bluuebunny/crossref_metadata_2025_split huggingface dataset:
INGROWTH OF NEURAL ELEMENTS INTO THE ANNULUS FIBROSUS OF OVINE INTERVERTEBRAL DISC IN AN ACUTE AND SUBACUTE EXPERIMENTAL DISC INJURY
Authors: Lappalainen A. K. , Kääpä E. , Grönblad M. 
Published: May 2003

Ingrowth of nerves and blood vessels is regarded as a part of disc degeneration. Schwann cells, which guide the development and regeneration of nerves both in the central and peripheral nervous system, have recently been located in degenerated human discs. The purpose of this study was to investigate by immunohistochemical methods, whether or not there was nerve, Schwann cell and blood vessel ingrowth in experimentally induced acute (3 weeks) and subacute (3 months) annular tears; and to study the detailed topography of such nerve ingrowth when present. Ingrowth of nerves and Schwann cells has so far not been studied in experimentally induced acute annular tears. A stab incision with a scalpel blade was made in two adjacent lumbar discs in adult sheep (n = 9). The L2–L3 discs were injured superficially, whereas in L3–L4 discs the incision reached the nucleus pulposus (full-thickness injury). The animals were sacrificed three weeks (acute injury, n = 3) or three months (subacute injury, n = 6) post-operatively. Discs were immunoassayed for general neuronal markers (protein gene product 9.5, PGP 9.5 and synaptophysin, SYN), Schwann cell marker (glial fibrillary acidic protein, GFAP) and endothelial marker (CD 31). Nerves visualized with all antibodies employed were situated inside the injured area and mainly near amd around blood vessels although free nerve endings could be seen also. PGP 9.5-immunopositive nerves were evident in every sample. Immunoreactivity to SYN and GFAP was not observed in control discs. Such immunoreactivity appeared already at 3 weeks (acute injury) in a few samples, and was present in all samples at 3 months (subacute injury). For the superficial injury, nerves did not penetrate deeper than in control discs until at 3 months. With more extensive annular injury, mean values for both nerve and Schwann cell penetration were higher. Blood capillaries were visible deeper in the inner annulus than neural tissues immunopositive to PGP 9.5, GFAP or SYN. The results suggest an ingrowth of nerves and Schwann cells with time, following an injury of the annulus fibrosus. A trend for deeper penetration already in the acute stage, but only for deep lesions reaching all the way to the nucleus pulposus, may be suggested. Such ingrowth, also previously reported in degenerated human discs, may relate to mechanisms of low back pain, originating in the intervertebral disc.
TRIPWIRE: A SYNCHRONISATION PRIMITIVE FOR VIRTUAL MEMORY MAPPED COMMUNICATION
Authors: RIDDOCH DAVID , POPE STEVE , ROBERTS DEREK , MAPP GLENFORD , CLARKE DAVID , INGRAM DAVID , MANSLEY KIERAN , HOPPER ANDY 
Published: May 2003

Existing user-level network interfaces deliver high bandwidth, low latency performance to applications, but are typically unable to support diverse styles of communication and are unsuitable for use in multiprogrammed environments. Often this is because the network abstraction is presented at too high a level, and support for synchronisation is inflexible. In this paper we present a new primitive for in-band synchronisation: the Tripwire. Tripwires provide a flexible, efficient and scalable means for synchronisation that is orthogonal to data transfer. We describe the implementation of a non-coherent distributed shared memory network interface, with Tripwires for synchronisation. This interface provides a low-level communications model with gigabit class bandwidth and very low overhead and latency. We show how it supports a variety of communication styles, including remote procedure call, message passing and streaming.
Comparative Effects of Desloratadine versus Montelukast on Asthma Symptoms and Use of β<sub>2</sub>-Agonists in Patients with Seasonal Allergic Rhinitis and Asthma
Authors: Baena-Cagnani Carlos E. , Berger William E. , DuBuske Lawrence M. , Gurné Sandra E. , Stryszak Paul , Lorber Richard , Danzig Melvyn 
Published: May 2003

<i>Background:</i> Asthma and seasonal allergic rhinitis (SAR) are recognized as manifestations of a single airway disease. Desloratadine has demonstrated efficacy in treating SAR symptoms, including nasal obstruction. <i>Methods:</i> Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind, placebo-controlled trial of patients with SAR and symptoms of asthma, who were assigned randomly to once-daily treatment with desloratadine 5 mg, montelukast 10 mg, or placebo for 4 weeks. Change from baseline of AM/PM reflective total asthma symptom severity scores (TASS), FEV<sub>1</sub>, individual asthma symptom scores, and β<sub>2</sub>-agonist usage were assessed. <i>Results:</i> Desloratadine and montelukast each were associated with statistically significant reductions from baseline in the mean TASS averaged over the 4-week period (p ≤0.022 vs. placebo). Individual asthma symptom scores also improved significantly for both therapies (p ≤ 0.05). Patients treated with desloratadine or montelukast demonstrated improvement from baseline in FEV<sub>1</sub> versus placebo; significant improvement was seen in a subset of patients with baseline FEV<sub>1</sub> <80% of predicted normal (both p < 0.05). Both active therapies significantly reduced β<sub>2</sub>-agonist use (both p < 0.01). Improvements for both therapies were comparable for all efficacy parameters; they were tolerated well with adverse event profiles similar to placebo. <i>Conclusions:</i> Asthma symptoms and β<sub>2</sub>-agonist were improved significantly in patients with concomitant SAR and asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily. Both therapies significantly improved FEV<sub>1</sub> in a subset of patients with FEV<sub>1</sub> <80% of predicted normal at entry. Improvements in asthma symptoms were comparable for both active treatment groups.
Protective Influence of Experimentally Formed Salivary Pellicle on Enamel Erosion
Authors: Nekrashevych Yuriy , Stösser Lutz 
Published: May 2003

The purpose of this study was to evaluate dental erosion in 0.1 and 1.0% citric acid in vitro by several different methods and to assess the protective potential of experimentally formed salivary pellicle (24 h in vitro). Bovine enamel slabs were embedded in epoxy resin and polished. Erosion was performed in citric acid for 1, 5 or 10 min and recorded as microhardness loss, as changes of surface roughness (R<sub>a</sub>, R<sub>t</sub> and R<sub>zDIN</sub>) and as calcium release. Additionally, erosive alterations were observed with scanning electron microscopy. Significant microhardness loss on non-pellicle-covered specimens was measured after 1-min exposure to 0.1% citric acid. Microhardness loss was time- and concentration-dependent. Salivary pellicle significantly inhibited both microhardness loss, except after 10-min immersion in 1.0% citric acid, and significantly reduced the increase of surface roughness. There were, however, no significant differences in calcium release between pellicle-covered and non-covered enamel. The results support the general conclusion that salivary pellicle effectively protects enamel surface against short-term erosion in organic acids.
Effects of Cyclooxygenases Inhibitors on Vasoactive Prostanoids and Thrombin Generation at the Site of Microvascular Injury in Healthy Men
Authors: Tuleja Ewa , Mejza Filip , Cmiel Adam , Szczeklik Andrzej 
Published: May 2003

Objective—Balance between vasoactive prostanoids that contribute to homeostasis of the circulatory system can be affected by cyclooxygenases inhibitors. Results of a recent large clinical trial show that myocardial infarction was more frequent among patients with rheumatoid arthritis treated with the selective cyclooxygenase-2 inhibitor rofecoxib compared with those treated with naproxen. Whether this difference was attributable to deleterious cardiovascular effects of rofecoxib or cardioprotective effects of naproxen has not been determined. We tested the hypothesis that naproxen, contrary to rofecoxib, exerts antithrombotic effects.Methods and Results—Forty-five healthy men were randomized to receive a 7-day treatment with rofecoxib (50 mg/d), naproxen (1000 mg/d), aspirin (75 mg/d), or diclofenac (150 mg/d). Formation of thromboxane, prostacyclin, and thrombin in the bleeding-time blood at the site of standardized microvascular injury was assessed before and after treatment. Naproxen, like aspirin, caused significant reduction of both thromboxane and prostacyclin, whereas diclofenac depressed prostacyclin synthesis but had no effect on tromboxane formation. Naproxen and aspirin significantly suppressed thrombin generation. Diclofenac showed a similar tendency, which did not reach statistical significance. Rofecoxib had no effect on any variables measured.Conclusions—In healthy men, naproxen exerts an antithrombotic effect at least as potent as aspirin, whereas rofecoxib does not affect hemostatic balance.
Precision of Exocentric Distance Judgments in Desktop and Cube Presentation
Authors: Wartenberg Constanze , Wiborg Per 
Published: May 2003

Accuracy of space perception and distance estimation in virtual environments is an important precondition for the reliable use of virtual techniques in the design of products, workplaces, architecture, and production systems. The present study compares the accuracy of exocentric 1 distance estimations that a static perceiver achieves with two virtual presentation techniques: a desktop and an immersive cube presentation. Estimation accuracy in a physical mock-up is used as a point of reference. Subjects estimated exocentric distances in detailed models of a workplace previously unknown to them. All distances to be judged were located in the subjects' personal space (less than 1.5 m from the subject). Major differences between the two virtual presentation modes are that stereo information is available in the cube but not in desktop environment, and that, in the cube, changes in perspective are achieved by actually moving inside the cube instead of using a mouse. Furthermore, the cube provides a wider absolute field of view than the desktop environment. The experiment showed advantages of the cube over desktop presentation when estimating exocentric distances in “personal space” from a static position. The magnitude of distance estimation errors was significantly higher in the desktop than in the cube environment. However, estimation errors tended to be overestimations in the cube presentation, whereas over- and underestimation occurred with equal frequency in the desktop environment. In the discussion it is argued that the higher estimation accuracy in the cube environment may mainly be due to the availability of stereoscopic depth cues. According to Cutting (1997), these cues are especially relevant for spatial perception in “personal space.” 1 The term exocentric distance is used for distances between two points external to the perceiver indicating (for example) interobject distances or distances colinear with the side length of an object. These distances are to be distinguished from egocentric distances, those distances between the perceiver and one point in the environment (Waller, 1999).
CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras andjunD
Authors: Nicolaou Fotini , Teodoridis Jens M. , Park Heiyoung , Georgakis Alexander , Farokhzad Omid C. , Böttinger Erwin P. , Da Silva Nicolas , Rousselot Philippe , Chomienne Christine , Ferenczi Katalin , Arnaout M. Amin , Shelley C. Simon 
Published: May 2003

AbstractHairy cell leukemia (HCL) is a chronic lymphoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the β2 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL theCD11c gene promoter was characterized. Transfection of theCD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy cells reducedCD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal–regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11c promoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11cpromoter to levels equivalent to those in hairy cells. Together, these data indicate that the abnormal expression of the CD11cgene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD.
Src and phosphatidylinositol 3–kinase mediate soluble E-selectin–induced angiogenesis
Authors: Kumar Pawan , Amin Mohammad A. , Harlow Lisa A. , Polverini Peter J. , Koch Alisa E. 
Published: May 2003

AbstractAngiogenesis plays an important role in a variety of pathophysiologic processes, including tumor growth and rheumatoid arthritis. We have previously shown that soluble E-selectin (sE-selectin) is an important angiogenic mediator. However, the mechanism by which sE-selectin mediates angiogenesis is still unknown. In this study, we show that sE-selectin is a potent mediator of human dermal microvascular endothelial cell (HMVEC) chemotaxis, which is predominantly mediated through the Src and the phosphatidylinositiol 3–kinase (PI3K) pathways. Further, sE-selectin induced a 2.2-fold increase in HMVEC tube formation in the Matrigel in vitro assay. HMVECs pretreated with the Src inhibitor (PP2) and the PI3K inhibitor (LY294002) or transfected with Src antisense oligonucleotides or Akt dominant-negative mutants significantly inhibited sE-selectin–mediated HMVEC tube formation. In contrast, HMVECs transfected with an extracellular signal-related kinase 1/2 (ERK1/2) mutant or pretreated with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 failed to show sE-selectin–mediated HMVEC tube formation. Similarly, in the Matrigel-plug in vivo assay, sE-selectin induced a 2.2-fold increase in blood vessel formation, which was significantly inhibited by PP2 and LY294002 but not by PD98059. sE-selectin induced a marked increase in Src, ERK1/2, and PI3K phosphorylation. PI3K and ERK1/2 phosphorylation was significantly inhibited by PP2, thereby suggesting that both of these pathways may be activated via Src kinase. Even though the ERK1/2 pathway was activated by sE-selectin in HMVECs, it seems not to be essential for sE-selectin–mediated angiogenesis. Taken together, our data clearly show that sE-selectin–induced angiogenesis is predominantly mediated through the Src-PI3K pathway.
Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells
Authors: Wang Xiuli , Ge Shundi , McNamara George , Hao Qian-Lin , Crooks Gay M. , Nolta Jan A. 
Published: May 2003

AbstractRodent bone marrow cells can contribute to liver. If these findings are applicable to humans, marrow stem cells could theoretically be harvested from a patient and used to repair his/her damaged liver. To explore this potential, CD34+ or highly purified CD34+CD38−CD7− human hematopoietic stem cells from umbilical cord blood and bone marrow were transplanted into immunodeficient mice. One month after transplantation, carbon tetrachloride (CCl4) was administered into the mice to induce liver damage and hepatocyte proliferation. Mice were analyzed in comparison with CCl4-injured mice that did not receive transplants and noninjured controls that received transplants with the same stem cell populations, one month after liver damage. Human-specific albumin mRNA and protein were expressed in the mouse liver and human albumin was detected in the serum of mice that had received CCl4 injury. Human alpha-fetoprotein was never expressed, but in some mice, human cytokeratin 19 was expressed, which may indicate bile duct development in addition to the albumin-secreting hepatocyte-like cells. Human albumin was not expressed in the starting stem cell populations in injured mice that did not receive transplants nor in noninjured mice that had received transplants of human stem cells. Human albumin expression was detected only in CCl4-treated mice that received transplants of human stem cells, and recovery was increased by administration of human hepatocyte growth factor 48 hours after the CCl4-mediated liver injury. Our studies provide evidence that human “hematopoietic” stem/progenitor cell populations have the capacity to respond to the injured liver microenvironment by inducing albumin expression.
Nodular sclerosing Hodgkin disease: new grading predicts prognosis in intermediate and advanced stages
Authors: von Wasielewski Sabine , Franklin Jeremy , Fischer Robert , Hübner Klaus , Hansmann Martin L. , Diehl Volker , Georgii Axel , von Wasielewski Reinhard 
Published: May 2003

AbstractThe prognostic value of histologic classification and single histomorphologic parameters in Hodgkin disease has been widely debated in the literature. Whereas several former studies identified single parameters to be of clinical relevance, some recent reports have doubted the prognostic value of histology using modern treatment. Grading of the largest histologic category of Hodgkin disease, nodular sclerosis (NS), has been controversially discussed concerning clinical relevance. In this study, 965 cases of NS were reviewed to assess 9 histomorphologic parameters. The histologic results were correlated with laboratory and clinical findings and with overall survival and disease-free survival. Based on these results, a new grading of the NS category was established. The new grading, based on the 3 criteria eosinophilia, lymphocyte depletion, and atypia of the Hodgkin/Reed-Sternberg cells, was a significant indicator of prognosis in intermediate and advanced stages. Patients investigated in this study represent an outstanding collection because all of them were enrolled in the prospective multicenter clinical trial of the German Hodgkin Lymphoma Study Group. All of them had been staged uniformly according to the Ann Arbor system and had received stage-adapted modern treatment according to multimodality protocols. A subtle analysis of histology could represent a possible way to identify patients with a significantly better or worse prognosis. This new grading should help to avoid overtreatment to reduce severe therapy-related side effects such as acute toxicity and chronic sequelae such as cardiopulmonary complications and secondary neoplasias.
Alternative 5′ exons and differential splicing regulate expression of protein 4.1R isoforms with distinct N-termini
Authors: Parra Marilyn K. , Gee Sherry L. , Koury Mark J. , Mohandas Narla , Conboy John G. 
Published: May 2003

AbstractAmong the alternative pre-mRNA splicing events that characterize protein 4.1R gene expression, one involving exon 2′ plays a critical role in regulating translation initiation and N-terminal protein structure. Exon 2′ encompasses translation initiation site AUG1 and is located between alternative splice acceptor sites at the 5′ end of exon 2; its inclusion or exclusion from mature 4.1R mRNA regulates expression of longer or shorter isoforms of 4.1R protein, respectively. The current study reports unexpected complexity in the 5′ region of the 4.1R gene that directly affects alternative splicing of exon 2′. Identified far upstream of exon 2 in both mouse and human genomes were 3 mutually exclusive alternative 5′ exons, designated 1A, 1B, and 1C; all 3 are associated with strong transcriptional promoters in the flanking genomic sequence. Importantly, exons 1A and 1B splice differentially with respect to exon 2′, generating transcripts with different 5′ ends and distinct N-terminal protein coding capacity. Exon 1A-type transcripts splice so as to exclude exon 2′ and therefore utilize the downstream AUG2 for translation of 80-kDa 4.1R protein, whereas exon 1B transcripts include exon 2′ and initiate at AUG1 to synthesize 135-kDa isoforms. RNA blot analyses revealed that 1A transcripts increase in abundance in late erythroblasts, consistent with the previously demonstrated up-regulation of 80-kDa 4.1R during terminal erythroid differentiation. Together, these results suggest that synthesis of structurally distinct 4.1R protein isoforms in various cell types is regulated by a novel mechanism requiring coordination between upstream transcription initiation events and downstream alternative splicing events.
Peptide decoys selected by phage display block in vitro and in vivo activity of a human anti-FVIII inhibitor
Authors: Villard Sylvie , Lacroix-Desmazes Sébastien , Kieber-Emmons Thomas , Piquer Dominique , Grailly Sabrina , Benhida Abdellah , Kaveri Srini V. , Saint-Remy Jean-Marie , Granier Claude 
Published: May 2003

Abstract
Hemophilia A is a life-threatening, hemorrhagic, X-linked recessive disorder resulting in deficient factor VIII (FVIII) activity. After the infusion of therapeutic FVIII, 25% of patients develop anti-FVIII antibodies that inhibit FVIII procoagulant activity, thus precluding further administration of FVIII. Here we report a novel approach aimed at neutralizing the activity of FVIII inhibitors by peptide epitope surrogates. To illustrate our concept, we chose the human anti-FVIII monoclonal antibody, Bo2C11, as a representative of anti-FVIII antibodies and a phage-displayed peptide library approach to obtain surrogate peptides. We selected a series of constrained dodecapeptides with the core sequence W-NR, which specifically interacts with the combining site of Bo2C11. The peptides mimic the epitope recognized by Bo2C11 and are able to inhibit specifically and in a dose-dependent manner the binding of Bo2C11 to FVIII. Peptide 107, in particular, neutralized the activity of Bo2C11 in vitro and restored normal hemostasis in hemophilic mice. Thus, the use of peptide decoys may be a promising new approach for the neutralization of pathologic antibodies.
The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome
Authors: Aird William C. 
Published: May 2003

AbstractSevere sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates. The development of novel therapies for sepsis is critically dependent on an understanding of the basic mechanisms of the disease. The pathophysiology of severe sepsis involves a highly complex, integrated response that includes the activation of a number of cell types, inflammatory mediators, and the hemostatic system. Central to this process is an alteration of endothelial cell function. The goals of this article are to (1) provide an overview of sepsis and its complications, (2) discuss the role of the endothelium in orchestrating the host response in sepsis, and (3) emphasize the potential value of the endothelium as a target for sepsis therapy.