bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfusion cell seeding on large porous PLA/calcium phosphate composite scaffolds in a perfusion bioreactor system under varying perfusion parameters
Authors: Koch M. A. , Vrij E. J. , Engel E. , Planell J. A. , Lacroix D.
Published: September 2010

A promising approach to bone tissue engineering lies in the use of perfusion bioreactors where cells are seeded and cultured on scaffolds under conditions of enhanced nutrient supply and removal of metabolic products. Fluid flow alterations can stimulate cell activity, making the engineering of tissue more efficient. Most bioreactor systems are used to culture cells on thin scaffold discs. In clinical use, however, bone substitutes of large dimensions are needed. In this study, MG63 osteoblast‐like cells were seeded on large porous PLA/glass scaffolds with a custom developed perfusion bioreactor system. Cells were seeded by oscillating perfusion of cell suspension through the scaffolds. Applicable perfusion parameters for successful cell seeding were determined by varying fluid flow velocity and perfusion cycle number. After perfusion, cell seeding, the cell distribution, and cell seeding efficiency were determined. A fluid flow velocity of 5 mm/s had to be exceeded to achieve a uniform cell distribution throughout the scaffold interior. Cell seeding efficiencies of up to 50% were achieved. Results suggested that perfusion cycle number influenced cell seeding efficiency rather than fluid flow velocities. The cell seeding conducted is a promising basis for further long term cell culture studies in large porous scaffolds. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: A Raman spectroscopic study
Authors: Pinheiro Antonio L. B. , Aciole Gilberth T. S. , Cangussú Maria Cristina T. , Pacheco Marcos T. T. , Silveira Landulfo
Published: September 2010

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15th day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Evolution of the radiographic appearance of the metaphyses over the first year of life in type V osteogenesis imperfecta: Clues to pathogenesis
Authors: Arundel Paul , Offiah Amaka , Bishop Nicholas J
Published: September 2010

We present the first report of the development of characteristic radiologic appearances of long bones during the first year of life in an infant with type V osteogenesis imperfecta (OI). We show the evolution of metaphyseal abnormalities from a rickets-like appearance to the classically described dense metaphyseal bands. These abnormalities suggest that the underlying defect in type V OI may involve a molecule common to both bone and cartilage that is involved in the regulation of growth plate development and metadiaphyseal ossification. Our findings provide new insights into skeletal development in type V OI and potentially yield useful clues to the identity of the defect underpinning the condition. © 2011 American Society for Bone and Mineral Research.
Therapeutic plasma exchange a potential strategy for patients with advanced heart failure
Authors: Torre‐Amione Guillermo , Orrego Carlos M. , Khalil Nashwa , Kottner‐Assad Christian , Leveque Christopher , Celis Rene , Youker Keith A. , Estep Jerry D.
Published: September 2010

Background: Previous reports had emphasized the importance of humoral immunity in heart failure in humans, primarily determined by the presence of circulating antibodies. However, there is little or no information about the frequency of anticardiac antibodies present in failing human myocardium. Methods: Clinical data and myocardial tissue samples were analyzed to determine the role of humoral immunity in patients with chronic heart failure (CHF) in different settings. Results: Anticardiac antibodies were found present in failing hearts but not in normal control hearts. Further, the level of expression of these anticardiac antibodies changed with the severity of the disease state; and in patients with acute heart failure, we found selective activation of B cells. Finally, treatment of CHF patients with therapeutic plasma exchange, a strategy that removes circulating antibodies, resulted in a reduction in anticardiac antibody deposition and improvements in cardiac function. Conclusion: These data collectively suggest a role of humoral immunity in the progression of heart failure. J. Clin. Apheresis, 2010. © 2010 Wiley‐Liss, Inc.
Screening and identification of differentially expressed genes in goose hepatocytes exposed to free fatty acid
Authors: Pan Zhixiong , Wang Jiwen , Kang Bo , Lu Lizhi , Han Chunchun , Tang Hui , Li Liang , Xu Feng , Zhou Zehui , LV Jia
Published: September 2010

The overaccumulation of triglycerides in hepatocytes induces hepatic steatosis; however, little is known about the mechanism of goose hepatic steatosis. The aim of this study was to define an experimental model of hepatocellular steatosis with TG overaccumulation and minimal cytotoxicity, using a mixture of various proportions of oleate and palmitate free fatty acids (FFAs) to induce fat‐overloading, then using suppressive subtractive hybridization and a quantitative PCR approach to identify genes with higher or lower expression levels after the treatment of cells with FFA mixtures. Overall, 502 differentially expressed clones, representing 21 novel genes and 87 known genes, were detected by SSH. Based on functional clustering, up‐ and down‐regulated genes were mostly related to carbohydrate and lipid metabolism, enzyme activity and signal transduction. The expression of 20 selected clones involved with carbohydrate and lipid metabolism pathways was further studied by quantitative PCR. The data indicated that six clones similar to the genes ChREBP, FoxO1, apoB, IHPK2, KIF1B, and FSP27, which participate in de novo synthesis of fatty acid and secretion of very low density lipoproteins, had significantly lower expression levels in the hepatocytes treated with FFA mixtures. Meanwhile, 13 clones similar to the genes DGAT‐1, ACSL1, DHRS7, PPARα, L‐FABP, DGAT‐2, PCK, ACSL3, CPT‐1, A‐FABP, PPARβ, MAT, and ALDOB had significantly higher expression levels in the hepatocytes treated with FFA mixtures. These results suggest that several metabolic pathways are altered in goose hepatocytes, which may be useful for further research into the molecular mechanism of goose hepatic steatosis. J. Cell. Biochem. 111: 1482–1492, 2010. © 2010 Wiley‐Liss, Inc.
Insulin stimulates gene expression of ferritin light chain in osteoblast cells
Authors: Han Su Hee , Odathurai Saminathan Sethuraman , Kim Sung‐Jin
Published: September 2010

We explored to identify differentially expressed gene(s) by insulin in osteoblast‐like UMR‐106 cells by employing annealing control primer (ACP)‐based GeneFishing PCR. UMR‐106 cells were treated with insulin and total RNA was isolated. The GeneFishing differential display (DD) PCR was carried out and the profiles of expressed genes were compared between control and insulin treated group, and followed by cloning, sequencing and screened by a BLAST search. It has been found that expression of a PCR product was significantly increased by insulin: It was identified as ferritin light chain. It was further confirmed by reverse transcriptase‐PCR (RT‐PCR) analysis that insulin significantly stimulates the mRNA expression of ferritin light chain. In a Western blot analysis, insulin also increased the protein expression of ferritin light chain. When ERK inhibitor or Casein Kinase II inhibitor (DRB) was pretreated, the stimulation of ferritin light chain expression by insulin was significantly inhibited, suggesting that ERK I/II or Casein Kinase II may play a role in the insulin stimulated increase of ferritin light chain. These results suggest that insulin may play an important role in Fe metabolism in osteoblast cells. J. Cell. Biochem. 111: 1493–1500, 2010. © 2010 Wiley‐Liss, Inc.
Osteoclastogenic activity and RANKL expression are inhibited in osteoblastic cells expressing constitutively active Gα12 or constitutively active RhoA
Authors: Wang Jun , Stern Paula H.
Published: September 2010

Gα12–RhoA signaling is a parathyroid hormone (PTH)‐stimulated pathway that mediates effects in bone and may influence genetic susceptibility to osteoporosis. To further elucidate effects of the pathway in osteoblasts, UMR‐106 osteoblastic cells were stably transfected with constitutively active (ca) Gα12 or caRhoA or dominant negative (dn) RhoA and co‐cultured with RAW 264.7 cells to determine effects on hormone‐stimulated osteoclastogenesis. Whereas PTH and calcitriol‐stimulated osteoclastogenesis in co‐cultures with UMR‐106 cells expressing pcDNA or dominant negative RhoA, the osteoclastogenic effects of PTH and calcitriol were significantly attenuated when the UMR‐106 cells expressed either caRhoA or caGα12. These inhibitory effects were partially reversed by the Rho kinase inhibitor Y27632. None of the constructs affected osteoclastogenesis in untreated co‐cultures, and the constructs did not inhibit the osteoclastogenic responses to receptor activator of NFκB ligand (RANKL). To investigate the mechanism of the inhibitory effects of caGα12 and caRhoA, expression of RANKL, osteoprotegerin (OPG), osteopontin (OPN), and intercellular adhesion molecule‐1 (ICAM) in response to PTH or calcitriol was examined in the UMR‐106 cells. In the cells expressing pcDNA or dnRhoA, PTH and calcitriol increased RANKL mRNA and decreased OPG mRNA, whereas these effects were absent in the cells expressing caGα12 or caRhoA. Basal expression of RANKL and OPG was unaffected by the constructs. The results suggest that Gα12–RhoA signaling can inhibit hormone‐stimulated osteoclastogenesis by effects on expression of RANKL and OPG. Since PTH can stimulate the Gα12–RhoA pathway, the current findings could represent a homeostatic mechanism for regulating osteoclastogenic action. J. Cell. Biochem. 111: 1531–1536, 2010. © 2010 Wiley‐Liss, Inc.
Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis
Authors: Vaillancourt France , Silva Patrick , Shi Qin , Fahmi Hassan , Fernandes Julio C. , Benderdour Mohamed
Published: September 2010

Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa. A few studies have shown that TQ exhibits anti‐inflammatory activities in experimental models of rheumatoid arthritis (RA) through mechanisms that are not fully understood. The aim of this work was to evaluate the in vitro and in vivo effects of TQ and to investigate its influence on the major signalling pathways involved in pathophysiological RA changes. We used isolated human RA fibroblast‐like synoviocytes (FLS) and a rat adjuvant‐induced arthritis model of RA. In isolated RA FLS, TQ (0–10 µM) was not cytotoxic and inhibited slightly lipopolysaccharide (LPS)‐induced FLS proliferation and strongly H2O2‐induced 4‐hydroxynonenal (HNE) generation. By studying different inflammatory and catabolic factors, we determined that TQ significantly abolished LPS‐induced interleukin‐1beta (IL‐1β), tumour necrosis factor‐alpha (TNFα), metalloproteinase‐13, cyclooxygenase‐2, and prostaglandin E2. Furthermore, LPS‐induced the phosphorylation of p38 mitogen‐activated protein kinase, extracellular‐regulated kinases ½, and nuclear factor‐kappaB‐p65 were also blocked by TQ in time‐dependent manner. In our experimental RA model, the oral administration of TQ 5 mg/kg/day significantly reduced the serum levels of HNE, IL‐1β and TNFα as well as bone turnover markers, such as alkaline phosphatase and tartrate‐resistant acid phosphatase. The protective effects of TQ against RA were also evident from the decrease in arthritis scoring and bone resorption. In conclusion, the fact that TQ abolishes a number of factors known to be involved in RA pathogenesis renders it a clinically valuable agent in the prevention of articular diseases, including RA. J. Cell. Biochem. 112: 107–117, 2011. © 2010 Wiley‐Liss, Inc.
Estimating sampling uncertainty in fixed‐depth and fixed‐isotherm estimates of ocean warming
Authors: Palmer Matthew D. , Brohan Philip
Published: September 2010

We present a simple, generic method for parameterising the sampling and measurement uncertainty for time series data that is based on the number of observations that constitutes each data point. The method is demonstrated using basin‐averaged monthly time series of (1) the mean temperature above 220 m depth (T220m); (2) the mean temperature above the 14 °C isotherm (T14C) and (3) the depth of the 14 °C isotherm (D14C). The T220m and T14C analyses are in some sense ‘equivalent’, since the spatial‐time‐mean depth of the 14 °C isotherm is approximately 220 m. In agreement with oceanographic theory, we find that the T14C time series has a consistently lower associated sampling uncertainty than T220m for all ocean basins considered in this study. We also note that the sampling uncertainty for all quantities for a given number of observations is dependent on ocean basin. Our results suggest that with the current observing array we are able to monitor global monthly values of T220m, T14C and D14C with a measurement and sampling uncertainty of approximately ± 0.07 °C, ± 0.04 °C and ± 2.4 m, respectively. However, these estimated uncertainties will become much larger on moving to regional or smaller scales. © Crown Copyright 2010. Published by John Wiley & Sons Ltd.
Urban‐scale CFD analysis in support of a climate‐sensitive design for the Tokyo Bay area
Authors: Ashie Yasunobu , Kono Takaaki
Published: September 2010

Recently, countermeasures against the urban heat island effect have become increasingly important in Tokyo. Such countermeasures include reduction of anthropogenic heat release and enhancement of urban ventilation. Evaluations of urban ventilation require construction of a high‐resolution computational fluid dynamics (CFD) model, which takes into account complex urban morphology. The morphological complexity arises from multi‐scale geometry consisting of buildings, forests, and rivers, which is superimposed on varying topography. Given this background, airflow and temperature fields over the 23 wards of Tokyo were simulated with a CFD technique using a total of approximately 5 billion computational grid cells with a horizontal grid spacing of 5 m. The root mean square (RMS) error of the air temperature between the simulation and observation results at 127 points was 1.1 °C. Using the developed model, an urban redevelopment plan for two districts in metropolitan Tokyo was examined from the viewpoint of air temperature mitigation. Numerical results showed that a reduction by 1 ha in the area covered by buildings increases the area with temperatures below 30 °C by 12 ha. Copyright © 2010 Royal Meteorological Society
Stability in solution and reactivity with soils and soil components of iron and zinc complexes
Authors: Lucena Juan J. , Gárate Agustín , Villén María
Published: September 2010

Naturally derived complexes with the ability to complex (unidentate) or chelate (polydentate) metals are a cheaper alternative to synthetic chelates to correct micronutrient deficiencies, but despite their widespread use there is a lack of knowledge on their agronomic performance. The aim of this paper was to evaluate the stability of iron (Fe) and zinc (Zn) lignosulfonate, gluconate, amino acid, and humate complexes in solution over time and at different pH values. Also, their stability in a concentrated nutrient solution and their reactivity with soils and soil components was evaluated. In our experimental conditions, all the complexes (except Fe amino acid) remained stable in solution for an extended period of time. All Zn complexes and the Fe lignosulfonate were stable in solution up to pH 7.0–7.5, while Fe gluconate only maintained 20%–40% of the iron in solution in the pH range 5–11 and Fe amino acid and humate complexes barely maintained small concentrations of Fe in solution above pH 3. Most of the complexes maintained Fe and Zn in concentrated nutrient solutions for irrigation systems, but Fe amino acid only maintained around 70% of the iron added. In general, the interactions of complexes with soils and soil components produced a high retention. The interaction of Fe lignosulfonate with peat, illite, and ferrihydrite, and Fe gluconate with peat and illite resulted in significant amounts of Fe to remain in solution, while for the Fe amino acid and humate the Fe remaining in solution was low. All Zn complexes were highly retained in an acidic peat, illite, and montmorillonite clays and soils, while no retention was observed on ferrihydrite. In conclusion, the stability of complexes in different conditions is related to the percentage of complexed element in the products. While complexes can be used to maintain micronutrients in solution in aqueous media (foliar and fertigation), their application to soil should be considered as a measure to increase metal availabilities but not their solubility.
Resistance of Medicago truncatula to salt stress is related to glutamine synthetase activity and sodium sequestration
Authors: Aydi Samir , Sassi Sameh , Debouba Mohamed , Hessini Kamel , Larrainzar Estíbaliz , Gouia Houda , Abdelly Chedly
Published: September 2010

The response to salinity may largely vary not only among species but even cultivars or lines of the same species. Knowledge of the reasons underlying these differential responses can be critical in breeding programs to obtain lines with enhanced performance under salinity. In this work, the responses to salt stress of three Medicago truncatula lines with contrasting salt resistance, TN6.18 (sensitive), Jemalong (reference line), and TN8.20 (resistant), have been assessed by analyzing a full array of nodule parameters (water relations, carbohydrates, ion concentrations, and enzyme activities). The aim of this work was to look for the most important criteria conferring resistance to the M. truncatula‐Sinorhizobium symbiosis under salinity. The resistance of M. truncatula to salt stress was related to nodule osmotic adjustment due to both sequestration of sodium and accumulation of soluble carbohydrates and free amino acids following protein degradation, together with an adequate nitrogen metabolism due to maintaining relatively high glutamine synthetase activity (GS) and stimulation of NADH‐dependent glutamate dehydrogenase (GDH). Glutamine synthetase activity differed clearly between the three studied lines. Thus, it may have a key role in the resistance of Medicago truncatula to salt stress.
The use of allograft shell with intramedullary vascularized fibula graft for intercalary reconstruction after diaphyseal resection for lower extremity bony malignancy
Authors: Li Jing , Wang Zhen , Guo Zheng , Chen Guo‐Jing , Fu Jun , Pei Guo‐Xian
Published: September 2010

Background

Reconstruction after excision of the femur and tibia malignancy is a challenging issue for the reconstructive surgeon. The combined use of a vascularized fibular flap and allograft can provide a reliable reconstructive option. This article describes the authors' experience with this technique for the treatment of large‐segmental bone defects after intercalary resection of lower extremity malignancy.

Methods

From 2003 to 2008, 11 patients that had intercalary resection of lower extremity malignancy underwent reconstruction with an allograft and vascularized fibular construct. Time to union was recorded through evaluation of plain radiographs. Patients were examined clinically and radiographically and were assessed functionally with MSTS score.

Result

The average age at time of operation was 18.5 years. The mean follow‐up time was 34.1 months. The oncology result was continuous disease free in 7 patients, no evidence of disease in 2, alive with disease in 1, and died of disease in 1. Free vascularized fibula flap was used in 7 patients and ispilateral pedicle vascularized fibula in 4. The average length of the resected segment was 12.1 cm and that of the fibula flap was 16.2 cm. The primary unions were achieved in all patients except one with tibia reconstruction. The average time for bone union was 5.4 months at fibula–host junction and 11.8 months at allograft–host junction. There were no allograft fractures and no infections. Five patients had 7 local complications. The MSTS average score was 91.8% at final follow‐up. The mean time of weight‐bearing was 12.4 months.

Conclusions

Intramedullary fibular flap in combination with massive allografts provide an excellent option for reconstruction of large‐bony defects after lower extremity malignancy extirpation. The viability of the fibula is a cornerstone in success of reconstruction that prevents allograft nonunion and result in decreased time to bone healing, leading to earlier patient recovery and return of function. J. Surg. Oncol. 2010;102:368–374. © 2010 Wiley‐Liss, Inc.
Is surgical resection justified for stage IV colorectal cancer patients having bilobar hepatic metastases?—an analysis of survival of 77 patients undergoing hepatectomy
Authors: Sakamoto Yoshihiro , Fujita Shin , Akasu Takayuki , Nara Satoshi , Esaki Minoru , Shimada Kazuaki , Yamamoto Seiichiro , Moriya Yoshihiro , Kosuge Tomoo
Published: September 2010

Background

Surgical indication for stage IV colorectal cancer patients with bilobar hepatic metastases may be controversial.

Methods

Retrospective cohort analysis was performed using data of 200 patients who underwent surgical resections for synchronous metastases of colorectal cancer between 1990 and 2005. Of these, 80 patients had solitary, 43 had unilobar multiple, and 77 had bilobar metastases. Prognostic factors of the 77 bilobar metastases were evaluated using multivariate analysis. The survival was compared with that of 95 patients undergoing chemotherapy for unresectable bilobar hepatic metastases.

Results

Univariate and multivariate analyses revealed that the number of metastasis (≥6) [relative risk (RR), 2.7; P = 0.002] and depth of invasion (T4) (RR, 2.0; P = 0.04) were predictors of survival of the 77 patients. The survival of 11 T4 cancer patients with six or more metastases was poor, but significantly better than that of 95 patients with unresectable bilobar metastases (P = 0.04).

Conclusion

Surgical resection in stage IV colorectal cancer patients having bilobar hepatic metastases was justified in the present setting. J. Surg. Oncol. 2010;102:784–788. © 2010 Wiley‐Liss, Inc.
Desarthrodesis and prosthetic reconstruction of the knee after resection of bone tumors
Authors: Ruggieri Pietro , Kasimatis Georgios , Errani Costantino , Bosco Giuseppe , Mercuri Mario
Published: September 2010

Background and Objectives

The aim of the present study was to review the long‐term results in patients who had undergone modular prosthetic reconstruction of the knee, following a failed arthrodesis performed after the resection of bone tumors.

Methods

We reviewed 16 desarthrodeses and prosthetic reconstructions of the knee following a failed artificial arthrodesis after bone tumor resection. Desarthrodeses and subsequent knee megaprosthesis were performed after breakage of the arthrodesis implant in 11 cases and following presumed eradication of infection in five cases.

Results

The mean follow‐up was 15.9 years. The mean post‐operative range of knee flexion was 70°, but only four patients had active extension of the knee. Functional results, according to the MSTS system, were satisfactory in 11 patients. Complications included deep infections in five patients, aseptic loosening in three patients, breakage of the joint hinge in one patient, and patellar tendon avulsion in one patient. Despite a high rate of complications, all but two patients were satisfied.

Conclusion

Our findings indicate that conversion of oncological knee arthrodesis to total knee arthroplasty should be taken into consideration only after giving the patient extensive information about the high risk of serious complications. J. Surg. Oncol. 2010;102:832–837. © 2010 Wiley‐Liss, Inc.
CD133 mRNA expression and microsatellite instability in colorectal carcinoma
Authors: Huh Jung Wook , Park Yeon Sun , Lee Jae Hyuk , Kim Hyeong Rok , Shin Myung Geun , Kim Young Jin
Published: September 2010

Objective

The present study was performed to examine the CD133 expression in colorectal cancer and to analyze its relationship with microsatellite instability (MSI) and the clinicopathological factors, including patient survival.

Methods

The CD133 mRNA levels in 61 primary colorectal adenocarcinomas were analyzed by reverse transcriptase‐polymerase chain reaction, with normalization relative to GAPDH. Five microsatellite markers were analyzed to evaluate MSI.

Results

A CD133 mRNA expression was significantly associated with the depth of invasion (P = 0.017), lymph node involvement (P = 0.012), and lymphovascular invasion (P = 0.019). A CD133 expression was significantly correlated with the MSI status (P = 0.035). With a median follow‐up period of 45 months, the 5‐year disease‐free survival rate of patients with a low CD133 mRNA expression was significantly higher than that of those patients with high levels of CD133 mRNA expression (82.9% and 59.0%, respectively; P = 0.027). However, on the multivariate analysis, a CD133 mRNA expression was not an independent predictor of disease‐free survival.

Conclusions

Elevated CD133 mRNA levels may represent more aggressive tumor biology and poorer survival in patients with colorectal cancer, correlating with a high level of MSI status. Larger prospective studies are required to confirm these findings. J. Surg. Oncol. 2010;102:765–770. © 2010 Wiley‐Liss, Inc.
Detection limits of intraoperative near infrared imaging for tumor resection
Authors: Thurber Greg M. , Figueiredo Jose‐Luiz , Weissleder Ralph
Published: September 2010

Background and Objectives

The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade‐offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation.

Methods

Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds.

Results

Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3–5 mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens.

Conclusions

A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real‐time feedback to obtain clean margins. J. Surg. Oncol. 2010;102:758–764. © 2010 Wiley‐Liss, Inc.
Biosilicification Templated by Amphiphilic Block Copolypeptide Assemblies
Authors: Xia Lin , Liu Yu , Li Zhibo
Published: September 2010

An amphiphilic poly(L‐lysine·HBr)‐block‐poly(L‐leucine) (KL) diblock copolypeptide and its supramolecular assembly are used as a template to direct silica formation, which proceeds by a cooperative process involving biomimetic mineralization and copolypetide reassembly under ambient conditions. Various silica structures can be obtained by using different counterions, changing the chain length of the KL diblocks, and applying a sol–gel mineralization method. We find that the chain length of the KL diblock is an important factor in terms of controlling biosilica morphologies. We also find that the nature of the counterions strongly affects the resulting silica structures. For the same KL diblock, variation of anions from phosphate to sulfate and to carbonate can produce hexagonal silica platelets, silica rods, and fused silica platelets, respectively. In contrast, application of a sol–gel method can replicate the copolypeptide fibril network morphology in water, while employment of ultrasonication to the sol–gel medium transforms the silica fibrils to rigid silica rods. The resulting silica morphology has been systematically characterized using SEM and TEM, and the polypeptide conformation is explored using FT‐IR and CD spectroscopy.

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Well‐Defined Cyclohexene Oxide Mid‐Chain Functional Polystyrene Macromonomer: Synthesis, Characterization and Photoinitiated Cationic Homo‐ and Copolymerization
Authors: Degirmenci Mustafa , Acikses Aslisah , Genli Nasrettin
Published: September 2010

In this article, we present the results of a study of the preparation of a cyclohexene oxide (CHO) mid‐chain functional macromonomer via ATRP of styrene (St) and epoxidation on work‐up with 3‐chloroperoxybenzoic acid. The ATRP initiator, BrCHBr, was synthesized by the condensation of 3‐cyclohexene‐1,1‐dimethanol with 2‐bromopropanoyl bromide. The ATRP of St with BrCHBr and Cu(I)/bpy yielded well‐defined polystyrene with a cyclohexene mid‐chain group (PStCHPSt). Epoxidation of the PStCHPSt was performed using 3‐chloroperoxybenzoic acid. GPC, IR and 1H NMR analyses revealed that a low polydispersity macromonomer of polystyrene with CHO functionality at the mid‐chain (PStCHOPSt) was obtained. The photoinduced cationic polymerization of PStCHOPSt yielded comb‐shaped and graft copolymers.

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Transparent Polysilsesquioxane Films Obtained from Bridged Ureasil Precursors: Tunable Photoluminescence Emission in the Visible Region and Filtering of UV‐Radiation
Authors: Gómez María L. , Fasce Diana P. , Williams Roberto J.J. , Previtali Carlos M. , Montejano Hernán A.
Published: September 2010

Bridged ureasil precursors were synthesized by the reaction of either ethylenediamine (1 mol) or m‐xylylenediamine (1 mol) with isocyanatepropyltriethoxysilane (2 mol). Transparent polysilsesquioxane films were obtained by the hydrolytic condensation of the pure precursors or their co‐condensation in a 50:50 molar ratio. Films based on pure ureasil precursors showed a blue photoluminescent emission band assigned to the photoinduced proton‐transfer among H‐bonded urea groups and the subsequent radiative recombination of ionized groups. Films synthesized by the co‐condensation of both precursors exhibited a significant red‐shift of their absorption, excitation, and emission spectra, associated to de‐localization of H‐bonds, and a high absorption of UV‐radiation.

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Nanosized Shape‐Changing Colloids from Liquid Crystalline Elastomers
Authors: Haseloh Sönke , Ohm Christian , Smallwood Fay , Zentel Rudolf
Published: September 2010

A method to prepare shape‐changing nanospheres from liquid crystalline elastomers is reported. The nanosized colloids are prepared by a miniemulsion process. During this process, colloids are prepared from a liquid crystalline (LC) main‐chain polyester and subsequently crosslinked into a nanometer‐sized LC elastomer. The ability of these LC elastomers to change their shape at the phase transition temperature from the smectic A to the isotropic phase was detected by temperature‐dependent transmission electron microscopy. The phase transition‐induced shape change leads to strongly shape anisotropic nanosized elastomer particles.

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Labeled Nanoparticles Based on Pharmaceutical EUDRAGIT® S 100 Polymers
Authors: Vollrath Antje , Schubert Stephanie , Windhab Norbert , Biskup Christoph , Schubert Ulrich S.
Published: September 2010

The pharmaceutically important polymer P(MAA–r–MMA)1:2 (EUDRAGIT® S100) was investigated concerning its behavior to form nanoparticles via nanoprecipitation. The particles obtained were characterized regarding their size, shape, and characteristics using DLS, SEM, and AUC. Furthermore, the P(MAA–r–MMA)1:2 copolymer was modified with different markers in order to achieve polymer‐based nanocarrier systems, which are detectable and may be useful for controlled drug delivery devices to monitor the drug pathways. The particles were labeled by physical entrapment as well as by covalent attachment of various markers, e.g., radicals, fluorescent‐, and near‐infrared dyes, to the polymer. Physical entrapment of radicals into the polymeric units was performed by co‐nanoprecipitation of P(MAA–r–MMA)1:2 and a radical marker. By means of covalent binding of the markers to the polymer, a stable and more defined labeling of the particles was also performed, leading only to a low degree of modification of the pharmaceutical polymer. After nanoprecipitation, the resulting labeled particles were characterized by SEM and DLS, whereas their biocompatibility was proven by in vitro studies. In order to ensure the possibility of detection of the particles inside the body for drug delivery‐, sensor‐, and imaging applications, the polymeric carriers were also investigated by electron spin resonance, fluorescence, as well as near‐infrared spectroscopy.

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A novel phase and frequency navigator for proton magnetic resonance spectroscopy using water‐suppression cycling
Authors: Ernst Thomas , Li Jikun
Published: September 2010

Magnetic resonance spectroscopy is sensitive to movements, in part, because of motion‐induced phase and frequency variations that lead to incoherent averaging. For in vivo proton magnetic resonance spectroscopy, the unsuppressed or under‐suppressed water signal can be used to restore coherent averaging; however, this approach results in baseline distortions due to the large water peak. Therefore, a novel water‐suppression cycling scheme was developed that alternates between positive and negative residual water signal. Using the residual water signal, the method allows for shot‐to‐shot phase and frequency correction of individual free induction decays and restoration of signal losses due to incoherent averaging, yet near‐complete elimination of residual water. It is demonstrated that the residual water signal can be used to restore metabolite peaks in a brain spectrum from a subject who performed intentional head movements. The ability to correct phase and frequency fluctuations during subject motion is vital for use with adaptive motion correction approaches that ensure proper voxel positioning during head movements. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
CAIPIRINHA accelerated SSFP imaging
Authors: Stäb Daniel , Ritter Christian Oliver , Breuer Felix A. , Weng Andreas Max , Hahn Dietbert , Köstler Herbert
Published: September 2010

Exciting multiple slices at the same time, “controlled aliasing in parallel imaging results in higher acceleration” (CAIPIRINHA) and “phase‐offset multiplanar” have shown to be very effective techniques in 2D multislice imaging. Being provided with individual rf phase cycles, the simultaneously excited slices are shifted with respect to each other in the FOV and, thus, can be easily separated. For SSFP sequences, however, similar rf phase cycles are required to maintain the steady state, impeding a straightforward application of phase‐offset multiplanar or controlled aliasing in parallel imaging results in higher acceleration. In this work, a new flexible concept for applying the two multislice imaging techniques to SSFP sequences is presented. Linear rf phase cycles are introduced providing both in one, the required shift between the slices and steady state in each slice throughout the whole measurement. Consequently, the concept is also appropriate for real‐time and magnetization prepared imaging. Steady state properties and shifted banding behavior of the new phase cycles were investigated using simulations and phantom experiments. Moreover, the concept was applied to perform whole heart myocardial perfusion SSFP imaging as well as real‐time and cine SSFP imaging with increased coverage. Showing no significant penalties in SNR or image quality, the results successfully demonstrate the general applicability of the concept. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Super‐resolution MRI using microscopic spatial modulation of magnetization
Authors: Ropele Stefan , Ebner Franz , Fazekas Franz , Reishofer Gernot
Published: September 2010

A new super‐resolution method is presented to overcome limitations of spatial resolution in MRI. In contrast to previous attempts that are based on simple field of view shifts, the new method additionally modulates the longitudinal magnetization within the imaging plane for each shift, allowing the acquisition of new and independent k‐space data. With this approach, resolution improvements in up to three dimensions are possible, and the total acquisition time linearly scales with the improvement factor for each dimension. First super‐resolution experiments in a geometric phantom and in brain tissue of two healthy volunteers clearly demonstrate the feasibility and advantages of this new method, which has the capability to extend current resolution limits in MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Improved radial GRAPPA calibration for real‐time free‐breathing cardiac imaging
Authors: Seiberlich Nicole , Ehses Philipp , Duerk Jeff , Gilkeson Robert , Griswold Mark
Published: September 2010

To generate real‐time, nongated, free‐breathing cardiac images, the undersampled radial trajectory combined with parallel imaging in the form of radial GRAPPA has shown promise. However, this method starts to fail at high undersampling factors due to the assumptions that must be made for the purposes of calibrating the GRAPPA weight sets. In this manuscript, a novel through‐time radial GRAPPA calibration scheme is proposed which greatly improves image quality for the high acceleration factors required for real‐time cardiac imaging. This through‐time calibration method offers better image quality than standard radial GRAPPA, but it requires many additional calibration frames to be acquired. By combining the through‐time calibration method proposed here with the standard through‐k‐space radial GRAPPA calibration method, images with high acceleration factors can be reconstructed using few calibration frames. Both the through‐time and the hybrid through‐time/through‐k‐space methods are investigated to determine the most advantageous calibration parameters for an R = 6 in vivo short‐axis cardiac image. Once the calibration parameters have been established, they are then used to reconstruct several in vivo real‐time, free‐breathing cardiac datasets with temporal resolutions better than 45 msec, including one with a temporal resolution of 35 msec and an in‐plane resolution of 1.56 mm2. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
Radiofrequency pulses for simultaneous short T2 excitation and long T2 suppression
Authors: Carl Michael , Bydder Mark , Du Jiang , Han Eric
Published: September 2010

Magnetic resonance imaging of short T2 musculoskeletal tissues such as ligaments, tendon, and cortical bone often requires specialized pulse sequences to detect sufficiently high levels of signal, as well as additional techniques to suppress unwanted long T2 signals. We describe a specialized radiofrequency technique for imaging short T2 tissues based on applying hard 180° radiofrequency excitation pulses to achieve simultaneous short T2 tissue excitation and long T2 tissue signal suppression for three‐dimensional ultrashort echo time applications. A criterion for the pulse duration of the 180° radiofrequency pulses is derived that allows simultaneous water and fat suppression. This opens up possibilities for direct imaging of short T2 tissues, without the need for additional suppression techniques. Bloch simulations and experimental studies on short T2 phantoms and specimen were used to test the sequence performance. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
Human imaging at 9.4 T using T2*‐, phase‐, and susceptibility‐weighted contrast
Authors: Budde Juliane , Shajan G. , Hoffmann Jens , Uğurbil Kâmil , Pohmann Rolf
Published: September 2010

The effect of susceptibility differences on an MR image is known to increase with field strength. Magnetic field inhomogeneities within the voxels influence the apparent transverse relaxation time T2*, while effects due to different precession frequencies between voxels caused by local field variations are evident in the image phase, and susceptibility‐weighted imaging highlights the veins and deep brain structures. Here, these three contrast mechanisms are examined at a field strength of 9.4 T. The T2* maps generated allow the identification of white matter structures not visible in conventional images. Phase images with in‐plane resolutions down to 130 μm were obtained, showing high gray/white matter contrast and allowing the identification of internal cortical structures. The susceptibility‐weighted images yield excellent visibility of small venous structures and attain an in‐plane resolution of 175 μm. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
A thermo‐mechanical model for the catastrophic collapse of large landslides
Authors: Cecinato Francesco , Zervos Antonis , Veveakis Emmanuil
Published: September 2010

In this work, a new thermo‐mechanical model is developed, applicable to large‐scale, deep‐seated landslides consisting of a coherent mass sliding on a thin clayey layer. The considered time window is that of catastrophic acceleration, starting at incipient failure and ending when the acquired displacement and velocity are such that the sliding material begins to break up into pieces. The model accounts for temperature rise in the slip zone due to the heat produced by friction, leading to water expansion, thermoplastic collapse of the soil skeleton, and subsequent increase of pore water pressure. The model incorporates the processes of heat production and diffusion, pore pressure generation and diffusion, and an advanced constitutive law for the thermo‐mechanical behavior of soil. An analysis of the Vajont landslide is presented as an example. A sensitivity analysis shows that friction softening is the mechanism most affecting the timescale of the final collapse of a slide, but also that the mechanism of thermal pressurization alone can cause a comparably catastrophic dynamic evolution. It is also shown that, all other factors being equal, thermo‐mechanical collapse will cause thicker slides to accelerate faster than shallow ones. Copyright © 2010 John Wiley & Sons, Ltd.
Maternal thyroid function at 11 to 13 weeks of gestation and subsequent development of preeclampsia
Authors: Ashoor Ghalia , Maiz Nerea , Rotas Micheal , Kametas Nikos A. , Nicolaides Kypros H.
Published: September 2010

Objective

To determine if maternal thyroid function in the first trimester is altered in pregnancies that subsequently develop preeclampsia (PE).

Methods

Mean arterial pressure (MAP), uterine artery pulsatility index (PI) maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) at 11 to 13 weeks of gestation were measured in 102 singleton pregnancies that subsequently developed PE, and the values were compared to the results of 4318 normal pregnancies.

Results

In both the PE groups that required delivery before 34 weeks (early‐PE) and the late‐PE group, compared with the unaffected group, the median MAP multiple of the normal median (MoM) and uterine artery PI MoM were significantly increased. In late‐PE but not in early‐PE, compared with the unaffected group, the median TSH MoM was significantly increased and the median FT4 MoM was decreased. Logistic regression analysis demonstrated that TSH MoM provided a significant contribution in the prediction of late‐PE.

Conclusion

Impaired thyroid function may predispose to the development of late‐PE, and measurement of maternal serum TSH can improve the prediction of late‐PE provided by a combination of factors in the maternal history and the measurements of MAP and uterine artery PI. Copyright © 2010 John Wiley & Sons, Ltd.
Matrix metalloproteinase‐8 in cervical fluid in early and mid pregnancy: relation to spontaneous preterm delivery
Authors: Rahkonen Leena , Rutanen Eeva‐Marja , Nuutila Mika , Sainio Susanna , Sorsa Timo , Paavonen Jorma
Published: September 2010

Objective

To evaluate whether matrix metalloproteinase‐8 (MMP‐8) concentrations in cervical fluid in early and mid pregnancy are associated with subsequent preterm delivery (PTD) preceded by premature preterm rupture of membranes (PPROMs) or preterm labour (PTL) with intact membranes.

Methods

Cervical swab samples were collected from 5180 women in early and mid pregnancy. MMP‐8 was determined by immunofluorometric assay (IFMA). The outcome measure was spontaneous PTD at < 37 weeks' gestation.

Results

The overall distribution and the median cervical fluid MMP‐8 concentrations in early and mid pregnancy did not differ in women with term delivery and those with subsequent PTD. However, cervical fluid MMP‐8 levels were lower in mid pregnancy in women with PTD preceded by PPROM at < 37 weeks as compared with women who delivered at term and women who had PTD initiated by spontaneous onset of labour (p = 0.016 and p = 0.023, respectively).

Conclusion

Our data suggest that molecular mechanisms underlying PTL and PPROM differ and MMP‐8 in cervical fluid may reflect different functions of this protease. Due to remarkable overlapping of cervical fluid MMP‐8 values, this molecule may not have clinical applicability as a biomarker in cervical fluid at least among asymptomatic women in early and mid pregnancy. Copyright © 2010 John Wiley & Sons, Ltd.