bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of hyaluronan synthesis in breast cancer cells by 4‐methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo
Authors: Urakawa Hiroshi , Nishida Yoshihiro , Wasa Junji , Arai Eisuke , Zhuo Lisheng , Kimata Koji , Kozawa Eiji , Futamura Naohisa , Ishiguro Naoki
Published: March 2011

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4‐methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the progression of bone metastasis via inhibition of HA synthesis. Here, we investigated the effects of MU on HA expression in MDA‐MB‐231 breast cancer cell line in addition to their tumorigenicity in vitro and in vivo. HAS2 mRNA expression was downregulated after 6 and 24 hr treatment with MU. Quantitative analysis of HA revealed that MU significantly inhibited the intracellular and cell surface HA. MU significantly inhibited cell growth and induced apoptosis as determined by cell proliferation and TUNEL assays, respectively. Phosphorylation of Akt was suppressed after 12 and 24 hr treatment with MU. MU treatment also inhibited cell motility as well as cell invasiveness. MU also inhibited cell growth and motility in murine fibroblast cell line NIH3T3. In vivo, administration of MU inhibited the expansion of osteolytic lesions on soft X‐rays in mouse breast cancer xenograft models. HA accumulation in bone metastatic lesions was perturbed peripherally. These data suggest that MU might be a therapeutic candidate for bone metastasis of breast cancer via suppression of HA synthesis and accumulation.
Expression of epithelial–mesenchymal transition‐inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy
Authors: Mego Michal , Mani Sendurai A. , Lee Bang‐Ning , Li Changping , Evans Kurt W. , Cohen Evan N. , Gao Hui , Jackson Summer A. , Giordano Antonio , Hortobagyi Gabriel N. , Cristofanilli Massimo , Lucci Anthony , Reuben James M.
Published: March 2011

Epithelial cancer cells are likely to undergo epithelial–mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT‐inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of patients with primary breast cancer (PBC). PB mononuclear cells were isolated from 52 patients with stages I–III PBC and 30 healthy donors (HDs) and were sequentially depleted of EpCAM+ cells and CD45+ leukocytes, henceforth referred to as CD45−. The expression levels of EMT‐inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) in the CD45− cells were determined using quantitative real‐time polymerase chain reaction. The highest level of expression by the CD45− cell fraction of HD was used as “cutoff” to determine if samples from patients with PBC overexpressed any EMT‐inducing TFs. In total, 15.4% of patients with PBC overexpressed at least one of the EMT‐inducing TF transcripts. Overexpression of any EMT‐inducing TF transcripts was more likely to be detected in patients with PBC who received neoadjuvant therapies (NAT) than patients who received no NAT (p = 0.003). Concurrently, CTCs were detected in 7 of 38 (18.4%) patients by CellSearch® and in 15 of 42 (35.7%) patients by AdnaTest™. There was no association between the presence of CTCs measured by CellSearch® or AdnaTest™. In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of patients with PBC and that NAT is unable to eliminate CTCs undergoing EMT.
Aberrant DNA methylation and tumor suppressive activity of the EBF3 gene in gastric carcinoma
Authors: Kim Jin , Min Sun Young , Lee Hee Eun , Kim Woo Ho
Published: March 2011

The early B‐cell factors (EBFs) are a group of four highly conserved DNA‐binding transcription factors with an atypical zinc‐finger and a helix‐loop‐helix domain. The EBF3 locus on chromosome 10q26.3 is epigenetically silenced or deleted in several types of cancers. In addition, EBF3 activates genes involved in cell cycle arrest and inhibits cell survival. However, inactivation of EBF3 gene expression was not fully studied in gastric carcinoma and the functions of EBF3 that underlie EBF3‐regulated tumor suppression have not been identified. In our study, we found that inactivation of the EBF3 gene is frequently accompanied by promoter region hypermethylation in several gastric cancer cell lines and that the gene is reactivated by 5‐aza‐2′‐deoxycytidine (5‐aza‐dc) and/or trichostatin A (TSA) in all ten gastric cancer cell lines. We performed functional analysis using small interfering RNA or expressional cDNA transfection in gastric cancer cell lines and demonstrate that EBF3 represses gastric cancer cell growth and migration, but activates cell cycle arrest and apoptosis. Promoter methylation of EBF3 was detected in 42/104 (40.4%) gastric cancer tissues but not in normal gastric tissues. Furthermore, promoter methylation of EBF3 was found to be significantly correlated with lymphatic invasion (p = 0.013) and poor survival (p = 0.038) in gastric carcinoma. These results suggest that EBF3 tumor suppressor is epigenetically silenced and that it serves as an independent prognostic marker in gastric carcinoma.
A fast, cost‐efficient and sensitive approach for KRAS mutation detection using multiplexed primer extension with IP/RP‐HPLC separation
Authors: Tierling Sascha , Sers Christine , Lehmann Annika , Walter Jörn
Published: March 2011

Mutations in the KRAS gene are very important diagnostic and prognostic markers in cancer. Particularly, KRAS mutations at codons 12 and 13 have a high prognostic value for EGFR‐directed antibody therapies. Several methods are available to detect the most common mutations, some of them are commercialized. The most frequently used techniques, allele‐specific PCR or direct sequencing, are not standardized and often lack sensitivity to detect low amounts of mutated tumor cells in paraffin‐embedded tissue‐blocks leading to a high number of false‐negatives. Here we present a reliable, fast, cost‐effective and sensitive approach for KRAS mutation detection that has a high potential for standardized large scale screening. The method is based on multiplexed primer extension reactions coupled to HPLC separation. The highly sensitive assay gives easily interpretable and reproducible results at affordable costs. We describe the method and an application example for diagnosis in early colorectal cancer screening.
Genetic variation in bone morphogenetic protein and colon and rectal cancer
Authors: Slattery Martha L. , Lundgreen Abbie , Herrick Jennifer S. , Kadlubar Susan , Caan Bette J. , Potter John D. , Wolff Roger K.
Published: March 2011

Bone morphogenetic proteins (BMP) are part of the TGF‐β‐signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study, we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs) and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population‐based case‐control studies (colon cancer n = 1,574 cases, 1,970 controls; rectal cancer n = 791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2 and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high‐risk genotypes. A summary of high‐risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR = 2.49 95% CI = 1.95, 3.18). BMPR2, BMPR1B, BMP2 and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI = 1.87, 4.72). Genes in the BMP‐signaling pathway were consistently associated with CIMP+ status in combination with both KRAS‐mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF‐β‐signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4 and Smad 7. Our data support a role for genetic variation in BMP‐related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF‐β‐signaling pathway.
Different effects of polycyclic aromatic hydrocarbons in artificial and in environmental mixtures on the free living nematode C. elegans
Authors: Liuzzi Vania Cosma , Daresta Barbara Elisabetta , de Gennaro Gianluigi , De Giorgi Carla
Published: March 2011

Polycyclic aromatic hydrocarbons (PAHs) are known to exert mutagenic and carcinogenic effects. Research on extracted organic matter (EOM) from environmental mixtures has indicated several mechanisms of intracellular damage in living organisms. The toxic effect of environmental pollutants is usually assessed on cell systems or in single species. We used the model organism Caenorhabditis elegans to compare the effect of synthetic PAHs with that of the EOM from environmental mixtures. The biological effect was measured by monitoring the expression level of some crucial genes, sensitive parameters of the organism's response. The results indicate the ability of C. elegans to counteract damage by mounting a stress‐response only in the presence of EOM. On the other hand the exposure of C. elegans to a mixture of synthetic PAHs determines the silencing of the transcriptional machinery, thus preventing the synthesis of proteins that are important for both the damage repair mechanism and survival itself. The results strongly indicate that the study of environmental toxicant effects at the molecular level may provide information on their mechanism of action. Copyright © 2011 John Wiley & Sons, Ltd.
Neural regrowth induced by PLGA nerve conduits and neurotrophin‐3 in rats with complete spinal cord transection
Authors: Fan Juan , Zhang Hongtian , He Jianghong , Xiao Zhifeng , Chen Bing , Xiaodan Jiang , Dai Jianwu , Xu Ruxiang
Published: March 2011

Biomaterials and neurotrophic factors represent two promising strategies for spinal cord injury repair. In this study, a combinatorial approach combining the PLGA nerve conduits and the recombinant human neurotrophin‐3 (rhNT3) was utilized in a spinal cord injury animal model. After complete transection of the thoracic cord in rats, rhNT3 was administered as a single dose to the host cord caudal to a 2‐mm conduit. Axonal regrowth was enhanced, as indicated by immunostaining and neurofilament‐positive area measurement. Neural regrowth was further demonstrated via the retrograde tracing across the lesion. The animals implanted with the PLGA scaffold and rhNT3 exhibited significantly improved performance in BBB rating scale and grid walk tests. These observations suggest that PLGA nerve conduits combined with exogenous NT3 may serve as an alternative therapeutic approach for spinal cord injury repair. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Bringing generalists into the hospital: Outcomes of a family medicine hospitalist model in Singapore
Authors: Hock Lee Kheng , Yang Yong , Soong Yang Kok , Chi Ong Biauw , Seong Ng Han
Published: March 2011

PURPOSE:

The aim of this study was to assess a newly introduced hospitalist care model in a Singapore hospital. Clinical outcomes of the family medicine hospitalists program were compared with the traditional specialists‐based model using the hospital's administrative database.

METHODS:

Retrospective cohort study of hospital discharge database for patients cared for by family medicine hospitalists and specialists in 2008. Multivariate analysis models were used to compare the clinical outcomes and resource utilization between patients cared for by family medicine hospitalists and specialist with adjustment for demographics, and comorbidities.

RESULTS:

Of 3493 hospitalized patients in 2008 who met the criteria of the study, 601 patients were under the care of family medicine hospitalists. As compared with patients cared for by specialists, patients cared for by family medicine hospitalists had a shorter hospital length of stay (adjusted LOS, geometric mean, GM, 4.4 vs. 5.3 days; P < 0.001) and lower hospitalization costs (adjusted cost, GM, $2250.7 vs. $2500.0; P= 0.003), but a similar in‐patient mortality rate (4.2% vs. 5.3%, P= 0.307) and 30‐day all‐cause unscheduled readmission rate (7.5% vs. 8.4%, P= 0.231) after adjustment for age, ethnicity, gender, intensive care unit (ICU) admission, numbers of organ failures, and comorbidities.

CONCLUSION:

The family medicine hospitalist model was associated with reductions in hospital LOS and cost of care without adversely affecting mortality or 30‐day all‐cause readmission rate. These findings suggest that the hospitalist care model can be adapted for health systems outside North America and may produce similar beneficial effects in care efficiency and cost savings. Journal of Hospital Medicine 2011. © 2011 Society of Hospital Medicine.
Early joint tissue changes are highly correlated with a set of inflammatory and degradative synovial biomarkers after ACL autograft and its sham surgery in an ovine model
Authors: Heard Bryan J. , Achari Yamini , Chung May , Shrive Nigel G. , Frank Cyril B.
Published: March 2011

While impossible in humans, the mechanisms of early cartilage, bone and meniscal damage can be quantified after anterior cruciate ligament (ACL) injury in animal models. We utilized an ovine model to determine if the mRNA expression of inflammatory and degradative molecules (IL‐1β, IL‐6, MMP‐1, 2, 3, and 13) in the synovium correlated to changes in joint tissues 2 weeks post‐ACL surgery, to test the hypothesis that synovial inflammation is a marker of these changes and possibly their originator. Nine “idealized” ACL autografts were performed and compared with three sham and six normal animals. Using validated protocols, early osteophyte formation, articular cartilage, and meniscal damage were quantified. Synovium was harvested and mRNA expression quantified using qPCR. Multiple linear regression analysis (MLRA) was utilized to correlate synovial mRNA expression in treated and contra‐lateral limbs, from all treatment groups with corresponding joint scores. Synovial mRNA expression was significantly elevated in all experimental and sham joints. The MLRA model was a significant predictive tool (p = 0.001, R2 = 0.70) of gross tissue scores with significant contributions from IL‐1β, IL‐6, and MMP‐3. Findings suggest that this set of synovial biomarkers is predictive (p < 0.009) of early gross changes of joint tissues after arthrotomy and likely directly involved in the relevant mechanisms, particularly early osteophyte formation, in vivo. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1185–1192, 2011
Effect of fertiliser on functional properties of flour from four rice varieties grown in Sri Lanka
Authors: Gunaratne Anil , Sirisena Nihal , Ratnayaka Upul Kumari , Ratnayaka Jennet , Kong Xiangli , Vidhana Arachchi Lal Peruma , Corke Harold
Published: March 2011

BACKGROUND: Fertiliser is an essential agro‐chemical input in modern rice farming. Fertiliser affects the grain quality and yield of rice. Although much research has been carried out to investigate the influence of fertiliser (recommended NPK addition) on yield and quality of rice grain, little is known about the effect of fertiliser on thermal, pasting, gelling and retrogradation properties of rice flour. The aim of this study was to investigate the influence of recommended fertilisation on functional properties of rice flour from four popular high yielding rice varieties grown in Sri Lanka.

RESULTS: Fertiliser (recommended NPK addition) increased the protein content but reduced the apparent amylose content in rice flour except in BG 357. Swelling power and amylose leaching of rice flour were also increased. Pasting onset temperature, cold paste viscosity and setback were increased but peak viscosity and granular breakdown decreased. In response to the fertiliser application, gelatinisation peak temperature was reduced in all varieties except BG 300. However, compared to pasting properties, gelatinisation parameters were not much affected by fertilisation. The extent of amylopectin retrogradation was decreased by fertiliser in BG 305 and BG 352 but unchanged in the other two varieties. Except in BG 305, fertiliser reduced the gel hardness of rice flour but increased the gel cohesiveness.

CONCLUSION: It is apparent that the increased protein and reduced amylose content caused by fertiliser affect the functional properties of rice flour. Copyright © 2011 Society of Chemical Industry
755 nm alexandrite laser for the reduction of tumor burden in basal cell Nevus syndrome
Authors: Ibrahimi Omar A. , Sakamoto Fernanda H. , Tannous Zeina , Anderson R. Rox
Published: March 2011

Background and Objective

Basal Cell Nevus syndrome (BCNS) is characterized by numerous basal cell carcinomas (BCCs). Multiple treatments with the pulsed dye laser (PDL) have been shown, in small studies, to be effective for the treatment of superficial and nodular BCCs. Like PDL, the alexandrite laser can be vessel‐selective, but has the added advantage of deeper tissue penetration. We evaluated the utility of the alexandrite laser in reducing the tumor burden in BCNS with a single treatment.

Study Design/Materials and Methods

A case report and review of the literature are presented. A 45‐year‐old man with BCNS and a history of radiation therapy presented with an extraordinarily high tumor burden (>250 BCCs). As a compassionate measure to reduce the tumor burden, we investigated the utility of a single treatment of the long‐pulsed 755 nm alexandrite laser to several BCC lesions. The treated lesions were evaluated at 2‐month and 7‐month clinical follow‐up. Histopathologic analysis of a treated lesion was performed at 7‐month clinical follow‐up.

Results

At 2‐month, and 7‐month clinical follow‐up, 15 of 18 treated lesions or about 83% of the alexandrite laser treated lesions showed a complete clinical response and appeared as hypopigmented areas with scarring. Histopathologic analysis of a treated lesion at 7‐month clinical follow‐up showed no evidence of residual tumor.

Conclusions

The long‐pulsed alexandrite laser may be helpful in significantly reducing tumor burden in difficult to manage BCNS patients with a single treatment. This provides a facile and practical treatment alternative for the management of challenging cases of BCNS. The limitation of this study is that it is a single case observation. Larger, prospective studies are needed to confirm these observations. Lasers Surg. Med. 42:68–71, 2011 © 2011 Wiley‐Liss, Inc.
Histologic analysis of a 2,940 nm fractional device
Authors: Kist David A. , Elm Courtney M.L. , Eleftheriou Lydia I. , Studer Jessica A. , Wallander Irmina D. , Walgrave Susan E. , Zelickson Brian D.
Published: March 2011

Background and Objectives

An evaluation of the histological effects of a 2,940 nm fractional erbium:YAG (Er:YAG) laser device with adjustable depth and coagulation settings in a human abdominoplasty model. The goal of this study was to use light and confocal microscopy to determine the dimensions of the microthermal zones (MTZs) created by this device in the epidermal and dermal layers.

Study Design/Materials and Methods

Three subjects were consented and treated after being randomly assigned to a laser depth of either 250 µm, 500 µm, or 1,000 µm. Four coagulation levels were tested in each subject. Two biopsies were taken immediately, 1 and 2 weeks post‐treatment from each zone and viewed by light and confocal microscopy. Two blinded observers examined the sections for changes in collagen and measured depth and width of the MTZs. Coagulation was assessed and recorded as the depth and width of denaturation; measured as the depth and width of ablation plus surrounding thickness of thermal necrosis from dissipated heat.

Results

Light microscopy findings in all treated samples showed a perforated epidermis and dermis immediately after treatment. The depths of ablation produced did not accurately reflect the three different laser settings. Depths of denaturation also did not increase with increased coagulation level settings as expected. The width of ablation in the MTZs, a non‐adjustable setting, was the most accurate and reproducible in all subjects. Confocal microscopy samples revealed the presence of collagen remodeling in the dermis, which increased significantly at 1 and 2 weeks post‐treatment.

Conclusions

Treatment with the 2,940 nm Er:YAG device led to significant changes of the dermis at light microscopy levels. The adjustable laser depth and coagulation settings did not produce predictable depths of ablation or denaturation, possibly as a result of the variation of tissue hydration properties among individuals. Increased collagen remodeling was seen in the dermis in all subjects at 1 and 2 weeks post‐treatment. Lasers Surg. Med. 42:79–91, 2011 © 2011 Wiley‐Liss, Inc.
Mass spectrometry‐based holistic analytical approaches for metabolite profiling in systems biology studies
Authors: Theodoridis Georgios , Gika Helen G. , Wilson Ian D.
Published: March 2011

Metabonomics and metabolomics represent one of the three major platforms in systems biology. To perform metabolomics it is necessary to generate comprehensive “global” metabolite profiles from complex samples, for example, biological fluids or tissue extracts. Analytical technologies based on mass spectrometry (MS), and in particular on liquid chromatography–MS (LC–MS), have become a major tool providing a significant source of global metabolite profiling data. In the present review we describe and compare the utility of the different analytical strategies and technologies used for MS‐based metabolomics with a particular focus on LC–MS. Both the advantages offered by the technology and also the challenges and limitations that need to be addressed for the successful application of LC–MS in metabolite analysis are described. Data treatment and approaches resulting in the detection and identification of biomarkers are considered. Special emphasis is given to validation issues, instrument stability, and QA/quality control (QC) procedures. © 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:884–906, 2011
Design and synthesis of polytripeptide (leuglnpro)n based upon the matrix protein amelogenin
Authors: Sogah Dotsevi Y. , Perle‐Treves Daniele , Voyer N. , Degrado W. F.
Published: March 2011

A linear neutral repetitive peptide, (Leu‐Gln‐Pro)n (n = 1‐100), an analog of the Ca2+ ion‐binding domain of the matrix protein, amelogenin, has been synthesized. The polypeptide is mostly unordered in trifluoroethanol (TFE) at 25°C and its circular dichroism (CD) spectrum resembles that of the protein itself. In TFE the CD spectrum of (Leu‐Gln‐Pro)n reveals that the polypeptide interacts strongly with divalent cations Mg2+, Ca2+, Sr2+, and Ba2+ accompanied by conformational rearrangement from a random to a more‐ordered one. In the presence of Li+, Na+ and K+ ions no such conformational change has been observed. The CD curves of the complexes suggest the presence of type I β‐turns and reinforce the hypothesis that the region Gln112‐Leu138 in amelogenin is the Ca2+‐binding domain. In the solid state, powder X‐ray diffraction suggests that the polymeric (LQP)n may exist as isolated “rigid rods”.
Hybrid materials from organic polymers and inorganic salts
Authors: Köberle Peter , Laschewsky André
Published: March 2011

The prepaparation of amorphous, homogeneous blends of zwitterionic polymers and transition metal salts was investigated. Homogeneous miscibility was achieved in many cases up to equimolar amounts of salt, depending on the anion and cation chosen. Various analytical techniques point to a solid state solution of the inorganic ions in the polymer matrix.
Emulsion polymerization with water soluble comonomers in batch and continuous reactors
Authors: Poehlein Gary W.
Published: March 2011

Emulsion copolymerization reactions which include monomers that have significant solubility in the water phase are described and modeled. The reactions that take place in the aqueous phase are considered as is the influence of water‐soluble comonomers on radical transport out of the monomer‐swollen polymer particles. Experimental characterization of the oligomers formed in the aqueous phase is also a subject of this paper.
Cationic latexes as catalytic media
Authors: Ford Warren T. , Lee Jeng‐Jong , Yu Hui , Ackerson Bruce J. , Davis Keith A.
Published: March 2011

Monodisperse cationic latexes containing 1–60 mol‐% of quaternary ammonium ion repeat units increase the rates of decarboxylation of 6‐nitro‐benzisoxazole‐3‐carboxylate and of o‐iodosobenzoate‐catalyzed hydrolysis of p‐nitrophenyl diphenyl phosphate by factors of up to 10500 and 6300 compared with the rates in aqueous solutions. The catalytic effects are due more to high local concentrations of reactants in the particles than to increased rate constants of reaction in particles.
Direct measurement of shear forces between polymer‐bearing surfaces sliding past each other
Authors: Klein Jacob , Kumacheva Eugenia , Mahalu Diana , Perahia Dvora
Published: March 2011

We have used a recently developed surface force balance to measure, with extreme sensitivity, both lateral and normal forces between interacting surfaces, for the case of simple liquids and particularly with surface‐attached polymers. The presence of polymers on the surfaces reduces drastically the force required to maintain them in sliding motion, under a given normal load, relative to the bare surface case. We believe this is due to the long range steric repulsion which can sustain a large normal load while maintaining a very fluid interfacial layer. The effect is much more marked for end‐tethered chains in a good solvent than for adsorbed chains in a θ‐solvent. This is attributed to the different extents of interpenetration of the compressed polymer layers.
Environmentally sound manufacturing and polymer industry for the 21st century
Authors: Yoda Naoya
Published: March 2011

Life cycle assessments to protect global environment and to control waste in the polymer industry are reviewed. It focused on 1) the environmentally sound technology, 2) the energy conservation, and 3) recycling of industrial products. The competitiveness of a nation depends on how to balance between economic development of sustainable growth and responsible care of global environment in borderless economy. It fully depends on the development of both the environmentally sound manufacturing and the effective products recycling technologies. Current environmental issues of the Japanese chemical industries as well as Toray's performance and new products development for environment business are reviewed; 1) Energy conservation and technology of Japanese manufacturing industry. 2) Development of environmentally sound technology. 3) Effective products recycling technologies, and 4) Sustainable growth of the new chemical age. The future issues of life cycle assessment and environmental protection in manufacturing industries are discussed.
Sophisticated macromolecular structures by cationic ring‐opening polymerizations
Authors: Goethals Eric J. , van Caeter Peter , Du Prez Filip E. , Dubreuil Marjorie F.
Published: March 2011

A combination of different types of cationic ring‐opening polymerizations (CROPs) has been used to construct macromolecular structures containing polymer segments with different physicochemical properties. The cyclic monomers used are tetrahydrofuran (THF), N‐tert‐butyl aziridine (TBA), 2‐methyl‐1, 3‐oxazoline (MeOX) and 1, 3‐dioxolane (DXL).

The macromolecular structures include different block and graft copolymers, telechelics and macromonomers, star‐ and comb‐shaped polymers, polymer networks and interpenetrating polymer networks (IPNs).
More fun & games with rings, strings & rods
Authors: Gibson Harry W. , Liu Shu , Lee Sang‐Hun , Marand Herve' , Prasad Abaneshwar , Wang Feng , Bheda Mukesh , Nagvekar Devdatt
Published: March 2011

The formation of polyrotaxanes of type 1 by “statistical” threading1 will be described. Examples will include polymerization in the presence of macrocycles and threading of preformed polymers and macrocycles. An analysis of the structural and experimental factors involved in the threading process will be presented. The solution and solid state behavior of the polyrotaxanes will be discussed, including situations in which Tg can be controlled by macrocycles that are compatible with the backbone and situations where the threaded macrocycles crystallize. The preparation of polyrotaxanes of type 3 by threading of polymacrocycles 2 with linear polymers and the resultant changes in physical properties will also be described.
Templated biological synthesis of polymers of abiological monomers
Authors: Kothakota Srinivas , Dougherty Michael J. , Fournier Maurille J. , Mason Thomas L. , Yoshikawa Eiichiro , Tirrell David A.
Published: March 2011

A general method for the in vivo incorporation of amino acid analogues into artificial proteins is described. The method involves the construction of an artificial gene encoding the sequence of interest (with the corresponding natural amino acid encoded in place of the analogue), transformation of a bacterial host strain that cannot synthesize the natural amino acid, and induction of protein synthesis in a host culture enriched in the analogue. Results are described for the amino acid analogues selenomethionine, p‐fluorophenylalanine, trifluoroleucine and 3‐thienylalanine.
Secondary doping: A new concept in conducting polymers
Authors: Macdiarmid Alan G. , Epstein Arthur J.
Published: March 2011

Phenomenologically, a primary dopant for a conducting polymer is a substance which drastically changes the electronic, optical, magnetic, and/or structural properties of the polymer and is accompanied by a large increase in conductivity. Phenomenologically, a secondary dopant is an apparently “inert” substance which, when applied to a primary‐doped polymer, induces still further changes in the above properties including a further increase in conductivity. The concept of secondary doping will be illustrated using polyaniline and its derivatives.
Epitaxy of helical polyolefins
Authors: Kopp Sophie , Wittmann Jean‐Claude , Lotz Bernard
Published: March 2011

The structural rules which govern the epitaxial crystallisation of polymers ‐ and especially polyolefins ‐ on organic substrates are established. Illustrative examples involve isotactic and syndiotactic polypropylenes and poly( l‐butene). Investigation of the film structure by electron microscopy, electron diffraction and atomic force microscopy reveals some unprecedented features, including in particular the selection of the contact plane according to the chirality of its constituent helices, and direct observation of both right and left hands of polyolefin helices.
Drugs that target dynamic microtubules: A new molecular perspective
Authors: Stanton Richard A. , Gernert Kim M. , Nettles James H. , Aneja Ritu
Published: March 2011

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule‐binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule‐targeting drugs work.   © 2011 Wiley Periodicals, Inc. Med Res Rev, 31, No. 3, 443‐481, 2011
Conjugated linoleic acid decreases prostaglandin synthesis in bovine luteal cells in vitro
Authors: May Katherine C.P. , Bobe Gerd , Mueller Chad J. , Cannon Matthew J.
Published: March 2011

Feeding conjugated linoleic acids (CLA) improves reproductive performance in dairy cows; however, the molecular mechanisms by which CLA improves reproduction are not understood. The effect of the CLA isomers, trans‐10, cis‐12 CLA and cis‐9, trans‐11 CLA on synthesis of progesterone, PGE2, and PGF2α, in bovine luteal cells was determined in this study. Luteal cells from three cows were cultured in medium containing 0 or 0.1 µM of trans‐10, cis‐12 CLA and cis‐9, trans‐11 CLA in varying ratios in the presence and absence of 1 µM of forskolin. Prostaglandin and progesterone concentrations were not altered by CLA isomer and ratio. Luteal cells cultured in the presence of CLA had lower PGF2α concentrations (62.6 ± 13.4 pg/ml vs. 55.7 ± 12.2 pg/ml; P = 0.005) and, in the absence of forskolin, lower PGE2 concentrations (65.3 ± 15.1 pg/ml vs. 32.4 ± 14.1 pg/ml; P = 0.002) in culture media, while progesterone concentrations were not altered (P = 0.63). Relative steady‐state mRNA amounts of COX‐2 (1.7‐fold decrease; P = 0.002), PGE synthase (1.5‐fold decrease; P = 0.03) and 3β‐hydroxysteroid dehydrogenase (1.6‐fold decrease; P = 0.0003) were lower in CLA‐treated cultures, but CLA did not significantly alter mRNA amounts of PGE2 9‐keto‐reductase, StAR, and cytochrome P450 side chain cleavage enzyme. In conclusion, a potential mechanism exists by which trans‐10, cis‐12 CLA and cis‐9, trans‐11 CLA may improve reproductive performance in dairy cows, by suppressing PGF2α synthesis in luteal cells via attenuation of COX‐2 gene expression. Mol. Reprod. Dev. 78:328–336, 2011. © 2011 Wiley‐Liss, Inc.
Hybrid state‐space time integration in a rotating frame of reference
Authors: Krenk Steen , Nielsen Martin B.
Published: March 2011

A time integration algorithm is developed for the equations of motion of a flexible body in a rotating frame of reference. The equations are formulated in a hybrid state‐space, formed by the local displacement components and the global velocity components. In the spatial discretization the local displacements and the global velocities are represented by the same shape functions. This leads to a simple generalization of the corresponding equations of motion in a stationary frame in which all inertial effects are represented via the classic global mass matrix. The formulation introduces two gyroscopic terms, while the centrifugal forces are represented implicitly via the hybrid state‐space format. An angular momentum and energy conserving algorithm is developed, in which the angular velocity of the frame is represented by its mean value. A consistent algorithmic damping scheme is identified by applying the conservative algorithm to a decaying response, which is rendered stationary by an increasing exponential factor that compensates the decay. The algorithmic damping is implemented by introducing forward weighting of the mean values appearing in the algorithm. Numerical examples illustrate the simplicity and accuracy of the algorithm. Copyright © 2011 John Wiley & Sons, Ltd.
The time to diagnosis in childhood lymphomas and other solid tumors
Authors: Cecen Emre , Gunes Dilek , Mutafoglu Kamer , Sarialioglu Faik , Olgun Nur
Published: March 2011

Background

There are few reports from developing countries on the factors that influence the time to diagnosis (TD) in childhood cancer. The purpose of this study was to investigate the determinants of the TD in Turkish cancer patients.

Procedure

A retrospective analysis was performed on 329 children diagnosed with cancer, excluding leukemia. The TD, including parent/patient time and physician time, was defined as the interval between the onset of symptoms and the final diagnosis.

Results

The median times for parent/patient, physician, and TD were 3, 28, and 53 days, respectively. For patient in the 1–9 years age group, physician time and TD were significantly shorter than in infants and those over 10 years. The longest median TD was recorded for children with germ cell tumors and retinoblastoma; the shortest was in children with renal tumors. When the first point of contact was a pediatrician, a private hospital or physician's office, a governmental educational hospital or a university hospital physician time was short. The longest TD was noted in patients who first contacted a non‐pediatric specialist. The most significant predictors of parent/patient, physician time, and TD were metastases at diagnosis, first medical center, and first health professional contacted, respectively.

Conclusions

The TD for childhood lymphomas and solid tumors was related to patient age, tumor type and location, the presence of distance metastases, first health professional, and center contacted. All physicians, especially other specialists seeing pediatric patients, need to be further sensitized to the signs and symptoms of childhood cancer. Pediatr Blood Cancer 2011; 57: 392–397. © 2011 Wiley‐Liss, Inc.
Nijmegen breakage syndrome (NBS) as a risk factor for CNS involvement in childhood acute lymphoblastic leukemia
Authors: Pastorczak Agata , Stolarska Malgorzata , Trelińska Joanna , Zawitkowska Joanna , Kowalczyk Jerzy , Mlynarski Wojciech ,   on behalf of the Polish Pediatric Leukemia/Lymphoma Study Group
Published: March 2011

Central nervous system (CNS) involvement is an independent risk factor for poor event‐free survival and relapse confined to the CNS. Knock‐out mice deprived of RAG2, the protein involved in DNA repair, developed leukemic infiltration within leptomeninges. Therefore, we hypothesized that DNA repair deficiencies in humans, such as Nijmegen breakage syndrome (NBS), may constitute a risk factor for CNS dissemination of acute lymphoblastic leukemia (ALL). Having analyzed the incidence of CNS2/CNS3 status at diagnosis of ALL in two independent cohorts from the Polish Pediatric Leukemia/Lymphoma Study Group, we noticed that among children with NBS CNS involvement was significantly frequent. Pediatr Blood Cancer 2011;57:160–162. © 2011 Wiley‐Liss, Inc.
Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations
Authors: Rottenkolber Dominik , Schmiedl Sven , Rottenkolber Marietta , Farker Katrin , Saljé Karen , Mueller Silke , Hippius Marion , Thuermann Petra A. , Hasford Joerg ,   for the Net of Regional Pharmacovigilance Centers
Published: March 2011

Purpose

German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR‐related economic burden (direct costs) of hospitalizations in internal medicine wards in Germany.

Methods

Record‐based study analyzing the patient records of about 57 000 hospitalizations between 2006 and 2007 of the Net of Regional Pharmacovigilance Centers (Germany). All ADRs were evaluated by a team of experts in pharmacovigilance for severity, causality, and preventability. The calculation of accurate person‐related costs for ADRs relied on the German DRG system (G‐DRG 2009). Descriptive and bootstrap statistical methods were applied for data analysis.

Results

The incidence of hospitalization due to at least ‘possible’ serious outpatient ADRs was estimated to be approximately 3.25%. Mean age of the 1834 patients was 71.0 years (SD 14.7). Most frequent ADRs were gastrointestinal hemorrhage (n = 336) and drug‐induced hypoglycemia (n = 270). Average inpatient length‐of‐stay was 9.3 days (SD 7.1). Average treatment costs of a single ADR were estimated to be approximately €2250. The total costs sum to €434 million per year for Germany. Considering the proportion of preventable cases (20.1%), this equals a saving potential of €87 million per year.

Conclusions

Preventing ADRs is advisable in order to realize significant nationwide savings potential. Our cost estimates provide a reliable benchmark as they were calculated based on an intensified ADR surveillance and an accurate person‐related cost application. Copyright © 2011 John Wiley & Sons, Ltd.
Gene‐centric view on the human proteome project: The example of the Russian roadmap for chromosome 18
Authors: Archakov Alexander , Aseev Alexander , Bykov Victor , Grigoriev Anatoly , Govorun Vadim , Ivanov Vadim , Khlunov Alexander , Lisitsa Andrey , Mazurenko Sergey , Makarov Alexander A. , Ponomarenko Elena , Sagdeev Renad , Skryabin Konstantin
Published: March 2011

During the 2010 Human Proteome Organization Congress in Sydney, a gene‐centric approach emerged as a feasible and tractable scaffold for assemblage of the Human Proteome Project. Bringing the gene‐centric principle into practice, a roadmap for the 18th chromosome was drafted, postulating the limited sensitivity of analytical methods, as a serious bottleneck in proteomics. In the context of the sensitivity problem, we refer to the “copy number of protein molecules” as a measurable assessment of protein abundance. The roadmap is focused on the development of technology to attain the low‐ and ultralow ‐“copied” portion of the proteome. Roadmap merges the genomic, transcriptomic and proteomic levels to identify the majority of 285 proteins from 18th chromosome – master proteins. Master protein is the primary translation of the coding sequence and resembling at least one of the known isoforms, coded by the gene. The executive phase of the roadmap includes the expansion of the study of the master proteins with alternate splicing, single amino acid polymorphisms (SAPs) and post‐translational modifications. In implementing the roadmap, Russian scientists are expecting to establish proteomic technologies for integrating MS and atomic force microscopy (AFM). These technologies are anticipated to unlock the value of new biomarkers at a detection limit of 10−18 M, i.e. 1 protein copy per 1μL of plasma. The roadmap plan is posted at www.proteome.ru/en/roadmap/ and a forum for discussion of the document is supported.
A PQL (protein quantity loci) analysis of mature pea seed proteins identifies loci determining seed protein composition
Authors: Bourgeois Michael , Jacquin Françoise , Cassecuelle Florence , Savois Vincent , Belghazi Maya , Aubert Grégoire , Quillien Laurence , Huart Myriam , Marget Pascal , Burstin Judith
Published: March 2011

Legume seeds are a major source of dietary proteins for humans and animals. Deciphering the genetic control of their accumulation is thus of primary significance towards their improvement. At first, we analysed the genetic variability of the pea seed proteome of three genotypes over 3 years of cultivation. This revealed that seed protein composition variability was under predominant genetic control, with as much as 60% of the spots varying quantitatively among the three genotypes. Then, by combining proteomic and quantitative trait loci (QTL) mapping approaches, we uncovered the genetic architecture of seed proteome variability. Protein quantity loci (PQL) were searched for 525 spots detected on 2‐D gels obtained for 157 recombinant inbred lines. Most protein quantity loci mapped in clusters, suggesting that the accumulation of the major storage protein families was under the control of a limited number of loci. While convicilin accumulation was mainly under the control of cis‐regulatory regions, vicilins and legumins were controlled by both cis‐ and trans‐regulatory regions. Some loci controlled both seed protein composition and protein content and a locus on LGIIa appears to be a major regulator of protein composition and of protein in vitro digestibility.
Distress in partners of individuals diagnosed with or at high risk of developing tumors due to rare hereditary cancer syndromes
Authors: Lammens C. R. M. , Bleiker E. M. A. , Verhoef S. , Ausems M. G. E. M. , Majoor‐Krakauer D. , Sijmons R. H. , Hes F. J. , Gómez‐García E. B. , Van Os T. A. M. , Spruijt L. , van der Luijt R. B. , van den Ouweland A. M. W. , Ruijs M. W. G. , Gundy C. , Nagtegaal T. , Aaronson N. K.
Published: March 2011

Objective: Li Fraumeni syndrome (LFS) and Von Hippel‐Lindau disease (VHL) are two rare hereditary tumor syndromes, characterized by a high risk of developing multiple tumors at various sites and ages for which preventive and treatment options are limited. For partners, it may be difficult to deal with the on‐going threat of tumors in both their spouse and children. Therefore, this study aims to evaluate the prevalence of and factors associated with psychological distress among partners of individuals with or at high risk of LFS or VHL.

Methods: As part of a nationwide, cross‐sectional study, partners of individuals diagnosed with or at high risk of LFS or VHL were invited to complete a self‐report questionnaire assessing distress, worries, and health‐related quality of life.

Results: Fifty‐five (58%) of those high‐risk individuals with a partner consented to having their partner approached for the study. In total, 50 partners (91%) completed the questionnaire, of whom 28% reported clinically relevant levels of syndrome‐related distress. Levels of distress and worries of the partners and their high‐risk spouse were significantly correlated. Younger age and a lack of social support were also associated significantly with heightened levels of distress and worries. The majority of partners (76%) believed that professional psychosocial support should be routinely offered to them.

Conclusions: Approximately one‐quarter of the partners exhibit clinically relevant levels of distress that warrant psychological support. The distress levels of the ‘patient’ could potentially be used to identify partners at risk of developing clinically relevant levels of distress. Copyright © 2011 John Wiley & Sons, Ltd.
Zinc‐oxide nanowires electrochemically grown onto sol–gel spin‐coated seed layers
Authors: Bojorge Claudia D. , Kent Vladimir R. , Teliz Erika , Cánepa Horacio R. , Henríquez Rodrigo , Gómez Humberto , Marotti Ricardo E. , Dalchiele Enrique A.
Published: March 2011

The electrochemical deposition of ZnO nanowires (NW) was optimized by growing onto a previously deposited seed layer. The ZnO seed layer was prepared by a sol–gel process from different precursor solutions and deposited onto FTO/glass by spin coating. Afterwards, NW were electrochemically grown onto those seed layers. The electrolyte was an aqueous solution of the Zn+2 precursor (1 mM zinc acetate) and a supporting electrolyte (0.1 M sodium acetate), saturated with bubbling oxygen. The films were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), and optical transmittance. The XRD measurements show typical diffraction pattern of ZnO wurtzite structure. The SEM micrographs show the presence of smooth NW with hexagonal sections with diameters ranging from 40 to 250 nm. The optical transmittance reveals the presence of ZnO with bandgap energy between 3.23 and 3.29 eV. These spectra show a monotonically increasing transmittance from the UV into the red part of the spectrum. This feature may be originated in the dispersion of light at the NW and can be used to enhance below‐gap absorption.

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