bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed effects of chronic variable stress during peripubertal‐juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats
Authors: Isgor Ceylan , Kabbaj Mohamed , Akil Huda , Watson Stanley J. 
Published: April 2004

AbstractAnimal studies on the effects of chronic variable stress during the peripubertal‐juvenile period on hippocampal structure and function are lacking. Twenty‐eight‐day‐old Sprague‐Dawley rats were subjected to random, variable physical or social stress regimens for 4 weeks. Hippocampal volume was found to continue to grow in all lamina examined during the transition into young adulthood. Our variable physical stress paradigm led to inhibition of this growth in the CA1 pyramidal cell layer (PCL) and in the dentate gyrus‐granular cell layer (DG‐GCL), which reached full arrest in the CA3‐PCL. Volume deficits were first observed after chronic stress exposure when 3 weeks, but not 24 h, of recovery had elapsed. Moreover, these volume deficits were associated with impairments in the Morris water‐maze navigation, sustained downregulation in the basal hippocampal glucocorticoid receptor gene expression, and deficits in the shutdown of acute stress‐induced corticosterone secretion. Volume changes both due to normal maturation and after chronic stress exposure were independent of neuron number. Thus, a peripubertal‐juvenile chronic stress paradigm that leads to significant alterations in the limbic‐hypothalamic‐pituitary‐adrenal axis can produce robust effects in hippocampal structure and cognitive ability, lasting into adulthood. © 2004 Wiley‐Liss, Inc.
Recollective qualities modulate hippocampal activation during autobiographical memory retrieval
Authors: Addis Donna Rose , Moscovitch Morris , Crawley Adrian P. , McAndrews Mary Pat 
Published: April 2004

AbstractRecent neuroimaging studies report preferential hippocampal engagement during autobiographical memory (AM) retrieval. Although the basis of this preferential activation remains unclear, it may be related to the temporal specificity, recency, or recollective qualities of AMs, such as detail, emotionality, and personal significance. Typically, however, these variables are confounded, and thus we sought to investigate the contributions of each to hippocampal activation during AM retrieval. We conducted an event‐related functional magnetic resonance imaging (fMRI) study in which participants retrieved temporally specific AMs and general, repeated AMs, and rated each for level of detail, emotion, or personal significance. These ratings, as well as the recency of AMs, were used in parametric modulation analyses to identify brain regions that correlated positively with ratings, independent of recency, and vice versa. Retrieval of AMs activated a number of regions, including the hippocampus. No differences in hippocampal activation were evident between specific and general AM retrieval, suggesting that temporal specificity, on its own, is not a key modulator of hippocampal activation. Activation of the left hippocampus during specific AM retrieval did vary with the level of detail, personal significance, and at a subthreshold level, emotionality, when the effect of recency was covaried out. Further, during general AM retrieval, all three recollective qualities modulated activity in the right hippocampus. Although the recency of specific AMs modulated hippocampal activation bilaterally, this effect dissipated in the left hippocampus when detail or emotionality was included as a covariate, and was no longer present in either hippocampus when personal significance was taken into account. Our results suggest that recollective qualities are important predictors of hippocampal engagement during AM retrieval independent of factors such as recency. These findings are consistent with theories of hippocampal function that emphasize its role in the recollection of multifaceted autobiographical experiences. © 2004 Wiley‐Liss, Inc.
Reversible lymphomagenesis in conditionally c‐MYC expressing mice
Authors: Marinkovic Dragan , Marinkovic Tatjana , Mahr Bettina , Hess Jochen , Wirth Thomas 
Published: April 2004

AbstractIt is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood. We have established a transgenic mouse model in which c‐MYC is conditionally expressed in lymphoid cells using the tetracycline‐regulated system of gene regulation. Mice with continuously expressed transgenic c‐MYC died of invasive T‐ or B‐cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c‐MYC dependent since doxycycline treatment led to tumor regression. Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation. This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination. Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c‐MYC. We observed that overexpression of c‐MYC is sufficient to induce recurrent patterns of genomic instability. The main observation was a gain of genomic material that corresponded to chromosome 15 in several T‐cell tumors, which could be identified as trisomy. © 2004 Wiley‐Liss, Inc.
Food groups and risk of prostate cancer in Italy
Authors: Bosetti Cristina , Micelotta Stefania , Dal Maso Luigino , Talamini Renato , Montella Maurizio , Negri Eva , Conti Ettore , Franceschi Silvia , La Vecchia Carlo 
Published: April 2004

AbstractAlthough several studies have been conducted, the relation between diet and prostate cancer remains unclear. The role of a wide range of foods on the risk of prostate cancer has thus been analyzed in a case‐control study conducted in Italy between 1991 and 2002. Cases were 1,294 patients below age 75 years with incident, histologically confirmed carcinoma of the prostate; controls were 1,451 subjects below age 75 years admitted to the same hospitals as cases for a wide spectrum of acute, non‐neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for major potential confounding factors, including calorie intake. Among the 19 food groups considered, 4 showed some significant association with prostate cancer risk. A significant trend of increasing risk with more frequent consumption was found for milk and dairy products (OR = 1.2 for highest vs. lowest quintile, p = 0.03) as well as bread (OR = 1.4, p = 0.01), whereas inverse associations were observed for soups (OR = 0.8, p = 0.02) and cooked vegetables (OR = 0.7, p = 0.01). This uniquely large study on prostate cancer and diet in a southern European population confirms that no strong association exists between any specific foods and prostate cancer, apart from an increased risk for milk and dairy products and a possible protective effect of vegetables. © 2004 Wiley‐Liss, Inc.
The Solow model with CES technology: nonlinearities and parameter heterogeneity
Authors: Masanjala Winford H. , Papageorgiou Chris 
Published: April 2004

AbstractThis paper examines whether nonlinearities in the aggregate production function can explain parameter heterogeneity in the Solow growth regressions. Nonlinearities in the production technology are introduced by replacing the commonly used Cobb–Douglas (CD) aggregated production specification with the more general Constant‐Elasticity‐of‐Substitution (CES) specification. We first justify our choice of production function by showing that cross‐country regressions favour the CES over the CD technology. Then, by using an endogenous threshold methodology we show that the Solow model with CES technology is consistent with the existence of multiple regimes. Copyright © 2004 John Wiley & Sons, Ltd.
Identification of goat sperm ecto‐cyclic AMP independent protein kinase substrate localized on sperm outer surface
Authors: Maiti Arunima , Mishra K.P. , Majumder G.C. 
Published: April 2004

AbstractWe have demonstrated the location of a cyclic AMP independent serine/threonine protein kinase (ecto‐CIK) on the outer surface of mature goat spermatozoa. We purified and characterized the major physiological protein substrate (MPS) of ecto‐CIK. 32P‐labeled membrane proteins phosphorylated by endogenous ecto‐CIK of intact cauda‐epididymal spermatozoa was solubilized with 1% Triton X‐100 and then fractionated by following several chromatographic techniques like Sephacryl S‐300 molecular sieve chromatography, DEAE–cellulose ion‐exchange chromatography and chromatofocussing. The MPS of ecto‐CIK has been purified to apparent homogeneity and it was found to be a monomeric protein of 100 kDa. Three isoforms of MPS have been found with pI of 6.37, 6.05, and 5.14 and all these isoforms served as the specific substrate of ecto‐CIK. The ecto‐kinase has nearly 30 times greater affinity for MPS as compared to casein the most potent exogenous protein substrate. Addition of MPS (pI 5.14) antibody caused head‐to‐head sperm agglutination. The Fv/Fab fragment of anti‐MPS caused significant inhibition of sperm motility. The data show that MPS is an ecto‐protein localized on the sperm head. MPS may thus play an important role for the regulation of sperm–egg interaction. © 2004 Wiley‐Liss, Inc.
Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells
Authors: Kang Mo K. , Kameta Ayako , Shin Ki‐Hyuk , Baluda Marcel A. , Park No‐Hee 
Published: April 2004

AbstractWe investigated the phenotypic and molecular alterations in normal human oral keratinocytes (NHOK) during in vitro replication in two different culture conditions. The cells were cultured either in chemically defined Keratinocyte Growth Medium (KGM) without feeder layers or in serum‐containing flavin‐adenine dinucleotide (FAD) medium with feeder layers. Primary NHOK underwent 22 ± 3 population doublings (PDs) in KGM and 42 ± 4 PDs in FAD medium, reflecting 52% increase in replication capacity with feeder layers. In both culture conditions, exponentially replicating NHOK demonstrated telomerase activity and expression of human telomerase reverse transcriptase (hTERT) gene. Telomerase activity and hTERT expression were rapidly diminished in senescing NHOK, which exhibited small decrease of telomere length for the remaining limited cellular replications until the complete arrest of cell division. However, telomere length in senescent NHOK was 6.7 ± 0.5 kilobase pairs (kbps), significantly longer than that (5.12 kbps) of senescent human fibroblasts. The onset of senescence was accompanied with marked induction of p16INK4A, and this occurred in both culture systems using either KGM or FAD medium. These results indicate that replicative senescence of NHOK is associated with loss of telomerase activity followed by limited telomere shortening. © 2003 Wiley‐Liss, Inc.
Intraocular gutless adenoviral‐vectored VEGF stimulates anterior segment but not retinal neovascularization
Authors: Oshima Yuji , Takahashi Kyoichi , Oshima Sachiko , Saishin Yoshitsugu , Saishin Yumiko , Silva Raquel Lima , Liang Xaoling , Reddy P. Seshidhar , Ganesh Shanthi , Brann Terrence , Liau Gene , Kaleko Michael , Connelly Sheila , Campochiaro Peter A. 
Published: April 2004

AbstractVascular endothelial growth factor (VEGF) and insulin‐like growth factor‐1 (IGF‐1) have been implicated as important stimulatory factors for retinal neovascularization. In this study, we used intraocular gene transfer with gutless adenoviral (AGV) vectors to determine the effect of increased intraocular expression of VEGF, IGF‐1, or sphingosine kinase (SPK), which produces sphingosine‐1‐phosphate, another angiogenic factor. Retinal neovascularization did not occur from intravitreous AGV‐vectored VEGF, IGF‐1, SPK, or combined VEGF and IGF‐1, except occasionally adjacent to the retinal penetration site from the injection. However, corneal and iris neovascularization occurred after 2 weeks in all eyes injected with AGV.VEGF, but not those injected with only AGV.IGF‐1 or AGV.SPK. These data suggest that the superficial capillary bed of the retina is relatively insensitive to VEGF, IGF‐1, or SPK in adult mice, except when combined with retinal trauma. However, AGV‐vectored VEGF is sufficient to consistently cause severe corneal and iris neovascularization. This provides a model for anterior segment neovascularization, which unlike previous models is relatively inexpensive and is not plagued by spontaneous regression, and therefore, may be useful for identification of new treatments. © 2004 Wiley‐Liss, Inc.
Three novel hormone‐responsive cell lines derived from primary human breast carcinomas: Functional characterization
Authors: Vázquez Stella Maris , Mladovan Alejandro , Garbovesky Carlos , Baldi Alberto , Lüthy Isabel Alicia 
Published: April 2004

AbstractHuman breast cancer primary cultures are useful tools for the study of several aspects of cancer biology, including the effects of chemotherapy and acute gene expression in response to different hormonal/chemotherapy treatments. The present study reports the conditions for primary culture of breast cancer samples from untreated patients and the most effective collagenization method to dissociate human samples consisting in an overnight incubation with 1 mg/ml types II or IV collagenase and further incubation in DMEM:F12 (1:1) medium supplemented with glutamine, bovine insulin, penicillin–streptomycin, HEPES, estradiol, cortisol (F), tri‐iodothyronine (T3), transferrine (TR), and 10% fetal calf serum (FCS). These conditions proved to be appropriate for both primary culture and the development of stable cell lines. Of the seven cell lines obtained, three fast growing and estrogen receptor (ER)+/progesterone receptor (PgR)+/EGF receptor (EGFR)+ have been characterized. The cells are able to grow both in soft agar and in nude mice, and express cytokeratins, all parameters characteristic of malignant epithelial cell lines. The cells also exhibit an increased proliferation rate in the presence of estradiol, progesterone, and EGF, suggesting the presence of the corresponding receptors. The mRNA expression of type α‐ and β‐ER as well as EGFR, was confirmed by RT‐PCR. In conclusion, the novel cell lines described, arose from primary tumors and are sensitive to estradiol, progesterone, and EGF. This not only expands the repertoire of breast cancer cells available as potentially useful tools for examining most parameters in breast cancer “in vitro”, but also provides unique new models to explore the complex regulation by steroids as well as growth factors in such cells. © 2003 Wiley‐Liss, Inc.
Notch‐1 regulates cell death independently of differentiation in murine erythroleukemia cells through multiple apoptosis and cell cycle pathways
Authors: Jang Mei‐Shiang , Miao Haixi , Carlesso Nadia , Shelly Leslie , Zlobin Andrei , Darack Nicole , Qin Jian‐Zhong , Nickoloff Brian J. , Miele Lucio 
Published: April 2004

AbstractNotch signaling is a potential therapeutic target for various solid and hematopoietic malignancies. We have recently shown that downregulation of Notch‐1 expression has significant anti‐neoplastic activity in pre‐clinical models. However, the mechanisms through which Notch modulation may affect cell fate in cancer remain poorly understood. We had previously shown that Notch‐1 prevents apoptosis and is necessary for pharmacologically induced differentiation in murine erythroleukemia (MEL) cells. We investigated the mechanisms of these effects using three experimental strategies: (1) MEL cells stably transfected with antisense Notch‐1 or constitutively active Notch‐1, (2) activation of Notch‐1 by a cell‐associated ligand, and (d3) activation of Notch‐1 by a soluble peptide ligand. We show that: (1) downregulation of Notch‐1 sensitizes MEL cells to apoptosis induced by a Ca2+ influx or anti‐neoplastic drugs; (2) Notch‐1 downregulation induces phosphorylation of c‐Jun N‐terminal kinase (JNK) while constitutive activation of Notch‐1 or prolonged exposure to a soluble Notch ligand abolishes it; (3) Notch‐1 has dose‐ and time‐dependent effects on the levels of apoptotic inhibitor Bcl‐xL and cell cycle regulators p21cip1/waf1, p27kip1, and Rb; and (4) Notch‐1 activation by a cell‐associated ligand is accompanied by rapid and transient induction of NF‐κB DNA‐binding activity. The relative effects of Notch‐1 signaling on these pathways depend on the levels of Notch‐1 expression, the mechanism of activation, and the timing of activation. The relevance of these findings to the role of Notch signaling in differentiation and cancer are discussed. © 2003 Wiley‐Liss, Inc.
Anaplastic lymphoma kinase proteins in growth control and cancer
Authors: Pulford K. , Morris S.W. , Turturro F. 
Published: April 2004

AbstractThe normal functions of full‐length anaplastic lymphoma kinase (ALK) remain to be completely elucidated. Although considered to be important in neural development, recent studies in Drosophila also highlight a role for ALK in gut muscle differentiation. Indeed, the Drosophila model offers a future arena for the study of ALK, its ligands and signalling cascades. The discovery of activated fusion forms of the ALK tyrosine kinase in anaplastic large cell lymphoma (ALCL) has dramatically improved our understanding of the pathogenesis of these lymphomas and enhanced the pathological diagnosis of this subtype of non‐Hodgkin's lymphoma (NHL). Likewise, the realisation that a high percentage of inflammatory myofibroblastic tumours express activated‐ALK fusion proteins has clarified the causation of these mesenchymal neoplasms and provided for their easier discrimination from other mesenchymal‐derived inflammatory myofibroblastic tumour (IMT) mimics. Recent reports of ALK expression in a range of carcinoma‐derived cell lines together with its apparent role as a receptor for PTN and MK, both of which have been implicated in tumourigenesis, raise the possibility that ALK‐mediated signalling could play a role in the development and/or progression of a number of common solid tumours. The therapeutic targeting of ALK may prove to have efficacy in the treatment of many of these neoplasms. © 2004 Wiley‐Liss, Inc.
TP53 in gastric cancer: Mutations in the L3 loop and LSH motif DNA‐binding domains of TP53 predict poor outcome
Authors: Migliavacca Manuela , Ottini Laura , Bazan Viviana , Agnese Valentina , Corsale Simona , Macaluso Marcella , Lupi Ramona , Dardanoni Gabriella , Valerio Maria Rosaria , Pantuso Gianni , Fede Gaetana Di , Tomasino Rosa Maria , Gebbia Nicola , Mariani‐Costantini Renato , Russo Antonio 
Published: April 2004

AbstractThe aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5–8 of the p53 gene was investigated in 62 cases using the PCR‐SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functional domains: 4/20 mutations (20%) were in the L3 loop and 3/20 (15%) in LSH motif. Eight of the 56 GC resulted MSI‐H, 5 (9%) MSI‐L, and 43 (77%) MSI stable (MSS). None of the 8 (14%) MSI‐H GC showed p53 mutations. p53 mutations were associated with intestinal histotype. Moreover, specific mutations in functional domain (L3 and LSH), together with advanced TNM stage, node involvement, depth of invasion, diffuse histotype, proved to be significantly related to quicker relapse and to shorter overall survival. Specific mutations in p53 functional domains, rather than any mutations in this gene, may be biologically more significant in terms of patients outcome, indicating that these mutations might have biological relevance to identify subgroups of patients at higher risk of relapse or death who might benefit from a more aggressive therapeutic approach. © 2004 Wiley‐Liss, Inc.
Apoptosis induced by interferon‐α and antagonized by EGF is regulated by caspase‐3‐mediated cleavage of gelsolin in human epidermoid cancer cells
Authors: Boccellino M. , Giuberti G. , Quagliuolo L. , Marra M. , D'Alessandro A.M. , Fujita H. , Giovane A. , Abbruzzese Alberto , Caraglia Michele 
Published: April 2004

AbstractWe have previously reported that interferon‐α (IFNα) induces apoptosis and EGF can antagonize this effect in human epidermoid cancer KB cells. Since apoptosis occurs together with cytoskeleton reorganization we have evaluated if IFNα and EGF could modulate cell remodeling in our experimental conditions. We have found that 48 h 1,000 IU/ml IFNα induced structural reorganization of stress fibers and membrane delocalization and partial capping of the actin severing protein gelsolin. The transfection of KB cells with both a wild type (WT) or a C‐terminal truncated form of gelsolin caused overexpression of the protein and an increase of both the spontaneous and IFNα‐induced apoptosis and cell cytoskeletal modifications. In fact, after 48 h of treatment IFNα induced 45% of apoptotic cell death in parental cells while an approximately 80% of cell population was apoptotic in transfected cells. These effects occurred together with an increase of the expression and consequent degradation of gelsolin. Again the addition of EGF to IFNα‐treated transfected cells caused a recovery of the apoptosis. Notably, IFNα and EGF did not modify the expression of other molecules associated to cytoskeleton such as focal adhesion kinase and vinculin. In the same experimental conditions IFNα induced also gelsolin cleavage that occurred together with caspase‐3 activation and release of cytochrome c. All these effects were antagonized by the exposure of IFNα‐treated KB to 10 nM EGF for the last 12 h. Moreover, the specific inhibition of caspase‐3 with 20 μM DEVD completely abrogated apoptosis and gelsolin cleavage induced by IFNα. In conclusion, our data are the first demonstration that IFNα can induce morphological cell changes that are peculiar of apoptosis onset through the caspase‐3‐mediated cleavage of gelsolin. Furthermore, we have demonstrated that EGF is able to antagonize these effects through the inhibition of caspase‐3 activation. J. Cell. Physiol. 201: 71–83, 2004. © 2004 Wiley‐Liss, Inc.
Judicious partitions of bounded‐degree graphs
Authors: Bollobás B. , Scott A. D. 
Published: April 2004

AbstractWe prove results on partitioning graphs G with bounded maximum degree. In particular, we provide optimal bounds for bipartitions V(G) = V1 ∪ V2 in which we minimize {e(V1), e(V2)}. © 2004 Wiley Periodicals, Inc. J Graph Theory 46: 131–143, 2004