bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory cell‐specific transgene expression system responding to Iκ‐B kinase beta activation
Authors: Asai Daisuke , Tsuchiya Akira , Kang Jeong‐Hun , Kawamura Kenji , Oishi Jun , Mori Takeshi , Niidome Takuro , Shoji Yoko , Nakashima Hideki , Katayama Yoshiki
Published: June 2009

Background

Control of inflammation is essential for the clinical management of many common human diseases. However, there are few generally applicable strategies to convert an abnormal intracellular signal into a gene expression that leads to normalization of the intracellular environment. Recently, we proposed a novel strategy termed D‐RECS (i.e. drug or gene delivery system responding to cellular signals) to convert an intracellular signal to transgene expression. In the present study, we applied this concept to inflammatory cells using Iκ‐B kinase as a signal molecule that triggers the gene expression.

Methods

Candidate cationic substrates of Iκ‐B kinase (IKK)β were synthesized and their reactivity was investigated. Then, polymers grafted with these peptides were prepared by radical polymerization. Polymer/DNA complexes (polyplexes) were prepared by mixing plasmid DNAs with the polymers. The behaviour of these polyplexes by adding IKKβ was examined. Furthermore, changes of gene expression were evaluated after the microinjection of polyplex into living cells under conditions of nuclear factor (NF)‐κB activation.

Results

Synthetic peptides with additional lysine residues were well phosphorylated by IKKβ. Both the polymer and the polyplex were also phosphorylated by IKKβ. The results of gel shift assay showed that the polyplex was disintegrated and free DNA was released in the presence of IKKβ. The polyplex comprising‐green fluorescent protein plasmid DNA and the polymer expressed the transgene in living cells exposed to a pro‐inflammatory stimulus.

Conclusions

Our concept of cell‐specific gene expression was demonstrated to work in inflammatory cells. This method may provide a unique strategy for gene therapy exclusively in inflammatory cells. Copyright © 2009 John Wiley & Sons, Ltd.
Associations between rainfall variability in the southwest and southeast of Australia and their evolution through time
Authors: Hope Pandora , Timbal Bertrand , Fawcett Robert
Published: June 2009

Significant rainfall declines have been observed across much of southern Australia over the last 50 years. In particular, strong declines occurred in the southwest of Western Australia (SWWA) from the late 1960s with further declines in the late 1990s, and in the southwest of eastern Australia (SWEA) from the mid‐1990s. As a result, most communities in these regions are facing water shortages. Meteorologically, the regions share a common winter‐maximum rainfall regime, with peak rainfall occurring from May to October. In both regions, the declines have mainly occurred in the early part of the winter half‐year (May–June–July, MJJ). This study aims to assess if there is an association between rainfall variability in these two regions on a range of time‐scales and whether that association has altered with the recent rainfall declines. Rainfall variability in the two regions is significantly related. On synoptic time‐scales, a weak but significant relationship was found in each month of the winter half‐year due to rain‐bearing disturbances travelling along the storm track affecting the two regions with a lag of approximately 3 days. On interannual time‐scales, the relationship is stronger because of the high correlation between mean sea‐level pressures (MSLP) over both regions. MJJ MSLP has seen significant increases over the last 50 years in both regions, reaching record values in 2006. In recent decades the interannual association between early winter rainfall totals has strengthened, however this is due in part to the decreasing variance at each location. The variability of the associations between these two regions provides a background on which to explore the strength and variability of the drivers that influence rainfall variability across southern Australia. Copyright © 2009 Royal Meteorological Society
Validation of a new method for determination of cup orientation in THA
Authors: Steppacher Simon D. , Tannast Moritz , Zheng Guoyan , Zhang Xuan , Kowal Jens , Anderson Suzanne E. , Siebenrock Klaus A. , Murphy Stephen B.
Published: June 2009

Our goal was to validate accuracy, consistency, and reproducibility/reliability of a new method for determining cup orientation in total hip arthroplasty (THA). This method allows matching the 3D‐model from CT images or slices with the projected pelvis on an anteroposterior pelvic radiograph using a fully automated registration procedure. Cup orientation (inclination and anteversion) is calculated relative to the anterior pelvic plane, corrected for individual malposition of the pelvis during radiograph acquisition. Measurements on blinded and randomized radiographs of 80 cadaver and 327 patient hips were investigated. The method showed a mean accuracy of 0.7 ± 1.7° (−3.7° to 4.0°) for inclination and 1.2 ± 2.4° (−5.3° to 5.6°) for anteversion in the cadaver trials and 1.7 ± 1.7° (−4.6° to 5.5°) for inclination and 0.9 ± 2.8° (−5.2° to 5.7°) for anteversion in the clinical data when compared to CT‐based measurements. No systematic errors in accuracy were detected with the Bland–Altman analysis. The software consistency and the reproducibility/reliability were very good. This software is an accurate, consistent, reliable, and reproducible method to measure cup orientation in THA using a sophisticated 2D/3D‐matching technique. Its robust and accurate matching algorithm can be expanded to statistical models. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1583–1588, 2009
The Antarctic palaeo record and its role in improving predictions of future Antarctic Ice Sheet change
Authors: Bentley Michael J.
Published: June 2009

This paper reviews the ways in which the palaeo record of Antarctic Ice Sheet change can be used to improve understanding of contemporary ice sheet behaviour, and thus enhance predictions of future sea‐level change. The main areas where the palaeo ice sheet record can contribute are understanding long‐term ice sheet trajectory; providing data against which ice sheet models can be tested; to identify and understand the range and types of natural ice sheet behaviour; to balance the global water budget; to correct contemporary glaciological measurements of mass change; and to understand the relationship between polar ecosystems and the ice sheet. I review each in turn and argue that research priorities include understanding past West Antarctic Ice Sheet collapse and its timing; a focus on the palaeo record of rapid retreat events and how these unfolded in the geological past; improving the number and range of ice sheet reconstructions, particularly through the Holocene; continuing to investigate the potential for using sediments and landforms to parameterise basal conditions in ice sheet models; and understanding past East Antarctic Ice Sheet dynamics, particularly the evidence for partial deglaciation. Copyright © 2009 John Wiley & Sons, Ltd.
A record of Lateglacial and early Holocene environmental and ecological change from southwestern Connecticut, USA
Authors: Oswald W. Wyatt , Foster David R. , Doughty Elaine D. , Faison Edward K.
Published: June 2009

Analyses of a sediment core from Highstead Swamp in southwestern Connecticut, USA, reveal Lateglacial and early Holocene ecological and hydrological changes. Lateglacial pollen assemblages are dominated by Picea and Pinus subg. Pinus, and the onset of the Younger Dryas (YD) cold interval is evidenced by higher abundance of Abies and Alnus viridis subsp. crispa. As climate warmed at the end of the YD, Picea and Abies declined and Pinus strobus became the dominant upland tree species. A shift from lacustrine sediment to organic peat at the YD–Holocene boundary suggests that the lake that existed in the basin during the Lateglacial interval developed into a swamp in response to reduced effective moisture. A change in wetland vegetation from Myrica gale to Alnus incana subsp. rugosa and Sphagnum is consistent with this interpretation of environmental changes at the beginning of the Holocene. Copyright © 2009 John Wiley & Sons, Ltd.
Chinese executives in foreign‐owned enterprises: managing in two cultures
Authors: Kong Siew‐Huat , Gao Bo‐Yang
Published: June 2009

This paper looks at the roles of Chinese managers in organizational change in foreign‐owned enterprises in China.

A multi‐case study approach was deployed with an in‐depth, semi‐structured ethnographic interview technique.

The study uncovered three categories of managers insofar as their roles in organizational change are concerned: (1) an agent of change, (2) a follower of change, and (3) an anti‐change agent.

This study further identified six factors that determine the kind of role this group of Chinese managers is likely to choose.

Copyright © 2009 John Wiley & Sons, Ltd.
Leadership discretion: a developmental experience
Authors: Kakabadse Nada K. , Lee‐Davies Linda , Kakabadse Andrew
Published: June 2009

By setting out to highlight the potential conflicts linked to the decision choices of the pressurized leader, this paper stokes a passionate argument about the components of leadership discretion. With a deliberate attempt to question all influencing aspects on the decision itself and contextualization of where that decision sits between corporate and personal interest, it clearly magnifies a number of governance issues for future consideration.

A focused study of CEOs provides firm qualitative underpinning for discussion. Honest comment is collected regarding the effect that personal influence can have, not just on the discretion application, but on its ultimate manifestation. The wide‐ranging opinion stresses the many levels of prior consideration necessary for most effective outcomes.

A self‐help message is left in legacy. As each leadership discretion situation is unique and no blanket answer possible for ensuring absolute success, self‐audit is encouraged so each individual works through their actual motivations with a democratic approach even where delivery must be, by necessity, more autocratic.

Copyright © 2009 John Wiley & Sons, Ltd.
The intelligence alchemy and the twenty‐first century organization
Authors: Maguire Stuart , Ojiako Udechukwu , Robson Ian
Published: June 2009

This paper examines the way that a major global organization manages organizational intelligence for competitive and strategic advantage.

We demonstrate the full complexity of organizational intelligence management through a case observation.

Earlier research has already established the fact that there is a direct relationship between good corporate intelligence and strategic change. The fact that businesses are operating within business environments that are even more complex and dynamic than before means that many firms are planning with less certainty than before. As we begin to explore possible competitive scenarios for the twenty‐first century organization, a radical rethink on current organizational intelligence strategy needs to commence, especially as companies deal with more challenging and disruptive scenarios such as terrorism and industrial espionage.

The research range will need to be expanded to ensure that its implications can be tested.

The procurement of more systems and data centers will not necessarily provide that strategic edge organizations need. Instead, organizations need to focus on enhancing the role of the intelligence analyst and managers.

A case study is used to support arguments that the twenty‐first century organization cannot be solely reliant for its strategic planning process on systems without substantial investment in the human aspects of intelligence management.

Copyright © 2009 John Wiley & Sons, Ltd.
A disintegrin and metalloprotease 12 (ADAM12) is a prognostic factor in resected pathological stage I lung adenocarcinoma
Authors: Mino Nobuya , Miyahara Ryo , Nakayama Ei , Takahashi Tsuyoshi , Takahashi Ayuko , Iwakiri Shotaro , Sonobe Makoto , Okubo Kenichi , Hirata Toshiki , Sehara Atsuko , Date Hiroshi
Published: June 2009

Background and Objectives

A disintegrin and metalloprotease 12 (ADAM12) has multiple domains and functions, and it plays important roles in the development of cancer. We conducted a retrospective study to determine whether the expression of the membrane type of ADAM12 (ADAM12‐L) could be a prognostic factor in resected pathological (p‐) stage I lung adenocarcinoma.

Methods

ADAM12‐L mRNA expression was quantified by a reverse‐transcription polymerase chain reaction in tissue samples from 84 completely resected p‐stage I lung adenocarcinoma patients. The patients were divided into ADAM12‐L‐Low and ADAM12‐L‐High groups, and correlations with clinicopathologic features were obtained.

Results

Five‐year survival rates of the ADAM12‐L‐Low and ADAM12‐L‐High groups were 95.1% and 71.9%, respectively. The postoperative prognosis for the ADAM12‐L‐High group was significantly poorer than for the ADAM12‐L‐Low group (P = 0.006). Multivariate analysis confirmed that high expression of ADAM12‐L was an independent factor for poor prognosis (P = 0.007, hazard ratio 8.288). The ADAM12‐L‐High group was less differentiated and had a significantly higher rate of cancer recurrence.

Conclusions

ADAM12‐L mRNA expression is an independent prognostic factor in resected p‐stage I lung adenocarcinoma, and is significantly correlated with tumor differentiation stage and postoperative cancer recurrence. J. Surg. Oncol. 2009;100:267–272. © 2009 Wiley‐Liss, Inc.
Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma
Authors: Chua Terence C. , Koh Ju‐Li , Yan Tristan D. , Liauw Winston , Morris David L.
Published: June 2009

Background

Small bowel adenocarcinoma is a rare malignancy that presents both a diagnostic and therapeutic challenge. The late presentation is often associated with disseminated carcinomatosis which is regarded a terminal event. We review our experience with small bowel peritoneal carcinomatosis following treatment with cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC).

Methods

From a prospective database of CRS and PIC, seven patients were identified to have undergone treatment for small bowel peritoneal carcinomatosis with CRS and hyperthermic intraperitoneal chemotherapy (Mitomycin C) and early postoperative intraperitoneal chemotherapy (5FU). A retrospective review was undertaken to describe the clinicopathological characteristics and survival outcomes.

Results

The median follow‐up was 17 months (range, 5–46 months). Six of seven patients have died. The disease‐free survival was 12 months and the overall median survival was 25 months. The 1‐, 2‐, and 3‐year survivals were 57%, 38%, and 20% respectively. Tumor histology of poorly differentiated adenocarcinoma with signet ring, lymphovascular invasion and perineural invasion appeared to be associated with a poor outcome.

Conclusion

Cytoreductive surgery and perioperative intraperitoneal chemotherapy is a treatment option for small bowel cancer peritoneal carcinomatosis with encouraging survival results. J. Surg. Oncol. 2009;100:139–143. © 2009 Wiley‐Liss, Inc.
Non‐ampullary duodenal adenocarcinoma: Factors important for relapse and survival
Authors: Struck Aaron , Howard Thomas , Chiorean Elena G. , Clarke Jeffrey M. , Riffenburgh Robert , Cardenes Higinia R.
Published: June 2009

Background

Duodenal adenocarcinoma (DA) is rare, but potentially curable. Prospective data on treatment outcomes is scarce and large retrospective studies show conflicting results on the impact of radical resection, node‐status, and adjuvant therapy.

Methods

In the past 17 years, 30 patients presented with resectable DA. Data on the aforementioned variables were acquired then analyzed for impact on recurrence and survival.

Results

Overall‐survival rates at 1, 2, and 3 years were 70.0%, 53.3%, and 33.3% respectively. Recurrence‐free survival rates at 1, 2, and 3 years were 53.3%, 30.0%, and 26.7%. Overall‐survival rates for patients with node‐positive disease at 1, 2, and 3 years were 68.8%, 43.8%, 12.5%, and for node‐negative 70%, 60%, 60%. Recurrence‐free survival in node‐positive disease at 1, 2, 3 years was 50%, 12.5%, 12.5%, and for node negative 50%, 50%, and 40%. Median survival from diagnosis was 27.5 months (0.5–226.7 months). Significant predictors of recurrence and survival were nodal‐status and AJCC stage (P < 0.001). Adjuvant therapy, surgical‐type, pathological tumor‐stage, and surgical margins were not significant.

Conclusion

Nodal‐status and overall pathological‐stage significantly affect the prognosis for patients with DA, while resection‐status and adjuvant therapy may not. The role of adjuvant therapy requires prospective trials for elucidation. J. Surg. Oncol. 2009;100:144–148. © 2009 Wiley‐Liss, Inc.
Revisiting the role of positron‐emission tomography/computed tomography in determining the need for planned neck dissection following chemoradiation for advanced head and neck cancer
Authors: Gourin Christine G. , Boyce Brian J. , Williams Hadyn T. , Herdman Anne V. , Bilodeau Paul A. , Coleman Teresa A.
Published: June 2009

Objectives/Hypothesis:

Planned neck dissection following chemoradiation (CR) has been advocated in patients with head and neck squamous cell cancer (HNSCC) with advanced nodal disease and a clinical complete response to CR because of the potential for residual occult nodal disease. The utility of positron‐emission tomography/computed tomography (PET‐CT) in identifying occult nodal disease in this scenario is controversial.

Methods:

The medical records of all patients treated with CR for advanced HNSCC with N2 or N3 disease from December 2003 to June 2007 were reviewed. Patients with a complete clinical response were included if PET‐CT performed 8 to 11 weeks after CR showed no distant disease and they underwent planned neck dissection.

Results:

Thirty‐two patients met study criteria. PET‐CT was positive for residual nodal disease in 20 patients (63%). Pathology revealed carcinoma in 10 patients (31%): six of 20 patients with positive PET‐CT scans (30%) and four of 12 patients with negative PET‐CT scans (33%). The sensitivity and specificity of PET‐CT was 60% and 36%. Regional recurrence developed in two patients (6%) who were not successfully salvaged.

Conclusions:

PET‐CT performed 8 to 11 weeks after CR does not reliably predict the need for planned post‐treatment neck dissection in patients with a complete clinical response following CR. Regional recurrence rates are comparable to those reported for patients observed with PET‐CT, suggesting no advantage for planned neck dissection, and salvage rates were poor. These data suggest that delaying the timing of PET‐CT, with surgery reserved for positive findings, is a reasonable alternative to planned neck dissection to avoid unnecessary surgery. Laryngoscope, 2009
A controlled safety study of diindolylmethane in the immature rat model
Authors: Elackattu Alphi P. , Feng Lining , Wang Zhi
Published: June 2009

Objectives/Hypothesis:

Diindolylmethane (DIM), a natural product from cruciferous vegetables, has been shown to be a dietary component that has inhibitory effects on some tumors (e.g., laryngeal papilloma). However, current evidence to support its safety is based on adult humans or mature animals. There is little to show on its safety in children. This study is designed to assess safety in the young rat model.

Study Design:

Prospective controlled animal study.

Methods:

Forty rats were separated into four treatment groups of 10 rats each, based on the amount of study drug they received in their daily food: 1) immature rats fed a low dose of DIM, (0.6 mg/kg/day); 2) immature rats fed a high dose of DIM (6.0 mg/kg/day); 3) immature rats fed no DIM (control); and 4) adult rats fed a high dose of DIM (6.0 mg/kg/day). At the conclusion of the study we collected blood to compare serum chemistries and vitamin D levels, and harvested organs to observe for any gross or histological changes among the groups. Statistical methods involved one‐way analysis of variance and pairwise comparisons with Tukey multiple comparison adjustment.

Results:

Although our numbers do not allow for statistical significance, there was no appreciable difference in rat weights among the immature groups, nor was there appreciable difference in serum chemistries, or gross or histological examination of liver, kidney, and bone.

Conclusions:

Diindolylmethane seems to have no adverse affects on the rat even when given in doses 3× what we propose to be therapeutic. This adds evidence to the safety of this drug in the pediatric population as a treatment option for recurrent respiratory papilloma. Laryngoscope, 2009
Dual‐Responsive Supramolecular Hydrogels from Water‐Soluble PEG‐Grafted Copolymers and Cyclodextrin
Authors: Ren Lixia , He Lihong , Sun Tongchen , Dong Xia , Chen Yongming , Huang Jin , Wang Chun
Published: June 2009

Novel temperature and pH dual‐responsive hydrogels were constructed by inclusion of poly(PEGMA)‐co‐poly(DMA) with α‐cyclodextrin in aqueous solution. The temperature‐ or pH‐induced sol/gel transition in the hydrogels was completely reversible. Studies on structure/property relationships show that chain uniformity, graft density and copolymer concentration affect the hydrogel behavior. A dual‐responsive mechanism is proposed. The in vitro release of a model drug from this hydrogel was studied. It was found that the release kinetics were greatly accelerated at higher temperature and at acidic pH conditions, indicating potential applications in controlled drug delivery.

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High‐Molecular‐Weight Polycarbonates Synthesized by Enzymatic ROP of a Cyclic Carbonate as a Green Process
Authors: Yamamoto Yoshio , Kaihara Sachiko , Toshima Kazunobu , Matsumura Shuichi
Published: June 2009

High‐molecular‐weight PTeMC and PHMC were prepared by the lipase‐catalyzed polymerization of butane‐1,4‐diol or hexane‐1,6‐diol and diphenyl carbonate via the formation of a cyclic dimer by a green process. Cyclic carbonate dimers were prepared by the lipase‐catalyzed condensation of diphenyl carbonate with butane‐1,4‐diol or hexane‐1,6‐diol in dilute toluene solution using an immobilized lipase from Candida antarctica, and was followed by the ring‐opening polymerization of the cyclic dimer in bulk with the same lipase to produce PTeMC with $\overline M _{\rm w}$ = 119 000 g · mol−1 and PHMC with $\overline M _{\rm w}$ = 399 000 g · mol−1, respectively. Additionally, enzymatic polymerization of cyclic carbonate dimer was analyzed with respect to the Km and Vmax for the lipase.

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Synthesis and Characterization of Melamine‐Urea‐Formaldehyde Microcapsules Containing ENB‐Based Self‐Healing Agents
Authors: Liu Xing , Sheng Xia , Lee Jong Keun , Kessler Michael R.
Published: June 2009

Microcapsules for self‐healing applications were produced with a melamine‐urea‐formaldehyde (MUF) polymer shell containing two different healing agent candidates, 5‐ethylidene‐2‐norbornene (ENB) and ENB with 10 wt.‐% of a norbornene‐based crosslinking agent (CL), by in situ polymerization in an oil‐in‐water emulsion. Relatively neat outer surfaces with minor roughness were observed on the MUF microcapsules under optical and scanning electron microscopy. Shell thickness of the capsules ranged from 700 to 900 nm. Particle size analysis of the microcapsules showed narrow size distributions with a mean diameter of 113 µm for ENB‐filled and 122 µm for ENB + CL‐filled microcapsules at an agitation rate of 500 rpm. The microcapsules were found to be thermally stable up to 300 °C and exhibited a 10 to 15% weight loss when isothermally held at 150 °C for 2 h from thermogravimetric analysis. Overall, these MUF microcapsules exhibited superior properties compared to the urea‐formaldehyde (UF) microcapsules used extensively for self‐healing composites to date. In addition, the manufacturing process of MUF microcapsules is much simpler than those made from UF. Additional advantages of MUF microcapsules for self‐healing composites are discussed.

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Compartmentalization in NMP in Dispersed Systems: Relative Contributions of Confined Space Effect and Segregation Effect Depending on Nitroxide Type
Authors: Zetterlund Per B. , Okubo Masayoshi
Published: June 2009

Modeling and simulations employing modified Smith‐Ewart equations have been performed to elucidate compartmentalization effects (the segregation effect and the confined space effect) in nitroxide‐mediated polymerization of styrene at 125 °C in dispersed systems using the nitroxides TEMPO and TIPNO. By proper choice of particle size, it is possible to improve both the level of control and livingness relative to the corresponding homogeneous (bulk/solution) systems.

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The Effect of Intramolecular Transfer to Polymer on Stationary Free‐Radical Polymerization of Alkyl Acrylates, 3 – Consideration of Solution Polymerization up to High Conversions
Authors: Nikitin Anatoly N. , Hutchinson Robin A. , Kalfas George A. , Richards John R. , Bruni Christopher
Published: June 2009

The kinetics of butyl acrylate solution polymerization up to high conversion are studied both experimentally and theoretically. New expressions taking into account both inter‐ and intra‐molecular transfer to polymer are derived for polymerization rate, average chain‐length and branching level. These expressions are used for comparative analysis of these two chain transfer events and for evaluation of the backbiting rate coefficient, kbb, and the constant of chain transfer to solvent (xylene), CtrS. Using batch experiments performed at 50, 60 and 70 °C, the Arrhenius parameters for kbb and CtrS are estimated to be, respectively, A(kbb) = (7.4 ± 1.5) × 107 s−1, Ea(kbb) = (32.7 ± 0.5) kJ · mol−1 and A(CtrS) = 10.5 ± 3.5, Ea(CtrS) = (26.9 ± 1.9) kJ · mol−1.

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Angiogenesis as a strategic target for prostate cancer therapy
Authors: Li Yong , Cozzi Paul J.
Published: June 2009

It is becoming increasingly clear that angiogenesis plays a crucial role in prostate cancer (CaP) survival, progression, and metastasis. Tumor angiogenesis is a hallmark of advanced cancers and an attractive treatment target in multiple solid tumors. By understanding the molecular basis of resistance to androgen withdrawal and chemotherapy in CaP, the rational design of targeted therapeutics is possible. This review summarizes the recent advancements that have improved our understanding of the role of angiogenesis in CaP metastasis and the potential therapeutic efficacy of inhibiting angiogenesis in this disease. Current therapeutic options for patients with metastatic hormone‐refractory CaP are very limited. Targeting vasculature is a developing area, which shows promise for the control of late stage and recurrent CaP disease and for overcoming drug resistance. We discuss angiogenesis and its postulated mechanisms and focus on the regulation of angiogenesis in CaP progression and the therapeutic beneficial effects associated with targeting of the CaP vasculature to overcome the resistance to current treatments and CaP recurrence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 1, 23–66, 2010
Promising tumor‐associated antigens for future prostate cancer therapy
Authors: Li Yong , Cozzi Paul J. , Russell Pamela J.
Published: June 2009

Prostate cancer (CaP) is one of the most prevalent malignant diseases among men in Western countries. There is currently no cure for metastatic castrate‐resistant CaP, and median survival for these patients is about 18 months; the high mortality rate seen is associated with widespread metastases. Progression of CaP from primary to metastatic disease is associated with several molecular and genetic changes that can affect the expression of specific tumor‐associated antigens (TAAs) or receptors on the cell surface. Targeting TAAs is emerging as an area of promise for controlling late‐stage and recurrent CaP. Several reviews have summarized the progress made in targeting signaling pathways for CaP but will not be discussed here. We describe some important CaP TAAs. These include prostate stem‐cell antigen, prostate‐specific membrane antigen, MUC1, epidermal growth factor receptor, platelet‐derived growth factor and its receptor, urokinase plasminogen activator and its receptor, and extracellular matrix metalloproteinase inducer. We summarize recent advancements in our understanding of their role in CaP metastasis, as well as potential therapeutic options for targeting CaP TAAs. We also discuss the origin, identification, and characterization of prostate cancer stem cells (CSCs) and the potential benefits of targeting prostate CSCs to overcome chemoresistance and CaP recurrence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 1, 67–101, 2010
Magnetic resonance imaging–guided adoptive cellular immunotherapy of central nervous system tumors with a T1 contrast agent
Authors: Sengar Raghvendra S. , Spokauskiene Laima , Steed Daniel P. , Griffin Patricia , Arbujas Norma , Chambers William H. , Wiener Erik C.
Published: June 2009

Dendritic cells (DCs) are the most effective antigen‐presenting cells (APCs) and are used in a variety of immunotherapeutic approaches. Adoptive cellular immunotherapy (ACI) of cancer using DCs has attracted much interest due to their capacity to promote immunity in prophylactic and therapeutic protocols. As one approach, DCs are injected into patients or tumor‐bearing animals, to trigger specific antitumor immunity. In that framework, several approaches to DC delivery have been reported, including direct intratumoral injection; this has yielded positive but variable results. The underlying reasons for this have not been fully determined, but major hypotheses include technical difficulties in delivering cells into tumors and tumor‐mediated immunosuppression. Image‐guided ACI offers the potential to establish that DCs are efficiently delivered to the tumor site, which might eliminate some of the variability. Therefore, we developed highly sensitive methods for monitoring the injection or trafficking of DCs into tumors using a clinically approved formulation of a gadolinium‐based magnetic resonance imaging (MRI) contrast agent, Gd(III)‐HP‐DO3A (ProHance™). We determined the labeling efficiency of DCs with this formulation; that labeling DCs with this agent did not inhibit expression of surface markers important for antigen presentation and activation of naive T cells; that their capacity to interact with natural killer (NK) cells was not reduced; and that their migration was not diminished. Further, we determined that ProHance™‐labeled DCs can be effectively imaged in vivo in established central nervous system tumors. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Structural modification of chitosan biopolymer as a novel polyelectrolyte membrane for green power generation
Authors: Dashtimoghadam Erfan , Hasani‐Sadrabadi Mohammad Mahdi , Moaddel Homayoun
Published: June 2009

In the present study, a series of bioresource polyelectrolytes based on chitosan were synthesized and assessed for applicability in direct methanol fuel cells (DMFCs). A binary cross‐linking agent (sulfosuccinic acid/glutaraldehyde) was used for the structural modification of chitosan and membranes comprising various amounts of sulfosuccinic acid (0, 8, 12, and 16 wt% SSA/wt chitosan) were prepared. It was found that by increasing the sulfonate groups' content up to 16 wt%, proton conductivity and methanol permeability properties reach the values of 0.0452 S cm−1 and 9.6 × 10−7 cm2 sec−1, respectively. Based on the membrane selectivity evaluation and activation energy measurements of proton conduction, the optimum composition of cross‐linking agent was determined. The optimum composition resulted in a relatively high proton conductivity of 0.0452 S cm−1 and a low methanol permeability of 9.6 × 10−7 cm2 sec−1. Moreover, the optimum proton exchange membrane exhibited selectivity value of 47,100 in comparison with the corresponding value of 40,500 for Nafion® 117. The fabricated membranes showed acceptable oxidative and hydrolytic stability. Furthermore, single cell DMFC performance test revealed a power density of 17 mW cm−2 at 30°C and 41 mW cm−2 at 60°C in a 2 M methanol feed. Hence, prepared proton‐conducting bioresource ionomers could have promising potential in the field of green power generation as a low cost and biodegradable polyelectrolyte. Copyright © 2009 John Wiley & Sons, Ltd.
c‐Rel is a transcriptional repressor of EPHB2 in colorectal cancer
Authors: Fu Tao , Li Peng , Wang Hanzhi , He Yujun , Luo Donglin , Zhang Anping , Tong Weidong , Zhang Lianyang , Liu Baohua , Hu Chuanmin
Published: June 2009

The receptor tyrosine kinase EPHB2 has recently been identified as a TCF4 transcriptional target that controls the intestinal epithelial architecture through repulsive interactions with Ephrin‐B ligands. Many reports have demonstrated that most human colorectal cancers lose EPHB2 expression despite constitutive Wnt activation. Therefore, we investigated the mechanisms that cause EPHB2 down‐regulation in colorectal cancer. In this study, we demonstrate that DNA hypermethylation was not responsible for the frequent loss of EPHB2 expression in colorectal cancer. Cloning and functional characterization of the EPHB2 gene 5′‐flanking region revealed a potential negative regulatory element in the distal regulatory region. In vitro electrophoretic gel mobility shift and in vivo chromatin immunoprecipitation assays demonstrated that c‐Rel directly binds to the putative element. Inhibiting c‐Rel activity or knocking down c‐Rel expression by RNA interference in colon cancer cells was sufficient to induce EPHB2 expression. Furthermore, transient transfection assays demonstrated that c‐Rel over‐expression repressed endogenous EPHB2 expression in colon cancer cells. We demonstrate for the first time that c‐Rel acts as a transcriptional repressor of EPHB2 and plays an active role in EPHB2 down‐regulation in colorectal cancers. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Non‐structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice
Authors: Wang Ai‐Guo , Lee Dong‐Seok , Moon Hyung‐Bae , Kim Jin‐Man , Cho Kyung‐Hyun , Choi Soo‐Ho , Ha Hye‐Lin , Han Ying‐Hao , Kim Dae‐Ghon , Hwang Soon B. , Yu Dae‐Yeul
Published: June 2009

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non‐structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV‐induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co‐localized with apolipoprotein A‐I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF‐κB and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
‘Introduction to Insulin’ classes: flexible approach to insulin initiation
Authors: Greenslade ME , Lunt H , Kendall D , Frampton CM
Published: June 2009

There is increased interest in undertaking task orientated patient education, such as commencement on insulin, in the group setting. Group education allows use of adult educational theory and may reduce educator time. The usual model of group education for commencing insulin is to delay insulin initiation until the first class. We describe an alternative flexible, hybrid model of education, combining initial 1:1 education in some patients with group classes (‘Introduction to Insulin’ classes), for initiation and stabilisation on insulin. This model was adopted primarily to ensure that insulin was commenced with minimal delay, once the decision to start it had been made.

Following piloting and design of the ‘Introduction to Insulin’ classes, a prospective audit was undertaken of the first 50 patients participating in the classes. By one year, HbA1c had fallen from 9.8% to 7.8% and there was an associated 2.7 kg weight gain. This model of insulin education is therefore as effective as traditional 1:1 education, yet has the potential to utilise less overall educator time. Copyright ©2009 John Wiley & Sons.
An international partnership to implement innovative systems of health care delivery for diabetes in a developing country
Authors: Gunathilake W , Idampitiya CA , Siriwardana A , Lenora D , Thomson GA , Fernando DJS
Published: June 2009

Sri Lanka currently faces a ‘double burden’ of non‐communicable and communicable diseases. Public institutions geared primarily to care for communicable diseases struggled to meet demand for quality care in non‐communicable diseases. The World Health Organization has developed tools for implementing appropriate health care for long‐term problems.

We piloted interventions in self‐management support, delivery system design, decision support and clinical information systems at sites in urban and rural Sri Lanka. This undertaking confirmed that interventions through adaptation of Sri Lanka's primary care infrastructure and establishment of innovative partnerships enable the effective implementation of care with existing resources in the short term. We demonstrated that media can be used as a powerful forum for educating the public, promoting new attitudes, providing skills for improving health status and influencing both planners and health care professionals. We also demonstrated that training and education of health care workers and research collaborations can influence policy makers. The collaboration to date has established a model for international collaboration providing both educational and technical support towards capacity building within the country. Collaborations with developing countries will enable the prevention and control of chronic disease in the developing world in keeping with the United Nations resolution regarding diabetes. Copyright © 2009 John Wiley & Sons, Ltd.
Providing optimal service delivery for children and adolescents with type 1 diabetes: a systematic review
Authors: Hatherly K , Overland J , Smith L , Taylor S , Johnston C
Published: June 2009

The purpose of this systematic review was (1) to perform a comprehensive examination of the literature to identify aspects of service delivery which are associated with improved glycaemic control in young people with type 1 diabetes, and (2) to identify gaps in the current literature and suggest areas for future research.

The online medical databases Medline, Embase, Psycinfo and Cinahl were searched using a series of keywords. We reviewed randomised controlled trials and cross‐sectional, comparison and retrospective audit studies from 1980 to December 2007 which involved children, adolescents and young adults with type 1 diabetes. In total, 540 studies were screened for inclusion, with 68 papers retrieved for further analysis 23 of which were retained for inclusion in the review.

The service delivery indicators identified in the review which have an impact on glycaemic control in young people with type 1 diabetes include access to specialist care, number of clinic visits attended, access to care from a multidisciplinary diabetes team and regular telephone contact.

This review confirmed that various aspects of paediatric diabetes service delivery do impact on the glycaemic control of children and adolescents with type 1 diabetes. It has also identified the need for studies to examine further the complex interplay of multiple aspects of service delivery, including the impact of a family‐centred model of care, on glycaemic control. Copyright © 2009 John Wiley & Sons, Ltd.
Hypoglycaemia followed by lactic acidosis in a diabetic patient on metformin
Authors: Langan J , Fisher M
Published: June 2009

A 71‐year‐old woman with a nine‐year history of type 2 diabetes was admitted with hypoglycaemia, acute renal failure, and lactic acidosis. She was treated with fluids and antibiotics for presumed infection, and metformin was discontinued.

Metformin‐associated lactic acidosis is a rare consequence of metformin therapy and, as in this case report, there are often other factors contributing to the lactic acidosis. Copyright ©2009 John Wiley & Sons.
Prostate growth inhibition by subtype‐selective alpha1‐adrenoceptor antagonist naftopidil in benign prostatic hyperplasia
Authors: Kojima Yoshiyuki , Sasaki Shoichi , Oda Nobuyuki , Koshimizu Taka‐Aki , Hayashi Yutaro , Kiniwa Mamoru , Tsujimoto Gozoh , Kohri Kenjiro
Published: June 2009

BACKGROUND

Recently, alpha1‐adrenoceptors (α1‐ARs) have been reported to play a prominent role in the growth of a variety of cells; however, little is known about prostate growth and subtype‐specific effects on cell proliferation. We examined the role of α1d‐AR in prostate growth and the effect of subtype‐selective α1‐AR antagonist, naftopidil, which has relatively higher affinity for α1d‐AR, on prostate growth in vitro and in vivo.

METHODS

First, we examined the effect of naftopidil on the cell proliferation of PrEC, PrSC, and PrSMC using WST‐1 assay. Second, we performed real‐time RT‐PCR to quantify each α1‐AR subtype mRNA expression level in a benign prostate hyperplasia (BPH) model rat, which was recently established to pathologically resemble human BPH patients. In addition, naftopidil was given to this model orally for 21 days and the proliferative and apoptotic indexes measured. Third, 18 BPH patients were administered naftopidil for 12 weeks and the proliferative and apoptotic indexes were compared before and after naftopidil administration.

RESULTS

Naftopidil significantly inhibited cell proliferation dose‐dependently in all cell lines that expressed α1d‐AR mRNA. The expression level of α1d‐AR during the growth process of the prostate in the BPH model rat was significantly higher than that in the normal prostate (P < 0.001). Naftopidil administration inhibited cell proliferation without apoptosis in the BPH model rat and BPH patients.

CONCLUSIONS

α1d‐AR may play an important role in the regulation of cellular proliferation in the prostate, and α1d‐AR blockage by naftopidil may not only improve lower urinary tract symptoms but also inhibit prostate growth in BPH patients. Prostate 69: 1521–1528, 2009. © 2009 Wiley‐Liss, Inc.
Evaluation of natural diatomaceous earth deposits from south‐eastern Europe for stored‐grain protection: the effect of particle size
Authors: Vayias Bill J , Athanassiou Christos G , Korunic Zlatko , Rozman Vlatka
Published: June 2009

BACKGROUND: The use of diatomaceous earths (DEs) provides a promising alternative to the use of contact insecticides in stored‐product IPM. Geographical origin and the physical properties of a given DE may affect its insecticidal activity. In the present study, DE samples were collected from different locations of south‐eastern Europe, and their efficacy was evaluated in the laboratory against Cryptolestes ferrugineus (Stephens) (Coleoptera: Cucujiidae), Sitophilus oryzae (L.) (Coleoptera: Curculionidae) and Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae). In addition, three fractions comprising particles of different size were obtained from each DE sample and assessed with regards to their effectiveness against the above stored‐product insect pests.

RESULTS: DE from the Greek region of Elassona was the most effective against C. ferrugineus and S. oryzae, whereas the DE Kolubara 518, mined in the Serbian region of Kolubara, was the most effective against R. dominica. Smaller particles were more effective than larger particles against the three tested species, although significant differences in the efficacy of fractions containing particles of 0–150 µm and particles with sizes of < 45 µm were not always recorded.

CONCLUSIONS: Deposits from south‐eastern Europe appeared to be very effective against the tested species, and therefore this region should be further evaluated as a source of development of commercial products. Particle size is a physical property that should always be taken into account during the DE manufacturing process, as it can strongly influence the insecticidal action of a given product. Copyright © 2009 Society of Chemical Industry
Magnetization dynamics in polycrystalline Permalloy and epitaxial Co platelets observed by time‐resolved photoemission electron microscopy
Authors: Wegelin Frederik , Krasyuk Alexander , Valdaitsev Dmitrii A. , Nepijko Sergej A. , Elmers Hans Joachim , Schönhense Gerd , Schneider Claus M.
Published: June 2009

We studied the dynamic magnetization response in rectangular polycrystalline Permalloy and also epitaxial Co structures (lateral sizes comprised tens of microns at a thickness of tens of nanometers) during the action of a magnetic field pulse, using time‐resolved X‐ray photoemission electron microscopy with a time resolution of 10 ps. In the case of Permalloy platelets the restoring torque that is necessary for the stroboscopic image acquisition is provided by the Landau flux closure structure representing a minimum of the free energy. We investigated the dynamic response of 90° Néel domain walls. The main results are: the maximum velocity of the domain wall is 1.5 × 104 m/s, the intrinsic frequency of the magnetization change in these structures is estimated to be several Gigahertz. For the case of epitaxial Co platelets grown on Mo(110) the magnetic uniaxial anisotropy with an easy axis along Mo[1$ \bar 1 $0] restores the homogeneous magnetization structure after each field pulse. We observed a rotation of the mean magnetization direction within the first 100 ps of the field pulse. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Orientation and electronic properties of phthalocyanines on polycrystalline substrates
Authors: Peisert Heiko , Biswas Indro , Knupfer Martin , Chassé Thomas
Published: June 2009

We review the molecular orientation of phthalocyanines as representatives of flat, π‐conjugated molecules on different polycrystalline substrates. Thin films with a thickness of ∼10–50 nm are often highly ordered on several substrates. The molecular orientation, however, can be radically different for single crystalline model substrates and for relatively ill defined polycrystalline substrates. Moreover, it is important to distinguish between the growth of the first organic layer(s) at the substrate surface and the growth in films of a thickness of several nanometers: Differently oriented, buried interfacial layers of few monolayers were observed in particular for polycrystalline substrates. The growth mode is discussed in terms of different molecule–molecule and molecule–substrate interactions. Consequences for our understanding of the behavior of such films in devices are considered in context with electronic interface properties. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)