SEARCH · PubMed Health

Results for “functionality”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

PubMed2005

Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects.

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.

Coronary Circulation↗

PubMed1997

FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements.

The ETS gene products are a family of transcriptional regulatory proteins that contain a highly conserved and structurally unique DNA binding domain, termed the ETS domain. Several ETS proteins bind to DNA as monomers, however it has been shown that the DNA binding activity is enhanced or modulated in the presence of other factors. By differential display and whole genome PCR techniques, we have recently shown that the Erg1 gene is a target for ETS proteins. The Egr1 promoter contains multiple ETS binding sites, three of which exist as parts of two serum response elements (SREI and SREII). The SRE is a cis-element that regulates the expression of many growth factor responsive genes. ELK1 and SAP1a have been shown to form ternary complexes with SRF on the SRE located in the c-fos promoter. Similarly, we examined whether the ELK1, SAP1a, FLI1, EWS-FLI1, ETS1, ETS2, PEA3 and PU.1 proteins can form ternary complexes with SRF on the Egr1 SREI and II. Our results demonstrate that indeed ELK1, SAPla, FLI1 and EWS-FLI1 are able to form ternary complexes with SRF on Egr1 SREs. In addition, ELK1 and SAP1a can also form quarternary complexes on the Egr1 SREI. However, the proteins ETS1, ETS2, PEA3 and PU.1 were unable to form ternary complexes with SRF on either the Egr1 or c-fos SREs. Our data demonstrate that FLI1 and EWS-FLI1 constitute new members of a subgroup of ETS proteins that can function as ternary complex factors and further implicate a novel function for these ETS transcription factors in the regulation of the Egr1 gene. By amino acid sequence comparison we found that, in fact, 50% of the amino acids present in the B-box of SAP1a and ELK1, which are required for interaction with SRF, are identical to those present in both FLI1 (amino acids 231- 248) and EWS-FLI1 proteins. This B-box is not present in ETS1, ETS2, PEA3 or PU.1 and these proteins were unable to form ternary complexes with SRF and Egrl-SREs or c-fos SRE. Furthermore, deletion of 194 amino terminal amino acids of FLI1 did not interfere with its ability to interact with SRF, in fact, this truncation increased the stability of the ternary complex. The FLI1 protein has a unique R-domain located next to the DNA binding region. This R-domain may modulate the interaction with SRF, providing a mechanism that would be unique to FLI1 and EWS-FLI1, thus implicating a novel function for these ETS transcription factors in the regulation of the Egr1 gene.

Animals↗

PubMed2001

A "no-hybrids" screen for functional antagonizers of human p53 transactivator function: dominant negativity in fission yeast.

We have developed a functional "no-hybrids" screen in the fission yeast Schizosaccharomyces pombe based on the transcription transactivator activity of human p53. The screen can be used to identify antagonizers and modulators of p53 activity. Expression of functional full-length human p53 is conditionally lethal to the screen reporter strains. Co-expression of specific inhibitory proteins promotes cell survival and growth. We have validated the "no-hybrids" system by (a) successful modeling of human wild-type p53 interaction with SV40 large T antigen, Mdm2 and a panel of tumor-derived human p53 mutants, (b) demonstrating the screening system's efficiency through identification of a dominant negative fragment of p53 itself in a library screen context and (c) using Drosophila p53 to demonstrate that the system can detect evolutionarily distant p53 homologues based on their transactivator activity. The "no-hybrids" screen will be of utility in searches for p53 function-modulators of both cellular and viral origin.

Animals↗

PubMed2006

Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.

Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are characterized by aberrant cytoplasmic localization of NPM, due to mutations within its last coding exon (exon 12) that cause a frameshift and the formation of novel C-termini. We report here our investigations on the molecular basis for the aberrant localization of mutated NPM. Alignment of the C-terminus of the various NPM mutants revealed the obligatory presence of four amino-acid residues that match a CRM1-dependent nuclear export signal (NES). Single alanine-substitutions at these sites provoked nuclear re-localization, while fusion of the mutated C-terminus to a heterologous nuclear protein induced CRM1-dependent cytoplasmic localization. Molecular characterization of one exceptional AML carrying cytoplasmic NPM and germ line exon 12 revealed a somatic mutation in the splicing donor site of exon 9 that caused the formation of a functional NES. It appears, therefore, that AMLs are frequently characterized by gain-of-function mutations of NPM that create functional NES, suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention.

Acute Disease↗

PubMed1974

Weighting functions and data truncation in the fitting of multi-exponential functions.

Artificial data were simulated by using two-exponential functions and normally distributed pseudo-random numbers. The variation corresponded to either constant or relative variance for the data error. These data were used to test (i) three different weighting functions and (ii) the effect of data truncation on the precision of estimating the parameters of two-exponential functions.

Analysis of Variance↗

PubMed1996

Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

Adaptation, Physiological↗

PubMed2003

Molecular, ultrastructural and functional characterization of a Spanish family with Hermansky-Pudlak syndrome: role of insC974 in platelet function and clinical relevance.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, which is genetically heterogeneous. In humans, mutations associated with this syndrome have been identified that affect four genes, most of them located in the HPS-1 gene. We evaluated the clinical, molecular, platelet ultrastructure and platelet function data obtained from one Spanish HPS patient and his relatives. The proband was compound heterozygous for a de novo nonsense mutation (Arg-131Stop), which has not been described previously, and for a common frameshift mutation (insC974). These two mutations were also identified by reverse transcription polymerase chain reaction (RT-PCR) in half the RNA, supporting the premise that they have minor effects on either transcription or RNA stability. The patient had an almost complete absence of platelet-dense granules. Accordingly, his platelets showed a small aggregatory response, reduced CD63 surface expression after platelet activation and minor serotonin uptake. Interestingly, despite the absence of clinical symptoms, two relatives carrying only one HPS-1 mutation (insC974) presented a decreased content of platelet-dense granules and showed significant reductions in platelet aggregation, expression of CD63 after platelet activation and serotonin uptake. Data show that the presence of a single mutation affecting one allele of the HPS-1 gene might have relevance in the organogenesis of platelet-dense granules, affecting platelet function. However, these functional defects were not of a great enough magnitude to have clinical significance and, thus, these subjects were clinically asymptomatic.

Blood Platelets↗

PubMed1999

Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules.

OBJECTIVE: To investigate the long-term effects of radioiodine (131I) on thyroid function and size in patients with a solitary toxic thyroid nodule. DESIGN: Prospective study of patients treated for a solitary autonomous toxic nodule, followed by evaluation of thyroid volume and function. PATIENTS: Sixty-two consecutive patients followed for a minimum of 12 months (range 12-168, median 60). Seventeen patients received antithyroid drug treatment before 131I. MEASUREMENTS: Standard thyroid function variables and ultrasonically determined thyroid volume before as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. RESULTS: 131I treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-h 131I uptake) was given as a single dose in 53 patients; six needed two doses and another three were given 3-5 131I treatments. The median initial dose was 310 MBq (140-666) and the median total dose was 332 MBq (148-1576). In patients receiving one 131I treatment (n = 53) the total thyroid volume decreased significantly from a median of 40 ml (range 19-77) to 24 ml (8-50) within 3 months. This represented a median reduction of 35%. A further significant decrease was seen after 24 months to a total reduction of 45%. In patients given more than one dose the thyroid volume was reduced from a median of 45 ml (19-104) before treatment to 30 ml (14-50) after a follow-up of 60 months (9-132) after the last 131I treatment. Patients without antithyroid pretreatment, receiving one 131I treatment (n = 39) became euthyroid after a median of 1.5 months (0.75-9) after treatment. Seventy-five per cent were euthyroid within 3 months. In patients pretreated with antithyroid drugs and treated with one dose of 131I (n = 14) euthyroidism was achieved after a median of 12 months (0.75-24) after 131I treatment. Hypothyroidism developed in five patients (8%) after a median of 36 months (6-60) after 131I treatment. CONCLUSION: A cure-rate of 75% within 3 months is seen when treating autonomous solitary toxic thyroid nodules with 131I. The thyroid volume is reduced by 35% within 3 months and 45% after 2 years. Side-effects are few and consist of hypothyroidism in less than 10% with a median follow-up of 5 years. This treatment should be regarded as the standard treatment for this condition until prospective comparisons with surgery and ethanol injection therapy have been performed.

Adult↗

PubMed1997

Environmental regulation of T-cell function in mice: group housing of males affects accessory cell function.

The number of mice housed in a cage was found to exert a major impact on immune function in male mice. Lymph node cells from hen lysozyme (HEL)-primed C57BL/6 male mice, housed in groups of 6/cage or individually, were tested for T-cell proliferative response. Group-housed males showed markedly lower responses than age-matched females. However, in males housed singly for 4-15 weeks, responses were considerably higher, approaching those of female controls. To examine the cellular site of action of the housing effect, the efficiency of splenic antigen-presenting cells (APC) was examined. APC from grouped males were considerably less efficient than APC from females, whereas males housed singly had increased APC function, reaching female levels. Our results demonstrate that environmental manipulation can profoundly modulate cellular immunity, and provide a first mechanistic indication that APC function is a major target for this modulation.

Animals↗

PubMed2003

Preliminary evaluation of a scale to assess cognitive function in adults with Down's syndrome: the Prudhoe Cognitive Function Test.

BACKGROUND: In the clinical diagnosis of dementia in Down's syndrome (DS), it may be difficult to distinguish between cognitive deterioration and the various degrees of pre-existing intellectual disability (ID). Serial measurements of both cognitive function and behaviour are required. The aim of the present study was to evaluate the performance of non-demented adults with DS on a subject-directed instrument, the Prudhoe Cognitive Function Test (PCFT), preliminary to its serial use in a prospective study. METHODS: From 1985 to 1986, 85 non-demented hospitalized adults with DS were interviewed using the PCFT. The Adaptive Behavior Scale (ABS) was administered to the carers. The subjects' levels of ID (graded from mild through moderate, severe and profound to untestable) were based on their scores on the Stanford-Binet Intelligence Scale, as reported in the medical records, and the relationship between level of disability and performance on the PCFT and ABS, and their respective domains, was examined. RESULTS: Both scales produced a wide range of scores and the correlation between them was highly significant. Both scales correlated highly significantly with the degree of ID, but more subjects with high levels (i.e. profound to untestable) of disability obtained very low or zero scores on the PCFT and its domains than on the ABS. CONCLUSIONS: The PCFT provides a reliable quantitative measure of cognitive function in subjects with DS, and could be a useful adjunct to the diagnosis of dementia in prospective studies. However, the almost uniformly low scores obtained by those with high levels of ID suggests that its power to detect cognitive decline will be limited to those who are less disabled, while the ABS may be more useful than the PCFT in detecting deterioration in people with profound ID.

Adult↗

PubMed1997

Functional unilateral posterior crossbite. Orthodontic and functional aspects.

The purpose of the study was to evaluate the effect of early orthodontic treatment of functional unilateral posterior crossbite (FUPC) and to evaluate temporomandibular function in the short and long term. Orthodontic treatment consisted of slow expansion of the maxillary dental arch by means of a removable expansion plate, with flat coverage of the occlusal surfaces of the left and right posterior teeth. Evaluation of the occlusion showed a strong correlation between the crossbite side and the direction of the RCP-ICP slide and with the side of first occlusal contact in RCP. In 26 of 27 children that were treated (one withdrew), the average time required for correction of the crossbite was 7 months, followed by a retention period, on average, for 6 months after completion of treatment. Early orthodontic treatment resulted in an elimination of occlusal disturbances, and the crossbite remained stable on follow-up during an average of 8 years after the retention period, except in two children with a class III tendency. In nine other children an orthodontic anomaly had developed requiring further treatment (two children showed crowding and seven children showed a class II malocclusion). This study showed that FUPC can be treated adequately by early orthodontic intervention; however, its correction does not guarantee the absence of functional disturbances at a later age. Therefore, FUPC should be treated early in order to achieve normal growth and development rather than to prevent temporomandibular disorders.

Child↗

PubMed2000

Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS).

Brainstem function was evaluated by proton magnetic resonance (MR) spectroscopy (1H-MRS) in a 69-year-old man with idiopathic rapid eye movement (REM) sleep behavior disorder. An analysis of spectral peak area ratios revealed an increase in the choline/creatine ratio. This change suggests that brainstem neurons have functional impairment at the cell membrane level. Further, our results suggest that 1H-MRS may provide for non-invasive, metabolic evaluation of brainstem neuronal function in REM sleep behavior disorder and find application in the differentiation of secondary REM sleep behavior disorders with neurodegenerative disorders from idiopathic disorders.

Aged↗

PubMed2003

Quantitation of papillary muscle function with tissue and strain Doppler echocardiography measures papillary muscle contractile functions.

UNLABELLED: It is well known that papillary muscle dysfunction may cause mitral regurgitation, however, there is not a standard technique to measure the papillary muscle function. The aim of this study is to investigate papillary muscle function by using tissue and strain rate Doppler echocardiography. METHOD: A study group (SG) of 42 patients (12 females, 30 males, mean age: 53.8 +/- 10.9 years) with coronary artery disease who have segmental left ventricular dysfunction and mitral regurgitation, and as a control group (CG) 20 patients (6 females, 14 males, mean age 52.5 +/- 10.2 years) who have no coronary artery disease and mitral regurgitation were studied. A subgroup 20 patients (7 females, 13 males, mean age 42.5 +/- 7.5 years) who have rheumatic mitral regurgitation was included to the study. The patients who have left ventricular and mitral annular dilatation were not included into the study. Longitudinal wall motion of mid-inferior segment (one point) and posterior papillary muscle (two point) of the left ventricle was assessed by tissue and strain rate Doppler echocardiography from the apical two-chamber view. Systolic tissue velocity (Sm), strain rate (SR), and strain (S) were measured from the two points in all patients. RESULTS: Comparing the one point values Sm, SR, and S were found less in SG than CG (respectively 4.2 +/- 1.4 vs 11.3 +/- 1.9 cm/sec, -1.0 +/- 0.4 vs -1.7 +/- 0.3 s-1, -13.5 +/- 5.0 vs -18.1 +/- 3.9%; P < 0.001 for all). Comparing the two point values Sm, SR and S were found less in SG than CG (respectively 2.8 +/- 1.2 vs 3.7 +/- 2.0 cm/sec, -0.8 +/- 0.4 vs -1.6 +/- 0.3 s-1, -9.7 +/- 4.6 vs -15.8 +/- 3.7%; P < 0.001 for all). Systolic mitral annulus, left ventricular systolic and diastolic dimensions were similar in two groups. Comparing the CG and subgroup, there were no significant differences with respect to Sm, SR, and S measured from the two points. CONCLUSIONS: Papillary muscle function may be assessed quantitatively by using tissue and strain rate Doppler echocardiography. Tissue velocity, strain rate, and strain values were found decreased in dysfunctional papillary muscle.

Adult↗

PubMed2001

Impaired drinking capacity in patients with functional dyspepsia: relationship with proximal stomach function.

BACKGROUND & AIMS: Impaired fundic accommodation to a meal and hypersensitivity to distention are increasingly recognized as important mechanisms underlying functional dyspepsia (FD). In the present study, we evaluated whether a drink test can predict such abnormalities and thus represent a noninvasive tool to study proximal stomach motor function. METHODS: Healthy volunteers (HV), nonconsulters with mild dyspeptic symptoms (MS), and patients with FD filled out a disease-specific questionnaire and underwent a drink test with either water or with a high calorie fluid. The maximal ingested volume and the subsequent symptoms were meticulously recorded. In addition, all subjects underwent a gastric barostat study assessing meal-induced relaxation and sensation to distention. RESULTS: Drinking capacity was not significantly related to any particular dyspeptic symptom. FD were able to consume less water (893 +/- 70 mL) and caloric liquid (767 +/- 50 mL) compared with HV (water, 1764 +/- 120 mL; caloric liquid, 1308 +/- 96 mL) or MS (water, 1645 +/- 120 mL; caloric liquid, 973 +/- 45 mL). Approximately half of the FD had an abnormal water or Nutridrink test compared with 9% of MS and 4% of HV. Furthermore, FD developed significantly more symptoms than MS or HV after both drink tests. The drinking capacity did not predict impaired fundic accommodation or visceral hypersensitivity. CONCLUSIONS: FD, but not MS, have an impaired drinking capacity to both water and a nutrient liquid. The drinking capacity is not related to a specific dyspeptic symptom and does not predict proximal stomach motor function.

Adult↗

PubMed1999

Effect of topically applied evening primrose oil on epidermal barrier function in atopic dermatitis as a function of vehicle.

The aim of this study was to establish the effect on barrier function in atopic dermatitis of topical evening primrose oil in an amphiphilic and a stable water-in-oil emulsion. The studies were vehicle-controlled in two populations of 20 atopic subjects. Barrier function was assessed in terms of transepidermal water loss and stratum corneum hydration after a 4-week treatment period and a 1-week treatment-free period. A barrier function test with sodium lauryl sulphate (SLS) and nicotinic acid ester was also carried out. Evening primrose oil proved to have a stabilising effect on the stratum corneum barrier, but this was apparent only with the water-in-oil emulsion, not the amphiphilic emulsion. The choice of vehicle is therefore an extremely important factor in the efficacy of topically applied evening primrose oil.

Administration, Topical↗

PubMedDate not supplied

[The Pediatric Musculoskeletal Functional Health Questionnaire. A function assessment questionnaire for detection of illnesses of the locomotor system in children and adolescents--initial results of validating a German version].

AIM: It was the purpose of this investigation to create a German version of the Pediatric Musculoskeletal Functional Health Questionnaire and to test its reliability, practicability and acceptance in children and adolescents with musculoskeletal disorders. METHODS: In a first step, the Pediatric Musculoskeletal Functional Health Questionnaire was translated into the German language. Then 147 patients with musculoskeletal disorders or respectively, their parents were asked to fill in the questionnaire, in order to test the reliability, the internal consistency, the practicability, and the acceptance of this instrument. RESULTS: The test-retest reliability for the subscales was high, it ranged between r = 0.56 and 0.93. Concerning the internal consistency of items and subscales we found only moderate results. The acceptance of the Questionnaire was high in patients or, respectively, their parents with 92%. Furthermore, the instrument has shown to be practicable and economical. CONCLUSION: With the German version of the Pediatric Musculoskeletal Functional Health Questionnaire a multidimensional instrument is now available that reliably measures health status as well as therapeutic effects in children and adolescents with musculoskeletal disorders.

Adolescent↗

PubMed2005

Electron tunneling of photochemical reactions on metal surfaces: nonequilibrium Green's function-density functional theory approach to photon energy dependence of reaction probability.

We have developed a theoretical model of photoinduced reactions on metal surfaces initiated by the substrate/indirect excitation mechanism using the nonequilibrium Green's function approach. We focus on electron transfer, which consists of (1) electron-hole pair creation, (2) transport of created hot electrons, and (3) tunneling of hot electrons to form an anion resonance. We assume that steps (1), (2), and (3) are separable. By this assumption, the electron dynamics might be restated as a tunneling problem of an open system. Combining the Keldysh time-independent formalism with the simple transport theory introduced by Berglund and Spicer, we present a practical scheme for first-principle calculation of the reaction probability as a function of incident photon energy. The method is illustrated by application to the photoinduced desorption/dissociation of O2 on a Ag(110) surface by adopting density functional theory.

Journal Article↗

PubMed2005

Generalized nuclear Fukui functions in the framework of spin-polarized density-functional theory.

An extension of Cohen's nuclear Fukui function is presented in the spin-polarized framework of density-functional theory (SP-DFT). The resulting new nuclear Fukui function indices PhiNalpha and PhiSalpha are intended to be the natural descriptors for the responses of the nuclei to changes involving charge transfer at constant multiplicity and also the spin polarization at constant number of electrons. These generalized quantities allow us to gain new insights within a perturbative scheme based on DFT. Calculations of the electronic and nuclear SP-DFT quantities are presented within a Kohn-Sham framework of chemical reactivity for a sample of molecules, including H2O, H2CO, and some simple nitrenes (NX) and phosphinidenes (PX), with X=H, Li, F, Cl, OH, SH, NH2, and PH2. Results have been interpreted in terms of chemical bonding in the context of Berlin's theorem, which provides a separation of the molecular space into binding and antibinding regions.

Journal Article↗