bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface force spectroscopic point load measurements and viscoelastic modelling of the micromechanical properties of air flow sensitive hairs of a spider (Cupiennius salei)
Authors: McConney Michael E. , Schaber Clemens F. , Julian Michael D. , Eberhardt William C. , Humphrey Joseph A.C. , Barth Friedrich G. , Tsukruk Vladimir V.
Published: December 2008

The micromechanical properties of spider air flow hair sensilla (trichobothria) were characterized with nanometre resolution using surface force spectroscopy (SFS) under conditions of different constant deflection angular velocities(rad s−1) for hairs 900–950 μm long prior to shortening for measurement purposes. In the range of angular velocities examined (4×10−4−2.6×10−1rad s−1), the torqueT(Nm) resisting hair motion and its time rate of change(Nm s−1) were found to vary with deflection velocity according to power functions. In this range of angular velocities, the motion of the hair is most accurately captured by a three-parameter solid model, which numerically describes the properties of the hair suspension. A fit of the three-parameter model (3p) to the experimental data yielded the two torsional restoring parameters,S3p=2.91×10−11 Nm rad−1and=2.77×10−11Nm rad−1and the damping parameterR3p=1.46×10−12Nm s rad−1. For angular velocities larger than 0.05 rad s−1, which are common under natural conditions, a more accurate angular momentum equation was found to be given by a two-parameter Kelvin solid model. For this case, the multiple regression fit yieldedS2p=4.89×10−11 Nm rad−1andR2p=2.83×10−14 Nm s rad−1for the model parameters. While the two-parameter model has been used extensively in earlier work primarily at high hair angular velocities, to correctly capture the motion of the hair at both low and high angular velocities it is necessary to employ the three-parameter model. It is suggested that the viscoelastic mechanical properties of the hair suspension work to promote the phasic response behaviour of the sensilla.
Stochastic dynamics and non-equilibrium thermodynamics of a bistable chemical system: the Schlögl model revisited
Authors: Vellela Melissa , Qian Hong
Published: December 2008

Schlögl's model is the canonical example of a chemical reaction system that exhibits bistability. Because the biological examples of bistability and switching behaviour are increasingly numerous, this paper presents an integrated deterministic, stochastic and thermodynamic analysis of the model. After a brief review of the deterministic and stochastic modelling frameworks, the concepts of chemical and mathematical detailed balances are discussed and non-equilibrium conditions are shown to be necessary for bistability. Thermodynamic quantities such as the flux, chemical potential and entropy production rate are defined and compared across the two models. In the bistable region, the stochastic model exhibits an exchange of the global stability between the two stable states under changes in the pump parameters and volume size. The stochastic entropy production rate shows a sharp transition that mirrors this exchange. A new hybrid model that includes continuous diffusion and discrete jumps is suggested to deal with the multiscale dynamics of the bistable system. Accurate approximations of the exponentially small eigenvalue associated with the time scale of this switching and the full time-dependent solution are calculated using Matlab. A breakdown of previously known asymptotic approximations on small volume scales is observed through comparison with these and Monte Carlo results. Finally, in the appendix section is an illustration of how the diffusion approximation of the chemical master equation can fail to represent correctly the mesoscopically interesting steady-state behaviour of the system.
High-pressure crystal structure of the non-linear optical compound BiB3O6 from two-dimensional powder diffraction data
Authors: Dinnebier R. E. , Hinrichsen B. , Lennie A. , Jansen M.
Published: December 2008

Our recently proposed method for automatic detection, calibration and evaluation of Debye–Scherrer ellipses using pattern-recognition techniques and advanced signal filtering was applied to the two-dimensional powder diffraction data of the non-ferroelectric, non-centrosymmetric non-linear optical (NLO) compound α-BiB3O6 as a function of pressure. At ambient conditions, α-BiB3O6 crystallizes in the space group C2 (phase I). In the pressure range between P = 6.09 and 6.86 GPa, it exhibits a first-order phase transition into a structure with the space group C1 (P1) [phase II at P = 8.34 GPa: a = 7.4781 (6), b = 3.9340 (4), c = 6.2321 (6) Å, α = 93.73 (1), β = 102.93 (1), γ = 90.76 (1)°, and V = 178.24 (3) Å3]. Non-linear compression behaviour over the entire pressure range is observed, which can be described by two Vinet relations in the ranges from P = 0.0 to 6.09 GPa, and from P = 6.86 to 11.6 GPa. The extrapolated bulk moduli of the high-pressure phases were determined to be K
0 = 38 (1) GPa for phase I, and K
0 = 114 (10) GPa for phase II. The crystal structures of both phases were refined against X-ray powder diffraction data measured at several pressures between 0.0 and 11.6 GPa. The structural phase transition of α-BiB3O6 is mainly characterized by a reorientation of the [BO3]3− triangles, the [BO4]5− tetrahedra and the lone electron pair which is localized at Bi3+, in order to optimize crystal packing.
Planar packing of tetrachlorodicyanobenzenes. II
Authors: Britton Doyle
Published: December 2008

Equimolar mixtures of ortho- and meta-, or ortho- and para-, or meta- and para-tetrachlorodicyanobenzene, C6Cl4(CN)2, form structures with disordered layers containing both kinds of molecules in rhombohedral or pseudo-rhombohedral cells. These structures are similar to the structure of the rhombohedral form of the meta isomer. The guiding force appears to be an intermolecular synthon, in which a nitrile group in one molecule interacts with Cl atoms in two adjacent molecules with N...Cl distances of approximately 3.1 Å.
Structural study of K
x
Na1 − x
NbO3 (KNN) for compositions in the range x = 0.24–0.36
Authors: Baker D. W. , Thomas P. A. , Zhang N. , Glazer A. M.
Published: December 2008

The structure of the A-site substituted perovskite K
x
Na1 − x
NbO3, x = 0.24–0.36, where a phase boundary was previously reported, has been determined by high-resolution X-ray powder and neutron powder diffraction studies. The structure of the x = 0.3 compound was refined in the monoclinic space group Pm at 293 K and in P4mm at 523 K. The Glazer tilt system of the room-temperature monoclinic phase is a
0
b
+
c
0, which has implications for the nature of the next symmetry change with composition towards pure potassium niobate. A phase-coexistence region at the transition between monoclinic and tetragonal phases was also identified, consistent with a first-order phase boundary. There is also evidence for an intermediate oxygen-octahedra tilted tetragonal phase.
Evidence for spatial limitation of the bluestripe snapper Lutjanus kasmira in French Polynesia from parasite and otolith shape analysis
Authors: Vignon M. , Morat F. , Galzin R. , Sasal P.
Published: December 2008

The study focused on small‐scale location and movement patterns of the bluestripe snapper Lutjanus kasmira on the north coast of Moorea (Society Archipelago, French Polynesia, south‐central Pacific). Juveniles of this species occur in the estuary, and adults occur widely in the lagoon, the outer slope and in the intermediate channel, where fish aggregate in large schools during daytime. While fish were all sampled within a few hundred metres, they exhibited significantly different parasite fauna and otolith shapes according to their locality: estuary, lagoon, channel and outer slope. While juveniles did not exhibit any parasites in the estuary parasitological and otolith‐shape data suggest that adults rarely move between their three adjoining habitats, and more interestingly that large aggregations in the channel are formed predominantly by resident individuals with limited local movement, including at night. Besides giving some information on the host biology, such findings may have application in local fisheries management.
Common relationships among proximate composition components in fishes
Authors: Hartman K. J. , Margraf F. J.
Published: December 2008

Relationships between the various body proximate components and dry matter content were examined for five species of fishes, representing anadromous, marine and freshwater species: chum salmon Oncorhynchus keta, Chinook salmon Oncorhynchus tshawytscha, brook trout Salvelinus fontinalis, bluefish Pomatomus saltatrix and striped bass Morone saxatilis. The dry matter content or per cent dry mass of these fishes can be used to reliably predict the per cent composition of the other components. Therefore, with validation it is possible to estimate fat, protein and ash content of fishes from per cent dry mass information, reducing the need for costly and time‐consuming laboratory proximate analysis. This approach coupled with new methods of non‐lethal estimation of per cent dry mass, such as from bioelectrical impedance analysis, can provide non‐destructive measurements of proximate composition of fishes.
Flexible migration of Japanese freshwater gobies Rhinogobius spp. as revealed by otolith Sr:Ca ratios
Authors: Tsunagawa T. , Arai T.
Published: December 2008

The migratory histories of six Rhinogobius spp., the cross‐band type (R. sp. CB), the large‐dark type (R. sp. LD), the dark type (R. sp. DA), the cobalt type (R. sp. CO), the orange type (R. sp. OR) and R. flumineus, were studied by examining strontium (Sr) and calcium (Ca) concentrations in their otoliths using wavelength dispersive X‐ray spectrometry on an electron microprobe. The Sr:Ca ratios in the otoliths changed both with the ontogenetic development and with the salinity level of the habitat. Most fishes had high Sr:Ca ratios around the otolith core in spite of the fact that those fishes live most of their lives in a freshwater environment. The high ratios in the otoliths were thought to be a physiological effect in those fishes. Thereafter, the Sr:Ca ratios changed remarkably along the life‐history transect, showing intraspecies and interspecies variations. The otolith Sr:Ca ratios of Rhinogobius sp. CB, R. sp. LD and R. sp. CO collected from three rivers connected to the sea were low around the core, subsequently increased sharply to the points 180–345 μm from the core and then decreased again towards the edge. They were thought to reflect the typical amphidromous life history. The R. sp. CO, however, remain in a brackish‐water environment after migration from the sea, while the other species showed typical amphidromous lives with complete freshwater residence after migration from the sea. The five species (R. sp. CB, R. sp. LD, R. sp. CO, R. sp. DA and R. sp. OR) collected above dams had never migrated to the sea, spending their whole life in a freshwater environment, although Rhinogobius species, except for the fluvial type, were thought to have an amphidromous life history according to previous studies. These species are thought to have a landlocked life cycle. The otolith Sr:Ca ratios of R. flumineus showed consistently low ratios towards the edge except for only around the core, although they were collected from a river connected to the sea. These species could have a fluvial life history corresponding to a previous study. The present study clearly suggests that the migratory histories of Rhinogobius spp. are highly different both within and between species and that they have flexible migratory patterns allowing them to utilize the full range of salinity during their life history.
High‐resolution isotope analysis of young alewife Alosa pseudoharengus otoliths: assessment of temporal resolution and reconstruction of habitat occupancy and thermal history
Authors: Dufour E. , Höök T. O. , Patterson W. P. , Rutherford E. S.
Published: December 2008

Otoliths of age 0 year alewife Alosa pseudoharengus collected in different Lake Michigan habitats were microsampled, and carbon and oxygen isotope ratios (δ18Ootolith and δ13Cotolith) of resulting microsamples were quantified. To assess the temporal resolution of the method, age and otolith growth rates were also estimated by counting otolith daily growth increments. Core and outer intra‐otolith samples averaged 36 and 23 days, respectively. Because of the accretionary nature of otolith growth, a habitat switch by a larva occurring between 0 and 18 days post‐hatch may not be recognized by this approach. Taking this temporal resolution into account, A. pseudoharengus habitat occupancy and thermal history in nearshore Lake Michigan, and a connecting drowned river‐mouth lake were documented. Comparisons between δ18Ootolith and δ13Cotolith profiles, and isotope values of Lake Michigan habitats suggested that movements by individual fish between a nearshore area of Lake Michigan proper and drowned river‐mouth lake habitats were rare. Some individuals evidently moved between habitats, and such movements occurred during different periods of ontogeny. Thermal reconstructions, based on δ18Ootolith values suggested that during early life (e.g. first month of life) young A.pseudoharengus appeared to inhabit microhabitats with temperatures greater than mean epilimnetic temperatures. This study demonstrates not only the utility of intra‐otolith geochemical analysis to describe the complexity of fish behaviour in fresh water but also identifies limitations of the present approach.
The ontogeny of chemically mediated antipredator responses of fathead minnows Pimephales promelas
Authors: Carreau‐Green N. D. , Mirza R. S. , MartÍnez M. L. , Pyle G. G.
Published: December 2008

The antipredator responses of adult and larval fathead minnows Pimephales promelas to chemical alarm cues prepared throughout ontogeny were tested using various behavioural assays. Larval epidermis was also examined during ontogeny using standard haematoxylin and eosin staining techniques. Adults elicited an antipredator response to chemical alarm cue made from larvae as young as 8–17 days post‐hatch. Interestingly, larvae did not possess visible club cells until 28–37 days post‐hatch and did not respond to conspecific chemical alarm cue until 48–57 days post‐hatch. These results suggest that chemical alarm cue may not be contained within club cells and that the components of larval and adult chemical alarm cue may be similar throughout ontogeny.
Temperature effects on otolith pattern formation in Atlantic cod Gadus morhua
Authors: Neat F. C. , Wright P. J. , Fryer R. J.
Published: December 2008

The effect of food intake and temperature on otolith macrostructure and microstructure was examined experimentally in Atlantic cod Gadus morhua. Daily increment formation was validated and otolith accretion rate and optical density quantified using image analysis. Two‐week periods of starvation had no discernable effect on otolith increment width or optical density, despite having negative effects on somatic growth. In contrast, temperature had a strong positive effect on otolith accretion rate and clear effects on optical density with the otolith becoming more translucent at higher temperatures. Somatic growth, otolith accretion and otolith optical density each had a significantly different response curve to temperature. No relationship was detected between individual somatic growth rates and the accretion rate or optical properties of the otolith. The experimental manipulation of temperature‐induced otolith patterns similar to the ‘false ring’ secondary structures sometimes observed in the otoliths of wild fish. The results suggest that otolith pattern arises from a combination of temperature and seasonal effects, but not directly from individual variation in somatic growth.
Geographical and typological changes in fish guilds of South African estuaries
Authors: Harrison T. D. , Whitfield A. K.
Published: December 2008

A comparative analysis of fish estuary association guilds was undertaken on some 190 South African estuaries. This pioneering study spanned three zoogeographic regions and included three broad estuarine types. The guild compositions of the estuaries were compared based on an importance value, incorporating taxonomic composition, numerical abundance and relative biomass. Multivariate analyses included both inter‐regional (zoogeographic) and intra‐regional (estuarine typology) comparisons. The major estuary‐associated guilds (estuarine species and marine migrant species) were important in all estuary types within all biogeographic regions. Significant differences both between regions and between estuary types within regions, however, were recorded. Cool–temperate estuaries were generally dominated by migratory species (estuarine migrants and marine migrant opportunists) while the importance of species dependent on estuaries (estuarine residents and estuarine‐dependent marine migrants) was higher in warm–temperate and subtropical regions. The significance of estuarine nursery areas, particularly in regions where estuaries are few in number, is highlighted. In terms of typology, migratory species assumed a greater importance in predominantly open systems, while freshwater and estuarine‐resident species were more important in predominantly closed systems. Predominantly closed estuaries, however, were also important for marine migrant species, which further highlights the significance of these systems as nursery areas for fishes.
Phenotypic characteristics and pathogenic ability across distinct morphotypes of Burkholderia pseudomallei DT
Authors: Chen Yao‐Shen , Lin Hsi‐Hsun , Hung Chih‐Chang , Mu Jung‐Jung , Hsiao Yu‐Shan , Chen Ya‐Lei
Published: December 2008

Burkholderia pseudomallei DT is unusual as it exhibits six distinct colony morphotypes. Types III and V show stronger motility, whereas type VI exhibits the highest levels of bacterial association with peritoneal exudate cells. Although the bacterial loads in the organs are not significantly different for infections by the six distinct morphotypes, higher mortality (100% and 89%, respectively) and larger areas of abnormal liver debris (20.6% and 22.4%, respectively) are found with types I‐ and III‐infected mice compared to the others. These morphotypes sometimes undergo switching to a mucoid type in the body of mice, but the reverse has never been observed.
Leptin induces functional activation of cyclooxygenase‐2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells
Authors: Gao Jingchun , Tian Jianxin , Lv Yunyi , Shi Fangxin , Kong Fandou , Shi Hong , Zhao Liyan
Published: December 2008

Hyperleptinemia is a common feature of obese women who have a higher risk of endometrial cancer than women with normal weights, and epidemiologic studies have suggested a correlation between obesity and endometrial carcinoma. Therefore, understanding of the molecular mechanism involved in leptin signaling transduction is important in endometrial cancer prevention and treatment. In this study, both isoforms of the leptin receptor (Ob‐R), the long form (Ob‐Rb) and short form (Ob‐Ra), were detected as being expressed in six endometrial cancer cell lines with various differentiation status by western blotting, and Ob‐Ra was found to be more abundant than Ob‐Rb in these cells. Moreover, the expressions of both isoforms were inversely correlated with histoprognostic grading. We also showed that leptin stimulated cell proliferation and induced activations of signal transducers and activators of transcription 3 (STAT3), extracellular signal‐regulated kinase (ERK1/2), AKT, and cyclooxygenase (COX)‐2 in endometrial cancer cells dose‐dependently by [3H] thymidine incorporation assay and western blotting. Leptin‐stimulation resulted in increased expression of COX‐2 mRNA and prostaglandin E2 (PGE2) production of endometrial cancer cells by reverse transcription–polymerase chain reaction and enzyme immunoassay, respectively, which was effectively blocked by pharmacological inhibitors of Janus tyrosine kinase 2 (JAK2), AG490; of mitogen‐activated protein kinase (MAPK) kinase, U0126; of phosphatidylinositol 3‐kinase (PI3K), LY294002; and of COX‐2, NS398. These results suggest that leptin promotes cell proliferation of endometrial cancer cells via the aforementioned multiple signal‐transduction pathways. Leptin‐induced functional activation of COX‐2 is JAK2/STAT3‐, MAPK/ERK‐, and PI3K/AKT‐dependent, indicating that COX‐2 may be a critical factor of endometrial carcinogenesis in obesity. (Cancer Sci 2009; 100: 389–395)
Essential contribution of Ets‐1 to constitutive Pim‐3 expression in human pancreatic cancer cells
Authors: Li Ying‐Yi , Wu Yu , Tsuneyama Koichi , Baba Tomohisa , Mukaida Naofumi
Published: December 2008

We previously demonstrated that the proto‐oncogene Pim‐3 with serine/threonine kinase activity was aberrantly expressed in cancer cells but not in the normal cells of the pancreas. In order to elucidate the molecular mechanism underlying aberrant Pim‐3 expression in pancreatic cancer cells, we constructed luciferase expression vectors linked to 5′‐flanking deletion mutants of the human Pim‐3 gene and transfected human pancreatic cancer cells with the resultant vectors. The region up to –264 bp was essential for constitutive Pim‐3 gene expression, and the mutation in the Ets‐1 binding site (between –216 and –211 bp) reduced luciferase activities. Moreover, Ets‐1 mRNA and protein were constitutively expressed together with Pim‐3 in human pancreatic cancer cell lines. Chromatin immunoprecipitation assay demonstrated constitutive binding of Ets‐1 to the 5′‐flanking region of human Pim‐3 gene between –249 and –183 bp. Pim‐3 promoter activity and its protein expression were induced by transfection with wild type‐Ets‐1 and were reduced by transfection with dominant negative‐Ets‐1 or Ets‐1 small‐interfering RNA (siRNA). Furthermore, dominant negative‐Ets‐1 and Ets‐1 siRNA reduced the amount of Bad phosphorylated at its Ser112 and induced apoptosis, when they were transfected into human pancreatic cancer cells. Finally, Pim‐3 cDNA transfection reversed Ets‐1 siRNA‐induced increase in apoptosis and decrease in Bad phosphorylation at its Ser112. These observations would indicate that the transcription factor Ets‐1 can induce aberrant Pim‐3 expression and subsequently prevent apoptosis in human pancreatic cancer cells. (Cancer Sci 2009; 100: 396–404)
Molecular imaging of cancer—evaluating characters of individual cancer by PET/SPECT imaging
Authors: Saga Tsuneo , Koizumi Mitsuru , Furukawa Takako , Yoshikawa Kyosan , Fujibayashi Yasuhisa
Published: December 2008

The present status of cancer molecular imaging (MI) with nuclear medicine techniques is reviewed, highlighting the Japanese activities in this field. With the progress in MI research, including significant contributions from Japanese studies, it has become possible to noninvasively evaluate various important characters of cancer in clinical patients, such as metabolism, cellular proliferation, tumor hypoxia, and receptor expression. Tumor metabolic information is used for tumor characterization, treatment response evaluation, and prognosis prediction. Hypoxia imaging is used for treatment planning and predicting treatment response. Receptor imaging can be used for the selection of the candidate for receptor‐targeted treatment. Various novel probes that can target cancer‐associated antigens, various cellular growth factor receptors, tumor angiogenesis, and so on, are under development, aiming for clinical evaluation. Application of radiolabeled ligands for treatment (targeted internal radiation therapy) is another important field in which MI technique can play a critical role. MI, which can deliver the outcome of basic oncological research to the bedside, is essential translational research for improved individualized patient management, and further advances in MI studies are eagerly awaited. (Cancer Sci 2009; 100: 375–381)
Chemokine CCL2 facilitates ICAM‐1‐mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes
Authors: Kawai Yoshiko , Kaidoh Maki , Yokoyama Yumiko , Sano Kenji , Ohhashi Toshio
Published: December 2008

We examined the effects of CCL1, CCL2, CCL12 and CCL21 on the expression of adhesion molecules in cultured human lymphatic endothelial cells using immunohistochemical staining or Western blot analysis. In addition, we investigated whether the expressed adhesion molecule was able to facilitate the attachment of carcinoma cells to the lymphatic endothelial cells as an in vitro micrometastatic model. CCL2 caused a selective and significant expression of ICAM‐1 on human lymphatic endothelial cells but CCL1, CCL12 and CCL21 did not. By increasing the stimulation time from 4 to 18 and 48 h, the intensity of immunoreactivity for ICAM‐1 was significantly increased in a time‐dependent manner up to 18 h. The ICAM‐1 mRNA levels were also elevated significantly up to 18 h. The CCL2‐mediated immunohistochemical expression of ICAM‐1 was dose‐dependently increased from 10 pg/mL to 1 ng/mL. The CCL2‐mediated expression of ICAM‐1 was significantly reduced by neutralization of CCL2 using a specific CCL2 antibody. The 18‐h treatment with CCL2 caused a significant facilitation of in vitro attachment of MDA‐MB‐231 and MCF‐7 cells to the lymphatic endothelial cells (LECs). The CCL2‐mediated response in the attachment assay was also significantly reduced either by the neutralization of CCL2 or by additional treatment with anti‐ICAM‐1 antibody. Immunohistochemical expression of ICAM‐1, but not E‐selectin, was strongly observed around and within the metastatic region of sentinel lymph node isolated from breast cancer patients. These findings suggest that CCL2 induces selective and significant expression of ICAM‐1 on cultured human lymphatic endothelial cells and then facilitates the attachment of carcinoma cells to the lymphatic endothelial cells, thus providing an in vitro micrometastatic model via the overexpression of ICAM‐1. (Cancer Sci 2009; 100: 419–428)
The prevalence, clinical features and association of HLA‐B27 in sacroiliitis associated with established Crohn’s disease
Authors: ORCHARD T. R. , HOLT H. , BRADBURY L. , HAMMERSMA J. , MCNALLY E. , JEWELL D. P. , WORDSWORTH B. P.
Published: December 2008

Background Sacroiliitis is a recognized complication of Crohn’s disease and may occur distinct from progressive ankylosing spondylitis (AS).

Aim To estimate prospectively the prevalence of sacroiliitis in patients with established Crohn’s disease, to characterize the clinical features and to correlate these with the presence of HLA‐B27.

Methods All Crohn's disease patients under active follow‐up of between 5 and 12 years duration were invited to participate. Patients underwent a clinical evaluation including symptom questionnaire, rheumatological examination and underwent HLA genotyping. Patients then underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The clinical and radiological factors were correlated with HLA‐B27 status.

Results 56 patients underwent initial assessment and 44 had MRI scans. Seventeen of 44 (39%) patients had MRI evidence of sacroiliitis, of whom 5 fulfilled the criteria for AS. Symptoms of low back pain were elicited in a majority of these patients – 11/17 (65%) compared to 3 of 27 (11%) patients with normal scans (P = 0.003). There were no differences in functional indices with the exception of patients with AS. HLA‐B27 was present in seven patients, and all seven had MRI evidence of sacroiliitis, five had AS.

Conclusions Sacroiliitis is common in patients with established Crohn’s disease and in the majority of cases, patients have symptoms of inflammatory low back pain if questioned carefully. HLA‐B27 is not associated with isolated sacroiliitis, but is associated with AS. However, possession of HLA‐B27 appears to convey a very high risk of developing axial inflammation in Crohn’s disease.
The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards
Authors: VAN VLIET E. P. M. , STEYERBERG E. W. , OTTEN H. J. A. M. , RUDOLPHUS A. , KNOESTER P. D. , HOOGSTEDEN H. C. , VAN GELDER T. , KUIPERS E. J. , SIERSMA P. D.
Published: December 2008

Background  It has been demonstrated that 40% of patients admitted to pulmonary medicine wards use proton pump inhibitors (PPIs) without a registered indication.

Aim  To assess whether implementation of a guideline for proton pump inhibitor (PPI) prescription on pulmonary medicine wards could lead to a decrease in use and improved appropriateness of prescription.

Methods  This prospective study comprised two periods, i.e. the situation before and after guideline implementation. In each period, 300 consecutive patients were included. We registered patient characteristics, medications and occurrence of upper gastrointestinal‐related disorders.

Results  After implementation, fewer patients were started on PPIs [21% vs. 13%; odds ratio (OR): 0.56; 95% confidence interval (CI): 0.33–0.97] and more users discontinued their use; however, the latter was not significant (3% vs. 6%; OR for continuation: 0.56; 95% CI: 0.14–2.23). Multivariable logistic regression analysis confirmed that PPI use during hospitalization decreased after implementation (adjusted pooled OR: 0.54; 95% CI: 0.32–0.90). Implementation did not result in a change in reported reasons for PPI prescription. There was no significant difference in the occurrence of upper GI‐related disorders in the first 3 months after discharge.

Conclusions  Guideline implementation for PPI prescription on two pulmonary medicine wards resulted in a reduction in the number of patients starting PPIs during hospitalization, but appropriateness of prescribing PPIs was not affected. Further studies are needed to determine how appropriateness of PPI prescription on pulmonary medicine wards can be further improved.
Administration of adalimumab in the treatment of Crohn’s disease of the ileal pouch
Authors: SHEN B. , REMZI F. H. , LAVERY I. C. , LOPEZ R. , QUEENER E. , SHEN L. , GOLDBLUM J. , FAZIO V. W.
Published: December 2008

Background  Crohn’s disease (CD) of the pouch can develop in patients with ileal pouch‐anal anastomosis (IPAA). Scant data are available on the treatment of this disease entity.

Aim  To evaluate efficacy and safety of adalimumab in treating CD of the ileal pouch.

Methods  From June 2007 to June 2008, 17 IPAA patients with inflammatory (n = 10), fibrostenotic (n = 2) or fistulizing (n = 5) CD of the pouch treated with adalimumab were evaluated. Inclusion criteria were CD of the pouch who failed medical therapy and were otherwise qualified for permanent pouch diversion or excision. All qualified patients received the standard dosing regimen of subcutaneous injection adalimumab (160 mg at week 0, 80 mg at week 1, and 40 mg every other week thereafter). Complete clinical response was defined as resolution of symptoms. Partial clinical response was defined as improvement in symptoms. Endoscopic inflammation before and after therapy was recorded, using the Pouchitis Disease Activity Index (PDAI) endoscopy subscores.

Results  The median age was 36 years with 12 patients (70.6%) being male. At 4 weeks, seven patients (41.2%) had a complete symptom response and 6 (35.3%) had a partial response. There was also a significant improvement in the PDAI endoscopy subscores at week 4 (P < 0.05). At the last follow‐up (median of 8 weeks), eight patients (47.1%) had a complete symptom response and 4 (23.5%) had a partial response. Four patients (23.6%) developed adverse effects. Three patients (17.7%) eventually had pouch failure after failing to respond to adalimumab therapy.

Conclusion  Adalimumab appeared to be well‐tolerated and efficacious in treating CD of the pouch in this open‐labelled induction study.
What is the scale of prescribing errors committed by junior doctors? A systematic review
Authors: Ross Sarah , Bond Christine , Rothnie Helen , Thomas Sian , Macleod Mary Joan
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Prescribing errors account for a substantial proportion of medication errors and cause the most significant problems.

• There is a dearth of accurate information on the prevalence of prescribing errors, with estimates from 1 to 100% of all patients admitted to hospital.

WHAT THIS STUDY ADDS

• This review reports the wide ranges of error rates seen, which cannot be compared due to differences in methodology and error definitions used.

• A well‐conducted study of prescribing errors by junior doctors using standard definitions and methodology is urgently needed to allow development and assessment of appropriate interventions.

AIMS

Prescribing errors are an important cause of patient safety incidents, generally considered to be made more frequently by junior doctors, but prevalence and causality are unclear. In order to inform the design of an educational intervention, a systematic review of the literature on prescribing errors made by junior doctors was undertaken.

METHODS

Searches were undertaken using the following databases: MEDLINE; EMBASE; Science and Social Sciences Citation Index; CINAHL; Health Management Information Consortium; PsychINFO; ISI Proceedings; The Proceedings of the British Pharmacological Society; Cochrane Library; National Research Register; Current Controlled Trials; and Index to Theses. Studies were selected if they reported prescribing errors committed by junior doctors in primary or secondary care, were in English, published since 1990 and undertaken in Western Europe, North America or Australasia.

RESULTS

Twenty‐four studies meeting the inclusion criteria were identified. The range of error rates was 2–514 per 1000 items prescribed and 4.2–82% of patients or charts reviewed. Considerable variation was seen in design, methods, error definitions and error rates reported.

CONCLUSIONS

The review reveals a widespread problem that does not appear to be associated with different training models, healthcare systems or infrastructure. There was a range of designs, methods, error definitions and error rates, making meaningful conclusions difficult. No definitive study of prescribing errors has yet been conducted, and is urgently needed to provide reliable baseline data for interventions aimed at reducing errors. It is vital that future research is well constructed and generalizable using standard definitions and methods.
Clinical implications of ELA2‐, HAX1‐, and G‐CSF‐receptor (CSF3R) mutations in severe congenital neutropenia
Authors: Zeidler Cornelia , Germeshausen Manuela , Klein Christoph , Welte Karl
Published: December 2008

Congenital Neutropenia (CN) is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoiesis at the level of the promyelocyte/myelocyte stage with peripheral blood absolute neutrophil counts below 0·5 × 109/l. There are two major subtypes of CN as judged by inheritance: an autosomal dominant subtype, e.g. defined by neutrophil elastase mutations (approximately 60% of patients) and an autosomal recessive subtype (approximately 30% of patients), both presenting with the same clinical and morphological phenotype. Different mutations have been described (e.g. HAX1, p14 etc) in autosomal recessive CN, with HAX1 mutations in the majority of these patients. CN in common is considered as a preleukemic syndrome, since the cumulative incidence for leukemia is more than 25% after 20 years of observation. Leukemias occur in both, the autosomal dominant and recessive subtypes of CN. The individual risk for each genetic subtype needs to be further evaluated. Numbers of patients tested for the underlying genetic defect are still limited. Acquired G‐CSFR (CSF3R) mutations are detected in approximately 80% of CN patients who developed acute myeloid leukemia independent of the ELA2 or HAX1 genetic subtype, suggesting that these mutations are involved in leukemogenesis. As the majority of patients benefit from G‐CSF administration, HSCT should be restricted to non‐responders and patients with leukaemic transformation.
Expansion of haematopoietic stem cells from normal donors and bone marrow failure patients by recombinant hoxb4
Authors: Tang Yong , Chen Jichun , Young Neal S.
Published: December 2008

In this study six versions of recombinant human hoxb4 proteins were produced and their effectiveness evaluated in expanding human haematopoietic stem and progenitor cells in vitro and in vivo. An N‐terminal‐tat and C‐terminal histidine‐tagged version of hoxb4 (T‐hoxb4‐H) showed the highest activity in expanding colony forming cells (CFCs) and long‐term culture‐initiating cells (LTC‐ICs) when used at 50 nmol/l concentration in cell culture. Human cord blood CD34+ cells cultured with 50 nmol/l T‐hoxb4‐H showed a significant increase in severe‐combined immunodeficient mouse‐repopulating cells (SRCs). In a mouse model of immune‐mediated bone marrow (BM) failure, T‐hoxb4‐H showed an additive effect with cyclosporine in alleviating pancytopenia. In addition, T‐hoxb4‐H expanded CFC and LTC‐IC on BM samples from patients with refractory severe aplastic anaemia and myelodysplastic syndromes: after culturing with 50 nmol/l T‐hoxb4‐H for 4 d, BM cells from 10 of the 11 patients showed increases in CFC and LTC‐IC, and the increase in LTC‐IC was statistically significant in samples from four patients. Recombinant human hoxb4 could be a promising therapeutic agent for BM failure.
Peripheral blood progenitor cell collection adverse events for childhood allogeneic donors: variables related to the collection and safety profile
Authors: Sevilla Julián , González‐Vicent Marta , Lassaletta Alvaro , Ramírez Manuel , Pérez‐Martínez Antonio , Madero Luis , Díaz Miguel Angel
Published: December 2008

The use of children as haematopoietic stem cell donors represents an ethical dilemma. For some investigators, this is even more questionable if the children underwent peripheral blood progenitor cell (PBPC) collection. Due to these controversies, information related to adverse events (AE) in paediatric donors and variables related to the collection is scanty. We analysed 152 PBPC collections, and compared the complications and results between young children, older children and adults. The pattern of AE was shown to vary according to the age of the donor. Older paediatric donors and adults had a higher incidence of complaints related to PBPC priming (54·3% vs. 79·7%, respectively) than the youngest children (12%). On the other hand, these donors had a lower incidence of AE during PBPC collection (19·6% older children, 37·3% adults) mainly related to hypocalcaemia, than the youngest donors, who suffered mainly cardiovascular complications due to hypovolaemia (51·7%). The only variables related to collected cell dose were total blood volume processed per donor body weight, and CD34+ cell count before apheresis. The donor/recipient body weight ratio predicted the outcome of collection in a single large volume leukapheresis. Donors with body weight ratio ≥0·75 had 4·69 times higher likelihood to reach the minimum target cell dose.
Identification, characterization and rescue of a novel vasopressin‐2 receptor mutation causing nephrogenic diabetes insipidus
Authors: Ranadive Sayali A. , Ersoy Baran , Favre Helene , Cheung Clement C. , Rosenthal Stephen M. , Miller Walter L. , Vaisse Christian
Published: December 2008

Objective  X‐linked nephrogenic diabetes insipidus (XNDI), caused by mutations in the V2 vasopressin receptor (V2R), is clinically distinguished from central diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and unresponsiveness to 1‐desamino‐8‐d‐arginine vasopressin (DDAVP). We report two infants with XNDI, and present the characterization and functional rescue of a novel V2R mutation.

Patients  Two male infants presented with poor growth and hypernatraemia. Both patients had measurable pretreatment serum AVP and polyuria that did not respond to DDAVP, suggesting NDI. However, both also had absent posterior pituitary bright spot on MRI, which is a finding more typical of CDI.

Methods  The AVPR2 gene encoding V2R was sequenced. The identified novel missense mutation was re‐created by site‐directed mutagenesis and expressed in HEK293 cells. V2R activity was assessed by the ability of transfected cells to produce cAMP in response to stimulation with DDAVP. Membrane localization of V2R was assessed by fluorescence microscopy.

Results  Patient 1 had a deletion of AVPR2; patient 2 had the novel mutation L57R. In transiently transfected HEK293 cells, DDAVP induced detectable but severely impaired L57R V2R activity compared to cells expressing wild‐type V2R. Fluorescence microscopy showed that myc‐tagged wild‐type V2R localized to the cell membrane while L57R V2R remained intracellular. A nonpeptide V2R chaperone, SR121463, partially rescued L57R V2R function by allowing it to reach the cell membrane.

Conclusions  L57R V2R has impaired in vitro activity that can be partially improved by treatment with a V2R chaperone. The posterior pituitary hyperintensity may be absent in infants with XNDI.
Functional analysis of two rare CYP21A2 mutations detected in Italian patients with a mildest form of congenital adrenal hyperplasia
Authors: Concolino Paola , Vendittelli Francesca , Mello Enrica , Minucci Angelo , Carrozza Cinzia , Rossodivita Aurora , Giardina Bruno , Zuppi Cecilia , Capoluongo Ettore
Published: December 2008

Background  More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21‐hydroxylase gene (CYP21A2) mutations. Most of these mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5–10% of 21‐hydroxylase deficiency alleles.

Objective  Functional analysis of two novel CYP21A2 missense mutations (p.R224W and p.D407N) was performed.

Design  Our study was composed of two Italian patients suffering from a very mild form of nonclassic CAH (NC‐CAH). To assay the enzymatic activity of mutants, the in vitro analysis was performed in transiently transfected COS‐1 cells.

Results  The residual activities obtained for p.R224W and p.D407N mutants allow their classification as NC‐CAH mutations. These results correlate with the rate of severity of the patients’ disease.

Conclusions  In this paper, we report two novel CYP21A2 mutations in two Italian individuals affected by 21‐hydroxylase deficiency. Based on the functional in vitro analysis we can classify these mutations as NC‐CAH variants.
1α,25‐dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection
Authors: Coussens Anna , Timms Peter M. , Boucher Barbara J. , Venton Timothy R. , Ashcroft Anthony T. , Skolimowska Keira H. , Newton Sandra M. , Wilkinson Katalin A. , Davidson Robert N. , Griffiths Christopher J. , Wilkinson Robert J. , Martineau Adrian R.
Published: December 2008

Matrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3], has previously been reported to inhibit secretion of MMP‐9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M. tuberculosis‐infected cells has not previously been investigated. We therefore determined the effects of 1α,25(OH)2D3 on expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis‐infected human leucocytes; we also investigated the effect of 1α,25(OH)2D3 on the secretion of interleukin‐10 (IL‐10) and prostaglandin E2 (PGE2), both transcriptional regulators of MMP expression. We found that M. tuberculosis induced expression of MMP‐1, MMP‐7 and MMP‐10 in MN and MMP‐1 and MMP‐10 in peripheral blood mononuclear cells (PBMC). 1α,25(OH)2D3 significantly attenuated M. tuberculosis‐induced increases in expression of MMP‐7 and MMP‐10, and suppressed secretion of MMP‐7 by M. tuberculosis‐infected PBMC. MMP‐9 gene expression, secretion and activity were significantly inhibited by 1α,25(OH)2D3 irrespective of infection. In contrast, the effects of 1α,25(OH)2D3 on the expression of TIMP‐1, TIMP‐2 and TIMP‐3 and secretion of TIMP‐1 and TIMP‐2 were small and variable. 1α,25(OH)2D3 also induced secretion of IL‐10 and PGE2 from M. tuberculosis‐infected PBMC. These findings represent a novel immunomodulatory role for 1α,25(OH)2D3 in M. tuberculosis infection.
CD56bright natural killer (NK) cells: an important NK cell subset
Authors: Poli Aurélie , Michel Tatiana , Thérésine Maud , Andrès Emmanuel , Hentges François , Zimmer Jacques
Published: December 2008

Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/− and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.
Oil extractability from enzymatically treated goldenberry (Physalis peruviana L.) pomace: range of operational variables
Authors: Ramadan Mohamed Fawzy , Moersel Joerg‐Thomas
Published: December 2008

Goldenberry pomace (seeds and skins) represents a large portion of the waste generated during juice processing (ca. 27.4% of fruit weight). The potential of goldenberry agro‐industrial wastes for use as raw material for production of edible oil was evaluated. Fruit pomace, contained 6.6% moisture, 17.8% protein, 3.10% ash, 28.7% crude fibre and 24.5% carbohydrates. The n‐hexane‐extractable oil content of the raw by‐products was estimated to be 19.3%. Aqueous enzymatic extraction was investigated for recovery of oil from the fruit pomace. The most significant factors affecting extraction were enzyme concentration, the time of digestion with enzymes, substrate concentration in water and the particle size of substrate. A broad variation in oil recovery was obtained depending on the operational conditions during the enzyme‐aided aqueous extraction. The optimum and economical values were those obtained for 4:0.02:1 water:enzyme:substrate ratio. Generally, enzymatic treatment increased the extraction yield. The more than 42% yield by enzymation compared with the nearly 3% yield in the control process (without enzyme) implies a significant increase in yield by about 92.8%. In single‐enzyme trials, cellulase EC gave the best yield. Although proteases slightly improve yield, the enhancement values are much lower than those obtained with Cellulase EC and Pektinace L40. Rapid increase in oil yield occurred as the enzyme concentration increased from 1 to 2 g/100 g substrate. Yield increased with dilution, but it began to fall when the substrate became more diluted. Moreover, extractability increased significantly when particle size reduced. Concerning the oil composition, there were no great changes in the fatty acid pattern of the oils extracted with different hydrolytic enzymes when compared with each other or to the solvent extracted oil. The main purpose of this study was to maximise the efficiency of the enzymatic treatment for oil recovery from goldenberry pomace. As a first step toward developing goldenberry as a commercial crop, the results provide important information for the industrial application of the fruit.