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Publication
Journal: Ethnicity and Disease
April/23/2009
Abstract
Health-related knowledge is an important component in the self-management of chronic illnesses. The objective of this study was to more accurately assess racial differences in hypertension knowledge by using a latent variable modeling approach that controlled for sociodemographic factors and accounted for measurement issues in the assessment of hypertension knowledge. Cross-sectional data from 1,177 participants (45% African American; 35% female) were analyzed using a multiple indicator multiple causes (MIMIC) modeling approach. Available sociodemographic data included race, education, sex, financial status, and age. All participants completed six items on a hypertension knowledge questionnaire. Overall, the final model suggested that females, Whites, and patients with at least a high school diploma had higher latent knowledge scores than males, African Americans, and patients with less than a high school diploma, respectively. The model also detected differential item functioning (DIF) based on race for two of the items. Specifically, the error rate for African Americans was lower than would be expected given the lower level of latent knowledge on the items, on the questions related to: (a) the association between high blood pressure and kidney disease, and (b) the increased risk African Americans have for developing hypertension. Not accounting for DIF resulted in the difference between Whites and African Americans to be underestimated. These results are discussed in the context of the need for careful measurement of health-related constructs, and how measurement-related issues can result in an inaccurate estimation of racial differences in hypertension knowledge.
Publication
Journal: Journal of Affective Disorders
July/28/2011
Abstract
BACKGROUND
This study examines the psychometric properties and presence of gender bias in the major depression criteria using data from the Australian general population.
METHODS
Data came from a subsample of respondents from the 1997 National Survey of Mental Health and Wellbeing (NSMHWB; n=2061). A two-parameter logistic model was employed to yield severity and discrimination parameters, and the IRT log-likelihood-ratio test for differential item functioning (IRTLRDIF) procedure was utilized to evaluate gender bias.
RESULTS
DIF analyses indicated that the psychomotor difficulties criterion was endorsed at lower levels of severity by males than females. In general, the criteria were arrayed along a continuum of depression severity. Discrimination was greatest for concentration difficulties/indecision and lowest for death/suicidal thoughts and worthlessness/guilt. Worthlessness/guilt, psychomotor difficulties, and death/suicidal thoughts tapped the severe end of the depression continuum, whereas concentration difficulties/indecision and sleep disturbance tapped the mild range.
CONCLUSIONS
The inclusion of stem questions precluded examination of two core symptoms of depression (depressed mood and loss of interest).
CONCLUSIONS
Collectively, the criteria performed well in defining a latent continuum of major depression. Few gender differences were observed, with the exception of the psychomotor difficulties criterion. Quantitative and qualitative analyses collectively hold promise of providing a scientifically rigorous basis for empirically-based modifications to the psychiatric classification system.
Publication
Journal: Experimental Cell Research
August/3/1993
Abstract
The requirements for the terminal differentiation process of the stalk pathway (from prestalk to stalk) of Dictyostelium discoideum were analyzed by using a low-cell-density culture system with prestalk cells isolated from normally developed slugs. Any of the substances, such as differentiation-inducing factor-1 (DIF-1), DIF-2, dimethyloxazolidinedione, and adenosine, that had been shown to promote prestalk/stalk differentiation did not cause an efficient and consistent induction of prestalk-to-stalk conversion, either alone or in combination. However, the addition of 8-bromoadenosine 3',5'-cyclic monophosphate (Br-cAMP) resulted in high efficiency (80-90%) of stalk cell formation which accompanied the accumulation of a stalk-specific protein, wst34. The maturation process was inhibited by Ca2+ but not by Mg2+. More importantly, the Br-cAMP-induced stalk cell differentiation was neither inhibited nor promoted by DIF-1, cAMP, or ammonia and occurred even at very low cell densities if only Br-cAMP was supplied. Since Br-cAMP is though to penetrate into the cells and to activate the intracellular protein kinase A, the present results suggest that the activation of protein kinase A is sufficient for prestalk-to-stalk conversion.
Publication
Journal: Molecular and Cellular Biology
November/4/1998
Abstract
Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. In Dictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1's mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.
Publication
Journal: European journal of biochemistry
October/12/1992
Abstract
Differentiation-inducing factor 1 (DIF-1) is a dichlorinated alkyl phenone (1-[(3,5-dichloro-2,6-dihydroxy-4-methoxy)phenyl]hexan-1-one) from Dictyostelium discoideum, that induces amoebae to differentiate into stalk cells. It was shown previously that DIF-1 is rapidly metabolized into a series of more polar compounds by living cells [Traynor, D. & Kay, R.R. (1991) J. Biol. Chem. 266, 5291-5297]. The first step in DIF-1 metabolism is the formation of DIF metabolite 1 (now known to be DIF-3) by a monodechlorination. We report here the discovery of the enzyme activity catalyzing this dechlorination. A very sensitive enzyme assay was developed, using [3H]DIF-1 and a TLC system to separate DIF-1 from the product, DIF-3. DIF-1 3(5)-dechlorinase is present in the high-speed supernatant of cell lysates, and uses glutathione, at physiological concentrations, as cofactor. Kinetic measurements indicate a Km for DIF-1 of about 70 nM. The enzyme activity is inhibited by DIF-2 (the pentan-1-one analogue of DIF-1), with a median inhibitor concentration (IC50) of 1 microM, and DIF-3 (IC50 = 5 microM), which presumably act as substrates, but other compounds structurally related to DIF-1 were much less effective. Aurothioglucose, an inhibitor of selenocysteine enzymes, inhibited DIF-1 3(5)-dechlorinase with IC50 = 100 nM. DIF-1 3(5)-dechlorinase activity is developmentally regulated. It is essentially absent from growing cells and increases at the end of aggregation to reach a first peak of activity at the first finger stage, with a further rise at culmination.
Publication
Journal: Schizophrenia Research
June/21/2015
Abstract
OBJECTIVE
The aim of this study was to adapt the Schizophrenia - Quality of Life short-version questionnaire (SQoL18) for use in three middle-income countries in Latin America and to evaluate the factor structure, reliability, and external validity of this questionnaire.
METHODS
The SQoL18 was translated into Spanish using a well-validated forward-backward process. We evaluated the psychometric properties of the SQoL18 in a sample of 253 patients with schizophrenia attending outpatient mental health services in three Latin American countries. For participants in each country (Bolivia, N=83; Chile, N=85; Peru, N=85), psychometric properties were compared to those reported from the reference population (507 patients with schizophrenia) assessed in the validation study. In addition, differential item functioning (DIF) analyses were performed to see whether all items behave in the same way in each country.
RESULTS
Factor analysis performed in the 3 countries showed that the questionnaire's structure adequately matched the initial structure of the SQoL18. The unidimensionality of the dimensions was preserved, and the internal/external validity indices were close to those of the reference population. However, one dimension of the SQoL18 (resilience) presented some unsatisfactory properties including low Cronbach's alpha coefficients, one INFIT value higher than 1.2, and one item showing DIF between the 3 countries.
CONCLUSIONS
These results demonstrate the satisfactory acceptability and psychometric properties of the SQoL18, suggesting the relevance of this questionnaire among patients with schizophrenia in these 3 Latin American countries.
Publication
Journal: British Journal of Ophthalmology
September/19/2001
Abstract
OBJECTIVE
To evaluate the ability of different commercially available cell culture solutions to preserve human donor corneas during 3 weeks of "closed system" organ culture at physiological temperature. This screening was performed in an attempt to establish a rational basis for the development of a serum-free organ culture medium for eye banking.
METHODS
72 normal human donor corneas were organ cultured for 21 days at 31 degrees C in eight different test media (nine corneas in each group). The basic culture solutions included: minimal essential medium (MEM), MEM with stabilised L-glutamine, M199, DIF-1000, SFM, F99, and F99 with ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids (termed F99-Sr). All media were supplemented with 2% fetal calf serum (FCS), except for MEM, which was also studied at 8% FCS. The evaluation parameters included: (1) the endothelial cell loss as evaluated using trypan blue staining; (2) the ability of keratocytes and endothelial cells to incorporate tritiated uridine into RNA as evaluated using autoradiography and digital image analysis; (3) the leakage of immunogenic keratan sulphate as assessed using ELISA; and (4) changes in storage medium pH, glucose, and lactate content.
RESULTS
SFM induced the lowest endothelial cell loss of 14% (SD 2%) and the highest RNA synthesis rates of all test solutions supplemented with 2% FCS. Corneas stored in SFM also showed the least leakage of keratan sulphate and the highest glucose consumption and lactate production. In five media (MEM with 2% FCS, MEM with stabilised L-glutamine, M199, F99, and F99-Sr), comparable and intermediate potentials for organ culture were observed with endothelial cell loss of 16-19%. By contrast, 29% (4%) of the endothelium was lost after storage in DIF-1000. Interestingly, the use of 8% FCS (in MEM) had a marked protective effect on the endothelium, which showed the highest RNA synthetic activity combined with a cell loss of only 11% (4%), compared with 19% (6%) at 2% FCS (p<0.05).
CONCLUSIONS
Among the present test solutions, SFM appears to be the most prominent candidate for a new corneal organ culture medium and should be further tested and possibly refined to effectively substitute serum addition.
Publication
Journal: International Journal of Methods in Psychiatric Research
August/11/2008
Abstract
The Hospital Anxiety and Depression Scale (HADS) is a widely used screening instrument for depression and anxiety in medically compromised patients. The purpose of this study was to examine the differential item functioning (DIF) of the anxiety subscale of the HADA (HADS-A). A research assistant administered the HADS-A to 166 Chinese patients with chronic obstructive pulmonary disease (COPD) who were consecutively admitted to a rehabilitation hospital. Although the HADS-A was overall uni-dimensional, there were one mute item and two items with borderline misfit. Only one item had a DIF for arterial oxygen saturation. No item had DIF for other indicators of the severity of COPD. In conclusion, this study found that for one item the HADS-A has significant item bias for the severity of disease in patients with COPD.
Publication
Journal: International Journal of Behavioral Medicine
October/13/2009
Abstract
BACKGROUND
Little is known about cross-language measurement equivalence of the job content questionnaire (JCQ) PURPOSE: The purposes of this study were to assess the extent of cross-language differential item functioning (DIF) of the 27 JCQ items in six languages (French, Dutch, Belgian-French, Belgian-Dutch (Flemish), Italian, and Swedish) from six European research centers and to test whether its effects on the scale-level mean comparisons among the centers were substantial or not.
METHODS
A partial gamma coefficient method was used for statistical DIF analyses where the Flemish JCQ was the reference for other language versions. Additionally, equivalence between the Flemish and Dutch translations was subjected to a judgmental review.
RESULTS
On average, 36% to 39% of the total tested items appeared to be cross-language DIF items in the statistical analyses. The judgmental review indicated that half of the DIF items may be associated with translation difference. The impacts of the DIF items on the mean comparisons of the JCQ scales between the centers were non-trivial: underestimated skill discretion (Milan), underestimated decision authority (Leiden), underestimated psychological demands (Milan women), and incomparable coworker support (Gothenburg 95).
CONCLUSIONS
Cross-language DIF of the JCQ among European countries should be considered in international comparative studies on psychosocial job hazards using JCQ scales.
Publication
Journal: Journal of Cellular Physiology
November/20/1985
Abstract
The present study was carried out to determine if an insulin-like growth factor (IGF) type activity might be produced by embryonal carcinoma-derived cells. The cell line used to condition growth medium for the isolation of secreted growth factors was a newly established Dif 5 cell type. Dif 5 cells are a differentiated endoderm-like cell type derived from F9 embryonal carcinoma cells (which possess properties similar to mouse embryonic stem cells) following extensive exposure to retinoic acid. When growth medium conditioned by Dif 5 cells is chromatographed on Sephadex G-75 in 1 M acetic acid two peaks of activity are observed which compete for specific [125I]iodo multiplication stimulating activity (MSA) binding to PYS cells. MSA is the rat homologue of human IGF-II. The high molecular weight fraction (Mr approximately 60K) apparently corresponds to IGF-binding protein as determined by its ability to bind [125I]iodo-MSA. The low molecular weight fraction (Mr approximately 8K) is biologically active as this fraction stimulates [3H]thymidine incorporation into serum-starved chick embryo fibroblasts. Radioimmunoassay data indicate that the IGF-like activity produced by Dif 5 cells is more closely related to IGF-II than to IGF-I. Undifferentiated embryonal carcinoma stem cell lines (F9, Nulli, and PCC4) produced little of this MSA-like activity, while PYS-2 (parietal endoderm-like) cells produced about 16 ng MSA/10(6) cells/24 hr as determined by radioimmunoassay. Dif 5 and PSA-5E (visceral endoderm-like) cells, are found to secrete significant amounts of MSA into the growth medium (30-50 ng MSA/10(6) cells/24 hr). These findings offer further support to a proposal that MSA (IGF-II) produced by endoderm cells, particularly visceral endoderm, may serve as an early embryonic growth factor.
Publication
Journal: Journal of Bacteriology
April/17/2011
Abstract
In Bacillus subtilis, chromosome dimers that block complete segregation of sister chromosomes arise in about 15% of exponentially growing cells. Two dedicated recombinases, RipX and CodV, catalyze the resolution of dimers by site-specific recombination at the dif site, which is located close to the terminus region on the chromosome. We show that the two DNA translocases in B. subtilis, SftA and SpoIIIE, synergistically affect dimer resolution, presumably by positioning the dif sites in close proximity, before or after completion of cell division, respectively. Furthermore, we observed that both recombinases, RipX and CodV, assemble on the chromosome at the dif site throughout the cell cycle. The preassembly of recombinases probably ensures that dimer resolution can occur rapidly within a short time window around cell division.
Publication
Journal: Journal of Investigative Dermatology
February/5/1989
Abstract
In evaluating patients we have noted disparity between the locations of bound immunoreactants and the level of blistering in epidermolysis bullosa acquisita (EBA). We examined 10 consecutive EBA patients by routine histology, direct (DIF) and indirect (IIF; intact and NaCl-split skin) immunofluorescence, immunofluorescence mapping (IM), and/or direct immunoelectron microscopy (DIEM). DIF was positive in each. IIF was positive in 3/8 and 6/7 patients when intact and split skin were used as substrates. DIEM revealed immunoreactants within the lamina densa (LD) in 6/10, sub-LD in 1/10, and both LD and sub-LD in 3/10 patients. In contrast, by DIEM and IM, blister formation was noted within the lamina lucida (LL) in 7/9 and 8/10, sub-LD in 1/9 and 1/10, and within both LL and sub-LD in 1/9 and 1/10, respectively. In the presence of neutrophils within the upper dermis (n = 6), cleavage occurred within the LL in 5 specimens; in one additional specimen containing predominantly neutrophils, cleavage occurred within both LL and sub-LD. In the presence of mononuclear cells (n = 2), intra-LL cleavage occurred. In the presence of eosinophils, cleavage occurred within both LL and sub-LD. In the one specimen lacking any infiltrate, the cleavage plane was exclusively sub-LD. Intra-LL cleavage planes are more common than sub-LD ones in at least early cases of EBA. These findings likely represent the intra-LL-separating effect of leukocyte-derived proteolytic enzymes, when such cells are chemoattracted to the dermoepidermal junction by bound immuno-reactants.
Publication
Journal: Genetics
March/22/1993
Abstract
Mutations at the ovarian tumor (otu) gene of Drosophila melanogaster cause female sterility and generate a range of ovarian phenotypes. Quiescent (QUI) mutants exhibit reduced germ cell proliferation; in oncogenic (ONC) mutants germ cells undergo uncontrolled proliferation generating excessive numbers of undifferentiated cells; the egg chambers of differentiated (DIF) mutants differentiate to variable degrees but fail to complete oogenesis. We have examined mutations caused by insertion and deletion of P elements at the otu gene. The P element insertion sites are upstream of the major otu transcription start sites. In deletion derivatives, the P element, regulatory regions and/or protein coding sequences have been removed. In both insertion and deletion mutants, the level of otu expression correlates directly with the severity of the phenotype: the absence of otu function produces the most severe QUI phenotype while the ONC mutants express lower levels of otu than those which are DIF. The results of this study demonstrate that the diverse mutant phenotypes of otu are the consequence of different levels of otu function.
Publication
Journal: Journal of Histochemistry and Cytochemistry
September/14/1981
Abstract
Paired staining with the unlabeled antibody peroxidase-antiperoxidase (PAP) method and direct immunofluorescence (DIF) differentiated distinctly between gastrin- and somatostatin-producing cells in the human gastric antrum. Similar paired staining of complexed lambda and alpha chains in immunoglobulin (Ig)A myeloma cells, of kappa and free J chains in IgG myeloma cells, and of secretory IgA and its epithelial transport protein, the free secretory component (SC), in colonic crypt cells, demonstrated that PAP staining inhibits subsequent DIF staining of an antigenic determinant present on the same molecule as the antigen revealed by the brown color of diaminobenzidine (DAB) or present or an unassociated molecule in the same cell. A quenching effect of the DAB reaction product was noted for both fluorescein (green) and rhodamine (red) emissions. In addition, a blocking effect of the DAB deposits has been demonstrated and is assumed to be the principal methodological basis for the paired PAP-DIF staining approach omitting intermediate antibody elution, as well as for the more time-consuming sequential PAP staining with DAB substrate for the first and 4-chloro-1-naphthol (CN) for the second antigen. The quenching and blocking effects limit in practice the paired PAP-DIF method to the localization of antigens present in separate cells.
Publication
Journal: Cell Journal
April/13/2015
Abstract
OBJECTIVE
The peroxisome proliferator-activated receptors (PPARs) are a group of nu- clear receptor proteins whose functions as transcription factors regulate gene expres- sions. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. This study attempts to determine the effect of baicalin, a PPARγ activator, on erythroid differentiation of cluster of differentiation 133(+)(CD133(+)) cord blood hematopoietic stem cells (HSCs).
METHODS
In this experimental study, in order to investigate the effects of the PPARγ agonists baicalin and troglitazone on erythropoiesis, we isolated CD133(+) cells from human umbilical cord blood using the MACS method. Isolated cells were cultured in erythroid-inducing medium with or without various amounts of the two PPARγ activa- tors (baicalin and troglitazone). Erythroid differentiation of CD133(+)cord blood HSCs were assessed using microscopic morphology analysis, flow cytometric analysis of erythroid surface markers transferrin receptor (TfR) and glycophorin A (GPA) and bycolony forming assay.
RESULTS
Microscopic and flow cytometric analysis revealed the erythroid differentiation of CD133(+)cord blood HSCs under applied erythroid inducing conditions. Our flow cytometric data showed that the TfR and GPA positive cell population diminished significantly in the presence of either troglitazone or baicalin. The suppression of erythroid differentiation in response to PPARγ agonists was dose-dependent. Erythroid colony-forming ability of HSC decreased significantly after treatment with both PPARγ agonists but troglitazone had a markedly greater effect.
CONCLUSIONS
Our results have demonstrated that PPARγ agonists modulate erythroid dif- ferentiation of CD133(+)HSCs, and therefore play an important role in regulation of normal erythropoiesis under physiologic conditions. Thus, considering the availability and applica- tion of this herbal remedy for treatment of a wide range of diseases, the inhibitory effect of baicalin on erythropoiesis should be noted.
Publication
Journal: Helicobacter
March/11/2013
Abstract
BACKGROUND
Xer-cise is an efficient selectable marker removal technique that was first applied in Bacillus subtilis and Escherichia coli for the construction of markerless gene deletions. Xer-cise marker excision takes advantage of the presence of site-specific Xer recombination in most bacterial species for the resolution of chromosome dimers at the dif site during replication. The identification and functional characterization of the difH/XerH recombination system enabled the development of Xer-cise in Helicobacter pylori.
METHODS
Markerless deletions were obtained by a single natural transformation step of the Xer-cise cassette containing rpsL and cat genes, for streptomycin susceptibility and chloramphenicol resistance respectively, flanked by difH sites and neighboring homologous sequences of the target gene. Insertion/deletion recombinant H. pylori were first selected on chloramphenicol-containing medium followed by selection on streptomycin-containing medium for clones that underwent XerH mediated excision of the rpsL-cat cassette, resulting in a markerless deletion.
RESULTS
XerH-mediated removal of the antibiotic marker was successfully applied in three different H. pylori strains to obtain markerless gene deletions at very high efficiencies. An unmarked triple deletion mutant was also constructed by sequential deletion of ureA, vacA and HP0366 and removal of the selectable marker at each step. The triple mutant had no growth defect suggesting that multiple difH sites per chromosome can be tolerated without affecting bacterial fitness.
CONCLUSIONS
Xer-cise eliminates the need for multiple passages on non selective plates and subsequent screening of clones for loss of the antibiotic cassette by replica plating.
Publication
Journal: Environmental Science & Technology
December/15/2003
Abstract
The technique of diffusive gradients in thin films (DGT) has been suggested to sample an available fraction of metals in soil. The objectives of this study were to compare DGT measurements with commonly measured fractions of Zn in soil, viz, the soil solution concentration and the total Zn concentration. The DGT technique was used to measure fluxes and interfacial concentrations of Zn in three series of field-contaminated soils collected in transects toward galvanized electricity pylons and in 15 soils amended with ZnCl2 at six rates. The ratio of DGT-measured concentration to pore water concentration of Zn, R, varied between 0.02 and 1.52 (mean 0.29). This ratio decreased with decreasing distribution coefficient, Kd, of Zn in the soil, which is in agreement with the predictions of the DGT-induced fluxes in soils (DIFS) model. The R values predicted with the DIFS model were generally larger than the observed values in the ZnCl2-amended soils at the higher Zn rates. A modification of the DIFS model indicated that saturation of the resin gel was approached in these soils, despite the short deployment times used (2 h). The saturation of the resin with Zn did not occur in the control soils (no Zn salt added) or the field-contaminated soils. Pore water concentration of Zn in these soils was predicted from the DGT-measured concentration and the total Zn content. Predicted values and observations were generally in good agreement. The pore water concentration was more than 5 times underpredicted for the most acid soil (pH = 3) and for six other soils, for which the underprediction was attributed to the presence of colloidal Zn in the soil solution.
Publication
Journal: Experientia
July/31/1989
Abstract
IL-6/IFN-beta 2 appears to be one of the important mediators of the response to viral and bacterial infections and to shock. The biological effects now associated with IL-6/IFN-beta 2 include: stimulation of immunoglobulin secretion by mature B lymphocytes (BSF-2 activity), growth stimulation of plasmacytomas and hybridomas (HGF activity), activation of T cells, stimulation of hepatic acute phase protein synthesis (HSF activity), stimulation of hematopoiesis, cell differentiation (DIF activity), inhibition of tumor cell growth (AP activity) and other IFN-like effects. As a typical cytokine, IL-6/IFN-beta 2 is secreted by many cell types and acts in various combinations with other interleukins and interferons.
Authors
Publication
Journal: Experimental Cell Research
December/14/2005
Abstract
Differentiation-inducing factors (DIFs) are morphogens which induce cell differentiation in Dictyostelium. We reported that DIF-1 and DIF-3 inhibit proliferation and induce differentiation in mammalian cells. In this study, we investigated the effect of DIF-1 on oral squamous cell carcinoma cell lines NA and SAS, well differentiated and poorly differentiated cell lines, respectively. Although DIF-1 did not induce the expression of cell differentiation makers in these cell lines, it inhibited the proliferation of NA and SAS in a dose-dependent manner by restricting the cell cycle in the G0/G1 phase. DIF-1 induced cyclin D1 degradation, but this effect was prevented by treatment with lithium chloride and SB216763, the inhibitors of glycogen synthase kinase-3beta (GSK-3beta). Depletion of endogenous GSK-3beta by RNA interference also attenuated the effect of DIF-1 on cyclin D1 degradation. Therefore, we investigated the effect of DIF-1 on GSK-3beta and found that DIF-1 dephosphorylated GSK-3beta on Ser9 and induced the nuclear translocation of GSK-3beta, suggesting that DIF-1 activated GSK-3beta. Then, we examined the effect of DIF-1 on cyclin D1 mutants (Thr286Ala, Thr288Ala, and Thr286/288Ala). We revealed that Thr286Ala and Thr286/288Ala mutants were highly resistant to DIF-1-induced degradation compared with wild-type cyclin D1, indicating that the phosphorylation of Thr286 was critical for cyclin D1 degradation induced by DIF-1. These results suggest that DIF-1 induces degradation of cyclin D1 through the GSK-3beta-mediated phosphorylation of Thr286.
Publication
Journal: Investigative Ophthalmology and Visual Science
September/25/2014
Abstract
OBJECTIVE
To develop a questionnaire (in Spanish) to measure computer-related visual and ocular symptoms (CRVOS).
METHODS
A pilot questionnaire was created by consulting the literature, clinicians, and video display terminal (VDT) workers. The replies of 636 subjects completing the questionnaire were assessed using the Rasch model and conventional statistics to generate a new scale, designated the Computer-Vision Symptom Scale (CVSS17). Validity and reliability were determined by Rasch fit statistics, principal components analysis (PCA), person separation, differential item functioning (DIF), and item-person targeting. To assess construct validity, the CVSS17 was correlated with a Rasch-based visual discomfort scale (VDS) in 163 VDT workers, this group completed the CVSS17 twice in order to assess test-retest reliability (two-way single-measure intraclass correlation coefficient [ICC] and their 95% confidence intervals, and the coefficient of repeatability [COR]).
RESULTS
The CVSS17 contains 17 items exploring 15 different symptoms. These items showed good reliability and internal consistency (mean square infit and outfit 0.88-1.17, eigenvalue for the first residual PCA component 1.37, person separation 2.85, and no DIF). Pearson's correlation with VDS scores was 0.60 (P < 0.001). Intraclass correlation coefficient for test-retest reliability was 0.849 (95% confidence interval [CI], 0.800-0.887), and COR was 8.14.
CONCLUSIONS
The Rasch-based linear-scale CVSS17 emerged as a useful tool to quantify CRVOS in computer workers. : Spanish Abstract.
Publication
Journal: Investigational New Drugs
November/29/2000
Abstract
Protracted intravenous regimens of fluorouracil (5-FU) may be superior and better tolerated than intravenous bolus dosing. An effective oral regimen would allow a protracted course of 5-FU without the need for central venous lines and the associated increase in complications. Approximately 85% of 5-FU is degraded by dihydropyrimidine dehydrogenase (DPD); inhibition of this enzyme pathway can increase the amount of circulating 5-FU. Two oral fluoropyrimidines commonly referred to as DPD inhibitory fluoropyrimidines, or DIFs, UFT plus leucovorin (LV) and S-1 are reviewed herein. These agents represent an approach to more convenient, less toxic 5-FU therapy. In two multicenter, randomized, phase III trials in patients with advanced colorectal cancer, UFT/LV produced equivalent activity compared with intravenous 5-FU/LV but with significantly less major toxicity. The predominant side effect of UFT, diarrhea, is generally self-limited and easily managed. Myelosuppression and hand-foot syndrome were rarely noted in the schedules used in these trials. S-1 has demonstrated promising activity in phase II trials conducted in patients with gastric, colorectal, breast, and head and neck cancers. Ongoing trials are defining the roles of these agents in a variety of malignancies.
Authors
Publication
Journal: BMC Musculoskeletal Disorders
November/8/2009
Abstract
BACKGROUND
Recent approaches to outcome measurement involving Computerized Adaptive Testing (CAT) offer an approach for measuring disability in low back pain (LBP) in a way that can reduce the burden upon patient and professional. The aim of this study was to explore the potential of CAT in LBP for measuring disability as defined in the International Classification of Functioning, Disability and Health (ICF) which includes impairments, activity limitation, and participation restriction.
METHODS
266 patients with low back pain answered questions from a range of widely used questionnaires. An exploratory factor analysis (EFA) was used to identify disability dimensions which were then subjected to Rasch analysis. Reliability was tested by internal consistency and person separation index (PSI). Discriminant validity of disability levels were evaluated by Spearman correlation coefficient (r), intraclass correlation coefficient [ICC(2,1)] and the Bland-Altman approach. A CAT was developed for each dimension, and the results checked against simulated and real applications from a further 133 patients.
RESULTS
Factor analytic techniques identified two dimensions named "body functions" and "activity-participation". After deletion of some items for failure to fit the Rasch model, the remaining items were mostly free of Differential Item Functioning (DIF) for age and gender. Reliability exceeded 0.90 for both dimensions. The disability levels generated using all items and those obtained from the real CAT application were highly correlated (i.e.>> 0.97 for both dimensions). On average, 19 and 14 items were needed to estimate the precise disability levels using the initial CAT for the first and second dimension. However, a marginal increase in the standard error of the estimate across successive iterations substantially reduced the number of items required to make an estimate.
CONCLUSIONS
Using a combination approach of EFA and Rasch analysis this study has shown that it is possible to calibrate items onto a single metric in a way that can be used to provide the basis of a CAT application. Thus there is an opportunity to obtain a wide variety of information to evaluate the biopsychosocial model in its more complex forms, without necessarily increasing the burden of information collection for patients.
Publication
Journal: Psychiatry Research
May/25/2015
Abstract
The role of depression in the expression of alexithymia in anorexia nervosa (AN) has been controversially explained and several variables that may mask or increase the presence of emotional difficulties have scant examination in previous studies. This study aims to analyze the associations between alexithymia and state variables, such as age, BMI, illness duration, treatment duration, and medication status in AN participants, and to test the mediating role of depression in emotional difficulties. The Toronto Alexithymia Scale (TAS-20) and the Zung Self-Rating Depression Scale were administrated to 160 females: 80 participants with AN and 80 healthy controls. High levels of alexithymia were not a function of state variables. The mediating role of depression differed by the alexithymia dimension, with total mediation found for the TAS-DDF and partial mediation found for the TAS-DIF. Alexithymia is a relevant feature throughout the spectrum of AN and does not seem to be related to developmental maturation and some clinical features. Depression is probably the variable that best accounts for the variance in alexithymia, but is not a complete explanation for the known cognitive-affective disturbances in AN. Specific emotional competencies require scrutiny during psychiatric treatment.
Publication
Journal: Optometry and Vision Science
March/26/2014
Abstract
OBJECTIVE
This article presents a theoretical interpretation of patient-reported outcomes of low-vision rehabilitation (LVR) using rating scale questionnaires and uses previously published results of LVR outcome studies to illustrate theoretical points and validate assumptions.
BACKGROUND
Patients' judgments of the difficulty they have performing tasks are interpreted as magnitude estimates of their functional reserve for each task, which is the difference between their visual ability and the visual ability demanded by the task. We assume that improvements in functional reserve can occur by increasing the patient's visual ability with medical, surgical, or refractive interventions or decreasing the visual ability demanded by the item with activity-specific vision assistive equipment, adaptations, and environmental modifications. Activity-specific interventions cause differential item functioning (intervention-related DIF). Intervention-related DIF makes the measured size of the treatment effect dependent on the item content and the mix of responsive and unresponsive items to intervention.
CONCLUSIONS
Because intervention-related DIF depends on the choice of items, the outcome measure selected should be appropriate to the aims of the intervention and the impairment level of the sample to demonstrate the full effects of an intervention. Items that are given extreme positive ratings at preintervention baseline (e.g., "not difficult") have no room for improvement. These items must also be filtered out because they will dilute the measured effect of the activity-specific interventions of LVR.
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