Biomedical subjects

M Fransen

Publications and source records attributed to M Fransen.

At least 19 recordsLinked to original sources

PubMed2006

Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells.

Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells.

Alkyl and Aryl Transferases↗

PubMed2006

Shift work and work injury in the New Zealand Blood Donors' Health Study.

OBJECTIVE: To investigate associations between work patterns and the occurrence of work injury. METHODS: A cross sectional analysis of the New Zealand Blood Donors Health Study conducted among the 15 687 (70%) participants who reported being in paid employment. After measurement of height and weight, a self-administered questionnaire collected information concerning occupation and work pattern, lifestyle behaviour, sleep, and the occurrence of an injury at work requiring treatment from a doctor during the past 12 months. RESULTS: Among paid employees providing information on work pattern, 3119 (21.2%) reported doing shift work (rotating with nights, rotating without nights, or permanent nights) and 1282 (8.7%) sustained a work injury. In unadjusted analysis, work injury was most strongly associated with employment in heavy manual occupations (3.6, 2.8 to 4.6) (relative risk, 95% CI), being male (1.9, 1.7 to 2.2), being obese (1.7, 1.5 to 2.0), working rotating shifts with nights (2.1, 1.7 to 2.5), and working more than three nights a week (1.9, 1.6 to 2.3). Snoring, apnoea or choking during sleep, sleep complaints, and excessive daytime sleepiness were also significantly associated with work injury. When mutually adjusting for all significant risk factors, rotating shift work, with or without nights, remained significantly associated with work injury (1.9, 1.5 to 2.4) and (1.8, 1.2 to 2.6), respectively. Working permanent night shifts was no longer significantly associated with work injury in the adjusted model. CONCLUSION: Work injury is highly associated with rotating shift work, even when accounting for increased exposure to high risk occupations, lifestyle factors, and excessive daytime sleepiness.

Accidents, Occupational↗

PubMed2004

Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty.

BACKGROUND: Heterotopic bone formation (HBF) in the soft tissues surrounding the hip joint is a frequent complication of hip surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) administered in the immediate perioperative period reduce the risk of HBF. However, the magnitude of the effect on HBF, and the effects on other associated outcomes, such as pain and physical function, are uncertain. OBJECTIVES: To determine the effects of perioperative NSAID therapy versus control on the risk of HBF and other outcomes in patients undergoing hip arthroplasty. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (October 2002), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 3, 2002), MEDLINE (1966 to October 2002), EMBASE (1988 to 2002 Week 43), CURRENT CONTENTS (1993 Week 27 to 2002 Week 44) and reference lists of articles. We also contacted trialists and drug manufacturers. SELECTION CRITERIA: All trials which enrolled patients scheduled to undergo hip arthroplasty with random or quasi-random allocation to perioperative NSAID or control and that recorded post-operative radiographically determined HBF. The primary outcome was post-operative radiographic HBF. Secondary outcomes were pain, function (including range of motion), gastro-intestinal and other bleeding complications, and other causes of major morbidity or mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed methodological quality and extracted data. All analyses were conducted on dichotomised outcomes. MAIN RESULTS: Sixteen randomised and two quasi-randomised trials involving a total of 4,763 patients were included. Overall, in 17 trials that examined the effects of medium to high doses of NSAIDs, there was a reduced risk of developing HBF after hip surgery (59% reduction, 95% confidence interval 54% to 64% reduction). In contrast, one large trial examining low-dose aspirin, demonstrated no effect on the risk of HBF (2% reduction, 95% confidence interval 15% reduction to 12% increase). There was strong evidence of differences in the size of the treatment effects observed between the trials examining medium to high doses of NSAIDs, but reasons were not clearly identified. There was a non-significant one third increased risk of gastro-intestinal side effects among patients assigned NSAIDs (29% increase, 95% confidence interval 0% to 76% increase). Most of this increase was due to an increased risk of minor gastro-intestinal complications. Data on the late post-operative outcomes of pain, impaired physical function and range of joint movement were few and no formal overviews of the effects of NSAIDs on these outcomes were possible. REVIEWERS' CONCLUSIONS: Perioperative NSAIDs, apart from low dose aspirin, appear to produce between a one half and two thirds reduction in the risk of HBF. With routine use, such agents may be able to prevent 15-20 cases of HBF among every 100 total hip replacements performed. However, while medium to high doses of perioperative NSAIDs clearly produce a substantial reduction in the incidence of radiographic HBF, there remains some uncertainty about short-term side effects of treatment and substantial uncertainty about effects on long-term clinical outcomes such as chronic pain and impaired physical function. The net effect of routine HBF prophylaxis with NSAIDs requires formal assessment in a randomised trial designed to determine the balance of benefits and risks for all outcomes.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Effects of a perindopril-based blood pressure-lowering regimen on disability and dependency in 6105 patients with cerebrovascular disease: a randomized controlled trial.

BACKGROUND AND PURPOSE: We sought to quantify the effects of blood pressure lowering on long-term disability and dependency among patients with cerebrovascular disease. METHODS: We performed a randomized, double-blind, placebo-controlled trial. A total of 6105 participants with a history of stroke or transient ischemic attack in the past 5 years were recruited from 172 hospital outpatient clinics in 10 countries. Subjects were randomly assigned to the following groups: active treatment (angiotensin-converting enzyme inhibitor perindopril [4 mg/d] for all patients, with the diuretic indapamide added at the discretion of treating physicians) or matching placebo(s). Measurements were disability (defined as a Barthel Index score < or =99/100) and dependency (a positive response to the following question: "In the last 2 weeks has the patient required regular help with everyday activities?"). RESULTS: The median duration of follow-up was 4 years. At the last available assessment, 19% of the active treatment group and 22% of the placebo group were disabled (adjusted odds ratio, 0.76; 95% CI, 0.65 to 0.89; P<0.001). Twelve percent of the active treatment group and 14% of the placebo group were dependent (adjusted odds ratio, 0.84; 95% CI, 0.71 to 0.99; P=0.04). The effects of treatment appeared to be mediated primarily through the prevention of disability and dependency associated with recurrent stroke. Four-year treatment with the study drug regimen would be expected to result in the avoidance of 1 case of long-term disability for every 30 (95% CI, 19 to 79) patients. CONCLUSIONS: Among individuals with cerebrovascular disease, a perindopril-based blood pressure-lowering regimen not only reduced the risk of stroke and major vascular events but also substantially reduced the risks of associated long-term disability and dependency.

Activities of Daily Living↗

PubMed2003

Exercise for osteoarthritis of the hip or knee.

BACKGROUND: Biomechanical factors, such as reduced muscle strength and joint mal-alignment, have an important role in the initiation and progression of osteoarthritis (OA) of the hip or knee. Currently, there is no known cure for OA, however, disease-related factors, such as impaired muscle function and reduced fitness, are potentially amenable to therapeutic exercise. OBJECTIVES: To determine whether land-based therapeutic exercise is beneficial for people with OA of the hip or knee in terms of reduced joint pain, improved physical function and/or the patient's global assessment of therapeutic effectiveness. SEARCH STRATEGY: Five databases (the Cochrane Controlled Trials Register, the Cochrane Musculoskeletal Group Trials Register, MEDLINE, CINAHL, PEDro) were searched up until November 2002. SELECTION CRITERIA: All randomized controlled trials comparing some form of land-based therapeutic exercise (as opposed to exercises conducted in the water) with a non-exercise group. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed methodological quality. All analyses were conducted on continuous outcomes. MAIN RESULTS: Only 2 studies totaling about 100 participants, could potentially provide data on people with OA of the hip. However, for OA of the knee, 17 included studies provided data on 2562 participants. For pain, combining the results revealed a beneficial treatment effect (standardised mean difference) of.39 (95% confidence interval (CI).30 -.47) while for self-reported physical function a beneficial treatment effect of.31 (95% CI.23 -.39). Group format programs appeared to be as effective as treatments provided on a one-to-one basis. The results were sensitive to various aspects of study design methodology. REVIEWER'S CONCLUSIONS: Land-based therapeutic exercise was shown to reduce pain and improve physical function for people with OA of the knee. There were insufficient data to provide useful guidelines on optimal exercise type or dosage. Supervised exercise classes appeared to be as beneficial as treatments provided on a one-to-one basis.

Exercise Therapy↗

PubMed2001

Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase.

Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568), the cDNA of the human counterpart was cloned. It contained an open reading frame of 878 bases encoding a protein of 291 amino acids (calculated molecular mass 30778 Da), being 83% identical to the rat reductase. The gene, encompassing nine exons, is located at chromosome 16p13. Bacterially expressed poly(His)-tagged reductase was active not only towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA. Hence, the reductase does not seem to constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid. The reduction of docosaheptaenoyl-CoA, however, was severely decreased in the presence of albumin.

Acyl Coenzyme A↗

PubMed2001

Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals.

Based on peroxin protein 5 (Pex5p) homology searches in the expressed sequence tag database and sequencing of large full-length cDNA inserts, three novel and related human cDNAs were identified. The brain-derived cDNAs coded for two related proteins that differ only slightly at their N-terminus, and exhibit 39.8% identity to human PEX5p. The shorter liver-derived cDNA coded for the C-terminal tetratricopeptide repeat-containing domain of the brain cDNA-encoded proteins. Since these three proteins specifically bind to various C-terminal peroxisome-targeting signals in a manner indistinguishable from Pex5p and effectively compete with Pex5p in an in vitro peroxisome-targeting signal 1 (PTS1)-binding assay, we refer to them as 'Pex5p-related proteins' (Pex5Rp). In contrast to Pex5p, however, human PEX5Rp did not bind to Pex14p or to the RING finger motif of Pex12p, and could not restore PTS1 protein import in Pex5(-/-) mouse fibroblasts. Immunofluorescence analysis of epitope-tagged PEX5Rp in Chinese hamster ovary cells suggested an exclusively cytosolic localization. Northern-blot analysis showed that the PEX5R gene, which is localized to chromosome 3q26.2--3q27, is expressed preferentially in brain. Mouse PEX5Rp was also delineated. In addition, experimental evidence established that the closest-related yeast homologue, YMR018wp, did not bind PTS1. Based on its subcellular localization and binding properties, Pex5Rp may function as a regulator in an early step of the PTS1 protein import process.

Amino Acid Sequence↗

PubMed2001

Fibroblast studies documenting a case of peroxisomal 2-methylacyl-CoA racemase deficiency: possible link between racemase deficiency and malabsorption and vitamin K deficiency.

BACKGROUND: 2-Methylacyl-CoA racemase interconverts the 2-methyl group of pristanoyl-CoA or the 25-methyl group of hydroxylated cholestanoyl-CoAs, allowing further peroxisomal desaturation of these compounds in man by the branched chain acyl-CoA oxidase, which recognise only the S-isomers. Hence, oxidation studies in fibroblasts, currently based on the use of racemic substrates such as [1-14C] pristanic acid, do not allow us to distinguish between a deficient racemase or an impaired oxidase. DESIGN: To evaluate the racemase activity directly, the 2R-isomer of[1-14C] pristanic acid, as well as the 2R-isomer of 2-methyl-[1-14C] hexadecanoic, a synthetic pristanic acid substitute, were prepared and their degradation by cultured human skin fibroblasts was compared to that of the racemic substrates. RESULTS: In fibroblasts in a young girl, presenting with elevated urinary levels of trihydroxycholestanoic acid metabolites but normal plasma levels of very long chain fatty acids, a partial deficient degradation of racemic [1-14C] pristanic acid was observed. Incorporation of 2R-[1-14C] pristanic acid in glycerolipids of the patient's fibroblasts proceeded normally, but breakdown was impaired. Similar findings were seen with the 2R-isomer of 2-methyl-[1-14C] hexadecanoic. These data, combined with the fact that the branched chain acyl-CoA oxidase, catalyzing the first oxidation step of pristanic acid and bile acid intermediates in man, appeared normal, suggested a peroxisomal beta-oxidation defect in the patient at the level of 2-methylacyl-CoA racemase. CONCLUSION: Carboxy-labelled 2R-methyl branched chain fatty acids might be useful tools to document cases of racemase deficiencies. Because a brother of the patient died with a diagnosis of vitamin K deficiency, an impaired racemase might be responsible for other cases of unexplicable malabsorption.

Cells, Cultured↗

PubMed2001

Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences.

The molecular machinery underlying peroxisomal membrane biogenesis is not well understood. The observation that cells deficient in the peroxins Pex3p, Pex16p, and Pex19p lack peroxisomal membrane structures suggests that these molecules are involved in the initial stages of peroxisomal membrane formation. Pex19p, a predominantly cytosolic protein that can be farnesylated, binds multiple peroxisomal integral membrane proteins, and it has been suggested that it functions as a soluble receptor for the targeting of peroxisomal membrane proteins (PMPs) to the peroxisome. An alternative view proposes that Pex19p functions as a chaperone at the peroxisomal membrane. Here, we show that the peroxisomal sorting determinants and the Pex19p-binding domains of a number of PMPs are distinct entities. In addition, we extend the list of peroxins with which human Pex19p interacts to include the PMP Pex16p and show that Pex19p's CaaX prenylation motif is an important determinant in the affinity of Pex19p for Pex10p, Pex11pbeta, Pex12p, and Pex13p.

Amino Acid Sequence↗

PubMed2001

Identification of a novel human peroxisomal 2,4-dienoyl-CoA reductase related protein using the M13 phage protein VI phage display technology.

Recently, we reported the successful use of the gVI-cDNA phage display technology to clone cDNAs coding for novel peroxisomal enzymes by affinity selection using immobilized antisera directed against peroxisomal subfractions (Fransen, M.; Van Veldhoven, P.P.; Subramani, S. Biochem. J., 1999, 340, 561-568). To identify other unknown peroxisomal enzymes, we further exploited this promising approach. Here we report the isolation and cloning of another novel human cDNA encoding a protein ending in the tripeptide AKL, a C-terminal peroxisomal targeting signal (PTS1). Primary structure analysis revealed that this molecule shared the highest sequence similarity to members of the 2,4-dienoyl-CoA reductase (DCR) family. However, functional analysis indicated that a recombinantly expressed version of the novel protein did not possess DCR activity with either 2-trans,4-trans-hexadienoyl-CoA or 2-trans,4-trans-decadienoyl-CoA as a substrate. The recombinant protein interacted with HsPex5p, the human PTS1-binding protein. Binding was competitively inhibited by a PTS1-containing peptide and was abolished when the last amino acid of the PTS1 signal was deleted. Transfection of mammalian cells with gene fusions between green fluorescent protein (GFP) and the human cDNA confirmed a peroxisomal localization and, therefore, the functionality of the PTS1. These results further demonstrate the suitability of the gVI-cDNA phage display technology for cDNA expression cloning using an antibody as a probe.

Amino Acid Sequence↗

PubMed2001

Physical therapy is effective for patients with osteoarthritis of the knee: a randomized controlled clinical trial.

OBJECTIVE: To assess the effectiveness of physical therapy, given either as an individually attended treatment or in a small group format, in terms of pain, physical function, and health related quality of life for patients with osteoarthritis (OA) of the knee. METHODS: After 2 baseline assessments, 126 patients were randomized into one of 3 allocation arms: individual treatments (n = 43), small group format program (n = 40), and waiting list control (n = 43). After reassessment at 8 weeks, patients allocated to waiting list control were randomized into one of the 2 active treatment arms. Assessments included both self-report measures (WOMAC, SF-36) and objective measures of physical performance (gait analysis and muscle strength). RESULTS: Both physical therapy treatment allocations resulted in significant improvements in pain, physical function, and health related quality of life above the control group (standardized response mean 0.36 to 0.65). Improvements in the self-report measures were substantiated by significant correlated improvements in knee extensor strength and fast walking speed (rho 0.36-0.42). There were no significant differences in effectiveness between the 2 physical therapy allocations for any of the measured outcomes. Improvements gained were maintained for at least 2 months. Responsiveness to treatment was modified by loss of medial joint space width, the interaction being significant for physical function, gait, and knee extensor strength. CONCLUSION: Physical therapy, either as an individually delivered treatment or in a small group format, is an effective intervention for patients with knee OA. Responsiveness to this 8 week intervention was modified by loss of medial joint space width.

Aged↗

PubMed2000

Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty.

BACKGROUND: Heterotopic bone formation (HBF) in the soft tissues surrounding the hip joint is a frequent complication of hip surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) administered in the immediate perioperative period reduce the risk of HBF. However, the magnitude of the effect on HBF, and the effects on other associated outcomes are uncertain. OBJECTIVES: To determine the effects of perioperative NSAID therapy versus control on the risk of HBF and other outcomes in patients undergoing hip arthroplasty. SEARCH STRATEGY: Medline, Current Contents and Cochrane Controlled Trials Register, and reference lists of all relevant reports were searched. Principal investigators and the manufacturers of the study drugs of eligible trials were approached. The most recent search was conducted in July 1998. SELECTION CRITERIA: All trials which enrolled patients scheduled to undergo hip arthroplasty with random or quasi-random allocation to perioperative NSAID or control and that recorded post-operative radiographically determined HBF. The primary outcome was post-operative radiographic HBF. Secondary outcomes were pain, disability, gastro-intestinal and other bleeding complications, and other causes of major morbidity or mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed methodological quality and extracted data. All analyses were conducted on dichotomised outcomes. MAIN RESULTS: Twelve randomised and two quasi-randomised trials involving a total of 4,377 patients were included. Overall, in 13 trials that examined the effects of medium to high doses of NSAIDs, there was a reduced risk of developing HBF after hip surgery (62% reduction, 95% confidence interval 56% to 67% reduction). In contrast, one large trial examining low-dose aspirin, demonstrated no effect on the risk of HBF (2% reduction, 95% confidence interval 15% reduction to 12% increase). There was strong evidence of differences in the size of the treatment effects observed between the trials examining medium to high doses of NSAIDs, but reasons were not clearly identified. There was a non-significant one third increased risk of gastro-intestinal side effects among patients assigned NSAIDs (29% increase, 95% confidence interval 5% reduction to 76% increase). Most of this increase was due to an increased risk of minor gastro-intestinal complications. Data on the late post-operative outcomes of pain, impaired physical function and range of joint movement were few and no formal overviews of the effects of NSAIDs on these outcomes were possible. REVIEWER'S CONCLUSIONS: Perioperative NSAIDs appear to produce between a one half and two thirds reduction in the risk of HBF. With routine use, such agents may be able to prevent 15-20 cases of HBF (3-4 severe) among every 100 total hip replacements performed. However, while medium to high doses of perioperative NSAIDs clearly produce a substantial reduction in the incidence of radiographic HBF, there remains some uncertainty about short-term side effects of treatment and substantial uncertainty about effects on long-term clinical outcomes such as chronic pain and impaired physical function. The net effect of routine HBF prophylaxis with NSAIDs requires formal assessment in a randomised trial designed to determine the balance of benefits and risks for all outcomes.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

How peroxisomes arise.

Peroxisomes are formed by the synthesis and assembly of membrane proteins and lipids, the selective import of proteins from the cytosol, and the growth and division of resultant organelles. To date, 23 proteins, called peroxins, are known to participate in these processes. This review summarizes recent progress in peroxin characterization and examines the underlying molecular mechanisms of peroxisome biosynthesis.

Animals↗

PubMed2000

Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans.

2-Methylacyl-CoA racemase is an auxiliary enzyme required for the peroxisomal beta-oxidative breakdown of (2R)-pristanic acid and the (25R)-isomer of C(27) bile acid intermediates. The enzyme activity is found not only in peroxisomes but also is present in mitochondria of human liver and fibroblasts. The C terminus of the human racemase, a protein of 382 amino acids with a molecular mass of 43,304 daltons as deduced from its cloned cDNA, consists of KASL. Hitherto this sequence has not been recognized as a peroxisomal targeting signal (PTS1). From the in vitro interaction between recombinant racemase and recombinant human PTS1 receptor (Pex5p), and the peroxisomal localization of green fluorescent protein (GFP) fused to the N terminus of full-length racemase or its last six amino acids in tranfected Chinese hamster ovary (CHO) cells, we concluded that ASL is a new PTS1 variant. To be recognized by Pex5p, however, the preceding lysine residue is critical. As shown in another series of transfection experiments with GFP fused to the C terminus of the full-length racemase or racemase with deletions of the N terminus, mitochondrial targeting information is localized between amino acids 22 and 85.Hence, our data show that a single transcript gives rise to a racemase protein containing two topogenic signals, explaining the dual cellular localization of the activity.

Amino Acid Sequence↗

PubMed1999

Identification of peroxisomal proteins by using M13 phage protein VI phage display: molecular evidence that mammalian peroxisomes contain a 2,4-dienoyl-CoA reductase.

To elucidate unknown mammalian peroxisomal enzymes and functions, we subjected M13 phage expressing fusions between the gene encoding protein VI and a rat liver cDNA library to an immunoaffinity selection process in vitro (biopanning) with the use of antibodies raised against peroxisomal subfractions. In an initial series of biopanning experiments, four different cDNA clones were obtained. These cDNA species encoded two previously identified peroxisomal enzymes, catalase and urate oxidase, and two novel proteins that contained a C-terminal peroxisomal targeting signal (PTS1). A primary structure analysis of these novel proteins revealed that one, ending in the tripeptide AKL, is homologous to the yeast peroxisomal 2,4-dienoyl-CoA reductase (EC 1.3.1.34; DCR), an enzyme required for the degradation of unsaturated fatty acids, and that the other, ending in the tripeptide SRL, is a putative member of the short-chain dehydrogenase/reductase (SDR) family, with three isoforms. Green fluorescent protein (GFP) fusions encoding GFP-DCR-AKL, GFP-DCR, GFP-SDR-SRL and GFP-SDR were expressed in mammalian cells. The analysis of the subcellular location of the recombinant fusion proteins confirmed the peroxisomal localization of GFP-DCR-AKL and GFP-SDR-SRL, as well as the functionality of the PTS1. That the AKL protein is indeed an NADPH-dependent DCR was demonstrated by showing DCR activity of the bacterially expressed protein. These results demonstrate at the molecular level that mammalian peroxisomes do indeed contain a DCR. In addition, the results presented here indicate that the protein VI display system is suitable for the isolation of rare cDNA clones from cDNA libraries and that this technology facilitates the identification of novel peroxisomal proteins.

Alcohol Dehydrogenase↗

PubMed1999

Gait variables: appropriate objective outcome measures in rheumatoid arthritis.

OBJECTIVE: To assess the reliability and responsiveness of gait speed, cadence and stride length at two self-selected speeds (SSS) in subjects with rheumatoid arthritis (RA). METHODS: Thirty-one subjects with RA were assessed on three occasions. At each assessment session, subjects were asked to self-report walk pain on visual analogue scales, rate physical function using the Health Assessment Questionnaire, and walk five times at both a normal SSS and a fast SSS along an 8 m electric footswitch walkway. RESULTS: Despite stability of pain and physical function, there were significant gait changes from the first to the second assessment session at the normal SSS, although this 'learning' effect was not evident at either SSS between the second and the third assessment session. CONCLUSION: If the recommended protocol is followed, quantitative gait variables can provide reliable and responsive outcome measures in this population for use in evaluating therapeutic interventions.

Adult↗

PubMed1999

Reliability and validity of the EuroQol in patients with osteoarthritis of the knee.

OBJECTIVE: To assess the reliability and validity of the EuroQol (EQ-5D) for osteoarthritis of the knee (OA knee). METHODS: Eighty-two patients with OA knee were asked to complete on two occasions, separated by 1 week, the EQ-5D, the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and the 36-item short form of the Medical Outcomes Study (SF-36). RESULTS: In this patient population, < 10% of the 243 EQ-5D health states were active. The EQ-5D demonstrated a non-Gaussian distribution. Reliability [intraclass correlation coefficient (ICC) = 0.70] is acceptable for aggregate level data. There were significant rank correlations with both the WOMAC and SF-36. CONCLUSIONS: This study provides some evidence of EQ-5D construct validity and reliability. However, the restricted and non-normal distribution of scores, the marked difference between patients' self evaluation and derived societal utility tariffs, as well as the lack of discriminative ability for patients with 'moderate' morbidity within each of the five EQ-5D dimensions, are of concern.

Aged↗

PubMed1998

The difference in recognition of terminal tripeptides as peroxisomal targeting signal 1 between yeast and human is due to different affinities of their receptor Pex5p to the cognate signal and to residues adjacent to it.

Pex5p is the receptor for the peroxisomal targeting signal 1 (PTS1) that consists of a C-terminal tripeptide (consensus (S/A/C)(K/R/H)(L/M)). Hexadecapeptides recognized by Pex5p from Homo sapiens and Saccharomyces cerevisiae were identified by screening a two-hybrid peptide library, and the targeting ability of the peptides was demonstrated using the green fluorescent protein as reporter. The PTS1 receptors recognized in a species-specific manner a broad range of C-terminal tripeptides, and these are reported herein. In addition, residues upstream of the tripeptide influenced the strength of the interaction in the two-hybrid system as well as in an in vitro competition assay. In peptides interacting with the human protein, hydrophobic residues were found with high frequency especially at positions -2 and -5, whereas peptides interacting with S. cerevisiae Pex5p were more hydrophilic and frequently contained arginine at position -2. In instances where the terminal tripeptide deviated from the consensus, upstream residues exerted a greater influence on the ability of the hexadecapeptides to bind Pex5p.

Amino Acid Sequence↗