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PubMed2002

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Acute Disease↗
PubMed2006

Differential item functioning analysis with ordinal logistic regression techniques. DIFdetect and difwithpar.

INTRODUCTION: We present an ordinal logistic regression model for identification of items with differential item functioning (DIF) and apply this model to a Mini-Mental State Examination (MMSE) dataset. We employ item response theory ability estimation in our models. Three nested ordinal logistic regression models are applied to each item. Model testing begins with examination of the statistical significance of the interaction term between ability and the group indicator, consistent with nonuniform DIF. Then we turn our attention to the coefficient of the ability term in models with and without the group term. If including the group term has a marked effect on that coefficient, we declare that it has uniform DIF. We examined DIF related to language of test administration in addition to self-reported race, Hispanic ethnicity, age, years of education, and sex. METHODS: We used PARSCALE for IRT analyses and STATA for ordinal logistic regression approaches. We used an iterative technique for adjusting IRT ability estimates on the basis of DIF findings. RESULTS: Five items were found to have DIF related to language. These same items also had DIF related to other covariates. DISCUSSION: The ordinal logistic regression approach to DIF detection, when combined with IRT ability estimates, provides a reasonable alternative for DIF detection. There appear to be several items with significant DIF related to language of test administration in the MMSE. More attention needs to be paid to the specific criteria used to determine whether an item has DIF, not just the technique used to identify DIF.

Bias↗
PubMed1995

Diagnostic criteria for assessing obstruction in the newborn with unilateral hydronephrosis using the renal growth-renal function chart.

Previous studies in newborns with unilateral hydronephrosis demonstrated that the contralateral normal kidney can rapidly compensate for changes in function in the hydronephrotic kidney by increasing or decreasing its growth rate. To formulate diagnostic criteria for assessing obstruction using compensatory growth responses we developed a renal growth-renal function chart that graphically describes the normal renal growth rate in young children. This chart allows changes in function in the hydronephrotic kidney to be graphically compared to changes in length of the contralateral normal kidney. The renal growth-renal function chart was used to assess obstruction in 47 neonates with primary unilateral hydronephrosis. Four reproducible, clinically relevant diagnostic patterns of differential function and growth were identified: 1) obstruction, 2) corrected obstruction, 3) no obstruction with good differential function (greater than 40%) and 4) no obstruction but poor differential function (less than 40%). The renal growth-renal function chart helped to identify and exclude obstruction, and provided welcome reassurance that nonobstructive hydronephrosis was not harming the kidney. It appears to have potential for improving diagnostic accuracy in newborns with hydronephrosis.

Humans↗
PubMed1988

Role of glial cells in the differentiation and function of myelinated axons.

Myelinated axons are highly differentiated in the vicinity of the node of Ranvier, both structurally and with respect to ion channel distribution. Evidence is reviewed showing that axonal differentiation depends upon two distinct types of interaction between glial cells and the axolemma, one at the node itself, with astrocyte processes, and the second, more extensive one, in the paranodal region, with oligodendrocyte processes. In the peripheral nervous system, Schwann cells fulfill both roles. Glial or Schwann cell abnormalities, due to genetic deficiencies, diseases or experimental procedures, result in corresponding abnormalities in the axolemma and can have devastating effects on nerve fiber function. An example, the myelin-deficient mutant rat, is presented, and the defects underlying the profound and ultimately lethal neurological abnormalities seen in this mutant are discussed in relation to abnormalities in its axoglial interactions.

Animals↗
PubMed2004

Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that efficiently stimulate T cell responses.

Primary acute myeloid leukemia cells can be induced to differentiate into dendritic cells (DC). In the presence of GM-CSF, TNF-alpha, and/or IL-4, leukemia-derived DC are obtained that display features of immature DC (i-DC). The aim of this study was to determine whether i-DC of leukemic origin could be further differentiated into mature DC (m-DC) and to evaluate the possibility that leukemic m-DC could be effective in vivo as a tumor vaccine. Using CD40L as maturating agent, we show that leukemic i-DC can differentiate into cells that fulfill the phenotypic criteria of m-DC and, compared with normal counterparts, are functionally competent in vitro in terms of: 1) production of cytokines that support T cell activation and proliferation and drive Th1 polarization; 2) generation of autologous CD8(+) CTLs and CD4(+) T cells that are MHC-restricted and leukemia-specific; 3) migration from tissues to lymph nodes; 4) amplification of Ag presentation by monocyte attraction; 5) attraction of naive/resting and activated T cells. Irradiation of leukemic i-DC after CD40L stimulation did not affect their differentiating and functional capacity. Our data indicate that acute myeloid leukemia cells can fully differentiate into functionally competent m-DC and lay the ground for testing their efficacy as a tumor vaccine.

CD40 Ligand↗
PubMed2001

Detecting differential rater functioning over time (DRIFT) using a Rasch multi-faceted rating scale model.

This paper describes a class of rater effects that depict rater-by-time interactions. We refer to this class of rater effects as DRIFT differential rater functioning over time. This article describes several types of DRIFT (primacy/recency, differential centrality/extremism, and practice/fatigue) and Rasch measurement procedures designed to identify these types of DRIFT in rating data. These procedures are applied to simulated data and are shown to be useful in classifying raters as being aberrant or non-aberrant for primacy, recency, and differential centrality and extremism, particularly for moderate or larger effect sizes. Rates of correct classification for practice and fatigue were lower and statistical power exceeded.50 only with very large effect sizes. Type I error rates (i.e., incorrect nomination) were near expected levels in all cases.

Decision Theory↗
PubMed1992

Gestational age-dependent dual action of epidermal growth factor on human placenta early in gestation.

In order to better understand the role of epidermal growth factor (EGF) in the regulation of placental growth and function, effects of EGF on proliferative activity and differentiated function of trophoblast were examined. Explants from very early (4-5 week) placentas and early (6-7 week, 8-9 week, 10-12 week) placentas were respectively cultured under a serum-free condition in the absence or presence of EGF (100 micrograms/L) for the first 48 h, and the cultures were continued for subsequent 72 h without EGF. The proliferative potential and differentiated function of trophoblast were assessed by immunohistochemical Ki-67 staining and by determining the ability to secrete human CG (hCG) and human placental lactogen (hPL), respectively. Quantitative estimates of proliferative activity based on mean percentage of Ki-67 positive nuclei showed that EGF stimulated proliferative potential of cytotrophoblast in very early (4-5 week) placental explants. The EGF stimulation of trophoblast proliferation was apparent at a 12-h EGF-treated period. By contrast, early (6-12 week) placental explants did not respond to EGF with increase in trophoblast proliferation. Instead, in early placental explant culture EGF stimulated hCG and hPL secretion with a lag period of 72 h, whereas very early placental explants did not respond to EGF with increase in hCG and hPL secretion. These results suggest that EGF exerts gestational age-dependent dual action on the first-trimester placenta: one is to stimulate trophoblast proliferation in 4-5 week placenta and the other is to stimulate differentiated trophoblast function in 6-12 week placenta.

Cell Division↗
PubMed2003

Differentiation and function of osteoclasts.

Osteoclasts, which are responsible for bone resorption, are rare cells with only 2-3 cells seen per 1 mm3 of bone. However, the loss of function in osteoclasts, problems with their differentiation and decrease in their number lead to bone osteosclerosis/osteopetrosis. On the other hand, an increase in their number or function induces bone osteoporosis, indicating that osteoclasts play a pivotal role in bone homeostasis. It has been demonstrated that bone destruction and hypercalcemia induced by metastatic tumors are carried out by osteoclasts activated by the tumor cells, and the inhibition of osteoclast formation prevents the bone destruction and even bone metastasis. Abnormal osteoclast function is closely related to various diseases. Furthermore, osteoclasts are indispensable in forming bone marrow to produce blood cells, and the absence of osteoclasts causes osteopetrosis, resulting in extramedullary hematopoiesis. Although the physiological roles of osteoclasts are well described, the mechanisms of their differentiation remain to be elucidated. Recently, RANK (receptor activator of nuclear factor kappaB) and its ligand (RANKL) have been identified and their essential roles in osteoclastogenesis have been demonstrated, which has provided new insights into the osteoclast differentiation pathway. We have established an in vitro osteoclast culture system by isolating osteoclast precursor cells and culturing them in the presence of macrophage colony stimulating factor (M-CSF) and soluble RANKL. This system has enabled us to analyze the regulation mechanisms in osteoclast formation.

Bone Resorption↗
PubMed2006

Detecting differential item functioning with confirmatory factor analysis and item response theory: toward a unified strategy.

In this article, the authors developed a common strategy for identifying differential item functioning (DIF) items that can be implemented in both the mean and covariance structures method (MACS) and item response theory (IRT). They proposed examining the loadings (discrimination) and the intercept (location) parameters simultaneously using the likelihood ratio test with a free-baseline model and Bonferroni corrected critical p values. They compared the relative efficacy of this approach with alternative implementations for various types and amounts of DIF, sample sizes, numbers of response categories, and amounts of impact (latent mean differences). Results indicated that the proposed strategy was considerably more effective than an alternative approach involving a constrained-baseline model. Both MACS and IRT performed similarly well in the majority of experimental conditions. As expected, MACS performed slightly worse in dichotomous conditions but better than IRT in polytomous cases where sample sizes were small. Also, contrary to popular belief, MACS performed well in conditions where DIF was simulated on item thresholds (item means), and its accuracy was not affected by impact.

Discrimination, Psychological↗
PubMed1994

[Differentiation and function of human monocytes].

We found that human monocytes differentiate into macrophages (Mp) by GM-CSF and M-CSF. The Mp induced by GM-CSF and M-CSF are different in their morphology, cell surface antigen expression and functions. In the course of that study, we found that IL-4 modulate the differentiation of monocytes induced by GM-CSF and M-CSF. IL-4 alone did not induce the proliferation and differentiation of monocytes. IL-4, however, inhibited the proliferative response of monocytes to GM-CSF. When monocytes were incubated with GM-CSF and IL-4 simultaneously, the cells recovered were non-adherent, non-phagocytic, and did not form rosette with EA. The cells were also negative in nonspecific esterase and showed an appearance of dendritic cells (DC). The DC-like cells expressed CD1, DR, DQ and CD11c, but not CD14, CD71 and 710F. The cells showed strong APC activity in alogeneic and autologous mixed lymphocyte reaction (MLR). When monocytes were incubated with M-CSF and IL-4, TRAP positive multinucleated giant cells appeared. Taken together, these results suggest that IL-4 is a principal factor that control the differential development of human monocytes into DC and multinucleated giant cells.

Cell Differentiation↗
PubMed1990

[Modifications of protein kinase C activity and phosphorylation of lipocortin I in cultures of pig thyroid cells].

When cultured in the absence of thyreostimulin (TSH), thyroid cells lose some of their differentiated functions such as iodide transport and its incorporation into thyroglobulin. In the presence of TSH (0.1 mU/ml), these differentiated functions are preserved ("TSH cells"). The addition of tetradecanoyl phorbol 13 acetate (TPA) inhibits some differentiated functions of the cells and provokes important modifications of bio-signalling pathways. The protein kinase C (pKC) activity, unchanged in "control" and "TSH cells", was dramatically modified in TPA treated cells. After translocation, the pKC activity was down-regulated and the phosphorylation of its endogenous substrates (35-38 kDa) disappeared. Among these substrates, we identified the lipocortin I (LC I) (35 kDa), a phospholipase A2 inhibitory protein related to the Ca2+ binding protein family. By monodimensional electrophoresis (PAGE-SDS) and western-blot, we evidenced the presence of LCI in cytosols and particulate extracts. By 2 dimensional electrophoresis (PAGE-SDS and IEF) and western-blot we identified a phosphorylated and unphosphorylated LCI protein. The phosphorylation of LCI by pKC decreased its isoelectric point from 6.9-6.6. The modifications of pKC activity and LCI phosphorylation and the changes in the bio-signalling pathways can partly account for the loss of differentiation observed in control or TPA treated cells.

Animals↗
PubMed1993

The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium.

The morphogenesis and functional differentiation of mammary epithelium depends on signalling from systemic hormones and on cues from the local tissue microenvironment. With regard to the latter, regulatory cues are mainly provided by two subcompartments of the mesenchyme/stroma [fibroblastic and adipocyte] and the subjacent basement membrane. During embryogenesis, fibroblastic mesenchyme determines the sexual phenotype of the gland while adipocyte mesenchyme controls mammary-specific ductal morphogenesis. In the juvenile animal, adipocyte stroma continues to support ductal expansion while fibroblasts negatively regulate ductal outgrowth via interactions with the epithelium possibly involving TGF-beta mediated deposition of collagen I and chondroitin sulphate. In the adult, evidence from culture studies show that the signals required for the induction of tissue-specific differentiation during pregnancy and maintenance of function during lactation arise primarily from basement membrane. Beta-casein synthesis is induced in single mammary epithelial cells embedded within a basement membrane matrix via an integrin-dependent pathway. Further support for a critical role for basement membrane in the functional differentiation of the gland comes from studies in involution where degradative loss of basement membranes correlates with loss of functional activity in the epithelium. Thus the extracellular matrix in conjunction with certain cytokines plays a central role in coordinating mammary epithelial development. The findings discussed give further credence to a modal where mammary epithelium, together with certain elements of the subjacent microenvironment, form a dynamic and reciprocally interactive functional unit that regulates tissue specific gene expression in the mammary gland.

Animals↗
PubMed1980

Hormonal regulation of the adrenocortical cell.

Monolayer cultures of bovine and human adrenocortical cells have been used to study regulation of growth and function. Homogeneous bovine adrenocortical cells exhibit a finite life span of approximately 60 generations in culture. Full maintenance of differentiated function (steroid hormone synthesis) requires an inducer such as ACTH and antioxidizing conditions. Full induction of differentiated function occurs only when cellular hypertrophy is stimulated by growth factors such as fibroblast growth factor and serum. ACTH and other agents that increase cellular cAMP inhibit replication but do not block growth factor-induced cellular hypertrophy. ACTH and growth factors together result in a hypertrophied, hyperfunctional cell. Replication ensues only when desensitization to the growth inhibitory effects of ACTH occurs. Cultures of the definitive and fetal zones of the human fetal adrenal cortex synthesize the steroids characteristic of the two zones in vivo. ACTH stimulates production of dehydroepiandrosterone (DHA), the major steroid product of the fetal zone, and of cortisol, the characteristic steroid product of the definitive zone. Prolonged ACTH treatment of fetal zone cultures results in a preferential increase in cortisol production so that the pattern of steroid synthesis becomes that of the definitive zone. The preferential increase in cortisol production by fetal Zone cultures results from induction of 3 beta-hydroxysteroid dehydrogenase, delta 4,5 isomerase activity, which is limiting in fetal zone cells. ACTH thus causes a phenotypic change in fetal zone cells to that of definitive zone cells. In both bovine and human adrenocortical cells, the principal effect of ACTH is to induce full expression of differentiated function. This occurs only under conditions where growth substances and nutrients permit full amplification.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Optimizing background correction when calculating differential renal function in the presence of hydroureteronephrosis using 99Tc(m)-DTPA.

We performed a prospective study to establish the optimal background correction algorithm for the determination of differential renal function (DRF), using 99Tc(m)-diethylenetriamine pentaacetate (99Tc(m)-DTPA) in the presence of unilateral hydronephrosis, with 24 h 99Tc(m)-dimercaptosuccinic acid (99Tc(m)-DMSA) uptake as the 'gold standard'. From September 1996 to June 1997, 12 males and 4 females (mean age 10 years, range 1 month to 72 years), presenting with unilateral hydronephrosis, were studied. All patients underwent both DTPA renography and quantitative DMSA scintigraphy within 24 h. In all patients, using a surface method, the DRF of the obstructed kidney was determined using infrarenal, suprarenal and perirenal background correction, time intervals of 60-180 s (t1), 120-180 s (t2) and 80-140 s (t3), and the application or non-application of a Rutland-Patlak correction (RPC). In the absence of RPC, for all three types of background correction, no difference in DTPA DRF for any of the three time intervals was noted; higher DTPA DRF values were found (mean +/- S.D.: overestimates of 7.8+/-24.4%, 6.5+/-9.5% and 3.3+/-14.9% for suprarenal, infrarenal and perirenal background correction, respectively). Application of RPC resulted in an overall decrease in both the mean and standard deviation values, which was most pronounced with infrarenal background correction: -0.38+/-6.5% for t1, 0.31+/-6.3% for t2 and -1.3 +/-6.9% for t3 (t1 vs t2, P = 0.06; t3 vs t1 or t2, P = 0.04). Our results suggest that infrarenal background correction using t1 or t2 and RPC is the best algorithm for DRF estimation using 99Tc(m)-DTPA renography.

Adult↗
PubMed2006

Different approaches to differential item functioning in health applications. Advantages, disadvantages and some neglected topics.

BACKGROUND AND OBJECTIVES: Reviewed in this article are topics related to the study of invariance and differential item functioning (DIF) that have received relatively little attention in the literature. Several factors influence DIF detection; these include (1) model fit, (2) model assumptions, (3) disability distributions, (4) purification, (5) cutoff values for magnitude measures, and (6) sample and scale size. METHODS: Approaches to DIF detection are discussed in terms of model assumptions, purification, magnitude and impact, and possible advantages and disadvantages of each method. CONCLUSIONS: An integrated approach to the examination of measurement equivalence, invariance, and DIF is necessary for measurement in an increasingly multi-ethnic society. Ideally, qualitative analyses should be performed in an iterative fashion to inform about findings of DIF. However, if an already-developed measure is being evaluated, then the steps might be to focus first on dimensional invariance using factor analytic methods, followed by DIF analyses examining both significance and magnitude of DIF, accompanied by formal tests of the impact of DIF. The DIF analytic method selected in the second step might be determined based on the findings summarized in the table presented within this paper.

Bias↗
PubMed1990

[The growth of children and thyroid function in differentiation disorders of renal tissue].

The growth of children and thyroid function were examined in abnormal differentiation of renal tissue. Forty-four children with different varieties of renal dysembryogenesis were examined. Seventy-three children with acquired renal pathology made up a reference group. Children with congenital nephropathies manifested a higher incidence of delayed growth. The majority of patients with renal dysembryogenesis showed the laboratory signs of both primary and secondary hypothyrosis. The role of thyroid hormones in the genesis of delayed growth and development of children afflicted with renal diseases is under discussion.

Adolescent↗
PubMed1987

[Bipolarity, monopolarity and "dichotomous functional decay" as principles of differential diagnosis and "functional pathology" of endogenous psychoses].

On the basis of Leonhard's Classification of the endogenous psychoses an attempt is made to trace the phenomenology of the monopolar and bipolar affective psychoses as well as Leonhard's "unsystematic schizophrenias" to three different functional anomalies. The differential diagnosis between the "cycloid psychoses" and the "unsystematic schizophrenias" as well as the problem of the so-called schizoaffective psychoses connected with them, is of particular interest. The arrangement to "functional areas" seems to be suitable.

Affective Disorders, Psychotic↗
PubMed2005

Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.

Cell Differentiation↗