bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of second cancer after lymphohematopoietic neoplasm
Authors: Royle Jill S. , Baade Peter , Joske David , Fritschi Lin
Published: September 2010

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site‐specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non‐Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation‐ and immunosuppression‐related cancers, after an LHN in Australia.
The antimalarial agent artesunate possesses anticancer properties that can be enhanced by combination strategies
Authors: Liu Wai M. , Gravett Andrew M. , Dalgleish Angus G.
Published: September 2010

Artemisinins are a class of compounds that are first‐line treatment options for malaria. They also have potent antiproliferative activity, which makes them potential anticancer drugs. We have previously demonstrated anticancer activity of a number of these compounds in vitro; however, cytotoxic activities were compromised by drug‐induced cell cycle arrests. In this study, we have explored further the activity of the clinical lead artemisinin‐drug artesunate (ART), used either alone or in combination with established chemotherapy. Also, by using a cell line expressing polyploidy character, have also explored the impact of cell cycle arrest in determining overall drug activity. Results showed that ART caused dose‐dependent decreases in cell number, which were associated with either increased cytotoxicity or cytostasis. Cytostasis appeared to be a consequence of a simultaneous arrest at all phases of the cell cycle, a deduction that was supported by molecular profiling, which showed reductions in cell cycle transit proteins. ART appeared to maintain cells in this arrested state; however, reculturing these treated cells in drug‐free medium resulted in significant reductions in viabilities. We also showed that ART maintained activity in polyploidy cells, and that an impressive enhancement to its activity was achievable through a combination with the immunomodulatory drug lenalidomide. Taken together, these observations indicate ART and its related compounds may be effective for the treatment of tumours, and that activity is related to schedule. Therefore, it is important to carefully select the most appropriate schedule to maximise ART efficacy.
Economic evaluation of strategies for managing women with equivocal cytological results in Brazil
Authors: Vanni Tazio , Legood Rosa , Franco Eduardo L. , Villa Luisa L. , Luz Paula Mendes , Schwartsmann Gilberto
Published: September 2010

In Brazil, current management of women with screening results of atypical squamous cells of undetermined significance (ASC‐US) is to offer repeat testing at 6‐month intervals. Alternative management strategies that have been adopted in many high‐income settings are to offer immediate colposcopy referral or to utilise human papillomavirus (HPV) DNA testing as a triage for colposcopy referral, and to consider different strategies according to women's age. The objective of our study was to evaluate the lifetime cost effectiveness in terms of cost per years of life saved (YLS) of these alternative strategies for a middle income setting. A Markov model was developed using data from the Ludwig‐McGill cohort and calibrated to independent observational datasets and local cost estimates obtained. In the base‐case analysis, repeat cytology was the least costly strategy but also the least effective. Based on the WHO threshold for very cost‐effective interventions, HPV triage for women above 30 years‐old was the strategy with the highest probability of being cost effective. HPV triage including younger women with ASCUS results would also be a cost‐effective option. Whilst there was a slight further gain in effectiveness with immediate colposcopy referral, it was also more expensive and did not appear to be cost effective. Threshold analysis indicated that an HPV test would have to be more than twice as expensive as a cytology test for HPV triage to no longer be cost effective. In conclusion, our results indicate that in middle income settings HPV triage is likely to be the optimal strategy for managing women presenting with ASC‐US results.
Arg72Pro TP53 polymorphism and cancer susceptibility: A comprehensive meta‐analysis of 302 case‐control studies
Authors: Francisco Guilherme , Menezes Paulo Rossi , Eluf‐Neto José , Chammas Roger
Published: September 2010

Arg72Pro is a common polymorphism in TP53, showing differences in its biological functions. Case‐control studies have been performed to elucidate the role of Arg72Pro in cancer, although the results are conflicting and heterogeneous. Here, we analyzed pooled data from case‐control studies to determine the role of Arg72Pro in different cancer sites. We performed a systematic review and meta‐analysis of 302 case‐control studies that analyzed Arg72Pro in cancer susceptibility. Odds ratios were estimated for different tumor sites using distinct genetic models, and the heterogeneity between studies was explored using I2 values and meta‐regression. We adopted quality criteria to classify the studies. Subgroup analyses were done for tumor sites according to ethnicity, histological, and anatomical sites. Results indicated that Arg72Pro is associated with higher susceptibility to cancer in some tumor sites, mainly hepatocarcinoma. For some tumor sites, quality of studies was associated with the size of genetic association, mainly in cervical, head and neck, gastric, and lung cancer. However, study quality did not explain the observed heterogeneity substantially. Meta‐regression showed that ethnicity, allelic frequency and genotyping method were responsible for a substantial part of the heterogeneity observed. Our results suggest ethnicity and histological and anatomical sites may modulate the penetrance of Arg72Pro in cancer susceptibility. This meta‐analysis denotes the importance for more studies with good quality and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of Arg72Pro in cancer.
External sense receptors in microdrile oligochaetes (Annelida, Clitellata) as revealed by scanning electron microscopy: Typology and patterns of distribution in the main taxonomic groups
Authors: Caramelo Carlos , Martínez‐Ansemil Enrique
Published: September 2010

This work summarizes the observations on 30 species of microdriles belonging to the families Naididae (Rhyacodrilinae, Pristininae, Naidinae, Phallodrilinae, and Tubificinae), Phreodrilidae, Lumbriculidae, and Enchytraeidae using scanning electron microscopy. The lumbricid Eiseniella tetraedra, a megadrile species common in typical microdrile habitats, was used for comparison. Microdriles display external ciliate sense structures along the entire body; even at the clitellum and in budding and regeneration zones. According to the shape of the cilia, these sense structures can be divided into receptors of blunt cilia, receptors of sharp cilia, and composed receptors. Sense receptors can be morphologically unconspicuous or clearly defined on sensory buds or papillae. All microdriles studied have receptors of blunt cilia. Enchytraeids have characteristic receptors of short cilia. Pristina (Pristininae), Chaetogaster, Ophidonais, and Stylaria (Naidinae) have receptors of long blunt cilia. Composed receptors were found only in some microdriles and E. tetraedra. Receptors of sharp cilia have been found in most microdriles. Enchytraeids might be the only exception, but sharp cilia are probably present in the amphibiotic Cognettia sphagnetorum. Sensory cells with long sharp cilia might play a rheoreceptor role, and their presence in E. tetraedra and C. sphagnetorum would imply the reappearing of an ancient character that was probably lost with the transit from aquatic to terrestrial habitats. Some lumbriculids have ciliated fields. Anatomically, these structures appear as intermediate between the typical isolate sensory structures of microdriles and the sensillae of the hirudineans. The general pattern in microdriles is that uniciliate receptors and multiciliate receptors are separated, which supports the presumed aquatic origin of the clitellates. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
The effects of low‐intensity pulsed ultrasound upon diabetic fracture healing
Authors: Coords Michael , Breitbart Eric , Paglia David , Kappy Nikolas , Gandhi Ankur , Cottrell Jessica , Cedeno Natalie , Pounder Neill , O'Connor J. Patrick , Lin Sheldon S.
Published: September 2010

In the United States, over 17 million people are diagnosed with type 1 diabetes mellitus (DM) with its inherent morbidity of delayed bone healing and nonunion. Recent studies demonstrate the utility of pulsed low‐intensity ultrasound (LIPUS) to facilitate fracture healing. The current study evaluated the effects of daily application of LIPUS on mid‐diaphyseal femoral fracture growth factor expression, cartilage formation, and neovascularization in DM and non‐DM BB Wistar rats. Polymerase chain reaction (PCR) and ELISA assays were used to measure and quantify growth factor expression. Histomorphometry assessed cartilage formation while immunohistochemical staining for PECAM evaluated neovascularization at the fracture site. In accordance with previous studies, LIPUS was shown to increase growth factor expression and cartilage formation. Our study also demonstrated an increase in fracture callus neovascularization with the addition of LIPUS. The DM group showed impaired growth factor expression, cartilage formation, and neovascularization. However, the addition of LIPUS significantly increased all parameters so that the DM group resembled that of the non‐DM group. These findings suggest a potential role of LIPUS as an adjunct for DM fracture treatment. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:181–188, 2011
Effects of estrogen deficiency and bisphosphonate therapy on osteocyte viability and microdamage accumulation in an ovine model of osteoporosis
Authors: Brennan Orlaith , Kennedy Oran D. , Lee T. Clive , Rackard Susan M. , O'Brien Fergal J.
Published: September 2010

It has been proposed that osteocyte viability plays an important role in bone integrity, and that bone loss in osteoporosis may be partially due to osteocyte cell death following estrogen depletion. Osteoporosis treatments such as bisphosphonates can inhibit osteocyte apoptosis which in turn may also reduce remodeling. Consequently, microcracks in bone which are normally repaired by bone remodeling may accumulate. This study used an ovine model of osteoporosis to examine the effects of estrogen depletion and bisphosphonates on osteocyte apoptosis and microdamage accumulation. Skeletally mature ewes were randomly assigned into two equal groups; ovariectomy (OVX) and a non‐treatment group (control). Half of these animals were sacrificed 12 months post‐OVX. Twenty months post‐OVX, a number of OVX animals were randomly selected and each received a supra‐pharmacological dose of the bisphosphonate, zoledronic acid (Zol). This group and all the remaining animals were sacrificed 31 months post‐OVX. A compact bone specimen was removed from the left metacarpal of each animal; half was used for osteocyte apoptosis detection and the remainder for microdamage analysis. Estrogen deficiency resulted in significant increases in the levels of osteocyte apoptosis while zoledronic acid significantly reduced the level of apoptosis in osteocytes. Zoledronic acid treatment resulted in the formation of more microcracks. However, these cracks were shorter than in control or OVX groups which may provide one explanation as to why increased damage levels following bisphosphonate treatment have not lead to increased fractures. This study also provides additional evidence of the importance of estrogen in preserving the osteocyte network. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:419–424, 2011
Joint mobilization improves spatiotemporal postural control and range of motion in those with chronic ankle instability
Authors: Hoch Matthew C. , McKeon Patrick O.
Published: September 2010

The purpose of this study was to examine the effects of a single joint mobilization treatment on dorsiflexion range of motion (DF ROM), posterior talar glide, and dynamic and static postural control in individuals with self‐reported chronic ankle instability (CAI). In this randomized cross‐over study, subjects received a Maitland Grade III anterior‐to‐posterior joint mobilization treatment and a control treatment of rest for 5 min. Weight‐bearing DF ROM, instrumented posterior talar displacement and posterior stiffness, the anterior, posteromedial, and posterolateral reach directions of the Star Excursion Balance Test (SEBT), and time‐to‐boundary (TTB) single‐limb stance static postural control were assessed on both treatment days in 9 males and 11 females with CAI. The results indicated that the joint mobilization treatment was associated with significantly greater DF ROM (p = 0.01) and TTB in the anterior–posterior direction with eyes‐open (p < 0.05). Although not significant, trends were identified in posterior talar displacement (p = 0.08) and the mean of TTB in the medial‐lateral (ML) direction (p = 0.07). No significant differences were observed in the standard deviation of TTB in the ML direction, the SEBT, or posterior stiffness (p > 0.05). This indicates that a single joint mobilization treatment has mechanical and functional benefits for addressing impairments in sensorimotor function and arthrokinematic restrictions commonly experienced by individuals with CAI. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:326–332, 2011
Leptin‐mediated cytoskeletal remodeling in chondrocytes occurs via the RhoA/ROCK pathway
Authors: Liang Jinqian , Feng Juefei , Wu William Ka Kei , Xiao Jun , Wu Zhihong , Han Dong , Zhu Yong , Qiu Guixing
Published: September 2010

Leptin affects a number of cell signaling pathways, at present, the mechanism(s) by which leptin affects the cartilage cells in OA patient is not well understood. The current study seeks to elucidate whether leptin induces cytoskeletal remodeling in chondrocytes and the possible involvement of the RhoA/ROCK pathway and its downstream mediators in this process. Fluorescent resonance energy transfer (FRET) and western analysis were used to determine the activations of the key proteins in the RhoA/LIMK1/Cofilin pathway. Accompanying cytoskeletal remodeling was elucidated. Upon leptin stimulation, a substantial increase of RhoA activity localized at one end of the cell was observed from 2 to 30 min post‐stimulation. The results of Western blot showed leptin significantly increased LIMK1 and cofilin‐2 phosphorylation in a time‐dependent manner with maximal stimulation attained 60 min and 24 h post‐stimulation, respectively. Chondrocytes stimulated with leptin exhibited an epithelioid morphology with increased cellular spreading. F‐actin in leptin‐stimulated chondrocytes also showed more intense cytoplasmic staining with occasional localization along filamentous structures. The results indicate that leptin activates the RhoA/ROCK/LIMK/cofilin pathway, which results in cytoskeletal reorganization in chondrocytes. These findings provide novel evidence supporting the possible involvement of leptin and the RhoA pathway in the pathogenesis of OA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:369–374, 2011
The impact of re‐excision of inadequately resected soft tissue sarcomas on surgical therapy, results, and prognosis: A single institution experience with 682 patients
Authors: Funovics Philipp T. , Vaselic Sanja , Panotopoulos Joannis , Kotz Rainer I. , Dominkus Martin
Published: September 2010

Background and Objectives

Due to their rare incidence soft tissue sarcomas (STS) are often resected without clear margins. The aim of this study was to investigate the impact of re‐excision of STS on survival.

Methods

Out of 752 patients with STS (406 men and 346 women, average age 51 years), 310 patients were referred after an inadequate resection, 442 patients presented for primary treatment. Six hundred eighty‐two patients were compared over a mean period of 65 months (median, 36 months) according to the treatment groups regarding their survival, clinical, surgical, and pathological data.

Results

The 5‐year survival rate of 621 surgically treated patients was 53.9%. There was a continuous improvement in survival during the whole treatment period in the respective decades. The overall survival rate in both groups was not significantly different regardless of low‐ or high‐grade malignancies. Patients with a re‐resection did not have a higher rate of local recurrences; patients with a primary resection had a worse prognosis regarding metastases. A re‐resection within 12 weeks indicated a better prognosis.

Conclusions

An inadequate excision of a STS does not cogently mean deterioration of overall survival but necessitates an ample and quick re‐resection. J. Surg. Oncol. 2010;102:626–633. © 2010 Wiley‐Liss, Inc.
18Fluoro‐deoxy‐glucose positron emission tomography in assessing tumor response to preoperative chemoradiation therapy for locally advanced rectal cancer
Authors: Hur Hyuk , Kim Nam Kyu , Yun Mijin , Min Byung Soh , Lee Kang Young , Keum Ki Chang , Ahn Jung Bai , Kim Hoguen
Published: September 2010

Background

This study aims to evaluate the efficacy of 18F‐FDG PET in assessing tumor response after preoperative chemoradiation therapy (CRT) for rectal cancer.

Methods

Maximum standardized uptake value (SUV) was measured for 37 patients who underwent 18F‐FDG PET before and 4 weeks after completion of preoperative CRT. Pre‐SUV, post‐SUV, the difference between pre‐ and post‐SUV (ΔSUV), and reduction rate (RR) were correlated with tumor response.

Results

A lower mean post‐SUV and a higher mean RR were shown in good tumor response (T‐downstaging(+) and tumor regression grade 1, 2). Considering pathologic complete response (pCR), the mean post‐SUV and the mean RR were significantly different between pCR (+) patients (N = 13) and pCR (−) patients (N = 24) (2.7 vs. 4.8, P < 0.001, 73.9% vs. 58.7%, P = 0.009). With a 3.35 cut‐off value for the post‐SUV by receiver operating characteristic analysis, 84.6% sensitivity, 79.2% specificity, and 81.2% overall accuracy were obtained for discriminating between pCR (+) and pCR (−) (area under the curve = 0.885, P < 0.001).

Conclusions

18F‐FDG PET is potentially useful as a method for assessing tumor response after preoperative CRT for rectal cancer. Post‐SUV and RR were significantly associated with pathological treatment response, especially in pCR. J. Surg. Oncol. 2011;103:17–24. © 2010 Wiley‐Liss, Inc.
Clinical implication of CD166 expression in gastric cancer
Authors: Ishigami Sumiya , Ueno Shinichi , Arigami Takaaki , Arima Hideo , Uchikado Yasuto , Kita Yoshiaki , Sasaki Ken , Nishizono Yuka , Omoto Itaru , Kurahara Hiroshi , Matsumoto Masataka , Kijima Yuko , Natsugoe Shoji
Published: September 2010

Background

CD166 is one of the cell‐surface immunoglobulins, and is well known to regulate leukocyte mobility. Its expression is associated with aggressive tumor behavior. CD166 expression is a prognostic marker in several cancers, but the predictive value of CD166 expression in gastric cancer has not been clarified yet.

Patients and Methods

A total of 142 gastric cancer patients who consecutively received curative gastrectomy in Kagoshima University Hospital were enrolled in the current study. The patients were composed of 99 men and 43 women, ranging in age from 42 to 84 years (mean 63 years). Cancerous CD166 expression was evaluated immunohistochemically.

Results

Cancerous CD166 expression was identified in not only cellular membrane but also cytoplasm. The rates of membranous and cytoplasmic CD166 positivities were 25.4% and 34.4%, respectively. Cytoplasmic and membranous CD166 positivities were significantly correlated with nodal involvement and vascular invasion. Survival analysis of the 142 gastric cancer patients revealed that membranous CD166‐positive group (median survival 18.6 months, range 0.3–104.5 months) had a significantly poorer outcome than CD166‐negative group (median 25.7 months range 1.4–106 months) (P < 0.05).

Conclusions

Membranous CD166‐positivity may contribute to one of the promising prognostic markers in gastric cancer. J. Surg. Oncol. 2011;103:57–61. © 2010 Wiley‐Liss, Inc.
Quantification of histidine, 1‐methylhistidine and 3‐methylhistidine in plasma and urine by capillary electrophoresis UV‐detection
Authors: Zinellu Angelo , Sotgia Salvatore , Pisanu Elisabetta , Scanu Bastianina , Sanna Manuela , Deiana Luca , Carru Ciriaco
Published: September 2010

We describe a new CE method with UV‐detection for the quantification of histidine (His) and its methylated forms 1‐methylhistidine and 3‐methylhistidine, both in plasma and urine. Analytes were basically resolved using a 60 mmol/L Tris‐phosphate run buffer pH 2.2 in less than 12 min. The use of a mixture of ACN/ammonia (80:20) for protein precipitation allows the quantitative recovery of all His from plasma. The optimization of the sample volume injection permits to reach an LOD of 20 nmol/L, thus improving the sensitivity of about hundred times in comparison to the previous described assays. Moreover, the opportunity to also measure creatinine in the same run makes it possible to evaluate the renal function contemporarily, thus avoiding further dosages with significant time saving. The application method has been proved by measuring His, 1‐methylhistidine and 3‐methylhistidine in 44 healthy subjects. In conclusion, our new method seems to be an inexpensive, fast and specific tool to assess large numbers of patients for routine analysis both in clinical and research laboratories.
Flow field‐flow fractionation and multiangle light scattering for ultrahigh molecular weight sodium hyaluronate characterization
Authors: Moon Myeong Hee
Published: September 2010

This review describes the utility of flow field‐flow fractionation coupled with multiangle light scattering and differential refractive index (FlFFF‐MALS‐DRI) detection methods for the separation of ultrahigh molecular weight sodium hyaluronate (NaHA) materials and for the characterization of molecular weight distribution as well as structural determination. The sodium salt of hyaluronic acid (HA), NaHA, is a water‐soluble polysaccharide with a broad range of molecular weights (105–108) found in various naturally occurring fluids and tissues. Basic principles of FlFFF‐MALS using field programming for the separation of the degraded products of NaHA prepared by treating raw materials with depolymerization or degradation processes such as membrane filtration, enzymatic degradation, ultrasonic degradation, alkaline reaction, irradiation by γ‐rays, and thermal treatment for the development of pharmaceutical applications are introduced. Changes in molecular weight distribution and conformation of NaHA materials due to external stimuli are also discussed.
Extraction of hyaluronic acid (HA) from rooster comb and characterization using flow field‐flow fractionation (FlFFF) coupled with multiangle light scattering (MALS)
Authors: Kang Dong Young , Kim Won‐Suk , Heo In Sook , Park Young Hun , Lee Seungho
Published: September 2010

Hyaluronic acid (HA) was extracted in a relatively large scale from rooster comb using a method similar to that reported previously. The extraction method was modified to simplify and to reduce time and cost in order to accommodate a large‐scale extraction. Five hundred grams of frozen rooster combs yielded about 500 mg of dried HA. Extracted HA was characterized using asymmetrical flow field‐flow fractionation (AsFlFFF) coupled online to a multiangle light scattering detector and a refractive index detector to determine the molecular size, molecular weight (MW) distribution, and molecular conformation of HA. For characterization of HA, AsFlFFF was operated by a simplified two‐step procedure, instead of the conventional three‐step procedure, where the first two steps (sample loading and focusing) were combined into one to avoid the adsorption of viscous HA onto the channel membrane. The simplified two‐step AsFlFFF yielded reasonably good separations of HA molecules based on their MWs. The weight average MW (Mw) and the average root‐mean‐square (RMS) radius of HA extracted from rooster comb were 1.20×106 and 94.7 nm, respectively. When the sample solution was filtered through a 0.45 μm disposable syringe filter, they were reduced down to 3.8×105 and 50.1 nm, respectively.
Determination of antioxidants in polyolefins using total dissolution methodology followed by RPLC
Authors: Green Shayne , Bai Snow , Cheatham Mike , Cong Rongjuan , Yau Wallace
Published: September 2010

Antioxidants are added to polyolefins to improve the stability of the resin from oxidation and degradation during processing of the finished article and to increase product lifetime. Without antioxidants, polyolefins would quickly degrade during and after the extrusion or thermoforming process, which would cause inferior appearance and physical properties. The proper level must be added to protect the polymer and to minimize cost. Antioxidants are usually extracted from the resin and the extract is analyzed by RPLC, GC, or Fourier transform infrared spectroscopy. Unfortunately, many of these procedures require significant manual labor, time, and solvent, rendering them impractical for high‐throughput work processes. In addition, they may not provide complete extraction of the additives depending upon the type of resin. A validated analytical method was needed for the determination of three common antioxidants, Irganox®1010, Irganox®1076, and Irgafos®168 in polyolefin resins. This paper shows the determination of these antioxidants using dissolution followed by precipitation witho‐xylene and methanol. Direct analysis of the solution is achieved in 8 min using RPLC.
Hydrodynamic chromatography of latex blends
Authors: Brewer Amandaa K. , Striegel André M.
Published: September 2010

The ability to characterize the size and shape distributions of broadly polydisperse analytes is a driving force in particle size analysis. Multi‐detector hydrodynamic chromatography (HDC), which has previously shown promise in its ability to characterize the size and shape of monodisperse, spherical polystyrene latex standards, is applied here to include the characterization of bi‐, tri‐, and tetramodal latex blends and their constituents varying in size, chemistry, and compactness. The ability of multi‐detector HDC to distinguish between similar‐sized particles of different chemistry is realized by the coupling of a concentration‐sensitive detector and two different types of light scattering detectors. The use of both multi‐angle static and quasi‐elastic light scattering permits for determination of two different size parameters across the elution profiles of the blends. Combining the size information obtained from both light scattering methods provides a measure of how particle compactness changes as a function of size in a latex blend. Multi‐detector HDC was shown to be a rapid and precise method for characterizing particle size, shape, and their distributions of broadly polydisperse analytes.
Release Kinetics and in vitro Bioactivity of Basic Fibroblast Growth Factor: Effect of the Thickness of Fibrous Matrices
Authors: Kim Min Sup , Shin Young Min , Lee Ji‐hye , Kim Sun I. , Nam Young Soo , Shin Choongsoo S. , Shin Heungsoo
Published: September 2010

In this study, we fabricated non‐woven matrices using blends of polycaprolactone and gelatin with various spinning volumes to control the immobilized heparin content, which was ultimately intended to increase the immobilization efficiency of bFGF. The amount of bFGF on the heparin conjugated fibrous matrices depended on the thicknesses of the swollen matrices ranging from 35.4 ± 6.5 to 162.3 ± 14.0 ng and ≈90% of the bFGF was gradually released over a period of up to 56 d. The released bFGF enhanced the proliferation of human umbilical vein endothelial cells and human mesenchymal stem cells. In conclusion, our heparin‐conjugated fibrous matrices have the potential to be used as a growth factor delivery system in tissue engineering applications.

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Novel Vesicles Self‐Assembled From Amphiphilic Star‐Armed PEG/Polypeptide Hybrid Copolymers for Drug Delivery
Authors: Wang Kang , Dong Hai‐Qing , Wen Hui‐Yun , Xu Meng , Li Cao , Li Yong‐Yong , Jones Helen N. , Shi Dong‐Lu , Zhang Xian‐Zheng
Published: September 2010

A novel amphiphilic four‐armed [poly(ε‐benzyloxycarbonyl‐L‐lysine)]2‐block‐poly(ethylene glycol)‐block‐[poly(ε‐benzyloxycarbonyl‐L‐lysine)]2 hybrid copolymer has been prepared. The cytotoxicity study shows that the copolymer has good biocompatibility with no obvious inhibition effect on cell growth. The amphiphilic copolymers could self‐assemble to form vesicles in aqueous solution. DOX · HCl, as a hydrophilic drug, can be loaded into the vesicles, and then successfully internalized by human breast cancer MCF‐7 cells. Importantly, the DOX‐loaded vesicles show a greatly improved drug release behavior with a zero‐order release at the initial stage, suggesting a great potential as the carrier of hydrophilic drugs for controlled drug delivery.

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Miniemulsion Polymerizations Using Static Mixers: Towards High Biocompatible Hydrophobe Contents
Authors: Rahme Roland , Graillat Christian , Farzi Gholamali , McKenna Timothy F. L. , Hamaide Thierry
Published: September 2010

Simple static mixers have been used as homogenization devices to perform polymerizable miniemulsion dispersions with negligible heat generation from mixtures containing vinyl acetate as the monomer and high amounts of biocompatible viscous oils (Miglyol and vitamin E acetate) as the hydrophobic components. A triblock non‐ionic copolymer was used as surfactant. The size of the initial droplets was in the 100–300 nm range, increasing with the amount of the hydrophobe oil. These droplets have successfully been polymerized by using lauroyl peroxide or H2O2/ascorbic acid as initiators in order to get non‐charged primary radicals. Stable nanoparticles with sizes around 300 nm have been obtained that display colloidal stabilization at 4 and 25 °C upon a long storage time.

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Photoinduced Controlled Radical Polymerization in Methanol
Authors: Tasdelen Mehmet Atilla , Uygun Mustafa , Yagci Yusuf
Published: September 2010

Photoinduced CRP of methyl methacrylate initiated by in situ generation of copper (I) complex from higher oxidation state species in methanol was investigated. The polymerizations proceeded in a well‐controlled manner under UV light at room temperature as evidenced by kinetic and chain extension studies. The evolution of molecular weight with conversion showed good correlation between experimental and theoretical molecular weights, which confirmed good control over polymerization and ensured a narrow MWD. The effect of the methanol on the polymerization was also investigated, and a better agreement between experimental and theoretical molecular weights with a quite narrow MWD was obtained by using methanol as solvent.

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Self‐Assembly Behavior of Bis(terpyridine) and Metallo‐bis(terpyridine) Pluronics in Dilute Aqueous Solutions
Authors: Chiper Manuela , Hoeppener Stephanie , Schubert Ulrich S. , Fustin Charles‐André , Gohy Jean‐François
Published: September 2010

Bis(terpyridine) and metallo‐bis(terpyridine) Pluronics have been synthesized starting from commercially available P105 and P123 hydroxytelechelic Pluronics. The grafting of terpyridine ligands at the extremity of the Pluronic chains results in the further association of the Pluronic micelles in water. Increasing temperature decreases the solubility of the Pluronics, but also increases the solubility of the terpyridine groups. The addition of 0.5 equiv. nickel(II) ions compared to terpyridine groups induces the formation of bis(terpyridine) nickel(II) complexes and disrupts the initial hydrophobic terpyridine aggregates. In that case, formation of flower‐like micelles in which the coronal chains form loops due to the terpyridine nickel(II) complexes is observed in the dilute regime.

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Effective Static Dissipation of Bilayer Thermoplastic Nanocomposites at Low Nanofiber Loadings
Authors: Li Bin , Zhong Wei‐Hong
Published: September 2010

A bilayer‐structured PEI/CNF composite fabricated by a facile solution casting method is described, showing dramatically improved static dissipation properties at a rather low loading level. Compared to the conventional monolayer nanocomposite with high static dissipation rate, the bilayer‐structured composite exhibited a 91.4 wt.‐% reduction in CNF loading, while it is volumetric and surface static dissipation rates were ca. 1 000 and 20 times higher, respectively. The interface region in the bilayer structure accounts for such a remarkable improvement. It is believed that this design could significantly benefit the applications requiring high antistatic capability of polymeric materials.

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Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells
Authors: Stavik Benedicte , Skretting Grethe , Sletten Marit , Sandset Per Morten , Iversen Nina
Published: September 2010

Thrombosis is a major complication and an important cause of death in cancer patients. Tumor cells may trigger coagulation and induce a prothrombotic phenotype, which in return may enhance angiogenesis, tumor growth, and metastasis. Tissue factor pathway inhibitor (TFPI) has been reported to reduce tumor growth and metastasis in vivo and to induce apoptosis and inhibit proliferation in normal cells in vitro. However, no effect has so far been observed in cancer cells. We therefore aimed to characterize the functional effects of ectopic overexpression and endogenous downregulation of TFPI in cancer cells, and to elucidate possible mechanisms involved. The tumor derived breast cancer cells SK‐BR‐3 and Sum102 were used to construct stable cell lines overexpressing TFPIα and TFPIβ, and with TFPI knocked down, respectively. Effects of altered TFPI expression were evaluated by measuring apoptosis and proliferation of the cells, and gene expressions were analyzed using PCR arrays. Increased DNA fragmentation and Caspase 3 activity was observed in SK‐BR‐3 cells overexpressing TFPIα and TFPIβ, while a decrease in apoptosis was seen in Sum102 cells with TFPI expression knocked down. An increase and reduction in expression of pro‐ and anti‐apoptotic genes, respectively, were seen in TFPI overexpressing cells, and the majority of the upregulated genes encoded proteins involved in the death receptor pathway, among them the death receptor ligand TNF‐α. In conclusion, TFPIα and TFPIβ induced apoptosis in breast cancer cells and increased expression of apoptotic genes indicating a possible involvement of the death receptor pathway. © 2010 Wiley‐Liss, Inc.
The oviduct as a complex mediator of mammalian sperm function and selection
Authors: Holt William V. , Fazeli Alireza
Published: September 2010

The fallopian tube, or oviduct, is no longer considered merely a conduit that joins the uterine horns and the ovaries, being recognised as a venue for the capacitation of spermatozoa and fertilisation. However, recent evidence has implicated the oviduct in the stringent selection of spermatozoa prior to fertilisation, sperm storage prior to fertilisation, the regulation of sperm motility and possibly the guidance of spermatozoa towards the egg. Moreover, the arrival of spermatozoa within the oviduct is now known to regulate gene expression in oviductal epithelial cells with the consequent up‐ and downregulation of various proteins. In this review, we examine the emerging significance of sperm–oviduct interactions, as they relate to both physiological functions and the likelihood that the oviduct has a role in post‐copulatory sperm selection by females (cryptic female choice) under conditions of sperm competition. The mechanisms by which sperm selection might operate still remain a mystery, especially when the underlying rationale for such mechanism appears to require the recognition by the female tract of sperm qualities related to the intrinsic integrity and information content of the sperm DNA. The oviduct not only selects against spermatozoa containing fragmented DNA but also imposes selection related to the fitness or quality of individual males. This implies the existence of, as yet unrecognised, mechanisms for the detection and interpretation of sperm‐surface markers that link phenotypic and genotypic qualities of each individual cell. Mol. Reprod. Dev. 77:934–943, 2010. © 2010 Wiley‐Liss, Inc.
Influence of stimulus pulse width on M‐waves, H‐reflexes, and torque during tetanic low‐intensity neuromuscular stimulation
Authors: Lagerquist Olle , Collins David F.
Published: September 2010

Neuromuscular electrical stimulation (NMES) has been shown to generate contractions that include a central recruitment of motoneurons; however, the effect of pulse width on electromyographic (EMG) and torque responses during NMES are not well documented. Soleus EMG and isometric plantarflexion torque were recorded from 14 subjects with NMES delivered to the tibial nerve using 50, 200, 500, and 1000 μs pulse widths. M‐waves were significantly smaller during 20 HZ NMES compared with responses evoked by single pulses of 200, 500, and 1000 μs, but not 50 μs pulse widths. At all pulse widths, stimulation at 20 HZ depressed soleus H‐reflexes compared with single pulses. Two seconds of 100 HZ NMES significantly increased H‐reflexes and torque during the subsequent 20 HZ NMES with 200, 500, and 1000 μs, but not 50 μs, pulse widths. NMES delivered using wide pulses generated larger contractions with a relatively greater central contribution than narrow pulses. This may help reduce atrophy and produce fatigue‐resistant contractions for rehabilitation. Muscle Nerve, 2010
Application of angiotensin ii to healthy rat sciatic nerve can produce neuropathy without associated vasculopathy
Authors: Kasselman Lora J. , Rutkove Seward B.
Published: September 2010

Elevated angiotensin II (AII) levels have been associated with hypertension, diabetes, and polyneuropathy. It is unknown whether AII applied to healthy nerve can be used to model a confined neuronal injury by producing localized vasculopathy and associated neuropathy. In this study, angiotensin II (2.2 μg/ml) or saline was infused constantly via osmotic pump onto the sciatic nerve of 20 rats for 12 weeks. Nerve conduction studies were repeated every 4 weeks, and sciatic nerve was collected for pathological analysis at 12 weeks. Animals infused with AII showed a significant decrease in nerve fiber diameter (P< 0.001), axon diameter (P< 0.001), and myelin thickness (P< 0.001), despite the absence of electrophysiological changes. Surprisingly, there was no significant difference in vessel diameter or wall thickness. AII can cause structural alterations in healthy nerve without associated changes in vasculature, implying the existence of additional previously unrecognized mechanisms of AII‐induced neuronal injury. Muscle Nerve, 2010
Two children with “dropped head” syndrome due to lamin A/C mutations
Authors: Chemla Jeremy C. , Kanter Ronald J. , Carboni Michael P. , Smith Edward C.
Published: September 2010

LMNA‐related congenital muscular dystrophy (L‐CMD) is a recently described disorder characterized by infantile‐onset myopathy due to mutations in the lamin A/C (LMNA) gene. We report the genetic and clinical characteristics of two unrelated L‐CMD patients. Patient 1 harbored a novel, L35P mutation and patient 2 a previously reported R249W mutation. The striking phenotype associated with L‐CMD is important to recognize, as molecular diagnostic testing can spare patients unnecessary procedures and prompt the physician to monitor for associated cardiac arrhythmias. Muscle Nerve, 2010
Alpha1‐Adrenoceptor Antagonists Improve Bladder Storage Function Through Reduction of Afferent Activity in Rats With Bladder Outlet Obstruction
Authors: Yazaki Junji , Aikawa Ken , Shishido Keiichi , Yanagida Tomohiko , Nomiya Masanori , Ishibashi Kei , Haga Nobuhiro , Yamaguchi Osamu
Published: September 2010

Aims

Using a rat BOO model, we determined whether α1‐adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract.

Materials and Methods

Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO‐rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post‐drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c‐Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre‐ and post‐drug conditions.

Results

Metabolic cage study showed the voiding behavior of BOO‐rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c‐Fos‐positive cell significantly increased in BOO‐rats, while significantly decreased in those receiving αl‐AR antagonists.

Conclusions

The present study demonstrates that α1‐AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl‐AR, particularly αlA‐AR, may play an important role in the activation of the afferent pathway. Neurourol. Urodynam. 30:461–467, 2011. © 2010 Wiley‐Liss, Inc.
Accuracy of MRI/MRSI‐based transrectal ultrasound biopsy in peripheral and transition zones of the prostate gland in patients with prior negative biopsy
Authors: Testa Claudia , Schiavina Riccardo , Lodi Raffaele , Salizzoni Eugenio , Tonon Caterina , D'Errico Antonietta , Corti Barbara , Morselli‐Labate Antonio Maria , Franceschelli Alessandro , Bertaccini Alessandro , Manferrarik Fabio , Grigioni Walter Francesco , Canini Romeo , Martorana Giuseppe , Barbiroli Bruno
Published: September 2010

The purpose of the study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS‐biopsy) performed on regions with abnormal MRI and/or MRSI for both the transition (TZ) and the peripheral (PZ) zones in patients with suspected prostate cancer with prior negative biopsy, and to analyze the relationship between MRSI and histopathological findings. MRI and MRSI were performed in 54 patients (mean age: 63.9 years, mean PSA value: 11.4 ng/mL) and the ability of MRI/MRSI‐directed TRUS biopsy was evaluated. A three‐point score system was used for both techniques to distinguish healthy from malignant regions. Descriptive statistics and ROC analyses were performed to evaluate the accuracy and the best cut‐off in the three‐point score system. Twenty‐two out of 54 patients presented cancer at MRI/MRSI‐directed TRUS biopsy, nine presented cancer only in PZ, eight both in PZ and TZ, and five exclusively in TZ. On a patient basis the highest accuracy was obtained by assigning malignancy on a positive finding with MRSI and MRI even though it was not significantly greater than that obtained using MRI alone (area under the ROC curve, AUC: 0.723 vs 0.676). On a regional (n = 648) basis the best accuracy was also obtained by considering positive both MRSI and MRI for PZ (0.768) and TZ (0.822). MRSI was false positive in 11.9% of the regions. Twenty‐eight percent of cores with prostatitis were false positive findings on MRSI, whereas only 2.7% of benign prostatic hyperplasia was false positive. In conclusion, the accuracy of MRI/MRSI‐directed biopsies in localization of prostate cancer is good in patient (0.723) and region analyses (0.768). The combination of both MRI and MRSI results makes TRUS‐biopsy more accurate, particularly in the TZ (0.822) for patients with prior negative biopsies. Histopathological analysis showed that the main limitation of MRSI is the percentage of false positive findings due to prostatitis. Copyright © 2010 John Wiley & Sons, Ltd.
Fitzroy's fighting Fuegians: Comparison of palaeopathological and ethnographic indications of fighting behaviour in an extinct human population
Authors: Underdown S.
Published: September 2010

The Selk'nam were an indigenous population of Tierra del Fuego that are now extinct. Contemporary accounts, including those of Robert Fitzroy and Charles Darwin, attest to their prodigious size and strength. These accounts and others record that the Selk'nam were enthusiastic wrestlers and fought till one or other of the opponents could no longer continue. Presented here is a case of traumatic injury to the ulnae and radii of a Selk'nam male that is concomitant with injuries sustained during such activity and as such would provide intriguing evidence of this practice in the skeletal record of an extinct human population. Copyright © 2010 John Wiley & Sons, Ltd.
Dual energy landscape: The functional state of the β‐barrel outer membrane protein G molds its unfolding energy landscape
Authors: Damaghi Mehdi , Sapra K. Tanuj , Köster Stefan , Yildiz Özkan , Kühlbrandt Werner , Muller Daniel J.
Published: September 2010

We applied dynamic single‐molecule force spectroscopy to quantify the parameters (free energy of activation and distance of the transition state from the folded state) characterizing the energy barriers in the unfolding energy landscape of the outer membrane protein G (OmpG) from Escherichia coli. The pH‐dependent functional switching of OmpG directs the protein along different regions on the unfolding energy landscape. The two functional states of OmpG take the same unfolding pathway during the sequential unfolding of β‐hairpins I–IV. After the initial unfolding events, the unfolding pathways diverge. In the open state, the unfolding of β‐hairpin V in one step precedes the unfolding of β‐hairpin VI. In the closed state, β‐hairpin V and β‐strand S11 with a part of extracellular loop L6 unfold cooperatively, and subsequently β‐strand S12 unfolds with the remaining loop L6. These two unfolding pathways in the open and closed states join again in the last unfolding step of β‐hairpin VII. Also, the conformational change from the open to the closed state witnesses a rigidified extracellular gating loop L6. Thus, a change in the conformational state of OmpG not only bifurcates its unfolding pathways but also tunes its mechanical properties for optimum function.