Fluctuations of cell geometry and their nonequilibrium thermodynamics in living epithelial tissue.

We measure different contributions to entropy production in a living functional epithelial tissue. We do this by extracting the functional dynamics of development while at the same time quantifying fluctuations. Using the translucent Drosophila melanogaster pupal epithelium as an ideal tissue for high-resolution live imaging, we measure the entropy associated with the stochastic geometry of cells in the epithelium. This is done using a detailed analysis of the dynamics of the shape and orientation of individual cells which enables separation of local and global aspects of the tissue behavior. Intriguingly, we find that we can observe irreversible dynamics in the cell geometries but without a change in the entropy associated with those degrees of freedom, showing that there is a flow of energy into those degrees of freedom. Hence, the living system is controlling how the entropy is being produced and partitioned into its different parts.

An analysis of signal processing algorithm performance for cortical intrinsic optical signal imaging and strategies for algorithm selection.

Intrinsic Optical Signal (IOS) imaging has been used extensively to examine activity-related changes within the cerebral cortex. A significant technical challenge with IOS imaging is the presence of large noise, artefact components and periodic interference. Signal processing is therefore important in obtaining quality IOS imaging results. Several signal processing techniques have been deployed, however, the performance of these approaches for IOS imaging has never been directly compared. The current study aims to compare signal processing techniques that can be used when quantifying stimuli-response IOS imaging data. Data were gathered from the somatosensory cortex of mice following piezoelectric stimulation of the hindlimb. The effectiveness of each technique to remove noise and extract the IOS signal was compared for both spatial and temporal responses. Careful analysis of the advantages and disadvantages of each method were carried out to inform the choice of signal processing for IOS imaging. We conclude that spatial Gaussian filtering is the most effective choices for improving the spatial IOS response, whilst temporal low pass and bandpass filtering produce the best results for producing temporal responses when periodic stimuli are an option. Global signal regression and truncated difference also work well and do not require periodic stimuli.

Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: increased binding of cyclin A negatively regulates E2F transactivation activity.

Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G1 phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F-1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21cip1 to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c-myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A-negative regulation of E2F-mediated transcription.

The p120-v-Abl protein interacts with E2F-1 and regulates E2F-1 transcriptional activity.

The E2F family of transcription factors regulates cell cycle progression, and deregulated expression of E2F-1 can lead to neoplastic transformation. In myeloid cells, introduction and expression of the Abelson leukemia virus causes growth factor independence. Here, the p120 v-Abl protein activates E2F-1-mediated transcription through a physical interaction with the E2F-1 transcription factor. BCR-Abl and c-Abl also stimulate E2F-1-mediated transcription. Our results suggest a new mechanism by which v-Abl leads to factor-independent myeloid cell proliferation: the activation of E2F-1-mediated transcription.

Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells.

Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-alpha-tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells. VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway. Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas ligand (Fas-L) were increased following VES treatment. In addition, VES increased cell surface Fas expression. Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis. The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy.

Data mining: a strategy for knowledge development and structure in nursing practice.

Data mining is an emerging technique used more widely by the business world than the world of nursing and health care. However, this strategy can be helpful for improving the quality of decision making by clinicians and health care administrators. This paper addresses the concepts and techniques of data mining that could be useful for practicing nurses as well as nurse administrators. Data mining can be an important tool for the development of nursing knowledge and knowledge structures. An example of the use of the technique in an inpatient setting is provided and insights from the process are discussed.

Developing informatics as a discipline.

Informatics is developing in all of the disciplines related to healthcare. There are many aspects to informatics development which frequently appear to be unrelated and to lack cohesion. This paper builds on the development of a model for nursing informatics and proposes how the components of that model can interact to provide an outline for the development of informatics as a discipline. A understanding of the disciple allows us to organize the existing research and more importantly to understand the areas where research is lacking as the discipline is evolving.

Transforming growth factor beta 1 functions in monocytic differentiation of hematopoietic cells through autocrine and paracrine mechanisms.

This study examined the role of transforming growth factor beta 1 (TGF-beta 1) in monocytic differentiation of hematopoietic cells. TGF-beta 1 and retinoic acid (RA) inhibited HL-60 cell growth in a dose-dependent fashion. Treatment of HL-60 cells with a combination of TGF-beta 1 and a 50% optimal dose of RA (RA + TGF-beta 1) resulted in increased growth suppression compared to the individual treatments. Morphological studies revealed that TGF-beta 1 induced promonocytic differentiation (68%), RA induced granulocytic differentiation (98%), and RA + TGF-beta 1 induced monocytic (54%) and granulocytic (46%) differentiation of HL-60 cells. Induction of the monocyte-specific marker, nonspecific esterase, was markedly increased by TGF-beta 1 and RA + TGF-beta 1 treatment but not by RA treatment. Both TGF-beta 1 treatment and RA treatment increased TGF-beta ligand and TGF-beta receptor protein and mRNA levels. To determine whether RA mediated HL-60 cell growth inhibition and differentiation through the autocrine expression of TGF-beta 1, experiments using TGF-beta 1 antisense oligonucleotides or TGF-beta 1-neutralizing antibodies were conducted. TGF-beta 1 antisense oligonucleotides and neutralizing antibodies partially blocked RA-induced inhibition of proliferation, and TGF-beta 1 antisense oligonucleotides reversed RA-induced granulocytic maturation, demonstrating that RA signals autocrine expression of TGF-beta 1 and TGF-beta receptors. The effect of TGF-beta 1 on normal hematopoiesis was also studied using primary human fetal liver cells. TGF-beta 1 alone and in the presence of interleukin 3 promoted macrophage differentiation of primitive fetal liver cells. Cell surface expression of the monocyte/macrophage-specific marker c-fms was increased 3.1-fold following TGF-beta 1 treatment. In addition, TGF-beta 1-treated cells displayed a 51% increase in phagocytosis as compared to interleukin 3-treated control cells. These studies define a role for TGF-beta 1 in the autocrine and paracrine regulation of monocyte/macrophage differentiation.

Nursing decision making and the science of the concrete.

Information systems are going to change our understanding of nursing as a discipline and as a practice. The act of decision making will be the focus of the impact of information systems on nursing. The article models types of nursing knowledge, organizing them into concrete and abstract knowledge. Information systems will allow the inclusion of concrete science data, which has not been possible previously. Role performance is seen as a mechanism for the integration of the two sciences, and a new understanding for nursing decision making is proposed.

p120-v-Abl expression overcomes TGF-beta1 negative regulation of c-myc transcription but not cell growth.

Transformation of interleukin-3 dependent (IL-3) 32D-123 myeloid cells by p120-v-Abl produced the factor-independent 32D-abl cell line. In 32D-abl cells, myc expression was found to be significantly higher than in the parental cells and was correlated with increased E2F-1 protein expression and DNA binding ability. Surprisingly, in 32D-abl cells, TGF-beta1, a potent G1/S inhibitor of 32D-123 and 32D-abl cell growth, increased E2F transactivation as shown by increased c-myc promoter-CAT and GAL4-E2F-1 activity. In addition, TGF-beta1 was also found to increase E2F-1 protein levels but had no effect on steady-state retinoblastoma (RB) protein levels or phosphorylation state. In the absence of TGF-beta1, transient expression of RB in v-Abl expressing cells resulted in decreased c-myc transcription, inhibition of GAL4-E2F-1 driven transactivation and inhibition of cellular proliferation. RB and v-Abl were found to physically associate in vivo and in vitro via v-Abl's ATP binding region. In summary, these studies established that in myeloid cells: (1) v-Abl binds RB resulting in increased E2F-1-driven c-myc transcription, and (2) an alternative pathway exists for TGF-beta1-mediated growth inhibition of v-Abl-transformed cells, in which increased rather than decreased E2F-mediated c-myc transcription is observed.

Toward a model for nursing informatics.

PURPOSE: To propose a new model for the development of nursing informatics based on historical precedent. SIGNIFICANCE: Nursing informatics is expanding rapidly. The proposed model aids in understanding the areas of research, relating them to each other, and it shows areas where work is missing or should be extended. ORGANIZING FRAMEWORK: Nursing informatics as the interaction of cognitive science, computer science, and information science resting on a base of nursing science. IMPLICATIONS: As this model is tested, it can act as an organizing framework to understand and relate studies of nursing informatics and give organization for future research, education, and development.

Nuclear localization of v-Abl leads to complex formation with cyclic AMP response element (CRE)-binding protein and transactivation through CRE motifs.

Deregulated expression of v-abl and BCR/abl genes has been associated with myeloproliferative syndromes and myelodysplasia, both of which can progress to acute leukemia. These studies identify the localization of the oncogenic form of the abl gene product encoded by the Abelson murine leukemia virus in the nuclei of myeloid cells and the association of the v-Abl protein with the transcriptional regulator cyclic AMP response element-binding protein (CREB). We have mapped the specific domains within each of the proteins responsible for this interaction. We have shown that complex formation is a prerequisite for transcriptional potentiation of CREB. Transient overexpression of the homologous cellular protein c-Abl also results in the activation of promoters containing an intact CRE. These observations identify a novel function for v-Abl, that of a transcriptional activator that physically interacts with a transcription factor.

Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta.

Vitamin E succinate (VES) and all-trans-retinoic acid (RA) were determined to be growth inhibitory for B lymphoma cells in vitro. RL, an Epstein-Barr virus-negative human cell line, was growth suppressed 87% with VES (5 micrograms/ml) and 58% with RA (10(-6) M); both agents blocked the cells in G1 of the cell cycle. The antiproliferative effect of VES seems to be independent of its potential antioxidant property because both fat- and water-soluble antioxidants were found to have no effect on RL cell proliferation. VES and RA increased IgM antibody concentrations in cell supernatants 5.8- and 9.9-fold, respectively. DNA fragmentation and flow cytometry studies showed VES- and RA-induced apoptosis in RL cells. VES- and RA-treated RL cells gradually underwent apoptosis over time with maximal induction occurring at days 6 and 5 of culture, respectively. A role for transforming growth factor beta in VES- and RA-mediated RL growth suppression is indicated by increased ligand and type II receptor protein expression. Furthermore, neutralizing antibodies to transforming growth factor beta 1 partially blocked the growth suppressive action of both VES and RA, thus suggesting that a TGF-beta autocrine negative loop was involved in VES and RA suppression of RL cell growth.

Vitamin E succinate induction of HL-60 cell adhesion: a role for fibronectin and a 72-kDa fibronectin-binding molecule.

HL-60 cells, growing as single cells in suspension, exhibit marked cell-cell adhesion when treated for 24 hours with 10 micrograms/ml RRR-alpha-tocopheryl succinate, also called vitamin E succinate (VES). VES-induced cell-cell adhesion is dependent on divalent cations and a functional cytoskeleton and is protein mediated. Cell adhesion molecules CD11a/CD18, CD11b/CD18, CD29, and CD54 do not appear to be mediating VES-induced cell adhesion. HL-60 cells treated with VES adhere to fibronectin-coated plastic and secrete elevated levels of fibronectin. A 72-kDa fibronectin-binding membrane molecule was detected on VES-treated HL-60 cells, and antibodies to fibronectin were shown to inhibit VES-induced cell aggregation. VES induction of HL-60 cell-cell adhesion is proposed to result from increased amounts of extracellular fibronectin binding to VES-induced cell surface fibronectin-binding molecules.

Professional culture models of science and data types for computerized health records.

This paper examines the influence of professional culture and the types of science on clinical judgments and decision making. The advent of electronic records that can store richer and more complex data types will allow different professional disciplines to store data that more appropriately reflect the profession and its decisions. The results should be improved patient care.

Inflammatory myopathy--early diagnosis and management by serum myosin light chains measurements.

The use of serum myosin light chain 1 (MLC1) in the diagnosis and treatment response of a patient with biopsy proven inflammatory myopathy is presented. A serum MLC1 level was elevated at presentation despite a normal creatine phosphokinase level. MLC1 levels more closely paralleled the clinical status than the aspartate aminotransferase and lactate dehydrogenase levels. The results suggest that MLC1 levels may facilitate the early diagnosis and management of patients with inflammatory myopathy. Moreover, the excellent response of our patient to low dose prednisone might suggest that the results of treatment could be improved by early detection and institution of therapy.

Femoral neuropathy in renal transplantation.

Acute femoral neuropathy after renal transplantation is an uncommon and rarely recognized complication. Recovery of the nerve is usual. Although rare, five cases have come to our attention in the past twenty years. A detailed clinical and electrophysiological analysis with a six month follow-up is presented. A review of sixteen other reported cases is also provided. The possible pathophysiology including direct compression and nerve ischemia, is discussed. We believe that nerve ischemia, possibly caused by a steal phenomenon, occurs in all cases following the anastomosis of the graft renal artery to the internal iliac artery, with a superimposed component of compression in some cases. The severity of ischemia probably determines the degree of recovery.