bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug induced nightmares—an etiology based review
Authors: Pagel J. F. , Helfter P. 
Published: January 2003

AbstractObjectiveRecent clinical trials have included patient complaints of nightmares as a category of reportable medication side effects. This study integrates that data into current experimental and theoretical research of drug effects that may alter dreaming and nightmares. The objective is to provide a clinical and theoretical framework useful in categorizing the potential and reported drug effects on nightmares.MethodologyThis study reviews case reports and clinical trials that have reported nightmares or alterations in dreaming occurring secondary to medication usage. These data are analysed as to the probability of the drug/nightmare association, and integrated into current electrophysiological and neurochemical theories of dreaming and nightmares.ResultsPharmacological agents affecting the neurotransmitters norepinephrine, serotonin and dopamine are clearly associated with patient reports of nightmares. Agents affecting immunological response to infectious disease are likely to induce nightmares in some patients. A possible association exists between reports of nightmares and agents affecting the neurotransmitters acetylcholine, GABA and histamine, as well as for some anesthetics, antipsychotics and antiepileptic agents.ConclusionBy utilizing our current experimental and theoretical knowledge base, the potential etiology of a majority of reported drug effects on nightmares can be classified. These data support current neurochemical theories of dreaming, as well as suggesting that the biochemical basis for dreaming and nightmare induction may be more complex than generally suggested. Copyright © 2003 John Wiley & Sons, Ltd.
Actigraphy in human psychopharmacology: a review
Authors: Stanley Neil 
Published: January 2003

AbstractOver the last 25 years wrist actigraphy has predominantly been used in sleep research and chronobiology where the technique has proved useful in the measurement of sleep and the characterisation of the sleep/wake cycle. Whilst there are a large number of studies published that have used actigraphy, there have only been relatively few studies that have shown that the technique is capable of measuring drug‐induced changes in nocturnal and/or diurnal behaviour. Thus the use of actigraphy to measure drug effects in clinical trials has up till now remained on the periphery of psychopharmacology. However this may be because of the disparate nature of the studies published rather than lack of usefulness. This paper reviews the relevant literature and in doing so concludes that there is a convincing body of evidence for the utility of actigraphy as a technique in human psychopharmacology. Copyright © 2003 John Wiley & Sons, Ltd.
Spontaneous activation and signaling by overexpressed epidermal growth factor receptors in glioblastoma cells
Authors: Thomas Christopher Y. , Chouinard Michael , Cox Michael , Parsons Sarah , Stallings‐Mann Melody , Garcia Roy , Jove Richard , Wharen Robert 
Published: January 2003

AbstractOverexpressed epidermal growth receptor factor receptors (EGFRs) are thought to contribute to the malignant phenotype of human glioblastomas (GBMs), but the mechanism is not well understood. We found that SKMG‐3 cells, a rare GBM cell line that maintains EGFR gene amplification in vitro, produced high levels of EGFR protein. The cells also expressed the related receptors HER2/neu and HER4, but not HER3. Immunoblots and tryptic phosphopeptide maps showed that the SKMG‐3 EGFRs were intact and functional and that a subset of these receptors were spontaneously autophosphorylated. EGF treatment stimulated phosphorylation of the EGFRs as well as the downstream effectors Erk, AKT1, stat3 and c‐Cbl. Under minimal growth conditions, the unstimulated SKMG‐3 cells contained constitutively phosphorylated Erk and AKTI but no detectable stat3 DNA‐binding complexes. The EGFR kinase inhibitor PD158780 reduced the constitutive phosphorylation of the receptor and Erk but not that of AKT1. In contrast, inhibition of phosphatidylinositol‐3‐kinase (PI3K) blocked the constitutive phosphorylation of Erk and AKT‐1 but not the EGFR. We conclude that the SKMG‐3 cells represent the subset of GBMs with amplified EGFR genes that overexpress intact receptors. The results also suggest that in some GBMs, signals from overexpressed EGFRs contribute to the constitutive phosphorylation of Erk, but these signals may not required for the constitutive activation of PI3K or AKT1. © 2002 Wiley‐Liss, Inc.
Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q
Authors: Stone Brad , Schummer Michèl , Paley Pamela J. , Thompson Lucas , Stewart Julie , Ford Molly , Crawford Meghan , Urban Nicole , O'Briant Kathy , Nelson Brad H. 
Published: January 2003

AbstractWe utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late‐stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20–45 normal female serum donors. These antigens include p53, NY‐ESO‐1, UBQLN1, HOXB6, TOP2A, putative helicase‐RUVBL (RUVBL), HMBA‐inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox‐B7 and BRCA1. Real‐time RT‐PCR analysis showed that mRNA for HER2/neu and 3 SEREX‐defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy. © 2002 Wiley‐Liss, Inc.
Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene
Authors: Sakano Shigeru , Berggren Petra , Kumar Rajiv , Steineck Gunnar , Adolfsson Jan , Onelöv Erik , Hemminki Kari , Larsson Per 
Published: January 2003

AbstractPoint mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population‐based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor‐tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3′ UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ‐line. Frequencies of the 500 C→G and 540 C→T polymorphisms in the 3′ UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor‐specific survival was significantly shorter in patients with either the 500 C→G or 540 C→T polymorphism than those with wild‐type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3′ UTR polymorphisms in the CDKN2A gene in tumor invasiveness. © 2002 Wiley‐Liss, Inc.
The E2F‐1 transcription factor is negatively regulated by its interaction with the MDMX protein
Authors: Strachan Gordon D. , Jordan‐Sciutto Kelly L. , Rallapalli Ravikumar , Tuan Rocky S. , Hall David J. 
Published: January 2003

AbstractSeveral proteins with important roles in oncogenesis have been shown to regulate the function of the E2F‐1 transcription factor, which is known to activate the expression of genes required for proliferation and apoptosis. Here we identify the MDMX oncoprotein as an E2F‐1‐binding factor, from a yeast‐two hybrid screen using a portion of the E2F‐1 protein as “bait.” We demonstrate that the region within MDMX needed for the E2F‐1:MDMX interaction is located in the central part of the protein, C‐terminal of the p53‐binding domain. The region within E2F‐1 needed for this association is adjacent to the DNA binding domain. Further, when expressed in vivo or in vitro the MDMX protein migrates as two isoforms on SDS‐PAGE, the faster migrating isoform having the stronger affinity for the E2F‐1 proteins. It appears that this interaction reduces the ability of E2F‐1 to bind DNA. Expression of MDMX along with E2F‐1 and Dp‐1 in Saos2 cells reduces the ability of E2F‐1 to bind to its consensus DNA sequence, without altering E2F‐1 protein levels. These data indicate that the MDMX protein is capable of associating with E2F‐1 and negatively regulating its DNA binding ability. © 2002 Wiley‐Liss, Inc.
Gene therapy and tissue engineering in repair of the musculoskeletal system
Authors: Wu Daniel , Razzano Pasquale , Grande Daniel A. 
Published: January 2003

AbstractHistorically, surgeons have sought and used different procedures in order to augment the repair of various skeletal tissues. Now, with the completion of the Human Genome Project, many researchers have turned to gene therapy as a means to aid various ailments. In the orthopedic field, many strides have been made toward using gene therapy and tissue engineering in a clinical setting. In this review, several studies are outlined in different areas that gene therapy has or will influence orthopedic surgery. Gene therapy and tissue engineering can aid in fracture healing and spinal fusions by inducing bone formation, ligamentous repairs by increasing the production of connective tissue fibers, intervertebral disc disease by creating potential replacements, and articular cartilage repairs by providing means to improve cartilage. As we continue to see great contributions, such as the few mentioned here, this field will continue to mature and develop. © 2002 Wiley‐Liss, Inc.
Differential regulation of cellular adhesion and migration by recombinant laminin‐5 forms with partial deletion or mutation within the G3 domain of α3 chain
Authors: Kariya Yoshinobu , Tsubota Yoshiaki , Hirosaki Tomomi , Mizushima Hiroto , Puzon‐McLaughlin Wilma , Takada Yoshikazu , Miyazaki Kaoru 
Published: January 2003

AbstractThe basement membrane protein laminin‐5 promotes cell adhesion and migration. The carboxyl‐terminal G3 domain in the α3 chain is essential for the unique activity of laminin‐5. To investigate the function of the G3 domain, we prepared various recombinant laminin‐5 forms with a partially deleted or mutated G3 domain. The deletion of the carboxyl‐terminal 28 amino acids (region III) markedly decreased the cell adhesion activity with a slight loss of the cell motility activity toward BRL and EJ‐1 cells. This change was attributed to the loss of Lys‐Arg‐Asp sequence. Further deletion of 83 amino acids (region II) led to almost complete loss of the cell motility activity. All charged amino acid residues tested in this region were not responsible for the activity loss. These results suggest that the G3 domain contains two distinct regions that differently regulate cell adhesion and migration. Analysis of laminin‐5 receptors showed that integrins α3β1, α6β1, and α6β4 had different but synergistic effects on cell adhesion and migration on laminin‐5. However, the structural change of the G3 domain appeared not to change integrin specificity. The present study demonstrates that the G3 domain in laminin‐5 plays a central role to produce different biological effects on cells. © 2002 Wiley‐Liss, Inc.
Phosphorylation of proteins in neuron terminals: Specificity depends on coincidental signaling
Authors: Zhang Lixing , Tinette Sylvette , Robichon Alain 
Published: January 2003

AbstractWe investigate the role of neuronal coincidental signaling mediated by the second messengers, on phosphorylation of three major proteins of neurosecretory vesicles. Our data show that different combinations of coincidental signaling generate specific pattern of phosphoproteins and not strictly additional effects. This suggests that an added phosphate on a site might ‘mask’ or ‘unmask’ the next sites for specific kinases and phosphatases action by inducing conformation change or protein association. We show that a function of vesicles such as the uptake of glutamate is highly regulated by coincidental signaling. © 2002 Wiley‐Liss, Inc.
Mutation analysis of the non‐muscle myosin light chain kinase (MLCK) deletion constructs on CV1 fibroblast contractile activity and proliferation
Authors: Wadgaonkar Raj , Nurmukhambetova Saule , Zaiman Ari L. , Garcia Joe G.N. 
Published: January 2003

AbstractSmooth muscle myosin light chain kinase (MLCK) is a multifunctional molecule composed of an N‐terminal actin binding domain, a central kinase domain, and C‐terminal calmodulin‐ and myosin‐binding domains. We previously cloned and characterized a novel MLCK isoform from endothelial cells (EC MLCK) consisting of 1,914 amino acids displaying a higher molecular weight (210 kDa) and a novel‐amino‐terminal stretch of 922 amino acids not shared by the smooth muscle isoform (smMLCK, 150 kDa). To further define the role of specific EC MLCK motifs in endothelial and non‐muscle cells, we constructed two epitope‐tagged EC MLCK deletion mutants in mammalian expression vectors lacking either the C‐terminal auto‐inhibitory and calmodulin‐binding domain (EC MLCK1745) or the ATP‐binding site (EC MLCKATPdel). Expression of EC MLCK1745 in CV1 fibroblasts showed increased basal actin stress fiber formation, which was markedly enhanced after tumor necrosis factor (TNF‐α) or thrombin treatment. Distribution of EC MLCK1745 was largely confined to stress fibers, cortical actin filaments, and focal adhesion contacts, and co‐localized with myosin light chains (MLCs) diphosphorylated on Ser19 and Thr18. In contrast, immunofluorescence staining demonstrated that EC MLCKATPdel abolished thrombin‐ and TNFα‐induced stress fiber formation and MLC phosphorylation, suggesting this kinase‐dead mutant functions as a dominant‐negative MLCK construct, thereby confirming the role of EC MLCK in stress fiber formation. Finally, we compared the serum‐stimulated growth rate of mutant MLCK‐transfected fibroblasts to sham controls, and found EC MLCK1745 to augment thymidine incorporation whereas EC MLCKATPdel reduced CV1 growth rates. These data demonstrate the necessary role for MLCK in driving the contractile apparatus via MLC phosphorylation, which can alter fibroblast growth and contractility. © 2002 Wiley‐Liss, Inc.
IRES‐dependent translational control of Cbfa1/Runx2 expression
Authors: Xiao Zhou‐Sheng , Simpson Leigh G. , Quarles L. Darryl 
Published: January 2003

AbstractThe P1 and P2 promoters of the Cbfa1/Runx2 gene produce Type I and II mRNAs with distinct complex 5′‐untranslated regions, respectively designated UTR1 and UTR2. To evaluate whether the 5′‐UTRs impart different translational efficiencies to the two isoforms, we created SV40 promoter‐UTR–luciferase reporter (luc) constructs in which the translational potential of the 5′‐UTR regions was assessed indirectly by measurement of luciferase activity in transfected cell lines in vitro. In MC3T3‐E1 pre‐osteoblasts, UTR2 was translated approximately twice as efficiently as the splice variants of UTR1, whereas translation of unspliced UTR1 was repressed. To determine if the UTRs conferred internal ribosome entry site (IRES)‐dependent translation, we tested bicistronic SV40 promoter‐Rluc‐UTR‐Fluc constructs in which Fluc is expressed only if the intercistronic UTR permits IRES‐mediated translation. Transfection of bicistronic constructs into MC3T3‐E1 osteoblasts demonstrated that both UTR2 and the spliced forms of UTR1 possess IRES activity. Similar to other cellular IRESs, activity increased with genotoxic stress induced by mitomycin C. In addition, we observed an osteoblastic maturation‐dependent increase in IRES‐mediated translation of both UTR2 and the spliced forms of UTR1. These findings suggest that Cbfa1 UTRs have IRES‐dependent translational activities that may permit continued Cbfa1 expression under conditions that are not optimal for cap‐dependent translation. © 2003 Wiley‐Liss, Inc.
Raf‐independent and MEKK1‐dependent activation of NF‐κB by hydrogen peroxide in 70Z/3 pre‐B lymphocyte tumor cells
Authors: Lee Michael , Koh Woo Suk 
Published: January 2003

AbstractWe have previously demonstrated that hydrogen peroxide (H2O2) treatment of murine 70Z/3 pre‐B lymphocytes inhibits the immune response to lipopolysaccharide by attenuating signaling through c‐Jun N‐terminal kinase (JNK) activation. In the present study, we further examined the signaling intermediates responsible for immunosuppression by H2O2, focusing on NF‐κB, a dimeric transcription factor whose activation is implicated in a number of immune response. Treatment of 70Z/3 pre‐B cells with H2O2 caused activation of NF‐κB in the nuclei by detection of NF‐κB specific DNA binding, concomitant with phosphorylation of IκBα. H2O2 stimulation of NF‐κB occurred within 20 min of treatment, reached maximum level at 60 min, and sustained for 2 h or more. Especially, MEK1 may contribute to H2O2‐induced NF‐κB activation as shown in the inhibition of NF‐κB binding activity by the MEK1 inhibitor, PD 98059, and H2O2‐induced MEK1 activation. However, H2O2 exhibited no effect on the activity of Raf‐1 kinase, which was an upstream activator of MEK1. Furthermore, B‐58l and α‐hydroxyfarnesylphosphonic acid, two inhibitors of Ras, did not block NF‐κB activation. In addition, the transient transfection of a dominant negative Ras (RasN17) construct showed a negligible inhibitory effect on the activation of NF‐κB by H2O2. Instead, treatment of 70Z/3 cells with H2O2 resulted in the activation of MAPK kinase kinase 1 (MEKK1) as well as JNK. Therefore, our data suggest that H2O2 regulates the activity of NF‐κB by MEK1 activation through MEKK1‐dependent but Ras/Raf‐independent mechanism. © 2002 Wiley‐Liss, Inc.
Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP‐1 transactivation
Authors: Ontiveros C. , McCabe Laura R. 
Published: January 2003

AbstractConditions of disuse such as bed rest, space flight, and immobilization result in decreased mechanical loading of bone, which is associated with reduced bone mineral density and increased fracture risk. Mechanisms involved in this process are not well understood but involve the suppression of osteoblast function. To elucidate the influence of mechanical unloading on osteoblasts, a rotating wall vessel (RWV) was employed as a ground based model of simulated microgravity. Mouse MC3T3‐E1 osteoblasts were grown on microcarrier beads for 14 days and then placed in the RWV for 24 h. Consistent with decreased bone formation during actual spaceflight conditions, alkaline phosphatase and osteocalcin expression were decreased by 80 and 50%, respectively. In addition, runx2 expression and AP‐1 transactivation, key regulators of osteoblast differentiation and bone formation, were reduced by more than 60%. This finding suggests that simulated microgravity could promote dedifferentiation and/or transdifferentiation to alternative cell types; however, markers of adipocyte, chondrocyte, and myocyte lineages were not induced by RWV exposure. Taken together, our results indicate that simulated microgravity may suppress osteoblast differentiation through decreased runx2 and AP‐1 activities. © 2002 Wiley‐Liss, Inc.
Catalytic combustion of chlorinated ethylenes over H‐zeolites
Authors: López‐Fonseca R , Gutiérrez‐Ortiz J I , Gutiérrez‐Ortiz M A , González‐Velasco J R 
Published: January 2003

AbstractSeveral H‐zeolites (H‐Y, H‐ZSM‐5 and H‐MOR) were investigated for the catalytic combustion of chlorinated ethylenes, namely 1,1‐dichloroethylene and trichloroethylene. Conversion was inversely related to the chlorine content of the feed molecule. H‐ZSM‐5 zeolite was the most active catalyst in 1,1‐dichloroethylene combustion whereas H‐MOR was the most effective zeolite for trichloroethylene destruction. Temperature‐programmed desorption of ammonia and diffuse reflectance FT‐IR measurements of adsorbed pyridine revealed that strong Brønsted acidity plays an important role in controlling the activity of H‐zeolites. The main combustion products were CO, CO2, HCl, and Cl2. Additionally, small amounts of highly chlorinated by‐products were also detected, namely trichloroethylene and tetrachloroethylene. H‐zeolites showed a great selectivity to HCl formation.© 2002 Society of Chemical Industry
Metal sorption by biomass of melanin‐producing fungi grown in clay‐containing medium
Authors: Fomina Marina , Gadd Geoffrey M 
Published: January 2003

AbstractThe sorption of toxic metals by fungal mycelia grown in clay‐containing medium is reported in this work. Biomass of melanin‐producing microfungi of the genus Cladosporium (C cladosporioides, C resinae and C herbarum) and Aureobasidium pullulans, clay minerals and fungal mycelia grown in clay‐containing medium were compared for their equilibrium Cu and Cd uptake from pH‐buffered solutions using experimental sorption isotherms. Bentonite (Cherkassy) in the natural form was shown to be the best Cu sorbent compared with the other clays and clay minerals tested. Cu sorption isotherms fitted the Langmuir sorption model for all cases. Comparison of Cu and Cd uptake for biomass and bentonite showed a lower biomass uptake capacity but a considerably higher affinity of the biosorbent for the solute. The presence of kaolinite and palygorskite in the medium generally reduced both Cu and Cd sorption capacity and the metal‐binding ability of the fungal–clay mixtures. In contrast, addition of bentonite into the medium did not appreciably alter the Cd sorption ability but increased the sorption of Cu by A pullulans and C cladosporioides grown in this medium. A common feature for all fungi grown in the presence of bentonite was an increase in the Cu sorption capacity (Qmax) of the biomineral sorbents and a reduction in their affinity (Langmuir parameter b) compared with control biomass. A difference between predicted and experimental data obtained for biomass grown on bentonite medium was also observed. The connection between the sorption capacity of biomass grown in clay‐containing medium, mycelial morphology and the structure of fungal pellets is discussed and a mechanism for the changed sorption capacity of the combined biomineral sorbents is proposed which involves blocking or modification of binding sites on biotic and abiotic components of the ‘biomineral’ association.© 2002 Society of Chemical Industry