bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructure of mitosis and cytokinesis during spermatogenesis inPorphyra yezoensis(Bangiales, Rhodophyta)
Authors: Ueki Chika , Nagasato Chikako , Motomura Taizo , Saga Naotsune
Published: April 2009

We studied mitosis and cytokinesis during spermatogenesis in the red algaPorphyra yezoensisUeda using electron microscopy with the cryofixation-freeze-substitution technique and by fluorescence microscopy using tubulin immunofluorescence and SYBR Gold staining. Spermatogenesis occurred along the blade margin with a series of cell divisions. During interphase, two nucleus-associated organelles (NAOs) were located close to the nuclear envelope and had a ring-on-ring morphology. In prophase, the NAOs migrated to the future mitotic poles. The nuclear envelope of prometaphase nuclei became deeply depressed below each NAO, and the two rings of the NAOs appeared to separate until early telophase. The chromosomes became aligned at the equator in metaphase, although individual chromosomes and their kinetochores were not clearly defined. The two rings of the NAO moved next to each other on the nuclear envelope during mid-telophase, and then NAO replication occurred. In late telophase, the pair of NAOs repositioned on the nuclear envelope. Cytokinesis started with furrowing of the plasma membrane.
Algal cell biology and genomics
Authors: Heimann Kirsten , Katsaros Christos
Published: April 2009

No abstract available
Chapter 11-Bone Morphogenetic Protein (BMP) Implants as Bone Graft Substitutes-Promises and Challenges
Authors: Attawia M , Rosier R , Sampath TK , Reddi AH
Published: March 2009

BONE MORPHOGENETIC PROTEINS (BMPS) ARE GROWTH and differentiation factors originally isolated from bone matrix based on their ability to induce new bone formation in vivo, and form a large family of proteins structurally related to TGF-βs and activins. Recombinant human BMP, when implanted with an appropriate carrier matrix at defect sites, is capable of inducing new bone formation and restoring the lost bone by initiating a cellular process that mirrors embryonic bone formation. BMP containing osteogenic devices have been shown to be efficacious for the treatment of delayed and non-union fractures of long bone and anterior inter-body fusions of the spine and have been found to be equivalent to that of autograft in prospective, randomized, controlled and multicentered clinical trials. Recently, regulatory agencies in USA, Europe, Canada, and Australia have approved BMP-7 (OP-1™) and BMP-2 (InFuse™) containing osteogenic devices as bone graft substitutes for the treatment of long bone fractures and inter-body fusions in the spine. BMP is the first recombinant protein approved for orthopedic use and thus offers significant promise in the field of regenerative medicine.
The relationship between leptin, gonadotropic hormones, and body composition during puberty in a Dutch children cohort
Authors: Rutters F , Nieuwenhuizen A G , Verhoef S P M , Lemmens S G T , Vogels N , Westerterp-Plantenga M S
Published: March 2009

Objective

To investigate the relationship between leptin concentrations, gonadotropic hormone concentrations, and body composition during puberty in a Dutch children cohort.

Design

In a cohort of 98 children, we determined anthropometric measurements, body composition, and concentrations of leptin, FSH, and LH.

Results

Sex differences were observed from Tanner stage 1 onwards in weight, body fat percentage, and leptin/fat mass ratio. In boys and girls, the relationship between leptin concentrations and FM was weaker at Tanner stage 2 (R2=0.33 andR2=0.39;P<0.001), 3 (R2=0.27 andR2=0.36;P<0.002), and 4 (R2=0.21 andR2=0.28;P<0.03) than at Tanner stage 1 (R2=0.51 andR2=0.67;P<0.001) and 5 (R2=0.46 andR2=0.78;P<0.01). In girls, a peak in leptin concentrations (8.5±6.0 ng/ml) preceded a peak in LH and FSH concentrations (15.1±3.5 and 5.0±4.5 IU/l). A lead/lag relationship was observed of leptin at Tanner stage 1 to LH and FSH at Tanner stage 2 (R2=0.12,P<0.05 andR2=0.18,P<0.05). In boys, there was no peak in leptin, LH, and FSH; additionally, leptin at Tanner stage 3 was related FSH at Tanner stage 4 (R2=0.17,P<0.04).

Conclusion

In boys and girls during puberty, factors independent of fat mass become (transiently) more important in the regulation of plasma leptin concentrations. Moreover, in girls, leptin is suggested to act as a permissive factor for the onset of puberty, while, in boys, leptin has a different timing and possibly different function.
Regulation of cardiac fatty acids metabolism in transgenic mice overexpressing bovine GH
Authors: Bogazzi Fausto , Raggi Francesco , Ultimieri Federica , Russo Dania , D'Alessio Aldo , Manariti Antonella , Brogioni Sandra , Manetti Luca , Martino Enio
Published: April 2009

Cardiac energy metabolism depends mainly on fatty acid (FA) oxidation; however, regulation of FA metabolism in acromegalic (Acro) heart is unknown. The aim of the study was to evaluate cardiac expression of key proteins of FA metabolism in young and elder transgenic mice overexpressing bovine GH Acro. Expression of proteins regulating FA entry into the cells, their uptake by mitochondria and β-oxidation were evaluated by western blot, while FA content by Fourier transform infrared microspectrometry. Regulatory mechanisms of key steps of FA metabolism were also studied. The expression of plasma-membrane FA carriers (fatty acid-binding protein and fatty acid transport protein-1) and acylCoA synthetase was higher in young and lower in elder Acro than in corresponding controls; likewise, expression of cytoplasm to mitochondria-1 (CPT-1), the key enzyme of mitochondrial FA uptake, and that of medium-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, two regulatory β-oxidation dehydrogenases, followed a similar pattern. FA content was lower in young and higher in elder Acro than in wild-type, suggesting an increased utilisation in young animals. GH regulated expression of key proteins of FA metabolism through changes in peroxisome proliferator-activated receptor α (PPARα) expression, which varied accordingly. GH effect was confirmed by treatment of Acro mice with a receptor antagonist, which abolished changes in key proteins of FA metabolism in young Acro. GH increased phosphorylation of AMP-activated protein kinase and anti-acetyl-CoA-carboxylase, two regulatory kinases, leading to lower CPT-1 inhibition by malonyl-CoA, and intervened in regulating PPARα expression through the ERK 1/2 pathway. In conclusion, chronic GH excess increased FA metabolism in the young age, whereas its action was overwhelmed in elder ages likely by GH-independent mechanisms, leading to reduced expression of key enzyme of FA metabolism.
Magnesium‐Enriched Hydroxyapatite Versus Autologous Bone in Maxillary Sinus Grafting: Combining Histomorphometry With Osteoblast Gene Expression Profiles Ex Vivo
Authors: Crespi Roberto , Mariani Elisabetta , Benasciutti Elisa , Capparè Paolo , Cenci Simone , Gherlone Enrico
Published: March 2009

Background: Many biomaterials are proposed for sinus floor lifting and grafting in the posterior maxilla for insufficient bone volume (BV). The aim of this study was to compare the use of magnesium‐enriched hydroxyapatite (mHA) versus autogenous bone graft (AB) for maxillary sinus lift procedures by histomorphometric and ex vivo gene expression profiling.

Methods: Fifteen patients requiring bilateral maxillary sinus augmentation received autologous bone particles (group A) and mHA (group B) (split‐mouth design). Five months later, implants were placed, and biopsies were obtained. Bone specimens were analyzed by histomorphometry, BV and vital bone (VB) percentages were calculated, and ex vivo osteoblast expansion followed by highly sensitive osteoblast specific gene expression profiling for cbfa1, osteocalcin, osteopontin, collagen type I, receptor activator of nuclear factor‐kappa B ligand (RANKL), and osteoprotegerin (OPG) by quantitative real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) were performed. Comparisons were made using the Student t test.

Results: After healing with no complications, BV was comparable in the two groups (80.79% ± 14.27% for autologous versus 76.72% ± 11.47% for mHA; P = not statistically significant), but VB was lower in the mHA group (29.65% ± 9.81% versus 78.40% ± 16.72%; P <0.05). Real‐time RT‐PCR analyses showed significantly higher expression of the osteoblast differentiation factor Cbfa1 and the matrix formation marker osteocalcin in the mHA group compared to the AB group, whereas type I collagen was comparable, and osteopontin was decreased. Attesting to a lower osteoclastogenic potential, the RANKL/OPG ratio was diminished.

Conclusions: Autogenous bone samples provided higher vital over comparable total bone levels than mHA‐grafted sites. Osteoblast gene expression profiles from mHA grafts revealed higher expression of certain specific markers of osteoblast differentiation and bone formation, associated with a lower osteoclastogenic potential.
Implant Compression Necrosis: Current Understanding and Case Report
Authors: Bashutski Jill D. , D'Silva Nisha J. , Wang Hom‐Lay
Published: March 2009

Background: Implants fail for a variety of reasons; it can be difficult to determine the exact cause of failure, especially if there are multiple contributing factors. Overcompression of the adjacent bone during implant placement is a potential contributing factor to implant failure that is not well documented in the literature.

Methods: This case report reviews the concept of bone loss induced by overcompression and presents a case of implant failure with overcompression as a potential etiology. Histology, radiographs, and clinical data are presented that document the failure of four implants placed in the posterior mandible of a 48‐year‐old female patient.

Results: After uneventful implant placement, one implant exfoliated 3 weeks postoperatively. The other three implants were removed because of severe bone loss up to 2 months later. Histology of the area revealed non‐viable bony sequestra with bacterial colonization.

Conclusions: This case highlights unusual implant failures that likely occurred as a result of overcompression of the bone during placement. Areas involving dense bone seem to be at increased risk for compression necrosis.
Planning, Execution and Verification of a Coiled Tubing Gravel Pack Job in the Statfjord Field
Authors: Sehnal Zdenek , Østvang Knut , Hermansson Lasse , Sanders Mike , de Haas Arie-Jan
Published: April 2009

This paper describes the initial planning and pre-job laboratory testing for a gravel pack operation using coiled tubing in the Statfjord Field. The paper also describes the execution of the operations and methods involved.

Potential problems related to the placement of the gravel were identified in pre-job meetings and were verified through a comprehensive test programme. A well specific cased hole completion was modelled using an acrylic gravel pack simulator, and a number of tests were performed to determine the optimum solution for gravel concentration, brine viscosity, viscosifier and slurry placement rate. The tests were utilised as an aid in designing the actual gravel placement operation.

The gravel packing operation was conducted using small batches of slurry consisting of a non-viscosified brine carrier fluid along with a low gravel concentration. Two separate radioactive tracers were injected into the slurry to give better resolution of the gravel pack logs. The operation and completion technique is reviewed and verified by extensive post completion analysis. This includes calculated sand height verified by gravel pack placement logs.

Initial gravel pack productivity is comparable to conventionally gravel packed wells.
FEM Simulations and Experiments of Different Loading Conditions for a 12 kW Direct Driven PM Synchronous Generator for Wind Power
Authors: Eriksson Sandra , Bernhoff Hans , Leijon Mats
Published: March 2009

Results from experiments on a direct driven permanent magnet synchronous generator are presented. Dynamic simulations have been performed using the finite element method in order to study the generator. The simulations are performed by using an electromagnetic model, which is described by a combined field and circuit equation model and is solved in a finite element environment. The stator winding of the generator consists of circular cables and the rotor has surface-mounted, arched, permanent magnets. A complete experimental setup has been used consisting of a motor, a frequency converter, a gearbox and electrical loads. The generator is connected to a purely resistive load. Measurements have been performed for different rotational speeds and different loads. Furthermore, the generator has been studied for the realistic wind turbine loading conditions for operation at the optimum tip speed ratio. The variable speed operation in a wind turbine is evaluated and discussed. The agreement between experimental results and simulations based on finite element calculations is high, indicating precise simulations. The measurement errors are calculated and discussed. Furthermore, other sources of error are suggested and discussed that could explain the differences between the simulations and the measured data.
Discriminating Structural Characteristics of Starch Extrudates through X-ray Micro-tomography using a 3-D Watershed Algorithm
Authors: Plews Andrew G , Atkinson Alan , McGrane Scott
Published: April 2009

X-ray micro-tomography (XMT) was used to characterise the pore structure of two open-cell biopolymer foams (starch extrudates). A three-dimensional watershed algorithm was applied to XMT images to segment pore structure. Distributions of pore sizes and interconnecting pore aperture sizes were determined and pore geometry was visualised. The technique was used to analyse samples having an inhomogeneous porosity distribution. Results were not sensitive to threshold values set during image analysis. Pore size and pore aperture distributions were extracted. Pore size was based on volume fraction, aperture size was based on area fraction and both on number frequency. Volume fraction of porosity was calculated from image analysis and compared with that deduced from density measurements. The value from image analysis was sensitive to the set threshold contrast. Average cell wall thickness was calculated from two-dimensional image analysis. This shows that XMT, with appropriate data processing, is a powerful method for structural characterisation of starch extrudates.
Stochastic Controllability of Systems with Multiple Delays in Control
Authors: Klamka Jerzy
Published: April 2009

Stochastic Controllability of Systems with Multiple Delays in Control

Finite-dimensional stationary dynamic control systems described by linear stochastic ordinary differential state equations with multiple point delays in control are considered. Using the notation, theorems and methods used for deterministic controllability problems for linear dynamic systems with delays in control as well as necessary and sufficient conditions for various kinds of stochastic relative controllability in a given time interval are formulated and proved. It will be proved that, under suitable assumptions, relative controllability of an associated deterministic linear dynamic system is equivalent to stochastic relative exact controllability and stochastic relative approximate controllability of the original linear stochastic dynamic system. As a special case, relative stochastic controllability of dynamic systems with a single point delay is also considered. Some remarks and comments on the existing results for stochastic controllability of linear dynamic systems are also presented.
Dynamic External Force Feedback Loop Control of a Robot Manipulator Using a Neural Compensator—Application to the Trajectory Following in an Unknown Environment
Authors: Ferguene Farid , Toumi Redouane
Published: April 2009

Dynamic External Force Feedback Loop Control of a Robot Manipulator Using a Neural Compensator—Application to the Trajectory Following in an Unknown Environment

Force/position control strategies provide an effective framework to deal with tasks involving interaction with the environment. One of these strategies proposed in the literature is external force feedback loop control. It fully employs the available sensor measurements by operating the control action in a full dimensional space without using selection matrices. The performance of this control strategy is affected by uncertainties in both the robot dynamic model and environment stiffness. The purpose of this paper is to improve controller robustness by applying a neural network technique in order to compensate the effect of uncertainties in the robot model. We show that this control strategy is robust with respect to payload uncertainties, position and environment stiffness, and dry and viscous friction. Simulation results for a three degrees-of-freedom manipulator and various types of environments and trajectories show the effectiveness of the suggested approach compared with classical external force feedback loop structures.
The distribution of green algae species from the Ulva genera (syn. Enteromorpha; Chlorophyta) in Polish inland waters
Authors: Messyasz Beata , Rybak Andrzej
Published: April 2009

Marine algae in inland waters in Poland have been rarely recorded. The distribution of 5 species and 1 subspecies of the Ulva genus (syn. Enteromorpha, Chlorophyta) observed in different inland aquatic ecosystems is reported. The algal distribution was established on the basis of the available literature, unpublished material, and oral reports. Information about the algal morphology and habitat conditions, from all of the 58 reported locations of ulvas in Poland, were assimilated and are presented here.

The most widespread species of Ulva in inland waters in Poland was U. intestinalis (syn. Enteromorpha intestinalis) reported at 34 sites, while the rarest species was U. paradoxa (syn. Enteromorpha paradoxa), recorded at 2 sites.

Species of Ulva have been reported at a range of inland aquatic ecosystems, but most commonly in lakes and small water-courses, such as ditches, channels and creeks. Most of the reported sites of penetration of Ulva (Enteromorpha) inland are concentrated in northwestern and central Poland.
Use of the preliminary Jedlice Reservoir for water protection in the Turawa Reservoir on the Mała Panew River
Authors: Wiatkowski Mirosław , Czerniawska-Kusza Izabela
Published: April 2009

Physico-chemical variables of water quality and benthic community structure were assessed in order to evaluate the need for reinstating the use of the preliminary Jedlice Reservoir. The waters of the Mała Panew River carry a significant load of nutrient compounds, particularly nitrates and phosphates. Deteriorating water quality results in permanent algal blooms and changes in the macrofauna structure. It was confirmed that the use of a preliminary reservoir could contribute to the protection of the Turawa Dam Reservoir against pollutants transported by the waters of the Mała Panew River.
Optimised Routines for Monitoring of Treated Late Latent Syphilis Patients
Authors: Ozoliņš Dzintars , Hartmane Ilona , Mikažāns Ingmārs , Paegle Daina , Ančupāne Ināra , Žileviča Aija
Published: April 2009

Optimised Routines for Monitoring of Treated Late Latent Syphilis Patients

Highly sensitive and specific tests are needed in monitoring of the serological activity and efficacy of treatment of late latent syphilis. In a retrospective study, the data of 52 patients who had received treatment for late latent syphilis were analysed in the Clinical Centre of Skin and Sexually Transmitted Diseases, Latvia. The diagnostic sensitivity and specificity was calculated by Syphilis Immunoblot IgG, Treponema Pallidum Immobilisation Reaction (TPIR) and Syphilis Express Diagnosis (SED). The correlation between Treponema Pallidum Immobilisation Reaction (TPIR) and Syphilis Immunoblot IgG, SED and TPIR results were estimated. Syphilis Immunoblot IgG is useful for latent syphilis diagnostics. The values of the synthetic peptide TmpA, TmpN15 and TmpN47 on the Syphilis Immunoblot IgG strip are useful for monitoring of the treatment of late latent syphilis patients.
Cross-Species Applicability of Microsatellite Markers for Investigation of Sea Ducks (Mergini) Genetic Differentiation
Authors: Sruoga Aniolas , Slavėnaitė Sigita , Butkauskas Dalius , Gražulevičius Gediminas
Published: April 2009

Cross-Species Applicability of Microsatellite Markers for Investigation of Sea Ducks (Mergini) Genetic Differentiation

Genetic studies of waterfowl have provided insufficient information on the evolutionary history of the sea duck tribe (Mergini, Anseriformes), as highly variable molecular markers have not been identified. Cross-species applicability of microsatellites has been shown for several bird families. Therefore, the objective of our work was to examine whether specific primers used previously for Anatidae, Phasianidae and Laridae taxons could amplify microsatellite loci of sea duck species: Long-tailed duck (Clangula hyemalis), Goosander (Mergus merganser) and Velvet Scoter (Melanitta fusca). Tissue samples were collected and DNA was extracted by rapid salt extraction method. Amplification of DNA fragments was carried out using specific microsatellite primers of APH21, Aalmu1, Sfimu4, Sfimu5 (Anatidae), ADL209, ADL115 (Phasianidae) and K71, RGB28 (Laridae). Four primer pairs (APH21, Aalmu1, K71, and nSfimu4) were suitable for investigation of interspecies genetic variability among Long-tailed duck and Velvet Scoter. Intraspecies specificity has been detected for primer pair ADL 209 in all three duck species. The primer pair APH21 was selected as most promising for investigation of intraspecies variability of Long-tailed duck and Velvet Scoter.
Understanding and treating moyamoya disease in children
Authors: Smith Jodi L.
Published: March 2009

Moyamoya disease, a known cause of pediatric stroke, is an unremitting cerebrovascular occlusive disorder of unknown etiology that can lead to devastating, permanent neurological disability if left untreated. It is characterized by progressive stenosis of the intracranial internal carotid arteries and their distal branches and the nearly simultaneous appearance of basal arterial collateral vessels that vascularize hypoperfused brain distal to the occluded vessels. Moyamoya disease may be idiopathic or may occur in association with other syndromes. Most children with moyamoya disease present with recurrent transient ischemic attacks or strokes. Although there is no definitive medical treatment, numerous direct and indirect revascularization procedures have been used to improve the compromised cerebral circulation, with outcomes varying according to procedure type. Such techniques improve the long-term outcome of patients with both idiopathic and syndrome-associated moyamoya disease. This review provides a comprehensive discussion of moyamoya disease in children, with an emphasis on the most effective surgical treatment options.
Cerebral hemodynamics as a predictor of stroke in adult patients with moyamoya disease: a prospective observational study
Authors: Zipfel Gregory J. , Sagar James , Miller J. Phillip , Videen Tom O. , Grubb Robert L. , Dacey Ralph G. , Derdeyn Colin P.
Published: March 2009

Moyamoya disease is an obliterative vasculopathy of the large arteries at the base of the brain. In the US, it most commonly affects women in their 3rd and 4th decades of life, frequently causing ischemic stroke. The natural history of this disorder is not well described. It is very likely that hemodynamic factors play an important role in the risk of future stroke, as has been established in atherosclerotic carotid occlusive disease.

The authors describe an ongoing, prospective observational study designed to test the hypothesis that increased oxygen extraction in the cerebral hemisphere beyond the occlusive lesion is a predictor of subsequent risk of ipsilateral stroke in medically treated patients with moyamoya phenomenon. On enrollment, all patients undergo regional measurements of cerebral oxygen extraction fraction (OEF) with PET. Information on baseline clinical, laboratory, epidemiological, and angiographic risk factors are obtained at the time of the PET study. Decisions regarding surgery are made by the treating physicians based on clinical information while being blinded to PET data. Patients undergo follow-up at 6-month intervals to determine the subsequent risk of ipsilateral stroke. All patients will return at 1 and 3 years for repeat PET studies. Secondary, exploratory, aims of this longitudinal and blinded study are to determine other predictive factors for stroke in this population; to determine preliminary estimates of the effects of different medical treatment regimens in this population; to determine the temporal changes in hemodynamic impairment in medically treated patients; to determine the effects of surgery on hemodynamic impairment in the subset of patients who undergo surgical revascularization; and to obtain estimates of surgical complication rates for patients with and without hemodynamic impairment.
Pial synangiosis in patients with moyamoya syndrome and sickle cell anemia: perioperative management and surgical outcome
Authors: Smith Edward R. , McClain Craig D. , Heeney Matthew , Scott R. Michael
Published: March 2009

Object

Many children with sickle cell anemia (SCA) also have clinical and radiographic findings of an arteriopathy suggestive of moyamoya syndrome. These patients may continue to experience strokes despite optimal medical management. The authors wished to define features of moyamoya syndrome associated with SCA and determine the results of surgical revascularization in these patients at early and late follow-up.

Methods

The authors reviewed the clinical and radiographic records of all patients with moyamoya syndrome and SCA who underwent cerebral revascularization surgery using a standardized surgical procedure—pial synangiosis—from 1985 to 2008.

Results

Twelve patients had SCA and moyamoya syndrome. Six patients were female and 6 were male. The average patient age at surgery was 11.3 years (range 3–22 years). All patients presented with ischemic symptoms, 11 (92%) with previous transient ischemic attacks, and 10 (83%) with completed strokes. Eleven patients (92%) had radiographic evidence of previous stroke at presentation. None presented with hemorrhage. Surgical treatment included pial synangiosis in all patients. Complications included 1 perioperative stroke, 1 wound infection, and 1 perioperative pneumonia. The average length of hospital stay was 5.7 days (including a 24-hour preoperative admission for hydration) and average blood loss was 92.5 ml/hemisphere (in a total of 19 hemispheres). Clinical and radiographic follow-up with an average of 49 months (range 9–144 months) demonstrated no worsening in neurological status in any patient. No clinical or radiographic evidence of new infarcts was observed in any patient at late follow-up, despite disease progression in 13 (68%) of 19 hemispheres.

Conclusions

The clinical and radiographic features of moyamoya syndrome associated with SCA appear comparable to primary moyamoya disease. Successful treatment of these patients requires multidisciplinary care involving hematologists, anesthesiologists, and neurosurgeons. Operative treatment of moyamoya syndrome using pial synangiosis appears to be safe and confers long-lasting protection against further stroke in this population, and provides an alternative for failure of optimal medical therapy in patients. This study underscores the potential merit of screening patients with SCA for moyamoya syndrome.
Introduction: Moyamoya Disease
Authors: Scott R. Michael , Smith Edward R.
Published: March 2009

This issue of Neurosurgical Focus is devoted to the topic of moyamoya disease/syndrome. When the senior editor (R.M.S.) was a neurosurgical resident in the late 1960s and early 1970s, the condition was virtually unknown in the Western hemisphere, and patients with “cerebrovascular insufficiency” and the typical arterial findings on angiography were believed to have a type of arteritis. The refinement of catheter angiography techniques and the development of the imaging modalities of CT and MR imaging clarified the significance of making the correct diagnosis of moyamoya disease in affected patients, and with the development of direct and then indirect revascularization procedures during this same period, neurosurgeons became involved in the disease's treatment.
Resumed Publication of Pharmaceuticals in 2009
Authors: Lin Shu-Kun , McPhee Derek
Published: March 2009

After a five year hiatus, we are pleased to announce the resumption of publication of the MDPI journal Pharmaceuticals (ISSN 1424-8247). First launched in 2004, few suitable papers were submitted and only one was published [1], before our limited editorial resources at the time led us to temporarily discontinue publication. Several things have changed since then. First, there has been an explosive growth in the number of manuscripts submitted and published in MDPI’s various current journals [2], whose topics clearly fall within the intended scope of Pharmaceuticals and we feel that these manuscripts merit a dedicated forum. Second, the expansion of MDPI, now with Editorial Offices and staff in Basel (Switzerland) and Beijing (China), allows us to provide Pharmaceuticals’ authors with all the services they could desire and deserve: a simple manuscript submission process, rigorous peer review, quick revision turnaround, Open Access publication on a new and attractive platform and coverage by all the major abstracting services. In addition, a new Editorial Board comprised of noted academic and industry scientists has been set up for Pharmaceuticals. Finally, to better focus the subject matter published in Pharmaceuticals on molecular medicines, we have also set up a special section in International Journal of Molecular Sciences (IJMS, ISSN 1422-0067) for papers on nutraceuticals or chemopreventives. We look forward to receiving and publishing your papers and as always, we welcome your comments and suggestions. [...]
Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis
Authors: MOURÃO ANA FILIPA , CAETANO-LOPES JOANA , COSTA PAULA , CANHÃO HELENA , SANTOS MARIA JOSÉ , PINTO PATRÍCIA , BRITO IVA , NICOLA PAULO , CAVALEIRO JOÃO , TELES JOSÉ , SOUSA ARTUR , GOMES JOSÉ MELO , BRANCO JAIME , da COSTA JOSÉ TEIXEIRA , PEDRO JOÃO GOMES , de QUEIROZ MÁRIO VIANA , FONSECA JOÃO EURICO
Published: April 2009

Objective.

Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.

Methods.

Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.

Results.

One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.

Conclusion.

TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.
CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis
Authors: SAITO AKIKO , MURO YOSHINAO , SUGIURA KAZUMITSU , IKENO MASASHI , YODA KINYA , TOMITA YASUSHI
Published: April 2009

Objective.

CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases.

Methods.

Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens.

Results.

Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O.

Conclusion.

CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is an ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity.
Safety and Efficacy of the Selective Costimulation Modulator Abatacept in Patients with Rheumatoid Arthritis Receiving Background Methotrexate: A 5-year Extended Phase IIB Study
Authors: WESTHOVENS RENE , KREMER JOEL M. , MORELAND LARRY W. , EMERY PAUL , RUSSELL ANTHONY S. , LI TRACY , ARANDA RICHARD , BECKER JEAN-CLAUDE , QI KEQIN , DOUGADOS MAXIME
Published: April 2009

Objective.

To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis.

Methods.

Patients were randomized to abatacept 10 or 2 mg/kg or placebo, plus MTX. Patients completing the 1-year, double-blind period entered the longterm extension, where all patients received a fixed dose of abatacept ~10 mg/kg. We describe safety analyses for all patients who received at least 1 dose of abatacept and efficacy analyses for the original ~10 mg/kg abatacept-treated group, over 5 years.

Results.

Of the 235 abatacept- or placebo-treated patients completing the double-blind period, 219 entered the longterm extension; 130 (59.4%) were continuing at Year 5. No unexpected safety events were observed during the longterm extension compared with the double-blind period. Incidence rates of adverse events (AE) and serious AE were 489.7 and 20.0/100 patient-years in Year 1 versus 374.9 and 18.9/100 patient-years in the cumulative period, respectively. Using exploratory analyses, improvements observed at Year 1 in the 10 mg/kg group were maintained at Year 5, as assessed by ACR responses (ACR20 = 77.1% vs 82.7%; ACR50 = 53.0% vs 65.4%; ACR70 = 28.9% vs 40.4% at Years 1 and 5, respectively) and disease activity (Low Disease Activity State = 48.2% vs 58.5%; Disease Activity Score-28-defined remission = 25.3% vs 45.3% at Years 1 and 5, respectively).

Conclusion.

Abatacept maintained the efficacy observed at Year 1 over 5 years of treatment, and demonstrated consistent safety and tolerability. These data, along with relatively high retention rates, support the longterm clinical benefit provided by selective T cell costimulation modulation. Clinical trial registry: ClinicalTrials.gov; clinical trial registration number: NCT00254293.
Ethnic Influence on Disease Manifestations and Autoantibodies in Chinese-Descent Patients with Systemic Sclerosis
Authors: LOW ANDREA H.L. , JOHNSON SINDHU R. , LEE PETER
Published: April 2009

Objective.

To investigate ethnic influence on disease manifestations and autoantibody profile in patients of Chinese descent with systemic sclerosis (SSc).

Methods.

In a retrospective study of a multiethnic SSc cohort followed over a 17-year period, disease manifestations and autoantibody profile of patients of European and Chinese descent were compared.

Results.

There were 300 patients of European descent and 36 of Chinese descent, with similar proportions of women (81% and 72%, respectively) and patients with diffuse SSc (50% and 56%). Patients of Chinese descent [mean age ± standard deviation (SD) 52 ± 16 yrs; p = 0.05] were diagnosed at an older age compared to patients of European descent (mean ± SD 46 ± 12 yrs). Patients of Chinese descent compared to those of European descent had less frequent joint (69% vs 86%; p = 0.01) and gastrointestinal involvement (78% vs 94%; p = 0.004), but increased prevalence of myositis (17% vs 5%; p = 0.01). Patients of Chinese descent had less frequent digital ulceration (36% vs 55%; p = 0.04), and an absence of renal crisis. The frequency of cardiac and pulmonary involvement was similar in both groups. More patients of Chinese than of European descent were positive for anti-topoisomerase-I (47% vs 27%; p = 0.02), anti-Ro (36% vs 10%; p = 0.001), and anti-U1RNP (17% vs 5%; p = 0.03) antibodies. The observed differences for anti-topoisomerase-I, anti-Ro, and joint and gastrointestinal manifestations persisted in the subgroup analysis of patients matched for sex, disease subtype, and age at diagnosis.

Conclusion.

Patients of Chinese descent have milder SSc disease with less frequent joint and gastrointestinal manifestations, less severe vasculopathy, but increased prevalence of myositis and certain autoantibodies. Research is needed to identify determinants (genetic, environmental, and cultural factors) of the relationship between ethnicity and disease.
Correlation of Biomarkers of Endothelium Dysfunction and Matrix Remodeling in Patients with Systemic Sclerosis
Authors: BLAISE SOPHIE , MAAS RENKE , TROCME CANDICE , KOM GHAINSOM D. , ROUSTIT MATTHIEU , CARPENTIER PATRICK H. , CRACOWSKI JEAN-LUC
Published: March 2009

Objective.

Systemic sclerosis (SSc) is a multisystem disease characterized by microvascular dysfunction and excessive fibrosis. However, the relationship between these 2 features remains unclear. Endothelial dysfunction can be assessed by quantifying plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase. Matrix remodeling can be assessed by quantifying serum tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Both biomarkers are elevated in patients with SSc. Our objective was to test whether plasma ADMA is correlated with serum TIMP-1.

Methods.

We enrolled 91 subjects, 39 patients with SSc, 28 patients with primary Raynaud’s phenomenon (RP), and 24 healthy volunteers. Plasma ADMA concentrations were measured by liquid chromatography-tandem mass spectrometry. Serum TIMP-1 concentrations were determined by ELISA.

Results.

Mean ADMA concentrations were higher in patients with SSc (0.68 μM ± 0.12) than in patients with primary RP or healthy volunteers (respectively, 0.56 μM ± 0.14 and 0.62 μM ± 0.12; p = 0.002). Median serum TIMP-1 concentrations were increased in patients with SSc compared to primary RP and healthy volunteers [12 (9–15), 11 (8–13), and 10 (7–13) nM, respectively; p = 0.05]. In the SSc group, we observed a statistically significant correlation between plasma ADMA and serum TIMP-1 (r = 0.34, p = 0.035).

Conclusion.

These data are consistent with our hypothesis of an association of endothelial dysfunction and matrix remodeling in scleroderma spectrum disorders.
Femmes et immigrées : corvéables à merci
Authors: Puech Isabelle
Published: March 2009

Résumé Dans le secteur des services, des milliers de femmes connaissent des formes d’exploitation salariale diffuses, peu visibles, socialement tolérées. Cet article propose de mettre en lumière un mode de gestion de la main-d’œuvre non qualifiée qui, sous couvert de flexibilité et de compression maximale des coûts, utilise les femmes les plus vulnérables sur le marché du travail – en particulier les femmes immigrées – comme variable d’ajustement. À partir d’une enquête de terrain menée auprès d’une population de femmes de chambre, l’article s’attachera à mettre au jour une face cachée des emplois précaires. Des emplois souvent à durée indéterminée qui ne protègent pas des conditions de travail pénibles, des temps de travail à rallonge, des salaires au rabais et des pratiques patronales frauduleuses.
El Primer Congreso de la Cultura del Olivo
Authors: Criado Costa Joaquín
Published: March 2009

Se estudia la convocatoria, organización y desarrollo del Primer Congreso de la Cultura del Olivo como actividad conjunta de la CECEL, el Instituto de Estudios Jiennenses, el Instituto de Estudios Manchegos y la Real Academia de Ciencias, Bellas Letras y Nobles Artes de Córdoba, con el patrocinio de la Diputación Provincial de Jaén.
Relación de las publicaciones periódicas de los Centros que integran la CECEL
Authors: De Salazar y Acha Eduardo
Published: March 2009

Se relacionan las revistas editadas por los Centros de la CECEL ordenadas por autonomías y provincias. Se suministran los datos de sus ISSN’s, Periodicidad y fecha de inicio de cada publicación.
Industrializar
Authors: Pérez Arroyo S.
Published: April 2009

En este artículo se buscan, en la España actual, diferentes maneras de industrializar la construcción. Centrándose principalmente en el sistema de construcción de viviendas y analizando el poco éxito de las experiencias anteriores, se explican los beneficios económicos y sociales relacionados con un nuevo objetivo político dirigido hacia la industrialización. El autor cree que la industrialización es la única manera de luchar contra la crisis económica y contribuir a la sostenibilidad. El futuro equilibrio entre las necesidades sociales y de mercado debe ser construido a través de la nueva industria de la construcción.
Proyecto de investigación INVISO: industrialización de viviendas sostenibles
Authors: Queipo J. , Navarro J. M. , Izquierdo M. , Del Águila A. , Guinea D. , Villamor M. , Vega S. , Neila J.
Published: April 2009

El proyecto singular y estratégico INVISO (Industrialización de viviendas sostenibles), que comenzó en el año 2006, pretende optimizar la producción de viviendas por medio de la industrialización de los procesos constructivos, generando el diseño de nuevos materiales y sistemas y elaborando herramientas de diseño y gestión que faciliten este proceso.
A Ditopic Ion‐Pair Receptor Based on Stacked Nucleobase Quartets
Authors: van der Wijst Tushar , Fonseca Guerra Célia , Swart Marcel , Bickelhaupt F. Matthias , Lippert Bernhard
Published: March 2009

Reichen Sie bitte das Salz!Die Ergebnisse hochleistungsfähiger Rechnungen sprechen dafür, dass der Stapelkomplex aus einem Guanin‐ und einem Adeninquartett (G4A4) in wässriger Lösung als wirksamer ditoper Rezeptor für NaCl fungieren kann (siehe Bild; Na+, Cl− gelb, O rot, N blau, C schwarz, H weiß).

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High‐density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
Authors: Namjou Bahram , Sestak Andrea L. , Armstrong Don L. , Zidovetzki Raphael , Kelly Jennifer A. , Jacob Noam , Ciobanu Voicu , Kaufman Kenneth M. , Ojwang Joshua O. , Ziegler Julie , Quismorio Francesco P. , Reiff Andreas , Myones Barry L. , Guthridge Joel M. , Nath Swapan K. , Bruner Gail R. , Mehrian‐Shai Ruth , Silverman Earl , Klein‐Gitelman Marisa , McCurdy Deborah , Wagner‐Weiner Linda , Nocton James J. , Putterman Chaim , Bae Sang‐Cheol , Kim Yun Jung , Petri Michelle , Reveille John D. , Vyse Timothy J. , Gilkeson Gary S. , Kamen Diane L. , Alarcón‐Riquelme Marta E. , Gaffney Patrick M. , Moser Kathy L. , Merrill Joan T. , Scofield R. Hal , James Judith A. , Langefeld Carl D. , Harley John B. , Jacob Chaim O.
Published: March 2009

Objective

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT‐1 and STAT‐4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility.

Methods

Fifty‐six single‐nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population‐based case–control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated.

Results

We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 × 10−25). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4.

Conclusion

Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
On a new goodness‐of‐fit process for families of copulas
Authors: Mesfioui Mhamed , Quessy Jean‐François , Toupin Marie‐Hélène
Published: March 2009

A goodness‐of‐fit procedure is proposed for parametric families of copulas. The new test statistics are functionals of an empirical process based on the theoretical and sample versions of Spearman's dependence function. Conditions under which this empirical process converges weakly are seen to hold for many families including the Gaussian, Frank, and generalized Farlie–Gumbel–Morgenstern systems of distributions, as well as the models with singular components described by Durante [Durante (2007) Comptes Rendus Mathématique. Académie des Sciences. Paris, 344, 195–198]. Thanks to a parametric bootstrap method that allows to compute valid P‐values, it is shown empirically that tests based on Cramér–von Mises distances keep their size under the null hypothesis. Simulations attesting the power of the newly proposed tests, comparisons with competing procedures and complete analyses of real hydrological and financial data sets are presented. The Canadian Journal of Statistics 37: 80‐101; 2009 © 2009 Statistical Society of Canada
CD4+ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis
Authors: Zhang Sheng , Bernard Dannie , Khan Waliul I. , Kaplan Mark H. , Bramson Jonathan L. , Wan Yonghong
Published: March 2009

Previous reports have suggested that autoimmune sequelae may be an unavoidable consequence of successful immunization against tumor‐associated antigens, which are typically non‐mutated self‐antigens. Using a melanoma model, we demonstrated that CD4+ T‐cell‐mediated anti‐tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis. Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti‐tumor immunity is mediated via a STAT6 and IL‐4‐dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN‐γ. Our results offer a possibility to elicit specific anti‐tumor responses without triggering unwanted tissue autoimmune diseases.