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T Badea

Publications and source records attributed to T Badea.

7 recordsLinked to original sources
PubMed2001

Calcium imaging of epileptiform events with single-cell resolution.

Epileptic discharges propagate through apparently normal circuits, although it is still unclear how this recruitment takes place. To understand the role of different classes of neurons in neocortical epilepsy, we have developed a novel imaging assay that detects which neurons participate in epileptiform discharges. Using calcium imaging of neuronal populations during bicuculline-induced spontaneous epileptiform events in slices from juvenile mouse somatosensory cortex, we find that fast calcium transients correlate with epileptiform field potentials and intracellular depolarizing shifts and can be used as an optical signature that a given neuron has participated in an epileptiform event. Our results demonstrate a novel method to characterize epileptiform events with single-cell resolution. In addition, our data are consistent with an important role for layer 5 in generating neocortical seizures and indicate that subgroups of neurons are particularly prone to epileptiform recruitment.

Action Potentials↗
PubMed1999

Sublytic C5b-9 induces proliferation of human aortic smooth muscle cells: role of mitogen activated protein kinase and phosphatidylinositol 3-kinase.

Proliferation of vascular smooth muscle cells contributes to initimal hyperplasia during atherogenesis, but the factors regulating their proliferation are not well known. In the present study we report that sublytic C5b-9 assembly induced proliferation of differentiated human aortic smooth muscle cells (ASMC) in culture. Cell cycle re-entry occurred through activation of cdk4, cdk2 kinase and the reduction of p21 cell cycle inhibitor. We also investigated if C5b-9 cell cycle induction is mediated through activation of mitogen activated protein kinase (MAPK) pathways. Extracellular signal regulated kinase (ERK) 1 activity was significantly increased, while c-jun NH2-terminal kinase (JNK) 1 and p38 MAPK activity were only transiently increased. Pretreatment with wortmannin inhibits ERK1 activation by C5b-9, suggesting the involvement of phosphatidylinositol 3-kinase (PI 3-kinase). Both PI 3-kinase and p70 S6 kinase were activated by C5b-9 but not by C5b6. C5b-9 induced DNA synthesis was abolished by pretreatment with inhibitors of ERK1 and PI 3-kinase, but not by p38 MAPK. These data indicated that ERK1 and PI 3-kinase play a major role in C5b-9 induced ASMC proliferation.

Androstadienes↗
PubMed1999

Tyrosine phosphorylation and activation of Janus kinase 1 and STAT3 by sublytic C5b-9 complement complex in aortic endothelial cells.

The pathway involving Janus kinase (JAK) and signal transducers and activators of transcription (STATs) plays an important role in differentiation and proliferation of cells initiated by receptor activation. In the present study we identified the JAK and STAT proteins activated by C5b-9 in human aortic endothelial cells (AEC). JAK1 but not JAK2 was tyrosine phosphorylated in response to sublytic C5b-9. STAT3 was rapidly tyrosine phosphorylated also by C5b-9. Pertussis toxin inhibited the C5b-9 induced JAK1 activation. However, phosphorylation of STAT3 was not inhibited by Pertussis toxin, although C5b-9 induced a time-dependent nuclear translocation of STAT3. These observations indicated that JAK1 is phosphorylated by C5b-9 through activation of trimeric G proteins of the Gi/Go family. Raf-1 and ERK1 were also activated by C5b-9 in human AEC in a G protein dependent manner. Therefore, JAK1 activity may be involved in activation of Raf-1 and ERK1 via G proteins activated by C5b-9. This study demonstrates the ability of membrane-inserted C5b-9 to activate JAK1 and STAT3 proteins, thus defining new signalling pathway by which C5b-9 may regulate gene activation.

Adult↗
PubMed1997

Terminal complement complexes induce cell cycle entry in oligodendrocytes through mitogen activated protein kinase pathway.

Sublytic complement attack through C5b-9 assembly induces oligodendrocytes (OLG) to express proto-oncogenes and to enter the cell cycle from resting G0/G1 phase to S phase. We have investigated whether cell cycle induction by C5b-9 is mediated by mitogen activated protein kinase (MAPK) pathway in OLG. C5b-9 but not C5b6 induced activation of both ERK1 and c-jun NH2 terminal kinases 1 (JNK1) in OLG. The increased ERK1 and JNK1 activities are transient, reaching a maximum around 20 min following exposure to C5b-9. Activation of Raf-1 and MEK1, upstream kinases of ERK1, was shown by increased Raf-1 kinase activity in anti-Raf-1 immunoprecipitates of OLG treated with C5b-9 and ERK1 activity that can be inhibited by PD098,059, a specific MEK1 inhibitor. Requirement for the ERK1 pathway in DNA synthesis was then evaluated using PD098,059. Enhanced DNA synthesis induced by serum complement was completely abolished when OLG were pretreated with PD098,059. On the other hand, c-fos mRNA expression induced by complement was inhibited only 50% by PD098,059, while the c-jun mRNA level was not affected by this MEK1 inhibitor. Interestingly, p70 S6 kinase, an important ribosomal kinase in mitogenesis, was also activated by C5b-9. These findings indicated that the MAPK pathways appears to play a major role in inducing OLG to enter the S phase of the cell cycle from the resting G1/G0 phase.

Animals↗
PubMed1995

Clinical evaluation of antineutrophil cytoplasmic autoantibodies in ANCA-associated diseases.

Antineutrophil cytoplasmic autoantibodies have been performed in 110 patients referred to the laboratory as a presumptive systemic vasculitis, idiopathic crescentic glomerulonephritis, inflammatory bowel disease or SLE with vascular manifestation. 25 patients were found to be positive with c-, or p-ANCA patterns in indirect immunofluorescent test. We describe several cases in which histological confirmation is not available, an early consideration of a positive ANCA test may offer a reliable diagnosis and effective therapeutic handling, while the cases when the test was not considered, the occurence of relapse was inevitable.

Antibodies, Antineutrophil Cytoplasmic↗
PubMedDate not supplied

Antineutrophil cytoplasmic autoantibodies (ANCA)--markers in diagnosis and monitoring systemic vasculitides.

We present a new class of autoantibodies--ANCA (antineutrophil cytoplasmic autoantibodies) which recognize as target antigen different enzyme constituents of primary granules of neutrophil granulocytes. These autoantibodies are present in a large number of diseases, such as: systemic vasculitides, idiopathic crescentic glomerulonephritis, inflammatory bowel diseases and in some other conditions, including rheumatoid arthritis, SLE, Felty syndrome, acute and chronic infections. ANCA not only facilitate the diagnosis but also have a pathophysiological role for some of the idiopathic vasculitides. In our study, including 110 patients referred to the laboratory for ANCA testing by indirect immunofluorescence technique, only 25 patients were positive with a diffuse cytoplasmic (c ANCA) or perinuclear (p-ANCA) pattern on alcohol fixed slides. Some relevant cases are presented in order to emphasize that ANCA antibodies are a useful marker in the early diagnosis of systemic vasculitides, allowing effective therapeutic handling.

Antibodies, Antineutrophil Cytoplasmic↗