bluuebunny/crossref_metadata_2025 huggingface dataset:
The Conformational Behavior of Novel Glycosidase Inhibitors with Substituted Azepan Structures: An NMR and Modeling Study
Authors: Martínez‐Mayorga Karina , Medina‐Franco José L. , Mari Silvia , Cañada F. Javier , Rodríguez‐García Eliazar , Vogel Pierre , Li Hongqing , Blériot Yves , Sinaÿ Pierre , Jiménez‐Barbero Jesús
Published: September 2004

The conformational analysis of a series of configurational isomers of 2‐(hydroxymethyl)azepan‐3,4,5,6‐tetrols 1−4 has been carried out. 1H NMR spectroscopic data, especially vicinal J couplings and nuclear Overhauser enhancements (NOE), assisted by molecular mechanics, molecular dynamics and Monte Carlo calculations, have been used. A fairly good agreement between experimental and calculated data has been found. The different isomers exist in a conformational equilibrium between two chair‐like structures. TR‐NOE experiments have also allowed us to demonstrate that the bound conformation of compound 2 to the β‐glucosidase from almonds is the major one of this compound present in solution. Finally, molecular docking of the different conformations of these compounds in the binding site of three different enzymes has been performed in order to try to rationalize the observed inhibition of these molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Functionalized 1‐Substituted Alkenylsilanols and Establishment of Conditions for Their Palladium‐Catalyzed Cross‐Coupling Reactions To Afford 1‐Substituted Styrene Derivatives
Authors: Ghosh Sunil K. , Singh Rekha , Singh Gobind C.
Published: September 2004

An efficient method for the quantitative conversion of 1‐substituted alkenyl(phenyl)silanes into the corresponding alkenylsilanols has been developed and used in their palladium(0)‐catalyzed, tetrabutylammonium fluoride‐promoted cross‐coupling reaction with aryl iodides. Copper(I) chloride modulated the reactivity of TBAF in such a way that it virtually eliminated the protiodesilylation of alkenylsilanols, thus favoring the formation of ipso‐coupled products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
1,3‐Dipolar Cycloaddition Reactions with 1,2,3‐Triazinium Ylides
Authors: Mättner Michael , Neunhoeffer Hans
Published: September 2004

1,3‐Dipolar cycloadditions were carried out with 1,2,3‐triazinium 2‐dicyanomethylylides 4 and deprotonated 2‐ethyl‐1,2,3‐triazinium salts 2. Pyrazolo[2,1‐a]‐ and pyrazolo[1,2‐b][1,2,3]triazines 5 and 9 were synthesized, representing new heterocyclic systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A Convenient New Synthesis of 3‐Substituted β‐Lactams Formally Derived from 1‐(Aminomethyl)cyclopropanecarboxylic Acids
Authors: Zanobini Alessandra , Gensini Martina , Magull Jörg , Vidović Denis , Kozhushkov Sergei I. , Brandi Alberto , de Meijere Armin
Published: September 2004

1,3‐Dipolar cycloaddition of N‐benzyl‐C‐(methoxycarbonyl)nitrone (3a), N‐benzyl‐C‐phenylnitrone (3b), N‐benzyl‐C‐cyanonitrone (3c), N‐(p‐methoxybenzyl)‐C‐cyanonitrone (3d), N‐phenyl‐ (3e) and N‐(2‐pyridyl)‐C‐methylnitrones (3f) to bicyclopropylidene (2) gave the corresponding cycloadducts 5a−f in 100, 95, 94, 100, 93 and 71% yields, respectively. Treatment of these bisspirocyclopropanated isoxazolidines with trifluoroacetic acid in acetonitrile furnished the corresponding 3‐spirocyclopropanated β‐lactams 7a−f in 78, 75, 75, 94, 96 and 96% yields, respectively. The structures of the cycloadduct 5b and of the β‐lactam 9a were proved by X‐ray crystal structure analyses. Thus, this new method furnishes compounds with a 5‐azaspiro[2.3]hexan‐4‐one skeleton in 68−94% overall yield in two simple steps. β‐Lactams 7a, 7b, and 7d were converted into their N‐acyl derivatives 9a, 9b, 9d and 11 in 44, 28, 39 and 78% yields, respectively. Heating of the β‐lactams 9b and 11 with tert‐butyl glycinate (12) or with tert‐butyl (S)‐phenylalaninate (14) in DMF led to ring‐opening of the β‐lactam moiety to give β‐dipeptides 15, 16 and 17 in 61, 84 and 79% yields, respectively, while β‐lactam 9a gave the amide 13 (51% yield). β‐Lactams 7e and 7f turned out not to be transformable into such peptide products (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Determination of the Boron/Lead Ratio in Ceramic Materials Based on Electrochemical Quartz Crystal Microbalance
Authors: Doménech‐Carbó A. , Sánchez‐Ramos S. , Yusá‐Marco D. J. , Moya‐Moreno M. , Gimeno‐Adelantado J. V. , Bosch‐Reig F.
Published: September 2004

A method for quantitatively determining the relationship boron/lead in ceramic materials is presented. It is based on the attachment of microsamples of ceramic frits to an electrochemical quartz crystal microbalance (EQCM). After a reductive deposition step in the −0.25 to −0.85 V (vs. AgCl/Ag) potential range, well‐defined stripping peaks are recorded in 0.10 M NaCl plus 0.10 M mannitol. The deposition of boron and lead from suspensions of solid materials, and its subsequent oxidative dissolution can be monitorized at the EQCM. The quotient between the maximum mass gain and the corresponding charge passed enables for a direct quantitation of the boron/lead molar ratio in ceramic materials. Addition methods based on the EQCM examination of i) sample plus lead white (2PbCO3.Pb(OH)2) and ii) sample plus Li2B4O7 mixtures are also presented. Results for boron‐containing ceramic frits are in excellent agreement with those obtained by reference methods.
Voltammetric Determination of Antibacterial Nitro‐Compounds at Activated Carbon Fibre Microelectrodes
Authors: Guzmán A. , Agüí L. , Pedrero M. , Yáñez‐Sedeño P. , Pingarrón J. M.
Published: September 2004

The electrochemical behavior of the nitrofuran antibiotics nitrofurantoin (NFA) and nitrofurazone (NFZ), as well as the related nitroimidazole drug, metronidazole (MNZ) at electrochemically activated carbon fibre microelectrodes (CFMEs) is reported. These nitrofurans have been widely used in the form of feed additives for the treatment of gastrointestinal infections in cattle, pigs and poultry. Electrochemical activation of CFMEs by repetitive square‐wave (SW) voltammetric scans between 0.0 and +2.6 V, produced an unexpected high cathodic response from these compounds. This is attributed to the increase of the carbon fibre surface area due to its fracture and the appearance of deep fissures along the main fibre axis. Penetration of the nitroderivative compounds into the micro‐channels of the activated fibres was profited to develop a sensitive and selective method for NFA based on stripping SW voltammetry. The metabolite of NFA, 1‐aminohydantoin (AHD), did not exhibit cathodic response in the potential range between −0.9 and +0.1 V. However, AHD gave a SW oxidation signal at activated CFMEs, with a potential of +0.95 V, which did not appear at non‐activated microelectrodes. Based on this finding, the simultaneous determination of NFA and AHD was performed by amperometry using two activated CFMEs in a parallel configuration connected to a multichannel detector. This methodology was also used to carry out degradation studies of NFA in acidic and basic media under photodegradation or thermal degradation conditions.
Coupled Electron‐Proton Transport in Electropolymerized Methylene Blue and the Influences of Its Protonation Level on the Rate of Electron Exchange with β‐Nicotinamide Adenine Dinucleotide
Authors: Komura T. , Niu G. Y. , Yamaguchi T. , Asano M. , Matsuda A.
Published: September 2004

This paper describes electrochemical characteristics of poly(methylene blue) electrolytically deposited on glassy carbon and examines the electrocatalytic activity of the polymer toward oxidation of the coenzyme NADH. Redox‐active properties of the cationic polyelectrolyte arose from both electron self‐exchange between electroactive sites and a high ionic film‐conductivity. The diffusion coefficient of charge carriers in the film increased with decreasing solution pH, indicating the pH dependence of the electron diffusion coefficient. The electrocatalytic oxidation of NADH at the polymer‐modified electrode proceeded via an intermediate charge‐transfer complex of the reduced polymer with the oxidized coenzyme. The complex dissociated more rapidly into the oxidation products as the reduced polymer protonated. Thus, the rate constant for the cross‐exchange reaction rose with a decrease in pH. For NADH oxidation, the polyelectrolyte exhibited an electrocatalytic activity higher than the monomeric dye because of a stronger oxidizing power of the second oxidized form of the polymer.
Comparison of an Electronic Nose with the Sensory Evaluation of Food Products by “Triangle Test”
Authors: Benedetti Simona , Pompei Carlo , Mannino Saverio
Published: September 2004

In this paper a novel approach for performing discriminative test in food quality control is reported. The method is based on the use of an electronic nose equipped with 10 Metal Oxide Semiconductor Field Effect Transistor (MOSFET) sensors, 12 Metal Oxide Semiconductor (MOS) sensors and one humidity sensor. The pattern of the sensor responses generated by the electronic nose has been used for performing “objective” triangle tests in several food products. The results were compared with the data obtained by using standard methodology (triangle test) of sensory analysis (UNI ISO 4120 Norm). The e‐nose is able to classify correctly all the samples under study, while the sensory panel is able to correctly perform the test only in 50% of the cases. As compared with the sensory test, the electronic nose methodology is simple, rapid and results suggest that it can be useful tool for performing discriminative testing.
Attachment of Amine‐ and Maleimide‐Containing Ferrocene Derivatives onto Self‐Assembled Alkanethiol and Alkanedithiol Monolayers: Voltammetric Evaluation of Cross‐Linking Efficiencies and Surface Coverage of Electroactive Groups
Authors: Wang Yunfeng , Yao Xin , Wang Jianxiu , Zhou Feimeng
Published: September 2004

Ferrocene derivatives containing primary amines and maleimide groups were attached covalently onto N‐hydrosuccinimidyl (NHS)‐terminated alkanethiol self‐assembled monolayers (SAMs) and SAMs of alkanedithiol. The surface coverage and efficiencies of the two cross‐linking reactions were evaluated with cyclic voltammetry. All the ferrocene derivatives attached onto the alkanethiol or alkanedithiol SAMs exhibit reversible redox waves. The surface coverage of the aminated ferrocene groups was compared to that of N‐hydrosuccinimidyl (NHS)‐terminated alkanethiol SAM. The covalent attachment of β‐ferrocenylethylamine onto a 11,11′‐dithio‐bis(succinimidylundecanoate) SAM yielded an efficiency as high as 63.1%. The cross‐linking efficiency of this reaction was found to increase with the nucleophilicity of the amino groups. SAMs of longer alkyl chains favor the attachment of a greater number of ferrocene derivatives. As for the Michael‐type electrophilic addition between the sulfhydryl groups of the alkanedithiol SAMs and the ferrocenyl maleimide, the cross‐linking efficiencies were found to range from 6.5% to 25.7%, depending on the alkanedithiol chain length. The difference in the efficiencies between the two types of cross‐linking reactions might be partially attributable to the steric hindrance imposed by the SAMs and the relative sizes of the functional groups.
Detecting Both Physical and (Bio‐)Chemical Parameters by Means of ISFET Devices
Authors: Poghossian Arshak , Schöning Michael J.
Published: September 2004

A multi‐parameter sensor system for the detection of eight (bio‐)chemical and physical parameters (pH, potassium concentration, penicillin concentration, diffusion coefficient of H+‐ and OH –‐ions, temperature, flow velocity, flow direction and liquid level) is realized by using the same transducer principle. A Ta2O5‐gate ISFET (ion‐sensitive field‐effect transistor) is applied as basic transducer for all kinds of sensors. The multi‐parameter detection is achieved by means of sequentially or simultaneously scheduling of the hybride sensor modules consisting of four ISFET structures and an ion generator in different sensor arrangements and/or different operation modes. Thus, more parameters (eight) can be detected than the number of sensors (four) in the system.
Revisiting the role of Broca's area in sentence processing: Syntactic integration versus syntactic working memory
Authors: Fiebach C.J. , Schlesewsky M. , Lohmann G. , von Cramon D.Y. , Friederici A.D.
Published: September 2004

Most previous neuroimaging studies of sentence processing have associated Broca's area with syntactic processing; however, the exact nature of the processes subserved by this brain region is yet not well understood. Although some authors suggest that Brodmann area (BA) 44 of the left inferior frontal gyrus (i.e., Broca's area) is relevant for syntactic integration processes, others claim that it is associated with working memory mechanisms relevant for language processing. To dissociate these two possible functions, the present study investigated hemodynamic responses elicited while participants processed German indirect wh‐questions. Activation increases were observed in left BA 44 together with superior temporal areas and right hemispheric homologues for sentences with noncanonical word order, in which a verb argument was dislocated from its canonical position over a relatively long distance. In these sentences, syntactic working memory load was assumed to be greatest. In contrast, no activation increase was elicited by object–initial as opposed to subject–initial sentences that did not differ with respect to working memory costs but with respect to syntactic integration costs. These data strongly suggest that Broca's area plays a critical role in syntactic working memory during online sentence comprehension. Hum. Brain Mapping 24:79–91, 2005. © 2004 Wiley‐Liss, Inc.
Antitumor activity of the intratumoral injection of fowlpox vectors expressing a triad of costimulatory molecules and granulocyte/macrophage colony stimulating factor in mesothelioma
Authors: Triozzi Pierre L. , Aldrich Wayne , Allen Karen O. , Lima Jose , Shaw Denise R. , Strong Theresa V.
Published: September 2004

Deficiency in costimulatory molecule expression has been implicated in the ability of tumors to escape immune effectors. The activity of the intratumoral administration of recombinant fowlpox vectors expressing a triad of costimulatory molecules (rF‐TRICOM) was evaluated in the asbestos‐induced AB12 and AC29 mouse models of mesothelioma. Mesothelioma cell infected with rF‐TRICOM expressed high levels of the costimulatory molecules. Prolongation of survival was observed in mice receiving rF‐TRICOM in AB12 and AC29 intraperitoneal models. Complete tumor regressions were observed in mice receiving intratumoral rF‐TRICOM in the AB12 subcutaneous tumor model. Tumor regressions were associated with the development of serum IgG reactivities to mesothelioma‐associated determinants and specific systemic cytolytic activity, and responding mice were capable of rejecting tumors upon re‐challenge. Antitumor activity was also observed in mice with established AB12 tumor vaccinated with irradiated rF‐TRICOM‐infected AB12 cells. The antitumor activity of intratumoral rF‐TRICOM was superior to that of the intratumoral injection of a fowlpox vector expressing granulocyte‐macrophage colony stimulating factor (rF‐GM‐CSF). AB12 and AC29 tumors were found to produce GM‐CSF and to have substantial macrophage infiltration. Production of GM‐CSF decreased in vivo in tumors injected with rF‐TRICOM. rF‐TRICOM and wild‐type fowlpox inhibited the growth of AB12 and AC29 cells in vitro; less inhibition was observed with rF‐GM‐CSF. These results indicate that the intratumoral injection of rF‐TRICOM has significant activity in mouse models of mesothelioma and can elicit a systemic antitumor immune response. The results also suggest potential limitations to the intratumoral administration of cytokines, such as GM‐CSF, in mesothelioma.
Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors
Authors: Möllemann Maria , Wolter Marietta , Felsberg Jörg , Collins V. Peter , Reifenberger Guido
Published: September 2004

Allelic losses on the chromosome arms 1p and 19q have been associated with favorable response to chemotherapy and good prognosis in anaplastic oligodendroglioma patients, but the molecular mechanisms responsible for this relationship are as yet unknown. The DNA repair enzyme O6‐methylguanine DNA methyltransferase (MGMT) may cause resistance to DNA‐alkylating drugs commonly used in the treatment of anaplastic oligodendrogliomas and other malignant gliomas. We report on the analysis of 52 oligodendroglial tumors for MGMT promoter methylation, as well as mRNA and protein expression. Using sequencing of sodium bisulfite‐modified DNA, we determined the methylation status of 25 CpG sites within the MGMT promoter. In 46 of 52 tumors (88%), we detected MGMT promoter hypermethylation as defined by methylation of more than 50% of the sequenced CpG sites. Real‐time reverse transcription‐PCR showed reduced MGMT mRNA levels relative to non‐neoplastic brain tissue in the majority of tumors with hypermethylation. Similarly, immunohistochemical analysis showed either no or only small fractions of MGMT positive tumor cells. MGMT promoter hypermethylation was significantly more frequent and the percentage of methylated CpG sites in the investigated MGMT promoter fragment was significantly higher in tumors with loss of heterozygosity on chromosome arms 1p and 19q as compared to tumors without allelic losses on these chromosomes arms. Taken together, our data suggest that MGMT hypermethylation and low or absent expression are frequent in oligodendroglial tumors and likely contribute to the chemosensitivity of these tumors.
Fruits, vegetables and risk of renal cell carcinoma: A prospective study of Swedish women
Authors: Rashidkhani Bahram , Lindblad Per , Wolk Alicja
Published: September 2004

Findings of epidemiologic studies on the relationship between fruit and vegetable consumption and renal cell carcinoma (RCC) risk have been inconclusive. To study the association between fruits and vegetables and risk of RCC in a population‐based prospective cohort study of Swedish women, we collected dietary information from 61,000 women age 40–76 years by a food‐frequency questionnaire. During 13.4 years of follow‐up 122 women developed RCC. Cox proportional hazards models were used to estimate relative risks (RR) with 95% confidence interval (CI). Women consuming 5 or more servings of fruit and vegetables daily had a relative risk of 0.59 (95% CI = 0.26–1.34) in comparison to them consuming less than once daily. When fruits and vegetables were examined separately, those who consumed more than 75 servings per month of fruits or vegetables had multivariate relative risk of 0.59 (95% CI = 0.27–1.25) and 0.60 (95% CI = 0.31–1.17) respectively, compared to those consuming 11 or less servings per month. Within the group of fruits, the strongest inverse association was observed for banana (p = 0.07 by Wald test). The risk of RCC increased monotonically with increasing intake frequencies of fruit juice (p‐value for trend = 0.10). Within the group of vegetables, the strongest inverse association was observed for root vegetables (p = 0.03 by Wald test). The risk of RCC decreased with increasing consumption frequencies of white cabbage (p for trend = 0.07). Frequent consumption of salad vegetables (once or more per day) decreased the risk by 40% (RR = 0.60; 95% CI = 0.30–1.22), in comparison to no consumption. Our results suggested that high consumption of fruits and vegetables might be associated with reduced risk of RCC.
Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors
Authors: Spangler E. , Zeigler‐Johnson C.M. , Malkowicz S.B. , Wein A.J. , Rebbeck T.R.
Published: September 2004

Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse‐free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case‐control study between 1995 and 2002. Self‐reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00–2.05) or moderate (OR = 1.48, 95% CI = 1.0‐2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28–3.75) or moderate (OR = 2.15, 95% CI = 1.2–3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08–6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25–4.95 and HR = 2.46, 95% CI = 1.17–5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06–4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.
JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats
Authors: Wei Min , Morimura Keiichirou , Wanibuchi Hideki , Shen Jun , Salim Elsayed I. , Moku Masaharu , Hakoi Katsuo , Fukushima Shoji
Published: September 2004

We have previously demonstrated that JTE‐522, a selective cyclooxygenase‐2 (COX‐2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a putative preneoplastic lesion in colon, and suggested its inhibitory potential in rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE‐522, the present study was design to evaluate the inhibitory effects of JTE‐522 on rat colon tumorigenesis induced by 1,2‐dimethylhydrazine (DMH). Rats at 6 weeks of age were divided into 4 groups. One week after the start of the experiment, all rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week for 4 successive weeks. As the initiation and postinitiation treatment groups, groups 1–3 were fed diets containing 0, 50, or 150 ppm JTE‐522, respectively, from the start of the study to the end. As the postinitiation treatment group, group 4 was given 150 ppm JTE‐522 from 1 week after the last DMH injection to the end of the study. Forty weeks after the start of the experiment, administration of 150 ppm JTE‐522 during both initiation and postinitiation stages significantly inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well as total tumors in the colon. The inhibitory effect of JTE‐522 was most prominent for tubular adenocarcinomas, but was not observed in the nontubular carcinomas (signet‐ring cell and mucinous carcinomas). Almost equal inhibitory effects on tubular adenocarcinomas were also observed in the rats given 150 ppm JTE‐522 during the postinitiation stage, suggesting that its major anticancer action is at the postinitiation phase. However, JTE‐522 had no effect on the size or invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses revealed that JTE‐522 had no effect on gene expression levels in DMH‐induced tubular adenocarcinomas. These findings suggest that JTE‐522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon. In view of the significant inhibitory effects of JTE‐522 on ACF, its major anticancer action may occur in the postinitiation stage but before the malignant conversion stage of DMH‐induced colon carcinogenesis.
Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma
Authors: Kwong Joseph , Lo Kwok‐Wai , Chow Lillian Shuk‐Nga , Chan Franky Leung , To Ka‐Fai , Huang Dolly P.
Published: September 2004

Tazarotene‐induced gene 1 (TIG1) and Tazarotene‐induced gene 3 (TIG3) are retinoid acid (RA) target genes as well as candidate tumor suppressor genes in human cancers. In our study, we have investigated the expression of TIG1 and TIG3 in nasopharyngeal carcinoma (NPC). Loss of TIG1 expression was found in 80% of NPC cell lines and 33% of xenografts, whereas TIG3 was expressed in all NPC samples and immortalized nasopharyngeal epithelial cells. In order to elucidate the epigenetic silencing of TIG1 in NPC, the methylation status of TIG1 promoter was examined by genomic bisulfite sequencing and methylation‐specific PCR (MSP). We have detected dense methylation of TIG1 5′CpG island in the 5 TIG1‐negative NPC cell lines and xenograft (C666‐1, CNE1, CNE2, HONE1 and X666). Partial methylation was observed in 1 NPC cell line HK1 showing dramatic decreased in TIG1 expression. Promoter methylation was absent in 2 TIG1‐expressed NPC xenografts and the normal epithelial cells. Restoration of TIG1 expression and unmethylated alleles were observed in NPC cell lines after 5‐aza‐2′‐deoxycytidine treatment. Moreover, the methylated TIG1 sequence was detected in 39 of 43 (90.7%) primary NPC tumors by MSP. In conclusion, our results showed that TIG1 expression is lost in the majority of NPC cell lines and xenografts, while promoter hypermethylation is the major mechanism for TIG1 silencing. Furthermore, the frequent epigenetic inactivation of TIG1 in primary NPC tumors implied that it may play an important role in NPC tumorigenesis.
Lower levels of nuclear β‐catenin predict for a poorer prognosis in localized prostate cancer
Authors: Horvath Lisa G. , Henshall Susan M. , Lee C.‐Soon , Kench James G. , Golovsky David , Brenner Phillip C. , O'Neill Gordon F. , Kooner Raji , Stricker Phillip D. , Grygiel John J. , Sutherland Robert L.
Published: September 2004

β‐catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of β‐catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for β‐catenin expression using immunohistochemistry. Nuclear β‐catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear β‐catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse‐free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate‐specific antigen (PSA) levels (p = 0.01). Analysis of the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear β‐catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear β‐catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear β‐catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear β‐catenin expression may be of clinical utility as a preoperative prognostic marker in low‐risk localized PC.
Cervical carcinoma in Algiers, Algeria: Human papillomavirus and lifestyle risk factors
Authors: Hammouda Doudja , Muñoz Nubia , Herrero Rolando , Arslan Annie , Bouhadef Anissa , Oublil Malika , Djedeat Belhout , Fontanière Bernard , Snijders Peter , Meijer Chris , Franceschi Silvia
Published: September 2004

We conducted a hospital‐based case‐control study in Algiers, Algeria. A total of 198 cervical carcinoma (CC) cases (including 15 adeno‐ and adenosquamous carcinomas) and 202 age‐matched control women were included. Human papillomavirus (HPV) DNA in cervical cells was evaluated using a PCR assay. Odds ratios and corresponding confidence intervals were computed by means of unconditional multiple logistic regression models. HPV infection was detected in 97.7% of CC cases and 12.4% of control women (OR = 635). Nineteen different HPV types were found. HPV 16 was the most common type in both CC cases and control women, followed by HPV 18 and 45. Twelve types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 66 and 73) were found as single infections in CC cases. Multiple HPV infections did not show a higher odds ratio for CC than single infections. In addition to HPV infection, husband's extramarital sexual relationships with other women (OR = 4.8) or prostitutes (OR = 3.2), residing in a rural environment for most of one's life (OR = 4.9) and indicators of poor sanitation or poor hygiene were the strongest risk factors for CC. Oral contraceptive use was unrelated to CC risk, while multiparity emerged as a significant risk factor after adjustment for sexual habits. Intrauterine device users showed a lower CC risk than nonusers. The role of major risk factors, except inside toilet, was confirmed in the analysis restricted to HPV‐positive women. The distribution of HPV types in CC cases and control women in Algeria is more similar to the one found in Europe than the one in sub‐Saharan Africa, where HPV 16 is less prevalent. A vaccine against HPV 16 and 18 may be effective in more than 3/4 of CCs in Algeria.
High throughput functional genomics: Identification of novel genes with tumor suppressor phenotypes
Authors: Koenig‐Hoffmann Kerstin , Bonin‐Debs Angelika L. , Boche Irene , Gawin Beate , Gnirke Andrea , Hergersberg Christoph , Madeo Frank , Kazinski Michael , Klein Matthias , Korherr Christian , Link Dieter , Röhrig Sascha , Schäfer Rolf , Brinkmann Ulrich
Published: September 2004

We have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome‐wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro‐apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS‐like suppressor 3, DPH2L1‐like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG‐like phenotype by functionally defining their growth inhibitory or pro‐apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH‐) loci for which cancer‐associated deletions are described. The pro‐apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors.
Differential expression of Protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples
Authors: Grisaru‐Granovsky Sorina , Salah Zaidoun , Maoz Myriam , Pruss Diana , Beller Uziel , Bar‐Shavit Rachel
Published: September 2004

Protease activated receptors (PAR) form a family of G‐protein coupled receptors (GPCR) encoding their own ligands and uniquely activated via proteolytic cleavage. Although proteases in general have been implicated in the remodeling of the extracellular tumor microenvironment, the role of cell surface receptors activated by proteolysis is now emerging. In our present study we investigated the expression pattern of protease activated receptor 1 hPar1 in ovarian carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in “low malignant potential” and in invasive carcinomas, regardless of the histological subtype. In contrast, no hPar1 expression was detected on the cell surface of normal ovarian epithelium. The differential expression pattern of hPar1 was shown by in situ hybridization, immunohistochemistry and semi‐quantitative RT‐PCR analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal ovary showed strong PAR1 expression as opposed to the lack of expression in the ovarian epithelium obtained from normal individuals. In parallel, we analyzed the expression pattern of αvβ5 integrin and of activated focal adhesion kinase (FAK), a major focal contact protein, in these tissues. Although abundant expression of αvβ5 integrin was observed in all tissues specimens examined, regardless of either normal or malignant, the level of activated FAK was differentially expressed. Phosphorylated FAK was seen in invasive ovarian carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in pathological malignant ovarian carcinoma is likely to transmit signals leading to the phosphorylation of FAK and thereby alterations in the integrin functional state. Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy.
Hsp90 inhibitors deplete key anti‐apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin
Authors: Bagatell Rochelle , Beliakoff Jason , David Cynthia L. , Marron Marilyn T. , Whitesell Luke
Published: September 2004

Drugs that inhibit the function of heat shock protein 90 (Hsp90) are of interest in the treatment of pediatric cancers because these agents deplete the cellular levels of signaling molecules that are important for the growth and survival of many childhood tumors. To generate preclinical data in anticipation of clinical trials of Hsp90 inhibitors in children, we evaluated the effects of the Hsp90 inhibitor geldanamycin (GA) alone and in combination with cis‐platinum (II)‐diamine dichloride (cisplatin) in pediatric tumor cells. Immunoblotting demonstrated depletion of the Hsp90 client proteins AKT and the type 1 insulin‐like growth factor receptor (IGF1R) in a panel of pediatric tumor cell lines after exposure to GA. Drug exposure also led to a dramatic decrease in cell survival/proliferation in MYCN‐amplified and non‐amplified neuroblastoma cells. Moderate inhibition of survival/proliferation was observed in RB‐deficient and wild‐type osteosarcoma cells. Treatment of neuroblastoma and osteosarcoma cell lines with GA in combination with cisplatin resulted in greater than additive inhibition of survival/proliferation based on median dose analysis. Exposure to this drug combination also resulted in a marked increase in nuclear fragmentation as assessed by terminal deoxynucleotide transferase‐mediated UTP nick end labeling (TUNEL) analysis. Combined exposure also abrogated the ability of GA to induce a cytoprotective heat shock response and resulted in Hsp90 adduct formation. Our findings suggest that Hsp90 inhibitors may prove useful either alone or as a component of multi‐drug regimens in the treatment of neuroblastoma and osteosarcoma.
The asymmetric effects of uncertainty on inflation and output growth
Authors: Grier Kevin B. , Henry Ólan T. , Olekalns Nilss , Shields Kalvinder
Published: September 2004

We study the effects of growth volatility and inflation volatility on average rates of output growth and inflation for post‐war US data. Our results suggest that increased growth uncertainty is associated with significantly lower average growth, while higher inflation uncertainty is significantly negatively correlated with lower output growth and lower average inflation. Both inflation and growth display evidence of significant asymmetric response to positive and negative shocks of equal magnitude. Copyright © 2004 John Wiley & Sons, Ltd.
Interferon‐α and antisense K‐ras RNA combination gene therapy against pancreatic cancer
Authors: Hatanaka Kazuteru , Suzuki Koichi , Miura Yoshiaki , Yoshida Kimiko , Ohnami Shumpei , Kitade Yukio , Yoshida Teruhiko , Aoki Kazunori
Published: September 2004

Interferon alpha (IFN‐α) is used worldwide for the treatment of a variety of cancers. For pancreatic cancer, recent clinical trials using IFN‐α in combination with standard chemotherapeutic drugs showed some antitumor activity of the cytokine, but the effect was not significant enough to enlist pancreatic cancer as a clinically effective target of IFN‐α. In general, an improved therapeutic effect and safety are expected for cytokine therapy when given in a gene therapy context, because the technology would allow increased local concentrations of this cytokine in the target sites. In this study, we first examined the antiproliferative effect of IFN‐α gene transduction into pancreatic cancer cells. The expression of IFN‐α effectively induced growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another strategy we have been developing for pancreatic cancer targets its characteristic genetic aberration, K‐ras point mutation, and we reported that the expression of antisense K‐ras RNA significantly suppressed the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K‐ras RNA significantly enhanced IFN‐α‐induced cell death (1.3‐ to 3.5‐fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. Because the 2′,5′‐oligoadenylate synthetase/RNase L pathway, which is regulated by IFN and induces apoptosis of cells, is activated by double‐strand RNA, it is plausible that the double‐strand RNA formed by antisene and endogeneous K‐ras RNA enhanced the antitumor activity of IFN‐α. This study suggested that the combination of IFN‐α and antisense K‐ras RNA is a promising gene therapy strategy against pancreatic cancer. Copyright © 2004 John Wiley & Sons, Ltd.
Participation in the design of performance management systems: a quasi‐experimental field study
Authors: Kleingeld Ad , Van Tuijl Harrie , Algera Jen A.
Published: September 2004

In the literature on the relationship between participation in decision making and performance, a tell‐and‐sell strategy is considered a viable alternative to participation. In contrast, we argue that in organizational settings, when a sensitive and important issue is at stake, participation of a form to be characterized as formal, long term, direct, and with a high degree of participant influence is more effective than a tell‐and‐sell strategy. Using a quasi‐experimental design with a participation, a tell‐and‐sell, and a control condition, a ProMES performance management system was implemented in the field service department of a Dutch supplier of photocopiers. Outcome feedback to individual technicians resulted in an average performance increase in the participation condition that was significantly higher than the increase found in the tell‐and‐sell condition. Satisfaction with the program, and the perceived usefulness of the feedback, were significantly higher in the participation condition. In both experimental conditions, the performance increase was significant compared to the control condition. An explanation for these findings is discussed, as are implications for theory and practice. Copyright © 2004 John Wiley & Sons, Ltd.
Job and industry fit: the effects of age and gender matches on career progress outcomes
Authors: Goldberg Caren B. , Finkelstein Lisa M. , Perry Elissa L. , Konrad Alison M.
Published: September 2004

Using a sample of 232 MBA alumni, we tested the impact of respondent age, gender, and their interaction on career progress outcomes (managerial level, number of promotions, and salary) and whether age‐ and gender‐type of contexts moderated these relationships. Women's salaries did not increase much with age, whereas men's salaries showed a marked increase with age. We also found a gender × job gender‐type effect on salary, such that women earned somewhat higher salaries in masculine‐typed jobs, while men earned considerably higher salaries in feminine‐typed jobs. In addition, we observed a three‐way interaction between gender, age, and age‐type of industry indicating that younger men received more promotions in old‐typed industries, while younger women received more promotions in young‐typed ones. Results are discussed in light of cognitive matching approaches and status characteristics theory. Copyright © 2004 John Wiley & Sons, Ltd.
Quantification of N2 fixation and annual N benefit from N2 fixation in soybean accrued to the soil under soybean‐wheat continuous rotation
Authors: Singh Muneshwar , Kundu Samaresh , Biswas Ashis K. , Saha Jayanta K. , Tripathi Awadhesh K. , Acharya Chuni L.
Published: September 2004

A computational exercise was undertaken to quantify the percent N derived from atmosphere %Ndfa) in soybean and consequent N benefit from biological N2‐fixation process annually accrued to the soil by the soybean crop using average annual N‐input/‐output balance sheet from a 7 yr old soybean‐wheat continuous rotational experiment on a Typic Haplustert. The experiment was conducted with 16 treatments comprised of combinations of four annual rates of farmyard manure (FYM ≅ 0, 4, 8, and 16 t ha–1) and four annual rates of fertilizer N (≅ 0, 72.5, 145, and 230 kg N ha–1) applications. The estimated N contributed through residual biomass of soybean (RBNS) consisting of leaf fall, root, nodules, and rhizodeposition varied in the ranges of 7.02–16.94, 11.65–28.83, 3.31–8.91, and 11.3–23.8 kg N ha–1 yr–1, respectively. A linear relationship was observed between RBNS and harvested biomass N (HBNS) of soybean in the form of RBNS = 0.461 × HBNS – 20.67 (r = 0.989, P < 0.01), indicating that for each 100 kg N assimilated by the harvested biomass of soybean, 25.4 kg N was added to the soil through residual biomass. The Ndfa values ranged between 13% and 81% depending upon the annual rates of application of fertilizer N and FYM. As per the main effects, the %Ndfa declined from 76.4 to 26.0 with the increase in annual fertilizer‐N application from 0 to 230 kg N ha–1, whereas %Ndfa increased from 40.8 to 65.8 with the increase in FYM rates from 0 to 16 t ha–1, respectively. The N benefit from biological N2 fixation accrued to the soil through residual biomass of soybean ranged from 7.6 to 53.7 kg N ha–1 yr–1. The treatments having %Ndfa values higher than 78 showed considerable annual contribution of N from N2 fixation to the soil which were sufficient enough to offset the quantity of N removed from the soil (i.e., native soil N / FYM‐N / fertilizer‐N) with harvested biomass of soybean.
Effect of post‐methanation effluent on soil physical properties under a soybean‐wheat system in a Vertisol
Authors: Hati Kuntal M. , Biswas Ashis K. , Bandyopadhyay Kalikinkar , Misra Arun K.
Published: September 2004

Post‐methanation effluent (PME) generated through bio‐methanation of distillery effluent, a foul‐smelling, dark colored by‐product of distillery industries, is applied to arable land in some areas near the vicinity of the distillery industries as an amendment. The PME contains considerable amount of organic matter and salt besides its high plant‐nutrient content. The present investigation was conducted for three years during 1999–2002 on soybean‐wheat cropping sequence to evaluate the effect of graded levels of post‐methanation effluent (PME) on soil physical properties and crop productivity in a deep Vertisol of central India. Six application doses of PME viz. S2.5+W0: 2.5 cm PME applied to soybean and wheat on residual nutrition, S2.5+W1.25: 2.5 cm PME to soybean and 1.25 cm to wheat, S5.0+W0: 5 cm PME to soybean and wheat on residual nutrition, S5.0+W2.5: 5.0 cm PME to soybean and 2.5 cm to wheat, S10.0+W0: 10 cm PME to soybean and wheat on residual nutrition, and S10.0+W5.0: 10.0 cm PME to soybean and 5.0 cm to wheat, were compared with 100% recommended NPK+FYM ≅ 4 Mg ha–1 and control (no fertilizer, manure or PME). The application of PME increased the organic carbon content and electrical conductivity of the soil compared to control and 100% NPK+FYM treatment. The organic C content was maximum in S10.0+W5.0 (11.2 g kg–1) and minimum in control (5.2 g kg–1). Electrical conductivity increased from 0.47 dS m–1 in control to 1.58 dS m–1 in highest dose of PME (S10.0+W5.0). The PME treatments have not affected the soil pH. The application of PME showed a significant improvement in the physical properties of the soil. The mean weight diameter (MWD), percent water‐stable aggregation (% WSA), saturated hydraulic conductivity (Ksat), and water retention (WR) at 0.033 MPa suction were significantly (P < 0.05) more while bulk density (BD) and penetration resistance was significantly less in PME‐treated plots than that of control. The MWD showed a linear and positive relationship (r = 0.89**) with the soil organic C. Soybean recorded significantly higher seed yield at all PME treatments than control. Highest average soybean yield (2.39 Mg ha–1) was recorded in S10.0+W0 but yield decreased significantly in S10.0+W5.0 (2.08 Mg ha–1). In wheat, all the PME‐treated plots except S2.5+W0 yielded significantly higher than control while the 100% NPK+FYM treatment yielded (3.46 Mg ha–1) at par with the S10.0+W5.0 (4.0 Mg ha–1) and S5.0+W2.5 (3.66 Mg ha–1). Fresh application of PME to wheat resulted in significant improvement in grain yield over that grown on residual fertility. Thus, application of PME to arable land, as an amendment, could be considered as a viable option for the safe disposal of this industrial waste.
Entwicklung, Eigenschaften und Klassifikation von Dünenböden der Ostfriesischen Inseln – am Beispiel Spiekeroogs
Authors: Giani Luise , Buhmann Sonja
Published: September 2004

Ziel dieser Arbeit war die eingehende Untersuchung und exakte bodentypologische Benennung von Dünenböden der Ostfriesischen Inseln. Innerhalb der Dünensukzession zeichnen sich auf der Grundlage der Laboranalytik die Bodenentwicklungsprozesse Humusakkumulation und ‐verlagerung, Entkalkung, Versauerung, Umladung der Bodenkolloide und Abnahme der Basensättigung ab. Ungestützt durch Labordaten war im Gelände eine leichte Verbraunung erkennbar. Bei exakter Anwendung der diagnostischen Horizonte entsprechend der deutschen Systematik fehlen die quantitativen und qualitativen Grundlagen zur Klassifikation dieser Böden als Regosole, Braunerden und Podsole. Nach der WRB‐Systematik entsprechen sie exakt den Arenosolen.