the triad of congenital ichthyosis, mental deficiency, and spastic diplegia or tetraplegia. Less common features are retinal changes, short stature, kyphoscoliosis, preterm birth, photophobia, reduction of visual acuity, seizures, and delayed speech. SLS is characterized by a genetic block in the oxidation of fatty alcohol to fatty acid because of deficient activity of fatty aldehyde dehydrogenase (FALDH), a component of the fatty alcohol: NAD oxidoreductase enzyme complex. As in other rare multisystem diseases, the diagnosis of SLS is often delayed. The definitive test for SLS is considered the measurement of FALDH or fatty alcohol: NAD oxidoreductase in cultured skin fibroblasts. Nevertheless, if specific FALDH activity test or DNA FALDH gene mutation tests are not available (as in our country), a reliable diagnosis of SLS is also possible when it is based on the matching of peculiar clinical, histologic and ultrastructural, laboratoristic, and imaging features. The simultaneous presence of cutaneous histologic features including hyperkeratosis, orthokeratosis, thickening of granular layer, abnormal lamellar inclusions in the cytoplasm of granular and horny cells (demonstrated by light and electron microscopy) in a child with ichthyosis, and typical neurologic abnormalities is highly suggestive of SLS. We describe the case of a young Moroccan boy presenting with ichthyosis, mental retardation, spastic diplegia, and peculiar skin histologic findings.
Histological evolution of lentiginous melanoma: a report of five new cases
Authors: Davis Tracy , Zembowicz Artur
Published: October 2006

Background:  The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single‐cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases.

Methods:  Histological review of routine sections with clinicopathological correlation.

Results:  Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma.

Conclusions:  Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non‐severely sun‐damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment.
Tumoral melanosis involving the sentinel lymph nodes: a case report
Authors: Satzger Imke , Völker Bernward , Kapp Alexander , Gutzmer Ralf
Published: October 2006

Abstract:  Tumoral or nodular melanosis is characterized by a clinical lesion suspicious for malignant melanoma, the histopathological correlate is a nodular accumulation of melanophages in the dermis. We present a patient with nodular melanosis involving also the sentinel lymph nodes and discuss possible differential diagnoses as well as prognostic and therapeutic implications.