bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of vertical scanning interferometry as a novel method for acquiring chondrocyte geometry
Authors: Scott C. Corey , Luttge Andreas , Athanasiou Kyriacos A. 
Published: November 2004

AbstractChondrocytes are sensitive to changes in shape which depend on the type of substrate, mechanical factors, or biochemical stimuli. Shape changes can cause metabolic and phenotypic alterations. Cell geometry is also important for mechanical models, determination of mechanical properties, and the study of cell attachment and spreading. In this study, a novel method called vertical scanning interferometry (VSI) was developed to allow rapid and straightforward determination of the height, diameter, surface area, volume, and curvature of single chondrocytes. The dimensions of single chondrocytes at 4 and 18 h were obtained and validated. Differences in the heights of zonal chondrocytes were found to be statistically significant. This method was also used to capture the geometry of a cell dehydrating as it was exposed to air. VSI has advantages over confocal microscopy and atomic force microscopy in terms of speed, ease of use, field of view, and precision. VSI quickly obtains and graphically represents the three‐dimensional geometry of chondrocytes in a simple format. These methods could be expanded to image many types of cells on various biomaterials to assess biocompatibility and attachment and cell spreading characteristics. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 83–90, 2005
Proliferation, activity, and osteogenic differentiation of bone marrow stromal cells cultured on calcium titanium phosphate microspheres
Authors: Barrias Cristina C. , Ribeiro Cristina C. , Lamghari Meriem , Miranda Clara Sá , Barbosa Mário A. 
Published: November 2004

AbstractIn this study, the behavior of bone marrow stromal cells cultured on calcium titanium phosphate (CTP) microspheres was analyzed. Cell adhesion and proliferation were estimated by the neutral red assay and by total DNA quantification. Morphology and deposition of extracellular matrix were assessed by confocal laser scanning microscopy and/or scanning electron microscopy. The expression of the osteoblastic phenotype was evaluated by monitoring alkaline phosphatase activity and osteocalcin secretion. Results revealed that cells were able to attach and spread on the surface of CTP microspheres, and gradually grow into nearly confluent monolayers. Moreover, cells were able to bridge adjacent microspheres forming microsphere–cell clusters. Cells produced an abundant amount of fibrillar extracellular matrix that covered the substrate surface. Alkaline phosphatase activity peaked around days 7–14 and then decreased until day 21. Cells secreted osteocalcin, with higher levels being detected at day 14 than at day 21. Taken together, these results suggest that CTP microspheres are appropriate scaffolds for the growth and differentiation of cells along the osteoblastic lineage. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 57–66, 2005
Extended release of a novel antidepressant, venlafaxine, based on anionic polyamidoamine dendrimers and poly(ethylene glycol)‐containing semi‐interpenetrating networks
Authors: Yang Hu , Lopina Stephanie T. 
Published: November 2004

AbstractThe multiple daily administration of venlafaxine, a novel third‐generation antidepressant, was reduced based on polyamidoamine and polyethylene glycol (PEG)‐containing semi‐interpenetrating network (IPN), respectively. Venlafaxine was covalently linked to water‐soluble G2.5 anionic polyamidoamine dendrimer via a hydrolyzable ester bond. Semi‐IPN hydrogels were prepared by crosslinking acrylamide in the presence of PEG, and venlafaxine with predetermined amounts was loaded in situ. Dendrimer–venlafaxine conjugate and semi‐IPNs were characterized by proton nuclear magnetic resonance and Fourier transform infrared, respectively. The effect of PEG concentration and molecular weight was studied and discussed for an optimal controlled release. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 107–114, 2005
Up‐regulation of the association between heat shock protein 90 and endothelial nitric oxide synthase prevents high glucose‐induced apoptosis in human endothelial cells
Authors: Lin Lian‐Yu , Lin Chien‐Yu , Ho Fong‐Ming , Liau Chiau S. 
Published: November 2004

AbstractHyperglycemia is the hallmark of diabetes mellitus. Poor glycemic control is correlated with increased cardiovascular morbidity and mortality. High glucose can trigger endothelial cell apoptosis by de‐activation of endothelial nitric oxide synthase (eNOS). eNOS was recently demonstrated to be extensively regulated by Akt and heat shock protein 90 (HSP90). Yet, little is known about the molecular mechanisms that regulate eNOS activity during high glucose exposure. The present study was designed to determine the involvement of protein interactions between eNOS and HSP90 in high glucose‐induced endothelial cell apoptosis. The protein interaction of eNOS/HSP90 and eNOS/Akt were studied in cultured human umbilical vein endothelial cells (HUVECs) exposed to either control‐level (5.5 mM) or high‐level (33 mM) glucose for different durations (2, 4, 6, and 24 h). The results showed that the protein interactions between eNOS and HSP90 and between eNOS and Akt and the phosphorylation of eNOS were up‐regulated by high glucose exposure for 2–4 h. With longer exposures, these effects decreased gradually. During early hours of exposure, the protein interactions of eNOS/HSP90 and eNOS/Akt and the phosphorylation of eNOS were all inhibited by geldanamycin, an HSP90 inhibitor. High glucose‐induced endothelial cell apoptosis was also enhanced by geldanamycin and was reversed by NO donors. LY294002, a phosphatidylinositol 3 (PI3) kinase inhibitor, inhibited the association of eNOS/Akt and the phosphorylation of eNOS but had no effect on the interaction between eNOS and HSP90 during early hours of exposure. From our results we propose that, in HUVECs, during early phase of high glucose exposure, apoptosis can be prevented by enhancement of eNOS activity through augmentation of the protein interaction between eNOS and HSP90 and recruitment of the activated Akt. With longer exposure, dysregulation of eNOS activity would result in apoptosis. The present study provides a molecular basis for the effects of eNOS in the prevention of endothelial cells apoptosis during early phase of high glucose exposure. These observations may contribute to the understanding of the pathogenesis of vascular complications in diabetes mellitus. © 2004 Wiley‐Liss, Inc.
Deregulation of DNA methyltransferases and loss of parental methylation at the insulin‐like growth factor II (Igf2)/H19 loci in p53 knockout mice prior to tumor development
Authors: Park In Young , Sohn Bo Hwa , Choo Jung Ha , Joe Cheol O. , Seong Je Kyung , Lee Young Ik , Chung Jae Hoon 
Published: November 2004

AbstractTo ascertain whether p53 deficiency in vivo leads to the deregulation of DNA methylation machinery prior to tumor development, we investigated the expression profile of DNA methyltransferases in the thymus and the liver of p53+/+, p53+/−, and p53−/− mice at 7 weeks of age before tumor development. The expression of DNA methyltransferases was examined in the thymus at 7 weeks of age, since the malignant T‐cell lymphoma develops most frequently in p53−/− mice around 20 weeks of age. Both mRNA and protein levels of Dnmt1 and Dnmt3b were increased in the thymus and the liver of p53‐deficient mice. The expression of Dnmt3a was also increased in the liver but not in the thymus of p53‐deficient mice. Dnmt3L expression was reduced in the thymus of p53+/− and p53−/− mice. The total 5‐methylcytosine (5‐MeC) in the genomic DNA of p53+/+, p53+/−, and p53−/− mice was quantitated by dot‐blot using antibody against 5‐MeC. Global methylation was increased in the thymus and the liver of p53‐deficient mice. To correlate the deregulated expression of DNA methyltransferases with the disturbance of the epigenetic integrity, we examined the DNA methylation of the imprinting control region (ICR) at the insulin‐like growth factor II (Igf2)/H19 loci in the thymus and the liver of p53+/+, p53+/−, and p53−/− mice. The region containing two CCCTC binding factor (CTCF) binding sites in the 5′‐ICR tended to be hypomethylated in the thymus of p53−/− mice, but not in the liver. The expression profile of Igf2 and H19 indicated that the thymus‐specific changes of Igf2 and H19 expression were coherent to the hypomethylation of the ICR in the thymus. Our results suggest that p53 is required for the maintenance of DNA methylation patterns in vivo. © 2004 Wiley‐Liss, Inc.
Co‐localization of poly(ADPR)polymerase 1 (PARP‐1) poly(ADPR)polymerase 2 (PARP‐2) and related proteins in rat testis nuclear matrix defined by chemical cross‐linking
Authors: Tramontano Filomena , Di Meglio Silvia , Quesada Piera 
Published: November 2004

AbstractPoly(ADPR)polymerase 1 and 2 (PARP‐1, PARP‐2) are nuclear enzymes which function is based on specific interactions with DNA and nuclear proteins. PARPs targets include proteins involved in DNA replication, repair, and transcription and their function can be modulated either by protein–protein interaction with native PARP‐1 and by non‐covalent interaction with poly(ADP‐ribose) (pADPR) linked to the auto‐modified PARP‐1. Moreover, the association of pADPR and PARP‐1 with the nuclear matrix (NM) has been reported, based on the poly(ADP‐ribosyl)ation of nuclear matrix proteins (NMPs). In the present article, by the use of DNA and protein cross‐linking reactions, by cis‐diamminedichloroplatinum II (cDDP) and sodium tetrathionate (NaTT) respectively, we present more evidences about the association of PARP‐1, PARP‐2, and PARPs related proteins with the NM. Our findings confirmed that NM could be seen as a fraction greatly enriched in transcription factors (i.e., C/EBP‐β) and enzymes (DNA Topo II, DNA PK) that co‐localize with PARP‐1 and ‐2 at the matrix associated regions (MARs) of chromatin. Moreover, pADPR contributes to PARP‐1 localization at the NM, showing that PARP(s) activity co‐operates to the functions of this nuclear fraction. © 2004 Wiley‐Liss, Inc.
Osteoblasts lacking the vitamin D receptor display enhanced osteogenic potential in vitro
Authors: Sooy Karen , Sabbagh Yves , Demay Marie B. 
Published: November 2004

Abstract1,25‐Dihydroxyvitamin D plays an important role in the regulation of osteoblast gene expression, regulating the expression of bone matrix proteins as well as that of Runx2, a key regulator of osteoblast differentiation. Studies in mice lacking the vitamin D receptor (VDR) have revealed that the actions of the VDR on the skeleton are not required in the setting of normal mineral ion homeostasis. Since paracrine and endocrine factors can compensate for gene defects in vivo, studies were performed to determine whether ablation of the VDR alters the program of osteoblast differentiation in vitro. Studies in primary calvarial cultures revealed that ablation of the VDR enhanced osteoblast differentiation. The cells from the VDR null mice exhibited an earlier onset and increased magnitude of alkaline phosphatase activity, as well as an earlier and sustained increase in mineralized matrix formation, demonstrating that this enhancement persists throughout the program of osteoblast differentiation. The expression of bone sialoprotein, which enhances mineralization, was also increased in the VDR null cultures. To determine whether the increase in osteoblast differentiation was associated with an increase in the number of osteogenic progenitors, the number of osteoblastic colony forming units (CFU‐OB) was evaluated. There was a twofold increase in the number of CFU‐OB in the cultures isolated from the VDR null mice. Furthermore, the VDR null CFU‐OB demonstrated an earlier onset and higher magnitude of expression of alkaline phosphatase activity when compared to the CFU‐OB from their wild‐type control littermates. These studies demonstrate that the VDR attenuates osteoblast differentiation in vitro and suggest that other endocrine and paracrine factors modulate the effect of the VDR on osteoblast differentiation in vivo. © 2004 Wiley‐Liss, Inc.
HHV‐6 and 7 DNA loads in lung tissues collected from patients with interstitial pneumonia
Authors: Yamamoto Keizo , Yoshikawa Tetsushi , Okamoto Souki , Yamaki Kenichi , Shimokata Kaoru , Nishiyama Yukihiro 
Published: November 2004

AbstractThe aim of this study is to determine whether human herpesvirus 6 (HHV‐6) and HHV‐7 might play an important role in causing interstitial pneumonia in patients who have not undergone transplantation. HHV‐6 and HHV‐7 DNAs were quantitated by real‐time polymerase chain reaction (PCR) in paraffin embedded lung tissues collected from 24 patients having the disease. Control tissues (without fibrosis) were also collected from 19 of the 24 patients. Statistical analysis was carried out by the Wilcoxon signed rank test or the Mann–Whitney U‐test. HHV‐6 DNA was detected in 3 (12.5%) of the 24 target tissues and 3 (15.8%) of the 19 control tissues, respectively. In contrast, HHV‐7 DNA was detected in 19 (79.2%) of the 24 target tissues and 11 (57.9%) of the 19 control tissues. Neither HHV‐6 DNA load (P = 0.6395) nor HHV‐7 DNA load (P = 0.5966) in target tissues differed between males and females. Neither HHV‐6 DNA load (P = 0.9589) nor HHV‐7 DNA load (P = 0.7419) in target tissues differed between cases with and without underlying collagen disease. While HHV‐6 DNA load did not differ between the target and control tissues (P > 0.9999), the HHV‐7 DNA load was significantly higher in the target tissue than in the control tissue (P = 0.0298). This study suggests that HHV‐7 may play an important role in causing interstitial pneumonia in patients who are not transplant recipients. J. Med. Virol. 75:70–75, 2005. © 2005 Wiley‐Liss, Inc.
Laboratory diagnosis and surveillance of human respiratory viruses by PCR in Victoria, Australia, 2002–2003
Authors: Druce Julian , Tran Thomas , Kelly Heath , Kaye Matthew , Chibo Doris , Kostecki Renata , Amiri Abdul , Catton Mike , Birch Chris 
Published: November 2004

AbstractRespiratory viruses were identified by the polymerase chain reaction (PCR) in more than 4,200 specimens collected during 2002 and 2003 in Victoria, Australia from patients admitted to hospitals or participating in an influenza surveillance program. Influenza viruses and picornaviruses were important causes of morbidity in both years. Additional testing of picornavirus‐positive samples suggested that rhinoviruses but not enteroviruses were more likely to be associated with respiratory symptoms, irrespective of the season in which they circulated. Detection of influenza viruses was strongly associated with the clinical symptoms of cough, fever, and fatigue; but each of the other respiratory viruses occasionally caused these symptoms or was responsible for symptoms severe enough to require hospitalization. Human coronaviruses HCoV‐OC43 and HCoV‐229E circulated at low levels throughout the study period with peak activity in winter, but overall did not circulate as widely as has often been reported for these agents. Evidence for the human metapneumovirus (hMPV) was only sought in the second year of the study and revealed low‐level circulation of this virus, mainly in the cooler months among the very young and adult populations. The detection rate of all viruses declined with increasing age of the patient, particularly in hospital patients. Infection with more than one respiratory virus occurred in a small number of patients; picornaviruses were most commonly implicated in these dual infections. J. Med. Virol. 75:122–129, 2005. © 2005 Wiley‐Liss, Inc.
Measles virus genotype circulation in Spain after implementation of the national measles elimination plan 2001–2003
Authors: Mosquera María Mar , Ory Fernando de , Echevarría Juan Emilio ,   The Network of Laboratories in the Spanish National Measles Elimination Plan
Published: November 2004

AbstractMolecular characterization of measles virus is important for disease surveillance and for monitoring elimination of the virus throughout the world. Furthermore, knowledge of genotype distribution in as many countries as possible, is useful for tracing the origin of a strain, especially in countries without endemic measles disease, where most cases are imported. Data on genotypes circulating in Spain from 1970 to 1997 showed the prevalence of genotypes C1, C2, and D6, with subsequent replacement of each other. After the establishment of the Spanish Measles Elimination Plan, genotyping with a new retrotranscriptase polymerase chain reaction (RT‐PCR) was undertaken directly on 92 specimens, corresponding to 90 patients, which were positive for measles by a different diagnostic RT‐PCR. Genotypes B3, D4, D8, A, C2, H1, and D7 were found in different autonomous communities (Madrid, Balearic Islands, Valencia Community, Extremadura, Andalusia, Canary Islands and Murcia) between 2001 and 2003 with none of these genotypes being prevalent. After the introduction of the vaccine in 1978, the incidence of the disease decreased from 150,000 cases in 1977 to 64 in 2002. This could be the reason for the change observed in the pattern of measles genotype circulation, since this pattern was reported in countries at an advanced stage of eradication of measles. This report considers that Spain is on the way to eradicating measles. J. Med. Virol. 75:137–146, 2005. © 2005 Wiley‐Liss, Inc.
ADAM23 is a cell‐surface glycoprotein expressed by central nervous system neurons
Authors: Goldsmith Alexander P. , Gossage Samuel J. , ffrench‐Constant Charles 
Published: November 2004

AbstractSeveral members of the ADAM (a disintegrin and metalloprotease) family of proteins have been implicated in biological processes ranging from fertilization to myoblast fusion and neural cell fate determination. These proteins have so far been studied mostly in terms of their protease activity, but a considerable amount of evidence suggests that many ADAMs are also important as receptors for cell‐surface integrins. We have shown that, for one such member of the family, ADAM23, mRNA transcripts are expressed in neuronal cells throughout the rat brain, at all stages of postnatal development, and that particularly high transcript concentrations are found in the hippocampus and cerebellum. Using an antibody that we raised against the rat ADAM23 disintegrin domain, we found that ADAM23 is present at detectable levels only in nervous system tissue. Our analysis of ADAM23 expression in cultured cerebellar granule cells (CGCs) furthermore suggested that this protein is synthesized as a glycosylated precursor of about 100 kD whose maturation depends on cleavage by furin or a related enzyme. We have also shown ADAM23 to be expressed primarily as a cell‐surface protein that appears to be localized to sites of intercellular contact. Taken together, these data are consistent with a model wherein ADAM23 serves to mediate cell–cell interactions within the mammalian CNS. © 2004 Wiley‐Liss, Inc.
Increased GABAergic function in mouse models of Huntington's disease: Reversal by BDNF
Authors: Cepeda Carlos , Starling Amaal J. , Wu Nanping , Nguyen Oanh K. , Uzgil Besim , Soda Takahiro , André Veronique M. , Ariano Marjorie A. , Levine Michael S. 
Published: November 2004

AbstractHuntington's disease (HD) is characterized by loss of striatal γ‐aminobutyric acid (GABA)ergic medium‐sized spiny projection neurons (MSSNs), whereas some classes of striatal interneurons are relatively spared. Striatal interneurons provide most of the inhibitory synaptic input to MSSNs and use GABA as their neurotransmitter. We reported previously alterations in glutamatergic synaptic activity in the R6/2 and R6/1 mouse models of HD. In the present study, we used whole‐cell voltage clamp recordings to examine GABAergic synaptic currents in MSSNs from striatal slices in these two mouse models compared to those in age‐matched control littermates. The frequency of spontaneous GABAergic synaptic currents was increased significantly in MSSNs from R6/2 transgenics starting around 5–7 weeks (when the overt behavioral phenotype begins) and continuing in 9–14‐week‐old mice. A similar increase was observed in 12–15‐month‐old R6/1 transgenics. Bath application of brain‐derived neurotrophic factor, which is downregulated in HD, significantly reduced the frequency of spontaneous GABAergic synaptic currents in MSSNs from R6/2 but not control mice at 9–14 weeks. Increased GABA current densities also occurred in acutely isolated MSSNs from R6/2 animals. Immunofluorescence demonstrated increased expression of the ubiquitous α1 subunit of GABAA receptors in MSSNs from R6/2 animals. These results indicate that increases in spontaneous GABAergic synaptic currents and postsynaptic receptor function occur in parallel to progressive decreases in glutamatergic inputs to MSSNs. In conjunction, both changes will severely alter striatal outputs to target areas involved in the control of movement. © 2004 Wiley‐Liss, Inc.
Neurotoxic prostaglandin J2 enhances cyclooxygenase‐2 expression in neuronal cells through the p38MAPK pathway: A death wish?
Authors: Li Zongmin , Jansen Marlon , Ogburn Kenyon , Salvatierra Laura , Hunter Lavonne , Mathew Sneha , Figueiredo‐Pereira Maria E. 
Published: November 2004

AbstractThe role of the proinflammatory and inducible form of cyclooxygenases (COX‐2) in neurodegeneration is not well defined. Some of its metabolic products, such as prostaglandins (PG) of the J2 series, are known to be neurotoxic. Here we demonstrate that PGJ2 enhances COX‐2 gene expression without elevating COX‐1 levels in neuronal cells. PGJ2 also increased PGE2 production, establishing that the de novo synthesized COX‐2 is enzymatically active. PGJ2 derivatives, such as 15d‐PGJ2, are known activators of PPARγ, a nuclear receptor that activates gene expression. However, the selective PPARγ agonist ciglitazone failed to up‐regulate COX‐2, indicating that the PGJ2 effect on COX‐2 is PPARγ independent. Furthermore, PGJ2 stabilized IκBα levels, indicating that NFκB is not active under these conditions. The blocking of neuronal NFκB activity by PGJ2 may be an important contributor to its neurotoxicity, insofar as NFκB transactivation seems to be required for neuronal survival in the CNS. Interleukin‐1 (IL1) is a proinflammatory cytokine known to stimulate the expression of genes associated with inflammation, including COX‐2. Notably, IL1 mRNA levels in the neuronal cells were increased by PGJ2 treatment. The proinflammatory cytokine may mediate COX‐2 up‐regulation by PGJ2 through p38MAPK and not JNK activation, in that only an inhibitor of the former prevented the COX‐2 increase. Thiol‐reducing agents, such as N‐acetylcysteine, protected the neuronal cells from the deleterious effects of PGJ2, whereas ascorbic acid did not. Collectively, our findings suggest that proinflammatory conditions that lead to COX‐2 up‐regulation and the concomitant production of PGJ2 initiate a mechanism of self‐destruction through an autotoxic loop between PGJ2 and COX‐2 that may exacerbate neurodegeneration beyond a point of no return. Thiol‐reducing antioxidants may offer an optimal strategy for halting this neurodegenerative process. © 2004 Wiley‐Liss, Inc.