bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population
Authors: Lu Wenfu , Xing Deyin , Qi Jun , Tan Wen , Miao Xiaoping , Lin Dongxin 
Published: October 2002

AbstractMyeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S‐transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A ‐463G→A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR‐SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency‐matched controls. The allele frequency for MPO ‐463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO ‐463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one ‐463A variant allele (adjusted odds ratio [OR] 2.35; 95% confidence interval [CI] 1.40–3.94). Stratified analysis suggested an interaction between heavy smoking (≥26 pack‐years) and the MPO‐463GG genotype. The adjusted OR of lung SCC for those having MPO‐463GG genotype and smoked ≥26 pack‐years was 20.50 (95% CI 5.58–75.33) compared to 6.22 (95% CI 1.72–22.47) for those smoked ≥26 pack‐years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer. © 2002 Wiley‐Liss, Inc.
DNase I sensitive site in the core region of the human β‐globin origin of replication
Authors: Djeliova Vera , Russev George , Anachkova Boyka 
Published: October 2002

AbstractHeLa cells were synchronized at late G1, early S, and late S phase of the cell cycle by nocodazole treatment. The cells were permeabilized with Triton X‐100, digested with DNAse I, and extracted with 0.2 M ammonium sulfate to remove the digested chromatin. DNA was isolated from the residual chromatin attached to the nuclear matrix, digested with Hind III, and subjected to hybridization with [32P] labeled probe located upstream of the core region of the human β‐globin replication origin. The hybridization pattern revealed the existence of a DNase I sensitive site in the core region of the β‐globin replicator. The results suggest that association with the nuclear matrix induce alteration in the chromatin structure of the origin of replication that represents a more open chromatin configuration. J. Cell. Biochem. 87: 279–283, 2002. © 2002 Wiley‐Liss, Inc.
Roles for cytoplasmic polyadenylation in cell cycle regulation
Authors: Read Rebecca L. , Norbury Chris J. 
Published: October 2002

AbstractPolyadenylation of eukaryotic mRNAs in the nucleus promotes their translation following export to the cytoplasm and is an important determinant of mRNA stability. An additional level of control of gene expression is provided by cytoplasmic polyadenylation, which activates translation of a number of mRNAs important in orchestrating cell cycle events in oocytes. Recent studies indicate that cytoplasmic polyadenylation may be a mechanism of translational activation that is more widespread in eukaryotic cells. Here we discuss the roles of a recently identified family of nucleotidyl transferases (encoded by the cid1 gene family) in cell cycle regulation. To date, this family has been characterised mainly in yeasts, but it is conserved throughout the eukaryotes. Biochemical studies have indicated that a subset of members of this family function as cytoplasmic poly(A) polymerases targeting specific mRNAs for translation. This form of translational control appears to be particularly important for cell cycle regulation following inhibition of DNA synthesis. J. Cell. Biochem. 87: 258–265, 2002. © 2002 Wiley‐Liss, Inc.
TNF‐α suppresses bone sialoprotein (BSP) expression in ROS17/2.8 cells
Authors: Samoto Hiroshi , Shimizu Emi , Matsuda‐Honjo Yuko , Saito Ryoichiro , Yamazaki Muneyoshi , Kasai Kazutaka , Furuyama Shunsuke , Sugiya Hiroshi , Sodek Jaro , Ogata Yorimasa 
Published: October 2002

AbstractTumor necrosis factor‐alpha (TNF‐α) is a major mediator of inflammatory responses in many diseases that inhibits bone formation and stimulates bone resorption. To determine molecular mechanisms involved in the suppression of bone formation we have analyzed the effects of TNF‐α on BSP gene expression. Bone sialoprotein (BSP) is a mineralized tissue‐specific protein that appears to function in the initial mineralization of bone. Previous studies have demonstrated that BSP mRNA expression is essentially restricted to fully‐differentiated cells of mineralized connective tissues and that the expression of BSP is developmentally regulated. Treatment of rat osteosarcoma ROS 17/2.8 cells with TNF‐α (10 ng/ml) for 24 h caused a marked reduction in BSP mRNA levels. The addition of antioxidant N‐acetylcysteine (NAC; 20 mM) 30 min prior to stimulation with TNF‐α attenuated the inhibition of BSP mRNA levels. Transient transfection analyses, using chimeric constructs of the rat BSP gene promoter linked to a luciferase reporter gene, revealed that TNF‐α (10 ng/ml) suppressed expression in all constructs, including a short construct (pLUC3; nts −116 to +60), transfected into ROS17/2.8 cells. Further deletion analysis of the BSP promoter showed that a region within nts −84 to −60 was targeted by TNF‐α, the effects which were inhibited by NAC and the tyrosine kinase inhibitor, herbimycin A (HA). Introduction of 2bp mutations in the inverted CCAAT box (ATTGG; nts −50 and −46), a putative cAMP response element (CRE; nts −75 to −68), and a FGF response element (FRE; nts −92 to −85) showed that the TNF‐α effects were mediated by the CRE. These results were supported by gel mobility shift assays, using a radiolabeled double‐stranded CRE oligonucleotide, which revealed decreased binding of a nuclear protein from TNF‐α‐stimulated ROS 17/2.8 cells. Further, the inhibitory effect of TNF‐α on CRE DNA–protein complex was completely abolished by NAC or HA treatment. These studies, therefore, show that TNF‐α suppresses BSP gene transcription through a tyrosine kinase‐dependent pathway that generates reactive oxygen species and that the TNF‐α effects are mediated by a CRE element in the proximal BSP gene promoter. J. Cell. Biochem. 87: 313–323, 2002. © 2002 Wiley‐Liss, Inc.
Proliferation marker pKi‐67 affects the cell cycle in a self‐regulated manner
Authors: Schmidt Mirko H.H. , Broll Rainer , Bruch Hans‐Peter , Duchrow Michael 
Published: October 2002

AbstractThe proliferation marker pKi‐67 is commonly used in research and pathology to detect proliferating cells. In a previous work, we found the protein to be associated with regulators of the cell cycle, controlling S‐phase progression, as well as entry into and exit from mitosis. Here we investigate whether pKi‐67 has a regulative effect on the cell cycle itself. For that purpose we cloned four fragments of pKi‐67, together representing nearly the whole protein, and an N‐terminal pKi‐67 antisense oligonucleotide into a tetracycline inducible gene expression system. The sense fragments were C‐terminally modified by addition of either a nuclear localization sequence (NLS) or a STOP codon to address the impact of their intracellular distribution. FACS based cell cycle analysis revealed that expression of nearly all pKi‐67 domains and the antisense oligonucleotide led to a decreased amount of cells in S‐phase and an increased number of cells in G2/M‐ and G1‐phase. Subsequent analysis of the endogenous pKi‐67 mRNA and protein levels revealed that the constructs with the most significant impact on the cell cycle were able to silence pKi‐67 transcription as well. We conclude from the data that pKi‐67 influences progression of S‐phase and mitosis in a self‐regulated manner and, therefore, effects the cell cycle checkpoints within both phases. Furthermore, we found pKi‐67 mediates an anti‐apoptotic effect on the cell and we verified that this marker, although it is a potential ribosomal catalyst, is not expressed in differentiated tissues with a high transcriptional activity. J. Cell. Biochem. 87: 334–341, 2002. © 2002 Wiley‐Liss, Inc.
BMP‐2, BMP‐4, and PDGF‐bb stimulate chemotactic migration of primary human mesenchymal progenitor cells
Authors: Fiedler Jörg , Röderer Götz , Günther Klaus‐Peter , Brenner Rolf E. 
Published: October 2002

AbstractFor bone development, remodeling, and repair; the recruitment of mesenchymal progenitor cells (MPC) and their differentiation to osteoblasts is mandatory. The process of migration is believed to be regulated in part by growth factors stored within the bone matrix and released by bone resorption. In this study, primary human MPCs and to osteoblasts differentiated progenitor cells were examined for chemotaxis in response to human basic fibroblast growth factor (rhbFGF), human transforming growth factor beta 1 (rhTGF‐β1), human platelet derived growth factor bb (rhPDGF‐bb), human bone morphogenetic protein‐2 (rhBMP‐2), and recombinant bone morphogenetic protein‐4 of Xenopus laevis (rxBMP‐4) from 0.001 to 1.0 ng/ml each. The results of migration were expressed as a chemotactic index (CI). Migration of primary human progenitor cells was stimulated by rhBMP‐2, rxBMP‐4, and rhPDGF‐bb in a dose‐dependent manner. The increase of CI was up to 3.5‐fold for rhBMP‐2, 3.6‐fold for rxBMP‐4, and up to 22‐fold for rhPDGF‐bb, whereas rhTGF‐β1 and rhbFGF did not stimulate cell migration in the concentration range tested. In contrast differentiated progenitor cells behave similar to primary human osteoblasts. RhBMP‐2, rhPDGF‐bb, and rhTGF‐β1 stimulated the migration from 2.2 to 2.4‐fold each, while rxBMP‐4 and rhbFGF reached only a CI of 1.7–1.6. The effect of rhBMP‐2, rxBMP‐4, and rhPDGF‐bb as chemoattractive proteins for primary human MPC, including the change in response to growth factors after differentiation suggests a functional role for recruitment of MPCs during bone development and remodeling, as well as fracture healing. J. Cell. Biochem. 87:305‐312, 2002. © 2002 Wiley‐Liss, Inc.
Retinoid signalling and gene expression in neuroblastoma cells: RXR agonist and antagonist effects on CRABP‐II and RARβ expression
Authors: Hewson Quentin Campbell , Lovat Penny E. , Pearson Andrew D.J. , Redfern Christopher P.F. 
Published: October 2002

Abstract9‐cis Retinoic acid (RA) induces gene expression in neuroblastoma cells more effectively and with different kinetics than other RA isomers, and could be acting in part through Retinoid X Receptors (RXRs). The aim of this study was to characterise the effects of an RXR agonist and RXR homodimer antagonist on the induction of cellular RA binding protein II (CRABP‐II) and RA receptor‐β (RARβ) in neuroblastoma cells in response to different retinoids. The RXR agonist, LDG1069, was as effective as all‐trans RA in inducing gene expression, but less effective than 9‐cis RA. The RXR‐homodimer antagonist, LG100754, inhibited the induction of CRABP‐II mRNA in SH‐SY5Y neuroblastoma cells by 9‐cis RA or the RXR‐specific agonist LGD1069, but had no effect when used with all‐trans RA. Conversely, LG100754 did not inhibit induction of RARβ mRNA by 9‐cis or all‐trans RA, or by LGD1069. RAR‐ and RXR‐specific ligands used together induced CRABP‐II and RARβ as effectively as 9‐cis RA. These results demonstrate the value of combining RXR‐ and RAR‐specific ligands to regulate RA‐inducible gene expression. The possibility that RXR‐homodimers mediate, in part, the induction of CRABP‐II by 9‐cis RA and RXR‐specific ligands is discussed. J. Cell. Biochem. 87: 284–291, 2002. © 2002 Wiley‐Liss, Inc.
Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up‐regulation of tumor necrosis factor‐α, inducible nitric oxide synthase, p53, c‐myc, and bax‐α, and suppression of bcl‐2
Authors: Islam Najmul , Haqqi Tariq M. , Jepsen Karl J. , Kraay Matthew , Welter Jean F. , Goldberg Victor M. , Malemud Charles J. 
Published: October 2002

AbstractHydrostatic pressure (HP) is thought to increase within cartilage extracellular matrix as a consequence of fluid flow inhibition. The biosynthetic response of human articular chondrocytes to HP in vitro varies with the load magnitude, load frequency, as well as duration of loading. We found that continuous cyclic HP (5 MegaPascals (MPa) for 4 h; 1 Hz frequency) induced apoptosis in human chondrocytes derived from osteoarthritic cartilage in vitro as evidenced by reduced chondrocyte viability which was independent of initial cell densities ranging from 8.1 × 104 to 1.3 × 106 cells ml−1. HP resulted in internucleosomal DNA fragmentation, activation of caspase‐3, and cleavage of poly‐ADP‐ribose polymerase (PARP). At the molecular level, induction of apoptosis by HP was characterized by up‐regulation of p53, c‐myc, and bax‐α after 4 h with concomitant down‐regulation of bcl‐2 after 2 h at 5 MPa as measured by RT‐PCR. In contrast, β‐actin expression was unchanged. Real‐time quantitative RT‐PCR confirmed a HP‐induced (5 MPa) 1.3–2.6 log‐fold decrease in bcl‐2 mRNA copy number after 2 and 4 h, respectively, and a significant increase (1.9–2.5 log‐fold) in tumor necrosis factor‐α (TNF‐α) and inducible nitric oxide synthase (iNOS) mRNA copy number after 2 and 4 h, respectively. The up‐regulation of p53 and c‐myc, and the down‐regulation of bcl‐2 caused by HP were confirmed at the protein level by Western blotting. These results indicated that HP is a strong inducer of apoptosis in osteoarthritic human chondrocytes in vitro. J. Cell. Biochem. 87: 266–278, 2002. © 2002 Wiley‐Liss, Inc.
Amyloid β‐protein affects cholesterol metabolism in cultured neurons: Implications for pivotal role of cholesterol in the amyloid cascade
Authors: Gong Jian‐Sheng , Sawamura Naoya , Zou Kun , Sakai Juro , Yanagisawa Katsuhiko , Michikawa Makoto 
Published: October 2002

AbstractRecently, we have found that alterations in cellular cholesterol metabolism are involved in promotion of tau phosphorylation (Fan et al. [2001] J. Neurochem. 76: 391–400; Sawamura et al. [2001] J. Biol. Chem. 276:10314–10319). In addition, we have shown that amyloid β‐protein (Aβ) promotes cholesterol release to form Aβ‐lipid particles (Michikawa et al. [2001] J. Neurosci. 21:7226–7235). These lines of evidence inspired us to conduct further studies on whether Aβ affects cholesterol metabolism in neurons, which might lead to tau phosphorylation. Here, we report the effect of Aβ1‐40 on cholesterol metabolism in cultured neurons prepared from rat cerebral cortex. Oligomeric Aβ1‐40 inhibited cholesterol synthesis and reduced cellular cholesterol levels in a dose‐ and time‐dependent manner, while freshly dissolved Aβ had no effect on cholesterol metabolism. However, oligomeric Aβ had no effect on the proteolysis of sterol regulatory element binding protein‐2 (SREBP‐2) or protein synthesis in cultured neurons. Oligomeric Aβ did not enhance lactate dehydrogenase (LDH) release from neuronal cells or decrease signals in the cultures reactive to 3,3′‐Bis[N,N‐bis(carboxymethyl)aminomethyl]fluorescein, hexaacetoxymethyl ester (calcein AM) staining, indicating that Aβ used in this experiment did not cause neuronal death during the time course of our experiments. Since alterations in cholesterol metabolism induce tau phosphorylation, our findings that oligomeric Aβ alters cellular cholesterol homeostasis may provide new insight into the mechanism underlying the amyloid cascade hypothesis. © 2002 Wiley‐Liss, Inc.
Cholesterol and pathological processes in Alzheimer's disease
Authors: Yanagisawa Katsuhiko 
Published: October 2002

AbstractFundamental questions on the pathogenesis of Alzheimer's disease (AD) are how nontoxic, soluble amyloid β‐protein (Aβ) is converted to its toxic, aggregated form and how functional tau is hyperphosphorylated to form neurofibrillary tangles. Growing evidence from recent biochemical and cell biological studies suggests that altered cholesterol metabolism in neurons may underlie such pathological processes. The possibility that cholesterol is a risk factor in the development of AD has also been supported by recent epidemiological studies. Based on this line of evidence, it is noteworthy to examine the potency of cholesterol‐lowering medicine and/or diet in suppressing the development or the progression of AD. © 2002 Wiley‐Liss, Inc.
Remarkable increase in the concentration of 8‐hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease
Authors: Abe Takashi , Tohgi Hideo , Isobe Chiaki , Murata Takahiko , Sato Chigumi 
Published: October 2002

AbstractTo investigate the possible role of oxidative RNA damage in the pathogenesis of Alzheimer's disease (AD), the concentrations of the oxidative stress marker 8‐hydroxyguanosine (8‐OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with AD and control subjects. The concentration of 8‐OHG in CSF in AD patients was approximately fivefold that in controls (P < 0.001). The concentration of 8‐OHG in CSF decreased significantly with the duration of illness (rs = −0.48, P < 0.05) and the progression of cognitive dysfunctions (rs = 0.67, P < 0.01). However, the concentration of 8‐OHG in CSF showed no correlation with that in serum in both the controls and AD patients. In addition, the concentration of 8‐OHG in serum was not significantly altered in AD patients compared to that in controls, suggesting that the 8‐OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8‐OHG and increased oxidative RNA damage in the early stage of the development of AD. © 2002 Wiley‐Liss, Inc.
Isoaspartate formation at position 23 of amyloid beta peptide enhanced fibril formation and deposited onto senile plaques and vascular amyloids in Alzheimer's disease
Authors: Shimizu Takahiko , Fukuda Hiroyuki , Murayama Shigeo , Izumiyama Naoki , Shirasawa Takuji 
Published: October 2002

AbstractSenile plaques and amyloid‐bearing vessels consisting of fibrillar amyloid β peptides (Aβ) are characteristic neuropathological features of Alzheimer's disease (AD). Aβ undergo spontaneous post‐translational modifications, such as isomerization and racemization, at their aspartyl residues in AD brains. Here we present evidence that Aβ isomerized at position 23 are deposited on plaques and vascular amyloids using an anti‐isomerized Aβ antibody. In vitro experiments showed that isomerization at position 23, but not position 7, enhanced aggregation. Furthermore, Aβ with the Dutch mutation, but not the Flemish mutation, also showed greatly enhanced aggregation. These results suggest that mutations or modifications at positions Glu22 and Asp23 have a pathogenic role in the deposition of Aβ. The development and progression of sporadic AD may be accelerated by spontaneous isomerization at position 23 of Aβ. © 2002 Wiley‐Liss, Inc.
Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down‐regulation and up‐regulation of apoptotic and pro‐inflammatory signaling
Authors: Colangelo Vittorio , Schurr Jill , Ball Melvyn J. , Pelaez Ricardo Palacios , Bazan Nicolas G. , Lukiw Walter J. 
Published: October 2002

AbstractAlterations in transcription, RNA editing, translation, protein processing, and clearance are a consistent feature of Alzheimer's disease (AD) brain. To extend our initial study (Alzheimer Reports [2000] 3:161‐167), RNA samples isolated from control and AD hippocampal cornu ammonis 1 (CA1) were analyzed for 12633 gene and expressed sequence tag (EST) expression levels using DNA microarrays (HG‐U95Av2 Genechips; Affymetrix, Santa Clara, CA). Hippocampal CA1 tissues were carefully selected from several hundred potential specimens obtained from domestic and international brain banks. To minimize the effects of individual differences in gene expression, RNA of high spectral quality (A260/280 ≥ 1.9) was pooled from CA1 of six control or six AD subjects. Results were compared as a group; individual gene expression patterns for the most‐changed RNA message levels were also profiled. There were no significant differences in age, postmortem interval (mean ≤ 2.1 hr) nor tissue pH (range 6.6–6.9) between the two brain groups. AD tissues were derived from subjects clinically classified as CDR 2‐3 (CERAD/NIA). Expression data were analyzed using GeneSpring (Silicon Genetics, Redwood City, CA) and Microarray Data Mining Tool (Affymetrix) software. Compared to controls and 354 background/alignment markers, AD brain showed a generalized depression in brain gene transcription, including decreases in RNA encoding transcription factors (TFs), neurotrophic factors, signaling elements involved in synaptic plasticity such as synaptophysin, metallothionein III, and metal regulatory factor‐1. Three‐ or morefold increases in RNAs encoding DAXX, cPLA2, CDP5, NF‐κBp52/p100, FAS, βAPP, DPP1, NFIL6, IL precursor, B94, HB15, COX‐2, and CEX‐1 signals were strikingly apparent. These data support the hypothesis of widespread transcriptional alterations, misregulation of RNAs involved in metal ion homeostasis, TF signaling deficits, decreases in neurotrophic support and activated apoptotic and neuroinflammatory signaling in moderately affected AD hippocampal CA1. © 2002 Wiley‐Liss, Inc.
Turnover of synaptic membranes: Age‐related changes and modulation by dietary restriction
Authors: Ando Susumu , Tanaka Yasukazu , Toyoda (nee Ono) Yuriko , Kon Kazuo , Kawashima Sei‐ichi 
Published: October 2002

AbstractWe examined age‐related changes in the turnover rates of synaptic membrane components that might underlie the decrease in synaptic functions in senescence. Synaptic membrane constituents were labeled in vivo with deuterium and the disappearance of the deuterated molecules from synaptic membranes was measured by mass spectrometry. The turnover rates of phosphatidylcholine, phosphatidylethanolamine, cholesterol, and synaptophysin were all shown to slow down with aging. Dietary restriction, which is known to retard various aging processes, was found to decrease the turnover rates of membrane lipid species. Consequently, the fatty acid composition in phospholipids remained unchanged in the synaptic plasma membranes of food restricted mice. In contrast, the turnover rate of synaptophysin was accelerated under dietary restriction. This may mean that increased turnover enhances the removal of damaged proteins from membranes. © 2002 Wiley‐Liss, Inc.