bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlocomotor and Locomotor Hindlimb Responses Evoked by Electrical Microstimulation of the Lumbar Cord in Spinalized Cats
Authors: Barthélemy Dorothy , Leblond Hugues , Provencher Janyne , Rossignol Serge
Published: August 2006

As a preliminary step to using intraspinal microstimulation (ISMS) for rehabilitation purposes, the distribution of various types of hindlimb responses evoked by ISMS in spinal cats (T13) is described. The responses to ISMS applied through a single electrode was assessed, before and after an intravenous injection of clonidine (noradrenergic agonist), using kinematics and electromyographic recordings in subacute (5–7 days, untrained) or chronic (3–5 wk trained on a treadmill) spinal cats. ISMS was applied in the dorsal, intermediate and ventral areas of segments L3–L7, from midline to 3 mm laterally. Uni- and bilateral non-locomotor responses as well as rhythmical locomotor responses were evoked. In the subacute cats, ipsilateral flexion was elicited in the dorsal region of L3–L7, whereas ipsilateral extension was evoked more ventrally and mainly in the caudal segments. Dorsal stimuli could induce ipsilateral flexion followed by ipsilateral extension. Sites inducing bilateral flexion and bilateral extension were similarly distributed to those evoking ipsilateral flexion and extension in the rostrocaudal axis but were evoked from more medial sites. Ipsilateral flexion with crossed extension was evoked from intermediate and ventral zones of all segments and lateralities. Unilateral ipsilateral locomotion was rarely observed. Contralateral locomotion was more frequent and mainly evoked medially, whereas bilateral locomotion was evoked exclusively from dorsal regions. With some exceptions, those distribution gradients were similar in the four conditions (subacute, chronic, pre- and postclonidine), but the proportion of each response could vary. The distribution of ISMS-evoked responses is discussed as a function of known localization of interneurons and motoneurons.
Opposing Modifications in Intrinsic Currents and Synaptic Inputs in Post-Traumatic Mossy Cells: Evidence for Single-Cell Homeostasis in a Hyperexcitable Network
Authors: Howard Allyson L. , Neu Axel , Morgan Robert J. , Echegoyen Julio C. , Soltesz Ivan
Published: August 2006

Recent experimental and modeling results demonstrated that surviving mossy cells in the dentate gyrus play key roles in the generation of network hyperexcitability. Here we examined if mossy cells exhibit long-term plasticity in the posttraumatic, hyperexcitable dentate gyrus. Mossy cells 1 wk after fluid percussion head injury did not show alterations in their current-firing frequency ( I-F) and current-membrane voltage ( I-V) relationships. In spite of the unchanged I-F and I-V curves, mossy cells showed extensive modifications in Na+, K+ and h-currents, indicating the coordinated nature of these opposing modifications. Computational experiments in a realistic large-scale model of the dentate gyrus demonstrated that individually, these perturbations could significantly affect network activity. Synaptic inputs also displayed systematic, opposing modifications. Miniature excitatory postsynaptic current (EPSC) amplitudes were decreased, whereas miniature inhibitory postsynaptic current (IPSC) amplitudes were increased as expected from a homeostatic response to network hyperexcitability. In addition, opposing alterations in miniature and spontaneous synaptic event frequencies and amplitudes were observed for both EPSCs and IPSCs. Despite extensive changes in synaptic inputs, cannabinoid-mediated depolarization-induced suppression of inhibition was not altered in posttraumatic mossy cells. These data demonstrate that many intrinsic and synaptic properties of mossy cells undergo highly specific, long-term alterations after traumatic brain injury. The systematic nature of such extensive and opposing alterations suggests that single-cell properties are significantly influenced by homeostatic mechanisms in hyperexcitable circuits.
Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of coregulation and potential transcriptional regulators
Authors: Keller M. A. , Addya S. , Vadigepalli R. , Banini B. , Delgrosso K. , Huang H. , Surrey S.
Published: August 2006

Deciphering the molecular basis for human erythropoiesis should yield information benefiting studies of the hemoglobinopathies and other erythroid disorders. We used an in vitro erythroid differentiation system to study the developing red blood cell transcriptome derived from adult CD34+ hematopoietic progenitor cells. mRNA expression profiling was used to characterize developing erythroid cells at six time points during differentiation ( days 1, 3, 5, 7, 9, and 11). Eleven thousand seven hundred sixty-three genes (20,963 Affymetrix probe sets) were expressed on day 1, and 1,504 genes, represented by 1,953 probe sets, were differentially expressed (DE) with 537 upregulated and 969 downregulated. A subset of the DE genes was validated using real-time RT-PCR. The DE probe sets were subjected to a cluster metric and could be divided into two, three, four, five, or six clusters of genes with different expression patterns in each cluster. Genes in these clusters were examined for shared transcription factor binding sites (TFBS) in their promoters by comparing enrichment of each TFBS relative to a reference set using transcriptional regulatory network analysis. The sets of TFBS enriched in genes up- and downregulated during erythropoiesis were distinct. This analysis identified transcriptional regulators critical to erythroid development, factors recently found to play a role, as well as a new list of potential candidates, including Evi-1, a potential silencer of genes upregulated during erythropoiesis. Thus this transcriptional regulatory network analysis has yielded a focused set of factors and their target genes whose role in differentiation of the hematopoietic stem cell into distinct blood cell lineages can be elucidated.
Chemotaxis-Inspired Load Balancing
Authors: Canright Geoffrey , Deutsch Andreas , Urnes Tore
Published: August 2006

We present an approach to the problem of load balancing on networks of nodes. Our approach is inspired by the phenomenon of negative chemotaxis in living systems. We use a diffusing signal (which is emitted by load, and moves faster than the load) to guide the movement of load towards the balanced state. Our reference system (for comparison) is unguided, diffusing load, moving at the same speed. Our tests show that the chemotaxis system can give large improvements over the reference system in convergence speed, as well as showing much reduced sensitivity to variations in network topology and in initial load distribution.
Elements about the Emergence Issue: A Survey of Emergence Definitions
Authors: Deguet Joris , Demazeau Yves , Magnin Laurent
Published: August 2006

Emergence, a concept that first appeared in philosophy, has been widely explored in the domain of complex systems and is sometimes considered to be the key ingredient that makes ‘complex systems’ ‘complex’. Our goal in this paper is to give a broad survey of emergence definitions, to extract a shared definition structure and to discuss some of the remaining issues. We do not know of any comparable surveys about the emergence concept. For this presentation, we start from a broadly applicable approach and finish with more specific propositions. We first present five selected works with a short analysis of each. We then propose a merged analysis in which we isolate a common structure through all definitions but also what we think needs further research. Finally, we briefly describe some perspectives about the emergence engine idea also referred to as emergent engineering.
The POEtic Electronic Tissue and Its Role in the Emulation of Large-Scale Biologically Inspired Spiking Neural Networks Models
Authors: Moreno J.Manuel , Thoma Yann , Sanchez Eduardo , Eriksson Jan , Iglesias Javier , Villa Alessandro
Published: August 2006

One of the major obstacles found when trying to construct artefacts derived from principles observed in living beings is the lack of actual dynamic hardware with autonomous capabilities. Even if programmable devices offer the possibility of modifying the functionality implemented in the device, they rely on external hardware and software elements to provide its physical configuration. In this paper we present a new family of electronic devices, called POEtic, whose architecture has been derived from the basic properties that can be extracted from the three major organization principles present in living beings: phylogenesis, ontogenesis and epigenesis. We will demonstrate that the capabilities present in these new programmable devices make them an ideal candidate for the real-time emulation of large-scale biologically inspired spiking neural network models.
An Electronically Controlled Microfluidic Approach towards Artificial Cells
Authors: Tangen Uwe , Wagler Patrick F. , Chemnitz Steffen , Goranovic Goran , Maeke Thomas , McCaskill John S.
Published: August 2006

This work focuses on the application of on-line programmable microfluidic bioprocessing as a complementation vehicle towards the design of artificial cells. The electronically controlled collection, separation and channel transfer of the biomolecules are monitored by a sensitive fluorescence setup. Two different physical effects, electrophoresis and electroosmotic flow, are used to allow for a detailed micro-control of fluids in micro-reaction environments. A combination of these two basic electronically controlled input reaction chambers makes combinatorial fluidic networks and indefinitely sustained biochemical or chemical reaction networks feasible. Experimental data showing the power of this approach is presented. Not only does this processing power pave the way towards the development of artificial cells (using a technology to complement not yet established autonomous metabolic or replication capabilities) but it also opens up new processes for applications of combinatorial chemistry and lab-on-a-chip biotechnology to drug discovery and diagnosis.
Message-Passing Algorithms for Non-Linear Nodes and Data Compression
Authors: Ciliberti Stefano , Mézard Marc , Zecchina Riccardo
Published: August 2006

The use of parity-check gates in information theory has proved to be very efficient. In particular, error correcting codes based on parity checks over low-density graphs show excellent performances. Another basic issue of information theory, namely data compression, can be addressed in a similar way by a kind of dual approach. The theoretical performance of such a parity source coder can attain the optimal limit predicted by the general rate-distortion theory. However, in order to turn this approach into an efficient compression code (with fast encoding/decoding algorithms) one must depart from parity checks and use some general random gates. By taking advantage of analytical approaches from the statistical physics of disordered systems and SP-like message passing algorithms, we construct a compressor based on low-density non-linear gates with a very good theoretical and practical performance.
Understanding Fractal Analysis? The Case of Fractal Linguistics
Authors: Jelinek Herbert F. , Jones Cameron L. , Warfel Matthew D. , Lucas Cecile , Depardieu Cecile , Aurel Gaelle
Published: August 2006

Terms such as ‘self-similarity’, ‘space filling’, ‘fractal dimension’, and associated concepts have different meanings to different people depending on their background. We examine how methodology in fractal analysis is influenced by diverse definitions of fundamental concepts that lead to difficulties in understanding fundamental issues. The meaning of terms associated with fractal analysis needs to be clarified if this method is to be useful in diverse disciplines. It is our premise that communications that are result focused constitute a danger in perpetuating misconceptions of terms due to the concise nature of the writing and the reliance on references to fill in the procedural and conceptual gaps. Communicating effectively requires a sound understanding of the terminology and a clear and meaningful presentation. We address here communication and the nature of scientific discourse, ‘fractal linguistics’.
Ambiguity in Art
Authors: Yevin Igor
Published: August 2006

A non-linear theory proposed different models of perception of ambiguous patterns, describing different aspects of multistable behaviour of the brain. This paper aims to review the phenomenon of ambiguity in art and to show that the mathematical models of the perception of ambiguous patterns should be regarded as one of the basic models of artistic perception. The following type of ambiguity in art will be considered. Visual ambiguity in painting, semantic (meaning) ambiguity in literature (for instance, ambiguity which V. Shklovsky called ‘the man who is out of his proper place’), ambiguity in puns, jokes and anecdotes, and mixed (visual and semantic) ambiguity in acting and sculpture. The complexity theory of the brain revealed that the human brain as a complex system operates close to the point of instability and ambiguity in art must be regarded as an important tool for supporting the brain near this critical point that gives human beings possibilities for better adaptation.
Sampling of Networks with Traceroute-Like Probes
Authors: Barrat Alain , Alvarez-Hamelin Ignacio , Dall’Asta Luca , Vázquez Alexei , Vespignani Alessandro
Published: August 2006

A large part of the recent development of the interest in complex networks has been triggered by the observation of particular characteristics of real world networks, such as the small-world properties or the heavy-tailed distributions of degrees. Many datasets are, however, the result of an incomplete sampling of the underlying real networks, and it has been argued that sampling procedures might introduce uncontrolled biases in the statistical properties of the sampled graph. In this paper, we explore this issue in the case of the Internet, which is generally mapped from a limited set of sources by using traceroute-like probes. The origin of the biases introduced by such a sampling process is investigated and related with the global topological properties of the underlying network. We complement the analytical discussion with a thorough numerical investigation of simulated mapping strategies in network models with different topologies.
Emergent Group Level Selection in a Peer-to-Peer Network
Authors: Hales David
Published: August 2006

Many peer-to-peer (P2P) applications benefit from node specialization: for example, the use of supernodes, the semantic clustering of media files or the distribution of different computing tasks among nodes. We describe simulation experiments with a simple selfish re-wiring protocol (SLAC) that can spontaneously self-organize networks into internally specialized groups (or ‘tribes’). Peers within the tribes pool their specialisms, sharing tasks and working altruistically as a team – or ‘tribe’ – even though their individual behaviour is selfish. This approach is scalable, robust and self-organizing. These results have implications and applications in many disciplines and areas beyond P2P systems.
Measuring the Dynamical State of the Internet: Large-Scale Network Tomography via the ETOMIC Infrastructure
Authors: Simon Gábor , Stéger József , Hága Péter , Csabai István , Vattay Gábor
Published: August 2006

In this paper we show how to go beyond the study of the topological properties of the Internet, by measuring its dynamical state using special active probing techniques and the methods of network tomography. We demonstrate this approach by measuring the key state parameters of Internet paths, the characteristics of queuing delay, in a part of the European Internet. In the paper we describe in detail the ETOMIC measurement platform that was used to conduct the experiments, and the applied method of queuing delay tomography. The main results of the paper are maps showing various spatial structure in the characteristics of queuing delay corresponding to the resolved part of the European Internet. These maps reveal that the average queuing delay of network segments spans more than two orders of magnitude, and that the distribution of this quantity is very well fitted by the log-normal distribution.
Is Selection Optimal for Scale-Free Small Worlds?
Authors: Palotai Zs. , Farkas Cs. , Lorincz A.
Published: August 2006

The ‘no free lunch theorem’ claims that for the set of all problems no algorithm performs better than random search and, thus, selection can be advantageous only on a limited set of problems. In this paper we investigate how the topological structure of the environment influences algorithmic efficiency. We study the performance of algorithms, using selective learning, reinforcement learning, and their combinations, in random, scale-free, and scale-free small world (SFSW) environments. The learning problem is to search for novel, not-yet-found information. We ran our experiments on a large news site and on its downloaded portion. Controlled experiments were performed on this downloaded portion: we modified the topology, but preserved the publication time of the news. Our empirical results show that the selective learning is the most efficient in SFSW topology. In non-small world topologies, however, the combination of the selective and reinforcement learning algorithms performs the best.
Homocysteine Levels Are Associated with Increased Risk of Congestive Heart Failure in Patients with and without Coronary Artery Disease
Authors: May Heidi T. , Alharethi Rami , Anderson Jeffrey L. , Muhlestein Joseph B. , Reyna Sandra P. , Bair Tami L. , Horne Benjamin D. , Kfoury Abdallah G. , Carlquist John F. , Renlund Dale G.
Published: August 2006

Background: Increased homocysteine (HCY) is associated with increased risk of vascular disease. Whether HCY affects development of congestive heart failure (CHF) independent of coronary artery disease (CAD) is uncertain. We evaluated whether increased HCY predicts low ejection fraction or clinical CHF. Methods: Patients (n = 2,842) undergoing coronary angiography had HCY measured between 1994 and 1999 and were prospectively studied. Left ventricular dysfunction (LVD) was defined as ejection fraction ≤40%. Multivariable regressions assessed predictive strength of HCY for LVD or LVD/CHF. Results: The average age was 64 ± 12 years; 69% were men, and 74% had CAD. LVD was present in 12% and the combination of either LVD or clinical CHF was present in 21.9%. Quartiles of HCY were: ≤10.5 (Q1), 10.5–13.2 (Q2), 13.3–17.0 (Q3) and ≧17.1 µmol/l (Q4). LVD and LVD/CHF were more prevalent in Q3 (15, 25%) and Q4 (15, 27%) than in Q1 HCY (8.4, 18%; p < 0.001 vs. Q4). After adjustment, Q3 and Q4 HCY independently predicted LVD (OR = 1.7, 95% CI 1.2–2.5, p = 0.004; OR = 1.8, 95% CI 1.3–2.6, p = 0.002) or LVD/CHF (OR = 1.4, 95% CI 1.04–1.8, p = 0.03; OR = 1.7, 95% CI 1.3–2.2, p < 0.001). Findings did not differ by disease etiology: for Q4 among non-CAD patients, OR = 1.7 for LVD and OR = 1.7 for LVD/CHF. Further, there was no interaction of results with gender. Conclusion: High HCY levels (Q3/4 ≧13.3 µmol/l) are associated with LVD and combined endpoint of LVD/clinical CHF. This relationship is independent of CHF etiology and gender. Further research is indicated to distinguish between a causal or noncausal mechanism for this association.
Cardiac Index and Exercise during VDD/DDD versus VVIR Pacing in Children
Authors: Baspinar Osman , Celiker Alpay , Karagoz Tevfik
Published: August 2006

Twelve children with a VDD/DDD pacemaker during 100, 125, 150, 200 ms atrioventricular delays and VVIR pacing, cardiac index was measured at rest and evaluated by endurance time during exercise stress test. The optimal atrioventricular delay, which provides highest cardiac index, was 100 ms in three, 125 ms in two, and 150 ms in four and 200 ms in three patients. VDD/DDD pacing with different atrioventricular intervals resulted in a significantly higher cardiac index (6.70 ± 3.06, 6.49 ± 2.51, 6.15 ± 2.35, 6.37 ± 2.69 l/min/m2, respectively) than VVIR pacing (5.25 ± 2.39 l/min/m2) at the rest. However, endurance times to treadmill exercise were similar in both the optimal atrioventricular delay (21.6 ± 3.7 min) and VVIR mode (22.4 ± 3.4 min) (p > 0.05).
Role of Completion Pancreatectomy as a Damage Control Option for Post-Pancreatic Surgical Complications
Authors: Tamijmarane A. , Ahmed I. , Bhati C.S. , Mirza D.F. , Mayer A.D. , Buckels J.A.C. , Bramhall S.R.
Published: August 2006

Introduction: Management of pancreatic leak and haemorrhage is complex with high mortality rates. In this study, the results of completion pancreatectomy which was performed as a last resort option were analysed. Patients and Methods: 25 patients who had completion pancreatectomy from among 677 patients who had pancreatoduodenectomy or distal pancreatectomy over a period of 18 years were analysed in terms of the indications for completion pancreatectomy, outcome and survival data. Results: Indications for completion pancreatectomy include pancreatic leak in 12 patients (48%), both bleeding and pancreatic leak in 8 (32%), and haemorrhage alone in 5 (20%) patients. 18 (72%) patients also had splenectomy. Median ITU stay was 4 and 8 days for those who survived and died post-completion pancreatectomy, respectively. 36% patients had septicaemia and 32% patients had multiple organ failure. 12 patients survived the operation with a median survival of 52 months. Conclusion: 25 (3.6%) patients required surgical intervention for pancreatic complications. The incidence of splenectomy was 84.6% in those who died after completion pancreatectomy compared to 58.3% of those who survived (Fisher’s exact test two-sided 0.20). Despite significant morbidity and mortality, completion pancreatectomy has a role in the management of post-pancreatic surgical complications.
Crohn’s Disease Activity Index and Vienna Classification – Is It Worthwhile to Calculate before Surgery?
Authors: Rentsch M. , Beham A. , Schlitt H.J. , Jauch K.W.
Published: August 2006

Background: Crohn’s disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The ‘Crohn’s disease activity index’ (CDAI) and the ‘Vienna classification’ (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. ‘strictureplasty’ in ‘stricturing disease’, ‘colon surgery’ in ‘colon involvement’), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 ‘surgical sites’ 425 ± 25 vs. 223.3 ± 25) and complications (357.1 ± 36.9 (with) vs. 244.4 ± 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications.
Endoscopic Transpapillary Stenting of Pancreatic Duct Disruption
Authors: Brennan P.M. , Stefaniak T. , Palmer K.R. , Parks R.W.
Published: August 2006

Background/Aims: Endoscopic transpapillary stenting of the pancreatic duct is increasingly being used in the management of pancreatic duct disruption. In contrast to its more established role in pancreatic duct obstruction, little is reported on the spectrum of indications and outcome in management of pancreatic duct disruption. Methods: The indication for and outcome of transpapillary pancreatic duct stenting was analysed retrospectively in a UK supra-regional specialist pancreatobiliary centre, between January 1998 and August 2004. Results: Data were obtained on 30 patients (19 male, 11 female, median age 53 years). The main indications for pancreatic duct stenting were: pancreatic pseudocyst, pancreatic ascites, pancreatic duct leak following necrosectomy, and pancreaticopleural fistula. The median duration of stenting was 6 weeks for fistulae and 10 weeks for pseudocysts. Twenty-one patients (70%) had complete resolution. After a median follow-up of 45 months, no recurrence was noted in successfully treated patents. Conclusion: Endoscopic transpapillary pancreatic duct stenting is an increasingly valuable treatment option in the management of pancreatic fistulae and pseudocysts.
Decreased Growth Rate of Lung Metastatic Lesions after Splenectomy in Mice
Authors: Sonoda Kazuya , Izumi Koichi , Matsui Yoko , Inomata Masafumi , Shiraishi Norio , Kitano Seigo
Published: August 2006

Background: The effect of splenectomy on hematogenous metastases of malignant tumors remains controversial. The aim of this study was to clarify the effect of splenectomy on hematogenous metastases in an animal model. Methods: Colon 26 cancer cells were inoculated into the lateral tail vein of 90 mice. The mice were then assigned to a splenectomy group or a control group. Lung weight, number of lung metastases, size of metastatic nodules, and serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels after the surgical procedure were measured and compared between the two groups. Results: The lung nodules were significantly smaller in the splenectomy group than in the control group. In both groups, the serum VEGF levels increased on day 1 and then decreased. The serum VEGF levels on day 5 were significantly lower in the splenectomy group than in the control group. The serum bFGF levels were significantly lower in the splenectomy group than in the control group on days 1 and 5. Immunohistochemical study showed that bFGF was produced by reticuloendothelial cells of the spleen. Conclusion: The growth rate of hematogenous metastatic lesions appears to decrease after splenectomy and may be associated with decreases in serum levels of VEGF and bFGF induced by splenectomy.
Fine vs. Coarse Atrial Fibrillation: Which One is More Risky?
Authors: Yilmaz Mehmet Birhan , Guray Yesim , Guray Umit , Cay Serkan , Caldir Vedat , Biyikoglu Senay Funda , Sasmaz Hatice , Korkmaz Sule
Published: August 2006

Background: Atrial fibrillation (AF) is a frequent arrhythmia, associated with morbidity and mortality. It is identified by two types on surface electrocardiogram as fine and coarse AF. We aimed to search the association of subtypes of AF with clinical parameters. Methods: Eight hundred and eleven consecutive patients, who had AF attack which lasted longer than 24 h or more, were evaluated along with clinical and laboratory data. Results: Coarse AF was noticed in 51.7% (n = 419), and fine AF in 48.3% (n = 392). Sex was associated with subtype of AF such that coarse AF was present in 46.5% of male patients, but in 56.1% of female patients (p = 0.009). Coarse AF was present in 85.3% of patients with mitral stenosis, whereas it was present in 35.3% of patients with normal heart valve (p < 0.001). ). Patients having fine AF were significantly older than those having coarse AF (64 ± 12, 57 ± 13 years, p < 0.001). 19.6% of those with coarse AF had history of cerebrovascular event (CVE), whereas 13.5% of those with fine AF had history of CVE (p = 0.021). After controlling for age in the multivariable logistic regression analysis, presence of coarse AF (B = 1.585, p = 0.031) was found to be independently associated with the history of CVE. Conclusion: AF is identified by two morphological forms on the surface electrocardiogram. These two forms were found to be associated with different clinical parameters, acting on vascular endpoints differently.
Management of Acute Severe Hyperlipidemic Pancreatitis
Authors: Kyriakidis A.V. , Raitsiou B. , Sakagianni A. , Harisopoulou V. , Pyrgioti M. , Panagopoulou A. , Vasilakis N. , Lambropoulos S.
Published: August 2006

Background/Aim: Hypertriglyceridemia is rare and can provoke acute severe hyperlipidemic pancreatitis when triglyceride levels exceed 11.3 mmol/l. In 10 patients we evaluated the therapeutic guidelines for severe hyperlipidemic pancreatitis. Methods: Ten patients (8 men and 2 women) were admitted to the intensive care unit with a diagnosis of acute severe hyperlipidemic pancreatitis. They underwent standard treatment. Heparin, insulin and antihyperlipidemic drugs were used to lower the triglyceride levels. The patients underwent plasmapheresis within 48 h of admission, and fat-free parenteral nutrition was used. Two of the patients underwent surgery because of infection of necrotic segments. Results: Standard treatment was essential for all the patients but plasmapheresis was the procedure that lowered the triglyceride and lipid levels in all cases. It improved abdominal pain, clinical state, and signs and symptoms of the disease. Two patients underwent surgery due to infection of the necrotic segments and one of them died. Follow-up lasted 4–54 months with no recurrences of pancreatitis. Conclusion: Our study shows that standard treatment is essential, but plasmapheresis successfully lowered lipid levels with no complications and relieved the patients from the symptoms in the acute phase of the disease. Hyperlipidemic pancreatitis should initially be treated conservatively. Plasmapheresis is a method that has lately been used successfully for hyperlipidemic pancreatitis. It seems that all therapeutic measures should be applied as early as possible, within the first 48 h.
Decrease in the Allergenicity of Japanese Cedar Pollen Allergen by Treatment with Positive and Negative Cluster Ions
Authors: Kawamoto Seiji , Oshita Masatosi , Fukuoka Norihiko , Shigeta Seiko , Aki Tsunehiro , Hayashi Takaharu , Nishikawa Kazuo , Ono Kazuhisa
Published: August 2006

Background: Japanese cedar pollinosis is a severe allergic disease in Japan. The most effective means of decreasing allergic inflammation reactions is still avoidance of the aeroallergen. Recently, a novel air purification system using positively and negatively charged cluster ions was developed to create comfortable living environments. We aimed to assess the ability of existing technology to lower allergenicity of Japanese cedar pollen. Methods: A Japanese cedar pollen extract was nebulized from the top of a cylindrical container with 2 or 4 ion-generating devices. The extract in a mist was passed through the space filled with or without plasma cluster ions for 90 s, and the ion-treated or nontreated extract was then collected in a Petri dish at the bottom of the container. Results: The ion-exposed extract was significantly diminished in its reactivities to anti-Cry j 1 or anti-Cry j 2 antiserum and to human allergic sera IgE on ELISA. SDS-PAGE analysis revealed that ion exposure induced protein degradation in the pollen extract. Similarly, the ion treatment impaired about 80% of the binding to pooled sera IgE from patients allergic to Japanese cedar pollen on ELISA inhibition. Furthermore, intracutaneous and conjunctival reaction tests showed a remarkable diminution in the allergenicity of the ion-irradiated extract. Conclusion: Ion irradiation resulted in a remarkable decrease in in vitro and in vivo allergenicities of atomized Japanese cedar pollen extracts.
Application of Immunoreaction Enhancer Solutions to an Enzyme-Linked Immunosorbent Assay for Antigen-Specific IgE in Mice Immunized with Recombinant Major Mite Allergens or Ovalbumin
Authors: Kikuchi Yuko , Takai Toshiro , Ota Mikiko , Kato Takeshi , Takeda Ken , Mitsuishi Kouichi , Ikeda Shigaku , Okumura Ko , Ogawa Hideoki
Published: August 2006

Background: Weak signals for allergen-specific IgE are a problem in murine models for the study of allergies. It has been reported that the removal of IgG from murine sera enhances signal intensity. Very recently, buffer solutions designed to enhance signals in immunoassays have been developed and made commercially available. Methods: Sera from mice immunized either with a recombinant form of one of the major mite allergens Der p 1, Der f 1 and Der f 2, or with ovalbumin adsorbed to alum were used for the assays. Total IgE was measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Allergen-specific IgE was assayed using plates coated with the allergens after the removal of IgG from sera with protein G-coupled sepharose beads in wells of other plates or with the use of commercially available enhancer solutions without the removal of IgG. IgE binding was detected with horseradish peroxidase-conjugated anti-murine IgE monoclonal antibody as the secondary antibody. Results: Significant levels of total IgE were produced after the immunizations. The in-well pretreatment of diluted sera (1/10 dilution) with protein G-coupled beads enhanced the signals for allergen-specific IgE. The use of the enhancer solutions for dilution of the sera and secondary antibody and prolonged incubation remarkably enhanced the signals at a more extensive dilution of sera (1/200 or less) without the removal of IgG. Conclusions: An ELISA simply modified with the use of immunoreaction enhancer solutions has advantages in terms of signal intensity and ease of handling for the detection of allergen-specific murine IgE and would be useful for the study of allergies with murine models.
Genetic Association Studies between the T Cell Immunoglobulin Mucin (TIM) Gene Locus and Childhood Atopic Dermatitis
Authors: Page Natalie S. , Jones Graham , Stewart Graeme J.
Published: August 2006

Background: The T cell immunoglobulin mucin (TIM) gene family is involved in T cell proliferation and differentiation and has been implicated in allergic disease. We have tested whether TIM gene polymorphisms are associated with atopic dermatitis (AD) in an Australian cohort. Methods: Transmission disequilibrium testing of 15 single nucleotide polymorphisms across TIM-1, TIM-3 and TIM-4 in 93 Caucasian families, and of a tri-allelic (0, 15 and 18 base pairs) TIM-1 insertion polymorphism in 123 Caucasian and Asian families, was carried out in proband-parent trio families. Results: Transmission of the 18-base pair variant of this insertion was significantly under-represented in the childhood AD cohort (p = 0.02), which is in agreement with a previous study on asthma in an African-American cohort. We also found a novel association between AD and the major haplotype of TIM-4 (p = 0.016). There was no evidence for an association between AD and TIM-3. Conclusions: In addition to confirming the importance of genetic variation in TIM-1, our results also suggest that genetic variants in the ligand for TIM-1, TIM-4, also contribute to the presentation of AD and related disorders.
Effects of Tributyltin on the Development of Atopic Dermatitis-Like Eruptions in DS-Nh Mice
Authors: Iwamura Chiaki , Aihara Michiko , Nakazawa Masatoshi , Takahashi Kazuo , Yoshioka Naoya , Matsukura Setsuko , Hirasawa Tsutomu , Minami Mutsuhiko , Ikezawa Zenro
Published: August 2006

Background: In the last few decades, numerous chemical compounds have been produced as a result of industrial development. At the same time, the number of atopic dermatitis (AD) patients has been increasing. It has been reported that tributyltin (TBT) compounds have effects not only on the reproductive system but also on the immune system. Objective: To investigate whether TBT has an effect on AD, we fed a diet containing TBT to DS-Nh mice, which spontaneously developed dermatitis under conventional conditions. Methods: DS-Nh mice fed TBT or a control diet were examined for skin changes, number of Staphylococcus aureus on the skin and serum IgE levels. To determine Th1/Th2 cytokine production by lymphocytes, lymphocytes of DS-Nh mice fed TBT and of controls were cultured with staphylococcal enterotoxin B and cytokine levels in the supernatants were measured by ELISA. We observed not only spontaneous dermatitis but also dermatitis induced by sensitization with 2,4,6-trinitrochlorobenzene (TNCB). Results and Conclusion: The AD-like lesions induced by TNCB sensitization were more severe in the mice fed TBT than in those fed the control diet. A greater increase in S. aureus on the skin was observed in the mice fed TBT than in the mice fed the control diet. A decrease in IFN-γ production and an increase in IL-5 and IL-13 production were observed in the mice fed the TBT diet and treated with TNCB. These findings suggest that the increase in S. aureus and the enhancement of Th2 response induced by TBT exacerbate the AD-like lesions in mice treated with TNCB.
Murine TLR4 Is Implicated in Cigarette Smoke-Induced Pulmonary Inflammation
Authors: Maes Tania , Bracke Ken R. , Vermaelen Karim Y. , Demedts Ingel K. , Joos Guy F. , Pauwels Romain A. , Brusselle Guy G.
Published: August 2006

Background: Chronic obstructive pulmonary disease (COPD) is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. We investigated whether Toll-like receptor 4 (TLR4) is implicated in cigarette smoke (CS)-induced pulmonary inflammation in a murine model of COPD. Methods: C3H/HeOuJ (Tlr4WT) and C3H/HeJ (Tlr4defective) mice were exposed to air or CS for 5 weeks (subacute) and 26 weeks (chronic), and pulmonary inflammation was evaluated. Results: In Tlr4WT mice, subacute and chronic CS exposure induced a substantial pulmonary infiltration of macrophages, neutrophils, lymphocytes and dendritic cells (DCs), that was absent in air-exposed mice. CS exposure increased the costimulatory marker expression on DCs, the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage (BAL) fluid and induced the pulmonary expression of matrix metalloproteinase-12 (MMP-12), TLR4 and TLR2. In contrast, after subacute CS exposure, Tlr4defective mice showed a limited (5-fold lower) increase of DCs and lymphocytes in BAL fluid, lower costimulatory marker expression on DCs and lower MCP-1 and TNF-α levels in BAL fluid compared to Tlr4WT animals. After chronic CS exposure, however, the difference in pulmonary inflammation between Tlr4WT and Tlr4defective mice was less pronounced and both strains showed similar MCP-1 and TNF-α levels in BAL and similar pulmonary MMP-12, TLR4 and TLR2 expression. Conclusions: We demonstrated that the TLR4 mutation in C3H/HeJ mice is protective against CS-induced pulmonary influx of neutrophils, DCs and lymphocytes upon subacute CS exposure. However, TLR4 is only of minor importance in chronic CS-induced inflammation in mice.
A Cutaneous Allergen Neutralisation Test That Correlates with the Duration of Venom Immunotherapy
Authors: Senti Gabriela , Johansen Pål , Oliver Ruben , Prinz Vavricka Bettina M. , Graf Nicole , Wüthrich Brunello , Kündig Thomas M.
Published: August 2006

Background: Despite the well-documented efficacy of Hymenoptera specific immunotherapy (SIT), there is no safe method to reliably characterise the patient level of protection. Only poor correlations between protection and allergen-specific serum immunoglobulins have been found, and a sting challenge is the only means to evaluate the efficacy of immunotherapy. Therefore, we aimed to develop a cutaneous test that measures in vivo neutralisation of the Hymenoptera venom. Materials and Methods: Twenty-four patients with wasp venom allergy were included in the study. Wasp-specific serum IgE, IgG and IgG4 were measured by ImmunoCAP. Dilutions of the individual patient sera were intradermally injected into the forearm. Then, wasp venom extract was injected into these sites to quantitatively assess the formation of wheals and flares. Results: The results show that during the course of SIT, patient sera gained the capacity to neutralise skin reactions to wasp venom extracts in vivo. The test correlated with the duration of SIT as well as with the concentration of IgG and IgG4. Conclusion: The in vivo neutralisation test may become a promising tool in allergy diagnostics as well as in monitoring the success of SIT in patients undergoing allergen SIT.
Nasal Resistance and Allergic Inflammation Depend on Allergen Type
Authors: Gelardi Matteo , Maselli Del Giudice Alessandro , Candreva Teresa , Fiorella Maria Luisa , Allen Michaela , Klersy Catherine , Marseglia Gian Luigi , Ciprandi Giorgio
Published: August 2006

Background: Allergic rhinitis is characterized by inflammatory cell infiltrate and increased nasal airflow resistance. Objective: The aim of this study was to evaluate the relationship between sensitization type, inflammatory cell pattern, and nasal airflow resistance in a group of rhinitics with monosensitization. Methods: Seventy-seven subjects (40 males and 37 females, with a mean age of 33 ± 4.4 years) suffering from allergic rhinitis were studied. Skin prick test, nasal cytology and electronic rhinomanometry were assessed in all subjects. Results: The number of subjects monosensitized to house dust mites was 23, to grasses 20, to cypress 17, to Parietaria 11, and to olive tree 6. Significant differences were observed between each type of allergen sensitization concerning both the nasal airflow resistance (p = 0.002) and the nasal cytology pattern: eosinophils (p = 0.004), degranulated eosinophils (p = 0.002), mast cells (p = 0.006) and degranulated mast cells (p = 0.008). Furthermore, goblet cells were higher in house dust mite-sensitized subjects compared with the pollen-sensitized group (p = 0.018), in which a prevalence of eosinophils, degranulated eosinophils, mast cells and degranulated mast cells was observed (p = 0.049, p < 0.001, p = 0.022 and p = 0.007, respectively). Nasal resistances were higher in the pollen group (p = 0.001). Conclusions: This study provides evidence that inflammatory cell pattern and nasal resistance depend on the type of allergen sensitization.
Honeybee Interference as a Novel Aid to Reduce Pollen Exposure and Nasal Symptoms among Greenhouse Workers Allergic to Sweet Bell Pepper (Capsicum annuum) Pollen
Authors: de Jong Nicolette W. , van der Steen Josef J.M. , Smeekens Christ C. , Blacquière Tjeerd , Mulder Paul G.H. , van Wijk Roy Gerth , de Groot Hans
Published: August 2006

Background: In 1999, an extensive study among bell pepper growers showed a prevalence of 53.8% work-related symptoms and 35.4% sensitisation to bell pepper pollen. Experiments with bees to remove pollen from bell pepper flowers have been done for a few years. Objectives: It was the aim of this study to investigate whether bees can reduce the pollen exposure in bell pepper greenhouses and whether this reduction results in a decrease in allergic complaints in the greenhouse workers. Methods: Eighteen greenhouses were selected for the study. In each greenhouse, pollen exposure was estimated. In 6 and 3 of the greenhouses, high, respectively low, numbers of honeybees were placed throughout the pollen season of the sweet bell pepper plant. Nine greenhouses without honeybees were used as control. At baseline, as well as after 4 and 8 months, nasal symptoms assessed with a visual analogue score and lung function parameters were used as outcome measure. Results: Forty-four of the 133 employees invited reported work-related symptoms. High numbers of bees reduced the pollen amount in a dose-dependent way to 18% of the baseline exposure. A significant trend relationship between the visual analogue scale in nasal symptoms and the number of colonies of bees was seen. Conclusions: The interference of bees in bell pepper greenhouses significantly reduces the pollen amount. This reduction is associated with less work-related rhinitis symptoms in allergic greenhouse workers. This intervention study supports the hypothesis that allergic work-related complaints of greenhouse workers, sensitised to bell pepper pollen, are caused by occupational exposure to this pollen in the greenhouse.
Endotoxin Levels in Rural Thai and Urban Singaporean Homes
Authors: Lee A. , Sangsupawanich P. , Ma S. , Tan T.-N. , Shek L.P. , Goh D.L.M. , Ho B. , van Bever H. , Lee B.W.
Published: August 2006

Background: Exposure to dust endotoxin and allergens in early childhood may influence the development of allergic diseases. Aims: This study aimed to evaluate dust endotoxin and dust mite allergens in urban Singapore and rural Thai homes of young children and study potential environmental influences. Methods: Mattress dust endotoxin and Der p 1, Der f 1, group 2 (Der f 2 and Der p 2) and Blo t 5 allergen levels were quantified in 101 infant mattress dust samples, 51 from urban Singapore and 50 from rural Thailand. Comprehensive questionnaires on the home environment and cleaning practices were completed. Results: Endotoxin levels in rural Thailand were significantly higher than in urban Singapore (geometric mean 26,334.12 ± 4.60 and 18,377.85 ± 2.52 endotoxin units/g, respectively; p = 0.032). In contrast, higher levels of Der f 1 (p = 0.02), group 2 (p < 0.01) and Blo t 5 (p < 0.01) allergens were found in Singapore homes compared with rural Thai homes. Multiple logistic regression analysis showed that the use of detergents (p = 0.001) and disinfectants (p = 0.024) to clean floors and mattress protectors (p = 0.021) were independently associated with lower endotoxin levels. Conclusion: Endotoxin levels are higher in rural compared with urban homes in South East Asia. The reverse was true for dust mite allergen levels. Certain identifiable home environmental conditions and practices accounted for the differences in endotoxin levels.
The Intestinal Intraepithelial Lymphocytes with T Cell Receptor αβ Express Toll-Like Receptor 4 and Are Responsive to Lipopolysaccharide
Authors: Ma Chi , Xu Chunping , Duan Lian , He Wei
Published: August 2006

Background: Intestinal intraepithelial lymphocytes (iIELs) play an important role in intestinal innate immunity and oral immune tolerance. To compare the differences in gene expression between murine iIELs and splenic T lymphocytes, we established the cDNA subtractive library of iIELs and analyzed the iIELs special genes. Our study focused on the relationship between Toll-like receptor 4 (TLR4), TLR5 and iIELs. Methods: Ninety percent purified iIELs and splenic T lymphocytes were isolated by density-gradient centrifugation in a Percoll and nylon column, respectively. We then established the cDNA subtractive library of iIELs via improved subtractive hybridization. The special expressed sequence tags of iIELs were screened by reverse Northern blot. The expressions of TLR4 and TLR5 were analyzed by RT-PCR and fluorescence staining. The proliferation of T cells was determined by 3H-TdR incorporation. Results: TLR4, but not TLR5, was detected in iIELs by RT-PCR and fluorescence staining. However, TLR4 was only found in αβ iIELs. Furthermore, iIELs were observed to proliferate in response to lipopolysaccharide in vitro, with upregulation of IRAK-1 mRNA expression. Conclusion: αβ iIELs can recognize lipopolysaccharide via TLR4, which may play an important role in the intestinal innate immunity.