bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Extended Aryl‐Substituted Bisoxazoline Ligands in Asymmetric Synthesis – Efficient Synthesis and Application of 4,4′‐Bis(1‐Naphthyl)‐, 4,4′‐Bis(2‐Naphthyl)‐ and 4,4′‐Bis(9‐Anthryl)‐2,2′‐isopropylidenebis(1,3‐oxazolines)
Authors: van Lingen Hester L. , van Delft Floris L. , Storcken Roy P. M. , Hekking Koen F. W. , Klaassen Anouk , Smits Jan J. M. , Ruskowska Patrycja , Frelek Jadwiga , Rutjes Floris P. J. T.
Published: October 2005

The steric influence of extended aryl substituents on 2,2′‐bis(1,3‐oxazoline) ligands was investigated in a series of asymmetric catalytic reactions such as Mukaiyama aldol and Michael reactions, hetero‐Diels–Alder processes, and allylic alkylation reactions. 4,4′‐(2‐Naphthyl)‐ and 4,4′‐(9‐anthryl)‐substituted isopropylidene‐bridged 2,2′‐bis(1,3‐oxazolines) were synthesized and their enantioselective and catalytic properties in combination with different metals evaluated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Cover Picture: The Asymmetric Suzuki Coupling Route to Axially Chiral Biaryls (Eur. J. Org. Chem. 20/2005)
Authors: Baudoin Olivier
Published: October 2005

The cover picture shows the general scheme for the asymmetric biaryl Suzuki coupling, which is surrounded by examples of axially chiral biaryls attainable by this method (bioactive natural products and chiral metal ligands). Various diastereoselective approaches with planar‐to‐axial or central‐to‐axial chirality induction, as well as diastereo‐ or enantio stereoselective approaches with chiral palladium ligands were described in recent years and are presented in the Micro review by O. Baudoin on p. 4223 ff.
Visualization of episomal and integrated Epstein‐Barr virus DNA by fiber fluorescence in situ hybridization
Authors: Reisinger Jürgen , Rumpler Silvia , Lion Thomas , Ambros Peter F.
Published: October 2005

For many Epstein‐Barr virus (EBV)‐associated malignancies, it is still a matter of controversy whether infected cells harbor episomal or chromosomally integrated EBV genomes or both. It is well established that the expression of EBV genes per se carries oncogenic potential, but the discrimination between episomal and integrated forms is of great relevance because integration events can contribute to the oncogenic properties of EBV, whereas host cells that exclusively harbor viral episomes may not carry the risks mediated by chromosomal integration. This notion prompted us to establish a reliable technique that not only allows to unequivocally discriminate episomal from integrated EBV DNA, but also provides detailed insights into the genomic organization of the virus. Here, we show that dynamic molecular combing of host cell DNA combined with fluorescence in situ hybridization (FISH) using EBV‐specific DNA probes facilitate unambiguous discrimination of episomal from integrated viral DNA. Furthermore, the detection of highly elongated internal repeat 1 (IR1) sequences provides evidence that this method permits detection of major genomic alterations within the EBV genome. Thus, fiber FISH may also provide valuable insights into the genomic organization of viral genomes other than EBV. © 2005 Wiley‐Liss, Inc.
Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer
Authors: Wolf Stephan , Mertens Daniel , Pscherer Armin , Schroeter Petra , Winkler Dirk , Gröne Hermann‐Josef , Hofele Christof , Hemminki Kari , Kumar Rajiv , Steineck Gunnar , Döhner Hartmut , Stilgenbauer Stephan , Lichter Peter
Published: October 2005

Allelic loss of chromosome 8p21–22 is a frequent event in various human cancers including mantle cell lymphoma (MCL), prostate cancer, head and neck squamous cell carcinoma (HNSCC) and bladder cancer. The tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) receptors, including TNFRSF10A and TNFRSF10B, are located within this chromosomal region. Since recent studies demonstrate that chronic lymphocytic leukemia (CLL) and prostate cells are TRAIL induced apoptosis, TRAIL‐receptors are strong tumor suppressor candidate genes in human cancers exhibiting loss of chromosomal material in 8p21.3. However, no mutation of the TRAIL receptor genes has been reported in CLL, MCL, prostate cancer, HNSCC so far. In this study we analyzed the complete coding region of TNFRSF10A and TNFRSF10B in a series of 32 MCL and 101 CLL samples and detected a single nucleotide polymorphism (SNP) in TNFRSF10A (A683C) with tumor specific allele distribution. We examined allele distribution in 395 samples of different tumor entities (prostate cancer, n = 43; HNSCC, n = 40; bladder cancer, n = 179) and compared them to 137 samples from healthy probands. We found the rare allele of TNFRSF10A is more frequent in CLL, MCL, prostate cancer, bladder cancer and HNSCC. The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683A→C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies. © 2005 Wiley‐Liss, Inc.
Targeting the epidermal growth factor receptor by erlotinib (Tarceva™) for the treatment of esophageal cancer
Authors: Sutter Andreas P. , Höpfner Michael , Huether Alexander , Maaser Kerstin , Scherübl Hans
Published: October 2005

Esophageal cancer is the sixth most common cause of cancer‐related death worldwide. Because of very poor 5‐year survival new therapeutic approaches are mandatory. Erlotinib (Tarceva™), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR‐TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored. We therefore studied the antineoplastic potency of erlotinib in human esophageal cancer cells. Erlotinib induced growth inhibition of the human esophageal squamous cell carcinoma (ESCC) cell lines Kyse‐30, Kyse‐70 and Kyse‐140, and the esophageal adenocarcinoma cell line OE‐33, as well as of primary cell cultures of human esophageal cancers. Combining erlotinib with the EGFR‐receptor antibody cetuximab, the insulin‐like growth factor receptor tyrosine kinase inhibitor tyrphostin AG1024, or the 3‐hydroxy‐3‐methylglutaryl coenzyme. A reductase (HMG‐CoAR) inhibitor fluvastatin resulted in additive or even synergistic antiproliferative effects. Erlotinib induced cell cycle arrest at the G1/S checkpoint. The erlotinib‐mediated signaling involved the inactivation of EGFR‐TK and ERK1/2, the upregulation of the cyclin‐dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. However, erlotinib did not induce immediate cytotoxicity or apoptosis in esophageal cancer cells. The inhibition of EGFR‐TK by erlotinib appears to be a promising novel approach for innovative treatment strategies of esophageal cancer, as it powerfully induced growth inhibition and cell cycle arrest in human esophageal cancer cells and enhanced the antineoplastic effects of other targeted agents. © 2005 Wiley‐Liss, Inc.
Evaluation of cervical screening strategies with adjunct high‐risk human papillomavirus testing for women with borderline or mild dyskaryosis
Authors: Berkhof Johannes , de Bruijne Martine C. , Zielinski Gilda D. , Bulkmans Nicole W.J. , Rozendaal Lawrence , Snijders Peter J.F. , Verheijen René H.M. , Meijer Chris J.L.M.
Published: October 2005

The management of women with a smear read as borderline/mild dyskaryosis (BMD) found by cervical cancer screening is still under discussion as only few of these cases are associated with high‐grade lesions. To determine the optimal screening strategy for these women, a simulation model of cervical cancer development was used that is based on high‐risk human papillomavirus (hrHPV) infection. The current strategy of repeat cytological testing at 6 and 18 months after BMD was compared to strategies with adjunct hrHPV testing. Calculations were done for both conventional and liquid‐based cytology as the primary screening tool. In comparison to current screening, adjunct hrHPV testing was more effective in preventing cancer and more woman‐friendly (reduction in colposcopy referrals with outcome < cervical intraepithelial neoplasia (CIN2) of up to 56% and in repeat smears of 30–100%). In combination with conventional cytology, cost‐effective strategies were the ones in which a sample for high‐risk human papillomavirus (hrHPV) testing is collected at a return visit within 1 month or in which hrHPV testing is restricted to repeat smears taken at 6 and 18 months. For these strategies, co‐collection of samples for hrHPV testing at baseline is not necessary which has organizational and cost advantages. In combination with liquid‐based cytology, it was cost‐effective to perform a reflex hrHPV test at baseline from the liquid‐based specimen. Liquid‐based screening was more effective than conventional screening, but annual diagnosis costs were €5 million higher (population size 16 million). In conclusion, our calculations indicate that implementation of hrHPV testing for the management of women with borderline or mild dyskaryosis (BMD) is feasible both in settings where conventional and liquid‐based cytology is current practice. © 2005 Wiley‐Liss, Inc.
From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer
Authors: Le Page Cécile , Ouellet Véronique , Madore Jason , Hudson Thomas J. , Tonin Patricia N. , Provencher Diane M. , Mes‐Masson Anne‐Marie
Published: October 2005

We used an oligonucleotide‐based DNA microarray to identify potential markers in 39 primary cultures of ovarian cancer specimens compared with 11 primary cultures of normal ovarian epithelia. Differential gene expression of IL‐18 and FGF‐2 was validated on a subset of samples by quantitative PCR and by IHC, using an independent tissue array of 90 cores of 20 normal ovarian surface epithelia and 70 EOCs representing different grades and pathologies of ovarian disease. We further compared, by ELISA, these two markers with CA125 in sera from 25 cancer‐free and 47 ovarian cancer patients. IL‐18 and FGF‐2 proteins were significantly elevated in tumor tissues (p<0.04) and sera (p<0.05) from patients with ovarian cancer. In combination, the three markers (IL‐18, FGF‐2, and CA125) showed similar sensitivity in scoring for ovarian cancer (35/45 patients) compared to that of CA125 alone (37/45) and significantly improved the specificity of detection (20/25 patients) compared to each marker individually (15/25 for CA125; 18/25 FGF‐2; 16/25 for IL‐18). In conclusion we show that a combination of the three serum markers (IL‐18, FGF‐2 and CA125) is associated with EOC, with higher specificity than CA125 alone. Prospective studies with a large cohort of susceptible ovarian cancer patients will be required to expand these findings. © 2005 Wiley‐Liss, Inc.
Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation
Authors: Awano Shuji , Dawson Louise A. , Hunter Alison R. , Turner Anthony J. , Usmani Badar A.
Published: October 2005

The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin‐1 (ET‐1), its receptors (endothelin‐A receptor (ETAR) and endothelin‐B receptor (ETBR)) and isoforms of its specific converting enzyme (ECE‐1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE‐specific inhibitor (ECE‐i) and siRNA targeting of the ECE‐1 gene on SCC cell proliferation. We observed the expression of ET‐1, ETAR, ETBR and all endothelin‐converting enzyme‐1 (ECE‐1) isoforms in oral SCC cells, but only the expression of ET‐1, ETBR and ECE‐1 was increased when compared to normal human epidermal keratinocytes. ET‐1 alone stimulated proliferation of oral SCC cells. Antagonists of either ETAR or ETBR inhibited ET‐1‐mediated proliferation. Decreased ECE‐1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE‐i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer. © 2005 Wiley‐Liss, Inc.
Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I‐deficient and ‐proficient HPV16‐associated tumours
Authors: Reiniš Milan , Šímová Jana , Bubeník Jan
Published: October 2005

Unmethylated oligodeoxynucleotides containing guanine–cytidine dimers (CpG ODN) have been described as potent inducers of selected antitumour immune responses and the immunotherapeutic efficacy of CpG ODN has been examined either alone or as a vaccine adjuvant. We hypothesized that CpG ODN therapy could be an effective tool for immunotherapy of not only conventional MHC class I+ tumours but also of those tumours that have lost MHC class I expression during their progression. To address this hypothesis, we employed the animal model resembling MHC class I‐proficient and ‐deficient human papilloma virus (HPV) 16‐associated tumours. A cell line transformed with HPV16 E6 and E7 oncogenes, TC‐1, as a prototype of MHC class I‐positive line, and its MHC class I‐deficient sublines TC‐1/A9 and TC‐1/P3C10 were injected into syngeneic C57BL/6 mice and the growing tumours were subjected to immunotherapy with CpG ODN 1826. The therapy started either 1 day after the challenge with the tumour cells or later, when the tumours had reached a palpable size. In both settings, CpG ODN 1826 significantly reduced the growth of MHC class I‐proficient and ‐deficient tumours. Furthermore, we demonstrated that CpG ODN 1585, whose mechanism of action preferably involves indirect activation of the natural killer cells, induced regression of the MHC class I‐deficient tumours TC1/A9 but not of the MHC class I‐proficient tumours TC‐1. This study infers that synthetic CpG ODN have a potential for the therapy of both MHC class I‐proficient and ‐deficient tumours and thus could be also used against tumours that tend to down‐regulate their MHC class I expression. © 2005 Wiley‐Liss, Inc.
The pro‐cell death Bcl‐2 family member, BNIP3, is localized to the nucleus of human glial cells: Implications for glioblastoma multiforme tumor cell survival under hypoxia
Authors: Burton Teralee R. , Henson Elizabeth S. , Baijal Priti , Eisenstat David D. , Gibson Spencer B.
Published: October 2005

The Bcl‐2 nineteen kilodalton interacting protein 3 (BNIP3) is a hypoxia‐inducible proapoptotic member of the Bcl‐2 family that induces cell death by associating with the mitochondria. Under normal conditions, BNIP3 is expressed in skeletal muscle and in the brain at low levels. In many human solid tumors, BNIP3 is upregulated in hypoxic regions but paradoxically, this BNIP3 expression fails to induce cell death. Herein, we have determined that BNIP3 is primarily localized to the nucleus of glial cells of the normal human brain, as well as in the malignant glioma cell line U251. Upon exposure of U251 cells to hypoxia, BNIP3 expression in the cytoplasm increases and localizes with the mitochondria, contributing to induction of cell death. In contrast, when BNIP3 is forcibly over expressed in the nucleus, it fails to induce cell death. Expression of N‐terminal BNIP3 (lacking the transmembrane and conserved domains) in U251 cells blocks hypoxia‐induced cell death acting as a dominant negative protein by binding to wild‐type BNIP3 and blocking its association with the mitochondria. In glioblastoma multiforme (GBM) tumors, BNIP3 expression is increased in hypoxic regions of the tumor and is primarily localized to the nucleus in ∼80% of tumors. Hence, BNIP3 is sequestered in the nucleus within the brain but under hypoxic conditions, BNIP3 becomes primarily cytoplasmic, promoting cell death. In GBMs, BNIP3 expression is increased but it remains sequestered in the nucleus in hypoxic regions, thereby blocking BNIP3's ability to associate with the mitochondria, providing tumor cells with a possible survival advantage. © 2005 Wiley‐Liss, Inc.
Dietary carbohydrate, fibre, glycaemic index, glycaemic load and the risk of postmenopausal breast cancer
Authors: Giles Graham G. , Simpson Julie A. , English Dallas R. , Hodge Allison M. , Gertig Dorota M. , MacInnis Robert J. , Hopper John L.
Published: October 2005

Evidence that the insulin pathway may be involved in breast carcinogenesis has increased the interest in dietary factors that influence insulin secretion and resistance. We investigated dietary carbohydrate, fibre, glycaemic index (GI) and glycaemic load (GL) in a prospective study of 324 breast cancers diagnosed in 12,273 post‐menopausal women. Although an increase of 1 standard deviation in carbohydrate was marginally associated with risk of breast cancer, relative risk (RR) 1.31 (95% CI, 0.98, 1.75), there were no significant associations with fibre, 1.08 (0.92, 1.26), GI, 0.98 (0.88, 1.10) or GL, 1.19 (0.93, 1.52) or with carbohydrate foods (bread, rice, pasta). The RR for carbohydrate and localized disease was elevated, 1.40 (1.02, 1.92), but like those for fibre, GI and GL did not differ significantly between localized and non‐localized disease. RRs for grade I, but not grade II or III, tumours were elevated for fibre, 1.38 (1.08, 1.75), carbohydrate, 1.56 (1.08, 2.25) and GL, 1.41 (1.01, 1.98) but not for GI, 0.84 (0.65, 1.09). The RRs for fibre and oestrogen receptor (ER) positive (+) and progesterone receptor (PR) positive (+) tumours, 1.36 (1.10, 1.67), differed significantly from those for ER positive (+) and PR negative (−) tumours, 1.01 (0.61, 1.69) and ER−/PR− tumours, 0.65 (0.43, 0.99), p = 0.005. Our data do not support a strong role for GI and GL in breast carcinogenesis but suggest that increased intake of fibre and carbohydrate may be associated with the diagnosis of cancers of more favourable prognosis. © 2005 Wiley‐Liss, Inc.
Accelerated repair and reduced mutagenicity of oxidative DNA damage in human bladder cells expressing the E. coli FPG protein
Authors: Ropolo Monica , Geroldi Alessandro , Degan Paolo , Andreotti Virginia , Zupo Simona , Poggi Alessandro , Reed April , Kelley Mark R. , Frosina Guido
Published: October 2005

Repair of some oxidized purines such as 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) is inefficient in human cells in comparison to repair of other major endogenous lesions (e.g. uracil, abasic sites or oxidized pyrimidines). This is due to the poor catalytic properties of hOGG1, the major DNA glycosylase involved in 8‐oxoG removal. The formamidopyrimidine DNA glycosylase (FPG) protein from E. coli is endowed with a potent 8‐oxoG glycolytic activity coupled with a β,δ‐AP lyase. In this study, we have expressed FPG fused to the enhanced green fluorescent protein (EGFP) in human bladder cells to accelerate the repair of oxidative DNA damage. Cells expressing the fusion protein EGFP–FPG repaired 8‐oxoG and AP sites at accelerated rates, in particular via the single‐nucleotide insertion base excision repair (BER) pathway and were resistant to mutagenicity of the oxidizing carcinogen potassium bromate. FPG may stably protect human cells from some harmful effects of oxidative DNA damage. © 2005 Wiley‐Liss, Inc.
Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas
Authors: Luo Liqiong , Qiao Haiquan , Meng Fanqiang , Dong Xuesong , Zhou Baoguo , Jiang Hongchi , Kanwar Jagat R , Krissansen Geoffrey W , Sun Xueying
Published: October 2005

Arsenic trioxide (As2O3), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As2O3 against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL‐4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As2O3 would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7–0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As2O3 was preceded by in situ gene transfer of B7H3. In contrast, neither As2O3 nor B7H3 monotherapy was effective. The antitumor activity of As2O3 was attributed to increased tumor‐cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD8+ and NK cells that was effective in combating a systemic challenge of 1 × 107 parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN‐γ and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3‐mediated immunotherapy with As2O3 warrants investigation as a therapeutic strategy to combat HCC, and other malignancies. © 2005 Wiley‐Liss, Inc.
siRNA gelsolin knockdown induces epithelial‐mesenchymal transition with a cadherin switch in human mammary epithelial cells
Authors: Tanaka Hiroki , Shirkoohi Reza , Nakagawa Koji , Qiao Hongjiang , Fujita Hisakazu , Okada Futoshi , Hamada Jun‐ichi , Kuzumaki Satoshi , Takimoto Masato , Kuzumaki Noboru
Published: October 2005

Epithelial‐mesenchymal transition (EMT) describes a process occurring during development and oncogenesis by which epithelial cells obtain fibroblast‐like properties and show reduced cell adhesion and increased motility. In this report, we demonstrated typical EMT in human mammary epithelial MCF10A small interfering (si)RNA gelsolin‐knockdown cells. EMT was characterized by fibroblastic morphology, loss of contact inhibition and focus formation in monolayer growth, enhanced motility and invasiveness in vitro, increased actin filaments, overexpression of RAC, activation of both extracellular signal‐regulated kinase and AKT, inactivation of glycogen synthase kinase‐3, conversion of cadherin from the E‐ to N‐type and induction of the transcription factor Snail. These results suggested that gelsolin functions as a switch that controls E‐ and N‐cadherin conversion via Snail, and demonstrated that its knockdown leads to EMT in human mammary epithelial cells and possibly to the development of human mammary tumors. © 2005 Wiley‐Liss, Inc.
Never smokers and lung cancer risk: A case‐control study of epidemiological factors
Authors: Gorlova Olga Y. , Zhang Yiqun , Schabath Matthew B. , Lei Lei , Zhang Qing , Amos Christopher I. , Spitz Margaret R.
Published: October 2005

We performed an analysis of potential epidemiological risk factors for lung cancer using data from 280 cases and 242 hospital‐based controls, all lifetime never smokers (those who had smoked <100 cigarettes in their lifetimes) and frequency matched on age, gender and ethnicity. The data on demographic characteristics, medical history of respiratory diseases (asthma, emphysema, pneumonia and hay fever), weight and height, family history, female characteristics and environmental tobacco smoke (ETS) and dust exposure were derived from personal interviews. We performed a logistic regression analysis of these variables adjusting for age, gender, ethnicity, income and years of education. Exposure to ETS (OR = 2.08, 95% CI [1.25–3.43]) and dusts (OR = 2.43, 95% CI [1.53–3.88]) were associated with significantly increased risk. In the analysis for joint effects, exposure to both ETS and dusts conferred a higher risk (OR = 3.25, 95% CI [1.58–6.70]) than exposure to either alone. Family history of any cancer with onset before age 50 in at least 1 first degree relative was a significant risk predictor (OR = 1.70, 95% CI [1.10–2.64]). Individuals with a self‐reported physician‐diagnosed history of hay fever, but not asthma, had a decreased lung cancer risk (OR = 0.57, 95% CI [0.35–0.92]). In the multivariate analysis, exposure to ETS and dusts, and family history of cancer with onset before age 50 were significant risk factors, while a history of hay fever (occurring without asthma) was significantly protective. © 2005 Wiley‐Liss, Inc.
Cigarette smoking and risk of glioma: A prospective cohort study
Authors: Silvera Stephanie A. Navarro , Miller Anthony B. , Rohan Thomas E.
Published: October 2005

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. N‐nitroso compounds are known carcinogens, which are found in cigarette smoke and can induce gliomas in rats. On this basis, it has been hypothesized that cigarette smoking may be associated with an increased risk of glioma. We investigated the association between cigarette smoking and glioma risk in the National Breast Screening Study, which included 89,835 Canadian women aged 40–59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow‐up ending between 1998 and 2000. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and risk of glioma. During a mean of 16.4 years of follow‐up, we observed 120 incident glioma cases. Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97–2.34), while current smokers did not appear to have an increase in risk. When the association with former smokers was further examined by years since quitting, women who had quit smoking >10 years before baseline were at a decreased risk of glioma compared with women who had quit within the 10 years prior to baseline (HR = 0.55, 95% CI = 0.29–1.07), indicating that the association between former smokers and glioma may be driven by women, who recently quit smoking. Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack‐years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest. The present study provides some support for a positive association between cigarette smoking and risk of glioma. © 2005 Wiley‐Liss, Inc.
Surface chemistry and biological responses to synthetic octacalcium phosphate
Authors: Suzuki Osamu , Kamakura Shinji , Katagiri Takenobu
Published: October 2005

Octacalcium phosphate (OCP) has been suggested as a precursor of biological apatite in bone, dentin, and cementum because its existence explains the nonstoichiometry of apatite crystals in their compositions. Synthetic inorganic calcium phosphate compounds have been used clinically to fill bone defects, and sintered hydroxyapatite (HA) and beta‐tricalcium phosphate (β‐TCP), bone substitute materials, are known to be osteoconductive, with β‐TCP also being bioresorbable. Nonsintered synthetic OCP has been shown to enhance bone regeneration accompanied by conversion into hydrolyzed apatitic products in situ and biodegradation. The surfaces of the OCP implant and the converted apatite seem to be continuously exposed to biological constituents, such as extracellular matrices, inorganic biominerals, and cellular components. This article reviews the surface reaction of OCP implants and the biological responses, such as experimentally stimulated bone formation on synthetic OCP, the mechanism of OCP hydrolysis into apatite, and the adsorption of biomolecules onto OCP and the converted apatite, of particular interest in reactive bone induction with synthetic OCP implants. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Effect of prestrain on martensitic transformation in a Ti46.4Ni47.6Nb6.0 superelastic alloy and its application to medical stents
Authors: Takagi T. , Sutou Y. , Kainuma R. , Yamauchi K. , Ishida K.
Published: October 2005

The effect of applied strain on martensitic transformation in a superelastic Ti46.4Ni47.6Nb6.0 alloy at room temperature was investigated by tensile tests, differential scanning calorimetry measurements, and X‐ray diffraction. Reverse transformation starting (As) and finishing (Af) temperatures increased with the application of tensile‐strain over 13%, the undeformed specimen showing As = −29.2°C and Af = 17.9°C, while the 13% predeformed alloy exhibited As = 37.1°C and Af = 40.2°C. Furthermore, the values of the As and Af for the predeformed alloy almost recovered to those of the undeformed alloy when heated to about 42°C and then showed superelasticity again at room temperature. This characteristic is significant for application in sensors, actuators, and medical devices. Especially, medical stents with such qualities show promise as a new class of self‐expandable stents with both excellent mountability and deliverability. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Over‐expression of heme oxygenase‐1 promotes oxidative mitochondrial damage in rat astroglia
Authors: Song Wei , Su Haixiang , Song Sisi , Paudel Hemant K. , Schipper Hyman M.
Published: October 2005

Glial heme oxygenase‐1 is over‐expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up‐regulation of HO‐1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO‐1 induction promotes mitochondrial oxidative stress, assays for 8‐epiPGF2α (ELISA), protein carbonyls (ELISA) and 8‐OHdG (HPLC‐EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole‐cell compartments derived from cultured rat astroglia engineered to over‐express human (h) HO‐1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO‐1 over‐expression (×3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 µM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up‐regulation of HO‐1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme‐derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO‐1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. © 2005 Wiley‐Liss, Inc.
A common pathway in differentiation and inflammation: p38 mediates expression of the acute phase SIP24 iron binding lipocalin in chondrocytes
Authors: Ulivi Valentina , Tutolo Giorgia , Mallein‐Gerin Frédéric , Daga Antonio , Cancedda Ranieri , Cancedda Fiorella Descalzi
Published: October 2005

SIP24 is an acute phase iron binding lipocalin physiologically expressed in vivo in developing cartilage by prehypertrophic/hypertrophic chondrocytes. Taking advantage of the chondrocytic cell line MC615 and using SIP24 as a marker we investigated the pathways active in cartilage differentiation and inflammation. MC615 cells were cultured as: (i) proliferating prechondrogenic cells expressing type I collagen (ii) differentiated hyperconfluent cells expressing Sox9 and type II collagen. In proliferating cells the pathway PKC/ERK1, ERK2 was activated and SIP24 was not expressed while in differentiated cells the pathway p38/NF‐κB was activated and SIP24 was expressed. Proliferating cells treated with inflammatory agents expressed a large amount of SIP24 and showed activation of p38/NF‐κB pathway and inhibition of PKC/ERK1, ERK2 pathway indicating that in inflammation and differentiation the same factors are activated (p38, NF‐κB) or inactivated (PKC, ERKs). Treatment of proliferating cells with the p38 specific inhibitor SB203580 inhibited the inflammation induced activation of p38 and the synthesis of SIP24. PMA treatment induced activation of PKC, inactivation of p38 and suppression of SIP24 synthesis, suggesting that PKC activation inhibits p38 activation. In differentiated hyperconfluent cells the same factors (p38/NF‐κB/SIP24) are constitutively activated: treatment with inflammatory agents does not increase synthesis of SIP24 while treatment with SB203580 and with PMA does not repress activation of p38 nor synthesis of SIP24. We propose that the SIP24 stress related protein is expressed via p38 activation/NF‐κB recruitment both in chondrocyte differentiation and inflammation and that a signaling pathway active in the acute phase response is physiologically activated in differentiation. © 2005 Wiley‐Liss, Inc.
Limitation of size by hypoxia in the fruit fly Drosophila melanogaster
Authors: Peck Lloyd S. , Maddrell Simon H.P.
Published: October 2005

The size of an organism is of fundamental importance in all biological processes. It dictates many of the critical interactions and physical factors that delimit the envelope within which an organism can grow. We investigated the effects of reduced oxygen on size and development in the fruit fly Drosophila melanogaster, and showed that limiting the oxygen in the environment limits both whole animal and cell size. When oxygen levels were reduced from 20% in nitrogen to 15%, 10% and 7.5%, there was a linear decrease in both male and female mass. Both cell size and cell number decreased in low oxygen, but changes in cell size accounted for a larger proportion of the overall change in fly size. Cell numbers decreased by a maximum of 11% between flies reared in 20% oxygen and those reared in 7.5% oxygen, whereas cell surface area decreased by 17%. Low oxygen levels increased development time and mortality, but reduced fecundity. Reducing the level of oxygen available significantly slowed development times, with flies reared in 10% oxygen emerging on average 1.5 days later than those in 20% oxygen. The effect of oxygen on size is reversible during embryonic and larval development up to the pupal stage, when final size is set. J. Exp. Zool. 303A:968–975, 2005. © 2005 Wiley‐Liss, Inc.
Adaptation of a nematode parasite to living within the mammalian epithelium
Authors: Tilney Lewis G. , Connelly Patricia S. , Guild Gregory M. , Vranich Kelly A. , Artis David
Published: October 2005

Trichuris muris is a large metazoan pathogen that has been proposed to live intracellularly within living host intestinal epithelial cells. We sought to determine how Trichuris bores its way through the mucosal epithelium and to elucidate the parasite strategies for taking advantage of this intracellular niche. Since the apical surface of the mucosal epithelium is stabilized by the actin cytoskeleton and cell junctions, it remains intact over the worm following its entry into cells. In contrast, non‐stabilized lateral membranes of the host epithelial cells are ruptured and cells are killed to form an inert syncytial tunnel. The ventral surface of the nematode worm is studded by pores that overlie bacillary cells; these pores penetrate through the cuticle and are in direct contact with host cytoplasm. From scanning electron micrographs of isolated worms, we calculate that each adult contains approximately 50,000 bacillary cells. The apical surface of the bacillary cells is extensively folded into plicae 40 nm in diameter, thereby increasing the surface area many‐fold. Bacillary cells lack organelles for enzyme synthesis and secretion and fail to export protons. However, by confocal light microscopy it was observed that fluorescent macromolecules in excess of 100,000 Da can penetrate into the pores. Taken together, we conclude that the bacillary cells are essential for living inside host epithelium and function predominantly in absorption of soluble molecules from the host mucosal cytoplasm, in essence behaving as an external gut epithelium that is protected from abrasion by the cuticle that surrounds the openings of the bacillary cells. J. Exp. Zool. 303A:927–945, 2005. © 2005 Wiley‐Liss, Inc.
Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis
Authors: Arresta Emiliano , Bernardini Sergio , Bernardini Enrico , Filoni Sergio , Cannata Stefano M.
Published: October 2005

This study examines the retinal transdifferentiation (TD) of retinal pigmented epithelium (RPE) fragments dissected from Xenopus laevis larvae and implanted into the vitreous chamber of non‐lentectomized host eyes. In these experimental conditions, most RPE implants transformed into polarized vesicles in which the side adjacent to the lens maintained the RPE phenotype, while the side adjacent to the host retina transformed into a laminar retina with the photoreceptor layer facing the cavity of the vesicle and with the ganglionar cell layer facing the host retina. The formation of a new retina with a laminar organization is the result of depigmentation, proliferation and differentiation of progenitor cells under the influence of inductive factors from the host retina. The phases of the TD process were followed using BrdU labelling as a marker of the proliferation phase and using a monoclonal antibody (mAbHP1) as a definitive indicator of retina formation. Pigmented RPE cells do not express Pax6. In the early phase of RPE to retinal TD, all depigmented and proliferating progenitor cells expressed Pax6. Changes in the Pax6 expression pattern became apparent in the early phase of differentiation, when Pax6 expression decreased in the presumptive outer nuclear layer (ONL) of the new‐forming retina. Finally, during the late differentiation phase, the ONL, which contains photoreceptors, no longer expressed Pax6, Pax6 expression being confined to the ganglion cell layer and the inner nuclear layer. These results indicate that Pax6 may have different roles during the different phases of RPE to retinal TD, acting as an early retinal determinant and later directing progenitor cell fate. J. Exp. Zool. 303A:958–967, 2005. © 2005 Wiley‐Liss, Inc.
Effects of Low pH acute exposure on survival and gill morphology inTriturus italicuslarvae
Authors: Brunelli Elvira , Tripepi Sandro
Published: October 2005

We examined, from a morphological and ultrastructural point of view, the gill epithelium ofTriturus italicus, both in basal conditions and after acute exposure to low pH. Our analysis of gill morphology began with the aim of determining lethal pH levels; we found that the pH value at which 50% of mortality occurs (LC50) is 4.0. We then investigated the effects of the larvae's exposure to a critical value of pH (pH 4.5).

No change was observed in the gill during the first 24 hr. After 48 hr, a cellular response was evident and the gills appeared covered with a dense mucous layer. Observations that were carried out by light microscopy (LM) and electron microscopy, both scanning (SEM) and transmission (TEM), showed considerable histological and ultrastructural changes.

As regards the principal filament, the alterations resulted in the presence of an external keratinized layer. More changes affected the mitochondria‐rich cells (MRCs) in both a qualitative and quantitative way; this cell type shows a wide surface and seems to protrude more than the near pavement cells that, in normal conditions, partially cover the MRCs, thus reducing their external surface. The microvilli were extremely lengthened and often anatomized each other. Changes in the secondary filament affected the thickness of the epithelium, which appeared considerably smaller in the gills of the newts exposed to acid stress. The ciliated cells appeared to be more numerous than in the control specimens and the MRCs showed a widening of the apical surface.J. Exp. Zool. 303A:946–957, 2005. © 2005 Wiley‐Liss, Inc.
Stressed mothers lay eggs with high corticosterone levels which produce low‐quality offspring
Authors: Saino Nicola , Romano Maria , Ferrari Raffaella Paola , Martinelli Roberta , Møller Anders Pape
Published: October 2005

Organisms frequently encounter stressful ecological conditions. In vertebrates, a major mechanism of physiological response to stress is mediated by the hypothalamic–pituitary–adrenal axis and results in increased secretion of glucocorticosteroids, which can have adverse consequences on diverse phenotypic traits affecting fitness. Maternal stress may thus have carry‐over effects on progeny if it influences pre‐natal offspring environment in terms of glucocorticosteroid concentration, although this hypothesis has never been tested in any species under field conditions. We manipulated stress experienced by female barn swallows Hirundo rustica, by exposing them to a predator during laying and measured egg corticosterone concentration. Stressed females laid eggs with greater corticosterone concentration than controls exposed to a herbivore. In another experiment, we injected physiological doses of corticosterone in the egg albumen and compared the phenotype of offspring originating from these eggs with their control siblings originating from either sham‐inoculated or unmanipulated eggs and reared in the same nest. Eggs injected with corticosterone had lower hatchability and produced fledglings with smaller body size and slower plumage development than did control eggs. Nestling body size in our study population predicts long‐term survival. Thus, maternal stress impaired offspring phenotype and viability by increasing transmission of glucocorticosteroids to the eggs. This study identifies a novel mechanism mediating early maternal effects whereby maternal stress affects offspring quality. These results are relevant to biological conservation because they disclose a mechanism that can link environmental conditions to population productivity and viability. J. Exp. Zool. 303A:998–1006, 2005. © 2005 Wiley‐Liss, Inc.
Germ cell death in the testis and its relation to spermatogenesis in the wax moth, Galleria mellonella (Lepidoptera: Pyralidae), effects of facultative diapause
Authors: Polanska Marta Anna , Ciuk Marcin Adam , Cymborowski Bronislaw , Bebas Piotr
Published: October 2005

The dichotomous spermatogenesis of many Lepidopterans results in the production of two types of sperm: eupyrene sperm possessing a cell nucleus which participates in fertilisation, and apyrene ones, which lose their nuclei during development and whose function remains a mystery. The goal of our study was to analyse spermatogenesis at the end of the larval development of the wax moth, Galleria mellonella, at an optimal temperature of 30°C as well as to describe how they are affected by diapause brought on by a reduction of temperature to 18°C. Spermatogenesis in non‐diapausing insects did not differ significantly from that described in other species of Lepidoptera, and any differences found were compared against available literature. Based on the results presented, it may be unequivocally stated that changes in spermatogenesis occur in diapause caused by a suboptimal temperature of 18°C. The main effect of diapause observed in the testes is the degeneration of germ cells, immediately following their differentiation from bipotential spermatocytes. Eupyrene cells seem to reach a more advanced stage of development. Due to the absence of secondary eupyrene spermatocytes in the testis of diapausing insects, it may be surmised that the meiotic divisions, which lead to the formation of secondary spermatocytes and eventually spermatids, do not occur, or are somehow altered. Lastly, terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling (TUNEL) analyses we performed show that the degenerative changes of eupyrene cells are apoptotic in character. J. Exp. Zool. 303A:1013–1029, 2005. © 2005 Wiley‐Liss, Inc.
Isolation of the Feline α1,3‐Galactosyltransferase Gene, Expression in Transfected Human Cells and its Phylogenetic Analysis
Authors: Roy Bibhuti Bhusan , Jinno‐oue Atsushi , Shinagawa Masahiko , Shimizu Akira , Tamura Kazushi , Shimizu Nobuaki , Tanaka Atsushi , Hoshino Hiroo
Published: October 2005

The enzyme alpha 1,3‐galactosyltransferase (α1,3‐GT), which catalyzes synthesis of terminal α‐galactosyl epitopes (Gal α1,3Gal β1‐4GlcNAc‐R), is produced in non‐primate mammals, prosimians and new‐world monkeys, but not in old‐world monkeys, apes and humans. We cloned and sequenced a cDNA that contains the coding sequence of the feline α1,3‐GT gene. Flow cytometric analysis demonstrated that the α‐galactosyl epitope was expressed on the surface of a human cell line transduced with an expression vector containing this cDNA, and this α‐galactosyl epitope expression subsided by α‐galactosidase treatment. The open reading frame of the feline α1,3‐GT cDNA is 1,113 base pairs in length and encodes 371 amino acids. The nucleotide sequence and its deduced amino acid sequence of the feline α1,3‐GT gene are 88–90% and 85–87%, respectively, similar to the reported sequences of the bovine, porcine, marmoset and cebus monkey α1,3‐GT genes, while they are 88% and 82–83%, respectively, similar to those of the orangutan and human α1,3‐GT pseudogenes, and 81% and 77%, respectively, similar to the murine α1,3‐GT gene. Thus, the α1,3‐GT genes and pseudogenes of mammals are highly similar. Ratios of non‐synonymous nucleotide changes among the primate pseudogenes as well as the primate genes are still higher than the ratios of non‐primates, suggesting that the primate α1,3‐GT genes tend to be divergent. J. Exp. Zool.(Mol. Dev. Evol.) 306B, 2006. © 2005 Wiley‐Liss, Inc.
Dmrt1 expression in response to estrogen treatment in a reptile with temperature‐dependent sex determination
Authors: Murdock Chris , Wibbels Thane
Published: October 2005

Dmrt1 has been implicated as an important factor in sex determination in all classes of vertebrates, including reptiles with temperature‐dependent sex determination (TSD). Specifically, early embryonic expression of Dmrt1 appears to be an integral part of normal testicular development in vertebrates. Recently, a number of TSD studies have placed Dmrt1 expression at the top of a short list of putative temperature‐sensitive events for TSD. Dmrt1 expression has been shown to be up‐regulated at male‐producing temperatures during the thermosensitive period (TSP) of several TSD reptile species. An interesting finding in Dmrt1 studies of fish and amphibians has been that in species where exogenous steroids can stimulate sex reversal, Dmrt1 expression can also be manipulated by these steroid treatments. In the current study, we examine the effects of exogenous 17β‐estradiol treatment on Dmrt1 expression at male‐producing temperature (26°C) in a reptile with TSD, the red‐eared slider turtle, Trachemys scripta. Previous studies have demonstrated that exogenous estrogens can stimulate sex reversal (at male‐producing temperatures) in this species of turtle. In the current study, T. scripta embryos that received estradiol treatment displayed a significant decrease in Dmrt1 expression during the TSP, while embryos in the control group (no estradiol treatment) showed significant increases in Dmrt1 expression during the TSP. Furthermore, the pattern of Dmrt1 expression for the estradiol‐treated group was similar to the pattern we previously reported for Dmrt1 at female‐producing temperature (31°C). These findings indicate that exogenous estrogen is acting at or before the Dmrt1 event in the sex determination/sex differentiation cascade of T. scripta. Further, the results are consistent with the hypothesis that exogenous estrogen could be exerting its feminizing effect by down‐regulating the expression of Dmrt1. J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2005 Wiley‐Liss, Inc.