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Assessment of differential item functioning for demographic comparisons in the MOS SF-36 health survey.

OBJECTIVE: To investigate whether items of the Medical Outcomes Study (MOS) 36-Item Short-Form Health Status Survey (SF-36) exhibited differential item functioning (DIF) with respect to age, education, race, and gender. METHODS: The data for this study come from two large national datasets, the MOS and the 1990 National Survey of Functional Health Status (NSFHS). We used logistic regression to identify items exhibiting DIF. RESULTS: We found DIF to be most problematic for age comparisons. Items flagged for age DIF were vigorous activities, bend/kneel/stoop, bathing or dressing, limited in kind of work, health in general, get sick easier than others, expect health to get worse, felt calm and peaceful, and all four vitality items. Items flagged for education DIF include vigorous activities, health in general, health is excellent, felt calm and peaceful, and been a happy person. Vigorous activities, walk more than a mile, health in general, and expect health to get worse were identified as DIF when comparing African-Americans with whites. No items were identified for gender DIF. CONCLUSIONS: We found several consistent patterns of DIF using two national datasets with different population characteristics. In the current study, the effect of DIF rarely transferred to the scale level. Further research is needed to corroborate these results and determine qualitatively why DIF may occur for these specific items.

Adolescent↗

[Differentiation and function of human dendritic cells influenced by heat shock protein gp96 purified from K562 cells].

This study was to establish the method of purifying heat shock protein GP96 from K562 cells and explore the differentiation and function of human DC influenced by heat shock prolein (HSP). Using ammonium sulfate precipitation, conA-sepharose affinity chromatography and DEAE-sephacel anion exchange chromatography GP96 from K562 cells lysate was isolated and purified. The identification of the purified protein was controlled by Western blot with anti-human GP96 IgG. Human dendritic cell derived from peripheral blood mononuclear cell were cultured with purified GP96. The phenotype changes of DC were analyzed by flow cytometry and MLR was detected by MTT. The results showed that 60-80 microg GP96 was purified successfully from 1 x 10(10) K562 cells. DC stimulated with HSP-GP96 had higher expression rates of CD83, CD86, HLA-DR and lower expression rates of CD1a and had stronger ability to induce T cells proliferation. It is concluded that heat shock protein GP96 can be isolated and purified from K562 cells and could induce maturation of dendritic cell. HSP-DC vaccine show stronger ability to induce T cell proliferation than DC.

Antigens, Neoplasm↗

Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites.

Ipriflavone (IP), an isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and perhaps stimulating bone formation. In this study, we have analyzed the effect of IP and its metabolites on the differentiation and function of human osteoblastic cells. Bone marrow stromal osteoprogenitor cells (BMC) and trabecular bone osteoblasts (HOB) were isolated from human donors. The former can be induced to differentiate by treatment with dexamethasone, whereas the latter represent a more differentiated osteoblast. Incubation of BMC with metabolite III (10(-5) M) for 1 week induced modest but significant changes of alkaline phosphatase activity. Though both IP and metabolite III stimulated the expression of bone sialoprotein mRNA, a protein involved in cell attachment to the matrix, only metabolite III increased the steady-state level of decorin mRNA, a collagen fibrillogenesis-regulating proteoglycan. Metabolites III and V, but not the other isoflavones, increased the expression of type I collagen mRNA in HOB, whereas no detectable changes were observed in BMC cells with any of the experimental compounds. In HOB, an increased abundance of osteopontin and bone sialoprotein mRNA were also obtained after 1-week treatment with IP or metabolite V. No appreciable effects of IP or its metabolites were seen on osteocalcin expression and synthesis by either cell type. Finally, IP consistently increased the amount of 45Ca incorporated into the cell layer by BMC, and stimulated mineralization of both BMC and HOB, assessed by von Kossa staining. Thus, IP and its metabolites regulate the differentiation and biosynthetic properties of human bone-forming cells by enhancing the expression of some important matrix proteins and facilitating the mineralization process.

Alkaline Phosphatase↗

A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function.

Osteoclasts, the multinucleated giant cells that resorb bone, develop from monocyte-macrophage lineage cells. Osteoblasts or bone marrow stromal cells have been suggested to be involved in osteoclastic bone resorption. The recent discovery of new members of the tumor necrosis factor (TNF) receptor-ligand family has elucidated the precise mechanism by which osteoblasts/stromal cells regulate osteoclast differentiation and function. Osteoblasts/stromal cells express a new member of the TNF-ligand family "osteoclast differentiation factor(ODF)/osteoprotegerin ligand (OPGL)/TNF-related activation-induced cytokine (TRANCE)/receptor activator of NF-kB ligand (RANKL)" as a membrane associated factor. Osteoclast precursors which possess RANK, a TNF receptor family member, recognize ODF/OPGL/TRANCE/RANKL through cell-to-cell interaction with osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of macrophage colony-stimulating factor. Mature osteoclasts also express RANK, and their bone-resorbingactivity is also induced by ODF/OPGL/TRANCE/RANKL which osteoblasts/stromal cells possess. Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF)/TNF receptor-like molecule 1 (TR1) is a soluble decoy receptor for ODF/OPGL/TRANCE/RANKL. Activation of NF-kB and c-Jun N-terminal kinase through the RANK-mediated signaling system appears to be involved in differentiation and activation of osteoclasts.

Animals↗

Evolutionary process of amino acid biosynthesis in Corynebacterium at the whole genome level.

Corynebacterium glutamicum, which is the closest relative of Corynebacterium efficiens, is widely used for the large scale production of many kinds of amino acids, particularly glutamic acid and lysine, by fermentation. Corynebacterium diphtheriae, which is well known as a human pathogen, is also closely related to these two species of Corynebacteria, but it lacks such productivity of amino acids. It is an important and interesting question to ask how those closely related bacterial species have undergone such significant functional differentiation in amino acid biosynthesis. The main purpose of the present study is to clarify the evolutionary process of functional differentiation among the three species of Corynebacteria by conducting a comparative analysis of genome sequences. When Mycobacterium and Streptomyces were used as out groups, our comparative study suggested that the common ancestor of Corynebacteria already possessed almost all of the gene sets necessary for amino acid production. However, C. diphtheriae was found to have lost the genes responsible for amino acid production. Moreover, we found that the common ancestor of C. efficiens and C. glutamicum have acquired some of genes responsible for amino acid production by horizontal gene transfer. Thus, we conclude that the evolutionary events of gene loss and horizontal gene transfer must have been responsible for functional differentiation in amino acid biosynthesis of the three species of Corynebacteria.

Amino Acids↗

Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors.

We studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells. These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.

Candida albicans↗

Formation of actin filament networks in cultured rat hepatocytes treated with DMSO and glucagon.

Actin filament organization may play an important role in the maintenance of differentiated functions in epithelial cells. We previously reported our success in inducing and maintaining gap junctions, which are two kinds of differentiated function, in primary rat hepatocytes cultured with 2% DMSO and 10-7 M glucagon. In the present study, we demonstrated the formation of actin filament networks in the hepatocytes cultured with 2% DMSO and 10-7 M glucagon. Actin filaments in hepatocytes cultured in medium with only 2% DMSO added from 96 h after plating were concentrated under the plasma membrane and were observed to be circumferential. In hepatocytes cultured in the medium with both 2% DMSO and 10-7 M glucagon added from 96 h, not only the circumferential actin filaments but also the formation of actin filament networks were observed and the networks developed well with time in culture. The networks were observed as a dome-like structure under the cell face and terminated at the circumferential actin filaments. They were composed of electron-dense star-like vertices connected by microfilament bundles of varying length and were also very sensitive to the actin disruptor cytochalasin B. However, during the network formation, there were no significant increases in the amounts of actin protein and mRNA. The actin filament networks of the hepatocytes in this culture system might be closely related to the maintenance of differentiated functions.

Actins↗

[Differentiation and function of monocyte/macrophage lineage cells and osteoblasts].

Macrophages, osteoclasts and dendritic cells are derived from hematopoietic stem cells through monocyte/macrophage lineage common precursor cells. Macrophages are induced in the presence of M-CSF alone whereas osteoclasts are induced by M-CSF and RANKL. The cooperation of transcription factors, c-Fos and NFATc1 is essential for osteoclast differentiation. GM-CSF is an inducer of dendritic cells, and in contrast to osteoclast differentiation, M-CSF and c-Fos are inhibitors of dendritic cell differentiation. On the other hand, mesenchymal stem cells(MSCs) give rise to osteoblasts. In embryonic stage, MSCs in perichondrium are marked by ALCAM. Recently, osteoblasts are reported to provide 'Niche' for hematopoietic stem cells in bone marrow. Here we review the differentiation and functions of monocyte/macrophage lineage cells and osteoblasts.

Animals↗

Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes.

OBJECTIVE: Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA). To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis. METHODS: We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNF alpha on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA. RESULTS: We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFN gamma was markedly reduced in GST-treated mDC. CONCLUSION: GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA.

Antirheumatic Agents↗

Identification of differential item functioning using item response theory and the likelihood-based model comparison approach. Application to the Mini-Mental State Examination.

BACKGROUND: An important part of examining the adequacy of measures for use in ethnically diverse populations is the evaluation of differential item functioning (DIF) among subpopulations such as those administered the measure in different languages. A number of methods exist for this purpose. OBJECTIVE: The objective of this study was to introduce and demonstrate the identification of DIF using item response theory (IRT) and the likelihood-based model comparison approach. METHODS: Data come from a sample of community-residing elderly who were part of a dementia case registry. A total of 1578 participants were administered either an English (n = 913) or Spanish (n = 665) version of the 21-item Mini-Mental State Examination. IRT was used to identify language DIF in these items with the likelihood-based model comparison approach. RESULTS: : Fourteen of the 21 items exhibited significant DIF according to language of administration. However, because the direction of the identified DIF was not consistent for one language version over the other, the impact at the scale level was negligible. CONCLUSIONS: IRT and the likelihood-based model comparison approach comprise a powerful tool for DIF detection that can aid in the development, refinement, and evaluation of measures for use in ethnically diverse populations.

Aged↗

Effect of tumor necrosis factor on growth and function in FRTL5 cells.

Tumor necrosis factor (TNF) is a cytokine produced by inflammatory macrophages and monocytes. FRTL5 cells are a continuous line of functional, nontransformed rat thyroid cells that depend on thyroid-stimulating hormone (TSH) for sustained growth. The following experiments characterize the effects of TNF on growth and differentiated functions in FRTL5 cells. Cells were incubated with different concentrations of TNF (1 to 100 ng/ml), alone or with TSH. FRTL5 cell proliferation was assessed by 3H-thymidine incorporation assays. Differentiated functions were studied by measuring radioactive iodine uptake (RAI) and triiodothyronine (T3) production. TNF inhibited FRTL5 cell growth both in basal conditions and after cells had been exposed to TSH. TNF caused small inhibition of both basal RAI uptake and T3 release but greatly decreased TSH-stimulated RAI uptake and T3 secretion. In summary, TNF appears to affect both growth and differentiated functions in the FRTL5 cell line. Although it is difficult to extrapolate these in vitro results to the human disease state, we postulate that TNF production in septic states may contribute to the pathogenesis of the low T3 syndrome; moreover, locally produced TNF may modulate thyroid function in autoimmune thyroid diseases.

Animals↗

Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells.

Smooth muscle is a major component of human tissues and is essential for the normal function of a multitude of organs including the intestine, urinary tract and the vascular system. The use of stem cells for cell-based tissue engineering and regeneration strategies represents a promising alternative for smooth muscle repair. For such strategies to succeed, a reliable source of smooth muscle precursor cells must be identified. Adipose tissue provides an abundant source of multipotent cells. In this study, the capacity of processed lipoaspirate (PLA) and adipose-derived stem cells to differentiate into phenotypic and functional smooth muscle cells was evaluated. To induce differentiation, PLA cells were cultured in smooth muscle differentiation medium. Smooth muscle differentiation of PLA cells induced genetic expression of all smooth muscle markers and further confirmed by increased protein expression of smooth muscle cell-specific alpha actin (ASMA), calponin, caldesmon, SM22, myosin heavy chain (MHC), and smoothelin. Clonal studies of adipose derived multipotent cells demonstrated differentiation of these cells into smooth muscle cells in addition to trilineage differentiation capacity. Importantly, smooth muscle-differentiated cells, but not their precursors, exhibit the functional ability to contract and relax in direct response to pharmacologic agents. In conclusion, adipose-derived cells have the potential to differentiate into functional smooth muscle cells and, thus, adipose tissue can be a useful source of cells for treatment of injured tissues where smooth muscle plays an important role.

Actins↗

Advances in osteoclast differentiation and function.

Osteoclasts are the sole bone resorbing cells. These cells are essential for skeletal development and remodeling throughout the life of animal and man. Deficiency of osteoclasts leads to osteopetrosis, a diseases manifested by increased non-remodeled bone mass, which ultimately leads to bone deformities and functional failure of other body systems. On the other hand, increased number and activity of osteoclasts under certain pathologic conditions causes accelerated bone resorption and may lead to osteoporosis and osteolytic diseases. To better understand the mechanisms underlying osteoclast-based diseases and design relevant therapies, one should unveil the molecular basis of osteoclast differentiation and function and regulatory mechanisms of osteoclast signaling. This review will outline up-to-date information regarding osteoclast differentiation and activation. Molecular mechanisms underlying osteoclast signaling pathways in inflammatory osteolysis and arthritis will be discussed. In addition, stimulators and inhibitors of osteoclasts, as well as current therapies for osteoclast activity will be addressed.

Animals↗

New perspectives on retinoblastoma family functions in differentiation.

Cell differentiation is a coordinated process that includes cell cycle exit and the expression of unique genes to specify tissue identity. The focus of this review is the recent progress in understanding the functions of the RB family (RB, p130,p107) in cell differentiation. Much work has focused on the functions of RB in G1 regulation. However, much evidence now suggests a diverse function in differentiation. For discussion, differentiation will be divided into three general steps: cell cycle exit, apoptosis protection, and tissue-specific gene expression. These processes are coordinated to provide the final and unique tissue characteristics. The RB family and targets such as E2F and HBP1 have functions in each step. While there is much knowledge on each separate step of differentiation, the mechanisms that coordinate cell cycle and tissue-specific events are still not known. New evidence suggests that this coordination contains both positive and negative regulation of tissue-specific gene expression. RB. p130, HBP1, and other proteins appear to have unexpected functions in regulating tissue-specific gene expression. The ubiquitous expressions of these proteins suggest membership in a new and general pathway to coordinate cell cycle events with tissue-specific gene expression during differentiation. The collective observations hypothesize the existence of a differentiation checkpoint to insure fidelity.

Adipocytes↗

Regulation of functional cytodifferentiation and histogenesis in mammary epithelial cells: role of the extracellular matrix.

Primary mammary epithelial cells provide a versatile system for the study of hormone and extracellular matrix (ECM) influences on tissue-specific gene expression. We have characterized the formation of alveolarlike morphogenesis and mammary-specific functional differentiation that occur when these cells are cultured on a reconstituted basement membrane (EHS). Cells cultured on EHS exhibit many ultrastructural and biochemical features indicative of polarized and functionally differentiated mammary epithelium in vivo. The increased expression and specific vectorial secretion of milk proteins into lumina formed in culture are accompanied by large increases in milk protein mRNA expression. However, when individual ECM components are tested, smaller increases in milk protein mRNA are measured on heparan sulfate proteoglycan (HSPG) and laminin, and these responses are not associated with full functional cytodifferentiation or histotypic configuration. This indicates that multiple levels of regulation are involved in mammary-specific gene expression, and that in addition to individual ligand requirements cooperative interactions between various ECM molecules and cells are necessary for functional differentiation in culture. We have also shown that endogenous production of ECM molecules and changes in cell geometry are correlated with changes in functional and histogenic gene expression. We have previously proposed a model of cell-ECM interactions that is consistent with these data.

Animals↗

Ikaros is critical for B cell differentiation and function.

The Ikaros gene encodes a zinc-finger transcription factor required during early B cell development, as B-lineage cells are absent in mice lacking Ikaros. Here we describe a novel Ikaros-targeted mouse line carrying a beta-galactosidase reporter in which low amounts of Ikaros proteins remain expressed. In homozygote animals, B cells are absent during fetal development, but develop postnatally from a reduced pool of precursors. In vitro, the proliferation and differentiation of B-lineage progenitors are severely impaired. These defects are attenuated in vivo, but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT, Rag-1, Rag-2 and lambda 5. These abnormalities suggest a partial block at the proB cell stage of differentiation. In the periphery, mature B cells exhibit a lower activation threshold but form fewer germinal centers in response to antigenic stimulation. Our results show that Ikaros controls multiple aspects of B cell differentiation and function.

Animals↗

Understanding sex biases in immunity: effects of estrogen on the differentiation and function of antigen-presenting cells.

The initiation and perpetuation of innate and adaptive immunity is dependent on the ability of professional antigen-presenting cells (APCs) to sense inflammatory stimuli; produce cytokines; and internalize, degrade, and present antigens via surface major histocompatibility complex (MHC) molecules. Dendritic cells (DCs), macrophages, and B lymphocytes express estrogen receptors, indicating that the steroid sex hormone estrogen might directly modulate the function of these cells during immune responses. Sex-specific parameters of immune function have been identified during autoimmunity and the pathogenesis of infectious disease, which show sex biases in their incidence and manifestation; female immunity also varies as estrogen levels change. In this article, we summarize studies that demonstrate effects of estrogen on the differentiation or function of APCs in model in vitro systems, or under circumstances of natural or imposed variation in estrogen levels in vivo.

Animals↗

The gp130-stimulating designer cytokine hyper-IL-6 promotes the expansion of human hematopoietic progenitor cells capable to differentiate into functional dendritic cells.

OBJECTIVE: Hyper-IL-6, a fusion protein of interleukin-6 and its specific receptor, together with stem cell factor leads to the proliferation of primitive hematopoietic progenitor cells. Based on these findings, the current study examined whether hyper-IL-6 promotes the growth of precursor cells that can be further differentiated into dendritic cells in the presence of additional cytokines. METHODS: Dendritic cell cultures were generated from CD34(+) hematopoietic progenitor cells derived either from bone marrow or from peripheral blood. CD34(+) cells were cultured in the presence of cytokines for 2 weeks and then used for phenotyping and T-cell stimulation assays. RESULTS: Hyper-IL-6 in the presence of stem cell factor induced a 60- to 80-fold expansion of CD34(+) progenitor cells following 2 weeks of culture in serum-free medium. The addition of granulocyte-macrophage colony-stimulating factor to hyper-IL-6 and stem cell factor was essential for the differentiation of expanded progenitor cells into antigen presenting cells capable of inducing a primary T-cell response to soluble protein, which is a typical feature of dendritic cells. Phenotypic analyses confirmed the expansion of immature dendritic cells, which could be further differentiated into mature CD83(+) dendritic cells under the influence of interleukin-4, interleukin-1beta, tumor necrosis factor-alpha, and prostaglandin E(2). The capacity of expanded dendritic cells to stimulate protein-specific CD4(+) T cells was used to stimulate a primary T-helper cell response to the recombinant protein of the hepatitis-B core antigen in healthy donors. CONCLUSION: The expansion and differentiation of functional dendritic cells from CD34(+) progenitor cells under serum-free culture conditions allow for the possibility to develop more effective ways to immunize against viral infections and tumor diseases.

Antigen Presentation↗