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At least 991 records · Page 55Linked to original sources
PubMed1999

Transcriptional regulation in B cell differentiation.

B cell development is a multistage differentiation process that ultimately generates antibody-secreting plasma cells. This model developmental pathway is governed by a choreographed pattern of expression from genes encoding stage and lineage-specific proteins. This is achieved by the interaction of distinct transcription factors with regulatory elements, placing these proteins in a central position in B cell ontogeny. The importance of distinct transcription factors is also supported by the notion that B cell development is disrupted in mice bearing homozygous null alleles of certain factors involved in the control of B-cell-specific genes. In this review we compare and contrast the transcriptional regulation of well-studied B lymphoid restricted genes, on a gene by gene basis, focusing on the functional structure of transcription control regions and interacting transcription factors.

Animals↗
PubMed2001

In situ NMR systems.

In situ NMR is becoming an established technology for applications in bioprocessing and metabolic engineering. The in situ NMR biosensor acts as a noninvasive pH, ion, and concentration meter, with 31P and 13C as the two main isotopes of study. A substantial data base now exists for phosphorus and carbon spectra of bacteria and yeast. In situ NMR can provide many of the state variables needed for modeling glycolytic pathway function. NMR micro-reactor technology has improved significantly in the last decade. Several designs for immobilized cell reactors have been tested, and in particular, considerable gains have been made in the feasibility of studying aerobic, chemostat cultures with in situ NMR. Acquisition of 31P spectra from cell suspensions of 3-5% v/v under controlled conditions can be made in 3-7 minute time resolution in several systems.

Cell Nucleus↗
PubMed2001

Trophic transfer and passive uptake of a polychlorinated biphenyl in experimental marine microbial communities.

To study the uptake mechanisms of 2,2',4,4',6,6'-hexachlorobiphenyl (HxCB 153) in microplankton with different feeding strategies, two laboratory communities were used. Trophic transfer of HxCB 153 was tested in a heterotrophic microbial food web consisting of bacteria, flagellates, and ciliates. Passive uptake was tested in a community consisting of algae and bacteria. The experiments were conducted over 6 d, and samples were retrieved daily. In the heterotrophic food web, a significant increase of the HxCB 153 concentration was observed in the top predator level (ciliates, p < 0.05), where the concentration doubled during the 3 d of the experiment. A concomitant decrease was observed in the ciliate prey (flagellates), indicating that HxCB 153 was redistributed due to trophic transfer. On average, 33% of the HxCB 153 was sorbed to ciliates over the course of the experiment. In the experiment with algae and bacteria, the HxCB 153 concentrations were relatively stable over time. The largest fraction partitioned into bacteria (57%), whereas only 4% of the HxCB 153 sorbed to the algae. The uptake was 8-fold higher in ciliates than in algae, although the algal biomass was 10-fold higher. The results imply that trophic transfer may be a significant transport route of more hydrophobic organic contaminants (HOCs) in plankton communities. In transfer models, this pathway may be taken into consideration so that the transport rate of HOCs to higher trophic levels is not underestimated.

Absorption↗
PubMed2004

PathoPlant: a database on plant-pathogen interactions.

Pathogen recognition and signal transduction during plant pathogenesis is essential for the activation of plant defense mechanisms. To facilitate easy access to published data and to permit comparative studies of different pathogen response pathways, a database is indispensable to give a broad overview of the components and reactions so far known. PathoPlant has been developed as a relational database to display relevant components and reactions involved in signal transduction related to plant-pathogen interactions. On the organism level, the tables 'plant', 'pathogen' and 'interaction' are used to describe incompatible interactions between plants and pathogens or diseases. On the molecular level, plant pathogenesis related information is organized in PathoPlant's main tables 'molecule', 'reaction' and 'location'. Signal transduction pathways are modeled as consecutive sequences of known molecules and corresponding reactions. PathoPlant entries are linked to associated internal records as well as to entries in external databases such as SWISS-PROT, GenBank, PubMed, and TRANSFAC. PathoPlant is available as a web-based service at http://www.pathoplant.de.

Computational Biology↗
PubMed2006

[Erythropoietin enhances the therapy potency of autologous bone marrow stromal cells in a rat heart infarction model via phosphatidylinositol-3-kinase/Akt pathway].

OBJECTIVES: Erythropoietin (EPO) induces angiogenesis and inhibits apoptosis through the phosphatidylinositol-3-kinase/Akt (PI3-K/Akt) pathway. Transplantation of mesenchymal stromal cells (MSC) has been shown to improve heart perfusion and function post myocardial ischemia. We investigated whether EPO enhances the therapeutic potency of MSC transplantation in rats with experimental myocardial infarction (MI). METHODS: Wistar rats were divided into four groups (n=8 each): myocardial infarction (MI) group, EPO group, MSC group and MSC-EPO group. MI was made by ligating the anterior descending coronary artery. MSC was injected in the infarcted area immediately after ligation in MSC group and MSC-EPO group. EPO (3000 U/kg) was administered i.p. in EPO group and MSC-EPO group for 3 days post MI and on the 14th to 16th day post MI. Cardiac function was measured by echocardiography at 2 and 21 days after MI. MI size was measured, and the level of phosphorylated Akt was assessed by Western blot and immunohistology at 21 days post MI. RESULTS: LVEF was significantly lower at 21 days than that at 2 days in MI group while significantly increased in other 3 groups, especially in MSC-EPO group at 21 days than that at 2 days. MI size was significantly lower (20.7%+/-2.3% vs. 24.0%+/-2.3%, 26.0%+/-0.9%, 28.1%+/-1.5%, all P<0.05), capillary density was significantly higher (12.95+/-2.11 vs. 10.78+/-0.99, 10.43+/-1.52 and 6.31+/-0.69, all P<0.05) in MSC-EPO group at 21 days than that in other groups and the ratio of phosphorylated Akt to total Akt measured by Western blot was also significantly higher in MSC-EPO group than other groups (0.36 vs. 0.32, 0.31 and 0.28, all P<0.05). Compared to other groups, Bcl-2 was significantly up-regulated and Bax down-regulated in MSC-EPO group. CONCLUSION: Our results demonstrated that MSC transplantation and EPO infusion could improve cardiac function and EPO enhances the therapeutic potency of MSC transplantation via PI3-K/Akt pathways.

Animals↗
PubMed1979

Mutagenesis and embryonal carcinogenesis.

The embryonal tumors of children occur in dominantly heritable and nonhereditary forms, which indicates that a dominant mutation can be on the carcinogenic pathway. A model which fits age-specific incidence hypothesizes that both forms arise as a consequence of two mutations. The background incidences of these tumors then reflect spontaneous mutation rates in germinal and somatic cells and may be increased by mutagens. The gene for one tumor (retinoblastoma) seems to be located on chromosome 13. Clues to the pathophysiology of these tumor genes come from consideration of their tissue specificity, origin from embryonal cells, and developmental effects. Childhood cancers may be manifestations of the homozygous states of a series of genes concerned with differentiation in specific embryonal tissues.

Child↗
PubMed1988

Structure and function of proparts in zymogens for aspartic proteinases.

Alignment of amino-acid sequences of zymogens for aspartic proteinases shows homology among the proparts corresponding to that observed for the active enzymes. The alignment indicates that all zymogens have a lysine residue at position p36 (porcine pepsinogen numbering). In the tertiary structure of porcine pepsinogen this residue is located between the two aspartic residues that participate in the catalytic mechanism of the active enzyme. It is suggested that Lys (p36) is essential for the correct folding of the zymogen molecule. Activation models and pathways are discussed.

Animals↗
PubMed1987

Transient requirement for prolactin as a growth initiator following treatment of autonomous Nb2 node rat lymphoma cell cultures with butyrate.

A previous study described the development of cultures of Nb2 node rat lymphoma cells which specifically require a lactogenic hormone, e.g., prolactin (PRL), as a growth factor. In the present study, sublines of these cultures have been established, including clones, which do not depend on exogenous lactogens for growth; the cells do not appear to produce autocrine, PRL-like substances. Although these autonomous cells grew readily in the complete absence of lactogens, their growth rate was stimulated (up to approximately 30%) by PRL concentrations greater than or equal to 0.1 ng/ml. When cultures of the lactogen-dependent and of the cloned, autonomous lymphoma cells were incubated for 3 days with sodium n-butyrate (NaBT; 2 mM), cells were arrested in the G1 phase of the cell cycle, as shown by flow cytometric analysis. A substantial proportion of the G1-arrested cells was viable and readily resumed growth, within 1 day, when transferred to NaBT-free medium containing PRL (1-100 ng/ml). The resumption of growth of the cells from the lactogen-dependent cultures was critically dependent on PRL; in its absence cells lysed. Surprisingly, the rapid recovery of the cells from the lactogen-independent cultures also depended on the presence of PRL in the medium; in its absence growth did not resume for at least 2.3 days. The acquired need of the NaBT-treated, autonomous cells for PRL was only transient, since such cells reverted fully to the PRL-independent state within about 3 days of culturing in PRL-containing, NaBT-free medium. It is proposed, as a working hypothesis, that the autonomous lymphoma cells can be mitogenically activated by two different pathways, one requiring exogenous lactogens and another which is independent of lactogens; the latter pathway recovers much more slowly from the treatment with NaBT than the lactogen-dependent pathway. This model could explain the sensitivity of the autonomous lymphoma cells to PRL and their transient dependency on exogenous lactogens during their recovery from NaBT treatment. NaBT would appear to be a useful agent for studying the mechanism(s) by which the autonomous lymphoma cells circumvent the need for mitogenic lactogens.

Animals↗
PubMed1996

Effect of phytohaemagglutinin on intestinal cell proliferation. Role of polyamines.

The polyamines, putrescine, spermidine and spermine, mediate the effects of hormones and growth factors as second messengers. They are necessary for every step of protein, RNA and DNA synthesis and are therefore essential for cell growth and proliferation. As with hormones and peptide growth factors, plant lectins which bind to cell surface receptors of the brush border membrane are powerful extraneous growth factors for the gut and as a result, by interacting with brush border epithelial receptors, induce extensive proliferation and changes in the metabolism of epithelial cells via activation of second messenger pathways. In model experiments with phytohaemagglutinin (PHA, the lectin from the kidney bean, Phaseolus vulgaris) it was shown that lectins which bind avidly to the mucosal surface induce dose- and time-dependent and fully reversible hyperplastic and hypertrophic growth of the small bowel. The resulting increase in crypt cell proliferation (CCPR) alters the gene expression in epithelial cells. These metabolic changes require vast amounts of polyamines, mostly spermidine. Thus, one of the first effects of the PHA signal is to stimulate the basolateral polyamine uptake system for the sequestration of polyamines from blood circulation in sufficient amounts to sustain the growth of the tissue. Our data indicate that the main source of polyamines to replenish those taken up by the gut is the diet. It has been shown repeatedly that, because of intensive cell proliferation, tumour growth requires large amounts of polyamines. PHA or other lectins accelerate normal metabolic reactions in a regulated way while maintaining their full reversibility and without causing irreversible aberrations. The fact that the lectin-induced growth of the gut requires large amounts of polyamines, suggests that lectins are ideal agents to limit the availability of polyamines for unwanted growth such as neoplastic proliferation of tumours. Accordingly, it may be possible to limit the availability of polyamines for tumour growth by inducing a competitive, but fully reversible, controlled growth of the gut tissue. The intensively but reversibly growing gut tissues can slow down tumour growth by sequestering polyamines and nutrients from circulation.

Animals↗
PubMed1986

The organization of spinal pathways to ventrobasal thalamus in an experimental model of pain (the arthritic rat). An electrophysiological study.

The spinal ascending pathways responsible for neuronal ventrobasal (VB) thalamic responses elicited by joint stimulation of the posterior paw were determined in arthritic rats used as a model of experimental pain. Responses of a same neurone to mechanical (movement--pressure--brushing) or thermal stimulation (50 degrees C) were analysed before and after discrete lesions in the white matter of the spinal cord. For 6 neurones responding exclusively to brushing applied on a small receptive field (RF) strictly contralateral to the recording site, responses were not altered as long as the contralateral dorsal column was intact. Twenty neurones exhibited bilateral symmetrical RF located on the posterior paws including the ankles and for some units the digits. They were driven by moderate pressure and/or mild sustained joint movement and by immersion in a hot water bath at 50 degrees C. Their responses were not significantly modified when the lesions destroyed most of the dorsal and the dorsolateral parts of the spinal cord. In 16/20 cases effect of one hemisection of the cord was studied: when the hemisection was contralateral to the recording site (n = 8) VB neuronal responses elicited from the paw ipsilateral to this side were eliminated in 6/8 cases; when the 1/2 section was ipsilateral to the recording site (n = 8) the lesion induced the elimination of the responses elicited from the paw opposite to the recorded VB for one unit only. The involvement of the spino-reticular pathways which have not only a crossed but also a non-crossed component is suggested. This hypothesis is discussed by comparison to data previously obtained, showing that by contrast in healthy rats the spino-thalamic tract is essential for VB neuronal responses to noxious stimuli.

Afferent Pathways↗
PubMed2003

Relaxin inhibits the activation of human neutrophils: involvement of the nitric oxide pathway.

In animal models of inflammation, the pregnancy hormone relaxin was shown to reduce the recruitment of leukocytes, especially neutrophils, in inflamed tissues. The current study was designed to clarify whether relaxin could inhibit activation of isolated human neutrophils and, if so, whether the nitric oxide (NO) biosynthetic pathway was involved, as occurs in other relaxin targets. Human neutrophils were preincubated with 1, 10, and 100 nmol/liter porcine relaxin for 1 h before activation with N-formyl-Met-Leu-Phe (10 micromol/liter) or phorbol-12-myristate-13-acetate (0.1 micromol/liter). In selected experiments, the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 micromol/liter) was added to the samples 30 min before relaxin. In other experiments, chemically inactivated relaxin (10 nmol/liter) was substituted for authentic relaxin. Untreated, nonactivated neutrophils were the controls. Relaxin reduced significantly and in a concentration-dependent fashion the expression of the surface activation marker CD11b, as well as the generation of superoxide anion, the rise of intracellular Ca(2+), the release of cytoplasmic granules, and the chemotactic migration. These effects of relaxin were blunted by N(G)-monomethyl-L-arginine and could not be reproduced by inactivated relaxin. Relaxin also increased neutrophil inducible NO synthase expression and NO generation. This study provides evidence that relaxin inhibits the activation of human neutrophils stimulated by different proinflammatory agents. This novel property of relaxin could be of relevance in toning down maternal neutrophil activation during pregnancy, thereby counteracting the occurrence of pregnancy-related disorders such as preeclampsia, which is regarded as an excess maternal inflammatory response to pregnancy.

Calcium↗
PubMed1998

A clinical pathway for ostomy care in the home: process and development.

The health care environment is changing rapidly both in form and funding. Recognition of the need for organized, cost-efficient services across the health care continuum has resulted in a model identified as a clinical pathway. This article compares and contrasts key elements of the clinical pathway model as they apply to the acute care setting versus the home care setting. An example of a clinical pathway for ostomy patients in the home care setting is presented, followed by a discussion of its development, pilot testing, and outcomes evaluation. Conclusions regarding the validity of clinical pathways in home care are discussed, and the need for further research is considered.

Community Health Nursing↗
PubMed2004

Expression of Notch signalling markers in bone marrow cells that differentiate into a liver cell lineage in a rat transplant model.

Notch signalling pathway plays an important role in cell differentiation. To investigate the implications of Notch signalling in the differentiation of rat bone marrow (BM) cells into a liver cell lineage, we used cultured BM cells to examine the mRNA expression of Musashi-1, which positively regulates Notch signalling, and made a transplant model to examine the protein expression of Notch signalling markers. For the in vivo experiment, BM cells were collected from transgenic rats expressing green fluorescence protein (GFP) and transplanted into the spleens of recipient rats, in which liver damage had been induced with carbon tetrachloride. The expression of Notch receptor 1 (Notch-1), Jagged-1 and Musashi-1, in the transplanted GFP-positive BM cells was investigated by immunohistochemistry. The expression of the liver-specific proteins, alpha-fetoprotein and cytokeratin19 was also investigated. Musashi-1 mRNA became detectable in the BM cells on culture day 7 in vitro. After transplantation, GFP-positive BM cells were observed in the portal areas of the recipient's livers. Notch-1, Jagged-1, Musashi-1, alpha-fetoprotein and cytokeratin19 were all expressed in the transplanted BM cells. These results suggest that the Notch signalling pathway plays a role in the differentiation of BM cells into a liver cell lineage.

Journal Article↗
PubMed1995

Electrophysiologic evaluation of the phrenic nerve-diaphragm pathway in an intact, conscious calf model.

Owing to technical and ethical limitations, a substantial part of the knowledge about the pathophysiologic mechanism of the human diaphragm has been obtained from studies in which phrenic nerve activation was usually carried out by direct surgical exposure of the nerves in the neck of deeply anesthetized, mechanically ventilated animals. Novel information has been gleaned from such studies, but the restrictive conditions under which it was collected preclude reliable extrapolation. We, therefore, addressed the question of whether accurate electrophysiologic evaluation of the phrenic nerve-diaphragm pathway can be performed in intact, nonanesthetized calves. Transjugular phrenic activation was well tolerated, safe, specific, and able to achieve constant symmetric and supramaximal phrenic stimulations during prolonged periods. Eighteen noninvasive cutaneous and esophageal reception circuits were tested for their ability to record the diaphragmatic evoked potential. In addition, they were compared for specificity and reproducibility of the recorded potentials during prolonged periods of tidal or stimulated respiration. The best diaphragmatic potential was recorded from surface electrodes attached to the skin of the ninth and tenth intercostal spaces, using a xyphoidian reference. We describe a method that allows easy, longterm, and reliable electrophysiologic evaluation of the phrenic nerve-diaphragm pathway in intact, conscious calves. It is hoped that such a model will produce relevant novel information regarding pathophysiology of the diaphragm.

Action Potentials↗
PubMed2001

Analysis of ubiquitination in vivo using a transgenic mouse model.

The primary pathway for the proteolytic destruction of cellular proteins is through ubiquitin-mediated targeting to the proteasome. This pathway is pivotal not only in the elimination of damaged or misfolded proteins but also in the temporal, developmental, or signal-mediated destruction of normal cellular substrates. The list of known substrates of the ubiquitin/proteasome pathway is long, but most substrates have been identified in yeast or, more recently, in cultured mammalian cells. It is likely that many mammalian substrates with developmental or disease relevance have yet to be identified because their ubiquitination occurs in tissue or organ systems that cannot be adequately modeled in vitro. We have developed a transgenic mouse model that will allow the isolation and identification of these substrates. The human UbC promoter was used to drive expression of a hexahistidine-tagged version of human ubiquitin in a variety of mouse tissues from early embryonic stages, as assessed by a green fluorescent protein marker. Cleavage of the fusion protein by endogenous enzymes produced epitope-tagged ubiquitin that was detected both in monomeric form and conjugated to cellular proteins. This mouse model should facilitate in the analysis of normal and disease-related ubiquitination events in vivo.

Animals↗
PubMed2000

A multiple transgenic mouse model with a partially humanized activation pathway for helper T cell responses.

Mice expressing human CD4 and human MHC II molecules provide a valuable model both for the investigation of the immunopathogenetic role of human autoantigens and for the development of therapeutic strategies based on modulating helper T cell activation in vivo. Here we present a novel mouse model expressing HLA-DR17 (a split antigen of HLA-DR3) together with human CD4 in the absence of murine cd4 (CD4/DR3 mice). Human CD4 accurately replaces murine cd4 within T cells. In particular, the preservation of cd8(+) and CD4(+) T cell subsets distinguishes CD4/DR3 mice from other multiple transgenic models in which the alternative T cell subsets are fundamentally disturbed. Moreover, human CD4 is also faithfully expressed on antigen presenting cells such as dendritic cells and monocyte/macrophages, so that the overall transgenic CD4 expression pattern resembles very closely that of humans. HLA-DR3 expression in the thymus correlates very closely to that of mouse MHC II. In contrast, only 70% of mouse MHC II positive cells in spleen, lymph node, and peripheral blood coexpress HLA-DR3. No significant bias was found with regard to particular leucocytes in this respect. The stimulation of helper T cells clearly depends on the interaction between the human transgene products, since mAbs to HLA-DR and/or CD4 completely blocked in vitro recall responses to tetanus toxoid. CD4/DR3 mice represent a partially humanized animal model which will facilitate studies of DR3-associated autoimmune responses and the in vivo determination of the therapeutic potential of mAbs to human CD4.

Animals↗