Biomedical subjects

Gareth R Jones

Publications and source records attributed to Gareth R Jones.

9 recordsLinked to original sources

PubMed2006

Community exercise program for older adults recovering from hip fracture: a pilot study.

Community-based rehabilitative exercise programs might be an effective means to improve functional outcomes for hip-fracture patients. The purpose of this study was to evaluate the effectiveness of a community exercise program (CEP) for older adults recovering from hip fracture. Twenty-five older adults (mean age 80.0 +/- 6.0 years; 24 women; 71 +/- 23 days post-hip fracture) participated in this pilot study (17 exercise, 8 control). The CEP involved functional stepping and lower extremity-strengthening exercises. Control participants received only standard outpatient therapy. Measures of functional mobility, balance confidence, falls efficacy, lower extremity strength, and daily physical activity were evaluated at baseline and at 16 weeks. Improvements for self-reported physical activity, mobility, balance, and knee-extensor strength were observed for the CEP group. This study demonstrated that a CEP is beneficial for community-dwelling older adults post-hip fracture.

Aged↗

PubMed2005

Evaluation of the restorative care education and training program for nursing homes.

Restorative care attempts to break the cycle of dependency and functional decline in nursing homes by addressing individual resident needs. The Restorative Care Education and Training (RCET) Program consists of a five-week workshop and resource manual for both supervisory and direct care staff. This paper describes the RCET approach and presents the implementation, process, and quasi-experimental outcome evaluation findings with 42 residents from six intervention sites and six ''wait-list'' facilities who received usual care. Baseline data supported the fact that staff primarily targeted residents with substantial functional impairments. Over four months, residents who received restorative care improved significantly on several functional outcome indicators, while the comparison sample declined in several areas of functioning. Interviews with facility directors and participating staff provided direction for modifying the RCET and insight regarding opportunities and challenges when implementing restorative care activities in nursing homes.

Adult↗

PubMed2005

Risk factors for falling among community-dwelling veterans and their caregivers.

PURPOSE: To assess the prevalence and strength of association of risk factors for falling in Canadian veterans of World War II and Korea and their caregivers. METHODS: Questionnaires were sent to addresses of 3,000 Canadian veterans (response rate(1/4)70%). Risk factors for falls and the frequency of falls and injurious falls in the past 12 months were collected. RESULTS: Veterans had more risk factors than did caregivers, and more had fallen in the past year (39.8% vs. 29.7%). Risk factors in the logistic model for veterans included lower extremity disability (odds ratio 1.98, 95% confidence interval 1.5-2.6); lower extremity weakness (OR 1.75, 95% CI 1.3-2.3); worse memory than peers (OR 1.67, 95% CI 1.1-2.5); one or more visits to the family doctor in the past month (OR 1.53, 95% CI 1.2-2.0); and worse memory than 5 years ago (OR 1.36, 95% CI 1.0-1.8). CONCLUSIONS: Veterans appear more frail and prone to falling than their caregivers.

Accidental Falls↗

PubMed2004

Plications of extended ultra-violet circular dichroism spectroscopy in biology and medicine.

Deep ultra-violet circular dichroism is fast becoming an important technique in structural biology. The exponential increase in the number of protein structures deposited in the Protein Data Bank together with programs that extract protein secondary structure from atomic coordinates and the advancement of the software to analyse circular dichroic spectra, have revolutionised the technique. In addition, the extended short wavelength data afforded by synchrotron radiation is set to have a major impact on the development of the area. We have selected three diverse areas of research and development in the biomedical sciences to illustrate the ubiquity of the technique for future applications in the area of biomedical research. For example, the high flux of synchrotron radiation has provided a gold standard for the assay of the lipoprotein HDL in serum which has been proven to reverse the effects of coronary heart disease. In a second example, the high flux of synchrotron radiation enables the recording of millisecond data during the conformational changes in proteins over their spectrum, mapping out changes to protein secondary structure and thus providing absolute structural measurements in the millisecond time regime. In the third example, subtle conformational changes are interpreted from the extended CD spectra on protein drug binding, distinguishing between induced binding effects and the conformational changes in the target protein. The strengths and weaknesses of extended ultra-violet circular dichroism using synchrotron radiation are discussed using these examples as a template.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Adenovirus type-5 entry and disassembly followed in living cells by FRET, fluorescence anisotropy, and FLIM.

We have used fluorescence resonance energy transfer (FRET) to follow the process of capsid disassembly for adenovirus (Ad) serotype 5 (Ad5) in living CHO-CAR cells. Ad5 were weakly labeled on their capsid proteins with FRET donor and acceptor fluorophores. A progressive decrease in FRET efficiency recorded during Ad5 uptake revealed that the time course of Ad5 capsid disassembly has two sequential protein dissociation rates with half-times of 3 and 60 min. Fluorescence anisotropy measurements of the segmental motions of fluorophores on Ad5 indicate that the first rate is linked to the detachment from the capsid of the protruding, flexible fiber proteins. The second rate was shown to report on the combined dissociation of protein IX, penton base, and hexons, which form the rigid icosahedral capsid shell. Fluorescence lifetime imaging microscopy measurements using a pH-sensitive probe provided information on the pH of the microenvironment of Ad5 particles during intracellular trafficking, and confirmed that the fast fiber dissociation step occurred at the onset of endocytosis. The slower dissociation phase was shown to coincide with the escape of Ad5 from endocytic compartments into the cytosol, and its arrival at the nuclear membrane. These results demonstrate a rapid, quantitative live-cell assay for the investigation of virus-cell interactions and capsid disassembly.

Adenoviruses, Human↗

PubMed2002

Stabilizing interactions between aromatic and basic side chains in alpha-helical peptides and proteins. Tyrosine effects on helix circular dichroism.

Here we investigate the structures and energetics of interactions between aromatic (Phe or Tyr) and basic (Lys or Arg) amino acids in alpha-helices. Side chain interaction energies are measured using helical peptides, by quantifying their helicities with circular dichroism at 222 nm and interpreting the results with Lifson-Roig-based helix/coil theory. A difficulty in working with Tyr is that the aromatic ring perturbs the CD spectrum, giving an incorrect helicity. We calculated the effect of Tyr on the CD at 222 nm by deriving the intensities of the bands directly from the electronic and magnetic transition dipole moments through the rotational strengths corresponding to each excited state of the polypeptide. This gives an improved value of the helix preference of Tyr (from 0.48 to 0.35) and a correction to the helicity for the peptides containing Tyr. We find that Phe-Lys, Lys-Phe, Phe-Arg, Arg-Phe, and Tyr-Lys are all stabilizing by -0.10 to -0.18 kcal.mol-1 when placed i, i + 4 on the surface of a helix in aqueous solution, despite the great difference in polarity between these residues. Interactions between these side chains have previously been attributed to cation-pi bonds. A survey of protein structures shows that they are in fact predominantly hydrophobic interactions between the CH2 groups of Lys or Arg and the aromatic rings.

Amino Acid Sequence↗

PubMed2002

Effect of phosphorylation on alpha-helix stability as a function of position.

We have investigated the effect of placing phosphoserine at the N-cap, N1, N2, N3, and interior position in alanine-based alpha-helical peptides. Helix contents of each peptide were measured by CD spectroscopy and titrations performed to determine pK(a) values. Data were analyzed with modified Lifson-Roig theory to determine helix-coil parameters (n, n(1), n(2), n(3), and w) and free energy changes for phosphoserine at each helical position. Results are given for a -1 and -2 phosphoserine charge state. Results show that phosphoserine stabilizes at the N-terminal positions by as much as 2.3 kcal.mol(-1), while destabilizes in the helix interior by 1.2 kcal.mol(-1), relative to serine. The rank order of free energies relative to serine at each position is N2 > N3 > N1 > N-cap > interior. Moreover, -2 phosphoserine is the most preferred residue known at each of these N-terminal positions. Experimental pK(a) values for the -1 to -2 phosphoserine transition are in the order N2 < N-cap < N1 < N3 < interior. This order agrees well with electrostatics calculations carried out with phosphoserine at the N-terminal positions and interior positions. Combining these with calculations at the C3, C2, C1, and C-cap positions gives results for phosphoserine along the length of the helix. We see a transition from phosphoserine stabilization at the N-terminus to destabilization at the C-terminus and can explain this in terms of the balance of protein solvation, favorable interactions, and dehydration. These results give insight into the phosphorylatable control of biological systems through positive or negative changes in stability.

Amino Acid Sequence↗

PubMed2002

Preformed oligomeric epidermal growth factor receptors undergo an ectodomain structure change during signaling.

Fluorescence resonance energy transfer (FRET) was used to reveal aspects of the mechanism of signal transduction by epidermal growth factor receptors (EGFR). The superpositions of epidermal growth factor (EGF), transforming growth factor-alpha (TGFalpha) and an antibody fragment (29.1) to the carbohydrate extremity of the receptor's ectodomain as measured by FRET, show that 14% of EGFRs in A431 cells are oligomerized before growth factor binding. After binding growth factor and signaling, these oligomers dissociate before releasing growth factor. Time courses of the FRET-derived distances between constitutively oligomerized EGFRs during signal transduction show a transient structural change in the extracellular domain, which occurs simultaneously with the production of intracellular Ca2+ signals. The FRET measurements also show a slow increase in oligomerization of EGFR monomers after growth factor binding. The structural change found in the extracellular domain of oligomeric EGFRs is similar to that shown by others for EPO, Neu, Fas, and tumor necrosis factor receptors, and may therefore be a common property of the transduction of the receptor-mediated signals.

Calcium Signaling↗

PubMed2002

Evaluation of rehabilitation outcomes in older patients with hip fractures.

OBJECTIVE: This study evaluated functional outcomes in patients with hip fracture after inpatient rehabilitation. DESIGN: The physical and cognitive functioning of 100 patients with hip fracture were determined by using the FIM instrument. The Montebello rehabilitation factor score was used to reflect rehabilitative outcome. Follow-up data were collected from 44 patients by using a telephone FIM interview. RESULTS: Discharge total FIM scores improved. The Montebello rehabilitation factor score for rehabilitation efficacy and efficiency scores both demonstrated improvement for patient function during inpatient rehabilitation. The mean motor FIM domain scores for transfer mobility and locomotion were lower at discharge compared with the domains of self-care and sphincter control. A subgroup of 44 patients showed no change in mean motor FIM domain scores. CONCLUSIONS: Inpatient rehabilitation improves overall functional independence as measured by the FIM instrument. Relative change, as measured by the Montebello rehabilitation factor score, indicated that rehabilitation outcome for locomotion was not maximized, despite exhibiting large absolute gains during inpatient rehabilitation. The improvements demonstrated at discharge were maintained at follow-up for a subgroup of 44 patients. Improved locomotion skills and maximizing ability to transfer independently are areas in which inpatient rehabilitation may be targeted to improve function in the future.

Aged↗