bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, Physicochemical and Anticonvulsant Properties of New N‐(Pyridine‐2‐yl) Derivatives of 2‐Azaspiro[4.4]nonane and [4.5]decane‐1,3‐dione. Part II
Authors: Kaminski Krzysztof , Obniska Jolanta , Zagorska Agnieszka , Maciag Dorota 
Published: March 2006

AbstractA series of N‐(pyridine‐2‐yl) derivatives of 2‐azaspiro[4.4]nonane‐ (1a–e), 2‐azaspiro[4.5]decane‐ (2a–e) and 6‐methyl‐2‐azaspiro[4.5]decane‐1,3‐dione (3a–e) were synthesized and tested for their anticonvulsant activity in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. To explain the possible mechanism of action, the most active compounds N‐(3‐methylpyridine‐2‐yl)‐2‐azaspiro[4.4]nonane‐1,3‐dione (1b), N‐(3‐methylpyridine‐2‐yl)‐2‐azaspiro[4.5]decane‐1,3‐dione (2b), N‐(4‐methylpyridine‐2‐yl)‐2‐azaspiro[4.5]decane‐1,3‐dione (2c), and N‐(3‐methylpyridine‐2‐yl)‐6‐methyl‐2‐azaspiro[4.5]decane‐1,3‐dione (3b) were tested in vitro for their influence on voltage‐sensitive calcium channel receptors, however, they revealed low affinities. For all synthesized compounds the lipophilicity was determined by use of RP‐TLC method. The correlation between the lipophilicity and anticonvulsant activity was obtained – the higher the lipophilicity the stronger the anticonvulsant efficacy.
A procedure for the computation of accurate PWL approximations of non‐linear dynamical systems
Authors: Repetto Lorenzo , Parodi Mauro , Storace Marco 
Published: March 2006

AbstractIn this paper we propose a variational method to find out piecewise‐linear (PWL) approximations of non‐linear dynamical systems in view of their circuit implementations. The method is based on some significant trajectories of the dynamical system and provides reasonably accurate PWL approximations with a relatively low number of parameters. The effectiveness of the method is validated by applying it to the approximation of limit cycles (both stable and unstable) in the Bautin system. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of cell:cell competition and BAFF expression on peripheral B cell tolerance and B‐1 cell survival in transgenic mice expressing a low level of Igκ‐reactive macroself antigen
Authors: Aït‐Azzouzene Djemel , Gavin Amanda L. , Skog Patrick , Duong Bao , Nemazee David 
Published: March 2006

AbstractIn mice carrying a synthetic Igκ‐reactive superantigen (“κ macroself antigen”), low level expression induced split peripheral B cell tolerance in the sIgκ+compartment, with striking reductions in follicular and marginal zone (MZ) B cells and the retention of significant numbers of sIgκ+B‐1a but not B‐1b cells in the peritoneum. Here, we characterize the transgenic line pKκ with this split tolerance phenotype and assess the effects of B cell competition and the survival cytokine BAFF (B cell activating factor belonging to the TNF family) on peripheral tolerance. In pKκ mice the surviving peritoneal and splenic κ+B cells were largely lost in mice carrying one copy of the human Cκ exon in place of the mouse version, a maneuver that generates additional antigen non‐reactive competitor B cells in this model. Furthermore, overexpression of BAFF suppressed κ‐macroself antigen‐induced deletion and promoted production of both IgM,κ and IgA,κ antibodies in mice with normal Igκ alleles but not in mice carrying one copy of the human Cκ allele. These findings suggest that BAFF overexpression has minimal effects on the survival of autoreactive B cells in a polyclonal immune system and that B cell:B cell competition plays a potent role in suppressing the survival of B‐1 and splenic B cells with excessive autoreactivity.
Prognosis of follicular lymphomas
Authors: Luminari Stefano , Federico Massimo 
Published: March 2006

AbstractFollicular lymphoma (FL) is as an indolent neoplasia with median survival measured in decades. Nevertheless, some patients have poor progression‐free survival and overall survival. Several treatment approaches are proposed for patients with FL, however criteria to rationalize treatment decisions are lacking. Studies have been performed to build up prognostic indices that are useful for defining risk‐adapted treatment recommendations. Available indices are based on parameters that have an independent role in predicting patient survival and that are variably correlated with the features of the disease, with the characteristics of the patient and with the effects of treatment. Two new prognostic indices have recently been proposed for FL: the Italian Lymphoma Intergroup (ILI) index and the Follicular Lymphoma International prognostic Index (FLIPI). Both indices are based on large series of patients and exhibit differences in their ability to discriminate between patients with different probabilities of survival. In recent years, with the advent of gene expression profile studies, our knowledge of the biology of FL is changing as novel data become available about the lymphoma cell and about the role of the microenvironment; these studies have already provided novel prognostic tools for identifying patients with more aggressive disease. Further data and large international cooperative studies are needed to translate into clinical practice the novel acquisitions of biology and therapeutics. Copyright © 2006 John Wiley & Sons, Ltd.
In vivo biodegradability and biocompatibility evaluation of novel alanine ester based polyphosphazenes in a rat model
Authors: Sethuraman Swaminathan , Nair Lakshmi S. , El‐Amin Saadiq , Farrar Robert , Nguyen My‐Tien N. , Singh Anurima , Allcock Harry R. , Greish Yaser E. , Brown Paul W. , Laurencin Cato T. 
Published: March 2006

AbstractAmino acid ester substituted polyphosphazenes are attractive candidates for various biomedical applications because of their biocompatibility, controllable hydrolytic degradation rates, and nontoxic degradation products. In this study, the biocompatibility of three L‐alanine ethyl ester functionalized polyphosphazenes was evaluated in a subcutaneous rat model. The polymers used in the study were poly[bis(ethylalanato)phosphazene] (PNEA), poly[(50% ethylalanato) (50% methylphenoxy) phosphazene] (PNEA50mPh50), and poly[(50% ethylalanato)(50% phenyl phenoxy) phosphazene] (PNEA50PhPh50). Polymer disks of diameter 7.5 mm were prepared by a solvent evaporation technique and were implanted subcutaneously in rats. After 2, 4, and 12 weeks, the polymer along with the surrounding tissues were excised, prepared, and viewed by light microscopy to evaluate the tissue responses of the implanted polymers. The tissue responses were classified as minimal, mild, or moderate, based on a biocompatibility scheme developed in our laboratory. Minimal inflammation was characterized by the presence of few neutrophils, erythrocytes, and lymphocytes; mild response was characterized by the predominant presence of macrophages, fibroblasts, or giant cells; and moderate inflammation was characterized by the abundance of macrophages, giant cells, and by the presence of tissue exudates. The in vivo degradation profiles of the polymers at various time points were evaluated by gel permeation chromatography (GPC). PNEA and PNEA50mPh50 matrices elicited varying levels of tissue responses during the 12‐week implantation period. At 2 weeks both polymers evoked a moderate response, and by 12 weeks the response was found to be mild. However, PNEA50PhPh50 elicited a mild response at the end of 2 weeks and demonstrated a further decreased inflammatory response after12 weeks. The in vivo degradation of the polymers was followed by determining the molecular weights of the explanted polymer disks. PNEA and PNEA50mPh50 disks showed significant decrease in molecular weight after 2 weeks of implantation. The molecular weights of PNEA and PNEA50mPh50 residues could not be determined by GPC after 12 weeks of implantation because of almost complete degradation. On the other hand the in vivo degradation of PNEA50PhPh50 was found to be slow, with a 63% loss in molecular weight in 12 weeks. Furthermore, this polymer maintained its shape and structure during the entire study. Thus, these polymers demonstrated excellent tissue compatibility and in vivo biodegradability and can be potential candidates for various biomedical applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Expansion on specific substrates regulates the phenotype and differentiation capacity of human articular chondrocytes
Authors: Barbero Andrea , Grogan Shawn Patrick , Mainil‐Varlet Pierre , Martin Ivan 
Published: March 2006

AbstractIn this study, we investigated if monolayer expansion of adult human articular chondrocytes (AHAC) on specific substrates regulates cell phenotype and post‐expansion multilineage differentiation ability. AHAC isolated from cartilage biopsies of five donors were expanded on plastic dishes (PL), on dishes coated with collagen type II (COL), or on slides coated with a ceramic material (Osteologic™, OS). The phenotype of expanded chondrocytes was assessed by flow cytometry and real‐time RT‐PCR. Cells were then cultured in previously established conditions promoting differentiation toward the chondrogenic or osteogenic lineage. AHAC differentiation was assessed histologically, biochemically, and by real‐time RT‐PCR. As compared to PL‐expanded AHAC, those expanded on COL did not exhibit major phenotypic changes, whereas OS‐expanded cells expressed (i) higher bone sialoprotein (BSP) (22.6‐fold) and lower collagen type II (9.3‐fold) mRNA levels, and (ii) lower CD26, CD90 and CD140 surface protein levels (1.4–11.1‐fold). Following chondrogenic differentiation, COL‐expanded AHAC expressed higher mRNA levels of collagen type II (2.3‐fold) and formed tissues with higher glycosaminoglycan (GAG) contents (1.7‐fold), whereas OS‐expanded cells expressed 16.5‐fold lower collagen type II and generated pellets with 2.0‐fold lower GAG contents. Following osteogenic differentiation, OS‐expanded cells expressed higher levels of BSP (3.9‐fold) and collagen type I (2.8‐fold) mRNA. In summary, AHAC expansion on COL or OS modulated the de‐differentiated cell phenotype and improved the cell differentiation capacity respectively toward the chondrogenic or osteogenic lineage. Phenotypic changes induced by AHAC expansion on specific substrates may mimic pathophysiological events occurring at different stages of osteoarthritis and may be relevant for the engineering of osteochondral tissues. J. Cell. Biochem. 98: 1140–1149, 2006. © 2006 Wiley‐Liss, Inc.
Identification of a PTH regulated gene selectively induced in vivo during PTH‐mediated bone formation
Authors: Robinson John A. , Susulic Vedrana , Liu Yao‐Bin , Taylor Chanda , Hardenburg Jill , Gironda Virginia , Zhao Weiguang , Kharode Yogendra , McLarney Sean , Bai Yuchen , Malone Daniel P. , Murrills Richard , Bex Fred 
Published: March 2006

AbstractThe biological activities of parathyroid hormone (PTH) on bone are quite complex as demonstrated by its catabolic and anabolic activities on the skeleton. Although there have been many reports describing genes that are regulated by PTH in osteoblast cells, the goal of this study was to utilize a well‐established in vivo PTH anabolic treatment regimen to identify genes that mediate bone anabolic effects of PTH. We identified a gene we named PTH anabolic induced gene in bone (PAIGB) that has been reported as brain and acute leukemia cytoplasmic (BAALC). Therefore, using the latter nomenclature, we have discovered that BAALC is a PTH‐regulated gene whose mRNA expression was selectively induced in rat tibiae nearly 100‐fold (maximal) by a PTH 1–34 anabolic treatment regimen in a time‐dependent manner. Although BAALC is broadly expressed, PTH did not regulate BAALC expression in other PTH receptor expressing tissues and we find that the regulation of BAALC protein by PTH in vivo is confined to mature osteoblasts. Further in vitro studies using rat UMR‐106 osteoblastic cells show that PTH 1–34 rapidly induces BAALC mRNA expression maximally by 4 h while the protein was induced by 8 h. In addition to being regulated by PTH 1–34, BAALC expression can also be induced by other bone forming factors including PGE2and 1,25 dihydroxy vitamin D3. We determined that BAALC is regulated by PTH predominantly through the cAMP/PKA pathway. Finally, we demonstrate in MC3T3‐E1 osteoblastic cells that BAALC overexpression regulates markers of osteoblast differentiation, including downregulating alkaline phosphatase and osteocalcin expression while inducing osteopontin expression. We also demonstrate that these transcriptional responses mediated by BAALC are similar to the responses elicited by PTH 1–34. These data, showing BAALC overexpression can mimic the effect of PTH on markers of osteoblast differentiation, along with the observations that BAALC is induced selectively with a bone anabolic treatment regimen of PTH (not a catabolic treatment regimen), suggest that BAALC may be an important mediator of the PTH anabolic action on bone cell function. J. Cell. Biochem. 98: 1203–1220, 2006. © 2006 Wiley‐Liss, Inc.
Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia
Authors: Tyagi Neetu , Ovechkin Alexander V. , Lominadze David , Moshal Karni S. , Tyagi Suresh C. 
Published: March 2006

AbstractAn elevated level of homocysteine (Hcy) limits the growth and induces apoptosis. However, the mechanism of Hcy‐induced programmed cell death in endothelial cells is largely unknown. We hypothesize that Hcy induces intracellular reactive oxygen species (ROS) production that leads to the loss of transmembrane mitochondrial potential (Δψm) accompanied by the release of cytochrome‐c from mitochondria. Cytochrome‐c release contributes to caspase activation, such as caspase‐9, caspase‐6, and caspase‐3, which results in the degradation of numerous nuclear proteins including poly (ADP‐ribose) polymerase (PARP), which subsequently leads to the internucleosomal cleavage of DNA, resulting cell death. In this study, rat heart microvascular endothelial cells (MVEC) were treated with different doses of Hcy at different time intervals. Apoptosis was measured by DNA laddering and transferase‐mediated dUTP nick‐end labeling (TUNEL) assay. ROS production and MP were determined using florescent probes (2,7‐dichlorofluorescein (DCFH‐DA) and 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐benzamidazolocarbocyanin iodide (JC‐1), respectively, by confocal microscopy. Differential gene expression for apoptosis was analyzed by cDNA array. The results showed that Hcy‐mediated ROS production preceded the loss of MP, the release of cytochrome‐c, and the activation of caspase‐9 and ‐3. Moreover the Hcy treatment resulted in a decrease in Bcl2/Bax ratio, evaluated by mRNA levels. Caspase‐9 and ‐3 were activated, causing cleavage of PARP, a hallmark of apoptosis and internucleosomal DNA fragmentation. The cytotoxic effect of Hcy was blocked by using small interfering RNA (siRNA)‐mediated suppression of caspase‐9 in MVEC. Suppressing the activation of caspase‐9 inhibited the activation of caspase ‐3 and enhanced the cell viability and MP. Our data suggested that Hcy‐mediated ROS production promotes endothelial cell death in part by disturbing MP, which results in subsequent release of cytochrome‐c and activation of caspase‐9 and 3, leading to cell death. J. Cell. Biochem. 98: 1150–1162, 2006. © 2006 Wiley‐Liss, Inc.
AUF1‐like protein binds specifically to DAS cis‐acting element that regulates mouse α‐fetoprotein gene expression
Authors: Jiao Ruiqing , He Qing‐Yu , Chen Hongmin , Hua Zichun , Jiao Qincai , Chiu Jen‐fu 
Published: March 2006

AbstractAlpha‐fetoprotein (AFP) is one of the major serum proteins in the early life of mammals. We have previously identified a novel cis‐acting element designated as DAS at the 5′‐flanking region of the AFP gene and demonstrated that the DAS sequence can be specifically recognized by nuclear protein DAP‐II in AFP‐producing hepatoma cells and retinoic acid (RA)‐induced AFP‐producing F9 cells. In this study, we used DNA affinity chromatography to purify the DAP‐II proteins from the nuclear extracts (NE) of RA‐treated F9 cells. The purified DAP‐II complex mainly contained five proteins, with molecular weights of 45, 42, 32, 30, and 20 kDa, respectively. The identification of these proteins was determined by MALDI‐TOF mass spectrometric analysis and a database search. These proteins were found to belong to the AUF1 RNA‐binding protein family. Protein (30 kDa), one of five proteins in an isolated DAP‐II complex, was matched with amino acid sequence highly similar to muAUF1‐3. The expression of this protein is inducible by RA, and the pattern of the protein expression is the same as DAP‐II proteins in F9 cells after treatment with RA during differentiation. Our results suggest that the 30‐kDa protein is a novel isoform of AUF1 family and is the main component of the DAP‐II complex that binds to the DAS sequence. J. Cell. Biochem. 98: 1257–1270, 2006. © 2006 Wiley‐Liss, Inc.
Osteoblast‐conditioned media influence the expression of E‐selectin on bone‐derived vascular endothelial cells
Authors: Makuch Lauren A. , Sosnoski Donna M. , Gay Carol V. 
Published: March 2006

AbstractBreast cancer cells frequently metastasize to the ends of long bones, ribs and vertebrae, structures which contain a rich microvasculature that is closely juxtaposed to metabolically active trabecular bone surfaces. This study focuses on the effects of osteoblast secretions on the surface presentation of adhesive proteins on skeletal vascular endothelial cells. Vascular endothelial cells were isolated from trabecular bone regions of the long bones of 7‐week‐old Swiss Webster mice and also from the central marrow cavity where trabecular bone is absent. Both types of endothelial cells were placed in culture for 7 days, then exposed 24 h to conditioned media from MC3T3‐E1 osteoblasts. Conditioned medium (CM) from two different stages of osteoblast development were tested: (1) from immature MC3T3‐E1 cells cultured for 5–7 days and (2) from mature MC3T3‐E1 cells cultured for 28–30 days. The immature osteoblasts were in a stage of rapid proliferation; the mature osteoblasts formed a matrix that mineralized. Following exposure to the conditioned media, the vascular cells were exposed to anti‐P‐selectin, anti‐E‐selectin, anti‐ICAM‐1, and anti‐VCAM‐1 to detect the corresponding adhesive proteins on their surfaces. Breast cancer cells are known to bind to these adhesive proteins. Of the four proteins evaluated, E‐selectin was consistently found on more cell surfaces (∼30%) of bone‐derived vascular endothelial cells (BVECs) when exposed to the immature CM whereas vascular endothelial cells from marrow (MVECs) did not show this response to either immature CM or mature CM. These studies suggest that the BVEC blood vessels near immature bone cells express more surface adhesive protein that could enhance entrapment and extravasation of breast cancer cells. Once cancer cells have undergone extravasation into marrow adjacent to bone, they could be readily attracted to nearby bone surfaces. J. Cell. Biochem. 98: 1221–1229, 2006. © 2006 Wiley‐Liss, Inc.
Loss of phosphatase activity in Ptp69D alleles supporting axon guidance defects
Authors: Marlo Joy E. , Desai Chand J. 
Published: March 2006

AbstractPTP69D is a receptor protein tyrosine phosphatase that was identified as a key regulator of neuromuscular axon guidance in Drosophila, and has subsequently been shown to play a similar role in the central nervous system and retina. Three Ptp69D alleles with mutations involving catalytically important residues exhibit a high degree of phenotypic variation with viability of mutant adult flies ranging from 0 to 96%, and ISNb motor nerve defects ranging from 11 to 57% [Desai and Purdy, 2003]. To determine whether mutations in Ptp69D affecting axon guidance and viability demonstrate losses of phosphatase activity and whether differences in catalytic potential underlie phenotypic variability, we expressed full‐length wild‐type and mutant PTP69D protein in Schneider 2 cells, and assessed phosphatase activity using the fluorogenic substrate 6,8‐difluoro‐4‐methylumbelliferone phosphate (DiFMUP). Detailed biochemical characterization of wild‐type PTP69D, including an examination of sensitivity to various inhibitors, in vitro catalytic efficiency, and the pH‐kcat profile of the enzyme, suggests a common tyrosine phosphatase reaction mechanism despite lack of sequence conservation in the WPD loop. Analysis of mutant proteins revealed that every mutant had less than 1% activity relative to the wild‐type enzyme, and these rates did not differ significantly from one another. These results indicate that mutations in Ptp69D resulting in axon guidance defects and lethality significantly compromise catalytic activity, yet the range of biological activity exhibited by Ptp69D mutants cannot be explained by differences in catalytic activity, as gauged by their ability to hydrolyze the substrate DiFMUP. J. Cell. Biochem. 98: 1296–1307, 2006. © 2006 Wiley‐Liss, Inc.
Fluid flow induces Rankl expression in primary murine calvarial osteoblasts
Authors: Mehrotra Meenal , Saegusa Masatomo , Wadhwa Sunil , Voznesensky Olga , Peterson Donald , Pilbeam Carol 
Published: March 2006

AbstractMechanical loading of bone generates fluid flow within the mineralized matrix that exerts fluid shear stress (FSS) on cells. We examined effects of FSS on receptor activator of nuclear factor κ B ligand (RANKL), a critical factor for osteoclast formation. Primary murine osteoblasts were subjected to pulsatile FSS (5 Hz, 10 dynes/cm2) for 1 h and then returned to static culture for varying times (post‐FSS). Protein levels were measured by Western analysis and mRNA by Northern analysis, RT‐PCR and quantitative PCR. There were 20‐ to 40‐fold increases in RANKL mRNA at 2–4 h post‐FSS. RANKL protein was induced by 2 h post‐FSS and remained elevated for at least 8 h. Effects were independent of cyclooxygenase‐2 activity. Small increases (up to three‐fold) in mRNA of the decoy receptor for RANKL, osteoprotegerin, were seen. Five min of FSS, followed by static culture, was as effective in stimulating RANKL mRNA as 4 h of continuous FSS. FSS induced cAMP activity, and H‐89, a protein kinase A (PKA) inhibitor, blocked the FSS induction of RANKL. H‐89 also inhibited the PKC pathway, but specific PKC inhibitors, GF109203X and Go6983, did not inhibit FSS‐induced RANKL. FSS induced phosphorylation of ERK1/2, and PD98059, an inhibitor of the ERK pathway, inhibited the FSS induction of RANKL mRNA 60%–90%. Thus, brief exposure to FSS resulted in sustained induction of RANKL expression after stopping FSS, and this induction was dependent on PKA and ERK signaling pathways. Increased RANKL after mechanical loading may play a role in initiating bone remodeling. J. Cell. Biochem. 98: 1271–1283, 2006. © 2006 Wiley‐Liss, Inc.
Doping effects on proton incorporation and conduction in SrZrO3
Authors: Shi Chunsheng , Morinaga Masahiko 
Published: March 2006

AbstractThe doping effects on the proton incorporation and protonic conductivity of perovskite‐type SrZrO3 were investigated using the density functional theory (DFT) with the generalized gradient approximation (GGA). The optimized geometries, formation energies of hydrogen defect and activation energies for hydrogen diffusion in SrZrO3 doped with Al, Sc, Ga, Y, Rh, In, and Yb were calculated. It was shown that the doping leads to large local distortions around hydrogen and dopant ion, affecting the protonic conduction in these oxides. The alignment of hydrogen levels varies with the dopant introduced into the SrZrO3. In In‐, Y‐, Sc‐, Ga‐, and Al‐doped SrZrO3, the H+ is the lowest energy state in all the bandgap. But for Yb‐ and Rh‐doped SrZrO3, the H+ is the lowest energy state only when the Fermi energy below 2.37 and 2.66 eV, respectively. The estimates of the activation energy show good agreement between the measured and calculated activation energies. Also, the hydrogen diffusion seems to become more difficult as the distance between hydrogen and dopant ion decreases. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 711–718, 2006