bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck
Authors: Ho Tang , Wei Qingyi , Sturgis Erich M.
Published: February 2007

The risk association between tobacco and alcohol use with squamous cell carcinoma of the head and neck (SCCHN) is well recognized. However, clearly not all individuals who smoke or drink develop SCCHN. Individual genetic susceptibility differences in carcinogen‐metabolizing enzyme function, mutagen sensitivity, apoptosis, and chromosomal aberrations either alone or in combination have been theorized to modify the risk of SCCHN. Nearly all carcinogens and procarcinogens require activation by metabolizing enzymes. Similarly, detoxifying enzymes exist and deactivate carcinogens as well as their intermediate by‐products. Together these enzymes are termed xenobiotic‐metabolizing enzymes; genetic polymorphisms of these enzymes can modify an individual's response to carcinogens and hence the carcinogenic potential of such exposures. In this review, we explore the available evidence in recent literature regarding the risk association between SCCHN and various xenobiotic‐metabolizing enzymes, including cytochrome P450s, glutathione S‐transferases, N‐acetyltransferases, NAD(P)H:quinone oxidoreductase 1, alcohol dehydrogenase, and aldehyde dehydrogenase. © 2007 Wiley Periodicals, Inc. Head Neck 2007
The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance
Authors: Schittek Birgit , Psenner Karin , Sauer Birgit , Meier Friedegund , Iftner Thomas , Garbe Claus
Published: February 2007

In previous studies we identified the transcription/translation factor Y‐box‐binding protein (YB‐1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB‐1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB‐1 expression is increased in melanoma cells in vitro and in vivo and that YB‐1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB‐1 in melanoma progression we achieved a stable downregulation of YB‐1 using shRNA in metastatic melanoma cells. Interestingly, YB‐1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three‐dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP‐2, bcl‐2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB‐1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB‐1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB‐1 may be a promising molecular target in melanoma therapy. © 2007 Wiley‐Liss, Inc.
Genetic redundancy in human cervical carcinoma cells: Identification of cells with “normal” properties
Authors: Bachmann Anastasia , Zawatzky Rainer , Rösl Frank
Published: February 2007

Although it is generally assumed that cancer arises from a singular cell, a tumor must be considered as a dynamic and emergent biological structure, whose organizing principle is determined by genetic and epigenetic modifications, occurring variably in response to microenvironmental selection conditions. As previously shown, HPV‐positive cervical carcinoma cells have lost their ability to induce IFN‐β upon TNF‐α treatment. However, regarding cancer as a non‐linear system, which may, even in the absence of an apparent selection pressure, fluctuate between different “metastable” phenotypes, we demonstrate that TNF‐α mediated IFN‐β induction is not irreversibly disturbed in all cells. Using the IFN‐β sensitive Encephalomyocarditis virus (EMCV) as a tool to monitor antiviral activity in long‐term established malignant HeLa cells, rare IFN‐β expressing clones were rescued from a population of non‐responsive and EMCV‐sensitive cells. Antiviral activity was mediated by the re‐expression of IRF‐1 and p48 (IRF‐9), both key regulatory molecules normally found to be suppressed in cervical carcinoma cells. Upon inoculating of selected clones into immunocompromised animals, a reduced or even an absence of tumorigenicity of initially highly malignant cells could be discerned. These data indicate that both the absence of interferon signaling and the ability to form tumors were reversed in a minority of cells. We provide a paradigm for the existence of innate genetic redundancy mechanisms, where a particular phenotype persists and can be isolated without application of drugs generally changing the epigenetic context. © 2007 Wiley‐Liss, Inc.
Body mass index and pancreatic cancer risk: A meta‐analysis of prospective studies
Authors: Larsson Susanna C. , Orsini Nicola , Wolk Alicja
Published: February 2007

A number of studies have examined the association between body mass index (BMI) and risk of pancreatic cancer, but uncertainty about the relationship remains. We performed a meta‐analysis to summarize the evidence from prospective studies investigating this association. We searched MEDLINE for studies published in any language from 1966 to November 2006. Prospective studies were included if they reported relative risks (RRs) with 95% confidence intervals (CIs) for the association between BMI and pancreatic cancer incidence or mortality. Study‐specific RR estimates were combined by use of a random‐effects model. A total of 21 independent prospective studies, involving 3,495,981 individuals and 8,062 pancreatic cancer cases, met the inclusion criteria. The estimated summary RR of pancreatic cancer per 5 kg/m2 increase in BMI was 1.12 (95% CI, 1.06–1.17; p‐heterogeneity = 0.13) in men and women combined, 1.16 (95% CI, 1.05–1.28; p‐heterogeneity = 0.001) in men, and 1.10 (95% CI, 1.02–1.19; p‐heterogeneity = 0.12) in women. There was no evidence of publication bias (p = 0.58). Findings from this meta‐analysis of prospective studies support a positive association between BMI and risk of pancreatic cancer in men and women. © 2007 Wiley‐Liss, Inc.
Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas
Authors: Kaz Andrew , Kim Young‐Ho , Dzieciatkowski Slavomir , Lynch Henry , Watson Patrice , Kay Washington Mary , Lin Li , Grady William M.
Published: February 2007

Colorectal cancer (CRC) forms through a series of histologic steps that are accompanied by mutations and epigenetic alterations, which is called the polyp‐cancer sequence. The role of epigenetic alterations, such as aberrant DNA methylation, in the polyp‐cancer sequence in sporadic CRC and particularly in hereditary colon cancer is not well understood. Consequently, we assessed the methylation status of CDKN2A/p16, MGMT, MLH1 and p14ARF in adenomas arising in the Lynch syndrome, a familial colon cancer syndrome caused by MLH1 and MSH2 mutations, to determine if DNA methylation is a “second hit” mechanism in CRC and to characterize the role of DNA methylation in the polyp phase of the Lynch syndrome. We found MLH1 and p14ARF are methylated in 53 and 60% of the Lynch syndrome adenomas and in 4 and 20% of sporadic adenomas, whereas CDKN2A/p16 and MGMT are methylated in 6 and 14% of the Lynch syndrome adenomas versus 50 and 64% of sporadic adenomas. Therefore, the frequency and pattern of gene methylation varies between the Lynch syndrome and sporadic colon adenomas, implying differences in the molecular pathogenesis of the tumors. MLH1 methylation in the Lynch syndrome adenomas suggests gene methylation might have a role in the initiation of these neoplasms. © 2007 Wiley‐Liss, Inc.
Dynamic stromal‐epithelial interactions during progression of MCF10DCIS.com xenografts
Authors: Tait Larry R. , Pauley Robert J. , Santner Steven J. , Heppner Gloria H. , Heng Henry H. , Rak Janusz W. , Miller Fred R.
Published: February 2007

MCF10DCIS.com cells form comedo type ductal carcinoma in situ in immune‐deficient mice before forming invasive ductal carcinoma. As the lesions mature, both stromal and epithelial cells undergo phenotypic changes detected by immunohistochemistry. Myofibroblasts are present before the formation of carcinoma in situ and after development of invasive carcinoma. MCF10DCIS. com lesions develop a myoepithelial layer prior to exhibiting a basement membrane surrounding the ductal mass. TGFβ1 is initially expressed by the epithelial cells but is expressed by stroma in invasive carcinoma. Stromal derived factor‐1 is detected in epithelial cells in early carcinoma in situ but is produced in stromal cells in invasive carcinoma. The receptor CXCR4 is expressed by epithelial cells in the xenografts at all times, as is the hepatocyte growth factor receptor c‐met. MCF10DCIS.com xenografts illustrate the dynamic interplay of epithelium and stroma in the development of carcinoma in situ and subsequent invasive carcinoma. Although the phenotype of the epithelial cells may be dependent upon the stroma, the malignant epithelium induces the development of the stroma necessary for progression to the invasive stage. © 2007 Wiley‐Liss, Inc.
Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre‐pulse inhibition and open field behavior in mice
Authors: Dubovicky M. , Paton S. , Morris M. , Mach M. , Lucot J. B.
Published: February 2007

The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre‐pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg−1day−1for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non‐significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. Copyright © 2007 John Wiley & Sons, Ltd.
Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesis
Authors: Harvey Philip W. , Everett David J. , Springall Christopher J.
Published: February 2007

The adrenal is the most common toxicological target organ in the endocrine system in vivo and yet it is neglected in regulatory endocrine disruption screening and testing. There has been a recent marked increase in interest in adrenal toxicity, but there are no standardised approaches for assessment. Consequently, a strategy is proposed to evaluate adrenocortical toxicity. Human adrenal conditions are reviewed and adrenocortical suppression, known to have been iatrogenically induced leading to Addisonian crisis and death, is identified as the toxicological hazard of most concern. The consequences of inhibition of key steroidogenic enzymes and the possible toxicological modulation of other adrenal conditions are also highlighted. The proposed strategy involves an in vivo rodent adrenal competency test based on ACTH challenge to specifically examine adrenocortical suppression. The H295R human adrenocortical carcinoma cell line is also proposed to identify molecular targets, and is useful for measuring steroids, enzymes or gene expression. Hypothalamo‐pituitary‐adrenal endocrinology relevant to rodent and human toxicology is reviewed (with an emphasis on multi‐endocrine axis effects on the adrenal and also how the adrenal affects a variety of other hormones) and the endocrinology of the H295R cell line is also described. Chemicals known to induce adrenocortical toxicity are reviewed and over 60 examples of compounds and their confirmed steroidogenic targets are presented, with much of this work published very recently using H295R cell systems. In proposing a strategy for adrenocortical toxicity assessment, the outlined techniques will provide hazard assessment data but it will be regulatory agencies that must consider the significance of such data in risk extrapolation models. The cases of etomindate and aminoglutethimide induced adrenal suppression are clearly documented examples of iatrogenic adrenal toxicity in humans. Environmentally, sentinel species, such as fish, have also shown evidence of adrenal endocrine disruption attributed to exposure to chemicals. The extent of human sub‐clinical adrenal effects from environmental chemical exposures is unknown, and the extent to which environmental chemicals may act as a contributory factor to human adrenal conditions following chronic low‐level exposures will remain unknown unless purposefully studied. Copyright © 2007 John Wiley & Sons, Ltd.
Pre‐culture period of mesenchymal stem cells in osteogenic media influences their in vivo bone forming potential
Authors: Castano‐Izquierdo Harold , Álvarez‐Barreto José , Dolder Juliette van den , Jansen John A. , Mikos Antonios G. , Sikavitsas Vassilios I.
Published: February 2007

The objective of this study was to investigate if the in vitro pre‐culture period in osteogenic media of rat mesenchymal stem cells (MSCs), influences their ability to regenerate bone when implanted in a critical size cranial defect. MSCs were harvested from the bone marrow of 6–8 weeks old male Fisher rats and expanded in vitro in osteogenic media for different time periods (4, 10, and 16 days) in tissue culture plates (TCP), seeded on sintered titanium fiber meshes without the extracellular matrix (ECM) generated in vitro, and implanted in the rat cranium after 12 h. Thirty two adult Fisher rats received the implants, divided in four groups. Three groups were implanted with cells cultured for 4, 10, or 16 days in osteogenic media and at that time their alkaline phosphatase activity and mineral deposition denoted that they were at different stages of their osteoblastic maturation (undifferentiated MSC, committed, and mature Osteoblasts, respectively). MSCs cultured without osteogenic media for 6 days were used as controls. The constructs were retrieved 4 weeks later and processed for histomorphometric analysis. Implants seeded with cells that have been cultured with osteogenic media for only 4 days revealed the highest bone formation. The lowest bone formation was obtained with the implants seeded with MSCs cultured for 16 days in the presence of osteogenic media. The results of this study suggested that the in vitro pre‐culture period of MSCs is a critical factor for their ability to regenerate bone when implanted to an orthotopic site. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Design of a biomimetic polymer‐composite hip prosthesis
Authors: Bougherara Habiba , Bureau Martin , Campbell Melissa , Vadean Aurelian , Yahia L'Hocine
Published: February 2007

A new biomimetic composite hip prosthesis (stem) was designed to obtain properties similar to those of the contiguous bone, in particular stiffness, to allow normal loading of the surrounding femoral bone. This normal loading would reduce excessive stress shielding, known to result in bone loss, and micromotions at the bone‐implant interface, leading to aseptic prosthetic loosening. The design proposed is based on a hollow substructure made of hydroxyapatite‐coated, continuous carbon fiber (CF) reinforced polyamide 12 (PA12) composite with an internal soft polymer‐based core. Different composite configurations were studied to match the properties of host tissue. Nonlinear three‐dimensional analysis of the hip prosthesis was carried out using a three‐dimensional finite element bone model based on the composite femur. The performance of composite‐based hip and titanium alloy‐based (Ti‐6Al‐4V) stems embedded into femoral bone was compared. The effect of core stiffness and ply configuration was also analyzed. Results show that stresses in composite stem are lower than those in Ti stem, and that the femoral bone implanted with composite structure sustains more load than the one implanted with Ti stem. Micromotions in the composite stem are significantly smaller than those in Ti stem over the entire bone‐implant surface because of the favorable interfacial stress distribution. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
RUNX regulates stem cell proliferation and differentiation: Insights from studies of C. elegans
Authors: Kagoshima Hiroshi , Shigesada Katsuya , Kohara Yuji
Published: February 2007

The RUNX genes encode conserved transcription factors that play vital roles in the development of various animals and human diseases. Recent studies by a few groups including ours have demonstrated that this gene family, as represented by a single ortholog designeated rnt‐1, also occurs and plays intriguing roles in the simple model organism, Caenorhabditis elegans. Our genetic and molecular analyses revealed that rnt‐1 is allelic to mab‐2, which had previously been known to cause an abnormal development of the male tail. rnt‐1 was further shown to be predominantly expressed in the stem cell‐like lateral seam hypodermal cells. These cells are characterized by their abilities to undergo stem cell‐like asymmetric divisions giving rise to self‐renewing seam cells and various differentiated descendants of hypodermal and neuronal fates. We found that rnt‐1 mutants exhibit an impaired asymmetry in the division of T cells, the posterior‐most member of the seam cells. Mutant analysis indicated that rnt‐1 is involved in regulating T blast cell polarity in cooperation with the Wnt signaling pathway. On the other hand, Nimmo et al. independently discovered that rnt‐1 acts as a rate limiting regulator of cell proliferation in the seam cells, V1‐6. In this review, we will outline these new findings and discuss their general implications in the mechanism of coordination between proliferation and differentiation of stem cells. J. Cell. Biochem. 100: 1119–1130, 2007. © 2007 Wiley‐Liss, Inc.
Stromal biology of pancreatic cancer
Authors: Chu Gerald C. , Kimmelman Alec C. , Hezel Aram F. , DePinho Ronald A.
Published: February 2007

The genetic paradigm of cancer, focused largely on sequential molecular aberrations and associated biological impact in the neoplastic cell compartment of malignant tumors, has dominated our view of cancer pathogenesis. For the most part, this conceptualization has overlooked the dynamic and complex contributions of the surrounding microenvironment comprised of non‐tumor cells (stroma) that may resist, react to, and/or foster tumor development. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease in which a prominent tumor stroma compartment is a defining characteristic. Indeed, the bulk of PDAC tumor volume consists of non‐neoplastic fibroblastic, vascular, and inflammatory cells surrounded by immense quantities of extracellular matrix, far exceeding that found in most other tumor types. Remarkably, little is known about the composition and physiology of the PDAC tumor microenvironment, in particular, the role of stroma in tumor initiation and progression. This review attempts to define key challenges, opportunities and state‐of‐knowledge relating to the PDAC microenvironment research with an emphasis on how inflammatory processes and key cancer pathways may shape the ontogeny of the tumor stroma. Such knowledge may be used to understand the evolution and biology of this lethal cancer and may convert these insights into new points of therapeutic intervention. J. Cell. Biochem. 101: 887–907, 2007. © 2007 Wiley‐Liss, Inc.
Tl(I)‐the strongest structure‐breaking metal ion in water? A quantum mechanical/molecular mechanical simulation study
Authors: Vchirawongkwin Viwat , Hofer Thomas S. , Randolf Bernhard R. , Rode Bernd M.
Published: February 2007

Structural and dynamical properties of the Tl(I) ion in dilute aqueous solution have been investigated by ab initio quantum mechanics in combination with molecular mechanics. The first shell plus a part of the second shell were treated by quantum mechanics at Hartree‐Fock level, the rest of the system was described by an ab initio constructed potential. The radial distribution functions indicate two different bond lengths (2.79 and 3.16 Å) in the first hydration shell, in good agreement with large‐angle X‐ray scattering and extended X‐ray absorption fine structure spectroscopy results. The average first shell coordination number was found as 5.9, and several other structural parameters such as coordination number distributions, angular distribution functions, and tilt‐ and θ‐angle distributions were evaluated. The ion–ligand vibration spectrum and reorientational times were obtained via velocity auto correlation functions. The TlO stretching force constant is very weak with 5.0 N m−1. During the simulation, numerous water exchange processes took place between first and second hydration shell and between second shell and bulk. The mean ligand residence times for the first and second shell were determined as 1.3 and 1.5 ps, respectively, indicating Tl(I) to be a typical “structure‐breaker”. The calculated hydration energy of −84 ± 16 kcal mol−1 agrees well with the experimental value of −81 kcal mol−1. All data obtained for structure and dynamics of hydrated Tl(I) characterize this ion as a very special case among all monovalent metal ions, being the most potent “structure‐breaker”, but at the same time forming a distinct second hydration shell and thus having a far‐reaching influence on the solvent structure. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Kinetic mechanism of the hydrogen abstraction reactions of the chlorine atoms with CH3CF2Cl and CH3CFCl2: A dual level direct dynamics study
Authors: Ji Yue‐meng , Zhao Xiao‐lei , Li Ze‐sheng , Liu Jing‐yao
Published: February 2007

The mechanisms of the reactions: CH3CFCl2 + Cl (R1) and CH3CF2Cl + Cl (R2) are studied over a wide temperature range (200–3000 K) using the dual‐level direct dynamics method. The minimum energy path calculation is carried out at the MP2/6‐311G(d,p) and B3LYP/6‐311G(d,p) levels, and energetic information is further refined by the G3(MP2) theory. The H‐abstraction from the out‐of‐plane for (R1) is the major reaction channel, while the in‐plane H‐abstraction is the predominant route of (R2). The canonical variational transition‐state theory (CVT) with the small‐curvature tunneling (SCT) correction method is used to calculate the rate constants. Using group‐balanced isodesmic reactions and hydrogenation reactions as working chemical reactions, the standard enthalpies of formation for CH3CFCl2, CH3CF2Cl, CH2CFCl2, and CH2CF2Cl are evaluated at the CCSD(T)/6‐311 + G(3df,2p)//MP2/6‐311G(d,p) level of theory. The results indicate that the substitution of fluorine atom for the chlorine atom leads to a decrease in the CH bond reactivity with a small increase in reaction enthalpies. Also, for all reaction pathways the variational effect is small and the SCT effect is only important in the lower temperature range on the rate constants. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Computation of large systems with an economic basis set: Structures and reactivity indices of nucleic acid base pairs from density functional theory
Authors: Fan W. J. , Zhang R. Q. , Liu Shubin
Published: February 2007

We show here that an economic basis set can describe nucleic acid base pairs involving the hydrogen bond interactions in density functional calculations. The economic basis set in which the polarization function is added only to oxygen and nitrogen atoms of strong electronegativity can predict reliable geometric structures and dipole moment of nucleic acid base pairs, comparable to those obtained from the basis set of 6‐31G* in B3LYP calculations. Combining single point calculations with the standard basis set on the geometric structures optimized by the economic basis set, the present approach has predicted accurate natural bond orbital charge, binding energy, electronegativity, hardness, softness, and electrophilicity index. The principle for basis selection presented in this study can be regarded as a general guideline in the computation of large biological systems with considerably high accuracy and low computational expense. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
About paths with two blocks
Authors: Sahili Amine El , Kouider Mekkia
Published: February 2007

The function f(n) is defined to be the smallest integer such that any f(n)‐chromatic digraph contains all paths with two blocks P(k,j) with k + j = n − 1. El Sahili conjectured that f(n) = n. We prove in this paper that f(n) ≤ n + 1. Our argument yields a very short and direct proof of the Gallai–Roy result about directed paths. We also treat the problem under some supplementary conditions. One of them is used to give a simple proof of a result of Saks and Sós about claws. © 2007 Wiley Periodicals, Inc. J Graph Theory 55: 221–226, 2007
Effect of dietary supplementation with vitamin E on characteristics of vacuum‐packed lamb
Authors: de la Fuente Jesús , Díaz Maria Teresa , Álvarez Inmaculada , Lauzurica Sara , Cañeque Vicente , Pérez Concha
Published: February 2007

The effect of dietary vitamin E supplementation on lamb during vacuum‐packed storage was studied. Thirty‐six weaned male Manchego breed lambs were offered four dietary treatments (20, 270, 520 and 1020 mg vitamin E kg−1 feed). Lambs were fed the vitamin E‐supplemented diet from 13 until 26 kg live weight. Pieces of M. longissimus dorsi were stored under vacuum at 2 ± 1 °C in the dark and meat quality was assessed after 5, 14 and 28 days of storage. Dietary supplementation significantly increased the α‐tocopherol concentration in the muscle (P < 0.001). Initially, lipid oxidation, meat colour and bacterial load were similar in all groups. In meat of non‐supplemented lambs the thiobarbituric acid reactive substance value increased throughout storage, whereas in meat of supplemented lambs it did not increase. Meat pigments and discolouration proportion were significantly affected by storage time (P < 0.001). The bacterial load was low initially, but after 28 days of storage it was close to 7 log10 colony‐forming units (cfu) cm−2 and Enterobacteriaceae surpassed the limit of acceptability of 2.5 log10 cfu cm−2, making the lamb unsuitable for human consumption. Meat of supplemented lambs displayed less lipid oxidation than that of their non‐supplemented counterparts, while meat colour and bacterial load were not affected by supplementation. Copyright © 2007 Society of Chemical Industry
Iron and zinc concentration of native Andean potato cultivars from a human nutrition perspective
Authors: Burgos Gabriela , Amoros Walter , Morote Maximo , Stangoulis James , Bonierbale Merideth
Published: February 2007

The determination of iron (Fe) and zinc (Zn) concentrations in 49 native Andean potato varieties revealed significant genotypic variation. Comparison of mineral concentrations of 37 of these germplasm accessions grown in two highland locations further revealed significant variation due to environments and genotype × environment interaction. Concentrations in raw, peeled tubers ranged from 9 to 37 mg Fe kg−1 and 8 to 20 mg Zn kg−1 (dry weight) with accessions 703274 and 701165 showing the highest levels of Fe and Zn, respectively, in both locations. Fe and Zn concentrations were significantly and positively correlated on a fresh weight basis in each site. Assessment of Fe and Zn retention during processing revealed no losses due to cooking, and the only significant differences found in iron content of peeled versus unpeeled potatoes could be attributed to contamination with soil iron, as confirmed by elevated levels of aluminium in the samples. The ranges of micronutrient concentrations reported indicate ample genetic diversity that might be exploited in breeding programmes seeking to increase Fe and Zn levels in human diets. Copyright © 2007 Society of Chemical Industry
Enantiomeric resolution of new triazole compounds by high‐performance liquid chromatography
Authors: Lv Chunguang , Jia Guifang , Zhu Wentao , Qiu Jing , Wang Xinquan , Zhou Zhiqiang
Published: February 2007

Cellulose tris(3,5‐dimethylphenylcarbamate) (CDMPC) was synthesized and coated on aminopropylsilica to prepare a chiral stationary phase (CSP). HPLC methods were developed for the direct enantioseparation of 12 chiral triazole compounds on the CSP. The separations were made using normal phase methodology with a mobile phase consisting of n‐hexane‐alcohol (ethanol, 1‐propanol, 1‐butanol, 2‐propanol, and t‐butanol) in various portions. The column temperatures were studied for the optimization of the resolutions. The effects of structural features of the solutes on the discrimination between the enantiomers were examined. Baseline separation was easily obtained in many cases.
Determination of methylmalonic acid and glutaric acid in urine by aqueous‐phase derivatization followed by headspace solid‐phase microextraction and gas chromatography‐mass spectrometry
Authors: Li Ning , Deng Chunhui , Zhang Xiangmin
Published: February 2007

In this work, a novel technique of aqueous‐phase derivatization followed by headspace solid‐phase microextraction and gas chromatography‐mass spectrometry was developed for the determination of organic acids in urine. The analytical procedure involves derivatization of organic acids to their ethyl esters with diethyl sulfate, headspace sampling, and GC/MS analysis. The proposed method was applied to the determination of methylmalonic acid and glutaric acid in urine. The experimental parameters and method validation were studied. Optimal conditions were obtained: PDMS fiber, extraction temperature 55°C, extraction time 30 min, and 60 μL of diethyl sulfate as derivatization reagent with 2 mg of the ion pairing agent tetrabutylammonium hydrogensulfate. The method was linear over three orders of magnitude, and detection limits were 21 nM for methylmalonic acid and 34 nM for glutaric acid, respectively. Consequently, in‐situ derivatization/HS‐SPME/GC/MS is an alternative and powerful method for determination of organic acids as biomarkers in biological fluids.
Recent advances in capillary electrophoresis for biomarker discovery
Authors: Bakry Rania , Huck Christian W. , Najam‐ul‐Haq Muhammed , Rainer Matthias , Bonn Günther K.
Published: February 2007

The use of non‐invasive methods for detecting biomarkers opens a new era in patient care, since clinical investigators have long been searching for accurate and reproducible measurements of putative biomarkers. There are many factors which make this research challenging, beginning with lack of standardization of sample collection and continuing through the entire analytical procedure. Among the variety of methods so far used for biomarker screening, capillary electrophoresis represents a robust, reliable, and widely used analytical tool. This review will focus on recent applications of CE to the analysis of body fluids and tissues for identification of biomarkers.
Global boundary regularity for the $ \bar \partial $‐equation on q‐pseudoconvex domains
Authors: Ahn Heungju
Published: February 2007

We introduce a notion of q ‐pseudoconvex domain of new type for a bounded domain of ℂn and prove that for given a $ \bar \partial $‐closed (p, r)‐form, r ≥ q, that is smooth up to the boundary, there exists a (p, r – 1)‐form smooth up to the boundary which is a solution of $ \bar \partial $‐equation on a bounded q ‐pseudoconvex domain. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Cousin problem for systems of PDE
Authors: Shankar Shiva
Published: February 2007

This article formulates an additive Cousin type problem for systems of partial differential equations. The obstruction to the solution of this problem, like the obstruction in the classical Cousin problem, lies in a first cohomology module, viz. in an Ext1 module associated to the problem. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Some degenerate elliptic systems and applications to cusped plates
Authors: Jaiani G. , Schulze B.‐W.
Published: February 2007

We study the tension‐compression vibration of an elastic cusped plate under (all reasonable) boundary conditions at the cusped edge and given displacements at the non‐cusped edge and stresses at the upper and lower faces of the plate. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: Results from a multi‐center, randomized, active controlled trial
Authors: Trenkwalder Claudia , Benes Heike , Grote Ludger , Happe Svenja , Högl Birgit , Mathis Johannes , Saletu‐Zyhlarz Gerda M. , Kohnen Ralf ,   CALDIR study group
Published: February 2007

We report the first large‐scale double‐blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 ± 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 ± 6.8. The baseline‐adjusted mean change from baseline to week 6 in IRLS sum score was d = −16.1 in the CAB group and d = −9.5 in the levodopa group (d = −6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log‐rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large‐scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30‐week long‐term therapy. Tolerability was found more favorable with levodopa than with cabergoline. © 2007 Movement Disorder Society
Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence
Authors: Edwall Lena , Carlström Kjell , Jonasson Aino Fianu
Published: February 2007

Aims

To investigate possible differences in androgen/estrogen status between patients with stress urinary incontinence (SUI) and healthy women's and to study possible associations between circulating estrogens and androgens on the one hand and collagen synthesis and metabolism in urogenital tissue on the other.

Methods

Markers of collagen turnover, the carboxy‐terminal propeptide of type I procollagen (PICP), the carboxy‐terminal telopeptide of type I collagen (ICTP), and the amino‐terminal propeptide of procollagen III (PIIINP), were assayed in urogenital tissue homogenates and estradiol‐17β (E2), total testosterone (T), and sex‐hormone‐binding globulin (SHBG) were assayed in peripheral serum from 58 patients with SUI and 30 urologically healthy women. Apparent concentrations of free testosterone (fT) were calculated from T, SHBG, and a fixed albumin value.

Results

Significant positive correlations were found between E2 and PICP in controls and between E2 and ICTP in SUI patients without exogenous hormones. Significant negative and sometimes strong correlations were found between serum T and fT on the one hand and all three collagen turnover markers on the other. These correlations were strengthened when parity and/or body mass index (BMI) were reduced. No correlations between T and fT and collagen turnover markers were found in the controls. There were no significant differences between any of the groups in serum E2, T, or fT.

Conclusion

Estrogens may increase collagen turnover in urogenital tissue, however, the clinical significance of this is still unclear. Androgens may affect urogenital tissue negatively by slowing down collagen turnover, probably by inhibition of matrix metalloprotease (MMP) synthesis and/or activity. Urogenital tissue in SUI patients and in urologically healthy women may differ in androgen sensitivity. Neurourol. Urodynam. 26:410–415, 2007. © 2007 Wiley‐Liss, Inc.
Pre‐junctional α2‐adrenoceptors modulation of the nitrergic transmission in the pig urinary bladder neck
Authors: Hernández Medardo , Recio Paz , Victoria Barahona María , Bustamante Salvador , Peña Lidia , Cristina Martínez Ana , García‐Sacristán Albino , Prieto Dolores , Orensanz Luis M.
Published: February 2007

Aims

To investigate the nitric oxide (NO)‐mediated nerve relaxation and its possible modulation by pre‐junctional α2‐adrenoceptors in the pig urinary bladder neck.

Methods

Urothelium‐denuded bladder neck strips were dissected, and mounted in isolated organ baths containing a physiological saline solution (PSS) at 37°C and continuously gassed with 5% CO2 and 95% O2, for isometric force recording. The relaxations to transmural nerve stimulation (electrical field stimulation [EFS]) or exogenously applied NO were carried out on strips pre‐contracted with 1 µM phenylephrine (PhE) and treated with guanethidine (10 µM) and atropine (0.1 µM), to block noradrenergic neurotransmission and muscarinic receptors, respectively.

Results

EFS (0.2–1 Hz, 1 msec duration, 20 sec trains, current output adjusted to 75 mA) evoked frequency‐dependent relaxations which were abolished by the neuronal voltage‐activated Na+ channel blocker tetrodotoxin (TTX, 1 µM). These responses were potently reduced by the nitric oxide synthase (NOS) inhibitor NG‐nitro‐L‐arginine (L‐NOARG, 30 µM) and further reversed by the NO synthesis substrate L‐arginine (L‐ARG, 3 mM). The α2‐adrenoceptor agonist BHT‐920 (2 µM) reduced the electrically evoked relaxations, its effectiveness being higher on the responses induced by low frequency stimulation. BHT‐920‐elicited reductions were fully reversed by the α2‐adrenoceptor antagonist rauwolscine (RAW, 1 µM). Exogenous NO (1 µM–1 mM) induced concentration‐dependent relaxations which were not modified by BHT‐920, thus eliminating a possible post‐junctional modulation.

Conclusions

These results indicate that NO is involved in the non‐adrenergic non‐cholinergic (NANC) inhibitory neurotransmission in the pig urinary bladder neck, the release of NO from intramural nerves being modulated by pre‐junctional α2‐adrenoceptor stimulation. Neurourol. Urodynam. 26:578–583, 2007. © 2007 Wiley‐Liss, Inc.
Role of urothelial nerve growth factor in human bladder function
Authors: Birder Lori A. , Wolf‐Johnston Amanda , Griffiths Derek , Resnick Neil M.
Published: February 2007

Aims

To test whether nerve growth factor (NGF) concentration in human bladder urothelium/suburothelium is related to detrusor overactivity (DO), bladder sensation, detrusor contractility, or other aspects of lower urinary tract function.

Materials and Methods

Concentration of NGF was measured (using ELISA) in superficial bladder biopsies from 27 women (mean age 52 years, range 22–82) after comprehensive videourodynamics and bladder diary. Approximately half (12/27) showed clear DO and half did not.

Results

There was no evidence for increased NGF concentration in subjects with DO (association negative by Mann–Whitney test, P = 0.23). NGF was not significantly associated with two measures of detrusor contractility (Spearman's r = −0.29, P = 0.17; r = −0.20, P = 0.33); nor with four measures inversely related to sensation: volume at strong desire to void and maximum capacity on cystometry (r = −0.13, P = 0.53; r = −0.23, P = 0.28), and maximum voided volume and mean daytime voided volume on bladder diary (r = −0.29, P = 0.16; r = −0.16, P = 0.44). It was significantly associated with 24‐hr urine output on bladder diary (Spearman's r = −0.55, P = 0.004).

Conclusions

Elevated NGF levels in human urothelium/suburothelium are not strongly associated with DO, detrusor contractility or increased bladder sensation. NGF levels are lower in subjects with higher 24‐hr urine output. This observation is consistent with a role for NGF in an active process (trafficking) involved in bladder filling. Neurourol. Urodynam. 26:405–409, 2007. © 2007 Wiley‐Liss, Inc.
Kinetics of PME/Pi in pig kidneys during cold ischemia
Authors: von Elverfeldt Dominik , Niekisch Miriam , Quaschning Thomas , Saman Andre El , Kirste Günter , Krämer‐Guth Annette , Hennig Jürgen
Published: February 2007

Quality assessment of renal grafts via 31P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (PiO) within the organ (PME/PiO) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross‐match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/PiO kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80 h via 31P MRS at 2 T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1 × 1 × 4 cm3, it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/PiO ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/PiO for histidine–tryptophane–alpha‐ketoglutarate (HTK)‐perfused kidneys during cold ischemia was observed, and the determined value of the decay constant α was 0.0099 ± 0.0012 h−1. In University of Wisconsin solution (UW)‐perfused kidneys, an α of 0.0183 ± 0.0053 h−1 was determined. Determination of the decay constant enables a usable extrapolation of PME/PiO for quality assessment of UW perfusion and a reliable extrapolation for HTK‐perfused human renal grafts. Copyright © 2007 John Wiley & Sons, Ltd.
Design sensitivity analysis and optimization for minimizing springback of sheet‐formed part
Authors: Yi Kiyoung , Choi K. K. , Kim Nam H. , Botkin Mark E.
Published: February 2007

The springback is a manufacturing defect in the stamping process and causes difficulty in product assembly. An impediment to the use of lighter‐weight, higher‐strength materials in manufacturing is relative lack of understanding about how these materials respond to complex forming processes. The springback can be reduced by using an optimized combination of die, punch, and blank holder shapes together with friction and blank‐holding force. An optimized process can be determined using a gradient‐based optimization to minimize the springback. For an effective optimization of the stamping process, development of an efficient design sensitivity analysis (DSA) for the springback with respect to these process parameters is crucial. A continuum‐based shape and configuration DSA method for the stamping process has been developed using a non‐linear shell model. The material derivative is used to develop the continuum‐based design sensitivity. The design sensitivity equation is solved without iteration at each converged load step in the finite deformation elastoplastic non‐linear analysis with frictional contact, which makes sensitivity calculation very efficient. Numerical implementation of the proposed shape and configuration DSA method is performed using the meshfree method. The accuracy and efficiency of the proposed method are illustrated by minimizing the springback in a benchmark S‐rail problem. Copyright © 2007 John Wiley & Sons, Ltd.
Preparation and swelling behavior of amphoteric superabsorbent composite with semi‐IPN composed of poly(acrylic acid)/Ca‐bentonite/poly(dimethyldiallylammonium chloride)
Authors: Zheng Liuchun , Xu Shimei , Peng Yang , Wang Jide , Peng Gui
Published: February 2007

Amphoteric superabsorbent composite with semi‐interpenetrating polymer networks (semi‐IPN) composed of poly(acrylic acid) (PAA)/Ca‐bentonite/poly(dimethyldiallylammonium chloride) (PDMDAAC) was prepared by a combination of intercalative polymerization and a sequential IPN method and the effects of reaction parameters on the swelling capacity were studied. PDMDAAC was used as a polycation to modify bentonite and form semi‐IPN with lightly crosslinked PAA. FTIR and TG were used to characterize the amphoteric superabsorbent composites with semi‐IPN. The thermal stability of the product was not degraded as in the case of using small molecular surfactant to modify bentonite. The contents of carboxylic groups and nitrogen had been determined. This indicated that the product with certain content of carboxylic groups and nitrogen is inclined to exhibit excellent swelling capacity. The presence of PDMDAAC improved the swelling capacity. The resulting amphoteric superabsorbent composite showed excellent swelling capacity of 1578 g/g in distilled water and 136 g/g in 0.9 wt% NaCl solution. Copyright © 2007 John Wiley & Sons, Ltd.
Immune stimulating activity of an atrophic rhinitis vaccine associated to pegylated chitosan microspheres in vitro
Authors: Jiang Hu‐Lin , Park In‐Kyu , Kang Mi‐Lan , Yoo Han‐Sang , Choi Yun‐Jaie , Akaike Toshihiro , Cho Chong‐Su
Published: February 2007

It has previously been found that chitosan microspheres are easily aggregated due to their physical and storage instabilities. In this study, to overcome their instability, chitosan was covalently conjugated with poly(ethylene glycol). Pegylated chitosan microspheres were prepared through the ionic gelation process of pegylated chitosan with tripolyphosphate. Bordetella bronchiseptica dermonecrotoxin, major virulence factor of atrophic rhinitis causative agent, was loaded onto pegylated chitosan microspheres for nasal vaccination. Average particle sizes of Bordetella bronchiseptica dermonecrotoxin‐loaded pegylated chitosan microspheres were 5.47 µm. Microspheres obtained from pegylated chitosan microspheres were physically more stable than those from chitosan microspheres, and Bordetella bronchiseptica dermonecrotoxin‐loaded pegylated chitosan microspheres released more Bordetella bronchiseptica dermonecrotoxin than Bordetella bronchiseptica dermonecrotoxin‐loaded chitosan microspheres in vitro. Macrophage RAW264.7 cells stimulated with Bordetella bronchiseptica dermonecrotoxin‐loaded pegylated chitosan microspheres gradually secreted tumor necrosis factor α and nitric oxide, suggesting that pegylated chitosan microspheres are very promising vaccine delivery systems. Copyright © 2007 John Wiley & Sons, Ltd.