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At least 19 recordsLinked to original sources
PubMed2006

[Integral syndrome differentiation, local syndrome differentiation and microcosmic syndrome differentiation --thinking on the modern TCM system of syndrome differentiation dependent treatment].

From the historic and realistic viewpoints, the authors discussed the theory of TCM syndrome differentiation, pointing out that the modern TCM system of syndrome differentiation dependent treatment should consist of three components, the integral syndrome differentiation, local syndrome differentiation and microcosmic syndrome differentiation, they are independent comparatively and supplementary with each other.

Diagnosis, Differential↗
PubMed1976

Biogenesis of mitochondrial membranes in Neurospora crassa during cellular differentiation: ultrastructural changes accompanying differentiation.

The ultrastructural characteristics of Neurospora cells during dedifferentiation and redifferentiation of conidiospores into vegetative cells have been determined. This germination process occurs between 2 and 5 h after inoculation; by 3-5 h, approximately 50% of the cells have germinated. The cells enter the exponential phase of dry-weight gain between 4 and 5 h after inoculation. Several unusual structures are observed in Neurospora cells during germination. Whorled structures are frequently seen in the cytoplasm during germination, and occasionally at other times. They appear to be derived from the cytoplasmic membrane. Whorled structures of different appearance were observed in the mitochondria between 2 and 4 h after inoculation. Their number was related to the level of metabolizable carbohydrate, and was higher in 15% glucose-than in 2% sucrose-supplemented medium, and very low in medium containing 15% mannitol, or 2% sucrose+13% 2-deoxyglucose, or no added carbohydrate. The mitochondrial inclusions were osmiophilic and could be removed by treatment with 90% aqueous acetone in the cold, indicating that they were composed at least in part of lipid. The strong dependence of the number of mitochondrial inclusions on time and on carbohydrate supplementation, suggests that there is a physiological basis for these structures and that they reflect changes occurring in the mitochondria at times significant to cellular differentiation.

Carbohydrate Metabolism↗
PubMed1991

Differential effects of insulin-like growth factors I and II on growth, differentiation and glucoregulation in differentiating chondrocyte cells in culture.

Insulin-like growth factors I and II have been shown differentially to affect the growth and carbohydrate metabolism of differentiating cartilage developed from mouse embryonic limb buds in organ culture. To gain insight into the relative importance of IGF-I and II actions in different stages of development of cartilage we have established a primary culture of differentiating chondrocytes from mouse embryonic limb buds. Trypsin digested limb bud cells from 9-11 day old mouse embryos differentiated into chondrocytes by 5-7 days in culture. At all stages of differentiation, distinct receptors of IGF-I and II were observed. IGF-I stimulated growth and sulphate incorporation of the non-differentiated and differentiated chondrocytes. IGF-II stimulated growth of the non-differentiated cells and had no effect on growth or sulphate incorporation by the differentiated cells. IGF-II, however, stimulated the glucose uptake by the cells at all stages of differentiation. These data confirm our previous suggestion that IGF-I in cartilage is the regulator of growth and differentiation, while IGF-II may be an important regulator of glucose metabolism in the tissue.

Animals↗
PubMed1991

Differential regulation of c-myc and transforming growth factor-alpha messenger RNA expression in poorly differentiated and well-differentiated colon carcinoma cells during the establishment of a quiescent state.

A previous report from this laboratory indicated that a transformed fibroblast cell line up-regulated c-myc by as much as 14-fold as cultures approached saturating densities, whereas the untransformed counterparts displayed little alteration in c-myc expression (Cancer Res., 49: 2320, 1989). The results suggested a mechanism for the growth advantage of the transformed cells at postconfluent densities. Similarly, the present results indicate that regulation of c-myc expression during establishment of a quiescent state markedly differed in poorly differentiated versus well-differentiated human colon carcinoma cells. While c-myc expression increased 2- to 3-fold during this period in the poorly differentiated cells, expression levels for this protooncogene showed little variation in the well-differentiated cells. There was, however, no correlation between degree of differentiation and c-myc mRNA levels in growing cultures (i.e., cells in late log phase). Another proliferation-associated mRNA, transforming growth factor alpha (TGF-alpha), was also differentially regulated in the two groups of colon carcinoma cells as cultures approached quiescence. Further, addition of exogenous growth-stimulatory factors (epidermal growth factor plus insulin plus transferrin) to quiescent, well-differentiated cells resulted in an up-regulation of TGF-alpha mRNA levels by 9-fold over a 24-h period. In contrast, poorly differentiated cells displayed little alteration in TGF-alpha mRNA levels under similar conditions. The results suggest that inappropriate kinetic regulation of c-myc and TGF-alpha mRNAs at quiescence may be related to the growth factor independence of the poorly differentiated colon carcinoma cells. Furthermore, altered temporal regulation of c-myc and TGF-alpha expression appears to be more relevant to differentiation status in human colon carcinoma cells than are absolute expression levels.

Carcinoma↗
PubMed2006

Differential expression changes in K562 cells during the hemin-induced erythroid differentiation and the phorbol myristate acetate (PMA)-induced megakaryocytic differentiation.

K562 cell line has been used as a model of common progenitor of erythroblasts and magakaryocytes and can be differentiated into erythroid and megakaryocytic lineages by hemin and phorbol myristate acetate (PMA) respectively. We analyzed mRNA expression in un-induced, hemin-induced and PMA-induced K562 cells by differential display reverse transcription polymerase chain reaction (DDRT-PCR) method. 314 differential expression sequence tags (ESTs) were obtained. Among them, 201 ESTs displayed up-regulation and 85 ESTs down-regulation after hemin induction, 186 ESTs showed up-regulation and 72 ESTs down-regulation after PMA induction. The differentially expressed genes included those encoding transcription factors, signaling factors, apoptosis-associated factors and others. 45 of these ESTs stand for genes whose open reading frames were found but whose functions remain unknown. 4 ESTs represent possibly new genes. Furthermore we compared differences of gene expression during hemin-induced erythroid differentiation and PMA-induced megakaryocytic differentiation and found that the expressional changes of some transcription factors and metabolism proteins are the common but the expressional changes of some signal pathways in these two differentiation processes are different. These results suggested that erythroid differentiation and megakaryocytic differentiation are associated in activation and repression of different signal pathways.

Blotting, Northern↗
PubMed1988

Lymphokine-induction of memory B-cell differentiation: differential stimulation of large virgin and memory B-cell differentiation.

In order to compare and contrast the requirements of virgin and memory B cells for B-cell differentiation factors, a model system was developed in which low-density rat B cells isolated from 4-week primed antigen-draining lymph nodes were cultured in vitro. This large low-density cell population contained B cells which were 90% surface IgM positive and 60% IgD positive and showed moderately elevated Ia staining. When the cell population was stimulated with antigen plus lymphokines or lymphokines alone, antigen-specific IgG antibody was secreted; this was used as a measure of memory cell differentiation. When the cell population was stimulated with mitogen (lipopolysaccharide plus dextran sulfate) plus lymphokines, polyclonal IgG and IgM secretion was seen and was used as a measure of virgin B-cell differentiation. Using this system, we found that lymphokines contained in a Con A-induced rat spleen cell supernatant (CSN) were sufficient to drive both memory and virgin B-cell differentiation. In contrast, lymphokines contained in the supernatant from the murine T-cell hybridoma B151K12 (B151CFS) were able to induce large amounts of polyclonal IgM and IgG secretion but did not support memory B-cell differentiation. When recombinant human IL-2 was added to these cultures, it acted synergistically to augment virgin B-cell differentiation, but this combination of lymphokines was still not able to support memory B-cell differentiation. Furthermore, recombinant rat interferon-gamma and a commercial source of human BCGF, with or without IL-2, were unable to promote significant virgin or memory B-cell differentiation. These data support the hypothesis that memory B cells and virgin B cells differ in their lymphokine requirements for differentiation into antibody-secreting cells.

Animals↗
PubMed2005

[Limitations of treatment based on syndrome differentiation and necessity of combining syndrome differentiation with disease differentiation].

Treatment based on syndrome differentiation, as a core of diagnostic and treatment methods in traditional Chinese medicine, now appears to be limited by some of its shortages during the high-speed development of medicine, such as no symptoms for differentiation in some patients, lack of objective standardization and pertinence, and limitations of the four diagnostic methods, etc. Combination of syndrome differentiation and disease differentiation can not only make up the shortages of syndrome differentiation but also expand the scope of diseases treated with traditional Chinese medicine and promote the modernization of traditional Chinese medicine. The author discusses the limitations of treatment based on syndrome differentiation as well as the advantages of combining syndrome differentiation with disease differentiation. It is also stated that this combination can make the system of syndrome differentiation perfect.

Diagnosis, Differential↗
PubMed2000

Differential display as an approach to study differentiation and differentiation therapy in AML.

Different subgroups of acute myeloid leukemia (AML) can be defined by the specific non-random chromosomal translocation that is present within the abnormal cell types. In one type of AML, acute promyelocytic leukemia (APL), the block in the normal process of differentiation can be circumvented by the addition of a chemical inducer, in this case retinoic acid. This is due to the defect in APL affecting the retinoic acid receptor gene. This type of therapy has become known as differentiation therapy. However, most types of leukemia do not respond to the retinoic acid, and therefore methods of differentiation therapy need to be developed by targeting other genes involved in the leukemia process. This requires the molecular characterizations of the genes that are expressed during differentiation and in particular those genes that show a differential expression in inducer sensitive cells and those resistant to induced differentiation. Therefore, therapeutic agents could be developed to specifically target these genes. This article describes how the technique of differential display, as one of several possible methods of molecular screening, may allow the identification of genes which can be targeted to induce differentiation.

Acute Disease↗
PubMed1999

Differentiation induction subtraction hybridization (DISH): a strategy for cloning genes displaying differential expression during growth arrest and terminal differentiation.

Human cancers often display aberrant patterns of differentiation. By appropriate chemical manipulation, specific human cancers, such as human melanoma, leukemia and neuroblastoma, can be induced to lose growth potential irreversibly and terminally differentiate. Treatment of HO-1 human melanoma cells with a combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (MEZ) results in irreversible growth arrest, a suppression in tumorigenic properties and terminal cell differentiation. A potential mechanism underlying these profound changes in cancer cell physiology is the activation of genes that can suppress the cancer phenotype and/or the inactivation of genes that promote the cancer state. To define the repertoire of genes modulated as a consequence of induction of growth arrest and terminal differentiation in human melanoma cells, we are using a differentiation induction subtraction hybridization (DISH) approach. A subtracted cDNA library, differentiation inducer treated cDNAs minus uninduced cDNAs, was constructed that uses temporally spaced mRNAs isolated from HO-1 cells treated with IFN-beta+MEZ. Approximately 400 random clones were isolated from the subtracted DISH library and analyzed by reverse Northern and Northern blotting approaches. These strategies resulted in the identification and cloning of both 30 known and 26 novel cDNAs displaying elevated expression in human melanoma cells induced to growth arrest and terminally differentiate by treatment with IFN-beta+MEZ. The DISH scheme and the genes presently identified using this approach should provide a framework for delineating the molecular basis of growth regulation, expression of the transformed phenotype and differentiation in melanoma and other cancers.

Antineoplastic Agents↗
PubMed1995

Factors controlling prespore cell differentiation in Dictyostelium discoideum: minute amounts of differentiation-inducing factor promote prespore cell differentiation.

Amoebae of strain V12M2 differentiate efficiently into prespore cells without cell contact in a salt solution containing cAMP, if the pH of the medium is maintained suitably acidic using a restricted buffer [31]. Under such conditions, most cells differentiate into prespore cells at pH 5.2. Using this developmental system, the elements controlling prespore-cell differentiation were analyzed. First, the dependence on cell density was examined. At a very low density (10(2) cells/cm2), most cells did not differentiate. As the density was increased the proportion of prespore cells differentiating increased, reaching a maximum at 5 x 10(3) cells/cm2. Conditioned medium could mimic the effects of cell density on cell differentiation. These findings suggest the presence of factor(s) released into the medium which are involved in inducing prespore-cell differentiation. The conditioned medium was found to contain at least two prespore-inducing components; one is a novel factor(s) and the other is DIF, which has previous only been considered to repress prespore-cell differentiation. These findings were supported by experiments using a DIF-deficient mutant, HM44.

Animals↗
PubMed1999

[Does the universal "signal transduction pathway of differentiation" exist? Comparison of different cell differentiation experimental models with differentiation of HL-60 cells in response to 1,25-dihydroxyvitamin D3].

The comparison of distinct cell-differentiation models can help to answer the question whether there are common signalling pathways activated in the cells during the differentiation process or not. The differentiation of PC12 pheochromocytoma cells in response to NGF, the differentiation of melanoma B16 cells triggered by alpha-MSH, the formation of myotubes by L6E9 skeletal muscle myoblasts deprived of FCS or differentiation of HL-60 cells in response to steroid hormone 1,25-dihydroxyvitamin D3 share some similarities in the activation of signal transduction pathways. Differentiation-inducing agents stimulate sustained activation and nuclear translocation of MAP kinases (ERK1 and ERK2). Some of differentiation-inducing agents activate PI3-kinase as well, and the inhibition of the PI3K/p70S6K pathway blocks the process of differentiation in the cells.

Animals↗
PubMed1992

Ultrastructural analysis of differentiation of rat endoderm in vitro. Adipose vascular-stromal cells induce endoderm differentiation, which in turn induces differentiation of the vascular-stromal cells into chondrocytes.

Isolated definitive endoderm from 9-day-old rat embryos was cultivated up to 24 days in plastic and glass petri dishes and on developing vascular-stromal cells (mesenchymal cells) from epididymal white and interscapular brown adipose tissue of 4-week-old male rats. Explants were analyzed histologically and ultrastructurally. Endoderm attached to the bottom of the glass or petri dishes degenerated under one week of cultivation. Endoderm free floating in the culture medium developed into unilaminar vesicles whose flat epithelium did not differentiate. However, endoderm inoculated on developing mesenchymal cells differentiated into glandular explants or into ciliated pseudostratified columnar respiratory epithelium. The glandular explants were made up of at least four different kinds of cells whose cytoplasm showed predominantly: a) polyribosomes, b) lysosomes, c) mitochondria or d) cytoskeletal filaments. Endodermal cells differentiated only if, during cultivation, they were in contact with or in close proximity to developing mesenchymal cells. Endoderm differentiating into the respiratory epithelium in turn directed differentiation of the underlying vascular-stromal cells into lamina propria cells and chondrocytes. Cultivated vascular-stromal cells in the upper layers became thicker, ellipsoid in shape and with enlarged intercellular space. They appeared to be lamina propria cells and, together with the respiratory epithelium, built folds of respiratory mucosa. The vascular-stromal cells in the layers close to the bottom developed into chondrocytes; i.e., the cells became oval and agglomerated in nest like structures with a defined extracellular matrix. Their cytoplasm contained abundant cisternae of rough endoplasmic reticulum and numerous vacuoles with PAS positive substance. These observations showed that even developing vascular-stromal cells from adipose tissue from postlactating rats can trigger the process of definitive endoderm differentiation. Once triggered, differentiating endoderm influenced differentiation of the vascular-stromal cells into the cells and tissues of a wall of the respiratory tract.

Adipose Tissue↗
PubMed1987

Enhanced c-fos expression in differentiated monomyelocytic cells is associated with differentiation and not with the position of the differentiated cells in the cell cycle.

Enhanced expression of the proto-oncogene c-fos is reported to be involved in the differentiation of monomyelocytic cells into mature macrophages. Such differentiated cells usually accumulate in the G1 phase of the cell cycle. M1 murine myeloid leukemia cells, which can be synchronized in early and late G1 and can also differentiate into mature macrophages when stimulated with granulocyte colony-stimulating factor (G-CSF), were used to investigate whether the enhanced expression of c-fos in differentiated monomyelocytic cells is associated with the position of the cells in the cell cycle or with their state of differentiation. Our data show that the enhanced expression of the c-fos gene occurs only in fully differentiated cells and not in proliferating or G1-arrested cells. These data imply that the enhanced expression of c-fos in M1 cells is restricted to functionally differentiated cells and not related to the position of the differentiated cells in the cell cycle.

Animals↗
PubMed2004

Differential expression of TGF-beta isoforms during differentiation of HaCaT human keratinocyte cells: implication for the separate role in epidermal differentiation.

The three mammalian isoforms of transforming growth factor-beta(TGF-beta1, beta2, beta3) are potent regulators of cell growth, differentiation, and extracellular matrix deposition. To study their role in skin differentiation, we investigated the expression of TGF-beta isoforms on cell growth and differentiation induction of the human keratinocyte cell line, HaCaT by elevating the Ca(2+) concentration. An ELISA and RT-PCR assay revealed secreted TGF-beta 1 protein and TGF-beta 1 mRNA were increased during calcium-induced differentiation. In contrast, major differences were seen for TGF-beta 2 and TGF-beta 3 mRNA which were decreased during differentiation, but TGF-beta 2 and TGF-beta3 protein were not evident on an ELISA. These results suggest different functions for each TGF-beta isoforms in epidermal differentiation, such that TGF-beta 1 is associated with the more differentiated state, and TGF-beta 2 and TGF-beta 3 may be associated the more proliferated state.

Cell Differentiation↗
PubMed1979

[Factors that control the differentiation of stem cells. I. The change in direction of hematopoietic stem cell differentiation under the effect of differentiating T-lymphocytes].

A mixed transplantation of bone marrow cells, and lymph nodes or thymic cells of mice CBA strain into lethally irradiated hybrid recipients (CBAXC57B1)F1 is accompanied with changes in the differentiation pattern from a mainly erythroid to a mainly granuloid way. Thymectomy of either donor of bone marrow cells or recipients, or both, destroys the stem cell differentiation in the direction of granulopoieseis. Intact syngeneic lymphocytes normalize differentiation of the stem cells, but in the presence of tissue antigens these provide for the stem cell differentiation mainly in the direction of granulopoiesis. The differentiation of stem haemopoietic cells is accomplished under the thymic and lymphocyte control. T-differentiating lymphocytes (Td) are the lymphocytes controlling the stem cell differentiation.

Animals↗
PubMed1997

Effects of drugs on response duration differentiation. V: differential effects under temporal response differentiation schedules.

The effects of methamphetamine, phencyclidine and delta9-tetrahydrocannabinol on responding under temporal response differentiation schedules were studied under three different time requirements. Under the schedules studied, Sprague-Dawley rats were required to make a continuous response for at least a minimum time duration, but not more than a maximum. Baseline performance under a temporal differentiation schedule usually produces a normal frequency distribution of response durations with the peak at or near the minimum duration required for delivery of the reinforcer. These frequencies were summed to calculate cumulative frequencies that were plotted as sigmoidal curves. Under the temporal differentiation 1-1.3 sec schedule, methamphetamine increased the frequency of short response durations at low doses, whereas high doses produced both long and short response durations, flattening the relative frequency distribution. Under the temporal differentiation 4-5.2 sec and 10-13 sec schedules, methamphetamine produced only short response durations, which shifted the relative frequency and cumulative frequency distribution of response durations leftward. delta9-Tetrahydrocannabinol had little effect under the temporal differentiation 1-1.3 sec and 4-5.2 sec schedules, but it greatly increased the relative frequency of short response durations under the 10-13 sec schedule. Phencyclidine produced a similar effect under all temporal differentiation schedules, increasing the relative frequency of short response durations. Thus the effect of drugs on timing behavior under these temporal differentiation schedules not only depended on the drug, but also depended on the dose and the time parameters of the schedule. These data suggest that drugs produce multiple effects on timing behaviors that depend on complex interactions among several factors.

Animals↗
PubMed2001

Establishment of serum-free pre-colony forming unit assays for differentiation of primitive hematopoietic progenitors: serum induces early macrophage differentiation and inhibits early erythroid differentiation of CD34++CD38- cells.

In this report we show that serum has differentiation-inducing effects on primitive hematopoietic progenitor cells with the CD34++CD38- immunophenotype. Using the pre-colony forming unit (pre-CFU) assay as a model for early myelopoiesis, we compared the effects of serum-containing and serum-free media and evaluated different cytokine cocktails [interleukin (IL)-1, IL-3, IL-6, kit ligand with and without the Flt3/Flk2 ligand (FL)]. In this assay, pre-CFUs are defined as cells unable to form colonies when plated directly in semi-solid assays, but which can differentiate into CFUs when cultured in liquid medium containing early-acting cytokines. In one of the investigated serum-free media, the average myeloid expansion in liquid medium reached up to more than 50% of that obtained in serum-containing medium. In addition, our experiments revealed differences in the clonogenic output between cells cultured in serum-free medium and those cultured in serum-containing medium, demonstrating that serum has a monocyte differentiation-inducing effect on primitive hematopoietic progenitors. Also in serum-free medium, higher proportions of erythroid progenitors were generated. These differentiation-inducing effects of serum further emphasize the need for serum-free culture protocols for hematopoietic graft engineering. Addition of FL to the culture media ameliorated cellular expansion and resulted in a decrease in the proportion of erythroid and granulocyte progenitors and an increase in the proportion of monocyte progenitors. In conclusion, this study shows that good serum-free conditions are available for differentiation assays with primitive hematopoietic progenitors and demonstrates that serum and FL have biasing effects on the initial phase of hematopoietic differentiation, favoring the monocyte lineage.

ADP-ribosyl Cyclase↗
PubMed1999

Differential effects of fibroblast growth factor (FGF) 9 and FGF2 on proliferation, differentiation and terminal differentiation of chondrocytic cells in vitro.

Fibroblast growth factor (FGF) 9 was compared with FGF2 in its ability to influence proliferation, differentiation, terminal differentiation and apoptosis in a rat calvaria-derived cell line (RCJ 3.1C5.18) that spontaneously undergoes chondrocyte differentiation in vitro. Like FGF2, FGF9 promoted proliferation, but to a lesser extent. In contrast to FGF2, which blocked chondrocytic differentiation, FGF9 had no effect on differentiation but inhibited terminal differentiation. FGF9 also stimulated expression of the mitotic inhibitor p21 to a greater extent than FGF2. Neither ligand influenced apoptosis. The results indicate that FGF9 could account for many of the physiological responses attributed to FGF-receptor activation in the growth plate.

Animals↗