bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Malformations Are Associated with Altered Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase Genes in Embryos of Diabetic Mice
Authors: Kumar Srinivasan Dinesh , Yong Sook-Kwin , Dheen S. Thameem , Bay Boon-Huat , Tay Samuel Sam-Wah
Published: September 2008

The aim of this study was to investigate the role of nitric oxide (NO), and the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) genes in developing hearts at embryonic day 13.5 of embryos from diabetic mice. The protein and mRNA expression levels of eNOS and VEGF were significantly altered in the developing hearts of embryos from diabetic mice. The NO level was significantly decreased, whereas the VEGF concentration was significantly increased in the developing hearts of the embryos from diabetic mice. In vitro study showed a significant reduction in eNOS expression and cell proliferation in cardiac myoblast cells exposed to high glucose concentrations. Further, high glucose induced apoptosis in myoblast cells. Ultrastructural changes characteristics of apoptosis, including cell blebbing, aggregation of ribosomes and vacuoles in the cytoplasm were also evident in myoblast cells exposed to high glucose. It is suggested that hyperglycemia alters the expression of eNOS and VEGF genes that are involved in the regulation of cell growth and vasculogenesis, thereby contributing to the cardiac malformations seen in embryos from diabetic mice.
The relationship between individual life events and preterm delivery
Authors: Whitehead Nedra
Published: September 2008

Stressful life events have been associated with preterm delivery in some studies but not in others. One cause of this inconsistency may be that different life events have different effects. The author used data collected by the Pregnancy Risk Assessment Monitoring System, a survey of American women with a recent live birth, for 1990–1995 to examine the relationship between individual life events and the risk of preterm delivery overall and by levels of severity. Four events of the 18 examined were associated with an increased risk of at least one category of preterm delivery: being in debt, being injured by a partner, having someone close attempt suicide, and being divorced. Women who reported being in debt had an increased risk of preterm delivery overall and for each level of severity. One event, having a partner who lost his (or her) job, was associated with a decreased risk of preterm delivery. These results provide some support for the theory that increased stress from life events causes preterm delivery. The lack of a pattern by type of stress, expected stressfulness, or severity of prematurity are hard to reconcile with those theories, however.
Willingness to pay for food produced in accordance with nature conservation criteria: A survey of the food chain
Authors: Wirthgen Antje
Published: September 2008

Within the European Union, environment-friendly food production is receiving increasing interest. This can be seen in the growing demand for organic food as well as in the policies of some countries which support the production and the marketing of environment-friendly food.

This contribution is part of an interdisciplinary project that is looking at the central question of how agriculture and nature conservation can be integrated. The main objective of the marketing part of this project and of this article is to identify the willingness of various segments in the food chain to pay for food produced in accordance with nature conservation criteria. A consumer survey was conducted and the results analysed by means of descriptive and multivariate data analysis (factor, linear and logit regression analysis). The data were used to indicate how willing consumers are to pay for food associated with nature conservation, to estimate the demand elasticity and, finally, to explain the consumers’ willingness. To complete the demand analysis, additional research was conducted in the form of a survey of food retailers, processors and caterers. The results indicate that there is a willingness throughout the whole food chain to pay for food produced in accordance with nature conservation criteria. In conclusion, this study shows that nature conservation can be advantageous for farmers - as one way of differentiating and adding value to raw products.
In search of anonymity in supply chains
Authors: Amanor-Boadu Vincent , Starbird S.
Published: September 2008

Enforcing compliance standards in supply chains using inspection and other traditional mechanisms may exacerbate the non-compliance effort by those who see these mechanisms as evidence of power imbalance in the relationship. The easier it is for anonymity to exist in supply chain relationships, the greater the incentive for non-compliance, thus creating value for anonymity. We argue that total chain performance can be enhanced by designing and operating supply chains in ways that provided enduring positive signals from the environment to minimize adverse perceptions of powerlessness, coercion and unfairness and increase members' perception of their identity with the organisation. We also explore the interaction between these perception factors and the human factors of opportunism, bounded rationality and risk aversion on the one hand and the environmental factors on the other.
Collaboration and competition: exploring the effects of alliances and networks on rivalry
Authors: de Man Ard-Pieter
Published: September 2008

The increase in collaboration between companies has a marked effect on competition. Counter to intuition, collaboration may lead to an increase in rivalry. Most companies collaborate for offensive instead of defensive reasons. They aim to innovate and learn, rather than corner markets and raise prices. Moreover, three new forms of competition have come into being that stimulate rivalry. The first form is co-opetition. Companies cooperate and compete simultaneously. Three types of co-opetition are distinguished: direct, indirect and asynchronous. A second new form of competition is group-based competition, which occurs when groups of companies compete with other groups of companies. The final new form of competition is organization-form-based competition, which occurs when a group of companies collaborates with for example a vertically integrated enterprise. A final reason why the recent trend towards collaboration may not pose a threat to competition is that collaborative structures are rarely stable. Instead companies enter and exit networks on a continuous basis. Any competition-limiting effect is therefore bound to be temporary. This analysis of competition in and around networks and alliances aims to explore the nature of competition in a network economy. It shows that alliances and networks only curb competition when three specific conditions are met. Implications for governmental policy, management and research are defined.
Traceability and vertical co-ordination in the Italian dairy chain: A transaction cost approach
Authors: Banterle A. , Stranieri S. , Baldi L.
Published: September 2008

The purpose of this paper is to analyse how the introduction of a voluntary traceability system affects the organisation of economic relationships throughout the Italian dairy chain. Using the theoretical framework of transaction cost economics, we assess whether traceability increases the degree of vertical co-ordination and changes the level of the transaction key features, i.e. degree of asset specificity, uncertainty and frequency of transactions. A survey was conducted by questionnaire to assess changes in vertical relations, and to underline the different organisational solutions of dairy firms we carried out factor and cluster analysis. The results show increased bilateral dependency among the economic agents as a consequence of the rise in human, physical and site assets. At the same time, growth in the frequency and quantity of information exchanged is observed. Moreover, for medium-sized firms economic incentives play an important role in guaranteeing the safeguarding of transactions, whereas big firms adopt contractual supports.
A broader view on vertical coordination: lessons from German pork production
Authors: Schulze Birgit , Spiller Achim , Theuvsen Ludwig
Published: September 2008

In the literature it is often hypothesised that contracts and vertical integration are of paramount importance for the future competitiveness of meat supply chains. The continued coexistence of two different types of pork production chains throughout the world - less integrated systems in, for instance, many Western European countries and stricter coordinated systems based on contracts and vertical integration in countries such as the U.S.A. and Denmark - is rarely discussed in the agribusines literature. Some authors expect a trend towards more intense vertical coordination and consider the loose relationships in some European markets as an obsolescent model. Based on an overview of theoretical approaches towards the organisation of meat supply chains, we confront the contract and integration hypothesis with current developments at the slaughterhouse level and in quality assurance systems as well as results from a recent survey among German pig producers concerning their attitudes towards contracts. A binary logit regression is carried out to test for the determinants of contracting decisions. Cluster analysis reveals four groups of farmers with very different attitudes, from inveterate antagonists to contract supporters. In conclusion, reflections on TCE indicate the long-term viability of slaughter pig markets with a low degree of vertical coordination, which may have efficiency advantages over more integrated meat supply chains. This argument is supported by the results of a large-scale survey among German pig producers, who strongly reject the notion of engaging in contracts with slaughterhouses. In this situation, trust management can be considered a suitable instrument for gaining some of the advantages usually attributed to contracts. Trust-building instruments should be integrated into a broader approach of supplier relationship management.
Effects of mycotoxins, aflatoxin B1 and deoxynivalenol, on the bioluminescence of Vibrio fischeri
Authors: Sarter S. , Metayer I. , Zakhia N.
Published: September 2008

The effects of aflatoxin B1 and deoxynivalenol on the luminescence of Vibrio fischeri were investigated to determine the conditions of using the bioluminescence as an indirect means for mycotoxin detection. The culture of Vibrio fischeri showed that bioluminescence reached a peak after 12 hours of incubation at 25 °C and then decreased drastically. During the lag phase which lasted 6 hours, light emission decreased drastically for both the mycotoxin assays – aflatoxin B1 10 µg/ml and deoxynivalenol 20 µg/ml – and the corresponding controls. Distinct bioluminescence inhibition appeared after this period of minimal bioluminescence of the controls and started with the exponential phase of growth. The percentage of bioluminescence inhibition for both mycotoxins was determined after 3.5, 10, 15 and 25 hours of incubation. The bioluminescence of Vibrio fischeri was inhibited with aflatoxin B1 and enhanced with deoxynivalenol. Both effects were delayed and required a long-term incubation over 10 hours, which may help to investigate bioassays for mycotoxin detection.
Aspergillus nomius, an important aflatoxin producer in Brazil nuts?
Authors: Olsen M. , Johnsson P. , Möller T. , Paladino R. , Lindblad M.
Published: September 2008

The relationship between aflatoxin B1 and G1 was examined in samples from 199 aflatoxin contaminated lots of inshell Brazil nuts imported to Europe. In most of the samples, the relationship between B1 and G1 were approximately 50/50 indicating that the major responsible aflatoxin producing fungi cannot be Aspergillus flavus, which produces solely B aflatoxins. Fungal strains were isolated from two batches of Brazil nuts and isolates of both A. nomius and A. flavus could be identified. The A. nomius isolates were good producers of both B and G aflatoxins, while the A. flavus strains only produced B aflatoxins. In conclusion, this study suggests that A. nomius is an important producer of aflatoxins in Brazil nuts and that its occurrence, and possibly other B and G aflatoxin producers, should be further examined since this may influence strategies for prevention and control of aflatoxins in Brazil nuts.
Ion trap lC-MS/MS as a valid multi-method to determine trichothecenes and zearalenone in the food industry
Authors: Suman M. , Catellani D.
Published: September 2008

In recent years the European Scientific Committee on Food has frequently expressed its opinion on Fusarium toxins, setting limits, regulations and guidelines in order to reduce their levels in raw materials and food commodities. Trichothecenes are known as DNA and mitochondrial metabolism inhibitors, representing the largest group (over 170 compounds) of Fusarium mycotoxins. Zearalenone (ZEA) is also produced by Fusarium species. It is found almost entirely in grains and has a mainly oestrogenic effect. Wheat-based products (such as bread and pasta) are the predominant source of deoxynivalenol (DON) and nivalenol (NIV) intake, while the highest amounts of T-2 and HT-2 toxins were observed mainly in oat-based products. Therefore, food companies are progressively being forced to set up analytical methods in their laboratories for determining these kinds of toxins in an accurate, sensitive and rapid way. Following this issue, we set up a liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-IonTrap-MS/MS) method for the simultaneous determination of several types of A and B trichothecenes, together with ZEA, minimising the matrix effect by using specific fragmentation parameters in positive or negative ion modes and dedicated internal standards: quantification of trichothecenes was done with isotope substituted (13C15)-deoxynivalenol, while quantification of ZEA was performed by the contemporaneous use of Zearalanone (ZAN). Sample extraction was performed with acetonitrile/water mixtures, MycoSep® columns were used for fast and effective clean-up procedure and detection was carried out in the multiple reaction monitoring (MRM) mode. Spiking blank cereal samples, the method was validated in terms of detection limits (reaching µg/ kg levels), linearity, recovery, precision (RSD<5%) and accuracy. Method performances were finally tested on oat and durum wheat samples. In conclusion, ion trap instruments can currently provide high-throughput LC/MSn mycotoxin analysis where sensitivity, reliability and productivity coexist in an interesting and good compromise for food industry applications.
Implication of pre-drying steps with natural fumonisin contamination levels in freshly harvested corn
Authors: Ono E. , Silva M. , Ono M. , Vizoni E. , Garcia G. , Kawamura O. , Sabino M. , Sugiura Y. , Hirooka E.
Published: September 2008

Maize quality regarding fumonisin contamination of 390 freshly harvested samples used by maize processing industries in the Northern region of Parana State, Brazil (2003 crop) was evaluated and correlated to the time elapsed from harvesting to the pre-drying step. Sampling was carried out at three points of the maize production chain, immediately after harvesting (n=100), at the industry delivery posts (n=200) and before the drying process (n=90). Fumonisin B1 (FB1) was detected in all the samples from the three points of the maize production chain. FB1 levels ranged from 0.11 to 12.68 µg/g (mean 1.81±2.12 µg/g) in the field samples, 0.10 to 11.83 µg/g (mean 1.83±1.75 µg/g) in the reception samples and from 0.02 to 10.98 µg/g (mean 2.31±2.38 µg/g) in the pre-drying samples. FB2 levels ranged from 0.01 to 5.26 µg/g (mean 0.84±0.94 µg/g) in the field samples, from 0.02 to 5.25 µg/g (mean 0.74±0.69 µg/g) in the reception samples and from 0.07 to 7.89 µg/g (mean 1.25±1.29 µg/g) in the pre-drying samples. Although there was no significant difference in mean fumonisin levels among the field, reception and pre-drying samples by the Tukey multiple comparison test (P<0.05), there was a positive correlation (P<0.05) between fumonisin levels and the time elapsed (p=0.95) from harvesting to the pre-drying step. Therefore reduction in the harvest/drying interval would be essential to assure product quality and safety and minimise potential health hazards.
The 'omics' tools: genomics, proteomics, metabolomics and their potential for solving the aflatoxin contamination problem
Authors: Bhatnagar D. , Rajasekaran K. , Payne G. , Brown R. , Yu J. , Cleveland T.
Published: September 2008

Aflatoxins are highly carcinogenic secondary metabolites produced primarily by the fungi Aspergillus flavus and
Aspergillus parasiticus. Aflatoxin contamination of food and feed is an age old problem of particular concern over
the last four decades. Now, for the first time control measures for this problem appear within reach. For practical and
sustainable control of aflatoxin contamination to be realised, however, additional information is needed rather rapidly,
particularly for understanding the specific molecular factors (both in the plant and the fungus) involved during host
plant-fungus interaction. The information derived from the use of novel tools such as genomics, proteomics and
metabolomics provides us with the best and the quickest opportunity to achieve a clear understanding of the survival
of toxigenic fungi in the field, the ability of the fungus to invade crops, and the process of toxin contamination under
various environmental conditions. Significant progress has been made recently in understanding the genomic makeup
of the most significant aflatoxin producing field fungus, namely Aspergillus flavus. Progress also has been made
in the study of host crop resistance to fungal invasion through the use of proteomics. The information available on
production of aflatoxin and other metabolites by Aspergillus flavus is reasonably extensive, although the application of metabolomics as a tool in this study is relatively new. In this review there is a discussion of the use of genomics,
proteomics and metabolomics in deriving the requisite information for developing effective strategies to interrupt
the machinery in the fungus for production of these toxins, as well as to assist in the development of host-resistance
against fungal invasion and aflatoxin contamination of crops.
Occurrence of fungi and their mycotoxins in individual Turkish dried figs
Authors: Şenyuva H. , Gilbert J. , Samson R. , Özcan S. , Öztürkoğlu Ş. , Önal D.
Published: September 2008

Fifty individual figs which had been rejected as potentially contaminated by sorting under UV light were separately
analysed to identify the presence of fungi and their mycotoxins. Aflatoxin B1 was found in 49 samples with levels ranging from 0.7 to 222 ng g-1, with 40 individual figs containing more than 2 ng g-1, indicating the efficacy of the UV screening process in identifying contaminated fruit. Ochratoxin A (OTA) was found in 32 of the figs at levels
from 0.4 to 1710 ng g-1, with 50% of the samples containing levels above 1 ng g-1. There was no evident correlation between levels of aflatoxin B1 and levels of OTA. Twenty fungal species were isolated from the outer and inner
surfaces of the figs, some of which were subsequently cultured on YES and PDB and the media analysed for the
presence of aflatoxin B1 and OTA to establish their toxigenicity.
A tale of two commodities: how EU mycotoxin regulations have affected u.s. tree nut industries
Authors: Wu F.
Published: September 2008

The European Union (EU) has some of the strictest standards for mycotoxins in food and feed in the world. This paper
explores the economic impacts of these standards on other nations that attempt to export foods that are susceptible
to one mycotoxin, aflatoxin, to the EU. The current EU standard for total aflatoxins in food is 4 ng/g in food other
than peanuts, and 15 ng/g in peanuts. Under certain conditions, export markets may actually benefit from the strict
EU standard. These conditions include a consistently high-quality product, and a global scene that allows market
shifts. Even lower-quality export markets can benefit from the strict EU standard, primarily by technology forcing.
However, if the above conditions are not met, export markets suffer from the strict EU standard. Two case studies
are presented to illustrate these two different scenarios: the U.S. pistachio and almond industries. Importantly, within
the EU, food processors may suffer as well from the strict aflatoxin standard. EU policymakers should consider these
more nuanced economic impacts when developing mycotoxin standards for food and feed.
Determination of sterigmatocystin in beer by high performance liquid chromatography with ultraviolet detection
Authors: Veršilovskis A. , De Saeger S. , Mikelsone V.
Published: September 2008

A new method for the determination of sterigmatocystin in beer was developed. This method consists of a solid phase extraction procedure of light and dark beer and reversed phase high performance liquid chromatography with ultraviolet detection. Recoveries of sterigmatocystin from beer samples spiked at levels from 0.5 to 100 µg/l ranged from 81 to 126% for light beer and from 88 to 126% for dark beer with coefficients of variation between 2.2 and 14%. From the total of 26 analysed Latvian beer samples only two (7.7%) were contaminated with sterigmatocystin.
Thermal properties of extruded and injection‐molded poly(lactic acid)‐based cuphea and lesquerella bio‐composites
Authors: Mohamed Abdellatif , Finkenstadt V. L. , Rayas‐Duarte P. , Debra E Palmquist , Gordon Sherald H.
Published: September 2008

The degree of compatibility between poly (lactic acid) (PLA) and different bio‐fillers was examined using thermal methods. The biofillers were fibers extracted from cuphea and lesquerella seeds. Bio‐composites of PLA:Fiber were prepared at 85 : 15, 70 : 30, and 100 : 00 and blended by extrusion and then injection molding. Thermal properties of the extruded (EX) and the extruded‐injection molded (EXIM) composites were examined using differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Composites analysis using DSC provided information essential for determining: (1) glass transition (Tg); (2) crystallization and melting temperatures and ΔH; (3) percent crystallinity; and (4) Enthalpic Relaxation (ER). TGA was used to measure the mechanism of the thermal decomposition of the composites. The effect of fiber composition, processing conditions, and aging time on the thermal properties of the bio‐composites was used to examine the relative compatibility of the fibers with PLA. The data showed that ER increased steadily as a function of aging. Because of the difference in protein content between cuphea and lesquerella, the two fibers influenced the Tg (temperature and ΔCp) differently. The percent crystallinity of neat PLA was significantly reduced by EX or EXIM, while the enzymatic degradation showed that EX composites are more biodegradable than EXIM. The TGA profiles indicated a multi‐step degradation especially in air. The largest value of q, which indicated that, intermolecular interaction was strongest between lesquerella and PLA extruded materials, compared to the other three blends, possibly due to the higher protein content. Results also indicated that intermolecular interaction was least strong (q = −33.9156) in the EXIM PLA‐cuphea. Although the q values of both cuphea composites were significantly lower than those of the lesquerella samples, this greater effect of extrusion over injection molding on intermolecular interaction was also seen in the q value of the EX and EXIM samples. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Production of mouse interleukin‐12 is greater in tobacco hairy roots grown in a mist reactor than in an airlift reactor
Authors: Liu Chunzhao , Towler Melissa J. , Medrano Giuliana , Cramer Carole L. , Weathers Pamela J.
Published: September 2008

We compared the growth and productivity of a tobacco line of hairy roots that produces murine interleukin 12 (mIL‐12) grown in three different culture systems: shake flasks, an airlift reactor, and a scalable mist reactor. Of the total mIL‐12 produced by cultures grown in shake flasks (∼434.8 µg L−1), almost 21% was recovered from the medium. In contrast to roots harvested from shake flasks and the mist reactor, roots were not uniformly distributed in the airlift reactor. Roots formed a dense ring around the wall of the reactor and surrounding the central rising column of fine aeration bubbles. Root quality was also better in both the shake flasks and mist reactor than in the airlift reactor. There were more pockets of dark roots in the airlift reactor suggesting some of the roots were nutrient starved. Although the best root growth (7 g DW L−1) was in the shake flasks, both reactors produced about the same, but less dry mass, nearly 5 g DW L−1. Total mIL‐12 concentration was highest in the mist reactor at 5.3 µg g−1 FW, but productivity, 31 µg g−1 FW day−1 was highest in shake flasks. Roots grown in the mist reactor produced about 49.5% more mIL‐12 than roots grown in the airlift reactor. Protease activity in the media increased steadily during culture of the roots in all three systems. The comparisons of protease activity, protein and mIL‐12 levels done in the shake flask system suggest that the increase in proteases associated with progression into stationary phase is most detrimental to mIL‐12 concentration. This is the first description of the design and operation of a scalable version of a mist bioreactor that uses a plastic bag. This also the first report of reasonable production levels of functional mIL‐12, or any protein, produced by hairy roots grown in a mist reactor. Results will prove useful for further optimization and scale‐up studies of plant‐produced therapeutic proteins. Biotechnol. Bioeng. 2009;102: 1074–1086. © 2008 Wiley Periodicals, Inc.
A rapid and specific approach for direct measurement of donepezil concentration in human plasma by LC‐MS/MS employing solid‐phase extraction
Authors: Shah Hiten J. , Kundlik Mohan L. , Pandya Ankit , Prajapati Shivkumar , Subbaiah Gunta , Patel Chhagan N. , Patel Dasharath M. , Suhagiya Bhanu N.
Published: September 2008

A selective, rapid and simple liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method is described for assay of donepezil in human plasma using escitalopram as an internal standard. Chromatographic separation was achieved on a Betabasic‐C8, 5 µm, 100 × 4.6 mm column using methanol:water:formic acid (90:9.97:0.03, v/v/v) as mobile phase. Detection of donepezil and internal standard was achieved by ESI MS/MS in positive ion mode using 380.20/91.10 and 325.13/262.00 transitions, respectively. The linearity over the concentration range of 0.15–50 ng/mL for donepezil was obtained and the lower limit of quantification was 0.15 ng/mL. For each level of quality control samples, inter‐day and intra‐day precisions (RSD) were ≤8.92 and 10.35% and accuracy (%RE) were ≤7.33% and 9.33%, respectively. The recovery was more than 88.50% for both donepezil and internal standard by solid‐phase extraction, eliminating evaporation and reconstitution steps. Copyright © 2008 John Wiley & Sons, Ltd.
A Modular “Toolbox” Approach to Flexible Branched Multimacrocyclic Hosts as Precursors for Multiply Interlocked Architectures
Authors: Baytekin Bilge , Zhu Sascha S. , Brusilowskij Boris , Illigen Jens , Ranta Jenni , Huuskonen Juhani , Russo Luca , Rissanen Kari , Kaufmann Lena , Schalley Christoph A.
Published: September 2008

Tetralactam macrocycles can be functionalized by a variety of cross‐coupling reactions. A modular “toolbox” strategy is presented that allows 1) several tetralactam macrocycles to be covalently connected with each other or with a central spacer, 2) the macrocycles to be substituted with or connected to different chromophores, and 3) metal‐coordination sites to be attached to the macrocycles. With this approach a series of different oligo‐macrocyclic hosts was obtained with great structural diversity and enormous potential for further functionalization. Rotaxanes made on the basis of these macrocycles have been synthesized to demonstrate their utility in building more complex supramolecular architectures.
Phase 2 study of gemcitabine and irinotecan in metastatic breast cancer with correlatives to determine topoisomerase I localization as a predictor of response
Authors: Moulder Stacy , Valkov Nickola , Neuger Anthony , Choi Jimin , Lee Ji Hyun , Minton Susan , Munster Pamela , Gump Jana , Lacevic Mira , Lush Richard , Sullivan Dan
Published: September 2008

BACKGROUND.

Gemcitabine incorporation into DNA enhances cleavage complexes in vitro when combined with topoisomerase I inhibitors and demonstrates synergy in cancer cells when given with irinotecan. Topoisomerase I inhibitors require that topoisomerase I interacts with DNA to exert activity.

METHODS.

Patients who had received previous anthracycline therapy or were not candidates for anthracycline therapy received gemcitabine at a dose of 1000 mg/m2 intravenously over 30 minutes followed by irinotecan at a dose of 100 mg/m2 over 90 minutes on Days 1 and 8 of a 21‐day cycle. The primary endpoint was improvement in response from that historically observed with gemcitabine (from 25% to 45%) as measured by Response Evaluation Criteria in Solid Tumors. Correlative studies included characterization of cellular levels and nuclear distribution of topoisomerase I and pharmacokinetic analysis of gemcitabine and irinotecan.

RESULTS.

Forty‐nine patients were assessed for response. The response rate was approximately 25% (all partial responses [PRs], 12 patients; 95% confidence interval [95% CI], 13‐39). Six patients had stable disease (SD) for ≥6 months for a clinical benefit rate (PR + SD) of 39%. The median time to disease progression was 3.7 months (95% CI, 2.5 months‐4.6 months), and median survival was 11.6 months (95% CI, 8.9 months‐15 months). Toxicities included neutropenia, nausea, and vomiting. Seven of 9 tissue biopsies were assessable for topoisomerase I. Tumors with the 2 lowest nuclear to cytoplasmic ratios demonstrated no response to irinotecan.

CONCLUSIONS.

Gemcitabine and irinotecan are active in metastatic breast cancer, but response did not meet predetermined response parameters, and the null hypothesis was accepted. Topoisomerase I localization can be measured in metastatic breast cancer. Further validation is needed to determine whether this assay can predict response. Cancer 2008. © 2008 American Cancer Society.
Taxpropellane: A Novel Taxane with an Unprecedented Polycyclic Skeleton from the Needles of Taxus canadensis
Authors: Zhang Man‐Li , Dong Mei , Huo Chang‐Hong , Li Li‐Geng , Sauriol Françoise , Shi Qing‐Wen , Gu Yu‐Cheng , Makabe Hidefumi , Kiyota Hiromasa
Published: September 2008

Taxpropellane, the first example of a taxane with an unprecedented 6/5/5/6/4/5‐membered ring hexacyclic skeleton ([3.3.2]propellane), was isolated from the needles of Taxus canadensis. This compound would be derived from a normal 6/8/6 taxane by a [2+2] cycloaddition reaction between the 3,4‐ and 11,12‐double bonds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Glycosidase Inhibitory Study of New Polyhydroxylated Indolizidines
Authors: Baumann Delphine , Bennis Khalil , Ripoche Isabelle , Théry Vincent , Troin Yves
Published: September 2008

The synthesis of two polyhydroxylated indolizidines as potenticial glycosidase inhibitors is reported. The piperidine ring was formed by an intramolecular Mannich‐type reaction between ethyl trans‐4‐oxo‐2‐butenoate and the two β‐amino ketones (–)‐1‐(2‐methyl‐1,3‐dioxan‐2‐yl)propan‐2‐amine and(+)‐1‐(benzyloxymethyl)‐2‐(2‐methyl‐1,3‐dioxan‐2‐yl)ethylamine. The synthesis of this amine was performed in eight steps from L‐aspartic acid. The key steps of the formation of the framework involved dihydroxylation, nucleophilic substitution, and reduction. The last hydroxy group was introduced by hydrolysis of the acetal moiety followed by reduction of the resulting ketone. The inhibitory properties of the two synthesized indolizidines were evaluated against a variety of commercial glycosidases. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Alternating Layers of Iron(III) Tetra(N‐methyl‐4‐pyridyl)‐porphyrin and Copper Tetrasulfonated Phthalocyanine for Amperometric Detection of 4‐Nitrophenol in Nanomolar Levels
Authors: Lima Phabyanno Rodrigues , de Jesus Rodrigues Santos Wilney , Goulart Marília Oliveira Fonseca , Tanaka Auro Atsushi , Tanaka Sônia Maria Carvalho Neiva , Kubota Lauro Tatsuo
Published: September 2008

The present work describes the development of a highly sensitive amperometric sensor for 4‐NP in nanomolar levels using a glassy carbon electrode modified with alternating layers of CuTSPc and FeT4MPyP. After optimizing the operational conditions, the sensor provided a linear response range for 4‐NP from 5 up to 100 nmol L−1 with sensitivity, detection, and quantification limits of 14 nA L nmol−1, 1.9 nmol L−1, and 5.4 nmol L−1, respectively. The proposed sensor showed a stable response for at least 200 successive determinations. This modified electrode can be used to the determination of 4‐NP in water samples.
Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy
Authors: Dubernard Gil , Oster Michel , Chareyre Fabrice , Antoine Martine , Rouzier Roman , Uzan Serge , Aractingi Selim , Khosrotehrani Kiarash
Published: September 2008

Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal‐derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of “pregnancy‐associated” breast carcinoma. We bred virgin MMTV‐H‐Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells—expressing cytokeratin—are always present in murine breast carcinomas associated with gestation. Interestingly, high‐grade tumors contain more fetal cells. © 2008 Wiley‐Liss, Inc.
Real‐time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV‐1h68 in an immunocompetent animal model
Authors: Kelly Kaitlyn J. , Brader Peter , Woo Yanghee , Li Sen , Chen Nanhai , Yu Yong A. , Szalay Aladar A. , Fong Yuman
Published: September 2008

There is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (MM). We aimed to investigate the use of recombinant vaccinia virus GLV‐1h68, expressing green fluorescent protein (GFP), for real‐time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. Mice bearing foot pad tumors received intratumoral injections of GLV‐1h68, and 48 hr later were evaluated for popliteal lymph node metastasis using noninvasive bioluminescence imaging and fluorescence imaging. Histologic analysis of lymph nodes was performed to determine sensitivity and specificity of virus‐mediated detection. Intratumoral injection of GLV‐1h68 into primary foot pad melanoma tumors resulted in viral transmission to popliteal lymph nodes, infection of lymphatic metastases, and transgene expression that was reliably and easily detected. Histologic confirmation demonstrated favorable operating characteristics of this assay (sensitivity 80%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 91%). Detection of marker gene expression by GLV‐1h68 allowed the detection of lymphatic metastases in an immunocompetent animal model of MM. This assay is rapid, sensitive, specific and easy to perform and interpret. As a candidate gene therapy virusfor killing cancer, GLV‐1h68 may also have significant concomitant diagnostic utility in the staging of cancer patients. © 2008 Wiley‐Liss, Inc.
Green light stimulates somatic growth in the barfin flounder Verasper moseri
Authors: Yamanome Takeshi , Mizusawa Kanta , Hasegawa Ei‐ichi , Takahashi Akiyoshi
Published: September 2008

We examined the effects of different light wavelengths—blue, green, and red—on the somatic growth of the barfin flounder Verasper moseri, a flatfish. The light sources used were fluorescent lamps and a combination of daylight and fluorescent lamps that produced ambient light. These light sources were filtered using blue, green, or red filters. During the experiments, the fish were reared in indoor tanks with running seawater of natural temperature and fed with commercial pellets twice daily until satiety. The tanks were white in color. Fish were exposed to constant light emitted from the fluorescent lamps (9:15, light:dark; 08:00–17:00, light) for 14 weeks from October or September to January or to ambient light with a 14‐week natural photoperiod from September to December. The wavelengths that were filtered from the fluorescent lamp light modified the growth of the fish, i.e., fish reared under green or blue light exhibited a greater total length (TL; P<0.01) and body weight (BW; P<0.01) than those reared under red light. In contrast, in the case of fish exposed to filtered ambient light, fish reared under green light exhibited a greater TL (P<0.01) and BW (P<0.01) than fish exposed to other wavelengths—blue‐, red‐, and nonfiltered ambient light. Our results indicate that flounder growth was modified by certain wavelengths, namely, green and red light, which had growth‐stimulating and growth‐inhibiting effects, respectively. J. Exp. Zool. 311A:73–79, 2009. © 2008 Wiley‐Liss, Inc.
Effects of experimental acidification and alkalinization on soil and growth and health of Acer saccharum Marsh.
Authors: Ouimet Rock , Moore Jean‐David , Duchesne Louis
Published: September 2008

Experimental application of eight acidifying, neutral, or alkalizer compounds (range: –16 to 16 kmol ha–1 of acid‐neutralizing capacity [ANC]) was realized in two northern hardwood stands having significantly different soil base saturation (BS) (a “poor” and a “rich” site) to assess responses of soil physico‐chemical properties, and nutrition, growth, and health of sugar maple (Acer saccharum Marsh.) trees in the short (3 y) and longer term (10 y). The treatments influenced the main indicators of acidity in the forest floor (soil exchangeable‐Ca saturation [SCa], BS, exchangeable‐acidity saturation [SH+Al], and the SCa/SH+Al ratio) at both sites, their values increasing (decreasing for SH+Al) along the ANC treatment gradient in both the short and longer term, except for pH. Base saturation of the upper 15 cm of the mineral B horizons of soils was influenced at the two sites 10 y after treatment application. Although ANC treatments affected nutrient concentrations of tree foliage in the short term, their effect was no longer detectable after 10 y at the two sites. Growth, however, was strongly related to ANC treatments after 10 y, but only at the poor site. From 1990 to 2000, the basal‐area growth rate of trees at the poor site was (mean ± SE) –0.62 ± 0.28 cm2 y–2 tree–1 for the most negative ANC treatment to +0.90 ± 0.20 cm2 y–2 tree–1 for the most positive ANC treatment. A climatic‐stress episode occurring in 1995/96 appeared to accentuate the growth decline of trees subjected to the most negative ANC treatment at the poor site. The experimental results support the hypothesis that atmospheric acid deposition load can cause forest soil base‐cation depletion, acidification, and predispose sugar maple to health and growth decline in the longer term in base‐cation‐poor soils, and that the phenomenon may be reversible by adding alkalizers.
Regression algorithm correcting for partial volume effects in arterial spin labeling MRI
Authors: Asllani Iris , Borogovac Ajna , Brown Truman R.
Published: September 2008

Partial volume effects (PVE) are a consequence of limited spatial resolution in brain imaging. In arterial spin labeling (ASL) MRI, the problem is exacerbated by the nonlinear dependency of the ASL signal on magnetization contributions from each tissue within an imaged voxel. We have developed an algorithm that corrects for PVE in ASL imaging. The algorithm is based on a model that represents the voxel intensity as a weighted sum of pure tissue contribution, where the weighting coefficients are the tissue's fractional volume in the voxel. Using this algorithm, we were able to estimate cerebral blood flow (CBF) for gray matter (GM) and white matter (WM) independently. The average voxelwise ratio of GM to WM CBF was ∼3.2, in good agreement with reports in the literature. As proof of concept, data from PVE‐corrected method were compared with those from the conventional, PVE‐uncorrected method. As hypothesized, the two yielded similar CBF values for voxels containing >95% GM and differed in proportion with the voxels' heterogeneity. More importantly, the GM CBF assessed with the PVE‐corrected method was independent of the voxels' heterogeneity, implying that estimation of flow was unaffected by PVE. An example of application of this algorithm in motor‐activation data is also given. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
Do not resuscitate does not mean do not treat: how palliative care and other modalities can help facilitate communication about goals of care in advanced illness
Authors: Smith Cardinale B. , Bunch O'Neill Lynn
Published: September 2008

A do‐not‐resuscitate (DNR) order is commonly used for hospitalized patients with advanced illness. It reflects only the desires of a patient once he or she suffers a full cardiopulmonary arrest. It does not reflect preferences about other forms of life‐sustaining treatments. This article reviews the definition of a DNR order, describes the evidence suggesting that physicians use a DNR order in making determinations about other life‐sustaining treatments, and will provide tools such as the use of palliative care consultations and combined directives in discussing overall goals of care. Mt Sinai J Med 75: 460–465, 2008. © 2008 Mount Sinai School of Medicine
The ‘Distress Barometer’: validation of method of combining the Distress Thermometer with a rated complaint scale
Authors: Bauwens S. , Baillon C. , Distelmans W. , Theuns P.
Published: September 2008

Objective: Screening instruments may enhance the clinician's ability to detect elevated levels of distress in cancer patients, but these are often neither suitable nor effective for the routine of daily care for cancer patients. The newly developed Distress Barometer (DB) was intended to provide medical doctors with a convenient tool to interpret ‘at single glance’ the nature and the intensity of distress in ambulatory cancer patients. The DB, i.e. a combination of the Distress Thermometer (DT) and a new tool, the Colored Complaint Scale was developed to improve the specificity of distress screening without decreasing the sensitivity of the Distress Thermometer.

Methods: Distress was screened in a sample of 538 out‐patients, using the Hospital Anxiety and Depression Scale (HADS) and the new Distress Barometer (DB).

Results: The results confirm the validity of the Dutch version of the DT against the HADS as standard measure. In addition, it was found that the overall accuracy of the new DB was higher, with a sensitivity of 0.79 and a specificity of 0.81.

Conclusion: These results indicate that the Distress Barometer, which is convenient for both patients and doctors, can be used as an acceptable, brief and sufficiently accurate method for detecting distress in cancer patients. Copyright © 2008 John Wiley & Sons, Ltd.
Monitoring of Venturia inaequalis harbouring the QoI resistance G143A mutation in French orchards as revealed by PCR assays
Authors: Fontaine Séverine , Remuson Florent , Fraissinet‐Tachet Laurence , Micoud Annie , Marmeisse Roland , Melayah Delphine
Published: September 2008

BACKGROUND: Genetic resistance to QoI fungicides may account for recent failures to control Venturia inaequalis (Cooke) Winter in French orchards. Two PCR‐based assays were developed to detect the G143A point mutation in the fungal mitochondrial cytochrome b gene. The mutation is known to confer a high level of resistance to QoI fungicides. Occurrence of the G143A mutation in French field isolates collected from 2004 to 2007 was monitored.

RESULTS: The QoI‐resistant cytochrome b allele was specifically detected either following the cleavage of the amplified marker by a restriction endonuclease (CAPS assay) or its amplification using an allele‐specific PCR primer. Using either method, the G143A mutation was found in 42% of the 291 field samples originating from French orchards in which apple scab proved difficult to be controlled. Monitoring of the G143A mutation in orchards located in 15 French administrative regions indicated that the mutation was detected at least once in nine of the regions, and its presence ranged from 33% to 64% of the orchards analysed in 2004 and in 2007 respectively.

CONCLUSION: The PCR‐based methods developed in this study efficiently reveal the presence of the G143A mutation in French V. inaequalis field populations. Copyright © 2008 Society of Chemical Industry
Ultrasound-guided core needle biopsy of parotid gland swellings
Authors: Pratap R , Qayyum A , Ahmed N , Jani P , Berman L H
Published: September 2008

Objective:

To determine whether ultrasound-guided core needle biopsy is a safe and reliable investigation in cases of parotid swelling in which fine needle aspiration cytology has failed to give a definitive diagnosis.

Design:

Analysis of 66 ultrasound-guided core biopsy specimens of the parotid gland (the largest series reported thus far) sample number refers to histological samples throughout the paper.

Subjects:

All the 184 cases of parotid surgery with a histological diagnosis were included.

Main outcome measures:

The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology and ultrasound-guided core needle biopsy, as compared with the final histological analysis.

Results:

Of a total of 184 patients, 89.1 per cent (164/184) had benign parotid lesions excised. The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology for benign lesions were 76.2, 84.2 and 87.5 per cent, respectively, and those of ultrasound-guided core needle biopsy were 91.7, 98.2 and 96.4 per cent, respectively. Twenty of 184 patients (10.9 per cent) had malignant lesions. The sensitivity, positive predictive value and diagnostic accuracy of fine needle aspiration cytology for detection of malignant lesions were 60, 75 and 75 per cent, respectively, while those of ultrasound-guided core biopsy were 89, 100 and 100 per cent, respectively. Non-diagnostic rates were 25.8 per cent for fine needle aspiration cytology and 4.5 per cent for ultrasound-guided core biopsy. Only one case of complications (a sub-clinical haematoma) occurred in the ultrasound-guided core biopsy group.

Conclusion:

We propose ultrasound-guided core needle biopsy as a very safe and effective tool in cases of parotid swelling in which fine needle aspiration cytology has failed to give a definitive diagnosis.