SEARCH · Search PubMed

Results for “functional profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 1,279 records · Page 71Linked to original sources

PubMed2000

Efficient presentation of tumor idiotype to autologous T cells by CD83(+) dendritic cells derived from highly purified circulating CD14(+) monocytes in multiple myeloma patients.

To generate mature and fully functional CD83(+) dendritic cells derived from circulating CD14(+) cells highly purified from the leukapheresis products of multiple myeloma patients.CD14(+) monocytes were selected by high-gradient magnetic separation and differentiated to immature dendritic cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 6-7 days and then induced to terminal maturation by the addition of tumor necrosis factor-alpha or stimulation with CD40 ligand. Dendritic cells were characterized by immunophenotyping, evaluation of soluble antigens uptake, cytokine secretion, capacity of stimulating allogeneic T cells, and ability of presenting nominal antigens, including tumor idiotype, to autologous T lymphocytes. Phenotypic analysis showed that 90% +/- 6% of cells recovered after granulocyte-macrophage colony-stimulating factor and interleukin-4 stimulation expressed all surface markers typical of immature dendritic cells and demonstrated a high capacity of uptaking soluble antigens as shown by the FITC-dextran assay. Subsequent exposure to maturation stimuli induced the downregulation of CD1a and upregulation of CD83, HLA-DR, costimulatory molecules and induced the secretion of large amounts of interleukin-12. Mature CD83(+) cells showed a diminished ability of antigen uptake whereas they proved to be potent stimulators of allogeneic T cells in a mixed lymphocyte reaction. Monocyte-derived dendritic cells, pulsed before the addition of maturation stimuli, were capable of presenting soluble proteins such as keyhole limpet hemocyanin and tetanus toxoid to autologous T cells for primary and secondary immune response, respectively. Conversely, pulsing of mature (CD83(+)) dendritic cells was less efficient for the induction of T-cell proliferation. More importantly, CD14(+) cells-derived dendritic cells stimulated autologous T-cell proliferation in response to a tumor antigen such as the patient-specific idiotype. Moreover, idiotype-pulsed dendritic cells induced the secretion of interleukin-2 and gamma-interferon by purified CD4(+) cells. T-cell activation was better achieved when Fab immunoglobulin fragments were used as compared with the whole protein. When dendritic cells derived from CD14(+) cells from healthy volunteers were analyzed, we did not find any difference with samples from myeloma patients as for cell yield, phenotypic profile, and functional characteristics. These studies demonstrate that mobilized purified CD14(+) cells represent the optimal source for the production of a homogeneous cell population of mature CD83(+) dendritic cells suitable for clinical trials in multiple myeloma.

Antigen Presentation↗

PubMed2006

Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy.

OBJECTIVE: To investigate the sleep architecture and breathing as well as quality of life (QoL) in adults with GH deficiency (GHD) before and 6 months after GH replacement therapy. DESIGN: A prospective observational study. PATIENTS: Nineteen consecutive adults with GHD (11 men, eight women; mean age 53, range 21-73 years) were studied. MEASUREMENTS: An overnight sleep study was performed and the Minor Symptom Evaluation Profile (MSEP), Functional Outcome of Sleep Questionnaire (FOSQ), Short Form 36 (SF-36) and Epworth Sleepiness Scale (ESS) questionnaires were applied at baseline and after the treatment period. RESULTS: For the whole group, there were no significant changes in mean total sleep time (TST; 370 min vs. 374 min), proportion of slow-wave sleep (SWS; 17.8%vs. 18.4%) and rapid eye movement (REM) sleep (12.1%vs. 13.9%) on GH replacement. Mean apnoea-hypopnoea index (AHI) was high and remained unchanged (28.2/h before vs. 28.0/h following GH replacement). Twelve patients (63%) were found to have obstructive sleep apnoea (OSA; AHI >or= 10/h) at baseline. Compared with GH-deficient patients without OSA (AHI 3.9/h), the OSA patients (AHI 42.4/h) had less SWS (11.4%vs. 28.6%, P = 0.010) and REM sleep (10.1%vs. 15.5%, P = 0.036). A marginal increase was observed in REM sleep time (10.1% before vs. 12.7% after GH; P = 0.048) while SWS was unchanged in this group. Moreover, MSEP for General Well-being and Responsiveness, FOSQ scores for General Productivity, Activity Level and Vigilance as well as SF-36 domains for Vitality and Mental Health were improved. CONCLUSIONS: Contrary to some previous observations in a smaller group of patients, our data suggest that GH therapy does not induce or aggravate OSA in GH-deficient adults. Moreover, GH therapy may improve some of the QoL dimensions in these patients.

Adult↗

PubMed2002

A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR.

The mammalian DAF-16-like transcription factors, FKHR, FKHRL1, and AFX, function as key regulators of insulin signaling, cell cycle progression, and apoptosis downstream of phosphoinositide 3-kinase. Gene activation through binding to insulin response sequences (IRS) has been thought to be essential for mediating these functions. However, using transcriptional profiling, chromatin immunoprecipitation, and functional experiments, we demonstrate that rather than activation of IRS regulated genes (Class I transcripts), transcriptional repression of D-type cyclins (in Class III) is required for FKHR mediated inhibition of cell cycle progression and transformation. These data suggest that a novel mechanism of FKHR-mediated gene regulation is linked to its activity as a suppressor of tumor growth.

Adenoviridae↗

PubMedDate not supplied

Functional amnesia: clinical description and neuropsychological profile of 10 cases.

We carried out the first neuropsychological study of a series of patients with functional amnesia. We evaluated 10 patients, first with a neurological examination and then with three tests of anterograde amnesia and four tests of retrograde amnesia. Excluding one patient who later admitted to malingering, all patients had a significant premorbid psychiatric history and one or more possible precipitating factors for their amnesia. Eight of the 10 patients still had persistent retrograde amnesia at our last contact with them (median = 14 mo after the onset of amnesia). On tests of anterograde amnesia, the patients performed normally as a group, though some patients scored poorly on tests of verbal memory. On tests of retrograde amnesia, all patients had difficulty re-collecting well-formed autobiographical memories of specific events from their past. In contrast, patients performed as well as controls at distinguishing the names of cities from fictitious city names. On remote memory tests for past public events and famous faces, different patients exhibited different but internally consistent patterns of impaired and spared performance. The variability in the clinical and neuropsychological findings among our patients may be understood by supposing that memory performance is poor in proportion to how directly a test appears to assess a patient's common sense concept of memory. The presentation of patients with functional amnesia is as variable as humankind's concept of what memory is and how it works.

Adult↗

PubMed2004

Functional assessment of injured workers: a profile of assessor practices.

BACKGROUND: Considerable controversy and limited information surrounds the use of performance-based functional assessments for determining an injured worker's ability to function at work. PURPOSE: Amidst a variety of protocols, philosophies and tools, the key aspects of different assessment approaches are described and compared across a range of assessment provider organizations. METHOD: Qualitative and quantitative strategies were used to generate an in-depth understanding of the different assessment practices among 23 Southern Ontario assessment providers. RESULTS: Assessment approaches share common elements and variations that can be described along the continua of five dimensions: nature of assessor-evaluee interactions, fixed or flexible protocol delivery, efforts to contextualize, perceptions and use of evidence, and provider organizational environment. These approach dimensions are offered as a focus for appraising practices. PRACTICE IMPLICATIONS: Assessors need to reflect upon to what extent they are using a whole person, client-centred approach directed by clinical reasoning amidst a market driven industry.

Adult↗

PubMed1980

Objective assessment of laryngectomized patients with surgical reconstruction.

The assessment of worth of the neoglottic procedure has been, for the most part, subjective in nature. Evaluation by means of sequential objective measures has been developed. The following procedures are employed in our assessment: transcription intelligibility by judges unfamiliar with the passage; rate of speech; relative intensity range; intratracheal air pressure; continuous speech per breath; functional communication profile; weight status; contrast swallow study; swallow-aspiration diary; and tumor status. Data from a patient with a Staffieri neoglottis procedure illustrate the method.

Deglutition↗

PubMed1987

Targeted early childhood programming. The promise half fulfilled.

A group of 169 children was followed up from birth to second grade in a community-based early identification and early intervention project. Periodic assessments of health and function yielded profiles of concerns. Over the first five years of life, 39% of the children had health concerns, 20% had cognitive concerns, 25% had motor concerns, 15% had social adjustment problems, and 12% had early attentional problems. Children at the highest risk of having reading and behavioral problems in second grade were those with early attentional disability. At the second-grade level, 31% of the children with early attention concerns were one full grade behind in reading and 38% had behavioral problems; among the youngsters without early attentional concerns, 6% demonstrated a reading delay and 8% had behavioral problems. In addition, children of highly educated mothers were more likely to benefit from the multidisciplinary program than were children of less educated mothers, for whom the intervention effected only a modest improvement when contrasted with randomly selected comparison children. For instance, among children with early cognitive problems and whose mothers had little education, 31% of these children had reading problems in second grade as opposed to 10% of those whose mothers had high educational attainment. Similarly, 39% of children with the combined risks of low maternal education and early attentional problems had reading problems in second grade compared with none of the attention-problem children of highly educated mothers. This study shows that while early identification of health and developmental problems can be carried out in a community-based project, strategies for the early intervention of developmental concerns among children of low socioeconomic status remain less than completely effective.

Boston↗

PubMed1996

MMPI-2 patterns in African-American females.

Researchers have reported conflicting conclusions about the relation of the MMPI (MMPI-2) clinical scale elevations and race. Consequently, this study examined the concurrent validity of the MMPI-2 in evaluating African-American females. Seventy-eight (78) African American college student volunteers were administered the MMPI-2, along with other measures of personality, achievement, and coping style. Scores revealed 76% of the sample had elevated profiles. Subjects were divided into three groups based on frequency of clinical scale code type. Subjects with the 5/9 profile elevations functioned as well as normals on measures of coping skills and mood disorders. Discussion emphasizes the importance of clinical interpretation of MMPI data in research programs and the relationship of the data to coping style.

Adaptation, Psychological↗

PubMed1999

Do memory clinics improve the quality of life of carers? A randomized pilot trial.

OBJECTIVE: To determine the effects of attendance at a memory clinic on the psychosocial health of carers. DESIGN: Randomized control trial. PARTICIPANTS: Fifty community dwelling subjects with mild to moderate dementia and their carers. MAIN OUTCOME MEASURES: Carer burden, psychological morbidity and psychosocial health related quality of life at 6 and 12 months post intervention. MAIN RESULTS: There was significant improvement in psychosocial health related quality of life of carers as measured by the psychosocial domain of the Functional Limitation Profile (FLP) at 6 months (p < 0.01), including improvement in the subgroups of alertness behaviour (p < 0.05) and social interaction (p < 0.01), after adjustment for age of subject and baseline scores. The improvement in social interaction was maintained at 12 months (p < 0.05). There was no significant difference in carer psychological morbidity (General Health Questionnaire), carer burden (Zarit family interview) or carer knowledge of dementia (Dementia Knowledge Test) at 6 or 12 months, between groups. CONCLUSIONS: These results demonstrate improved psychosocial health related quality of life for carers of those with mild to moderate cognitive impairment attending a memory clinic. Further research in this area is indicated, comparing memory clinic intervention with alternative support.

Aged↗

PubMed2000

Evaluation of automated single mass spectrometry to tandem mass spectrometry function switching for comprehensive drug profiling analysis using a quadrupole time-of-flight mass spectrometer.

A liquid chromatographic mass spectrometric strategy for systematic toxicological analysis (STA) is presented using the automatic 'on-the-fly' single mass spectrometry mode to tandem mass spectrometry mode (MS to MS/MS) switching abilities of a quadrupole time-of-flight (Q-TOF) instrument. During the chromatographic run, the quadrupole is initially set to transmit all masses until (an) ion(s) reaches a certain set threshold. Thereupon, the quadrupole automatically switches to the MS/MS mode, selecting the ion(s), which are subsequently fragmented in the high-efficiency hexapole collision cell, thus generating product ions that are further mass analyzed by the TOF. By limiting the TOF spectral accumulation time in the MS/MS mode to a statistically acceptable minimum, the quadrupole almost instantly switches back to the MS mode. Qualitative information, comprising the complementary MS ([M + H](+) ion mass) and MS/MS (informative product ion profile) data, as well as quantitative information obtained by integration of the MS extracted ion chromatogram(s), can be obtained in one single acquisition. Optimization of the automatic switching parameters, such as threshold, TOF spectral accumulation time, detection window and collision energy, was carried out by injection of a mix of 17 common drugs which were not necessarily baseline separated in the chromatographic system used. Indeed, the complete separation of the drugs is not deemed necessary since up to 8 different ions can 'simultaneously' be selected for MS/MS if they reach the preset criteria. In addition, the quantitative performance of the method was defined. In a second phase, the developed method was field-tested. To that end, the resulting data from extracts of urine samples were compared with and found to be in close concordance with those obtained by a standard toxicological analysis. This innovative approach clearly holds the potential for a substantial advance in the introduction of LC/MS in STA.

Autoanalysis↗

PubMed1994

MMPI profiles in PTSD as a function of comorbidity.

A sample of 135 Vietnam veteran inpatients with combat-related PTSD was sorted into three groups, depending upon the presence of concurrent psychiatric disorders: Depression (n = 68), Psychosis (n = 31), and Other (n = 36). Pairwise comparisons were made on the MMPI with respect to the validity indicators, clinical scales, four relevant Harris-Lingoes subscales, the Psychoticism content scale, and the MMPI-PTSD subscale. Results indicate variations in scale elevations as a function of comorbid diagnosis. Various items and scales appear to differentiate the Psychosis group due to greater psychopathology. In general, the results spotlight the heterogeneous aspects that comorbidity brings to PTSD assessment.

Adult↗

PubMed2005

Reduced p53 in peripheral blood mononuclear cells from patients with rheumatoid arthritis is associated with loss of radiation-induced apoptosis.

OBJECTIVE: Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. This profile includes, at least in part, a collection of underexpressed genes that encode proteins that inhibit cell cycle progression and stimulate apoptosis. We aimed to determine whether this gene expression profile confers functional liability on lymphocytes from patients with rheumatoid arthritis (RA). METHODS: Viability studies in response to a panel of proapoptotic stimuli revealed that T lymphocytes from patients with RA were resistant to gamma radiation-induced apoptosis, a process known to be dependent on p53. To assess p53 function in RA peripheral blood mononuclear cells, baseline levels of p53 protein and TP53 transcript were measured in patients with RA and controls. The cellular p53 response to gamma radiation was also assessed by immunoblotting. RESULTS: Lymphocytes from patients with RA had lower baseline levels of TP53 messenger RNA (mRNA) and p53 protein than did those from control subjects and were deficient in their ability to increase p53 after exposure to gamma radiation. A subgroup of patients with RA had a second biochemical defect characterized by expression of very low baseline levels of checkpoint kinase 2 mRNA and protein. CONCLUSION: We conclude that defects in the expression of TP53 mRNA and, in a subgroup, defects in expression of CHK2 mRNA, lead to severe defects in apoptosis in patients with RA. We hypothesize that this liability may contribute to autoimmunity.

Adult↗

PubMed1996

Association of conventional and exertional coronary heart disease risk factors in 5,000 apparently healthy men.

BACKGROUND AND HYPOTHESIS: The aim of this study was to define the prevalence of previously undetected coronary heart disease among asymptomatic males, aged 30-65 years, by means of resting and exercise electrocardiography in conjunction with an analysis of conventional and exertional coronary risk factors. METHODS: Between January 1985 and December 1989 we examined 5,000 clinically asymptomatic subjects. A detailed case history was obtained for each individual, followed by a complete physical examination, comprehensive blood (including lipid) profile, lung function tests, chest x-ray, a resting 12-lead electrocardiogram (ECG), and a maximal treadmill exercise ECG. Whenever possible, on-line computerized respiratory analysis (Beckman Metabolic Measurement Cart) was carried out during the exercise tests. Conventional and exertional coronary heart disease risk factors were also recorded. RESULTS: A total of 162 persons (3.2%) showed abnormal S-T segment responses during the exercise or recovery period. Of these, 92 subjects underwent further investigations: coronary angiography (79), 201thallium scanning (13), 201thallium scanning followed by coronary angiography (7). Of the 86 patients who proceeded to coronary angiography, 19 (22%) had either normal coronary artery anatomy or only insignificant disease. Among the 67 (78%) of patients with significant angiographically demonstrable disease, 26 received coronary artery bypass grafting, 7 underwent coronary angioplasty, and the remainder continued on medical management. CONCLUSIONS: These results are discussed in relation to a variety of conventional and exertional coronary risk factors.

Adult↗

PubMed2006

Comparative genomic and expression analysis of group B1 sox genes in zebrafish indicates their diversification during vertebrate evolution.

Group B1 Sox genes encode HMG domain transcription factors that play major roles in neural development. We have identified six zebrafish B1 sox genes, which include pan-vertebrate sox1a/b, sox2, and sox3, and also fish-specific sox19a/b. SOX19A/B proteins show a transcriptional activation potential that is similar to other B1 SOX proteins. The expression of sox19a and sox3 begins at approximately the 1,000-cell stage during embryogenesis and becomes confined to the future ectoderm by the shield stage. This is reminiscent of the epiblastic expression of Sox2 and/or Sox3 in amniotes. As development progresses, these six B1 sox genes display unique expression patterns that overlap distinctly from one region to another. sox19a expression is widespread in the early neuroectoderm, resembling pan-neural Sox2 expression in amniotes, whereas zebrafish sox2 shows anterior-restricted expression. Comparative genomics suggests that sox19a/b and mammalian Sox15 (group G) have an orthologous relationship and that the B1/G Sox genes arose from a common ancestral gene through two rounds of genome duplication. It seems likely, therefore, that each B1/G Sox gene has gained a distinct expression profile and function during vertebrate evolution.

Animals↗

PubMed1996

T lymphocytes from the normal human peritoneum contain high frequencies of Th2-type CD8+ T cells.

The majority of peritoneal T lymphocytes have been shown to be CD8+ and to co-express CDw60. Expression of CDw60 characterizes CD8 T cells capable of secreting interleukin (IL)-4 and supporting IgG production by B cells. We analyzed at the clonal level the functional cytokine profile of CD8+ T lymphocytes from the normal human peritoneum. While the majority of the clones produced interferon (IFN)-gamma and exhibited high alloantigen-specific cytolytic activity, some clones secreted IL-4 and IL-5 but no detectable IFN-gamma. These Th2-type CD8+ T cell clones provided substantial B cell help for IgG and IgA synthesis and exhibited reduced cytolytic activity. Our results suggest that distinct subsets of CD8+ T cell may occur in different immune compartments.

Antigens, CD↗

PubMed2004

Hepatic dendritic cell subsets in the mouse.

The CD11c(+) cell population in the non-parenchymal cell population of the mouse liver contains dendritic cells (DC), NK cells, B cells and T cells. In the hepatic CD11c(+) DC population from immunocompetent or immunodeficient [recombinase-activating gene-1 (RAG1)(-/-)] C57BL/6 mice (rigorously depleted of T cells, B cells and NK cells), we identified a B220(+) CD11c(int) subset of 'plasmacytoid' DC, and a B220(-) CD11c(+) DC subset. The latter DC population could be subdivided into a major, immature (CD40(lo) CD80(lo) CD86(lo) MHC class II(lo)) CD11c(int) subset, and a minor, mature (CD40(hi) CD80(hi) CD86(hi) MHC class II(hi)) CD11c(hi) subset. Stimulated B220(+) but not B220(-) DC produced type I interferon. NKT cell activation in vivo increased the number of liver B220(-) DC three- to fourfold within 18 h post-injection, and up-regulated their surface expression of activation marker, while it contracted the B220(+) DC population. Early in virus infection, the hepatic B220(+) DC subset expanded, and both, the B220(+) as well as B220(-) DC populations in the liver matured. In vitro, B220(-) but not B220(+) DC primed CD4(+) or CD8(+)T cells. Expression of distinct marker profiles and functions, and distinct early reaction to activation signals hence identify two distinct B220(+) and B220(-) subsets in CD11c(+) DC populations freshly isolated from the mouse liver.

Animals↗

PubMed1979

Establishment and characterization of human B-lymphocytic lymphoma cell lines (BALM-3, -4 and -5); intraclonal variation in the B-cell differentiation stage.

This study describes the establishment of three non-Burkitt B-lymphoma cell lines (BALM-3, BALM-4 and BALM-5) originating from the pleural effusion of a patient with a poorly differentiated diffuse lymphocytic lymphoma. The cells of BALM-3, -4 and -5 exhibited a number of properties which distinguish them from the usual B-cell type lymphoblastoid cell lines. Thus, they lacked the Epstein-Barr virus genome and had abnormal chromosome constitutions including a 14q+ marker. The presence of the identical surface immunoglobulin isotypes (gamma and chi chain determinants), and Ia-like B-cell-associated antigen in the cultured cells and in the "fresh" lymphoma cells in vivo was demonstrated. These findings strongly suggested that these cell lines have B-cell characteristics and were derived from the original tumor cell population. BALM-5 cells, however, showed somewhat different growth, cell surface marker profile and functional characteristics compared to those of BALM-3, and -4 cells. These variations suggest that the BALM-5 cells were probably at different stages of B-cell maturation than those of BALM-3 and -4, even though all three cell lines (established in three separate flasks) originated from the cells of the same pleural effusion of a lymphoma with monoclonal B-cell characteristics.

Antigens, Surface↗

PubMed1990

Human melanoma cells with high susceptibility to cell-mediated lysis can be identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability.

Marked heterogeneity for susceptibility to lysis by autologous CTL clones and allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with the highest susceptibility to lysis had increased ICAM-1 antigen expression. Phenotype analysis for the presence of extracellular matrix receptors in the beta 1- and beta 3-integrin families revealed that the tumor clones with the highest susceptibility to lysis were also characterized by frequent expression or increased expression of multiple receptors in the beta 1 family including VLA-1, -2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility to lysis, seen at the clonal level, was confirmed by selection experiments on the uncloned metastasis Me665/2. In fact, the neoplastic population surviving 3 cycles of immunoselection with IL-2-activated lymphocytes exhibited, in comparison to the unselected metastasis: (1) reduced susceptibility to lysis and (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens were observed on melanoma cells recovered after invading a reconstituted basement membrane. These data indicate that melanoma cells with enhanced susceptibility to cell-mediated lysis can be identified on the basis of phenotypic characteristics (ICAM-1 and VLA antigen profile) and functional features (invasive ability on reconstituted basement membranes).

Antibodies, Monoclonal↗