bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybridization and enzyme blocking method to enrich minor cDNA sequences
Authors: Henry Lynda , Gannon Frank
Published: February 2005

A method is presented which allows for the enrichment of low frequency cDNA sequences. The crucial step in the procedure is the hybridization of a pool of cDNA to homologous or heterologous RNA to a Rot value which will leave minor sequences in a single strand cDNA form while the major sequences form cDNA:RNA hybrids. This allows subsequent enzymatic differentiation between major and minor sequences resulting ultimately in the degradation of the major sequences. The procedure is general and simple as it requires no column chromatography step. The method is designed to integrate into a widely used cDNA cloning protocol and results either in double-stranded cDNA which can be used for molecular cloning or as a source of probes for hybridization.
Effect of E. coli endotoxin on temperature, oxygen consumption and brown adipose tissue thermogenesis in rats and mice
Authors: Jennings G. , Elia M.
Published: February 2005

The effects of E. coli endotoxin 0127 B8 on oxygen consumption, temperature, and on the activity of the proton conductance pathway in brown adipose tissue (BAT) were investigated in rats and mice. In rats an increase was observed in rectal and skin temperature, whole body oxygen consumption and GDP binding in BAT. In mice only the rise in rectal and skin temperature were significantly changed by endotoxin administration.

These findings suggest that in some species BAT is involved in the production of endotoxin induced fever and increased energy expenditure.
The Registration of Complications in Surgery: A Learning Curve
Authors: Veen Eelco J. , Janssen‐Heijnen Maryska L. G. , Leenen Loek P. H. , Roukema Jan A.
Published: February 2005

Registration of complications in surgery is an important method used for quality improvement. Unfortunately many different definitions and classification systems have been used, which influences the interpretation and the outcome of complication registration. Since 1986 complications have been registered on a daily basis in our surgical department. We focus in this article on the influence of changes in interpretation of the definition and registration methods used on the incidence of registered complications. Between 1986 and 1993 complications registered were strictly related to surgical procedures. In the second period, between 1993 and 2001, the interpretation of the definition changed and all adverse events were registered in a patient‐centred way, not only related to the surgical procedure. The definition used in both periods did not change. In 1993 we started with the implementation of a fully automated registration system in our surgical department. In the first period 1699 (7%) complications in 24,201 surgical procedures were registered and in the second period 8335 (27%) complications were registered in 31,161 surgical procedures. A dramatic increase in the total number of registered complications was seen with the implementation of a fully automated registration system and a patient‐centred way of registering complications. In the context of the evolving discussion of quality of care, a uniform definition and registration system has to be used to assure reliable outcome data in surgery and to form a basis for comparison.
Intestinal Anastomoses Prior to 1882; a Legacy of Ingenuity, Persistence, and Research Form a Foundation for Modern Gastrointestinal Surgery
Authors: Dietz Ulrich A. , Debus Eike‐Sebastian
Published: February 2005

This review describes some of the main intestinal suture and anastomosis techniques up to 1882. The disparity between the great variety of proposed techniques and the paucity of actual clinical application is highlighted. Additionally, the statistical reviews of Rydygier (1881) and Madelung (1882), sources originally written in German and only rarely cited, are compared and analyzed. Historical terminology regarding anastomoses is clarified, and the contribution made by experimental surgery toward the establishment of modern suture technique is discussed. The technique of Philipp Ramdohr (1727) is presented in greater detail.
High sensitivity to multisensory conflicts in agoraphobia exhibited by virtual reality
Authors: Viaud-Delmon Isabelle , Warusfel Olivier , Seguelas Angeline , Rio Emmanuel , Jouvent Roland
Published: February 2005

The primary aim of this study was to evaluate the effect of auditory feedback in a VR system planned for clinical use and to address the different factors that should be taken into account in building a bimodal virtual environment (VE). We conducted an experiment in which we assessed spatial performances in agoraphobic patients and normal subjects comparing two kinds of VEs, visual alone (Vis) and auditory–visual (AVis), during separate sessions. Subjects were equipped with a head-mounted display coupled with an electromagnetic sensor system and immersed in a virtual town. Their task was to locate different landmarks and become familiar with the town. In the AVis condition subjects were equipped with the head-mounted display and headphones, which delivered a soundscape updated in real-time according to their movement in the virtual town. While general performances remained comparable across the conditions, the reported feeling of immersion was more compelling in the AVis environment. However, patients exhibited more cybersickness symptoms in this condition. The result of this study points to the multisensory integration deficit of agoraphobic patients and underline the need for further research on multimodal VR systems for clinical use.
Arabidopsis ADC genes involved in polyamine biosynthesis are essential for seed development
Authors: Urano Kaoru , Hobo Tokunori , Shinozaki Kazuo
Published: February 2005

Arginine decarboxylase (ADC) is a rate‐limiting enzyme that catalyzes the first step of polyamine (PA) biosynthesis in Arabidopsis thaliana. We generated a double mutant deficient in Arabidopsis two ADC genes (ADC1
−/−
ADC2
−/−) and examined their roles in seed development. None of the F2 seedlings from crosses of adc1‐1 and adc2‐2 had the ADC1
−/−
ADC2
−/− genotype. In addition, some abnormal seeds were observed among the ADC1
+/−
ADC2
−/− and ADC1
−/−
ADC2
+/− siliques. Viable offspring with the ADC1
−/−
ADC2
−/− genotype could not be obtained from the ADC1
+/−
ADC2
−/− and ADC1
−/−
ADC2
+/− plants. These results indicate that AtADC genes are required for production of polyamines that are essential for normal seed development in Arabidopsis.
Gene expression profile of murine long-term reconstituting vs. short-term reconstituting hematopoietic stem cells
Authors: Zhong Jiang F. , Zhao Yi , Sutton Susan , Su Andrew , Zhan Yuxia , Zhu Lunjian , Yan Chunli , Gallaher Tim , Johnston Patrick B. , Anderson W. French , Cooke Michael P.
Published: February 2005

The hematopoietic stem cell (HSC) compartment is composed of long-term reconstituting (LTR) and short-term reconstituting (STR) stem cells. LTR HSC can reconstitute the hematopoietic system for life, whereas STR HSC can sustain hematopoiesis for only a few weeks in the mouse. Several excellent gene expression profiles have been obtained of the total hematopoietic stem cell population. We have used five-color FACS sorting to isolate separate populations of LTR and STR stem cell subsets. The LTR HSC has the phenotype defined as Lin-Sca+Kit+38+34-; two subsets of STR HSC were obtained with phenotypes of Lin-Sca+Kit+38+34+and Lin-Sca+Kit+38-34+. The microarray profiling study reported here was able to identify genes specific for LTR functions. In the interrogated genes (≈12,000 probe sets corresponding to 8,000 genes), 210 genes are differentially expressed, and 72 genes are associated with LTR activity, including membrane proteins, signal transduction molecules, and transcription factors. Hierarchical clustering of the 210 differentially expressed genes suggested that they are not bone marrow-specific but rather appear to be stem cell-specific. Transcription factor-binding site analysis suggested that GATA3 might play an important role in the biology of LTR HSC.
Fasudil prevents KATP channel-induced improvement in postischemic functional recovery
Authors: Nishizawa Kenya , Wolkowicz Paul E. , Yamagishi Tadashi , Guo Ling-Ling , Pike Martin M.
Published: February 2005

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.
Effects of Noisy Drive on Rhythms in Networks of Excitatory and Inhibitory Neurons
Authors: Börgers Christoph , Kopell Nancy
Published: February 2005

Synchronous rhythmic spiking in neuronal networks can be brought about by the interaction between E-cells and Icells (excitatory and inhibitory cells). The I-cells gate and synchronize the E-cells, and the E-cells drive and synchronize the I-cells. We refer to rhythms generated in this way as PING (pyramidal-interneuronal gamma) rhythms. The PING mechanism requires that the drive II to the I-cells be sufficiently low; the rhythm is lost when II gets too large. This can happen in at least two ways. In the first mechanism, the I-cells spike in synchrony, but get ahead of the E-cells, spiking without being prompted by the E-cells. We call this phase walkthrough of the I-cells. In the second mechanism, the I-cells fail to synchronize, and their activity leads to complete suppression of the E-cells. Noisy spiking in the E-cells, generated by noisy external drive, adds excitatory drive to the I-cells and may lead to phase walkthrough. Noisy spiking in the I-cells adds inhibition to the E-cells and may lead to suppression of the E-cells. An analysis of the conditions under which noise leads to phase walkthrough of the I-cells or suppression of the E-cells shows that PING rhythms at frequencies far below the gamma range are robust to noise only if network parameter values are tuned very carefully. Together with an argument explaining why the PING mechanism does not work far above the gamma range in the presence of heterogeneity, this justifies the “G” in “PING.”
On Convergence Conditions of an Extended Projection Neural Network
Authors: Xia Youshen , Feng Gang
Published: February 2005

The output trajectory convergence of an extended projection neural network was developed under the positive definiteness condition of the Jacobian matrix of nonlinear mapping. This note offers several new convergence results. The state trajectory convergence and the output trajectory convergence of the extended projection neural network are obtained under the positive semidefiniteness condition of the Jacobian matrix. Comparison and illustrative examples demonstrate applied significance of these new results.
Estimating the Posterior Probabilities Using the K-Nearest Neighbor Rule
Authors: Atiya Amir F.
Published: February 2005

In many pattern classification problems, an estimate of the posterior probabilities (rather than only a classification) is required. This is usually the case when some confidence measure in the classification is needed. In this article, we propose a new posterior probability estimator. The proposed estimator considers the K-nearest neighbors. It attaches a weight to each neighbor that contributes in an additive fashion to the posterior probability estimate. The weights corresponding to the K-nearest-neighbors (which add to 1) are estimated from the data using a maximum likelihood approach. Simulation studies confirm the effectiveness of the proposed estimator.
Supervised Learning Through Neuronal Response Modulation
Authors: Swinehart Christian D. , Abbott L. F.
Published: February 2005

Neural networks that are trained to perform specific tasks must be developed through a supervised learning procedure. This normally takes the form of direct supervision of synaptic plasticity. We explore the idea that supervision takes place instead through the modulation of neuronal excitability. Such supervision can be done using conventional synaptic feedback pathways rather than requiring the hypothetical actions of unknown modulatory agents. During task learning, supervised response modulation guides Hebbian synaptic plasticity indirectly by establishing appropriate patterns of correlated network activity. This results in robust learning of function approximation tasks even when multiple output units representing different functions share large amounts of common input. Reward-based supervision is also studied, and a number of potential advantages of neuronal response modulation are identified.
Political Preferences and Attitudes Towards the Welfare State: Cross-National Comparison of Germany, Sweden, the U.S. and Japan
Authors: Kim Pil
Published: February 2005

This study attempts to build a causal model of attitudes towards the welfare state in Japan and to compare it to those of Germany, Sweden and the U.S., which represent conservative, socialist, and liberal welfare regime respectively. The effect of political preferences on attitudes towards the welfare state is the focus of the comparison. The basic premise of this comparison is that welfare attitudes vary across countries, bearing the characteristics of the given welfare regime that they belong to. Structural equation modeling and path analysis are conducted on a large-scale international survey dataset, ISSP 1996. Each country is first analyzed separately, and then all four countries are compared to each other. The single-country analysis reveals the cross-national diversity of welfare attitudes, while the effect of political preferences on the welfare attitudes exhibits a bifurcate pattern: in Sweden and the U.S. it is quite strong, relatively weak in Germany, and not even statistically significant in Japan. The comparative analysis further confirms this pattern. Therefore, I conclude that Japan is closest to the German conservative regime in terms of attitudes and political preferences, sharing welfare conservatism that credits the conservative party for building a welfare state.
The Cultural-Economic Syndrome: Impediments to Democracy in the Middle East
Authors: Weiffen Brigitte
Published: February 2005

Compared to other world regions, the Middle East is exceptional in its resistance to democratization. Whereas a cultural explanation for this democracy gap refers to historical legacies, especially to the dominant role of Islam, an economic explanation emphasizes oil wealth as the main barrier to democracy. According to various quantitative studies, both claims seem to be valid. Nevertheless, none of the explanations is uncontested, as there are always examples that demonstrate the opposite. This paper argues that it is exactly the combination of culture and economic structure that makes democracy in the Middle East unlikely. Both factors mutually reinforce each other on the macro, meso and micro level and thus constitute a cultural-economic syndrome with a strong negative impact on democratic performance. Regression analyses demonstrate the significance of this interaction effect: If the cultural-economic syndrome of Islam and oil wealth is present in a country, its negative impact on democratic performance becomes even stronger than the sum of the additive effects of Islam and oil wealth.
Citizenship, Social Structure and Culture: A Comparative Analysis
Authors:   Oommen
Published: February 2005

There are two competing orientations prevalent among social science disciplines. If one of these advocate universality, the other prefers indigeneity. But a careful analysis of even such concepts as citizenship widely believed to be of universal validity unfold, that (a) its substance varies across different polities; (b) this difference exists not only between the First, Second and Third Worlds but also among the polities within them. It has been demonstrated that the variations can be traced to the historical background, social structure and cultural patterns between polities. This has been attempted in this paper through a general comparative analysis of the three worlds and a systematic comparison of India, a multinational state and the West European countries, the cradle of nation-states. Through this comparative analysis some of the established notions in western political sociology have been interrogated.
Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination
Authors: Kim Jong R , Lim Hyung W , Kang Seung G , Hillsamer Peter , Kim Chang H
Published: February 2005

Background

The function of CD57+ CD4+ T cells, constituting a major subset of germinal center T (GC-Th) cells in human lymphoid tissues, has been unclear. There have been contradictory reports regarding the B cell helping function of CD57+ GC-Th cells in production of immunoglobulin (Ig). Furthermore, the cytokine and co-stimulation requirement for their helper activity remains largely unknown. To clarify and gain more insight into their function in helping B cells, we systematically investigated the capacity of human tonsil CD57+ GC-Th cells in inducing B cell Ig synthesis.

Results

We demonstrated that CD57+ GC-Th cells are highly efficient in helping B cell production of all four subsets of Ig (IgM, IgG, IgA and IgE) compared to other T-helper cells located in germinal centers or interfollicular areas. CD57+ GC-Th cells were particularly more efficient than other T cells in helping GC-B cells but not naïve B cells. CD57+ GC-Th cells induced the expression of activation-induced cytosine deaminase (AID) and class switch recombination in developing B cells. IgG1-3 and IgA1 were the major Ig isotypes induced by CD57+ GC-Th cells. CD40L, but not IL-4, IL-10 and IFN-γ, was critical in CD57+ GC-Th cell-driven B cell production of Ig. However, IL-10, when added exogenously, significantly enhanced the helper activity of CD57+ GC-Th cells, while TGF-β1 completely and IFN-γ partially suppressed the CD57+ GC-Th cell-driven Ig production.

Conclusions

CD57+CD4+ T cells in the germinal centers of human lymphoid tissues are the major T helper cell subset for GC-B cells in Ig synthesis. Their helper activity is consistent with their capacity to induce AID and class switch recombination, and can be regulated by CD40L, IL-4, IL-10 and TGF-β.
Cross-talk between phosphatidic acid and ceramide during ethanol-induced apoptosis in astrocytes
Authors: Schatter Beate , Jin Shenchu , Löffelholz Konrad , Klein Jochen
Published: February 2005

Background

Ethanol inhibits proliferation in astrocytes, an effect that was recently linked to the suppression of phosphatidic acid (PA) formation by phospholipase D (PLD). The present study investigates ethanol's effect on the induction of apoptosis in astrocytes and the formation of ceramide, an apoptotic signal. Evidence is presented that the formation of PA and ceramide may be reciprocally linked during ethanol exposure.

Results

In cultured rat cortical astrocytes, ethanol (0.3–1 %, v/v) induced nuclear fragmentation and DNA laddering indicative of apoptosis. Concomitantly, in cells prelabeled with [3H]-serine, ethanol caused a dose-dependent, biphasic increase of the [3H]-ceramide/ [3H]-sphingomyelin ratio after 1 and 18 hours of incubation. As primary alcohols such as ethanol and 1-butanol were shown to inhibit the phospholipase D (PLD)-mediated formation of PA, a mitogenic lipid messenger, we tested their effects on ceramide formation. In astrocytes prelabeled with [3H]-serine, ethanol and 1-butanol, in contrast to t-butanol, significantly increased the formation of [3H]-ceramide. Moreover, exogenous PA, added to transiently permeabilized astrocytes, suppressed ethanol-induced [3H]-ceramide formation. Vice versa, addition of C2-ceramide to astrocytes inhibited PLD activity induced by serum or phorbol ester.

Conclusion

We propose that the formation of ceramide in ethanol-exposed astrocytes is secondary to the disruption of phospholipase D signaling. Ethanol reduces the PA:ceramide ratio in fetal astrocytes, a mechanism which likely participates in ethanol-induced glial apoptosis during brain development.
Monsoon reconstruction from radiocarbon dated tropical Indian speleothems
Authors: Yadava M. G. , Ramesh R.
Published: February 2005

The potential of tropical speleothems as a climate proxy has been investigated. Amplitudes of 180 and 813C variations are found to be large and are likely to be primarily controlled by past rainfall. Contribution from past temperature variations seems to be relatively small. The amount effect in rainfall has been observed and quantified by analysing rainwater samples collected during a monsoon season. A tentative chronology to these speleothems is asssigned by the 14C radiometric dating method. Assuming that the variations in the 180 of cave carbonates are solely due to the past variations in rainfall, a history of the latter has been reconstructed. A high-resolution rainfall reconstruction up to the last ∼3400 years is now available from Gupteswar cave, Orissa, subject to validation of dates by the U-Th method. It is observed that in a tropical speleothem 513C is dominantly controlled by rainfall. The study has shown that tropical Indian speleothems faithfully record the annual (∼monsoon) rainfall in the cave site.
Surgical decompression versus local steroid injection in carpal tunnel syndrome: A one‐year, prospective, randomized, open, controlled clinical trial
Authors: Ly‐Pen Domingo , Andréu José‐Luis , de Blas Gema , Sánchez‐Olaso Alberto , Millán Isabel
Published: February 2005

Objective

Optimal treatment of carpal tunnel syndrome (CTS) has not been established. This study compared the effects of local steroid injection versus surgical decompression in new‐onset CTS of at least 3 months' duration.

Methods

In a 1‐year, prospective, randomized, open, controlled clinical trial, we studied the effects of surgical decompression versus local steroid injection in 163 wrists with a clinical and neurophysiologic diagnosis of CTS. Clinical assessments were done at baseline and at 3, 6, and 12 months after treatment. The primary end point was the percentage of wrists that reached a ≥20% improvement in the visual analog scale score for nocturnal paresthesias at 3 months of followup. Statistical analysis was done by Student's t‐test for continuous variables and by chi‐square test for categorical variables. Analyses were performed on an intent‐to‐treat basis. P values less than 0.05 were considered statistically significant.

Results

Both treatment groups had comparable severity of CTS at baseline. Eighty wrists were randomly assigned to the surgery group and 83 wrists to the local steroid injection group. In the intent‐to‐treat analysis, at 3 months of followup, 94.0% of the wrists in the steroid injection group versus 75.0% in the surgery group reached a 20% response for nocturnal paresthesias (P = 0.001). At 6 and 12 months, the percentages of responders were 85.5% versus 76.3% (P = 0.163) and 69.9% versus 75.0% (P = 0.488), for local steroid injection and surgical decompression, respectively.

Conclusion

Over the short term, local steroid injection is better than surgical decompression for the symptomatic relief of CTS. At 1 year, local steroid injection is as effective as surgical decompression for the symptomatic relief of CTS.
CXCL13 neutralization reduces the severity of collagen‐induced arthritis
Authors: Zheng Biao , Ozen Zeynep , Zhang Xuejun , De Silva Swanthri , Marinova Ekaterina , Guo Linjie , Wansley Daniel , Huston David P. , West Michael R. , Han Shuhua
Published: February 2005

Objective

To investigate the role of CXCL13 in the development and pathogenesis of collagen‐induced arthritis (CIA), and to determine the mechanisms involved in the modulation of arthritogenic response by CXCL13 neutralization.

Methods

Mice were immunized with type II collagen (CII) and treated with anti‐CXCL13 or control antibodies during boosting. Mice were monitored for the development and severity of arthritis. The effects of CXCL13 neutralization on immune response to CII were evaluated by cytokine production by CII‐specific T cells and CII‐specific antibody production. Follicular response in the spleen and in synovial tissue was determined by in situ immunohistology.

Results

Mice receiving neutralizing antibodies to CXCL13 developed significantly less severe arthritis compared with mice injected with phosphate buffered saline or control antibodies. Follicular response both in the spleen and in synovial tissue was inhibited by anti‐CXCL13 treatment. Injection with anti‐CXCL13 antibodies did not significantly affect antigen‐specific recall lymphocyte proliferation or type 1 cytokine production in vitro. Antibody response specific to CII was not inhibited by anti‐CXCL13 treatment. However, anti‐CXCL13 treatment induced significantly higher levels of interleukin‐10 production after in vitro CII stimulation.

Conclusion

Neutralization of CXCL13 inhibits the development of CIA and reduces follicular response in both lymphoid and nonlymphoid tissues. These findings may have important implications regarding the pathogenesis and treatment of autoimmune arthritis.
Identification of the epidermal growth factor–TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue
Authors: Kop Else N. , Kwakkenbos Mark J. , Teske Gwendoline J. D. , Kraan Maarten C. , Smeets Tom J. , Stacey Martin , Lin Hsi‐Hsien , Tak Paul P. , Hamann Jörg
Published: February 2005

Objective

EMR2 and CD97 are closely related members of the epidermal growth factor (EGF)–TM7 family of adhesion class 7‐span transmembrane (TM7) receptors. Chondroitin sulfates (CS) have recently been identified as ligands for EMR2 and CD97. CS have been implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine the expression of EMR2 and the distribution of EMR2 and CD97 ligands within RA synovial tissue (ST).

Methods

ST samples were obtained by arthroscopy from 19 patients with RA, 13 patients with inflammatory osteoarthritis (OA), and 13 patients with reactive arthritis (ReA). Immunohistochemistry was performed with a monoclonal antibody against EMR2, and stained STs were analyzed by digital image analysis. Coexpression of EMR2 with cell lineage– and activation‐specific markers was determined by double immunofluorescence microscopy. To evaluate the expression of EMR2 and CD97 ligands in RA synovium, binding assays were performed using EMR2‐ and CD97‐specific multivalent fluorescent probes.

Results

EMR2 expression in the synovial sublining was found to be significantly higher in RA patients compared with OA and ReA control patients. Most EMR2+ cells were macrophages and dendritic cells expressing costimulatory molecules and tumor necrosis factor α. Dermatan sulfate was shown to be the ligand of the largest isoforms of EMR2 and CD97 in rheumatoid synovium. In addition, the smaller isoforms of CD97, but not those of EMR2, bound CD55 on fibroblast‐like synoviocytes.

Conclusion

The EGF‐TM7 receptors EMR2 and CD97 are abundantly expressed on myeloid cells in ST of RA patients where their cognate ligands dermatan sulfate and CD55 are detected. These results suggest that these interactions may facilitate the retention of activated macrophages in the synovium.
Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus‐prone NZB × NZW mice
Authors: Dong Li , Ito Shuichi , Ishii Ken J. , Klinman Dennis M.
Published: February 2005

Objective

Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ‐specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic autoimmunity, by evaluating their effect on the progression of lupus‐like disease in NZB × NZW (NZB/NZW) mice.

Methods

We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease.

Results

Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti–double‐stranded DNA autoantibody production and by significantly reduced secretion of interferon‐γ and interleukin‐12 in vivo.

Conclusion

Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.
Efficacy and safety of infliximab in patients with ankylosing spondylitis: Results of a randomized, placebo‐controlled trial (ASSERT)
Authors: van der Heijde Désirée , Dijkmans Ben , Geusens Piet , Sieper Joachim , DeWoody Kimberly , Williamson Paul , Braun Jürgen
Published: February 2005

Objective

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease‐modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials. The objective of this multicenter, randomized, placebo‐controlled study was to evaluate the efficacy and safety of infliximab in patients with AS.

Methods

Patients were randomly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12, and 18. Efficacy was assessed using the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), night pain, patient's global assessment, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, the Mander enthesis index, the total swollen joint index, the C‐reactive protein level, and the Short Form 36 (SF‐36) health survey questionnaire. The primary end point in this study was the proportion of patients with a 20% improvement response according to the ASAS International Working Group criteria (ASAS20 responders) at week 24.

Results

Of the 357 patients screened, 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo. After 24 weeks, 61.2% of patients in the infliximab group were ASAS20 responders compared with 19.2% of patients in the placebo group (P < 0.001). Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24‐week study period. Patients receiving infliximab also showed significant improvements in the BASDAI, BASFI, BASMI, chest expansion, and physical component summary score of the SF‐36. Adverse events were reported by 82.2% of patients receiving infliximab and by 72.0% of patients receiving placebo; however, most adverse events in both treatment groups were mild or moderate in severity.

Conclusion

Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24‐week study period.
Long‐term open‐label preliminary study of the safety and efficacy of leflunomide in patients with polyarticular‐course juvenile rheumatoid arthritis
Authors: Silverman Earl , Spiegel Lynn , Hawkins David , Petty Ross , Goldsmith Donald , Schanberg Laura , Duffy Ciaran , Howard Paul , Strand Vibeke
Published: February 2005

Objective

To obtain preliminary data regarding the efficacy and long‐term safety of leflunomide in patients with refractory polyarticular‐course juvenile rheumatoid arthritis (JRA).

Methods

Twenty‐seven patients were entered into the initial 26‐week open‐label study of leflunomide therapy; 17 entered the extension phase (maximum 107 weeks). Mean disease duration at study entry was 7.0 years. All patients had ≥5 joints with active arthritis and had received methotrexate for a mean of 36.0 months. Following a loading dose, patients initially received leflunomide at a dosage of 10 mg/1.73 m2/day, which could be increased to 20 mg/1.73 m2/day (maximum 20 mg/day) beginning at week 8. The primary efficacy outcome was the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement. Last observation carried forward (LOCF) analysis was used, and all patients were entered into an intent‐to‐treat analysis. Intraarticular corticosteroids (maximum of 2 in the initial 26 weeks) were allowed, but no new disease‐modifying antirheumatic drug or change in nonsteroidal antiinflammatory drug was allowed throughout the study.

Results

Seventeen of the 27 patients (63%) completed the initial 26‐week study. Fourteen patients (52%) met the ACR Pedi 30 response criteria at week 26. Seventeen patients entered into the extension phase (13 who met response criteria and 4 who failed to meet response criteria but decided to continue). Nine of the 17 patients (53%) who entered the extension phase either completed all 30 months of study or the study ended prior to the month 30 visit. Five patients withdrew because of failure to maintain efficacy, 2 withdrew their consent, and 1 withdrew because of an adverse event. Using LOCF analysis, 65% of patients met ACR Pedi 30 response criteria at 1 year and 2 years (weeks 50 and 106, respectively) and 53% at the end of the study. Good response rates were also seen using ACR Pedi 50 and ACR Pedi 70 criteria (47% and 24% at week 106, respectively).

Conclusion

In this open‐label study of JRA patients who either failed to respond to, or were intolerant of, methotrexate, the majority met the ACR Pedi 30 response criteria at week 26. The response was durable, since 53% of patients who entered into the extension phase (maximum 30 months) responded at the end of this phase. Our findings support the further study of the role of leflunomide in the treatment of polyarticular‐course JRA.
The impact of increased lupus activity on obstetric outcomes
Authors: Clowse Megan E. B. , Magder Laurence S. , Witter Frank , Petri Michelle
Published: February 2005

Objective

Systemic lupus erythematosus is associated with multiple adverse pregnancy outcomes. We examined the impact of disease activity on spontaneous abortions, perinatal mortality, preterm delivery, and birth weight.

Methods

The study was designed to assess all pregnancies in a cohort of lupus patients who were observed prospectively from 1987 to 2002. At each visit, the physician's estimate of lupus activity was determined on a visual analog scale (high‐activity lupus defined as a score of ≥2). Disease activity in each trimester was compared. We assessed the impact of high‐activity lupus during pregnancy on gestational age, live birth rate, and small for gestational age babies. Potential confounders, including demographics of the women as well as maternal history of lupus, renal lupus, and antiphosphoplipid antibody syndrome, were analyzed through multivariate analysis.

Results

Two hundred sixty‐seven pregnancies were observed. Of these, 229 (85.8%) resulted in a live birth. High‐activity lupus occurred in 57 pregnancies (21%). Fewer pregnancies among women with high‐activity lupus ended with live births (77% versus 88% of those with low‐activity lupus; P = 0.063). Full‐term delivery was achieved in 15 pregnancies (26%) among women with high‐activity lupus, compared with 127 pregnancies (61%) achieving full‐term in those with no or mild lupus activity (P < 0.001). High‐activity lupus in the first and second trimesters led to a 3‐fold increase in pregnancy loss (miscarriages and perinatal mortality).

Conclusion

High‐activity lupus during pregnancy leads to increased premature birth and a decrease in live births, with almost one‐quarter of these pregnancies resulting in fetal loss. Pregnancies in lupus patients must be closely watched and treated during all trimesters to improve pregnancy outcomes.
Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet's disease
Authors: Amoura Zahir , Dodé Catherine , Hue Sophie , Caillat‐Zucman Sophie , Bahram Seiamak , Delpech Marc , Grateau Gilles , Wechsler Bertrand , Piette Jean‐Charles
Published: February 2005

Objective

Behçet's disease is a chronic, relapsing, multisystemic inflammatory disorder characterized by recurrent oral and genital ulcers and by ocular, articular, vascular, and central nervous system involvement. The tumor necrosis factor α (TNFα) pathway is likely involved in the pathophysiology of Behçet's disease. One of the 2 TNFα receptors is TNF receptor superfamily 1A (TNFRSF1A). We searched for R92Q TNFRSF1A mutations in patients with Behçet's disease.

Methods

A search for TNFRSF1A mutations was performed by polymerase chain reaction amplification of the TNFRSF1A gene, followed by denaturing high‐performance liquid chromatography scanning.

Results

Among the 74 unrelated European patients with Behçet's disease, 5 (6.8%) carried the R92Q TNFRSF1A mutation. The frequency of the R92Q mutation in patients with Behçet's disease was significantly higher than that in controls (P = 0.006 by Fisher's exact test). Deep vein thrombosis was significantly associated with the R92Q mutation (P = 0.001 [with Bonferroni adjustment for multiple comparisons]). Among the 30 patients with thrombosis, 10 had cerebral thrombophlebitis. None of these patients had the R92Q mutation. Among the 20 patients with Behçet's disease who had extracranial deep vein thrombosis, 6 had the R92Q mutation, whereas 14 did not (P < 0.0001)

Conclusion

The R92Q mutation in patients with Behçet's disease is associated with an increased risk of extracranial venous thrombosis. This new finding may help in understanding the complex prothrombotic state in patients with Behçet's disease.
Chaos in a quasar model with a disk and a massive nucleus
Authors: Papadopoulos N. J. , Caranicolas N. D.
Published: February 2005

We present a quasar model with a rotating disk and a massive nucleus. We use this model in order to characterize the motion in the model (regular or chaotic) and to connect the extent of the chaotic regions to the physical parameters of the model. Numerical experiments suggest that, there are connections between the extent of the chaotic areas and the parameters of the system. Furthermore, it is shown that the form of numerically found relationships can be expressed analytically. Comparison to previous work is also made. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A new algorithm for differential photometry: computing anoptimum artificial comparison star
Authors: Broeg Ch. , Fernández M. , Neuhäuser R.
Published: February 2005

Our new algorithm for differential photometry solves the problem of identifying proper comparison stars without a prior detailed study of the field of view. The comparison stars' variability is determined in a self‐consistent way, and their weighted average is used as a reference level. The maximum error in differential photometry using objects and reference stars of different spectral types is estimated. The results from these calculations show that the photometric band chosen greatly determines the level of accuracy achieved. Finally, an important application of high‐precision differential photometry are planetary transits. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Weighing the cusp at the Galactic Centre
Authors: Mouawad N. , Eckart A. , Pfalzner S. , Schödel R. , Moultaka J. , Spurzem R.
Published: February 2005

As stars close to the galactic centre have short orbital periods it has been possible to trace large fractions of their orbits in the recent years. Previously the data of the orbit of the star S2 have been fitted with Keplerian orbits corresponding to a massive black hole (MBH) with a mass of MBH = 3–4 × 106M⊙ implying an insignificant cusp mass. However, it has also been shown that the central black hole resides in a ∼1″ diameter stellar cluster of a priori unknown mass. In a spherical potential which is neither Keplerian nor harmonic, orbits will precess resulting in inclined rosetta shaped trajectories on the sky. In this case, the assumption of non‐Keplerian orbits is a more physical approach. It is also the only approach through which cusp mass information can be obtained via stellar dynamics of the cusp members. This paper presents the first exemplary modelling efforts in this direction. Using positional and radial data of star S2, we find that there could exist an unobserved extended mass component of several 105M⊙ forming a so‐called ‘cusp’ centered on the black hole position. Considering only the fraction of the cusp mass M within the apo‐center of the S2 orbit we find as an upper limit that M/(MBH + M) ≤ 0.05. A large extended cusp mass, if present, is unlikely to be composed of sub‐solar mass constituents, but could be explained rather well by a cluster of high M/L stellar remnants, which we find to form a stable configuration. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Investigations of Stephenson's Hα stars
Authors: Emprechtinger M. , Kimeswenger S. , Kronberger T. , Mair M. , Weratschnig J.
Published: February 2005

Hitherto unstudied objects from Stephenson's list of Hα emission line objects at high galactic latitude were observed spectroscopically to prove their nature. 9 out of 11 objects show Hα in emission. Spectroscopy combined with photometric information indicates most of them being classical Be stars, while one object is a Post‐AGB star and one a T‐Tauri star. The classification of two objects, which are showing Hα in emission, is unclear. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modellierung und Simulation von Chemiereaktoren – Aspekte einer zeitgemäßen Ingenieurausbildung
Authors: Hagen J.
Published: February 2005

Die Durchführung chemischer Prozesse in der Technik unter möglichst optimalen Bedingungen setzt ein Grundverständnis für die Arbeitsweise von Chemiereaktoren voraus. Grundlage der Modellierung von Chemiereaktoren sind die Stoff‐ und Wärmebilanz und die Kinetik der Reaktion. Nur in einfachen Fällen lassen sich analytische Lösungen für Problemstellungen aus der Praxis durch Integration der Differentialgleichungen finden. Das in der Chemieingenieurausbildung eingesetzte Softwarepaket POLYMATH ist sehr anwenderfreundlich und einfach zu erlernen. Es wird u. a. eingesetzt, um gekoppelte Differentialgleichungen simultan zu lösen und Datenanalyse durch Regression durchzuführen. Mit einem einmal aufgestellten Modell lässt sich der Einfluss verschiedener Reaktionsparameter auf den Gesamtprozess leicht nachvollziehbar simulieren.
Selbstorganisation von Tensiden: Biomimetische Synthesen von Nanomaterialien
Authors: Rehage Heinz
Published: February 2005

Tenside sind amphiphile Moleküle, die sich an Grenzflächen anreichern und im Inneren von Lösungen definierte Aggregate (Mizellen) bilden. Im Bereich höherer Konzentrationen dienen die Mizellen wiederum als Bausteine für komplexe, dreidimensionale Strukturen, die isotrope oder anisotrope Eigenschaften besitzen. All diese verschiedenen Phasen bilden sich durch Prozesse der Selbstorganisation; eine fundamentale Eigenschaft, die auch lebende Systeme kennzeichnet. Aufgrund ihrer geringen Größe, der leichten Herstellung und der verschiedenen Gestalt besitzen Tensidfilme und Tensidaggregate interessante Eigenschaften, die zur Herstellung verschiedener Arten von Kristallen und Nanomaterialien gezielt genutzt werden können.
Funktionalisierte Kohlenstoff‐Nanoröhren: Nanozylinder mit hohem Anwendungspotential
Authors: Balasubramanian Kannan , Burghard Marko
Published: February 2005

Laborübliche Mengen an Kohlenstoff‐Nanoröhren sind mittlerweile erschwinglich und es stehen effektive Verfahren zu ihrer Reinigung zur Verfügung. Ihr Anwendungsspektrum erfährt durch die zur Verfügung stehenden Methoden zur chemischen Funktionalisierung eine erhebliche Bereicherung. Obwohl sich bereits mehrere Reaktionstypen für den Einsatz in der Nanoröhren‐Forschung etabliert haben, besteht noch erheblicher Klärungsbedarf hinsichtlich des Reaktionsmechanismus und der Struktur der modifizierten Röhren. Von Interesse ist ferner die Frage, inwieweit die chemische Reaktivität von der detaillierten Struktur der Röhren abhängt. Die weitere Entwicklung dieses faszinierenden Gebiets wird u.a. davon abhängen, ob spezifische Synthesemethoden für Nanoröhren mit gewünschter Struktur gefunden werden können.
Nanokomposite: anorganisch + organisch: Homogen und doch so heterogen
Authors: Kickelbick Guido
Published: February 2005

Durch die Kombination von anorganischen und organischen Komponenten, wobei mindestens eine der Komponenten Dimensionen in der Nanometer‐Längenskala besitzt, werden anorganisch‐organische Nanokomposite erhalten. In diesem Beitrag werden insbesondere Prinzipien für die Herstellung stabiler und homogener Materialien erläutert. Anhand verschiedener Beispiele, von molekularen Bausteinen über Nanopartikeln bis hin zu schichtartig aufgebauten Mineralien und porösen Strukturen, wird auf die Verbindung der anorganischen Nanobausteine mit organischen Einheiten eingegangen. Die Eigenschaften der entstehenden Materialien sind durch die Kombination verschiedener Bausteine auf der Nanometerskala in einem Material vielfältig einstellbar.
Nanostrukturwissenschaften Uni Kassel
Authors: Faust Rüdiger
Published: February 2005

Wie optimiert man die Oberfläche von Keramikkacheln, damit Raumfahrzeuge beim Eintauchen in die Erdatmosphäre effektiv vor Hitze geschützt werden? Welchen Einfluss hat die Teilchengröße der Zusätze einer Gummimischung auf den Grip eines Autoreifens? Wie formt man Farbpigmente, damit ein schimmernder Perglanzeffekt entsteht? Wie bringt man einen pharmazeutischen Wirkstoff unverändert und funktionsbereit an seinen zellulären Wirkort? Welche Komponenten benötigt ein optischer Computer?
Neue wässrige Beschichtungssysteme
Authors: Wiese Harm , Xue Zhijian , Leuninger Joerg
Published: February 2005

Polymerdispersionen sind wässrige Dispersionen feinster Polymerteilchen. Die Teilchendurchmesser liegen typischerweise zwischen 100 und 300 nm, ein Bereich, den man heute als Nanotechnologie bezeichnet, der jedoch klassisch der Kolloidik zuzurechnen ist.
Die Chemie eines kleinen Spinners
Authors: Roth Klaus
Published: February 2005

Schmetterlinge haben aus gutem Grund Angst vor Spinnen, schließlich sind sie deren Lieblingsspeise. Einmal im Spinnennetz gefangen, versuchen sie, durch hektisches Flügelschlagen zu entfliehen. Der kleine Bärenspinner Utetheisa ornatrix bleibt in dieser Situation völlig cool. Die Spinne stürzt herbei, betastet kurz die Beute und schneidet sofort um den Bärenspinner ein Loch ins Netz. Der Schmetterling fällt herunter und bevor er den Boden erreicht, spannt er die Flügel auf und flattert von dannen. Er war sich seiner Sache von Anfang an sicher, sein Geheimnis: von klein auf die richtige Ernährung, ordentlicher Sex und eine gute Portion Chemie.