bluuebunny/crossref_metadata_2025 huggingface dataset:
Unreinforced spatial (latent) learning is mediated by a circuit that includes dorsal entorhinal cortex and fimbria fornix
Authors: Gaskin Stephane , White Norman M.
Published: April 2007

The relationship of the entorhinal cortex (EC) and fimbria‐fornix (FF) in unreinforced spatial (latent) learning was studied using the conditioned‐cue‐preference task on an eight‐arm radial maze. The maze was turned before every trial to eliminate the use of local cues. During three pre‐exposure sessions, food‐deprived rats explored the center platform and two adjacent arms of the maze. Since most of the same cues were visible from both arm locations, discriminating them required spatial learning. The rats were then alternately confined to the end of each arm over several days: one arm always contained food, the other was empty. Finally, the rats were allowed free access to both arms with no food present. Normal rats spent more time in their food‐paired than in their unpaired arms showing that they learned to discriminate between the arm locations. Bilateral micro‐injections of muscimol into the dorsal, but not into the ventral EC, given before the pre‐exposure sessions only, impaired the discrimination. The discrimination was also impaired in rats with unilateral lesions of FF and contralateral injections of muscimol into the dorsal EC given before the pre‐exposure sessions. Ipsilateral FF lesions and entorhinal inactivation had no effect. These results indicate that the acquisition of information during unreinforced exploration of a novel environment requires an intact circuit involving the dorsal EC and fimbria fornix. Together with previous reports, that this form of learning does not require a functional hippocampus, (Gaskin et al. (2005) Hippocampus 15:1085–1093) the findings also suggest that the acquisition of certain kinds of unreinforced information by this circuit is independent of the hippocampus. © 2007 Wiley‐Liss, Inc.
Human hippocampal‐dependent tasks: Is awareness necessary or sufficient?
Authors: Greene Anthony J.
Published: April 2007

The hippocampus has been shown to be required for the acquisition of declarative or explicit memory. Whether all hippocampal‐dependent forms of learning and memory are explicit is an open question. Controversy has emerged about the existence of implicit hippocampal‐dependent tasks. Two implicit tasks that may involve the hippocampusare a relational eye tracking task (Ryan et al. (2000) Psychol Sci 11:454–461) and transitive inference (Greene et al. (2006) J Cognit Neurosci 18:1156–1173; Greene et al. (2001) Mem Cognit 29:893–902). Recently, it was shown that both of these tasks may depend upon task awareness (Smith et al. (2006) J Neurosci 26:11304–11312; Smith and Squire (2005) J Neurosci 25:10138–10146). It is argued that in both cases, distinct, explicit versions of the tasks were created, which do not disprove the implicit nature of the original tasks. © 2007 Wiley‐Liss, Inc.
Syndecan‐1, a key regulator of cell viability in endometrial cancer
Authors: Choi Dong Soon , Kim Ji‐Hye , Ryu Hee‐Sug , Kim Hyon Chang , Han Jae Ho , Lee Jong Soo , Min Churl K.
Published: April 2007

Syndecan‐1 is one of the major proteoglycans on cell surfaces involved in major biological processes. Although loss of syndecan‐1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan‐1 also coincides with adverse outcomes in some cancers, including breast, ovarian and pancreatic cancers. For this Janus‐faced attitude of syndecan‐1, we sought to examine expression patterns of syndecan‐1 in endometrial carcinoma (EC) and gain insight into the roles of syndecan‐1. Immunohistochemical examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC uteri revealed that syndecan‐1 expression was significantly upregulated in EC compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions of syndecan‐1, its expression level was altered, and subsequent outcomes were examined using human endometrial cancer cell lines such as HEC‐1A, AN3CA and KLE cells. Overexpression of syndecan‐1 increased the growth of HEC‐1A cells regardless of anchorage dependence while silencing syndecan‐1 by antisense RNAs caused apoptotic cell death. Consistent with decreased viability, the loss of syndecan‐1 was also accompanied by a decrease in the activation of Erk and Akt and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are known as negative and positive regulators of Akt activation, respectively. These down‐regulatory effects were reversed upon overexpression of syndecan‐1. Collectively together, the aforementioned findings lend support to the notion that upregulation of syndecan‐1 may be a critical element for endometrial cancers in maintaining their viability and thus can serve as a cancer specific therapeutic and diagnostic marker. © 2007 Wiley‐Liss, Inc.
Colorectal cancer survival in the Nordic countries and the United Kingdom: Excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000
Authors: Engholm Gerda , Kejs Anne Mette T. , Brewster David H. , Gaard Maria , Holmberg Lars , Hartley Roger , Iddenden Robert , Møller Henrik , Sankila Risto , Thomson Catherine S. , Storm Hans H.
Published: April 2007

A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15–89 in the period 1994–2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five‐year relative period survival using deaths in 1999–2000 following cancers diagnosed in 1994–2000 was analysed with excess mortality risk modelling. Follow‐up time since diagnosis with age as an effect‐modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow‐up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5–5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age‐intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies. © 2007 Wiley‐Liss, Inc.
Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group
Authors: Beckers Thomas , Burkhardt Carmen , Wieland Heike , Gimmnich Petra , Ciossek Thomas , Maier Thomas , Sanders Karl
Published: April 2007

Advanced second generation inhibitors of histone deacetylases (HDAC) are currently used in clinical development. This study aimed at comparing the pharmacological properties of selected second generation HDAC inhibitors with the hydroxamate and benzamide head group, namely SAHA, LAQ824/LBH589, CI994, MS275 and MGCD0103. In biochemical assays using recombinant HDAC1, 3, 6 and 8 isoenzymes, SAHA and LAQ824/LBH589 behave as quite unselective HDAC inhibitors. In contrast, the benzamides CI994, MS275 and MGCD0103 are more selective, potent inhibitors of at least HDAC1 and HDAC3. All HDAC inhibitors induce histone H3 hyperacetylation, correlating with inhibition of proliferation, induction of cell differentiation and apoptosis. A broad cytotoxicity is seen across cell lines from different tumor entities with LAQ824/LBH589 being the most potent agents. The apoptosis inducing activity is evident in arrested and proliferating RKO colon cancer cells with inducible, heterologous p21waf1 expression, indicative for a cell‐cycle independent mode‐of‐action. Differentiation of MDA‐MB468 breast cancer cells is induced by benzamide and hydroxamate analogs. The reversibility of drug action was evaluated by pulse treatment of A549 lung cancer cells. Whereas paclitaxel induced irreversible cell cycle alterations already after 6 hr treatment, HDAC inhibitor action was retarded and irreversible after >16 hr treatment. Interestingly, pulse treatment was equally effective as continous treatment. Finally, the efficacy of LAQ824, SAHA and MS275 in A549 nude mice xenografts was comparable to that of paclitaxel at well tolerated doses. We conclude that despite a different HDAC isoenzyme inhibition profile, hydroxamate and benzamide analogs as studied display similar cellular profiles. © 2007 Wiley‐Liss, Inc.
Synthesis and characterization of radiopaque magnetic core‐shell nanoparticles for X‐ray imaging applications
Authors: Galperin Anna , Margel Shlomo
Published: April 2007

Radiopaque magnetic γ‐Fe2O3/poly(2‐methacryloyloxyethyl(2,3,5‐triiodobenzoate)) core‐shell nanoparticles of narrow size distribution were prepared by emulsion polymerization of the iodinated monomer 2‐methacryloyloxyethyl(2,3,5‐triiodobenzoate) in the presence of maghemite (γ‐Fe2O3 nanoparticles coated with a dextran shell are commonly used as contrast agents for magnetic resonance imaging (MRI). The present nanoparticles have similar core‐shell structure substituting the dextran for the iodo polymer. These core‐shell nanoparticles may therefore be useful as imaging contrast agents to detect various pathogenic zones and to observe different disease states in both modes: X‐ray and MRI. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Development of an engineering autologous palatal mucosa‐like tissue for potential clinical applications
Authors: Luitaud C. , Laflamme C. , Semlali A. , Saidi S. , Grenier G. , Zakrzewski A. , Rouabhia M.
Published: April 2007

The goal of this study was to optimize key processes in recreating functional and viable palatal mucosa‐like tissue that would be easy to handle and would promote wound healing. Normal human gingival fibroblasts and epithelial cells and a clinically useful biomaterial, CollaTape®, were used. Structural and ultrastructural analyses showed that the gingival fibroblasts and epithelial cells adhered to the biomaterial and proliferated. Following a 6‐day culture, using 105 fibroblasts and 106 epithelial cells, a well‐organized palatal mucosa‐like tissue was engineered. The engineered epithelium displayed various layers, including a stratum corneum, and contained cytokeratin 16‐positive cells located in the supra‐basal layer. This palatal mucosa‐like engineered tissue was designed to meet a variety of surgical needs. The biodegradable collagen membrane (CollaTape) contributed to the flexibility of the engineered tissue. This engineered innovative tissue may contribute to the reconstruction of oral soft‐tissue defects secondary to trauma, congenital defects, and acquired diseases. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Surface micro‐analyses of long‐term worn retrieved “Osteal™” alumina ceramic total hip replacement
Authors: Tateiwa Toshiyuki , Clarke Ian C , Pezzotti Giuseppe , Sedel Laurent , Kumakura Tsuyoshi , Shishido Takaaki , Yamamoto Kengo
Published: April 2007

We analyzed wear pattern of long‐term retrieved alumina‐alumina hip prostheses from Osteal™, which were implanted for 15–19 years. A comparison was carried out with our previous study of 17‐year Biolox™ alumina‐on‐alumina hip prostheses, (Shishido et al., J Biomed Mater Res B 2003;67:638–647) and all‐alumina total hip replacement run under microseparation simulator tests. Of particular interest was the occurrence of stripe wear in these first generation alumina ceramic bearings. Two balls of Osteal revealed only one stripe wear as did the respective liners on their rim areas. In these latter balls, the stripes were shallower than those previously observed in Biolox implants. A microscopic analysis of the bearing surface was carried out using scanning electron microscopy and fluorescence microprobe spectroscopy. On average, the Osteal retrievals had one grade lower wear than Biolox retrievals. Fluorescence microprobe maps showed that Biolox ball surfaces had higher compressive stress than the Osteal likely due to severe impingement and microseparation promoted by the bulky implant design. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2007
Development of a 95/5 poly(L‐lactide‐co‐glycolide)/hydroxylapatite and β‐tricalcium phosphate scaffold as bone replacement material via selective laser sintering
Authors: Simpson Rebecca Louise , Wiria Florencia Edith , Amis Andrew A. , Chua Chee Kai , Leong Kah Fai , Hansen Ulrich N. , Chandrasekaran Margam , Lee Mun Wai
Published: April 2007

95/5 Poly(L‐lactide‐co‐glycolide) was investigated for the role of a porous scaffold, using the selective laser sintering (SLS) fabrication process, with powder sizes of 50–125 and 125–250 μm. SLS parameters of laser power, laser scan speed, and part bed temperature were altered and the degree of sintering was assessed by scanning electron microscope. Composites of the 125–250 β‐tricalcium phosphate (CAMCERAM® II) were sintered, and SLS settings using 40 wt % CAMCERAM® II were optimized for further tests. Polymer thermal degradation during processing led to a reduction in number and weight averaged molecular weight of 9% and 12%, respectively. Compression tests using the optimized composite sintering parameters gave a Young's modulus, yield strength, and strain at 1% strain offset of 0.13 ± 0.03 GPa, 12.06 ± 2.53 MPa, and 11.39 ± 2.60%, respectively. Porosity was found to be 46.5 ± 1.39%. CT data was used to create an SLS model of a human fourth middle phalanx and a block with designed porosity was fabricated to illustrate the process capabilities. The results have shown that this composite and fabrication method has potential in the fabrication of porous scaffolds for bone tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Dextran‐sulfate‐adsorption of atherosclerotic lipoproteins from whole blood or separated plasma for lipid‐apheresis—Comparison of performance characteristics with DALI and lipidfiltration
Authors: Julius Ulrich , Parhofer Klaus G. , Heibges Andreas , Kurz Stefan , Klingel Reinhard , Geiss Hans‐Christian
Published: April 2007

For many years dextran sulfate adsorption (DSA) treatment of separated plasma has been an established technology for low‐density lipoprotein (LDL)‐elimination. Recently a system for the treatment of whole blood based on DSA was introduced into clinical practice. To further characterize DSA treatment of whole blood, the performance characteristics of both DSA modalities were compared at two investigational sites with two alternative LDL apheresis systems being already in routine clinical use. In prospective cross‐over design, DSA whole blood treatment was compared with a whole blood polyacrylate LDL adsorption system (DALI) in one study group. DSA for plasma treatment was compared with Lipidfiltration in cross‐over design in a second study group. In total, 12 patients on chronic LDL apheresis received 169 treatments. Six patients were treated twice with whole blood polyacrylate adsorption and twice with whole blood DSA. LDL‐cholesterol (74.9–78.0%) and lipoprotein (a) (72.1–73.3%) were reduced by both with equal efficacy. DSA achieved a significantly higher reduction rate of fibrinogen. Another six patients were treated eight times with DSA plasma adsorption followed by 16 Lipidfiltration treatments. LDL‐cholesterol (67.0–70.2%) and lipoprotein (a) (69.2–73.7%) were reduced by both with equal efficacy. Fibrinogen was eliminated more efficiently by Lipidfiltration (50.2 vs. 38.5%). DSA proved to be a safe and effective in both treatment modes, for plasma as well as for whole blood. At the discretion of the apheresis specialist, depending upon the status of national approval, DSA of whole blood complements the armamentarium of powerful modalities for extracorporeal elimination of atherosclerotic lipoproteins to meet specific individual, medical, or logistic needs. J. Clin. Apheresis., 2007 © 2007 Wiley‐Liss, Inc.
Constitutive collagenase‐1 synthesis through MAPK pathways is mediated, in part, by endogenous IL‐1α during fibrotic repair in corneal stroma
Authors: Jung Jae‐Chang , Huh Man‐Il , Fini M. Elizabeth
Published: April 2007

Collagenase‐1 is a protease expressed by active fibroblasts that is involved in remodeling of the extracellular matrix (ECM). In this study, we characterize the intracellular signaling mechanism of collagenase‐1 production by IL‐1α in subcultured normal fibroblasts (NF) from uninjured normal corneas, compared to that in repair wound fibroblasts (WF). In NF, collagenase‐1 was induced specifically after the exogenous addition of IL‐1α via activation of ERK and p38MAPK. Collagenase‐1 expression was strongly suppressed upon treatment with either a MEK or p38MAPK inhibitor. In contrast, repair WF constitutively synthesized both IL‐1α and collagenase‐1. Combined treatment with both mitogen‐activated protein kinase (MAPK) inhibitors dramatically reduced collagenase‐1 synthesis, while individual MEK1 or p38 inhibitors weakly modulated the collagenase‐1 level. The results indicate that both pathways are crucial in the regulation of collagenase‐1 synthesis. Furthermore, an IL‐1α receptor antagonist (IL‐1ra) could not abolish constitutive collagenase‐1 synthesis, even at high doses, suggesting that other cytokines/factors are additionally involved in this process. We propose that induction of collagenase‐1 by IL‐1α in both WF and NF depends on a unique combination of cell type‐specific signaling pathways. J. Cell. Biochem. 102: 453–462, 2007. © 2007 Wiley‐Liss, Inc.
RIF‐1, a novel nuclear receptor corepressor that associates with the nuclear matrix
Authors: Li Hui Joyce , Haque Zaffar K. , Chen Amy , Mendelsohn Michael
Published: April 2007

The retinoic acid receptors (RARs) are ligand‐dependent transcription factors that play critical roles in cell differentiation, embryonic development, and tumor suppression. RAR transcriptional activities are mediated by a growing family of nuclear receptor (NR) coregulators. Here we report the cloning and characterization of a novel protein RIF1 (receptor interacting factor) that interacts with RARα in vivo and in vitro. RIF1 encodes a novel 739 amino acid protein that is ubiquitously expressed in a variety of tissues and cell lines. GST‐pull down assays show that RIF1 also interacts with a number of other NRs. The interaction domain of RIF1 for RARα is located at the C‐terminal region of RIF1, between amino acids 512 and 674. RIF1 is localized exclusively in the cell nucleus and specifically to the nuclear matrix. Mutation of the nuclear localization signal abolishes this nuclear localization and causes RIF1 to appear in the cytoplasm. Co‐transfection of RIF1 with RAR causes RAR to localize to the nuclear matrix. RIF1 contains a strong transcriptional repression domain that robustly inhibits ligand‐dependent transcriptional activation by RARα. This domain is located to the distal C‐terminal 100 amino acids, distinct from the RARα‐interaction and nuclear matrix‐targeting domains. The transcriptional repression activity of RIF1 is mediated at least in part through direct recruitment of histone deacetylases. This study identifies RIF1 as a novel nuclear matrix transcription repressor, and suggests a potential role of RIF1 that regulates NR transcriptional activity. J. Cell. Biochem. 102: 1021–1035, 2007. © 2007 Wiley‐Liss, Inc.
A proximal direct repeat motif characterized as a negative regulatory element in the human renin gene
Authors: Konoshita Tadashi , Fuchs Sébastien , Makino Yasukazu , Wakahara Shigeyuki , Miyamori Isamu
Published: April 2007

The regulation of renin gene expression is thought to be fundamental to regulation of the total renin–angiotensin system. The human renin gene contains a direct repeat (DR) motif AGGGGTCAC–AGGGCCA in the proximal region (−259/−245 bp), which contains similar sequence for nuclear receptor superfamily binding core motif, AGGTCA, and is the most similar to COUP‐TFII consensus. The DR motif was evaluated as a functional cis‐element with renal cortex and chorio‐decidual cells by footprint assay, electromobility shift assay (EMSA) and reporter assay. The DR motif site was protected by footprint analysis with a clear hypersensitive and a minor hypersensitive region in good accordance with the DR of the consensus. One of the binding proteins was strongly suspected to be COUP‐TFII‐consensus‐specific by EMSA. The DNA/protein complexes obtained with nuclear extract of renin producing cells could be completely blocked by homologous competitor and strongly blocked by the second‐half mutant oligonucleotide of the DR motif but not by the first‐half mutant oligonucleotide. Finally, the transcriptional activity of second‐half mutant construct is slightly elevated and that first‐half mutant construct is significantly stronger by twofold compared with wild type construct in reporter assay. These findings suggest that the DR motif site of the human renin gene functions as a negative regulatory element involved in a twofold repression of transcription and that member(s) of nucleic receptor superfamily bind the site and play important roles in the human renin gene expression with a possibility that one of the binding protein is COUP‐TFII. J. Cell. Biochem. 102: 1043–1050, 2007. © 2007 Wiley‐Liss, Inc.
Nuclear structure as a source of cancer specific biomarkers
Authors: Leman Eddy S. , Getzenberg Robert H.
Published: April 2007

There are few biomarkers that have been developed which have proven clinical utility for the detection and prognosis of cancer. Cancer is diagnosed today, in large part, by examining cells under the microscope and determining the shape and texture of the nucleus. The molecular underpinnings of this hallmark of cancer are the components of the nuclear matrix. Utilizing proteomics focused on this subset of proteins, biomarkers have been identified that are specific for cancer types including prostate, colon and bladder cancer. These cancer biomarkers now serve as the basis of assays which can specifically identify individuals with cancer by sampling their blood and/or urine. In addition, these may serve as potential therapeutic targeting or imaging approaches. J. Cell. Biochem. 104: 1988–1993, 2008. © 2007 Wiley‐Liss, Inc.
Validation of critical points in the electron density as descriptors by building quantitative structure–property relationships for the atomic polar tensor
Authors: Buttingsrud Bård , Alsberg Bjørn K. , Åstrand Per‐Olof
Published: April 2007

A crucial component of research in the field of quantitative structure–activity/property relationships is the identification of molecular descriptors relevant to the activity or property of interest. Descriptors based on the topology of the electron density as formulated in Bader's theory of atoms in molecules are investigated in detail in this work. In a model study, the authors investigate their ability to predict the atomic polar tensor (the gradient of the molecular dipole moment), which contains information on the vibrational intensities in infrared spectroscopy and constitutes a scheme for partitioning the total charge distribution into atomic charges. The atomic polar tensor may therefore be used to investigate whether the descriptors give adequate information on the local electronic structure in the molecule. Both the trace of the atomic polar tensor and for planar molecules its out‐of‐plane component may be interpreted as definitions of atomic charges suitable for prediction. Hydrogen and carbon atoms in a set of 60 aromatic compounds with various substituents have been studied. Excellent results for prediction of hydrogen and carbon charges have been achieved with cross‐validated squared correlation coefficients between predicted and theoretical values varying from 0.92 and 0.977 for the most complex set of substituents when the value, Laplacian, and ellipticity of the electron density in the bond critical points are used as descriptors. The carbon charges defined from the trace of the atomic polar tensor are correlated with its out‐of‐plane component whereas such relationship is not observed for the hydrogen charges studied in this work. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Implementation of divide‐and‐conquer method including Hartree‐Fock exchange interaction
Authors: Akama Tomoko , Kobayashi Masato , Nakai Hiromi
Published: April 2007

The divide‐and‐conquer (DC) method, which is one of the linear‐scaling methods avoiding explicit diagonalization of the Fock matrix, has been applied mainly to pure density functional theory (DFT) or semiempirical molecular orbital calculations so far. The present study applies the DC method to such calculations including the Hartree‐Fock (HF) exchange terms as the HF and hybrid HF/DFT. Reliability of the DC‐HF and DC‐hybrid HF/DFT is found to be strongly dependent on the cut‐off radius, which defines the localization region in the DC formalism. This dependence on the cut‐off radius is assessed from various points of view: that is, total energy, energy components, local energies, and density of states. Additionally, to accelerate the self‐consistent field convergence in DC calculations, a new convergence technique is proposed. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Bicarbonate‐dependent pHi regulation by chondrocytes within the superficial zone of bovine articular cartilage
Authors: Simpkin Victoria L. , Murray Dianne H. , Hall Andrew P. , Hall Andrew C.
Published: April 2007

Control of chondrocyte pH (pHi) determines articular cartilage matrix metabolism. However, the transporters of chondrocytes in situ throughout cartilage zones are unclear, and we tested the hypothesis that chondocytes within the superficial zone (SZ) utilise a HCO‐dependent system absent from other zones. Imaging of single BCECF‐labelled cells was used to monitor the pHi of in situ chondrocytes within the cartilage zones, and also that of cells isolated from the SZ or full depth (FD) explants. Resting pHi and intrinsic buffering power (βi) in HEPES‐buffered saline was not different between SZ and DZ cells, however the pHi of SZ chondrocytes was lower in HCO saline. Ammonium pre‐pulse was used to acid‐load cells and pHi recovery by in situ or isolated SZ chondrocytes shown to be totally dependent on HCO. pHi recovery rate was significantly (P < 0.05) greater for in situ cells, suggesting that isolation damaged the HCO‐dependent system. Recovery of pHi by in situ cells was blocked by the anion transport inhibitor DIDS, and partially inhibited by EIPA probably non‐specifically. Recovery of pHi by acidified MZ or DZ cells or those isolated from FD explants was not affected by HCO (P > 0.05). Na+‐dependent HCO‐(NBC) transporters were identified in SZ chondrocytes by fluorescence immunohistochemistry suggesting that this system might account for the HCO‐dependent recovery of pHi. Bovine articular cartilage chondrocytes possess a HCO‐dependent transporter which plays a key role in pHi regulation in cells in the SZ, but not in chondrocytes within deeper cartilage zones. J. Cell. Physiol. 212:600–609, 2007. © 2007 Wiley‐Liss, Inc.
Psychosine‐induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients
Authors: Formichi Patrizia , Radi Elena , Battisti Carla , Pasqui Annalaura , Pompella Gerarda , Lazzerini Pietro Enea , Laghi‐Pasini Franco , Leonini Alessandra , Di Stefano Anna , Federico Antonio
Published: April 2007

Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder caused by galactosylceramidase deficiency. Progressive accumulation of psychosine is considered to be the critical pathogenetic mechanism of cell death in the Krabbe brain. Psychosine mechanism of action has not been fully elucidated. It seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and to up‐regulate inflammatory cytokines production resulting in oligodendrocyte loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and inflammatory response in a group of patients affected by KD using peripheral blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a cellular model. PBLs from KP and healthy controls were exposed to 20 µM psychosine and analysed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy. Our results showed that psychosine induces apoptosis in PBLs through a mitochondrial pathway, but the apoptotic response was quite low especially KP. The role of psychosine in the up‐regulation of cytokines (TNFalpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and controls after stimulation with LPS and phytohemagglutinin. Both in basal condition and after LPS stimulation, cells from KP showed a significant increase in TNF‐α production, reduced MCP1 levels and no modification in IL8. These results indicate that lymphomonocytes from KP had a basal proinflammatory pattern that was amplified by psychosine. In conclusion, the reduced apoptotic response and the atypical cytokine production observed in our experiments, suggest an involvement of inflammatory pattern in immune peripheral cells of KP. J. Cell. Physiol. 212:737–743, 2007. © 2007 Wiley‐Liss, Inc.
Accelerated and safe expansion of human mesenchymal stromal cells in animal serum‐free medium for transplantation and regenerative medicine
Authors: Lange Claudia , Cakiroglu Figen , Spiess Andrej‐Nikolai , Cappallo‐Obermann Heike , Dierlamm Judith , Zander Axel R.
Published: April 2007

Human bone marrow mesenchymal stromal cells (hMSC) are currently investigated for a variety of therapeutic applications. However, most expansion protocols still use fetal calf serum (FCS) as growth factor supplement which is a potential source of undesired xenogeneic pathogens. We established an expansion protocol for hMSC based on the use of GMP‐produced basic medium LP02 supplemented with 5% of platelet lysate (PL) obtained from human thrombocyte concentrates. Compared to FCS‐supplemented culture conditions, we found a significant increase in both colony forming unit‐fibroblast (CFU‐F) as well as cumulative cell numbers after expansion. This accelerated growth is optimized by pooling of at least 10 thrombocyte concentrates. A minimal requirement is the use of 5% of PL with an optimal platelet concentration of 1.5 × 109/ml, and centrifugation of thawed lysate at high speed. Cells expanded by this protocol meet all criteria for mesenchymal stromal cells (MSCs), e.g. plastic adherence, spindle‐shaped morphology, surface marker expression, lack of hematopoietic markers, and differentiation capability into three mesenchymal lineages. MSC at passage 6 were cytogenetically normal and retained their immune‐privileged potential by suppressing allogeneic reaction of T‐cells. Additionally, gene expression profiles show increased mRNA levels of genes involved in cell cycle and DNA replication and downregulation of developmental and differentiation genes, supporting the observation of increased MSC‐expansion in PL‐supplemented medium. In summary, we have established a GMP‐compatible protocol for safe and accelerated expansion of hMSC to be used in cell and tissue therapy. J. Cell. Physiol. 213: 18–26, 2007. © 2007 Wiley‐Liss, Inc.
Morphology of the femoral glands in the lizard Ameiva ameiva (teiidae) and their possible role in semiochemical dispersion
Authors: Imparato Beatriz A. , Antoniazzi Marta M. , Rodrigues Miguel T. , Jared Carlos
Published: April 2007

Many lizards have epidermal glands in the cloacal or femoral region with semiochemical function related to sexual behavior and/or territorial demarcation. Externally, these glands are recognized as a row of pores, opening individually in the center of a modified scale. In many species the pores are used as systematic characters. They form a glandular cord or, in some species, a row of glandular beads below the dermis, and are connected to the exterior through the ducts, which continuously liberate a solid secretion. Dead cells, desquamated from the secretory epithelium, constitute the secretion, known as “a secretion plug.” The present work focusses on the morphology of the femoral glands of the teiid lizard Ameiva ameiva, correlating it to the way in which the secretion is deposited in the environment. The results here obtained are compared to those available for other lizards and amphisbaenians. We observed that the diameter of the glandular pores did not show significant differences between males and females. The glands comprise germinative and secretory cells, which pass through at least three stages of differentiation, during which an accumulation of cytoplasmic granules, with a glycoprotein content, occurs. The cells eventually die and desquamate from the secretory epithelium, forming a secretory plug mostly constituted by juxtaposed nonfragmented secretory cells. Because of the arrangement of the rosette‐like scales surrounding the femoral pores, we suggest that when the animal is in a resting position, with its femoral regions touching the ground, these scales may be involved in the breakage of their respective plugs, depositing tiny portions on the substrate. In this manner, it seems that the method for signal dispersion in this species involves specifically adapted structures and does not simply involve the chance breakage of the plug, as the gland secretes it. Signal dispersion must also be intimately associated with the animal's movement within its territory. J. Morphol., 2007. © 2007 Wiley‐Liss, Inc.
Sperm transfer and reproductive biology in species of hermaphroditic bivalves (Galeommatoidea: Montacutidae)
Authors: Fox Thomas H. , Jespersen Åse , Lützen Jørgen
Published: April 2007

The histology of the reproductive organs is studied in the protandric hermaphroditicTellimya ferruginosa.In NW Europe the species reproduces from May through August. Sperm transfer takes place when mature testis follicles are transplanted to the gills or walls of the mantle cavity in recipient hermaphroditic or female bivalves. Transplantation is accompanied by histological changes and sperm cells are released when transplants perish with age. Details are given on the reproduction inMontacuta percompressawhich takes place from March through October in North Carolina, USA. All shelled bivalves are females and it is postulated that spermatogenic bodies attached to gills or other surfaces in the female's mantle cavity and previously considered to be dwarf males arise from transplanted larval gonads. The ultrastructure of the euspermatozoa and/or the anucleate paraspermatozoa is described inT. ferruginosa, T. tenella,andM. percompressa. The sperm of the first two species share a number of significant apomorphies with those of another montacutid,Brachiomya stigmatica. In the simultaneous hermaphroditicM. substriatathe nucleate paraspermatozoa associate with the euspermatozoa to form spherical spermatozeugmata that are stored in the testis. © 2007 Wiley‐Liss, Inc.
Protective effect of HLA‐B57 on HCV genotype 2 infection in a West African population
Authors: Chuang Wing Chia‐Ming , Sarkodie Francis , Brown Colin J. , Owusu‐Ofori Shirley , Brown Juliette , Li Chengyao , Navarrete Cristina , Klenerman Paul , Allain Jean‐Pierre
Published: April 2007

Recovery from Hepatitis C virus (HCV) infection is considered infrequent (<20%) in western populations but reaches 50% in West Africa where genotype 2 infection is predominant. To investigate the role of cellular immune responses and host genetics in this phenomenon, samples from 104 Ghanaian blood donors reactive with anti‐HCV assays were collected between 2000 and 2005. HCV antibody was confirmed by Western blot using genotype 2 recombinant core, E2 and NS3 proteins. Viral load and genotype were determined. Samples were stratified into 37 chronic, 35 recovered infections and 32 false positive. Eighty‐one percentage of subjects with chronic infection (RNA positive) carried genotype 2 HCV. Cellular immune response was investigated in 35 frozen peripheral blood mononuclear cell (PBMC) samples suitable for interferon‐gamma ELISPOT assay. Twelve out of 24 confirmed recovered, 1 out of 5 chronically infected and none of the 6 false‐positive controls reacted to recombinant proteins. HLA‐A, ‐B and ‐DR types were determined by DNA methodology. HLA‐B*57 was significantly more frequent in the group which had recovered from HCV infection compared with chronically infected subjects (P = 0.0053, OR = 8.02). In conclusion, it is hypothesized that the dominance of genotype 2 HCV strains may be an important factor explaining the high rate of recovery from HCV infections in Ghana via an efficient contribution of HLA‐B*57 which is relatively frequent in the population. J. Med. Virol. 79: 724–733, 2007. © 2007 Wiley‐Liss, Inc.
Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicity
Authors: Nicholls David G. , Johnson‐Cadwell Linda , Vesce Sabino , Jekabsons Mika , Yadava Nagendra
Published: April 2007

The pathologic activation of NMDA receptors by glutamate is a major contributor to neuronal cell death after stroke. Receptor activation causes a massive influx of calcium into the neuron that is accumulated by the mitochondria. The favored hypothesis is that the calcium loaded mitochondria generate reactive oxygen species that damage and ultimately killed the neuron. In this review this hypothesis is critically re‐examined with an emphasis on the role played by deficits in ATP generation. Novel techniques are developed to monitor the bioenergetic status of in situ mitochondria in cultured neurons. Applying these techniques to a model of glutamate excitotoxicity suggests that enhanced reactive oxygen species are a consequence rather than a cause of failed cytoplasmic calcium homeostasis (delayed calcium deregulation, [DCD]), but that prior oxidative damage facilitates DCD by damaging mitochondrial ATP generation. This impacts on current hypotheses relating to the neuroprotective effects of mild mitochondrial uncoupling. © 2007 Wiley‐Liss, Inc.
Regulation of Toll‐like receptor 4 expression and its signaling by hypoxia in cultured microglia
Authors: Ock Jiyeon , Jeong Jaeyoon , Choi Wan Sung , Lee Won‐Ha , Kim Sang‐Hyun , Kim In Kyeom , Suk Kyoungho
Published: April 2007

Hypoxia is an important biological signal that regulates a wide variety of physiological responses. At the same time, hypoxia is involved in multiple pathological situations. In particular, hypoxia is closely associated with neural injury in the brain. Hypoxia has been recently proposed as a neuroinflammatogen, as it can induce the inflammatory activation of microglia, a major cellular source of inflammatory mediators in the brain. In this article, we present evidence that hypoxia enhances Toll‐like receptor 4 (TLR4) expression in cultured microglia and differentially regulates the downstream signaling pathways of TLR4. Hypoxia up‐regulated TLR4 expression at the mRNA and protein levels in a microglia cell line, as well as in primary microglia cultures. Hypoxia, however, differentially regulated MyD88‐dependent and ‐independent pathways of TLR4 signaling: Hypoxia enhanced lipopolysaccharide (LPS)–induced interferon regulatory factor–3 (IRF‐3) activation and the subsequent expression of IFNβ (MyD88‐independent pathway), whereas it suppressed LPS‐induced NF‐κB activation (MyD88‐dependent pathway). Hypoxia did not affect IFNγ signaling, which was represented by signal transducer and activator of transcription–1 (STAT1) activation and interferon‐regulatory factor‐1 (IRF‐1) induction. Taken together, although hypoxia up‐regulates TLR4 expression, its downstream signaling pathways appear to be differentially modulated by hypoxia. © 2007 Wiley‐Liss, Inc.
Effects of elevated temperature and mobile phase composition on a novel C18 silica column
Authors: Lippert J. Andreas , Johnson Todd M. , Lloyd Jarem B. , Smith Jared P. , Johnson Bryce T. , Furlow Jason , Proctor Angela , Marin Stephanie J.
Published: April 2007

A novel polydentate C18 silica column was evaluated at an elevated temperature under acidic, basic, and neutral mobile phase conditions using ACN and methanol as the mobile phase organic modifier. The temperature range was 40–200°C. The mobile phase compositions were from 0 to 80% organic–aqueous v/v and the mobile phase pH levels were between 2 and 12. The maximum operating temperature of the column was affected by the amount and type of organic modifier used in the mobile phase. Under neutral conditions, the column showed good column thermal stability at temperatures ranging between 120 and 200°C in methanol–water and ACN–water solvent systems. At pH 2 and 3, the column performed well up to about 160°C at two fixed ACN–buffer compositions. Under basic conditions at elevated temperatures, the column material deteriorated more quickly, but still remained stable up to 100°C at pH 9 and 60°C at pH 10. The results of this study indicate that this novel C18 silica‐based column represents a significant advancement in RPLC column technology with enhanced thermal and pH stability when compared to traditional bonded phase silica columns.
Separation and evaluation of free radical‐scavenging activity of phenol components of Emblica officinalis extract by using an HPTLC–DPPH• method
Authors: Pozharitskaya Olga N. , Ivanova Svetlana A. , Shikov Alexander N. , Makarov Valery G.
Published: April 2007

A new procedure has been developed to separate and quantify the free radical‐scavenging activity of individual compounds from an Emblica officinalis extract based on the combination of HPTLC with a diode array detector (DAD) and postchromatographic DPPH• radical derivatization. Free gallic and ellagic acids and emblicanins A and B in the E. officinalis extract were separated by TLC and identified. All the compounds of the extract were capable of scavenging of DPPH• radicals. It was established that the DPPH• scavenging activity of emblicanins A and B was 7.86 and 11.20 times more than that of ascorbic acid and 1.25 and 1.78 times more than gallic acid, respectively. From the estimated ID50 values, it can be seen that the increasing order of activity was emblicanin B > emblicanin A > gallic acid > ellagic acid > ascorbic acid. Probably, the antioxidant activity of E. officinalis extract is associated with the presence of hydrolyzable tannins having ascorbic acid‐like action.
HPLC analysis of selected xanthones in mangosteen fruit
Authors: Walker Edward B.
Published: April 2007

Xanthones are unique chemical compounds found in nature, composed of a tricyclic aromatic system with a variety of phenolic, methoxy, and isoprene substituents, giving rise to numerous derivatives. They dissolve to varying degrees in solvents ranging from alcohol to hexane. An optimum solvent mixture of acetone/water (80:20) selectively and effectively extracts a wide variety of xanthones. Subsequent HPLC analysis using standard C‐18 RP and a 30‐min gradient of 65–90% MetOH in 0.1% formic acid detects and separates numerous different xanthones with UV detection at 254 nm. The xanthones alpha‐mangostin, 8‐desoxygartanin, gartanin, beta‐mangostin, 3‐mangostin, and 9‐hydroxycalabaxanthone have been extracted, identified, and quantitatively determined using this method. This analytical method is applied to the analysis of these xanthones in the rind of the mangosteen fruit, Garcinia mangostana.
Fundamental and practical aspects of ultrahigh pressure liquid chromatography for fast separations
Authors: Wu Naijun , Clausen Andrew M.
Published: April 2007

The ongoing development of HPLC has been focused on increasing the speed and efficiency of separations over the past decade. The advances in separation speed have been primarily related to the development of column technology and instrumentation. Relatively short columns packed with sub‐2 μm particles provide high‐speed separations while maintaining or increasing resolution. Ultrahigh pressure pump systems have been developed to overcome the high‐pressure drop generated by such sub‐2 μm packings. In this review, fundamental and practical aspects of ultrahigh pressure or ultrahigh performance liquid chromatography (U‐HPLC) are discussed. Applications of fast U‐HPLC separations are also presented.
Kinetics and dynamics of O + OClO reaction in a modified many‐body expansion potential energy surface for ClO3
Authors: Teixeira O. B. M. , Marques J. M. C. , Varandas A. J. C.
Published: April 2007

The ClO3 many‐body expansion potential energy surface of Farantos and Murrell (Int J Quantum Chem 1978, 14, 659) has been modified along the minimum energy path for the reaction O + OClO → ClO + O2 such as to conform with the available kinetics data. The dynamics of the title reaction is also studied for temperatures of relevance in stratospheric chemistry. Two mechanisms for ClO + O2 formation are identified: (i) direct abstraction of a terminal oxygen atom from the OClO reactant and (ii) formation of an intermediate ClO3 complex followed by dissociation. The novel potential energy surface gives also a good description of the kinetics of the reaction Cl + O3 → ClO + O2. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 422–430, 2007
Generalized k‐linear equations over a finite field
Authors: van Meter Robert G.
Published: April 2007

A generalization of a theorem of A. D. PORTER on the number of solutions of the k‐linear equation over a finite field is given.

AMS Subject Classifications. Primary 1225.
A Note on the Convergence of KAMPÉ DE FÉRIET's Double Hypergeometric Series
Authors: Srivastava H. M. , Daoust Martha C.
Published: April 2007

By using a technique of HORN [4], the authors discuss here the convergence conditions of the double hypergeometric series of the generalized KAMPÉ DE FÉRIET function introduced earlier by them [7]. It is shown that the recent observations of RAGAB [6] would follow fairly easily by suitably specializing the results of the present note. Also the method employed here is appropriately extended to obtain the domain of convergence of the authors' multiple hypergeometric series associated with the generalized LAURICELLA function of several variables [8].
On Δ‐principal directions of a congruence of curves in a FINSLER hypersurface
Authors: Prasad C. M.
Published: April 2007

In the existing literature of FINSLER spaces, it has been stressed [ELIOPOULOS 1959, RUND 1956] that the process of Δ‐differentiation leads to the use of DUPIN's indicatrix in finding out the principal directions at a point of a hypersurface which are indeterminate. The process of Δ‐differentiation [4, 7] requires the use of the osculating DUPIN's indicatrix corresponding to a line‐element of FINSLER hypersurface which leads to the linear eigen value problem and thereby helps in determining the principal directions of a congruence of curves. This fact increases the scope of the theory of FINSLER spaces to a considerable extent. In this paper, therefore, an attempt has been made to find the Δ‐principal directions, generalized EULER's theorem, minimal congruences, Δ‐geodesic principal directions and Δ‐absolute curvature of the congruence with respect of a curve of Fn −1.
LEVINSONtheorem, instabile Eigenwerte und Streuquerschnittmaxima
Authors: Wollenberg M.
Published: April 2007

Mit Hilfe des Begriffs der Spektralverschiebungsfunktion wird eine Verallgemeinerung des aus der Streutheorie bekannten LEVINSONtheorems und eine Beziehung zwischen instabilen Eigenwerten und Maxima im Streuquerschnitt hergeleitet.