bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive oxygen species mediate chloroquine‐induced expression of chemokines by human astroglial cells
Authors: Park Jinseu , Choi Kyungsun , Jeong Eunjoo , Kwon Daeho , Benveniste Etty N. , Choi Chulhee
Published: April 2004

We have previously demonstrated that chloroquine may evoke inflammatory responses in the central nervous system by inducing expression of pro‐inflammatory cytokines by astroglial cells. In this study, we further examined the molecular mechanism responsible for chloroquine‐induced activation of NF‐κB and subsequent expression of chemokines by astroglial cells. We observed that (1) chloroquine induced expression of chemokines such as CCL2 and CXCL8 in a dose‐ and time‐dependent manner in human astroglial cells; (2) other lysosomotropic agents such as ammonium chloride and bafilomycin A1 had minimal effects on chemokine expression; (3) inhibition of NF‐κB by MG‐132 and TPCK suppressed chloroquine‐induced mRNA expression of chemokines; (4) chloroquine increased the intracellular level of reactive oxygen species (ROS) in a dose‐ and time‐dependent manner by human astroglial cells, but not by monocytic/microglial cells; (5) chloroquine‐induced increase of intracellular ROS level was suppressed by pre‐incubation with diphenyl iodonium (DPI) and N‐acetyl cysteine (NAC); and (6) inhibition of chloroquine‐induced ROS production by DPI or NAC suppressed chloroquine‐mediated activation of NF‐κB and subsequent mRNA expression of chemokines in astroglial cells. These results collectively suggest that chloroquine generates ROS, which is responsible for NF‐κB activation and subsequent expression of pro‐inflammatory chemokines in human astroglial cells. © 2004 Wiley‐Liss, Inc.
Expression of clusterin in Müller cells of the rat retina after pressure‐induced ischemia
Authors: Gwon Jae‐Sung , Kim In‐Beom , Lee Mun‐Yong , Oh Su‐Ja , Chun Myung‐Hoon
Published: April 2004

We have investigated the expression and cellular localization of clusterin in the rat retina following ischemia induced by transiently increasing the intraocular pressure. In the normal retina, weak clusterin immunoreactivity was visible in Müller cell profiles located in the inner nuclear layer. Following ischemia and reperfusion, strong immunoreactivity appeared in Müller cell somata and processes up to 3 days postlesion. Quantitative evaluation by immunoblotting confirmed that clusterin expression continuously increased and showed a peak value at 3 days after ischemic injury (to 1300% of control levels), and then decreased again to 400% of controls at 4 weeks postlesion. Immunocytochemistry using antisera against clusterin or glutamine synthase combined with the TUNEL method or immunocytochemistry using antisera activated caspase 3 and electron microscopy revealed that some clusterin‐labeled Müller cells underwent apoptotic cell death. Our findings demonstrate that some Müller cells die by apoptosis, and suggest that clusterin produced and released by Müller cell may play an important role in the pathogenesis of ischemic injury in the rat retina. © 2004 Wiley‐Liss, Inc.
Expression of novel isoforms of the CIC‐1 chloride channel in astrocytic glial cells in vitro
Authors: Zhang Xiao‐Dong , Morishima Shigeru , Ando‐Akatsuka Yuhko , Takahashi Nobuyuki , Nabekura Takashi , Inoue Hana , Shimizu Takahiro , Okada Yasunobu
Published: April 2004

Chloride channels play an important role in glial astrocyte function. However, in astrocytes, no chloride channels besides the γ‐aminobutyric acid (GABA)A receptor, glycine receptor, and ClC‐2 chloride channels have been molecularly identified. In this study, we examined the expression of the ClC‐1 chloride channel in rat astrocytic glioma C6 cells and rat primary astrocytes. Five isoforms of ClC‐1, but not skeletal muscle ClC‐1 (SM ClC‐1), were found to be expressed in C6 cells. Comparison with rat SM ClC‐1 showed that common features shared by these isoforms are a short 3′ end with a deletion of the nucleotides from 3115 to 3197 and a substitution of T by C at nucleotides 480 and 1733. Three of the five isoforms, M1, M2, and M3, were produced by partial deletion of ClC‐1 exon 7, partial insertion of ClC‐1 exon 7a, and a TAG insertion at nucleotide 858, respectively. One of the two remaining isoforms, M4, was produced by partial deletion of ClC‐1 exon 8 at nucleotide 937; the other, M5, was the same as SM ClC‐1 except for the short 3′ end and substitutions at the two positions. Only the M5 isoform could be expressed as a functional channel in Xenopus oocytes. This glial isoform exhibited less dependence on voltage and extracellular Cl− than rat SM ClC‐1. However, the anion selectivity sequence and the anthracene‐9‐carboxylic acid (9‐AC) sensitivity of this channel were the same as for SM ClC‐1. Since whole‐cell recordings failed to detect ClC‐1‐like Cl− currents in C6 cells, it appears that the ClC‐1 isoform is functioning in intracellular organelles. In rat primary astrocytes, we found that the M2 isoform as well as two additional distinct isoforms were expressed. The present study showed that astrocytic glial cells express multiple isoforms of the ClC‐1 chloride channel, which has been thought to be expressed almost exclusively in the skeletal muscle. © 2004 Wiley‐Liss, Inc.
Clinical utility of computed tomography in the assessment of dementia: a memory clinic study
Authors: Condefer Kelly A. , Haworth Judith , Wilcock Gordon K.
Published: April 2004

Objective

To define the influence of computed tomography (CT) on clinical decision‐making in the outpatient evaluation of dementia.

Design

A case series in which two physicians reviewed standardised data extracted from clinical records, first blind to CT results, and then with CT results. Clinical decisions made with and without the input of CT were compared. The study was based in an outpatient referral centre for the assessment of memory disorders and dementia. The study involved 146 participants who were diagnosed with dementia after their first clinic visit, had Mini Mental State Examination scores >12, were aged >65 years, and had no history of neurologic disease.

Results

CT impacted on diagnosis in an average of 12% (±2), and on treatment plan in 11% (±2) of cases. Physicians predicted a priori which cases CT may influence with an average sensitivity of 28% (±2), and specificity of 78.5% (±1.5). There was no statistically significant relationship between diagnostically uncertain cases and helpful CT scans [average χ2 = 1.121 (±1.116), p = ns]. Blind to CT physicians appropriately identified cerebrovascular disease with an average sensitivity of 63% (±3), and specificity of 93.5% (±3.5).

Conclusions

In the outpatient setting, CT may be expected to impact on diagnosis and treatment of dementia in 10% to 15% of cases. Memory clinic physicians recognise and treat cerebrovascular risk factors with reasonable sensitivity and specificity without the input of CT. Copyright © 2004 John Wiley & Sons, Ltd.
Presentations and management of Post Traumatic Stress Disorder and the elderly: a need for investigation
Authors: Busuttil Walter
Published: April 2004

Background

With an aging population increasing presentations of cases of Post Traumatic Stress Disorder (PTSD) can be expected to old age services. While progress has been made in recent years in relation to the understanding and development of aetiological theories, classification, assessment and management strategies and protocols in the adult population, similar advances have lagged behind for the elderly.

Aims

To review the adult literature regarding PTSD and discuss how this might apply to an elderly population. An attempt is made to highlight a better awareness of the field of psychological trauma in the elderly in the hope of stimulating debate and research.

Method

A review of the adult literature is conducted relating to classification, aetiology, demographic features, vulnerability, assessment, clinical management including psychotherapy and medications and how these may apply to the elderly.

Results

Little has been published in this field that directly relates to the elderly. The adult literature allows insight into understanding how PTSD may present in the elderly, and how they may be managed.

Conclusions

Further specific research is needed in the elderly in order to facilitate a better understanding of PTSD that present in this unique population. This will lead to better clinical assessment, management and treatment provision. Copyright © 2004 John Wiley & Sons, Ltd.
A community‐based study of depression in older people in Hefei, China—the GMS‐AGECAT prevalence, case validation and socio‐economic correlates
Authors: Chen Ruoling , Hu Zhi , Qin Xia , Xu Xiaochao , Copeland John R. M.
Published: April 2004

Objective

Previously published studies of prevalence of depression in older people in China showed much variation in the results, while the pooled prevalence is low. In this study we used a standardised method, the Geriatric Mental State (GMS) to investigate the prevalence of depression in older people in China, validate the GMS‐AGECAT depression cases and examine the relationship between depression and socio‐economic deprivation.

Methods

1736 subjects aged ≥65 were recruited from Hefei city, China. They were interviewed at home by a survey team from Anhui Medical Universtiy using the GMS and other interviews. Their mental disorders were diagnosed by the Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT). Chinese psychiatrists re‐examined depression cases and their controls.

Results

39 depressed cases were diagnosed by the GMS‐AGECAT. Age‐standardised prevalence was 2.2% (95% CI 1.5–2.9), which was about five‐times lower than that of older people in Liverpool, UK. Agreement on depression diagnoses between the GMS‐AGECAT and local Chinese psychiatrists was 83.6%, with a Kappa of 0.67 (p<0.001). Depression was significantly related to socio‐economic deprivation.

Conclusions

This community‐based study suggested a low prevalence of depression in older people in urban China. Approved training in the use of the GMS‐AGECAT in mainland China should make it possible to carry out a large scale epidemiological study on depression in the Chinese elderly population to investigate its geographic variation and risk factors. The dose‐response relation between socio‐economic deprivation and depression indicates that strategies for tackling inequality in depression in elderly are urgently needed in China. Copyright © 2004 John Wiley & Sons, Ltd.
Memantine enhances autonomy in moderate to severe Alzheimer's disease
Authors: Rive Benoît , Vercelletto Martine , Delamarre Damier Florence , Cochran John , François Clément
Published: April 2004

Background

Alzheimer's disease (AD) is the leading cause of dementia and its course renders patients functionally disabled. Memantine is the first drug to demonstrate a clinical benefit in the treatment of patients with moderately‐severe to severe AD.

Objectives

Our objective was to illustrate the benefits of memantine on functional disability.

Methods

We classified 252 patients from a randomised 28‐week clinical trial of memantine vs placebo according to their Activities of Daily Living capabilities measured by the ADCS‐ADLsev scale. The scale was divided into two sub‐scores: basic and instrumental. The relevance of this classification was validated by comparing clinical and socio‐demographic parameters between the different autonomy classes (autonomous and dependent). The effect of memantine was estimated by using a logistic regression model on the autonomy status of patients at week 28, controlling for confounding factors (Observed Cases analysis).

Results

Our results showed that dependent patients (n = 106) had significantly longer disease duration, poorer cognition, greater severity, more behavioural alterations and higher total societal costs compared with autonomous patients (n = 146). When controlling for autonomy and severity at baseline, memantine‐treated patients were three times more likely [Odds Ratio (OR) = 3.03; 95% Confidence Intervals (CI) = (1.38, 6.66)] to remain autonomous after 28 weeks. Analysis of the Treated Per Protocol set and the use of Last Observation Carried Forward analyses confirmed this finding.

Conclusions

Memantine enhances autonomy in patients with moderately‐severe to severe AD by increasing the probability of their remaining autonomous, therefore delaying transition to the dependent stage. Copyright © 2004 John Wiley & Sons, Ltd.
Adverse effects of depression and cognitive impairment on rehabilitation participation and recovery from hip fracture
Authors: Lenze Eric J. , Munin Michael C. , Dew Mary Amanda , Rogers Joan C. , Seligman Karen , Mulsant Benoit H. , Reynolds Charles F.
Published: April 2004

Objectives

This study examines the effects of depression and cognitive impairment in elderly hip fracture patients receiving inpatient rehabilitation. Our goal was to determine whether any association of depression and cognitive impairment with rehabilitation outcome is accounted for by more immediate effects of these variables on rehabilitation participation.

Methods

We measured depression using the Hamilton Rating Scale for Depression (Ham‐D), cognition using the Mini Mental State Examination (MMSE), and rehabilitation outcomes using the motor scale of the Functional Independence Measure (motor FIM) in a prospective observational study of 57 elderly rehabilitation hospital patients admitted to a university‐affiliated, freestanding rehabilitation hospital with primary diagnosis of hip fracture. We also assessed rehabilitation participation, to determine whether this accounted for (mediated) any relationship of depression and cognitive impairment with rehabilitation outcome.

Results

Baseline Ham‐D and MMSE scores were correlated with motor FIM efficiency—those with higher depressive symptoms had lower efficiency (r = −0.44, p < 0.001); similarly, those with more cognitive impairment had lower motor FIM efficiency (r = 0.52, p < 0.001). Rehabilitation participation was a mediator of this association: greater depressive symptoms and cognitive impairment predicted poorer rehabilitation participation which, in turn, predicted lower motor FIM efficiency. Ham‐D and MMSE scores were predictors of discharge location: subjects with high depressive symptoms and greater cognitive impairment were more likely to go to a nursing home or personal care home upon discharge.

Conclusions

Depression and cognitive impairment are predictive of negative outcomes in elderly patients' rehabilitation from hip fracture. This effect is mediated by rehabilitation participation, and ratings in this area may serve as a potentially useful clinical and research tool for the rehabilitation environment. Copyright © 2004 John Wiley & Sons, Ltd.
Affective disorders in older inpatients
Authors: Wetterling Tilman , Junghanns Klaus
Published: April 2004

Background

After dementia the group of depressive disorders is considered to be the second most common psychiatric disorder in the elderly. There is dispute regarding whether depression in the elderly differs from depression in the younger age groups by a longer duration of inpatient treatment, a more frequent occurrence of delusions, more cognitive impairment or by a more frequent co‐occurrence of physical disease. This study aimed to compare younger with older inpatients with respect to these aspects.

Methods

Retrospective chart review of all admissions to the psychiatric department of a General University Hospital (n=9400) and review of the documentation of 15 348 psychiatric consultations in the years 1990–1998. The clinical diagnoses were made according to the ICD‐10 criteria.

Results

15.5% of the psychiatric inpatients in this period suffered from depressive episodes (ICD‐10 F31.3–31.5,32,33). The proportion of depressive episodes increased with age, making up 5.4% in the age group below 30 years and 37.4% in the age group of 70–79 years. On the basis of the ICD‐10 criteria for the severity of depressive episodes no significant differences could be demonstrated between the younger (< 65 years) and the older inpatients (≥ 65 years). In particular, no higher frequency of psychotic symptoms with increasing age could be found. The length of inpatient treatment did not significantly differ between both age groups. The elder patients showed less suicidal attempts prior to admission and less psychiatric comorbidity, but a significantly higher rate of concurrent physical illness. In 923 inpatients a psychiatrist was consulted by the other medical departments because of a co‐occurrence of physical with affective disorders, making up 8.6% of the total seen by the psychiatric consultation service. Here again, the proportion of depressive episodes increased with age. The pattern of the depressive episodes in these patients did not differ from that seen in the psychiatric inpatients.

Limitations

Only clinical diagnoses made by experienced psychiatrists were evaluated.

Conclusions

According to our results older depressive inpatients differ from younger ones only with regard to concurrent comorbidity but not with respect to the duration of inpatient treatment or the pattern or severity of depressive symptoms. They more frequently suffered from physical illness but less often showed concurrent psychiatric comorbidity. Copyright © 2004 John Wiley & Sons, Ltd.
Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest
Authors: van de Ven Vincent G. , Formisano Elia , Prvulovic David , Roeder Christian H. , Linden David E.J.
Published: April 2004

Cortical functional connectivity, as indicated by the concurrent spontaneous activity of spatially segregated regions, is being studied increasingly because it may determine the reaction of the brain to external stimuli and task requirements and it is reportedly altered in many neurological and psychiatric disorders. In functional magnetic resonance imaging (fMRI), such functional connectivity is investigated commonly by correlating the time course of a chosen “seed voxel” with the remaining voxel time courses in a voxel‐by‐voxel manner. This approach is biased by the actual choice of the seed voxel, however, because it only shows functional connectivity for the chosen brain region while ignoring other potentially interesting patterns of coactivation. We used spatial independent component analysis (sICA) to assess cortical functional connectivity maps from resting state data. SICA does not depend on any chosen temporal profile of local brain activity. We hypothesized that sICA would be able to find functionally connected brain regions within sensory and motor regions in the absence of task‐related brain activity. We also investigated functional connectivity patterns of several parietal regions including the superior parietal cortex and the posterior cingulate gyrus. The components of interest were selected in an automated fashion using predefined anatomical volumes of interest. SICA yielded connectivity maps of bilateral auditory, motor and visual cortices. Moreover, it showed that prefrontal and parietal areas are also functionally connected within and between hemispheres during the resting state. These connectivity maps showed an extremely high degree of consistency in spatial, temporal, and frequency parameters within and between subjects. These results are discussed in the context of the recent debate on the functional relevance of fluctuations of neural activity in the resting state. Hum. Brain Mapp. 22:165–178, 2004. © 2004 Wiley‐Liss, Inc.
Protocol for volumetric segmentation of medial temporal structures using high‐resolution 3‐D magnetic resonance imaging
Authors: Bonilha Leonardo , Kobayashi Eliane , Cendes Fernando , Min Li Li
Published: April 2004

Quantitative analysis of brain structures in normal subjects and in different neurological conditions can be carried out in vivo through magnetic resonance imaging (MRI) volumetric studies. The use of high‐resolution MRI combined with image post‐processing that allows simultaneous multiplanar view may facilitate volumetric segmentation of temporal lobe structures. We define a protocol for volumetric studies of medial temporal lobe structures using high‐resolution MR images and we studied 30 healthy subjects (19 women; mean age, 33 years; age range, 21–55 years). Images underwent field non‐homogeneity correction and linear stereotaxic transformation into a standard space. Structures of interest comprised temporopolar, entorhinal, perirhinal, parahippocampal cortices, hippocampus, and the amygdala. Segmentation was carried out with multiplanar assessment. There was no statistically significant left/right‐sided asymmetry concerning any structure analyzed. Neither gender nor age influenced the volumes obtained. The coefficient of repeatability showed no significant difference of intra‐ and interobserver measurements. Imaging post‐processing and simultaneous multiplanar view of high‐resolution MRI facilitates volumetric assessment of the medial portion of the temporal lobe with strict adherence to anatomic landmarks. This protocol shows no significant inter‐ and intraobserver variations and thus is reliable for longitudinal studies. Hum. Brain Mapp. 22:145–154, 2004. © 2004 Wiley‐Liss, Inc.
Activation of cerebellar hemispheres in spatial memorization of saccadic eye movements: An fMRI study
Authors: Nitschke Matthias F. , Binkofski Ferdinand , Buccino Giovanni , Posse Stefan , Erdmann Christian , Kömpf Detlef , Seitz Rüdiger J. , Heide Wolfgang
Published: April 2004

What mechanisms allow us to direct a precise saccade to a remembered target position in space? The cerebellum has been proposed to be involved not only in motor and oculomotor control, but also in perceptual and cognitive functions. We used functional MRI (Echoplanar imaging at 1.5 T) to investigate the role of the cerebellum in the control of externally triggered and internally generated saccadic eye movements of high and low memory impact, in six healthy volunteers. Memory‐guided saccades to remembered locations of 3 targets (triple‐step saccades) in contrast to either central fixation or to visually guided saccades activated the cerebellar hemispheres predominantly within lobuli VI‐crus I. The same areas were activated when an analogous visuospatial working memory task was contrasted to the triple‐step saccades. Visually guided saccades activated the posterior vermis and the triple‐step saccades, contrasted to the working memory task, activated predominantly the posterior vermis and paravermal regions. Our data confirm the primary involvement of the posterior vermis for visually‐triggered saccadic eye movements and present novel evidence for a role of the cerebellar hemispheres in the mnemonic and visuospatial control of memory‐guided saccades. Hum. Brain Mapp. 22:155–164, 2004. © 2004 Wiley‐Liss, Inc.
Expansion of donor hepatocytes after recombinant adenovirus-induced liver regeneration in mice
Authors: Peeters Vrancken M T F , Patijn G A , Lieber A , Perkins J , Kay M A
Published: April 2004

Hepatocyte transplantation is a potential form of therapy for patients with genetic hepatodeficiency disorders. Unfortunately, hepatocellular transplantation has been limited because of the relatively low numbers of donor cells that can ultimately take up residence in the host liver. To give the donor cells a proliferative stimulus, a recombinant adenovirus vector that expresses a nonsecreted urokinase (urokinase-type plasminogen activator) was transduced into the livers of recipient animals before transplantation. Because urokinase production in hepatocytes causes the slow turnover of hepatocytes, 2 days after adenovirus-mediated gene transfer into the livers of recipient mice, 2 × 106 congenic donor cells tagged with β-galactosidase (β-Gal) reporter were implanted via the portal vein. As a result, on average, 8.6% of the recipient hepatocytes in the livers were derived from donor cells-a 20-fold increase compared with control animals in which no proliferative stimulus was present.
Decision–Analysis of Transjugular Intrahepatic Portosystemic Shunt Versus Distal Splenorenal Shunt for Portal Hypertension
Authors: Zacks Steven L. , Sandler Robert S. , Biddle Andrea K. , Mauro Matthew A. , Brown Robert S.
Published: April 2004

Transjugular intrahepatic portosystemic shunt (TIPS) and surgical distal splenorenal shunt (DSRS) are treatments for complications of portal hypertension. TIPS is widely used because it is relatively easy to place. Because TIPS may malfunction over time, it is unclear whether TIPS is superiorto DSRS in patients with Child's class A cirrhosis who enjoy a longer survival. This study compared the cost–effectiveness of TIPS to DSRSfor portal hypertension in Child's class A cirrhosis. A decision analysis model was used to evaluate the number of procedures, life expectancy, and costs over the first 2 years in patients with Child's class A cirrhosis who underwent a TIPS or DSRS. Patients who received TIPS survived 1.96 years, required 1.7 procedures, and incurred $41,685 in costs. Patients who underwent a DSRS survived 1.86 years, required 1.0 procedure, and incurred $26,951 in costs. The cost–effectiveness of TIPS compared with DSRS was $147,340 per life–year saved. Adjusting the rate of TIPS dysfunction, 1–year survival, or the number of ultrasounds to detect TIPS dysfunction did not change the results. In patients with Child's class A cirrhosis, DSRS is a more cost–effective treatment than TIPS. Until the results of a randomized controlled trial comparing TIPS with DSRS are available, TIPS should be regarded as experimental and prohibitively expensive in Child's class A cirrhosis
Combination of ziprasidone and clozapine in treatment‐resistant schizophrenia
Authors: Zink M. , Mase E. , Dressing H.
Published: April 2004

In cases of treatment‐resistant schizophrenia the combined application of antipsychotic drugs often becomes necessary. Clozapine has been combined successfully with other atypical antipsychotic drugs such as risperidone or amisulpride in the past.

We report the difficult treatment of a 28‐year‐old schizophrenic woman. Psychotic symptoms were found resistant to monotherapy with clozapine or ziprasidone. In contrast, combined application led to a marked improvement in both positive and negative symptoms of schizophrenia along with a decrease of side effects.

The reported combination is a promising option in cases of treatment‐resistant schizophrenia and should be further evaluated in prospective studies. Copyright © 2004 John Wiley & Sons, Ltd.
Maternal sensitivity in interactions with three‐ and 12‐month‐old infants: Stability, structural composition, and developmental consequences
Authors: Lohaus Arnold , Keller Heidi , Ball Juliane , Voelker Susanne , Elben Cornelia
Published: April 2004

This study addresses three topics related to the structural components of maternal sensitivity: (a) The stability of sensitivity over a nine‐month period, (b) the predictability of maternal sensitivity assessed at 12 months from early parameters of parenting and (c) the relation between maternal sensitivity and developmental outcomes assessed at 12 months. Maternal sensitivity and its components (signal perception, correct interpretation, prompt, and appropriate reaction) were evaluated for 60 mother–infant‐dyads when their infants were aged three and 12 months. Additional parameters of early parenting were maternal emotional warmth and behavioural contingency. Developmental outcome measures were the amount of infant crying and the quality of attachment at twelve months. The results showed close correlations between the sensitivity components suggesting a unidimensional structure for maternal sensitivity. The sensitivity assessments were significantly related to measures of maternal warmth. Stability of maternal sensitivity over time was, however, quite low. There was no relation between the early sensitivity assessments and later developmental outcomes, whereas there was a significant relation between the sensitivity parameters assessed at twelve months and developmental outcomes. The results indicate changes in the meaning of maternal sensitivity during infants' development. Copyright © 2004 John Wiley & Sons, Ltd.
Does well‐being contribute to performance? Emotional security, teacher support and learning behaviour in kindergarten
Authors: Koomen Helma M.Y. , van Leeuwen Mirella G.P. , van der Leij Aryan
Published: April 2004

In this study, we examined relations between kindergartner's emotional security, task involvement and achievement and teacher's supportive presence in a cognitive training setting, in which the familiarity of the teacher was varied. Participants were 48 kindergarten children (mean age=51.65 months); 16 children were trained by their regular teacher (experimental group 1), 16 by a less familiar teacher (experimental group 2) and 16 received no training (control group). In three training sessions, children worked in pairs on a new categorization and recall task. Trained observers rated children's emotional insecurity and task involvement and teacher's supportive presence. Furthermore, spontaneous recall during the training was assessed. In addition, categorization and spontaneous recall was measured in various test sessions. Children's emotional insecurity during training negatively affected involvement. Involvement on its turn positively influenced spontaneous recall during training. In addition, emotional insecurity had a direct negative effect on spontaneous recall in a test situation. No effect of familiarity or supportive presence of the teacher on emotional security was found. Training conditions did not affect test performances. Findings suggest that children's involvement is important for learning and that experiences of emotional insecurity may negatively affect task involvement, test performance and eventually school achievement. Teachers in general seem capable of providing children with some sense of security. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of salvicine‐resistant lung adenocarcinoma A549/SAL cell line
Authors: Miao Ze‐Hong , Tong Lin‐Jiang , Zhang Jin‐Sheng , Han Jia‐Xian , Ding Jian
Published: April 2004

Salvicine is a diterpenoid quinone derived from a traditional Chinese medication that has been shown to possess potent in vitro and in vivo antitumor effects. This compound, which inhibits the activity of Topoisomerase II, was found to equipotently kill various multidrug‐resistant tumor cells and their corresponding parental counterparts in vitro and to inhibit mdr1/P‐gp expression in multidrug‐resistant K562/A02 cells. To examine the features of tumor resistance to salvicine, we established a salvicine‐resistant tumor cell subline of A549 lung adenocarcinoma cells. Compared with parental cells, A549/SAL cells displayed 8.91‐fold resistance to salvicine and an average of 6.70‐fold resistance to the antimetabolites. A549/SAL cells, however, were not resistant to alkylating agents, platinum compounds and other naturally‐derived antineoplastics. RT‐PCR analysis showed that the expression of mRNAs from the mdr‐1, MRP, PCNA, topoisomerase II α and β, GSTπ, p21 and GADD45 genes was not altered in the salvicine‐resistant subline. In contrast, expression of p53 and bax mRNA was significantly lower, and expression of mdm2 mRNA was significantly higher, in A549/SAL cells compared to A549 cells. A549/SAL cells grew more slowly, and in a more scattered pattern, than A549 cells. In addition, the A549/SAL cells showed enhanced ability to migrate and invade in comparison to the parental cells. These results indicate that exposure to salvicine does not induce a tumor multidrug‐resistant phenotype. © 2004 Wiley‐Liss, Inc.
Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP
Authors: Kan Shu‐Fen , Huang William J. , Lin Lie‐Chwen , Wang Paulus S.
Published: April 2004

Evodiamine, isolated from a Chinese herbal drug named Wu‐Chu‐Yu, possesses many biological functions. Recently, it has been reported that Wu‐Chu‐Yu exerts an antiproliferative effect on several cancers. Prostate carcinoma initially occurs as an androgen‐dependent tumor and is the second leading cause of cancer death in American males. In the present study, the effect of evodiamine on the growth of androgen‐dependent prostate cancer cell line LNCaP in vitro was examined. Based on [3‐(4,5‐dimethylthiazol‐2‐yle)2,5‐diphenyltetrazolium bromide] (MTT) assay, evodiamine significantly inhibited the growth of LNCaP cells in a concentration‐dependent manner. A significant and concentration‐dependent inhibitory effect of evodiamine on LNCaP cell growth was observed at 24 hr and persisted for 96 hr. The examination of lactate dehydrogenase (LDH) assay showed that the cytotoxic effects of evodiamine on LNCaP cells were concentration dependent. Furthermore, we examined the influences of evodiamine on cell death and cell cycle. The flow cytometric analysis of evodiamine‐treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest reached a maximum at 24 hr after evodiamine treatment. The G2/M arrest was accompanied by an elevated p34cdc2 kinase activity and an increase in the protein expression of cyclin B1 and phosphorylated form of p34cdc2 (Thr 161). Examination of TUNEL showed that evodiamine‐induced apoptosis was observed at 24 hr and extended for 72 hr. Evodiamine elevated caspase‐3, and caspase‐9 activities and the processing of caspase‐3 and caspase‐9. These results suggested that evodiamine inhibits the growth of prostate cancer cell line, LNCaP, through an accumulation of cell cycle at G2/M phase and an induction of apoptosis. © 2004 Wiley‐Liss, Inc.
MRP1 and glucosylceramide are coordinately over expressed and enriched in rafts during multidrug resistance acquisition in colon cancer cells
Authors: Klappe Karin , Hinrichs John W.J. , Kroesen Bart‐Jan , Sietsma Hannie , Kok Jan Willem
Published: April 2004

Previously we have described a novel multidrug‐resistant cell line, HT29col, which displayed over expression of the multidrug‐resistance protein 1 (MRP1) and an altered sphingolipid composition, including enhanced levels of glucosylceramide (GlcCer; Kok JW, Veldman RJ, Klappe K, Koning H, Filipeanu C, Muller M. Int J Cancer 2000;87:172–8). In our study, long‐term screening revealed that, during colchicine‐induced acquisition of multidrug resistance in a new HT29col cell line, increases in GlcCer occurred concomitantly with upregulation of MRP1 expression. Both MRP1 and GlcCer were found enriched in Lubrol‐insoluble membrane domains. The expression of MRP1 and GlcCer were tightly correlated, as indicated also by a reversal of both at the later stage of colchicine consolidation. Resistance to colchicine was determined by MRP1, while glucosylceramide synthase (GCS) did not contribute: 1) Resistance was fully inhibited by MK571. 2) GCS expression and activity were not upregulated in HT29col cells. 3) Inhibition of GCS did not affect MRP1‐mediated efflux function or sensitivity to colchicine. Instead, overall sphingolipid metabolism was upregulated through an increased rate of ceramide biosynthesis. In conclusion, upregulation of MRP1 occurs in concert with upregulation of GlcCer during multidrug‐resistance acquisition, and both are enriched in rafts. The increased GlcCer pool does not directly modulate MRP1 function and cell survival. © 2004 Wiley‐Liss, Inc.
Gene expression analysis in Interleukin‐12‐induced suppression of mouse mammary carcinoma
Authors: Shi Xiaoyan , Liu Jianguo , Xiang Zhaoying , Mitsuhashi Maki , Wu Rita S. , Ma Xiaojing
Published: April 2004

Interleukin‐12 (IL‐12) has potent antitumor activities via natural killer cells and cytotoxic T lymphocytes. However, the molecular mechanisms whereby IL‐12 induces tumoricidal activities are poorly understood. Here, we report the genome‐wide analysis of gene expression in a primary murine mammary carcinoma model that resembles human breast cancer, following the therapeutic application of recombinant IL‐12, which restricted tumor growth and metastasis. IL‐12 was able to curtail neovascularization in the tumor as well as enhance the number of tumor‐infiltrating lymphocytes. Comprehensive examination of global gene expression revealed IL‐12‐induced molecular changes associated with tumor regression and reduced lung metastasis, thus providing a high‐resolution snapshot of a host response against a developing malignancy and a rich source of potential targets for therapeutic intervention of breast cancer. © 2004 Wiley‐Liss, Inc.
Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1ahighCD86−Langerin‐ and CD1a+CD86+Langerin+ phenotypes
Authors: Thomachot Marie Cécile , Bendriss‐Vermare Nathalie , Massacrier Catherine , Biota Cathy , Treilleux Isabelle , Goddard Sophie , Caux Christophe , Bachelot Thomas , Blay Jean Yves , Menetrier‐Caux Christine
Published: April 2004

Primary breast carcinoma are frequently infiltrated by dendritic cells (DC). The mechanisms involved in the localization and status of activation of DC within primary breast carcinoma were investigated. CCL20/MIP3α, a chemokine involved in immature DC and their precursors attraction, was detected by immunohistochemistry on cryopreserved tissue sections of primary breast tumors and by ELISA and biological assay in metastatic effusion fluids from breast cancer patients but not from other tumors. In vitro, irradiated breast carcinoma cell lines (BCC) as well as their conditioned media promoted CD34+ cell differentiation into CD1a+ Langerhans cells (LC) precursors as early as day 6, while at day 12, 2 different CCR6+ subpopulations of DC with a Langerhans cell (CD1a+Langerin+CD86+) and an immature DC (CD1ahighLangerin‐CD86−HLA‐DRlowCD40low) phenotype were observed. This phenomenon was partly driven by a TGFβ‐dependent mechanism since a pan TGFβ polyclonal antibody completely blocks BCC‐induced LC differentiation and partly reduces immature DC development. These DC failed to maturate in response to sCD40L or LPS stimuli and CD1ahighLangerin−CD86− cells have a reduced T‐cell stimulatory capacity in MLR experiments. The absolute number of T cells was reduced by 50% in both the CD4+ or CD8+ compartments, these T cells expressing lower levels of the CD25 Ag and producing less IFNγ. These results show that breast carcinoma cells produce soluble factors, which may attract DC and their precursors in vivo, and promote the differentiation of the latter into LC and immature DC with altered functional capacities. The infiltration of BCC by these altered DC may contribute to the impaired immune response against the tumor. © 2004 Wiley‐Liss, Inc.
Polymorphisms in the one‐carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study
Authors: Chen Jia , Kyte Charles , Valcin Martin , Chan Wendy , Wetmur James G. , Selhub Jacob , Hunter David J. , Ma Jing
Published: April 2004

One‐carbon (e.g., folate) metabolism plays a pivotal role in the etiology of colorectal cancer (CRC). Cytosolic serine hydroxymethyltransferase (cSHMT), methylenetetrahydrofolate dehydrogenase (MTHFD1) and glutamate carboxypeptidase II (GCPII) are key genes involved in this pathway. Several new polymorphisms have been identified and there is evidence implicating their functionality. We examined whether polymorphisms in these genes, i.e., cSHMT L474F, MTHFD1 R653Q and GCPII H475Y, modify the risk of CRC in the prospective Physicians' Health Study. Among the 270 incident CRC cases and 453 controls, none of the one‐carbon polymorphisms were associated with risk of CRC. Compared to the wild‐type genotype, the multivariate‐adjusted relative risks and 95% confidence intervals were 1.14 [0.68, 1.93] for cSHMT 474FF, 1.04 [0.67, 1.62] for MTHFD1 653QQ and 1.00 [0.55, 1.82] for GCPII 474HY. Furthermore, we examined the associations between one‐carbon polymorphisms and folate status in terms of plasma folate and homocysteine levels in this population. No independent gene effect was observed. Although compound homozygous variants at cSHMT and MTHFD1 loci had the lowest plasma folate levels compared to other compound genotypes, no significant gene‐gene interactions were observed. Findings from our prospective investigation indicate that these newly identified polymorphisms in one‐carbon metabolizing genes have limited functionality in modifying folate status and related CRC risk. © 2004 Wiley‐Liss, Inc.
Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice
Authors: Murakami Akira , Tanaka Takuji , Lee Ji‐Yoon , Surh Young‐Joon , Kim Ha Won , Kawabata Kyuichi , Nakamura Yoshimasa , Jiwajinda Suratwadee , Ohigashi Hajime
Published: April 2004

We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti‐tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2‐stage carcinogenesis model. A single topical pretreatment to mouse skin (2 μmol) 24 hr before application of dimethylbenz[a]anthracene (0.2 μmol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post‐initiation phase reduced the number of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA, 1.6 nmol)‐induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 μmol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase‐1, glutathione S‐transferase‐P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome P450 1A1 or 1B1. Further, it diminished TPA‐induced cyclooxygenase‐2 protein expression and phosphorylation of extracellular signal‐regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application‐induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen‐labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti‐oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways. © 2004 Wiley‐Liss, Inc.
Maternal breast cancer risk after the death of a child
Authors: Lambe Mats , Cerrato Ruha , Askling Johan , Hsieh Chung‐cheng
Published: April 2004

The possible association between a severe traumatic life event (death of a child) and breast cancer risk was examined in a case‐control study nested within a nation‐wide cohort in Sweden. Our study population included 27,571 women with breast cancer and 141,798 control women born between 1925–1976. After adjustment for age, parity, age at first birth and education, the overall risk estimate for breast cancer among all women that had experienced the death of a child was 1.05 (95% confidence interval [CI] = 0.96–1.15). Among uniparous women the corresponding odds ratio (OR) was 1.27 (95% CI = 0.98–1.64). When stratifying for child's age at death a significant risk increase was detected among women that had lost their only child when the child was between 1–4 years of age (OR = 2.65; 95% CI = 1.06–6.60). These findings do not support an overall increase in breast cancer risk after the death of a child, a severe traumatic life event. Based on a small number of subjects, our finding of an increased risk in a subgroup of uniparous women losing their only child could be due to chance. © 2004 Wiley‐Liss, Inc.
Promoter polymorphisms of tumor necrosis factor‐α are associated with risk of gastric mucosa–associated lymphoid tissue lymphoma
Authors: Wu Ming‐Shiang , Chen Li‐Tzong , Shun Chia‐Tung , Huang Shih‐Pei , Chiu Han‐Mo , Wang Hsiu‐Po , Lin Ming‐Tsang , Cheng Ann‐Lii , Lin Jaw‐Town
Published: April 2004

Genes involved in regulating antimicrobial immunity and inflammation may modulate the risk of Helicobacter pylori–associated diseases. IL‐1 and TNF‐α are major cytokines detected in H. pylori–infected tissues. We aimed to determine the role of gene polymorphisms for these cytokines and their receptors in 2 distinct H. pylori–related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping for IL‐1β (–31 C/T, –511 C/T), TNF‐α (–238 G/A, –308 G/A, –857 C/T, –863 C/A, –1031 T/C), TNFR1 (–383 A/C) and TNFR2 (196 G/T) was undertaken for 70 patients with maltoma and 204 patients with noncardia GAC and compared to 210 unrelated healthy controls. Genotype frequencies showed no differences among patients with GAC or maltoma and controls for IL‐1β, TNFR1 or TNFR2. The TNF‐α –857 T variant was significantly underrepresented in maltoma compared to controls (6.4% vs. 14.3%, p = 0.018), conferring a 3‐fold decrease in risk (OR = 0.33, 95% CI 0.15–0.75). Comparison of allele frequencies between GAC and controls failed to show any statistical significance for TNF‐α polymorphisms. We concluded that TNF‐α –857 T itself or a neighboring gene may modify the risk of maltoma. The differences in genetic background as well as divergent clinicopathologic features between GAC and maltoma support the notion that fundamental mechanistic differences exist in these 2 well‐defined H. pylori–related malignancies. © 2004 Wiley‐Liss, Inc.
Poly(phosphoester) ionomers as tissue‐engineering scaffolds
Authors: Wan Andrew C. A. , Mao Hai‐Quan , Wang Shu , Phua Su Hui , Lee Gin Ping , Pan Jisheng , Lu Shen , Wang Jun , Leong Kam W.
Published: April 2004

Regenerative medicine requires scaffolds of divergent physicochemical properties for different tissue‐engineering applications. To this end, a series of biodegradable poly(phosphoester) ionomers of the general composition [p(BHET‐EOP‐HOP/TC)] was synthesized, with BHET(bis‐hydroxyl ethylene phosphate):EOP(ethylene phosphate):HOP(free phosphate) ratios of 60:20:20, 70:10:20, and 75:5:20, respectively. The 60/20/20 ionomer possessed the best tensile properties, exhibiting an average tensile modulus of 68 MPa and strain at break of 31%. Calcium treatment of the ionomer films led to significantly higher hardness and elastic moduli as measured by indentation. Calcium binding was evident from the increase in glass transition and melting temperatures, and a shift in the P→O absorption in the FTIR spectrum. Stable N‐hydroxysuccinimide ester (NHS) of the ionomers could be synthesized to facilitate derivatization, as demonstrated by conjugation of GRGDS in this study. The polymers conjugated with NHS were hydrolyzed in a biphasic mode, with a fast initial phase occurring in the first few hours, followed by a slower phase in the next few days. These ionomers represent a novel class of biomaterials with readily controllable physical and chemical attributes for tissue engineering. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 91–102, 2004