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[Childhood psychoses and organic pathology: results of a study of 144 cases].

The records of 144 patients of Child Psychiatry Units of Alsace (France), with childhood psychosis (CP) or pervasive developmental disorders (PDD) have been systematically screened for previous or associated pathological events. Half of the children studied have been or are still affected by severe somatic disorders, but none of the diagnostic subcategories (referring to DSM III or CFTMEA) appeared significantly more frequently affected. In our population, the severity of organic disorders was positively correlated with: the age of the mother: more severe cases were reported when the mother was younger than 20 or older than 40 at the moment of childbirth; pathological events during pregnancy; early mother-child separation during the first year of life. The most frequent associated disorders however (neonatal pathology 45% of the cases, epilepsy 17% of the cases, neurological or neurosensorial pathology 15% of the cases) were associated neither with a specific diagnostic nor with a clinical and social specific pattern. The only statistically significant correlation was found between neurological pathology and a relatively low level of cognitive and social functioning. All these results were confirmed by multivariate statistical analysis. A main component analysis integrating all quantified data concerning organic pathology was performed: it emphasizes the independence of the different pathological events reported. The factorial analysis including the clinical, diagnostical and somatic event-related data failed to show any statistical profile associating functional features of the children with any particular previous or existing somatic disorders. Our results suggest that a history of organic pathological events is frequent not only in autistic disorders but in any kind of PDD or early CP - associated with moderate to severe mental retardation, in most cases of our study. However, this does not demonstrate that this type of pathological events constitute the direct and unique cause of PDD and CP: the concept of the aetiology of these severe diseases must take account of other factors - such as relational disruption -, also frequently seen in these children.

Adolescent↗

Nitric oxide generation by soybean embryonic axes. Possible effect on mitochondrial function.

Nitric oxide (NO) generation and its effect on mitochondrial enzymes were investigated in soybean embryonic axes at the onset of germination. NO was detected in homogenates from soybean embryonic axes by EPR. Enzymatic sources of NO, such as nitrate reductase activity and nitric oxide synthase, assessed as NADPH-diaphorase activity, were measured in homogenates incubated up to 48 h. Both NO content and the activity of the enzymes showed a similar profile as function of the imbibition time, with maximal levels at 15-24h. Total O2 consumption in enriched-mitochondrial fraction was inhibited by NO in a concentration-dependent manner. O2 consumption dependent on cytochrome oxidase activity was more sensitive than alternative oxidase pathway to NO exposure. Half maximal effects of NO at 0.3 and 3.6 microM were measured for cytochrome oxidase and alternative oxidase, respectively. Enriched-mitochondrial fractions from soybean embryonic axes treated with NO (up to 1 microM) showed increased H2O2 production. The data presented suggest that NO could modulate O2 consumption in soybean embryonic axes. This process could affect the pro-oxidant/antioxidant balance and the cellular energy yield in the germinating embryonic axes, and could have a role in soybean germination.

Electron Spin Resonance Spectroscopy↗

Prospective evaluation of abnormal liver function tests in pregnancy.

Abnormalities in liver function tests (LFT) during pregnancy are a commonly encountered problem often associated with serious consequences especially when it occurs in the third trimester. The spectrum of abnormal liver functions in pregnancy can be fairly wide and diagnostic work up often challenging. There is insufficient prospective data on the spectrum and outcome of liver disease in pregnant population from south India. This study was performed to assess the causes of deranged liver function in the pregnant population and also to prospectively determine the outcome of liver dysfunction in pregnancy. All abnormal LFT results observed in serum samples from pregnant patients attending the obstetric unit of our hospital from January 2003 to January 2005 were evaluated and prospectively followed throughout pregnancy. Laboratory investigations included coagulation profile, renal function tests, serology for viral markers (HBsAg, anti-HCV, IgM anti-HEV and IgM anti-HAV) and other relevant biochemical tests. In those with liver dysfunction in the third trimester the maternal and perinatal outcome was evaluated. A total of 125 patients were identified with abnormalities in LFT results during this period. The majority of causes were related to pregnancy specific conditions (57.6%). Most episodes of abnormal LFT occurred in the third trimester (59.2%). Hyperemesis gravidarum (55.8%) and viral hepatitis (47%) were the most common causes of abnormal LFT in the first and second trimesters respectively. HELLP (28.3%) and AFLP (14.8%) were the most common causes of abnormal LFT in the third trimester. There were no mAternal deaths due to liver dysfunction in the first or second trimester. Liver dysfunction in the third trimester (74 patients) was associated with serious consequences. DIC was the most common complication (20.2%). The overall and perinatal mortality was 20.2% and 24.6% respectively. AFLP and HELLP syndromes were associated with poor maternal and fetal outcome. We conclude that liver dysfunctions were directly related to pregnancy in the majority of patients especially in the third namely trimester. Incidence of the most serious conditions AFLP and HELLP syndromes is much greater than what has been reported and is often associated with a high maternal mortality and poor perinatal outcome.

Adult↗

[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↗

The current excitement in bioinformatics-analysis of whole-genome expression data: how does it relate to protein structure and function?

Whole-genome expression profiles provide a rich new data-trove for bioinformatics. Initial analyses of the profiles have included clustering and cross-referencing to 'external' information on protein structure and function. Expression profile clusters do relate to protein function, but the correlation is not perfect, with the discrepancies partially resulting from the difficulty in consistently defining function. Other attributes of proteins can also be related to expression-in particular, structure and localization-and sometimes show a clearer relationship than function.

Computational Biology↗

Functional protein nanoarrays for biomarker profiling.

The use of microarrays for parallel screening of nucleic acid profiles has become an industry standard. Similar efforts for screening protein-protein interactions are gaining momentum, however, they remain limited by the requirement for relatively large sample volumes. One strategy for overcoming this problem is to significantly decrease the size and consequently the sample volume of the protein interaction assay. We report here on our progress over the last two years in the construction of ultraminiaturized, functional protein capture assays. Each one micron spot in these array-based assays covers less than 1/1000(th) of the surface area of a conventional microarray spot while still maintaining enough antibodies to provide a useful dynamic range. These nanoarray assays can be read by conventional optical fluorescence microscopy as well as by novel label-free methods such as atomic force microscopy. The size reduction realized by functional protein nanoarrays also creates opportunities for novel applications including highly multiplexed single cell analysis and integration with microfluidics and other "lab-on-a-chip" technologies.

Biomarkers↗

Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immunologic profile in relation to pulmonary function in cystic fibrosis.

We developed a solid-phase radioimmunoassay with a reference standard pseudomonas antigen and used this with 125I-labeled anti-human immunoglobulin to evaluate specific antibodies to Pseudomonas aeruginosa, qualitatively and quantitatively, in sera from children with cystic fibrosis (CF) whose lungs were colonized by this bacterium. The results of this IgG assay correlated with the number of precipitin antibodies to the standard reference antigen determined by cross-immunoelectrophoresis in the same sera. Forced expiratory volume (FEV1; percentage predicted), determined as an indicator of lung injury in CF, was evaluated as an immunologic response to pseudomonas, against a profile derived from combined serial data on both the circulating immune complexes (CIC) and the Ps. aeruginosa antibodies (N = 25 CF patients; 108 sera). This revealed that in CF patients who had no specific IgG antibodies to Ps. aeruginosa and no IgG-CIC had the best pulmonary function (FEV1 = 115 +/- 14.52%) and those with high levels of antibodies to this organism and high IgG-CIC levels had the poorest lung function (FEV1 = 69.75 +/- 10.99%) (P less than 0.05). We believe that this indicates an immunologic basis for lung injury in cystic fibrosis.

Antibodies, Bacterial↗

Thyroid function in children with different lipoprotein profiles: observations in a biracial (black/white) population--the Bogalusa Heart Study.

Abnormalities of thyroid function are associated with hyperlipidemia, a risk factor for coronary artery disease that starts in childhood. We investigated the age-, race-, and sex-related differences in thyroid function and its relation to serum lipoprotein levels in children (n = 363) aged 6 to 18 years from the biracial (black/white) community of Bogalusa, Louisiana, using an ultrasensitive thyroid-stimulating hormone (TSH) assay. Serum levels of lipoprotein cholesterol fractions, triglycerides, triiodothyronine (T3), thyroxine (T4), and the Tanner stage of sexual development were determined. Serum T3 (P < 0.0001), T4 (P < 0.0001), and TSH (P < 0.0020) levels decreased significantly with Tanner stage. Serum T4 levels were significantly higher (P < 0.0001) in both black and white females than their male counterparts. An unexpected finding was a significantly increased mean serum TSH in whites (2.09 + 0.91; mean + standard error of mean) when compared to blacks (1.74 + 0.10; P = 0.0185). Overall, no significant correlation was noted between serum lipoprotein variables and TSH. However, those with the highest low-density lipoprotein to very low-density lipoprotein cholesterol fractions had a higher T4 and a T4/TSH ratio than those with the lowest low-density lipoprotein to very low-density lipoprotein cholesterol fractions. In summary, it is concluded that there is no simple relationship between lipoproteins and TSH or thyroid hormone levels in children.

Adolescent↗

The genetic epidemiology of multiple sclerosis.

Multiple sclerosis (MS) is a debilitating immunological and neurodegenerative disorder. Epidemiological studies have provided overwhelming evidence of complex genetic susceptibility to MS. However, with the exception of the human leukocyte antigen (HLA) locus, genetic studies have failed to consistently identify significant linkage or association with genes that modulate MS disease expression. Numerous functional candidate gene studies, linkage genomic screens, and locational candidate gene studies have been performed in an attempt to identify additional loci. However, these methods have demonstrated insufficient power to consistently identify genes or epigenetic factors for MS. More current approaches integrate information from a variety of sources (e.g. consistent linkage data, gene expression profiling, and functional characterization studies) and utilize high throughput methods (e.g. genotyping high density markers, utilizing pooling schemes and performing new statistical analyses) in an attempt to overcome power issues. The following article presents a review of MS genetics research and a brief overview of methods that are currently being developed and utilized for fine localization of MS loci, such as the method employed in the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) study that is presented elsewhere in this journal. It is the hope of researchers that these methods will lead to the identification of susceptibility genes for MS that aid in elucidating pathogenic mechanisms and potential therapeutic strategies for this debilitating disease.

Genetic Testing↗

Smoking patterns in African Americans and whites with advanced COPD.

BACKGROUND: The prevalence and mortality associated with COPD increases with age, with higher rates observed in whites than African Americans. Causes and explanations for smoking-related racial differences on the respiratory system have not been determined. OBJECTIVE: To investigate racial differences in smoking patterns and lung function in patients with advanced COPD. DESIGN: Retrospective record review of patients with advanced COPD. SETTING: Outpatient pulmonary clinic in a tertiary-care urban hospital. PATIENTS: One hundred sixty patients with advanced COPD (80 African Americans and 80 whites) referred for either lung volume reduction surgery or transplantation evaluation. DATA COLLECTION: Demographics, smoking profile, pulmonary function testing, arterial blood gases, and exercise stress tests were compared between African-American and white patients. RESULTS: Despite comparable pulmonary function, African Americans were younger at presentation and had lower overall pack-years of smoking than whites (58 +/- 10 years vs 62 +/- 8 years, and 44 +/- 23 pack-years vs 66 +/- 31 pack-years, respectively; p < 0.05 [mean +/- SD]). Additionally, African Americans started smoking later in life than whites (18 +/- 5 years vs 16 +/- 4 years). Similarly, women presented at a younger age and smoked less compared to men (58 +/- 9 years vs 62 +/- 9 years, and 49 +/- 28 pack-years vs 61 +/- 29 pack-years, respectively; p < 0.05), without showing any difference in lung function or exercise performance. CONCLUSION: Among susceptible patients with advanced COPD, African Americans and women seem more prone to the effects of tobacco smoke than their counterparts.

Black or African American↗

Developmental changes in the modulation of cyclic amp accumulation by activation of metabotropic glutamate receptors.

Physiological functions of glutamic acid, the major neurotransmitter in the central nervous system, are mediated by the two receptor families: ionotropic glutamate receptors (iGluRs), and metabotropic glutamate receptors (mGluRs). Eight mGluR subtypes (mGluR1-mGluR8), together with splice variants, have been identified and classified into three groups. One of the features of mGluRs is their profile of functional expression throughout postnatal development. Several lines of evidence suggest age-dependent differences in the pattern or amount of mGluR-mediated phosphatidylinositol (P1) turnover as well as in the expression of mGluRs. The aim of the present study was to investigate how the different effects of mGluR agonists on cAMP accumulation change during rat postnatal life. We have found that the stimulatory effect of glutamate and/or 1S,3R-ACPD on cAMP accumulation predominates in young animals and decreases in the adults. We have also shown that the enhancement of the effect of noradrenaline on cAMP accumulation by 1S,3R-ACPD in rats is an age-dependent phenomenon which reaches its maximum in 14-30-day-old rats and gradually decreases during their maturation. On the basis of our studies, we conclude that the activation of mGluRs resulting in cAMP accumulation depends on the age of an animal.

Adenosine Deaminase↗

Sickness Impact Profile: the state of the art of a generic functional status measure.

The Sickness Impact Profile (SIP) is a widely used health status measure, known to be valid and reliable. After the final development and testing in 1978, however, in which several methodological aspects were investigated, no descriptions of research projects that systematically evaluate the methodological and theoretical aspects of the instrument were found. In this article a review is presented of literature on the SIP. This review is the first step taken in a project that evaluates the SIP. The instrument appears to be a reliable instrument with sufficient content validity. It shows good correlations with other health status and functional status measures. Yet a number of questions about the SIP remain unanswered. Theoretical implications of the construct of sickness, the effect of age and gender on SIP scores, the construct validity judged by factor analysis, the responsiveness of the instrument, and the possibilities to use proxy-respondents or to shorten the list and to simplify the scoring procedure still have to be studied. If the instrument is to be used as an international standard measure of functional status, these topics should be thoroughly examined.

Activities of Daily Living↗

Genome-Wide Identification of the LdARF Gene Family in Lilium davidii var. unicolor and Transient Functional Analysis of LdARF17 in Bulblet Regeneration.

Auxin response factors (ARFs) are key transcriptional regulators of the auxin signaling pathway and play important roles in plant organogenesis and regeneration. However, the functions of ARF family genes in lily scale-derived bulblet regeneration remain largely unclear. In this study, 24 LdARF genes were identified from the genome of Lilium davidii var. unicolor. Phylogenetic analysis revealed that LdARF proteins showed evolutionary conservation with ARF homologs from other monocot species. Genome-wide identification, phylogenetic analysis, and expression profiling revealed functional divergence among LdARF genes during scale-derived bulblet regeneration. Among them, LdARF17 exhibited a distinct regeneration-associated expression pattern, characterized by rapid induction after scale excision and sustained high expression during subsequent bulblet initiation and formation. Subcellular localization analysis demonstrated that LdARF17 is localized in the nucleus. Transient overexpression of LdARF17 significantly promoted bulblet regeneration and was associated with increased expression of auxin-responsive and regeneration-related genes, including IAA14, LBD16, and LBD29. These findings suggest that LdARF17 acts as a positive regulator of lily scale regeneration and may influence auxin-responsive transcriptional processes associated with early cell proliferation, providing new insights into the molecular mechanisms underlying vegetative regeneration in lilies.

Auxin response factor↗

Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study.

Research indicates that the use of recreational drugs, including MDMA ('ecstasy') can result in impairments in cognitive functioning. Recent evidence, based on accounts of 'on drug' effects and cortical binding ratios suggests that women may be more susceptible to the effects of MDMA; however, no research has explored whether there are differences in the long-term behavioural sequelae of the drug between men and women. In addition, little is known about the profile of functioning of the 'typical' user. The present investigation accessed a large sample of recreational drug users, using the Internet, to obtain self-reports of memory functioning with a view to exploring any differences in self-reported ability amongst male and female users, and the level of difficulty reported by the 'typical' ecstasy user. A web site (www.drugresearch.org.uk) was developed and used for data collection. Prospective memory ability was assessed using the Prospective Memory Questionnaire. Self-report of day-to-day memory performance was investigated using the Everyday Memory Questionnaire. The UEL Drug Questionnaire assessed the use of other substances. The number of mistakes made while completing the questionnaires was also taken as an objective measure of performance errors. Findings, based on datasets submitted from 763 respondents, indicate no differences in self-reports of functioning between male and female participants. An overall dissociation between the effects of cannabis and ecstasy on self-reported memory functioning and on the likelihood of making an error during the completion of the questionnaire was found. Typical ecstasy users were found to report significantly more difficulties in long-term prospective memory and to make more completion errors than users of other substances and drug naive controls. Whilst taking into account the fact that participants were recruited via the World Wide Web and that a number of stringent exclusion criteria were applied to the data, a number of conclusions can be drawn. Recreational drug users perceive their memory ability to be impaired compared to non-users. The type of memory difficulties reported varies depending upon the drug of choice. These difficulties are exacerbated in ecstasy users. Individuals reporting average levels of use of ecstasy are more likely to report memory problems than non-ecstasy drug users or drug free individuals. The deleterious effects of ecstasy are therefore not restricted to heavy or chronic users. No gender differences were detected, suggesting that there may be a dissociation between cognitive impairment and cortical binding worthy of further exploration.

Amphetamine-Related Disorders↗

Immunosenescence: potential causes and strategies for reversal.

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.

Aging↗

Comparing consumer and clinician values for alternative functional states: application of a new feature trade-off consensus building tool.

OBJECTIVE: To present the Features-Resource Trade-Off Game (Features Game) as a new method for comparing preferences for alternative outcomes among different groups of people. DESIGN: The Features Game is illustrated by comparing preferences for recovery among the 18 functional status items making up the Functional Independence Measure. Methods involved trading levels of independence (resources) across the different items (features). SETTING: Ten community-dwelling consumers with physical disabilities and 10 rehabilitation clinicians participated in four separate expert panels-two in Houston and two in Philadelphia. MAIN OUTCOME MEASURES: Five sets of hierarchical stages defined by the four separate panels specifying the profiles of function believed to most foster independent living. RESULTS: Cognitive and communication skills were selected preferentially over the recovery of physical tasks by all panels, but, in comparison to clinicians, consumers were more willing to accept mild deficits in cognitive skills as trade for realizing earlier recovery of physical abilities. CONCLUSION: The overwhelming choice of cognitive and communication abilities over physical abilities suggests a need to enhance therapeutic efforts in those areas. More subtle differences in consumer and clinician preferences emphasize the importance of establishing consumer-oriented goals.

Activities of Daily Living↗

Acute normovolaemic haemodilution decreases postoperative allogeneic blood transfusion after total knee replacement.

We hypothesized that the success of postoperative blood conservation after acute normovolaemic haemodilution (NVHD) is influenced by the extent of intraoperative bleeding and surgical trauma, and the timing of autologous blood transfusion. As total knee replacement is associated with minimal intraoperative but extensive postoperative blood loss, this procedure is ideally suited to acute NVHD. Therefore, to test our hypothesis, 30 patients undergoing elective total knee replacement were enrolled in a prospective, randomized, controlled study. In groups NVHD-2 and NVHD-6, before induction of anaesthesia patients were bled to a target packed cell volume (PCV) of 28-30%, and in the post-anaesthesia care unit autologous blood was transfused over a 2-h period terminating after operation at 2 and 6 h, respectively. In the control group, NVHD was not performed. After operation, platelets, fibrinogen, prothrombin and partial thromboplastin time, and liver function, urea and electrolytes were measured and compared with preoperative baseline values. Significantly (P < 0.024) more allogeneic blood was transfused in the control group (21 u.) compared with either group NVHD-2 (7 u.) or group NVHD-6 (5 u.). In the control group, despite the allogeneic blood transfusion, postoperative PCV decreased until day 4 after operation. Coagulation profile, liver function and urea and electrolytes concentrations were unaffected by the method of treatment. We conclude that for total knee replacement, acute NVHD is an effective blood conservation strategy. However, there was no difference in allogeneic blood administration between the two NVHD groups. Coagulation and liver function, and urea and electrolyte concentrations were unaffected by treatment.

Aged↗

In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development.

Rod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were however not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes but an activator of only a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild-type retina also generated rod-like cells. The dual regulatory function of NR2E3 was not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of NRL-expressing photoreceptor precursors during retinal neurogenesis.

Animals↗