bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemokine gene activation in human bone marrow‐derived osteoblasts following exposure to particulate wear debris
Authors: Fritz Elizabeth A. , Glant Tibor T. , Vermes Csaba , Jacobs Joshua J. , Roebuck Kenneth A.
Published: January 2006

Particulate wear debris induces the expression of pro‐inflammatory cytokine and chemokine genes in various cell types of the periprosthetic region. We have previously reported that titanium particles stimulate the selective induction of interleukin‐8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) chemokines in human osteoblast‐like osteosarcoma cells. In this study, we characterize the human bone marrow‐derived osteoblast chemokine response to titanium particles. We demonstrate that titanium particles result in enhanced IL‐8 and MCP‐1 protein secretion as well as differential chemokine gene activation. Osteoblast chemokine expression was regulated at the level of gene transcription, with a time‐dependent induction of NF‐κB activation. Inhibition studies with N‐acetyl‐L‐cysteine (Nac) and MG‐132 suggest that titanium particle activation of NF‐κB activity and IL‐8 chemokine exression involves oxidant signaling and IκBα‐proteasomal degradation. Activation of the NF‐κB transcription factor, as well as the IL‐8 gene, are redox‐regulated. We also demonstrate that while cytochalasin D, a potent inhibitor of phagocytosis, suppressed the titanium particle effect on IL‐8 protein release in human bone marrow‐derived osteoblasts, the inhibitor had no effect on IL‐8 expression in MG‐63 osteoblast‐like cells. Collectively, these results provide insight into the potential mechanisms responsible for the particulate activation of osteoblast chemokine expression and suggest an important role for the osteoblast in the pathogenesis of periprosthetic osteolysis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effect of degradation rates of resorbable phosphate invert glasses on in vitro osteoblast proliferation
Authors: Brauer Delia S. , Rüssel Christian , Li Wu , Habelitz Stefan
Published: January 2006

Four resorbable phosphate invert glasses for use as bone replacement were synthesized in the system P2O5CaOMgONa2O. TiO2 and SiO2 were added at concentrations of 1 and 5.5 mol % to control solubility and crystallization. Both bulk glasses and samples with an open porosity of 65% and pore sizes of 150 to 400 μm were produced using a salt sintering process. Addition of TiO2 decreased the solubility in water and simulated body fluid, while the glass with addition of SiO2 showed a higher dissolution rate than did the original glass. The hypothesis that dissolution rates of the glasses will affect cell proliferation of osteoblastlike cells was tested using a MC3T3‐E1.4 murine preosteoblast cell line. Cells were cultured on nonporous polished and porous glasses with tissue culture polystyrene (TCPS) as control. Cell proliferation was studied over 24 and 72 h in culture. Cells proliferated on all polished glasses, but proliferation on porous glasses showed variations with glass composition. Cell proliferation increased with decreased solubility of the glass. It is suggested that resorbable implant materials require the adjustment of dissolution rate so as to facilitate cell adhesion and proliferation and thus a gradual transition from artificial implant to new bone structure. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Fabrication of microporous polyurethane by spray phase inversion method as small diameter vascular grafts material
Authors: Khorasani M.T. , Shorgashti S.
Published: January 2006

Microporous polyurethane vascular prostheses with a 4 mm diameter and 0.3–0.4 mm wall thickness were fabricated by a spray phase inversion technique. In this study, the effect of distance between spray guns (SG) and rotating mandrel (RM), the effect of rate of rotating mandrel (RRM), and the type of nonsolvent on pore morphology of PU films were evaluated using scanning electron microscopy (SEM) technique. It was observed that when the distance between SG and RM was increased or the rate of RM was decreased, the porosity of PU films increased and consequently the tensile strength decreased and compliance value increased. Compliance was measured in vitro by volume and vessel diameter changes. Furthermore, when the coagulant (water) was changed to the water/methanol, the porosity of PU film increased and porous morphology changed to filamentous morphology. Attachment of anchorage dependent cells, namely L929 fibroblast cells, were investigated in stationary culture conditions. The cells adhesion and cells growth were studied using optical photomicrographs. The results show that by increasing the porosity content of PU films would consequently increase the cell ingrowths. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Physicochemical properties of TTCP/DCPA system cement formed in physiological saline solution and its cytotoxicity
Authors: Dagang Guo , Kewei Xu , Haoliang Sun , Yong Han
Published: January 2006

In this paper, the physicochemical properties and cytotoxicity of calcium phosphate cement (CPC), prepared by mixing cement powders of tetracalcium phosphate (TTCP) and dicalcium phosphate (DCPA) with a cement liquid of physiological saline solution, were investigated. The microstructure evolution of various hardened cement bodies and their hydration crystals as a function of immersion time in similar physiological fluids, physiological saline solution (0.9% NaCl), or simulated body fluids (SBF), were also studied. Results show that the setting time of CPC is in the range of 12–15 min, which meets the clinical application demands. We also found that the mean compressive strength of the CPC samples immersed in SBF for 3 days is 104 ± 10 MPa which reaches the transverse compressive strength, 106–133 MPa, of human long bone. The results obtained from both the X‐ray powder diffraction analyses (XRD) and scanning electron microscopy (SEM) observations indicated that a reinforcing effect of some remaining TTCP particles in the early stages of immersion is mainly responsible for the increase in the initial strength. Although the CPC failed to keep this high level when immersed for a longer time, the initial reinforcing effect of the remaining TTCP particles provides advantages for clinical applications. This would be effective when the material is loaded at the very beginning of the implantation, especially for the material used as a fixation, which requires a certain initial strength in the early stages of the implantation. The cytotoxicity results showed that the relative growth rate (RGR%) of L929 cells on the CPC samples using physiological saline solution as a cement liquid was slightly superior to that of the samples using the 0.5 mol/L phosphate acid solution as the cement liquid. This was most likely caused by the pH difference between the two CPC samples immersed in a DMEM–BFS medium. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Crosslinked poly(ϵ‐caprolactone/D,L‐lactide)/bioactive glass composite scaffolds for bone tissue engineering
Authors: Meretoja V.V. , Helminen A.O. , Korventausta J.J. , Haapa‐aho V. , Seppälä J.V. , Närhi T.O.
Published: January 2006

A series of elastic polymer and composite scaffolds for bone tissue engineering applications were designed. Two crosslinked copolymer matrices with 90/10 and 30/70 mol % of ϵ‐caprolactone (CL) and D,L‐lactide (DLLA) were prepared with porosities from 45 to 85 vol % and their mechanical and degradation properties were tested. Corresponding composite scaffolds with 20–50 wt % of particulate bioactive glass (BAG) were also characterized. Compressive modulus of polymer scaffolds ranged from 190 ± 10 to 900 ± 90 kPa. Lactide rich scaffolds absorbed up to 290 wt % of water in 4 weeks and mainly lost their mechanical properties. Caprolactone rich scaffolds absorbed no more than 110 wt % of water in 12 weeks and kept their mechanical integrity. Polymer and composite scaffolds prepared with P(CL/DLLA 90/10) matrix and 60 vol % porosity were further analyzed in simulated body fluid and in osteoblast culture. Cell growth was compromised inside the 2 mm thick three‐dimensional scaffold specimens as a static culture model was used. However, composite scaffolds with BAG showed increased osteoblast adhesion and mineralization when compared to neat polymer scaffolds. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effects of surface roughness and maximum load on the mechanical properties of cancellous bone measured by nanoindentation
Authors: Donnelly Eve , Baker Shefford P. , Boskey Adele L. , van der Meulen Marjolein C.H.
Published: January 2006

The effects of two key experimental parameters on the measured nanomechanical properties of lamellar and interlamellar tissue were examined in dehydrated rabbit cancellous bone. An anhydrous sample preparation protocol was developed to maintain surface integrity and produce RMS surface roughnesses ∼10 nm (5 × 5‐μm2 area). The effects of surface roughness and maximum nanoindentation load on the measured mechanical properties were examined in two samples of differing surface roughness using maximum loads ranging from 250 to 3000 μN. As the ratio of indentation depth to surface roughness decreased below ∼3:1, the variability in material properties increased substantially. At low loads, the indentation modulus of the lamellar bone was ∼20% greater than that of the interlamellar bone, while at high loads the measured properties of both layers converged to an intermediate value. Relatively shallow indentations made on smooth surfaces revealed significant differences in the properties of lamellar and interlamellar bone that support microstructural observations that lamellar bone is more mineralized than interlamellar bone. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Protein transduction into human cells by adenovirus dodecahedron using WW domains as universal adaptors
Authors: Garcel A. , Gout E. , Timmins J. , Chroboczek J. , Fender P.
Published: January 2006

Background

Direct protein transduction is a recent technique that involves use of peptide vectors. In this study, we demonstrate that adenovirus dodecahedron (Dd), a virus‐like particle devoid of DNA and able to penetrate cells with high efficiency, can be used as a vector for protein delivery.

Methods

Taking advantage of Dd interaction with structural domains called WW, we have elaborated a universal adaptor to attach a protein of interest to this vector.

Results

A tandem of three WW structural domains derived from the Nedd4 protein enables the formation of stable complexes with Dd, without impairing its endocytosis efficiency. Our protein of interest fused to the triple WW linker is delivered by the dodecahedron in 100% of cells in culture with on average more than ten million molecules per cell.

Conclusion

These data demonstrate the great potential of adenovirus dodecahedron in combination with WW domains as a protein transduction vector. Copyright © 2006 John Wiley & Sons, Ltd.
Mixed hematopoietic molecular chimerism results in permanent transgene expression from retrovirally transduced hepatocytes in mice
Authors: Pichard Virginie , Bellodi‐Privato Marta , Gournay Jérôme , Ferry Nicolas
Published: January 2006

Background

Cytotoxic immune elimination of transduced hepatocytes may limit gene therapy for inherited liver diseases. Using β‐galactosidase as a marker gene, we studied whether creation of mixed β‐galactosidase molecular hematopoietic chimerism could induce tolerance to β‐galactosidase‐transduced hepatocytes.

Methods

Molecular hematopoietic chimerism was established in irradiated recipient mice by transplantation of either a mixture of wild‐type and β‐galactosidase‐transgenic bone marrow or autologous bone marrow stem cells that were transduced with β‐galactosidase lentiviral vectors. After transplantation, mice were hepatectomized and injected with β‐galactosidase recombinant retroviruses to transduce regenerating hepatocytes. We monitored the presence of β‐galactosidase‐expressing hepatocytes as well as the appearance of anti‐β‐galactosidase antibodies during the time.

Results

In control animals, anti‐β‐galactosidase antibodies and cytotoxic T‐lymphocyte (CTL) response developed as early as 3 weeks after gene transfer. Transduced hepatocytes disappeared concomitantly. In bone marrow transplanted mice, tolerance could be observed in a significant proportion of animals. Tolerance resulted in permanent liver transgene expression and was absent unless a chimerism above 1% was achieved, demonstrating a threshold effect.

Conclusions

Creation of a molecular hematopoietic chimerism can result in transgene tolerance and evade immune rejection of retrovirally transduced hepatocytes. This strategy may be useful for hepatic inherited diseases in which the transgene product behaves as a non‐self protein. Copyright © 2006 John Wiley & Sons, Ltd.
Brain engraftment and therapeutic potential of stem/progenitor cells derived from mouse skin
Authors: Tunici Patrizia , Bulte Jeff W. M. , Bruzzone Maria Grazia , Poliani Pietro Luigi , Cajola Laura , Grisoli Marina , Douglas Trevor , Finocchiaro Gaetano
Published: January 2006

Skin stem/progenitor cells (SKPs) derive from the dermis and in culture can generate mesodermal and neural progenies. To investigate their potential for the treatment of brain diseases, we first injected SKPs into the brain of syngeneic mice. Brain histology indicated that most SKPs remained undifferentiated and clustered at the injection site, while, in vitro, 17% of SKPs expressed neural markers, as assessed by flow cytometry. After labeling with magnetodendrimers, murine and human SKPs were detected by magnetic resonance imaging even 5 months after brain injection. To evaluate their therapeutic potential on malignant gliomas, IL‐4 SKPs (i.e. SKPs transduced by a lentiviral vector carrying the cDNA of the anti‐glioma cytokine interleukin‐4) were injected into GL261 experimental gliomas. IL‐4‐SKPs prolonged significantly the survival of tumor‐bearing mice: furthermore, GL261 gliomas attracted SKPs originally injected into the contralateral hemisphere. Thus, prolonged survival, capacity for transgene expression, and lack of uncontrolled proliferation suggest that SKPs warrant further consideration as therapeutic tools for brain tumors and, possibly, other neurological disorders. Copyright © 2006 John Wiley & Sons, Ltd.
Convenient synthesis of deuterated glutamic acid, proline and leucine via catalytic deuteration of unsaturated pyroglutamate derivatives
Authors: Oba Makoto , Ohkuma Kosuke , Hitokawa Hiroshi , Shirai Ayumi , Nishiyama Kozaburo
Published: January 2006

Novel 3,4‐didehydropyroglutamate derivatives, the key intermediates in this synthesis, were obtained from a protected pyroglutamate by the well‐known selenenylation‐oxidative deselenenylation method and were catalytically deuterated using a slow‐addition technique. The obtained deuterated pyroglutamates were converted to [3,4‐2H2]glutamic acid, [3,4,5‐2H3]proline, and [3,4,5,5,5‐2H5]leucine via an appropriate functional group interconversions followed by the standard deprotection procedure. Copyright © 2006 John Wiley & Sons, Ltd.
A novel asymmetric synthesis of tritium and carbon‐14 labeled (R)‐ibuprofen
Authors: Zhang Yinsheng , Hong Yang , Huang Che C. , Belmont Daniel
Published: January 2006

An efficient asymmetric synthesis of tritium and carbon‐14 labeled R‐ibuprofen was achieved in good overall yield (15% and 47%, respectively) and excellent enantiomerical excess (>98% e.e.), using (4R, 5S)‐4‐methyl‐5‐phenyl‐2‐oxazolidinone as a chiral auxiliary. Copyright © 2006 John Wiley & Sons, Ltd.
Acoustic communication and burrow acoustics are reflected in the ear morphology of the coruro (Spalacopus cyanus, Octodontidae), a social fossorial rodent
Authors: Begall Sabine , Burda Hynek
Published: January 2006

We studied the middle and inner ears of seven adult coruros (Spalacopus cyanus), subterranean and social rodents from central Chile, using free‐hand dissection and routine staining techniques. Middle ear parameters that were focused on here (enlarged bullae and eardrums, ossicles of the “freely mobile type”) are believed to enhance hearing sensitivity at lower frequencies. The organ of Corti was of a common mammalian type and revealed three peaks of higher inner hair cell densities. Based on a position frequency map, frequencies were assigned to the respective peaks along the basilar membrane. The first peak at around 300–400 Hz is discussed with respect to the burrow acoustics, while the peak around 10–20 kHz is probably a plesiomorphic feature. The most pronounced peak at around 2 kHz reflects the frequency at which the main energy of vocal communication occurs. The morphology of the ear of the coruro corresponds to the typical pattern seen in subterranean rodents (low frequency and low‐sensitivity hearers), yet, at the same time, it also deviates from it in several functionally relevant features. J. Morphol. © 2006 Wiley‐Liss, Inc.
Gravity‐dependent signal gradients on MR images of the lung in supine and prone positions: A comparison with isogravitational signal variability
Authors: Bankier Alexander A. , Storey Pippa , Mai Vu M. , Edelman Robert R. , Chen Qun
Published: January 2006

Purpose

To investigate the tendency of proton MR signal intensity (SI) gradients to be steeper in the supine than in the prone body position, and to quantify the relation between gravity‐related and isogravitational changes of SI on proton MR images of the lung.

Materials and Methods

In eight healthy volunteers, MR images were obtained in the supine and prone positions using a multiple inversion recovery turbo spin‐echo (TSE) sequence. The variation in SI along the gravity‐dependent direction and within isogravitational planes was measured on a pixel‐by‐pixel basis. Ratios of slopes were calculated for comparisons among volunteers. Comparisons of ratios were made using Fisher's exact test. Isogravitational variability was compared with the mean SI, the signal‐to‐noise ratio (SNR), and the image noise.

Results

The average ratios of slopes showed that the overall SI gradient was steeper in the supine than the prone position, with a substantial difference in the supine/prone ratios between inspiration (1.21) and expiration (1.72). In both the supine and prone positions, gravity‐dependent gradients were steeper in expiration than in inspiration (P = 0.001). The SI variability along the gravitational direction was larger than the isogravitational variability. The isogravitational variability in turn was larger than the image noise but smaller than the mean SI of the MR images.

Conclusion

Gravity‐dependent gradients in proton MR SI are steeper in the supine than in the prone position. The magnitudes of these gradients were larger than the isogravitational signal variability, showing that MRI is sensitive to gravitationally induced effects. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Administration of baclofen, a γ‐aminobutyric acid type B agonist in the thalamic ventrobasal complex, attenuates allodynia in monoarthritic rats subjected to the ankle‐bend test
Authors: Potes Catarina Soares , Neto Fani Lourença , Castro‐Lopes José Manuel
Published: January 2006

γ‐Aminobutyric acid type B (GABAB) receptors are involved in the modulation of neuronal activity in response to chronic noxious input. However, the effect of their activation in chronic inflammatory pain in relay thalamic nuclei such as the ventrobasal complex (VB) is not known. In this study, experimental groups of 2, 4, and 14 days monoarthritic (MA) rats were injected with saline (controls) or baclofen (0.875 μg), a specific GABAB receptor agonist, in the VB contralateral to the inflamed joint, and the ankle‐bend test was performed. Ankle‐bend scores in control animals were near the maximum and were rather constant throughout the entire experimental period, indicating severe nociception. The same was observed in 2 days MA rats injected with baclofen. In the 4 days MA group, the response to baclofen injection was inconsistent among different animals, whereas, in 14 days MA rats, baclofen caused clear antinociceptive effects. Additionally, a 0.5 μg dose of baclofen was tested in 14 days MA rats, but no effect was observed, whereas a 1.25 μg dose produced visible side effects. Baclofen injections that did not target the VB but reached neighboring nuclei were ineffective in reducing nociception. Data demonstrate that the activation of the GABAB receptors by baclofen in the VB of MA rats leads to a decrease of nociception. Moreover, the response depends on the time course of the disease, suggesting the occurrence of different excitatory states of thalamic VB neurons. In conclusion, GABAB receptors in the VB play an important role in chronic inflammatory pain processing. © 2006 Wiley‐Liss, Inc.
In utero transplantation of human bone marrow‐derived multipotent mesenchymal stem cells in mice
Authors: Chou Shiu‐Huey , Kuo Tom K. , Liu Ming , Lee Oscar K.
Published: January 2006

Mesenchymal stem cells (MSCs) are multipotent cells that can be isolated from human bone marrow and possess the potential to differentiate into progenies of embryonic mesoderm. However, current evidence is based predominantly on in vitro experiments. We used a murine model of in utero transplantation (IUT) to study the engraftment capabilities of human MSCs. MSCs were obtained from bone marrow by negative immunoselection and limiting dilution, and were characterized by flow cytometry and by in vitro differentiation into osteoblasts, chondrocytes, and adipocytes. MSCs were transplanted into fetal mice at a gestational age of 14 days. Engraftment of human MSCs was determined by flow cytometry, polymerase chain reaction, and fluorescence in situ hybridization (FISH). MSCs engrafted into tissues originating from all three germ layers and persisted for up to 4 months or more after delivery, as evidenced by the expression of the human‐specific β‐2 microglobulin gene and by FISH for donor‐derived cells. Donor‐derived CD45+ cells were detectable in the peripheral blood of recipients, suggesting the participation of MSCs in hematopoiesis at the fetal stage. This model can further serve to evaluate possible applications of MSCs. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:301–312, 2006
Modelling international tourism demand and volatility in small island tourism economies
Authors: Shareef Riaz , McAleer Michael
Published: January 2006

Small island tourism economies (SITEs) vary in their size, land area, location, narrow resource bases, economic development, overwhelming reliance on tourism and consistent inflow of foreign direct investment for economic growth. Small island tourism economics differ in their ethnic diversity, political systems, economic and environmental vulnerability, ecological fragility and the risks facing investors. Owing to natural disasters, ethnic conflicts, crime and the threat of global terrorism, there have been dramatic changes in the arrivals of international tourists to SITEs. These variations in international tourism demand to SITEs, particularly the conditional variance (or volatility) in international tourist arrivals, have not previously been analysed in the tourism research literature. An examination of the conditional volatility of international tourist arrivals is essential for policy analysis and marketing purposes. This paper models the conditional mean and conditional variance of the logarithm of monthly international tourist arrivals and the growth rate (or log‐difference) in the monthly international tourist arrivals for six SITEs, namely Barbados, Cyprus, Dominica, Fiji, Maldives and Seychelles. Diagnostic checks of the regularity conditions of the logarithm of monthly international tourist arrivals and their growth rates suggest that the estimated univariate models of trends and volatility are statistically adequate. Therefore, the estimated models are appropriate for purposes of public and private sector management of tourism. Copyright © 2005 John Wiley & Sons, Ltd.
Capsaicin delays regeneration of the neuromuscular junction of rat extensor digitorum longus muscle after ischemia
Authors: Turchányi Béla , Hamar János , Tömböl Teréz , Siklós László
Published: January 2006

Trauma or the tourniquet used in orthopedic surgery is often associated with ischemia–reperfusion (I/R) injury with a consequent decrease of muscle power. To explore whether components of the neuromuscular junction (NMJ) are involved in this muscle dysfunction, NMJs were ultrastructurally characterized in the extensor digitorum longus muscle of rats at reperfusion times of 1, 24, 72, and 168 h after a 120‐min arterial occlusion. Disorganization of the presynaptic membrane and mitochondrial injury was noted at 1 h, followed by fragmentation and partial engulfment of nerve terminals by Schwann cells at 24 and 72 h. The magnitude of degenerative changes declined at 168 h, suggesting the commencement of regeneration. The postsynaptic membrane remained intact throughout the whole period. In our previous study, deafferentation with pretreatment of the sciatic nerve with capsaicin, which reduces neurogenic inflammation and has a selective effect on nociceptive fibers, improved functional recovery of the muscle after I/R. The present results document a significantly delayed structural regeneration of the motor nerve terminals after combined capsaicin and I/R treatment. Since capsaicin treatment alone had no discernible effect on the structure of NMJs, the findings point to a possibly indirect effect of capsaicin on the motor nerves, which may predispose them to increased susceptibility unmasked only by a subsequent injury. The mismatch between the enhanced functional improvement of the muscle and delayed regeneration of the nerve after capsaicin pretreatment questions the efficient use of such deafferentation to protect the integrity of neuromuscular junctions in I/R injury. Muscle Nerve, 2006
Repetitive nerve stimulation of facial muscles in musk antibody–positive myasthenia gravis
Authors: Oh Shin J. , Hatanaka Yuki , Hemmi Shoji , Young Angela M. , Scheufele Mia L. , Nations Sharon P. , Lu Liang , Claussen Gwen C. , Wolfe Gil I.
Published: January 2006

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle‐specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab–positive, 73 acetylcholine receptor antibody (AChR Ab)–positive, and 22 MuSK and AChR Ab–negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab–positive and 82% of AChR Ab–positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab–positive patients than the other two groups. Single‐fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab–positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab–positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients. Muscle Nerve, 2006
Luminescent properties of PP and LDPE films and rods doped with the Eu(III)‐La(III) complex
Authors: Pogreb Roman , Popov Oleg , Lirtsman Vlad , Pyshkin Oleg , Kazachkov Alexander , Musin Albina , Whyman Gene , Finkelshtein Binyamin , Shmukler Yuri , Davidov Dan , Gladkikh Alexander , Bormashenko Edward
Published: January 2006

The work is devoted to luminescent properties of trivalent lanthanide complexes dispersed in thermoplastic host matrices. Polyethylene films and polypropylene‐rods, both doped with these complexes, were manufactured using an extrusion technique. Two kinds of dopants were used: Eu(III)‐thenoyltrifluoroacetone‐1,10‐phenanthroline complex (1) and Eu(III)‐La(III)‐1,10‐phenanthroline complex (2). Absorption, excitation, emission spectra and lifetime of luminescence were studied. The impact of the polymer matrix on the emission spectra was investigated. Emission spectra of the films were studied at room and helium temperatures. Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) surface mapping showed that in the Eu(III)‐La(III) complex europium forms islands (clusters) with a dimension of 1 µm, whereas lanthanum was dispersed more uniformly in the polymer matrix. Dependence of emission intensity on the excitation was determined. Copyright © 2006 John Wiley & Sons, Ltd.
Research, audit, practice development and service evaluation: implications for research and clinical governance
Authors: Gerrish Kate , Mawson Susan
Published: January 2006

The importance of ensuring a high level of scientific and ethical standards in health and social care research underpins the Department of Health's framework for research governance (DOH, 2001). This paper presents our current thinking regarding some areas of ambiguity. The explanations offered are open to challenge and we see the paper as a contribution to the debates surrounding these different activities rather than providing a template for making decisions about what constitutes research, audit, practice development and service evaluation. However, we also hope that the paper will provide some practical guidance in undertaking these activities. Copyright © 2005 Whurr Publishers Ltd.
Design and implementation of an observation chart with an integrated early warning score
Authors: McCormick Joanna
Published: January 2006

This paper details the design and implementation of a physiological observation chart with an integrated early warning score. The observation chart was piloted over a 6‐week period with patients admitted to three acute surgical wards including those admitted from accident and emergency and the post‐operative recovery ward. Copyright © 2005 Whurr Publishers Ltd.
Utilizing practice development to implement an integrated care pathway for self‐harm
Authors: Harrison Anthony , Hillier David , Redman Rachael
Published: January 2006

This paper provides an overview of the development and implementation of an integrated care pathway for self‐harm across a range of health and social care organizations. The focus of the pathway and the practice development journey was to enable ownership and active collaboration in the assessment and care of people who are either considered at risk of self‐harm, or who have engaged in self‐harming behaviour. The core elements of a practice development methodology were used to plan and manage a significant piece of work aimed at securing lasting changes across a health community by working at individual, team and organizational levels. The value of utilizing a practice development strategy to provide focus for the process, and a collaborative structure for improvements in patient care are illustrated. Practice development has provided a positive and enabling structure that has allowed those involved to enhance practice and care in an area of health care that is often viewed as unpopular and unrewarding. Copyright © 2005 Whurr Publishers Ltd.
Incidence of clinically diagnosed systemic lupus erythematosus 1992–1998 using the UK General Practice Research Database
Authors: Nightingale Alison L. , Farmer Richard D. T. , de Vries Corinne S.
Published: January 2006

Purpose

To determine the age‐ and sex‐specific incidence rates of systemic lupus erythematosus (SLE) in the population of the General Practice Research Database (GPRD) between 1.1.1992 and 31.12.1998.

Methods

We searched the GPRD for incident cases of clinically diagnosed SLE with supporting evidence of diagnosis in their medical record. Cases must have had at least 3 years of data in their record prior to date of first diagnosis. We calculated the annual and age‐ and sex‐specific incidence rates of SLE.

Results

We identified 390 incident cases of SLE yielding an incidence rate (IR) of 3.02/100 000/year (CI95 2.72, 3.32). There were 41 males (IR 0.65/100 000/year (CI95 0.45, 0.85)) and 349 females (IR 5.30/100 000/year (CI95 4.75, 5.86)). The median age at diagnosis for males and females was 54 and 46 years, respectively, and the peak incidence rates were amongst women aged 30–69 years. The incidence rate ratio for females to males was 8.15 (CI95 5.9, 11.6).

Conclusions

This is the first UK‐wide study of the incidence of SLE. The results of this study are consistent with previous smaller studies conducted in Nottingham and Birmingham. Although recording of symptoms of SLE is not complete in the GPRD, we conclude that incident cases can be successfully identified because generally there is supporting evidence of diagnosis in medical record. Copyright © 2005 John Wiley & Sons, Ltd.
Estimation of time‐dependent rate ratios in case‐control studies: comparison of two approaches for exposure assessment
Authors: Lefebvre Geneviève , Angers Jean‐François , Blais Lucie
Published: January 2006

Purpose

In pharmacoepidemiology, it is well recognized that the rate of adverse events may vary as a function of the cumulative duration of the drug exposure and/or the time since the end of the exposure. In case‐control studies, two different approaches have been used to estimate temporal effects of drug exposure: the time‐windows (T‐Ws) approach and the duration‐specific (D‐S) approach. We decided to conduct a simulation study to compare the two approaches when the rate ratios (RRs) vary as a function of the cumulative duration of exposure and/or the time since the end of exposure.

Methods

We generated three cohorts of 500 000 individuals in which the rate of the event was varying as a function of the cumulative duration of exposure and the time since the end of exposure. For each cohort, a nested case‐control analysis was performed using both the D‐S and the T‐Ws approaches. In the T‐Ws approach, a RR is estimated within specific periods of time prior to the outcome, while a RR is estimated within periods of cumulative duration of exposure and time since the end of exposure in the D‐S approach.

Results

We found that the RRs obtained from the D‐S approach exactly corresponded to the RRs obtained from the cohort analyses, while the RRs obtained from the T‐Ws approach generally not. RRs obtained from the T‐Ws approach were difficult to interpret in terms of the effect of the duration and timing of the exposure.

Conclusion

The D‐S approach should be used to investigate the duration‐related effects of exposure in case‐control studies. Copyright © 2005 John Wiley & Sons, Ltd.
Proteome analysis of glandular parotid and submandibular‐sublingual saliva in comparison to whole human saliva by two‐dimensional gel electrophoresis
Authors: Walz Anke , Stühler Kai , Wattenberg Andreas , Hawranke Eva , Meyer Helmut E. , Schmalz Gottfried , Blüggel Martin , Ruhl Stefan
Published: January 2006

The secretions of the salivary parotid and submandibular‐sublingual (SMSL) glands constitute the main part of whole human saliva (WS) in which proline‐rich proteins (PRPs) and mucins represent dominant groups. Although proteome analysis had been performed on WS, no identification of PRPs or mucins by 2‐DE and MS was achieved in WS and no comprehensive analysis of both glandular secretions is available so far. The aim of this study was to compare the protein map of WS to parotid and SMSL secretions for the display of PRPs and mucins. WS and glandular secretions were subjected to 2‐DE and spots were analyzed by MALDI‐MS. New components identified in WS were cyclophilin‐B and prolyl‐4‐hydroxylase. Also acidic and basic PRPs as well as the proline‐rich glycoprotein (PRG) could now be mapped in WS. Acidic PRPs were found equally in parotid and SMSL secretions, whereas basic PRPs and PRG were found primarily in parotid secretion. Salivary mucin MUC7 was identified in SMSL secretion. Thus, the more abundant proteins of WS can be explained mainly by mixed contributions of parotid and SMSL secretions with only few components remaining that may be derived from local sources in the oral cavity.
Two‐dimensional electrophoretic profiling of atopic dermatitis in primary cultured keratinocytes from patients
Authors: Park Yong‐Doo , Jang Hee‐Sun , Kim So‐yeon , Ko Sung‐Kyun , Lyou You‐Jeong , Lee Dong‐Youn , Paik Young‐Ki , Yang Jun‐Mo
Published: January 2006

Recently, we reported altered protein expression in primary cultured fibroblasts from atopic dermatitis (AD) patients. As a sequential study, we conducted proteomic analysis of primary keratinocytes derived from AD patients to further identify AD‐related proteins. Three pH ranges, 4–7, 6–9, and 7–11, were used to profile the altered protein expression in AD. We obtained 46 candidate spots from the 2‐D gel image analysis: 18 proteins were up‐regulated and 27 proteins were down‐regulated. Among the several important candidate proteins, NCC27 showed the same profile of a defect in PTM in both AD‐derived keratinocytes and fibroblasts. On the basis of current and previous reports, real‐time PCR was performed on select candidate genes to compare RNA and protein expression levels in AD‐derived keratinocytes and fibroblasts. Our results provide new clues to aid in understanding the mechanism of atopic alterations in keratinocytes and suggest new AD‐associated proteins that are important in AD pathogenesis.
Functional and phenotypic relevance of differentially expressed proteins in calcineurin mutants of Caenorhabditis elegans
Authors: Ahn Do‐Hwan , Singaravelu Gunasekaran , Lee Sooung , Ahnn Joohong , Shim Yhong‐Hee
Published: January 2006

Calcineurin is a heterodimeric serine/threonine protein phosphatase, important for many cellular processes such as T‐cell regulation, cardiac hypertrophy and kidney development. We previously reported the characterization of Caenorhabditis elegans calcineurin mutants as providing a simple but excellent genetic model system for studying in vivo functions of calcineurin. Calcineurin loss‐of‐function mutants, cnb‐1(lf), and gain‐of‐function mutants, tax‐6(gf), show certain opposite phenotypes as well as some similar phenotypes. In order to explain the phenotypic similarity observed in both loss‐of‐function and gain‐of‐function mutants, we examined the proteins that followed similar trends in both mutants relative to wild‐type worms by using 2‐DE. Interestingly, VHA‐13, HSP‐6 and phosphoenolpyruvate carboxykinase are down‐regulated in both mutants. A total of 96 differentially regulated proteins were identified by MALDI‐TOF/MS. Among these, 42 proteins are up‐regulated and 54 proteins are down‐regulated in calcineurin mutants. Furthermore, knock‐down of about 30% of the genes, which are down‐regulated in calcineurin mutants, showed some of the phenotypes of calcineurin‐null mutants. This analysis suggests the functional relevance of these proteins to calcineurin activity in C. elegans.
A proteomic approach for unraveling the oncogenic H‐Ras protein networks in NIH/3T3 mouse embryonic fibroblast cells
Authors: Park Jung Wook , Kim Seyoon , Lim Kook Jin , Simpson Richard J. , Kim Yu Sam , Bahk Young Yil
Published: January 2006

To elucidate the oncogenic H‐Ras network, we have established various stable and inducible oncogenic H‐Ras‐expressing NIH/3T3 mouse embryonic fibroblast cell clones, which express G12V H‐Ras and G12R H‐Ras proteins under the influence of a strong cytomegalovirus promoter and under the tight control of expression by an antibiotic, doxycycline, respectively. Here we provide a catalogue of proteome profiles in total cell lysates derived from oncogenic H‐Ras‐expressing NIH/3T3 cells. In this biological context, we compared total proteome changes by the combined methods of 2‐DE, quantitative image analysis and MALDI‐TOF MS analysis using both a stable expression system as well as an inducible expression system. There were a large number of common targets for oncogenic H‐Ras, which were identified in both cell lines and consisted of 64 proteins (36 up‐regulated and 28 down‐regulated). Differentially regulated expression was further confirmed for some subsets of candidates by Western blot analysis using specific antibodies. Taken together, the results presented here show that comparative analysis of the proteome from the oncogenic H‐Ras‐expressing cells yielded interpretable data to elucidate protein networks directly and/or indirectly.
Kinetics and mechanism of the reactions of polyallylamine with aryl acetates and aryl methyl carbonates
Authors: Castro Enrique A. , Echevarría Gerardo R. , Opazo Alejandra , Robert Paz S. , Santos José G.
Published: January 2006

The reactions of polyallylamine (PAA) with 4‐nitrophenyl acetate (NPA), 2,4‐dinitrophenyl acetate (DNPA), 2,4,6‐trinitrophenyl acetate (TNPA), 4‐nitrophenyl methyl carbonate (NPC), 2,4‐dinitrophenyl methyl carbonate (DNPC) and 2,4,6‐trinitrophenyl methyl carbonate (TNPC) at pH 7.0–11.5 were subjected to a kinetic investigation in aqueous solution at 25.0 °C and an ionic strength of 0.1 M (KCl). Potentiometric titration curves were obtained at different polymer concentrations under the same conditions as for the kinetic measurements. The degree of dissociation (α) and pKapp values for PAA at each pH were found from the titration curves. The shape of these curves shows a conformational change of the polymer at α > 0.7. Similar behavior was observed through the dependence of logkN on either pH or α, where kN is the second‐order rate constant for the title reactions. The kN value is influenced by the electrostatic interactions in the polymer chain and the conformational changes that PAA undergoes in solution. The Brønsted‐type plots (logkN vs pKapp) are linear with slopes (β values) of 0.5, 0.4, 0.5, 0.7, 0.6 and 0.7 for the reactions of PAA with NPA, DNPA, TNPA, NPC, DNPC and TNPC, respectively. These data are consistent with concerted mechanisms. The kN values increase in the sequence TNPA > DNPA > NPA and TNPC > DNPC > NPC. These results are in accordance with those found for the reactions with monomeric amines, which are due to the increasing nucleofugality of the leaving groups, and also the increasing electrophilic character of the carbonyl carbon, as more nitro groups are added to the substrate. Acetates are more reactive than the corresponding methyl carbonates, which can be explained by the larger electron‐releasing effect exerted by MeO relative to Me. PAA destabilizes the putative tetrahedral intermediate relative to the monomeric amines and the stability of tetrahedral intermediates would decrease in the sequence pyridines > anilines > secondary alicyclic amines > quinuclidines > PAA. Copyright © 2006 John Wiley & Sons, Ltd.
Preparation, characterization, and polymerization of maleimidobenzoxazine monomers as a novel class of thermosetting resins
Authors: Agag Tarek , Takeichi Tsutomu
Published: January 2006

New series of benzoxazine‐based monomers, namely maleimidobenzoxazines, were prepared with hydroxyphenylmaleimide, formalin, and various amines (e.g., aniline, allylamine, and aminophenyl propargyl ether). The structure of the novel monomers was confirmed by IR, 1H NMR, and elemental analysis. The monomers were easily dissolved in many common organic solvents. Differential scanning calorimetry of the novel monomers showed exotherms at different temperature ranges that corresponded to the polymerization regime of benzoxazine and maleimide along with other functionalities such as allyl or propargyl, if any. IR was studied to follow the progress of the curing reaction of maleimidobenzoxazine after various thermal treatments. The thermal cure of the monomers at 250 °C afforded a novel network structure that combined polybenzoxazine and polymaleimide. The dynamic mechanical analyses showed that the storage moduli of the thermosets derived from maleimidobenzoxazine were kept constant up to high temperatures. The glass‐transition temperatures were as high as 241–335 °C. Moreover, thermogravimetric analyses revealed that the thermosets did not show any weight loss up to about 350 °C, with char yields ranging from 62 to 70% at 800 °C. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1424–1435, 2006
Pigeon Breeder's Lung in Childhood: Is Family Screening Necessary?
Authors: Ceviz Naci , Kaynar Hasan , Olgun Haşim , Onbaş Ömer , Misirligil Zeynep
Published: January 2006

In this paper, we report on clinical and laboratory findings of pigeon breeder's lung (PBL) in a mother and her 2 children: 2 with the chronic recurrent form, and 1 with the chronic insidious form without any symptoms or signs, who was diagnosed during family screening. The index case was diagnosed as having primary pulmonary hypertension on admission. However, on evaluation, the diagnosis was of pigeon breeder's lung in the index case and her symptomatic mother. High‐resolution computerized tomography (HRCT) revealed interstitial lung disease in an asymptomatic sister of the index case. All cases responded to steroid treatment, and at the end of the third month, HRCT findings disappeared. In conclusion, in patients with acute respiratory symptoms and rapidly recovering pulmonary hypertension after hospitalization, PBL should be remembered. All family members of the index case should be screened by HRCT in terms of interstitial lung disease, even if they are asymptomatic. Pediatr Pulmonol. © 2006 Wiley‐Liss, Inc.
Molecular mechanisms of pH‐driven conformational transitions of proteins: Insights from continuum electrostatics calculations of acid unfolding
Authors: Fitch Carolyn A. , Whitten Steven T. , Hilser Vincent J. , García‐Moreno E. Bertrand
Published: January 2006

The acid unfolding ofstaphylococcalnuclease (SNase) is very cooperative (Whitten and García‐Moreno, Biochemistry 2000;39:14292–14304). As many as seven hydrogen ions (H+) are bound preferentially by the acid‐unfolded state relative to the native (N) state in the pH range 3.2–3.9. To investigate the mechanism of acid unfolding, structure‐based pKacalculations were performed with a variety of continuum electrostatic methods. The calculations reproduced successfully the H+binding properties of the N state between pH 5 and 9, but they systematically overestimated the number of H+bound upon acid unfolding. The calculated pKavalues of all carboxylic residues in the N state were more depressed than they should be. The discrepancy between the observed and the calculated H+uptake upon acid unfolding was not improved by using high protein dielectric constants, structures relaxed with molecular dynamics, or other empirical modifications implemented previously by others to maximize agreement between measured and calculated pKavalues. This suggests an important role for conformational fluctuations of the backbone as important determinants of pKavalues of carboxylic groups. Because no global or subglobal conformational changes have been observed previously for SNase under acidic conditions above the acid‐unfolding region, these fluctuations must be local. The acid unfolding of SNase does not seem to involve the disruption of the N state by accruement of intramolecular repulsive interactions, nor the protonation of key ion paired carboxylic residues. It is more consistent with modest contributions from many H+binding groups, with an important role for local conformational fluctuations in the coupling between H+binding and the global structural transition. Proteins 2006. © 2006 Wiley‐Liss, Inc.