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Results for “functionality”

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PubMed1996

[Alteration of cognitive functions during extended wakefulness: role of the brain functional asymmetry].

The study was aimed at looking into the effects of prolonged wakefulness on the activities predominantly governed by the left or right hemisphere. To this end, the subjects were requested to fulfill tests of manual/verbal interaction (1), establishment of similarity through the names of two tachistoscopic letters (2), evaluation of spatial proportions when using the right or left hand (3). The experiment was run with 16 male-subjects eight of which were tested following sleepless night whereas the other eight subjects had a normal night rest. In test 1, the deprived subjects exhibited lower tapping rate of both right and left hands than their counterparts; this fact may point to deteriorated function of anterior hemisphere compartments. The fact that under the effect of competing verbal activity both groups slowed down tapping by either hand at the same rate speaks in favor of immutability of the relative activation of anterior compartments of the right and left hemispheres, maintenance of the norm-specific basal profile of functional asymmetry after sleep deprivation. During prolonged sleep deprivation, test 2 displayed dominance of the right hemisphere in correct identification of letters which was not the case in the control. In deprived subjects test 3 showed overestimation of the left part of space when determining line lengths. Hence, results of experiments 2 and 3 suggest a relative activation of the caudal compartments of the right hemisphere during long wakefulness.

Adolescent↗

PubMed1999

Submillimeter functional localization in human striate cortex using BOLD contrast at 4 Tesla: implications for the vascular point-spread function.

Using multislice segmented echoplanar imaging at 4 T, we have measured an upper bound to the cortical vasculature point-spread function (PSF) using functional magnetic resonance imaging (fMRI) in humans. Our experiments demonstrate that cortical subunits that are approximately 700 microm apart can be resolved using the early part of the hyperoxygenation phase of the blood oxygenation level-dependent (BOLD) effect. This was accomplished using brief (4 sec) single trials of monocular and binocular stimulation of ocular dominance columns in human primary visual cortex. The data suggest that at even higher magnetic fields, the cortical vasculature PSF may be limited by the extent and nature of horizontal connections and not signal-to-noise ratio.

Adult↗

PubMed2000

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

PubMed2000

Locating and fractionating working memory using functional neuroimaging: storage, maintenance, and executive functions.

Working memory encompasses the short-term store of information and operations on that information. We review functional neuroimaging studies that have attempted to determine cortical areas involved in working memory functions. Current research suggests distinct systems for verbal information, visual objects, and spatial locations. Passive storage buffers appear to be located in posterior brain areas, whereas active maintenance of the information involves ventrolateral prefrontal areas. More complex, executive operations appear to recruit dorsolateral prefrontal cortex and anterior cingulate cortex. The possible involvement of reciprocal circuits including frontal cortex, basal ganglia, and thalamus is also discussed.

Brain↗

PubMed1992

Activity-induced pain in rheumatoid arthritis functional class II and its relations with demographic, medical, functional, psychosocial, and work variables. Result of a survey in Bollnäs Medical District, Sweden, II.

One aim of this study was to describe inflammatory activity, joint destruction, work status, and demographic factors in a group of 69 American Rheumatism Association functional class-II rheumatoid arthritis patients: 56 women and 13 men, mean age 54 years (SD 11), mean symptom duration 14 years (SD 11). Another aim was to determine correlations between activity-induced pain and other variables. Patients were assessed with Ritchie's articular index, Larsen's radiologic index, and laboratory tests. Deformity in hands and knee joints, and grip strength, were determined. Results from earlier investigations of functional impairment and psychosocial capacity were also used. Of the patients, 4% had high inflammatory activity. Joint erosions were found in between 4% (knee joints) and 55% (wrists) of the joints examined. Of the patients aged less than 65, 43% were working. Activity-induced pain was related with work status (p = 0.0002). It also correlated significantly (p less than or equal to 0.01) with inflammatory activity (r(s) = 0.34), but not with joint destruction (r(s) = 0.21).

Activities of Daily Living↗

PubMedDate not supplied

Monitoring of polymorphonuclear leukocyte functions in diabetes mellitus--a comparative study of conventional radiometric function tests and low-light imaging systems.

In this study neutrophil (PMN) phagocytic capacity was investigated using a conventional radiometric ingestion assay (IN) in comparison with PMN respiratory burst activity assessed by luminol-enhanced chemiluminescence (LCL) in response to phorbolesters and LCL induction during phagocytosis of opsonized Staphylococcus aureus (STLCL) in diabetes mellitus and healthy controls. PMN ingestion was measured with 3H-thymidine-labelled S. aureus in a kinetic radiometric assay. LCL and STLCL were assessed in a parallel detecting microtitre-plate luminometer (MTP-Reader). PMN of diabetic subjects showed a highly significant reduction of peak LCL in response to PMA as well as during phagocytosis of S. aureus (STLCL) compared to non-diabetic controls (p < 0.001 respectively). PMN ingestion in diabetic patients (51.8 +/- 4.6%) was significantly reduced compared to controls (78.3 +/- 6.2%) (p < 0.01). The in vitro data displayed impaired PMN oxidative burst activity at glucose concentrations > or = 13.8 mmol/L, whereas PMN IN was significantly reduced at glucose levels > or = 27.75 mmol/L. The control group showed a positive correlation of peak LCL response and IN (p < 0.05) but not of STCL and IN; in diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearly demonstrated impaired PMN respiratory burst activity and markedly reduced phagocytic PMN functions in diabetic patients ex vivo and in vitro as measured by LCL and by ingestion of 3H-thymidine-labelled S. aureus suggesting inhibitory effects of elevated glucose concentrations on various PMN-functions, which might be of clinical importance concerning altered host defence.

Adolescent↗

PubMed1980

Ontogeny of B lymphocyte function. VIII. Failure of thymus cells from aged donors to induce the functional maturation of B lymphocytes from immature donors.

The role of thymus cells in mediating a step in the ontogeny of the capacity of the B cell population to produce a heterogeneous, high-affinity, primary, plaque-forming cell (PFC) response was further investigated. It was shown that the thymus acquires the capacity to facilitate this step in B cell differentiation between 3 and 4 weeks of age in C57BL/6 mice. This corresponds to the age at which te splenic B cell population of these mice naturally acquires the capacity to produce high-affinity PFC. The differentiation of the B cell population. It was further shown that regulates this step in the cells to facilitate the maturation of B cell population. It was further shown that the ability of thymus cells to facilitate the maturation of the B cell population decreases with age and is already markedly reduced in 30-week-old, long-lived, C57BL/6 mice. A qualitative or quantitative decrease in thymic function may thus be responsible for age-related changes in the function of the B cell population.

Aging↗

PubMed1993

Dissection of human Langerhans cells' allostimulatory function: the need for an activation step for full development of accessory function.

In the present study, we analyzed the mechanism by which human Langerhans cells (LC), the dendritic cells (DC) from epidermis, support the induction of a primary allogeneic T cell response. We reported that paraformaldehyde (PF) fixation completely abrogated the stimulatory property of freshly isolated LC, although the level of major histocompatibility complex (MHC) class II antigen (Ag) expression was unaltered by the fixative. Addition of either interleukin (IL)-1 beta and/or IL-6, during the mixed epidermal cell lymphocyte reaction, failed to restore the proliferative response. By contrast, when human LC were incubated for 3 days in culture medium before fixation, they retained a low but significant allostimulatory capacity. Trypsin treatment of incubated LC before fixation did not impair their function, suggesting that stimulatory activity by fixed incubated LC did not merely reflect a repair of LC membrane after trypsin trauma suffered during epidermal cell (EC) isolation. More interestingly, we found that addition of interferon-gamma during LC incubation mediated an enhanced allostimulatory activity by the PF-fixed LC. Acquisition of allostimulatory property by in vitro activated and fixed LC did not correlate with increased MHC class II Ag expression at the cell surface. By contrast, we showed that ICAM-1 Ag expression by human LC is involved in this maturation process. Finally, we found that once human LC have been activated, IL-1 beta, but not IL-6, could serve as a costimulatory factor in the primary allogeneic T cell response. In conclusion, the data suggest that human LC accessory function is not constitutive but requires an activation step which can be provided by interferon-gamma during LC-T cell interaction.

Antigen-Presenting Cells↗

PubMed2003

Germ-line transcription occurs on both the functional and the non-functional alleles of immunoglobulin constant heavy chain genes.

In B cells undergoing class switching, recombination is usually directed to the same switch sequences on both homologous chromosomes and is generally preceded by germ-line transcription initiated from I promoters upstream of immunoglobulin constant heavy chain genes. Whether germ-line transcription occurs on both alleles or is restricted to the productive one has not been directly addressed before. To clearly distinguish between these two possibilities, a system is needed in which one might detect allele-specific germ-line transcripts. We used homologous recombination to set up two in vivo systems in which one gamma3 allele was marked by a loxP sequence whereas the other allele was silenced by inhibiting mu heavy chain production. Here, we provide evidence that germ-line transcription occurs on both the functional and the non-functional alleles.

Alleles↗

PubMed1998

European Functional Analysis Network (EUROFAN) and the functional analysis of the Saccharomyces cerevisiae genome.

Less than two yeras after the sequence of its genome was completed, the baker's yeast, Saccharomyces cerevisiae, is a leading organism in the rapidly growing field of functional genomics. Two thousands novel protein coding genes, nearly all of them "orphans", have already been disrupted by the coordinated efforts of a large consortium of European laboratories, EUROFAN, and other initiatives. The mutants are submitted to many specialized functional assays, and studies are performed in parallel at the transcriptome and the proteome levels. With a central repository of mutant yeast strains, and a centralized database, EUROFAN lays the foundations for the future of genomics with yeast serving both as a model and a tool.

DNA Transposable Elements↗

PubMed2006

Functional role of calcium signals for microglial function.

In this review we summarize mechanisms of Ca(2+) signaling in microglial cells and the impact of Ca(2+) signaling and Ca(2+) levels on microglial function. So far, Ca(2+) signaling has been only characterized in cultured microglia and thus these data refer rather to activated microglia as observed in pathology when compared with the resting form found under physiological conditions. Purinergic receptors are the most prominently expressed ligand-gated Ca(2+)-permeable channels in microglia and control several microglial functions such as cytokine release in a Ca(2+)-dependent fashion. A large variety of metabotropic receptors are linked to Ca(2+) release from intracellular stores. Depletion of these intracellular stores triggers a capacitative Ca(2+) entry. While microglia are already in an activated state in culture, they can be further activated, for example, by exposure to bacterial endotoxin. This activation leads to a chronic increase of [Ca(2+)](i) and this Ca(2+) increase is a prerequisite for the release of nitric oxide and cytokines. Moreover, several factors (TNFalpha, IL-1beta, and IFN-gamma) regulate resting [Ca(2+)](i) levels.

Animals↗

PubMed2005

Cerebellum and auditory function: an ALE meta-analysis of functional neuroimaging studies.

Over the past two decades neuroimaging data have accumulated showing that the cerebellum, traditionally viewed only as a motor structure, is also active in a wide variety of sensory and cognitive tasks. We have proposed that instead of explicit involvement in any particular motor, sensory, or cognitive task, the cerebellum performs a much more fundamental computation involving the active acquisition of sensory data. We carried out an activation likelihood estimate (ALE) meta-analysis to determine whether neuroimaging results obtained during a wide range of auditory tasks support this proposal. Specifically, we analyzed the coordinates of 231 activation foci obtained in 15 different auditory studies selected through an extensive search of the positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) literature. The studies selected represent a wide variety of purely auditory tasks using highly controlled synthesized acoustic stimuli. The results clearly revealed that in addition to temporal auditory areas of cerebral cortex, specific regions in the cerebellum are activated consistently across studies regardless of the particular auditory task involved. In particular, one area in left lateral crus I area showed the greatest volume and ALE peak value among the extratemporal regions. A subanalysis was carried out that ruled out the specific association of this cerebellar cluster with attentional demand. The results are consistent with the hypothesis that the cerebellum may play a role in purely sensory auditory processing, and are discussed in light of the broader idea of the cerebellum subserving a fundamental sensory function.

Acoustic Stimulation↗

PubMed2000

Functional magnetic resonance imaging reflects changes in brain functioning with sedation.

Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2006

Functional cognitive assessment scale (FUCAS): a new scale to assess executive cognitive function in daily life activities in patients with dementia and mild cognitive impairment.

BACKGROUND: Several tests have been developed to examine performance of demented patients in daily life activities. However, most of them are based either on the subjective evaluation of performance by the patient him/herself, or on the reports of relatives. Functional Cognitive Assessment Scale (FUCAS) is a new reliable (alpha > 0.89 - 0.92) cognitive-behavioral scale that assesses executive function in daily life activities directly in patients with dementia. AIMS: This study aimed at testing FUCAS' internal consistency of items, criterion-related validity, interrater reliability, discriminative ability, and effect of age, sex, and education on FUCAS scores. RESULTS: Criterion-related validity was supported by significant correlations between FUCAS, CAMCOG, MMSE, and FRSSD. The interrater reliability of FUCAS' total score for two raters was r 0.997 and we found no significant effect of age, sex, or education on FUCAS' total performance. Discriminant analysis has identified that FUCAS was able to sufficiently discriminate the patients with MCI from those with moderate-severe dementia. CONCLUSION: FUCAS is a useful and reliable diagnostic tool for MCI. Cognitive-behavioral assessment such as that provided by FUCAS can provide objective information that can serve to enhance the quality of clinical decision-making.

Activities of Daily Living↗

PubMed1993

The tyrosine phosphorylation site of the acetylcholine receptor beta subunit is located in a highly immunogenic epitope implicated in channel function: antibody probes for beta subunit phosphorylation and function.

Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) seems to be involved in AChR desensitization and localization on the postsynaptic membrane. This study reveals a probable function of the single known beta subunit phosphorylation site (beta Tyr355) and provides suitable tools for its study. The epitopes for 15 monoclonal antibodies (mAbs) against the cytoplasmic side of the AChR beta subunit were precisely mapped using > 100 synthetic peptides attached on polyethylene rods. Eleven mAbs bound to a very immunogenic cytoplasmic epitope (VICE-beta) on Torpedo beta 352-359, which contains the beta Tyr355, and to the corresponding sequence of human AChR. The contribution of each VICE-beta residue to mAb binding was then studied by peptide analogues having single residue substitutions. Overall, each of the residues beta 354-359, including beta Tyr355, proved critical for mAb binding. Two of our four mAbs known to block the ion channel were found to bind at (mAb148) or close (mAb10) to VICE-beta. Tyrosine phosphorylation of Torpedo AChR by endogenous kinase(s) selectively reduced binding of some VICE-beta mAbs, including the channel blocking mAb148. We conclude that VICE-beta probably plays a key role in AChR function. Elucidation of this role should be facilitated by the identified mAb tools.

Amino Acid Sequence↗

PubMed2003

Wave functions derived from experiment. V. Investigation of electron densities, electrostatic potentials, and electron localization functions for noncentrosymmetric crystals.

The constrained Hartree-Fock method using experimental X-ray diffraction data is extended and applied to the case of noncentrosymmetric molecular crystals. A new way to estimate the errors in derived properties as a derivative with respect to added Gaussian noise is also described. Three molecular crystals are examined: ammonia [NH(3)], urea [CO(NH(2))(2)], and alloxan [(CO)(4)(NH)(2)]. The energetic and electrical properties of these molecules in the crystalline state are presented. In all cases, an enhancement of the dipole moment is observed upon application of the experimental constraint. It is found that the phases of the structure factors are robustly determined by the constrained Hartree-Fock model, even in the presence of simulated noise. Plots of the electron density, electrostatic potential, and the electron localization function for the molecules in the crystal are displayed. In general, relative to the Hartree-Fock model, there is a depletion of charge around hydrogen atoms and lone pair regions, and a build-up of charge within the molecular framework near nuclei, directed along the bonds. The electron localization function plots reveal an increase in the pair density between vicinal hydrogen atoms.

Journal Article↗

PubMed1984

Characterization of purified cryopreserved human monocyte function in assays of superoxide production, accessory cell function, chemotaxis, and in fluorescent cell sorter analysis.

The ability to use highly purified cryopreserved human monocytes in various in vitro assays has a number of practical and theoretical advantages, including convenience and the potential for enhanced reproducibility. Large numbers (up to 1 X 10(9)) human monocytes can be isolated from a single donor in a purified suspension state, by a combination of leukapheresis and counter-current centrifugal elutriation (CCE) technologies. Following short- and long-term periods of cryopreservation, the viability and phagocytic function of these CCE-purified monocytes was unimpaired. Cryopreserved monocytes were similar to fresh cells in their ability to release superoxide anion (O2-), although unstimulated and stimulated O2- release values tended to increase slightly following weeks to months of cryopreservation. In contrast, even short-term cryopreservation diminished both the random migration and chemotactic responses of human monocytes; however, cryopreserved monocytes could be employed in this assay provided the calculated chemotactic ratio (chemotactic migration/spontaneous migration) was used. Cryopreserved monocytes demonstrate 70% of fresh monocyte accessory cell function in pokeweed mitogen-induced lymphocyte proliferation assays. When the binding of OKT3, OKM1, anti-DR, and fluoresceinated pokeweed mitogen to monocytes was analyzed in the fluorescence activator cell sorter (FACS), cryopreserved and fresh monocytes displayed a similar pattern of membrane reactivity.

Chemotaxis, Leukocyte↗

PubMed1997

Structure and function of embryonic growth plate in the absence of functioning skeletal muscle.

Normal growth and development of the skeleton require the presence of viable, actively contracting skeletal muscle throughout the fetal period. A chick embryo model of midgestation chemical paralysis and secondary muscle atrophy was used to test the hypothesis that functioning muscle stimulates the growth of long bones by influencing the proliferation, differentiation, and hypertrophy of chondrocytes in cartilage of the epiphysis and growth plate. Paralysis did not alter the overall developmental stage of the long bone or the organization of the growth plate. Compared with controls, however, uptake of bromodeoxyuridine in the paralyzed chick was reduced by 27-55% in the chondroepiphysis and uppermost zone of the tibial growth plate, indicating reduced proliferation of chondrocytes. A specific reduction in the size of the proliferative zone and a reduced number of proliferating cells were also observed. By contrast, in the second, post-proliferative zone of the growth plate, the height of the zone was unchanged and its area was only slightly reduced compared with controls. Finally, median hypertrophic cell profile area, a measure of cell size, was not significantly affected by paralysis, although frequency analysis revealed modest numerical reductions in the population of the largest hypertrophic chondrocytes in the paralyzed group. These data suggest that the role of functioning fetal muscle in maintaining proper skeletal growth may be mediated primarily through specific stimulation of the recruitment or proliferation of immature chondrocytes, or of both.

Animals↗