bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosing Alzheimer's disease—non‐clinicians and computerised algorithms together are as accurate as the best clinical practice
Authors: Foy Catherine M. L. , Nicholas Helen , Hollingworth Paul , Boothby Harry , Willams Julie , Brown Richard G. , Al‐Sarraj Safa , Lovestone Simon
Published: May 2007

Background

An accurate diagnosis of Alzheimer's disease and an exclusion of other dementias is important in many clinical studies. Obtaining such a clinical diagnosis in epidemiological studies and clinical trials that recruit large numbers of patients is time consuming.

Objectives

To construct an algorithm using a limited number of data points to generate a diagnosis of the commonest forms of dementia using information collected by non clinicians.

Methods

We constructed a computer algorithm to generate a diagnosis of Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), frontotemporal dementia (FTD), vascular dementia or to flag the case as needing a clinical review based on a limited number of data points taken from a largely structured interview using widely used scales. The diagnosis generated in life by the algorithm in a prospective, longitudinal study was compared to definitive diagnosis at post mortem.

Results

Post mortem diagnosis was available for 43 cases. The positive predictive value of the algorithm was greater than 95%. AD was diagnosed by the algorithm and at post mortem in 36 of the cases. Two cases with FTD were wrongly diagnosed as having AD by the algorithm, five cases were flagged as needing a clinical review due to concomitant medical conditions of whom four had AD and one, who had been diagnosed clinically as having AD, was diagnosed on post mortem with corticobasal degeneration.

Conclusions

A combination of non‐clinical researchers, a structured interview and a computerised algorithm is as effective at identifying AD as highly trained and skilled clinicians. Copyright © 2007 John Wiley & Sons, Ltd.
Subjective memory complaints in an elderly sample: a cross‐sectional study
Authors: Minett Thaís Soares Cianciarullo , Da Silva Rosimeire Vieira , Ortiz Karin Zazo , Bertolucci Paulo Henrique Ferreira
Published: May 2007

Background

Community based studies show that neurological or psychiatric symptoms are very frequent among the elderly population, with poor memory complaints being the most common. However, the relationship between poor memory complaints and objective memory performance is unclear. We designed this study to evaluate whether subjective memory complaints (SMC) are associated with objective cognitive performance or depression amongst the elderly Brazilian generation.

Methods

A cross‐sectional study was carried out in 114 patients who were 50+, with or without SMC having no obvious cognitive impairment at its baseline (this was screened by the Mini‐Mental State Examination with cut‐off values adapted according to the subjects' educational background). Subjects were assessed regarding memory difficulty complaints, demographic data and underwent a neuropsychological assessment made up of nine cognitive tests (Rey Auditory Verbal Learning Test, Visual Reproduction Test, Logic Memory—History A, Free and Cued Selective Reminding Test, Stroop Test, Digit Span, Digit Symbol, Trail Making Test, fluency tests: naming animals and fruits) and the Geriatric Depression Scale.

Results

Twenty‐one percent of the subjects had subjective memory complaints. The scores in the cognitive assessment of subjects with SMC did not differ from the scores of subjects without SMC. However, patients with subjective memory complaints had lower scores in the fluency test—category animals and the Geriatric Depression Scale.

Conclusions

These results support the finding from other cross‐sectional studies showing that subjective memory complaints are associated with depressive symptoms rather than objective cognitive performance. Copyright © 2007 John Wiley & Sons, Ltd.
Cost‐effectiveness analysis of donepezil for mild to moderate Alzheimer's disease in Taiwan
Authors: Fuh Jong‐Ling , Wang Shuu‐Jiun
Published: May 2007

Background

Donepezil is a drug used for treatment in patients with Alzheimer's disease (AD). Information regarding the cost‐effectiveness of this medication was previously rare in Asia. We used techniques of decision analysis and economic evaluation in conjunction with available local epidemiological and clinical data on costs of mild to moderate AD to assess the cost‐effectiveness of donepezil in Taiwan.

Methods

A four‐state Markov model was built to simulate the disease progression of AD patients. Local transition probabilities and costs of different stages were from the studies published earlier.

Results

Over a 5‐year span, donepezil treatment for mild or moderate AD patients is predicted to result in the gain of 0.505 QALYs when comparing to usual care, while at the same time reducing the cost by US$7,691. The incremental cost was US$3,647 from the payer perspective; thus, the incremental cost‐effectiveness ratio was estimated to be US$7,226 when considering only the medical expenditures.

Conclusions

Under some assumptions, donepezil treatment might be a cost saving strategy for mild to moderate AD patients in Taiwan from a societal perspective. It is inconclusive from the payer's part since we still lack a consensus for judging the cost‐effectiveness of a new health care technology. Copyright © 2007 John Wiley & Sons, Ltd.
A randomized, two‐year study of the efficacy of cognitive intervention on elderly people: the Donostia Longitudinal Study
Authors: Buiza Cristina , Etxeberria Igone , Galdona Nerea , González María Feliciana , Arriola Enrique , de Munain Adolfo López , Urdaneta Elena , Yanguas José Javier
Published: May 2007

Background

Research on non‐pharmacological therapies (cognitive rehabilitation) in old age has been very limited, and most has not considered the effect of interventions of this type over extended periods of time.

Objective

To investigate a new cognitive therapy in a randomized study with elderly people who did not suffer cognitive impairment.

Methods

The efficacy of this therapy was evaluated by means of post‐hoc analysis of 238 people using biomedical, cognitive, behavioural, quality of life (QoL), subjective memory, and affective assessments.

Results

Scores for learning potential and different types of memory (working memory, immediate memory, logic memory) for the treatment group improved significantly relative to the untreated controls.

Conclusions

The most significant finding in this study was that learning potential continued at enhanced levels in trained subjects over an intervention period lasting two years, thereby increasing rehabilitation potential and contributing to successful ageing. Copyright © 2007 John Wiley & Sons, Ltd.
Cortical thinning in obsessive compulsive disorder
Authors: Shin Yong‐Wook , Yoo So Young , Lee Jun Ki , Ha Tae Hyon , Lee Kyung Jin , Lee Jong Min , Kim In Young , Kim Sun I. , Kwon Jun Soo
Published: May 2007

Although studies of obsessive–compulsive disorder (OCD) over the last 20 years have suggested abnormalities in frontal‐subcortical circuitry, evidences of structural abnormalities in those areas are still imperfect and contradictory. With recent advances in neuroimaging technology, it is now possible to study cortical thickness based on cortical surfaces, which offers a direct quantitative index of cortical mass. Using the constrained Laplacian‐based automated segmentation with proximities (CLASP) algorithm, we measured cortical thickness of 55 patients with OCD (33 men and 22 women) and 52 age‐ and sex‐matched healthy volunteers (32 men and 20 women). We found multiple regions of cortical thinning in OCD patients compared to the normal control group. Patients with OCD had thinner left inferior frontal, left middle frontal, left precentral, left superior temporal, left parahippocampal, left orbitofrontal, and left lingual cortices. Most thinned regions were located in the left ventral cortex system, providing a new perspective that this ventral cortical system may be involved in the pathophysiology of OCD. Hum Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Hemodynamic response to visual stimulation in newborn infants using functional near‐infrared spectroscopy
Authors: Karen Tanja , Morren Geert , Haensse Daniel , Bauschatz Andrea S. , Bucher Hans Ulrich , Wolf Martin
Published: May 2007

Brain activity is associated with physiological changes, which alter the optical properties of tissue. These changes can be detected by near‐infrared spectroscopy (NIRS). Aim of the study was to determine changes in cerebral oxygenation in response to stimulation in the visual cortex in newborn infants during spontaneous sleep in the first days of life. We used an in‐house developed multichannel NIRS imaging instrument, the MCP‐II, to measure changes in concentration of oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) in specific brain areas. In 10 out of 15 subjects, a significant increase in O2Hb and/or a significant decrease in HHb were found in one or more channels over the occipital cortex. During stimulation, O2Hb increased by a mean of 0.98 μmol/l, HHb decreased by a mean 0.17 μmol/l, and total‐Hb increased by a mean of 0.81 μmol/l. The hemodynamic response to visual stimulation in the occipital cortex in newborn infants is similar to adults. The increase in O2Hb and the simultaneous decrease in HHb during stimulation suggest an increase in cerebral blood flow (CBF) that overcompensates for the increased oxygen consumption (CMRO2) in the activated cortical area. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Surface‐based morphometry of the anterior cingulate cortex in first episode schizophrenia
Authors: Fornito Alex , Yücel Murat , Wood Stephen J. , Adamson Chris , Velakoulis Dennis , Saling Michael M. , McGorry Patrick D. , Pantelis Christos
Published: May 2007

The anterior cingulate cortex (ACC) appears to be critically involved in the pathophysiology of schizophrenia, but past attempts at characterizing pathological changes in the region using magnetic resonance imaging have been restricted by a limited appreciation of its functional and anatomical diversity and a reliance on relatively coarse metrics (e.g., volume) to index anatomical change. In this study, we applied a novel, surface‐based protocol to T1‐weighted scans acquired from 40 first episode schizophrenia patients and 40 healthy controls individually matched for age, sex, and morphology of the paracingulate sulcus, a major anatomical variation that has been shown to affect morphometric estimates in the region. The surface‐based approach enabled calculation of regional grey matter volume, surface area and curvature, cortical thickness, and depth of the cingulate sulcus, with sub‐millimeter precision. Relative to controls, schizophrenia patients displayed a bilateral reduction in thickness of paralimbic regions of the ACC, along with a concomitant increase in surface area of both the limbic and paralimbic ACC. No differences were identified for regional grey matter volume, surface curvature, or CS depth. These findings illustrate the advantages of moving beyond traditional volume‐based approaches when investigating cortical morphometry, and indicate that the early stages of schizophrenia are associated with a specific pattern of ACC abnormalities that cannot be attributed to variations in sulcal and gyral morphology. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
An fMRI study of prefrontal brain activation during multiple tasks in patients with major depressive disorder
Authors: Fitzgerald Paul B. , Srithiran Anusha , Benitez Jessica , Daskalakis Zafiris Z. , Oxley Tom J. , Kulkarni Jayashri , Egan Gary F.
Published: May 2007

Objective: Previous research has provided conflicting information regarding the pattern of brain activation associated with cognitive performance in depressed people. We aimed to assess brain activation related to cognitive performance during planning and working memory tasks. Method: fMRI scans were conducted using a modified Tower of London task and a 2‐back task in 13 patients with major depressive disorder and a matched control group. Results: Task performance was impaired in the depressed group on the Tower of London task but there were no differences between the groups in task performance on the n‐back task. The patient group showed widespread increased brain activation in both tasks. There was considerable overlap in increased activation between the two tasks, especially in right prefrontal cortical regions. Conclusions: Patients with depression exhibit increased brain activation, especially in right prefrontal regions, across several types of cognitive task activity. Patients with depression may recruit greater brain regions to achieve similar or even poorer task performance than control subjects. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study
Authors: Bryant Richard A. , Kemp Andrew H. , Felmingham Kim L. , Liddell Belinda , Olivieri Gloria , Peduto Anthony , Gordon Evian , Williams Leanne M.
Published: May 2007

Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level‐dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex‐matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Laryngeal schwannoma in an 8‐year‐old boy with inspiratory dyspnea
Authors: Rognone Elisa , Rossi Andrea , Conte Massimo , Nozza Paolo , Tarantino Vincenzo , Fibbi Antonio , Saetti Roberto , Cutrone Cesare , Tortori‐Donati Paolo
Published: May 2007

Background

Schwannomas of the larynx are rare lesions in the pediatric age group.

Methods

In this article, we report on the neuroimaging features of a schwannoma arising from the left aryepiglottic fold in an 8‐year‐old boy with a 6‐month history of inspiratory dyspnea.

Results

Neuroimaging showed a well‐defined, avoid mass originating from the left aryepiglottic fold. The lesion was removed endoscopically.

Conclusion

Complete removal of laryngeal schwannomas is curative, and adjuvant treatment is not required. © 2007 Wiley Periodicals, Inc. Head Neck, 2007
Bile salt–dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4
Authors: Morita Shin-ya , Kobayashi Aya , Takanezawa Yasukazu , Kioka Noriyuki , Handa Tetsurou , Arai Hiroyuki , Matsuo Michinori , Ueda Kazumitsu
Published: May 2007

Human ABCB4 (multidrug resistance [MDR]3 P-glycoprotein) is expressed in the canalicular membrane of the hepatocyte. ABCB4 has been shown to be required for phosphatidylcholine (PC) secretion into the bile and to translocate PC across the plasma membrane. To further investigate the function of ABCB4, we established a cell line stably expressing ABCB4 (human embryonic kidney [HEK]/ABCB4). The efflux of phospholipids from HEK/ABCB4 cells was remarkably increased by the addition of taurocholate. In addition, the cholesterol efflux from HEK/ABCB4 cells was also enhanced in the presence of taurocholate. Light scattering measurements suggested that the taurocholate monomer plays an important role in ABCB4-mediated lipid secretion. On the other hand, the efflux of phospholipids and cholesterol was not mediated by ABCB1 (MDR1) even in the presence of taurocholate. Taurocholate promoted the efflux of phospholipids and cholesterol from HEK/ABCB4 cells more efficiently than glycocholate and cholate. ABCB4-K435M and ABCB4-K1075M, Walker A lysine mutants, did not mediate the phospholipid and cholesterol efflux in the presence of taurocholate, suggesting that ATP hydrolysis is essential for the efflux. Verapamil completely inhibited the taurocholate-dependent efflux of phospholipids and cholesterol from HEK/ABCB4 cells. Mass spectrometry revealed that, in the presence of taurocholate, HEK/ABCB4 cells preferentially secreted PC compared to sphingomyelin. PC vesicles induced cholesterol diffusion from cell membrane, but did not accept cholesterol from ABCB4.

Conclusion:

ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis. (HEPATOLOGY 2007.)
Impairment of liver regeneration correlates with activated hepatic NKT cells in HBV transgenic mice
Authors: Dong Zhongjun , Zhang Jianhong , Sun Rui , Wei Haiming , Tian Zhigang
Published: May 2007

A fraction of HBV carriers have a risk to develop liver cancer. Because liver possesses a strong regeneration capability, surgical resection of cancerous liver or transplantation with healthy liver is an alternate choice for HBV-caused hepatocarcinoma therapy. How HBV infection affects the regeneration of hepatectomized or transplanted liver remains elusive. We report that partial hepatectomy (PHx)-induced liver regeneration was reduced in HBV transgenic (HBV-tg) mice, a model of human HBV infection. PHx markedly triggered natural killer T (NKT) cell accumulation in the hepatectomized livers of HBV-tg mice, simultaneously with enhanced interferon gamma (IFN-γ) production and CD69 expression on hepatic NKT cells at the early stage of liver regeneration. The impairment of liver regeneration in HBV-tg mice was largely ameliorated by NKT cell depletion, but not by natural killer (NK) cell depletion. Blockage of CD1d-NKT cell interaction considerably alleviated NKT cell activation and their inhibitory effect on regenerating hepatocytes. Neutralization of IFN-γ enhanced bromodeoxyuridine incorporation in HBV-tg mice after PHx, and IFN-γ mainly induced hepatocyte cell cycle arrest. Adoptive transfer of NKT cells from regenerating HBV-tg liver, but not from normal mice, could inhibit liver regeneration in recipient mice.

Conclusion:

Activated NKT cells negatively regulate liver regeneration of HBV-tg mice in the PHx model. (Hepatology 2007.)
Endotoxemia produces coma and brain swelling in bile duct ligated rats
Authors: Wright Gavin , Davies Nathan A. , Shawcross Debbie L. , Hodges Stephen J. , Zwingmann Claudia , Brooks Heather F. , Mani Ali R. , Harry David , Stadlbauer Vanessa , Zou Zheng , Williams Roger , Davies Ceri , Moore Kevin P. , Jalan Rajiv
Published: May 2007

This study explores the hypothesis that the inflammatory response induced by administration of lipopolysaccharide (LPS) exacerbates brain edema in cirrhotic rats; and if so whether this is associated with altered brain metabolism of ammonia or anatomical disturbance of the blood-brain barrier. Adult Sprague-Dawley rats 4 weeks after bile duct ligation (BDL)/Sham-operation, or naïve rats fed a hyperammonemic diet (HD), were injected with LPS (0.5 mg/kg, intraperitoneally) or saline, and killed 3 hours later. LPS administration increased brain water in HD, BDL, and sham-operated groups significantly (

P

< 0.05), but this was associated with progression to pre-coma stages only in BDL rats. LPS induced cytotoxic brain swelling and maintained anatomical integrity of the blood-brain barrier. Plasma/brain ammonia levels were higher in HD and BDL rats than in sham-operated controls and did not change with LPS administration. Brain glutamine/myoinositol ratio was increased in the HD group but reduced in the BDL animals. There was a background pro-inflammatory cytokine response in the brains of cirrhotic rats, and plasma/brain tumor necrosis factor alpha (TNF-α) and IL-6 significantly increased in LPS-treated animals. Plasma nitrite/nitrate levels increased significantly in LPS groups compared with non-LPS controls; however, frontal cortex nitrotyrosine levels only increased in the BDL + LPS rats (

P

< 0.005 versus BDL controls).

Conclusion:

Injection of LPS into cirrhotic rats induces pre-coma and exacerbates cytotoxic edema because of the synergistic effect of hyperammonemia and the induced inflammatory response. Although the exact mechanism of how hyperammonemia and LPS facilitate cytotoxic edema and pre-coma in cirrhosis is not clear, our data support an important role for the nitrosation of brain proteins. (Hepatology 2007.)
Nicotine prevents disruption of the late phase LTP‐related molecular cascade in adult‐onset hypothyroidism
Authors: Alzoubi K.H. , Aleisa A.M. , Alkadhi K.A.
Published: May 2007

We have shown previously that chronic nicotine treatment reverses adult‐onset hypothyroidism‐induced impairment of late‐phase long‐term potentiation (L‐LTP) in area CA1 of the hippocampus. In the present study, basal and stimulated levels of signaling molecules essential for the expression of L‐LTP were determined in area CA1. Immunoblots analysis showed that chronic nicotine treatment of hypothyroid rats prevented the reduction in the basal protein levels of adenylyl cyclase I (ACI), mitogen‐activated protein kinases [MAPKp44/42 (ERK1/2)], calcium‐calmodulin‐dependent protein kinase IV (CaMKIV), and cyclic‐AMP response element binding protein [CREB; phosphorylated (P‐) and total]. A significant increase in the levels of P‐CREB, P‐MAPKp44, P‐MAPKp42 and brain derived neurotrophic factor (BDNF) was seen 4 h after multiple train high frequency stimulation (MHFS) in nicotine‐treated hypothyroid and control animals, but not in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42, and CaMKIV were elevated in all groups 4 h after MHFS. These findings suggest that prevention of the reduced basal level of CaMKIV, MAPKp44/42, and CREB by nicotine along with the regained ability of MHFS to induce MAPKp44/42 and CREB phosphorylation in nicotine treated hypothyroid animals may be responsible for the reversal of L‐LTP impairment by chronic nicotine treatment in this disease model. © 2007 Wiley‐Liss, Inc.
The effects of supportive management and job quality on the turnover intentions and health of military personnel
Authors: Dupré Kathryne E. , Day Arla L.
Published: May 2007

To be competitive in today's increasingly complex and rapidly changing envi‐ronment, organizations must retain personnel and promote the well‐being of employees. We examine the relationship of both support provided to person‐nel and job quality with employee health and turnover intentions among a sample of 450 military personnel. Factors involving the supportive manage‐ment of personnel (i.e., supervisory support, organizational support, and work‐life balance) and factors pertaining to job quality (i.e., work stimulation and job clarity) were indirectly related to health and to turnover intentions through the mediating influence of job satisfaction. © 2007 Wiley Periodicals, Inc.
Bias against overweight job applicants: Further explorations of when and why
Authors: Finkelstein Lisa M. , Frautschy Demuth Rachel L. , Sweeney Donna L.
Published: May 2007

We investigated the impact of job candidate weight (average or overweight) on several job‐related ratings following a videotaped mock interview. In ad‐dition to weight, we manipulated the race of the applicant, level of job qual‐ifications, and type of job (e.g., public or private contact). We also measured the effect of rater race and negative affect on multiple work‐relevant ratings. Weight, applicant race, job qualifications, and job type each had a modest but significant impact on ratings of hireability, performance capacity, adapt‐ability, and interpersonal skills, in varying combinations. The implications of these results for practice and future research are provided. © 2007 Wiley Pe‐riodicals, Inc.
An examination of the use of high‐investment human resource systems for core and support employees
Authors: Lepak David P. , Taylor M. Susan , Tekleab Amanuel G. , Marrone Jennifer A. , Cohen Debra J.
Published: May 2007

In this study, we examine two competing perspectives regarding the relative use of high‐investment human resource (HIHR) systems for core and support employees within establishments. Using data from 420 establishments, we compare a universal perspective suggesting that the level of HIHR exposure core employees receive is always greater than the level of exposure for sup‐port employees, with a contingency perspective suggesting that the relative level of exposure for these employee groups is contingent on strategy, HR philosophy, or industry.The results did not provide support for the universal prediction that core employees always receive higher levels of exposure to HIHR systems than support employees within the same establishment. Moreover, while strategy and HR philosophy were positively related to the level of HIHR system use across establishments, they did not influence the relative level of exposure to HIHR systems for core and support employees. Interestingly, however, industry did exert a unique impact such that core em‐ployees received significantly greater exposure to HIHR systems than sup‐port employees in nonmanufacturing firms.There were no significant differ‐ences in exposure for these two groups in manufacturing industries. Implications of the findings are discussed. © 2007 Wiley Periodicals, Inc.
Externalizing the core: Firms' use of employment intermediaries in the information and communication technology industries
Authors: Nesheim Torstein , Olsen Karen M. , Kalleberg Arne L.
Published: May 2007

Recent research suggests that nonstandard employment relations may be a source of innovation for the firm. In this article, we analyze firms' strategic correlates and perceived benefits from using two types of employment in‐termediaries—consulting firms and temporary help agencies—in their core activities. Organizations with an innovation strategy are more likely to use consulting firms in their core activities, while organizations that compete on the basis of low cost are more apt to use temporary help agencies. Moreover, managers say that consulting firms are more likely than temporary help agencies to provide them with special competencies in their core activities. © 2007 Wiley Periodicals, Inc.
To be strategic in the new public sector, HR must remember its operational activities
Authors: Teo Stephen T. T. , Rodwell John J.
Published: May 2007

This article examines the level of operational and strategic involvement by human resource departments, the influence of HR departments, and the level of strategic integration as predictors of human resource management per‐formance. Surveys from 146 senior line managers and HR executives in com‐mercialized and noncommercialized public‐sector agencies in Australia were the basis of organizational‐ and individual‐level analyses. Results indicate positive relationships between the degree to which operational HR activities are transferred to line managers, HR influence, strategic integration, and the performance of the HRM function. Interestingly, no relationship was found between the level of strategic involvement by HR departments and the per‐ceived performance of the function. Analysis of the individual‐level data sup‐ports the multiple‐constituency approach to HRM, with differences in the evaluation of HRM by respondents from different job functions. The study highlights challenges faced by HR practitioners needing to be operational, to be valued strategically. © 2007 Wiley Periodicals, Inc.
Multisource feedback: Lessons learned and implications for practice
Authors: Atwater Leanne E. , Brett Joan F. , Charles Atira Cherise
Published: May 2007

Organizations around the world are using multisource, or 360‐degree, feed‐back. Although many HR practitioners embrace it as an important mecha‐nism for leadership development, organizations must attend to and address several issues in order to maximize the utility of multisource feedback (MSF). We discuss current research findings and highlight issues for managers to consider both before starting a multisource feedback process and after the feedback is given, plus we review potential outcomes of the process. We also describe lessons learned from an intensive three‐year investigation of an MSF implementation in two organizations. © 2007 Wiley Periodicals, Inc.
Evapotranspiration rates and crop coefficients for a restored marsh in the Sacramento–San Joaquin Delta, California, USA
Authors: Drexler Judy Z. , Anderson Frank E. , Snyder Richard L.
Published: May 2007

The surface renewal method was used to estimate evapotranspiration (ET) for a restored marsh on Twitchell Island in the Sacramento–San Joaquin Delta, California, USA. ET estimates for the marsh, together with reference ET measurements from a nearby climate station, were used to determine crop coefficients over a 3‐year period during the growing season. The mean ET rate for the study period was 6 mm day−1, which is high compared with other marshes with similar vegetation. High ET rates at the marsh may be due to the windy, semi‐arid Mediterranean climate of the region, and the permanently flooded nature of the marsh, which results in very low surface resistance of the vegetation. Crop coefficient (Kc) values for the marsh ranged from 0·73 to 1·18. The mean Kc value over the entire study period was 0·95. The daily Kc values for any given month varied from year to year, and the standard deviation of daily Kc values varied between months. Although several climate variables were undoubtedly responsible for this variation, our analysis revealed that wind direction and the temperature of standing water in the wetland were of particular importance in determining ET rates and Kc values. Published in 2007 by John Wiley & Sons, Ltd.
Interferon‐γ regulation of TNFα‐induced matrix metalloproteinase 3 expression and migration of human glioma T98G cells
Authors: Cheng Sherman M. , Xing Bing , Li James C.B. , Cheung Benny K.W. , Lau Allan S.Y.
Published: May 2007

Induction of proinflammatory cytokines in response to malignant cells is an integral component of immune response to control tumor development. However, recent evidences have suggested that tumor cells may evade the immune system and exploit inflammatory responses to enhance its own growth. An exemplary example is the highly invasive and tumor necrosis factor (TNF)α‐resistant glioblastoma, whose growth is associated with TNFα expression. We thus examined whether the tumor takes advantage of TNFα overexpression to enhance its invasiveness. To delineate the contribution of inflammation in tumor migration, we demonstrated that the role of proinflammatory cytokines on matrix metalloproteinases‐3 (MMP‐3) expression, and its consequent effects on the invasiveness of a human glioma cell‐line, T98G. By using Matrigel Invasion Chamber, T98G cell migration was significantly enhanced in response to TNFα. In contrast, interferon‐γ (IFNγ) reduced both basal and TNFα‐enhanced cell invasion. To investigate the mechanisms involved, we demonstrated that TNFα upregulated mRNA and protein expression of MMP‐3 in T98G cells, whereas IFNγ downregulated the MMP‐3 expression. The role of MMP‐3 in glioma invasiveness was further confirmed by transfecting MMP‐3 siRNA in T98G to abrogate the TNFα‐enhanced cell invasion. To delineate the mechanisms further, we showed that IFNγ exerts an inhibitory effect on the binding of TNFα‐activated Ets‐1 and NFκB to their respective enhancer elements found in MMP‐3 promoter. In summary, our results indicated that TNFα enhances the invasiveness of T98G glioma cells through MMP‐3 induction, and such enhancement of cell migration can be inhibited by IFNγ. © 2007 Wiley‐Liss, Inc.
Methylseleninic acid enhances the effect of etoposide to inhibit prostate cancer growth in vivo
Authors: Gonzalez‐Moreno Oscar , Segura Victor , Serrano Diego , Nguewa Paul , de las Rivas Javier , Calvo Alfonso
Published: May 2007

New therapeutic agents are needed for the treatment of androgen‐independent prostate cancer (PrCa). We have investigated the effect of methylseleninic acid (MSA) on tumor stage‐specific prostate cells derived from the C3 (1)/Tag model for PrCa: Pr111, a slow‐growing and nontumorigenic cell line isolated from a prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from a primary tumor; and Pr14C1, a sub‐clone of Pr14 explanted from a lung metastasis. We demonstrate that MSA strongly inhibits cell growth and induces apoptosis in C3 (1)/Tag tumor cells, in a dose‐dependent manner. A decrease in phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111. Microarray analysis using affymetrix showed that the number of genes with an altered expression in tumor cells is significantly higher (p < 0.01) than in nontumoral cells. Pathways analyses revealed a decrease in the expression of genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT), angiogenesis (neuropilin‐1, Flt‐4) and transcription (cAMP response element‐binding protein) in tumor cells. The expression of neuropilin‐1, a protein involved in VEGF signaling and tumor angiogenesis, was 97‐fold repressed in Pr14 cells treated with MSA. Combination treatments using low doses of etoposide or taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14 cells xenografted into nude mice demonstrated that MSA significantly enhances the chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth inhibition. These results suggest that MSA could be used against PrCa to enhance the effect of etoposide. © 2007 Wiley‐Liss, Inc.
The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFNγ
Authors: Arina Ainhoa , Murillo Oihana , Hervás‐Stubbs Sandra , Azpilikueta Arantza , Dubrot Juan , Tirapu Iñigo , Huarte Eduardo , Alfaro Carlos , Pérez‐Gracia Jose L. , González‐Aseguinolaza Gloria , Sarobe Pablo , Lasarte Juan J. , Jamieson Amanda , Prieto Jesús , Raulet David H. , Melero Ignacio
Published: May 2007

Better understanding of the mechanisms that mediate spontaneous immune rejections ought to be important in the quest for improvements in immunotherapy of cancer. A set of intraperitoneal tumors of mesenchymal origin that had been chemically induced in ubiquitously expressing EGFP transgenic mice provided a model in which both T and NK cells were absolutely required for tumor rejection. Tumor cells were traceable because of being fluorescent and readily grafted in RAG1−/− immunodeficient mice, whereas they were rejected in a majority of syngeneic C57BL/6 and EGFP‐transgenic mice. Tumor‐cell clones with the highest EGFP expression tended to be rejected, but a direct involvement of EGFP as the antigen recognized for the immune rejections was ruled out. Rejections were absolutely dependent on NK cells as well as on CD4+ and CD8+ T lymphocytes according to selective depletion studies. Furthermore, CD8+ and CD4+ T lymphocytes as well as NK cells were detected in the inflammatory infiltrate that mediates tumor rejection along with some DC. The effects of IFNγ, produced at the tumor site by T and NK lymphocytes, were only required at the malignant cell level and were necessary for tumor eradication. NK recognition of tumor cells was mediated by the NKG2D‐activating receptor and blocking its function in vivo partially interfered with rejection. Therefore, complete rejection of these mesenchymal tumors requires a concerted set of activities including direct tumor‐cell destruction and IFNγ production that are mediated by both NK and T cells. © 2007 Wiley‐Liss, Inc.
Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/β‐catenin pathway
Authors: Li Lin‐Na , Zhang Hua‐Dong , Yuan Shou‐Jun , Tian Zeng‐Yue , Wang Lin , Sun Zhi‐Xian
Published: May 2007

Artesunate (ART), a remarkable antimalarial agent, also inhibited the growth of human colorectal carcinoma. As determined by MTT assay, flow cytometry analysis on apoptosis and indirect immunofluorescence analysis on the proliferation‐associated marker Ki67, ART suppressed the proliferation and promoted the apoptosis of colorectal cancer cells in a dose‐dependent manner. Furthermore, immunofluorescence analysis on β‐catenin and RT‐PCR analysis on Wnt/β‐catenin target genes demonstrated ART translocated β‐catenin from nucleus to adherent junctions of membrane and reduced transcription mediated by β‐catenin. These results suggested the anticancer activity of ART correlated with the inhibition of hyperactive Wnt/β‐catenin signaling pathway. In vivo, ART significantly slowed the growth of colorectal tumor xenografts. Bioluminescent imaging also revealed that ART decreased the physiological activity of tumor xenografts and delayed spontaneous liver metastasis. These antitumor effects were related to the membranous translocation of β‐catenin and the inhibition of the unrestricted activation of Wnt/β‐catenin pathway, which was confirmed by the immunohistochemical staining of tumor tissues. These results and the known low toxicity are clues that ART might be a promising candidate drug for the treatment of colorectal carcinoma. © 2007 Wiley‐Liss, Inc.
Increased HIF1α in SDH and FH deficient tumors does not cause microsatellite instability
Authors: Lehtonen Heli J. , Mäkinen Markus J. , Kiuru Maija , Laiho Päivi , Herva Riitta , Minderhout Ivonne van , Hogendoorn Pancras C.W. , Cornelisse Cees , Devilee Peter , Launonen Virpi , Aaltonen Lauri A.
Published: May 2007

Germline mutations in nuclear genes encoding mitochondrial enzymes fumarate hydratase (FH) and succinate dehydrogenase (subunits SDHB/C/D) have been implicated in the development of tumor syndromes referred to as hereditary leiomyomatosis and renal cell cancer (HLRCC) and hereditary paragangliomatosis (HPGL), respectively. FH and SDH are operating in the tricarboxylic acid cycle (the TCA cycle, the Krebs cycle). In the FH and SDH deficient tumors, accumulation of the substrates, fumarate and succinate, has been shown to cause stabilization of hypoxia inducible factor 1α (HIF1α). According to recent studies, HIF1α could contribute to the hypoxia induced genomic instability seen in many cancers, through repression of mismatch repair (MMR) protein MSH2. In this study, in agreement with previous works, we found HIF1α to be moderately or highly stabilized in 67% (16/24) and 77% (48/62) of HLRCC tumors and SDHB/C/D paragangliomas (PGL) and pheochromocytomas (PHEO), respectively. In addition, a set of 54 other familial and nonfamilial PGLs/PHEOs were studied. Moderately or highly stabilized HIF1α was present in 68% (26/38) of the PGLs but in PHEOs (n = 16) no such pattern was observed. We then analyzed the suggested link between HIF1α stabilization and MSH2 repression, in HLRCC and HPGL tumor material. No microsatellite instability (MSI) or lack of MSH2 expression was, however, observed. Thus we failed to provide in vivo evidence for the proposed link between HIF1α stabilization and functional MMR deficiency, in TCAC deficient tumors. © 2007 Wiley‐Liss, Inc.
Cyclin‐dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug‐resistant osteosarcoma and Ewing's family tumor cells
Authors: Li Yan , Tanaka Kazuhiro , Li Xu , Okada Takamitsu , Nakamura Tomoyuki , Takasaki Minoru , Yamamoto Shunsaku , Oda Yoshinao , Tsuneyoshi Masazumi , Iwamoto Yukihide
Published: May 2007

Multimodal therapies play important roles in the treatment of osteosarcoma (OS) and Ewing's family of tumors (EFTs), two most frequent malignant bone tumors. Although the clinical outcome of primary OS and EFTs is greatly improved, the relapsed cases often are associated with multidrug resistance of the tumors and the prognosis of these patients is still poor. Flavopiridol, a pan cyclin‐dependent kinase (CDK) inhibitor is a novel antitumor agent that can induce cell cycle arrest and apoptosis in many cancer cells. However, there have been no studies about the effects of flavopiridol on drug‐resistant OS and EFTs. Here, we demonstrated that flavopiridol induced the cleavage of poly‐ADP‐ribose polymerase (PARP) in a time and dose dependent manner in adriamycin‐resistant OS and EFTs cells expressing P‐glycoprotein (P‐gp) and multidrug resistance‐associated protein 1 (MRP1) as effectively as in their parental cells. Our data also showed that flavopiridol caused the release of mitochondrial cytochrome c and the activation of caspase‐9, caspase‐8 and caspase‐3, with an increase ratio of the proapoptotic protein level (Bax) to the antiapoptotic protein level (Bcl‐2 and Bcl‐XL), while apoptosis was inhibited by pan caspase inhibitor (Z‐VAD‐FMK) and caspase‐3 inhibitor (Z‐DEVD‐FMK), not by caspase‐8 inhibitor (Z‐IETD‐FMK). The treatment with flavopiridol further inhibited the tumor growth in mouse models of the drug‐resistant OS and EFTs. These results suggest that flavopiridol might be promising in clinical therapy for the relapsed OS and EFTs. © 2007 Wiley‐Liss, Inc.
Transforming properties of TC‐1 in human breast cancer: Interaction with FGFR2 and β‐catenin signaling pathways
Authors: Yang Zeng‐Quan , Moffa Allison B. , Haddad Ramsi , Streicher Katie L. , Ethier Stephen P.
Published: May 2007

Breast cancer development is associated with gene amplification and over expression that is believed to have a causative role in oncogenesis. Previous studies have demonstrated that over expression of TC‐1(C8orf4) mRNA occurs in ∼50% of breast cancer cell lines and primary tumor specimens. Here, we show that TC‐1 has transforming properties in human mammary epithelial (HME) cells and its expression is mechanistically linked to FGFR signaling cascades. In vitro experiments demonstrate that TC‐1 over expression mediates both anchorage‐independent and growth factor‐independent proliferation of HME cells. TC‐1 was down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM‐52 that also has an FGFR2 gene amplification and over expression. Furthermore, forced expression of FGFR2 in HME cells increased the level of expression of endogenous TC‐1 mRNA. TC‐1 has been implicated as a modulator of Wnt/β‐catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of β‐catenin target genes in TC‐1 over expressing cells, we did not find an association of TC‐1 with global expression of β‐catenin target genes in our cells. Taken together, our data suggest that TC‐1 over expression is transforming and may link with the FGFR pathway in a subset of breast cancer. © 2007 Wiley‐Liss, Inc.
IGF‐I and mammographic density in four geographic locations: A pooled analysis
Authors: Maskarinec Gertraud , Takata Yumie , Chen Zhao , Gram Inger Torhild , Nagata Chisato , Pagano Ian , Hayashi Kentaro , Arendell Leslie , Skeie Guri , Rinaldi Sabina , Kaaks Rudolph
Published: May 2007

Insulin‐like growth factor (IGF‐I) and prolactin have been found to be associated with breast cancer risk and with mammographic density. In a pooled analysis from 4 geographic locations, we investigated the association of percent mammographic density with serum levels of IGF‐I, IGFBP‐3 and prolactin. The pooled data set included 1,327 pre‐ and postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum samples were assayed for IGF‐I, IGFBP‐3 and prolactin levels using ELISA assays. Mammographic density was quantified using a computer‐assisted density method. After stratification by menopausal status, multiple regression models estimated the relation between serum analytes and breast density. All serum analytes except prolactin among postmenopausal women differed significantly by location/ethnicity group. Among premenopausal subjects, IGF‐I levels and the molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona. For IGFBP‐3, the order was reversed. Among postmenopausal subjects, Norwegian women had the highest IGF‐I levels and women in Arizona had the lowest while women in Japan and Hawaii had intermediate levels. We observed no significant relation between percent density and IGF‐I or prolactin levels among pre‐and postmenopausal women. The significant differences in IGF‐I levels by location but not ethnicity suggest that environmental factors influence IGF‐I levels, whereas percent breast density varies more according to ethnic background than by location. Based on this analysis, the influence of circulating levels of IGF‐I, IGFBP‐3, and prolactin on percent density appears to be very small. © 2007 Wiley‐Liss, Inc.
Re‐expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia
Authors: Shiotani Akiko , Uedo Noriya , Iishi Hiroyasu , Tatsuta Masaharu , Ishiguro Shingo , Nakae Yukinori , Kamada Tomoari , Haruma Ken , Merchant Juanita L.
Published: May 2007

Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6–13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4–24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication. © 2007 Wiley‐Liss, Inc.