bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+CD25hi regulatory T‐cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia
Authors: Molling Johan W. , de Gruijl Tanja D. , Glim Judith , Moreno Maria , Rozendaal Lawrence , Meijer Chris J.L.M. , van den Eertwegh Alfons J.M. , Scheper Rik J. , von Blomberg Mary E. , Bontkes Hetty J. 
Published: June 2007

AbstractCD4+CD25hiCTLA4+FoxP3+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T‐cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre‐malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL‐2 producing T‐helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV‐persistence‐associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia. © 2007 Wiley‐Liss, Inc.
Relationship between ornithine decarboxylase levels in anaplastic gliomas and progression‐free survival in patients treated with DFMO–PCV chemotherapy
Authors: Levin Victor A. , Jochec Jacob L. , Shantz Lisa M. , Aldape Kenneth D. 
Published: June 2007

AbstractThe purpose of this study was to assess the relationship between progression‐free survival (PFS) in patients treated with DFMO + PCV (procarbazine, CCNU, vincristine) chemotherapy for malignant gliomas with tumor cell ornithine decarboxylase (ODC) activity. Formalin‐fixed slides were obtained for study patients with anaplastic gliomas (AGs) and glioblastoma treated on protocol DM92‐035. ODC levels were measured using an antibody to ODC coupled to Alexa 647 dye (Ab‐ODC‐Alexa 647). Ab‐ODC‐Alexa 647 intensity in transgenic murine hearts of differing ODC activity was used to calculate ODC activity in tumor cell nucleoplasm. In total, tumor specimens for 31 of 114 (27%) patients treated on the AG strata and 10 patients from the GBM strata were obtained. We found that tumor ODC level heterogeneity increased with increasing tumor malignancy. In a Cox proportional hazards model, PFS was found to be inversely related to median tumor ODC activity, with an unadjusted hazard ratio for median ODC group (>3.3 vs. ≤3.3 nmol/30 min/μg protein) of 5.8 (p < 0.0001); a median PFS of 522 weeks for patients with AGs with median ODC activity ≤ 3.3 and 31 weeks for the 8 AG and 10 glioblastoma patients with ODC activity > 3.3 nmol/30 min/μg protein. Of AG tumors in which ODC activity was evaluated, 26% had ODC levels > 3.3 nmol/30 min/μg protein. This study shows that Ab‐ODC‐Alexa 647 fluorescence intensity can be used as a surrogate marker of ODC biochemical activity in AGs and can predict PFS to DFMO‐based chemotherapy. © 2007 Wiley‐Liss, Inc.
Lymphocyte radiosensitivity in BRCA1 and BRCA2 mutation carriers and implications for breast cancer susceptibility
Authors: Barwell Julian , Pangon Laurent , Georgiou Anne , Kesterton Ian , Langman Caroline , Arden‐Jones Audrey , Bancroft Elizabeth , Salmon Ashi , Locke Imogen , Kote‐Jarai Zsofia , Morris Joanna R. , Solomon Ellen , Berg Jonathan , Docherty Zoe , Camplejohn Richard , Eeles Rosalind , Hodgson Shirley V. 
Published: June 2007

AbstractThere is conflicting evidence as to whether individuals who are heterozygous for germ‐line BRCA1 or BRCA2 mutations have an altered phenotypic cellular response to irradiation. To investigate this, chromosome breakage and apoptotic response were measured after irradiation in peripheral blood lymphocytes from 26 BRCA1 and 18 BRCA2 mutation carriers without diagnosed breast cancer, and 38 unaffected age, ethnically and sex‐matched controls. To assess the role of BRCA1 and BRCA2 in homologous recombination, an S phase enrichment chromosome breakage assay was used. BrdUrd incorporation studies allowed verification of the correct experimental settings. We found that BRCA1 mutation carriers without cancer had increased chromosome breaks as well as breaks and gaps per cell post irradiation using the classical G2 assay (p = 0.01 and 0.004, respectively) and the S phase enrichment assay (p = 0.01 and 0.01, respectively) compared to age‐matched unaffected controls. BRCA2 mutation carriers without cancer had increased breaks as well as breaks and gaps per cell post irradiation using the S phase enrichment assay (p = 0.045 and 0.012, respectively). No difference was detected using the G2 assay (p = 0.88 and 0.40 respectively). BRCA1 and BRCA2 mutation carriers had normal cell cycle kinetics and apoptotic response to irradiation compared to age‐matched controls. Our results show a demonstrable impairment in irradiation induced DNA repair in women with heterozygous germline BRCA1 and BRCA2 mutations prior to being diagnosed with breast cancer. © 2007 Wiley‐Liss, Inc.
ATM sequence variants associate with susceptibility to non‐small cell lung cancer
Authors: Yang Hushan , Spitz Margaret R. , Stewart David J. , Lu Charles , Gorlov Ivan P. , Wu Xifeng 
Published: June 2007

AbstractATM gene mutations have been implicated in many human cancers. However, the role of ATM polymorphisms in lung carcinogenesis is largely unexplored. We conducted a case‐control analysis of 556 Caucasian non‐small‐cell lung cancer (NSCLC) patients and 556 controls frequency‐matched on age, gender and smoking status. We genotyped 11 single nucleotide polymorphisms of the ATM gene and found that compared with the wild‐type allele‐containing genotypes, the homozygous variant genotypes of ATM08 (rs227060) and ATM10 (rs170548) were associated with elevated NSCLC risk with ORs of 1.55 (95% CI: 1.02–2.35) and 1.51 (0.99–2.31), respectively. ATM haplotypes and diplotypes were inferred using the Expectation‐Maximization algorithm. Haplotype H5 was significantly associated with reduced NSCLC risk in former smokers with an OR of 0.47 (0.25–0.96) compared with the common H1 haplotype. Compared with the H1–H2 diplotype, H2–H2 and H3–H4 diplotypes were associated with increased NSCLC risk with ORs of 1.58 (0.99–2.54) and 2.29 (1.05–5.00), respectively. We then evaluated genotype–phenotype correlation in the control group using the comet assay to determine DNA damage and DNA repair capacity. Compared with individuals with at least 1 wild‐type allele, the homozygous variant carriers of either ATM08 or ATM10 exhibited significantly increased DNA damage as evidenced by a higher mean value of the radiation‐induced olive tail moment (ATM08: 4.86 ± 2.43 vs. 3.79 ± 1.51, p = 0.04; ATM10: 5.14 ± 2.37 vs. 3.79 ± 1.54, p = 0.01). Our study presents the first epidemiologic evidence that ATM genetic variants may affect NSCLC predisposition, and that the risk‐conferring variants might act through down‐regulating the functions of ATM in DNA repair activity upon genetic insults such as ionizing radiation. © 2007 Wiley‐Liss, Inc.
Zinc toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes
Authors: Lemire Joseph , Mailloux Ryan , Appanna Vasu D. 
Published: June 2007

AbstractAlthough zinc (Zn) is a known environmental toxicant, its impact on the cellular energy‐producing machinery is not well established. This study investigated the influence of this divalent metal on the oxidative ATP producing network in human hepatocellular carcinoma (HepG2) cells. Zn‐challenged cells contained more oxidized proteins and lipids compared with control cells. Zn severely impeded mitochondrial functions by inhibiting aconitase, α‐ketoglutarate dehydrogenase, isocitrate dehydrogenase‐NAD+ dependent, succinate dehydrogenase and cytochrome C oxidase Zn‐exposed cells had a disparate mitochondrial metabolism compared with the control cells and produced significantly less ATP. However, the expression of isocitrate dehydrogenase‐NADP+ dependent was more prominent in cells treated with Zn. Hence, Zn‐induced pathologies may be due to the inability of the mitochondria to generate energy effectively. Copyright © 2007 John Wiley & Sons, Ltd.
The antioxidant and pro‐oxidant activity of vitamin C and trolox in vitro: a comparative study
Authors: Poljšak Borut , Raspor Peter 
Published: June 2007

AbstractThe antioxidant and pro‐oxidant properties of ascorbic acid (vitamin C) and the water‐soluble analogue of α‐tocopherol (trolox) were compared. Trolox has advantages over α‐tocopherol, the latter being only lipid‐soluble due to the presence of a carboxyl group in lieu of a phytol chain which imparts trolox with water solubility. Trolox is used as a standard antioxidant in biochemical studies against which the antioxidant capacity of compounds is compared. Although ascorbic acid and tocopherols possess strong antioxidant properties, they might also exhibit pro‐oxidant properties in the presence of free transition metals. Thus, reactions detailed in this study were performed in the presence of Cr(VI) in an effort to investigate the potential of ascorbic acid and trolox to generate hydroxyl radicals in a Fenton‐like reaction. Results obtained were derived from reactions containing the same concentration of ascorbic acid and trolox under identical experimental conditions. Hydroxyl radical formation was observed in the reaction of Cr(VI) with ascorbic acid resulting from ascorbic acid auto‐oxidation and H2O2 formation. Hydroxyl radical formation was only detected in the reaction mixture containing Cr(VI) and trolox following the addition of H2O2. Copyright © 2007 John Wiley & Sons, Ltd.
Captan: Transition from ‘B2’ to ‘not likely’. How pesticide registrants affected the EPA Cancer Classification Update
Authors: Gordon Elliot 
Published: June 2007

AbstractOn 24 November 2004 EPA changed the cancer classification of captan from a ‘probable human carcinogen’ (Category B2) to ‘not likely’ when used according to label directions. The new cancer classification considers captan to be a potential carcinogen at prolonged high doses that cause cytotoxicity and regenerative cell hyperplasia. These high doses of captan are many orders of magnitude above those likely to be consumed in the diet, or encountered by individuals in occupational or residential settings. This revised cancer classification reflects EPA's implementation of their new cancer guidelines. The procedures involved in the reclassification effort were agreed upon with EPA and involved an Independent Transparent Review as it related to four components that formed the basis of the original 1986 B2 classification: mouse tumors; rat tumors; mutagenicity; and structural similarity to other carcinogens. A Peer Review Panel organized and administered by Toxicology Excellence for Risk Assessment (TERA) met on 2–3 September 2003. The Panel concluded that captan acted through a non‐mutagenic threshold mode of action that required prolonged irritation of the duodenal villi as the initial key event. EPA's Cancer Assessment Review Committee (CARC) met on 9 June 2004 and endorsed the Peer Review findings. EPA intended to have the FIFRA Scientific Advisory Panel (SAP) consider the basis for this reclassification but found the science was robust and judged that a SAP review was not warranted. Using the revised classification, the margin of exposure is approximately 1,200,000, supporting the ‘not likely’ characterization. Copyright © 2007 John Wiley & Sons, Ltd.
Urinary excretion of toluene diisocyanates in rats following dermal exposure
Authors: Yeh Hui‐Jung , Lin Wei‐Chao , Shih Tung‐Sheng , Tsai Perng‐Jy , Wang Shan‐Tair , Chang Ho‐Yuan 
Published: June 2007

AbstractToluene diisocyanates (TDI) are commonly used in polyurethane (PU)‐related products. TDIs have been documented as the leading cause of occupational asthma. Skin exposure to TDI in the workplace is common. However, no studies in the literature have investigated the exact biomarker concentration profile for skin TDI absorption through any in vivo animal studies. In this study a rat model was used to evaluate the TDI skin absorption to explore the dose‐response pattern and to determine the kinetic characteristics of urinary toluene diamine (U‐TDA) during skin exposure. TDIs were topically exposed on the dorsum of rat skin at 0.2%, 1% and 5%. Consecutive urine samples were collected for 6 days and U‐TDA were analysed using GC/ECD. It was demonstrated in this rat study that absorption of 2,4‐ and 2,6‐TDI through skin contact is possible. A clear dose‐dependent skin absorption relationship for 2,4‐ and 2,6‐TDI was demonstrated by the AUC, Cmax findings and accumulative amounts (r ≥ 0.968). U‐TDA concentration profiles in 6‐day consecutive urine samples fit well in the first‐order kinetics, although higher order kinetics could not be excluded for the high dose. The apparent half‐lives for excretory urinary TDA were about 20 h consistent at various skin exposures. It is concluded that skin absorption of TDI was confirmed in a rat model and a clear dose‐dependent skin absorption relationship for 2,4‐ and 2,6‐TDI was demonstrated. Excretory U‐TDA concentrations in 6‐day consecutive urine samples via skin exposure reveal the first‐order kinetics and the half‐lives were about 20 h. Copyright © 2007 John Wiley & Sons, Ltd.
Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion
Authors: Struve Melanie F. , Turner Katie J. , Dorman David C. 
Published: June 2007

AbstractIn vitro, the organophosphate insecticide fenitrothion is a potent competitive androgen receptor antagonist, whereas in vivo it affects the development of the male rat reproductive system. The purpose of this pilot study was to determine whether prenatal exposure to fenitrothion affects development of the rat sexually dimorphic nucleus of the medial preoptic area (SDN‐POA). Pregnant rats (n = 5–6 litters/group) were orally dosed with corn oil (vehicle) or fenitrothion (20 or 25 mg kg−1 day−1) from gestation day (GD) 12–21. Offspring were euthanized after reaching sexual maturity (females 60–65 days old and males 96–105 days old) and the SDN‐POA volumes determined for two rats/sex/litter. Tremors, increased lacrimation and decreased body weight gain were observed in dams from both fenitrothion exposure groups. Reproductive effects in male offspring, including reduced anogenital distance on postnatal day (PND) 1 and increased retention of areolae (PND 13) were observed following fenitrothion exposure at these dose levels. These effects did not persist into adulthood. There was a dose‐related increase in the SDN‐POA volume in males and a dose‐related decrease in SDN‐POA volume in females exposed to fenitrothion. These SDN‐POA volume changes contrast with those seen with flutamide, another potent anti‐androgen, and suggest that fenitrothion may have mixed endocrine effects on the developing brain. Copyright © 2007 John Wiley & Sons, Ltd.
Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury
Authors: Zareba Grazyna , Cernichiari Elsa , Hojo Rieko , Nitt Scott Mc , Weiss Bernard , Mumtaz Moiz M. , Jones Dennis E. , Clarkson Thomas W. 
Published: June 2007

AbstractThimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg−1) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11–14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury‐treated group. In the brain, thimerosal‐exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury‐exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal‐exposed mice retained significantly higher inorganic mercury levels than methyl mercury‐treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal‐exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury. Copyright © 2007 John Wiley & Sons, Ltd.
Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy
Authors: Qin Xu‐Jun , He Wei , Hai Chun‐Xu , Liang Xin , Liu Rui 
Published: June 2007

AbstractAdriamycin is an effective anthracycline anti‐tumor antibiotic. However, the clinical use of adriamycin has been restricted by its serious side effects. Some reports indicated that the side effects of adriamycin could cause systemic injury, in which reactive oxygen species (ROS) play an important role. ROS are a large family of oxygen free radical and non‐free radical active oxygen‐containing molecules, including superoxide radical, hydrogen peroxide and hydroxyl radical, which contribute to oxidative stress. Although antioxidant treatment is a promising method to prevent the side effects, protection by a single antioxidant is limited. The Chinese herbal medicine ANTIOXIN is a multiple antioxidant that can effectively block oxidative stress. It was hypothesized that ANTIOXIN could effectively reduce the side effects of adriamycin. A rat tumor model with a transplanted tumor in the liver was treated with adriamycin and ANTIOXIN was used as a protection. Oxidative stress and antioxidant enzymes were evaluated. The results showed that adriamycin chemotherapy increased the level of malondialdehyde (MDA), nitrogen oxide (NO) and decreased the activities of total superoxide dismutase (T‐SOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAC). Adriamycin chemotherapy also decreased the expression of Bcl‐2, increased the expression of iNOS and cell apoptosis in the liver and kidney. Multiple antioxidants ANTIOXIN had an antagonistic effect on these changes and significantly decreased the mortality of the experimental rats. These data demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of ‘multiple antioxidant chain’ had effective protection. Copyright © 2007 John Wiley & Sons, Ltd.
On the independence number of the Erdős‐Rényi and projective norm graphs and a related hypergraph
Authors: Mubayi Dhruv , Williford Jason 
Published: June 2007

AbstractThe Erdős‐Rényi and Projective Norm graphs are algebraically defined graphs that have proved useful in supplying constructions in extremal graph theory and Ramsey theory. Their eigenvalues have been computed and this yields an upper bound on their independence number. Here we show that in many cases, this upper bound is sharp in the order of magnitude. Our result for the Erdős‐Rényi graph has the following reformulation: the maximum size of a family of mutually non‐orthogonal lines in a vector space of dimension three over the finite field of order q is of order q3/2. We also prove that every subset of vertices of size greater than q2/2 + q3/2 + O(q) in the Erdős‐Rényi graph contains a triangle. This shows that an old construction of Parsons is asymptotically sharp. Several related results and open problems are provided. © 2007 Wiley Periodicals, Inc. J Graph Theory 56: 113–127, 2007
Synthesis of carbon‐14‐labeled isotopomer of 6‐(4‐methanesulfonylphenyl)‐5‐[4‐(2‐piperidin‐1‐yl‐ethoxy)phenoxy]‐naphthalen‐2‐ol HCL salt (LY2066948‐[14C] HCL salt)
Authors: Kuo Fengjiun , Clodfelter Dean K. , Priest Tamara R. 
Published: June 2007

AbstractCarbon‐14‐labeled 6‐(4‐methanesulfonylphenyl)‐5‐[4‐(2‐piperidin‐1‐yl‐ethoxy)phenoxy]naphthalen‐2‐ol, a novel selective estrogen receptor modulator (SERM) was synthesized. The key component, 6‐methoxy‐1‐tetralone‐[carbonyl‐14C], was synthesized from 3‐(3‐methoxyphenyl)‐propionic acid via an intra‐molecular Friedel–Crafts acylation of 4‐(3‐methoxyphenyl)butanoic acid‐[carboxy‐14C]. A palladium catalyzed alpha‐keto arylation of 6‐methoxy‐1‐tetralone with 4‐methanesulfonyl‐phenyl bromide, followed by a sequence of bromination, DDQ dehydrogenation, aryl Ullmann reaction, and demethylation with BBr3 gave the desired product LY2066948‐[14C]. Copyright © 2007 John Wiley & Sons, Ltd.
Interaction of Polyelectrolytes with Proteins, 3
Authors: Shalova Irina N. , Naletova Irina N. , Saso Luciano , Muronetz Vladimir I. , Izumrudov Vladimir A. 
Published: June 2007

AbstractThe ability of quaternized polyamines (poly‐N‐alkyl‐4‐vinylpyridinium bromides possessing a number, m, of methylene groups in the N‐alkyl substituent or a degree of alkylation, β, and n,n‐ionene bromides) to suppress the thermoaggregation of glyceraldehyde‐3‐phosphate dehydrogenase increased in the order m = 1 < 3 < 5, β = 95 < 85 < 70 $\ll$ 45 < 35 < 20 and n = 3 < 6 < 10, which agrees well with the increase, in the same order, in the hydrophobicity of the chains. Complexing suppressed thermoaggregation, but not thermodenaturation of the enzyme, which was even encouraged by the polycations and occurred at room temperature when the most efficient suppressor (with β = 20) was used. The adverse effect was reduced by the addition of sodium chloride which destroyed the complex and resulted in a noticeable reactivation.magnified image