bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population‐based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study
Authors: Lyketsos Constantine G. , Toone Leslie , Tschanz JoAnn , Corcoran Christopher , Norton Maria , Zandi Peter , Munger Ron , Breitner John C.S. , Welsh‐Bohmer Kathleen 
Published: April 2006

AbstractBackgroundThe relationship between coronary artery bypass graft (CABG) surgery and cognitive decline remains uncertain, in particular with regard to whether there is delayed cognitive decline associated with this procedure.MethodsThis was a population‐based cohort study involving participants in the Cache County Study of Memory Health and Aging. At baseline the study enrolled 5,092 persons age 65 and older and followed them up three years later and again four years after that. Individuals who reported having undergone CABG surgery at study baseline or had this surgery in between follow‐up waves were compared to individuals who never reported having the surgery. The main outcome measure was the Modified Mini Mental State (3MS). Multilevel models were used to examine the relationship between CABG surgery and cognitive decline over time.ResultsStudy participants who had CABG surgery evidenced 0.95 points of greater decline relative to baseline on the 3MS at the first follow‐up interview after CABG, and an average of 1.9 points of greater decline at the second follow‐up interview, than those without CABG (t = −2.51, df = 2,316, p = 0.0121), after adjusting for several covariates, including number of vascular conditions. This decline was restricted to individuals who were more than five years past the procedure and was not evident in the early years after the surgery.ConclusionsCABG surgery is associated with accelerated cognitive decline more than five years after the procedure in a long‐lived population. This decline is small and its clinical significance is uncertain. We could not find an association between CABG and decline in the first five post‐operative years. Copyright © 2006 John Wiley & Sons, Ltd.
Correlational study of the Chinese version of the executive interview (C‐EXIT25) to other cognitive measures in a psychogeriatric population in Hong Kong Chinese
Authors: Chan Sau Man Sandra , Chiu Fung Kum Helen , Lam Chiu Wa Linda 
Published: April 2006

AbstractObjectivesThis study is designed to pilot test the feasibility and correlational properties of the adapted Chinese version of Executive Interview (C‐EXIT25) to other cognitive measures in a psychogeriatric population in Hong Kong Chinese.MethodEighty‐five community dwelling elders from different levels of residential care facilities were assessed with C‐EXIT25, Cantonese version of Mini‐Mental State Examination (C‐MMSE), Chinese version of Mattis Dementia Rating Scale (CDRS) and Nelson's Modified Card Sorting Test (MCST).ResultsThe C‐EXIT25 has high internal consistency (Cronbach's α = 0.7995) and inter‐rater reliability (r = 0.91). The C‐EXIT25 has superior correlational property to performance indices of MCST than the C‐MMSE and CDRS, after adjusting for age, gender and educational level. It also discriminates among subjects at different stages on Clinical Dementia Rating.ConclusionsThe C‐EXIT25 is a potentially feasible and valid bedside tool for assessment of executive cognitive functions in the psychogeriatric population in Hong Kong Chinese. Copyright © 2006 John Wiley & Sons, Ltd.
Deliberate self‐harm in people aged 60 years and over: characteristics and outcome of a 20‐year cohort
Authors: Hawton Keith , Harriss Louise 
Published: April 2006

AbstractBackgroundLittle information is available about older deliberate self‐harm (DSH) patients and their outcome.MethodsThis study is a prospective investigation and follow‐up of 730 consecutive patients (459 females and 271 males) aged 60 years and over who presented to a general hospital following DSH over a 20‐year period, 1978–1997. Outcome has been examined in terms of repetition of DSH, and deaths by the end of 2000 identified through official death registers.ResultsDSH involved self‐poisoning in 88.6% of cases, 49.3% of the overdoses including paracetamol (acetaminophen), 24.0% minor tranquillizers, and 15.9% antidepressants. Nearly three‐quarters of episodes involved high suicidal intent. Common problems preceding DSH were physical illness (46.1%), social isolation (33.5%), relationship problems with family (29.4%) or partner (25.9%), and bereavement or loss (16.7%). Repetition of DSH occurred in 15.3% of cases, 8.2% in the first year following DSH. By the end of 2000, 432/661 (65.4%) of traced patients had died. There were 30 suicides and open verdicts, which were 49 times and 33 times more frequent respectively than expected from general population death rates. Prior DSH before initial presentation was the main risk factor for suicide, with some evidence of high suicide intent being another factor. There were also excess deaths due to several types of physical disorder.ConclusionsDSH in older people is closely related to suicide, both in terms of suicidal intent and risk of eventual suicide, especially when DSH is repeated. The range of problems experienced by older DSH patients requires extensive and multidisciplinary clinical interventions. Copyright © 2006 John Wiley & Sons, Ltd.
High salt diets dose‐dependently promote gastric chemical carcinogenesis in Helicobacter pylori‐infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells
Authors: Kato Sosuke , Tsukamoto Tetsuya , Mizoshita Tsutomu , Tanaka Harunari , Kumagai Toshiko , Ota Hiroyoshi , Katsuyama Tsutomu , Asaka Masahiro , Tatematsu Masae 
Published: April 2006

AbstractIntake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose‐dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N‐methyl‐N‐nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose‐dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti‐H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose‐dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose‐dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori‐infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis. © 2006 Wiley‐Liss, Inc.
In vitro and in vivo evaluation of WK‐X‐34, a novel inhibitor of P‐glycoprotein and BCRP, using radio imaging techniques
Authors: Jekerle Veronika , Klinkhammer Werner , Scollard Deborah A. , Breitbach Kerstin , Reilly Raymond M. , Piquette‐Miller Micheline , Wiese Michael 
Published: April 2006

AbstractOverexpression of the multidrug resistance proteins P‐glycoprotein (Pgp) and breast cancer resistance protein (BCRP) results in treatment failure of many malignancies including ovarian cancer. Dual inhibition of Pgp and BCRP may restore the sensitivity of resistant cells to anticancer drugs. We report the synthesis and characterization of a novel anthranilic‐acid based Pgp and BCRP modulator, WK‐X‐34. In vitro inhibition of Pgp activity was evaluated using 99mTc‐Sestamibi and daunorubicin accumulation in Pgp overexpressing human ovarian cancer cells (A2780/Adr) and its sensitive counterpart (A2780/wt). Interaction with BCRP was examined with a mitoxantrone‐efflux assay in BCRP‐overexpressing MCF7/mx cells, with flow cytometry. Interactions with the multidrug resistance associated proteins (MRP) were evaluated in transfected MRP1, MRP2 and MRP3 cell lines, using a 5‐CFDA efflux assay. In vivo99mTc‐Sestamibi imaging of human ovarian cancer xenografts was used to evaluate the in vivo efficacy of WK‐X‐34 in mice. Daunorubicin accumulation in A2780/Adr cells was inhibited by WK‐X‐34 at nanomolar concentrations (IC50: 82.1 ± 6 nM). WK‐X‐34 inhibited mitoxantrone accumulation in BCRP‐overexpressing cells at micromolar concentrations (IC50 = 26.5 ± 4.6 μM), whereas WK‐X‐34 did not significantly alter 5‐CFDA accumulation in MRP transfected cells. In vivo, uptake of 99mTc‐Sestamibi was significantly increased in A2780/Adr xenograft tumors, brain and intestine (AUCs0‐4h 136%, 147% and 138%; p < 0.05) in mice dosed with WK‐X‐34 (20 mg/kg i.p.). WK‐X‐34 selectively modulates Pgp and BCRP in vitro and in vivo in multidrug resistant ovarian cancer cells, and thus may have potential utility in the treatment of multidrug resistant tumors. © 2006 Wiley‐Liss, Inc.
Clinically tolerable concentrations of arsenic trioxide induce p53‐independent cell death and repress NF‐κB activation in Ewing sarcoma cells
Authors: Mathieu Julie , Besançon Françoise 
Published: April 2006

AbstractEwing sarcoma (ES), a highly malignant pediatric tumor, is consistently associated with translocations that fuse the EWS gene with a member of the ETS family gene, most commonly FLI‐1. Despite significant advances with multiagent chemotherapy, surgery and radiotherapy, about 40% of ES patients still die from the disease. It is therefore necessary to explore novel agents for possible treatment of this tumor. Here the authors investigated the sensitivity of ES cells to clinically tolerable concentrations of arsenic trioxide (As2O3), a compound known to induce differentiation and apoptosis of other types of malignant cells. The authors report that As2O3 uniformly induced death of 6 ES‐derived cell lines irrespective of their p53 status. As2O3 resulted in an apoptotic phenotype which was inhibited by the broad‐spectrum caspase inhibitor ZVAD‐fmk. These effects correlated with prolonged c‐jun N‐terminal kinase activation, which is a signal for apoptosis in ES cells. As2O3 also decreased basal and cytokine‐induced NF‐κB activity. Since the authors previously demonstrated that NF‐κB exerts an antiapoptotic action in ES cells, As2O3 treatment may also result in a sensitization of these cells to other drugs used in combination therapy. These effects, combined with its antiangiogenic action, define As2O3 as a good candidate for future protocols to improve treatments of Ewing sarcomas, irrespective of the p53 status of the tumor. © 2006 Wiley‐Liss, Inc.
ARLTS1 variants and melanoma risk
Authors: Frank Bernd , Meyer Peter , Boettger Melanie Barbara , Hemminki Kari , Stapelmann Henrike , Gast Andreas , Schmitt Christina , Kumar Rajiv , Sergi Consolato , Burwinkel Barbara 
Published: April 2006

AbstractVariants in the tumor suppressor gene ARLTS1 (ADP‐ribosylation factor‐like tumor‐suppressor gene 1) have been shown to influence familial cancer risk. Both Cys148Arg and Trp149Stop were associated with an increased risk of familial or high‐risk familial breast cancer, respectively. We studied the impact of these gene variants on melanoma risk, investigating 351 melanoma patients and 804 control subjects. While ARLTS1 Trp149Stop did not influence melanoma risk (OR = 0.83, 95% CI = 0.37–1.88, p = 0.65), Cys148Arg revealed a statistically significant association with an increased risk for heterozygous carriers (OR = 1.43, 95% CI = 1.05–1.95, p = 0.02). An additional risk enhancement, though statistically non‐significant, was observed in individuals with multiple melanomas (OR = 2.33, 95% CI = 0.87–6.26, p = 0.08). © 2006 Wiley‐Liss, Inc.
Dietary folate is associated with p16INK4A methylation in head and neck squamous cell carcinoma
Authors: Kraunz Kim S. , Hsiung Debra , McClean Michael D. , Liu Mei , Osanyingbemi Joyce , Nelson Heather H. , Kelsey Karl T. 
Published: April 2006

AbstractInactivation of the p16INK4A (CDKN2A) gene in the Rb pathway is among the most common somatic alterations observed in tobacco‐related solid tumors, including head and neck squamous cell carcinoma (HNSCC). In addition, a low folate diet is an important risk factor for HNSCC. Decreased dietary folate in an animal model of hepatocellular carcinoma has been associated with the induction of epigenetic silencing of the p16INK4A gene. In an ongoing population‐based study of HNSCC, we sought to extend this observation to human disease testing the hypothesis that p16INK4A methylation is associated with decreased dietary folate. We also investigated the association of methylation silencing with functional polymorphisms in the folate metabolism enzyme methylene tetrahydrofolate reductase (MTHFR). In 169 HNSCCs, the odds ratio for p16INK4A methylation among those with low dietary folate intake was 2.3 (95% CI = 1.1–4.8) when compared with those with high folate intake. Furthermore, this increased risk for epigenetic silencing at p16INK4A was modified by the MTHFR alleles previously associated with diminished serum folate levels. Hence, in HNSCC low dietary intake of folate is associated with p16INK4A methylation, and this relationship is modified by the MTHFR genotype. Our data provides important evidence for a mechanism of action of folate deficiency in cancer. © 2006 Wiley‐Liss, Inc.
2‐Deoxy‐L‐ribose inhibits the invasion of thymidine phosphorylase‐overexpressing tumors by suppressing matrix metalloproteinase‐9
Authors: Nakajima Yuichi , Haraguchi Misako , Furukawa Tatsuhiko , Yamamoto Masatatsu , Nakanishi Hayao , Tatematsu Masae , Akiyama Shin‐ichi 
Published: April 2006

AbstractThymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet‐derived endothelial cell growth factor. 2‐Deoxy‐D‐ribose (D‐dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2‐Deoxy‐L‐ribose (L‐dRib), a stereoisomer of D‐dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP‐overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)‐9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L‐dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor‐bearing mice. L‐dRib also reduced MMP‐9 mRNA levels in KB/TP tumors. Furthermore, L‐dRib suppressed the mRNA level of MMP‐9 in cultured KB/TP cells, and the invasive activity of the cells. L‐dRib may be useful for the suppression of invasion of TP‐expressing tumor cells. © 2006 Wiley‐Liss, Inc.
Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: A prospective cohort study
Authors: Suzuki Reiko , Rylander‐Rudqvist Tove , Ye Weimin , Saji Shigehira , Wolk Alicja 
Published: April 2006

AbstractAlthough obesity is one of the established risk factors for postmenopausal breast cancer, it is not clear whether this positive association differs across estrogen receptor (ER) and progesterone receptor (PR) status of breast tumors. We evaluated the association between body weight and ER/PR defined breast cancer risk stratified by postmenopausal hormone (PMH) use and a family history of breast cancer in the population‐based Swedish Mammography Screening Cohort comprising 51,823 postmenopausal women. Relative body weight was measured by body mass index (kg/m2) based on self‐reported weight and height collected in 1987 and 1997. Relative risks (RRs) were estimated by hazard ratios derived from Cox proportional hazards regression models. During an average of 8.3‐year follow‐up, 1,188 invasive breast cancer cases with known ER and PR status were diagnosed. When comparing to normal weight group, we observed a positive association between obesity and risk for the development of ER+ PR+ tumors (RR = 1.67, 95% CI = 1.34–2.07) and an inverse association for the development of all PR− tumors (RR = 0.68, 95% CI = 0.47–0.98). Statistically significant heterogeneity was observed in the RRs between ER+ PR+ tumors and all PR− tumors (pheterogeneity < 0.0001). The positive association of obesity with the development of ER+ PR+ tumors was confined to never‐users of PMHs (RR = 1.90 (CI 95%:1.38–2.61)) and to those without a family history of breast cancer (RR = 1.82 (CI 95%:1.45–2.29)). Our results support the hypothesis that excess endogenous estrogen due to obesity contributes to an increased risk of ER+ PR+ postmenopausal breast cancer. © 2006 Wiley‐Liss, Inc.
Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7‐specific antitumor effects in C57/BL6 mice
Authors: Poo Haryoung , Pyo Hyun‐Mi , Lee Tae‐Young , Yoon Sun‐Woo , Lee Jong‐Soo , Kim Chul‐Joong , Sung Moon‐Hee , Lee Seung‐Hoon 
Published: April 2006

AbstractThe mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7‐expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly‐γ‐glutamic acid (γ‐PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei‐PgsA‐E7. E7‐specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 ± 1.8) and IFN‐γ secreting cells [510 ± 86 spot‐forming cells/106cells] among splenocytes and increased IFN‐γ in supernatants of vaginal lymphocytes. Furthermore, in an E7‐based mouse tumor model, animals receiving orally administered L. casei‐PgsA‐E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei‐PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. © 2006 Wiley‐Liss, Inc.
Human fibroblasts undergo oxidative stress‐induced apoptosis without internucleosomal DNA fragmentation
Authors: Formichi P. , Radi E. , Battisti C. , Tarquini E. , Leonini A. , Di Stefano A. , Federico A. 
Published: April 2006

AbstractIn order to evaluate the reliability of fibroblasts as a cell model for studying apoptosis, we tested the response of normal human fibroblasts to the oxidative stress inducers H2O2 and 2‐deoxy‐D‐ribose (dRib). Our results showed that fibroblasts treated with dRib and H2O2 are induced to undergo apoptosis as demonstrated by reduction in total cell number, chromatin condensation, phosphatidylserine (PS) exposure, activation of caspase‐3 and 7, changes in mitochondrial membrane potential and increase in the number of terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive nuclei. However we only found a slight increase in the percentage of cells in the sub‐G1 region evaluated by flow cytometry, and we did not observe DNA fragmentation by agarose gel electrophoresis. Early in apoptosis, DNA cleavage generates high molecular weight (HMW) fragments which can be detected by TUNEL assay; successively followed by a pronounced DNA brake down into low molecular weight (LMW) fragments, detected as a “DNA ladder” by conventional agarose gel electrophoresis and as an hypodiploid peak by propidium iodide (PI) flow cytometry assay. Our results thus suggest that only HMW fragmentation occurs in fibroblasts exposed to dRib or H2O2 and the lack of internucleosomal DNA fragmentation may depend on the peculiar characteristics of human fibroblasts themselves, irrespective of the apoptotic stimulus used. The existence of distinct events leading to cell death in different cell types makes it necessary to use a combination of strategies and techniques to evaluate the occurrence of apoptosis. J. Cell. Physiol. 208: 289–297, 2006. © 2006 Wiley‐Liss, Inc.
Ionizing radiation enhances adenoviral vector expressing mda‐7/IL‐24‐mediated apoptosis in human ovarian cancer
Authors: Emdad Luni , Sarkar Devanand , Lebedeva Irina V. , Su Zao‐zhong , Gupta Pankaj , Mahasreshti Parameshwar J. , Dent Paul , Curiel David T. , Fisher Paul B. 
Published: April 2006

AbstractOvarian cancer is the fifth most common cause of cancer‐related death in women. Current interventional approaches, including debulking surgery, chemotherapy, and/or radiation have proven minimally effective in preventing the recurrence and/or mortality associated with this malignancy. Subtraction hybridization applied to terminally differentiating human melanoma cells identified melanoma differentiation associated gene‐7/interleukin‐24 (mda‐7/IL‐24), whose unique properties include the ability to selectively induce growth suppression, apoptosis, and radiosensitization in diverse cancer cells, without causing any harmful effects in normal cells. Previously, it has been shown that adenovirus‐mediated mda‐7/IL‐24 therapy (Ad.mda‐7) induces apoptosis in ovarian cancer cells, however, the apoptosis induction was relatively low. We now document that apoptosis can be enhanced by treating ovarian cancer cells with ionizing radiation (IR) in combination with Ad.mda‐7. Additionally, we demonstrate that mda‐7/IL‐24 gene delivery, under the control of a minimal promoter region of progression elevated gene‐3 (PEG‐3), which functions selectively in diverse cancer cells with minimal activity in normal cells, displays a selective radiosensitization effect in ovarian cancer cells. The present studies support the use of IR in combination with mda‐7/IL‐24 as a means of augmenting the therapeutic benefit of this gene in ovarian cancer, particularly in the context of tumors displaying resistance to radiation therapy. J. Cell. Physiol. 208: 298–306, 2006. © 2006 Wiley‐Liss, Inc.