bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging‐related alterations in the distribution of Ca2+‐dependent PKC isoforms in rabbit hippocampus
Authors: Van der Zee E.A. , Palm I.F. , O'Connor M. , Maizels E.T. , Hunzicker‐Dunn M. , Disterhoft J.F. 
Published: March 2004

AbstractThe immunocytochemical and subcellular localization of the Ca2+‐dependent protein kinase C (cPKC) isoforms (PKCα, β1, β2, and γ) was examined in rabbit hippocampus of young (3 months of age; n = 11) and aging (36 months of age; n = 14) subjects. Detailed immunocytochemical analyses revealed a significant increase in PKCβ1, β2, and γ immunoreactivity in principal cell bodies and associated dendrites, and interneurons of the hilar region in the aging rabbits. The number of PKCα‐ and γ‐positive interneurons in the aging stratum oriens declined significantly. PKCα was least affected in principal cells, showing an increase in immunostaining in granule cells only. Weakly PKC‐positive principal cells intermingled between densely stained ones were seen in parts of the hippocampus in most of the aging rabbits, showing that the degree of aging‐related alterations in PKC‐immunoreactivity varies between neurons. Changes in PKC expression in the molecular and subgranular layer of the aging dentate gyrus suggested a reorganization of PKC‐positive afferents to this region. Western blot analysis revealed a significant loss of PKC in the pellet fraction for all isoforms, and a tendency for increased levels of cytosolic PKC. However, no significant changes were found in total PKC content for any PKC isoform. A concurrent dramatic loss of the PKC anchoring protein receptor for activated C kinase (RACK1) in the pellet fraction was shown by Western blotting. These findings suggest that the loss of RACK1 contributes to the dysregulation of the PKC system in the aging rabbit hippocampus. The enhanced PKC‐immunoreactivity might relate to reduced protein‐protein interactions of PKC with the anchoring protein RACK1 leading to increased access of the antibodies to the antigenic site. In conclusion, the results suggest that memory deficits in aging rabbits are (in part) caused by dysregulation of subcellular PKC localization in hippocampal neurons. © 2004 Wiley‐Liss, Inc.
Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both?
Authors: Latour Patrick , Biraben Arnaud , Polard Elisabeth , Bentué‐Ferrer Danièle , Beauplet Anne , Tribut Olivier , Allain Hervé 
Published: March 2004

AbstractSix severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1) a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2) a pharmacodynamic mechanism due to a direct toxicity of TPM in at‐risk epileptic patients. Copyright © 2004 John Wiley & Sons, Ltd.
Combination of mood stabilizers with quetiapine for treatment of acute bipolar disorder: an open label study
Authors: Bahk Won‐Myong , Yoon Bo‐Hyun , Lee Kyoung‐Uk , Chae Jeong‐Ho 
Published: March 2004

AbstractObjectivesThe atypical antipsychotics are being increasingly used to control acute manic episodes, and data are emerging to support their mood‐stabilizing and antidepressant properties. This study investigated the short‐term efficacy of quetiapine as an add‐on therapy in the treatment of acute mania.MethodThis study was a 4‐week, open‐label, add‐on, prospective investigation using quetiapine in addition to mood stabilizers. Data on 18 patients fulfilling DSM‐IV diagnostic criteria for bipolar I disorder were analysed. The Young mania rating scale (YMRS), the Hamilton scale for depression (HDRS), the brief psychiatric rating scale (BPRS) and extrapyramidal symptom rating scale (ESRS) were applied at baseline and at weeks 1, 2 and 4. The clinical global impression scale (CGI) was evaluated at baseline and week 4.ResultsThe addition of quetiapine produced a statistically significant improvement on the YMRS, HDRS, BPRS and CGI score at week 4 from baseline (p<0.005). Quetiapine was well tolerated, with no subjects discontinuing because of side effects.ConclusionsThe combination of quetiapine was associated with a substantial symptomatic improvement in patients with acute mania. Randomized placebo‐controlled prospective studies are needed. Copyright © 2004 John Wiley & Sons, Ltd.
Ziprasidone‐related neuroleptic malignant syndrome in a patient with Parkinson's disease: a diagnostic challenge
Authors: Gray Nicola S. 
Published: March 2004

AbstractA case of neuroleptic malignant syndrome (NMS) in a patient with Parkinson's disease (PD) is presented. The syndrome was precipitated by the atypical antipsychotic, ziprasidone. The challenge of recognizing NMS in a patient with underlying parkinsonian symptoms, where prominent symptom overlap can occur, is discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Ex vivo generation and expansion of anti‐tumor cytotoxic T‐cell lines derived from patients or their HLA‐identical sibling
Authors: Montagna Daniela , Schiavo Roberta , Gibelli Nadia , Pedrazzoli Paolo , Tonelli Roberto , Pagani Sara , Assirelli Elisa , Locatelli Franco , Pession Andrea , Fregoni Vittorio , Montini Elisa , Da Prada Gian Antonio , Siena Salvatore , Maccario Rita 
Published: March 2004

AbstractSuccessful ex‐vivo priming and long‐term maintenance of anti‐tumor cytotoxic T‐cell (CTL) lines are preliminary conditions for their use in approaches of adoptive immunotherapy for patients with cancer. We describe the results of a novel procedure for generating in vitro anti‐tumor CTL using CD8‐enriched peripheral blood mononuclear cells (PBMC) and dendritic cells (DC), pulsed with irradiated tumor cells (TC) as source of tumor antigen. Eight patients were enrolled in our study: 4 sarcoma, 2 renal cell carcinoma, 1 ovarian carcinoma and 1 breast carcinoma. Ten anti‐tumor CTL‐lines cytotoxic towards patient TC were generated. Five CTL‐lines were obtained using both DC and PBMC from the patients (autologous setting). For 5 CTL‐lines, DC derived from an HLA‐identical sibling were employed (allogeneic setting): patients or siblings PBMC were used to generate CTL‐lines in 2 and 3 cases, respectively,. After tumor‐specific rounds of stimulation, followed by antigen‐independent cycle of expansion, CTL‐lines obtained in both autologous and allogeneic setting showed an expansion of the absolute number of cultured cells. In 6 of 10 CTL‐lines, the majority of effector cells (>70%) were CD3+/CD8+, while in the remaining 4, 40–70% of effector cells were CD3+/CD4+. Both CD8+ and CD4+ T cells displayed anti‐tumor cytotoxic activity. Spectratyping analysis of the TCR‐Vβ subfamilies revealed a preferential expansion of oligoclonal populations in 18 of 24Vβ subfamily. Altogether these results demonstrate that our experimental approach is suitable for efficiently generating and expanding anti‐solid tumor CTL to be used for adoptive immunotherapy. © 2004 Wiley‐Liss, Inc.
Bikunin plus paclitaxel markedly reduces tumor burden and ascites in mouse model of ovarian cancer
Authors: Kobayashi Hiroshi , Yagyu Tatsuo , Inagaki Kiyokazu , Kondo Toshiharu , Suzuki Mika , Kanayama Naohiro , Terao Toshihiko 
Published: March 2004

AbstractOur previous studies of intraperitoneal ovarian carcinoma in a mouse model demonstrated that bikunin gene transfection could prevent ascites formation and intraperitoneal disseminated metastasis. Although ascites was almost completely inhibited, tumor burden was variably reduced. Several reports have indicated that bikunin may be involved in tumor survival. In the present study, the effectiveness of exogenous bikunin and the biodistribution characteristics of 125I‐bikunin were initially examined in a mouse model of human ovarian cancer HRA cells. The once‐daily i.p. administration of bikunin significantly decreased progressive growth of HRA tumors and ascites formation in a dose‐dependent manner. Maximal radioisotope tumor uptake peaked at 7.4% injected dose/g at 3 hr. Bikunin binding specificity was demonstrated by reduced tumor uptake after coinjection of excess nonradioactive bikunin. Bikunin was rapidly excreted renally. The bikunin therapy produced the significant inhibition in expression of the proteolysis (uPA and uPAR) and angiogenesis‐related molecules (VEGF and bFGF). The second purpose of our study was to optimize the antimetastatic activity of bikunin in combination with paclitaxel against HRA cells growing orthotopically in mice. The once‐daily i.p. administration of bikunin (25 μg/g body weight/day) in combination with paclitaxel (i.p., 100 μg/20 g at days 2 and 5) significantly decreased progressive growth of HRA cells in a synergistic fashion. In conclusion, combination therapy with bikunin plus paclitaxel may be an effective way to markedly reduce i.p. tumor growth and ascites in ovarian carcinoma possibly through suppression of uPA, uPAR, VEGF and bFGF expression. © 2004 Wiley‐Liss, Inc.
Nanoindentation of soft hydrated materials for application to vascular tissues
Authors: Ebenstein D. M. , Pruitt L. A. 
Published: March 2004

AbstractSoft hydrated materials, such as vascular tissues and other biomaterials, provide a number of challenges in the field of nanoindentation. However, the ability of nanoindentation to probe local, nanoscale mechanical properties of heterogeneous materials makes it desirable to adapt this technique for application to biologic tissues. To develop the field of nanoindentation for the analysis of soft hydrated materials, the goals of this study were fourfold: develop a sample hydration system, select an appropriate tip for soft material indentation, identify a substrate to be used for blunt tip alignment, and determine an appropriate control material for the development of future indentation protocols. A hydration system was developed that maintained sample hydration for over 8 h without completely submerging the sample. Further, a 100‐μm radius of curvature conospherical tip was shown to be a suitable tip for indenting a variety of soft hydrated materials and back‐illuminated agarose gel was found to be an effective material for use in tip alignment. Finally, agarose gel demonstrated similar qualitative and quantitative nanomechanical behavior to vascular tissue, suggesting that it will be an appropriate control material for the development of future indentation protocols for soft biologic tissues. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 222–232, 2004
Self‐hardening calcium phosphate cement–mesh composite: Reinforcement, macropores, and cell response
Authors: Xu Hockin H. K. , Simon Carl G. 
Published: March 2004

AbstractCalcium phosphate cement (CPC) self‐hardens to form hydroxyapatite, has excellent osteoconductivity and bone‐replacement ability, and is promising for craniofacial and orthopedic repair. However, its low strength limits CPC to only nonstress repairs. This study aimed to reinforce CPC with meshes to increase strength, and to form macropores in CPC for bone ingrowth after mesh dissolution. A related aim was to evaluate the biocompatibility of the new CPC–mesh composite. Absorbable polyglactin meshes, a copolymer of poly(glycolic) and poly(lactic) acids, were incorporated into CPC to provide strength and then form interconnected cylindrical macropores suitable for vascular ingrowth. The composite flexural strength, work‐of‐fracture, and elastic modulus were measured as a function of the number of mesh sheets in CPC ranging from 1 (a mesh on the tensile side of the specimen) up to 13 (mesh sheets throughout the entire specimen), and as a function of immersion time in a physiological solution from 1 to 84 days. Cell culture was performed with osteoblast‐like cells and the cell viability was quantified using an enzymatic assay. The strengths (mean ± SD; n = 6) of CPC containing 13 or 6 meshes were 24.5 ± 7.8 and 19.7 ± 4.3 MPa, respectively, not significantly different from each other; both were significantly higher than 8.8 ± 1.9 MPa of CPC without mesh (Tukey's at 0.95). The work‐of‐fracture of CPC with 13 or 6 meshes was 3.35 ± 0.80 and 2.95 ± 0.58 kJ/m2, respectively, two orders of magnitude higher than 0.021 ± 0.006 kJ/m2 of CPC without mesh. Interconnected macropores were formed in CPC at 84 days' immersion. The new CPC–mesh formulation supported the adhesion, spreading, proliferation, and viability of osteoblast‐like cells in vitro. In conclusion, absorbable meshes in CPC increased the implant strength by three‐fold and work‐of‐fracture by 150 times; interconnected macropores suitable for bone ingrowth were created in CPC after mesh dissolution. The higher strength may help extend the use of CPC to larger stress‐bearing repairs, and the macropores may facilitate tissue ingrowth and integration of CPC with adjacent bone. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 267–278, 2004
Micro‐Raman spectroscopic investigation of dental calcified tissues
Authors: Schulze K. A. , Balooch M. , Balooch G. , Marshall G. W. , Marshall S. J. 
Published: March 2004

AbstractThe purpose of this study was to determine if dental calcified junctions (DEJs/CDJs) in human teeth contain different compositional phases compared to the adjacent dental calcified tissues. Peak positions and intensities were determined from micro‐Raman spectra for PO and the CH modes and compared among the mineralized tissues and their junctions. Values of width were determined from the intersections of intensity regression lines through the junctions and in the adjacent tissues. The peaks were measured in 1‐μm steps along a l00‐μm line across the junction. High‐resolution analysis revealed that PO band peaks for dentin, the DEJ, enamel, the CDJ, and cementum were at the same position (959 cm−1), while for the CH stretching mode a significant shift of 4.6 cm−1 was found between enamel, the DEJ, and dentin. The mean width of the DEJ was 7.6 (± 2.8) μm using the PO band and 8.6 (± 3.6) μm using the CH stretching mode. Across the DEJ, the mineral content monotonically decreased from enamel to dentin while the organic component monotonically increased. The DEJ width was in agreement with prior nanoindentation studies. No width estimate was possible for the CDJ because the compositional differences between cementum and dentin were small. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 286–293, 2004
Evaluation of thermoreversible polymers containing fibroblast growth factor 9 (FGF‐9) for chondrocyte culture
Authors: Au Angela , Polotsky Anna , Krzyminski Karol , Gutowska Anna , Hungerford David S. , Frondoza Carmelita G. 
Published: March 2004

AbstractWe previously evaluated a thermoreversible polymer gel composed of N‐isopropylacrylamide and acrylic acid as a cell culture substrate and cell‐delivery vehicle. The copolymer promoted phenotype expression and amplification of chondrocytes. In this study, we determined whether addition of fibroblast growth factor 9 (FGF‐9), which is mitogenic for chondrocytes, would further enhance cell proliferation and phenotype expression in the polymer. We tested the hypothesis that the thermoreversible polymer containing FGF‐9 would promote increased chondrocyte proliferation and phenotype expression. Articular chondrocytes (1 × 105/150 μL) were plated onto control (without gel) and gel containing 24‐well plates. The gels were prepared in media alone or in media containing heparin (100 μg/mL) and FGF‐9 (5 μg/mL). The cultures were incubated at 37°C in 5% CO2 for 3 days. Cells remained viable in the thermoreversible polymer in the presence or absence of FGF‐9. Addition of FGF‐9 to the copolymer did not induce proliferation and the cell numbers did not increase. Reverse transcription polymerase chain reaction (RT‐PCR)‐determined expression of chondrocyte markers collagen type II and aggrecan. FGF‐9 did not enhance chondrocyte proliferation nor alter the phenotype after 3 days in culture. These findings suggest the poly(NiPA‐co‐AAc) gel alone may provide the optimal 3D environment for propagation of chondrocytes. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 367–372, 2004
Wheat germ lectin induces G2/M arrest in mouse L929 fibroblasts
Authors: Liu W.K. , Sze S.C.W. , Ho J.C.K. , Liu B.P.L. , Yu M.C. 
Published: March 2004

AbstractWheat germ lectin (WGA) is a cytotoxic lectin for many cell lines [Wang et al., 2000], but its underlying mechanism is not clear. In this report, we found that incubation of synchronized mouse L929 fibroblasts with WGA resulted in a dose‐dependent reduction of intracellular incorporation of 3H‐thymidine and MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide)‐conversion activity (IC50 ≅ 0.4 μM). Fluorescein‐conjugated WGA was demonstrated to transport from the cell surface into the paranuclear region of cultured L929 cells within 30 min, and subsequently evoked lipid peroxidation of plasma membrane and vacuolation in the cytoplasm of these cells. Studies with tritiated thymidine incorporation, immunofluorescence microscopy, immunoblotting analysis and flow cytometry revealed that WGA inhibited cell cycle progression after one replication, resulting in G2/M arrest and alteration of cell cycle regulatory proteins, particularly activation of p21Cip1/WAF1 and suppression of cyclin B and cdc 2. Although there was an increase of cytosolic caspase 3 and bax protein expression, no apoptotic bodies were observed by both fluorescence and transmission electron microscopy. These results suggest that WGA arrested L929 proliferation after one cell cycle in the G2/M phase through activation of the p21Cip1/WAF1 and suppression of Cyclin B–Cdc2. © 2004 Wiley‐Liss, Inc.
Vascular progenitors derived from murine bone marrow stromal cells are regulated by fibroblast growth factor and are avidly recruited by vascularizing tumors
Authors: Annabi Borhane , Naud Emmanuelle , Lee Ying‐Ta , Eliopoulos Nicoletta , Galipeau Jacques 
Published: March 2004

AbstractBone marrow‐derived stromal cells (BMSC) possess a population of vascular progenitor cells that enable them to acquire a histology and immunophenotype coherent with endothelial cells (EC). Recent evidence indicates that a hypoxic environment such as that encountered in tumor masses regulates BMSC angiogenic properties by pathways that remain to be defined. It is also unclear as to what extent these marrow‐derived precursor cells could contribute to the growth of endothelium‐lined vessels at the vicinity of tumor masses. In this study, we found that BMSC exhibited the ability to generate three‐dimensional capillary‐like networks on Matrigel, and that this property was up‐regulated by growth factors‐enriched conditioned media isolated from several tumor‐derived cell lines. In particular, basic fibroblast growth factor, a key mediator of angiogenesis, was found to be the most potent growth factor for inducing BMSC proliferation, migration, and tubulogenesis. The setup of a new two‐dimensional in vitro co‐culture assay further showed that BMSC were massively recruited when cultured in the presence of either cancerous or differentiated EC lines. In vivo, subcutaneous co‐injection of BMSC with U‐87 glioma cells in nude mice resulted in the formation of highly vascularized tumors, where BMSC differentiated into CD31‐positive cells and localized at the lumen of vascular structures. Our data suggest that BMSC could be recruited at the sites of active tumor neovascularization through paracrine regulation of their angiogenic properties. These observations may have crucial implications in the development of novel therapies using BMSC engineered to secrete anti‐cancerous agents and to antagonize tumor progression. © 2004 Wiley‐Liss, Inc.
Role of protein kinase C in arginine vasopressin‐stimulated ERK and p70S6 kinase phosphorylation
Authors: Ghosh Paramita M. , Bedolla Roble , Thomas Charles A. , Kreisberg Jeffrey I. 
Published: March 2004

AbstractWe previously showed in rat renal glomerular mesangial cells, that arginine vasopressin (AVP)‐stimulated cell proliferation was mediated by epidermal growth factor receptor (EGF‐R) transactivation, and activation (phosphorylation) of ERK1/2 and p70S6 kinase (Ghosh et al. [2001]: Am J Physiol Renal Physiol 280:F972–F979]. In this paper, we extend these observations and show that different protein kinase C (PKC) isoforms play different roles in mediating AVP‐stimulated ERK1/2 and p70S6 kinase phosphorylation and cell proliferation. AVP treatment for 0–60 min stimulated the serine/threonine phosphorylation of PKC isoforms α, δ, ε, and ζ. The activation of PKC was dependent on EGF‐R and phosphatidylinositol 3‐kinase (PI3K) activation. In addition, inhibition of conventional and novel PKC isoforms by chronic (24 h) exposure to phorbol 12‐myristate 13‐acetate (PMA) inhibited AVP‐induced activation of ERK and p70S6 kinase as well as EGF‐R phosphorylation. Rottlerin, a specific inhibitor of PKCδ, inhibited both ERK and p70S6 kinase phosphorylation and cell proliferation. In contrast, a PKCε translocation inhibitor decreased ERK1/2 activation without affecting p70S6 kinase or cell proliferation, while a dominant negative PKCζ (K281W) cDNA delayed p70S6 kinase activation without affecting ERK1/2. On the other hand, Gö6976, an inhibitor of conventional PKC isoforms, did not affect p70S6 kinase, but stimulated ERK1/2 phosphorylation without affecting cell proliferation. Our results indicate that PKCδ plays an important role in AVP‐stimulated ERK and p70S6 kinase activation and cell proliferation. © 2004 Wiley‐Liss, Inc.