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PubMed2005

CD31- but Not CD31+ cardiac side population cells exhibit functional cardiomyogenic differentiation.

Heart failure remains a leading cause of morbidity and mortality. The cellular mechanism underlying the development of cardiac dysfunction is a decrease in the number of viable cardiomyocytes. Recent observations have suggested that the adult heart may contain a progenitor cell population. Side population (SP) cells, characterized by a distinct Hoechst dye efflux pattern, have been shown to exist in multiple tissues and are capable of tissue-specific differentiation. In this report, we confirm the existence of a cardiac SP cell population, immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate that among cardiac SP cells, the greatest potential for cardiomyogenic differentiation is restricted to cells negative for CD31 expression and positive for stem cell antigen 1 (Sca1) expression (CD31-/Sca1+). Furthermore, we determine that CD31-/Sca1+ cardiac SP cells are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, with expression of cardiomyocyte-specific transcription factors and contractile proteins, as well as stimulated cellular contraction and intracellular calcium transients indistinguishable from adult cardiomyocytes. We also determine the necessity of cell-extrinsic signaling through coupling, although not fusion, with adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP cells. We, therefore, conclude that CD31-/Sca1+ cardiac SP cells represent a distinct cardiac progenitor cell population, capable of cardiomyogenic differentiation into mature cardiomyocytes through a process mediated by cellular coupling with adult cardiomyocytes.

Animals↗
PubMed1998

Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation.

Human luteal cells have been reported to express human leukocyte antigen-DR and lymphocyte functional antigen-3 on the cell surface, suggesting physiological interaction between luteal cells and T-lymphocytes through the menstrual cycle into early pregnancy. To elucidate the role of peripheral lymphocytes on corpus luteum differentiation, the effect of peripheral blood mononuclear cells (PBMC) on steroidogenesis by luteal cells was investigated. The production of Th-2 cytokines such as interleukin (IL)-4 and IL-10 by the co-cultured cells was also examined, and the effects of these cytokines on progesterone production by luteal cells were investigated. Corpora lutea were obtained from eight non-pregnant women in the luteal phase and five women in early pregnancy for luteal cell culture. PBMC were isolated from unrelated women in the follicular phase, secretory phase, and early pregnancy. After coculture with allogenic PBMC for 48 h, progesterone production was significantly enhanced by PBMC from the secretory phase and early pregnancy in the non-pregnant luteal cell culture. In the pregnant luteal cell culture, a significant increase in progesterone production was also observed by the co-culture with PBMC from women in early pregnancy, showing that PBMC have a luteotrophic effect. The stimulatory effects of PBMC were also observed in co-culture conditions which prevented direct cell-to-cell interaction with luteal cells, showing the minor influence of mixed lymphocyte reaction. By co-culture with PBMC, the production of IL-10, but not IL-4, was significantly augmented in luteal cell culture derived from non-pregnant women, whereas the production of both IL-4 and IL-10 was significantly enhanced in the luteal cell culture derived from pregnant women. Moreover, IL-4 and IL-10 promoted progesterone production by cultured luteal cells, especially in the luteal cell culture derived from corpora lutea of early pregnancy. These findings indicate that PBMC stimulate progesterone production by luteal cells and suggest the involvement of PBMC in corpus luteum function and differentiation probably via the Th-2-type lymphocytes.

Adult↗
PubMed2004

Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation.

Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation.

Actins↗
PubMed1994

Use of log-linear models for assessing differential item functioning in a measure of psychological functioning.

Log-linear models are used to investigate contingency tables that cross-classify respondents according to item response, mental health status (MHS), and the background variables of ethnicity and gender. Specifically, log-linear models are used to examine item validity, defined as an item response by MHS interaction, and differential item functioning (DIF), defined as an interaction between item response and a background variable. The investigation focused on a set of items that measure subjective well-being and coping behavior. Female (n = 627) and male (n = 338) respondents represented 3 ethnic groups: African American, Anglo-American, and Hispanic/Latino. Strong evidence of item validity and some evidence of DIF was found. Most of the interaction between item response and either ethnicity or gender occurred among respondents with diminished mental health.

Adaptation, Psychological↗
PubMed1970

Differential renal function studies in the diagnosis of renal hypertension.

Over a 10-year period, positive criteria of the Howard test and the Rapoport Index have shown consistently good correlation with sustained relief or marked improvement in hypertension, in patients with main renal artery lesions. Similar correlation was obtained with ischemic criteria from histopathologic studies.Differential function studies did not reveal positive ischemic criteria in any patient operated upon for unilateral parenchymal disease. Histopathologic criteria of ischemia were also infrequent in this group. Nevertheless, marked improvement or cure of hypertension occurred in 62% of the latter. No factor can be used to predict improvement in this type of renal hypertension. Differential renal function criteria may occasionally appear to indicate renal artery ischemia in the more normal kidney in patients with unilateral parenchymal renal disease; wrong interpretation is avoided by taking differential creatinine clearance into account. Until vasopressor substances can be easily measured and accurately interpreted, aortography is indicated in selected patients.

Aortography↗
PubMed1994

Peptide hormone and growth factor regulation of nuclear proto-oncogenes and specific functions in adrenal cells.

Among the large number of immediate early genes, nuclear proto-oncogenes of the Fos and Jun families, have been postulated to be involved in the long-term effects of several growth factors on cell differentiation and/or multiplication. Since adrenal cell differentiated functions appear to be regulated by specific hormones and growth factors, the effects of these factors on proto-oncogene mRNA levels were analysed in bovine adrenal fasciculata cells (BAC) in culture. Corticotropin (ACTH) and insulin-like growth factor I increased c-fos and jun-B mRNA, but had no effect on c-jun mRNA and these early changes were associated with a later increase in BAC specific function [ACTH receptors, cytochrome P450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)] and an enhanced steroidogenic responsiveness to both ACTH and angiotensin-II (A-II). On the other hand, A-II increased the three proto-oncogene (c-fos, c-jun and jun-B) mRNAs, induced a decrease of P450 17 alpha and 3 beta-HSD and caused a marked homologous and heterologous (ACTH) densitization. Transforming growth factor beta 1 which only increased jun-B mRNA, markedly reduced BAC differentiated functions and the steroidogenic responsiveness to both ACTH and A-II. Thus, it is postulated that the proto-oncoproteins encoded by the immediate early genes may play a role in the long-term effects of peptide hormones and growth factors on BAC differentiated functions.

Adrenal Glands↗
PubMed2004

Progesterone and placental hormone actions on the uterus: insights from domestic animals.

Progesterone is unequivocally required for maternal support of conceptus (embryo/fetus and associated extraembryonic membranes) survival and development. In cyclic sheep, progesterone is paradoxically involved in suppressing and then initiating development of the endometrial luteolytic mechanism. In cyclic and pregnant sheep, progesterone negatively autoregulates progesterone receptor (PR) gene expression in the endometrial luminal (LE) and superficial glandular epithelium (GE). In cyclic sheep, PR loss is closely followed by increases in epithelial estrogen receptor (ERalpha) and then oxytocin receptor (OTR), allowing oxytocin to induce uterine release of luteolytic prostaglandin F2alpha pulses. In pregnant sheep, the conceptus produces interferon tau (IFNtau) that acts on the endometrium to inhibit transcription of the ERalpha gene and thus development of the endometrial luteolytic mechanism. After Day 13 of pregnancy, the endometrial epithelia do not express the PR, whereas the stroma and myometrium remain PR positive. The absence of PR in the endometrial GE is required for onset of differentiated function of the glands during pregnancy. The sequential, overlapping actions of progesterone, IFNtau, placental lactogen (PL), and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function during gestation. In pigs, estrogen, the pregnancy-recognition signal, increases fibroblast growth factor 7 (FGF-7) expression in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the receptor for FGF-7. Strategic manipulation of these physiological mechanisms may offer therapeutic schemes to improve uterine capacity, conceptus survival, and reproductive health of domestic animals and humans.

Animals↗
PubMed1999

A novel molecular mechanism modulating osteoclast differentiation and function.

Osteoclasts, the multinucleated giant cells that resorb bone, develop from hematopoietic cells of the monocyte/ macrophage lineage. Osteoblasts, as well as bone marrow stromal cells, support osteoclast development through a mechanism of cell-to-cell interaction with osteoclast progenitors. We recently purified and molecularly cloned osteoclastogenesis inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF, a secreted member of the tumor necrosis factor (TNF) receptor family, inhibited differentiation and activation of osteoclasts. A single class of high-affinity binding sites for OPG/OCIF appeared on a mouse bone marrow stromal cell line, ST2, in response to 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and dexamethasone (Dex). When the binding sites were occupied by OPG/OCIF, ST2 cells failed to support the osteoclast formation from spleen cells. To identify an OPG/OCIF ligand, we screened a cDNA expression library of ST2 cells treated with 1,25(OH)2D3 and Dex using OPG/OCIF as a probe. The cloned molecule was found to be a member of the membrane-associated TNF ligand family, and it induced osteoclast formation from mouse and human osteoclast progenitors in the presence of macrophage colony-stimulating factor (M-CSF) in vitro. Expression of its gene in osteoblasts/stromal cells was up-regulated by osteotropic factors, such as 1,25(OH)2D3, prostaglandin E2 (P(GE2), parathyroid hormone (PTH), and interleukin (IL)-11. A polyclonal antibody against this protein, as well as OPG/OCIF, negated not only the osteoclastogenesis induced by the protein, but also bone resorption elicited by various osteotropic factors in a fetal mouse long bone culture system. These findings led us to conclude that the protein is osteoclast differentiation factor (ODF), a long sought-after ligand that mediates an essential signal to osteoclast progenitors for their differentiation into active osteoclasts. Recent analyses of ODF receptor demonstrated that RANK, a member of the TNF receptor family, is the signaling receptor for ODF in osteoclastogenesis, and that OPG/OCIF acts as a decoy receptor for ODF to compete against RANK. The discovery of ODF, OPG/OCIF, and RANK opens a new era in the investigation of the regulation of osteoclast differentiation and function.

Animals↗
PubMed2004

The modulation of thymosin alpha 1 in the maturation, differentiation and function of murine bone marrow-derived dendritic cells in the absence or presence of tumor necrosis factor-alpha.

Thymosin alpha 1 (Talpha1) has immunomodulatory effects on T-cells, NK-cells and macrophages, but its action on dendritic cells (DCs), which are recognized as the sole professional antigen presenting cells (APCs) capable of priming naïve T-cells, is poorly understood. In this study, the effect of Talpha1 in vitro on murine bone marrow-derived DCs (BMDCs) maturation, differentiation, and function with or without tumor necrosis factor-alpha (TNF-alpha), which is one of the important inflammatory parameters, has been investigated. We have shown, through flow cytometry, ELISA and mixed leukocyte reaction (MLR), that Talpha1 promoted CD4-expressed DC differentiation and the expression of activation markers, but did not influence IL-12 production and T cell-stimulatory capacity of DCs in the absence of TNFalpha during BMDCs maturation. Furthermore, in the presence of TNF-alpha, Talpha1 has been shown not only to promote the expression of CD4 on MHC class II+ DCs and enhance the up-regulated levels of mature markers induced by TNF-alpha, but also to suppress the up-regulated IL-12 production. Particularly, thus effects seen were obvious at pharmacological Talpha1 concentrations. However, Talpha1 did not inhibit TNF-alpha-induced T-cell stimulating function of DCs. This is the first reported example of a direct Talpha1-DC interaction and suggests a mechanism by which Talpha1 may in part affect T-cell responses by acting at the DC level and it may play an important role in the modulation of the local inflammatory responses in vivo.

Adjuvants, Immunologic↗
PubMed2002

Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes.

Embryonic stem (ES) cells have a potential to differentiate into various progenitor cells. Here we investigated the differentiation capacity of mouse ES cells into hepatocytes both in vitro and in vivo. During the culture of embryoid bodies (EBs) derived from ES cells, albumin (ALB) messenger RNA (mRNA) was expressed within 12 days after removal of leukemia inhibitory factor, and alpha-fetoprotein (AFP) mRNA was observed within 9 days without additional exogenous growth factors. In ES cells and early EBs, by contrast, neither ALB mRNA nor AFP mRNA was observed. ALB protein was first detected at day 15 and the level increased with the culture period. The differentiation of EBs facilitated the synthesis of urea with the culture period, whereas early EBs and ES cells produced no urea. These results suggest that cultured EBs contain hepatocytes capable of producing ALB and urea. ES cells and the isolated cells from EBs were transplanted through portal vein to the liver after 30% partial hepatectomy of female mice pretreated with 2-acetylaminofluorene. Four weeks after transplantation with isolated cells from day-9 EBs, ES-derived cells containing Y-chromosome in the liver were positive for ALB (0.2% of total liver cells), whereas teratoma was found in mice transplanted with ES cells or EBs up to day 6. The incidence of teratoma was decreased with the culture duration and no teratoma was observed in the liver transplanted with isolated cells from day-9 EBs. In conclusion, our in vitro and in vivo experiments revealed that cultured EBs contain functional hepatocytes or hepatocyte-like cells.

2-Acetylaminofluorene↗
PubMed1999

Detecting differential item functioning with five standardized item-fit indices in the Rasch model.

This study examined five Rasch-model-based item-fit indices: unweighted and weighted standardized indices (denoted UWz and Wz), standardized likelihood index (denoted Lz), and Extended Caution Indices (denoted ECI2z and ECI4z), in terms of their distributional properties and the power of detecting item bias or Differential Item Functioning (DIF). The results indicated that although these five standardized item-fit indices did not depart significantly from a normal distribution, it appeared that the Type I error rates were not reasonable. For the power of five standardized item-fit indices to detect DIF, the results showed that all indices did perform poorly across various conditions. These findings lead to the conclusion that all indices used in this study are inadequate fit measures for detecting DIF.

Bias↗
PubMed1992

Induction of c-fos but not c-myc in S-91 cells by melanization signals.

Synthesis of the pigment melanin is a complex differentiated function performed by pigment cells in response to a variety of stimuli. The possible roles of the proto-oncogenes c-fos and c-myc in the control of pigmentation were studied using subconfluent, actively proliferating Cloudman S-91 murine melanoma cells stimulated to synthesize melanin by melanocyte stimulating hormone (MSH) or forskolin. Stimulation caused a significant increase in melanin synthesis when compared to control cells, but had no effect on cell growth. Northern analysis of total cellular RNA demonstrated rapid, transient induction of c-fos mRNA as early as 30 min after stimulation with MSH or forskolin. In contrast, there was no effect on the high constitutive expression of c-myc in these actively proliferating cells. These data strongly suggest that the induction of c-fos mRNA is an early genetic event in stimulation of melanin synthesis and thus this proto-oncogene may play a major role in the regulation of this differentiated function, as reported for other forms of cellular differentiation. In contrast, c-myc expression is unaffected and instead correlated with cellular proliferative capacity. These results are consistent with the hypothesis that the down-regulation of c-myc frequently observed during cell differentiation is not a necessary event, but rather reflects an associated decrease in cell growth rate. The S-91 melanoma system appears to provide a convenient model for study of the regulation for a single, well defined differentiated function that is independent of growth rate.

Animals↗
PubMed2005

Measurement equivalence and differential item functioning in family psychology.

Several hypotheses in family psychology involve comparisons of sociocultural groups. Yet the potential for cross-cultural inequivalence in widely used psychological measurement instruments threatens the validity of inferences about group differences. Methods for dealing with these issues have been developed via the framework of item response theory. These methods deal with an important type of measurement inequivalence, called differential item functioning (DIF). The authors introduce DIF analytic methods, linking them to a well-established framework for conceptualizing cross-cultural measurement equivalence in psychology (C.H. Hui and H.C. Triandis, 1985). They illustrate the use of DIF methods using data from the Project on Human Development in Chicago Neighborhoods (PHDCN). Focusing on the Caregiver Warmth and Environmental Organization scales from the PHDCN's adaptation of the Home Observation for Measurement of the Environment Inventory, the authors obtain results that exemplify the range of outcomes that may result when these methods are applied to psychological measurement instruments.

Adolescent↗
PubMed1988

Cytolocalization of prosomes as a function of differentiation.

Prosomes, ubiquitous ribonucleoprotein (RNP) particles of defined biochemical and morphological structure, first isolated as a subcomplex of the repressed globin mRNP in avian and mouse erythroblasts, were also found in the cytoplasm of other vertebrates associated with other mRNAs. Here we show that prosomes are also present in the cell nucleus and, furthermore, that the cytolocalization of specific prosomal peptides is a function of differentiation. Four monoclonal antibodies, raised against the duck prosomal proteins, p27K, p28K, p29K and p31K (K = 10(3) Mr) react to variable degree with prosomes of chicken, mouse, and human cells. Immunocytochemical and biochemical analyses show that all four antigens are present in both the cytoplasm and the nucleus of avian erythroblasts and avian erythroblastosis virus (AEV)-transformed erythroleukaemic cells. Interestingly, the prosomes disappear in the course of the terminal differentiation of erythroblasts to mature erythrocytes. Although all the four prosomal antigens tested are present in both the nuclear and cytoplasmic compartments, slight differences in the immunofluorescent patterns indicate that each antigen may have a particular cytological distribution that varies in the course of differentiation.

Animals↗
PubMed2005

The role of the orphan nuclear receptor Rev-Erb alpha in adipocyte differentiation and function.

Lipid and carbohydrate homeostasis in higher organisms is governed by an integrated system that has a capacity to rapidly respond to metabolic changes. Numerous signals reciprocally convey information about body fat status from the periphery to central nervous system in the attempt to maintain body weight nearly stable throughout life. The role of adipocyte in energy homeostasis extends its function as a simple energy storage cell. Indeed, adipose tissue not only secretes fatty acids, but is also an active endocrine and paracrine organ due to the production of secreted proteins and lipid indicators collectively called adipokines. These observations have spurred interest in the identification of the transcriptional and other regulatory pathways of adipocyte differentiation. The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma) (NR1C3) and members of the CCAAT enhancer-binding protein (C/EBP) family are central mediators controlling adipocyte differentiation and function. Rev-erb alpha (NR1D1) is an orphan nuclear receptor encoded on the opposite strand of the thyroid receptor alpha gene. Rev-erb alpha acts as a negative regulator of transcription binding to the same response element than another orphan nuclear receptor, ROR alpha. Rev-erb alpha is highly expressed in adipose tissue, skeletal muscle, heart, liver and brain. Rev-erb alpha expression increases during adipocyte differentiation of 3T3-L1 cells and is induced by PPAR gamma activation in both 3T3-L1 cells in vitro and in rat adipose tissue in vivo via a direct repeat (DR2) in the Rev-erb alpha promoter. Ectopic expression of Rev-erb alpha potentiates the adipocyte differentiation in 3T3-L1 cells. Recent results in vascular smooth muscle cells (VSMCs) indicate that Rev-erb alpha also controls inflammation by regulating NF-kappa B responsive genes, such as IL-6 and COX-2. Future studies on a potential role of Rev-erb alpha on glucose homeostasis and/or inflammation control are thus warranted.

Adipocytes↗
PubMed2002

Education and sex differences in the mini-mental state examination: effects of differential item functioning.

Years of completed education is a powerful correlate of performance on mental status assessment. This analysis evaluates differences in cognitive performance attributable to level of education and sex. We analyzed Mini-Mental State Examination responses from a large community sample (Epidemiologic Catchment Area study, N = 8,556), using a structural equation analytic framework grounded in item response theory. Significant sex and education group differential item functioning (DIF) were detected. Those with low education were more likely to err on the first serial subtraction, spell world backwards, repeat phrase, write, name season, and copy design tasks. Women were more likely to err on all serial subtractions, men on spelling and other language tasks. The magnitude of detected DIF was small. Our analyses show that failing to account for DIF results in an approximately 1.6% overestimation of the magnitude of difference in assessed cognition between high- and low-education groups. In contrast, nearly all (95%) of apparent sex differences underlying cognitive impairment are due to DIF. Therefore, item bias does not appear to be a major source of observed differences in cognitive status by educational attainment. Adjustments of total scores that eliminate education group differences are not supported by these results. Our results have implications for future research concerning education and risk for dementia.

Aged↗
PubMed2005

Ethnic differential item functioning in the assessment of quality of life in cancer patients.

BACKGROUND: Past research has shown that Filipino cancer patients report lower levels of quality of life (QoL) than other ethnic groups. One possible explanation for this is that Filipinos do not define QoL in the same manner as others, resulting in bias in their assessments. Hence, Filipinos would not necessarily have lower QoL. METHODS: Item response theory methods were used to assess differential item functioning (DIF) in the quality of life (measured by the EORTC QLQ-C30) of cancer patients across four ethnic groups (Caucasian, Filipino, Hawaiian, and Japanese). The sample consisted of 359 cancer patients. RESULTS: Results showed the presence of DIF on several items, indicating ethnic differences in the assessment of quality of life. Relative to the Caucasian and Japanese groups, items related to physical functioning, cognitive functioning, social functioning, nausea and vomiting, and financial difficulties exhibited DIF for Filipinos. On these items Filipinos exhibited either higher or lower QoL scores, even though their overall QoL was the same. CONCLUSION: This evidence may explain why Filipinos have previously been found to have lower overall QoL. Although Filipinos score lower on QoL than other groups, this may not reflect lower QoL, but rather differences in how QoL is defined. The presence of DIF did not appear, however, to alter the psychometric properties of the QLQ-C30.

Aged↗
PubMed2001

Rat macrophages: membrane glycoproteins in differentiation and function.

Macrophages (mphi) play a crucial role in the immune system. The rat offers unique advantages for studying the biology of mphi. Firstly, monoclonal antibodies (mAb) against many rat mphi surface glycoproteins have become available. These have not only demonstrated a considerable heterogeneity among mphi, but have also allowed the characterization of various mphi surface molecules in terms of structure, expression regulation and function. Furthermore, substantial numbers of rat mphi can be isolated from various sites (e.g. blood, peritoneal cavity, lung and other tissues), enabling proper molecular and functional analysis of these mphi populations. Finally, a number of (unique) experimental models for human diseases have been developed in the rat, making possible the evaluation of the involvement of mphi in pathogenesis. For this, a method for the selective elimination of mphi from various tissues in vivo has proven very useful. Here, we will review the contribution that the rat has made to understanding the immunobiology of mphi. In particular, we will discuss the surface (glyco)proteins on rat mphi in differentiation and function, and the involvement of mphi in rat models of disease.

Animals↗