ACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2009
R. H. Perlis
Objective:, Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD). Method:, Logistic regression was used to identify features associated with presence of irritability on the clinician-rated Inventory of Depressive Symptomatology. Results:, Of 2307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts and suicidal ideation. Bipolar spectrum features were not more common among those with irritability. Conclusion:, Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity and suicidality. [source]

A preliminary linkage map of the hard tick, Ixodes scapularis

INSECT MOLECULAR BIOLOGY, Issue 2 2003
A. J. Ullmann
Abstract A linkage map of the Ixodes scapularis genome was constructed, based upon segregation amongst 127 loci. These included 84 random amplified polymorphic DNA (RAPD) markers, 32 Sequence- Tagged RAPD (STAR) markers, 5 cDNAs, and 5 microsatellites in 232 F1 intercross progeny from a single, field-collected P1 female. A preliminary linkage map of 616 cM was generated across 14 linkage groups with one marker every 10.8 cM. Assuming a genome size of , 109 bp, the relationship of physical to genetic distance was found to be , 300 kb/cM in the I. scapularis genome. [source]

Arbitrage Bounds and the Time Series Properties of the Discount on UK Closed-End Mutual Funds

JOURNAL OF BUSINESS FINANCE & ACCOUNTING, Issue 1-2 2007
Laurence Copeland
Abstract:, In a dataset of weekly observations over the period since 1990, the discount on UK closed-end mutual funds is shown to be nonstationary, but reverting to a nonzero long run mean. Although the long run discount could be explained by factors like management expenses etc., its short run fluctuations are harder to reconcile with an arbitrage-free equilibrium. In time series terms, there is evidence of long memory in discounts consistent with a bounded random walk. This conclusion is supported by explicit nonlinearity tests, and by results which suggest the behaviour of the discount is perhaps best represented by one of the class of Smooth-Transition Autoregressive (STAR) models. [source]

The performance of non-linear exchange rate models: a forecasting comparison

JOURNAL OF FORECASTING, Issue 7 2002
Gianna Boero
Abstract In recent years there has been a considerable development in modelling non-linearities and asymmetries in economic and financial variables. The aim of the current paper is to compare the forecasting performance of different models for the returns of three of the most traded exchange rates in terms of the US dollar, namely the French franc (FF/$), the German mark (DM/$) and the Japanese yen (Y/$). The relative performance of non-linear models of the SETAR, STAR and GARCH types is contrasted with their linear counterparts. The results show that if attention is restricted to mean square forecast errors, the performance of the models, when distinguishable, tends to favour the linear models. The forecast performance of the models is evaluated also conditional on the regime at the forecast origin and on density forecasts. This analysis produces more evidence of forecasting gains from non-linear models. Copyright © 2002 John Wiley & Sons, Ltd. [source]

How close is close enough?

JOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 3 2007
Evaluating propensity score matching using data from a class size reduction experiment
In recent years, propensity score matching (PSM) has gained attention as a potential method for estimating the impact of public policy programs in the absence of experimental evaluations. In this study, we evaluate the usefulness of PSM for estimating the impact of a program change in an educational context (Tennessee's Student Teacher Achievement Ratio Project [Project STAR]). Because Tennessee's Project STAR experiment involved an effective random assignment procedure, the experimental results from this policy intervention can be used as a benchmark, to which we compare the impact estimates produced using propensity score matching methods. We use several different methods to assess these nonexperimental estimates of the impact of the program. We try to determine "how close is close enough," putting greatest emphasis on the question: Would the nonexperimental estimate have led to the wrong decision when compared to the experimental estimate of the program? We find that propensity score methods perform poorly with respect to measuring the impact of a reduction in class size on achievement test scores. We conclude that further research is needed before policymakers rely on PSM as an evaluation tool. © 2007 by the Association for Public Policy Analysis and Management [source]

Improved target volume characterization in stereotactic treatment planning of brain lesions by using high-resolution BOLD MR-venography

NMR IN BIOMEDICINE, Issue 7-8 2001
Lothar R. Schad
Abstract In this methodological paper I report the stereotactic correlation of different magnetic resonance imaging (MRI) techniques [MR angiography (MRA), MRI, blood bolus tagging (STAR), functional MRI, and high-resolution BOLD venography (HRBV)] in patients with cerebral arterio-venous malformations (AVM) and brain tumors. The patient's head was fixed in a stereotactic localization system which is usable in both MR-systems and linear accelerator installations. Using phantom measurements global geometric MR image distortions can be ,corrected' (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth-order two-dimensional polynomial. Further object-induced local distortions can be corrected by additionally measured field maps. Using this method multimodality matching could be performed automatically as long as all images are acquired in the same examination and the patient is sufficiently immobilized to allow precise definition of the target volume. Information about the hemodynamics of the AVM was provided by a dynamic MRA with the STAR technique, leading to an improved definition of the size of the nidus, the origin of the feeding arteries, whereas HRBV imaging yielded detailed and improved information about the venous pattern and drainage. In addition, functional MRI was performed in patients with lesions close to the primary motor cortex area, leading to an improved definition of structures at risk for the high-dose application in radiosurgery. In patients with brain tumors the potential of HRBV to probe tumor angiogenesis and its use in intensity-modulated treatment planning is still hampered by the open question of how to translate a BOLD signal pattern measured in the tumor to a dose distribution, which should be addressed in future studies. Copyright © 2001 John Wiley & Sons, Ltd. [source]

(216) Pain and Addiction: Screening Patients at Risk

PAIN MEDICINE, Issue 3 2001
Victor Li
Introduction: Addictive disease is a common co-morbidity in chronic pain patients [1]. 26% of patients on methadone treatment believed that prescribed opioids led to their addiction [2]. We report initial validation of a Screening Tool for Addiction Risk (STAR). Methods: Questions based on prior studies of pain and addiction, addiction-screening tools [3,4], discussions with clinicians experienced in pain medicine and addiction, and our clinical experience were used to develop the STAR. After obtaining IRB approval, chronic pain patients completed the 14-item STAR questionnaire. 14 patients with chronic pain and history of drug addiction (DSM-IV Criteria) and 34 additional chronic pain patients completed the survey as part of their initial clinical evaluation. Patient responses were compared to determine which were questions accounted for statistically significant differences. Results: Questions related to respondent classification of addict based on chi-square analysis and Fisher's exact test were: prior treatment in a drug rehabilitation facility (p < 0.00001), nicotine use (p < 0.0032), feeling of excessive nicotine use (p < 0.0007), and treatment in another pain clinic (p < 0.018). A factor analysis linked addiction to first three questions mentioned above. Question: "Have you ever been treated in a drug or alcohol rehabilitation facility?" had a positive predictive value of 93% for addiction. Responses to recreational substance use, alcohol abuse, recent anxiety or depression, unemployment, emergency room visits, family history of drug or alcohol abuse, multiple physicians prescribing pain medication, or a prior history of physical or emotional abuse were not different between either patient group. Discussion: Screening for addiction is an important part of management of chronic pain patients. A history of treatment in drug or alcohol rehabilitation facility and questions related to cigarette smoking may be useful to screen for potential risk of addiction. Further investigations needed to validate results of this study. [source]

Substance Use Disorder Comorbidity in Major Depressive Disorder: A Confirmatory Analysis of the STAR*D Cohort

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2006
Lori L. Davis MD
The demographics and clinical features were compared between those with (29.4%) and without concurrent substance use disorder (SUD) in 2541 outpatients with major depression (MDD) enrolled in the Sequenced Treatment Alternatives to Relieve Depression study. Compared to those without SUD, MDD patients with concurrent SUD were more likely to be younger, male, divorced or never married, and at greater current suicide risk, and have an earlier age of onset of depression, greater depressive symptomatology, more previous suicide attempts, more frequent concurrent anxiety disorders, and greater functional impairment (p = 0.048 to < 0.0001). They were also less likely to be Hispanic and endorse general medical comorbidities (p = 0.006 and 0.002, respectively). [source]

From Adjuvant Therapy to Breast Cancer Prevention: BCPT and STAR

THE BREAST JOURNAL, Issue 3 2001
Barbara K. Dunn MD
Abstract: The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events. [source]

Computer-assisted tibia preparation for total ankle arthroplasty: a cadaveric study

THE INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY, Issue 4 2007
Samuel B. Adams Jr
Abstract Background Most surgeons performing total ankle arthroplasty (TAA) suggest that accurate tibial preparation perpendicular to the tibial shaft axis improves outcomes. Recent studies demonstrate that computerized surgical navigation significantly improves the accuracy of tibial preparation in total knee arthroplasty (TKA). Methods We performed the tibial preparation for TAA in seven matched pairs of cadaver lower extremities. One set of matched pairs was prepared using the conventional external tibial alignment guide/cutting block from the Scandanavian Total Ankle Replacement system (STAR, Waldemar Link GmbH & Co., Hamburg, Germany) under fluoroscopic guidance. The second set of matched pairs was prepared using the VectorVision® navigation system (BrainLAB, Munich, Germany), with currently available computed tomography (CT)-based TKA software. Pre-operative CT data were used to assess the tibial mechanical axis. In both groups, accuracy of the tibial plafond preparation relative to the tibial shaft axis in both the coronal and sagittal planes was determined by fluoroscopic, radiographic and CT analysis. Results Mean values of the tibial cut for the set of matched-pair tibiae prepared by the conventional surgical method ranged across the three imaging assessment techniques in the ranges 89.3,89.6° (coronal plane, anteroposterior) and 90.3,90.4° (sagittal plane, lateral). For the computer-navigated set, the values were 89.7,89.9° (coronal) and 89.1,89.4° (sagittal). Comparison between the conventional and computer-navigated tibial measurements were not different at the 95% confidence interval (CI) for CT, fluoroscopy or radiographic assessments. Conclusions Our results demonstrate that accuracy of TAA tibial preparation using computer-navigation equals that of the conventional technique performed by a foot and ankle surgeon experienced in TAA. We anticipate that this investigation will encourage the development of computer-navigation applications specific to TAA, with the potential of improving accuracy over conventional methods. Copyright © 2008 John Wiley & Sons, Ltd. [source]

The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans

ACTA PHYSIOLOGICA, Issue 2 2009
K. Sakuma
Abstract Aim:, To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF-linked (RhoA, RhoGDI, STARS and SRF), myostatin-linked (myostatin, Smad2, Smad3 and FLRG) and Foxo-linked (P-Akt, Foxo1, Foxo3a and Atrogin-1) mediators. Methods:, A single lower limb of each of eight healthy men was suspended for 20 days. Biopsy specimens were obtained from the vastus lateralis muscle pre- and post-suspension. Results:, The volume of the vastus lateralis muscle was significantly decreased after unloading. The amount of RhoA, RhoGDI or SRF protein in the muscle was not significantly changed post-suspension. An RT-PCR semiquantitative analysis showed increased levels of myostatin mRNA but not Smad2, Smad3 or FLRG mRNA. Unloading did not elicit significant changes in the amount of p-Smad3 or myostatin protein in the muscle. The amount of p-Akt protein was markedly reduced in the unloaded muscle. Lower limb suspension did not influence the expression pattern of Foxo1, Foxo3a or Atrogin-1. Conclusion:, Unloading inducing a mild degree of muscle atrophy may decrease p-Akt and increase myostatin but not SRF-linked mediators. [source]

The Quality of Local District Assessments Used in Nebraska's School-Based Teacher-Led Assessment and Reporting System (STARS)

EDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2005
Susan M. Brookhart
A sample of 293 local district assessments used in the Nebraska STARS (School-based Teacher-led Assessment and Reporting System), 147 from 2004 district mathematics assessment portfolios and 146 from 2003 reading assessment portfolios, was scored with a rubric evaluating their quality. Scorers were Nebraska educators with background and training in assessment. Raters reached an agreement criterion during a training session; however, analysis of a set of 30 assessments double-scored during the main scoring session indicated that the math ratings remained reliable during scoring, while the reading ratings did not. Therefore, this article presents results for the 147 mathematics assessments only. The quality of local mathematics assessments used in the Nebraska STARS was good overall. The majority were of high quality on characteristics that go to validity (alignment with standards, clarity to students, appropriateness of content). Professional development for Nebraska teachers is recommended on aspects of assessment related to reliability (sufficiency of information and scoring procedures). [source]

Introduction to the Special Issue on Nebraska's Alternative Approach to Statewide Assessment

EDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2004
Deborah L. Bandalos
Nebraska's Standards-based, Teacher-led Assessment and Reporting System (STARS) is unique in its focus on locally developed, classroom-based assessments in lieu of a state test. The purpose of this special issue is to introduce the STARS model and discuss the problems inherent in such a system. Other articles in this issue address issues of quality control and comparability of assessments, the development of teacher assessment literacy, and teachers' reactions to the implementation of STARS. [source]

History and Background of Nebraska's School-based Teacher-led Assessment and Reporting System (STARS)

EDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2004
Pat Roschewski
Nebraska's approach to standards, assessment, and accountability, the School-based Teacher-led Assessment and Reporting System (STARS) is based upon local control and the belief that classrooms and teachers must be at the heart of student learning and accountability. STARS relies on locally-developed assessment systems to accurately measure and report student performance on state content standards. Each local system in Nebraska's 500+ school districts is reviewed for technical quality, and districts are publicly rated for assessment quality and student performance. The purpose of this article is to establish the historical background. [source]

Implementation of remote monitoring and diffraction evaluation systems at the Photon Factory macromolecular crystallography beamlines

JOURNAL OF SYNCHROTRON RADIATION, Issue 3 2008
Yusuke Yamada
Owing to recent advances in high-throughput technology in macromolecular crystallography beamlines, such as high-brilliant X-ray sources, high-speed readout detectors and robotics, the number of samples that can be examined in a single visit to the beamline has increased dramatically. In order to make these experiments more efficient, two functions, remote monitoring and diffraction image evaluation, have been implemented in the macromolecular crystallography beamlines at the Photon Factory (PF). Remote monitoring allows scientists to participate in the experiment by watching from their laboratories, without having to come to the beamline. Diffraction image evaluation makes experiments easier, especially when using the sample exchange robot. To implement these two functions, two independent clients have been developed that work specifically for remote monitoring and diffraction image evaluation. In the macromolecular crystallography beamlines at PF, beamline control is performed using STARS (simple transmission and retrieval system). The system adopts a client,server style in which client programs communicate with each other through a server process using the STARS protocol. This is an advantage of the extension of the system; implementation of these new functions required few modifications of the existing system. [source]

Another Breed of "Service" Animals: STARS Study Findings About Pet Ownership and Recovery From Serious Mental Illness

AMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 3 2009
Jennifer P. Wisdom PhD
This study elucidates the role of pets in recovery processes among adults with serious mental illness. Data derive from interviews with 177 HMO members with serious mental illness (52.2% women, average age 48.8 years) in the Study of Transitions and Recovery Strategies (STARS). Interviews and questionnaires addressed factors affecting recovery processes and included questions about pet ownership. Data were analyzed using a modified grounded theory method to identify the roles pets play in the recovery process. Primary themes indicate pets assist individuals in recovery from serious mental illness by (a) providing empathy and "therapy"; (b) providing connections that can assist in redeveloping social avenues; (c) serving as "family" in the absence of or in addition to human family members; and (d) supporting self-efficacy and strengthening a sense of empowerment. Pets appear to provide more benefits than merely companionship. Participants' reports of pet-related contributions to their well-being provide impetus to conduct more formal research on the mechanisms by which pets contribute to recovery and to develop pet-based interventions. [source]

Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy

THE JOURNAL OF PHYSIOLOGY, Issue 8 2009
Séverine Lamon
Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as ,-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, ,-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy. [source]

Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary

DEVELOPMENTAL DYNAMICS, Issue 4 2001
Yayoi Ikeda
Abstract Treatment of newborn female rats with estrogens significantly inhibits the growth and differentiation of the ovary. To understand the molecular mechanism of estrogen action in the induction of abnormal ovary, we examined the expression profiles of steroidogenic factor 1 (SF-1) and several of its target genes in the developing ovaries after neonatal exposure to synthetic estrogen, estradiol benzoate (EB) by using reverse transcriptase polymerase chain reaction, in situ hybridization, and immunohistochemistry. Morphologic examination indicated inhibitory effects of estrogen on the stratification of follicles and development of theca and interstitial gland during postnatal ovarian differentiation. The expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450SCC), which are both essential for steroid biosynthesis, markedly decreased in theca and interstitial cells throughout the postnatal development of the EB-treated ovary. However, expression of the transcriptional activator of the two genes, SF-1 was unaffected in theca and interstitial cells, although the number of these cells was lower in the EB-treated ovary than in the control ovary. The expression of the estrogen mediator, estrogen receptor-, (ER-,), diminished specifically in theca cells at P6 and recovered by P14 in the EB-treated ovary. These results indicate that the effect of estrogens is mediated by means of ER-, resulting in the down-regulation of StAR and P450SCC genes during early postnatal development of the ovary. These results suggest that the abnormal ovarian development by neonatal estrogen treatment is closely correlated with the reduced steroidogenic activity, and the data obtained by using this animal model may account in part the mechanism for aberrant development and function of the ovary in prenatally estrogen-exposed humans. © 2001 Wiley-Liss, Inc. [source]

Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2007
Ling Ding
Abstract Brominated flame retardants (BFRs) and brominated dioxins are emerging persistent organic pollutants that are ubiquitous in the environment and can be accumulated by wildlife and humans. These chemicals can disturb endocrine function. Recent studies have demonstrated that one of the mechanisms of endocrine disruption by chemicals is modulation of steroidogenic gene expression or enzyme activities. In this study, an in vitro assay based on the H295R human adrenocortical carcinoma cell line, which possesses most key genes or enzymes involved in steroidogenesis, was used to examine the effects of five bromophenols, two polybrominated biphenyls (PBBs 77 and 169), 2,3,7,8-tetrabromodibenzo- p -dioxin, and 2,3,7,8-tetrabromodibenzofuran on the expression of 10 key steroidogenic genes. The H295R cells were exposed to various BFR concentrations for 48 h, and the expression of specific genes,cytochrome P450 (CYP11A, CYP11B2, CYP17, CYP19, and CYP21), 3,-hydroxysteroid dehydrogenase (3,HSD2), 17,-hydroxysteroid dehydrogenase (17,HSD1 and 17,HSD4), steroidogenic acute regulatory protein (StAR), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR),was quantitatively measured using real-time polymerase chain reaction. Cell viability was not affected at the doses tested. Most of the genes were either up- or down-regulated, to some extent, by BFR exposure. Among the genes tested, 3,HSD2 was the most markedly up-regulated, with a range of magnitude from 1.6- to 20-fold. The results demonstrate that bromophenol, bromobiphenyls, and bromodibenzo- p -dioxin/furan are able to modulate steroidogenic gene expression, which may lead to endocrine disruption. [source]

Steroidogenic gene expression in H295R cells and the human adrenal gland: adrenotoxic effects of lindane in vitro

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2006
Agneta Oskarsson
Abstract The focus on the refinement, reduction and replacement of animal use in toxicity testing requires the development of cell-based systems that mimic the effects of xenobiotics in human tissues. The human adrenocortical carcinoma cell line, H295R, has been proposed as a model for studies on adrenal steroidogenesis and its disruption. In this study, expression profiles for nine adrenal steroidogenic genes were characterized in H295R cells using real-time RT-PCR. Treatment with forskolin increased cortisol secretion and stimulated transcription of all the steroidogenic genes except SULT2A1. The transcript profile from H295R cells in the presence and absence of forskolin was compared with the transcript profile from human adrenal glands. The gene expression pattern observed in the forskolin-treated H295R cells was more similar to that in the human adrenal gland, than the expression pattern in untreated cells. To examine H295R cells as a possible in vitro system for the assessment of adrenal disruption using molecular endpoints, the insecticide lindane (, -hexachlorocyclohexane) was used. In vivo, lindane has been shown to inhibit testicular, ovarian and adrenal steroidogenesis. It was demonstrated that lindane reduced cortisol secretion, downregulated the expression of a subset of the genes encoding steroidogenic enzymes and repressed transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene promoter. Thus the H295R cell line provides a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression. This in vitro test can be used for the rapid detection of adrenal endocrine disruption and as a tool for mechanistic studies. Copyright © 2006 John Wiley & Sons, Ltd. [source]

The adrenal cortex and steroidogenesis as cellular and molecular targets for toxicity: critical omissions from regulatory endocrine disrupter screening strategies for human health?

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2003
Philip W. Harvey
Abstract Current testing strategies to assess the endocrine disrupting properties of chemicals have omitted examination of the adrenal gland and do not adequately cover the process of steroidogenesis. Steroidogenesis is critical for adrenocortical function as well as that of the testes and ovaries, and presents multiple molecular targets for toxicity, ranging from general effects on all steroidogenic tissues (e.g. via StAR protein or CYP11A1 cholesterol side-chain cleavage) through to speci,c targets affecting only adrenocortical function (e.g. CYP11,/18 and glucocorticoid synthesis). Numerous chemicals of environmental relevance are now being shown to affect adrenocortical function both in vivo in aquatic species and in vitro in human cell lines, and given the vital role of the adrenal gland to human health and development, there is a strong case for including dedicated assessment techniques in screening batteries for endocrine-disrupting chemicals, not least to assist in general data interpretation (e.g. whether adrenal hypertrophy is due to stress or to a more sinister adrenocortical insuf,ciency). Cell lines such as H295R (derived from a human adrenocortical adenocarcinoma) currently exist that will allow assessment of cortisol production and most of the major enzymes and functional proteins in the steroidogenic pathway (e.g. StAR; CYP11A1/scc; CYP11,/18; CYP17; CYP19; CYP21; 3, -hydroxysteroid dehydrogenase). Adequate assessment of adrenocortical function, as with any component of the integrated endocrine system, probably also will require the development of speci,c in vivo methodology to include effects on hypothalamo-pituitary function. Finally, although there is currently no direct evidence that environmental exposure to endocrine-disrupting (oestrogenic) chemicals has actually caused adverse human health effects, lessons have been learned on their potential from the diethylstilboestrol case. Similar evidence exists from aminoglutethimide and etomidate on the lethal impact of unpredicted chemically induced adrenal insuf,ciency in sensitive human subgroups, and it would seem prudent to incorporate relevant tests for adrenal function and steroidogenesis into current regulatory validation programmes. Published in 2003 by John Wiley & Sons, Ltd. [source]

Mechanisms of inhibition of dehydroepiandrosterone upon corticosterone release from rat zona fasciculata-reticularis cells,

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008
Ling-Ling Chang
Abstract We have demonstrated that dehydroepiandrosterone (DHEA) acts directly on rat zona fasciculata-reticularis (ZFR) cells to diminish corticosterone secretion by an inhibition of post-cAMP pathway, and decreases functions of steroidogenic enzymes after P450scc as well as steroidogenic acute regulatory (StAR) protein expression. However, the mechanisms by which DHEA engages with environmental messenger signals which translate into interfering StAR protein expression are still unclear. This study explored the effects of DHEA on the phosphorylation/activation of extracellular signal-regulated kinases (ERKs). ERK activation resulted in enhancing phosphorylation of steroidogenic factor-1 (SF-1) and increased StAR protein expression. ZFR cells were incubated in the presence or absence of adrenocorticotropin (ACTH), forskolin (FSK), 25-OH-cholesterol, U0126, and H89 at 37°C. The concentration of corticosterone released into the media was measured by radioimmunoassay (RIA). The cells were used to extract protein for Western blot analysis of ERKs or StAR protein expression or immunoprecipitation of SF-1 analysis. The results suggested that (1) ERK pathway of rat ZFR cells might be PKA dependent, (2) ERK activity was required for SF-1 phosphorylation to upregulate steroidogenesis in rat ZFR cells, and (3) DHEA did not affect ERK phosphorylation, however, it attenuated forskolin-stimulated SF-1 phosphorylation to affect StAR protein expression. J. Cell. Biochem. 104: 359,368, 2008. © 2007 Wiley-Liss, Inc. [source]

Quantitative analysis of messenger RNA expression of matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitor-2 of matrix metalloproteinases (TIMP-2), and steroidogenic enzymes in bovine placentomes during gestation and postpartum

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2007
M. Takagi
Abstract The relationship between the mRNA expression of proteolytic and steroidogenic enzymes in bovine placentomes was examined. Caruncle and cotyledon tissues were collected every 6 hr after spontaneous parturition until the fetal membranes were released. Based on the time of fetal membrane release after parturition, the specimens were classified as follows: (1) the early group, in which the fetal membranes were released within 6 hr after parturition; and (2) the late group, in which the fetal membranes were released 6,12 hr after parturition. The placentomes from a slaughterhouse were additionally collected as samples for the examination of enzymes during the gestation period. The mRNA expression of steroidogenic enzymes in the cotyledon was observed to be higher than that in caruncle tissues; however, the mRNA expression patterns of P450scc and StAR tended to be similar in both placental tissues. On the other hand, although the expression levels of TIMP-2 mRNA in both caruncle and cotyledon tissues were similar, during gestation and postpartum the expression levels of MMP-2 and MMP-9 mRNA were approximately 10 times higher in caruncle than in cotyledon tissue. Marked contrasting changes in mRNA expression patterns between pre- and postpartum periods were observed for MMP-2 and MMP-9 in caruncle tissues and for MMP-9 and TIMP-2 in cotyledon tissues. The present study provides the first evidence that MMP-2, MMP-9, and TIMP-2 mRNAs are expressed in bovine placentomes during the gestational and postpartum periods and suggests that these enzymes, in conjunction with steriodogenic enzymes, mediate fetal membrane detachment after parturition. Mol. Reprod. Dev. 74: 801,807, 2007. © 2006 Wiley-Liss, Inc. [source]

Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistance

THE PROSTATE, Issue 3 2010
Jennifer A. Locke
Abstract BACKGROUND De novo androgen synthesis and subsequent androgen receptor (AR) activation has recently been shown to contribute to castration-resistant prostate cancer (CRPC) progression. Herein we provide evidence that fatty acids (FA) can trigger androgen synthesis within steroid starved prostate cancer (CaP) tumor cells. METHODS Tumoral FA and steroid levels were assessed by GC,MS and LC,MS, respectively. Profiles of genes and proteins involved in FA activation of steroidogenesis were assessed by fluorescence microscopy, immunohistochemistry, microarray expression profiling and Western blot analysis. RESULTS In human CaP tissues the levels of proteins responsible for FA activation of steroid synthesis were observed to be altered during progression to CRPC. Further investigating this mechanism in LNCaP cells, we demonstrate that specific FA, arachidonic acid, is synthesized in an androgen-dependent and AR-mediated manner. Arachidonic acid is known to induce steroidogenic acute regulatory protein (StAR) in steroidogenic cells. When bound to hormone sensitive lipase (HSL), StAR shuttles free cholesterol into the mitochondria for downstream conversion into androgens. We show that arachidonic acid induces androgen production in steroid starved LNCaP cells coincidently in the same conditions that HSL and StAR are predominantly localized in the mitochondria. Furthermore, their activities are verified by a functional increase in mitochondrial uptake of cholesterol in this steroid starved environment. CONCLUSIONS We propose that this characterized arachidonic acid induced steroidogenesis mechanism significantly contributes to the activation of AR in CRPC progression and therefore recommend that fatty acid pathways be targeted therapeutically in progressing CaP. Prostate 70: 239,251, 2010. © 2009 Wiley-Liss, Inc. [source]

Initiation of Steroidogenesis Precedes Expression of Cholesterologenic Enzymes in the Fetal Mouse Testes

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2009
T. Büdefeld
Summary Sexual differentiation is a carefully regulated process that ultimately results in a development of the male or female phenotype. Proper development of the male phenotype is dependent upon the action of testosterone and anti-mullerian hormone. Leydig cells start to produce testosterone around day 12.5 in the fetal mouse testis, and continue to produce high levels of this hormone throughout gestation. In the present study, we examined whether expression of lanosterol 14,-demethylase (cyp51) and cytochrome P450 NADPH reductase, both involved in the cholesterol production, occurs simultaneously with proteins required for the production of steroid hormones. Immunocytochemical staining with the antibodies against cyp51, cytochrome P450 NADPH reductase, steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid dehydrogenase I (3,-HSD I) was used to determine the ontogeny of expression of these four proteins. As expected, 3,-HSD I and StAR proteins were detected on day 12.5 p.c., while expression of cyp51 and NADPH cytochrome P450 reductase appeared 1 day later, on day 13.5. Thereafter, the expression of all four proteins remained strong throughout gestation. Results of this study suggest that initial steps of steroid hormone production in murine Leydig cells are mostly dependent on exogenously derived cholesterol, while from day 13.5 onwards, mouse Leydig cells are able to synthesize cholesterol and are therefore not dependent on exogenous cholesterol resources. [source]

Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model

ACTA NEUROLOGICA SCANDINAVICA, Issue 2009
M. W. Gustavsen
Objectives, To better understand the interaction of antiepileptic drugs and production of sex hormones, possible effects of valproate (VPA), levetiracetam (LEV) and carbamazepine (CBZ) on steroidogenesis were investigated in the human adrenal carcinoma cell line H295R. Materials and methods, H295R cells were exposed to different concentrations of VPA, LEV or CBZ for 48 h. Sex hormone concentrations and mRNA expression levels were analyzed via radioimmunoassay and quantitative real time (RT)-PCR, respectively. Results, In VPA-exposed cells estradiol levels decreased in a dose-dependent manner, while testosterone and progesterone levels were unaffected. Expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), steroidogenic acute regulatory protein (StAR), CYP11a, CYP17, CYP21, 3,HSD2, 17,HSD1 was downregulated and expression of CYP11,2 was upregulated. No effect on sex hormone production was observed under influence of LEV or CBZ. Expression of StAR, CYP17, CYP19 and 3,HSD2 was downregulated in LEV-exposed cells, and expression of HMGR, CYP11,2 and CYP17 was downregulated in CBZ-exposed cells. Conclusions, VPA exposure resulted in a decrease in estradiol levels and a general downregulation of expression of genes encoding for enzymes early in steroidogenesis. No consistent changes were seen with LEV or CBZ exposure. [source]

The role of TASK1 in aldosterone production and its expression in normal adrenal and aldosterone-producing adenomas

CLINICAL ENDOCRINOLOGY, Issue 1 2010
Edson F. Nogueira
Summary Objectives, Aldosterone production in the adrenal glomerulosa is mainly regulated by angiotensin II and K+. Adrenal glomerulosa cells are uniquely sensitive to extracellular K+. Genetic deletion of subunits of K+ -selective leak-channels (KCNK), TASK1 and/or TASK3, in mice generates animals with hyperaldosteronism and histological changes in the adrenal cortex. Herein, we studied the expression of TASK1 in human adrenocortical cells, as well as its role in aldosterone production in H295R cells. Design, TASK1 expression was investigated by comparative microarray analysis of aldosterone-producing adenomas (APA) and normal adrenals (NAs). The effects of TASK1 knockdown by siRNA transfection were investigated in H295R cells. Fluo-4 fluorescent measurements of intracellular Ca2 + and pharmacological inhibition of Ca2 + -dependent calmodulin kinases (CaMK) were performed to better define the effects of TASK1 on Ca2 + signalling pathways. Results, Microarray analysis of APA and NA showed similar expression of TASK1 between these two groups. However, in APA, NA and H295R cells the expression of TASK1 was predominant when compared with other KCNK family members. Knockdown of TASK1 (with siRNA) induced the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2), and also stimulated pregnenolone and aldosterone production. Cells transfected with siTASK1 had increased intracellular Ca2 + , leading to activation of CaMK and increased expression of CYP11B2. Conclusions, Our study reveals the predominant expression of TASK1 over other KCNK family genes in the human adrenal cortex. Herein, we also described the role of TASK1 in the regulation of human aldosterone production through regulation of intracellular Ca2 + and CaMK signalling pathways. [source]

Handmade Guns in Trabzon, Turkey

JOURNAL OF FORENSIC SCIENCES, Issue 4 2009
Riza Yilmaz M.D.
Abstract:, A wide variety of handmade firearms have been involved in criminal cases in the city of Trabzon, Turkey. Although they are often very similar to commercially manufactured firearms in terms of design, loading and locking mechanisms, and cocking and firing arrangements, these guns are constructed from cheap materials and are not safe for firing. Handmade firearms manufactured in the Black Sea region of Turkey, particularly in the city of Trabzon, are similar to pistols manufactured by Browning, Luger, Star, Smith and Wesson, Berretta, and MAB. A total of 201 handmade guns referred to the Criminal Police Laboratories for examination from 2003 to 2005 were evaluated with respect to type, number of barrels, size and caliber, rifling, design, mechanism, operability, legality, and similarity to commercial models. We found that most of these handmade guns resembled commercial models in several aspects. [source]

Star coloring planar graphs from small lists

JOURNAL OF GRAPH THEORY, Issue 4 2010
André Kündgen
Abstract A star coloring of a graph is a proper vertex-coloring such that no path on four vertices is 2-colored. We prove that the vertices of every planar graph of girth 6 (respectively 7, 8) can be star colored from lists of size 8 (respectively 7, 6). We give an example of a planar graph of girth 5 that requires 6 colors to star color. © 2009 Wiley Periodicals, Inc. J Graph Theory 63: 324,337, 2010 [source]

Perforation of Aortic Root as Secondary Complication after Implantation of Patent Foramen Ovale Occlusion Device in a 31-Year-Old Woman

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2006
STEFAN A. LANGE M.D.
Transesophageal echocardiography (TEE) revealed a 3-mm-large patent foramen ovale (PFO). No other reason for these neurological events could be found and the patient underwent percutaneous closure of the PFO with a CARDIA® Star 03/30 device without periprocedural complications. Four weeks later, the patient underwent a routine control of device without any adverse clinical symptoms. Surprisingly, echocardiography revealed a perforation of the aortic root by an umbrella strut with a small shunt from the aortic root to the right atrium. Magnetic resonance imaging (MRI) confirmed the diagnosis of device malposition. Consecutively, the patient underwent minimal invasive surgery. After removal of the single perforating strut, the bleeding lesion was closed. The patient remained free of any additional complications during the postoperative course and up until now has had uneventful follow-ups. [source]