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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 433 records · Page 24Linked to original sources

Ictal and enduring interictal disturbances in emotional behaviour in an animal model of temporal lobe epilepsy.

Unilateral microinjections of kainic acid (4.7 nmol) were made into the dorsal hippocampus of 17 unanesthetized freely moving cats. These injections provoked an acute period of intense seizure activity (first 48-72 h) which in 10 cats was followed by a chronic period of recurrent spontaneous complex partial seizures persisting for as long as the cats were studied (up to 4 months). During the chronic epileptic period 8 of these 10 cats demonstrated both ictal and interictal emotional behaviour disturbances. The ictal events included behaviour similar to a 'defensive rage' reaction. Interictally, each of the cats demonstrated an emotional lability. That is, although they behaved in a normal manner if handled affectionately, any mild provocation triggered an explosive defensive rage reaction. As well, the thresholds for electrical brain stimulation induced defensive rage were lowered. That the interictal emotional behaviour disturbances were related to the presence of an active epileptogenic process was suggested by the finding that during periods when no spontaneous seizures were observed for several days, the cats reverted to a less emotionally reactive state and the thresholds for stimulation-induced defence reactions returned to baseline. The results indicate that epileptogenic lesions of the temporal lobe alone can induce an enduring disturbance of emotional behaviour. They support the view that emotional disturbances in patients with epilepsy may sometimes result from pathophysiological mechanisms related to the epileptogenic process, and further suggest that such emotional disturbances might be reversed or prevented if the epileptic seizures could be controlled.

Animals↗

The Lennox-Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography.

We employed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) to study local cerebral glucose utilization in 15 children who had Lennox-Gastaut syndrome. Our results show that LGS can be classified into four predominant subtypes, each with a distinct metabolic pattern: unilateral focal hypometabolism, unilateral diffuse hypometabolism, bilateral diffuse hypometabolism, and normal. Functional disturbances seen on FDG-PET did not always correlate with abnormalities revealed by x-ray computed tomographic scan. This classification of Lennox-Gastaut syndrome into four major metabolic subtypes not only provides a new perspective toward understanding cerebral function in this complex syndrome, but may also prove useful in the clinical management of these patients.

Brain↗

The magnetic field of complex partial seizures agrees with intracranial localizations.

The magnetoencephalogram (MEG) was recorded during 63 complex partial seizures in 4 patients. The MEG showed large biomagnetic signals occurring at the same time as discharges recorded from scalp electroencephalogram (EEG). These MEG signals had the same morphology and frequency as the discharges from the EEG. The location of the seizure focus was verified by depth electrode recordings in 2 patients and by lesions shown on computed tomographic scan and magnetic resonance imaging in the other 2. In each patient, MEG localization estimates were consistent with the location of the seizure focus shown by other methods. When seizures were recorded repeatedly and mapped with a single-channel magnetometer placed at different scalp locations in a single patient, the MEG localization agreed with the electrographic seizure focus localized from depth electrodes. In the maps, the MEG resolved an ambiguity in the scalp EEG and therefore increased the confidence of localization. MEG recordings of seizures may help localize epileptic foci noninvasively.

Cerebral Cortex↗

Brain uptake and CNS levels of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU).

The uptake of 14C-labeled 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU) into the brain was investigated in the rat after intracarotid injection according to the method of OLDENDORF, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug. The brain uptake index was 31.9 +/- 2.9%. Cerebrospinal fluid/blood quotients after i.v. injection were 0.82 at 10 min and 1.10 at 60 min. The results of both methods clearly show that HECNU, in spite of its hydrophilic property, easily penetrates the blood-brain barrier.

Animals↗

The role of three dimension computerized imaging in hand surgery.

Three-dimensional computerized imaging is a new modality of radiological imaging. This new technique transforms the two-dimensional slices of bi-plane CT into a three-dimensional picture by a computer's monitor adjusted to the system. This system enables the physician to rotate the angle of viewing of the desired region to any desired angle. Moreover, this system can delete certain features of different densities from the picture, such as silicone implants, thus improving visualization. Our preliminary results using this technique are presented. The advantages, pitfalls, and suggested future applications of this new technique in hand surgery are discussed.

Adolescent↗

Limbic postictal events: anatomical substrates and opioid receptor involvement.

1. Amygdaloid kindled seizures in rats produce postictal motor deficits, disruption of affective responding to sensory input, postictal explosiveness, and seizure suppression that may be similar to events following complex partial seizures in humans. 2. Preliminary 2DG studies in kindled rats indicate that postictal motor deficits may be mediated by the substantia nigra. Disruption of affective responding and postictal seizure suppression may be mediated by the hippocampus. 3. Data from the literature indicates that postictal motor deficits may be mediated by mu and kappa opioid receptors. The disruption of affective responding may be mediated primarily be delta and maybe also by kappa receptors. Postictal explosiveness may involve either a non-mu receptor or it may be a non-opioid effect. Kindling-induced postictal seizure suppression may be mediated by kappa receptors and perhaps also by mu receptors. 4. Mechanisms underlying postictal effects of complex partial seizures in humans are suggested by the data in this manuscript. New approaches to the treatment of these postictal events are also proposed.

Animals↗

Anticancer drugs: estrophilic cisplatin derivatives.

Our approach to develop platinum complexes with a selective effect on the hormone-dependent MC by exchanging the two NH3 groups of cisplatin by an 1,2-bis(4-hydroxy-phenyl)ethylenediamine derivative which possesses estrogenic activity, was successful. The most interesting compound of this new platinum complex series, meso-(1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine)dichloroplati num(II) (meso-1-PtCl2) and its water soluble sulfatoplatinum(II) derivative (meso-1-PtSO4) were significantly more active on the DMBA-MC and the receptor positive MXT-MC than cisplatin and the related ligand 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (meso-1). According to our proposed mechanism of action, meso-1-PtX (X = Cl2 or SO4) should be enriched in the nuclei of mammary tumor cells, which possess an intact ER system (i.e. an intact cytoplasma nucleus translocation process), thereby causing very strong tumor growth inhibition. Preliminary studies of meso-1-PtSO4 on the DMBA-MC confirm this assumption. In the tumor tissue we found higher Pt-levels than in uterine tissue, which also contains ERs. The Pt-levels of the tumor tissue are much higher than those of skeletal muscle and of blood. In therapeutic dosages meso-1-PtSO4 does not cause kidney damages in rats.

Animals↗

Activation mechanisms of mafosfamide and the role of thiols in cyclophosphamide metabolism.

cis-Mafosfamide (cis-5) (ASTA Z7557), a stable analogue of cis-4-hydroxycyclophosphamide (cis-2), undergoes rapid decomposition in aqueous phosphate buffer or plasma at pH 7.4 and 37 degrees C. The reaction kinetics of cis-5 are complex, and trans-mafosfamide (trans-5) and cis-2 are produced and subsequently disappear over the course of the reaction. The rates of decomposition of cis-5 as well as cis-2 were much faster in plasma than in buffer. The cis-trans isomerization of cis-5 occurred by a specific-base-catalyzed process via iminocyclophosphamide (8) as a transient intermediate. In contrast, formation of cis- and trans-mafosfamide (5) from cis-2 and MESNA (sodium 2-mercaptoethanesulfonate) proceeded by an acid-catalyzed process via the hemithioacetal intermediate (6). The significance of these findings with respect to cyclophosphamide metabolism is discussed.

Antineoplastic Agents↗

Foreign body ingestion: review and suggested guidelines for management.

Eighty percent of ingested foreign bodies which reach to stomach will pass uneventfully through the gastrointestinal tract. The remainder may cause obstruction, perforation or hemorrhage. The risk of complications is increased with long sharp metal objects and animal bones, and may be higher in patients with adhesions due to prior abdominal surgery. Pre-existing intestinal disease such as Crohn's or intestinal stenosis may predispose to complications. The use of overtubes has made endoscopic removal of sharp objects safer. In patients at increased risk for complications, we recommended early endoscopic retrieval of ingested foreign objects.

Child↗

Effects of diazepam, ethanol and Ro 15-1788 on ultrasonic vocalization, locomotor activity and body righting in the neonatal rat.

It has been suggested that ethanol, besides its stimulating, sedative and ataxic effects, also exerts anxiolytic effects similarly to diazepam. In the present study we tested this hypothesis on ultrasonic distress crying in neonatal rats separated from mother and litter-mates. The results showed that both ethanol and diazepam reduced crying in a dose-dependent manner and at doses not affecting the level of motor activity. It was found that the effects of diazepam, but not that of ethanol, was antagonized by the specific benzodiazepine-receptor-antagonist Ro 15-1788. The effects of ethanol were antagonized by the GABA-ergic antagonist picrotoxin. Assessing the sedative/ataxic effects of ethanol and diazepam by the surface body righting response, it was found that the effect of diazepam, but not of ethanol, was antagonized by Ro 15-1788. The results support the hypothesis that ethanol exerts similar anxiolytic actions as diazepam, but that the effects are mediated by different mechanisms.

Animals↗

Characterization of dimer subunits of intermediate filament proteins.

The fundamental subunit of the various types of intermediate-sized filaments (IF) has been shown to be a tetramer that is thought to represent a double dimer, i.e. an array of two laterally packed coiled-coils of alpha-helices. The two-chain state of intact IF proteins had up to this point not been isolated and characterized as has been done for other fibrous alpha-helical coiled-coil proteins. Using buffers containing 3 M-guanidinium hydrochloride we prepared dimers by depolymerization of IF or by reconstitution from fully denatured molecules. Dimers of desmin (from chicken gizzard), vimentin (from bovine lens tissue and cultured human fibroblasts) and the neurofilament protein NF-L (from bovine brain) as well as in vitro formed homodimers of human and rat cytokeratins numbers 8 (A), 18 (D) and 19 ("40K"), are characterized by ultracentrifugation techniques (sedimentation velocity and equilibrium), electron microscopy and chemical cross-linking. The results show that IF proteins from discrete complexes of two polypeptide chains in parallel orientation and probably in coiled-coil configuration, which apparently have a high tendency to further associate into double dimers. Implications of these results for concepts of IF organization and IF protein assembly are discussed.

Animals↗