bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes
Authors: Vondracek Martin , Weaver David A. , Sarang Zsolt , Hedberg Jesper J. , Willey James C. , Wärngård Lars , Grafström Roland C.
Published: August 2002

The metabolic detoxification capacity may critically regulate the susceptibility of human tissues to cancer development. We used standardized and quantitative, reverse transcription‐polymerase chain reaction (StaRT‐PCR) and microarray chip techniques to analyze transcript levels of multiple detoxification enzymes in cultured normal human oral keratinocytes (NOK) and the Siman virus 40 T antigen‐immortalized oral keratinocyte line SVpgC2a, viewing the latter as a model of a benign tumor state. With good agreement between the 2 methodologies, NOK and SVpgC2a were found to express transcripts for cytochrome P450 enzymes (CYPs), factors related to CYP induction and enzymes involved in conjugation reactions or detoxification of reactive oxygen. The cell types expressed similar levels of CYP 2B6/7, CYP 2E1, P450 oxidoreductase, the aryl hydrocarbon receptor nuclear translocator, sulfotransferase 1A1, sulfotransferase 1A3, epoxide hydrolase, glutathione S‐transferase M3, glutathione S‐transferase pi and catalase, superoxide dismutase 1, glutathione peroxidase 1 and glutathione peroxidase 3. In contrast, SVpgC2a exhibited comparatively higher levels of CYP1A1, 1B1, aryl hydrocarbon receptor, glutathione S‐transferase M1, 2, 4, 5, glutathione S‐transferase theta 1 and superoxide dismutase 2 and comparatively lower levels of UDP glycosyltransferase 2 and microsomal glutathione S‐transferase 1. Some transcripts, e.g., CYP 2A6/7, were not detected by either standard, non quantitative RT‐PCR or the above methods, whereas others were barely quantifiable by StaRT‐PCR, i.e., were present at 1–10 molecules/106 molecules of actin. Overall, the expression analysis demonstrated presence of mRNA for multiple enzymes involved in foreign compound metabolism and detoxification pathways, including several enzymes not previously reported for oral epithelium. Generally, the comparison of NOK from 2 individuals indicated relatively similar transcript levels of these enzymes. In contrast, differences between NOK and SVpgC2a, e.g., for CYP1B1, may reflect alteration caused by immortalization and aid identification of early stage tumor markers in oral epithelium. © 2002 Wiley‐Liss, Inc.
MSI in endometrial carcinoma: Absence of MLH1 promoter methylation is associated with increased familial risk for cancers
Authors: Whelan Alison J. , Babb Sheri , Mutch David G. , Rader Janet , Herzog Thomas J. , Todd Christina , Ivanovich Jennifer L. , Goodfellow Paul J.
Published: August 2002

Loss of DNA mismatch repair occurs in a variety of malignancies and is associated with genome‐wide instability of microsatellite repeats, a molecular phenotype referred to as microsatellite instability (MSI). MSI is a consistent feature of colorectal and endometrial tumors from patients with hereditary non‐polyposis colorectal cancer (HNPCC). Sporadic colorectal and endometrial cancers that exhibit MSI frequently have methylation of the MLH1 promoter. We undertook a detailed family and medical history study to compare family cancer risk for women with MSI‐positive and ‐negative endometrial cancers. The MLH1 promoter methylation status was determined for all cancers. Family histories were developed for 80 probands (40 with MSI‐positive and 40 with MSI‐negative tumors). The numbers of reported cancers in first‐ and second‐degree relatives of the 2 groups were similar. There was a modest increase in familial cancer clustering for MSI‐positive probands. When MSI‐positive tumors were subclassified according to MLH1 promoter methylation, a clear association between methylation status and familial cancer risk was evident. Women with MSI‐positive endometrial cancers in which the MLH1 promoter was unmethylated had a 7‐fold relative risk (RR) of demonstrating familial clustering of cancers [RR 7.07 (95% confidence interval 2.29–21.81)]. The women with MSI‐positive, MLH1‐unmethylated tumors were significantly younger than the rest of the study population (56.1 years vs. 65.4, p ≤ 0.01). Age of onset and tumor MSI not associated with MLH1 promoter methylation may point to women with a genetic susceptibility to malignancies. © 2002 Wiley‐Liss, Inc.
Identification and characterization of 9D7, a novel human protein overexpressed in renal cell carcinoma
Authors: Klade Christoph S. , Dohnal Alexander , Fürst Walter , Sommergruber Wolfgang , Heider Karl‐Heinz , Gharwan Helen , Ratschek Manfred , Adolf Günther R.
Published: August 2002

With the objective of discovering novel tumor‐associated antigens of the cancer/testis type, we compared the transcriptional profiles of renal cell carcinoma (RCC) and non‐tumorous kidney and further screened for genes expressed in RCC and testis, but not other normal tissues. In a first step, a representational difference analysis library consisting of approximately 1,900 RCC cDNA clones was generated. Clones were then spotted onto filters and hybridized with cDNA probes derived from a testis‐specific cDNA library, a pool of RCCs and a pool of 10 healthy normal tissues, respectively. Based on strong hybridization signals with both RCC and testis, but not normal tissue probes, 185 clones were sequenced and annotated. After EST‐database comparison, 35 clones were selected for experimental analysis, including conventional and quantitative RT‐PCR as well as Northern blotting. Clone 9D7 showed strong mRNA expression in RCC as well as in several other major tumor types. In normal tissues there was little or no mRNA expression with the exception of heart. 9D7 was cloned to full‐size and found to represent a novel human gene containing 5 exons residing on chromosome 14. Alternative splicing within exon 1 generates 2 open‐reading‐frames consisting of 717 or 435 bp corresponding to predicted proteins of 239 or 145 amino acids. 9D7 shows high homology (227/239 amino acids or 95% identity) to a growth factor‐inducible gene of Rattus norvegicus involved in apoptosis. In situ hybridization as well as immunohistochemical analysis using 9D7‐specific antisera confirmed overexpression of 9D7 in RCCs as compared to normal kidney tissue. © 2002 Wiley‐Liss, Inc.
Resistance to tamoxifen‐induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer
Authors: Chung Yih‐Lin , Sheu Meei‐Ling , Yang Shun‐Chun , Lin Chi‐Hung , Yen Sang‐Hue
Published: August 2002

Overexpression of Her2/neu is implicated in the development of resistance to the antiestrogen tamoxifen (TAM) that exerts its inhibitory effect through interaction with estrogen receptor (ER). Whereas Her2/neu and ER are believed to be important cell survival/death factors in human breast cancer cells, if and how they interact to confer resistance to hormone therapy is not known. This prompted us to investigate whether modulation of the effect of TAM occurs via the Her2/neu pathway and whether targeting the interaction between the Her2/neu pathway and the ER pathway is beneficial. There are 2 forms of ER that are localized to the cell membrane and to the nucleus. For the first time, we found that Her2/neu directly interacts with ER at the cell membrane. We then investigated the role of Her2/neu overexpression in the regulation of the cell membrane ER pathway in TAM‐resistant breast cancer cells and the nature of this interaction in apoptotic signaling. Relief of TAM resistance was associated with Her2/neu downregulation and ER upregulation. TAM‐induced apoptosis occurred immediately after dissociation of Her2/neu from cell membrane ER. These results demonstrate a novel mechanism by which Her2/neu regulates the cell membrane ER‐coupled apoptosis and the possible involvement of the Her2/neu in TAM resistance of breast cancer cells. Moreover, the antiproliferative activity of TAM should rely on the integration between the signal transduction from the cell membrane ER and the gene regulation by the nuclear ER. Coordinated modulation on the cell membrane ER/Her2/neu pathway and the nuclear ER/RAR pathway may provide a new approach for treatment of ER‐positive, Her2/neu overexpressing breast cancer. © 2001 Wiley‐Liss, Inc.
Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum
Authors: Cheng Wei‐min , Chan Kwok Hung , Chen Hong‐lin , Luo Rui‐xian , Ng S. Park , Luk Winsie , Zheng Bo‐jian , Ji Ming‐fang , Liang Jin‐sheng , Sham Jonathan S.T. , Wang De‐Kun , Zong Yong‐sheng , Ng Mun Hon
Published: August 2002

We have evaluated the performance of 3 new EBV ELISA for the diagnosis of nasopharyngeal carcinoma (NPC). The tests were specific for EBNA 1 IgA, EBNA 1 IgG and zta IgG, respectively. Their distinct antigenic specificity permits these assays to be used in concert in an approach that differentiates patients and apparently healthy subjects on the basis of their antibody spectrum. By so exploiting a distinguishing feature of NPC first described by the late Werner Henle that the patients sustain high levels of a broad spectrum of serum EBV antibodies, this approach achieved a sensitivity of 92% and a specificity of 93%, surpassing the performance of each of these assays individually. The enhanced performance is especially useful in population screening. It was shown that relative risk of NPC sustained by apparently healthy subjects residing in a high incidence area for NPC in the Pearl River estuary in Southern China may vary according to EBV antibody spectrum. The risk of the cancer was markedly reduced with odds ratios of 0.009 for 59% of those who had low level of all 3 antibodies. The risk was increased as antibody spectrum broadens and the risk was the highest with an odds ratio of 138 for 0.4% of those who had high levels of all 3 antibodies. Thus, EBV antibody spectrum may serve to guide follow‐up measures for early detection of the cancer and/or risk counseling according to level of the risk of the cancer sustained by the screened individuals. © 2001 Wiley‐Liss, Inc.
Getting dads involved: Predictors of father involvement in Early Head Start and with their children
Authors: Roggman Lori A. , Boyce Lisa K. , Cook Gina A. , Cook Jerry
Published: August 2002

Father characteristics and psychosocial functioning were examined as predictors of father involvement both with an Early Head Start (EHS) program and with their infant. Variables examined as potential predictors were selected based on the program's emphasis on building relationships as their primary intervention strategy. The 72 low‐income fathers included in this study were predominantly Caucasian and married or living with their child's mother. Fathers' characteristics predicted their involvement in expected ways. Fathers were rated as more involved, both with their infants and with the EHS program, when they were better educated, less depressed, more likely to use social support especially spiritual support, and more active in their religion. Fathers who had better relationships with home visitors were those who had these same characteristics and also were less anxious about close relationships. In addition, fathers who were later rated as more engaged with their infants reported doing more activities with their infants at 10 months. These results suggest that the fathers who most need support to become more involved with their children are likely to be those who are the most difficult to get involved in an EHS program. ©2002 Michigan Association for Infant Mental Health.
Full cost or “sustainability cost” pricing in irrigated agriculture. Charging for water can be effective, but is it sufficient?
Authors: Tardieu Henri , Préfol Bernard
Published: August 2002

In France, the water management issue is no longer a matter of developing stakeholder participation or transferring state competence to user associations. But, as for other countries with a significant irrigated agriculture, two socio‐economic questions need to be answered: (i) How to ensure the sustainability of investments by raising the price of water without discouraging economic development? (ii) How to share water between users when resources are scarce?

Answering these questions brings up the two basic principles of good water management for sustainable development: as it consumes more than 70% of the available water of low flow periods, irrigated agriculture must respect the other uses by limiting its demand to the allocated volume; as it involves large and long‐term public investments, irrigated agriculture must at least bear the “sustainability cost” of the irrigation schemes including the upstream water resources. Such a general answer is of course largely case‐specific and should be adjusted to each institutional framework. In France today, the Sociétés d'Aménagement Régional (SARs) are currently applying these principles. This paper will address both socio‐economic questions stated above, with a specific discussion on the case of a water‐stressed basin in the south west of France where a specific step‐pricing and quota system has been set up in order to regulate the demand. It is argued that “full cost pricing of water services”, as recommended in the World Water Vision (The Hague 2000), is not practical in the short term and, if pursued, could lead to very undesirable results. As a conclusion, two recommendations are proposed with a view to developing best practices in charging for water. Copyright © 2002 John Wiley & Sons, Ltd.
Potential protective role of angiotensin‐converting enzyme inhibitors captopril and enalapril against adriamycin‐induced acute cardiac and hepatic toxicity in rats
Authors: Abd El‐Aziz M. A. , Othman A. I. , Amer M. , El‐Missiry M. A.
Published: August 2002

Captopril and enalapril—angiotensin‐converting enzyme (ACE) inhibitors—were evaluated for their antioxidative protective action against adriamycin‐induced cardiac and hepatic toxicity. Rats were treated with either captopril (10 mg kg−1) or enalapril (2 mg kg−1) intragastrically (i.g.) daily for 7 days before single intraperitoneal (i.p.) injection with adriamycin (15 mg kg−1). The animals were killed 30 h after adriamycin administration. Adriamycin produced significant elevation in thiobarbituric acid reactive substances (TBARS), which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues, with a significant rise in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK‐MB) and lactic dehydrogenase (LDH), indicating acute cardiac toxicity. A single injection of adriamycin did not affect the cardiac or hepatic glutathione (GSH) content or cardiac catalase (CAT) activity, but hepatic CAT activity was elevated. Pretreatment with ACE inhibitors significantly reduced the TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, the ACE inhibitors significantly improved the serum levels of GOT, GPT, CK‐MB and LDH in adriamycin‐treated rats. Thus, these results suggest that captopril and enalapril possess antioxidative potential that may protect the heart against adriamycin‐induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress. Copyright © 2001 John Wiley & Sons, Ltd.
Cationic lipid‐mediated transfection of bovine aortic endothelial cells inhibits their attachment
Authors: Kader Khalid N. , Sweany Jon M. , Bellamkonda Ravi V.
Published: August 2002

The need for a small‐diameter vascular graft for coronary artery and peripheral vascular replacement is great and is projected to increase as the population ages. Synthetic small‐diameter vascular grafts fail because of acute thrombosis or chronic intimal hyperplasia leading to restenosis. Endothelial cell seeding has been attempted with limited success in the femoral artery by Zilla and others. However, patency rates have not increased sufficiently to justify large clinical trials. Genetic engineering of endothelial cells before seeding has been proposed to encourage endothelial cell phenotypes that would predispose the graft to patency. In this study, we investigate the effect cationic lipid‐mediated transfection of endothelial cells with respect to their attachment to a potential graft material, Fluoropassiv™ (Vascutek). Liposomal transfection was optimized for maximum gene expression. We report that transfection decreases the ability of bovine aortic endothelial cells to attach by approximately 100% as compared with nontransfected control over 18 h. Further, when placed under physiologic shear conditions, this difference is sustained. The effects of gene transfer on endothelial cell adhesion must be included as an important optimization criterion along with gene expression for engineered endothelial cell‐seeding applications. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 405–410, 2002; DOI 10.1002/jbm.10062
Analysis of acid‐treated dentin smear debris and smear layers using confocal Raman microspectroscopy
Authors: Wang Yong , Spencer Paulette
Published: August 2002

Smear layers are generally present on any dentin surface prepared with cutting instruments and are often the only available substrate for bonding. It is commonly reported that acid removes these layers, but to date there has been no chemical evidence to support this observation. Confocal Raman microspectroscopy was used to investigate changes in the composition and molecular structure of acid‐treated smear debris and in situ dentin smear layers. The exposed dentin in human molars was abraded with 600‐grit silicon carbide sandpaper. Raman spectra were acquired on the smear debris and collected from the sandpaper before and after treatment with 10% citric acid, 35% H3PO4, or 0.5M ethylenediaminetetraacetic acid (EDTA). The resultant smeared dentin samples were treated with one of the aforementioned reagents, and spectra were acquired at 1.0‐μm intervals across the interfaces of the smear layers/demineralized dentin/mineralized dentin. Corresponding specimens were morphologically analyzed with scanning electron microscopy (SEM). The results showed that the composition of the smear debris and the in situ smear layers was a mixture of disorganized collagen and mineral. Spectral changes in the smear debris suggested that the disorganized collagen was denatured by acid treatment. The denatured collagen formed a gelatinous matrix around the mineral in the smear layer, thereby shielding it from the acid. The smear layers were not apparent in the SEM micrographs of acid‐etched dentin prepared and processed with conventional techniques. The micro‐Raman spectroscopic results presented in this study provide the first direct evidence that partially denatured collagen within smear layers is not removed and that the mineral is only partially removed with acids that represent conventional dentin adhesive etchants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 300–308, 2002; DOI 10.1002/jbm.10108
Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester‐urethane)ureas based on poly(caprolactone) and putrescine
Authors: Guan Jianjun , Sacks Michael S. , Beckman Eric J. , Wagner William R.
Published: August 2002

The engineering of tissue for mechanically demanding applications in the cardiovascular system is likely to require mechanical conditioning of cell–scaffold constructs prior to their implantation. Scaffold properties amenable to such an application include high elasticity and strength coupled with controllable biodegradative and cell‐adhesive properties. To fulfill such design criteria, we have synthesized a family of poly(ester‐urethane)ureas (PEUUs) from polycaprolactone and 1,4‐diisocyanatobutane. Lysine ethyl ester (Lys) or putrescine was used as chain extenders. To encourage cell adhesion, PEUUs were surface modified with radio‐frequency glow discharge followed by coupling of Arg‐Gly‐Asp‐Ser (RGDS). The synthesized PEUUs were highly flexible, with breaking strains of 660–895% and tensile strengths from 9.2–29 MPa. Incubation in aqueous buffer for 8 weeks resulted in mass loss, from >50% (Lys chain extender) to 10% (putrescine chain extender). Human endothelial cells cultured for 4 days with medium containing the degradation products from PEUUs with either the Lys or putrescine chain extender showed no toxic effects. Cell adhesion was 85% of that measured on tissue‐culture polystyrene for unmodified PEUU surfaces (p < 0.01) and >160% (p < 0.001) of polystyrene on RGDS‐modified PEUUs. These biodegradable PEUUs demonstrate potential for future application as cell scaffolds in cardiovascular tissue‐engineering or other soft‐tissue applications. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 493–503, 2002
Hydroxyapatite ceramic bodies with tailored mechanical properties for different applications
Authors: Rodríguez‐Lorenzo L. M. , Vallet‐Regí M. , Ferreira J. M. F. , Ginebra M. P. , Aparicio C. , Planell J. A.
Published: August 2002

A perfect control on the final ceramic features will enable the research/clinical community to spread the use of calcium phosphate ceramic bodies to a large number of applications and/or requirements. The mechanical properties of hydroxyapatite ceramic bodies manufactured by different techniques and with different porosities is presented. The flexural strength, hardness, fracture toughness, surface roughness, and their evolution after immersion in SBF are studied. An increase of the mechanical properties with density is observed. The factors governing these results are analyzed. The increase of the porosity percentage of the bodies results in an increase on the surface roughness. The degradation studies show that the HA ceramics keep their integrity and mechanical properties under physiological conditions during the soaking time studied. The OHAp ceramic bodies with controlled porosity could be appropriated for hard tissue substitution or as a carriers for controlled delivery of drugs or as scaffolds for tissue engineering. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 159–166, 2002
Mediator caused induction of a human bradykinin B1 receptor minigene: Participation of c‐Jun in the process
Authors: Yang Xionghu , Taylor Linda , Yu Jun , Fenton Matthew J. , Polgar Peter
Published: August 2002

The bradykinin B1 receptor (BKB1R) gene is expressed in selected tissues such as lung and kidney. In these tissues it is expressed at a very low level until induced by inflammatory mediators. Our aim has been to understand the mechanism of this regulatory process. A human BKB1R minigene was constructed. It contained a 1.8 kb promoter, the entire exon I, 1.5 kb of intron I, the entire exon II and intron II, and the luciferase gene as a reporter. Transient transfection of the minigene into SV40‐transformed IMR90 cells (IMRSV) resulted in a promoter activity which was activated by the mediators, lipopolysaccharide and (LPS) desArg10‐kallidin. In contrast, these mediators did not induce the activity of the 1.8 kb promoter construct alone. Thus, motifs exclusive of the promoter such as 5′‐UTR and/or intron regions are required for mediator‐induced expression of this gene. Promoter activities of both the minigene and the 1.8 kb promoter construct were enhanced in a dose‐dependent manner upon cotransfection with c‐Jun. Furthermore, cotransfecting c‐Jun with the minigene achieved the maximal promoter activity with no further increase in response to mediators. Conversely, the induction of the minigene promoter activity by mediators was abolished upon cotransfection with a dominant negative mutant of c‐Jun. Other experiments suggest that multiple AP‐1 sites are interactive with the c‐Jun upregulation of this gene. Taken together, these results point to c‐Jun as a key intermediary in the activation of the expression of this gene by mediators. However, participation of motifs outside of the promoter are necessary to obtain this inducible expression. J. Cell. Biochem. 82: 163–170, 2001. © 2001 Wiley‐Liss, Inc.
Heat shock factor‐4 (HSF‐4a) is a repressor of HSF‐1 mediated transcription*
Authors: Zhang Yan , Frejtag Wojciech , Dai Rujuan , Mivechi Nahid F.
Published: August 2002

Heat shock transcription factors (HSFs) regulate the expression of heat shock proteins and other molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation and apoptosis. Among the human HSFs, HSF‐4 is expressed as at least two splice variants. One isoform (HSF‐4b) possesses a transcriptional activation domain, but this region is absent in the other isoform (HSF‐4a). We have recently shown that the HSF‐4a isoform represses basal transcription from heterologous promoters both in vitro and in vivo. Here we show that HSF‐4a and HSF‐4b have dramatically different effects on HSF‐1‐containing nuclear bodies, which form after heat shock. While the expression of HSF‐4b colocalizes with nuclear granules, the expression of HSF‐4a prevents their formation. In addition, there is a concurrent reduction of HSF‐1 in the nucleus, and there is reduction in its DNA binding activity and in HSE‐dependent transcription of a reporter gene. To better understand the mechanism by which HSF‐4a represses transcription, we inducibly expressed HSF‐4a in cells and found that HSF‐4a binds to the heat shock element (HSE) during attenuation of the heat shock response. Thus HSF‐4a is an active repressor of HSF‐1‐mediated transcription. This repressor function makes the HSF‐4a isoform unique within the HSF family. J. Cell. Biochem. 82: 692–703, 2001. © 2001 Wiley‐Liss, Inc.
High dose of dexamethasone upregulates TCR/CD3‐induced calcium response independent of TCR ζ chain expression in human T lymphocytes*
Authors: Nambiar Madhusoodana P. , Enyedy Edith J. , Fisher Carolyn U. , Warke Vishal G. , Tsokos George C.
Published: August 2002

Glucocorticoids are very potent anti‐inflammatory and immunosuppressive agents that modulate cellular immune responses, although, the molecular mechanisms that impart their complex effects have not been completely defined. We have previously demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, biphasically modulates the expression of TCR (T cell receptor) ζ chain in human T cells. At 10 nM, it induced the expression of TCR ζ chain whereas at 100 nM, it inhibited its expression. In parallel to the upregulation of TCR ζ chain, the TCR/CD3‐mediated [Ca2+]i response was enhanced in 10 nM Dex‐treated cells. However, at 100 nM, Dex treatment enhanced TCR/CD3‐mediated [Ca2+]i response without the induction of TCR ζ chain expression. Because the classical transcriptional model of glucocorticoid action cannot account for the effects of high dose of Dex, here we studied alternative mechanisms of action. We show that, increased and more sustained TCR/CD3‐mediated [Ca2+]i response was also observed in 100 nM Dex‐treated cells in the presence of actinomycin D or cycloheximide suggesting that cellular transcription and/or de novo protein synthesis are not required for the induction. The TCR/CD3‐mediated hyper [Ca2+]i response in 100 nM Dex‐treated cells was readily reversible by short‐term culture in steroid‐free medium. RU‐486, a competitive antagonist of Dex, inhibited the increase in [Ca2+]i response suggesting that the effect of Dex is mediated through the glucocorticoid receptor. Although the lipid‐raft association of the TCR ζ chain was not significantly increased, high‐dose of Dex increased the amount of ubiquitinated form of the TCR ζ chain in the cell membrane along with increased levels of actin. Fluorescence microscopy showed that high‐dose of Dex alters the distribution of the TCR ζ chain and form more distinct clusters upon TCR/CD3 stimulation. These results suggest that high dose of Dex perturbs the membrane distribution of TCR ζ chain leading to more functional signaling clusters that result in increased TCR/CD3‐mediated [Ca2+]i response independent of TCR ζ chain expression. J. Cell. Biochem. 83: 401–413, 2001. © 2001 Wiley‐Liss, Inc.
Ab initioconformational studies on diols and binary diol‐water systems using DFT methods. Intramolecular hydrogen bonding and 1:1 complex formation with water
Authors: Klein Roger A.
Published: August 2002

Studies on the conformational equilibrium for the following diols, ethane‐1,2‐diol (12EG, CAS 107‐21‐1), 2R‐D‐(−)‐propane‐1,2‐diol (12PG, CAS 4254‐14‐2), (2S,3S)‐L‐(+)‐butane‐2,3‐diol (L23BD, CAS 19132‐06‐0), and (2S,3R)‐meso‐butane‐2,3‐diol (m23BD, CAS 5341‐95‐7), are described using Gaussianab initiocalculations involving density functional theory (DFT) methods. We also report in this article results on the stability and conformation for the 1:1 water‐diol complex formed by ethane‐1,2‐diol, propane‐1,2‐diol, and L‐ andmeso‐butane‐2,3‐diol. The relative stability of the intramolecular (internal) hydrogen bond in a range of diols (n= 2 to 6), based onab initiogeometry optimization and determination of the O…H distance,dOH, and OH…O angle, θ, increases through the sequence 1,2 ≈ 2,3 < 1,3 < 1,4 ≈ 1,5 ≈ 1,6, as judged from the bond linearity and O…H separation. Quantum mechanical and topological analysis of possible intramolecular hydrogen bonding in this complete series of diols provides convincing evidence for this in diols in which the hydroxyl groups are separated by three or more carbon atoms, that is, in (n,n+m) diols form≥ 2, but not for ethane‐1,2‐diol or other vicinal diols, which do not satisfy Popelier's topological and electron density criteria based on the AIM theory of Bader. Based on these criteria it is unlikely that vicinal diols are in fact capable of forming an intramolecular hydrogen bond, in spite of geometric and spectroscopic data in the literature suggesting otherwise. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 585–599, 2002
Simulated pain on the Symptom Checklist 90‐Revised
Authors: McGuire Brian E. , Shores E. Arthur
Published: August 2002

This study investigated whether a pain clinical sample and pain simulators could be distinguished by their responses on the Symptom Checklist 90‐Revised (SCL‐90‐R). Fifty patients with a pain condition completed the SCL‐90‐R under normal instructions while 20 students responded under instructions to feign a pain disorder to obtain compensation but to attempt to avoid detection. Pain patients obtained generalized elevations, with the highest scores on Depression, Obsessive‐Compulsive, and Somatization. The simulators exceeded the pain group on all clinical scales of the SCL‐90‐R, tending to greatly overestimate the degree of psychological distress in pain patients. Simulators had extreme elevations and were more likely to obtain a T score greater than 70 on each of the clinical scales. Sensitivity, specificity, positive and negative predictive power values, and optimal diagnostic cutoff scores for the clinical scales are reported. The recommended Positive Symptom Total (PST) cutoff score for “faking bad” in the SCL manual had poor specificity. The SCL‐90‐R warrants further study as an aid to identifying pain simulation. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 1589–1596, 2001.
Forgiveness and romantic relationships in college: Can it heal the wounded heart?
Authors: Rye Mark S. , Pargament Kenneth I.
Published: August 2002

This study evaluated the effects of two versions of a six‐week group forgiveness intervention for college women who had been wronged in a romantic relationship. Participants (N = 58) were randomly assigned to a secular, religiously integrated, or no‐intervention comparison condition. Participants completed a variety of forgiveness and mental health measures at one‐week pretest, one‐week posttest, and six‐week follow‐up. Participants in both intervention conditions improved significantly more than did those in the comparison condition on two measures of forgiveness and a measure of existential well‐being. Program effects were maintained at six‐week follow‐up. Contrary to hypotheses, there were no differential treatment effects when comparing participants in the secular and the religiously integrated conditions. Participants generally rated the programs favorably. Forgiveness strategies utilized by participants also were examined. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 419–441, 2002.
Factor structure, reliability, and validity of the Beck Anxiety Inventory in adolescent psychiatric inpatients
Authors: Osman Augustine , Hoffman Joseph , Barrios Francisco X. , Kopper Beverly A. , Breitenstein Joseph L. , Hahn Susan K.
Published: August 2002

The purpose of this study was to examine further the factor structure, reliability, and validity of the Beck Anxiety Inventory (BAI) in samples of adolescents, ages 14 to 18 years. The BAI is a 21‐item self‐report measure of anxiety severity. The BAI total score differentiated between the inpatient and high‐school adolescents. In the psychiatric inpatient sample, girls obtained higher anxiety‐severity scores than boys; no gender differences were obtained for the BAI total score in the high‐school sample. Confirmatory factor analyses did not provide adequate fit for the two‐
factor oblique BAI models to the separate male and female psychiatric inpatient data. Principal axes with varimax and promax rotations initially identified a four‐factor solution in the separate male and female inpatient participants. However, second‐order analyses of the primary factors provided stronger support for a single‐factor structure in each sample. Estimates of reliability for the BAI were adequate in samples of psychiatric inpatient and high‐school adolescents. Evidence for convergent and discriminant validity of the BAI was investigated separately in the male and female inpatient samples. Overall, the BAI showed acceptable psychometric properties in these populations. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 443–456, 2002.
Factorial structure of the Perceived Neighborhood Scale (PNS): A test of longitudinal invariance
Authors: Martinez M. Loreto , Black Maureen , Starr Raymond H.
Published: August 2002

This article analyzes the invariance of the factor structure of the Perceived Neighborhood Scale (PNS)—a measure of neighborhood perceptions for parents of young children—across two waves of data. Scale items were theoretically derived to represent four dimensions of neighborhood context: social embeddedness, sense of community, satisfaction with neighborhood, and fear of crime. The longitudinal invariance of the factor structure of the scale was confirmed by testing the goodness‐of‐fit of four nested models. Results from longitudinal confirmatory factor analytic models (a) provide support for the hypothesized scale structure, (b) demonstrate convergent validity, and (c) demonstrate nonmetric and strict metric invariance. In addition, correlation analyses examining the associations between neighborhood characteristics and scale scores indicated external validity. Both sense of community and satisfaction with neighborhood were significantly associated with parental sense of efficacy. Findings are discussed in light of the implications for longitudinal research with children and the effects of neighborhood characteristics on parenting and the development of preschool children. © 2002 John Wiley & Sons, Inc.
IGF‐I mediates the stimulatory effect of high phosphate concentration on osteoblastic cell proliferation
Authors: Kanatani Masanori , Sugimoto Toshitsugu , Kano Junichi , Chihara Kazuo
Published: August 2002

Although high concentrations of inorganic phosphate (Pi) are known to have a distinct anabolic effect on bone structure and metabolism, the precise mechanism by which phosphate possesses anabolic effect on bone formation has not been elucidated. The present study was performed to examine the effects of an increase in extracellular Pi concentration ([Pi]e) on the proliferation of osteoblastic MC3T3‐E1 cells. Increase in [Pi]e(2–4 mM) dose‐dependently stimulated DNA synthesis. Indomethacin, an inhibitor of prostaglandin synthesis, did not affect high [Pi]e‐induced DNA synthesis. DNA synthesis first increased affer a 3 h exposure to 4 mM [Pi]e and its stimulatory effect was observed in a time‐dependent manner up to 24 h. On the other hand, DNA synthesis was significantly but partially blocked by cycloheximide, suggesting that this stimulatory effect of high [Pi]e was at least in part dependent on new protein synthesis. There is recent evidence that MG3T3‐E1 cells constitutively produce and secrete insulin‐like growth factor‐I (IGF‐I) and possess IGF‐I receptors. IGF‐I antiserum (1:10,000 to 1:100) significantly but partially blocked the stimulatory effect of [Pi]e (4 mM) on DNA synthesis in a concentration‐dependent manner. A neutralizing IGF‐I antibody as well as IGF‐I receptor antibody also significantly but partially blocked DNA synthesis stimulated by high [Pi]e in a concentration‐dependent manner, indicating that IGF‐I at least in part mediated the high [Pi]e‐induced effect. Actually, high [Pi]e significantly increased the secretion of immunoreactive IGF‐I into the medium as well as the expression of IGF‐I mRNA. Present findings indicate that an increase in [Pi]e stimulated DNA synthesis partly via an increase in IGF‐I action. J. Cell. Physiol. 190: 306–312, 2002. © 2002 Wiley‐Liss, Inc.
Autocrine TGFβ signaling mediates vitamin D3 analog‐induced growth inhibition in breast cells
Authors: Yang Limin , Yang Junhua , Venkateswarlu Srinivas , Ko Tien , Brattain Michael G.
Published: August 2002

In this study, we address whether TGFβ signaling mediates vitamin D3 analog‐induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGFβ was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGFβ. MCF7L TGFβRII‐transfected cells, which have autocrine TGFβ activity, were more sensitive to EB1089 than MCF7L cells. TGFβ neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGFβ signaling mediates the anti‐proliferative effects of the vitamin D3 analogs in these cells. The expression of TGFβ isoforms and/or TGFβ receptors was induced by the analogs in the vitamin D3 and TGFβ sensitive cells. Vitamin D3 analogs did not induce TGFβ or TGFβ receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGFβ activity through increasing expression of TGFβ isoforms and/or TGFβ receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089‐induced VDR‐dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGFβ signaling mediator, coactivated VDR‐dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGFβ signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also indicate that Smad3 is not of itself sufficient to coactivate VDR in TGFβ/vitamin D3 resistant MCF7L cells and other factors are required. We found that the PI 3‐kinase pathway inhibitor LY29004 inhibited the synergy of TGFβ and EB1089 on VDR‐dependent transactivation activity. This indicates that the crosstalk between TGFβ and vitamin D signaling is also PI 3‐kinase pathway dependent. © 2001 Wiley‐Liss, Inc.
Effect of a gas–liquid separator on the hydrodynamics and circulation flow regimes in internal‐loop airlift reactors
Authors: Klein Jaroslav , Godo Štefan , Dolgoš Ondrej , Markoš Jozef
Published: August 2002

The role of the gas–liquid separator on hydrodynamic characteristics in an internal‐loop airlift reactor (ALR) was investigated. Both gas holdup and liquid velocity were measured in a 30 dm3 airlift reactor with two different head configurations: with and without an enlarged separator. A magnetic tracer method using a neutrally buoyant magnetic particle as flowfollower was used to measure the liquid velocity in all sections of the internal‐loop airlift reactor. Average liquid circulation velocities in the main parts of the ALR were compared for both reactor configurations. At low air flow rates the separator had no influence on gas holdup, circulation velocity and intensity of turbulence in the downcomer and separator. At higher superficial air velocities, however, the separator design had a decisive effect on the hydrodynamic parameters in the downcomer and the separator. On the other hand, the gas holdup in the riser was only slightly influenced by the separator configuration in the whole range of air flow. Circulation flow regimes, characterising the behaviour of bubbles in the downcomer, were identified and the effect of the separator on these regimes was assessed.

© 2001 Society of Chemical Industry
Dendrimers: a review of their appeal and applications
Authors: Dykes Graham M
Published: August 2002

Dendrimer chemistry is one of the most fascinating and rapidly expanding areas of modern chemistry. This review attempts to uncover the appeal of these structurally‐perfect branched macromolecules. The three intriguing regions of a dendritic molecule are discussed: the multifunctional surface, the tailored sanctuary within the branches, and the encapsulated core. The advantages of dendritic structures for property modification, and their potential applications in very diverse areas are illustrated. The exciting merger of dendrimer chemistry with self‐assembly offers new, stimulating avenues for exploration. Consequently, self‐assembling dendrimers comprise a major section of this article.

© 2001 Society of Chemical Industry
Activity‐related, dynamic neuron‐glial interactions in the hypothalamo‐neurohypophysial system
Authors: Miyata Seiji , Hatton Glenn I.
Published: August 2002

Magnocellular neurons located in the supraoptic nucleus send their principal axons to terminate in the neurohypophysis, where they release vasopressin and oxytocin into the blood circulation. This magnocellular hypothalamo‐neurohypophysial system is known to undergo dramatic activity‐dependent structural plasticity during chronic physiological stimulation, such as dehydration and lactation. This structural plasticity is accompanied not only by synaptic remodeling, increased direct neuronal membrane apposition, and dendritic bundling in the supraoptic nucleus, but also organization of neurovascular contacts in the neurohypophysis. The adjacent glial cells actively participate in these plastic changes in addition to magnocellular neurons themselves. Many molecules that are possibly concerned with dynamic structural remodeling are highly expressed in the hypothalamo‐neurohypophysial system, although they are generally at low expression levels in other regions of adult brains. Interestingly, some of them are highly expressed only in embryonic brains. On the basis of function, these molecules are classified mainly into two categories. Cytoskeletal proteins, such as tubulin, microtubule‐associated proteins, and intermediate filament proteins, are responsible for changing both glial and neuronal morphology and location. Cell adhesion molecules, belonging to immunoglobulin superfamily proteins and extracellular matrix glycoproteins, also participate in neuronal–glial, neuronal–neuronal, and glial–glial recognition and guidance. Thus, the hypothalamo‐neurohypophysial system is an interesting model for elucidating physiological significance and molecular mechanisms of activity‐dependent structural plasticity in adult brains. Microsc. Res. Tech. 56:143–157, 2002. © 2002 Wiley‐Liss, Inc.
Chronic intrathecal infusions after spinal cord injury cause scarring and compression
Authors: Jones Leonard L. , Tuszynski Mark H.
Published: August 2002

Intrathecal infusions are used in a number of rodent studies to deliver substances to the injured spinal cord. Whereas this method has been successful in certain paradigms, two potential limitations of this model have not been extensively reported: (1) scar formation at the catheter tip, which can lead to infusion failure, and (2) damage to the spinal cord caused by the catheter itself. Thus, the purpose of the present study was threefold: (1) to determine intrathecal infusion efficiency over 14 days following spinal cord injury; (2) to examine possible secondary damage caused by intrathecal tubing; and (3) to explore whether alternative protocols that avoid such damage are effective. Adult Fischer 344 rats were subjected to spinal cord lesions at T7, followed by placement of an intrathecal catheter attached to an Alzet minipump. Seven or 14 days following injury and catheter placement, tube patency was evaluated by diffusion of Evans Blue dye from the minipump. Results indicate that infusion was efficient 7 days following injury but was markedly reduced after 14 days. Further, histology and immunocytochemistry 14 days after injury demonstrated compression damage to the cord where the tubing rested. Alternative protocols, including intrathecal infusions through metal cannulae, or “drip” infusions directly over the lesion, did not improve delivery. These data suggest that results from rodent studies using infusion from catheters placed adjacent to lesion sites may be attributable to acute or subacute effects of the delivered substance. Future rodent studies using intrathecal infusions should include rigorous evaluation of infusion efficiency and possible secondary tissue damage. Microsc. Res. Tech. 54:317–324, 2001. © 2001 Wiley‐Liss, Inc.
Origins of flower morphology
Authors: Endress Peter K.
Published: August 2002

Flowers evolved in many steps, probably starting long before flowering plants (angiophytes) originated. Certain parts of flowers are conservative and have not changed much during evolution; others are evolutionarily highly plastic. Here conservative features are discussed and an attempt is made to trace them back through their evolutionary history. Microsporangia and ovules (which develop into seeds) are preangiophyte floral elements. Angiospermy, combined with postgenital fusion, was the most prominent key innovation in angiophytes. Angiospermy and thecal organization of stamens originated earlier than all clades of extant angiosperms (the crown group of angiophytes). Differentiation of a perianth into calyx and corolla and syncarpy appeared after the first branching of the basalmost clades of extant angiosperms. Sympetaly and floral tubes as well as tenuinucellar, unitegmic ovules originated as major innovations in the clade that led to asterids. An obvious trend in flower evolution is increased synorganisation of parts, which led to new structures. Fixation of floral organ number and position was a precondition for synorganization. Concomitantly, plasticity changed from number and position of organs to shape of the new structures. Character distribution mapped onto cladograms indicates that key innovations do not appear suddenly, but start with trials and only later become deeply rooted genetically in the organization. This is implied from the common occurrence of reversals in the early history of an innovation. J. Exp. Zool. (Mol. Dev. Evol.) 291:105–115, 2001. © 2001 Wiley‐Liss, Inc.