bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury
Authors: Dell'Accio Francesco , De Bari Cosimo , El Tawil Noha MF , Barone Francesca , Mitsiadis Thimios A , O'Dowd John , Pitzalis Costantino 
Published: August 2006

AbstractAcute full thickness joint surface defects can undergo repair, which involves tissue patterning and endochondral bone formation. Molecular signals regulating this process may contribute to the repair outcome, chronic evolution and, eventually, the onset of osteoarthritis. We tested the hypothesis that mechanical injury modulates morphogenetic pathways in adult human articular cartilage explants. Adjacent articular cartilage explants were obtained from preserved areas of the femoral condyles of patients undergoing arthroplasty for osteoarthritis, or from a normal joint of a patient undergoing lower limb amputation. Paired explants were individually maintained in explant culture. From each pair, one explant was mechanically injured and the other left uninjured as a control. Cultures were terminated at different time points for histochemistry, immunohistochemistry and gene expression analysis by reverse transcription real time PCR. Bone morphogenetic protein 2 (BMP-2) mRNA was upregulated in the injured explants. We detected phosphorylation of SMAD-1 and SMAD-5, consistent with activation of the bone morphogenetic protein (BMP) pathway. FRZB-1 mRNA was downregulated in the injured explants, suggesting de-repression of WNT signaling. Accordingly, expression of the canonical WNT target genes Axin-2 and c-JUN was upregulated in the injured explants. Activation of the canonical WNT signaling pathway by LiCl treatment induced upregulation of COL2A1 and Aggrecan mRNA, suggesting an anabolic effect. Phosphorylation of SMAD-1/-5 and downregulation of FRZB were confirmed in vivo in a mouse model of joint surface injury. Taken together, these data show modulation of the BMP and WNT pathways following mechanical injury in vitro and in vivo, which may play a role in the reparative response of the joint surface. These pathways may, therefore, represent potential targets in protocols of biological joint surface defect repair.
Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis
Authors: Appel Heiner , Loddenkemper Christoph , Grozdanovic Zarko , Ebhardt Harald , Dreimann Marc , Hempfing Axel , Stein Harald , Metz-Stavenhagen Peter , Rudwaleit Martin , Sieper Joachim 
Published: August 2006

AbstractAnkylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI.
In vitrosynergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells
Authors: Ural A Ugur , Avcu Ferit , Candir Muhammed , Guden Metin , Ozcan M Ali 
Published: August 2006

AbstractIntroductionBisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells.MethodsHuman MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation.ResultsZoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis.ConclusionThese data constitute the firstin vitroevidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma.
Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets
Authors: Carvalho Alysson Roncally S , Jandre Frederico C , Pino Alexandre V , Bozza Fernando A , Salluh Jorge I , Rodrigues Rosana S , Soares João HN , Giannella-Neto Antonio 
Published: August 2006

Abstract
Introduction
Atelectasis and distal airway closure are common clinical entities of general anaesthesia. These two phenomena are expected to reduce the ventilation of dependent lung regions and represent major causes of arterial oxygenation impairment in anaesthetic conditions. The behaviour of the elastance of the respiratory system (Ers), as well as the lung aeration assessed by computed tomography (CT) scan, was evaluated during a descendent positive end-expiratory pressure (PEEP) titration. This work sought to evaluate the potential usefulness of Ers monitoring to set the PEEP in order to prevent tidal recruitment and hyperinflation of healthy lungs under general anaesthesia.

Methods
PEEP titration (from 16 to 0 cmH2O, tidal volume of 8 ml/kg) was performed, and at each PEEP, CT scans were obtained during end-expiratory and end-inspiratory pauses in six healthy, anaesthetized and paralyzed piglets. The distribution of lung aeration was determined and the tidal re-aeration was calculated as the difference between end-expiratory and end-inspiratory poorly aerated and normally aerated areas. Similarly, tidal hyperinflation was obtained as the difference between end-inspiratory and end-expiratory hyperinflated areas. Ers was estimated from the equation of motion of the respiratory system during all PEEP titration with the least-squares method.

Results
Hyperinflated areas decreased from PEEP 16 to 0 cmH2O (ranges decreased from 24–62% to 1–7% at end-expiratory pauses and from 44–73% to 4–17% at end-inspiratory pauses) whereas normally aerated areas increased (from 30–66% to 72–83% at end-expiratory pauses and from 19–48% to 73–77% at end-inspiratory pauses). From 16 to 8 cmH2O, Ers decreased with a corresponding reduction in tidal hyperinflation. A flat minimum of Ers was observed from 8 to 4 cmH2O. For PEEP below 4 cmH2O, Ers increased in association with a rise in tidal re-aeration and a flat maximum of the normally aerated areas.

Conclusion
In healthy piglets under a descending PEEP protocol, the PEEP at minimum Ers presented a compromise between maximizing normally aerated areas and minimizing tidal re-aeration and hyperinflation. High levels of PEEP, greater than 8 cmH2O, reduced tidal re-aeration but increased hyperinflation with a concomitant decrease in normally aerated areas.
In vitro modeling of the HIV-macrophage reservoir
Authors: Brown Amanda , Zhang Hao , Lopez Peter , Pardo Carlos A , Gartner Suzanne 
Published: August 2006

Abstract
Macrophages are recognized as a putative reservoir for HIV-1, but whether HIV can establish latent infection in this cell type is not known. An in vitro model using long-term cultured primary human monocyte-derived macrophages (MDM) infected with an M-tropic, enhanced green fluorescent protein (EGFP) tagged reporter virus was developed to test the hypothesis that HIV can establish a latent infection of this cell type. The EGFP-IRES-Nef cassette allowed detection of early gene transcription. The expression of GFP+ MDM was followed with time and the GFP- population was purified and analyzed for evidence of latent infection. Interestingly, in MDM cultures propagated for over two months, distinct subpopulations of infected GFP+ cells were observed and quantitated. In particular, infected MDM that displayed a high level of transcription, characterized as the GFP hi group, yet produced low levels of the late viral gene product, p24, increased with time and represented 10% of the GFP+ population in long-term cultures. The high level production of early genes such as Nef, a protein that can facilitate viral immune escape, but low level of structural proteins such as p24 in the GFP hi population suggests that a subset of infected MDM can exhibit an alternative mode of replication. The GFP- MDM population obtained by a two-step purification protocol using flow cytometry and laser ablation contained integrated provirus as assessed by Alu-LTR real-time PCR analyses. A subset of these, were replication competent as shown by their ability to express GFP and/or p24 antigen after reactivation with IL-4.
Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques
Authors: Kennedy Paul E , Bera Tapan K , Wang Qing-Cheng , Gallo Maria , Wagner Wendeline , Lewis Mark G , Berger Edward A , Pastan Ira 
Published: August 2006

Abstract
Highly active antiretroviral therapy (HAART) against human immunodeficiency virus type 1 (HIV-1) infection dramatically suppresses viral load, leading to marked reductions in HIV-1 associated morbidity and mortality. However, infected cell reservoirs and low-level replication persist in the face of suppressive HAART, leading invariably to viral rebound upon cessation of treatment. Toxins engineered to target the Env glycoprotein on the surface of productively infected cells represent a complementary strategy to deplete these reservoirs. We described previously highly selective killing of Env-expressing cell lines by CD4(178)-PE40 and 3B3(Fv)-PE38, recombinant derivatives of Pseudomonas aeruginosa exotoxin A containing distinct targeting moieties against gp120. In the present report, we compare the in vitro potency and breadth of these chimeric toxins against multiple clinical HIV-1 isolates, replicating in biologically relevant primary human target cell types. In PBMCs, 3B3(Fv)-PE38 blocked spreading infection by all isolates examined, with greater potency than CD4(178)-PE40. 3B3(Fv)-PE38 also potently inhibited spreading HIV-1 infection in primary macrophages. Control experiments demonstrated that in both target cell types, most of the 3B3(Fv)-PE38 activity was due to selective killing of infected cells, and not merely to neutralization by the antibody moiety of the chimeric toxin. High-dose treatment of rhesus macaques with 3B3(Fv)-PE38 did not induce liver toxicity, whereas equivalent dosage of CD4(178)-PE40 induced mild hepatotoxicity. These findings highlight the potential use of 3B3(Fv)-PE38 for depleting HIV-infected cell reservoirs persisting in the face of HAART.
Retroviral E-DNA: persistence and gene expression in nondividing immune cells
Authors: Cara Andrea , Klotman Mary E 
Published: August 2006

Abstract
Following retroviral infection of cells, not only is the proviral DNA integrated into the host genome, but there is also an accumulation of unintegrated extrachromosomal DNA (E-DNA), both linear and circular. Although the integrated DNA is responsible for the production of viral proteins and new viral progeny, the role of E-DNA has remained uncertain. Several reports have shown that E-DNA is transcriptionally active producing both RNA, as well as viral proteins and that circular E-DNA can persist in nondividing cells, raising questions regarding the potential consequences of this reservoir. Furthermore, integrase inhibitors, presently in clinical trials, shifts the balance of proviral DNA to the E-DNA form. This review is focused on recent work in this field with an emphasis on exploring the potential role of E-DNA in both pathogenesis of retroviral infections, especially HIV-1, and as a tool to deliver and express genes.
HIV interactions with dendritic cells: has our focus been too narrow?
Authors: Donaghy Heather , Wilkinson John , Cunningham Anthony L 
Published: August 2006

Abstract
Although few in number, dendritic cells (DCs) are heterogeneous, ubiquitous, and are crucial for protection against pathogens. In this review, the different DC subpopulations have been described and aspects of DC biology are discussed. DCs are important, not only in the pathogenesis of HIV, but also in the generation of anti-HIV immune responses. This review describes the roles that DC are thought to play in HIV pathogenesis, including uptake and transport of virus. We have also discussed the effects that the virus exerts on DCs such as infection and dysfunction. Then we proceed to focus on DC subsets in different organs and show how widespread the effects of HIV are on DC populations. It is clear that the small number of studies on tissue-derived DCs limits current research into the pathogenesis of HIV.
Sensitivity of a computer adaptive assessment for measuring functional mobility changes in children enrolled in a community fitness programme
Authors: Haley Stephen M , Fragala-Pinkham Maria , Ni Pengsheng 
Published: August 2006

Objective: To examine the relative sensitivity to detect functional mobility changes with a full-length parent questionnaire compared with a computerized adaptive testing version of the questionnaire after a 16-week group fitness programme. Design: Prospective, pre- and posttest study with a 16-week group fitness intervention. Setting: Three community-based fitness centres. Subjects: Convenience sample of children ( n = 28) with physical or developmental disabilities. Interventions: A 16-week group exercise programme held twice a week in a community setting. Main measures: A full-length (161 items) paper version of a mobility parent questionnaire based on the Pediatric Evaluation of Disability Inventory, but expanded to include expected skills of children up to 15 years old was compared with a 15-item computer adaptive testing version. Both measures were administered at pre- and posttest intervals. Results: Both the full-length Pediatric Evaluation of Disability Inventory and the 15- item computer adaptive testing version detected significant changes between pre and posttest scores, had large effect sizes, and standardized response means, with a modest decrease in the computer adaptive test as compared with the 161-item paper version. Correlations between the computer adaptive and paper formats across pre and posttest scores ranged from r = 0.76 to 0.86. Conclusions: Both functional mobility test versions were able to detect positive functional changes at the end of the intervention period. Greater variability in score estimates was generated by the computerized adaptive testing version, which led to a relative reduction in sensitivity as defined by the standardized response mean. Extreme scores were generally more difficult for the computer adaptive format to estimate with as much accuracy as scores in the mid-range of the scale. However, the reduction in accuracy and sensitivity, which did not influence the group effect results in this study, is counterbalanced by the large reduction in testing burden.
The effect of lifting and lowering an external load on repositioning error of trunk flexion-extension in subjects with and without low back pain
Authors: Lin Yang Hua , Sun Ming Hui 
Published: August 2006

Objective: To determine whether the repositioning error of trunk flexion-extension in individuals with low back pain is different from that in those not experiencing low back pain when lifting and lowering external loads. Design: A case-control study. Setting: Physical therapy department of a medical centre. Subjects: Twenty subjects with subacute low back pain and 20 control subjects without low back pain. Interventions: Tasks with and without lifting and lowering an external load. Main outcome measures: The trunk repositioning errors were measured with Measurand Shape Tape. Results: In subjects with low back pain, trunk repositioning errors were significantly reduced when lifting and lowering an external load in the direction of flexion (3.779 ±1.26 degrees in a loaded condition versus 4.82±2.97 degrees in an unloaded condition; P B< 0.05) and extension (3.17±2.15 degrees in a loaded condition versus 5.039±3.74 degrees in an unloaded condition; p < 0.05). In control subjects, trunk repositioning errors were not significantly changed when lifting and lowering an external load in the direction of flexion (2.80±1.39 degrees in a loaded condition versus 2.63±1.24 degrees in an unloaded condition; p < 0.05) and extension (2.87±1.40 degrees in a loaded condition versus 3.15±1.50 degrees in an unloaded condition; P>0.05). The direction of motion (trunk flexion or extension) was not shown to be significant in this study. Conclusion: Performing the task whilst lifting or lowering a submaximal load showed a reduced trunk repositioning error in subjects with subacute low back pain. Lifting and lowering a submaximal load might be considered as one of the rehabilitative strategies to hasten a return to work.
Evaluation of the Swedish version of the Modified Elderly Mobility Scale (Swe M-EMS) in patients with acute stroke
Authors: Linder Annika , Winkvist Lisa , Nilsson Lena , Sernert Ninni 
Published: August 2006

Objective: To investigate the inter-rater reliability and validity of the Swedish version of the Modified Elderly Mobility Scale (Swe M-EMS). Design: A correlation study. Setting: A stroke unit which provides acute care and rehabilitation for all stroke admissions in Northern Alvsborg County Hospital, Sweden. Subjects: Thirty consecutive patients with an acute first-time stroke. Seventeen were women and 13 were men, with a median age of 79 years (41-92) and with a median hospital stay of 21 days (8-35). Intervention: The patients were assessed twice with the Swe M-EMS on admission and at discharge, before and after midday, by two independent physiotherapists. They were assessed by an independent physiotherapist using the three evaluation instruments on admission, once a week during their hospital stay and at discharge. Main outcome measures: The primary evaluation instrument was the Swe M-EMS. The two other evaluation instruments were the Modified Motor Assessment Scale of Uppsala Akademiska Sjukhus-95 (M-MAS UAS-95) and the Berg Balance Scale (BBS). Results: The Swe M-EMS was a reliable instrument (ICC 0.98-0.99). It correlated well with both the M-MAS UAS-95 (rs=0.69-0.88) and the BBS (rs=0.86-0.94). The Swe M-EMS was sensitive to change over time, but the patients obtained the maximum score quickly. Conclusion: The instrument shows a high inter-rater reliability. The Swe M-EMS correlates well with both the M-MAS UAS-95 and the BBS and is sensitive to change. However, it is not sensitive enough to use as a single instrument in evaluating the improvement of a patient with acute stroke.
Effects of lower limb intensive mass practice in poststroke patients: single-subject experimental design with long-term follow-up
Authors: Marklund Ingela , Klässbo Maria 
Published: August 2006

Objective: To investigate the effects of two weeks of intensive mass practice with a constraint-induced movement therapy approach for the lower extremity in five chronic poststroke patients, and the persistence of effects at three and six months. Design: A single-subject experimental design (SSED) was used with an AB design and follow-ups three and six months later. Setting: Outpatient rehabilitation at Torsby Hospital in Sweden. Main measures: Motor function in lower extremity, mobility, dynamic balance, weight-bearing symmetry and walking ability were measured on six occasions during two weeks (A phase), with the Fugl-Meyer assessment for lower extremity, the Timed Up and Go, the Step Test, the Timed Walking Test and the Six-Minute Walk Test. During the intervention's B phase, six measurements were performed with the same time intervals as in the A phase. There were follow-ups three and six months later. Intervention: The intervention (B phase) consisted of bicycling, training in water, strength training, standing weight-bearing, walking up and down stairs, walking indoors and outdoors and flexibility training of the lower extremity, on all weekdays, 6 h a day for two weeks. Results: The results showed improvements in 23/30 variables (77%), 12 of them statistically significant (52%). At follow-up, 22/23 improvements persisted. For example, three of five subjects walked significantly further after the intervention and the follow-ups showed that they still walked further than before the intervention. Conclusion: Intensive mass practice with constraint-induced movement therapy for the lower extremity can improve motor function, mobility, dynamic balance, weight-bearing symmetry and walking ability in chronic poststroke patients.Long-term follow-up showed that the effects persisted for these five subjects.
Assessment of unilateral spatial neglect post stroke in Canadian acute care hospitals: are we neglecting neglect?
Authors: Menon-Nair Anita , Korner-Bitensky Nicol , Wood-Dauphinee Sharon , Robertson Elizabeth 
Published: August 2006

Objective: To estimate the prevalence, timing and frequency of use of standardized and non-standardized assessments to detect unilateral spatial neglect in acute care patients post stroke. Design and setting: Multicentred, retrospective study on medical charts from 10 randomly selected acute care hospitals in Ontario, Canada. Subjects: Three hundred and twenty-four randomly selected medical charts of adult subjects with a primary diagnosis of stroke admitted in 2002 to the participating acute care hospitals. Results: Out of 248 subjects who should have been assessed, 38% received some form of unilateral spatial neglect assessment. Only 13% were assessed with a standardized assessment and of these, 4% within 48 h post stroke or within 48 h of the patient regaining consciousness as recommended by clinical practice guidelines for stroke. Bivariate analysis found significant associations between severity of cognitive impairment and being ever assessed, as well as between the severity of motor deficits of the upper extremity and being ever assessed. Conclusion: Routine standardized assessment of unilateral spatial neglect during the acute care phase post stroke was not incorporated into daily practice in this study sample.