Biomedical subjects

M Forgione

Publications and source records attributed to M Forgione.

5 recordsLinked to original sources

PubMed2000

Do reactive post-resection "injury" spikes exist?

PURPOSE: New post-resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post-resection injury spikes by eliminating the possibility of residual epileptogenic tissue. METHODS: Preresection and post-resection ECoG was performed on seven patients with an intra-axial neocortical tumor (glioblastoma multiforme or metastasis) and no history of seizures. All tumors were gross-totally resected. RESULTS: The mean age of the patients was 59 years. The tumor location was frontal in four patients, parietal in two, and temporal in one. Two patients had preresection spikes with an average rate of 68 spikes/min that disappeared after surgery. Two different patients had new post-resection spikes, with an average firing rate of 4 spikes/min, despite normal preresection ECoG. In one of these patients, the new spikes were superimposed over a burst suppression pattern. Neither patient developed seizures after surgery. CONCLUSIONS: Surgical irritation of the neocortex is sufficient to produce reactive post-resection epileptogenic discharges surrounding an intra-axial neocortical tumor even in the absence of preoperative seizures and spikes. Injury spikes fire at a slow rate and are not predictive of clinical seizures.

Adult↗

PubMed1995

Propagation patterns of temporal spikes.

In standard EEG recordings, spikes appear as single events characterized mainly by the scalp location of the their peak voltage. The signal-to-noise ratio of raw EEG is usually too high to permit more detailed analysis. We used spike averaging to improve the resolution of interictal spikes in 40 patients with temporal lobe epilepsy. Spikes were identified visually in raw, digitally stored EEG. When multiple spike types were present in a patient, they were grouped separately. Spikes were synchronized for averaging by aligning their negative peaks in a designated channel. Sixteen patients demonstrated spike propagation from anterior temporal to posterior temporal electrode locations. Thirty-six patients demonstrated spread of spikes from anterior temporal to fronto-polar electrode sites. While anterior temporal and fronto-polar spikes were often synchronous, fronto-polar spikes followed anterior temporal discharges in 25% of cases and preceded them in 13%. Spike averaging revealed propagation patterns not apparent on visual inspection of raw EEG. We speculate that these patterns may reflect inherent physiological properties of temporal and frontal neuronal circuits, possibly utilized by the epileptogenic process.

Adolescent↗

PubMed1994

Roles of v-erbA homodimers and heterodimers in mediating dominant negative activity by v-erbA.

v-erbA, a viral oncogenic homolog of thyroid hormone receptor (TR), blocks the effect of T3 in TR-mediated transcription. The mechanism(s) for this dominant negative effect by v-erbA on TRs is unknown but may involve competition between v-erbA and TR-containing complexes for binding to thyroid hormone response elements (TREs) and/or protein-protein interactions between v-erbA and TR. To investigate these potential mechanisms, we used the electrophoretic mobility shift assay to compare in vitro translated v-erbA and TR alpha binding to two TREs-chick lysozyme TRE (F2) and direct repeat TRE (DR4). v-erbA bound as a homodimer to these TREs, whereas TR alpha bound as a homodimer and monomer. T3 decreased TR alpha homodimer binding to the TREs as we reported previously; however, surprisingly, high concentrations of T3 (10(-6) M) also decreased v-erbA homodimer binding to the TREs. Additionally, v-erbA formed heterodimers with nuclear proteins such as retinoid X receptor and T3 receptor auxiliary protein as well as with TR alpha. These dimers remained bound to DNA in the presence of T3. Finally, v-erbA could not mediate ligand-dependent transcriptional activation even at 10(-6) M T3 but could block ligand-dependent TR-mediated transactivation in co-transfection experiments. v-erbA also exhibited differential dominant negative activity on F2 and DR4 suggesting that half-site sequence and/or orientation may influence v-erbA-dominant negative activity. In sum, there are multiple v-erbA complexes that bind to TREs in the presence of T3, which all may contribute to v-erbA's dominant negative effect on TR-mediated transcription by competing with TR-containing complexes for binding to TREs.

Base Sequence↗

PubMed1993

Region-specific anti-thyroid hormone receptor (TR) antibodies detect changes in TR structure due to ligand-binding and dimerization.

There are multiple factors that potentially can induce structural changes in DNA-bound thyroid hormone receptors (TRs) including protein-protein interactions, ligand-binding to TRs, and the thyroid hormone response element (TRE) sequence. We used a battery of anti-TR antibodies that recognize the amino-terminal, hinge, or carboxy-terminal regions of TRs to study changes in the epitope regions of in vitro translated TRs in electrophoretic mobility shift assays. We found that the carboxy-terminal and hinge region antibodies recognized TR homodimers but not TR/T3-receptor auxiliary protein or TR/retinoid X receptor heterodimers. The amino-terminal antibodies detected conformational changes due to ligand binding. In contrast, each antibody recognized TR complexes bound to TREs containing half-sites arranged in three different orientations. These results suggest that dimerization with nuclear proteins and ligand-binding, rather than the orientation of TRE half-sites, cause changes in several TR subregions.

Antibody Specificity↗

PubMed1992

Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers.

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand.

Animals↗