bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison and evaluation of the predictions of relational and conjunctive accounts of hippocampal function
Authors: Moses Sandra N. , Ryan Jennifer D.
Published: November 2005

Relational and conjunctive memory theory each postulate that the hippocampus participates in the formation of long‐term memory representations comprised of associations between multiple elements. The goals of the current work were to clarify and contrast these theories by outlining the nature of the representations that are spared vs. impaired following hippocampal damage according to each theoretical perspective. Relational theory predicts that hippocampal lesions will impair performance on tasks that require the formation of new long‐term representations in which distinct elements must be regarded in relation to all other elements. Representations that remain intact despite hippocampal damage include separate representations of distinct individual elements or multiple stimuli fused into a static “blend” such as several elements viewed from one vantage point. Additionally, the relational account predicts that rapid incidental online processing of the relations can be achieved through structures other than the hippocampus, but this information will not be stored. In contrast, conjunctive theory predicts that hippocampal damage will impair the rapid formation of unitary representations that contain features of elements and their relative relationships bound in an inflexible manner. Deficits in the rapid formation of these conjunctive representations result in impaired performance on tasks that require rapid incidental stimulus binding. However, intact formation of conjunctive representations can occur over multiple trials in the service of problem solving. Using these theoretical frameworks, recent findings from the human and nonhuman animal literature are reexamined in order to determine whether one theory better accounts for current findings. We discuss empirical studies that serve as “critical experiments” in addressing the relational vs. conjunctive debate, and find that the predictions of relational theory are supported by existing findings over those from the conjunctive account. © 2005 Wiley‐Liss, Inc.
Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the freely moving rat
Authors: Bland Brian H. , Bird Jen , Jackson Jesse , Natsume Kiyohisa
Published: November 2005

Rats implanted with hippocampal recording electrodes were tested in a wheel‐running apparatus under three conditions: (1) independent electrical stimulation of the medial septal nucleus (MS); (2) independent electrical stimulation of the posterior hypothalamic nucleus (PH); and (3) combined electrical stimulation of the MS and PH using pairings of two stimulation conditions, 7 or10 Hz stimulation of the MS, and a low‐ or high‐intensity PH stimulation. Quantitative measures of running speed were taken, and hippocampal recordings were subjected to fast‐Fourier transform analysis. Electrical stimulation of the PH induced wheel‐running behavior; running speed and the accompanying hippocampus (HPC) theta frequency increased with increase in stimulation intensity. Electrical stimulation of the MS failed to induce wheel‐running behavior despite the fact that HPC theta was induced at the frequency of the applied stimulation (7 and 10 Hz). Electrical stimulation of the MS reset the frequency of HPC theta induced by PH stimulation in both the upward and downward directions and increased theta power, while wheel‐running speed was modulated in a downward direction only. © 2005 Wiley‐Liss, Inc.
Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the rat
Authors: Majchrzak M. , Ferry B. , Marchand A.R. , Herbeaux K. , Seillier A. , Barbelivien A.
Published: November 2005

Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham‐lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham‐operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal‐lesioned rats showed higher freezing scores than those of sham‐lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing. © 2005 Wiley‐Liss, Inc.
Lateralized functional components of spatial cognition in the avian hippocampal formation: Evidence from single‐unit recordings in freely moving homing pigeons
Authors: Siegel Jennifer J. , Nitz Douglas , Bingman Verner P.
Published: November 2005

Previous research has revealed that the functional components of spatial cognition are lateralized in the forebrain of birds, including the hippocampal formation (HF). To investigate how HF cells in the left and right avian brain may differentially participate in representations of space, we recorded single‐units from the HF of homing pigeons as they ran a plus maze for food. The rate maps of left HF cells often displayed elongated regions of increased activity in the center of the maze and along the maze corridors, whereas right HF cells tended to display patches at the ends of maze arms at/near goal locations. Left HF cells displayed a higher degree of spatial‐specificity compared with right HF cells, including higher patch‐specificity, higher reliability, and a higher incidence of location‐correlated activity. Analysis of speed‐correlated and trajectory‐dependent activity also revealed significant HF‐lateralized differences. Right HF cells tended to display significant negative correlations between spike rate and speed, although speed‐dependent rate maps indicate that this relationship did not explain their space‐specific activity. Left HF cells displayed a significantly higher incidence of trajectory‐dependent space‐specific activity than was observed in the right HF, suggesting that left HF cells may participate in navigating among goal locations. Differences in the correlates of left and right pigeon HF cells are consistent with unilateral HF‐lesion data suggesting that the functional components of spatial cognition are lateralized in the avian brain, and furthermore, provide a basis for hypotheses regarding how the left and right HF support different aspects of spatial cognition. © 2005 Wiley‐Liss, Inc.
Mixed convective heat transfer of water in a pipe under supercritical pressure
Authors: Xu Feng , Guo Liejin , Bai Bofeng
Published: November 2005

Because of the rapid properties variation of fluid under supercritical pressure, there is a violent secondary flow in a heated pipe, which will certainly complicate the heat transfer of fluid in a pipe under supercritical pressure. In this paper, a numerical study is conducted for the laminar developing mixed convective heat transfer of water under supercritical pressure. The velocity field and temperature field are given, and the influence of different parameters on flow and heat transfer is investigated in detail. The results show that secondary flow has a great influence on velocity and temperature distributions and thus affects the friction factor and the Nusselt number remarkably. © 2005 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(8): 608–619, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20079
Fluid flow and heat transfer of opposing mixed convection adjacent to vertical heated plates
Authors: Kitamura Kenzo , Yamamoto Manabu , Kimura Fumiyoshi
Published: November 2005

Opposing mixed convective flows induced around heated vertical plates were investigated experimentally. The experiments have been carried out with air and test plates of 100 mm and 200 mm long. The flow fields over the heated plates were visualized and the local heat transfer coefficients of the plates were measured for a wide range of Reynolds and Rayleigh numbers; ReL = 7 × 102−1.5 × 104, Ra = 9 × 106−8 × 108. The visualization experiments showed that the separation of the boundary layer appears first at the trailing edge of the plate when the non‐dimensional parameter of (Gr/Re) = 0.35, and that the separation point reaches the leading edge when (GrL*/ReL2.5) = 1.0. The heat transfer experiments showed that the above flow separation retards the heat transfer significantly from that of pure forced convection. It was also revealed that the flows over the heated plates can be categorized into forced, natural, and combined convection using the above parameter, (Gr/Re), as (Gr/Re) < 0.2, (Gr/Re) > 3 and 0.2 < (Gr/Re) < 3, respectively. © 2005 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(8): 595–607, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20080
Pattern analysis of a single droplet impinging onto a heated plate
Authors: Wang An‐Bang , Lin Chih‐Hung , Cheng Chi‐Chang
Published: November 2005

The time scale for measuring the heat transfer phenomena, such as the Leidenfrost phenomenon, is much longer than the hydrodynamic transient period of a droplet impinging onto a heated surface. However, the Leidenfrost temperature has been long since taken as the criterion to classify characteristic regimes for not only heat transfer but also hydrodynamic impact patterns of liquid‐solid‐interface problems in the literature. The impingement phenomena of a single droplet onto a heated plate for We <200 were experimentally classified as five different characteristic patterns in this paper. They are [I] completely wet, [II] wet film boiling, [III] transition, [IV] dry rebounding, and [V] satellite dry rebounding impact patterns. The former two patterns belong to wet impact, while the latter two are dry impact. This work reveals that the hydrodynamic impact parameter does influence the classification of characteristic impact patterns, especially for the dry impact patterns. For high impact Weber numbers, the dry impact happens to the plate surface temperature much lower than the commonly believed Leidenfrost temperature due to the squeeze film effect. The evolutions that impact changes from one to another characteristic patterns are also discussed. This paper offers a systematic and reliable database for future numerical simulations. © 2005 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(8): 579–594, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20089
The dynamic characteristics of a thermal control system using latent heat: Comparison between analytical and experimental results
Authors: Fujii Terushige , Kawasaki Haruo , Tooyama Shinichi , Sugimoto Katsumi , Asano Hitoshi
Published: November 2005

The two‐phase flow thermal control system, using latent heat of the internal fluid, has received a great deal of research interest as a method for heat removal on the space station and the Space Solar Power System (SSPS). The system has a much lower weight than the single‐phase flow, and the temperature can be accurately controlled by changing the saturated pressure inside the loop. To date, this system has not been put into practical use. Numerical analyses were therefore used to investigate the dynamic responses of the loop and to investigate the operational characteristics of the thermal control system. A simulation model was constructed, and the results of the numerical analysis were compared with the experimental results. Good agreement was obtained between analytical and experimental results. © 2005 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(8): 564–578, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20090
Effect of fins on forced convection heat transfer around a tube in an aligned‐arranged tube bundle
Authors: Hashizume Kenichi , Sueoka Yoshiaki
Published: November 2005

The effect of fins on heat transfer around a tube in an aligned‐arranged tube bundle was investigated experimentally, and the obtained results were compared for three arrangements, i.e., single tube, single tube row, and staggered‐arrangement. It was found from the experiment that the effect of fins begins to appear in an aligned‐arrangement with larger fin spacing than in a staggered‐arrangement. The degradation in the local heat transfer coefficient due to fins can be recognized not only on the rear region of the tube, as observed in other arrangements, but also on the frontal region. As a result of this phenomenon, the degradation in the average heat transfer coefficient in an aligned‐arrangement becomes larger than in other arrangements with the same fin spacing. © 2005 Wiley Periodicals, Inc. Heat Trans Asian Res, 34(8): 555–563, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20091
Molecular analysis of the PI3K‐AKT pathway in uterine cervical neoplasia: Frequent PIK3CA amplification and AKT phosphorylation
Authors: Bertelsen Bjørn I. , Steine Solrun J. , Sandvei Roar , Molven Anders , Laerum Ole Didrik
Published: November 2005

Uterine cervical carcinogenesis is probably dependent on cellular genetic damage in addition to the integration of high‐risk HPV DNA in the epithelial cell genome. Gain of chromosome 3q24–29 is commonly observed in cervical neoplasia. The putative oncogene PIK3CA located in this region encodes a phosphatidylinositol 3‐kinase (PI3K). In a process reversed by PTEN, PI3K generates inositol phospholipids that trigger AKT phosphorylation, which in turn effects tumor driving signals. We studied 46 specimens of formalin‐fixed, paraffin‐embedded cervical neoplastic tissue. The activation state of the PI3K‐AKT pathway was assessed immunohistochemically using an antibody with specificity towards serine 473‐phosphorylated AKT. AKT phosphorylation was found in 39 out of 46 examined specimens. To examine the possible molecular basis for this activation, we searched for PIK3CA amplification using quantitative real‐time polymerase chain reaction. PIK3CA gene copy number was estimated to be 3 or more in 28 out of 40 successfully examined cases. Further, a PTEN mutation analysis of all 9 PTEN exons was carried out, but except for 1 metastasis with an exon 9 V369I heterozygosity, all cases showed normal PTEN sequence. Immunohistochemical staining for PTEN was strong in all lesions. In conclusion, an increased activation state of AKT kinase appears to be present in cervical carcinogenesis, and may be accounted for by PIK3CA amplification, whereas PTEN mutation seems to be of little importance. © 2005 Wiley‐Liss, Inc.
Prevalence of MYH germline mutations in Swiss APC mutation‐negative polyposis patients
Authors: Russell Anna M. , Zhang Jian , Luz Judith , Hutter Pierre , Chappuis Pierre O. , Berthod Claudine Rey , Maillet Philippe , Mueller Hansjakob , Heinimann Karl
Published: November 2005

In 10–30% of patients with classical familial adenomatous polyposis (FAP) and up to 90% of those with attenuated (<100 colorectal adenomas; AFAP) polyposis, no pathogenic germline mutation in the adenomatous polyposis coli (APC) gene can be identified (APC mutation‐negative). Recently, biallelic mutations in the base excision repair gene MYH have been shown to predispose to a multiple adenoma and carcinoma phenotype. This study aimed to (i) assess the MYH mutation carrier frequency among Swiss APC mutation‐negative patients and (ii) identify phenotypic differences between MYH mutation carriers and APC/MYH mutation‐negative polyposis patients. Seventy‐nine unrelated APC mutation‐negative Swiss patients with either classical (n = 18) or attenuated (n = 61) polyposis were screened for germline mutations in MYH by dHPLC and direct genomic DNA sequencing. Overall, 7 (8.9%) biallelic and 9 (11.4%) monoallelic MYH germline mutation carriers were identified. Among patients with a family history compatible with autosomal recessive inheritance (n = 45), 1 (10.0%) out of 10 classical polyposis and 6 (17.1%) out of 35 attenuated polyposis patients carried biallelic MYH alterations, 2 of which represent novel gene variants (p.R171Q and p.R231H). Colorectal cancer was significantly (p < 0.007) more frequent in biallelic mutation carriers (71.4%) compared with that of monoallelic and MYH mutation‐negative polyposis patients (0 and 13.8%, respectively). On the basis of our findings and earlier reports, MYH mutation screening should be considered if all of the following criteria are fulfilled: (i) presence of classical or attenuated polyposis coli, (ii) absence of a pathogenic APC mutation, and (iii) a family history compatible with an autosomal recessive mode of inheritance. © 2005 Wiley‐Liss, Inc.
T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx
Authors: Hoffmann Thomas K. , Arsov Christian , Schirlau Kerstin , Bas Murat , Friebe‐Hoffmann Ulrike , Klussmann Jens Peter , Scheckenbach Kathrin , Balz Vera , Bier Henning , Whiteside Theresa L.
Published: November 2005

Squamous cell carcinomas of the oropharynx (SCCO) are often infected with oncogenic human papilloma virus (HPV) subtype 16. To determine the frequency of T cells specific for human leukocyte antigen (HLA)‐A2.1 restricted HPV16 E7 protein‐derived epitopes, tetramer analysis was performed using peripheral blood lymphocytes of 20 HLA‐A2.1+ patients and 20 HLA‐A2.1+ healthy individuals. Tetramers specific for 3 HPV16 peptides (E711–20, E782–90 and E786–93), an influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel antigen) were used in multicolor flow analysis. The HPV‐specific T‐cell frequencies were correlated with the HPV16 E7 and p16 status in tumor sections. In vitro stimulation (IVS) with autologous dendritic cells (DC) pulsed with HPV16 E7 epitopes was performed to demonstrate proliferation and antitumor activity of the HPV‐responsive T cells. Frequencies of CD8+ T cells specific for HPV16 E7 peptides were not significantly different in patients with SCCO relative to normal donors. However, patients with tumors expressing HPV16 E7 (60%) and p16 (50%) had an increased frequency (p < 0.05) of T cells specific for the E711–20 epitope compared to those with tumors negative for both markers. HPV16 E711–20 and HPV16 E786–93 specific T cells were expandable upon IVS with cognate peptide‐pulsed DC and were reactive against peptide‐pulsed targets or, in case of the E711–20 epitope‐specific T cells, against HPV16 E7 expressing CaSki cell line. Thus, in patients with HPV16+ SCCO, precursor T cells specific for E711–20 epitope are present (1/3,947) in the circulation, are responsive to stimulation with the cognate viral peptide and recognize in vitro HPV16 E7+ tumor cells. Further studies have to elucidate why those T cells are unable to eliminate the tumor in vivo and this might also allow for finding potential strategies that will increase the chances of developing a future HPV‐based vaccine in patients with SCCO. © 2005 Wiley‐Liss, Inc.
Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer
Authors: Wiedswang Gro , Borgen Elin , Schirmer Cecilie , Kåresen Rolf , Kvalheim Gunnar , Nesland Jahn M. , Naume Bjørn
Published: November 2005

Immunocytochemical (ICC) detection of disseminated tumor cells (DTC) in bone marrow (BM) in early breast cancer is an independent prognostic factor. The significance of circulating tumor cells (CTC) in peripheral blood (PB) needs further exploration and comparison to DTC detection. PB and BM were prospectively collected from 341 breast cancer patients median 40 months after operation. PB samples were analyzed for tumor cells by a negative immunomagnetic technique (10 × 106 cells/test). BM aspirates were analyzed by standard ICC (2 × 106 cells/test). CTC were present in 10% of the patients and DTC in 14%. Thirty‐seven relapses and 14 breast cancer deaths have occurred at median 66 months after diagnosis. Both CTC‐status and DTC‐status were significantly associated with disease free survival (DFS) (event rate: CTC‐positive 26.5% vs. CTC‐negative 9.1%; DTC‐positive 29.2% vs. DTC‐negative 7.8%) (p < 0.001/p < 0.001, log rank) and breast cancer specific survival (event rate: CTC‐positive 17.6% vs. CTC‐negative 2.6%; DTC‐positive 12.5% vs. DTC‐negative 2.7%) (p < 0.001/p < 0.001). The presence of both CTC and DTC (n = 8) resulted in an especially poor prognosis (p < 0.001). In node negative patients, DTC‐status, but not CTC‐status, predicted differences in DFS (p = 0.006 vs. p = 0.503). Excluding 23 patients with breast cancer‐related events prior to the sample collections, CTC detection was not significantly associated with DFS/distant‐DFS (p = 0.158/0.193), in contrast to DTC detection (p < 0.001/<0.001). Presence of CTC and absence of DTC did not affect DFS (p = 0.516). Applied to early stage disease, CTC analysis of increased volumes of PB appears less sensitive and prognostic than standard DTC analysis. Currently, this does not support an exchange of BM with PB for analysis of occult tumor cells. © 2005 Wiley‐Liss, Inc.
Tubal sterilization in relation to breast cancer risk
Authors: Eliassen A. Heather , Colditz Graham A. , Rosner Bernard , Hankinson Susan E.
Published: November 2005

Tubal sterilization methods may damage surrounding tissue, potentially disrupting the ovarian blood supply and hormonal functioning, and may decrease breast cancer risk. We examined this hypothesis, within the Nurses' Health Study, among 77,511 women, aged 30–55 years and free of cancer at the start of follow‐up in 1976. We documented 4,176 cases of invasive breast cancer from 1976 to 2000. Cox proportional hazards models, adjusting for multiple breast cancer risk factors, provided rate ratios (RR) and 95% confidence intervals (CI). Overall, tubal sterilization was not associated with breast cancer risk (RR = 0.95, 95% CI = 0.88–1.03). However, tubal sterilizations performed from 1970 to 1974 were inversely associated with risk (RR = 0.84, 95% CI = 0.73–0.97), while procedures performed in other years were not associated with risk. Among women with procedures performed in 1970–1974, those who were ≥35 years old at the time of sterilization were at the lowest risk (RR = 0.81, 95% CI = 0.66–0.98), while younger women had a suggested decreased risk (RR = 0.87, 95% CI = 0.72–1.06). Overall, tubal sterilization was not associated with breast cancer risk. However, a modest inverse association was observed at a time when the potentially destructive unipolar electrocautery method was commonly used, providing some support for an association between lower lifetime exposure to hormones and a decreased risk of breast cancer. © 2005 Wiley‐Liss, Inc.
Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor‐specific translocationt(X;6)(q13‐14;q22)
Authors: Storlazzi Clelia Tiziana , Wozniak Agnieszka , Panagopoulos Ioannis , Sciot Raf , Mandahl Nils , Mertens Fredrik , Debiec‐Rychter Maria
Published: November 2005

Subungual exostosis is a benign bone‐ and cartilage‐producing tumor occurring in the hands and feet of children and young adults. The recent identification of a recurrent chromosomal translocation t(X;6)(q24‐q26;q15‐21) in short‐term‐cultured tumor cells strongly suggests that subungual exostosis is a neoplastic lesion caused by rearrangement of genes in the two breakpoints. To identify the genes that are critical for neoplastic transformation, we have studied five subungual exostoses by interphase or metaphase FISH. The results of these analyses demonstrated a clustering of the breakpoints to the regions harboring the collagen genes COL12A1 and COL4A5 in chromosome bands 6q13‐14 and Xq22, respectively. Furthermore, in all but one case, these two genes were shown to colocalize on the derivative chromosomes X and 6, strongly suggesting that at least one of them is consistently involved in the formation of a chimeric fusion gene or in the exchange of regulatory sequences. Because collagen molecules are important for tissue remodeling during physiologic growth and differentiation, both COL12A1 and COL4A5 constitute good candidate target genes in the pathogenesis of subungual exostosis. Further investigations on the transcript level are required to elucidate the functional outcome of the t(X;6) translocation in subungual exostoses. © 2005 Wiley‐Liss, Inc.
Total and specific fluid consumption as determinants of bladder cancer risk
Authors: Villanueva Cristina M. , Cantor Kenneth P. , King Will D. , Jaakkola Jouni J.K. , Cordier Sylvaine , Lynch Charles F. , Porru Stefano , Kogevinas Manolis
Published: November 2005

We pooled the data from 6 case‐control studies of bladder cancer with detailed information on fluid intake and water pollutants, particularly trihalomethanes (THM), and evaluated the bladder cancer risk associated with total and specific fluid consumption. The analysis included 2,729 cases and 5,150 controls. Odds ratios (OR) and 95% confidence intervals (CI) for fluid consumption were adjusted for age, gender, study, smoking status, occupation and education. Total fluid intake was associated with an increased risk of bladder cancer in men. The adjusted OR for 1 l/day increase in intake was 1.08, (95% CI 1.03–1.14, p‐value for linear trend <0.001), while no trend was observed in women (OR = 1.04, 0.94–1.15; p‐value = 0.7). OR was 1.33 (1.12–1.58) for men in the highest category of intake (>3.5 l/day) as compared to those in the lowest (≤2 l/day). An increased risk was associated with intake of tap water. OR for >2 l/day vs. ≤0.5 l/day was 1.46 (1.20–1.78), with a higher risk among men (OR = 1.50, 1.21–1.88). No increased risk was observed for the same intake groups of nontap water in men (OR = 0.97, 0.77–1.22) or in women (OR = 0.85, 0.50–1.42). Increased bladder cancer risks were observed for an intake of >5 cups of coffee daily vs. <5 and for THM exposure, but neither exposure confounded or modified the OR for tap water intake. The association of bladder cancer with tap water consumption, but not with nontap water fluids, suggests that carcinogenic chemicals in tap water may explain the increased risk. © 2005 Wiley‐Liss, Inc.
A prospective study of breast size and premenopausal breast cancer incidence
Authors: Kusano Aaron S. , Trichopoulos Dimitrios , Terry Kathryn L. , Chen Wendy Y. , Willett Walter C. , Michels Karin B.
Published: November 2005

Studies of the association between breast size, as a proxy for mammary gland mass, and breast cancer risk have given equivocal results. Most have been case‐control studies with limited statistical power. We conducted a prospective analysis of the relation between breast size as measured by self‐reported bra cup size and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal women aged 29–47 in 1993. Subsequent incident cases of invasive breast cancer were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model adjusting for potential confounders and risk factors for breast cancer. During 622,732 person‐years of follow‐up, 803 premenopausal women were newly diagnosed with invasive breast cancer. For women with a BMI below 25 kg/m2, those with a bra cup size of “D or larger” had a significantly higher incidence of breast cancer than women who reported “A or smaller” (covariate adjusted HR = 1.80; 95% CI 1.13–2.88; ptrend = 0.01). There was no significant association among women with a BMI of 25 kg/m2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m2 gave similar results. Larger bra cup size at a young age is associated with a higher incidence of premenopausal breast cancer, though this association is limited to leaner women. © 2005 Wiley‐Liss, Inc.
Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells
Authors: Wang Zhiwei , Zhang Yuxiang , Banerjee Sanjeev , Li Yiwei , Sarkar Fazlul H.
Published: November 2005

This article has been retracted at the request of: Editor‐in‐Chief and Author

‘Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells’, by Wang, Z., Zhang, Y., Banerjee, S., Li, Y. and Sarkar, F. H.

The above article and associated erratum, published online on 11 November 2005 and 6 February 2014, respectively, in Wiley Online Library (wileyonlinelibrary.com), have been retracted by agreement between the authors, the journal Editor‐in‐Chief, Professor Peter Lichter, and Wiley Periodicals, Inc. In addition to what was corrected in the erratum, a university investigation involving the first and the corresponding author determined that several figures in this paper were re‐used, mislabeled, manipulated, or duplicated while processing/compiling the final figures assembled from the original data sources. Therefore, the authors are retracting the paper in its entirety although they maintain that these issues did not affect the major conclusions. They apologize for any inconvenience this may have caused.

Reference

Wang, Z., Zhang, Y., Banerjee, S., Li, Y. and Sarkar, F. H. (2006), Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells. Int. J. Cancer, 118:1930–1936. doi:10.1002/ijc.21589; corrected by Erratum: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells. Int. J. Cancer, 134: E3. doi: 10.1002/ijc.28709.
Inactivation of Id‐1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway
Authors: Zhang Xiaomeng , Ling Ming‐Tat , Wang Xianghong , Wong Y.C.
Published: November 2005

Resistance to anticancer drugs is the major problem in the treatment of many advanced cancers, including androgen‐independent prostate cancer. Recently, increased expression of Id‐1, a basic helix‐loop‐helix protein, is reported in several types of advanced cancer. It is suggested that high expression of Id‐1 may provide an advantage for cancer cell survival and inactivation of Id‐1 may be able to increase cancer cells' susceptibility to apoptosis. To test this hypothesis, in this study, by using RNA interfering technology, we inactivated the Id‐1 gene in 2 androgen‐independent prostate cancer cell lines, DU145 and PC3, and investigated whether downregulation of Id‐1 could lead to increased sensitivity to a commonly used anticancer drug, taxol. By using colony forming assay and MTT assay, we found that inactivation of Id‐1 resulted in both decreased colony forming ability and cell viability in prostate cancer cells, after taxol treatment. In addition, the si‐Id‐1‐induced sensitization to taxol was associated with activation of apoptosis pathway, which is demonstrated by increased apoptotic index, DNA laddering, sub‐G1 phase of the cell cycle, as well as cleaved‐PARP and Caspase 3. Furthermore, c‐Jun N‐terminal kinase (JNK), one of the common pathways responsible for taxol‐induced apoptosis, was also activated in the si‐Id‐1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the si‐Id‐1‐induced sensitivity to taxol. These results indicate that increased Id‐1 expression in prostate cancer cells may play a protective role against apoptosis, and downregulation of Id‐1 may be a potential target to increase sensitivity of taxol‐induced apoptosis in prostate cancer cells. © 2005 Wiley‐Liss, Inc.
The leukocyte protein L‐plastin induces proliferation, invasion and loss of E‐cadherin expression in colon cancer cells
Authors: Foran Eilis , McWilliam Peter , Kelleher Dermot , Croke David T. , Long Aideen
Published: November 2005

L‐plastin, a gene that codes for an actin‐bundling protein, is upregulated in the metastatic colon cancer cell line SW620, when compared to its premetastatic counterpart SW480. The aim of our study was to characterise the effect of L‐plastin overexpression on SW480 cells in the context of the acquisition of a metastatic phenotype. SW480 cell lines overexpressing L‐plastin were established (SW480‐LPL). Analysis of these cell lines revealed significantly higher rates of proliferation and invasion than the control cell line (SW480‐Ctrl). In addition, the expression of E‐cadherin was lost from SW480‐LPL cells. Treatment of SW480‐LPL cells with cytochalasin B, an inhibitor of endocytosis, attenuated the loss of E‐cadherin expression in these cells. The association of L‐plastin overexpression with an increased rate of proliferation and invasion, and loss of E‐cadherin expression in the SW480 colon cancer cell line indicates that L‐plastin plays an important mechanistic role in colorectal cancer metastasis (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html). © 2005 Wiley‐Liss, Inc.
High frequency of latent membrane protein‐1 30‐bp deletion variant with specific single mutations in Epstein‐Barr virus‐associated nasopharyngeal carcinoma in Moroccan patients
Authors: Dardari Rkia , Khyatti Meriem , Cordeiro Paulo , Odda Mohieddine , ElGueddari Brahim , Hassar Mohammad , Menezes José
Published: November 2005

Latent membrane protein 1 (LMP‐1) is an Epstein‐Barr virus‐encoded oncoprotein expressed in ∼50–70% of nasopharyngeal carcinoma (NPC). Previous studies have shown that NPC‐derived LMP‐1 variants carrying 30 bp deletion and specific mutations in the 3′C‐terminal region confer high oncogenic potential and a weak immunogenicity. Although numerous polymorphism studies of LMP‐1 have been carried out so far in the Asian population with NPC, very little is known in this regard on NPC patients from Northern Africa where there is a significantly high occurrence of this tumor. In our study, we examined the frequency of different LMP‐1 sequence variants derived from Moroccan NPC patients. As compared to healthy donors, NPC patients showed a high prevalence of the 30bp deletion variant of LMP‐1 (i.e. 84% vs. 36%; p < 0.0005). Moreover, the del‐LMP‐1 variant derived from NPC tumors shared identical amino acid substitutions at positions 322, 334, 338, 352 and 366 with the Mediterranean (Med) variant, whereas those derived from peripheral blood mononuclear cells (PBMC) had similar mutation pattern as China1 variant. Additional mutations within the 342–352 regions (identified in LMP‐1 variants without deletion derived from NPC tumors) were not found in healthy donors' PBMC. Our results support the assumption that the distribution of LMP‐1 variants in NPC tumors co‐segregate with geographic regions. Indeed, Med variant is found more frequently in tumors from NPC Moroccan patients, whereas China1 variant is more prevalent in tumors from NPC patients in endemic regions for NPC. © 2005 Wiley‐Liss, Inc.
Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression
Authors: Yang Xiaoqin , Lu Peirong , Fujii Chifumi , Nakamoto Yasunari , Gao Ji‐Liang , Kaneko Shuichi , Murphy Philip M. , Mukaida Naofumi
Published: November 2005

We previously observed that a chemokine, macrophage inflammatory protein‐1 α/CCL3, and its receptor, CCR1, were aberrantly expressed in human hepatocellular carcinoma (HCC) tissues. Here, we show that CCL3 and CCR1 are also expressed in 2 different models of this cancer; N‐nitrosodiethylamine (DEN)‐induced HCC and HCC induced by hepatitis B virus surface (HBs) antigen‐primed splenocyte transfer to myelo‐ablated syngeneic HBs antigen transgenic mice. At 10 months after DEN treatment, foci number and sizes were remarkably reduced in CCR1‐ and CCL3‐deficient mice, compared with those of wild‐type (WT) mice, although tumor incidence were marginally, but significantly, higher in CCR1‐ and CCL3‐deficient mice than in WT mice. Of note is that tumor angiogenesis was also markedly diminished in CCL3‐ and CCR1‐deficient mice, with a concomitant reduction in the number of intratumoral Kupffer cells, a rich source of growth factors and matrix metalloproteinases (MMPs). Among growth factors and MMPs that we examined, only MMP9 and MMP13 gene expression was augmented progressively in liver of WT mice after DEN treatment. Moreover, MMP9, but not MMP13, gene expression was attenuated in CCR1‐ and CCL3‐deficient mice, compared with that of WT mice. Furthermore, MMP9 was expressed mainly by mononuclear cells but not hepatoma cells, and MMP9‐expressing cell numbers were decreased in CCR1‐ or CCL3‐deficient mice, compared with WT mice. These observations suggest the contribution of the CCR1‐CCL3 axis to HCC progression. © 2005 Wiley‐Liss, Inc.
Interleukin‐10 expression significantly correlates with minor CD8+ T‐cell infiltration and high microvessel density in patients with gastric cancer
Authors: Sakamoto Teruhisa , Saito Hiroaki , Tatebe Shigeru , Tsujitani Shunichi , Ozaki Mitsuhiko , Ito Hisao , Ikeguchi Masahide
Published: November 2005

We aimed to investigate the relationships between interleukin‐10 (IL‐10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL‐10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL‐10 expression was determined in gastric cancer patients by reverse transcription‐polymerase chain reaction (RT‐PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL‐10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n = 11) by RT‐PCR. Immunohistochemical staining demonstrated that IL‐10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL‐10 expression and MV density. IL‐10 expression inversely correlated with CD8+ T‐lymphocyte infiltration. The prognoses of patients whose tumors expressed IL‐10 were significantly worse than those of patients whose tumors did not express IL‐10. Multivariate analysis indicated IL‐10 expression was an independent prognostic factor. IL‐10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer. © 2005 Wiley‐Liss, Inc.
Oxidation and inactivation of low molecular weight protein tyrosine phosphatase by the anticancer drug Aplidin
Authors: Taddei Maria Letizia , Chiarugi Paola , Cuevas Carmen , Ramponi Giampietro , Raugei Giovanni
Published: November 2005

The marine plitidepsin Aplidin derived from the Mediterranean tunicate Aplidium albicans is a strong apoptotic inducer with promising antitumor activity. However, little is known about the mechanism of action of the molecule. In this article, we report that Aplidin is cytotoxic for NIH3T3 cells and that its action is exerted through the production of reactive oxygen species (ROS). Rotenone, but not other selective inhibitors of ROS production, blocks the induction of ROS, suggesting the involvement of the mitochondrial respiratory chain in Aplidin action. The intracellular rise of redox potential caused by Aplidin inactivates several molecular targets. Among these targets, we focused our attention on protein tyrosine phosphatases (PTPs). In agreement with the well‐characterized effect of ROS‐mediated PTP oxidation, due to the presence of a cysteine residue in their catalytic site, we found that Aplidin induces a strong decrease in PTP activity. In particular, since the expression of low molecular weight‐PTP (LMW‐PTP) is strongly associated with tumor onset and progression, we investigated the effect of Aplidin on this enzyme. Our data show that LMW‐PTP is oxidized and inactivated during Aplidin treatment, thus causing a hyper‐phosphorylation of its substrate β‐catenin. These findings demonstrate that, at least in part, the antitumoral activity of Aplidin could be due to the direct inhibition of LMW‐PTP and its related oncogenic potential. © 2005 Wiley‐Liss, Inc.
Osteoprotegerin (OPG)—a potential new role in the regulation of endothelialcell phenotype and tumour angiogenesis?
Authors: Cross Simon S. , Yang Zhiyong , Brown Nicola J. , Balasubramanian Sabapathy P. , Evans Clair A. , Woodward Julia K. , Neville‐Webbe Helen L. , Lippitt Jenny M. , Reed Malcolm W.R. , Coleman Robert E. , Holen Ingunn
Published: November 2005

The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor‐ (TNF) related apoptosis‐inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord‐like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n = 512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n = 178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours. © 2005 Wiley‐Liss, Inc.
Antioxidant inhibition of poly(carbonate urethane) in vivo biodegradation
Authors: Christenson Elizabeth M. , Anderson James M. , Hiltner Anne
Published: November 2005

This study compared the effect of an antioxidant on the in vivo biodegradation of a poly(carbonate urethane) (PCU) and a poly(ether urethane) (PEU). Unstrained PEU and PCU films with and without Santowhite® were implanted subcutaneously into 3‐month‐old Sprague‐Dawley rats for 3, 6, and 12 months. Characterization of unstabilized PEU and PCU with ATR‐FTIR and SEM showed soft‐segment and hard‐segment degradation consistent with previous studies. In particular, evidence of chain scission and crosslinking of the surface was present in the ATR‐FTIR spectra of explanted specimens. Addition of 2.2 wt % antioxidant inhibited the in vivo degradation of both PCU and PEU. Although the antioxidant probably improved polyurethane biostability by decreasing the susceptibility of the polymer to degradation, modulation of the cellular response to prevent the release of degradative agents was also possible. To differentiate the effects, the foreign‐body response was investigated with the use of a standard cage implant protocol. Polyurethane films were implanted in wire mesh cages subcutaneously in rats for 4, 7, and 21 days. There were no statistical differences among materials in the inflammatory exudate cell counts, adherent cell densities, or percent fusion of macrophages into foreign‐body giant cells (FBGCs). Therefore, it was concluded that the antioxidant inhibited degradation by capturing oxygen radicals that would otherwise cause polyurethane chain scission and crosslinking. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effect of bioactive ceramic dissolution on the mechanism of bone mineralization and guided tissue growth in vitro
Authors: El‐Ghannam A. , Ning C. Q.
Published: November 2005

A major objective of this research work was to evaluate the effect of bone cells on the dissolution‐precipitation reaction in vitro. Rat bone marrow stem cells were seeded on silica‐calcium phosphate nano composite (SCPC) with different chemical compositions and crystalline structures. Measurements of the Ca, P, Si, and Na concentrations in the tissue culture media using inductively coupled plasma indicated that bone marrow stem cells attached to the surface of SCPC did not affect the dissolution behavior of the material. However, bone marrow stem cells interfered with the back precipitation reaction and inhibited the formation of a calcium phosphate (Ca‐P) layer on the material surface. Scanning electron microsope‐energy‐dispersive X‐ray analyses showed that, in the absence of cells, a Ca‐P layer formed on the material surface because of the dissolution‐precipitation reaction. Bone cells attached to SCPC that contains high silica content absorbed significantly higher concentrations of medium Ca than cells attached to SCPC that contains low silica content. In conjunction with the absorption of high Ca concentration, attached bone marrow stem cells produced calcified nodules and mineralized extracellular matrix, indicating osteoblastic differentiation. Results of the study strongly suggest that the mechanism of bone mineralization at the interface with bioactive ceramics is mainly cell mediated and is enhanced by the absorption of critical concentrations of dissolved Ca and P. The silicon‐rich phase also provided a guided cell adhesion and tissue growth in vitro. The enhanced bioactivity reactions and strong stimulatory effect on bone cell function are attributed to the modified crystalline structure of the SCPC material. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Enhancing surface free energy and hydrophilicity through chemical modification of microstructured titanium implant surfaces
Authors: Rupp F. , Scheideler L. , Olshanska N. , de Wild M. , Wieland M. , Geis‐Gerstorfer J.
Published: November 2005

Roughness‐induced hydrophobicity, well‐known from natural plant surfaces and intensively studied toward superhydrophobic surfaces, has currently been identified on microstructured titanium implant surfaces. Studies indicate that microstructuring by sandblasting and acid etching (SLA) enhances the osteogenic properties of titanium. The undesired initial hydrophobicity, however, presumably decelerates primary interactions with the aqueous biosystem. To improve the initial wettability and to retain SLA microstructure, a novel surface modification was tested. This modification differs from SLA by its preparation after acid etching, which was done under protective gas conditions following liquid instead of dry storage. We hypothesized that this modification should have increased wettability due to the prevention of contaminations that occurs during air contact. The main outcome of dynamic wettability measurements was that the novel modification shows increased surface free energy (SFE) and increased hydrophilicity with initial water contact angles of 0° compared to 139.9° for SLA. This hydrophilization was kept even after any drying. Reduced hydrocarbon contaminations were identified to play a possible role in altered surface thermodynamics. Such surfaces aim to retain the hydrophilicity and natural high surface energy of the Ti dioxide surface until surgical implants' insertion and are compared in this in vitro study with structural surface variants of titanium to compare roughness and chemically induced wettability. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006