bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study on the Effects of Molecular Structure on the Mode of Polymorphic Transition Inducing Preferential Enrichment
Authors: Horiguchi Masahiro , Yabunaka Shinsuke , Iwama Sekai , Shimano Eiji , Lepp Zsolt , Takahashi Hiroki , Tsue Hirohito , Tamura Rui
Published: May 2008

A series of (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpyrrolidinium p‐halobenzenesulfonates [(±)‐1a–c] were found to cause an unusual symmetry‐breaking enantiomeric resolution phenomenon called preferential enrichment, whereas the N‐methylpiperidinium analogues (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpiperidinium p‐halobenzenesulfonates [(±)‐2a–c] failed to show this phenomenon. By X‐ray crystallographic and ATR‐FTIR spectroscopic studies, (±)‐1a–c were found to undergo the desired solvent‐assisted solid‐to‐solid polymorphic transition of the first‐formed and metastable γ‐form into the stable δ‐form, which could induce preferential enrichment. In contrast, (±)‐2a–c were subject to the undesired solvent‐mediated polymorphic transition of the γ‐form into the α2‐form, and similarly, (±)‐1d and (±)‐2d bearing a p‐toluenesulfonate ion also showed the undesired solvent‐mediated polymorphic transition of the γ‐form into the β‐form; in these cases, preferential enrichment was not observed. Accordingly, the structure of the cyclic ammonium group as well as the basicity of the p‐substituted benzenesulfonate ion largely affected the mode of the polymorphic transition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Dynamic Kinetic Resolution of α‐Amino Acid Esters in the Presence of Aldehydes
Authors: Schichl Daniel A. , Enthaler Stephan , Holla Wolfgang , Riermeier Thomas , Kragl Udo , Beller Matthias
Published: May 2008

A convenient procedure for the racemization of α‐amino acid esters in the presence of catalytic amounts of salicylaldehydes is described. The combination of this racemization protocol with lipase‐catalyzed ester hydrolysis allows successful dynamic kinetic resolution of various α‐amino acid esters. The corresponding α‐amino acids are obtained in high yield and optical purity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Structural Characterization of Four Isomers of C70(n‐C3F7)8
Authors: Mutig Tatyana , Kemnitz Erhard , Troyanov Sergey I.
Published: May 2008

The first four isomers of C70(n‐C3F7)8 synthesized by the ampoule reaction of C70 with n‐C3F7I, isolated by HPLC, and characterized by X‐ray crystallography possess unprecedented addition patterns among C70X8 compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia
Authors: Gupta Manu , Raghavan Manoj , Gale Rosemary E. , Chelala Claude , Allen Christopher , Molloy Gael , Chaplin Tracy , Linch David C. , Cazier Jean‐Baptiste , Young Bryan D.
Published: May 2008

The acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15–55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate‐risk group as defined by cytogenetics. All cases with a high FLT3‐ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3‐ITD‐/FLT3‐TKD+ mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets. © 2008 Wiley‐Liss, Inc.
Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer
Authors: Veena Mysore S. , Lee Grant , Keppler Daniel , Mendonca Marc S. , Redpath J. Leslie , Stanbridge Eric J. , Wilczynski Sharon P. , Srivatsan Eri S.
Published: May 2008

We have previously localized a cervical cancer tumor suppressor gene to a 300 kb interval of 11q13. Analysis of candidate genes revealed loss of expression of cystatin E/M, a lysosomal cysteine protease inhibitor, in 6 cervical cancer cell lines and 9 of 11 primary cervical tumors. Examination of the three exons in four cervical cancer cell lines, 19 primary tumors, and 21 normal controls revealed homozygous deletion of exon 1 sequences in one tumor. Point mutations were observed in six other tumors. Two tumors contained mutations at the consensus binding sites for cathepsin L, a lysosomal protease overexpressed in cervical cancer. Introduction of these two point mutations using site directed mutagenesis resulted in reduced binding of mutated cystatin E/M to cathepsin L. Although mutations were not observed in any cell lines, four cell lines and 12 of 18 tumors contained promoter hypermethylation. Reexpression of cystatin E/M was observed after 5′aza 2‐deoxycytidiene and/or Trichostatin A treatment of cervical cancer cell lines, HeLa and SiHa, confirming promoter hypermethylation. Ectopic expression of cystatin E/M in these two cell lines resulted in growth suppression. There was also suppression of soft agar colony formation by HeLa cells expressing the cystatin E/M gene. Reexpression of cystatin E/M resulted in decreased intracellular and extracellular expression of cathepsin L. Overexpression of cathepsin L resulted in increased cell growth which was inhibited by the reintroduction of cystatin E/M. We conclude, therefore, that cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation. © 2008 Wiley‐Liss, Inc.
Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: Potential role in progression
Authors: Scotto Luigi , Narayan Gopeshwar , Nandula Subhadra V. , Arias‐Pulido Hugo , Subramaniyam Shivakumar , Schneider Achim , Kaufmann Andreas M. , Wright Jason D. , Pothuri Bhavana , Mansukhani Mahesh , Murty Vundavalli V.
Published: May 2008

Recurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of gain of the long arm of chromosome 20 (20q), one of the common chromosomal gains in CC, we evaluated CC at various stages of progression using single nucleotide polymorphism (SNP) array, gene expression profiling, and fluorescence in situ hybridization (FISH) analyses. This analysis revealed copy number increase (CNI) of 20q in >50% of invasive CC and identified two focal amplicons at 20q11.2 and 20q13.13 in a subset of tumors. We further demonstrate that the acquisition of 20q gain occurs at an early stage in CC development and the high‐grade squamous intraepithelial lesions (HSIL) that exhibit 20q CNI are associated (P = 0.05) with persistence or progression to invasive cancer. We identified a total of 26 overexpressed genes as consequence of 20q gain (N = 14), as targets of amplicon 1 (N = 9; two genes also commonly expressed with 20q gain) and amplicon 2 (N = 6; one gene also commonly expressed with 20q gain). These include a number of functionally important genes in cell cycle regulation (E2F1, TPX2, KIF3B, PIGT, and B4GALT5), nuclear function (CSEL1), viral replication (PSMA7 and LAMA5), methylation and chromatin remodeling (ASXL1, AHCY, and C20orf20), and transcription regulation (TCEA2). Our findings implicate a role for these genes in CC tumorigenesis, represent an important step toward the development of clinically significant biomarkers, and form a framework for testing as molecular therapeutic targets. © 2008 Wiley‐Liss, Inc.
Duplex architecture and late‐orogenic backthrusting in Foredeep Units of the Northern Apennines (Italy)
Authors: Feroni Andrea Cerrina , Levi Nicola , Ottria Giuseppe
Published: May 2008

The Northern Apennines of Italy is a fold and thrust belt that resulted from the NE‐ward progressive overthrusting of a Mesoalpine stacking (the ocean‐derived Ligurian Units) onto the detached sedimentary cover of the Adria plate continental margin (Foredeep Units). The Futa Pass area represents a key sector for the reconstruction of the deformation history of two Foredeep Units (Acquerino and Carigiola Units). The tectonic evolution of this sector is characterized by the superposition of three main deformation stages, with a constant NNE–SSW compression direction. The oldest structure is represented by the NNE‐verging Acquerino Unit duplex structure, the roof thrust of which is represented by the Ligurian stacking basal thrust. The interpretation of this structure as a large‐scale duplex is supported by the presence in the outer sectors of the Northern Apennines belt of Ligurian Units directly overthrust on younger Foredeep Units. In the second deformation stage the NNE‐verging Tavaiano Thrust developed. This regionally significant tectonic surface juxtaposes the Acquerino Unit (already developed as a duplex) and the overlying Ligurian Units, onto the Carigiola Unit. During this stage the fault pattern of the Carigiola Unit was also developed, characterized by two conjugate fault systems, coherent with a NNE–SSW maximum compression direction. During the last deformation stage, a backthrusting with a top‐to‐the SSW sense of movement (the Marcoiano Backthrust) brings the Carigiola Unit and its tectonic cover over the Acquerino and Ligurian Units, with the development of a large footwall syncline. The deformation history presented here differs from previous studies, and so provides a contribution to the debate on Northern Apennines tectonic evolution. Copyright © 2008 John Wiley & Sons, Ltd.
Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice
Authors: Ma Kun L. , Ruan Xiong Z. , Powis Stephen H. , Chen Yaxi , Moorhead John F. , Varghese Zac
Published: May 2008

The prevailing theory in non-alcoholic fatty liver disease (NAFLD) is the “two-hit” hypothesis. The first hit mainly consists of lipid accumulation, and the second is subsequent systemic inflammation. The current study was undertaken to investigate whether inflammatory stress exacerbates lipid accumulation in liver and its underlying mechanisms. We used interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) stimulation in human hepatoblastoma cell line (HepG2) cells and primary hepatocytes

in vitro,

and casein injection in apolipoprotein E knockout mice

in vivo

to induce inflammatory stress. The effects of inflammatory stress on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expressions of molecules involved in cholesterol trafficking were examined by real-time polymerase chain reaction (PCR) and western blot. Cytokine production in the plasma of apolipoprotein E knockout mice was measured by enzyme-linked immunosorbent assay. Our results showed that inflammatory stress increased cholesterol accumulation in hepatic cells and in the livers of apolipoprotein E knockout mice. Further analysis showed that inflammatory stress increased the expression of low-density lipoprotein (LDL) receptor (LDLr), sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2. Confocal microscopy showed that IL-1β increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum (ER) to Golgi in HepG2 cells, thereby activating LDLr gene transcription. IL-1β, TNF-α, and systemic inflammation induced by casein injection also inhibited expression of adenosine triphosphate–binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-α (PPAR-α), and liver X receptor-α (LXRα). This inhibitory effect may cause cholesterol efflux reduction.

Conclusion

: Inflammatory stress up-regulates LDLr-mediated cholesterol influx and down-regulates ABCA1-mediated cholesterol efflux

in vivo and in vitro

. This may exacerbate the progression of NAFLD by disrupting cholesterol trafficking control, especially during the second hit phase of liver damage. (Hepatology 2008.)
“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction
Authors: Strnad Pavel , Tao Guo-Zhong , So Phillip , Lau Kenneth , Schilling Jim , Wei Yuquan , Liao Jian , Omary Bishr M.
Published: May 2008

The cytoplasmic hepatocyte inclusions, Mallory-Denk bodies (MDBs), are characteristic of several liver disorders, including alcoholic and nonalcoholic steatohepatitis. In mice, MDBs can be induced by long-term feeding with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 3 to 4 months or rapidly reformed in DDC-induced then recovered mice by DDC refeeding or exposure to a wide range of toxins for only 5 to 7 days. The molecular basis for such a rapid reinduction of MDBs is unknown. We hypothesized that protein changes retained after DDC priming contribute to the rapid MDB reappearance and associate with MDB formation in general terms. Two-dimensional differential-in-gel-electrophoresis coupled with mass spectrometry were used to characterize protein changes in livers from the various treatment groups. The alterations were assessed by real-time reverse-transcription polymerase chain reaction and confirmed by immunoblotting. DDC treatment led to pronounced charged isoform changes in several chaperone families, including Hsp25, 60, 70, GRP58, GRP75, and GRP78, which lasted at least for 1 month after discontinuation of DDC feeding, whereas changes in other proteins normalized during recovery. DDC feeding also resulted in altered expression of Hsp72, GRP75, and Hsp25 and in functional impairment of Hsp60 and Hsp70 as determined using a protein complex formation and release assay. The priming toward rapid MDB reinduction lasts for at least 3 months after DDC discontinuation, but becomes weaker after prolonged recovery. MDB reinduction parallels the rapid increase in p62 and Hsp25 levels as well as keratin 8 cross-linking that is normally associated with MDB formation.

Conclusion:

Persistent posttranslational modifications in chaperone proteins, coupled with protein cross-linking and altered chaperone expression and function likely contribute to the “toxic memory” of DDC-primed mice. We hypothesize that similar changes are important contributors to inclusion body formation in several diseases. (Hepatology 2008.)
The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor
Authors: Frankenberg Tamara , Miloh Tamir , Chen Frank Y. , Ananthanarayanan Meena , Sun An-Qiang , Balasubramaniyan Natarajan , Arias Irwin , Setchell Kenneth D. R. , Suchy Frederick J. , Shneider Benjamin L.
Published: May 2008

Prior loss-of-function analyses revealed that

ATPase class I type 8B member 1

[familial intrahepatic cholestasis 1 (FIC1)] posttranslationally activated the farnesoid X receptor (FXR). Mechanisms underlying this regulation were examined by gain-of-function studies in UPS cells, which lack endogenous FIC1 expression. FXR function was assayed in response to wild-type and mutated FIC1 expression constructs with a human bile salt export pump (BSEP) promoter and a variety of cellular localization techniques. FIC1 overexpression led to enhanced phosphorylation and nuclear localization of FXR that was associated with FXR-dependent activation of the BSEP promoter. The FIC1 effect was lost after mutation of the FXR response element in the BSEP promoter. Despite similar levels of FIC1 protein expression, Byler disease FIC1 mutants did not activate BSEP, whereas benign recurrent intrahepatic cholestasis mutants partially activated BSEP. The FIC1 effect was dependent on the presence of the FXR ligand, chenodeoxycholic acid. The effect of FIC1 on FXR phosphorylation and nuclear localization and its effects on BSEP promoter activity could be blocked with protein kinase C zeta (PKC ζ) inhibitors (pseudosubstrate or small interfering RNA silencing). Recombinant PKC ζ directly phosphorylated immunoprecipitated FXR. The mutation of threonine 442 of FXR to alanine yielded a dominant negative protein, whereas the phosphomimetic conversion to glutamate resulted in FXR with enhanced activity and nuclear localization. Inhibition of PKC ζ in Caco-2 cells resulted in activation of the human apical sodium-dependent bile acid transporter promoter.

Conclusion:

These results demonstrate that FIC1 signals to FXR via PKC ζ. FIC1-related liver disease is likely related to downstream effects of FXR on bile acid homeostasis. Benign recurrent intrahepatic cholestasis emanates from a partially functional FIC1 protein. Phosphorylation of FXR is an important mechanism for regulating its activity. (Hepatology 2008;48:1896-1905.)
Influence of evaporation from the forest floor on evapotranspiration from the dry canopy
Authors: Daikoku Kenichi , Hattori Shigeaki , Deguchi Aiko , Aoki Yu , Miyashita Mari , Matsumoto Kazuho , Akiyama Junichi , Iida Shinichi , Toba Tae , Fujita Yuji , Ohta Takeshi
Published: May 2008

Evaporation from the forest floor (Ef) of a secondary broad‐leaved forest was monitored for 1 year at 30 min intervals using a closed chamber system. The diurnal and seasonal variation of Ef and forest structure were analysed for days undisturbed by rainfall. The diurnal change in Ef reached a maximum at about 14:00 and gradually decreased towards midnight along with the vapour pressure deficit (D). Although Ef comprised about 20% of evapotranspiration from the dry canopy (Et), it had only a small influence on diurnal evaporation efficiency (β) characteristics above the canopy because its diurnal range was much smaller than that of Et. Although leaf emergence and leaf fall clearly affected available energy (Ae) beneath the canopy, the influence was not clear with Ef. In contrast, seasonal variation in Ef was strongly correlated with D and Ae above the canopy, and the determination coefficient (R2) changed with the Bowen ratio (B). At night, Et was almost equal to Ef when the friction velocity (u*) ranged between 0·2 and 0·4 m s−1. The ratio of Ef to Et was exponentially correlated with leaf area index (LAI) when the soil was not dry. The ratio of Ef to Et was mainly influenced by LAI and soil moisture, but the existence of understory vegetation did not have a strong influence. Copyright © 2008 John Wiley & Sons, Ltd.
Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
Authors: Shabo Ivan , Stål Olle , Olsson Hans , Doré Siv , Svanvik Joar
Published: May 2008

Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour‐associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF‐β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM‐stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time. © 2008 Wiley‐Liss, Inc.
High preoperative plasma TIMP‐1 is prognostic for early relapse in primary breast carcinoma
Authors: Kuvaja Paula , Talvensaari‐Mattila Anne , Turpeenniemi‐Hujanen Taina
Published: May 2008

TIMP‐1 is a natural inhibitor of extracellular matrix degrading enzymes called matrix metalloproteinases. In addition to its capacity to inhibit matrix degradation, TIMP‐1 has been shown to promote cell growth and inhibit apoptosis. The expression of TIMP‐1 in tumor tissue, as well as in circulating blood, has therefore been shown to associate with worsened survival in several malignancies. In our study, a prospective series of 213 patients with primary breast carcinoma was assessed. Circulating pre‐ and postoperative TIMP‐1 levels were assayed using enzyme‐linked immunosorbent assay analysis. It was shown that high preoperative plasma TIMP‐1 was a powerful predictor of systemic early relapse in breast carcinoma, with HR 8.1 (95% CI 1.8–37.6) (p = 0.007) as a log‐transformed continuous variable in Cox regression univariate analysis. It was shown to be independent of, and superior to, nodal status as a prognostic variable in multivariate analysis, and not associated with any known prognostic clinicopathological parameters. Kaplan‐Meier analysis showed that the patients belonging to the highest quartile of circulating TIMP‐1 levels had a worsened recurrence‐free survival of 79% compared to 94% RFS among patients in the lower quartiles (p = 0.016). The postoperative levels of circulating plasma TIMP‐1 were not found to be prognostic for relapse. In conclusion, preoperative plasma TIMP‐1 was found to be a powerful prognostic factor for early systemic relapse in primary breast carcinoma. © 2008 Wiley‐Liss, Inc.
Blood transfusion, anesthesia, surgery and risk of non‐Hodgkin lymphoma in a population‐based case–control study
Authors: Cerhan James R. , Engels Eric A. , Cozen Wendy , Davis Scott , Severson Richard K. , Morton Lindsay M. , Gridley Gloria , Hartge Patricia , Linet Martha
Published: May 2008

The incidence of NHL has increased dramatically since at least the 1950s, and during this timeframe there has been a major increase in the use of blood transfusions, invasive surgical procedures and anesthesia, all of which can impact immune function. We evaluated these factors with NHL risk in a population‐based study of 759 cases and 589 frequency‐matched controls. Risk factor data were collected during in‐person interviews. Unconditional logistic regression was used to estimate ORs and 95% CIs, adjusted for the matching factors. History of transfusion was associated with a 26% higher risk of NHL (95% CI 0.91–1.73), and the elevated risk was specific to transfusions first given 5–29 years before the reference date (OR = 1.69; 95% CI 1.08–2.62) and transfusions given for a medical condition (OR = 2.09; 95% CI 1.03–4.26). The total number of surgeries and dental procedures (OR = 1.53 for 26+ surgeries compared to 0–6; 95% CI 1.02–2.29) and to a lesser extent the total number of exposures to general or local/regional anesthesia (OR = 1.35 for 24+ times compared to 0–6; 95% CI 0.91–2.02) were positively associated with risk of NHL. Inclusion of transfusion and surgery or transfusion and anesthesia in the same model did not attenuate these associations. All results were broadly consistent for both DLBCL and follicular subtypes. Blood transfusions were associated with NHL risk, but appear to be a marker for underlying medical conditions. Multiple surgical procedures and/or repeated administration of anesthesia have not been previously reported to be associated with risk of NHL and these exposures warrant further evaluation. Published 2008 Wiley‐Liss, Inc.
Prediction of the immunogenic potential of frameshift‐mutated antigens in microsatellite instable cancer
Authors: Speetjens Frank M. , Lauwen Marjolein M. , Franken Kees L. , Janssen‐van Rhijn Connie M. , van Duikeren Suzanne , Bres Sandra A. , van de Velde Cornelis J.H. , Melief Cornelis J.M. , Kuppen Peter J.K. , van der Burg Sjoerd H. , Morreau Hans , Offringa Rienk
Published: May 2008

Microsatellite instable (MSI) cancers express frameshift‐mutated antigens, the C‐terminal polypeptides of which are foreign to the immune system. Consequently, these antigens constitute a unique pool of tumor‐specific antigens that can be exploited for patient diagnosis and selective, immune‐mediated targeting of cancers. However, other than their sequence, very little is known about the characteristics of the majority of these proteins. We therefore developed a methodology for predicting their immunogenic behavior that is based on a gene‐expression system, in which each of the proteins was fused to a short C‐terminal polypeptide comprising two epitopes that can be readily detected by T‐cells and antibodies, respectively. In this manner, accumulation of the antigens and processing of peptides derived thereof into MHC can be monitored systematically. The antigens, which accumulate in the cells in which they are synthesized, are of primary interest for cancer immunotherapy, because peptide epitopes derived thereof can be presented by dendritic cells in addition to the tumor cells themselves. As a result, these antigens constitute the best targets for a coordinated immune response by both CD8+ and CD4+ T‐cells, which increases the likelihood that tumor‐induced immunity would be detectable against these antigens in cancer patients, as well as the potential value of these antigens as components of anticancer vaccines. Our data indicate that, of 15 frameshift‐mutated antigens examined in our study, 4 (TGFβR2‐1, MARCKS‐1, MARCKS‐2 and CDX2‐2) are of primary interest, and 4 additional antigens (TAF1B‐1, PCNXL2‐2, TCF7L2‐2 and Baxα+1) are of moderate interest for further tumor immunological research. © 2008 Wiley‐Liss, Inc.
Integrated gene copy number and expression microarray analysis of gastric cancer highlights potential target genes
Authors: Myllykangas Samuel , Junnila Siina , Kokkola Arto , Autio Reija , Scheinin Ilari , Kiviluoto Tuula , Karjalainen‐Lindsberg Marja‐Liisa , Hollmén Jaakko , Knuutila Sakari , Puolakkainen Pauli , Monni Outi
Published: May 2008

We performed an integrated array comparative genomic hybridization (aCGH) and expression microarray analysis of 8 normal gastric tissues and 38 primary tumors, including 25 intestinal and 13 diffuse gastric adenocarcinomas to identify genes whose expression is deregulated in association with copy number alteration. Our aim was also to identify molecular genetic alterations that are specific to particular clinicopathological characteristics of gastric cancer. Distinct molecular genetic profiles were identified for intestinal and diffuse gastric cancers and for tumors obtained from 2 different locations of the stomach. Interestingly, the ERBB2 amplification and gains at 20q13.12‐q13.33 almost exclusively discriminated intestinal cancers from the diffuse type. In addition, the 17q12‐q25 gain was characteristic to cancers located in corpus and the 20q13.12‐q13.13 gain was more common in the antrum. Statistical analysis was performed using integrated copy number and expression data to identify genes showing differential expression associated with a copy number alteration. Genes with the highest statistical significance included ERBB2, MUC1, GRB7, PPP1R1B and PPARBP with concomitant changes in copy number and expression. Immunohistochemical analysis of ERBB2 and MUC1 on a tissue microarray containing 78 independent gastric tissues showed statistically significant differences (p < 0.05 and <0.001) in immunopositivity in the intestinal (31 and 70%) and diffuse subtypes (14 and 41%), respectively. In conclusion, our results demonstrate that intestinal and diffuse type gastric cancers as well as cancers located in different sites of the stomach have distinct molecular profiles which may have clinical value. © 2008 Wiley‐Liss, Inc.
KIT overexpression induces proliferation in astrocytes in an imatinib‐responsive manner and associates with proliferation index in gliomas
Authors: Blom Tea , Fox Heli , Angers‐Loustau Alexandre , Peltonen Karita , Kerosuo Laura , Wartiovaara Kirmo , Linja Marika , Jänne Olli A. , Kovanen Panu , Haapasalo Hannu , Nupponen Nina N.
Published: May 2008

Activating gene mutations, gene amplifications and overexpressed proteins may be useful as targets for novel therapies. Alterations at chromosome locus 4q12 are associated with gliomas and the region harbors the receptor tyrosine kinase gene KIT, which is frequently amplified in gliomas, and also overexpressed in a subset of gliomas. KIT and its ligand stem cell factor are widely expressed in embryonic and adult mouse brain, and they play a role in many signal transduction pathways involved in cellular proliferation, differentiation and cancer cell metastasis. However, the function of KIT in gliomagenesis or disease progression remains unresolved as well as its role in neural and brain tumor development. In this study, we utilized lentivirus‐mediated gene transfer to deliver the KIT gene into mouse astrocytes. The growth properties of KIT overexpressing cells were analyzed using several in vitro functional assays. The effect of receptor tyrosine kinase inhibitor imatinib on astrocyte growth was also investigated. Our results indicate that overexpression of KIT in mouse astrocytes promotes cell proliferation, and the increased proliferation is partly inhibited by imatinib treatment. Furthermore, KIT overexpression induces phenotypic changes in the cells suggesting that KIT may play a role in astrocyte growth regulation. © 2008 Wiley‐Liss, Inc.
Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy
Authors: Flesch‐Janys Dieter , Slanger Tracy , Mutschelknauss Elke , Kropp Silke , Obi Nadia , Vettorazzi Eik , Braendle Wilhelm , Bastert Gunter , Hentschel Stefan , Berger Jürgen , Chang‐Claude Jenny
Published: May 2008

In a large population‐based case–control study in Germany, including 3,464 breast cancer cases aged 50–74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face‐to‐face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%‐confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55–1.94) and heterogeneous by histological type (p < 0.01), being more than 2‐fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04–1.06) for continuous combined estrogen–progestagen, 1.03 (95% CI, 1.02–1.04) for cyclical EP and 1.01 (95% CI, 1.00–1.03) for estrogen‐only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone‐ or levonorgestrel‐derived progestagens than for continuously administered progesterone‐derived progestagens (OR, 2.27, 95% CI, 1.98–2.62 vs. 1.47, 95% CI, 1.12–1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose. © 2008 Wiley‐Liss, Inc.
Noncovalent interactions in supramolecular complexes: A study on corannulene and the double concave buckycatcher
Authors: Wong Bryan M.
Published: May 2008

Stimulated by the recent observation of π–π interactions between C60 and corannulene subunits in a molecular tweezer arrangement (J Am Chem Soc 2007, 129, 3842), a density functional theory study was performed to analyze the electronic structure and properties of various noncovalent corannulene complexes. The theoretical approach is first applied to corannulene complexes with a series of benchmark molecules (CH4, NH3, and H2O) using several new‐generation density functionals. The performance of nine density functionals, illustrated by computing binding energies of the corannulene complexes, demonstrates that Zhao and Truhlar's MPWB1K and M05‐2X functionals provide energies similar to that obtained at the SCS‐MP2 level. In contrast, most of the other popular density functionals fail to describe this noncovalent interaction or yield purely repulsive interactions. Further investigations with the M05‐2X functional show that the binding energy of C60 with corannulene subunits in the relaxed molecular receptor clip geometry is −20.67 kcal/mol. The results of this calculation further support the experimental interpretation of pure π–π interactions between a convex fullerene and the concave surfaces of two corannulene subunits. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Fragment Molecular Orbital method‐based Molecular Dynamics (FMO‐MD) as a simulator for chemical reactions in explicit solvation
Authors: Komeiji Yuto , Ishikawa Takeshi , Mochizuki Yuji , Yamataka Hiroshi , Nakano Tatsuya
Published: May 2008

Fragment Molecular Orbital based‐Molecular Dynamics (FMO‐MD, Komeiji et al., Chem Phys Lett 2003, 372, 342) is an ab initio MD method suitable for large molecular systems. Here, FMO‐MD was implemented to conduct full quantum simulations of chemical reactions in explicit solvation. Several FMO‐MD simulations were performed for a sphere of water to find a suitable simulation protocol. It was found that annealing of the initial configuration by a classical MD brought the subsequent FMO‐MD trajectory to faster stabilization, and also that use of bond constraint in the FMO‐MD heating stage effectively reduced the computation time. Then, the blue moon ensemble method (Sprik and Ciccotti, J Chem Phys 1998, 109, 7737) was implemented and was tested by calculating free energy profiles of the Menschutkin reaction (H3N + CH3Cl → +H3NCH3 + Cl−) in the presence and absence of the solvent water via FMO‐MD. The obtained free energy profiles were consistent with the Hammond postulate in that stabilization of the product by the solvent, namely hydration of Cl−, shifted the transition state to the reactant‐side. Based on these FMO‐MD results, plans for further improvement of the method are discussed. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Kick: Constraining a stochastic search procedure with molecular fragments
Authors: Addicoat Matthew A. , Metha Gregory F.
Published: May 2008

An extension of the Kick program developed by Bera et al. (J Phys Chem A 2006, 110, 4287) is described in which chemically sensible molecular fragments are used in an automated stochastic search algorithm. This results in a vastly reduced region of the potential energy surface which can be explored very quickly. We present use of this modified algorithm to the search for low‐lying isomers, and we present candidates for the global energy minimum, for a range of chemical systems. We highlight the usefulness of this procedure for exploring reactions of molecules with transition metal clusters and to the microsolvation of a small dipeptide. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Response surface methodology applied for Orange II photocatalytic degradation in TiO2 aqueous suspensions
Authors: Betianu Camelia , Caliman Florentina A , Gavrilescu Maria , Cretescu Igor , Cojocaru Corneliu , Poulios Ioannis
Published: May 2008

BACKGROUND: Heterogeneous photocatalysis is influenced by a number of parameters involving synergistic effects; hence, an experimental strategy design that considers interactions between the main variables is needed. The response surface methodology was applied for the investigation of photodegradation of 20 mg L−1 Orange II in aqueous solutions and for optimization of color removal efficiency. Preliminary studies were performed to identify the parameters to be selected for optimization.

RESULTS: The input variables considered for experimental design were: solution initial pH, oxidizing agent (H2O2) initial concentration and UV‐A irradiation time. The multivariate experimental design allowed the development of a quadratic response surface model to be used for the prediction of color removal efficiency over the full range of the experimental region. Under the optimum conditions established in the region of experimentation (pH = 6.9, [H2O2]0 = 183 mg L−1 and t = 32 min), a 100% color removal efficiency was obtained in experiments.

CONCLUSIONS: It was found that the variables considered have important effects on color removal efficiency. The results demonstrate that the use of experimental design strategy is indispensable for successful investigation and adequate modeling of the process because the interdependence of the reaction parameters cannot be neglected. Copyright © 2008 Society of Chemical Industry
Studies in wet air oxidation of aqueous morpholine over Ru/TiO2 catalyst: an insight into the fate of the ‘N’ atom
Authors: Gunale Tukaram L. , Mahajani Vijaykumar V.
Published: May 2008

BACKGROUND: Wet air oxidation (WAO) is a very attractive process for the treatment of aqueous streams containing amino compounds. During WAO, it is important to ensure that the ‘N’ atom in various ‘N’ bearing organic compounds is converted into N2. Morpholine is selected as model pollutant for the present study. In order to reduce the severity of operating conditions and to maximize N2 formation, the suitability of a heterogeneous catalyst namely 5% (w/w) Ru/TiO2, was studied.

RESULTS: The studies were carried out at a morpholine concentration of 500 mg L−1. Among the various catalysts studied 5% (w/w) Ru/TiO2 was found to be an effective catalyst. The selectivity towards N2 varied between 47 and 56% in the temperature range 473–483 K at 0.66 kg m−3 catalyst loading and 0.69 MPa oxygen partial pressure. Below 473 K more NH4+ ions were formed and at higher temperatures (>483 K) more NO3− ions were generated. It was also observed that under the influence of diffusional resistance, selectivity towards N2 formation was enhanced considerably (80%) when compared with the kinetically controlled regime at 483 K. The experimental data can be well correlated by assuming dissociative adsorption of oxygen followed by surface reaction.

CONCLUSIONS: The heterogeneous catalyst 5% (w/w) Ru/TiO2 was found to be very effective in the complete (100%) degradation of morpholine. The highest selectivity for conversion of NH group in morpholine to N2 gas was obtained at 483 K. Under a partial mass transfer controlled regime, selectivity towards N2 formation was enhanced considerably relative to the kinetically controlled regime. Copyright © 2008 Society of Chemical Industry
Human and software error in ductus venosus Doppler waveform analysis
Authors: Szunyogh Norbert , Renate Becker Caroline , Visnovsky Jozef
Published: May 2008

Ductus venosus waveform analysis has become increasingly affected by technical errors; however, these errors could be avoided if more attention was paid during sampling and analysis. The most common misevaluations include incorrect tracing, under‐ or overestimation of the peak systolic velocity, overestimation of the end‐diastolic velocity, and, as a consequence, incorrect calculation of the pulsatility index facilitated either by human or software error. This article proposes practical suggestions to avoid technical errors in ductus venosus waveform analysis. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Lipoma of the right atrium
Authors: Gulmez Oyku , Pehlivanoglu Seckin , Turkoz Riza , Demiralay Ebru , Gumus Burcak
Published: May 2008

A 66‐year‐old asymptomatic woman was admitted to our hospital with the diagnosis of a right atrial mass detected on an outside transthoracic echocardiogram and confirmed on transesophageal echocardiography. Physical examination and basal electrocardiogram were normal. Transthoracic echocardiography revealed a 3.8 × 2.5 cm echogenic mass in the right atrium. A multislice CT examination demonstrated a right atrial mass with a fat density ranging from −80 to −110 HU. The patient had a successful surgical excision of the mass, and the diagnosis of lipoma was confirmed on histopathological examination. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Investigating exchange and multicomponent relaxation in fully‐balanced steady‐state free precession imaging
Authors: Deoni Sean C.L. , Rutt Brian K. , Jones Derek K.
Published: May 2008

Purpose

To investigate the effect of chemical exchange and multicomponent relaxation on the rapid T2 mapping method, DESPOT2 (driven equilibrium single pulse observation of T2) and the steady‐state free precession (SSFP) sequence upon which it is based. Although capable of rapid T2 determination, an assumption implicit of the method is single‐component relaxation. In many biological tissues (such as white and gray matter), it is well established that the T2 decay curve is more accurately described by the summation of more than one relaxation species.

Materials and Methods

The effects of exchange were first incorporated into the general SSFP magnetization expressions and its effect on the measured SSFP signal investigated using Bloch‐McConnell simulations. Corresponding imaging experiments were performed to support the presented theory.

Results

Simulations show the measured multicomponent SSFP signal may be expressed as a linear summation of signal from each species under usual imaging conditions where the repetition time is much less than T2. Imaging experiments performed using dairy cream demonstrate strong agreement with the presented theory. Finally, using a dairy cream model, we demonstrate quantification of multicomponent relaxation from multiangle SSFP data for the first time, showing good agreement with reference spin‐echo values.

Conclusion

SSFP and DESPOT2 may provide a new method for investigating multicomponent systems, such as human brain, and disease processes, such as multiple sclerosis. J. Magn. Reson. Imaging 2008;27:1421–1429. © 2008 Wiley‐Liss, Inc.
Characterization of spontaneous healing of chronic posterior cruciate ligament injury: Analysis of instability and magnetic resonance imaging
Authors: Jung Young‐Bok , Jung Ho‐Joong , Yang Jae Jun , Yang Dong‐Lyul , Lee Yong Seuk , Song In‐Sup , Lee Han Jun
Published: May 2008

Purpose

To explore the healing process of the injured posterior cruciate ligament (PCL) by evaluating instability measurements and magnetic resonance imaging (MRI) findings.

Materials and Methods

A retrospective cross‐sectional study of 46 cases of complete PCL tear who obtained MRI more than two months after injury.

Results

A total of 13 cases (28%) showed nearly normal PCL contour, 20 cases (44%) showed continuity but deformed PCL contour, and 13 cases (28%) showed discontinuity. The duration from injury to MRI was not directly correlated with continuity. However, the group that obtained MRI more than six months after injury showed more continuity than the group that obtained MRI within six months of the injury (P < 0.01). The group with nearly normal continuity showed better stability results in the KT‐1000 arthrometer and stress radiographs than the group with discontinuity (P < 0.05). The presence of other combined ligament injuries had a negative effect on regaining PCL continuity (P <0.05).

Conclusion

More than two‐thirds (72%) of chronic PCL injury cases showed ligamentous continuity on MRI, especially when the injury had occurred more than six months before. Stability may improve as continuity is regained. The presence of other combined ligament injuries appears to prohibit spontaneous PCL healing. J. Magn. Reson. Imaging 2008;27:1336–1340. © 2008 Wiley‐Liss, Inc.
Apparent diffusion coefficient in pancreatic cancer: Characterization and histopathological correlations
Authors: Muraoka Noriaki , Uematsu Hidemasa , Kimura Hirohiko , Imamura Yoshiaki , Fujiwara Yasuhiro , Murakami Makoto , Yamaguchi Akio , Itoh Harumi
Published: May 2008

Purpose

To clarify the components primarily responsible for diffusion abnormalities in pancreatic cancerous tissue.

Materials and Methods

Subjects comprised 10 patients with surgically confirmed pancreatic cancer. Diffusion‐weighted (DW) echo‐planar imaging (b value = 0, 500 s/mm2) was employed to calculate the apparent diffusion coefficient (ADC). ADC values of cancer and noncancerous tissue were calculated. Furthermore, ADC values of the cancer were compared with histopathological results.

Results

The mean (±standard deviation) ADC value was significantly lower for tumor (1.27 ± 0.52 × 10−3 mm2/s) than for noncancerous tissue (1.90 ± 0.41 × 10−3 mm2/s, P < 0.05). Histopathological examination showed similar proportions of fibrotic area, cellular component, necrosis, and mucin in each case. Regarding the density of fibrosis in cancer, three cases were classified in the loose fibrosis group and the remaining seven cases were classified in the dense fibrosis group. The mean ADC value was significantly higher in the loose fibrosis group (1.88 ± 0.39 × 10−3 mm2/s) than in the dense fibrosis group (1.01 ± 0.29 × 10−3 mm2/s, P < 0.05). In quantitative analysis, ADC correlated well with the proportion of collagenous fibers (r = −0.87, P < 0.05).

Conclusion

Collagenous fibers may be responsible for diffusion abnormalities in pancreatic cancer. J. Magn. Reson. Imaging 2008;27:1302–1308. © 2008 Wiley‐Liss, Inc.
Comparison of three physiologically‐based pharmacokinetic models for the prediction of contrast agent distribution measured by dynamic MR imaging
Authors: Barboriak Daniel P. , MacFall James R. , Viglianti Benjamin L. , Dewhirst DVM Mark W.
Published: May 2008

Purpose

To compare the performance of three physiologically‐based pharmacokinetic (PBPK) models for predicting gadolinium contrast agent concentration‐time curves (Gd‐CTCs) obtained in superior sagittal sinus (SSS), cerebral cortex, and psoas muscle.

Materials and Methods

Three published whole‐body PBPK models were modified to predict Gd‐CTCs in normal‐appearing tissue. The models differed in the number of organs modeled and total number of compartments, and were designated as the “well‐mixed,” “delay,” and “dispersion” models. The suitability of the three models to predict Gd‐CTC was studied using data from dynamic contrast‐enhanced MR perfusion imaging obtained at 1.5T from 10 patients with glioblastoma multiforme and at 3.0T from five patients with liver metastases.

Results

The dispersion model produced better fits than the delay model in the SSS (P < 0.0001) and cerebral cortex (P < 0.0001), and better fits than the well‐mixed model in psoas muscle (P < 0.005). No model produced better fits than the dispersion model at any of the three locations.

Conclusion

In this evaluation, the dispersion model was most robust for prediction of Gd‐CTCs derived from dynamic contrast‐enhanced (DCE)‐MRI. This represents a preliminary step in the development of a PBPK model useful for predicting Gd‐CTCs at a time resolution appropriate for dynamic MRI applications. J. Magn. Reson. Imaging 2008;27:1388–1398. © 2008 Wiley‐Liss, Inc.