Temporal and subunit-specific modulations of the Rel/NF-kappaB transcription factors through CD28 costimulation

Stimulation of highly purified primary T lymphocytes through CD2 and CD28 adhesion molecules induces a long-term proliferation, dependent on persistent autocrine secretion of interleukin 2 (IL-2), high and prolonged expression of inducible CD25/IL-2 receptor alpha chain (IL-2Ralpha), and secretion of growth factors such as the granulocyte-macrophage colony-stimulating factor (GM-CSF). CD28 costimulation appears to activate cytokine gene expression through conserved kappaB-related CD28 response (CD28RE) or cytokine 1 (CK-1) elements in addition to canonical NF-kappaB-binding sites. In this report, we assess: 1) the evolution of the expression, over an 8-day time period, of the Rel/NF-kappaB family of proteins in costimulated versus TcR/CD3-stimulated primary T cells; 2) the impact of changes on the in vitro occupancy of GM-CSF kappaB and CK-1, as well as IL-2Ralpha kappaB sites; and 3) the differential regulation of newly synthesized p65 and c-Rel by IkappaB proteins. We show that CD2+CD28 stimulation specifically induces, at maximal T cell proliferation phase, sustained nuclear overexpression of NFKB2 p52 and c-Rel subunits which might rely on long-lasting processing of p100 precursor for p52 and increased neosynthesis of c-Rel. This up-regulation correlates with sustained occupancy of GM-CSF kappaB and CK-1 elements by both proteins. Conversely, these subunits do not appear to bind to the IL-2Ralpha kappaB site. Costimulation, but not TcR/CD3 stimulation, appears supported by sustained down-regulation of both IkappaBalpha and -beta regulators. Furthermore, contrary to p65, c-Rel appears to display little affinity for p105, p100 and IkappaBalpha regulators.     

Recurrent congenital diaphragmatic hernia; which factors are involved?

In order to investigate the effect of the expression of Epstein-Barr virus gene BHRF1 on the apoptotic resistance of nasopharyngeal carcinoma cells to radiation, a highly expressing vector for BHRF1 was constructed and transfected into the nasopharyngeal carcinoma cell line CNE2. Then, the biologic alterations of the cells were tested after 60Co radiation. The results showed that, in the BHRF1-expressing cells, the apoptotic index was far lower than in the control groups after 60Co radiation, and cells recovered faster from the radiation, with a higher cell-proliferative rate, stronger ability of colony formation and tumor development in nude mice than that in the control groups. Given the functional homology of BHRF1 with bcl-2, our data indicate that BHRF1 expression could prohibit nasopharyngeal carcinoma cellular apoptosis caused by radiation and in this way contribute to oncogenic transformation.     

Regulation of erythropoiesis in fetus and mother during normal pregnancy

The activity of the hormone erythropoietin was assayed (1) in the amniotic fluid of healthy women in the tenth to 16th weeks of pregnancy who had artificial interruption of pregnancy and (2) in the urinary output of healthy pregnant and nonpregnant women. Erythropoietin activity in concentrated urine increased significantly between the 24th and 31st weeks of pregnancy. No erythropoietin activity was demonstrated in amniotic fluid at the tenth week of pregnancy, even when the fluid was concentrated, but it was demonstrated in concentrated amniotic fluid from the 11th to 16th weeks. The assay results prove, indirectly, the hypothesis that increased production of erythrocytes in pregnancy is mediated by the erythropoietin humoral mechanism in both fetus and mother. Erythropoiesis in the fetus probably is regulated by erythropoietin as early as the 11th week of pregnancy.     

Seven zinc-finger transcription factors are expressed sequentially during the development of anthers in petunia

BACKGROUND: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. METHODS: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56+/-8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71%+/-12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. RESULTS: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of beta-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. CONCLUSION: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events.     

A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus

BACKGROUND: Functional vision loss is a general term used to describe vision loss not associated with organic disease. Such cases are major challenges to the practitioner and demand a special workup. METHODS: Patients may manifest symptoms in typical ways that should alert the examiner to the possibility of functional vision loss. In addition, a variety of techniques help distinguish functional from organic causes of vision loss. These techniques include standard tests that yield characteristic findings in functional vision loss, as well as problem-specific procedures that have the specific aim of detecting functional vision loss. Techniques are described according to whether they are useful in monocular or binocular vision loss and in cases of moderate or severe vision loss. RESULTS: Three cases that illustrate the use of standard and select techniques to detect functional vision loss are presented. Differential diagnosis of functional from organic vision loss and special considerations in the management of patients with functional vision loss are also discussed. CONCLUSIONS: Although it is necessary to rule out underlying pathology in all cases of vision loss, a variety of techniques can provide positive evidence of functional vision loss.     

Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells

The nuclear factor kappaB (NF-kappaB) is involved in T cell activation and enhances HIV-1 gene expression. It is activated in response to numerous stimuli, including oxidative stress. Oxidative stress damages membrane lipids, proteins and nucleic acids. We have shown previously that oxidative DNA damage generated by photosensitization could trigger activation of NF-kappaB. We now show that a series of topoisomerase poisons (actinomycin D, camptothecin, daunomycin and etoposide) also activate NF-kappaB (NFKB1/RelA dimer) in ACH-2 and CEM cells. This activation is inhibited by pyrrolidine dithiocarbamate. In ACH-2 cells latently infected by HIV-1, camptothecin, daunomycin and etoposide are able to enhance virus production. Since topoisomerase poisons cause the formation of single- and double-strand breaks in DNA, these lesions might be capable of triggering NF-kappaB activation. Indeed, DNA damaging agents generating adducts (trans-platin and 4-nitroquinoline 1-oxide) and/or crosslinks in DNA (cisplatin and mitomycin C) do not or only weakly activate NF-kappaB in T cell lines.     

Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen

In a sample of 463 high school students, 43% reported being the victim of either sexual violence or severe physical violence by peers in the past year. Perpetrators were more likely to be known rather than unknown to the victim, or to be dating/ex-dating partners, and 70% of those who experienced violence by peers were girls. Findings support a view of high school peer violence that encompasses relationship, gender, effects on the victim, and beliefs about both male role power and personal power.     

Folding intermediates are involved in genetic diseases?

Recent experimental data show that some human genetic diseases are due to mutations in proteins which influence their trafficking and lead to retaining of proteins in the endoplasmic reticulum or their unproper processing. In this paper a hypothesis is proposed that these mutations are connected with an incomplete protein folding, blocking it at the stage of the kinetic molten globule or even earlier. If so, the specific drugs against these diseases may be ligands and other factors which facilitate the correct protein folding.