bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and numerical investigation of multipactor discharges in a coaxial waveguide
Authors: Kossyi I A , Luk'yanchikov G S , Semenov V E , Zharova N A , Anderson D , Lisak M , Puech J
Published: August 2010

An experimental and numerical investigation is made of multipactor discharges in a coaxial waveguide. Particular attention is given to the determination of the multipactor threshold and the distribution of the impact energy of the electrons. Simulations are carried out for different parameters of the secondary emission coefficient of the electrode surfaces. This makes it possible to determine these parameters through a comparison between the numerical and experimental results. The comparison also shows that the observed multipactor is mainly of polyphase (non-resonant) nature and represents a mixture of single- and double-surface multipactor discharges.
Mo bilayer for thin film photovoltaics revisited
Authors: Salomé P M P , Malaquias J , Fernandes P A , Cunha A F da
Published: August 2010

Thin film solar cells based on Cu(In,Ga)Se2 as an absorber layer use Mo as the back contact. This metal is widely used in research and in industry but despite this, there are only a few published studies on the properties of Mo. Properties such as low resistivity and good adhesion to soda lime glass are hard to obtain at the same time. These properties are dependent on the deposition conditions and are associated with the overall stress state of the film. In this report, a study of the deposition of a Mo bilayer is carried out by analysing first single and then bilayers. The best properties of the bilayer were achieved when the bottom layer was deposited at 10 × 10−3 mbar with a thickness of 500 nm and the top layer deposited at 1 × 10−3 mbar with a thickness of 300 nm. The films deposited under these conditions showed good adhesion and a sheet resistivity lower than 0.8 Ω□.
The Intermountain Risk Score (including the red cell distribution width) predicts heart failure and other morbidity endpoints
Authors: Horne Benjamin D. , May Heidi T. , Kfoury Abdallah G. , Renlund Dale G. , Muhlestein Joseph B. , Lappé Donald L. , Rasmusson Kismet D. , Bunch T. Jared , Carlquist John F. , Bair Tami L. , Jensen Kurt R. , Ronnow Brianna S. , Anderson Jeffrey L.
Published: August 2010

Aims

The complete blood count (CBC) and basic metabolic profile are common, low‐cost blood tests, which have previously been used to create and validate the Intermountain Risk Score (IMRS) for mortality prediction. Mortality is the most definitive clinical endpoint, but medical care is more easily applied to modify morbidity and thereby prevent death. This study tested whether IMRS is associated with clinical morbidity endpoints.

Methods and results

Patients seen for coronary angiography (n = 3927) were evaluated using a design similar to a genome‐wide association study. The Bonferroni correction for 102 tests required a P‐value of ≤ 4.9 × 10−4 for significance. A second set of angiography patients (n = 10 413) was used to validate significant findings from the first patient sample. In the first patient sample, IMRS predicted heart failure (HF) (Ptrend = 1.6 × 10−26), coronary disease (Ptrend = 2.6 × 10−11), myocardial infarction (MI) (Ptrend = 3.1 × 10−25), atrial fibrillation (Ptrend = 2.5 × 10−20), and chronic obstructive pulmonary disease (Ptrend = 4.7 × 10−4). Even more, IMRS predicted HF readmission [hazard ratio (HR) = 2.29/category, Ptrend = 1.2 × 10−6), incident HF (HR = 1.88/category, Ptrend = 0.02), and incident MI (HR = 1.56/category, Ptrend = 4.7 × 10−4). These findings were verified in the second patient sample.

Conclusion

Intermountain Risk Score, a predictor of mortality, was associated with morbidity endpoints that often lead to mortality. Further research is required to fully characterize its clinical utility, but its low‐cost CBC and basic metabolic profile composition may make it ideal for initial risk estimation and prevention of morbidity and mortality. An IMRS web calculator is freely available at http://intermountainhealthcare.org/IMRS.

Trial Registration: Database registry of the Intermountain Heart Collaborative Study: NCT00406185 (ClinicalTrials.gov).
Campylobacter fetus subspecies fetus spondylodiscitis
Authors: Chaillon Antoine , Baty Gaelle , Lauvin Marie Agnès , Besnier Jean Marc , Goudeau Alain , Lanotte Philippe
Published: August 2010

Campylobacter spp. are common causes of gastrointestinal infections. Campylobacter fetus is a much rarer pathogen in humans, and usually causes bacteraemia and systemic complications in patients with predisposing conditions. We report a case of spondylodiscitis caused by C. fetus subsp. fetus as revealed by vertebral biopsy culture. This identification was confirmed by sequencing the 16S rRNA gene and by phylogenetic analysis. Treatment consisted of 6 weeks antimicrobial therapy combined with a strict initial immobilization, followed by a re-education program. The patient's recovery was uneventful.
Bankruptcy in Russia: Away From Creditor Protection and Restructuring
Authors: Sonin Constantin , Zhuravskaya Ekaterina
Published: August 2010

Bankruptcy laws aim to protect creditors, introduce pressure on managers for financial discipline and restructuring and free assets from inefficient use. Effectiveness of Russian Bankruptcy law is undermined by the political capture of arbitration courts by the regional authorities. Governors in alliance with managers of large regional enterprises use bankruptcy procedure as a mechanism for expropriation of the federal government and outside investors. Recent amendments to the Bankruptcy law, formally motivated by the apparent inefficiencies of current bankruptcy practice, fail to improve creditors protection, while they provide additional power to incumbent managers and governmental agencies.
Transit Transports between Russia and the EU
Authors: Laurila Juhani
Published: August 2010

The European Union is an important trade partner for Russia. For example, in 2000 more than one third of Russia's foreign trade was with EU countries. By contrast, only a little over 1% of total EU foreign trade was with Russia. A quick look at the map shows that a substantial part of trade between Russia and the EU has to be transported through the region located between Russia and the European Union.

Following substantial statistical work we present in this study summary statistics about volumes as well as previously unpublished statistics on values of transit transport flows and their distribution by different corridors between Russia and the EU. The largest transit transport flows (more than 60% of volumes and more than half in value terms) between Russia and the EU use the Central European transport corridors. The statistics also reveal that average unit value of transit merchandise from the EU to Russia was more than seven times higher in 1999 than the average unit value of transit merchandise from Russia to the EU. The obvious reason is the structure of trade between Russia and the EU: Russia exports mainly fuels and raw materials but imports manufactured high‐value products.
International Activities of Russian Corporations — Where Does Russian Business Expansion Lead?
Authors: Liuhto Kari , Jumpponen Jari
Published: August 2010

Russian business activities abroad are expanding rapidly. The recorded FDI outflow from Russia was $3bn in 2000, and is expected to increase. This article describes foreign operations of some 15 of Russia's most internationalised corporations, and discusses the role of their foreign activities in integrating Russia with the global economy.
Establishing a Stabilisation Fund in Russia
Authors: Kadotchnikov Pavel
Published: August 2010

The situation that developed in 1999‐2001 on world commodity markets has imposed certain constraints on economic policy in Russia. Relatively high oil prices resulting in a high current account surplus caused the rouble to appreciate in real terms, which adversely affected national industries producing tradables, thus hampering sustainable growth. The lack of open market instruments for sterilisation of rouble emission resulting from mandatory sale of a part of dollar export earnings has made it very difficult for the Central Bank to pursue monetary and exchange rate policies, leading to a threat of inflation.

Sharp fluctuations of prices for oil and other commodities on world markets result in wide variations in tax revenues from the relevant industries, which has a serious impact on the budgetary system. In this context the establishment of a stabilisation fund as a mechanism to accumulate additional revenues and to smooth budget expenditures would be a rational and timely solution. A stabilisation fund could also compensate undesirable effects of the current account surplus by investing revenues of the fund on world capital markets or by repaying external debt. The fund could thus partly address problems associated with real appreciation of the rouble.
The Role of Consumer Countries in Determining International Oil Prices
Authors: Angelier Jean‐Pierre , Saadi Hadj
Published: August 2010

Since 1987 international oil trading has been conducted within the framework of a free and competitive market. However, whenever tensions push up oil prices, concerns become manifest. The Organisation of Petroleum‐Exporting Countries (OPEC) is singled out as an economic agent, which tends to hinder competitive play for its own profit, using a concerted policy of supply limitation to impose excessively high prices to its own advantage. We find these concerns unjustified. On the contrary, it seems that the main oil consumer countries give themselves the ability to influence oil prices, raising prices to levels, which are higher than they would be if competition mechanisms operated without asymmetry between market agents. Consumer countries limit their dependence on oil imports by implementing a heavy fiscal regime: high prices hold back demand growth, allow survival of domestic producers, whose oil production would otherwise be unprofitable, and favour development of oil‐substituting energy sources. This policy of heavy domestic taxation of oil products is all the more acceptable for consumer countries because it contributes significantly to maintaining the balance of their public finances.

We will present three main types of analysis of oil price setting mechanisms: consensus of analyses for the short and long term; analyses dealing with concentration of supply on the market as the main factor determining oil prices; and analyses in terms of competitive forces.
Fighting Inflation in Russia
Authors: Dabrowski Marek , Paczynski Wojciech , Rawdanowicz Lukasz
Published: August 2010

The purpose of this study is to explain the main sources of continued inflationary pressure in Russia and propose a policy remedy to this situation. In the transition period Russia has gone through different monetary and exchange rate regimes. The disinflation process has been marked by several reversals, the most recent being the consequence of the currency and banking crisis in August 1998. Although annual inflation was brought back down to a moderate two‐digit level (around 20%) in 2001, such a level cannot be considered as satisfactory from the viewpoint of a long‐term investment and growth climate.
The Northern Dimension — One Pillar of the Bridge Between Russia and the EU
Authors: Kivikari Urpo
Published: August 2010

Although Russia is not an applicant for membership of the European Union, it is linked to European integration in many ways. The EU Tacis programme, started at the beginning of the 1990s, provided early assistance for Russia’s transition to a market economy and market–oriented international integration. The Partnership and Cooperation Agreement (PCA) between the EU and Russia, which came into force in 1997, was a milestone, as were mutual cooperation strategies developed by each of the sides at the end of the 1990s. Naturally, Russia’s internal reform progress and its preparation for WTO membership are also significant for EU–Russia relations. Current steps towards creation of the Common European Economic Space, uniting the EU and Russia, represent a new level of cooperation.

In addition to EU programmes and projects, which are purely Russia–related, Russia also figures large in the so–called Northern Dimension (ND) policy of the EU. The role of the ND in the network of EU–Russia institutions and programmes, where the above–mentioned general elements are only small parts of the whole, needs further clarification. It so happens that the most promising opportunities and demanding challenges of the ND policy begin with the letter ‘e’. Omitting some key areas, such as economy and education, sub–sections of this article will be devoted to energy, environment, eDimension, enterprises and EU enlargement.
Proliferation of Cells in the Oral Mucosa, the Ear Skin and the Regional Lymph Nodes in Mice Sensitized and Elicited with a Hapten
Authors: Ahlfors E. , Sveinhaug M. M. , Nango G. , Johansen C. , Lyberg T.
Published: August 2010

During contact sensitivity reaction, immune cells proliferate. In order to study the histological picture of these proliferation phases, we used a mouse model of contact sensitivity in the oral mucosa and on skin. We also used bromodeoxyuridin (BrdU, an analogue to thymidin) that is incorporated into the nucleus during cell replication. The hapten oxazolone (OXA) was used to sensitize and elicit the oral mucosa and/or the ear skin. Mice were killed at various times after elicitation, and unsensitized animals were also exposed to the hapten as controls. BrdU (25 mg/kg animal) was injected i.p. 2 h before the kill. Specimens from the oral mucosa, ear skin and submandibular and auricular lymph nodes were cut and fixed in 4% paraformaldehyde. They were then treated with acid and biotinylated anti‐BrdU antibody and developed using ABC‐kit and DAB. The analyses were performed using a Leica light microscope and the computer program ANAlysis. In the oral mucosa, the frequency of proliferating cells were increasing during the observation period, 4–24 h after elicitation, regardless of site of sensitization. The proliferating cells were found mainly in the basal cell layer of the epithelium. Similar patterns were found in ear skin. The regional lymph nodes demonstrated a few scattered proliferating cells 4 h after elicitation. After 24 h, these cells were found frequently in the whole lymph node. Control animals exhibited considerable less proliferating cells at all times. We conclude that most proliferating cells were found 24 h after elicitation locally at the hapten‐exposed sites (the oral mucosa or the ear skin) as well as in the regional lymph nodes.
Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells
Authors: Karlsson H. , Larsson P. , Wold A. E. , Rudin A.
Published: August 2010

The normal gastrointestinal flora is crucial for the maturation of the acquired immunity via effects on antigen‐presenting cells (APCs). Here, we have investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal flora. Purified monocytes and monocyte‐derived DCs were stimulated with UV‐inactivated gram‐positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram‐negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of IL‐12p70 and TNF, as detected by ELISA, in response to L. plantarum than to E. coli and V. parvula. In contrast, DCs secreted high amounts of IL‐12p70, TNF, IL‐6 and IL‐10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of response to the gram‐positive strains correlated with a lower surface expression of Toll‐like reseptor 2 (TLR2) on DCs compared to monocytes. The surface expression of TLR4 on DCs was undetectable when analysed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that low TLR4 expression on DCs is sufficient to mount an inflammatory response to gram‐negative bacteria. IFN‐γ increased the expression of TLR4 on DCs and also potentiated the cytokine response to gram‐negative bacteria. Our results indicate that, when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, thereby becoming unresponsive to probiotic gram‐positive bacteria. These results may have important implications for the capacity of different groups of commensal bacteria to regulate mucosal and systemic immunity.
An Assay for Mannan‐Binding Lectin‐Associated Serine Protease 3, MASP‐3
Authors: Holmvad S. H. , Dahl M. , Jensenius J. C. , Thiel S.
Published: August 2010

The mannan‐binding lectin (MBL) pathway is part of the innate immune system providing a first line of defence against infections. MBL and ficolins circulate in complexes with MBL‐associated serine proteases (MASP‐1, ‐2 and ‐3). After recognition of a microorganism by MBL, activation of the complement system occurs. MASP‐1 and MASP‐3 share five domains (making up the so‐called A‐chain), whereas they have unique protease domains (B‐chains). Before the identification of MASP‐3, an assay for MASP was presented, based on antibodies against the A‐chain of MASP‐1. With the new knowledge of the three MASPs, and the sharing of domains by MASP‐1 and MASP‐3, assays specific for the protease domains have to be constructed, if one wishes to measure the proteins individually. We present an assay for quantifying total MASP‐3 in plasma and serum samples. The assay is a sandwich‐type assay using as catching antibody a monoclonal antibody against the common A‐chain of MASP‐1/3 and a developing secondary antibody against the C‐terminal part of the protease domain of MASP‐3. We have used this assay for estimating the normal concentration of the protein as well as the concentration in patients and also for characterizing by gel permeation chromatography the MASP‐3 protein in serum.
A Database Solution for Laboratory Information Management
Authors: Petersen M. S. , Fleischer C. C. , Agger R. , Hokland M.
Published: August 2010

In our laboratory, we have developed a database system, which we believe is of immediate interest to the general scientific community. The database represents a computer‐based replacement for the laboratory notebooks used in the majority of research laboratories worldwide. In addition, the database provides an effective tool for organizing and managing laboratory information at all levels, spanning from managing and revising standard operating procedures and producing documentation of research activities to keeping track of data and conclusions. Using the commercially available database toolkit software FileMaker Pro, we have developed a relational database solution for management of laboratory information. The system consists of a hierarchy of five interrelated databases, each pertaining to a separate type of information, namely, overall project information, information relating to individual experiment setups, documentation of daily research activity, generated data and descriptions of standard operating procedures. Like other databases, each individual database consists of a number of records, each comprised of a set of fields in which information is entered. In each record, a certain field is reserved to specify the relation of the record to a record in another database at a higher level. Thus, the database is essentially five databases linked by a hierarchy of one‐to‐many relations, organizing information in a folder‐like structure. Importantly, the database system allows multiple users to access and edit records simultaneously, and the data entered in one database immediately becomes accessible through the other databases. The limitations of laboratory notebooks are apparent when looking for information, which is dispersed throughout one or more notebooks, or possibly on loose sheets of paper or printouts ‘somewhere’. The often complicated process of gathering laboratory data or results when writing grant applications or research papers is made considerably easier with the database system. Thus, the database solution presented should be broadly attractive to researchers, irrespective of their scientific discipline.
SARS CTL Vaccine Candidates — HLA Supertype, Genome‐Wide Scanning and Biochemical Validation
Authors: Sylvester‐Hvid C. , Nielsen M. , Lamberth K. , Røder G. , Justesen S. , Lundegaard C. , Worning P. , Thomadsen H. , Lund O. , Brunak S. , Buus S.
Published: August 2010

An effective SARS vaccine is likely to include components that can induce specific cytotoxic T‐cell (CTL) responses. The specificities of such responses are governed by HLA‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information. The latter was recently established when a causative coronavirus (SARS CoV) was isolated and full‐length sequenced. Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype, genome‐wide scan for SARS‐specific cytotoxic T cell epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all major human populations. For each HLA supertype, we have selected the 15 top candidates for test in biochemical‐binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.
Functional and Molecular Characterization of Myeloid Suppressor Cells Expanded During Lymphoma Tumour Progression
Authors: Meerschaut S. , Liu Y. , Hassanzadeh G. H. G. , Raes G. , De Baetselier P. , Van Ginderachter J.
Published: August 2010

We previously reported that in mice with large progressing T‐cell lymphoma tumours, dysfunctions in the antitumour CTL activity occur, associated with an accumulation of splenic arginase‐producing myeloid suppressor cells (MSCs). In this study, we first demonstrate that both the presence and the activation state of these MSC depends on tumour evolution. While in tumour regressors hardly any arginase‐producing MSC can be found, both the amount and the arginase activity of this population expands from early over late progressors. This gradual induction of MSCs is paralleled by an increasing suppression of CTL activity and Th1, but not Th2, cytokine production. Upon analysing the molecular repertoire of MSC in vitro, we found, besides arginase1, a well‐established marker for alternatively activated myeloid cells or M2, a strong upregulation of FIZZ1 and Ym, two additional recently identified markers for M2. Further evaluation of molecular markers by microarray analysis in MSC yielded genes involved in wound healing (e.g. coagulation factor XIIIa), anti‐inflammation (e.g. selenoprotein P), immunomodulation (e.g. PD‐L2) and fat and sugar metabolism (e.g. leptin receptor). Of note, many of these genes are regulated by type 2 cytokines (IL‐4, IL‐13 and IL‐10) and are therefore rather M2 associated. Overall, our data provide new markers for MSC in cancer and further establish their M2 activation state.
Detection of Immune Responses in Sentinel Nodes Draining Human Urinary Bladder Cancer
Authors: Karlsson M. , Marits P. , Banèr J. , Sherif A. , Thörn M. , Landegren U. , Winqvist O.
Published: August 2010

Being the first lymph node to receive drainage from the tumour area, the sentinel node offers a unique possibility to obtain tumour‐reactive lymphocytes. We investigated antitumour immune responses in sentinel nodes from patients with bladder cancer, by assaying tumour‐specific proliferation and TCR Vβ repertoires. During tumour surgery, sentinel lymph nodes were identified by peri‐tumoural injection of blue dye. Fresh specimens of tumour, sentinel and nonsentinel lymph nodes were obtained, and single‐cell suspensions were prepared. Cells were assayed for reactivity against autologous tumour extract in [3H]‐thymidine incorporation assays and characterized by flow cytometry. Parallel analyses of the expression of Vβ gene families were performed with padlock probes, linear oligonucleotides which upon target recognition can be converted to circular molecules by a ligase. Probes were reacted with cDNA prepared from magnetically separated CD4+ cells, and the TCR repertoire was determined by hybridizing the products to oligonucleotide microarrays. Dose‐dependent proliferation in response to tumour extract could be detected in sentinel lymph nodes. Common clonal expansions were detected among tumour‐infiltrating lymphocytes and in sentinel lymph nodes. Nonsentinel lymph nodes displayed a divergent TCR Vβ repertoire. These results indicate an ongoing immune response against tumour antigens in sentinel nodes, draining urinary bladder cancer. Identification of sentinel lymph nodes makes it possible to obtain tumour‐reactive lymphocytes for use in adoptive immunotherapy.
Infliximab Treatment of Rheumatoid Arthritis Patients Simultaneously Increases TNF‐α Protein Levels and Reduces mRNA Expression in the Blood
Authors: Hjelmevik T. O. , Kvalvik A. G. , Knappskog P. M. , Lefsaker L. , Kleiven A. S. , Dyvik S. , Brun J. G. , Østergaard H. , Eiken H. G.
Published: August 2010

Objective:  Tumour necrosis factor‐α (TNF‐α) is an important mediator in the pathogenesis of rheumatoid arthritis (RA). We have investigated long‐term anti‐TNF‐α treatment with infliximab with respect to TNF‐α gene activity and protein levels in the blood of RA patients and disease activity score (DAS).

Methods:  TNF‐α mRNA and plasma protein in RA patients (n = 29) and healthy controls (n = 24) was determined before and during treatment with infliximab (3 mg/kg) using real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) and high sensitivity enzyme‐linked immunosorbent assay (ELISA), respectively. The disease activity of the patients was assessed as DAS value.

Results:  The TNF‐α mRNA levels of RA patients at baseline were higher than that of the control group (P = 0.0135) but were significantly reduced after initiation of treatment (P < 0.001). Low mRNA levels were sustained throughout the 54 weeks of the study. Baseline protein levels of RA patients were similar to the control group. After 2 weeks of treatment, the protein levels were significantly elevated from baseline (P = 0.0353) and increased throughout week 14. Clinical improvement for all RA patients was found upon infliximab treatment, as a reduction in DAS values (P < 0.001). The increase in protein and reduction in DAS value from week 2–14 was also correlated (P = 0.0374).

Conclusion:  During infliximab treatment of RA patients, there is an accumulation in immune‐reactive TNF‐α protein in blood plasma and simultaneously a reduction in TNF‐α gene expression in PBMC, which may in part explain the beneficial course of RA symptoms.
Citrullinated Proteins in Arthritis; their Presence in Joints and Effects on Immunogenicity
Authors: Lundberg K. , Nijenhuis S. , Vossenaar E. , Venrooij W. J. , Klareskog L. , Harris H. E.
Published: August 2010

Autoantibodies directed against citrulline‐containing proteins have an impressive specificity of nearly 100% in RA patients and a suggestive involvement in the pathogenesis. The targeted epitopes are generated by a post‐translational modification catalysed by the calcium‐dependent enzyme peptidyl arginine deaminase that converts the positively charged arginine to polar but uncharged citrullin. The aim of this study was to analyse the presence of citrulline in the joints at different time points of collagen‐induced arthritis in DA rats by immunohistochemistry and to investigate how immunogenicity and arthritogenicity was affected by citrullination of rat serum albumin (RSA) and collagen type II (CII). Our results indicate that citrulline could be detected in joints of arthritic animals, first appearance at the onset of disease and increasing as disease progressed into a chronic state. Unimmunized animals or time points before clinical signs of arthritis were negative. By morphology, we state that some infiltrating macrophages as well as the cartilage surface stain positive for citrulline, while the major source of citrullinated proteins appears to be fibrin depositions. A specific Cit‐RSA T‐cell response was observed in animals challenged by citrullinated RSA, no response was recorded when RSA was used as a stimulus. The IgG analysis reveals not only a response towards the modified protein but also cross‐reactivity to native RSA. No T‐cell or B‐cell response was noted in animals injected with unmodified RSA. Cit‐CII induced a disease with higher incidence and earlier onset than did the native counterpart. We conclude that, in contrast to the human disease, citrulline does not seem to appear before clinical signs. As inflammation proceeds, citrulline is detected specifically in the joints. All other organs investigated were negative. We also conclude that citrullination of a protein can break tolerance and increase its arthritogenic properties.
Protective DNA Vaccination Against MOG91‐108‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ
Authors: Wefer J. , Harris R. A. , Lobell A.
Published: August 2010

DNA vaccine coding for the encephalitogenic peptide MOG91‐108 protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection.
Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies
Authors: Reinholdt J. , Baxendale H. , Ekström N. , Kayhty H. , Poulsen K. , Kilian M.
Published: August 2010

Bacteria‐specific IgA antibodies are efficient opsonins for neutrophils and mononuclear phagocytes, provided that the phagocytes express the Fca receptor (CD89). Expression of CD89 can be stimulated by inflammatory cytokines, activated complement factors and certain microbial components. In one study, unstimulated phagocytes were able to ingest IgA antibody‐treated pneumococci, but only in the presence of complement, which was found to be activated by the IgA antibodies along the alternative pathway. Pneumococci produce IgA1 protease that cleaves human IgA1, but not IgA2, molecules in the hinge region. This leaves IgA1 as Fabα (monovalent) deprived of Fcα which contains the docking site for CD89. IgA1 is the vastly predominant subclass of IgA in the upper airways and circulation of humans.

Aims:  To examine the effects of IgA1 protease activity and complement on phagocytosis of IgA antibody‐coated pneumococci by an unstimulated human phagocytic cell line (hl60).

Materials and methods:  IgA1 and IgA2 monoclonal antibodies to serotype 4 pneumococcal capsular polysaccharide (ps) were generated by heterohybridoma technique involving B cells from human vaccinees. Isogenic serotype 4 pneumococci with and without IgA1 protease activity, respectively, were obtained after inactivation of the iga gene of the TIGR4 strain. Opsonophagocytosis was quantitated using the assay described by Romero‐Steiner et al. Based on enumeration of surviving bacteria by culture. The integrity of IgA molecules was examined by western blotting.

Results:  Both IgA1 and IgA2 antibody to type‐4 polysaccharide‐induced phagocytosis of IgA1 protease‐deficient type‐4 pneumococci equally well in the absence as in the presence of complement. Iga1 antibody to type‐4 polysaccharide displayed a fourfold higher opsonophagocytosis titer against IgA1 protease deficient compared to homologous wildtype target bacteria. A similar effect of IgA1 protease activity of the target bacteria was not observed in a parallel experiment where IgA2 antibody to type‐4 polysaccharide served as opsonin. IgA1 antibody extracted from IgA1 protease‐producing target bacteria was almost exclusively in the form of Fabα. Conversely, IgA1 from protease‐deficient bacteria and IgA2 from both types of bacteria were intact.

Conclusions:  These results indicate that the IgA1 protease activity of S. neumoniae may help the bacteria escape IgA1 antibody‐mediated opsonophagocytosis. Besides, in these experiments, IgA‐mediated opsonophagocytosis was independent of complement.
Mycobacterium Fortuitum Furunculosis in Pedicure Recipients; an Epidemic?
Authors: Abrishami P. , Cockerell C.
Published: August 2010

Isolated cases and outbreaks of mycobacterial furunculosis among patients receiving pedicures have been reported. The transmission of the mycobacteria likely occurs while soaking the legs in a whirlpool foot bath prior to the pedicure. Oils are often applied to the legs following the foot bath. Typically, patients present with multiple papules and pustules below the knees that, after several weeks or months, may become large, tender, and fluctuant furuncles. Histology usually demonstrates a suppurative folliculitis with or without associated suppurative granulomatous inflammation. We present a culture‐proven case of M. fortuitum furunculosis in a patient after receiving whirlpool leg soaking and pedicure in a foot salon. We also illustrate several other highly suspected cases in which cultures failed to grow the organism. It is important for clinicians and pathologists to recognize the gross and histological patterns of this under‐reported condition as cultures, particularly swabs, often fail to grow the organism.
D2–40 Expression in Hemangiomas and Lymphangiomas: Special Reference to its Differential Utility Between Kaposiform Hemangioendothelioma and Acquired Tufted Angioma
Authors: Arai E. , Kuramochi A. , Shimizu M. , Hirose T.
Published: August 2010

Recent investigations have demonstrated the utility of D2–40 as a marker for lymphatic endothelium and can be used for formalin‐fixed and paraffin‐embedded materials. We studied 13 capillary hemangiomas: kaposiform hemangioendothelioma (KH, 2), acquired tufted angioma (ATA, 5), juvenile hemangioma (JH, 2), granuloma pyogenicum (GP, 4); 6 other hemangiomas: cavernous hemangioma (3), arterio‐venous hemangioma (1), angiokeratoma (1), epithelioid hemangioma (1); Kaposi’s sarcoma (1); 12 lymphangiomas: lymphangioma circumscriptum (6), deep type of cutaneous lymphangioma (6). D2–40 monoclonal antibody, endothelial markers (CD31, CD34, Factor VIII related antigen) and juvenile hemangioma‐associated marker GLUT‐1 were applied. D2–40 was immunopositive for the peripheral area of proliferative capillaries and negative for surrounding dilated vessels in KH, but positive for surrounding dilated vessels and negative for tufted proliferative capillaries in ATA. KH and ATA were all positive for endothelial markers and negative for GLUT‐1. Other hemangiomas were negative for D2–40. Eight of 12 cases were positive for lymphangiomas. Based on these results, D2–40 is a useful additional immunostain for the discrimination of KH and ATA. KH and ATA may originate from different stage of both the lymphatic and blood vessel endothelial lineages.
Follicular Eruption in a Child With Alagille Syndrome
Authors: Armstrong A. , Liu V. , Strasswimmer J.
Published: August 2010

A 17 year‐old boy with a history of Alagille syndrome presented with three‐months duration of spontaneous eruption of multple non‐pruritic, non‐painful papules on the extremities. He also reported seeing “dark spots” at night. On physical examination, the patient was jaundiced and appeared smaller than his age. The skin examination revealed numerous 2–8 mm follicular, keratotic papules on the extensor surfaces of the patient’s arms and legs. H&E preparation of the skin biopsy revealed distention of the upper portion of the follicles with prominent keratotic plugging, as well as focal follicular perforation and acute inflammation. Laboratory examination revealed a vitamin A level of 11, carotene level of less than 2, and retinol binding protein of 2.1. The patient was diagnosed with phrynoderma and initiated on vitamin A therapy. After a two‐months course of vitamin A therapy, his serum vitamin A increased to 67, and he had dramatic improvement of the follicular eruption. This is a fascinating case of phrynoderma in a child with biliary dysfunction. The presence of perforating folliculitis on histology is curious, as there are less than 10 documented cases of perforating folliculitis in phrynoderma. This case illustrates the intriguing clinical and pathological presentations of phrynoderma.
Post‐Irradiation Vascular Proliferations: Potential Mimic of Kaposi’s Sarcoma
Authors: Bennett J. , McNiff J.
Published: August 2010

A variety of benign and malignant cutaneous vascular lesions occur in irradiated skin. We report two cases of vascular lesions that developed on the breast within a year after radiation therapy for breast carcinoma. Both cases mimicked Kaposi’s sarcoma (KS) histologically. We compare these with one case of post‐irradiation angiosarcoma and 3 cases of acquired progressive lymphangioma (APL) unrelated to radiation therapy. The post‐irradiation vascular lesions showed slit‐like vessels dissecting through superficial dermal collagen, leading to an initial diagnosis of KS by one contributing pathologist. Immunohistochemically, the vessels in both cases expressed CD31 and CD34, stained only partially for actin, and had a low Ki67 proliferation index. Neither case expressed HHV8. The post‐irradiation angiosarcoma occurred three years after radiation, and also exhibited a focal slit‐like growth pattern resembling KS. However, there was marked cytologic atypia, a high proliferation rate, and negative staining for HHV8. The APL were characterized by more ectactic vascular spaces and deeper involvement of the dermis than was present in the post‐irradiation lesions. These cases also failed to stain for HHV8. Recognition of the phenomenon of post‐irradiation vascular proliferations is important, especially because such lesions may resemble KS, yet invariably follow a benign clinical course.
Intravascular Lymphoma with NK Cell Immunophenotype
Authors: Brinster N. , Granter S. , Pinkus G. , Miller D.
Published: August 2010

Intravascular Lymphoma is a rare extranodal large cell lymphoma characterised by a neoplastic proliferation of lymphoid cells in small vessel lumina typically involving the skin and central nervous system. The malignant cells are most commonly of B cell origin, although rare T cell variants have been described. We report a rare case of intravascular lymphoma with an NK cell phenotype. The patient is a 65 year‐old man with a 5 year history of hypogammaglobulinemia and a six month history of tinea corporis involving the legs. Following topical antifungal treatment.asymptomatic erythematous plaques were noted on the lower extremities. A skin biopsy revealed intravascular thrombi with atypical malignant lymphoid cells which were immunoreactive for: CD3, CD2, LCA, CD56, perforin, granzyme B, and TIA‐1. There is one description of an NK‐like intravascular lymphoma in the literature and one of the authors (G.P.) has recently described two patients with intravascular lymphoma of definitive NK cell type (submitted for publication). Intravascular lymphoma is an aggressive malignancy with a poor prognosis. Recognition of this newly described variant will help to elucidate our understanding of its pathogenesis and natural history.
Tattoo Pigment in Sentinel Lymph Nodes: A Mimicker of Metastatic Malignant Melanoma
Authors: Chikkamuniyappa S. , Sjuve‐Scott R. , Yeh I.T.
Published: August 2010

Tattoo pigment in sentinel lymph nodes in melanoma patients is a clinical challenge. A 77‐year‐old man presented with a pink nodular lesion of the right upper arm. Biopsy revealed a 1.9 mm thick, Clark level 4 nodular melanoma. A wide local excision with 2 cm margins and sentinel lymph node (SLN) mapping was planned. Pre operative lymphoscintigraphy using technetium‐99 m demonstrated a single strongly pigmented SLN in the right axilla. A prominent tattoo was located on the patient’s upper arm in the area of the melanoma. The clinical impression was highly suspicious for metastatic disease and the tissue was sent to pathology for examination. Frozen section showed a lymph node with benign histiocytes. There were black non‐polarizable coarse granules in the subcapsular, sinusoidal areas and also in the histiocytes. Review of permanent hematoxylin and eosin sections as well as immunohistochemical analysis with MART‐1 and HMB‐45 showed no evidence of metastatic melanoma in the SLN. Pigmentation of lymph nodes is not pathognomic of malignant melanoma. Black pigmented lymph nodes can occur by carbon deposits of tattoo pigment as in our case. Histological confirmation of metastatic malignant melanoma in the SLN is imperative before proceeding to complete regional lymph node dissection.
Localized Chronic Fibrosing Vasculitis or Localized Erythema Elevatum Diutinum?
Authors: Clarke L. , Clarke J. , Helm K. ,   Penn State College of Medicine/MS Hershey Medical Center, Hershey, PA 17033
Published: August 2010

Localized chronic fibrosing vasculitis is a rare dermatosis that histologically resembles late‐stage erythema elevatum diutinum (EED) but has a different clinical presentation. A 62‐year‐old male presented with bilateral nodules on his heels that first appeared two years ago and over the past six months had become extremely painful. He denied any recent trauma to the sites, and his medical history was significant only for diabetes mellitus, coronary artery disease, and osteoarthritis. Physical exam demonstrated focally ulcerated violet‐red three‐centimeter nodules on the medial aspects of both heels. Biopsy revealed dense concentric and lamellar fibrosis with foci of leukocytoclastic debris and a sparse infiltrate of histiocytes, neutrophils, eosinophils, and lymphocytes. No granulomas were present, and histochemical stains and tissue cultures for microorganisms were negative. Imaging studies showed no evidence of underlying osteomyelitis, cellulitis, or abscess formation. Laboratory studies demonstrated a markedly elevated IgA level that was shown to be polyclonal on serum immunofixation studies. All peripheral blood cell counts were normal. Thorough evaluations for systemic vasculitides and connective tissue disorders were negative. A diagnosis of localized chronic fibrosing vasculitis was made. This case illustrates the clinicopathologic overlap between this disorder and EED.
Plexiform Fibrohistiocytic Tumor: A Rare Low‐Grade Myofibroblastic Tumor of Children and Young Adults
Authors: Comfere Nneka I. , Ahmed Iftikhar
Published: August 2010

We describe a 7‐year old male with a 7‐month history of a plexiform fibrohistiocytic tumor (PFT) presenting as an innocuous 0.5 × 0.5 cm nodule on the nasal dorsum. Following diagnostic sampling, Mohs’ micrographic surgery was performed to ensure adequate removal and patient continues to do well 1 year post‐surgery. PFT is a rare neoplasm described initially by Enzinger and Zhang in 1988. It afflicts children and young adults (median age: 14.5 years) and has a strong female predisposition. It typically occurs on the upper extremity. Histologically, the tumor has a bland appearance consisting of a biphasic population of varying numbers of fibroblast and histiocyte‐like cells. Cellular atypia and pleomorphism are lacking and mitotic activity is low. Immunohistochemically and ultrastructurally, the tumor demonstrates myofibroblastic differentiation. The constituent cells have a diploid DNA content. Unique cytogenetic aberrations have been anecdotally identified. PFT behaves in a locally aggressive fashion and regional nodal disease can occur despite adequate excision. In rare instances, metastasis to the lungs has been described. No association between specific clinicopathologic features and outcome has been identified. In summary, PFT is a rare but distinct low‐grade myofibroblastic tumor of children and young adults with a misleading clinical and histological appearance.
Tumor Lymphangiogenesis Predicts Melanoma Metastasis to Sentinel Lymph Nodes
Authors: Dadras Sam S. , Lange‐Asschenfeldt Bernhard , Muzikansky Alona , Mihm Martin C. , Detmar Michael
Published: August 2010

Cutaneous melanoma is a common and frequently lethal melanocytic neoplasm that can quickly metastasize to regional lymph nodes. Currently, prognosis is determined by measuring tumor thickness but more reliable markers for metastatic spread are urgently needed. We investigated whether the extent of tumor lymphangiogenesis can predict melanoma metastasis to sentinel lymph nodes (SLN). We quantified the extent of tumor lymphangiogenesis, as well as other factors, in excised primary tumors and in SLN biopsy samples from 45 patients with primary cutaneous melanoma. Primary melanomas from patients whose tumors had metastasized to the SLN, along with their metastastic foci, contained prominent hotspots of increased lymphatic vessel density, compared to non‐metastatic tumors. Multivariate risk analysis revealed that the lymphatic vascular area (LVA) of primary melanomas, an index of tumor lymphangiogenesis, was the most sensitive prognostic marker for SLN metastasis, and was even able to more accurately predict which tumors would become metastatic to SLN than measuring tumor thickness. The extent of tumor lymphangiogenesis is a highly sensitive (83%) and specific (89%) prognostic marker of lymph node metastasis. Assessment of lymphangiogenesis in primary melanomas may be a more effective approach than measuring tumor thickness in selecting patients with early metastatic disease for aggressive therapy.
The Role of P‐75 NGF‐R in the Diagnosis of Desmoplastic Melanoma
Authors: Ghosn S. , Radfar A. , Stefanato C.M. , Bhawan J.
Published: August 2010

The histologic diagnosis of desmoplastic melanoma is challenging, particularly when the overlying junctional component is absent and when the spindle cells lack melanin pigment. In these instances, the importance of immunohistochemistry cannot be overemphasized. S‐100 protein, with a sensitivity approaching 90%, is the primary immunohistochemical stain used for this purpose. HMB‐45, although a more specific marker for melanocytes, is often negative in these cases. A marker of schwannian differentiation, p‐75 NGF‐R has been shown to be a useful confirmatory marker for desmoplastic and neurotropic melanoma, with staining intensity comparable to or better than S‐100 protein. We report two cases of desmoplastic melanoma which stained focally and weakly with S‐100 protein in comparison with the stronger staining of p‐75 NGF‐R. In both cases, S‐100 staining could have been missed or interpreted as non‐confirmatory, thus misguiding the diagnosis. We therefore suggest that p‐75 NGF‐R be a complementary marker to S‐100 protein in differentiating desmoplastic melanoma from other non‐neural crest‐derived spindle cell tumors.