bluuebunny/crossref_metadata_2025 huggingface dataset:
Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report
Authors: McGibbon Chris A , Krebs David E , Parker Stephen W , Scarborough Donna M , Wayne Peter M , Wolf Steven L
Published: February 2005

Background

Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown.

Methods

We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity), were measured.

Results

Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship.

Conclusion

Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders.
Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis
Authors: Webb Meghan , Emberley Ethan D , Lizardo Michael , Alowami Salem , Qing Gefei , Alfia'ar Abdullah , Snell-Curtis Linda J , Niu Yulian , Civetta Alberto , Myal Yvonne , Shiu Robert , Murphy Leigh C , Watson Peter H
Published: February 2005

Background

The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis.

Methods

On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7.

Results

Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene.

Conclusion

These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.
Access to communication technologies in a sample of cancer patients: an urban and rural survey
Authors: Abdullah Ma'n , Theobald Dale E , Butler Donna , Kroenke Kurt , Perkins Anthony , Edgerton Sara , Dugan William M
Published: February 2005

Background

There is a growing awareness among providers of the symptom burden experienced by cancer patients. Systematic symptom screening is difficult. Our plan was to evaluate a technology-based symptom screening process using touch-tone telephone and Internet in our rural outreach cancer program in Indiana. Would rural patients have adequate access to technologies for home-based symptom reporting?

Objectives

1) To determine access to touch-tone telephone service and Internet for patients in urban and rural clinics; 2) to determine barriers to access; 3) to determine willingness to use technology for home-based symptom reporting.

Methods

Patients from representative clinics (seven rural and three urban) in our network were surveyed. Inclusion criteria were age greater than 18, able to read, and diagnosis of malignancy.

Results

The response rate was 97%. Of 416 patients completing the survey (230 rural, 186 urban), 95% had access to touch-tone telephone service, while 46% had Internet access (56% of urban patients, 38% of rural patients). Higher rates of Internet access were related to younger patient age, current employment, and higher education and income. The primary barrier to Internet access was lack of interest. Use of the Internet for health related activities was less than 50%. The preferred means of symptom reporting in patients with internet access were the touch-tone telephone (70%), compared to reporting by the Internet (28%).

Conclusion

Access to communication technologies appears adequate for home-based symptom reporting. The use of touch-tone telephone and Internet reporting, based upon patient preference, has the potential of enhancing symptom detection among cancer patients that is not dependent solely upon clinic visits and clinician inquiry.
Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus
Authors: Eberhart Charles G , Chaudhry Aneeka , Daniel Richard W , Khaki Leila , Shah Keerti V , Gravitt Patti E
Published: February 2005

Background

p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined.

Methods

p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction.

Results

p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected.

Conclusion

Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.
Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia
Authors: Jarnjak-Jankovic Silvija , Pettersen Rolf D , Sæbøe-Larssen Stein , Wesenberg Finn , Gaudernack Gustav
Published: February 2005

Background

Leukemia is a clonal disorder characterized by uncontrolled proliferation of haematopoietic cells, and represents the most common form of cancer in children. Advances in therapy for childhood leukemia have relied increasingly on the use of high-dose chemotherapy often combined with stem-cell transplantation. Despite a high success rate and intensification of therapy, children still suffer from relapse and progressive disease resistant to further therapy. Thus, novel forms of therapy are required.

Methods

This study focuses on dendritic cell (DC) vaccination of childhood leukemia and evaluates the in vitro efficacy of different strategies for antigen loading of professional antigen-presenting cells. We have compared DCs either loaded with apoptotic leukemia cells or transfected with mRNA from the same leukemia cell line, Jurkat E6, for their capacity to induce specific CD4+ and CD8+ T-cell responses. Monocyte-derived DCs from healthy donors were loaded with tumor antigen, matured and co-cultured with autologous T cells. After one week, T-cell responses against antigen-loaded DCs were measured by enzyme-linked immunosorbent spot (ELISPOT) assay.

Results

DCs loaded with apoptotic Jurkat E6 cells or transfected with Jurkat E6-cell mRNA were both able to elicit specific T-cell responses in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets.

Conclusion

The results indicate that loading of DCs with apoptotic leukemia cells or transfection with tumour mRNA represent promising strategies for development of cancer vaccines for treatment of childhood leukemia.
Low adherence with antihypertensives in actual practice: the association with social participation – a multilevel analysis
Authors: Johnell Kristina , Råstam Lennart , Lithman Thor , Sundquist Jan , Merlo Juan
Published: February 2005

Background

Low adherence is a key factor in explaining impaired effectiveness and efficiency in the pharmacological treatment of hypertension. However, little is known about which factors determine low adherence in actual practice.

The purpose of this study is to examine whether low social participation is associated with low adherence with antihypertensive medication, and if this association is modified by the municipality of residence.

Methods

1288 users of antihypertensive medication were identified from The Health Survey in Scania 2000, Sweden. The outcome was low adherence with antihypertensives during the last two weeks. Multilevel logistic regression with participants at the first level and municipalities at the second level was used for analyses of the data.

Results

Low social participation was associated with low adherence with antihypertensives during the last two weeks (OR = 2.05, 95% CI: 1.05–3.99), independently of low educational level. However, after additional adjustment for poor self-rated health and poor psychological health, the association between low social participation and low adherence with antihypertensives during the last two weeks remained but was not conclusive (OR = 1.80, 95% CI: 0.90–3.61). Furthermore, the association between low social participation and low adherence with antihypertensives during the last two weeks varied among municipalities in Scania (i.e., cross-level interaction).

Conclusion

Low social participation seems to be associated with low adherence with antihypertensives during the last two weeks, and this association may be modified by the municipality of residence. Future studies aimed at investigating health-related behaviours in general and low adherence with medication in particular might benefit if they consider area of residence.
Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions
Authors: O'Driscoll B Ronan , Hopkinson Linda C , Denning David W
Published: February 2005

Background

Multiple studies have linked fungal exposure to asthma, but the link to severe asthma is controversial. We studied the relationship between asthma severity and immediate type hypersensitivity to mold (fungal) and non-mold allergens in 181 asthmatic subjects.

Methods

We recruited asthma patients aged 16 to 60 years at a University hospital and a nearby General Practice. Patients were categorized according to the lifetime number of hospital admissions for asthma (82 never admitted, 53 one admission, 46 multiple admissions). All subjects had allergy skin prick tests performed for 5 mold allergens (Aspergillus, Alternaria, Cladosporium, Penicillium and Candida) and 4 other common inhalant allergens (D. pteronyssinus, Grass Pollen, Cat and Dog).

Results

Skin reactivity to all allergens was commonest in the group with multiple admissions. This trend was strongest for mold allergens and dog allergen and weakest for D. pteronyssinus. 76% of patients with multiple admissions had at least one positive mold skin test compared with 16%-19% of other asthma patients; (Chi squared p < 0.0001). Multiple mold reactions were also much commoner in the group with multiple admissions (50% V 5% and 6%; p < 0.0001). The number of asthma admissions was related to the number and size of positive mold skin allergy tests (Spearman Correlation Coefficient r = 0.60, p < 0.0001) and less strongly correlated to the number and size of non-mold allergy tests (r = 0.34, p = 0.0005). Hospital admissions for asthma patients aged 16–40 were commonest during the mold spore season (July to October) whereas admissions of patients aged above 40 peaked in November-February (Chi Squared, p < 0.02).

Conclusion

These findings support previous suggestions that mold sensitization may be associated with severe asthma attacks requiring hospital admission.
Is there value in using physician billing claims along with other administrative health care data to document the burden of adolescent injury? An exploratory investigation with comparison to self-reports in Ontario, Canada
Authors: Potter Beth K , Manuel Douglas , Speechley Kathy N , Gutmanis Iris A , Campbell M Karen , Koval John J
Published: February 2005

Background

Administrative health care databases may be particularly useful for injury surveillance, given that they are population-based, readily available, and relatively complete. Surveillance based on administrative data, though, is often restricted to injuries that result in hospitalization. Adding physician billing data to administrative data-based surveillance efforts may improve comprehensiveness, but the feasibility of such an approach has rarely been examined. It is also not clear how injury surveillance information obtained using administrative health care databases compares with that obtained using self-report surveys. This study explored the value of using physician billing data along with hospitalization data for the surveillance of adolescent injuries in Ontario, Canada. We aimed i) to document the burden of adolescent injury using administrative health care data, focusing on the relative contribution of physician billing information; and ii) to explore data quality issues by directly comparing adolescent injuries identified in administrative and self-report data.

Methods

The sample included adolescents aged 12 to 19 years who participated in the 1996–1997 cross-sectional Ontario Health Survey, and whose survey responses were linked to administrative health care datasets (N = 2067). Descriptive analysis was used to document the burden of injuries as a proportion of all physician care by gender and location of care, and to examine the distribution of both administratively-defined and self-reported activity-limiting injuries according to demographic characteristics. Administratively-defined and self-reported injuries were also directly compared at the individual level.

Results

Approximately 10% of physician care for the sample was identified as injury-related. While 18.8% of adolescents had self-reported injury in the previous year, 25.0% had documented administratively-defined injury. The distribution of injuries according to demographic characteristics was similar across data sources, but congruence was low at the individual level. Possible reasons for discrepancies between the data sources included recall errors in the survey data and errors in the physician billing data algorithm.

Conclusion

If further validated, physician billing data could be used along with hospital inpatient data to make an important and unique contribution to adolescent injury surveillance. The limitations inherent in different datasets highlight the need to continue rely on multiple information sources for complete injury surveillance information.
Malaria and urbanization in sub-Saharan Africa
Authors: Donnelly Martin J , McCall PJ , Lengeler Christian , Bates Imelda , D'Alessandro Umberto , Barnish Guy , Konradsen Flemming , Klinkenberg Eveline , Townson Harold , Trape Jean-Francois , Hastings Ian M , Mutero Clifford
Published: February 2005

There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.
Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study
Authors: Clayton Richard H , Holden Arun V
Published: February 2005

Background

The initiation of re-entrant cardiac arrhythmias is associated with increased dispersion of repolarisation, but the details are difficult to investigate either experimentally or clinically. We used a computational model of cardiac tissue to study systematically the association between action potential duration (APD) dispersion and susceptibility to re-entry.

Methods

We simulated a 60 × 60 mm 2 D sheet of cardiac ventricular tissue using the Luo-Rudy phase 1 model, with maximal conductance of the K+ channel gKmax set to 0.004 mS mm-2. Within the central 40 × 40 mm region we introduced square regions with prolonged APD by reducing gKmax to between 0.001 and 0.003 mS mm-2. We varied (i) the spatial scale of these regions, (ii) the magnitude of gKmax in these regions, and (iii) cell-to-cell coupling.

Results

Changing spatial scale from 5 to 20 mm increased APD dispersion from 49 to 102 ms, and the susceptible window from 31 to 86 ms. Decreasing gKmax in regions with prolonged APD from 0.003 to 0.001 mS mm-2 increased APD dispersion from 22 to 70 ms, and the susceptible window from <1 to 56 ms. Decreasing cell-to-cell coupling by changing the diffusion coefficient from 0.2 to 0.05 mm2 ms-1 increased APD dispersion from 57 to 88 ms, and increased the susceptible window from 41 to 74 ms.

Conclusion

We found a close association between increased APD dispersion and susceptibility to re-entrant arrhythmias, when APD dispersion is increased by larger spatial scale of heterogeneity, greater electrophysiological heterogeneity, and weaker cell-to-cell coupling.
Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals
Authors: Quintana Miguel , Lindell Peter , Saha Samir K , del Furia Francesca , Lind Britta , Govind Satish , Brodin Lars-Åke
Published: February 2005

Background

The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent.

Aims

To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers.

Subjects and methods

We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20–47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities.

Results

Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function.

Conclusion

TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function.
Rapid self-assembly of DNA on a microfluidic chip
Authors: Zheng Yao , Footz Tim , Manage Dammika P , Backhouse Christopher James
Published: February 2005

Background

DNA self-assembly methods have played a major role in enabling methods for acquiring genetic information without having to resort to sequencing, a relatively slow and costly procedure. However, even self-assembly processes tend to be very slow when they rely upon diffusion on a large scale. Miniaturisation and integration therefore hold the promise of greatly increasing this speed of operation.

Results

We have developed a rapid method for implementing the self-assembly of DNA within a microfluidic system by electrically extracting the DNA from an environment containing an uncharged denaturant. By controlling the parameters of the electrophoretic extraction and subsequent analysis of the DNA we are able to control when the hybridisation occurs as well as the degree of hybridisation. By avoiding off-chip processing or long thermal treatments we are able to perform this hybridisation rapidly and can perform hybridisation, sizing, heteroduplex analysis and single-stranded conformation analysis within a matter of minutes. The rapidity of this analysis allows the sampling of transient effects that may improve the sensitivity of mutation detection.

Conclusions

We believe that this method will aid the integration of self-assembly methods upon microfluidic chips. The speed of this analysis also appears to provide information upon the dynamics of the self-assembly process.
The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis
Authors: Keith James C , Albert Leo M , Leathurby Yelena , Follettie Max , Wang Lili , Borges-Marcucci Lisa , Chadwick Christopher C , Steffan Robert J , Harnish Douglas C
Published: February 2005

Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity.
Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab
Authors: Baraliakos Xenofon , Listing Joachim , Brandt Jan , Rudwaleit Martin , Sieper Joachim , Braun Juergen
Published: February 2005

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment ≥ 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician's global assessment was 4.4 ± 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (± 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.
Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts
Authors: Nakayamada Shingo , Kurose Hitoshi , Saito Kazuyoshi , Mogami Akira , Tanaka Yoshiya
Published: February 2005

Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Gα13 (an inhibitor of the interaction of receptors with G13). 4)Thrombin induced the secretion of IL-6 by RA SFs, but this action was blocked by p115RGS or Gα13. Our findings show that the actions of thrombin on the proliferation of RA SFs, cell-cycle progression to the S phase, and IL-6 secretion were mainly mediated by the G13 and RhoGEF pathways. These results suggest that p115RGS and Gα13 could be potent inhibitors of such functions. A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells.
Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis
Authors: Linsen Loes , Thewissen Marielle , Baeten Kurt , Somers Veerle , Geusens Piet , Raus Jef , Stinissen Piet
Published: February 2005

Natural killer T (NKT) cells have been implicated in the regulatory immune mechanisms that control autoimmunity. However, their precise role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMCs) from 23 RA patients and 22 healthy control individuals, including paired PBMC–synovial fluid samples from seven and paired PBMC–synovial tissue samples from four RA patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMCs from RA patients. NKT cells were present in paired synovial fluid and synovial tissue samples. Based on the reactivity of PBMC-derived NKT cells toward α-galactosylceramide, RA patients could be divided into responders (53.8%) and nonresponders (46.2%). However, NKT cells isolated from synovial fluid from both responders and nonresponders expanded upon stimulation with α-galactosylceramide. Analysis of the cytokine profile of CD4+ and CD4- PBMC derived NKT cell lines from RA patients revealed a significantly reduced number of IL-4 producing cells. In contrast, synovial fluid derived NKT cell lines exhibited a Th0-like phenotype, which was comparable to that in healthy control individuals. This suggests that synovial fluid NKT cells are functional, even in patients with nonresponding NKT cells in their blood. We conclude that, because the number of Vα24+Vβ11+CD3+ NKT cells is decreased and the cytokine profile of blood-derived NKT cells is biased toward a Th1-like phenotype in RA patients, NKT cells might be functionally related to resistance or progression of RA. Providing a local boost to the regulatory potential of NKT cells might represent a useful candidate therapy for RA.
A web tool for finding gene candidates associated with experimentally induced arthritis in the rat
Authors: Andersson Lars , Petersen Greta , Johnson Per , Ståhl Fredrik
Published: February 2005

Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study
Authors: Baer Heather J , Colditz Graham A , Rosner Bernard , Michels Karin B , Rich-Edwards Janet W , Hunter David J , Willett Walter C
Published: February 2005

Introduction

Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women.

Methods

Participants were 109,267 premenopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5–10 years) and adolescent (ages 10–20 years) fatness.

Results

Body fatness at each age was inversely associated with premenopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35–0.55) and 0.57 (95% CI 0.39–0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38–0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association.

Conclusion

Greater body fatness during childhood and adolescence is associated with reduced incidence of premenopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.
Protein kinase Cδ regulates p67phox phosphorylation in human monocytes
Authors: Zhao Xiaoxian , Xu Bo , Bhattacharjee Ashish , Oldfield Claudine M , Wientjes Frans B , Feldman Gerald M , Cathcart Martha K
Published: February 2005

Phosphorylation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components p67phox and p47phox accompanies the assembly and activation of this enzyme complex. We have previously reported that activation of human monocytes with opsonized zymosan (ZOP), a potent stimulator of NADPH oxidase activity, results in the phosphorylation of p67phox and p47phox. In this study, we investigated the regulation of p67phox phosphorylation. Although protein kinase C (PKC)α has previously been shown to regulate NADPH oxidase activity, we found that inhibition of PKCα had no effect on p67phox phosphorylation. Our studies demonstrate that pretreatment of monocytes with antisense oligodeoxyribonucleotides specific for PKCδ or rottlerin, a selective inhibitor for PKCδ, inhibited the phosphorylation of p67phox in monocytes, and Go6976, a specific inhibitor for conventional PKCs, PKCα and PKCβ, had no such inhibitory effect. Additional studies indicate that ZOP stimulation of monocytes induces PKCδ and p67phox to form a complex. We also demonstrate that lysates from activated monocytes as well as PKCδ immunoprecipitates from activated monocytes can phosphorylate p67phox in vitro and that pretreatment of monocytes with rottlerin blocked the phosphorylation in each case. We further show that recombinant PKCδ can phosphorylate p67phox in vitro. Finally, we show that PKCδ-deficient monocytes produce significantly less superoxide anion in response to ZOP stimulation, thus emphasizing the functional significance of the PKCδ regulation of p67phox phosphorylation. Taken together, this is the first report to describe the requirement of PKCδ in regulating the phosphorylation of p67phox and the related NADPH oxidase activity in primary human monocytes.
Fetal and neonatal murine skin harbors Langerhans cell precursors
Authors: Chang-Rodriguez S , Hoetzenecker W , Schwärzler C , Biedermann T , Saeland S , Elbe-Bürger A
Published: February 2005

Resident epidermal Langerhans cells (LC) in adult mice express ADPase, major histocompatibility complex (MHC) class II, and CD205 and CD207 molecules, while the first dendritic leukocytes that colonize the fetal and newborn epidermis are only ADPase+. In this study, we tested whether dendritic epidermal leukocytes (DEL) are end-stage cells or represent LC precursors. In epidermal sheets of fetal and neonatal mice, we found no apoptotic leukocytes, suggesting that these cells do not die in situ. To address whether DEL can give rise to LC, sorted DEL from murine newborn skin were cultured with cytokines used to generate LC from human CD34+ precursors. After 7–14 days, DEL proliferated and acquired the morphology and phenotype of cells reminiscent of LC. In concordance with this finding, we show that neonatal epidermis harbors 10–20 times the number of cycling MHC class II+ leukocytes as adult tissue. To test whether LC can differentiate from skin precursors in vivo, we developed a transplantation model. As it was impossible to transplant fetal epidermis, whole fetal skin was grafted onto adult severe combined immunodeficient mice. As opposed to the uniform absence of donor LC at the time of transplantation, examination of the epidermis from the grafts after 2–4 weeks revealed MHC class II+ donor cells, which had acquired CD205 and CD207, thus qualifying them as LC. Finally, we present evidence that endogenous LC persist in skin grafts for the observation period of 45 days. These studies show that hematopoietic precursors seed the skin during embryonic life and can give rise to LC.
Evaluation of traumatic brain injured patients in correlation with functional status by localized 1H-MR spectroscopy
Authors: Yoon Se Jin , Lee Jung Hee , Kim Sang Tae , Chun Min Ho
Published: February 2005

Objective: To determine whether proton magnetic resonance spectroscopy (1H-MRS) could be a useful tool for detecting microscopic diffuse axonal injury to evaluate the functional status of patients with traumatic brain injury (TBI).

Design: A comparative study.

Setting: An inpatient rehabilitation unit in Korea.

Subjects: We examined eight adult patients who had severe TBI approximately five months before. Fourteen normal controls were employed for comparison.

Main measures: Image-guided localized in vivo 1H-MRS was performed in the parietal white matter and occipital grey matter regions in brain in which no definite abnormalities in MR imaging were found at the time of 1H-MRS examination. We evaluated functional status for all patients with the Functional Independence Measure (FIM) on the same day as the 1H-MRS examination and compared the results.

Results: In the parietal white matter, the [N-acetyl aspartate/creatine] ratios were significantly lower, and the [choline/creatine] and [myo-inositol/creatine] ratios were significantly higher than those of normal controls. Significant correlations of the [N-acetyl aspartate/creatine] and [myo-inositol/creatine] ratios in the parietal white matter with FIM scores were observed (p≤0.05).

Conclusions: A spectral feature of the decreased [N-acetyl aspartate/creatine] and increased [choline/creatine] and [myo-inositol/creatine] ratios in parietal white matter may be a marker for diffuse axonal injury in patients with TBI and has a significant correlation with the functional status of the patients. Localized 1H-MRS has the potential to be used for detecting diffuse axonal injury in vivo in TBI patients, which can be used to guide evaluation of the functional status of TBI patients receiving rehabilitation.
The reliability of balance, mobility and self-care measures in a population of adults with a learning disability known to a physiotherapy service
Authors: Sackley Cath , Richardson Patricia , McDonnell Karen , Ratib Sonia , Dewey Michael , Hill Helen J
Published: February 2005

Objective: To estimate the reliability of three measures of balance, mobility and activity for use in clinical and research physiotherapy, with adults with a learning disability.

Design: Prospective study to investigate test-retest and inter-rater reliability.

Setting: Participants' homes and day centres.

Measures: The Berg Balance Scale (BBS), the Rivermead Mobility Index (RMI) and the Barthel Activities of Daily Living Index (BI).

Participants: Of the 181 adults known to the Nottingham Community Physiotherapy Service for Adults with Learning Disabilities, 64 with a known Rivermead Mobility score of less than three were excluded. Of 117 randomized, a further 21 were found to fail this criteria, 27 had acute medical, social or behavioural problems, 22 were unable to participate or refused: therefore 47 entered the study.

Methods: Participants were visited in their own homes by two researchers on two occasions, one week apart and rated independently by each rater. Agreement was assessed with the kappa statistic (k) and percentage agreement for each item in each scale, and described using standard classification. Intraclass correlation coefficients for inter-rater and test-retest total scores and average differences of total scores, their standard deviations and limits of agreement, were calculated.

Results: For inter-rater observations, the Barthel Index and the Rivermead Mobility Index had almost perfect agreement (k=0.86–1.00 and 0.89–1.00 respectively), with the Berg Balance Scale having substantial to almost perfect agreement (k=0.74–1.00). For test–retest comparisons, both the Barthel Index and the Rivermead Mobility Index demonstrated moderate to almost perfect agreement (k=0.57–1.00 and 0.45–1.00 respectively). Kappa scores for the Berg Balance Scale varied from low to almost perfect agreement (k=0.37–1.00).

Conclusions: The Berg Balance Scale, Rivermead Mobility Index and Barthel Activities of Daily Living Index are all reliable clinical and research tools for physiotherapists working with adults with learning disabilities.
Measuring energy expenditure using heart rate to assess the effects of wheelchair tyre pressure
Authors: Sawatzky B J , Miller W C , Denison I
Published: February 2005

Objective: To investigate the effects of wheelchair tyre pressure on mechanics and energy and explore the use of heart rate as a measurement of energy expenditure.

Design: A single factor repeated measures design was used. Four tyre pressures (100, 75, 50, 25 psi) represented a change of workload. Each subject wheeled at a constant self-selected wheeling velocity for 8 min. A total of four trials were completed with a 10-min rest between trials. Oxygen consumption, heart rate and distance travelled were collected during each trial.

Subjects: Three women and 11 men with spinal cord injury. The mean age for the whole group was 34.5 years. The range of lesion level was T4-L1.

Results: There was a significant increase is energy expenditure when tyres were deflated to 50 psi from 100 psi. The mean correlation between heart rate and oxygen consumption was 0.74 for all subjects. For the subjects with lesions above T6 and T6 and below the correlations were 0.55 and 0.82, respectively.

Conclusions: Tyre pressures below 50% inflation add an additional 25% increase in energy expenditure during wheeling. This could be detected using oxygen consumption or heart rate, as heart rate was shown to have a good correlation with oxygen consumption in the spinal cord injured with lesions below T5. Heart rate does have its limitations and it should only be used to measure within-subject differences.
An investigation of the impact of the Force Sensing Array pressure mapping system on the clinical judgement of occupational therapists
Authors: Crawford S A , Strain B , Gregg B , Walsh D M , Porter-Armstrong A P
Published: February 2005

Objectives: To examine the impact of pressure mapping technology on the clinical decisions of occupational therapists and to examine the role of the Braden Scale in assisting with the selection of pressure-reducing cushions.

Design: Case studies.

Setting: Community.

Subjects: Forty clients.

Interventions: Clients were pressure mapped on their current seating surface and on four pre-selected cushions by the principal researcher. An occupational therapist completed the Braden Scale and a decision tree to assist in recommending a suitable pressure-reducing cushion.

Main outcome measures: Interface pressure maps, Braden Scale, and the cushion recommended, using a decision tree to guide clinical judgement.

Results: Thirty per cent (12) of the 40 cushions recommended were changed when the pressure maps from the Force Sensing Array (FSA) system were viewed. In 70% (26) of cases, the maps supported the cushion recommended. In 25% (10) of the cases, the maps showed that the client's current seating surface was unsuitable. After viewing the pressure maps, a surface other than the client's current surface was recommended in 47% (19) of the cases. There was a lack of agreement between the risk level of the clients as identified by the Braden Scale score, and the risk level of the clients as identified by the occupational therapist using a decision tree and the FSA maps.

Conclusion: Pressure mapping technology has a positive impact on clinical decisions regarding the provision of pressure-reducing cushions. Future research should examine the predictive validity of this technology. The Braden Scale may underpredict the risk level of the clients.