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At least 955 records · Page 53Linked to original sources
PubMed2003

Molecular characterization, functional expression, and developmental profile of an ether à-go-go K+ channel in the tobacco hornworm Manduca sexta.

A very large number of evolutionarily conserved potassium channels have been identified but very little is known about their function or modulation in vivo. Metamorphosis of the tobacco hornworm, Manduca sexta, is a compelling model system for such studies because it permits analysis to be conducted at the level of identified neurons whose roles in simple behaviors and endocrine regulation are known. We present here the characterization of the first ion channel to be cloned from this animal. Partial genomic sequence for Manduca sexta ether à-go-go (Mseag) and a cDNA clone encoding the Mseag open reading frame were obtained. Genomic Southern analysis indicates that Manduca contains a single member of the eag subfamily per haploid genome. When expressed in Xenopus oocytes, MsEag channels conduct a voltage-dependent, K+ selective outward current with an inactivating component that closely resembles the Drosophila eag current. Mseag transcripts were restricted to the nervous system, adult antenna, and one set of larval skeletal muscles. Steroid hormonal regulation of Mseag expression is suggested by the temporal correlation of developmental changes in transcript expression with the changing steroid titers that promote metamorphosis. These results provide the foundation for functional and modulatory studies of the Eag family of K+ channels in Manduca, which will complement the genetic analysis in Drosophila.

Amino Acid Sequence↗
PubMed1982

Motor functions: associated primitive reflex profiles.

The results of reflex/motor activity interactions in 177 normal infants are evaluated. The asymmetrical tonic neck reflex, tonic labyrinthine reflex-supine, and Moro reflexes were assessed for each child at birth and at intervals up to 12 months. Ages of rolling prone to supine, rolling supine to prone, and sitting alone were elicited from parents. The effects of the primitive reflexes on early motor activity were assessed, and statistically significant correlations were demonstrated between decreased reflex activity and the emergence of motor milestones. The distinctive association of reflex activity with motor function suggests the interaction of several reflexes (a primitive reflex profile) rather than the influence of isolated reflex activity. Such patterns support the hypothesis that decreasing primitive reflex activity is associated with the onset of volitional motor activity in normal infants.

Developmental Disabilities↗
PubMed2006

Molecular signatures determining coronary artery and saphenous vein smooth muscle cell phenotypes: distinct responses to stimuli.

OBJECTIVE: Phenotypic differences between vascular smooth muscle cell (VSMC) subtypes lead to diverse pathological processes including atherosclerosis, postangioplasty restenosis and vein graft disease. To better understand the molecular mechanisms underlying functional differences among distinct SMC subtypes, we compared gene expression profiles and functional responses to oxidized low-density lipoprotein (OxLDL) and platelet-derived growth factor (PDGF) between cultured SMCs from human coronary artery (CASM) and saphenous vein (SVSM). METHODS AND RESULTS: OxLDL and PDGF elicited markedly different functional responses and expression profiles between the 2 SMC subtypes. In CASM, OxLDL inhibited cell proliferation and migration and modified gene expression of chemokines (CXCL10, CXCL11 and CXCL12), proinflammatory cytokines (IL-1, IL-6, and IL-18), insulin-like growth factor binding proteins (IGFBPs), and both endothelial and smooth muscle marker genes. In SVSM, OxLDL promoted proliferation partially via IGF1 signaling, activated NF-kappaB and phosphatidylinositol signaling pathways, and upregulated prostaglandin (PG) receptors and synthases. In untreated cells, alpha-chemokines, proinflammatory cytokines, and genes associated with apoptosis, inflammation, and lipid biosynthesis were higher in CASM, whereas some beta-chemokines, metalloproteinase inhibitors, and IGFBPs were higher in SVSM. Interestingly, the basal expression levels of these genes seemed closely related to their responses to OxLDL and PDGF. In summary, our results suggest dramatic differences in gene expression patterns and functional responses to OxLDL and PDGF between venous and arterial SMCs, with venous SMCs having stronger proliferative/migratory responses to stimuli but also higher expression of atheroprotective genes at baseline. CONCLUSIONS: These results reveal molecular signatures that define the distinct phenotypes characteristics of coronary artery and saphenous vein SMC subtypes.

Atherosclerosis↗
PubMed1992

Health status of the aged: medical profile of a group of functional elderly.

By studying a group of very elderly but generally functional people, we have compiled a medical profile that helps describe health-related characteristics of effective aging. We obtained functional, nutritional, and biochemical information regarding 61 men and women (mean age 86.8 years) attending a veterans' convention. Twenty-three out of 60 (38%) reported a fall in the previous year, with those who were less physically active falling more than the most active. Many of the men were thin or had lost weight, but at most 3 of the 25 male subjects were clinically malnourished. Many of the women were heavy but were otherwise healthy. Of the 36 women, 6 (17%) had an elevated level of thyroid-stimulating hormone (TSH). Five of 58 (9%) had low vitamin B12 levels. Even in the older old who seem to be aging well, falling is relatively common, and screening for certain laboratory abnormalities has a reasonably high yield.

Accidental Falls↗
PubMed2004

Cardiac function-related gene expression profiles in human atrial myocytes.

To obtain insights into the molecular pathogenesis of heart failure in humans, we have analyzed the expression profiles of>12,000 genes in a total of 17 human specimens of right atrial myocytes. From this large data set, we here tried to identify gene clusters, expression level of which is correlated precisely with clinical parameter values of cardiac function. We could reveal that cardiac myocytes with normal sinus rhythm were clearly differentiated, in the point of view of gene expression, from those with atrial fibrillation. Further, an expression profile-based prediction of arrhythmia by a newly developed "weighted-distance method" could efficiently diagnose our samples. We could even construct calculation formulae for the values of left ventricular ejection fraction based on the expression level of selected genes. To our best knowledge, this is the first report to indicate that pumping ability of heart can be predicted by any measures of atrium.

Adolescent↗
PubMedDate not supplied

Totally occluded coronary arteries with normal LV function: clinical and angiographic profile.

The clinical and coronary angiographic profile of 50 patients (Group I) with total occlusion of one or more major coronary arteries in the absence of electrocardiographic findings of myocardial infarction and normal segmental and global left ventricular (LV) functions were analysed to identify any variables responsible for this observation. Twenty five age and sex matched patients (Group II), who had 100% occlusion of at least one major coronary artery with significant wall motion abnormalities on LV angiograms, served as controls. The mean duration of angina before angiography or the occurrence of acute coronary event was significantly longer in Group I (2.8 +/- 2.2 yrs) compared to Group II (1.2 +/- 1.2 yrs; p less than .05) patients. RCA was found totally occluded more often in Group I as compared to Group II (60% vs 32%; p less than .05) patients, whereas complete occlusion of LAD occurred more frequently in Group II than in Group I (70% vs 32%; p less than .05). Significant stenoses in other arteries was found in 88% of Group I, compared to 48% of Group II patients (p less than .001). Although there was no significant difference in the frequency of collaterals feeding the totally occluded arteries in the two groups, 80% of patients in Group I had grade 3 collaterals compared to only 30% in Group II patients (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of isokinetic training on the rate of movement during ambulation in hemiparetic patients.

The purpose of this study was to determine the effects of isokinetic training on the rate of movement during ambulation in hemiparetic patients. Ten male and 10 female subjects, aged 40 to 75 years, participated in the study. The 20 hemiparetic subjects were assigned randomly to either a control group or an experimental group. All of the subjects participated in a conventional therapeutic exercise program and gait training. The experimental group also received isokinetic training on the Kinetron exercise machine as part of their program. Functional ambulation profile tests were administered to each subject before and after the five-week experimental period. All of the subjects showed improvement in the rate of ambulation and in overall ambulation performance. The differences in ambulation times and functional ambulation profile scores between the two groups were shown to be insignificant.

Adult↗
PubMed2003

Structure-based active site profiles for genome analysis and functional family subclassification.

In previous work, structure-based functional site descriptors, fuzzy functional forms (FFFs), were developed to recognize structurally conserved active sites in proteins. These descriptors identify members of protein families according to active-site structural similarity, rather than overall sequence or structure similarity. FFFs are defined by a minimal number of highly conserved residues and their three-dimensional arrangement. This approach is advantageous for function assignment across broad families, but is limited when applied to detailed subclassification within these families. In the work described here, we developed a method of three-dimensional, or structure-based, active-site profiling that utilizes FFFs to identify residues located in the spatial environment around the active site. Three-dimensional active-site profiling reveals similarities and differences among active sites across protein families. Using this approach, active-site profiles were constructed from known structures for 193 functional families, and these profiles were verified as distinct and characteristic. To achieve this result, a scoring function was developed that discriminates between true functional sites and those that are geometrically most similar, but do not perform the same function. In a large-scale retrospective analysis of human genome sequences, this profile score was shown to identify specific functional families correctly. The method is effective at recognizing the likely subtype of structurally uncharacterized members of the diverse family of protein kinases, categorizing sequences correctly that were misclassified by global sequence alignment methods. Subfamily information provided by this three-dimensional active-site profiling method yields key information for specific and selective inhibitor design for use in the pharmaceutical industry.

Algorithms↗
PubMed2000

Can shared care deliver better outcomes for patients undergoing total hip replacement? A prospective assessment of patient outcomes and associated service use.

OBJECTIVES: To assess whether shared care for patients undergoing total hip replacement delivers better outcomes compared to care as usual. DESIGN: Prospective, observational cohort study. SETTING: Two regions in The Netherlands where different organisational health care models have been implemented: a shared care setting (experimental group) and a care as usual setting (control group). PATIENTS: One hundred and fifteen patients undergoing total hip replacement: 56 in the experimental group and 59 in the control group. MAIN MEASURES: Functional health status according to the sickness impact profile, hip function, patient satisfaction and use of health care services. RESULTS: Two weeks before hip replacement both groups were comparable concerning patient characteristics, hip function and health status. The mean improvement of the total sickness impact profile score between two weeks before hip replacement and six months after was -1.92 in the shared care group, compared to -5.11 in care as usual group, a difference in favour of the control group (p=0.02). The mean length of hospital stay was comparable in both settings: 12.8 days in the shared care group and 13.2 days in the care as usual group. After hip replacement, compared to care as usual, patients in the shared care group received more homecare, with a higher frequency, and for a longer period of time. No differences in patient satisfaction between the two groups were found. CONCLUSIONS: Six months after hip replacement, the health status of patients in the care as usual group, using significantly less home care, was better than the status of patients in the shared care group. DISCUSSION: The utilisation of home care after hip replacement should be critically appraised in view of the need to stimulate patients' independence.

Journal Article↗
PubMed2004

Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia.

The molecular basis for the embryonic and perinatal clinical forms of biliary atresia is largely undefined. In this study, we aimed to: 1) determine if the clinical forms can be differentiated at the transcriptional level, and 2) search for molecular mechanisms underlying phenotypic differences. To this end, we generated biotinylated cRNA probes from livers of age-matched infants with the embryonic (n = 5) and perinatal (n = 6) forms of biliary atresia at the time of diagnosis and hybridized them against the Affymetrix human HG-U133 A and B microarrays containing 44,760 gene products. Data filtering and two-way cluster analysis of the gene expression platform identified 230 genes with an expression profile that is highly distinctive of the clinical phenotypes. Functionally, the profile did not reveal a higher-order function for a specific cell type; instead, it uncovered a coordinated expression of regulatory genes. These regulatory genes were predominantly represented in the embryonic form (45% of genes), with a unique pattern of expression of genes involved in chromatin integrity/function (Smarca-1, Rybp, and Hdac3) and the uniform overexpression of five imprinted genes (Igf2, Peg3, Peg10, Meg3, and IPW), implying a failure to downregulate embryonic gene programs. In conclusion, embryonic and perinatal forms of biliary atresia are distinguished by gene expression profiling. The coordinate expression of regulators of chromatin structure/function and of imprinted genes provides evidence for a transcriptional basis for the pathogenesis of the embryonic form of biliary atresia. Further studies exploring these biological processes are required to determine the significance of these findings.

Biliary Atresia↗
PubMed1989

The life skills profile: a measure assessing function and disability in schizophrenia.

We review limitations of representative measures of function and disability associated with schizophrenia and specify requirements of a suitable measure for service evaluation: It should reliably and validly assess constructs relevant to survival, function, and adaptation in the community. Additionally, it should be brief, comprise specific and jargon-free items assessing distinct behaviors, and therefore be capable of completion by family members and community housing managers as well as by professional staff. The initial development of such a measure, the 39-item Life Skills Profile (LSP), with its five scales, is described. We report data to suggest that it is likely to be a measure of considerable utility both in research studies and in defining and assessing clinical services.

Activities of Daily Living↗
PubMed1991

A comparison of demographic, behavioral, and ego function data in borderline and eating disorder patients.

Seven borderline personality and ten eating disorder patients were compared using demographic, descriptive/behavioral, and ego function measures on admission to an inpatient unit. Demographic and descriptive data analysis revealed areas of overlap, consistent with other reports of co-morbidity between the two groups. Ratings of intrapsychic function were made using Bellak's Ego Function Assessment profiles, and showed that the two groups shared deficits in the areas of impulse/affect control and sense of identity, but had otherwise easily distinguishable profiles. The authors feel that studying ego functioning is a useful way of assessing co-morbidity in borderline personality and eating disorder patients.

Adult↗
PubMed2005

Functional imaging of changes in cerebellar activity related to learning during a novel eye-hand tracking task.

Coordination between the eyes and the hand is likely to be based on a process of motor learning, so that the interactions between the two systems can be accurately controlled. By using an unusual tracking task we measured the change in brain activation levels, as recorded with 3T functional magnetic resonance imaging (fMRI), between naïve human subjects and the same subjects after a period of extended training. Initially the performance of the two groups was similar. One subject group was then trained in a synchronous, coordinated, eye-hand task; the other group trained with a 304 ms temporal offset between hand and eye tracking movements. After training, different patterns of performance were observed for the groups, and different functional activation profiles. Significant change in the relationship between functional activation levels and eye-hand task conditions was predominantly restricted to visuo-motor areas of the lateral and vermal cerebellum. In an additional test with one of the subject groups, we show that there was increased cerebellar activation after learning, irrespective of change in performance error. These results suggest that two factors contribute to the measured blood oxygen level-dependent (BOLD) signal. One declined with training and may be directly related to performance error. The other increased after training, in the test conditions nearest to the training condition, and may therefore be related to acquisition of experience in the task. The loci of activity changes suggest that improved performance is because of selective modified processing of ocular and manual control signals within the cerebellum. These results support the suggestion that coordination between eye and hand movement is based on an internal model acquired by the cerebellum that provides predictive signals linking the control of the two effectors.

Adult↗
PubMed2005

Prevalence of acid reflux in functional dyspepsia and its association with symptom profile.

AIM: A subset of functional dyspepsia patients respond to acid suppressive therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia and its relevance to symptoms have never been established. The aim of the present study was to study 24 hour pH monitoring in consecutive functional dyspepsia patients. METHODS: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study. In all patients, the severity of dyspeptic symptoms and the presence of heartburn was assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was performed. All patients underwent a gastric emptying breath test and in 113 a gastric barostat study was performed. RESULTS: Abnormal pH monitoring (acid exposure >5% of time) was found in 58 patients (23%). Of 21 patients with a positive heartburn questionnaire, 76% had pathological pH monitoring, while this was the case in only 18.5% of patients with a negative heartburn questionnaire. Demographic characteristics and the prevalence of other pathophysiological mechanisms did not differ between heartburn negative patients with normal or abnormal acid exposure. Pathological acid exposure in heartburn negative patients was associated with the presence of epigastric pain (65 v 84%, p<0.005) and of moderate or severe pain (48 v 69%, p = 0.005). CONCLUSION: Pathological oesophageal acid exposure is only present in a subset of heartburn negative functional dyspepsia patients, which are characterised by a higher prevalence of epigastric pain.

Adult↗
PubMed2004

Amenorrhea in female athletes is associated with endothelial dysfunction and unfavorable lipid profile.

The aim of this study was to evaluate endothelial function measured as flow-mediated dilatation (FMD) of the brachial artery and blood markers of cardiovascular disease in young female endurance athletes with menstrual disturbance. Age- and body mass index-matched groups of young endurance athletes with amenorrhea (n = 14), oligomenorrhea (n = 9), and regular cycles (n = 12) and sedentary controls (n = 12) were compared with respect to endothelial function, lipid profile, markers of inflammation, and endocrine status. We found a significantly decreased FMD in the amenorrheic athletes, compared with all other groups. Amenorrheic athletes also had the most unfavorable lipid profile with significantly higher total cholesterol and low-density lipoprotein, compared with the other athlete groups. The oligomenorrheic athletes had the lowest levels of total cholesterol, low-density lipoprotein, and apolipoprotein B of all groups and significantly lower in comparison with the amenorrheic group. However, with respect to FMD, the oligomenorrheic group represented an intermediate between amenorrheic and regularly cycling subjects. There was a gradual impairment of FMD and the lipid profile to the degree of menstrual disturbance supporting an association with estrogen status. We conclude that amenorrhea in young endurance athletes is associated with endothelial dysfunction and unfavorable lipid profile. Additional studies are needed to elucidate the clinical implications of these results with regard to long-term risk for cardiovascular disease.

Adolescent↗
PubMed2002

Influence of refractive-index mismatch in high-resolution three-dimensional confocal microscopy.

The effects of the refractive-index mismatch in confocal laser scanning microscopy were extensively studied. The axial aberration induced in the case of fluorescent microspheres was measured. The data were used to take into account the mismatch-induced aberrations and to consider object-size influence. Then we focused on the effect of refractive-index mismatch on the effective system's point-spread function under different mismatch conditions and on depth of focusing. We experimentally verified that the peak of the point-spread function intensity profile decreases and the point-spread function itself progressively broadens as a function of the combined effect of the refractive-index mismatch and of the penetration depth, leading to a worsening of the system's overall performances. We also performed these same measurements by embedding subresolution beads in an oocyte's cytoplasm, which can be considered a turbid medium. We found evidence consistent with the previously developed theoretical model; in particular we found a strong dependence of the intensity peak on the focusing depth.

Journal Article↗
PubMed1991

Isolation of c-kit receptor-expressing cells from bone marrow, peripheral blood, and fetal liver: functional properties and composite antigenic profile.

To define the cellular targets for c-kit ligand (KL) and to study their functional properties and composite antigenic profile, we isolated cells expressing c-kit receptor (KR) from bone marrow (BM), peripheral blood, and fetal liver (FL) using immunoadherence to a recently obtained antibody (SR-1) against the human KR. Cells isolated by this approach (designated SR-1Ad) have the morphology of blasts and represent 1% to 4% of the original BM or FL populations. SR-1Ad cells from either source are highly enriched in progenitors (12% to 73%) and respond to KL in distinct patterns. In SR-1Ad cells from BM, the greatest impact of KL stimulation is on burst-forming units-erythroid (BFU-E), whereas in SR1-Ad cells from FL, the most significant KL effect is on a mixed erythroid/nonerythroid progenitor (erythroid/macrophage, colony-forming unit-mix [CFU-Mix]). When antibody SR-1 is continually present in culture, it neutralizes the effects of added KL. Furthermore, in the absence of added KL, it greatly diminishes the erythropoietin- and interleukin-3-dependent BFU-E growth in BM; whereas in FL, a wider spectrum of inhibition is observed, with CFU-Mix most severely curtailed. SR-1Ad cells coexpress other progenitor-associated antigens in a combination reflecting the dominant presence of erythroid progenitors (high expression of CD34, DR, CD38, and Ep-1; low expression of CD33). Several cytoadhesion molecules, ie, alpha L/beta 2 and alpha 4/beta 1 integrins, and intercellular adhesion molecule 1 and homing cell adhesion molecule 1, are also coexpressed. Our data provide new information on the isolation and characterization of KR expressing cells from normal, adult, and fetal hematopoietic tissues. On these biologically relevant target cells, the impact of ligand-induced stimulation or antibody-mediated ablation of KR function has been gauged.

ADP-ribosyl Cyclase↗
PubMed2002

A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses.

Evidence for neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia, patients with chronic psychotic bipolar disorder and normal controls. Groups were comparable on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also relatively similar on age at onset and number of hospitalizations. Using multivariate analyses of variance with sex and parental SES as covariates (our primary analyses), patients with schizophrenia were significantly more impaired than controls on seven of eight neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on declarative verbal memory, and showed moderate-to-large effect size decrements on abstraction, perceptual-motor speed and vigilance. Results were not attenuated when IQ was controlled, which was significantly lower in patients with schizophrenia. Analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.

Adult↗