bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of chronic stress on hippocampal long‐term potentiation
Authors: Pavlides Constantine , Nivón Lucas G. , McEwen Bruce S. 
Published: August 2002

AbstractChronic stress causes atrophy of the apical dendrites of CA3 pyramidal neurons and deficits in spatial memory. We investigated the effects of chronic stress on hippocampal physiology and long‐term potentiation (LTP) in the CA3 and dentate gyrus (DG). Rats were subjected to chronic (21 days, 6 h/day) restraint stress and tested for LTP 48 h following the last stress episode. Control animals were briefly handled each day, similar to the experimental group but without restraint. To eliminate acute stress effects, a second control group of rats was subjected to a single acute (6 h) restraint stress and tested for LTP 48 h later. Field potential recordings were made, under chloropent anesthesia, from the stratum lucidum of CA3, with stimulation of either the mossy fiber or commissural/associational pathways, or in the DG granule‐cell layer, with stimulation of the medial perforant pathway. Chronic stress produced a suppression of LTP at 48 h compared to controls in a site‐specific manner, namely, significantly lower LTP in the medial perforant input to the DG and also in the commissural/associational input to the CA3, but not in the mossy fiber input to CA3. The animals subjected to acute stress and tested 48 h later did not show a suppression in LTP. High‐frequency stimulation (HFS) of the commissural/associational and mossy fiber inputs to CA3 produced epileptic afterdischarges in 56% of acutely stressed animals and in 29% of chronically stressed animals, whereas HFS caused afterdischarges in only 9% of nonstressed controls. No afterdischarges were seen in the medial perforant path input to DG. In order to explore the basis for these changes, we performed paired‐pulse inhibition/facilitation (PPI/F) and current‐source‐density (CSD) analysis in stressed and control animals. For PPI/F, acute stress caused an overall significant enhancement of excitation in the commissural/associational input to CA3 and medial perforant path input to DG. In contrast, chronic stress did not produce significant changes in PPI/F. The CSD analysis revealed significant chronic stress‐induced shifts in the current sources and sinks in the apical dendrites and pyramidal cell layers of the CA3 field but not in the DG. These results are consistent with the morphological findings for stress effects upon dendrites of CA3 neurons. Furthermore, they suggest that chronic stress produces changes in the input‐output relationship in the hippocampal trisynaptic circuit which could affect information flow through this structure. Hippocampus 2002;12:245–257. © 2002 Wiley‐Liss, Inc.
Factors affecting sediment trapping in vegetated filter strips: simulation study using VFSMOD
Authors: Abu‐Zreig Majed 
Published: August 2002

AbstractSoil and water conservation practices have been promoted for a long time, in order to sustain agricultural activities and prevent environmental pollution. Vegetated filter strips (VFS) have been used to reduce sediment pollution into water bodies at or near the pollutant source. However, factors effecting VFS performance under natural conditions have not been well understood owing to the physical, time and financial limitations of field experiments. The use of well‐validated simulation models to understand the performance of VFS and factors affecting sediment deposition is highly justified. The objective of this research is to investigate sediment trapping in VFS and to study various factors affecting VFS performance using the simulation model VFSMOD, which was developed by researchers at University of North Carolina. Recently, VFSMOD has been validated successfully by using 21 filters with varying length, slope and vegetated cover. A wide range of five parameters was selected for the simulations, namely filter length, filter slope, manning roughness coefficient, soil type and characteristics of incoming sediment from adjacent fields. Computer simulations revealed that the length of filter is the most significant factor affecting sediment trapping in VFS. The relative increase in trapping efficiencies was not linearly related to an increase in filter length. Inflow sediment class also has a major influence on sediment trapping in VFS. The trapping efficiency of clay sediments in a 15 m length VFS was 47% compared with 92% for silt from incoming sediment. Manning roughness coefficient had a moderate effect on sediment trapping and was more significant in short filters. Land slope and soil type of VFS had a minor influence on the performance of VFS. Copyright © 2001 John Wiley & Sons, Ltd.
To go or not to go: inhibitory control in ‘hard to manage’ children
Authors: Brophy Marcia , Taylor Eric , Hughes Claire 
Published: August 2002

AbstractThis study is an age‐7 follow‐up of 40 children who at age 4 were identified as ‘hard to manage’ and were compared to 40 age and sex matched typically developing peers on a set of simple, manually administered executive function tasks. At age 4, the ‘hard to manage’ group showed marked deficits in inhibitory control and planning, but showed intact set‐shifting and working memory (Hughes et al., 1998). The present study assessed the continuity of executive function deficits among these ‘hard to manage’ children, using computerized tests of planning, working memory and set‐shifting (from the Cambridge Neuropsychological Test Automated Battery (CANTAB)) and a computerized Go‐No‐Go test of inhibitory control (from the Maudsley Attention and Response Suppression task battery (MARS)). In addition, real‐time observational ratings were made via a questionnaire checklist. Compared with controls, children in the ‘hard to manage’ group showed impaired inhibitory control but intact planning, working memory and set‐shifting. Observational ratings confirmed the group difference in inhibitory control, as the ‘hard to manage’ group showed significantly more perseverative errors and rule violations. These findings raise important methodological issues concerning effects of task format and highlight the importance of combining experimental and observational approaches to assessing problems in executive control. Copyright © 2002 John Wiley & Sons, Ltd.
Antiangiogenic activity of endostatin inhibits c6 glioma growth
Authors: Peroulis Irene , Jonas Nadeen , Saleh Mary 
Published: August 2002

AbstractAngiogenesis is a vital component of the development and progression of many human solid tumors. Glioblastoma multiforme is one of the most highly vascularised class of solid tumors. Thus, we have investigated the potential antitumourigenic activity of endostatin, an angiogenic inhibitor, in the rat C6 glioma model. We have engineered C6 cells that endogenously express mouse endostatin in order to assess the growth of C6 tumors in vivo when endostatin is constitutively expressed. Endostatin secreted by stably transfected C6 cells is biologically active as shown by its inhibition (26%) of bFGF‐stimulated proliferation of BAECs in culture. The subcutaneous implantation of endostatin‐C6 cells in athymic (nu/nu) mice resulted in a reduced tumor growth rate (90% inhibition) compared to control cell lines throughout the duration of our experiments. Tumor inhibition was associated with a 50% reduction in the number of vessels, which were also smaller in morphology. However, endostatin‐C6 tumors were no more necrotic than control tumors. The implantation of endostatin‐C6 cells into immunocompetent Wistar rat brains also resulted in reduced tumor volumes (71% inhibition) compared to controls. Tumor cells were sparsely localised along the injection tract but had not formed discrete tumors. Despite the inhibitory response mediated by endostatin on C6 growth, complete tumor inhibition or dormancy was not observed in either the athymic or immunocompetent tumor models. These findings demonstrate that the endogenous expression of endostatin by C6 glioma cells results in a reduced tumor growth rate in vivo that is associated with an inhibition of tumor angiogenesis. Our data suggest that endostatin should be developed as an adjuvant gene therapy for the effective treatment of gliomas. © 2001 Wiley‐Liss, Inc.
Peptide‐specific CD8+ T‐cell evolution in vivo: Response to peptide vaccination with Melan‐A/MART‐1
Authors: Jäger Elke , Höhn Hauni , Necker Artje , Förster Reinhold , Karbach Julia , Freitag Kirsten , Neukirch Claudia , Castelli Chiara , Salter Russell D. , Knuth Alaxander , Maeurer Markus J. 
Published: August 2002

AbstractMonitoring of CD8+ T‐cell responses in cancer patients during peptide vaccination is essential to provide useful surrogate markers and to demonstrate vaccine efficacy. We have longitudinally followed CD8+ T‐cell responses in 3 melanoma patients who were immunized with peptides derived from Melan‐A/MART‐1. Recombinant HLA‐A2 tetramers loaded with the naturally presented Melan‐A/MART‐1 nonamer peptide (AAGIGILTV) and the Melan‐A/MART‐1 analog (ELAGIGILTV) were used in combination with phenotypical analysis for different T‐cell subsets including naive T cells, effector T cells, “true memory” T cells and “memory effector” T cells, based on CD45RA/RO and CCR7‐expression. At least in a single patient, T cells binding to the AAGIGILTV epitope were detected in naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding to the analog ELAGIGILTV peptide were identified in the terminally differentiated (CD45RA+/CCR7−) T‐cell subset. Molecular and functional analysis of tetramer‐binding T cells revealed that the T‐cell receptor (TCR) repertoire was oligo/polyclonal in AAGIGILTV‐reactive T cells, but different and restricted to a few TCR clonotypes in ELAGIGILTV‐reactive T cells prior to vaccination. The TCR repertoire reactive with Melan‐A/MART‐1 peptide epitopes was broadened during vaccination and exhibited a different profile of cytokine release after specific stimulation: tetramer‐binding T cells from 2/3 patients secreted granulocyte/macrophage colony‐stimulating factor (GM‐CSF) and interferon‐γ but not interleukin‐2 (IL‐2) in response to Melan‐A/MART‐1 peptides. In the third patient, tetramer‐binding T cells secreted IL‐2 exclusively. Our results show that T‐cell responses to peptide vaccination consist of different T‐cell subsets associated with different effector functions. Complementary analysis for TCR CDR3 and cytokine profiles may be useful to define the most effective CD8+ T‐cell population induced by peptide vaccination. © 2002 Wiley‐Liss, Inc.
Therapeutic efficacy of IL‐2‐loaded hydrogels in a mouse tumor model
Authors: De Groot Cornelis J. , Cadée Jenny A. , Koten Jan‐Willem , Hennink Wim E. , Den Otter Willem 
Published: August 2002

AbstractInterleukin‐2 (IL‐2) is a highly effective anticancer drug if it is applied locally for 5 consecutive days. In most cases this requires 5 invasive treatments, which is not usually acceptable for either the patient or the clinician. For this reason we have developed dextran‐based hydrogels from which the required amount of encapsulated IL‐2 (1–4 × 106 IU of IL‐2) is gradually released during 5–10 days. Initially IL‐2‐containing macroscopic cylinder‐shaped gels (implants), and later IL‐2‐containing injectable microspheres, were developed. These preparations were characterized in vitro, and the therapeutic activity was tested in DBA/2 mice with SL2 lymphosarcoma. The therapy was given to mice with a large and extensively metastasized tumor load (at least 5% of the body weight). If 1–4 × 106 IU of IL‐2 was slowly released from the hydrogels over a period of 5–10 days, the therapeutic effects were very good and comparable to the effects of free IL‐2 injections for 5 consecutive days. In conclusion, dextran‐based hydrogels are promising systems for the controlled release of IL‐2. © 2001 Wiley‐Liss, Inc.
CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk
Authors: Lei Haixin , Sjöberg‐Margolin Sara , Salahshor Sima , Werelius Barbro , Jandáková Eva , Hemminki Kari , Lindblom Annika , Vořechovský Igor 
Published: August 2002

AbstractMutations and diminished expression of the E‐cadherin gene (CDH1) have been identified in a number of epithelial malignancies. Although somatic CDH1 mutations were detected in lobular breast cancer with a frequency ranging from 10–56%, CDH1 alterations in more frequent ductal tumors appear to be rare. Here we have analyzed the coding region of CDH1 for mutations using denaturing high performance liquid chromatography and found 4 mutations in 83 ductal carcinomas (5%) and 3 mutations in 25 lobular carcinomas (12%). The germline of 13 patients with familial lobular tumors was also analyzed for mutations, but none were detected. In a case‐control study, we also tested whether a variant adenine allele in the promoter polymorphism −161C→A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer. No significant difference in the allelic frequency between patients with breast cancer (326/1,152, 28.3%) and controls (190/696, 27.3%, p > 0.05; relative risk 1.05, 95% confidence interval 0.85–1.30) was found. A novel promoter polymorphism was identified at position −152, but the frequency of the variant cytosine allele was also similar in patients with breast cancer and controls (0.71% vs. 0.21%, p = 0.23). Transient transfection experiments using reporter constructs containing the nucleotide substitutions −161C/−152C and −161A/−152T showed only a slight decrease in the transcription activity compared to the wild‐type construct. These results do not support CDH1 as a prominent low‐penetrance cancer susceptibility gene, but indicate that CDH1 mutations contribute to the progression of both lobular and ductal tumors. © 2001 Wiley‐Liss, Inc.
Overexpression of the eukaryotic translation initiation factor 4G (eIF4G‐1) in squamous cell lung carcinoma
Authors: Bauer Christine , Brass Nicole , Diesinger Isabel , Kayser Klaus , Grässer Friedrich A. , Meese Eckart 
Published: August 2002

AbstracteIF4G‐1 belongs to the family of translational initiation factors and is recognized as the central organizing protein in recruitment of mRNA during translational initiation. Previously published studies have provided some evidence that overexpression of translational factors is a general event in the process of carcinogenesis. We have characterized the expression of the eIF4G‐1 protein in 33 squamous cell carcinoma (SCC) of the lung by Western blotting. Overexpression of the eIF4G‐1 protein was detected in 61% of the tumors compared to the respective normal lung tissue. In addition, we analyzed the expression of this protein by immunohistochemistry in 138 SCC of the lung using a newly generated antibody that is specific for eIF4G‐1 as determined by Western blotting. This anti‐eIF4G‐1 antibody was suitable for the immunohistochemistry of paraffin‐embedded tissues. There is a strong cytoplasmic staining detected in the tumor areas that is consistent with the cytoplasmic localization of the translation factor eIF4G‐1. In 72% of the examined tissue sections of SCCs of the lung, we detected an overexpression of the eIF4G‐1 protein compared to the surrounding connective tissue. Two tumors that were analyzed by both methods showed an overexpression of eIF4G‐1 both with Western blot analysis and immunohistochemical staining. Overexpression of eIF4G‐1 may result in an increased amount of the translation initiation complex eIF4F, which in turn may activate the translation of the same target mRNAs as eIF4E. © 2001 Wiley‐Liss, Inc.
Expression of interleukin‐18 in human ovarian carcinoma and normal ovarian epithelium: Evidence for defective processing in tumor cells
Authors: Wang Zhao Yuan , Gaggero Alessia , Rubartelli Anna , Rosso Ombretta , Miotti Silvia , Mezzanzanica Delia , Canevari Silvana , Ferrini Silvano 
Published: August 2002

AbstractInterleukin‐18 (IL‐18) is a proinflammatory monokine structurally related to IL‐1β that stimulates interferon‐γ (IFN‐γ) production. IL‐18 is synthesized as an inactive precursor, pro‐IL‐18, which is cleaved by IL‐1β‐converting enzyme (ICE)/caspase‐1 in a mature protein. In view of the proposed use of IL‐18 in cancer immuno/gene therapy, we have studied the expression of IL‐18 in tumor cells. IL‐18 mRNA was detected by reverse transcriptase polymerase chain reaction in all human ovarian carcinoma cell lines tested (9/9) and in one‐half of tumor cell populations obtained from ovarian carcinoma patients (4/8). ICE mRNA was expressed in a smaller fraction of samples (3/9 cell lines and 3/8 samples from patients). IL‐18 protein was also found in 7/13 ovarian carcinoma solid tumors by immunohistochemic analysis. In tumor cell lines we were able to detect abundant intracellular pro‐IL‐18 (24 kDa) by Western blotting, whereas the mature form of IL‐18 was undetectable, irrespective of the presence of ICE mRNA and protein. Only pro‐IL‐18 was also found in the ovarian carcinoma cell supernatants, which did not display any IL‐18 biologic activity in functional assays. Normal cultured ovarian epithelial cells revealed the presence of both IL‐18 and ICE mRNA in all samples (5/5) and IL‐18 protein was expressed by the thin epithelial cell layer surrounding normal ovary. More importantly, normal ovarian epithelial cells released low but detectable amounts of mature IL‐18 in the culture supernatant, which displayed IL‐18‐like biologic activity in functional assays. These data suggest that mature biologically active IL‐18 production is a feature of the normal ovarian surface epithelium lost during neoplastic transformation. © 2002 Wiley‐Liss, Inc.
Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model
Authors: Froidevaux Sylvie , Eberle Alex N. , Christe Martine , Sumanovski Lazar , Heppeler Axel , Schmitt Jörg S. , Eisenwiener Klaus , Beglinger Christoph , Mäcke Helmut R. 
Published: August 2002

AbstractSomatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR‐expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes 67Ga and 68Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga‐labeled somatostatin analog suitable for targeting SSTR‐expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals 111In, 90Y and 67Ga. They were then evaluated for their performance in the AR4‐2J pancreatic tumor model by testing SSTR2‐binding affinity, internalization/externalization in isolated cells and biodistribution in tumor‐bearing nude mice. Surprisingly, we found that, compared to 111In or 90Y, labeling with 67Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. 67Ga‐labeled DOTA‐somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor‐to‐nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [67Ga]DOTATOC was strongly internalized by AR4‐2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga‐DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga‐DOTA somatostatin analogs will become an important tool in the management of SSTR‐positive tumors. © 2002 Wiley‐Liss, Inc.
Variation in breast cancer risk of heterozygotes for ataxia‐telangiectasia according to environmental factors
Authors: Geoffroy‐Perez Béatrice , Janin Nicolas , Ossian Katia , Laugé Anthony , Stoppa‐Lyonnet Dominique , Andrieu Nadine 
Published: August 2002

AbstractAtaxia‐telangiectasia (AT) is a rare autosomal recessive disorder, characterized by progressive neuronal degeneration, immunological deficiency, radio‐sensitivity and an increased risk of cancer. Although several studies have confirmed that AT heterozygosis increases the risk of breast cancer (BC), we do not know how exogenous factors affect this risk. We performed an epidemiological study on the cancer risks associated with AT heterozygosis in France and explored the variation in BC risk according to environmental factors, such as reproductive factors and exposure to ionizing radiation. Information on the amount of ionizing radiation received by an individual in their lifetime and on their reproductive life was collected from the living relatives of 34 AT children (175 female relatives). Consistent with previous reports and with our previous estimate on the entire retrospective cohort, we found that the risk of developing BC is 3.6‐fold higher among ATM heterozygous women. An increased risk was associated with an early age at menarche, a late age at first childbirth, nulliparity, premenopausal status and increasing periods of breast cell mitotic activity (BCMA) prior to the first childbirth. Age at menarche, age at 1st childbirth and BCMA seemed to have a stronger effect in ATM heterozygotes than in non‐ATM heterozygotes. However, the tests were not all statistically significant (only age at 1st childbirth). Surprisingly, the risk of BC decreased when the chest or breasts were irradiated. It is difficult to interpret the data because of the small sample size, but further investigations should provide a biological explanation for the variation in BC risk associated with exogenous factors according to ATM heterozygosis status. © 2002 Wiley‐Liss, Inc.
Ethni‐cities: residential patterns in the Northern European and Mediterranean metropolises – implications for policy design
Authors: Malheiros Jorge 
Published: August 2002

AbstractThis paper examines how the role of Southern Europe in international migration systems has changed, from that of a source to a destination region, and how this is reflected in the emergence of new patterns of ethnic segregation. Areas where immigrants cluster are also areas with relatively high levels of social and housing deprivation. As a result, ethnic residential segregation is in part an expression of social exclusion. In the first part of the paper, a statistical analysis of secondary data provides an overview of the levels and distribution of ethnic segregation in Greece, Italy, Portugal and Spain. The second part of the paper examines the implications of the spatial organisation of immigrant communities for the development of territorial policies, and explores this through a comparative study of Lisbon and Rotterdam. The analysis also deals with territorialised policies developed in areas where immigrants cluster. Copyright © 2002 John Wiley & Sons, Ltd.
Field‐scale modeling to explore salinity problems in irrigated agriculture1
Authors: Droogers P. , Torabi M. , Akbari M. , Pazira E. 
Published: August 2002

AbstractOne‐third of irrigated land is affected by salinity or is expected to become so in the near future. A rapid assessment to evaluate the effect of changes in the quality and quantity of irrigation water was tested for the Rudasht irrigation project in Iran. This was performed by using a physically based, well‐tested simulation model for crop growth, water and salt transport at field scale. Data used were from an existing dataset and missing data were obtained by converting data from the available set to the required ones. Results indicate that the current practice of 900 mm annual application rates for cotton, given the current salinity level of 4 dS m−1, is close to the optimal one. Graphs are presented to evaluate the effect of different combinations of application rates and salinity levels on yields, and the water and salt balances. It was concluded that the methodology presented here is versatile, rapid, and transferable to other conditions. Moreover, the method produces output at a high spatial and temporal resolution over a long time frame. Copyright © 2001 John Wiley & Sons, Ltd.