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Quadriceps function, proprioceptive acuity and functional performance in healthy young, middle-aged and elderly subjects.

BACKGROUND: Muscle functions to generate force-producing movement and also has a role in proprioception. If ageing compromises these sensorimotor functions of muscle, the ability of older subjects to detect and correct postural sway may be impeded, resulting in impairment of functional performance. METHOD: To see if age-related changes occurred and, if so, what their effects might be. Quadriceps strength, proprioception, postural stability and functional performance were assessed in young (n = 20, mean age 23 years), middle-aged (n = 10, mean age 56 years) and elderly (n = 15, mean age 72 years) subjects. RESULTS: With increasing age there were decreases in quadriceps strength (r = -0.511; P < 0.001), acuity of joint position sense (r = -0.603; P < 0.001) and postural stability (ANOVA < 0.002) during stance conditions which placed a greater reliance on muscle proprioceptors. These changes may decrease postural stability confidence, resulting in impaired performance of common activities of daily living (r = 0.635; P < 0.001). CONCLUSIONS: The age-related deterioration in sensorimotor function of muscle may contribute to the increased fear and frequency of falls in elderly subjects, thereby decreasing independence.

Accidental Falls↗

Proteasome mutants, pre4-2 and ump1-2, suppress the essential function but not the mitochondrial RNase P function of the Saccharomyces cerevisiae gene RPM2.

The Saccharomyces cerevisiae nuclear gene RPM2 encodes a component of the mitochondrial tRNA-processing enzyme RNase P. Cells grown on fermentable carbon sources do not require mitochondrial tRNA processing activity, but still require RPM2, indicating an additional function for the Rpm2 protein. RPM2-null cells arrest after 25 generations on fermentable media. Spontaneous mutations that suppress arrest occur with a frequency of approximately 9 x 10(-6). The resultant mutants do not grow on nonfermentable carbon sources. We identified two loci responsible for this suppression, which encode proteins that influence proteasome function or assembly. PRE4 is an essential gene encoding the beta-7 subunit of the 20S proteasome core. A Val-to-Phe substitution within a highly conserved region of Pre4p that disrupts proteasome function suppresses the growth arrest of RPM2-null cells on fermentable media. The other locus, UMP1, encodes a chaperone involved in 20S proteasome assembly. A nonsense mutation in UMP1 also disrupts proteasome function and suppresses Deltarpm2 growth arrest. In an RPM2 wild-type background, pre4-2 and ump1-2 strains fail to grow at restrictive temperatures on nonfermentable carbon sources. These data link proteasome activity with Rpm2p and mitochondrial function.

Alleles↗

Experimental evolution of a new enzymatic function. II. Evolution of multiple functions for ebg enzyme in E. coli.

The evolution of ebgo enzyme of Escherichia coli, an enzyme which is unable to hydrolyze lactose, lactulose, lactobionate, or galactose-arabinoside effectively, has been directed in successive steps so that the evolved enzyme is able to hydrolyze these galactosides effectively. I show that in order for a strain of E. coli with a lacZ deletion to evolve the ability to use lactobionate as a carbon source, a series of mutations must occur in the ebg genes, and that these mutations must be selected in a particular order. The ordered series of mutations constitutes an obligatory evolutionary pathway for the acquisition of a new function for ebgo enzyme. A comparison of newly evolved strains with parental strains shows that when ebg enzyme acquires a new function, its old functions often suffer; but that in several cases old functions are either unaffected or are improved. I conclude that divergence of functions catalyzed by an enzyme need not require gene duplication.

Biological Evolution↗

The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function.

BACKGROUND: Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function. METHODS: Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline. RESULTS: For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined. CONCLUSIONS: We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.

Aged↗

A reevaluation of the common factor theory of shared variance among age, sensory function, and cognitive function in older adults.

The common cause hypothesis of the relationship among age, sensory measures, and cognitive measures in very old adults was reevaluated. Both sensory function and processing speed were evaluated as mediators of the relationship between age and cognitive function. Cognitive function was a latent variable that comprised 3 factors including memory, speed, and verbal ability. The sample was population based and comprised very old adults (n = 894; mean age = 77.7, SD = 5.6 years) from the Australian Longitudinal Study of Ageing. The results showed that there was common variance in the cognitive factor shared by age, speed, vision, and hearing but that specific effects of age on cognition remained. Furthermore, speed did not fully mediate the effect of age or sensory function on cognition. Some age differences in cognitive performance are not explained by the same processes that explain age differences in sensory function and processing speed.

Aged↗

Non invasive assessment of regional diastolic left ventricular function with first pass radionuclide functional imaging in ischaemic heart disease.

Functional images of regional distribution of rapid filling (RF) rates have been developed and applied at rest and on exercise for regional analysis of 301 coronary artery territories (103 compromised by coronary narrowings, 198 normal). The observed time-interval of RF averaged 209 ms at rest (range 200 to 280) and 172 ms on exercise (range 125 to 200 ms). Normal RF is directed to the apex, and it is deviated from territories with reduced compliance to normal territories. Sensitivity in detection and localization of territories compromised by coronary narrowings exceeds 90% at rest for the anterior and infero-posterior wall and is higher than that obtained from systolic functional images. Specificity amounts also to over 90% and is much higher than that observed with systolic functional images. During RF, moderate to severe loss in compliance results in initial regional paradoxical inward motion in 40 to 45% of anterior or postero-inferior segments eventually accompanied by significant inward displacement of blood. Thus, with functional imaging of regional RF rates one can establish dysfunction and functional significance of coronary narrowings.

Adult↗

Influence of admission functional status on functional change after stroke rehabilitation.

OBJECTIVE: To determine whether the admission functional score influences the functional change after stroke rehabilitation. DESIGN: Two hundred forty-three patients who had received the Functional Independence Measure (FIM) assessment at admission and at discharge were enrolled in the study. The patients were stratified into three groups according to their FIM total scores at admission, i.e., < or =36, 37 to 72, and > or =73. RESULTS: The Scheffé's multiple comparison test showed that patients with FIM total scores of > or =73 at admission were significantly younger (58 +/- 11 [SD] yr) than those who had scores of 37 to 72 (64 +/- 11 yr) or < or =36 (66 +/- 12 yr). Patients with FIM total scores of 37 to 72 at admission showed significantly higher FIM gain (37 +/- 15) compared with those patients who had scores of > or =73 (20 +/- 10) or < or =36 (29 +/- 23). CONCLUSION: The functional levels of affected patients at admission stratified by the FIM scale roughly predict the degree of functional gain after rehabilitation in survivors with a first episode of ischemic stroke. Moderately affected patients will benefit from intensive rehabilitation. These findings may be useful for rehabilitation triage.

Aged↗

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

Brain↗

Restoration of function in the paralyzed rabbit orbicularis oculi muscle by direct functional electrical stimulation.

Restoration of the ability to blink and protect the eye in the patient with facial paralysis remains a challenge. Although many treatments exist, no one approach corrects all the deficits associated with the loss of orbicularis oculi function. In this study, the author investigated the feasibility of restoring function by direct electrical stimulation of the paralyzed orbicularis oculi muscle in the rabbit model. Using a pacing device developed by the author, functional restoration of a normal-appearing blink was produced throughout 30 days of continuous pacing in six rabbits with transected facial nerves. Histologic evaluations of the paced tissues demonstrated no evidence of detrimental effects attributable to the electrical stimulation. The findings of this study support the feasibility of employing direct electrical stimulation to restore the function of paralyzed orbicularis oculi muscles. Potential applications may also exist in other areas in which peripheral denervation creates functional impairment.

Animals↗

Integration of functional magnetic resonance imaging supported by magnetoencephalography in functional neuronavigation

OBJECTIVE: In this study, the intraoperative visualization of functional data provided by functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) leading to functional neuronavigation is demonstrated in surgery around the motor strip. METHODS: In seven patients with lesions adjacent to the central region, fMRI was performed with a 1.5-Tesla magnetic resonance system, using axial echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI and MEG were matched to an anatomic three-dimensional magnetic resonance image set by a contour fit. Then this three-dimensional image data set was transferred to the navigation microscope and displayed in the eyepieces of the microscope during surgery. Additionally, intraoperative recording of somatosensory evoked potentials was performed for verification of the central sulcus. RESULTS: In all cases, the projection of fMRI and MEG data into the operating viewing field allowed easy identification of the central region, which was confirmed by phase reversal of somatosensory evoked potentials in each case. fMRI and MEG measurements yielded corresponding results in each patient. CONCLUSION: Functional neuronavigation with integration of fMRI and MEG allows the fast identification of eloquent brain areas. The widespread availability of fMRI will result in a broad availability of functional neuronavigation, which will, in turn, contribute to the successful surgery of lesions in eloquent brain areas with lower morbidity.

Journal Article↗

An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.

OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Adolescent↗

Functional capacity and rehabilitation of recipients with a functioning renal allograft for ten years or more.

Forty-nine renal transplant recipients who had a single functioning allograft for ten or more years are reviewed. There were 17 cadaver recipients and 32 living-related recipients. Most patients have enjoyed excellent long-term renal function with stable mean daily dosages of azathioprine and prednisone. Fifty-three percent of patients never experienced a rejection episode, and 24% of patients experienced only one rejection episode. Five recipients (10%) developed malignancy following transplantation. Based on the Karnofsky activity scale, 80% of patients enjoyed unrestricted activity at ten years posttransplant. The two major factors contributing to declining activity were progression of systemic diseases such as atherosclerosis or diabetes, and declining allograft function. Following transplantation, all patients developed renewed interest in sexual activity, all men were potent, and all women experienced regular menses. Nine men achieved fatherhood and five women underwent successful pregnancy. Currently, 46 recipients are alive with a functioning allograft. These data confirm the ability of recipients with a long-term functioning renal allograft to return to the work force, participate in preillness levels of activity, and enjoy sexual activity and parenthood.

Activities of Daily Living↗

Glycaemic thresholds for hypoglycaemic symptoms, impairment of cognitive function, and release of counterregulatory hormones in subjects with functional hypoglycaemia.

Nine patients with food-relieved hypoglycaemic symptoms, in whom insulinoma and other organic diseases presenting with hypoglycaemia had been ruled out, and nine matched controls, participated in the study. Subjects were studied during a 5-h controlled (Biostator) insulin-induced (1-2 mU kg-1 min-1) hypoglycaemic clamp. After 1 h of euglycaemia, we aimed to lower the glucose level in arterialized venous blood in a stepwise manner at 30-min intervals to 3.5, 3.0, and 2.0 mmol l-1, and to withhold these levels for a further 30 min. At euglycaemia and at the end of the latter steps, the visual reaction time and cognitive function (digit span, letter cancellation and trail making) were tested, together with recording symptoms and signs of hypoglycaemia. Counter-regulatory hormones were measured at 20-min intervals. In the patients, clinical signs and symptoms of hypoglycaemia developed at median blood glucose levels of 2.6-2.8 and 2.8-3.1 mmol l-1, respectively. By contrast, the blood glucose levels were 0.4-0.8 mmol l-1 lower in control subjects (P less than 0.05). Similarly, the median threshold for deterioration of visual reaction time was 2.8 mmol l-1 in patients and 2.1 mmol l-1 in controls (P less than 0.01). A similar trend was observed for the results of the neuropsychological tests. Visual reaction time deteriorated in all subjects, whereas the cognitive function of some of the subjects in each group remained unchanged during hypoglycaemia. The glycaemic thresholds for release of cortisol, glucagon and growth hormone were significantly higher in patients (P less than 0.05), whereas the thresholds for catecholamine release showed no significant difference from controls. Despite the comparable glucose infusion rates required to sustain each of the hypoglycaemic levels in the two groups, the control subjects achieved lower glucose levels, suggesting that there is resistance to insulin or glucose in functional hypoglycaemia. In conclusion, the present study suggests that the existence of a higher threshold for symptoms and signs, as well as for deterioration of brain function, may explain every-day hypoglycaemic symptoms, despite normal glucose levels, in subjects with functional hypoglycaemia. However, the hypothesis should be tested further using a blinded approach, including euglycaemic control studies.

Adult↗

Cytochalasin modulation of nicotinic cholinergic receptor expression and muscarinic receptor function in human TE671/RD cells: a possible functional role of the cytoskeleton.

Previous studies have shown that cells of the TE671/RD human clonal line express muscle-type nicotinic acetylcholine receptors (nAChR) and m3-type muscarinic acetylcholine receptors (mAChR) whose numbers and function are regulated by agonist treatment and second messenger modulation. Here we show that cytochalasin treatment, which causes disruption of actin networks, induces marked changes in the numbers and distribution of nAChR, but not mAChR. Moreover, whereas cytochalasin treatment fails to alter nAChR function significantly, it acutely potentiates mAChR-mediated phosphoinositide hydrolysis. Treatment of TE671/RD cells with different cytochalasin analogues (rank order efficacy at 5 micrograms/ml is H > J = B = C = D > A = E) produces a two- to fourfold increase in numbers of membrane-bound nAChR (Bmax in units of specific 125I-labeled alpha-bungarotoxin binding per milligram of membrane protein). nAChR up-regulation is evident after 1-2 days of cytochalasin B exposure, is maximal after 3-6 days of drug treatment, and is dominated by an approximately 10-fold increase (per cell) in an intracellular nAChR pool. Cytochalasin-induced nAChR up-regulation is similar in magnitude to, but not additive with, up-regulation of nAChR following chronic exposure to nicotine or phorbol ester. Northern blot analysis shows a four- to five-fold coordinate increase in levels of mRNA that encode nAChR alpha, beta, gamma, or delta subunits in cytochalasin-treated cells, suggesting that nAChR up-regulation has a possible transcriptional basis. Studies done using a 86Rb+ efflux assay indicate that cytochalasin treatment has no significant effect on nAChR function. By contrast, cytochalasin treatment has no effect on the numbers of mAChR as assessed by binding studies with the radioantagonist 3H-labeled quinuclidinyl benzilate, but it induces marked enhancement of carbachol-stimulated, but not basal, phosphoinositide hydrolysis. These studies suggest that presumed modulation by cytochalasin treatment of cytoskeletal microfilament integrity can differentially influence expression and function of mAChR (a prototype of the metabotropic receptor superfamily) and nAChR (a prototype of the ligand-gated ion-channel superfamily). The results also suggest possible new roles for the cytoskeleton in regulation of membrane receptor expression, function, and cross talk.

Carbachol↗

Nutrition and function: is there a relationship between body mass index and the functional capabilities of community-dwelling elderly?

OBJECTIVE: To determine if there is a relationship between body mass index and the ability to perform the usual activities of living in a sample of community-dwelling elderly. DESIGN: Secondary data analysis of The National Health and Nutrition Examination Survey-I Epidemiologic Follow-up Study (1982-1984). Follow-up home interview of a population-based sample originally interviewed between 1971 and 1975 in the National Health and Nutrition Examination Survey-I (NHANES-I). PARTICIPANTS: Survivors of the original NHANES-I cohort who were 65 years of age or older and who were living at home at the time of the second interview (n = 3061). Excluded were those who could not be found, refused participation, or were institutionalized (n = 220), and those without complete height and weight data (n = 194). MAIN OUTCOME MEASURE: Functional status as measured by a 26-item battery. RESULTS: Bivariate analysis revealed a greater risk for functional impairment for subjects with a low body mass index or a high body mass index. The greater the extreme of body mass index (either higher or lower), the greater the risk for functional impairment. Logistic regression analysis indicated that both high and low body mass index continued to be significantly related to functional status when 22 other potential confounders were included in the model. CONCLUSION: The body mass index is related to the functional capabilities of community-dwelling elderly. The inclusion of this simple measurement in the comprehensive assessment of community-dwelling elderly is supported.

Activities of Daily Living↗

Retrograde migration of the site of functional block: a mechanism underlying resolution of functional retrograde bundle branch block during AV reentrant tachycardia.

INTRODUCTION: Functional bundle branch blocks during supraventricular tachycardia have been described, and their sustainment has been attributed to concealed conduction. Such blocks frequently resolve spontaneously, but the electrophysiologic mechanism of resolution has not been well described. This report describes the resolution of functional bundle branch block through proximal migration of the site of block. METHODS AND RESULTS: During electrophysiologic study of a patient with reentrant antidromic tachycardia via an atriofascicular accessory pathway, functional retrograde right bundle branch block could be readily induced following tachycardia initiation with right ventricular apical pacing. Resolution of this block was associated with shortening of the tachycardia cycle length. Electrogram recordings along the right bundle branch during tachycardia determined that resolution of the functional retrograde right bundle branch block was associated with migration of the site of block from the distal to the proximal right bundle. When the site of block was directly at the recording site, both anterograde and retrograde activation of the right bundle was demonstrated. CONCLUSION: Migration of the site of block is a mechanism of resolution for functional conduction blocks maintained by concealed conduction.

Adult↗

Characterization of the point spread function and modulation transfer function of scattered radiation using a digital imaging system.

A digital radiographic system was used to measure the distribution of scattered x radiation from uniform slabs of Lucite at various thicknesses. Using collimation and air gap techniques, [primary + scatter] images and primary images were digitally acquired, and subtracted to obtain scatter images. The scatter distributions measured using small circular apertures were computer fit to an analytical function, representing the circular aperture function convolved with a modified Gaussian point spread function (PSF). On the basis of goodness of fit criterion, the proposed Gaussian function is a very good model for the scatter PSF. The measured scatter PSF's are reported for various Lucite thicknesses. Using the PSF's, the modulation transfer functions are calculated, and this spatial frequency information may have value in analytical scatter removal techniques, grid design, and air gap optimization.

Computers↗

Bacteriophage P22 virion protein which performs an essential early function. II. Characterization of the gene 16 function.

P16 is a virion protein and, as such, is incorporated into the phage head as a step in morphogenesis. The role of P16 in assembly is not essential since particles are formed without this protein which appear normal by electron microscopy. P16 is essential when the particle infects a cell in the following cycle of infection. In the absence of functional P16, the infection does not appear to proceed beyond release of phage DNA from the capsid. No known genes are expressed, no DNA is transcribed, and the host cell survives the infection, continuing to grow and divide normally. The P16 function is required only during infection for the expression of phage functions. Induction in the absence of P16 proceeds with the expression of early and late genes and results in particle formation. P16 must be incorporated during morphogenesis into progeny particles after both infection and induction for the progeny to be infectious. The P16 function is necessary for transduction as well as for infection. Its activity is independent of new protein synthesis and it is not under immunity control. P16 can act in trans, but appears to act preferentially on the phage or phage DNA with which it is packaged. The data from complementation studies are compatible with P16 release from the capsid with the phage DNA. In the absence of P16 the infection is blocked, but the phage genome is not degraded. The various roles which have been ruled out for P16 are: (i) an early regulatory function, (ii) an enzymatic activity necessary for phage production, (iii) protection of phage DNA from host degradation enzymes, (iv) any generalized alteration of the host cell, (v) binding parental DNA to the replication complex, and (vi) any direct involvement in the replication of P22 DNA. P16 can be responsible for: (i) complete release of the DNA and disengagement from the capsid, (ii) bringing the released DNA to some necessary cell site or compartment such as the cytoplasm, (iii) removal of other virion proteins from the injected DNA, and (iv) alterations of the structure of the injected DNA.

Adsorption↗