bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of a Stable Antioxidant Response Element–Driven Reporter Gene Cell Line and Its Use to Show Redox-Dependent Activation of Nrf2 by Cancer Chemotherapeutic Agents
Authors: Wang Xiu Jun , Hayes John D. , Wolf C. Roland 
Published: November 2006

AbstractThe NF-E2 p45-related factor 2 (Nrf2) regulates cytoprotective genes that contain an antioxidant response element (ARE) in their promoters. To investigate whether anticancer drugs can induce ARE-driven gene expression, we have developed a stable human mammary MCF7-derived reporter cell line called AREc32, which contains a luciferase gene construct controlled by eight copies of the cis-element. In these cells, luciferase activity was increased up to 50-fold following treatment with 50 μmol/L tert-butylhydroquinone (t-BHQ). Basal and inducible luciferase activities in AREc32 cells were increased by forced overexpression of Nrf2 and reduced by knockdown of endogenous Nrf2 expression with RNA interference. Depletion of cellular reduced glutathione (GSH) by treatment of AREc32 cells with l-buthionine-S,R-sulfoximine (BSO) did not influence basal levels of luciferase activity, but pretreatment with BSO augmented induction of luciferase activity by t-BHQ. Induction of reporter activity by t-BHQ in AREc32 cells was suppressed markedly by the antioxidants N-acetylcysteine and GSH but only modestly by vitamins C or E, suggesting that ARE-luciferase expression is induced primarily by thiol-active electrophiles rather than free radicals. The anticancer drugs cisplatin, etoposide, mitoxantrone, chlorambucil, melphalan, and carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] weakly induced luciferase activity in AREc32 cells. Moreover, treatment of AREc32 cells with BSO immediately before exposure to anticancer drugs enhanced induction of ARE-driven luciferase activity by cisplatin, BCNU, chlorambucil, and melphalan and also induced endogenous AKR1C (AKR1C refers to AKR1C1 and AKR1C2), a target gene of Nrf2. Our findings show that Nrf2 can be activated by certain anticancer agents, and this will influence the effectiveness of chemotherapy. (Cancer Res 2006; 66(22): 10983-94)
Molecular Mechanisms of RET Receptor–Mediated Oncogenesis in Multiple Endocrine Neoplasia 2B
Authors: Gujral Taranjit S. , Singh Vinay K. , Jia Zongchao , Mulligan Lois M. 
Published: November 2006

Abstract
Multiple endocrine neoplasia 2B (MEN 2B) is an inherited syndrome of early onset endocrine tumors and developmental anomalies. The disease is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET); however, the molecular mechanisms that lead to the disease phenotype are unclear. In this study, we show that the M918T mutation causes a 10-fold increase in ATP binding affinity and leads to a more stable receptor-ATP complex, relative to the wild-type receptor. Further, the M918T mutation alters local protein conformation, correlating with a partial loss of RET kinase autoinhibition. Finally, we show that 2B-RET can dimerize and become autophosphorylated in the absence of ligand stimulation. Our data suggest that multiple distinct but complementary molecular mechanisms underlie the MEN 2B phenotype and provide potential targets for effective therapeutics for this disease. (Cancer Res 2006; 66(22): 10741-9)
A 12-week, double-blind, placebo-controlled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia
Authors: Lee Bong-Ju , Lee Jung-Goo , Kim Young-Hoon 
Published: November 2006

To study the effects of acetylcholinesterase inhibitors (AChEIs) in the management of cognitive impairments in patients with schizophrenia, we investigated the effects of 12 weeks of adjunctive therapy with donepezil on their cognitive impairments. Twenty-four subjects stabilized on haloperidol treatment (5—30 mg/day) for a minimum of 3 months were entered into a double-blind, placebo-controlled trial of donepezil as an adjunctive treatment. Subjects were randomly assigned under doubLe-blind conditions to receive either 5 mg/day donepezil ( N = 12) or pLacebo ( N = 12) for 12 weeks. The subjects were evaluated at baseline, and after 4, 8, and 12 weeks using the Korean version of Mini MentaL State Examination (K-MMSE), Brief Psychiatric Rating Scale (BPRS), and standard neuropsychological assessment. The K-MMSE scores improved significantly ( p < 0.05) but the BPRS scores did not improve significantly in patients given donepezil; subjects showed slight improvement in several cognitive measures. At the end of the study, the difference in the mean K-MMSE scores between the donepezil and placebo groups approached statistical significance ( p = 0.056). Of the several domains of cognitive functions assessed, verbaL recognition and visuaL recall memory improved significantly ( p < 0.05). But donepezil did not affect scores in the executive function tests. Our findings support a potential positive effect of AChEIs in the management of cognitive impairments in patients with chronic schizophrenia. Further studies with Large subjects are needed to confirm our findings.
Olanzapine prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current
Authors: Morissette Pierre , Hreiche Raymond , Mallet Louise , Vo Dean , Knaus Edward E. , Turgeon Jacques 
Published: November 2006

Prolongation of the QT interval has been observed during treatment with olanzapine, a thienobenzodiazepine antipsychotic agent. Our objectives were 1) to characterize the effects of olanzapine on cardiac repolarization and 2) to evaluate effects of olanzapine on the major time-dependent outward potassium current involved in cardiac repolarization, namely IKr (IKr: rapid component of the delayed rectifier potassium current). Isolated, buffer-perfused guinea pig hearts ( n = 40) were stimulated at different pacing cycle lengths (150—250 msec) and exposed to olanzapine at concentrations ranging from 1 to 100 µM. Olanzapine increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 6.7 ± 0.7 msec at 3 µM but by 26.0 ± 4.3 msec at 100 µM (250 msec cycle length). Increase in MAPD90 was also reverse frequency dependent; 30 µM olanzapine increased MAPD90 by 28.0 ± 6.2 msec at a pacing cycle length of 250 msec but by only 18.9 ± 2.2 msec at a pacing cycle length of 150 msec. Experiments in HERG-transfected (HERG: human ether-a-gogo-related gene) HEK293 cells ( n = 36) demonstrated concentration-dependent block of the rapid component (IKr) of the delayed rectifier potassium current: tail current was decreased 50% at olanzapine 3.8 µM. Olanzapine possesses direct cardiac electrophysiological effects similar to those of class III anti-arrhythmic drugs. These effects were observed at concentrations that can be measured in patients under conditions of impaired drug elimination such as renal or hepatic insufficiency, during co-administration of other CYP1A2 substrates/inhibitors or after drug overdose. These results offer a new potential explanation for QT prolonging effects observed during olanzapine treatment in patients.
Transformations des phyllosilicates dans un sol cryptopodzolique humifère du plateau de Millevaches, France
Authors: Righi D. , Girault P. , Meunier A. 
Published: November 2006

RésuméOn a étudié les transformations minéralogiques des argiles et des biotites isolées d'un sol cryptopodzolique humifère du Plateau de Millevaches, France. Pour les argiles, la diffraction de rayons X fait apparaître un comportement intergrade de plus en plus prononcé de l'horizon C vers l'horizon A1. La nature des éléments extraits par les traitements citratedithionite et Tamura indique que ce comportement est lié à la présence d'aluminium interfoliaire pour les argiles de l'horizon A1Bh, mais également à des résidus de chlorite altérée pour celles de l'horizon A1. Pour les biotites, on observe un comportement aux RX très voisin de celui de la fraction argileuse. On peut mettre en évidence dans l'espace interfoliaire des biotites altérées la présence d'ions alumineux et de composés organiques.
Chlorites and chloritic mixed-layer minerals in profiles on ultrabasic rocks from Moyango (Ivory Coast) and Angiquinho (Brazil)
Authors: Noack Y. , Colin F. 
Published: November 2006

AbstractDifferent types of chlorite and related mixed-layer minerals have been found in profiles developed on ultrabasic rocks of Ivory Coast and Brazil. Normal chlorites, with low K and Ni contents, are of hydrothermal origin and are situated at the bottom of the alteration profile. At the top of the profile the mixed-layer minerals are Ni-chlorite/vermiculite, which formed under weathering conditions, or K-chlorite/vermiculite, resulting from the alteration of mica. The Ni-content of the chlorite/vermiculite can reach 10% NiO.
The engineering geology of clay minerals: swelling, shrinking and mudrock breakdown
Authors: Taylor R. K. , Smith T. J. 
Published: November 2006

AbstractSwelling, shrinking and physical breakdown processes are reviewed with reference to well-known mudrock and overconsolidated clay formations in the UK and USA. Swelling results from two processes: the equilibration of depressed porewater pressures following stress relief, and the physico-chemical (osmotic) response of component clay minerals. Expansion in Na-smectite, and to a lesser extent Ca-smectite, clays is governed by double-layer swelling, whereas in kaolinites it is purely a mechanical unloading phenomenon; illites show an intermediate response. Intraparticle swelling in mudrocks older than the Silurian in the UK, or Upper Mississippian in the USA, can be expected to be reduced because of the removal of expandable layers by burial diagenesis. Shrinkage, like mudrock breakdown, is restricted to the partly saturated zone. Suction pressure-moisture content curves of indurated mudrocks are shown to be different from mudrocks and clays with high proportions of expandable clay minerals. Classification of expansion potential based on activity ratio poses problems with indurated types, but with some modification of method reasonable predictions can be made. Controls on physical disintegration are identified as: (i) incidence of sedimentary structures and discontinuities, (ii) slaking (air breakage), (iii) expandable clay mineral content, especially smectite, and (iv) clay mineral fabric orientation. Exceptionally high exchangeable sodium percentages have been measured in Coal Measures rocks susceptible to breakdown.
Clay mineralogy and plasticity of the Fuller's Earth Formation Bath, UK
Authors: Hawkins A. B. , Lawrence M. S. , Privett K. D. 
Published: November 2006

AbstractClay from the Fuller's Earth formation is shown to contain mainly illite, kaolinite and calcite, in contrast to the Fuller's Earth Bed in which montmorillonite is the main clay mineral. A negative correlation has been demonstrated between the calcite content and the plasticity as measured by the Atterberg limits. Fresh samples from the Fuller's Earth Bed have a higher plasticity than those of the fuller's earth clay with similar calcite percentages, due to the relative increases in the expanding lattice clay mineral. Weathering of the fuller's earth clay typically reduces the calcite content and increases the percentage of montmorillonite, resulting in a higher plasticity.
Time scale and dimension analysis of a budding yeast cell cycle model
Authors: Lovrics Anna , Csikász-Nagy Attila , Zsély István Gy , Zádor Judit , Turányi Tamás , Novák Béla 
Published: November 2006

Abstract

Background
The progress through the eukaryotic cell division cycle is driven by an underlying molecular regulatory network. Cell cycle progression can be considered as a series of irreversible transitions from one steady state to another in the correct order. Although this view has been put forward some time ago, it has not been quantitatively proven yet. Bifurcation analysis of a model for the budding yeast cell cycle has identified only two different steady states (one for G1 and one for mitosis) using cell mass as a bifurcation parameter. By analyzing the same model, using different methods of dynamical systems theory, we provide evidence for transitions among several different steady states during the budding yeast cell cycle.

Results
By calculating the eigenvalues of the Jacobian of kinetic differential equations we have determined the stability of the cell cycle trajectories of the Chen model. Based on the sign of the real part of the eigenvalues, the cell cycle can be divided into excitation and relaxation periods. During an excitation period, the cell cycle control system leaves a formerly stable steady state and, accordingly, excitation periods can be associated with irreversible cell cycle transitions like START, entry into mitosis and exit from mitosis. During relaxation periods, the control system asymptotically approaches the new steady state. We also show that the dynamical dimension of the Chen's model fluctuates by increasing during excitation periods followed by decrease during relaxation periods. In each relaxation period the dynamical dimension of the model drops to one, indicating a period where kinetic processes are in steady state and all concentration changes are driven by the increase of cytoplasmic growth.

Conclusion
We apply two numerical methods, which have not been used to analyze biological control systems. These methods are more sensitive than the bifurcation analysis used before because they identify those transitions between steady states that are not controlled by a bifurcation parameter (e.g. cell mass). Therefore by applying these tools for a cell cycle control model, we provide a deeper understanding of the dynamical transitions in the underlying molecular network.
Multiple enhancers contribute to spatial but not temporal complexity in the expression of the proneural gene, amos
Authors: Holohan Eimear E , zur Lage Petra I , Jarman Andrew P 
Published: November 2006

Abstract

Background
The regulation of proneural gene expression is an important aspect of neurogenesis. In the study of the Drosophila proneural genes, scute and atonal, several themes have emerged that contribute to our understanding of the mechanism of neurogenesis. First, spatial complexity in proneural expression results from regulation by arrays of enhancer elements. Secondly, regulation of proneural gene expression occurs in distinct temporal phases, which tend to be under the control of separate enhancers. Thirdly, the later phase of proneural expression often relies on positive autoregulation. The control of these phases and the transition between them appear to be central to the mechanism of neurogenesis. We present the first investigation of the regulation of the proneural gene, amos.

Results
Amos protein expression has a complex pattern and shows temporally distinct phases, in common with previously characterised proneural genes. GFP reporter gene constructs were used to demonstrate that amos has an array of enhancer elements up- and downstream of the gene, which are required for different locations of amos expression. However, unlike other proneural genes, there is no evidence for separable enhancers for the different temporal phases of amos expression. Using mutant analysis and site-directed mutagenesis of potential Amos binding sites, we find no evidence for positive autoregulation as an important part of amos control during neurogenesis.

Conclusion
For amos, as for other proneural genes, a complex expression pattern results from the sum of a number of simpler sub-patterns driven by specific enhancers. There is, however, no apparent separation of enhancers for distinct temporal phases of expression, and this correlates with a lack of positive autoregulation. For scute and atonal, both these features are thought to be important in the mechanism of neurogenesis. Despite similarities in function and expression between the Drosophila proneural genes, amos is regulated in a fundamentally different way from scute and atonal.
High blood pressure in school children: prevalence and risk factors
Authors: Urrutia-Rojas Ximena , Egbuchunam Christie U , Bae Sejong , Menchaca John , Bayona Manuel , Rivers Patrick A , Singh Karan P 
Published: November 2006

AbstractBackgroundThe purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age.MethodsElementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95thpercentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association.ResultsFemales, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85thpercentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors.ConclusionTwenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.
Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression
Authors: Rask Katarina , Zhu Yihong , Wang Wanzhong , Hedin Lars , Sundfeldt Karin 
Published: November 2006

Abstract

Background
The involvement of the cyclooxygenases (COX), in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs) as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18), benign (B) (n = 8), borderline type (BL) (n = 6) and malignant tumours (AC) (n = 22). The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB) and immunohistochemistry (IHC).

Results
The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p < 0.05) augmented in less differentiated AC (grades: moderately-, poorly- and undifferentiated). The increase of COX-2 was also correlated to stage (FIGO classification) with significant elevations in stages II and III. EP1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated). This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells), e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs.

Conclusion
The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The observed augmentations of COX-1, COX-2 and mPGES-1 have implications for future therapeutic strategies.
Nicotine and serotonin in immune regulation and inflammatory processes: a perspective
Authors: Cloëz-Tayarani Isabelle , Changeux Jean-Pierre 
Published: November 2006

AbstractNicotine and serotonin modulate the innate and adaptive immune responses and the inflammatory states. Several nicotinic cholinergic and serotonergic receptor subtypes have been characterized in B and T lymphocytes, monocytes, macrophages, and dendritic cells. The use of knockout mice has allowed a better characterization of nicotinic receptors and their role in anti-inflammatory processes in these cells. Cytokines play a crucial role in controlling inflammatory reactions. Nicotine and serotonin have been reported to regulate cytokine release. Cholinergic mechanisms also play an important role in inflammation through endogenous acetylcholine. Nicotine mimics this effect by activating the cholinergic anti-inflammatory pathways. New concepts of reciprocal interactions between nicotine and serotonin are emerging. The role of nicotine as an anti-inflammatory agent has been established, whereas that of serotonin remains more controversial.
Use of standardised outcome measures in adult mental health services
Authors: Slade Mike , McCrone Paul , Kuipers Elizabeth , Leese Morven , Cahill Sharon , Parabiaghi Alberto , Priebe Stefan , Thornicroft Graham 
Published: November 2006

BackgroundRoutine use of standardised outcome measures is not universal.AimsTo evaluate the effectiveness of standardised outcome assessment.MethodA randomised controlled trial, involving 160 representative adult mental health patients and paired staff (ISRCTN16971059). The intervention group (n=101) (a) completed monthly postal questionnaires assessing needs, quality of life, mental health problem severity and therapeutic alliance, and (b) received 3-monthly feedback. The control group (n=59) received treatment as usual.ResultsThe intervention did not improve primary outcomes of patient-rated unmet need and of quality of life. Other subjective secondary outcome measures were also not improved. The intervention reduced psychiatric inpatient days (3.5 v. 16.4 mean days, bootstrapped 95% CI 1.6-25.7), and hence service use costs were £2586 (95% CI 102-5391) less for intervention-group patients. Net benefit analysis indicated that the intervention was cost-effective.ConclusionsRoutine use of outcome measures as implemented in this study did not improve subjective outcomes, but was associated with reduced psychiatric inpatient admissions.
Brain volume changes in the first year of illness and 5-year outcome of schizophrenia
Authors: Cahn W. , van Haren N. E. M. , Pol H. E. Hulshoff , Schnack H. G. , Caspers E. , Laponder D. A. J. , Kahn R. S. 
Published: November 2006

SummaryProgressive brain volume changes have been reported in first-episode schizophrenia, but their relationship to the disease process or to other factors remains unclear. We examined such changes in the first year of illness, and related them to 5-year outcome. Progressive brain volume changes, in particular of grey matter, during the first year of illness were found to be significantly associated with clinical and functional outcome 5 years after the first episode. These findings suggest that early dynamic brain volume changes are related to the disease process and predict the longer-term outcome of schizophrenia.