bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel 3D collagen scaffolds fabricated by indirect printing technique for tissue engineering
Authors: Liu C. Z. , Xia Z. D. , Han Z. W. , Hulley P. A. , Triffitt J. T. , Czernuszka J. T.
Published: December 2007

This article reports the mechanical properties and in vitro evaluation of a collagen scaffold fabricated using an indirect 3D printing technique. Collagen scaffolds, featuring predefined internal channels and capillary networks, were manufactured using phase change printing. It was observed that the collagen scaffolds featured internal channels and a hierarchical structure that varied over length scales of 10–400 μm. In vitro evaluation using hMSCs demonstrated that the resultant collagen based scaffolds have the ability to support hMSC cell attachment and proliferation; cells can migrate and survive deep within the structure of the scaffold. The cell numbers increased 2.4 times over 28 days in culture for the lysine treated scaffolds. The cells were spread along the collagen fibers to form a 3D structure and extracellular matrix was detected on the surface of the scaffolds after 4 weeks in culture. The crosslinking treatment enhanced the biostability and dynamic properties of the collagen scaffolds significantly. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Effects of compaction pressure and particle shape on the porosity and compression mechanical properties of sintered Ti6Al4V powder compacts for hard tissue implantation
Authors: Güden Mustafa , Çelik Emrah , Hızal Alpay , Altındiş Mustafa , Çetiner Sinan
Published: December 2007

Sintered Ti6Al4V powder compacts potentially to be used in implant applications were prepared using commercially available spherical and angular powders (100–200 μm) within the porosity range of 34–54%. Cylindrical green powder compacts were cold compacted at various pressures and then sintered at 1200°C for 2 h. The final percent porosity and mean pore sizes were determined as functions of the applied compaction pressure and powder type. The mechanical properties were investigated through compression testing. Results have shown that yield strength of the powder compacts of 40–42% porosity was comparable with that of human cortical bone. As compared with previously investigated Ti powder compacts, Ti6Al4V powder compacts showed higher strength at similar porosity range. Microscopic observations on the failed compact samples revealed that failure occurred primarily by the separation of interparticle bond regions in the planes 45° to the loading axis. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Evaluation of the biocompatibility and osteoproductive activity of ostrich eggshell powder in experimentally induced calvarial defects in rabbits
Authors: Durmuş Ercan , Çelik İlhami , Aydın M. Faruk , Yıldırım Gülsün , Sur Emrah
Published: December 2007

The purpose of this study was to investigate the beneficial effects of particulate ostrich eggshell grafting on the healing of experimentally induced skull defects. The clinical, radiological, histological, and histomorphometrical findings of this material were compared with the results of commercially available demineralized bone matrix (DBM). The study was conducted on 18 adult New Zealand rabbits. One defect served as a control and the remaining ones either were filled with different sized eggshell particles or DBM, in each animal. Clinical and radiological inspections and histologic investigations of the animals were done at the 1st, 3rd, and 6th months of postoperative period. Radiologically, minimal bone regeneration was observed at the empty, control defect sites. The most advanced bone regeneration was in the DBM grafted defects. The eggshell particle grafted defect sites displayed weak bone regeneration at earlier stages, at 1st and 3rd months after operation when compared with demineralized bone matrix. Nevertheless, ossification was satisfactory at 6th month after operation when compared with the control defects. Within the limitations of this study, it was concluded that Ostrich eggshell powder (OSP) is a worth‐while bone substitute because it is a safe, cheap, and easily available material. Long‐term studies will clarify its possible role in maxillofacial surgery. Further sophisticated experiments should be undertaken before human implantation concerning its osteoproductive activity alone or in combination with other materials. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Decoupled syndecan 1 mRNA and protein expression is differentially regulated by angiotensin II in macrophages
Authors: Wang Wenli , Haller Carolyn A. , Wen Jing , Wang Peiyi , Chaikof Elliot L.
Published: December 2007

It has been established that syndecan‐1 is an important modulator of events relevant to acute tissue repair and chronic injury responses. The current studies were designed to examine syndecan‐1 expression during atherosclerotic lesion formation and whether angiotensin II influences syndecan‐1 expression in macrophages. ApoE knockout mice maintained on an atherogenic diet were treated for 8 weeks with an infusion of angiotensin II to induce atherosclerosis. Immunohistochemistry was employed to characterize the expression of syndecan‐1 in atherosclerotic lesions. Quantitative real‐time PCR (QRTPCR) was used to define the role of angiotensin II and responsible signaling pathways involved syndecan‐1 expression in RAW264.7 murine macrophages. Protein expression and shedding were characterized by fluorescence activated cell sorting (FACS) and slot blot analysis. Syndecan‐1 was abundantly expressed in macrophages located within early atherosclerotic lesions. Accordingly, we hypothesized that angiotensin II regulates syndecan‐1 expression in macrophages. A time‐ and dose‐dependent study was performed in RAW264.7 macrophages. QRTPCR demonstrated maximum syndecan‐1 mRNA up‐regulation at 6 h after 500 nM AgII stimulation (threefold; P < 0.05). Through administration of specific inhibitors, we established that ERK/MAPK, PI3K and JNK signaling pathways mediated this effect. FACS and slot blot analyses demonstrated that cAMP induced posttranscriptional syndecan‐1 protein expression in a dose‐dependent manner with or without initial angiotensin II stimulation. In particular, angiotensin II induced an increase in cell surface syndecan‐1 (mean fluorescence intensity: 147 ± 5.7 vs. 176 ± 4.8; P < 0.05; n = 3) and accelerated syndecan‐1 shedding. Angiotensin II is a potent regulator of syndecan‐1 expression in atherosclerotic lesions via a specific effect on macrophages that is mediated by ERK/MAPK, PI3K, and JNK signaling pathways. J. Cell. Physiol. 214: 750–756, 2008. © 2007 Wiley‐Liss, Inc.
Drug‐induced readthrough of premature stop codons leads to the stabilization of laminin α2 chain mRNA in CMD myotubes
Authors: Allamand Valérie , Bidou Laure , Arakawa Masayuki , Floquet Célia , Shiozuka Masataka , Paturneau‐Jouas Marion , Gartioux Corine , Butler‐Browne Gillian S. , Mouly Vincent , Rousset Jean‐Pierre , Matsuda Ryoichi , Ikeda Daishiro , Guicheney Pascale
Published: December 2007

Background

The most common form of congenital muscular dystrophy is caused by a deficiency in the α2 chain of laminin‐211, a protein of the extracellular matrix. A wide variety of mutations, including 20 to 30% of nonsense mutations, have been identified in the corresponding gene, LAMA2. A promising approach for the treatment of genetic disorders due to premature termination codons (PTCs) is the use of drugs to force stop codon readthrough.

Methods

Here, we analyzed the effects of two compounds on a PTC in the LAMA2 gene that targets the mRNA to nonsense‐mediated RNA decay, in vitro using a dual reporter assay, as well as ex vivo in patient‐derived myotubes.

Results

We first showed that both gentamicin and negamycin promote significant readthrough of this PTC. We then demonstrated that the mutant mRNAs were strongly stabilized in patient‐derived myotubes after administration of negamycin, but not gentamicin. Nevertheless, neither treatment allowed re‐expression of the laminin α2‐chain protein, pointing to problems that may have arisen at the translational or post‐translational levels.

Conclusions

Taken together, our results emphasize that achievement of a clinical benefit upon treatment with novel readthrough‐inducing agents would require several favourable conditions including PTC nucleotide context, intrinsic and induced stability of mRNA and correct synthesis of a full‐length active protein. Copyright © 2007 John Wiley & Sons, Ltd.
Efficient targeted transduction of primary human endothelial cells with dual‐targeted lentiviral vectors
Authors: Pariente Nonia , Mao Si‐Hua , Morizono Kouki , Chen Irvin S. Y.
Published: December 2007

Angiogenesis is a rate‐limiting factor for numerous human diseases. Angiogenic vessels and also the endothelium of certain organs such as the lung display molecular addresses that can be exploited for the selective delivery of gene therapeutics. Lentiviral vectors (LVs) are powerful tools for stable gene delivery but their integration and expression in undesired cell types poses a serious safety concern. We have developed a dual‐targeted LV that can specifically target primary endothelial cells (ECs). Cell selectivity is achieved during entry, using a modified Sindbis virus envelope, and during transcription, with an EC‐specific promoter. We evaluated four surface markers for EC targeting and seven promoter sequences from genes preferentially expressed in ECs. The efficiency and specificity of the double targeted vector were assayed in a panel of human primary cultures and tumor cell lines. A vector targeted to CD146, an endothelial adhesion molecule, and carrying a derivative of the EC tyrosine kinase Tie2 promoter, increased specificity of transduction up to 50 times and was also effective at selectively transducing ECs in a mixed coculture with human fibroblasts. The vector presented here is a potentially powerful tool that could be used in a variety of human diseases. Copyright © 2007 John Wiley & Sons, Ltd.
Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin
Authors: Kaczur Viktoria , Puskas Laszlo. G. , Nagy Zsuzsanna U. , Miled Nabil , Rebai Ahmed , Juhasz Ferenc , Kupihar Zoltan , Zvara Agnes , Hackler Laszlo , Farid Nadir R.
Published: December 2007

The thyrotropin receptor (TSHR) has a unique 50 residue (317–366) ectodomain insertion that sets it apart from other glycoprotein hormone receptors (GPHRs). Other ancient members of the leucine‐rich repeat G protein‐coupled receptor (GPCR) (LGR) family do exhibit ectodomain insertions of variable lengths and sequences. The TSHR‐specific insert is digested, apparently spontaneously, to release the ectodomain (A‐subunit) leaving the balance of the ectodomain attached to the serpentine (B‐subunit). Despite concerted efforts for the last 12 years by many laboratories, the enzyme involved in TSHR cleavage has not been identified and a physiologic role for this process remains unclear. Several lines of evidence had suggested that the TSHR protease is likely a member of the a disintegrin and metalloprotease (ADAM) family of metalloproteases. We show here that the expression of ADAM10 was specific to the thyroid by specially designed DNA microarrays. We also show that TSH increases TSHR cleavage in a dose‐dependent manner. To prove that ADAM10 is indeed the TSHR cleavage enzyme, we investigated the effect of TSH‐induced cleavage by a peptide based on a motif (TSHR residues 334–349), shared with known ADAM10 substrates. TSH increased dose dependently TSHR ectodomain cleavage in the presence of wild‐type peptide but not a scrambled control peptide. Interestingly, TSH increased the abundance of non‐cleaved single chain receptor, as well higher molecular forms of the A‐subunit, despite their enhancement of the appearance of the fully digested A‐subunit. This TSH‐related increase in TSHR digested forms was further increased by wild‐type peptide. We have identified for the first time ADAM10 as the TSHR cleavage enzyme and shown that TSH regulates its activation. Copyright © 2007 John Wiley & Sons, Ltd.
Different factors promote axonal regeneration of adult rat retinal ganglion cells after lens injury and intravitreal peripheral nerve grafting
Authors: Lorber Barbara , Berry Martin , Logan Ann
Published: December 2007

We have investigated the differential mediators of the neurotrophic effects of intravitreal peripheral nerve grafting and lens injury on adult rat retinal ganglion cells (RGC). Lens injury and intravitreal peripheral nerve grafting both stimulated RGC neurite growth in vitro and axon regeneration past the optic nerve lesion site in vivo concomitant with activation of retinal glia and invasion of macrophages into the eye. These observations, together with the results of coculture studies using a macrophage‐free intact peripheral nerve segment, a macrophage‐free intact lens, a macrophage‐rich peripheral nerve segment, or a macrophage‐rich injured lens in retinal cultures suggest that the stimulation of RGC axon regeneration by lens injury and intravitreal peripheral nerve grafting share a common macrophage‐derived component overlain by distinct lens‐derived and peripheral nerve‐derived neurotrophic factors, respectively. RGC axon regeneration following lens injury and intravitreal peripheral nerve grafting was similar in vivo, correlating with similar retinal glia activation whereas, in vitro, the level of RGC neurite outgrowth was significantly higher following intravitreal peripheral nerve grafting compared with lens injury, concomitant with the presence of increased numbers of activated retinal glia. This suggests that in vivo RGC axon regeneration induced by lens injury and peripheral nerve grafting may be limited, in part, by factors derived from activated retinal glia. © 2007 Wiley‐Liss, Inc.
Neuroprotective effects of prostaglandin A1in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation
Authors: Zhang Hui‐Ling , Gu Zhen‐Lun , Savitz Sean I. , Han Feng , Fukunaga Kohji , Qin Zheng‐Hong
Published: December 2007

We have previously reported that prostaglandin A1(PGA1) reduces infarct size in rodent models of focal ischemia. This study seeks to elucidate the possible molecular mechanisms underlying PGA1's neuroprotective effects against ischemic injury. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. PGA1was injected intracerebroventricularly (icv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in IκBα, pIKKα, and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ). Immunohistochemistry was used to confirm the nuclear translocation of nuclear factor‐κB (NF‐κB) p65 and the expression of PPAR‐γ. RT‐PCR was used to detect levels of c‐Myc mRNA. The contribution of PPAR‐γ to PGA1's neuroprotection was evaluated by pretreatment with the PPAR‐γ irreversible antagonist GW9662. A brief increase in pIKKα levels and rapid reduction in IκBα were observed after ischemia. PGA1blocked ischemia‐induced increases in pIKKα levels and reversed the decline in IκBα levels. Ischemia‐induced nuclear translocation of NF‐κB p65 was attenuated by PGA1. PGA1also repressed the ischemia‐induced increase in expression of NF‐κB target gene c‐Myc mRNA. Immunohistochemistry demonstrated an increase in PPAR‐γ immunoreactivity in the nucleus of striatal cells at 3 hr after pMCAO. Western blot analysis revealed that the expression of PPAR‐γ protein significantly increased at 12 hr and peaked at 24 hr. PGA1enhanced the ischemia‐triggered induction of PPAR‐γ protein. Pretreatment with the irreversible PPAR‐γ antagonist GW9662 attenuated PGA1's neuroprotection against ischemia. These findings suggest that PGA1‐mediated neuroprotective effect against ischemia appears to be associated with blocking NF‐κB activation and likely with up‐regulating PPAR‐γ expression. © 2007 Wiley‐Liss, Inc.
Real options and real strategies
Authors: Zarkos Stefanos , Morgan Robert E. , Kouropalatis Yiannis
Published: December 2007

The formulation of strategic plans within the real options framework promotes flexibility and provides an answer to critics of conventional strategic planning who argue that the deterministic and inflexible nature of that process might leave managers ill‐prepared to cope with uncertainty.

Although the merits of adopting real options as a way of thinking on a theoretical level are well documented, little, if any, guidance is given on how the proposed theoretical framework can actually be put into action by management to produce more flexible strategic plans.

This paper attempts to incorporate the real options framework into existing strategic tools that are widely used by managers such as SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis.

Copyright © 2007 John Wiley & Sons, Ltd.
Facilitating change: the role of educators as change agents
Authors: Dexter Barbara , Prince Christopher
Published: December 2007

Derby City Council and the Derbyshire Business School have worked closely together in the creation and evolution of a management and leadership development programme entitled the Leading Manager Programme. This followed the aim of the Council to improve middle manager leadership, to promote change across the Council and to gain ‘excellent’ status at its next audit. Recent research has shown that the Leading Managers are making an impact at organizational level, but that there are identified barriers that limit the level and extent of change within the organization. This paper explores the role of the educator as an agent of change in seeking to unlock the potential of the individual and so enhance and support organizational change.

Copyright © 2007 John Wiley & Sons, Ltd.
Skills Evaluator: a multicriteria decision support system for the evaluation of qualifications and skills in Information and Communication Technologies
Authors: Anestis George , Grigoroudis Evangelos , Krassadaki Evangelia , Matsatsinis Nikolaos F. , Siskos Yannis
Published: December 2007

Employees need to acquire new qualifications throughout their lives in order to deal with the multiple changes in the labour market. This knowledge and competences (formally or non‐formally acquired) must be identified and evaluated. For that reason, an integrated approach to the evaluation of Information and Communication Technology knowledge and skills is proposed. The multicriteria method that has been developed refers to professionals who wish to be accredited in a particular specialization through the evaluation of their professional experience, studies and vocational training. The aim of this paper is to present the multicriteria decision support system, Skills Evaluator, which brings into effect the aforementioned method. Copyright © 2007 John Wiley & Sons, Ltd.
Multi‐criteria evaluation of climate policy interactions
Authors: Konidari Popi , Mavrakis Dimitrios
Published: December 2007

The effectiveness of a national climate policy instrument is affected by the presence of policy interactions with other instruments that were not forecasted before its implementation. The problem can be confronted during the design of the instrument by determining forms, types and size of emerging interactions. This paper presents a systematic approach for evaluating the aggregate effect of interactions using a combination of three multi‐criteria methods, the analytical hierarchy process, the multi‐attribute utility theory and the Simple Multi‐Attribute Ranking Technique. The first is used for determining the weight coefficients for interaction forms and sub‐criteria. The other two are used for grading policy interactions under a set of three criteria and their sub‐criteria. The method is tested for two pairs of interactive instruments, IPPC and EU‐ETS, EU‐ETS and policies for the promotion of RES, within the Hellenic climate policy framework. Consistency and robustness tests are performed. Results are commented. Copyright © 2007 John Wiley & Sons, Ltd.
A multiple‐criteria decision‐making approach for the evaluation of retail location
Authors: Burnaz Sebnem , Topcu Y. Ilker
Published: December 2007

This study proposes an ANP‐based evaluation of retail locations. Authors acted as decision analysts and interacted with professionals in Turkish apparel retailing sector for acquiring their knowledge and expertise. As a result, evaluation criteria of the study were identified. These criteria are clustered into five groups: store, other retailers, shopping centre/business district, accessibility, and environmental. The relationship among criteria were assessed and a network was formed. ANP approach was then utilized in order to evaluate possible retail locations for the apparel stores. Besides global preferences of these alternatives, relative importance of the criteria was also revealed. Copyright © 2007 John Wiley & Sons, Ltd.
Combining scenario planning and multi‐criteria decision analysis in practice
Authors: Montibeller Gilberto , Gummer Haidee , Tumidei Daniele
Published: December 2007

The integrated use of scenario planning and multi‐criteria decision analysis (MCDA) has been advocated as a powerful combination for providing decision support in strategic decisions. Scenario planning helps decision makers in devising strategies and thinking about possible future scenarios; while MCDA can support an in‐depth performance evaluation of each strategy, as well as in the design of more robust and better options. One of the frameworks proposed recently, by Goodwin & Wright, suggests the use of scenario planning with multi‐attribute value theory, a mathematically simple, yet extensively researched and widely employed multi‐criteria method. However, so far, such framework has been presented only using hypothetical problems. In this paper, we describe two case studies where this approach was used to support real‐world strategic decisions. We discuss the challenges and limitations we encountered in applying it and suggest some possible improvements that could be made to such framework. Copyright © 2007 John Wiley & Sons, Ltd.
Planning a reader‐oriented strategy for a publishing company: a case study
Authors: Alexopoulos S. , Siskos Y. , Tsotsolas N.
Published: December 2007

Scientific research in the sector of press readability and specifically magazines is not particularly extensive. This paper suggests a framework for the development of strategic decisions based on reader satisfaction measurements. The methodology is illustrated through a real‐world application, i.e. customer‐oriented strategy planning for the leading monthly IT magazine in Greece. This study implements the MUSA (Multicriteria Satisfaction Analysis) method to evaluate reader satisfaction, in order to support the editor in making decisions while planning his editorial strategy. Reader satisfaction was analysed based on a tree containing seven main criteria and 32 sub‐criteria. Readers proved to be very satisfied and non‐demanding, which results in narrower margins for efficient improvement suggestions. However, the evaluation of the MUSA results led to putting forward suggestions that could support the editor in making amendment decisions. Some of these suggestions were successfully implemented within the scope of a new strategy. This revealed the need for two separate editions, an IT magazine for pupils and students as well as an IT magazine focused on women. The decision maker received suggestions on what these new publications' features should be, deriving from the study's quantitative results. Copyright © 2007 John Wiley & Sons, Ltd.
Medication adherence and associated outcomes in medicare health maintenance organization‐enrolled older adults with Parkinson's disease
Authors: Kulkarni Amit S. , Balkrishnan Rajesh , Anderson Roger T. , Edin Heather M. , Kirsch Jeff , Stacy Mark A.
Published: December 2007

Maintenance of symptom control in Parkinson's disease (PD) requires continuous titration of medication and addition of multiple therapies over the course of the disease. Adherence to medication is vital to symptom control and key to maximizing the efficacy of existing therapies. However, adherence is compromised by a variety of factors, including motor symptoms, complex dosing regimens, multiple medications, and lack of patient/physician awareness of the impact and prevalence of suboptimal adherence. This retrospective, longitudinal cohort study assessed the prevalence of suboptimal adherence [measured as the medication possession ratio (MPR)] to PD medications, and its impact on the worsening of PD symptoms (measured as increase in monotherapy dose, augmentation of therapy, PD‐related emergency department visit, or hospitalization), in a Medicare Health Maintenance Organization population in the United States. Irrespective of the MPR threshold chosen, a high percentage of patients were categorized as suboptimally adherent to their PD medications, and patients with suboptimal adherence to their PD medications had higher risks of worsening of PD symptoms, compared with those who were adherent. Increased awareness of both the magnitude and impact of suboptimal adherence to PD medications, coupled with dosage simplification and a unified effort by healthcare professionals and patients, may improve adherence to PD medications and ultimately improve symptom control. © 2007 Movement Disorder Society
Prolonged cortical silent period but normal sensorimotor plasticity in spinocerebellar ataxia 6
Authors: Teo James T.H. , Schneider Susanne A. , Cheeran Binith J. , Fernandez‐del‐Olmo Miguel , Giunti Paola , Rothwell John C. , Bhatia Kailash P.
Published: December 2007

Spinocerebellar ataxia 6 (SCA6) is a hereditary disease characterized by a trinucleotide repeat expansion in the CACNA1A gene and late‐onset bilateral cerebellar atrophy. It is unclear if there is significant pathology outside of the cerebellum. We used transcranial magnetic stimulation to assess sensorimotor cortical circuits and cortical plasticity in 8 SCA6 patients and 8 age‐matched controls. Behavioral performance was assessed using a rhythmic tapping task. Neurophysiological measures of SCA6 patients showed a prolonged cortical silent period (CSP) but normal MEP recruitment curve, short‐latency afferent inhibition, long‐latency afferent inhibition and ipsilateral silent period. Paired‐associative stimulation induction also increased motor‐evoked potentials normally. SCA6 patients had greater variability with cued rhythmic tapping than normals and deteriorated when the cue was removed; in comparison, normal subjects had similar variability between cued and uncued rhythmic tapping. Analysis using a Wing–Kristofferson timing model indicated that both clock variance and motor delay variance were abnormal. Conclusion. In SCA6, the circuits for sensorimotor integration and the mechanisms for LTP‐like plasticity in the sensorimotor cortex are unimpaired. A prolonged CSP in SCA6 just like in other cerebellar atrophies would suggest that this neurophysiological change typifies cerebellar dysfunction. © 2007 Movement Disorder Society
Predictors of deterioration in health‐related quality of life in Parkinson's disease: Results from the DATATOP trial
Authors: Marras Connie , McDermott Michael P. , Rochon Paula A. , Tanner Caroline M. , Naglie Gary , Lang Anthony E. ,   Parkinson Study Group DATATOP Investigators
Published: December 2007

The aim of this study was to investigate factors associated with decline in health‐related quality of life in Parkinson's disease, by a retrospective cohort study from referral centers in Canada and the United States. Subjects were patients with early Parkinson's disease (N = 362) enrolled in a clinical trial of deprenyl (selegiline) and tocopherol (DATATOP) and followed prospectively. The main outcome measure was change in health‐related quality of life using SF‐36 Mental and Physical Component Summary scores. The mean interval between SF‐36 measurements was 1.7 ± 0.1 years, beginning 5 to 6 years after enrolment into the trial. In multivariable analysis, baseline Hamilton Depression Scale scores and self‐rated cognitive function were associated with subsequent decline in Physical Component Summary scores, while older age and Schwab and England activities of daily living scores were associated with decline in Mental Component Summary scores. The Postural Instability Gait Disorder score was the only variable found to decline concurrently with HRQOL. Our results suggest that depression, self‐rated cognitive function, and one's degree of functional independence are predictors of subsequent changes in HRQOL. Our focus in clinical care needs to be broadened beyond assessing and treating Parkinsonism, recognizing the impact of mood, cognition and function on HRQOL. © 2007 Movement Disorder Society
A validation study of depressive syndromes in Parkinson's disease
Authors: Starkstein Sergio E. , Merello Marcelo , Jorge Ricardo , Brockman Simone , Bruce David , Petracca Gustavo , Robinson Robert G.
Published: December 2007

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinson's disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM‐IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self‐esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM‐IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM‐IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM‐IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation. © 2007 Movement Disorder Society
Clinical characteristics of restless legs syndrome in end‐stage renal failure and idiopathic RLS patients
Authors: Enomoto Minori , Inoue Yuichi , Namba Kazuyoshi , Munezawa Takashi , Matsuura Masato
Published: December 2007

This study was done to identify the clinical characteristics of uremic restless legs syndrome (RLS). Consecutive uremic RLS patients (n = 15) and idiopathic RLS patients (iRLS; n = 20) were evaluated. The groups were compared with respect to their clinical course, subjective symptoms [using the Pittsburgh Sleep Quality Index (PSQI) and the International Restless Legs Syndrome Severity Scale (IRLS)], polysomnographic (PSG) variables, the results of the suggested immobilization test (SIT), and the drug doses used to treat RLS. The duration of the disorder was significantly shorter in the uremic RLS group than in the iRLS group. The PSQI and IRLS scores before treatment were higher in the uremic RLS group than in the iRLS group. The periodic leg movement index (PLM index) on PSG and the SIT index were also higher in the uremic RLS group (P < 0.001, respectively). The bromocriptine equivalent dose of dopaminergic agonists used to treat RLS was significantly higher in the uremic RLS group (P < 0.001). Uremic RLS appears to deteriorate faster and to become more severe than iRLS. Moreover, uremic RLS patients appear to have a decreased response to dopaminergic agonists. © 2007 Movement Disorder Society
Exacerbation of blepharospasm associated with craniocervical dystonia after placement of bilateral globus pallidus internus deep brain stimulator
Authors: Reza Vagefi M. , Cheng Lin Chun , McCann John D. , Anderson Richard L.
Published: December 2007

To report a case of exacerbation of blepharospasm after bilateral globus pallidus internus (GPi) deep brain stimulator (DBS) placement. A 69‐year‐old male presented after bilateral GPi DBS placement for blepharospasm and craniocervical dystonia with worsening eyelid spasms and associated apraxia of lid opening (ALO). Numerous attempts to adjust DBS parameters were ineffective. Consequently, bilateral upper eyelid myectomy was performed. Myectomy surgery was free of complications. The patient had significant improvement of blepharospasm and ALO. Although early success has been reported with DBS placement in a small number of patients with focal dystonias, further studies and longer follow‐up are needed to demonstrate whether this will prove to be a useful approach in the treatment of blepharospasm. Upper eyelid myectomy can provide an effective means for treating blepharospasm and associated ALO. © 2008 Movement Disorder Society
Glucocerebrosidase gene mutations are associated with Parkinson's disease in southern Italy
Authors: De Marco Elvira V. , Annesi Grazia , Tarantino Patrizia , Rocca Francesca E. , Provenzano Giovanni , Civitelli Donatella , Cirò Candiano Innocenza C. , Annesi Ferdinanda , Carrideo Sara , Condino Francesca , Nicoletti Giuseppe , Messina Demetrio , Novellino Fabiana , Morelli Maurizio , Quattrone Aldo
Published: December 2007

Recent studies have reported an association between the glucocerebrosidase (GBA) gene and Parkinson's disease (PD). To elucidate the role of this gene in our population, we screened 395 PD patients and 483 controls from southern Italy for the N370S and the L444P mutations. We found 11 patients (2.8%) carrying a heterozygous mutant GBA allele, whereas only one control subject (0.2%) had a heterozygous substitution (P = 0.0018). These results strongly suggest that Italian carriers of a GBA mutation have an increased risk of developing PD. © 2007 Movement Disorder Society
The treatment of displaced femoral neck fractures with vascularized great trochanter periosteal flap transposition in children
Authors: Qi Baiwen , Yu Aixi , Zhang Gongli , Yu Guorong , Shi Yongyan , Zhu Shaobo , Pan Zhenyu
Published: December 2007

In this study, we investigated the clinical outcome of the treatment of displaced femoral neck fractures with vascularized great trochanter periosteal flap transposition in children. There were 23 children with displaced femoral neck fractures. Using Delbet classification, there were 2 type I (transepiphyseal), 12 type II (transcervical), and 9 type III (cervicotrochanteric). All the treatments were carried out with vascularized great trochanter periosteal flap transposition, and fixed by Kirschner needle or hollow screws. Both methods achieved healing and patients were followed from 9 months to 5 years, with average follow‐up of 3 years. Avascular necrosis (AVN) of the femoral head occurred in three children; early closure of epiphysis occurred in one child; and restricted movement was seen in three children. According to Ratliff function assessment and Harris hip score, the results were: 17 excellent, 3 good, and 3 poor. The excellent and good rates reached 87.1%. The vascularized greater trochanter periosteal flap transposition may accelerate the union of fractures, improve blood supply to the femoral head, and reduce the incidence rate of AVN. This flap is therefore an effective method for the treatment of displaced femoral neck fractures in children. © 2007 Wiley‐Liss, Inc. Microsurgery, 2008.
Xenobiotic activity in serum and sperm chromatin integrity in European and inuit populations
Authors: Krüger Tanja , Spanò Marcello , Long Manhai , Eleuteri Patrizia , Rescia Michele , Hjelmborg Philip S. , Manicardi Gian‐Carlo , Bizzaro Davide , Giwercman Alexander , Toft Gunnar , Bonde Jens Peter , Bonefeld‐Jorgensen Eva C.
Published: December 2007

Lipophilic persistent organic pollutants (POPs) are ubiquitous in the environment and suspected to interfere with hormone activities and reproduction. In previous studies we demonstrated that POP exposure can affect sperm DNA integrity and differences between Inuits and Europeans in sperm DNA integrity and xenobiotic activity were observed. The aim of this study was to investigate possible relations between human sperm chromatin integrity and the xenobiotic serum activity of lipophilic POPs assessed as effects on the estrogen (ER), androgen (AR), and/or aryl hydrocarbon (AhR) receptors. Human sperm chromatin integrity was assessed as DNA fragmentation index (%DFI) and high DNA stainability (%HDS) using the flow cytometric sperm chromatin structure assay (SCSA). Xenobiotic receptor activities were determined using chemically activated luciferase gene expression (CALUX) assay. The study included 53 Greenlandic Inuits and 247 Europeans (Sweden, Warsaw (Poland) and Kharkiv (Ukraine)). A heterogeneous pattern of correlations was found. For Inuits, ER and AhR activities and %DFI were inversely correlated, whereas a positive correlation between AR activity and %DFI was found for Europeans. In contrast, no correlation between receptor activities and %HDS was observed for Inuits but for Europeans positive and negative correlations were observed between ER and AR activities and %HDS, respectively. We suggest that the different patterns of xenobiotic serum activities, in combination with diet associated factors and/or genetics, might be connected to the observed differences in sperm chromatin integrity between the Inuits and Europeans. Mol. Reprod. Dev. 75: 669–680, 2008. © 2007 Wiley‐Liss, Inc.
Impact of breast cancer diagnosis and treatment on women's sexuality: a survey of Japanese patients
Authors: Takahashi Miyako , Ohno Shinji , Inoue Hiromichi , Kataoka Akemi , Yamaguchi Hiroshi , Uchida Yoko , Oshima Akira , Abiru Kinuko , Ono Kikuyo , Noguchi Rie , Kai Ichiro
Published: December 2007

Objective: Research on the impact of breast cancer on Asian women's sexual lives is extremely scarce. This study investigated the sexual changes experienced by breast cancer patients in Japan following surgery, and their sexuality‐related information needs.

Methods: An anonymous, cross‐sectional survey of breast cancer out‐patients was conducted in 2005. Data from 85 subjects, who were without recurrence and reported being sexually active pre‐surgery, were analyzed.

Results: Subjects were mainly in their 40's and 50's, and the median time since surgery was 43 months. Seventy‐three (85.9%) had resumed sex after surgery with the median time being 3.5 months after surgery. Among 73 who resumed sex, 43 reported that the frequency of sex decreased, and 72 reported at least one sexually related change. The multiple logistic regression analysis revealed that those who had perceived the sexual relationship with their partner important before surgery (OR, 6.705; 95%CI, 1.320–34.051; p = 0.022) were more likely to maintain the same frequency of sex as before surgery. Perceived changes in respondents' sexual relationship did not necessarily result in deterioration of the couple's overall relationship. Regarding sexuality‐related information needs, respondents wished to have information on treatment‐induced sexual changes as well as sexual and general inter‐couple communication strategies.

Conclusion: This research revealed that breast cancer patients in Japan experience various sexual problems following breast cancer treatment. Sexuality‐related information should be provided to all patients, regardless of patients age or type of surgery, as a part of routine treatment information giving. Copyright © 2007 John Wiley & Sons, Ltd.
Tissue expression and enzymologic characterization of human prostate specific membrane antigen and its rat and pig orthologs
Authors: Rovenská Miroslava , Hlouchová Klára , Šácha Pavel , Mlčochová Petra , Horák Vratislav , Zámečník Josef , Bařinka Cyril , Konvalinka Jan
Published: December 2007

BACKGROUND

Prostate specific membrane antigen (PSMA), also called glutamate carboxypeptidase II (GCPII), is a target enzyme for diagnosis and treatment of prostate cancer. Moreover, it is upregulated in the vasculature of most solid tumors and is therefore a potential target for the generation of novel antineoplastics. In this context, we analyze the possibility of using rat and pig as animal models for enzymologic and in vivo studies.

METHODS

We prepared the recombinant extracellular part of human, rat, and pig GCPII in S2 cell media and characterized the activity and inhibition profiles of the three orthologs by radioenzymatic assay. We performed Western blot analysis of GCPII expression in human, rat, and pig tissues using the monoclonal antibody GCP‐04 and confirmed these findings by activity measurements and immunohistochemistry.

RESULTS

The three recombinant proteins show similar specific enzymatic activities and inhibition profiles. Tissue expression analysis revealed that most of the pig and human tissues show at least some GCPII‐positivity, while the expression pattern in rat is more restricted. Moreover, tissues such as prostate and testes exhibit different GCPII expression levels among the species studied.

CONCLUSIONS

The rat and pig orthologs of GCPII seem to be suitable to approximate human GCPII in enzymologic studies. However, the diffuse expression pattern of GCPII in animal and human tissues could be a caveat for the potential utilization of GCPII‐targeted anticancer drugs. Furthermore, variations in GCPII tissue distribution among the species studied should be considered when using rat or pig as models for antineoplastic drug discovery. Prostate 68: 171–182, 2008. © 2007 Wiley‐Liss, Inc.
The C‐terminal region of thermophilic tRNA (m7G46) methyltransferase (TrmB) stabilizes the dimer structure and enhances fidelity of methylation
Authors: Tomikawa Chie , Ochi Anna , Hori Hiroyuki
Published: December 2007

Transfer RNA (m7G46) methyltransferase catalyzes methyl‐transfer from S‐adenosyl‐L‐methionine to N7 atom of the semi‐conserved G46 base in tRNA. Aquifex aeolicus is a hyper thermophilic eubacterium that grows at close to 95°C. A. aeolicus tRNA (m7G46) methyltransferase [TrmB] has an elongated C‐terminal region as compared with mesophilic counterparts. In this study, the authors focused on the functions of this C‐terminal region. Analytic gel filtration chromatography and amino acid sequencing reveled that the start point (Glu202) of the C‐terminal region is often cleaved by proteases during purification steps and the C‐terminal region tightly binds to another subunit even in the presence of 6M urea. Because the C‐terminal region contains abundant basic amino acid residues, the authors assumed that some of these residues might be involved in tRNA binding. To address this idea, the authors prepared eight alanine substitution mutant proteins. However, measurements of initial velocities of these mutant proteins suggested that the basic amino acid residues in the C‐terminal region are not involved in tRNA binding. The authors investigated effects of the deletion of the C‐terminal region. Deletion mutant protein of the C‐terminal region (the core protein) was precipitated by incubation at 85°C, while the wild type protein was soluble at that temperature, demonstrating that the C‐terminal region contributes to the protein stability at high temperatures. The core protein had a methyl‐transfer activity to yeast tRNAPhe transcript. Furthermore, the core protein slowly methylated tRNA transcripts, which did not contain G46 base. Moreover, the modified base was identified as m7G by two‐dimensional thin layer chromatography. Thus, the deletion of the C‐terminal region causes nonspecific methylation of N7 atom of guanine base(s) in tRNA transcripts. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Distant homology detection using a LEngth and STructure‐based sequence Alignment Tool (LESTAT)
Authors: Lee Marianne M. , Bundschuh Ralf , Chan Michael K.
Published: December 2007

A new machine learning algorithm, LESTAT (LEngth and STructure‐based sequence Alignment Tool) has been developed for detecting protein homologs having low‐sequence identity. LESTAT is an iterative profile‐based method that runs without reliance on a predefined library and incorporates several novel features that enhance its ability to identify remote sequences. To overcome the inherent bias associated with a single starting model, LESTAT utilizes three structural homologs to create a profile consisting of structurally conserved positions and block separation distances. Subsequent profiles are refined iteratively using sequence information obtained from previous cycles. Additionally, the refinement process incorporates a “lock‐in” feature to retain the high‐scoring sequences involved in previous alignments for subsequent model building and an enhancement factor to complement the weighting scheme used to build the position specific scoring matrix. A comparison of the performance of LESTAT against PSI‐BLAST for seven systems reveals that LESTAT exhibits increased sensitivity and specificity over PSI‐BLAST in six of these systems, based on the number of true homologs detected and the number of families these homologs covered. Notably, many of the hits identified are unique to each method, presumably resulting from the distinct differences in the two approaches. Taken together, these findings suggest that LESTAT is a useful complementary method to PSI‐BLAST in the detection of distant homologs. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The point mutation A34F causes dimerization of GB1
Authors: Jee JunGoo , Byeon In‐Ja L. , Louis John M. , Gronenborn Angela M.
Published: December 2007

The immunoglobulin‐binding domain B1 of streptococcal protein G (GB1), a very stable, small, single‐domain protein, is one of the most extensively used models in the area of protein folding and design. Variants derived from a library of randomized hydrophobic core residues previously revealed alternative folds, namely a completely intertwined tetramer (Frank et al., Nat Struct Biol 2002;9:877–885) and a domain‐swapped dimer (Byeon et al., J Mol Biol 2003;333:141–152). Here, we report the NMR structure of the single amino acid mutant Ala‐34‐Phe which exists as side‐by‐side dimer. The dimer dissociation constant is 27 ± 4 μM. The dimer interface comprises two structural elements: First, the β‐sheets of the two monomers pair in an antiparallel arrangement, thereby forming an eight‐stranded β‐sheet. Second, the α‐helix is shortened, ending in a loop that engages in intermolecular contacts. The largest difference between the monomer unit in the A34F dimer and the monomeric wild‐type GB1 is the dissolution of the C‐terminal half of the α‐helix associated with a pronounced slow conformational motion of the interface loop. This involves a large movement of the Tyr‐33 side chain that swings out from the monomer to engage in dimer contacts. Proteins 2008. © 2007 Wiley‐Liss, Inc.