bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tagging Single Nucleotide Polymorphisms in Cell Cycle Control Genes and Susceptibility to Invasive Epithelial Ovarian Cancer
Authors: Gayther Simon A. , Song Honglin , Ramus Susan J. , Kjaer Susan Krüger , Whittemore Alice S. , Quaye Lydia , Tyrer Jonathan , Shadforth Danielle , Hogdall Estrid , Hogdall Claus , Blaeker Jan , DiCioccio Richard , McGuire Valerie , Webb Penelope M. , Beesley Jonathan , Green Adele C. , Whiteman David C. ,   The Australian Ovarian Cancer Study Group,   The Australian Cancer Study (Ovarian Cancer), Goodman Marc T. , Lurie Galina , Carney Michael E. , Modugno Francesmary , Ness Roberta B. , Edwards Robert P. , Moysich Kirsten B. , Goode Ellen L. , Couch Fergus J. , Cunningham Julie M. , Sellers Thomas A. , Wu Anna H. , Pike Malcolm C. , Iversen Edwin S. , Marks Jeffrey R. , Garcia-Closas Montserrat , Brinton Louise , Lissowska Jolanta , Peplonska Beata , Easton Douglas F. , Jacobs Ian , Ponder Bruce A.J. , Schildkraut Joellen , Pearce C. Leigh , Chenevix-Trench Georgia , Berchuck Andrew , Pharoah Paul D.P. ,   on behalf of the Ovarian Cancer Association Consortium
Published: April 2007

Abstract
High-risk susceptibility genes explain &lt;40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)–tagging approach to evaluate common variants in 13 genes involved in cell cycle control—CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D—and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotyped in three studies from the United Kingdom, United States, and Denmark (∼1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States (∼2,000 cases and ∼3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk [OR, 0.91 (0.85–0.98) for rs3731257; and OR, 0.93 (0.87–0.995) for rs2066827]. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies. [Cancer Res 2007;67(7):3027–35]
Histone Deacetylase 2 Modulates p53 Transcriptional Activities through Regulation of p53-DNA Binding Activity
Authors: Harms Kelly Lynn , Chen Xinbin 
Published: April 2007

Abstract
Histone deacetylase (HDAC) inhibitors are emerging as promising cancer therapeutics. HDAC inhibitors have been found to induce cellular activities that are strikingly similar to p53-mediated responses to genotoxic stress. For example, HDAC inhibitors induce cell cycle arrest, apoptosis, and cellular senescence. Because at least 11 HDACs are affected by the current HDAC inhibitors, the HDAC critical for tumor cell survival and proliferation remains unknown. Thus, we sought to characterize the distinct roles of HDACs in the p53 pathway. Through the use of stable MCF7 cell lines which inducibly express short hairpin RNA targeting HDAC2, we found that HDAC2 plays important roles in the p53 pathway. Specifically, we found that knockdown of HDAC2 inhibited cellular proliferation in a dose-dependent manner which was also partly p53-dependent. Furthermore, knockdown of HDAC2 induced cellular senescence. Importantly, we found that knockdown of HDAC2 enhanced p53-dependent trans-repression and trans-activation of a subset of target genes. We found that the enhancement was due to increased p53-DNA binding activity but not alterations in p53 stability or posttranslational modification(s). Thus, for the first time, our data suggest that HDAC inhibitors function through the p53 pathway, at least in part, by activating p53-DNA binding activity. [Cancer Res 2007;67(7):3145–52]
Activation of a novel ataxia-telangiectasia mutated and Rad3 related/checkpoint kinase 1–dependent prometaphase checkpoint in cancer cells by diallyl trisulfide, a promising cancer chemopreventive constituent of processed garlic
Authors: Herman-Antosiewicz Anna , Stan Silvia D. , Hahm Eun-Ryeong , Xiao Dong , Singh Shivendra V. 
Published: April 2007

Abstract
Diallyl trisulfide (DATS), a cancer chemopreventive constituent of garlic, inhibits growth of cancer cells by interfering with cell cycle progression, but the mechanism is not fully understood. Here, we show the existence of a novel ataxia-telangiectasia mutated and Rad3 related (ATR)/checkpoint kinase 1 (Chk1)–dependent checkpoint partially responsible for DATS-mediated prometaphase arrest in cancer cells, which is different from the recently described γ irradiation–induced mitotic exit checkpoint. The PC-3 human prostate cancer cells synchronized in prometaphase by nocodazole treatment and released to DATS-containing medium remained arrested in prometaphase, whereas the cells released to normal medium exited mitosis and resumed cell cycle. The mitotic arrest was maintained even after 4 h of culture of DATS-treated cells (4-h treatment) in drug-free medium. The DATS-arrested mitotic cells exhibited accumulation of anaphase-promoting complex/cyclosome (APC/C) substrates cyclin A and cyclin B1 and hyperphosphorylation of securin, which was accompanied by increased phosphorylation of the APC/C regulatory subunits Cdc20 and Cdh1. The DATS-mediated accumulation of cyclin B1 and hyperphosphorylation of securin, Cdc20, and Cdh1 were partially but markedly attenuated by knockdown of Chk1 or ATR protein. The U2OS osteosarcoma cells expressing doxycycline-inducible kinase dead ATR were significantly more resistant not only to DATS-mediated prometaphase arrest but also to the accumulation of cyclin B1 and hyperphosphorylation of securin, Cdc20, and Cdh1 compared with cells expressing wild-type ATR. However, securin protein knockdown failed to rescue cells from DATS-induced prometaphase arrest. In conclusion, the present study describes a novel signaling pathway involving ATR/Chk1 in the regulation of DATS-induced prometaphase arrest. [Mol Cancer Ther 2007;6(4):1249–61]
H2AX phosphorylation marks gemcitabine-induced stalled replication forks and their collapse upon S-phase checkpoint abrogation
Authors: Ewald Brett , Sampath Deepa , Plunkett William 
Published: April 2007

Abstract
Gemcitabine is a nucleoside analogue that is incorporated into replicating DNA, resulting in partial chain termination and stalling of replication forks. The histone variant H2AX is phosphorylated on Ser139 (γ-H2AX) and forms nuclear foci at sites of DNA damage. Here, we characterize the concentration- and time-dependent phosphorylation of H2AX in response to gemcitabine-induced stalled replication forks. The number of γ-H2AX foci increased with time up to 2 to 6 h after exposure to gemcitabine, whereas longer exposures did not cause greater phosphorylation or increase cell death. The percentage of γ-H2AX–positive cells increased with concentrations of gemcitabine up to 0.1 μmol/L, and γ-H2AX was most evident in the S-phase fraction. Phosphorylation of ataxia-telangiectasia mutated (ATM) on Ser1981 was also associated with S-phase cells and colocalized in the nucleus with phosphorylated H2AX foci after gemcitabine exposure. Chemical inhibition of ATM, ATM- and Rad3-related, and DNA-dependent protein kinase blocked H2AX phosphorylation. H2AX and ATM phosphorylation were associated with inhibition of DNA synthesis, S-phase accumulation, and activation of the S-phase checkpoint pathway (Chk1/Cdc25A/cyclin-dependent kinase 2). Exposure of previously gemcitabine-treated cultures to the Chk1 inhibitor 7-hydroxystaurosporine (UCN-01) caused a 10-fold increase in H2AX phosphorylation, which was displayed as an even pan-nuclear staining. This increased phosphorylation was not due to apoptosis-induced DNA fragmentation and was associated with the S-phase fraction and decreased reproductive viability. Thus, H2AX becomes phosphorylated and forms nuclear foci in response to gemcitabine-induced stalled replication forks, and this is greatly increased upon checkpoint abrogation. [Mol Cancer Ther 2007;6(4):1239–48]
MAP-ing glioma invasion: Mitogen-activated protein kinase kinase 3 and p38 drive glioma invasion and progression and predict patient survival
Authors: Demuth Tim , Reavie Linsey B. , Rennert Jessica L. , Nakada Mitsutoshi , Nakada Satoko , Hoelzinger Dominique B. , Beaudry Christian E. , Henrichs Amanda N. , Anderson Eric M. , Berens Michael E. 
Published: April 2007

AbstractAlthough astrocytic brain tumors do not metastasize systemically, during tumorigenesis glioma cells adopt an invasive phenotype that is poorly targeted by conventional therapies; hence, glioma patients die of recurrence from the locally invasive tumor population. Our work is aimed at identifying and validating novel therapeutic targets and biomarkers in invasive human gliomas. Transcriptomes of invasive glioma cells relative to stationary cognates were produced from a three-dimensional spheroid in vitro invasion assay by laser capture microdissection and whole human genome expression microarrays. Qualitative differential expression of candidate invasion genes was confirmed by quantitative reverse transcription-PCR, clinically by immunohistochemistry on tissue microarray, by immunoblotting on surgical specimens, and on two independent gene expression data sets of glial tumors. Cell-based assays and ex vivo brain slice invasion studies were used for functional validation. We identify mitogen-activated protein kinase (MAPK) kinase 3 (MKK3) as a key activator of p38 MAPK in glioma; MKK3 activation is strongly correlated with p38 activation in vitro and in vivo. We further report that these members of the MAPK family are strong promoters of tumor invasion, progression, and poor patient survival. Inhibition of either candidate leads to significantly reduced glioma invasiveness in vitro. Consistent with the concept of synthetic lethality, we show that inhibition of invasion by interference with these genes greatly sensitizes arrested glioma cells to cytotoxic therapies. Our findings therefore argue that interference with MKK3 signaling through a novel treatment combination of p38 inhibitor plus temozolomide heightens the vulnerability of glioma to chemotherapy. [Mol Cancer Ther 2007;6(4):1212–22]
Investigation of Surface Duct Conditions over Istanbul, Turkey
Authors: Mentes ŞSibel , Kaymaz Zerefsan 
Published: April 2007

Abstract
A comprehensive examination of 2 yr of radiosonde data to determine the surface duct conditions over Istanbul (4°N, 29°E), Turkey, was made. The refractivity of the atmosphere is a function of air temperature and water vapor pressure. Any negative gradient in the modified refractivity results in the presence of a duct in the atmosphere. Therefore, the occurrence of ducts strongly depends upon both the synoptic and the local meteorological conditions that prevail over the region. The characteristics of surface ducts occurring over Istanbul were examined statistically. It was found that most of the ducts occur in May and July. The highest occurrence rate of surface ducts was observed in the summer season, and the lowest rate was observed in the winter season. The median duct thickness and duct strength are found to be the highest and the strongest in summer, whereas they are the lowest and the weakest in winter. When the data are separated into stable and unstable atmospheric subgroups, it is seen that surface duct characteristics show clear seasonal differences. Surface ducts in a stable atmosphere are found to be stronger than those in an unstable atmosphere. Also, daytime (1200 UTC) surface ducts occur more frequently than nighttime (0000 UTC) surface ducts in Istanbul. These statistics are discussed in association with local meteorological conditions and weather systems affecting the Istanbul region, and comments are made on the importance of their possible consequences in the region.
Low-Frequency Effects on Eddy Covariance Fluxes under the Influence of a Low-Level Jet
Authors: Prabha Thara V. , Leclerc Monique Y. , Karipot Anandakumar , Hollinger David Y. 
Published: April 2007

AbstractTurbulent bursts observed over a tall forest canopy during the initiation of a nocturnal low-level jet (LLJ) are studied with the help of wavelet analysis. The burst of turbulence is observed in response to a shear instability associated with the initiation of LLJ. Turbulent kinetic energy, momentum, and CO2-rich cold air are transferred downward by large eddies with length scales that are higher than the LLJ height. Microfronts are observed over the canopy as a secondary instability that enhances the mixing processes within and above the canopy. The scale-dependent wavelet correlation analysis reveals that countergradient fluxes result from low frequencies, whereas cogradient flux is associated with high-frequency turbulent motions. The countergradient flux is initially noted at low frequencies, and, through coherent motions, it is transferred to smaller scales with a nearly 20-min delay. The countergradient flux dominates at the initiation of the event and reduces net flux, whereas enhanced cogradient flux at the decay of the event increases the net flux. The wavelet correlation coefficient corresponding to cogradient and countergradient fluxes is applied to segregate three regions of the spectra corresponding to “turbulent,” “coherent,” and “noncoherent” large scales. These findings are used to examine the implications on eddy covariance flux measurements.
Lumbar Intervertebral Disk Degeneration in Elite Competitive Swimmers
Authors: Kaneoka Koji , Shimizu Ken , Hangai Mika , Okuwaki Toru , Mamizuka Naotaka , Sakane Masataka , Ochiai Naoyuki 
Published: April 2007

Background The majority of orthopaedic problems experienced by competitive swimmers are related to pain in the shoulder, low back, and knee. Three of 39 national swim team members were hampered in their performance due to lumbar disk herniation at an international competition in 2001. There has been no previous research into lumbar disk degeneration in elite competitive swimmers. Hypothesis Excessive competitive swimming activities accelerate lumbar disk degeneration. Study Design Case control study; Level of evidence, 3. Methods Fifty-six elite swimmers (high-load group, 35 men and 21 women; mean age, 19.6 years) and a control group of 38 university recreational level swimmers (low-load group, 24 men and 14 women; mean age, 21.1 years) were evaluated for lumbar disk degeneration using magnetic resonance imaging. We compared the prevalence of disk degeneration and the disk level between the 2 groups and further investigated the relationship among their symptoms, swimming styles, and disk degeneration. Results Thirty-eight (68%) elite swimmers and 11 (29%) controls had degenerated disks at various disk levels, and the prevalence was significantly greater in the elite swimmers (P = .0002). Comparison between the 2 groups of the prevalence of disk degeneration at each level revealed that the disk level of L5-S1 was significantly more frequently degenerated in the high-load group (P = .026). There was no significant relationship observed among the variables of low back pain symptoms, swimming strokes, and disk degeneration. Conclusion Excessive competitive swimming activities might exaggerate lumbar intervertebral disk degeneration, especially in the L5-S1 intervertebral segment. Keywords lumbar intervertebral disk; disk degeneration; swimming; sports
Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis
Authors: Cerboni Cristina , Zingoni Alessandra , Cippitelli Marco , Piccoli Mario , Frati Luigi , Santoni Angela 
Published: April 2007

AbstractRecent evidence indicates that natural killer (NK) cells can negatively regulate T-cell responses, but the mechanisms behind this phenomenon as a consequence of NK–T-cell interactions are poorly understood. We studied the interaction between the NKG2D receptor and its ligands (NKG2DLs), and asked whether T cells expressed NKG2DLs in response to superantigen, alloantigen, or a specific antigenic peptide, and if this rendered them susceptible to NK lysis. As evaluated by FACS, the major histocompatibility complex (MHC) class I chain-related protein A (MICA) was the ligand expressed earlier on both CD4+ and CD8+ T cells in 90% of the donors tested, while UL16-binding protein-1 (ULBP)1, ULBP2, and ULBP3 were induced at later times in 55%–75% of the donors. By carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling, we observed that NKG2DLs were expressed mainly on T cells that had gone through at least one division. Real-time reverse-transcription polymerase chain reaction confirmed the expression of all NKG2DLs, except ULBP4. In addition, T-cell activation stimulated phosphorylation of ataxia-telangiectasia mutated (ATM), a kinase required for NKG2DLs expression after DNA damage, and ATM/Rad3-related kinase (ATR) inhibitors blocked MICA induction on T cells with a mechanism involving NF-κB. Finally, we demonstrated that activated T cells became susceptible to autologous NK lysis via NKG2D/NKG2DLs interaction and granule exocytosis, suggesting that NK lysis of T lymphocytes via NKG2D may be an additional mechanism to limit T-cell responses.
Sickle cell trait and the risk of venous thromboembolism among blacks
Authors: Austin Harland , Key Nigel S. , Benson Jane M. , Lally Cathy , Dowling Nicole F. , Whitsett Carolyn , Hooper W. Craig 
Published: April 2007

AbstractPeople with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.
Patient feedback on services: a questionnaire survey approach
Authors: Kumar Palanivelu S. , McBride Andrew 
Published: April 2007

Aims and MethodThe aims of the project were to develop a simple, low-cost patient satisfaction questionnaire with face validity and to obtain patient feedback on a range of service areas in a community addiction team. A questionnaire was designed and revised after feedback from multidisciplinary team members and a pilot sample. The questionnaire was distributed until 100 correctly completed forms were received.ResultsThe survey took approximately 30 h of authors' time from commencement to completion and costs were minimal. The majority of the 12 areas evaluated were rated by patients as good or very good. Overall quality of care was rated as good or very good by 88% of participants. There was no enthusiasm in this sample for more active participation in service development.Clinical ImplicationsAll National Health Service staff and services are now enjoined to engage with service users and carers for the purposes of evaluation and development. Simple, affordable methods for obtaining such information about community services can contribute to this process.
Bilateral Adrenal Infiltration in Erdheim-Chester Disease. Report of Seven Cases and Literature Review
Authors: Haroche Julien , Amoura Zahir , Touraine Philippe , Seilhean Danielle , Graef Claire , Birmelé Béatrice , Wechsler Bertrand , Cluzel Philippe , Grenier Philippe A. , Piette Jean-Charles 
Published: April 2007

AbstractContext: Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis characterized by xanthomatous tissue infiltration with CD68+ CD1a− foamy histiocytes. Endocrine problems, such as diabetes insipidus and hypogonadotropic hypogonadism, frequently occur in ECD, but bilateral adrenal infiltration has rarely been reported in this disease.Objective: The aim of the study was to describe adrenal and periadrenal infiltration in ECD.Patients: A total of 22 patients with ECD undergoing systematic computed tomography to search for signs of adrenal enlargement participated in the study.Results: Of the 22 patients with ECD, seven (31.8%) displayed adrenal infiltration on computed tomography. In one case, autopsy confirmed that the adrenal enlargement was due to foamy histiocyte infiltration in the adrenal glands. Possible adrenal insufficiency was assessed in five of the seven patients. One developed signs of adrenal insufficiency, which was confirmed by adrenocorticotropin stimulation tests. Adrenal involvement was reported in only 15 of the 240 ECD cases published up to May 2006. This frequency is significantly lower than that in our series (P = 0.0008; Fisher’s exact test).Conclusion: Physicians should be aware of ECD as a possible cause of morphological changes in adrenal size and infiltration.