bluuebunny/crossref_metadata_2025 huggingface dataset:
Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes
Authors: Rossi Andrea , Mukerjee Ruma , Ferrante Pasquale , Khalili Kamel , Amini Shohreh , Sawaya Bassel E.
Published: May 2006

Previous examination of the effect of TCF-4 on transcription of the human immunodeficiency virus type 1 (HIV-1) promoter in human astrocytic cells found that TCF-4 affects the HIV-1 promoter through the GC-rich domain (nt −80 to nt −68). Here, the physical interaction and a functional consequence of TCF4–Sp1 contact were characterized. It was shown that expression of TCF-4 in U-87 MG (human astrocytic) cells decreased basal and Sp1-mediated transcription of the HIV-1 promoter. Results from a GST pull-down assay, as well as combined immunoprecipitation and Western blot analysis of protein extracts from U-87 MG cells, revealed an interaction of Sp1 with TCF-4. Using in vitro protein chromatography, the region of Sp1 that contacts TCF-4 was mapped to aa 266–350. It was also found that, in cell-free extracts, TCF-4 prevented dsDNA-dependent protein kinase (DNA-PK)-mediated Sp1 phosphorylation. Surprisingly, TCF-4 failed to decrease Sp1-mediated transcription of the HIV-1 long terminal repeat (LTR) and Sp1 phosphorylation in cells expressing HIV-1 Tat. Results from immunoprecipitation/Western blotting demonstrated that TCF-4 lost its ability to interact with Sp1, but not with Tat, in Tat-transfected cells. Taken together, these findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1, which is affected by Tat and DNA-PK. Interactions among TCF-4, Sp1 and/or Tat may determine the level of viral gene transcription in human astrocytic cells.
Sequence elements of the fusion peptide of human respiratory syncytial virus fusion protein required for activity
Authors: Martín Diana , Calder Lesley J. , García-Barreno Blanca , Skehel John J. , Melero José A.
Published: May 2006

We have reported previously the expression and purification of an anchorless form of the human respiratory syncytial virus (HRSV) F protein () representing the ectodomain of the full-length F.molecules are seen as unaggregated cones by electron microscopy but completion of proteolytic cleavage of the F0 monomers in thetrimer leads to a change in shape from cones to lollipops that aggregate into rosettes. This aggregation apparently occurs by interaction of the fusion peptides ofmolecules that are exposed after cleavage. Since exposure of the fusion peptide is a key event in the process of membrane fusion, changes associated withcleavage may reflect those occurring in full-length F during membrane fusion. Deletions or substitutions that changed either the length, charge or hydrophobicity of the fusion peptide inhibited aggregation of, and these mutants remained as unaggregated cones after cleavage. In contrast, more conservative changes did not inhibit the change of shape and aggregation of. When the same changes were introduced in the fusion peptide of full-length F, only the mutations that inhibited aggregation ofprevented membrane fusion. Thus, the conformational changes that follow completion of cleavage of theprotein require a functional fusion peptide. These sequence constraints may restrict accumulation of sequence changes in the fusion peptide of HRSV F when compared with other hydrophobic regions of the molecule.
Induction of hepatitis D virus large antigen translocation to the cytoplasm by hepatitis B virus surface antigens correlates with endoplasmic reticulum stress and NF-κB activation
Authors: Huang I-Cheng , Chien Chia-Ying , Huang Chi-Ruei , Lo Szecheng J.
Published: May 2006

It is known that hepatitis D virus (HDV) requires hepatitis B virus (HBV) for supplying envelope proteins (HBsAgs) to produce mature virions, and the HDV large antigen (LDAg) is responsible for interacting with HBsAgs. However, the signal molecules involved in the cross-talk between HBsAgs and LDAg have never been reported. It has been previously demonstrated that the small form of HBsAg can facilitate the translocation of HDV large antigen green fluorescent protein (GFP) fusion protein (GFP–LD) from the nucleus to the cytoplasm. In this study, it was confirmed that the small form of HBsAg can facilitate both GFP–LD and authentic LDAg for nuclear export. It was also shown that the three forms of HBsAgs (large, middle and small) induced various rates (from 35.4 to 57.2 %) of GFP–LD nuclear export. Since HBsAgs are localized inside the endoplasmic reticulum (ER), this suggests that ER stress possibly initiates the signal for inducing LDAg translocation. This supposition is supported by results that show that around 9 % of cells appear with GFP–LD in the cytoplasm after treatment with the ER stress inducers, brefeldin A (BFA) and tunicamycin, in the absence of HBsAg. Western blot and immunofluorescence microscopy results further showed that the activation of NF-κB is linked to the ER stress that induces GFP–LD translocation. Combining this with results showing that tumour necrosis factor alpha (TNF-α) can also induce GFP–LD translocation, it was concluded that LDAg translocation correlates with ER stress and activation of NF-κB. Nevertheless, TNF-α-induced GFP–LD translocation was independent of new protein synthesis, suggesting that a post-translational event occurs to GFP–LD to allow translocation.
Vaccinia virus strain Western Reserve protein B14 is an intracellular virulence factor
Authors: Chen Ron A.-J. , Jacobs Nathalie , Smith Geoffrey L.
Published: May 2006

A characterization of theB14Rgene fromVaccinia virus(VACV) strain Western Reserve (WR) is presented. Computational analyses of theB14Rgene indicated high conservation in orthopoxviruses but no orthologues outside thePoxviridae. To characterize the B14 protein, theB14Rgene was expressed inEscherichia coliand recombinant protein was purified and used to generate a rabbit polyclonal antiserum. This antiserum recognized a 15 kDa cytoplasmic protein in mammalian cells that were transfected with theB14Rgene or infected with VACV WR, but not from cells infected with a VACV mutant (vΔB14) from which theB14Rgene was deleted. Compared to wild-type and revertant virus controls, vΔB14 had normal growth kinetics in cell culture. The virulence of vΔB14 was assessed in twoin vivomodels. Mice infected intranasally with vΔB14 had similar weight loss compared to the controls, but in C57BL/6 mice infected intradermally vΔB14 induced a smaller lesion size compared with controls. Moreover, intradermal infection with vΔB14 caused an increased infiltration of cells into the infected lesion despite the smaller lesion size. Therefore, B14 is an intracellular protein that is non-essential for virus replication in cell culture but contributes to virus virulencein vivoand affects the host response to infection.
Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus
Authors: Ren Xiaofeng , Glende Jörg , Al-Falah Marwan , de Vries Victor , Schwegmann-Wessels Christel , Qu Xiuxia , Tan Lei , Tschernig Thomas , Deng Hongkui , Naim Hassan Y. , Herrler Georg
Published: May 2006

The primary target of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is epithelial cells in the respiratory and intestinal tract. The cellular receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2), has been shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate infection from the apical side of these cells. Here, these results were confirmed and extended by including a colon carcinoma cell line (Caco-2), a lung carcinoma cell line (Calu-3) and Vero E6 cells in our analysis. All three cell types expressed human ACE2 on the apical membrane domain and were infected via this route, as determined with vesicular stomatitis virus pseudotypes containing the S protein of SARS-CoV. In a histological analysis of the respiratory tract, ACE2 was detected in the trachea, main bronchus and alveoli, and occasionally also in the small bronchi. These data will help us to understand the pathogenesis of SARS-CoV infection.
The immune response during hepatitis B virus infection
Authors: Bertoletti Antonio , Gehring Adam J.
Published: May 2006

Hepatitis B virus(HBV) is a major cause of chronic liver inflammation worldwide. Recent knowledge of the virological and immunological events secondary to HBV infection has increased our understanding of the mechanisms involved in viral clearance and persistence. In this review, how the early virological and immunological events might influence the development of a coordinate activation of adaptive immunity necessary to control HBV infection is analysed. The mechanism(s) by which high levels of viral antigens, liver immunological features, regulatory cells and dendritic cell defects might maintain the HBV-specific immunological collapse, typical of chronic hepatitis B patients, is also examined.
Method of separated form factors for polydisperse vesicles
Authors: Pencer Jeremy , Krueger Susan , Adams Carl P. , Katsaras John
Published: May 2006

Use of the Schulz or Gamma distribution in the description of particle sizes facilitates calculation of analytic polydisperse form factors using Laplace transforms, {\cal L}[f(u)]. Here, the Laplace transform approach is combined with the separated form factor (SFF) approximation [Kiselevet al.(2002).Appl. Phys. A,74, S1654–S1656] to obtain expressions for form factors,P(q), for polydisperse spherical vesicles with various forms of membrane scattering length density (SLD) profile. The SFF approximation is tested against exact form factors that have been numerically integrated over the size distribution, and is shown to represent the vesicle form factor accurately for typical vesicle sizes and membrane thicknesses. Finally, various model SLD profiles are used with the SFF approximation to fit experimental small-angle neutron scattering (SANS) curves from extruded unilamellar vesicles.
Simple procedure for conformation-family search in multidimensional torsion-angle space
Authors: Pavelcik Frantisek , Vanco Jan
Published: May 2006

A method for studying conformation spaces inndimensions has been developed. The method is used to calculate preferences of conformation families for the purpose of model building.
Calculation of the instrumental function in X-ray powder diffraction
Authors: Zuev A. D.
Published: May 2006

A new method for calculating the total instrumental function of a conventional Bragg–Brentano diffractometer has been developed. The method is based on an exact analytical solution, derived from diffraction optics, for the contribution of each incident ray to the intensity registered by a detector of limited size. Because an incident ray is determined by two points (one is related to the source of the X-rays and the other to the sample) the effects of the coupling of specific instrumental functions, for example, equatorial and axial divergence instrumental functions, are treated together automatically. The intensity at any arbitrary point of the total instrumental profile is calculated by integrating the intensities over two simple rectangular regions: possible point positions on the source and possible point positions on the sample. The effects of Soller slits, a monochromator and sample absorption can also be taken into account. The main difference between the proposed method and the convolutive approach (in which the line profile is synthesized by convolving the specific instrumental functions) lies in the fact that the former provides an exact solution for the total instrumental function (exact solutions for specific instrumental functions can be obtained as special cases), whereas the latter is based on the approximations for the specific instrumental functions, and their coupling effects after the convolution are unknown. Unlike the ray-tracing method, in the proposed method the diffracted rays contributing to the registered intensity are considered as combined (part of the diffracted cone) and, correspondingly, the contribution to the instrumental line profile is obtained analytically for this part of the diffracted cone and not for a diffracted unit ray as in ray-tracing simulations.
Measurement of stress/strain in single-crystal samples using diffraction
Authors: Yan Hanfei , Noyan I. C.
Published: May 2006

Diffraction profiles from an Si-single-crystal strip deformed in cantilever bending are presented as a function of tip displacement and incident-beam energy. Data obtained with slit-based diffracted-beam optics contain a secondary peak in addition to the primary 004 reflection for all energies when the bending strain is finite. This secondary peak can be identified as a `mirage' peak, predicted by dynamical diffraction theory to occur in weakly deformed single-crystal samples. The integrated intensity of this mirage peak increases with increasing energy and tip displacement and exceeds the primary peak intensity at higher values. The mirage peak disappears when a monochromator is used in the diffracted-beam path. Data that show the effect of these mirage peaks on X-ray diffraction strain analysis are presented, and it is shown that a diffracted-beam monochromator may be used to eliminate these errors.
A program for automated optimization of initial crystallization conditions
Authors: Ben Haj Abdellatif Tahia , Kozielski Frank
Published: May 2006

Protein crystallization is a difficult and time-consuming task, because to obtain a crystal, optimization steps are required almost systematically. A tool that simplifies the optimization of crystallization conditions, and that can be used by any crystallographer to design a crystallization plate and to visualize its content, has become a paramount necessity. A free and open-source application has been developed to automate this task. It is based on a graphical user interface (GUI) that allows a personalized crystallization plate to be designed. All data used and generated are saved in XML documents, which allow reuse of the information. The steps involved in preparing a crystallization plate and the functions of the GUI designed to perform these steps are described. Plans for future development are presented. The program was written in Java. The application and its documentation are available under CeCILL license, which is a Free Software license agreement.
The instrumental resolution function of synchrotron radiation powder diffractometers in the presence of focusing optics
Authors: Gozzo Fabia , De Caro Liberato , Giannini Cinzia , Guagliardi Antonietta , Schmitt Bernd , Prodi Andrea
Published: May 2006

The theory developed by Caglioti and co-workers [Caglioti, Paoletti & Ricci (1958).Nucl. Instrum.3, 223–228; Caglioti, Paoletti & Ricci (1960).Nucl. Instrum. Methods,9, 195–198; Caglioti & Ricci (1962).Nucl. Instrum. Methods,15, 155–163] and Sabine [(1987).J. Appl. Cryst.20, 23–27, 173–178] that provides an analytical description of the instrumental resolution function of single-crystal and powder diffractometers consisting of sequences of collimators and crystals is extended by including the effect of collimating and refocusing mirrors. A simple analytical expression with only two fitting parameters (the beam divergence after reflection by the collimating and the refocusing mirrors) is determined, this expression being applicable to all mirror settings. The new theory is applied to experimental data collected at the Swiss Light Source Materials Science beamline powder diffractometer for three photon energies under extreme mirror bending conditions using the small-linewidth powder sample Na2Ca3Al2F14.
A direct method for the determination of the mean orientation-dependent elastic strains and stresses in polycrystalline materials from strain pole figures
Authors: Bernier Joel V. , Miller Matthew P.
Published: May 2006

A salient manifestation of anisotropy in the mechanical response of polycrystalline materials is the inhomogeneous partitioning of elastic strains over the aggregate. For bulk samples, the distributions of these intergranular strains are expected to have a strong functional dependence on grain orientations. It is then useful to formulate a mean lattice strain distribution function (LSDF) over the orientation space, which serves to characterize the micromechanical state of the aggregate. Orientation-dependent intergranular stresses may be recovered from the LSDFviaa constitutive assumption, such as anisotropic linear elasticity. While the LSDF may be determined directly from simulation data, its experimental determination relies on solving an inverse problem that is similar in character to the fundamental problem of texture analysis. In this paper, a versatile and robust direct method for determining an LSDF from strain pole figures is presented. The effectiveness of this method is demonstrated using synthetic strain pole figures from a model LSDF obtained from the simulated uniaxial deformation of a 1000-crystal aggregate.
Geometrical parameterization of the crystal chemistry ofP63/mapatite. II. Precision, accuracy and numerical stability of the crystal-chemical Rietveld refinement
Authors: Mercier Patrick H. J. , Le Page Yvon , Whitfield Pamela S. , Mitchell Lyndon D.
Published: May 2006

A script developed for crystal-chemical Rietveld refinement ofP63/mapatite withTOPASis implemented in parallel with standard structure refinement. Least-squares standard uncertainty (s.u.) values for directly extracted crystal-chemical parameters are nearly an order of magnitude lower than those obtained indirectly by analysis of atom coordinates derived by standard Rietveld refinement. This amazing finding originates partly in the reduction of the number of refinement parameters from 21 to 17 and partly in the fact that cell data now derive from crystal-chemical parameters instead ofvice versa. Great precision and accuracy otherwise funneled into unit-cell parameters is then more distributed among mostly crystal-chemical distance parameters. The least-squares s.u. values are supported by analysis of numerous refinements of the same experimental data with added artificial intensity noise. Structural parameters from single-crystal results agree better with those extracted by crystal-chemical refinement. On the basis of singular value decomposition analyses performed using the programSVDdiagnostic[Mercieret al.(2006).J. Appl. Cryst.39, 458–465], crystal-chemical and standard Rietveld refinements are shown to have similar numerical stability. Crystal-chemical parameters extracted by direct Rietveld refinement, therefore, are more precise than, more accurate than and numerically as reliable as those derived from analysis of regular crystallographic refinement of the same data.
SVDdiagnostic, a program to diagnose numerical conditioning of Rietveld refinements
Authors: Mercier Patrick H. J. , Le Page Yvon , Whitfield Pamela S. , Mitchell Lyndon D.
Published: May 2006

Singular value decomposition (SVD) of the matrix of normal equations is used here both passively to assess numerical stability, and actively to troubleshoot problem refinements, singular or not. Such systems can then either be cured by rank reduction or solved with arbitrary-precision arithmetic carrying a number of digits known to be sufficient. SVD analysis provides objective information about such required rank reduction or number of digits. Pre-conditioning of the normal matrix is seen to decrease its condition number by many orders of magnitude in actual cases, illustrating its great practical usefulness. The methods and tools developed here have general applicability to diagnose problems with least squares, in particular ill-conditioned Rietveld refinements. Crystal-chemical and standard refinements described in the work by Mercieret al.[J. Appl. Cryst.(2006),39, 369–375] are shown to have similar numerical stability. The programSVDdiagnosticis freely available at http://www.tothcanada.com.
Structural and microstructural characterization of bioapatites and synthetic hydroxyapatite using X-ray powder diffraction and Fourier transform infrared techniques
Authors: Chakraborty Santu , Bag Sandip , Pal Subrata , Mukherjee Alok K.
Published: May 2006

Bioapatite, the main constituent of mineralized tissue in mammalian bones and teeth, is similar in structure and composition to calcium hydroxyapatite (HAP), Ca10(PO4)6(OH)2. The crystallographic analyses of four bioapatites of human-, goat- and rabbit-bone and human-teeth origin, and one synthetic HAP preparedviamicrowave irradiation, have been carried out using X-ray powder diffraction techniques. Fourier transform infrared spectra and Rietveld analyses indicate partial replacement of PO43−ions by CO32−ions in all bioapatites.
Grazing-incidence small-angle X-ray scattering from thin polymer films with lamellar structures – the scattering cross section in the distorted-wave Born approximation
Authors: Busch P. , Rauscher M. , Smilgies D.-M. , Posselt D. , Papadakis C. M.
Published: May 2006

Grazing-incidence small-angle X-ray or neutron scattering of thin polymer films reveals information about the ordering and preferential orientations of the phase-separated microdomains within the films. The grazing-incidence geometry enhances the surface sensitivity; however, the scattering has to be treated within the framework of the distorted-wave Born approximation. In this work, the case of thin films with lamellar mesostructure is studied, where the orientation of the lamellae is either perpendicular or parallel to the film interfaces. For perpendicular lamellae, Bragg rods are found, which are extended along the film normal, whereas for parallel lamellae, peaks along the film normal appear. The positions of the maxima present in the latter case are explained by accounting for refraction at the film surface and reflection at the film–substrate interface. The results are relevant for thin films of lamellar diblock copolymers.
Immunohistochemical study of cyclooxygenase‐2 and p53 expression in skin tumors
Authors: KIM Kwang Ho , PARK Eun Joo , SEO Young Ju , CHO Han Suk , KIM Chul Woo , KIM Kwang Joong , PARK Hye Rim
Published: May 2006

Overexpression of cyclooxygenase‐2 (COX‐2) has been demonstrated in various cancers, including experimentally promoted tumors, gastrointestinal cancers, breast tumors and skin tumors. The mechanism that controls COX‐2 expression is not yet clear. Currently, it is reported that COX‐2 expression is frequently associated with mutated p53 genes. The goal of this study was to evaluate the expression patterns of COX‐2 and p53 in several skin tumors and their correlation. An immunohistochemical method was used to investigate the expression of COX‐2 and p53 proteins on formalin‐fixed, paraffin‐embedded tissue specimens of squamous cell carcinomas (SCC), basal cell carcinomas (BCC), Bowen's disease (BD), actinic keratosis (AK) and porokeratosis. The expression of COX‐2 increased in 50% (5/10) of SCC, 80% (8/10) of BCC, 40% (4/10) of BD, 50% (5/10) of AK, and 20% (2/10) of porokeratosis cases. The expression of p53 increased in 90% (9/10) of SCC, 70% (7/10) of BCC, 70% (7/10) of BD, 50% (5/10) of AK, and 40% (4/10) of porokeratosis cases. COX‐2 positivity rates of the p53‐positive skin tumors were 56%, 100%, 57%, 80% and 25% in SCC, BCC, BD, AK and porokeratosis, respectively. However, the correlation between p53 and COX‐2 expression in skin tumors was not statistically significant (P > 0.05). Our results indicate that skin COX‐2 and p53 may play roles in skin tumors, but that there is no apparent correlation between the two markers.
Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin
Authors: HAMA Naoto , OHTSUKA Tsutomu , YAMAZAKI Soji
Published: May 2006

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.
Aggressive conservative therapy for refractory ulcer with diabetes and/or arteriosclerosis
Authors: MOTOMURA Hisashi , OHASHI Natsuko , HARADA Teruichi , MURAOKA Michinari , ISHII Masamitsu
Published: May 2006

A foot ulcer due to diabetes and/or arteriosclerosis obliterans (ASO) frequently results in an intractable condition that resists treatment. To cope with this condition, we have developed a combination therapy that includes conventional conservative therapy plus surgical therapy. This aggressive conservative therapy using aggressive debridement, trafermin (Fiblast Spray, Kaken, Japan) treatment and vacuum‐assisted closure (VAC) therapy was adopted to treat seven patients suffering from diabetes and ASO‐related refractory foot ulcer accompanied by bone exposure. With the exception of one patient who died during the treatment, the remaining six patients obtained limb salvage. The mean time to cure was 8.3 months. This approach should be considered before amputation. Some patients may refuse amputation or cannot tolerate highly invasive surgical treatment including tissue transplantation. In such cases, this aggressive conservative therapy can be employed as a highly useful and reproducible technique requiring simple techniques.
Conjunctival squamous cell carcinoma in a patient with hemodialysis‐related porphyria cutanea tarda
Authors: AYDİNGÖZ İkbal Esen , MANSUR Ayşe Tülin , ERÇIN Zuhal
Published: May 2006

Hemodialysis‐related porphyria cutanea tarda (HRPCT) is characterized by porphyria‐like blisters on sun‐exposed parts of the face, arms and hands due to elevated porphyrin levels. Conjunctival squamous cell carcinoma (CSCC) is a rare cancer that typically occurs on the sun‐damaged ocular surface of elderly male patients. Herein, we report a case of CSCC in a 72‐year‐old patient who had been on hemodialysis for 8 years, and had been followed up with a diagnosis of HRPCT for 3 years. To our knowledge, this is the first case report documenting an association between HRPCT and CSCC, which may reflect a pathogenetic process connecting them.
A case of lymphangitic sporotrichosis occurring on both forearms with a published work review of cases of bilateral sporotrichosis in Japan
Authors: HARUNA Kunitaka , SHIRAKI Yumi , HIRUMA Masataro , IKEDA Shigaku , KAWASAKI Masako
Published: May 2006

The patient, 56‐year‐old man who was working as a clerk and a farmer, presented with nodules that had appeared on the dorsa of both his hands 3 months earlier. At the first examination, there were multiple dark‐red nodules scattered on the fingers, dorsa and wrists of both hands. The nodules were up to 3 cm in diameter and had crusts in the incenters. The patient was suspected to suffer from prurigo and was subsequently treated with topical steroid, but the nodules did not respond. Therefore, a skin biopsy and fungal culture were performed, and the patient was finally diagnosed as having bilateral multiple sporotrichosis. He was then successfully treated with local thermotherapy and oral potassium iodide. Bilaterally‐distributed lymphangitic sporotrichosis is very rare and often difficult to diagnose. Careful attention is required to avoid misdiagnosis.
A pilot study of atorvastatin treatment in dyslipemid, non‐alcoholic fatty liver patients
Authors: GÓMEZ‐DOMÍNGUEZ E. , GISBERT J. P. , MORENO‐MONTEAGUDO J. A. , GARCÍA‐BUEY L. , MORENO‐OTERO R.
Published: May 2006

Background

Non‐alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver injury. Currently, there are no proven effective therapies available. Atorvastatin is a new 3‐hydroxy‐3‐metylglutaryl coenzyme A reductase inhibitor that reduces lipid serum levels.

Aim

To evaluate the effectiveness and safety of atorvastatin in dyslipemid, non‐alcoholic fatty liver patients.

Patients and methods

We prospectively enrolled 25 patients with NAFLD; 22 of them completed the study. Body mass index, serum lipids, liver function tests and liver density assessed by echography were measured at baseline and after 1, 3, 6, 9 and 12 months of treatment. Normalization of transaminases and/or improvement in liver density were treatment end points. Patients received atorvastatin (10–80 mg/daily) according to basal serum choleresterol levels; additionally, they were given standard weight‐loss counselling and encouraged to follow a low fat diet.

Results

All 22 patients (14 men, mean age 47 ± 10 years) had high cholesterol levels at baseline and 11 (44%) also presented high trygliceride levels. After 6 months of treatment, eight patients (36.3%) presented normal transaminase levels. The remaining patients continued treatment for 12 months when 20% of patients presented with normal transaminase levels, while the other patients showed a 10% reduction in basal levels. Mean cholesterol levels were 268.5 ± 44.2 and 186.8 ± 14.4 mg/dL before and after treatment, respectively (P < 0.05). The mean body mass index was 27.4 ± 3.1 at baseline and 26.3 ± 2.8 kg/cm2at the end of treatment (P > 0.05). No side effects were reported.

Conclusions

Serum aminotransferase and lipid levels were reduced significantly in all patients with atorvastatin treatment. Therapy with atorvastatin in NAFLD patients with hyperlipidemia was found to be both effective and safe.
Determinants of healthcare‐seeking behaviour among subjects with irritable bowel syndrome
Authors: WILLIAMS R. E. , BLACK C. L. , KIM H.‐Y. , ANDREWS E. B. , MANGEL A. W. , BUDA J. J. , COOK S. F.
Published: May 2006

Background

Doctor visits for irritable bowel syndrome are associated with high medical costs. Predictors of medical consultation for irritable bowel syndrome remain poorly understood.

Aim

To determine factors associated with healthcare seeking for irritable bowel syndrome.

Methods

Subjects from previous US population‐based survey were contacted 2 years later. Those who continued to have irritable bowel syndrome were included.

Results

49% of subjects sought medical care for abdominal symptoms in the past year. Healthcare seeking did not differ significantly between males and females, but more females received an irritable bowel syndrome diagnosis. Predictors of irritable bowel syndrome healthcare seeking differed by gender. In multivariate analysis, age ≥55 years (OR = 2.8, 95% CI: 1.5–5.4), fear abdominal symptoms relates to serious illness (OR = 1.7, 95% CI: 0.95–3.1), decreased bowel movements (OR = 1.8, 95% CI: 0.98–3.2), dyspepsia (OR = 1.7, 95% CI: 0.94–3.2) and pelvic pain (OR = 2.3, 95% CI: 1.2–4.4) were associated with seeking care in females. Among males, being disabled (OR = 11.6, 95% CI: 2.4–56.1) and abdominal cramping (OR =4.3, 95% CI: 1.2–15.4) were associated with seeking care. Healthcare seekers had lower irritable bowel syndrome‐related quality of life. Neither pain severity nor mental health status was associated with seeking care.

Conclusion

Healthcare‐seeking behaviour among irritable bowel syndrome patients was determined by presence of comorbidities and extent that irritable bowel syndrome affected quality of life, not physical symptoms or mental health status.
Diagnosis of liver fibrosis by transient elastography (FibroScan) and non‐invasive methods in Crohn's disease patients treated with methotrexate
Authors: LAHARIE D. , ZERBIB F. , ADHOUTE X. , BOUÉ‐LAHORGUE X. , FOUCHER J. , CASTÉRA L. , RULLIER A. , BERTET J. , COUZIGOU P. , AMOURETTI M. , DE LÉDINGHEN V.
Published: May 2006

Background

Methotrexate is an effective treatment in Crohn's disease, which may induce liver fibrosis with high cumulative doses. Transient elastography (FibroScan, Echosens, Paris, France) is a new non‐invasive rapid, allowing assessment of liver fibrosis by measurement of liver stiffness.

Aim

A prospective study to evaluate liver fibrosis with FibroScan and non‐invasive biochemical methods in Crohn's disease patients treated with methotrexate.

Methods

Consecutive Crohn's disease patients had evaluation of liver fibrosis with non‐invasive methods. Two subgroups of patients were compared: cumulative dose of methotrexate of more than 1500 mg (group 1) and naive for methotrexate (group 2). Liver biopsy was performed in patients with persistent liver enzyme abnormalities or FibroScan value >8.7 kPa.

Results

Fifty‐four consecutive Crohn's disease patients were fully investigated (45 females, mean age 41 ± 14 years). Median FibroScan values were similar in group 1 (n = 21) and in group 2 (n = 33), 5.5 and 4.5 kPa, respectively. FibroScan values were not correlated with the cumulative dose of methotrexate.

Conclusion

In Crohn's disease patients treated with a high dose of methotrexate, significant liver fibrosis is rare and not accurately detected with liver enzymes abnormalities. FibroScan could be recommended and liver biopsy could be performed only with patients with high values and/or with chronic liver enzymes abnormalities.
Perivascular axillary brachial plexus block and patient positioning: the influence of a lateral, head‐down position
Authors: Orlowski O. , Bullmann V. , Vieth V. , Filler T. , Osada N. , Van Aken H. , Weber T. P.
Published: May 2006

The aim of this study was to examine the effect of a 20° Trendelenburg position on the blockade of nerves that exit the brachial plexus proximally in patients undergoing single‐injection axillary brachial plexus block. After a pilot study of eight cadavers suggested that a head‐down and lateral position would encourage the proximal spread of local anaesthetic, 72 patients undergoing elective surgery were divided into two equal groups: a Supine group and a Modified Position group (lateral position, 20° head‐down tilt). Patients were left in the allocated position for 30 min after an axillary block had been performed with alkalinised mepivacaine 1% 49.5 ml. Sensory and motor blockade evaluation showed that there was a significantly higher proportion of axillary nerve (76% vs. 0%, p < 0.001), thoracodorsal nerve (86% vs. 0%, p < 0.001) and subscapular nerve (89% vs. 0%, p < 0.001) blockade in the Modified Position group. Sensory block of the radial nerve was also improved by the modified position (100% vs. 86%, p < 0.05).
Evaluation of four airway training manikins as simulators for inserting the LMA Classic™*
Authors: Silsby J. , Jordan G. , Bayley G. , Cook T. M.
Published: May 2006

Airway manikins have traditionally been used for teaching mask ventilation and tracheal intubation. There is an increasing need to use manikins for training in procedures such as insertion of the laryngeal mask airway. We have assessed four new airway training manikins (latest versions of the Airway Trainer™ (Laerdal, Norway), Airway Management Trainer™(Ambu, UK), ‘Bill 1’™(VBM, Germany) and Airsim™(Trucorp, Ireland)) as simulators for insertion of the LMA Classic™ laryngeal mask airway. Twenty volunteer anaesthetists inserted a size‐4 laryngeal mask airway five times into each of the four manikins, in random order. Each insertion was assessed using objective and subjective tests. Subjective assessment varied widely but overall assessment indicated that the Airway Management Trainer was the poorest simulator for insertion of the laryngeal mask airway. The ‘Bill 1’ and Airsim manikins performed best as simulators for insertion of the laryngeal mask airway, although realistic ventilation with ‘Bill 1’ was not possible.
The Robinson‐Hooper connection*
Authors: Macdonald A. , Zuck D.
Published: May 2006

The search for a connection between James Robinson, the dental surgeon who on 19 December 1846 administered the first general anaesthetic in England by the inhalation of the vapour of ether, and William Hooper, the pharmaceutical chemist who produced the best publicised and most widely used of the early commercial ether vaporisers, has revealed hitherto unrecognised aspects of the early history of general anaesthesia.
Comparative genome‐wide profiling of post‐transplant lymphoproliferative disorders and diffuse large B‐cell lymphomas
Authors: Rinaldi Andrea , Kwee Ivo , Poretti Giulia , Mensah Afua , Pruneri Giancarlo , Capello Daniela , Rossi Davide , Zucca Emanuele , Ponzoni Maurilio , Catapano Carlo , Tibiletti Maria Grazia , Paulli Marco , Gaidano Gianluca , Bertoni Francesco
Published: May 2006

Post‐transplant lymphoproliferative disorders (PTLD) are a major complication of solid organ transplantation, representing a cause of severe morbidity and mortality. Apart from Epstein–Barr virus infection, knowledge of the pathogenesis of monoclonal PTLD is limited. Powerful analysis techniques, such as whole genomic DNA profiling (array comparative genomic hybridisation), can improve our understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix GeneChip Human Mapping 10 k 2·0 was performed on 20 PTLD cases and 25 cases of diffuse large B‐cell lymphoma (DLBCL) from immunocompetent patients as a control group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q, 3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p were commonly gained in PTLD–DLBCL. The latter had frequent losses of 6q, 17p, 1p and 9p. Chromosome 12p was the most frequent target of deletions among PTLD–DLBCL cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10 seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains, involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were identified. These data suggest that PTLD share, at a lower frequency, common genetic aberrations with DLBCL from immunocompetent patients. The demonstration of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination of DNA copy number and LOH assessment lead to the hypothesis that uniparental disomy may be a potential mechanism in B‐cell lymphomagenesis.
A tribute to Sidney Farber – the father of modern chemotherapy
Authors: Miller Denis R.
Published: May 2006

Sidney Farber, world‐renowned paediatric pathologist, made major contributions to his field but is acknowledged as the father of the modern era of chemotherapy. He recognised that folic acid stimulated leukaemic cell growth and enhanced disease progression. He hypothesised that folic acid antagonists would inhibit or arrest the proliferation of cancer cells. His landmark study, published in 1948, demonstrated that a number of folic acid antagonists, including 4‐aminopteroyl‐glutamic acid (aminopterin) produced temporary remissions in children with acute undifferentiated leukaemia. These observations lead to the development and use of other chemotherapeutic agents, either singly or, more effectively, in combination for treating childhood and adult malignancies. He introduced actinomycin D for the treatment of metastatic and localised Wilms tumour. Under his guidance and leadership, both the ‘Jimmy Fund’, one of the first comprehensive paediatric oncology treatment centres, and the Children's Cancer Research Foundation, which later became the Dana–Farber Cancer Institute, were founded.
The chitinase allergens Der p 15 and Der p 18 from Dermatophagoides pteronyssinus
Authors: O'Neil S. E. , Heinrich T. K. , Hales B. J. , Hazell L. A. , Holt D. C. , Fischer K. , Thomas W. R.
Published: May 2006

Background
House dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae cause allergic disease in humans as well as in dogs. In geographical regions where the two mite species coexist, they both elicit specific immunoglobulin (Ig E) responses in humans whereas dogs preferentially react to D. farinae extracts. In dogs the main IgE binding is directed to the D. farinae chitinase allergens Der f 15 and Der f 18 and not to the groups 1 and 2 allergens as found for humans. Although the IgE response of humans to Der f 18 has been investigated there is no report on Der f 15‐specific IgE in humans.

Objective
This study aimed to characterize the chitinase allergens Der p 15 and Der p 18 of D. pteronyssinus and to find out whether they are important allergens for humans.

Methods
cDNA was cloned by a polymerase chain reaction strategy from D. pteronyssinus libraries using primers based on conserved chitinase sequences. IgE binding to the recombinant polypeptides was measured by immunosorbent assay. Mice were immunized with the polypeptides and cross‐reactivity examined.

Results
Two variants of Der p 15 were isolated, encoding mature proteins of 58.8 and 61.4 kDa. The amino acid sequences had 90% identity to Der f 15. The cDNA for Der p 18 encoded a mature protein of 49.2 kDa with 88% sequence identity to Der f 18. Der p 15‐specific IgE was detected in 70% and Der p 18‐specific IgE in 63% of a panel of 27 human allergic sera.

Conclusions
The D. pteronyssinus chitinases Der p 15 and Der p 18 show a high frequency of binding to IgE in allergic human sera. They are therefore potentially important allergens for humans as well as dogs.
Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjunctival fibroblast cultures
Authors: Leonardi A. , Curnow S. J. , Zhan H. , Calder V. L.
Published: May 2006

Background
Several cytokines are involved in the recruitment and activation of inflammatory cells in ocular allergic diseases. The purpose of the study was to assay multiple cytokines and chemokines in tears, to compare subgroups of allergic conjunctivitis (AC) with controls, and in culture supernatants to determine whether conjunctival fibroblasts produce some of these cytokines.

Methods
Fifty to one hundred microlitre tears were obtained from patients with active seasonal allergic conjunctivitis (SAC; n=12), vernal keratoconjunctivitis (VKC; n=18), atopic keratoconjunctivitis (AKC; n=6) and non‐atopic controls (n=14). Primary conjunctival fibroblasts grown in vitro were stimulated with IL‐4, IL‐13 or TNF‐α for 24 h. Cell‐free tear and culture supernatants were assayed for IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12, IL‐13, IFN‐γ, TNF‐α, eotaxin, MCP‐1 and RANTES using multiplex bead analysis. Induction of chemokine gene expression was determined by PCR.

Results
IL‐1β, IL‐2, IL‐5, IL‐6, IL‐12, IL‐13, MCP‐1 were increased in all tears groups compared with controls, with highly significant correlations between many of these molecules. In addition IL‐4, IFN‐γ, and IL‐10 were elevated in SAC and VKC, while eotaxin and TNF‐α were only increased in VKC. IL‐6, IL‐8, MCP‐1, RANTES and eotaxin were detected from fibroblasts cultures, and were all up‐regulated by TNF‐α. By PCR, fibroblasts expressed MCP‐1 transcripts constitutively, whereas IP‐10 and Mig were up‐regulated by TNF‐α.

Conclusions
Differential cytokine levels support tears as a useful indicator of immune mechanisms occurring during AC. The striking similarities in chemokine profiles between tears and fibroblasts suggest these cells as likely sources of chemokines in tears.
Low‐dose endotoxin in allergic asthmatics: effect on bronchial and inflammatory response to cat allergen
Authors: Sohy C. , Pons F. , Casset A. , Chesnard M.‐P. , Lieutier‐Colas F. , Meyer P. , Pauli G. , De Blay F.
Published: May 2006

Background
Endotoxin was proposed to increase the severity of asthma. Endotoxin levels greatly differ according to settings. In domestic environments, airborne concentrations may be dramatically low compared with levels reported in occupational settings.

Objective
Our first objective was therefore to assess the effect of inhalation of low‐level lipopolysaccharide (LPS) on the immediate and late‐phase asthmatic bronchial response. Our second objective was to evaluate the effect of exposure to LPS on the local and systemic inflammatory response.

Methods
Nineteen asthmatics sensitized to cat underwent on two separate occasions a bronchial challenge test to cat allergen (cat BCT) preceded randomly by a pre‐exposure to either saline or LPS (2 μg). Methacholine challenge test was performed 24 h before exposure to LPS or saline. The Borg scale for dyspnoea and lung function were recorded before and after exposure to LPS or saline, and before and after cat BCT. Induced sputum and blood samples were collected before and after cat BCT, and analysed for cell counts and eosinophil cationic protein (ECP) levels.

Results
Inhalation of 2 μg LPS did not induce any changes in forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), FEF 25–75 and Borg scale of dyspnoea. It neither modified Fel d 1 PD20 (45.03 ng as compared with 87.03; P=0.42). As well, there was no significant difference in late‐phase reaction. Pre‐exposure to LPS did not influence eosinophil counts or ECP levels in blood and sputum.

Conclusion
Our study demonstrated that pre‐exposure to LPS at low levels, which may be encountered in domestic environment, had no significant effect on the immediate and late‐phase bronchial response to cat allergen. It neither modified local and systemic eosinophilic inflammation.
Primary role of growth‐related oncogene‐α and granulocyte chemotactic protein‐2 as neutrophil chemoattractants in chronic rhinosinusitis
Authors: Rudack C. , Sachse F. , Alberty J.
Published: May 2006

Background
The aetiology of chronic rhinosinusitis (CRS) remains unclear. The purpose of this study was to investigate neutrophil‐attracting chemokine patterns in CRS without nasal polyposis.

Methods
The biological activity of the chemokines was identified using a two‐step high‐performance liquid chromatography (HPLC) technique combined with a bioassay in extracts from 55 CRS patients, and in the turbinate mucosa (TM) of patients (N=51) undergoing septumplasty. The biologic activity of each chemokine was assessed using blocking antibodies to chemokines. Immunolocalization of detected neutrophil chemokines was performed by quantitative evaluation of immunohistochemistry. Besides, PCR analysis was performed to quantify neutrophil chemokine mRNA.

Results
In CRS, the chemokines primarily detected by two‐step HPLC were growth‐related oncogene‐α (GRO‐α) and the granulocyte chemotactic protein‐2 (GCP‐2). Blocking of GCP‐2 and GRO‐αḋ each resulted in chemotaxis inhibition rates of 43.3% and 35.9%, respectively, whereas anti‐IL‐8 and anti‐ENA‐78 had no effect. Both GCP‐2 and GRO‐αḋ were generally synthesized by the surface epithelium and mucosal glands while GRO‐α in particular was synthesized by endothelial cells, as shown by immunohistochemistry. The concentrations of the chemokines IL‐8 and epithelial cell‐derived neutrophil attractant‐78 (ENA‐78) were low in CRS and TM.

Conclusion
It appears that both GRO‐α and GCP‐2 contribute to neutrophil chemotaxis in CRS, whereas IL‐8 and ENA‐78 appear to be of secondary importance for the chemotaxis of neutrophils in this condition. The expression of chemokines in mucosal gland cells is the main phenomenon involved in constitutive neutrophil chemotaxis in the TM.