bluuebunny/crossref_metadata_2025 huggingface dataset:
Total hip replacement for high dislocated hips without femoral shortening osteotomy
Authors: Zhao X. , Zhu Z.-A. , Xie Y.-Z. , Yu B. , Yu D.-G.
Published: September 2011

When performing total hip replacement (THR) in high dislocated hips, the presence of soft-tissue contractures means that most surgeons prefer to use a femoral shortening osteotomy in order to avoid the risk of neurovascular damage. However, this technique will sacrifice femoral length and reduce the extent of any leg-length equalisation. We report our experience of 74 THRs performed between 2000 and 2008 in 65 patients with a high dislocated hip without a femoral shortening osteotomy. The mean age of the patients was 55 years (46 to 72) and the mean follow-up was 42 months (12 to 78). All implants were cementless except for one resurfacing hip implant. We attempted to place the acetabular component in the anatomical position in each hip. The mean Harris hip score improved from 53 points (34 to 74) pre-operatively to 86 points (78 to 95) at final follow-up. The mean radiologically determined leg lengthening was 42 mm (30 to 66), and the mean leg-length discrepancy decreased from 36 mm (5 to 56) pre-operatively to 8.5 mm (0 to 18) postoperatively. Although there were four (5%) post-operative femoral nerve palsies, three had fully resolved by six months after the operation. No loosening of the implant was observed, and no dislocations or infections were encountered.

Total hip replacement without a femoral shortening osteotomy proved to be a safe and effective surgical treatment for high dislocated hips.
A comparison of parallel and diverging screw angles in the stability of locked plate constructs
Authors: Wähnert D. , Windolf M. , Brianza S. , Rothstock S. , Radtke R. , Brighenti V. , Schwieger K.
Published: September 2011

We investigated the static and cyclical strength of parallel and angulated locking plate screws using rigid polyurethane foam (0.32 g/cm3) and bovine cancellous bone blocks. Custom-made stainless steel plates with two conically threaded screw holes with different angulations (parallel, 10° and 20° divergent) and 5 mm self-tapping locking screws underwent pull-out and cyclical pull and bending tests. The bovine cancellous blocks were only subjected to static pull-out testing. We also performed finite element analysis for the static pull-out test of the parallel and 20° configurations. In both the foam model and the bovine cancellous bone we found the significantly highest pull-out force for the parallel constructs. In the finite element analysis there was a 47% more damage in the 20° divergent constructs than in the parallel configuration. Under cyclical loading, the mean number of cycles to failure was significantly higher for the parallel group, followed by the 10° and 20° divergent configurations.

In our laboratory setting we clearly showed the biomechanical disadvantage of a diverging locking screw angle under static and cyclical loading.
The role of reactive oxygen species scavenging enzymes in the development of septic loosening after total hip replacement
Authors: Peng K.-T. , Hsu W.-H. , Shih H.-N. , Hsieh C.-W. , Huang T.-W. , Hsu R. W.-W. , Chang P.-J.
Published: September 2011

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.
Spontaneous compartment syndrome of the foot
Authors: Hill C. E. , Modi C. S. , Baraza N. , Mosleh-Shirazi M. S. , Dhukaram V.
Published: September 2011

Compartment syndrome of the foot is usually associated with trauma, and if untreated may result in deformity and loss of function. We report a case of spontaneous compartment syndrome of the foot presenting with severe unremitting pain. The diagnosis was supported by measurements of compartment pressures and the symptoms resolved after surgical decompression. Spontaneous compartment syndrome in the leg has been described in a small number of cases, but there has been no previous report involving the foot. We believe that this case highlights the importance of suspecting a spontaneous compartment syndrome of the foot if the appropriate symptoms are present but there is no clear cause. We also believe that compartment pressure measurement assists in the decision to undertake surgical decompression.
Application of Frequency Selective Circuits for Crack Detection in Concrete Elements
Authors: Pour-Ghaz Mohammad , Weiss Jason
Published: September 2011

Recent research has demonstrated that cracking can be monitored in concrete using conductive surface elements. One complication with using conductive surface elements is that each element requires a separate data acquisition channel. To overcome this hurdle, a frequency selective circuit (FSC) has been developed to rapidly and simultaneously interrogate the response of multiple conductive surface elements. The response of the FSC is analyzed using numerical methods and the use of the FSC is demonstrated using a pilot study in which conductive surface coatings were used to simultaneously monitor the time of cracking of multiple restrained concrete rings. Results indicate that the FSC can be used to monitor a large number of surface coating elements. This technology could be extended to other resistance based sensors. The FSC approach has the potential to be used for health monitoring of infrastructure elements where a large number of sensors are used.
Anthropogenic impact assessment of Niangziguan karst water
Authors: Gao Xubo , Wang Yanxin , Ma Teng , Hu Qinhong (Max) , Xing Xingli , Yu Qian
Published: September 2011

As the biggest karst spring system in northern China, the Niangziguan karst water system is the major source of water supply for Yangquan city, one of the most important bases of coal production in China. In this study, the chemical composition of karst groundwater was investigated with particular emphasis on identifying the sources of chemical variation. The results show significant geographic variation in chemical constituents through the karst groundwater system and also indicate that human activity is responsible for much of the observed hydrochemical variation. The addition of SO42−, Cl− and NO3− from human activities causes the groundwater hydrochemistry to vary from the HCO3-Ca-Mg or HCO3-SO4-Ca-Mg type to the SO4-HCO3-Ca, Cl-SO4-HCO3-Ca, SO4-Ca or SO4-Cl-Ca type. Results from factor analysis indicate that abnormally high levels of SO42− and Na+ are from sources related to coal mining activity, which is widely distributed in the study area. High concentrations of Cl− and NO3− result from sources related to human activities such as agriculture and mining wastewaters and sewage discharge. The results of cluster analysis in combination with hydrogeochemical analysis indicate that natural and anthropogenic processes jointly control the evolution of groundwater chemistry in regional groundwater systems like Niangziguan.
DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of Cx43
Authors: Szpak Katarzyna , Wybieralska Ewa , Niedziałkowska Ewa , Rak Monika , Bechyne Iga , Michalik Marta , Madeja Zbigniew , Czyż Jarosław
Published: September 2011

The formation of aqueous intercellular channels mediating gap junctional intercellular coupling (GJIC) is a canonical function of connexins (Cx). In contrast, mechanisms of GJIC-independent involvement of connexins in cancer formation and metastasis remain a matter of debate. Because of the role of Cx43 in the determination of carcinoma cell invasive potential, we addressed the problem of the possible Cx43 involvement in early prostate cancer invasion. For this purpose, we analysed Cx43-positive DU-145 cell subsets established from the progenies of the cells most readily transmigrating microporous membranes. These progenies displayed motile activity similar to the control DU-145 cells but were characterized by elevated Cx43 expression levels and GJIC intensity. Thus, apparent links exist between Cx43 expression and transmigration potential of DU-145 cells. Moreover, Cx43 expression profiles in the analysed DU-145 subsets were not affected by intercellular contacts and chemical inhibition of GJIC during the transmigration. Our observations indicate that neither cell motility nor GJIC determines the transmigration efficiency of DU-145 cells. However, we postulate that selective transmigration of prostate cancer cells expressing elevated levels of Cx43 expression may be crucial for the “leading front” formation during cancer invasion.
Surface induced self-organization of comb-like macromolecules
Authors: Popov Konstantin I , Palyulin Vladimir V , Möller Martin , Khokhlov Alexei R , Potemkin Igor I
Published: September 2011

We present a review of the theoretical and experimental evidence for the peculiar properties of comb copolymers, demonstrating the uniqueness of these materials among other polymer architectures. These special properties include an increase in stiffness upon increasing side-chain length, the spontaneous curvature of adsorbed combs, rod–globule transition, and specific intramolecular self-assembly. We also propose a theory of chemically heterogeneous surface nanopattern formation in ultrathin films of comblike macromolecules containing two different types (A and B) of incompatible side chains (so-called binary combs). Side chains of the binary combs are strongly adsorbed on a surface and segregated with respect to the backbone. The thickness of surface domains formed by the B side chains is controlled by the interaction with the substrate. We predict the stability of direct and inverse disc-, torus- and stripelike nanostructures. Phase diagrams of the film are constructed.
Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease
Authors: Sakakibara Ryuji , Kishi Masahiko , Ogawa Emina , Tateno Fuyuki , Uchiyama Tomoyuki , Yamamoto Tatsuya , Yamanishi Tomonori
Published: September 2011

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.
Just How Much Can School Pupils Learn from School Gardening? A Study of Two Supervised Agricultural Experience Approaches in Uganda
Authors: Okiror John James , Matsiko Buryabaho Frank , Oonyu Joseph
Published: September 2011

School systems in Africa are short of skills that link well with rural communities, yet arguments tovocationalize curricula remain mixed and school agriculture lacks the supervised practical component. This study, conducted in eight primary (elementary) schools in Uganda, sought to compare the learning achievement of pupils taught using supervised home–gardens and those taught using school gardens. The two gardening groups were tested using a t–test. Data were collected for a period of four school terms using pre and posttest questionnaires, focus group discussions (FGDs), interviews, observations, and a posttest examination. Findings showed no significant difference in knowledge achievement between the two groups of pupils (p
Exploring the vertical profile of atmospheric organic aerosol: comparing 17 aircraft field campaigns with a global model
Authors: Heald C. L. , Coe H. , Jimenez J. L. , Weber R. J. , Bahreini R. , Middlebrook A. M. , Russell L. M. , Jolleys M. , Fu T.-M. , Allan J. D. , Bower K. N. , Capes G. , Crosier J. , Morgan W. T. , Robinson N. H. , Williams P. I. , Cubison M. J. , DeCarlo P. F. , Dunlea E. J.
Published: September 2011

Abstract. The global organic aerosol (OA) budget is highly uncertain and past studies suggest that models substantially underestimate observed concentrations. Few of these studies have examined the vertical distribution of OA. Furthermore, many model-measurement comparisons have been performed with different models for single field campaigns. We synthesize organic aerosol measurements from 17 aircraft campaigns from 2001–2009 and use these observations to consistently evaluate a GEOS-Chem model simulation. Remote, polluted and fire-influenced conditions are all represented in this extensive dataset. Mean observed OA concentrations range from 0.2–8.2 μg sm−3 and make up 15 to 70% of non-refractory aerosol. The standard GEOS-Chem simulation reproduces the observed vertical profile, although observations are underestimated in 13 of the 17 field campaigns (the median observed to simulated ratio ranges from 0.4 to 4.2), with the largest model bias in anthropogenic regions. However, the model is best able to capture the observed variability in these anthropogenically-influenced regions (R2=0.18–0.57), but has little skill in remote or fire-influenced regions. The model bias increases as a function of relative humidity for 11 of the campaigns, possibly indicative of missing aqueous phase SOA production. However, model simulations of aqueous phase SOA suggest a pronounced signature in the mid-troposphere (2–6 km) which is not supported in the observations examined here. Spracklen et al. (2011) suggest adding ~100 Tg yr−1 source of anthropogenically-controlled SOA to close the measurement-model gap, which we add as anthropogenic SOA. This eliminates the model underestimate near source, but leads to overestimates aloft in a few regions and in remote regions, suggesting either additional sinks of OA or higher volatility aerosol at colder temperatures. Sensitivity simulations indicate that fragmentation of organics upon either heterogeneous or gas-phase oxidation could be an important (missing) sink of OA in models, reducing the global SOA burden by 15% and 47% respectively. The best agreement with observations is obtained when the simulated anthropogenically-controlled SOA is increased to ~100 Tg yr−1 accompanied by either a gas-phase fragmentation process or an increase in volatility away from source (by decreasing the enthalpy of vaporization from 42 kJ mol−1 to 25 kJ mol−1). These results illustrate that models may require both additional sources and additional sinks to capture the observed concentrations of organic aerosol.
The proton pressure tensor as a new proxy of the proton decoupling region in collisionless magnetic reconnection
Authors: Aunai N. , Retinò A. , Belmont G. , Smets R. , Lavraud B. , Vaivads A.
Published: September 2011

Abstract. Cluster data is analyzed to test the proton pressure tensor variations as a proxy of the proton decoupling region in collisionless magnetic reconnection. The Hall electric potential well created in the proton decoupling region results in bounce trajectories of the protons which appears as a characteristic variation of one of the in-plane off-diagonal components of the proton pressure tensor in this region. The event studied in this paper is found to be consistent with classical Hall field signatures with a possible 20% guide field. Moreover, correlations between this pressure tensor component, magnetic field and bulk flow are proposed and validated, together with the expected counterstreaming proton distribution functions.
GEOSPATIAL DATA FOR COMPUTERISATION OF PUBLIC ADMINISTRATION IN THE CZECH REPUBLIC
Authors: Cada V. , Mildorf T.
Published: September 2011

Abstract. The main aim of the eGovernment programme in the Czech Republic is to enhance the efficiency of public administration. The Digital Map of Public Administration (DMVS) should be composed of digital orthophotographs of the Czech Republic, digital and digitised cadastral maps, digital purpose cadastral map (ÚKM) and a technical map of municipality, if available. The DMVS project is a part of computerisation of public administration in the Czech Republic. The project enhances the productivity of government administration and also simplifies the processes between citizens and public administration. The DMVS project, that should be compliant with the INSPIRE (Infrastructure for Spatial Information in the European Community) initiative, generates definite demand for geodata on the level of detail of land data model. The user needs that are clearly specified and required are not met due to inconsistencies in terminology, data management and level of detail.
SPATIAL MODELS FOR ARCHITECTURAL HERITAGE IN URBAN DATABASE CONTEXT
Authors: Costamagna E. , Spanò A.
Published: September 2011

Abstract. Despite the GIS (Geographic Information Systems/Geospatial Information Systems) have been provided with several applications to manage the two-dimensional geometric information and arrange the topological relations among different spatial primitives, most of these systems have limited capabilities to manage the three-dimensional space. Other tools, such as CAD systems, have already achieved a full capability of representing 3D data. Most of the researches in the field of GIS have underlined the necessity of a full 3D management capability which is not yet achieved by the available systems (Rahman, Pilouk 2008) (Zlatanova 2002). First of all to reach this goal is important to define the spatial data model, which is at the same time a geometric and topological model and so integrating these two aspects in relation to the database management efficiency and documentation purposes. The application field on which these model can be tested is the spatial data managing of Architectural Heritage documentation, to evaluate the pertinence of these spatial models to the requested scale for the needs of such a documentation. Most of the important aspects are the integration of metric data originated from different sources and the representation and management of multiscale data. The issues connected with the representation of objects at higher LOD than the ones defined by the CityGML will be taken into account. The aim of this paper is then to investigate which are the favorable application of a framework in order to integrate two different approaches: architectural heritage spatial documentation and urban scale spatial data management.
CHANGES IN THE URBAN SPATIAL STRUCTURE OF THE GREATER CAIRO METROPOLITAN AREA, EGYPT
Authors: Hassan A. A. M.
Published: September 2011

Abstract. Since the 1980s, rapid population growth and urbanization have become issues in big cities like Greater Cairo (GC). As a consequence of explosive growth, the living conditions of Cairo Metropolis deteriorate. Development trends of the last twenty years have increased general wealth and modernization, this sets out how GC megacity is creating an increased demand for land combined with environmental degradation. Planning a sustainable development of mega cities requires understanding of physical change of the main environmental drivers. However, this talk will be concerned with monitoring and analysis of dynamic environment changes to capture and refine the urban patterns in Greater Cairo Metropolis on the basis of pixel-based and object-based classifications. Satellite images (TM, ETM+, & Spot) of different dates and resolutions, and ground truth data collected from available maps, field observation, and personal experience were used to execute the image segmentation analysis to reveal urban patterns and expansions. By using Erdas Imagine, and eCognition Developer software, land use/land cover image classifications were constructed, which detect regimes and trends in land changes. Two main types of urban patterns could be detected (passing from centre to periphery). The first one is informal and the second one is formal building. The informal type mainly comprises slums and urban encroachment on arable land. The formal one mostly consists of new cities and legal houses. Moreover, a rate of land cover changes in Greater Cairo during the last three decades could be described as a rapid progression. In contrast, the combination between field observations and classification analyses showed that the high urban densities based on classification of satellite images does not reflect the real densities of population in urban areas in Greater Cairo.
INTEGRATING QUALITY MANAGEMENT INTO A 3D GEOSPATIAL SERVER
Authors: Coors V. , Krämer M.
Published: September 2011

Abstract. In recent years the technology and workflow for producing and management of large 3D urban models has been established and widely been used. Standards such as CityGML enable the modelling and exchange of semantically enriched multi-purpose 3D urban models for applications like urban planning, public participation, environmental simulation and navigation. However, data quality management is essential to control and enhance the quality of these models in order to be able to meet the needs of the aforementioned applications. Quality management should be performed throughout the whole lifecycle of geospatial datasets – from data acquisition to processing, analysis and visualisation. In this paper, we therefore focus on the integration of a quality management software module into a 3D geospatial data server. First results of a prototype system developed at HFT Stuttgart together with Fraunhofer IGD will be presented in this paper as a starting point for further research into the field of quality management of 3D city models.
VALIDATION OF GEOGRAPHICAL DATASETS AGAINST SPATIAL CONSTRAINTS AT CONCEPTUAL LEVEL
Authors: Belussi A. , Liguori F. , Marca J. , Migliorini S. , Negri M. , Pelagatti G. , Visentini P.
Published: September 2011

Abstract. A huge amount of geographical datasets are becoming available in distributed environments like Spatial Data Infrastructures (SDI). These datasets are very heterogeneous since they come from different independent sources and surveys and are structured in different formats. In the context of a national SDI that needs to assure an adequate quality level of the data it provides, it is necessary to face the problem of data validation in an uniform way independently from the chosen implementation technology. In this paper we present the tools and methodology for data validation which have been developed to support the construction of the Italian SDI. These tools are conformant to the relevant ISO 19100 and Open Geospatial Consortium (OGC) standards.
Progressive Facial Hemiatrophy Revisited
Authors: Guo Zhen-Ni , Zhang Hong-Liang , Zhou Hong-Wei , Lan Wen-Jing , Wu Jiang , Yang Yi
Published: September 2011

Objective

To report a case of progressive facial hemiatrophy with unusual features of contralateral brain atrophy and transcranial Doppler ultrasound evidence of autonomic dysfunction.

Design

Case report.

Setting

A teaching hospital.

Patient

A 63-year-old man who presented with a 10-year history of progressive right-sided facial atrophy and recent facial pain.

Results

Brain magnetic resonance imaging revealed left frontoparietal atrophy. Transcranial Doppler ultrasound demonstrated evidence of autonomic dysfunction ipsilateral to brain atrophy.

Conclusion

This case expands the spectrum of findings in progressive facial hemiatrophy to include contralateral brain atrophy and suggests that sympathetic dysfunction might play a pathogenic role in progressive facial hemiatrophy.
Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition
Authors: Roe Catherine M. , Fagan Anne M. , Grant Elizabeth A. , Marcus Daniel S. , Benzinger Tammie L. S. , Mintun Mark A. , Holtzman David. M. , Morris John C.
Published: September 2011

Background

Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.

Objective

To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid42(Aβ42), tau, and phosphorylated tau (ptau181) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.

Design

Longitudinal cohort study.

Setting

Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University, St Louis, Missouri.

Participants

A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years.

Main Outcome Measure

Time to Clinical Dementia Rating ≥ 0.5.

Results

Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91;P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02).

Conclusion

In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.
Ordered Hierarchical Mesoporous/Microporous Carbon Derived from Mesoporous Titanium‐Carbide/Carbon Composites and its Electrochemical Performance in Supercapacitor
Authors: Liu Hai‐Jing , Wang Jie , Wang Cong‐Xiao , Xia Yong‐Yao
Published: September 2011

Novel ordered hierarchical mesoporous/microporous carbon (OHMMC) derived from mesoporous titanium‐carbide/carbon composites was prepared for the first time by synthesizing ordered mesoporous nanocrystalline titanium‐carbide/carbon composites, followed by chlorination of titanium carbides. The mesostructure and microstructure can be conveniently tuned by controlling the TiC contents of mesoporous TiC/C composite precursor, and chlorination temperature. By optimal condition, the OHMMC has a high surface area (1917 m2g−1), large pore volumes (1.24 cm3g−1), narrow mesopore‐size distributions (centered at about 3 nm), and micropore size of 0.69 and 1.25 nm, and shows a great potential as electrode for supercapacitor applications: it exhibits a high capacitance of 146 Fg−1 in noaqueous electrolyte and excellent rate capability. The ordered mesoporous channel pores are favorable for retention and immersion of the electrolyte, providing a more favorable path for electrolyte penetration and transportation to achieve promising rate capability performance. Meanwhile, the micropores drilled on the mesopore‐walls can increase the specific surface area to provide more sites for charge storage.
A 10‐year experience with treatment of high and standard risk Hodgkin disease: Six cycles of tailored BEACOPP, with interim scintigraphy, are effective and female fertility is preserved
Authors: Dann Eldad J. , Blumenfeld Zeev , Bar‐Shalom Rachel , Avivi Irit , Ben‐Shachar Menachem , Goor Odelia , Libster Diana , Gaitini Diana , Rowe Jacob M. , Epelbaum Ron
Published: September 2011

Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between July, 1999 and August, 2005. Patients with early unfavorable and advanced disease were eligible for the study. Patients were assigned to therapy based on international prognostic score (IPS). Those with IPS ≥ 3 received three cycles of escalated BEACOPP (EB). All others received two cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned according to early interim GA67 or positron emission tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were administered following a positive or negative scan, respectively. Complete remission rate, 10‐year progression free (PFS), and overall survival (OS) were 97, 87, and 88%, respectively, at a median follow‐up of 89 months (5–144). PFS and OS were similar in both groups. Fertility status was assessed in 38 females aged <40 years; 94% of females younger than 40 years preserved their cyclic ovarian function. Nineteen conceived during follow‐up for 30 pregnancies, delivering 24 babies. Deliveries were reported up to 7 years from diagnosis. Predictive value of negative interim Ga67 or PET/CT was 87 and 93%, respectively. Six cycles of tailored BEACOPP, for patients with adverse prognostic factors, provide encouraging long‐term PFS and OS, and fertility is preserved in most females. Am. J. Hematol. 2012. © 2011 Wiley Periodicals, Inc.
Identification of [PtCl2(phen)] Binding Modes in Amyloid‐β Peptide and the Mechanism of Aggregation Inhibition
Authors: Ma Guolin , Huang Fan , Pu Xuewei , Jia Liangyuan , Jiang Tao , Li Lianzhi , Liu Yangzhong
Published: September 2011

Platinum phenanthroline complexes inhibit amyloid‐β (Aβ) aggregation and reduce Aβ‐caused neurotoxicity [Proc. Natl. Acad. Sci., 2008, 105, 6813–6818]. In this study, we investigated the interactions of Aβ1–16 with [PtCl2(phen)] (phen=1,10‐phenanthroline) using HPLC, ESI‐MS, and NMR spectroscopy , and characterized the identity of products using tandem mass spectrometry. Results indicated that the phenanthroline ligand could induce noncovalent interactions between Aβ peptide and platinum complexes, leading to rapid Aβ platination. Multiple products were generated in the reaction, in which His6/His14 chelation was preferentially formed. Coordination of Asp7, His13, and Lys16 was also detected in other products. The majority of products were monoplatinated adducts with binding of the {Pt(phen)} scaffold, which impeded intermolecular interactions between Aβ peptides. Moreover, noncovalent interactions were confirmed by the interaction between Aβ peptide and [Pt(phen)2]Cl2. The synergistic roles of the phen ligand and platinum(II) atom in the inhibition of Aβ aggregation are discussed.
Earlier age of onset of BRCA mutation‐related cancers in subsequent generations
Authors: Litton Jennifer K. , Ready Kaylene , Chen Huiqin , Gutierrez‐Barrera Angelica , Etzel Carol J. , Meric‐Bernstam Funda , Gonzalez‐Angulo Ana M. , Le‐Petross Huong , Lu Karen , Hortobagyi Gabriel N. , Arun Banu K.
Published: September 2011

BACKGROUND:

Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations.

METHODS:

Of the 132 BRCA‐positive women with breast cancer who participated in a high‐risk protocol at The University of Texas MD Anderson Cancer Center (Gen 2), 106 women could be paired with a family member in the previous generation (Gen 1) who was diagnosed with a BRCA‐related cancer (either breast cancer or ovarian cancer). Age at diagnosis, location of the mutation, and year of birth were recorded. A previously published parametric anticipation model was applied in these genetically predisposed families.

RESULTS:

The median age of cancer diagnosis was 42 years (range, 28‐55 years) in Gen 2 and 48 years (range, 30‐72 years) in Gen 1 (P < .001). In the parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years (P < .0001). Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer‐identified and ovarian cancer‐identified families.

CONCLUSIONS:

Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations. The authors concluded that patients who are younger at the onset of BRCA‐related cancers should continue to be tracked to offer appropriate screening modalities at appropriate ages. Cancer 2011. © 2011 American Cancer Society.
DNA methylation profiling reveals a predominant immune component in breast cancers
Authors: Dedeurwaerder Sarah , Desmedt Christine , Calonne Emilie , Singhal Sandeep K. , Haibe‐Kains Benjamin , Defrance Matthieu , Michiels Stefan , Volkmar Michael , Deplus Rachel , Luciani Judith , Lallemand Françoise , Larsimont Denis , Toussaint Jérôme , Haussy Sandy , Rothé Françoise , Rouas Ghizlane , Metzger Otto , Majjaj Samira , Saini Kamal , Putmans Pascale , Hames Gérald , van Baren Nicolas , Coulie Pierre G. , Piccart Martine , Sotiriou Christos , Fuks François
Published: September 2011

Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known ‘expression subtypes’. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients.
Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix
Authors: Biggar Robert J. , Wohlfahrt Jan , Melbye Mads
Published: September 2011

Digoxin is a phyto‐estrogen capable of inducing hormonal effects. Use has been associated with increased risk of breast cancer, an estrogen‐sensitive malignancy. The incidence of corpus uteri (uterus) cancer is also strongly increased with exposure to estrogens. Therefore, we evaluated whether digoxin use might also increase its incidence. In all women in Denmark, we identified digoxin users from 1995 through 2008 using a nationwide pharmacy registry system. Cancer occurrence was obtained from Danish Cancer Registry. Relative risk was determined using incidence risk ratios (RR) and 95% confidence intervals (CIs) relative to non‐users after adjustment for age‐ and calendar‐time. For ovarian and cervical cancers, RRs in users and non‐users were similarly evaluated, these cancers representing gynecological cancers with weak or no associations to estrogen exposure. Of 2.1 million women, 104,648 (4.9%) had digoxin exposure and 137,493 6.5% had exposure to angina drugs but not digoxin during the study period. For uterus cancer, the RR was increased in current digoxin users (1.48, 95% CI: 1.32–1.65; N = 350). Incidence was marginally increased in former users. For ovary and cervix cancers, RRs in current digoxin users were 1.06 (95% CI: 0.92–1.22; N = 207) and 1.00 (95% CI: 0.79–1.25; N = 81), respectively. We examined risks in women using angina drugs but not digoxin to determine whether being under cardiac care affected risk. Among women using angina drugs only, RRs for uterus, ovary or cervix cancers were not statistically significant. We conclude that women currently using digoxin, a phyto‐estrogen, have an increased risk of developing uterus cancers.
Synthesis of novel folate conjugated fluorescent nanoparticles for tumor imaging
Authors: Hou Jie , Zhang Qi , Li Xia , Tang Yu , Cao Mei‐rong , Bai Fang , Shi Qian , Yang Cui‐hong , Kong De‐ling , Bai Gang
Published: September 2011

A novel folate fluorescent nanoconjugate was synthesized and used for detection of cancer cells overexpressing the folate receptor (FR). The folate conjugate (PCMS‐NA‐FA) was synthesized by conjugating folic acid (FA) and 4‐ethylnyl‐N‐ethyl‐1, 8‐naphthalimide (NA) to the polychloromethylstyrene (PCMS) functionalized with azido group (PCMS‐N3) through click reaction. The obtained conjugate had clear structure and could form PCMS‐NA‐FA nanoparticles with particle size around 86 nm in aqueous solution. Ability of PCMS‐NA‐FA targeting to cancerous cells was investigated by comparing the uptake of the nanoparticles by human adenocarcinoma HeLa cells and by non‐FR expressing human lung carcinoma A549 cells. Specificity of the PCMS‐NA‐FA nanoparticles targeting on FRs was verified with cellular uptake inhibition assay, in which HeLa cells were incubated with both nanoconjugate and free FA. In addition, the specificity was also confirmed by the collocation of the immunofluorescence staining of anti‐FR and the cellular uptake of the PCMS‐NA‐FA nanoparticles. Furthermore, the organ distribution of this folate nanoconjugate was studied on HeLa cell‐bearing mice via frozen slicing, and the results showed that the folate nanoparticles were preferentially accumulated in the tumor site rather than other tissues, indicating the desired specificity for tumor targeting and imaging. All these findings suggested that this practical synthetic strategy can potentially facilitate the preparation of multifunctional imaging probe in biology and diagnosis of disease. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
The roles of connective tissue growth factor and integrin‐linked kinase in high glucose‐induced phenotypic alterations of podocytes
Authors: Dai Hou‐Yong , Zheng Min , Lv Lin‐Li , Tang Ri‐Ning , Ma Kun‐Ling , Liu Dan , Wu Min , Liu Bi‐Cheng
Published: September 2011

Emerging evidence has suggested that podocytes undergo epithelial–mesenchymal transition (EMT) in diabetic nephropathy (DN). Connective tissue growth factor (CTGF) and integrin‐linked kinase (ILK) are involved in the progression of DN. However, the underlying mechanisms of EMT are not well understood. The study aimed to investigate the roles of CTGF and ILK in high glucose‐induced phenotypic alterations of podocytes and determine whether ILK signaling is downstream of CTGF. The epithelial marker of nephrin and the mesenchymal marker of desmin were investigated by real‐time RT‐PCR and Western blotting. The results demonstrated that podocytes displayed a spreading, arborized morphology in normal glucose, whereas they had a cobblestone morphology in high glucose conditions, accompanied by decreased nephrin expression and increased desmin expression, suggesting podocytes underwent EMT. In response to high glucose, CTGF and ILK expression in podocytes were increased in a dose‐ and time‐dependent manner, whereas the increase did not occur in the osmotic control. Furthermore, the inhibition of CTGF with anti‐CTGF antibody prevented the phenotypic transition, as demonstrated by the preservation of epithelial morphology, the suppression of high glucose‐induced desmin overexpression and the restoration of nephrin. Of note, the upregulation of ILK induced by high glucose was partially blocked by the inhibition of CTGF. In summary, these findings suggested that CTGF and ILK were involved in high glucose‐induced phenotypic alterations of podocytes. ILK acted as a downstream kinase of CTGF and high glucose‐induced ILK expression might occur through CTGF‐dependent and ‐independent pathways. J. Cell. Biochem. 113: 293–301, 2012. © 2011 Wiley Periodicals, Inc.
Down‐regulation of the cavin family proteins in breast cancer
Authors: Bai Lin , Deng Xiaoli , Li Qian , Wang Miao , An Wei , A Deli , Gao Zhuo , Xie Yuntao , Dai Yifan , Cong Yu‐Sheng
Published: September 2011

Caveolae are abundant membrane domain on the cell surface of many mammalian cell types and are implicated in a wide range of physiological processes. The caveolae structural protein caveolin‐1 is often mutated or deregulated in cancer, and cavin family protein serum deprivation response factor‐related gene product that binds to C‐kinase (SRBC) has been found to be epigenetically inactivated in lung, breast, and gastric cancer. Both caveolin‐1 and SRBC have been proposed to function as tumor suppressors. Polymerase 1 and transcript release factor (PTRF) is the essential component for caveolae formation. The regulation of PTRF expression in cancer has not been characterized. We report here that the cavin family protein PTRF, SRBC and serum deprivation response protein were down regulated in breast cancer cell lines and breast tumor tissue. We further show that down‐regulation of PTRF in breast cancer cells was associated with the promoter methylation. As caveolin‐1 and cavin family proteins are required for caveolae formation and function, the reported tumor suppression function of caveolin‐1 and SRBC may be due to the deregulation of caveolae and its down‐stream signaling. Thus, the caveolae is a potential therapeutic target and the expression of cavin family proteins could be a useful prognostic indicator of breast cancer progression. J. Cell. Biochem. 113: 322–328, 2012. © 2011 Wiley Periodicals, Inc.
Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts
Authors: Mendias Christopher L. , Gumucio Jonathan P. , Bakhurin Konstantin I. , Lynch Evan B. , Brooks Susan V.
Published: September 2011

Scleraxis is a basic helix–loop–helix transcription factor that plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. Mice with a targeted inactivation of scleraxis (Scx−/−) fail to properly form limb tendons, but the role that scleraxis has in regulating the growth and adaptation of tendons of adult organisms is unknown. To determine if scleraxis expression changes in response to a physiological growth stimulus to tendons, we subjected adult mice that express green fluorescent protein (GFP) under the control of the scleraxis promoter (ScxGFP) to a 6‐week‐treadmill training program designed to induce adaptive growth in Achilles tendons. Age matched sedentary ScxGFP mice were used as controls. Scleraxis expression was sparsely observed in the epitenon region of sedentary mice, but in response to treadmill training, scleraxis was robustly expressed in fibroblasts that appeared to be emerging from the epitenon and migrating into the superficial regions of tendon fascicles. Treadmill training also led to an increase in scleraxis, tenomodulin, and type I collagen gene expression as measured by qPCR. These results suggest that in addition to regulating the embryonic formation of limb tendons, scleraxis also appears to play an important role in the adaptation of adult tendons to physiological loading. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:606–612, 2012
Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament
Authors: Nishimori Makoto , Matsumoto Tomoyuki , Ota Shusuke , Kopf Sebastian , Mifune Yutaka , Harner Christopher , Ochi Mitsuo , Fu Freddie H. , Huard Johnny
Published: September 2011

We performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC‐VEGF), (2) soluble fms‐like tyrosine kinase‐1 (sFLT1, a VEGF‐specific antagonist) and nLacZ (MDSC‐sFLT1), and (3) nLacZ (MDSC‐nLacZ). After transecting the MCL of immunodeficient rats, 5 × 105 cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate‐buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and β‐galactosidase double positive cells in the rats transplanted with MDSC‐VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC‐VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC‐VEGF and MDSC‐nLacZ groups. On the other hand, the MDSC‐sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC‐sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:627–633, 2012
Lysine392, a K63‐linked ubiquitination site in NEMO, mediates inflammatory osteoclastogenesis and osteolysis
Authors: Alhawagri Muhammad , Yamanaka Yasuhiro , Ballard Dean , Oltz Eugene , Abu‐Amer Yousef
Published: September 2011

PMMA particles released from bone implants are considered major contributor to osteolysis and subsequent implant failure. Although the ensuing inflammatory response has been described, the mechanisms underlying PMMA particulate‐induced osteolysis remain enigmatic. In previous studies, we have established that activation of Nuclear factor kappa‐B (NF‐κB) and MAP kinase pathways plays a central role in the pathogenesis of inflammatory osteolysis. Specifically, we have shown that impeding IKK complex assembly, and thus subsequent NF‐κB activation, dampens particle‐induced osteolysis. The IKK complex consists of IKKα, IKKβ, and IKKγ, also known as NEMO. NEMO has no catalytic activity and serves as a scaffold protein facilitating assembly and distal activation of NF‐κB signaling. In fact, blocking binding of NEMO with IKKα/β abolishes NF‐κB activity. In the current study, we identify Lysine 392 residue in NEMO as crucial mediator of PMMA particle‐induced inflammatory osteoclastogenesis and osteolysis. Using mice in which NEMO‐K392R mutation has been introduced, we provide evidence that PMMA‐induced osteoclasts and osteolytic responses are impaired. Furthermore, we show that this impairment is likely due to poor activation of NF‐κB and Erk, but not other MAP kinases. Our findings suggest that NEMO Lysine392, a well‐established K63‐linked polyubiquitination site, is an important mediator of PMMA‐induced osteolysis. Therefore, this NEMO motif should be considered as a target to combat PMMA particle‐induced osteolysis. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:554–560, 2012