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PubMed1990

The impact of psychologic factors on measurement of functional status. Assessment of the sickness impact profile.

In this study the relationship between four psychologic health constructs (depression, anxiety, patient response bias, and hostility) and the Sickness Impact Profile (SIP) measurement of functional status was evaluated. The SIP, Carroll Depression Rating Scale (CDRS); and the Minnesota Multiphasic Personality Inventory (MMPI) were administered to 332 patients hospitalized for treatment of combined medical and psychiatric problems. Pearson's product-moment correlation was high between CDRS and SIP Total score (r = 0.67) and between CDRS and SIP Psychosocial subscale (r = 0.72); correlation was lower between CDRS and SIP Physical subscale (r = 0.44). Six MMPI scales (depression, anxiety, psychasthenia, lie, K, hostility) correlated with SIP Total score (r = 0.18 to 0.50), with SIP Psychosocial score (r = 0.28 to 0.65) and less well with SIP Physical subscale (r = 0.07 to 0.25). Factor analysis of the SIP categories showed two factors with eigenvalues greater than 1. Promax factor rotation showed all SIP Psychosocial categories and all measured psychologic variables loaded most heavily on factor 1. SIP Physical categories loaded most heavily on factor 2. Stepwise multiple regression analysis showed that psychologic variables account for 49% of the SIP total variance, 62% of SIP Psychosocial subscale variance, but only 19% of SIP Physical subscale variance. The CDRS accounts for the major portion of the explained variance with only minor additional contributions from the MMPI scales. We conclude that 1) the SIP discriminates psychosocial and physical dysfunction even in medical patients with extensive psychiatric comorbidity; 2) the SIP measures at least two dimensions of health, one of which is strongly related to depression; and 3) constructs measured by MMPI scales do not have substantial independent contribution to SIP variance.

Adult↗
PubMed2006

Effective similarity measures for expression profiles.

It is commonly accepted that genes with similar expression profiles are functionally related. However, there are many ways one can measure the similarity of expression profiles, and it is not clear a priori what is the most effective one. Moreover, so far no clear distinction has been made as for the type of the functional link between genes as suggested by microarray data. Similarly expressed genes can be part of the same complex as interacting partners; they can participate in the same pathway without interacting directly; they can perform similar functions; or they can simply have similar regulatory sequences. Here we conduct a study of the notion of functional link as implied from expression data. We analyze different similarity measures of gene expression profiles and assess their usefulness and robustness in detecting biological relationships by comparing the similarity scores with results obtained from databases of interacting proteins, promoter signals and cellular pathways, as well as through sequence comparisons. We also introduce variations on similarity measures that are based on statistical analysis and better discriminate genes which are functionally nearby and faraway. Our tools can be used to assess other similarity measures for expression profiles, and are accessible at biozon.org/tools/expression/

Algorithms↗
PubMed2006

Rapidly convergent procedure to solve the density profile equation in the classical density functional theory.

An efficient recursive procedure to solve the density profile equation in the classical density functional theory (DFT) using an inverse Broyden method is described. The present iterative procedure is free of calculation of the Jacobian matrix, and its inversion unavoidable for the well-known Newton-Raphson (NR) method and its variants. Numerical calculation indicates that only the approximate solution and iterative matrix of the lower bulk density case are employed as the corresponding initial guesses of the higher bulk density case, the present recursive procedure can converge quickly to the physical solution with an accuracy of epsilon = 10(-14); therefore, the procedure provides an efficient numerical algorithm for the theory in which acquirement of a density profile of high accuracy is a key step. Extensive numerical calculation shows the advantage of the present inverse Broyden method over Broyles' mixing procedure and a modified Powell hybrid algorithm (a variation of the NR method).

Journal Article↗
PubMed2006

Global analysis of gene function in yeast by quantitative phenotypic profiling.

We present a method for the global analysis of the function of genes in budding yeast based on hierarchical clustering of the quantitative sensitivity profiles of the 4756 strains with individual homozygous deletion of nonessential genes to a broad range of cytotoxic or cytostatic agents. This method is superior to other global methods of identifying the function of genes involved in the various DNA repair and damage checkpoint pathways as well as other interrogated functions. Analysis of the phenotypic profiles of the 51 diverse treatments places a total of 860 genes of unknown function in clusters with genes of known function. We demonstrate that this can not only identify the function of unknown genes but can also suggest the mechanism of action of the agents used. This method will be useful when used alone and in conjunction with other global approaches to identify gene function in yeast.

Cluster Analysis↗
PubMed2003

Metabolic profiles and progesterone cycles in first lactation dairy cows.

This study investigated the ovarian function, metabolic profiles and fertility in first lactation Holstein-Friesian dairy cows (mean 305 day milk yield: 7417+/-191kg, n=37). Reproductive profiles obtained from milk progesterone analysis were categorized into normal (n=17) and four abnormal profiles (delayed ovulation, DOV1, n=9; DOV2, n=2; persistent corpus luteum, PCL1, n=6; PCL2, n=4; 1: immediately post-calving, 2: subsequent cycles). Fifty-five percent of cows had abnormal profiles with half of these being categorized as DOV1. Fertility of DOV1 and DOV2 cows was reduced whereas PCL1 and PCL2 cows had similar reproductive competence to normal profile cows. DOV1 animals had higher milk energy values, lower energy balances, lower dry matter intakes (DMI) and greater body weight and body condition score (BCS) losses post-calving than normal profile animals. DOV1 animals also had lower insulin-like growth factor-I (IGF-I) and higher betahydroxybutyrate (BHB) concentrations and tended to have the lower insulin and glucose concentrations in the pre-service period than normal profile cows. All PCL animals had vulval discharges postpartum. Despite this, the DMI, body weight and BCS changes, IGF-I concentrations and fertility of PCL1 animals was similar to normal profile cows. In conclusion, the high prevalence of delayed ovulation post-calving (DOV1) in primiparous high yielding cows lasted long enough (71+/-8.3 days) to have a detrimental impact on fertility and was associated with significant physiological changes. This study did not establish any detrimental effects of PCL profiles on fertility or production parameters.

Animals↗
PubMed2005

Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with gammac cytokines.

The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4(+) and CD8(+) T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow-derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor(+) CD8(+) T cells releasing IFN-gamma and killing autologous B-cell tumor in an HLA-class I-restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to gammac cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.

Adult↗
PubMed2002

Domain-oriented functional analysis based on expression profiling.

BACKGROUND: Co-regulation of genes may imply involvement in similar biological processes or related function. Many clusters of co-regulated genes have been identified using microarray experiments. In this study, we examined co-regulated gene families using large-scale cDNA microarray experiments on the human transcriptome. RESULTS: We present a simple model, which, for each probe pair, distills expression changes into binary digits and summarizes the expression of multiple members of a gene family as the Family Regulation Ratio. The set of Family Regulation Ratios for each protein family across multiple experiments is called a Family Regulation Profile. We analyzed these Family Regulation Profiles using Pearson Correlation Coefficients and derived a network diagram portraying relationships between the Family Regulation Profiles of gene families that are well represented on the microarrays. Our strategy was cross-validated with two randomly chosen data subsets and was proven to be a reliable approach. CONCLUSION: This work will help us to understand and identify the functional relationships between gene families and the regulatory pathways in which each family is involved. Concepts presented here may be useful for objective clustering of protein functions and deriving a comprehensive protein interaction map. Functional genomic approaches such as this may also be applicable to the elucidation of complex genetic regulatory networks.

Amino Acid Sequence↗
PubMed1998

Characterization of 5-HT1A receptor functional coupling in cells expressing the human 5-HT1A receptor as assessed with the cytosensor microphysiometer.

The functional activity of a series of 5-HT1A receptor ligands has been evaluated in a cell line expressing the human 5-HT1A receptor (h5-HT1A x CHO) using the agonist-stimulated increase in extracellular acidification rate, measured with the microphysiometer, as a functional assay. Both 5-CT and 8-OH-DPAT were potent agonists in stimulating an increase in extracellular acidification rate in h5-HT1A x CHO cells with estimated EC50 values of 1.2 and 7.8 nM, respectively. Additionally, these two 5-HT1A receptor agonists elicited a similar maximum response. Concentration-dependent agonist activity was also observed in the presence of buspirone, ipsapirone, BMY7378, NAN-190 and WAY100135, and each of these compounds behaved as partial 5-HT1A receptor agonists. The selective 5-HT1A receptor antagonist WAY100635 produced a potent (IC50, 2.3 nM) and complete block of the 8-OH-DPAT-stimulated response. An evaluation of the inhibitory activity of a series of 5-HT1A receptor antagonists produced the following rank order of potency; WAY100635 > LY206130 (IC50, 7.1 nM) > WAY100135 (30.8 nM) > pindolol (76.2 nM) > (-)UH-301 (92.8 nM). Parallel studies on the inhibition of forskolin-stimulated adenylyl cyclase activity in hS-HT1A x CHO cells revealed that agonist potencies were generally similar between the two functional assays and were in good agreement with the estimated 5-HT1A receptor binding affinities. However, the relative efficacies determined for the partial agonists in the cAMP assay were substantially greater than those observed with the microphysiometer. Finally, antagonists were considerably weaker in the cAMP assay compared with the microphysiometer. The evaluation of 5-HT1A ligands using the microphysiometer, which represents a very distinct indice of 5-HT1A receptor function compared with the cAMP assay, results in a different profile of functional activity.

Animals↗
PubMed2005

Distinct defensin profiles in Neisseria gonorrhoeae and Chlamydia trachomatis urethritis reveal novel epithelial cell-neutrophil interactions.

Defensins are key participants in mucosal innate defense. The varied antimicrobial activity and differential distribution of defensins at mucosal sites indicate that peptide repertoires are tailored to site-specific innate defense requirements. Nonetheless, few studies have investigated changes in peptide profiles and function after in vivo pathogen challenge. Here, we determined defensin profiles in urethral secretions of healthy men and men with Chlamydia trachomatis- and Neisseria gonorrhoeae-mediated urethritis by immunoblotting for the epithelial defensins HBD1, HBD2, and HD5 and the neutrophil defensins HNP1 to -3 (HNP1-3). HBD1 was not detectable in secretions, and HBD2 was only induced in a small proportion of the urethritis patients; however, HD5 and HNP1-3 were increased in C. trachomatis infection and significantly elevated in N. gonorrhoeae infection. When HNP1-3 levels were low, HD5 appeared mostly as the propeptide; however, when HNP1-3 levels were >10 microg/ml, HD5 was proteolytically processed, suggesting neutrophil proteases might contribute to HD5 processing. HD5 and HNP1-3 were bactericidal against C. trachomatis and N. gonorrhoeae, but HD5 activity was dependent upon N-terminal processing of the peptide. In vitro proteolysis of proHD5 by neutrophil proteases and analysis of urethral secretions by surface-enhanced laser desorption ionization substantiated that neutrophils contribute the key convertases for proHD5 in the urethra during these infections. This contrasts with the small intestine, where Paneth cells secrete both proHD5 and its processing enzyme, trypsin. In conclusion, we describe a unique defensin expression repertoire in response to inflammatory sexually transmitted infections and a novel host defense mechanism wherein epithelial cells collaborate with neutrophils to establish an antimicrobial barrier during infection.

Chlamydia Infections↗
PubMed1981

Platelets in myeloproliferative disorders. III: Glycoprotein profile in relation to platelet function and platelet density.

Membrane glycoproteins (GP) are implicated in platelet functions. In myeloproliferative diseases (MD), some of these functions are known to be perturbed. 16 patients with various MD were investigated for platelet functions (retention to glass beads, epinephrine- and ristocetin-induced aggregation), platelet density distribution and PAS-staining glycoprotein profile on SDS-polyacrylamide-gel-electrophoresis. An abnormal GP pattern (moderate reduction of GP (Ib + Is) and GP IIb with corresponding increase in GP IIIb) was demonstrated but no relation to platelet dysfunction or density distribution was observed. No differences between the various types of MD were noticed although the group of polycythaemia vera was the less perturbed for platelet function, platelet density and also GP profile.

Blood Platelets↗
PubMed1977

[Hemodynamic profile of acute myocardial infarction as a function of electrocardiographic localization].

The haemodynamic profiles of 147 cases of myocardial infarction investigated within 30 hours of the clinical onset were studies in relation to the topography of the necrosis on the ECG: there were 36 inferior (I), 29 postero-inferior (PI), 22 antero-septal (AS), 38 antero-lateral (AL), 15 deep septal (DS), and 7 strictly posterior or lateral (PL). Simultaneous recordings of the diastolic pulmonary arterial pressures and the left ventricular diastolic pressures (pre-and post-a) have shown different degrees of correlation with the topographical site. The correlation found in AS, AL and I necrosis are clearer with respect to the pre-a. The PI necroses show no correlation. Graphs of left ventricular function as well as an analysis of the various other parameters show that the DS, the AL, and to a lesser extent the PI are associated with the grossest depression of left ventricular function. A study of the amplitude of the "a" wave also shows that the effect of infacts of the free wall of the left ventricule on the compliance is greater. A study of right ventricular function as well as the correlations between the pulmonary and right atrial pressures confirms the presence of right ventricular disfunction in DS and PI necroses. Impaired left ventricular function, impaired right ventricular function, and disorders of compliance seem to be the determining factors in changing the haemodynamics in the various ECG sites of infarction.

Acute Disease↗
PubMedDate not supplied

Number of active joints, not diagnosis, is the primary determinant of function and performance in early synovitis.

OBJECTIVE: A substudy within a larger study of patients with inflammatory arthritis of less than one year, to analyze baseline measures or joint counts, laboratory values, patient questionnaires and ARA diagnostic criteria for rheumatoid arthritis, as predictors of one year performance and functional status. METHODS: 229 patients with synovitis of less than one year were enrolled and evaluated at baseline and one year. Measures included the number of swollen or tender joints [active joint counts]; biological indices of inflammation [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]; and patient questionnaire measures of pain [Wisconsin Brief Pain Inventory], fatigue [multi-dimensional assessment of fatigue], depression [Center for Epidemiologic Studies--Depression Scale], sleep [Sleep Quality Index], performance [Human Activity Profile], and function [Sickness Impact Profile ambulation subscale and Health Assessment Questionnaire]. Correlations between these measures were evaluated using the Spearman rank order correlation. Patients were classified according to whether they met ARA criteria for RA, had high (> 7) or low (< or = 7) numbers of affected joints; and high, intermediate, or low levels of performance; and were compared using the Kruskal-Wallis test. RESULTS: At baseline, an active joint count of > 7 versus < or = 7 was associated significantly with higher age, rheumatoid factor positivity, a diagnosis of rheumatoid arthritis versus spondyloarthropathy or undifferentiated arthritis, and receiving a disease modifying antirheumatic drug (DMARD), but not with sex, race, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), or receiving prednisone. Furthermore, high baseline active joint counts were associated significantly with patient questionnaire scores for maximum activity, fatigue and depression, but differences were not significant for sleep, ambulation and pain scores. A comparison of patients who met or did not meet criteria for RA indicated significant differences only according to the fatigue scores, but none of the other questionnaire measures. Correlations of baseline measures with one-year performance were highest for the baseline active joint count compared to laboratory and questionnaire variables. The maximum activity score at one year was predicted significantly by the baseline maximum activity score, active joint count, and age, but not by laboratory tests or whether the patient met criteria for RA. CONCLUSION: The active joint count predicts subsequent performance and function for patients with recent onset, inflammatory synovitis more effectively than whether patients met ARA criteria for RA.

Adult↗
PubMed1996

Visual impairment in preterm children with periventricular leukomalacia--visual, cognitive and neuropaediatric characteristics related to cerebral imaging.

Thirteen preterm children, aged 4 to 14 years, with visual impairment due to periventricular leukomalacia (PVL) were evaluated for visual function, intellectual level, cognitive profile and motor function. Their visual impairment was characterized by low acuity, crowding, visual field defects and ocular motility disturbances. Their cognitive profile was uneven, often with considerably higher scores on verbal than on visual-spatial tasks. Nine children had normal intelligence, three had mild mental retardation and one had severe mental retardation. In all the children, visual impairment was complicated by visual perceptual difficulties, accounting for their greater visual handicap than would be expected from their visual acuities and strabismus alone. Though CT or MRI revealed bilateral PVL in all the children, six had no motor impairment consistent with cerebral palsy, which is an unexpected finding.

Adolescent↗
PubMed1995

Interaction of small peptides with lipid bilayers.

Molecular dynamics simulations of the tripeptide Ala-Phe-Ala-O-tert-butyl interacting with dimyristoylphosphatidylcholine lipid bilayers have been carried out. The lipid and aqueous environments of the peptide, the alkyl chain order, and the lipid and peptide dynamics have been investigated with use of density profiles, radial distribution functions, alkyl chain order parameter profiles, and time correlation functions. It appears that the alkyl chain region accommodates the peptides in the bilayer with minimal perturbation to this region. The peptide dynamics in the bilayer bound form has been compared with that of the free peptide in water. The peptide structure does not vary on the simulation time scale (of the order of hundreds of picoseconds) compared with the solution structure in which a random structure is observed.

Amino Acid Sequence↗
PubMed2004

Quantifying the relationship between co-expression, co-regulation and gene function.

BACKGROUND: It is thought that genes with similar patterns of mRNA expression and genes with similar functions are likely to be regulated via the same mechanisms. It has been difficult to quantitatively test these hypotheses on a large scale because there has been no general way of determining whether genes share a common regulatory mechanism. Here we use data from a recent genome wide binding analysis in combination with mRNA expression data and existing functional annotations to quantify the likelihood that genes with varying degrees of similarity in mRNA expression profile or function will be bound by a common transcription factor. RESULTS: Genes with strongly correlated mRNA expression profiles are more likely to have their promoter regions bound by a common transcription factor. This effect is present only at relatively high levels of expression similarity. In order for two genes to have a greater than 50% chance of sharing a common transcription factor binder, the correlation between their expression profiles (across the 611 microarrays used in our study) must be greater than 0.84. Genes with similar functional annotations are also more likely to be bound by a common transcription factor. Combining mRNA expression data with functional annotation results in a better predictive model than using either data source alone. CONCLUSIONS: We demonstrate how mRNA expression data and functional annotations can be used together to estimate the probability that genes share a common regulatory mechanism. Existing microarray data and known functional annotations are sufficient to identify only a relatively small percentage of co-regulated genes.

Gene Expression Profiling↗
PubMed1985

Functional and phenotypic studies of Japanese adult T cell leukemia cells.

The cell surface marker profile and functional analysis of peripheral blood lymphocytes from 11 Japanese adult T cell leukemia patients were studied. The phenotypic analysis of Japanese adult T cell leukemia (ATL) cells by a series of 13 monoclonal antibodies showed that all ATL cells are anti-T4 reactive but some differ in their expression of T3, T11, and T12 antigens. Thus, considerable phenotypic heterogeneity exists in these populations of leukemia cells. When analyzed in functional assays, ATL cells were suppressive when added to a pokeweed mitogen- (PWM) driven Ig synthesis system. However, the suppression mechanism seemed to be more complex than originally conceived. ATL cells examined in this study seem to function mainly as an inducer of suppressor cells, and as such, activate normal T8 precursors of suppressor cells rather than function as suppressor effector cells. In addition, no evidence was obtained to suggest that suppression of PWM-stimulated IgG synthesis was mediated by natural killer (NK) activity of ATL cells. Rather, ATL cells seem to be markedly deficient in NK activity. These studies suggest that the majority of ATL cells tested are representative of and seem to be the leukemic counterparts of the T4+ suppressor inducer subset.

Adult↗
PubMed2002

Comprehensive gene expression analysis by transcript profiling.

After the completion of the genomic sequence of Arabidopsis thaliana, it is now a priority to identify all the genes, their patterns of expression and functions. Transcript profiling is playing a substantial role in annotating and determining gene functions, having advanced from one-gene-at-a-time methods to technologies that provide a holistic view of the genome. In this review, comprehensive transcript profiling methodologies are described, including two that are used extensively by the authors, cDNA-AFLP and cDNA microarraying. Both these technologies illustrate the requirement to integrate molecular biology, automation, LIMS and data analysis. With so much uncharted territory in the Arabidopsis genome, and the desire to tackle complex biological traits, such integrated systems will provide a rich source of data for the correlative, functional annotation of genes.

Gene Expression Profiling↗
PubMed1989

[Functional asymmetry of the brain in patients with epilepsy].

Individual functional brain asymmetry profiles were different in epileptic patients and healthy individuals. The patients displayed reduced from 39.6% to 17.8% incidence of left profile and increased incidence of combined profile (from 60.4% to 81.5%). The relationship of functional asymmetry profiles to sex, lateralization of epileptic focus and clinical course of the disease was described, the regularities of the profiles' changes in the course of the disease analyzed.

Adolescent↗